Agnosic vision is like peripheral vision, which is limited by crowding

Publication date: Available online 1 February 2017
Source:Cortex
Author(s): Francesca Strappini, Denis G. Pelli, Enrico Di Pace, Marialuisa Martelli
Visual agnosia is a neuropsychological impairment of visual object recognition despite near-normal acuity and visual fields. A century of research has provided only a rudimentary account of the functional damage underlying this deficit. We find that the object-recognition ability of agnosic patients viewing an object directly is like that of normally-sighted observers viewing it indirectly, with peripheral vision. Thus, agnosic vision is like peripheral vision. We obtained 14 visual-object-recognition tests that are commonly used for diagnosis of visual agnosia. Our "standard" normal observer took these tests at various eccentricities in his periphery. Analyzing the published data of 32 apperceptive agnosia patients and a group of 14 Posterior Cortical Atrophy (PCA) patients on these tests, we find that each patient's pattern of object recognition deficits is well characterized by one number, the equivalent eccentricity at which our standard observer's peripheral vision is like the central vision of the agnosic patient. In other words, each agnosic patient's equivalent eccentricity is conserved across tests. Across patients, equivalent eccentricity ranges from 4 to 40 deg, which rates severity of the visual deficit.In normal peripheral vision, the required size to perceive a simple image (e.g. an isolated letter) is limited by acuity, and that for a complex image (e.g. a face or a word) is limited by crowding. In crowding, adjacent simple objects appear unrecognizably jumbled unless their spacing exceeds the crowding distance, which grows linearly with eccentricity. Besides conservation of equivalent eccentricity across object-recognition tests, we also find conservation, from eccentricity to agnosia, of the relative susceptibility of recognition of ten visual tests. These findings show that agnosic vision is like eccentric vision.Whence crowding? Peripheral vision, strabismic amblyopia, and possibly apperceptive agnosia are all limited by crowding, making it urgent to know what drives crowding. Acuity does not (Song et al., 2014), but neural density might: neurons per deg² in the crowding-relevant cortical area.



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Metabolomic study of the intervention effects of Shuihonghuazi Formula, a Traditional Chinese Medicinal formulae, on hepatocellular carcinoma (HCC) rats using performance HPLC/ESI-TOF-MS

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Yongrui Bao, Shuai Wang, Xinxin Yang, Tianjiao Li, Yueming Xia, Xiansheng Meng
Ethnopharmacological relevanceMetabolomics is the comprehensive assessment of endogenous metabolites of a biological system in a holistic context, and its property consists with the global view of Traditional Chinese Medicine (TCM). Shuihonghuazi Formula (SHHZF) has been used for liver cancer early treatment in clinical for more than thirty years, but its mechanism remains unclear completely. This paper was designed to explore the therapeutic effects of SHHZF on liver cancer and its metabolomic characters.Materials and methodsAll the rats were given diethylnitrosamine (DEN) at the dosage of 70mg/kg for 14 weeks. From the 7th weeks, SHHZF was given to the rats which lasted for 10 weeks. Therapeutic effects of SHHZF was compared with that of cyclophosphamide (CTX). High performance liquid-chromatography/electrospray-ionization time of flight mass spectrometer (HPLC/ESI-TOF-MS) combined with pattern recognition approaches including principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), was integrated to approximate the comprehensive metabolic signature and discover differentiating metabolites by Agilent MPP 12.1. The changes in metabolic profiling in plasma were restored to their baseline values after SHHZF treatment according to the PLS-DA score plots.ResultsThe results indicated that 23 ions as "differentiating metabolites". The alterations in those metabolites were associated with perturbations in fatty acid and bile acid metabolism, in response to liver cancer through immune and nervous system. And SHHZF could increase the uptake and utilization of linoleic acid and oleic acid, increase arachidonic acid-like substance content and enhance organism immunity of liver cancer rats. And it also could increase the translation from phosphatidylethanolamine (PE) to phosphatidylcholine (PC), linoleic acid metabolism and inhibits abnormal metabolism of bile acid.ConclusionsThe mechanism of therapeutic effects of SHHZF on liver cancer by adjusting the activities of PE N-methyl transferase (PEMT), Lysophospholipase D, methylenetetrahydrofolate reductase (MTHFR) and lysophospholipase was elucidated by the method of metabonomics for the first time.

Graphical abstract

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Understanding and predicting fracture risk in acromegaly

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Treatment pattern and frequency of serum TSH measurement in users of different levothyroxine formulations: a population-based study during the years 2009–2015

Abstract

Background

Several conditions can modify the intestinal absorption of levothyroxine tablets, with potential consequences on their therapeutic effect. Pre-dosed ampoules and oral drops have been recently made available to overcome this limitation.

Aims

To describe the pattern of use of different formulations of levothyroxine in a general population of Southern Italy and to perform an exploratory analysis investigating the effect of switching from levothyroxine tablets to oral liquid formulations.

Methods

Data were extracted from the Caserta Local Health Unit database. All patients receiving at least one levothyroxine prescription during the years 2009–2015 were identified. 1-year incidence of use of formulation-specific levothyroxine was calculated. Switchers between levothyroxine tablets and oral liquid formulations were identified and the frequency of thyroid-stimulating hormone measurement within 2 years prior and after the switch date was explored.

Results

Overall, 56,354 levothyroxine users were included in the study. Of these, 55,147 patients received at least one prescription for tablets (97.9%), 1867 pre-dosed ampoules (3.3%) and 1550 oral drops (2.8%). The proportion of levothyroxine users receiving oral liquid formulations slightly increased over time. Patients switching from tablets to oral liquid formulations showed a statistically significant reduction in the number of thyroid-stimulating hormone measurements after switching from tablets, especially in presence of drugs interacting with levothyroxine potentially altering its absorption.

Conclusions

Use of levothyroxine oral liquid formulations is increasing over time even though their use is still limited in a general population of Southern Italy. Our exploratory analysis showed that the frequency of thyroid-stimulating hormone measurement was reduced in patients switching from levothyroxine tablet to new formulations.

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Optimal vitamin D supplementation strategies

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MicroRNA-155 targets MAP3K10 and regulates osteosarcoma cell growth

Publication date: Available online 1 February 2017
Source:Pathology - Research and Practice
Author(s): Chuangjian Wang, Xiaobo Zhang, Chunlin Zhang, Fuying Zhai, Ying Li, Zongqiang Huang
Osteosarcoma is the most common type of bone cancer prevalent in young adults. Recent studies suggested that aberrant microRNA expression plays an essential role in osteosarcoma pathogenesis. In this study, we found miR-155 up-regulation in different osteosarcoma cell lines U2OS, Saos-2 and MG-63. Through bioinformatic prediction and analysis, we identified its target MAP3K10 that involved in cell proliferation and apoptosis. This work demonstrates novel interaction between microRNA, intercellular MAPK signaling and apoptosis in osteosarcoma, which will provide targets for therapeutic development.



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Effect of sex-hormone levels, sex, body mass index and other host factors on human craniofacial bone regeneration with bioactive tricalcium phosphate grafts

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Christine Knabe, Aynur Mele, Peter Herbert Kann, Barbara Peleska, Doaa Adel-Khattab, Harald Renz, Alexander Reuss, Marc Bohner, Michael Stiller
Little is known regarding the associations between sex-hormone levels, sex, body mass index (BMI), age, other host factors and biomaterial stimulated bone regeneration in the human craniofacial skeleton. The aim of this study was to elucidate the associations between these factors and bone formation after sinus floor augmentation procedures (SFA) utilizing a bioactive tricalcium phosphate (TCP) bone grafting material. We conducted a prospective study in a human population in which 60 male and 60 female participants underwent SFA and dental implant placement using a staged approach. BMI as well as levels of serum estradiol (E2), total testosterone (TT), and the free androgen index (FAI) were measured by radioimmunoassay and electrochemoluminescent-immunoassay. At implant placement, 6 months after SFA, bone biopsy specimens were harvested for hard tissue histology, the amount of bone formation was evaluated by histomorphometry and immunohistochemical analysis of osteogenic marker expression. The Wilcoxon rank-sum U test, Spearman correlations and linear regression analysis were used to explore the association between bone formation and BMI, hormonal and other host factors. BMI and log E2 were significantly positively associated with bone formation in male individuals (p < 0.05). Histomorphometry revealed trends toward greater bone formation and osteogenic marker expression with non-smokers compared to smokers. In male patients, higher E2 levels and higher BMI enhanced TCP stimulated craniofacial i.e. intramembranous bone repair.



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Preclinical evaluation of taxane-binding peptide-modified polymeric micelles loaded with docetaxel in an orthotopic breast cancer mouse model

Publication date: April 2017
Source:Biomaterials, Volume 123
Author(s): Jennifer Logie, Ahil N. Ganesh, Ahmed M. Aman, Rima S. Al-awar, Molly S. Shoichet
We developed a novel taxane-binding peptide (TBP) modified, biodegradable polymeric micelle that overcomes limitations of drug loading and poor serum stability typically seen with particle delivery, leading to enhanced pharmacokinetics and tumor distribution of docetaxel (DTX). The use of the taxane-binding peptide to increase docetaxel loading is particularly compelling as it takes advantage of a known intracellular binding mechanism in a new way. Docetaxel is a potent chemotherapeutic with a therapeutic index often limited by the toxicity of the excipients that are necessary to enhance its solubility for intravenous delivery. Our polymeric micelle has terminal furan groups that enable facile antibody Fab conjugation by Diels-Alder chemistry for targeted delivery. Compared to the conventional ethanolic polysorbate 80 formulation (Free DTX), our nanoparticle (NP DTX) formulation exhibited a two-fold increase in exposure and tumor accumulation. Notably, the reduced toxicity of the NP DTX formulation increased the therapeutic index and allowed for higher dosing regimens, with a maximum tolerated dose (MTD) 1.6-fold higher than that of the Free DTX formulation, which is significant and similar to enhancements observed in clinical products for docetaxel and other drugs. These improved properties led to enhanced mouse survival in an orthotopic model of breast cancer; however, the targeted formulation of Fab-NP DTX did not further improve efficacy. Together, these results clearly demonstrate the benefits of the TBP-modified polymeric micelles as promising carriers for docetaxel.



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Clinical outcome comparison of immediate blanket treatment versus a delayed pathogen-based treatment protocol for clinical mastitis in a New York dairy herd

Publication date: Available online 2 February 2017
Source:Journal of Dairy Science
Author(s): A.K. Vasquez, D.V. Nydam, M.B. Capel, S. Eicker, P.D. Virkler
The purpose was to compare immediate intramammary antimicrobial treatment of all cases of clinical mastitis with a selective treatment protocol based on 24-h culture results. The study was conducted at a 3,500-cow commercial farm in New York. Using a randomized design, mild to moderate clinical mastitis cases were assigned to either the blanket therapy or pathogen-based therapy group. Cows in the blanket therapy group received immediate on-label intramammary treatment with ceftiofur hydrochloride for 5 d. Upon receipt of 24 h culture results, cows in the pathogen-based group followed a protocol automatically assigned via Dairy Comp 305 (Valley Agricultural Software, Tulare, CA): Staphylococcus spp., Streptococcus spp., or Enterococcus spp. were administered on-label intramammary treatment with cephapirin sodium for 1 d. Others, including cows with no-growth or gram-negative results, received no treatment. A total of 725 cases of clinical mastitis were observed; 114 cows were not enrolled due to severity. An additional 122 cases did not meet inclusion criteria. Distribution of treatments for the 489 qualifying events was equal between groups (pathogen-based, n = 246; blanket, n = 243). The proportions of cases assigned to the blanket and pathogen-based groups that received intramammary therapy were 100 and 32%, respectively. No significant differences existed between blanket therapy and pathogen-based therapy in days to clinical cure; means were 4.8 and 4.5 d, respectively. The difference in post-event milk production between groups was not statistically significant (blanket therapy = 34.7 kg; pathogen-based = 35.4 kg). No differences were observed in test-day linear scores between groups; least squares means of linear scores was 4.3 for pathogen-based cows and 4.2 for blanket therapy cows. Odds of survival 30 d postenrollment was similar between groups (odds ratio of pathogen-based = 1.6; 95% confidence interval: 0.7–3.7) as was odds of survival to 60 d (odds ratio = 1.4; 95% confidence interval: 0.7–2.6). The one significant difference found for the effect of treatment was in hospital days; pathogen-based cows experienced, on average, 3 fewer days than blanket therapy cows. A majority (68.5%) of moderate and mild clinical cases would not have been treated if all cows on this trial were enrolled in a pathogen-based protocol. The use of a strategic treatment protocol based on 24-h postmastitis pathogen results has potential to efficiently reduce antimicrobial use.



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Supplemental methionine, choline, or taurine alter in vitro gene network expression of polymorphonuclear leukocytes from neonatal Holstein calves

Publication date: Available online 2 February 2017
Source:Journal of Dairy Science
Author(s): M.K. Abdelmegeid, M. Vailati-Riboni, A. Alharti, F. Batistel, J.J. Loor
Isolated PMNL from neonatal calves were used to evaluate the effect of Met, choline, and taurine supplementation on mRNA expression of genes related to the Met cycle and innate immunity. Five neonatal Holstein calves (3 wk old) were used for PMNL isolation and in vitro culture. The selected genes were related to the 1-carbon and Met cycles, cell signaling and cytokine mediators, inflammation, antimicrobial and killing mechanism associated genes, immune mediators, adhesion, and pathogen recognition. The results indicated that supplementation of Met, choline, and taurine increased homocysteine synthesis through upregulation of SAHH. Furthermore, the lower expression of CXCR1, IL10, IL6, IRAK1, NFKB1, NR3C1, SELL, TLR4, and TNFA indicated that all treatments mitigated the inflammatory activation of blood PMNL. As indicated by the modulation of GCLC and GPX1, choline and taurine supplementation also affected the antioxidant system. However, data indicate that oversupplementation could alter the inflammatory and oxidative status, suggesting the existence of cytotoxicity thresholds. Overall, multiple biological processes in calf PMNL related to inflammatory response and cytoprotection against oxidative stress were affected by Met, choline, and taurine supplementation. These data underscore an important role of these compounds in pre-weaning calf nutritional management.



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Influence of conjugated linoleic acid and vitamin E on performance, energy metabolism, and change of fat depot mass in transitional dairy cows

Publication date: Available online 2 February 2017
Source:Journal of Dairy Science
Author(s): S. Schäfers, D. von Soosten, U. Meyer, C. Drong, J. Frahm, J. Kluess, C. Raschka, J. Rehage, A. Tröscher, W. Pelletier, S. Dänicke
The objective of this experiment was to determine the effects of conjugated linoleic acid (CLA) and vitamin E as well as their interaction on performance variables and lipomobilization during late pregnancy and early lactation (wk 6 antepartum until wk 10 postpartum). For this purpose, 59 pluriparous German Holstein cows were assigned to 4 dietary groups in a 2 × 2 design with the factors CLA and vitamin E at 2 levels. For this trial, we selected cows with a high body condition score because they are more likely to mobilize fat and consequently are at a higher risk of developing ketosis. Furthermore, concentrate proportions were adjusted to provoke ketosis. Lactation performance variables were analyzed in 3 periods (d 42 antepartum until calving, 1 to 21 d in milk, 22 to 70 d in milk). Dry matter intake and net energy intake were reduced in animals receiving CLA. Milk fat content was reduced in the CLA group compared with the control group (4.83 vs. 5.46% in period 2; 3.36 vs. 4.57% in period 3). In the vitamin E and the CLA + vitamin E groups, reduction of milk fat content was observed in period 3 (3.76 vs. 4.57% compared with the control group). Milk yield was not affected by treatment. β-Hydroxybutyrate concentrations and liver lipid contents were not influenced by CLA or vitamin E. Moreover, longitudinal changes of adipose tissue depot mass were not affected by dietary treatments. Results suggest that the effects CLA had on milk composition were compensated by an increased milk yield and a decreased dry matter intake. Reduced milk energy output in CLA-treated animals was compensated by a reduced dry matter intake. Therefore, the net energy balance was not affected by either treatment. Consequently, we found no group effect on the mobilization of adipose tissue.



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A dairy herd-level study of postpartum diseases and their association with reproductive performance and culling

Publication date: Available online 2 February 2017
Source:Journal of Dairy Science
Author(s): J. Dubuc, J. Denis-Robichaud
The objectives of this study were to quantify the herd-level prevalence of postpartum diseases in a large number of dairy farms, and to identify prevalence alarm levels of these diseases based on association with a low prevalence of success at first service, with a high prevalence of pregnancy loss following pregnancy diagnosis at first service, and with a high prevalence of postpartum culling. A total of 126 commercial dairy herds were enrolled in this cohort study, and the herd was the unit of interest. Twenty cows from every herd were enrolled during the study period (a total of 2,520 lactating cows in the study). Cows were diagnosed with hyperketonemia, retained placenta, displaced abomasum, purulent vaginal discharge, cytological endometritis, leukocyte esterase endometritis, and prolonged anovulation. The prevalence of each of these diseases was computed for every herd. The study outcomes were the prevalence of success at first service, the prevalence of pregnancy loss following pregnancy diagnosis at first service, and the prevalence of postpartum culling (≤60 d in milk). Descriptive statistics of disease and outcome prevalence were computed. Logistic regression models were used to identify prevalence alarm levels associated with poor outcome prevalence. Median herd prevalence for hyperketonemia, retained placenta, displaced abomasum, purulent vaginal discharge, cytological endometritis, leukocyte esterase endometritis, and prolonged anovulation were 18.8, 4.9, 4.0, 5.0, 29.4, 43.8, and 35.2%, respectively. Herds were defined as having low prevalence of success at first service if <40.0%, as having a high prevalence of pregnancy loss if ≥6.3%, and as having a high prevalence of postpartum culling if ≥13.3%. Risk factors for herds having a low prevalence of success at first service were ≥11.8% hyperketonemia, ≥5.0% purulent vaginal discharge, ≥18.8% cytological endometritis, ≥35.3% leukocyte esterase endometritis, ≥21.0% prolonged anovulation, and ≥4.0% of displaced abomasum. Risk factors for herds having a high prevalence of pregnancy loss were ≥5.0% purulent vaginal discharge and ≥4.9% retained placenta. Risk factors for herds having a high prevalence of postpartum culling were ≥23.1% hyperketonemia, ≥4.9% retained placenta, and ≥4.0% displaced abomasum. Overall, postpartum diseases were prevalent in these dairy herds and alarm levels were identified as risk factors for poor reproductive performance and increased culling.



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Energy and protein requirements of crossbred (Holstein × Gyr) growing bulls

Publication date: Available online 2 February 2017
Source:Journal of Dairy Science
Author(s): D.B. Oss, F.S. Machado, T.R. Tomich, L.G.R. Pereira, M.M. Campos, M.M.D. Castro, T.E. da Silva, M.I. Marcondes
The objective of this study was to estimate the energy and protein requirements of crossbred (Holstein × Gyr) growing bulls. Twenty-four 10-mo-old bulls [initial body weight (BW) = 184 ± 23.4 kg] were used in a comparative slaughter trial. Six bulls were slaughtered at the beginning of the experiment as the reference group, to estimate initial empty body weight (EBW) and energy and protein contents of the remaining animals. The remaining bulls were assigned to a completely randomized design with 3 levels of dry matter intake and 6 replicates. The levels of dry matter intake were 1.2% of BW, 1.8% of BW, and ad libitum to target orts equal to 5% of the total amount that was fed. The remaining bulls were slaughtered at the end of the experiment. The bulls were fed a diet consisting of 59.6% corn silage and 40.4% concentrate on a dry matter basis. The equation that determined the relationship between EBW and BW was EBW = (0.861 ± 0.0031) × BW. The relationship between empty body gain (EBG) and average daily gain (ADG) was demonstrated by the following equation: EBG = (0.934 ± 0.0111) × ADG. Net energy for maintenance (NEM) was 74.8 ± 2.89 kcal/kg of EBW^0.75 per day, and metabolizable energy for maintenance (MEM) was 120.8 kcal/kg of EBW^0.75 per day. The detected efficiency of use of metabolizable energy for maintenance (km) was 61.9%. The equation used to estimate net energy for gain (NEG) was as follows: NEG = (0.049 ± 0.0011) × EBW^0.75 × EBG^{0.729 ± 0.0532}. The efficiency of use of metabolizable energy for gain (kg) was 35.7%. The metabolizable protein for maintenance (MPM) was 3.05 g/kg of BW^0.75. The equation used to estimate net protein requirements for gain (NPG) = (87.138 ± 65.1378 × EBG) + [(40.436 ± 21.3640) × NEG]. The efficiency of use of metabolizable protein for gain (k) was 35.7%. We concluded that the estimates of energy and protein requirements presented herein are more appropriate than the National Research Council dairy cattle model and the Brazilian BR-CORTE system to balance the diets of crossbred (Holstein × Gyr) growing bulls.



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β-Hydroxybutyrate (BHB) and glucose concentrations in the blood of dairy calves as influenced by age, vaccination stress, weaning, and starter intake including evaluation of BHB and glucose markers of starter intake

Publication date: Available online 2 February 2017
Source:Journal of Dairy Science
Author(s): F.X. Suarez-Mena, W. Hu, T.S. Dennis, T.M. Hill, R.L. Schlotterbeck
The objective of this research was to determine how blood β-hydroxybutyrate (BHB) and glucose are affected by age, time of day, stress, weaning, forced intake restriction, and voluntary starter intake in calves between 1 and 9 wk of age, and to evaluate if either is an acceptable proxy for starter intake. Holstein calves were fed a 27% crude protein, 17% fat milk replacer at 660 g of dry matter daily along with free-choice starter and water. Calves were weaned on d 42. Jugular blood was sampled at 0800, 1200, and 1600 h, and within 5 min of sampling BHB, and glucose concentrations were estimated using test strips (Nova Max Plus meter, Nova Biomedical Corporation, Waltham, MA). Age effects and time of day were estimated by sampling blood weekly (d 6, 13, 20, 27, 34, 41, and 48). To determine vaccination stress, a Pasteurella vaccine was administered after blood sampling at 0800 h on d 36. Effect of voluntary starter intake was tested by selecting calves for low and high intakes (d 35 to 39) and sampling on d 40, 41, 43, and 44. Starter intake restriction was tested by restricting intake in half of the calves and sampling on d 60 and 61. Data were analyzed with repeated measurements in a mixed model procedure with either within-calf effect (day or week) or within-calf effects (hour, and day or week) included in the model. Time of day did not affect blood BHB and glucose in the first 6 wk. Blood BHB was greater in wk 7 versus wk 1 to 6. Blood glucose was greater in the first 5 wk compared with wk 6 and 7. Blood BHB increased and glucose decreased with increasing starter intake. Blood BHB declined due to vaccination, but glucose was unaffected. Starter intake restriction reduced BHB for 3 d and glucose for 2 d after restriction. Both were affected by time of day. Around weaning (d 40 to 44), BHB and glucose increased with increasing starter intake. In this research, neither blood BHB nor glucose was a good proxy for starter intake. Blood BHB was positively and glucose negatively related to starter intake; however, relationships were weak, variable, and affected by time of day, stress, and intake restriction. Over 30% of calves tested ≤0.2 mmol/L BHB when consuming >1,250 g/d of starter, and test strip increments were 0.1 mmol/L, which represented >25% of the mean blood BHB concentration. In this study, neither blood BHB nor glucose was an acceptable proxy for estimating starter intake.



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The bovine colostrum microbiome and its association with clinical mastitis

Publication date: Available online 2 February 2017
Source:Journal of Dairy Science
Author(s): Svetlana F. Lima, Andre G.V. Teixeira, Fabio S. Lima, Erika K. Ganda, Catherine H. Higgins, Georgios Oikonomou, Rodrigo C. Bicalho
In an effort to characterize colostrum microbial diversity and its potential associations with early-lactation clinical mastitis, we used high-throughput sequencing of the 16S rRNA gene to investigate the bovine colostrum microbiome. A prospective observational study was conducted that included 70 Holstein cows; colostrum samples were collected from all 4 mammary gland quarters. Colostrum samples were categorized according to whether the quarter was diagnosed (CMC) or not diagnosed (NCMC) with clinical mastitis during the first 30 d postpartum. Colostrum samples were dominated by Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria, and Tenericutes phyla, with the 6 most common taxa order (o), family (f), and genus (g) being g_Staphylococcus, g_Prevotella, f_Ruminococcaceae, o_Bacteroidales, o_Clostridiales, g_Pseudomonas. The colostrum microbiota of primiparous cows was significantly richer (higher number of bacterial species) than that of multiparous cows, and differences in colostrum taxonomic structure between parities were also observed. The microbial community of NCMC samples of primiparous cows was significantly more diverse than that of CMC samples, and the relative abundances of the Tenericutes and Fusobacteria phyla as well as the Mycoplasma and Fusobacterium genera were significantly higher in NCMC than in CMC samples of primiparous cows. The colostrum core microbiome, defined as the bacterial taxa common to all colostrum samples examined, was composed of 20 taxa and included bacterial genera already known to be associated with mastitis (e.g., Staphylococcus, Mycoplasma, and Streptococcus spp.). Our results indicate that the colostrum microbiome of primiparous cows differs from that of multiparous cows, and it harbors some diversity and taxonomic markers of mammary gland health specific to primiparous cows only.



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Non-culture-based identification of mastitis-causing bacteria by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Publication date: Available online 2 February 2017
Source:Journal of Dairy Science
Author(s): Juliana Regina Barreiro, Juliano Leonel Gonçalves, Patrícia Aparecida Campos Braga, Aline Gerato Dibbern, Marcos Nogueira Eberlin, Marcos Veiga dos Santos
The purpose of this study was to evaluate the detection limit of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for direct identification, without previous microbiological culture, of bovine mastitis-causing bacteria from milk samples. Milk samples (n = 15) were experimentally contaminated with Staphylococcus aureus, Streptococcus uberis, Streptococcus agalactiae, Streptococcus dysgalactiae, and Escherichia coli to have bacterial counts ranging from 10³ to 10⁹ cfu/mL. These contaminated milk samples were subjected to a preparation protocol for bacterial ribosomal protein extraction using the MALDI Sepsityper kit (Bruker Daltonik, Bremen, Germany), which allowed MALDI-TOF MS coupled with Biotyper software (Bruker Daltonik) to identify bacterial fingerprints based on intact ribosomal proteins. The ability of MALDI-TOF MS to correctly identify bacterial strains from experimentally contaminated milk (without previous microbiological culture) depended on the bacterial count of the samples and on the species of the bacteria evaluated. Adequate identification at the bacterial species level (score ≥2.0) directly from milk samples required bacterial counts in the following ranges: ≥10⁶ cfu/mL of Staph. aureus, ≥10⁷ cfu/mL of E. coli, and ≥10⁸ cfu/mL of Strep. agalactiae, Strep. dysgalactiae, and Strep. uberis. We concluded that direct identification of mastitis-causing pathogens is possible for Staph. aureus, E. coli, Strep. agalactiae, Strep. dysgalactiae, and Strep. uberis, but correct identification depended on the bacterial count in the milk samples.



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Isolated pseudoabducens palsy in acute thalamic stroke

Publication date: Available online 1 February 2017
Source:Clinical Imaging
Author(s): Mehdi Ghasemi, Nazish Riaz, Anna Bjornsdottir, David Paydarfar
Oculomotor abnormalities are rarely noted in thalamic strokes. We describe isolated right pseudoabducens palsy in a young patient with acute left thalamic infarction revealed by diffusion-weighted magnetic resonance imaging. The patient's horizontal diplopia and oculomotor palsy resolved within 3days. This case supports the hypothesis that a lesion can cause isolated esotropia by interrupting descending inhibitory convergence pathways that traverse the paramedian thalamus and decussate in the subthalamic region to innervate the contralateral third oculomotor nucleus. Esotropia contralateral to the thalamic lesion results from tonic activation of the medial rectus, producing pseudoabducens palsy.



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Comparison of low-dose coronary artery calcium scoring using low tube current technique and hybrid iterative reconstruction vs. filtered back projection

Publication date: Available online 2 February 2017
Source:Clinical Imaging
Author(s): Nada Sulaiman, Jeanette Soon, Jong kwan Park, Christopher Naoum, Shaw-Hua Kueh, Philipp Blanke, Darra Murphy, Jennifer Ellis, Cameron Hague, Jonathon Leipsic
IntroductionWe sought to validate whether low dose CACS CT with hybrid IR (HIR) could replace standard dose filtered back projection (FBP).MethodWe enrolled 100 patients to undergo low dose CACS CT with HIR, in addition to routine full dose FBP.ResultsNo significant difference between full and low dose CT in Agatston score 138.2±360.6 vs. 137.3±356.4 (p=0.272) or calcium mass score 19±48.3 vs. 18.7±49 (p=0.8), respectively. Bland–Altman analysis showed no systematic bias. Calcium volume difference was statistically significant 57.2±134 vs. 55.1±130.2 (p=0.001).ConclusionLow dose CT for calcium scoring with HIR enables stable CACS Agatston score and calcium mass quantification as compared to full dose FBP.

Graphical abstract

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Evaluation of image quality of coronary artery plaque with rapid kVp-switching dual-energy CT

Publication date: Available online 1 February 2017
Source:Clinical Imaging
Author(s): Yasutoshi Ohta, Shinichiro Kitao, Tomomi Watanabe, Junichi Kishimoto, Kazuhiro Yamamoto, Toshihide Ogawa
We evaluated the virtual monochromatic imaging (VMI) energy levels that maximize image quality of each coronary plaque component in dual-energy computed tomography angiography in 495 coronary segments (45 for each energy level). Maximal signal-to-noise ratios were different for plaque, lumen, fat, and surrounding tissue (p<0.05). Maximal contrast-to-noise ratios were observed at 70keV for calcified plaque (CP), non-calcified plaque (NCP), and fat in comparison with the lumen (p<0.05), and 70keV and 120keV for NCP in comparison with fat (p=0.144).VMI demonstrated maximal image quality at different energy levels for each component of coronary artery plaque.



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Testosterone increases CCL-2 expression in visceral adipose tissue from obese women of reproductive age.

Publication date: Available online 1 February 2017
Source:Molecular and Cellular Endocrinology
Author(s): Nicolás Crisosto, Cristián Flores, Manuel Maliqueo, Bárbara Echiburú, Jaime Vásquez, Fernando Maluenda, Teresa Sir-Petermann
ContextHyperandrogenic states and obesity in women are associated with insulin-resistance. Androgens reduce glucose uptake in adipose cells and increase TNFα production in peripheral monocytes. Inflammatory cytokines have a known detrimental effect on insulin resistance. The aim of the present study was to explore the role of testosterone in local cytokine production in visceral adipose tissue from women of reproductive age.DesignTwenty-four women 18–40 years old, undergoing elective abdominal surgery for benign and non-inflammatory conditions, were recruited for the study. Women with clinical hyperandrogenism, diabetes, hepatic or renal dysfunction, hypothyroidism, BMI> 40 or drugs known to interfere with hormonal levels or fat metabolism were excluded. Women were classified into two groups according to BMI, non-obese (N-O; BMI < 30) and obese (O; BMI 30–40). A basal blood sample was drawn at the time of surgery for the measurement of glucose, insulin, total testosterone, lipid profile and circulating CCL-2, IL-6 and total adiponectin. Omental fat tissue (10 g) was obtained in all women. Samples of 300 mg of minced adipose tissue were incubated with vehicle (CTL) or testosterone (T) 10⁻⁹ M to 10⁻⁶ M for 24, 48 or 72 h. CCL-2, IL-6, TNFα, androgen Receptor (AR) mRNA levels were measured by Real Time quantitative polymerase chain reaction (qPCR) and normalized to GAPDH expression. Secretion of CCL-2 and IL-6 was measured in conditioned media by ELISA.ResultsExpression of CCL-2 and IL-6 at 24 h in CTLs was significantly higher in the obese group compared to the non-obese group (2.81 ± 0.43 fold for CCL-2; p = 0.005 and 3.26 ± 0.73 fold for IL-6; p = 0.03). At 48 and 72 h there were no differences between both groups in any of the markers. In the total group without T stimulation (CTL) there were significant correlations between: TNFα expression at 24 h and BMI (r = 0.708; p = 0.005), TGC levels (r = 0.904; p = 0.004), total Cholesterol (r = 0.904; p = 0.0046) and IL-6 expression at 24 h (r = 0.642; p = 0.015). CCL-2 expression at 24 h was correlated with BMI (r = 0.637; p = 0.007) and TGC levels (r = 0.700; p = 0.02). Stimulation with T 10⁻⁶ M for 72 h produced an increase in CCL-2 expression, which was significantly larger in the obese group compared to the non-obese group (2.04 ± 0.44 in obese vs 0.82 ± 0.11 in non-obese; p = 0.015). Moreover, in the whole group there was a positive correlation between CCL-2 expression in T-treated tissues (10⁻⁶ M 72 h) and BMI (r = 0.514; p = 0.017). Cytokine determinations followed the same pattern as mRNA but without significant differences.ConclusionsTestosterone increases CCL-2 expression in visceral adipose tissue from obese women of reproductive age. This response is associated to BMI. These results show new possible mechanisms connecting androgens to insulin resistance and chronic inflammation.



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Early bone formation around immediately loaded implants with nanostructured calcium-incorporated and machined surface: a randomized, controlled histologic and histomorphometric study in the human posterior maxilla

Abstract

Objective

The aim of this randomized, controlled histologic/histomorphometric study was to compare the early bone formation around immediately loaded implants with nanostructured calcium-incorporated (NCI) and machined (MA) surface, placed in the human posterior maxilla.

Materials and methods

Fifteen fully edentulous patients (six males; nine females; mean age 57.9 ± 6.7 years) were selected for this study. Each patient was installed with two temporary transmucosal implants, with different surfaces: one NCI (test) and one MA (control) implant. All temporary implants were placed in the posterior maxilla, according to a split-mouth design, to help to support an interim complete maxillary denture. After 8 weeks, all temporary transmucosal implants were retrieved for histologic/histomorphometric evaluation. The bone-to-implant contact (BIC%) and the bone density (BD%) were calculated. The Wilcoxon matched-pairs signed-rank test was used to evaluate differences (BIC%, BD%) between the surfaces. The level of significance was set at 0.05.

Results

Eight weeks after placement, 24 clinically stable implants (12 test, 12 control) were subjected to histologic/histomorphometric evaluation. In the MA implants, the histomorphometric evaluation revealed a mean BIC(±SD)% and BD(±SD)% of 21.2(±4.9)% and 29.8(±7.8)%, respectively. In the NCI implants, the histomorphometric analysis revealed a mean BIC(±SD)% and BD(±SD)% of 39.7(±8.7)% and 34.6(±7.2)%, respectively. A statistically significant difference was found between the two surfaces with regard to BIC% (p < 0.001), while no significant difference was found with regard to BD% (p = 0.09).

Conclusions

The NCI surface seems to increase the peri-implant endosseous healing properties in the native bone of the posterior maxilla, under immediate loading conditions, when compared with the MA surface.

Clinical relevance

Under immediate loading conditions in the human posterior maxilla, the nanostructured calcium-incorporated surface has led to better histologic and histomorphometric results than the machined surface; therefore, the clinical use of implants with nanostructured calcium-incorporated surface may be beneficial in the posterior maxilla, under immediate loading protocol.

http://ift.tt/2kZIomG

Injectable platelet rich fibrin (i-PRF): opportunities in regenerative dentistry?

Abstract

Objectives

Platelet rich plasma (PRP) has been utilized in regenerative dentistry as a supra-physiological concentrate of autologous growth factors capable of stimulating tissue regeneration. Despite this, concerns have been expressed regarding the use of anti-coagulants, agents known to inhibit wound healing. In this study, a liquid formulation of platelet rich fibrin (PRF) termed injectable-PRF (i-PRF) without the use of anti-coagulants was investigated.

Materials and methods

Standard PRP and i-PRF (centrifuged at 700 rpm (60G) for 3 min) were compared for growth factor release up to 10 days (8 donor samples). Furthermore, fibroblast biocompatibility at 24 h (live/dead assay); migration at 24 h; proliferation at 1, 3, and 5 days, and expression of PDGF, TGF-β, and collagen1 at 3 and 7 days were investigated.

Results

Growth factor release demonstrated that in general PRP had higher early release of growth factors whereas i-PRF showed significantly higher levels of total long-term release of PDGF-AA, PDGF-AB, EGF, and IGF-1 after 10 days. PRP showed higher levels of TGF-β1 and VEGF at 10 days. While both formulations exhibited high biocompatibility and higher fibroblast migration and proliferation when compared to control tissue-culture plastic, i-PRF induced significantly highest migration whereas PRP demonstrated significantly highest cellular proliferation. Furthermore, i-PRF showed significantly highest mRNA levels of TGF-β at 7 days, PDGF at 3 days, and collagen1 expression at both 3 and 7 days when compared to PRP.

Conclusions

i-PRF demonstrated the ability to release higher concentrations of various growth factors and induced higher fibroblast migration and expression of PDGF, TGF-β, and collagen1. Future animal research is now necessary to further validate the use of i-PRF as a bioactive agent capable of stimulating tissue regeneration.

Clinical relevance

The findings from the present study demonstrate that a potent formulation of liquid platelet concentrates could be obtained without use of anti-coagulants.

http://ift.tt/2k3tU7X

A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma

Glioblastoma (GBM) is a deadly brain cancer, and all attempts to control it have failed so far. However, the future looks bright, as we now know the molecular landscape of GBM through the work of The Cancer Genome Atlas (TCGA) program. GBMs exhibit significant inter- and intratumoral heterogeneity, and to control this type of tumor, a personalized approach is required. One target, whose gene is amplified and mutated in a large number of GBMs, is the epidermal growth factor receptor (EGFR). But all attempts to target it have been unsuccessful. We attribute the reason for this failure to the molecular heterogeneity of EGFR in GBM, as well as to the poor brain penetration of previously tested EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs). In this review, we discuss the molecular heterogeneity of EGFR and provide rational preclinical and clinical guidelines for testing AZD9291, a third generation, irreversible EGFR-TKI with both a high affinity for EGFRvIII and excellent brain penetration.

http://ift.tt/2kT2RdC

Contrast Functions of αA- and αB-Crystallins in Cancer Development

α-Crystallins, initially identified as the structural proteins of the ocular lens, belong to the small heat shock protein family. They play significant roles in maintaining the lens transparency and preventing protein aggregation. α-Crystallins exist in two isoforms: αA and αB, and they display differential tissue distribution. Their mutations are implicated in several human diseases including cardiac myopathies, neurodegenerative diseases, cataracts and various types of cancers. Increased αB expression was detected in retinoblastoma, breast cancer, glioblastoma, prostate and renal cell carcinomas, indicating its role in promoting tumor growth. A complex picture emerges for αA. Although earlier studies suggest that αA may promote cancer development, recent studies from our laboratory demonstrate that αA can act as a tumor suppressor inhibiting cell transformation and retarding cell migration through modulating MAP kinase activity. In this review, we summarize the recent progress about the functions of αA and αB in cancer development.

http://ift.tt/2kWEUlU

Our current practice of ‘group and save’ blood for nasopharyngeal tumour biopsy (NB), and to determine the rate of blood transfusions among patients who underwent NB under general anaesthesia

 Is 'Group and Save' Blood Request Routinely Required for Nasopharyngeal Biopsy?

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Transfer of malignant traits as opposed to migration of cells: A novel concept to explain metastatic disease.

Publication date: Available online 1 February 2017
Source:Medical Hypotheses
Author(s): Goffredo Orazio Arena, Vincenzo Arena, Manuel Arena, Mohamed Abdouh
Metastatic disease is believed to develop following dissemination of cells to target organs. Inability of this theory to effectively explain certain phenomena such as patterns of metastatic spread, late metastasis formation, different gene patterns between primary cancer and metastasis have brought forward the need for alternative models. Recent discoveries have strengthened the validity of theories supporting a humoral transfer of malignant traits as opposed to migration of malignant cells to explain metastatic disease in cancer patients.In light of this new evidence, we would like to highlight a model that offers a new perspective to explain cancer metastasis. In the system that we theorize genetic material released by cancer cells would travel, either free or packed in exosomes, through the blood. Target cells located in organs deriving from the same embryological layer might uptake this genetic material due to expression of specific receptors. Interplay with the immune system would determine the fate of these oncofactors and would regulate their ability to circulate in the blood, integrate in the genome and be transcribed. We also hypothesize that the expression of cell membrane receptors such as integrins, to which cancer exosomes ligate might be mediated by inherited or acquired oncosuppressor mutations.



http://ift.tt/2kl4SQd

Hypocapnic hypothesis of Leigh disease

Publication date: Available online 1 February 2017
Source:Medical Hypotheses
Author(s): Ewa Pronicka
Leigh syndrome (LS) is a neurogenetic disorder of children caused by mutations in at least 75 genes which impair mitochondrial bioenergetics. The changes have typical localization in basal ganglia and brainstem, and typical histological picture of spongiform appearance, vascular proliferation and gliosis. ATP deprivation, free radicals and lactate accumulation are suspected to be the causes.Hypocapnic hypothesis proposed in the paper questions the energy deprivation as the mechanism of LS. We assume that the primary harmful factor is hypocapnia (decrease in pCO2) and respiratory alkalosis (increase in pH) due to hyperventilation, permanent or in response to stress. Inside mitochondria, the pH signal of high pH/low bicarbonate ion (HCO^–3) is transmitted by soluble adenyl cyclase (sAC) through cAMP dependent manner. The process can initiate brain lesions (necrosis, apoptosis, hypervascularity) in OXPHOS deficient cells residing at the LS area of the brain. The major message of the article is that it is not the ATP depletion but intracellular alkalization (and/or hyperoxia?) which seem to be the cause of LS.The paper includes suggestions concerning the methodology for further research on the LS mechanism and for therapeutic strategy.



http://ift.tt/2jA8L6I

Cortical Gray Matter MR Imaging in Multiple Sclerosis

Publication date: Available online 1 February 2017
Source:Neuroimaging Clinics of North America
Author(s): Massimiliano Calabrese, Marco Castellaro

Teaser

Several neuropathologic and imaging studies have consistently confirmed that multiple sclerosis affects both white (WM) and gray matter (GM) and that GM damage plays a key role in disability progression. However, differently from WM damage, the less inflammatory cell infiltration, the absence of significant blood-brain barrier damage, the low myelin density in upper cortical layers, as well as technical constraints, make the GM damage almost undetectable by means of conventional MR imaging.


http://ift.tt/2jGRmEn

Radiologically Isolated Syndrome

Publication date: Available online 1 February 2017
Source:Neuroimaging Clinics of North America
Author(s): Darin T. Okuda

Teaser

Remarkable advances in the understanding of the biology of multiple sclerosis have been achieved through the use of conventional and novel MR imaging techniques of the central nervous system. With improvements in access by patients and utilization of MR imaging technology in health care, an increasing number of unanticipated structural anomalies are being appreciated. In certain instances, white matter abnormalities within the brain and spinal cord are discovered in subjects with no prior history of neurologic symptoms supportive of inflammatory demyelinating events.


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Pediatric Oncology Enters the Era of Precision Medicine

Publication date: Available online 1 February 2017
Source:Current Problems in Cancer
Author(s): Nita L. Seibel, Katherine Janeway, Carl E. Allen, Susan N. Chi, Y Jae Cho, Julia L. Glade Bender, AeRang Kim, Theodore W. Laetsch, Meredith S. Irwin, Naoko Takebe, James V. Tricoli, D. Williams Parsons
With the use of high-throughput molecular profiling technologies, precision medicine trials are ongoing for adults with cancer. Similarly, there is interest in how these techniques can be applied to tumors in children and adolescents to expand our understanding of the biology of pediatric cancers and evaluate the clinical implications of genomic testing for these patients. This article will review the early studies in pediatric oncology showing the feasibility of this approach, describe the future plans to evaluate the clinical implications in a multicenter clinical trial and identify the challenges of applying genomics in this patient population.



http://ift.tt/2kWCIL0

Corrigendum to “The role of H3K4me3 and H3K9/14ac in the induction by dexamethasone of Per1 and Sgk1, two glucocorticoid early response genes that mediate the effects of acute stress in mammals” [Biochim. Biophys. Acta 1839 (2014) 866–872]

Publication date: Available online 2 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): M. Xydous, A. Prombona, T.G. Sourlingas




http://ift.tt/2ktK9Mx

Erythroid specific activator GATA-1-dependent interactions between CTCF sites around the β-globin locus

Publication date: Available online 1 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Yujin Kang, Yea Woon Kim, Jin Kang, Won Ju Yun, AeRi Kim
CTCF sites (binding motifs for CCCTC-binding factor, an insulator protein) are located considerable distances apart on genomes but are closely positioned in organized chromatin. The close positioning of CTCF sites is often cell type or tissue specific. Here we analyzed chromatin organization in eight CTCF sites around the β-globin locus by 3C assay and explored the roles of erythroid specific transcription activator GATA-1 and KLF1 in it. It was found five CTCF sites convergent to the locus interact with each other in erythroid K562 cells but not in non-erythroid 293 cells. The interaction was decreased by depletion of GATA-1 or KLF1. It accompanied reductions of CTCF and Rad21 occupancies and loss of active chromatin structure at the CTCF sites. Furthermore Rad21 occupancy was reduced in the β-globin locus control region (LCR) hypersensitive sites (HSs) by the depletion of GATA-1 or KLF1. The role of GATA-1 in interaction between CTCF sites was revealed by its ectopic expression in 293 cells and by deletion of a GATA-1 site in the LCR HS2. These findings indicate that erythroid specific activator GATA-1 acts at CTCF sites around the β-globin locus to establish tissue-specific chromatin organization.



http://ift.tt/2jGAPR6

Epigenetic interplay at the β-globin locus

Publication date: Available online 1 February 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Wei Shern Lee, Bradley McColl, Jovana Maksimovic, Jim Vadolas
During development, the α- and β-globin genes exhibit a highly conserved pattern of expression, giving rise to several developmental stage-specific hemoglobin variants. Networks of regulatory proteins interact with epigenetic complexes to regulate DNA accessibility and histone modifications, thereby determining appropriate patterns of globin gene expression. In this review, we focus on recent advances in the understanding of the molecular mechanisms that underpin globin gene expression, focusing on multi-subunit regulatory complexes that bind to specific regions of DNA to orchestrate globin gene transcription throughout development.



http://ift.tt/2ktRknJ

Alterations of the optic pathway between unilateral and bilateral optic nerve damage in multiple sclerosis as revealed by the combined use of advanced diffusion kurtosis imaging and visual evoked potentials

Publication date: June 2017
Source:Magnetic Resonance Imaging, Volume 39
Author(s): Mariko Yoshida Takemura, Masaaki Hori, Kazumasa Yokoyama, Nozomi Hamasaki, Michimasa Suzuki, Koji Kamagata, Kouhei Kamiya, Yuriko Suzuki, Shinsuke Kyogoku, Yoshitaka Masutani, Nobutaka Hattori, Shigeki Aoki
ObjectivesWe investigated changes in the optic tract and optic radiation in patients with multiple sclerosis (MS) by comparing unilateral and bilateral optic nerve damage assessed based on visual evoked potentials (VEPs) using advanced diffusion MR metrics.MethodsIn 21 MS patients, diffusion MRI was performed. Maps of fractional anisotropy, apparent diffusion coefficient (ADC), and mean kurtosis (MK) were computed. On the basis of the P100 latency in VEPs, the MS patients were divided into three groups: bilateral (n=7), unilateral (n=7), and no abnormality (n=7). Their optic tracts and optic radiations were analyzed with diffusion MRI-based fiber tracking. We also investigated the correlations between diffusion parameters and VEPs (n=21).ResultsIn the optic tract, the diffusion changes in each of the three groups showed step-like changes. The diffusion changes in the optic radiations of the unilateral group were similar to those in the normal VEP group. Only the bilateral group showed significantly higher ADC and lower MK relative to the other two groups (P<0.05, Steel–Dwass multiple-comparison test). A significant positive correlation between VEP latency and ADC and a significant negative correlation between VEP latency and MK were observed (P<0.01, Spearman's correction).ConclusionsWe first evaluated the relationship between VEPs and DKI and concluded that the lateral geniculate nucleus may compensate for unilateral damage in the pre-geniculate optic pathway via neural plasticity.



http://ift.tt/2jA9ftv

Proteolysis of chloroplast proteins is responsible for accumulation of free amino acids in dark-treated tea (Camellia sinensis) leaves

Publication date: Available online 2 February 2017
Source:Journal of Proteomics
Author(s): Yiyong Chen, Xiumin Fu, Xin Mei, Ying Zhou, Sihua Cheng, Lanting Zeng, Fang Dong, Ziyin Yang
Shade management (dark treatment) on tea (Camellia sinensis) plants is a common approach to improve free amino acids in raw materials of tea leaves. However, the reason for amino acid accumulation in dark-treated tea leaves is still unknown. In the present study, dark treatment significantly increased content of free amino acids and reduced content of soluble proteins in tea leaves. Quantitative proteomics analysis showed that most enzymes involved in biosyntheses of amino acids were down-accumulated by dark treatment. Chloroplast numbers reduced in dark-treated leaves and the content of soluble proteins reduced in the chloroplasts isolated from dark-treated leaves compared to control. These suggest that proteolysis of chloroplast proteins contributed to amino acid accumulation in dark-treated leaves. Two chloroplasts proteases, ATP-dependent Clp protease proteolytic subunit 3 and protease Do-like 2, were up-accumulated in dark-treated leaves. This study firstly elucidated the mechanism of accumulation of amino acids in dark-treated tea leaves.Biological significanceEffect of dark on crop growth has been widely studied, while less attention has been paid to effect of dark on quality-related metabolites in crops. Shade management (dark treatment) on tea plants is a common approach to improve free amino acids in tea leaves. However, the reason for accumulation of free amino acids in dark-treated tea leaves is still unknown. In the present study, an iTRAQ-based quantitative proteomic analysis was performed and the results revealed the accumulation of free amino acids in dark-treated tea leaves was not due to activation of biosyntheses of amino acids, but resulted from proteolysis of chloroplast proteins. The information will advance our understanding of formation of quality or function-related metabolites in agricultural crops exposed to dark stress/shade management.

Graphical abstract

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Proteomic characterization of seminal plasma from alternative reproductive tactics of Chinook salmon (Oncorhynchus tswatchysha)

Publication date: Available online 2 February 2017
Source:Journal of Proteomics
Author(s): Robert Gombar, Trevor E. Pitcher, Jason A. Lewis, Janeen Auld, Panayiotis O. Vacratsis
Chinook salmon (Oncorhynchus tshawytscha) are external fertilizers that display sneak-guard alternative reproductive tactics. The larger hooknose males dominate mating positions, while the smaller jack males utilize sneak tactics to achieve fertilization. Although poorly understood, previous studies have suggested that differences in spermatozoa quality may play a critical role in sperm competition. Considering that the seminal plasma strongly regulates spermatozoa quality and other processes critical for fertilization success, we employed label free quantitative mass spectrometry utilizing ion mobility separation coupled to cross-species bioinformatics to examine the seminal plasma proteome of Chinook salmon. A total of 345 proteins were identified in all biological replicates analyzed, including many established seminal plasma proteins that may serve as future biomarkers for Chinook salmon fertility and sperm competition. Moreover, we elucidated statistically significant protein abundance differences between hooknose and jack male tactics. Proteins involved in membrane remodeling, proteolysis, hormonal transport, redox regulation, immunomodulation, and ATP metabolism were among the proteins reproducibly identified at different levels and represent putative factors influencing sperm competition between jack and hooknose males. This study represents the largest seminal plasma proteome from teleost fish and the first reported for Chinook salmon.SignificanceChinook salmon (Oncorhynchus tshawytscha) males represent an example of male alternative reproductive tactics where diverse reproductive strategies are thought to increase sexual selection. While seminal plasma has been shown to play an important regulatory role in sperm competition in many species, little is known about the protein composition of the seminal plasma of salmon. Therefore, seminal plasma isolated from the two alternative reproductive tactics of Chinook salmon (small sneaky jacks and large dominant hooknoses) were analyzed by label free quantitative mass spectrometry employing data independent acquisition and ion mobility separation. This yielded the largest proteome data set of the seminal plasma from salmon and the first to examine protein abundance differences between male alternative reproductive tactics. The quantitative proteomic data provides insight into possible unique mechanistic aspects of Chinook salmon alternative reproductive tactics utilized for sperm competition and fertilization success.

Graphical abstract

http://ift.tt/2kvwP9O

Interleukin-10 family cytokines pathway: genetic variants and psoriasis

Summary

Background

Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20, and IL-24 have been implicated in autoimmune diseases and we have previously reported that genetic variants in IL10 gene cluster were associated with psoriasis.

Objective

To analyze the relationship of genetic polymorphisms in the IL10 gene cluster with psoriasis. This study also explores whether there are gene–gene interactions among these genetic polymorphisms.

Methods

A total of 377 patients with psoriasis and 403 matched healthy controls were enrolled to carry out a case-control study for 48 SNPs of IL10 gene cluster. Genotyping for the SNPs was conducted on the Applied Biosystems 3730 DNA Analyzer using SNPlex^™ technology. Generalized multifactor dimensionality reduction (GMDR) analysis was applied to discover likely gene–gene interaction model among the SNPs.

Results

The results showed that the alleles distributions of IL10 gene cluster SNPs are significantly different between case and control groups. Carriers of IL10 T allele (rs1554286) and of IL20 T allele (rs1400986) conferred protection to psoriasis (OR = 0.63, Pc = 0.007; OR = 0.62, Pc = 0.038, respectively). GMDR analysis displayed a significant gene-gene interaction between IL10 (rs1554286) and IL20 (rs1518108) variants. The strongest protective effect was found with the block 1 haplotype ACATA in the IL10 gene (Pc = 0.004).

Conclusions

The novel finding of the present study is gene-gene interaction of the IL-10 pathway on the reduced risk of psoriais. Our results indicate that genetic variants of the immunomodulatory IL10 and IL20 genes may protective effect in the Europeans from Russia. Independent studies are needed to verify the results and find the possible functional explanation.

This article is protected by copyright. All rights reserved.

http://ift.tt/2jYS4xS

A Phase 1 clinical trial demonstrates nfP2X7 targeted antibodies provide a novel, safe and tolerable topical therapy for BCC

Abstract

Background

Expression of P2X₇, an ATP gated calcium channel, increases cancer cell proliferation and invasiveness. A variant of P2X₇ (termed nfP2X₇), in which a normally hidden epitope (E200) is exposed for antibody binding, is observed in a variety of different cancers.

Objectives

To investigate the safety, tolerability and pharmacokinetics and assess indicative efficacy of a novel antibody ointment as a therapeutic for BCC.

Methods

An open label, Phase 1 clinical trial was undertaken at 3 dermatology clinics to evaluate the safety and tolerability of topical administration of an ointment containing 10% sheep polyclonal anti-nfP2X₇ antibodies (BIL010t) to primary BCC lesions twice daily for 28 days. Twenty one patients with primary BCC lesions at least 0.5cm² in area and less than 2.0cm in diameter were enrolled. The primary endpoints were safety, tolerability and pharmacokinetics (PK).Change in lesion size after treatment was determined and histology was performed on pre-treatment and End of Treatment (EOT) biopsies.

Results

Compliance was very high, with treatment being well-tolerated. The most common adverse events were treatment site erythema, pruritus, dryness and pain. There was no evidence of systemic penetration of the sheep antibody. Lesions were measured prior to and after 28 days treatment, with 65% of patients showing a reduction in lesion area, 20% no change and 15% an increase. Histopathology of post-treatment excision of lesion sites showed 8 patients with stable disease, 9 with partial response and 3 with complete response.

Conclusions

Antibodies against nfP2X₇ (BIL010t) provide a novel, safe and well tolerated treatment for BCC.

This article is protected by copyright. All rights reserved.

http://ift.tt/2k2Yu1g

Bumetanide Reduce the Seizure Susceptibility Induced by Pentylenetetrazol via Inhibition of Aberrant Hippocampal Neurogenesis in Neonatal Rats after Hypoxia-Ischemia

Publication date: Available online 2 February 2017
Source:Brain Research Bulletin
Author(s): Jiang-jian Hu, Xing-liang Yang, Wen-di Luo, Song Han, Jun Yin, Wan-hong Liu, Xiao-Hua He, Bi-Wen Peng
Hypoxia-ischemia brain damage (HIBD) is one of prevalent causes of neonatal mortality and morbidity. Our data demonstrated that hypoxia-ischemia (HI) induced Na⁺-K⁺-Cl⁻-co-transporter 1 (NKCC1) increasing in hippocampus. Previous studies demonstrated that NKCC1 regulates various stages of neurogenesis. In this study, we studied the role of increased NKCC1 in regulating of HI-induced neurogenesis. HIBD model was established in 7days old Sprague-Dawley rat pup, and the expression of NKCC1 was detected by western blot and qPCR. Brain electrical activity in freely rats was monitored by electroencephalography (EEG) recordings. HI-induced neurogenesis was detected by immunofluorescence staining. Neurobehavioral test was to investigate the neuro-protective role of bumetanide, an inhibitor of NKCC1, on neonatal rats after HI. The results showed that bumetanide treatment significantly reduced brain electrical activity and the seizure stage of epilepsy induced by pentylenetetrazol (PTZ) in vivo after HI. In addition, bumetanide restored aberrant hippocampal neurogenesis and associated cognitive function. Our data demonstrated that bumetanide reduces the susceptibility of epilepsy induced by PTZ in rats suffering from HI injury during neonatal period via restoring the ectopic newborn neurons in dentate gyrus (DG) and cognitive function.



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Activation of cannabinoid receptors elicits antidepressant-like effects in a mouse model of social isolation stress

Publication date: Available online 1 February 2017
Source:Brain Research Bulletin
Author(s): Arvin Haj-Mirzaian, Hossein Amini-Khoei, Arya Haj-Mirzaian, Shayan Amiri, Maria Ghesmati, Mazyar Zahir, Hamed Shafaroodi, Ahmad Reza Dehpour
Social isolation stress (SIS) paradigm is a chronic stress procedure able to induce profound behavioral and neurochemical changes in rodents and evokes depressive and anxiety-like behaviors. Recent studies demonstrated that the cannabinoid system plays a key role in behavioral abnormalities such as depression through different pathways; however, there is no evidence showing a relation between SIS and the cannabinoid system. This study investigated the role of the cannabinoid system in depressive-like behavior and anxiety-like behavior of IC animals. For this purpose, NMRI mice were treated with WIN55, 212-2 (non-selective cannabinoid receptor agonist) and AM-251 (cannabinoid receptor type 1 antagonist) and AM-630 (cannabinoid receptor type 2 antagonist). We found that behavioral abnormality followed by SIS was mitigated after administration of WIN55, 212-2. Also, depressive-like effects induced by SIS were significantly increased following administration of AM-251 and AM-630. Co-administration of cannabinoid receptor antagonists (AM-251 and AM-630), significantly reversed the antidepressant effect of WIN55, 212-2 in IC animals. Our findings suggest that the cannabinoid system is involved in depressive-like behaviors induced by SIS. We showed that activation of cannabinoid receptors (type 1 and 2) could mitigate depression-like behavior induced by SIS in a mouse model.



http://ift.tt/2jGqzZ6

Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus

Publication date: Available online 1 February 2017
Source:Brain Research Bulletin
Author(s): Xiao-Jie Zhao, Zhan Zhao, Dan-Dan Yang, Lu-Lu Cao, Ling Zhang, Juan Ji, Jun Gu, Ji-Ye Huang, Xiu-Lan Sun
Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus.



http://ift.tt/2jGxuRW

Icariin enhances remyelination process after acute demyelination induced by cuprizone exposure

Publication date: Available online 1 February 2017
Source:Brain Research Bulletin
Author(s): Yifan Zhang, Linlin Yin, Na Zheng, Li Zhang, Jianghong Liu, Weixiong Liang, Qi Wang
Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remission period may play a great role for the regeneration of the myelin sheath. C57BL/6 mice were fed with cuprizone (CPZ, 0.2% w/w) for 5 weeks to induce acute demyelination and oligodendrocytes degeneration, after which CPZ was withdrawn to allow recovery. Icariin (ICA, 6.25, 12.5 and 25mg/kg/day), vehicle (0.5% sodium carboxymethyl cellulose solution) or water was administrated orally to mice for 1 week after CPZ withdrawal. Luxol-fast blue (LFB), immunohistochemical or immunofluorescence staining was used to detect morphological and biological changes in the brains. CPZ administration for 5 weeks resulted in completely demyelination and remyelination occurred when CPZ was withdrawn. ICA treatment during the recovery period for 1 week significantly improved myelin restoration, enhanced NF200-positive axons repair, increased the number of APC⁺/Olig2⁺ mature oligodendrocytes and prevented neuron-derived neurotrophic factor such as nerve growth factor (NGF) loss. Our results demonstrated that ICA treatment during the recovery period promotes remyelination and axon rewrapped, at least, in part, by promoting oligodendrogenesis and neurotrophic factor production.



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Preventive treatment of astaxanthin provides neuroprotection through suppression of reactive oxygen species and activation of antioxidant defense pathway after stroke in rats

Publication date: Available online 1 February 2017
Source:Brain Research Bulletin
Author(s): Lei Pan, Dong-dong Qin, Ying Zhou, Xiu-fang Li, Qing-jia Wan, Zheng-bo Wang, Xin-tian Hu, Yong Yin, Le-hua Yu
Astaxanthin, a natural antioxidant carotenoid, has been shown to reduce cerebral ischemic injury in rodents. However, there have not been any studies specifically addressing whether preventive administration of astaxanthin can protect against cerebral ischemia. The purpose of this study was to examine whether pretreatment of astaxanthin can protect against ischemic injuries in the adult rats. The rats were pre-administered intragastrically with astaxanthin for seven days (once a day), and middle cerebral artery occlusion was performed at 1hour after the final administration. It was found that astaxanthin prevented neurological deficits and reduced cerebral infarction volume. To evaluate the mechanisms underlying this protection, brain tissues were assayed for free radical damage, antioxidant gene expression, cell apoptosis and regeneration. The results showed that the mechanisms involved suppression of reactive oxygen species, activation of antioxidant defense pathway, and inhibition of apoptosis as well as promotion of neural regeneration. Astaxanthin did not alter body weights and the protective effect was found to be dose-dependent. Collectively, our data suggest that pretreatment of astaxanthin can protect against ischemia-related damages in brain tissue through multiple mechanisms, hinting that astaxanthin may have significant protective effects for patients vulnerable or prone to ischemic events.



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EEG Based Zero-phase Phase-locking Value (PLV) and Effects of Spatial Filtering During Actual Movement

Publication date: Available online 1 February 2017
Source:Brain Research Bulletin
Author(s): Wenjuan Jian, Minyou Chen, Dennis J. McFarland
Phase-locking value (PLV) is a well-known feature in sensorimotor rhythm (SMR) based BCI. Zero-phase PLV has not been explored because it is generally regarded as the result of volume conduction. Because spatial filters are often used to enhance the amplitude (square root of band power (BP)) feature and attenuate volume conduction, they are frequently applied as pre-processing methods when computing PLV. However, the effects of spatial filtering on PLV are ambiguous. Therefore, this article aims to explore whether zero-phase PLV is meaningful and how this is influenced by spatial filtering. Based on archival EEG data of left and right hand movement tasks for 32 subjects, we compared BP and PLV feature using data with and without pre-processing by a large Laplacian. Results showed that using ear-referenced data, zero-phase PLV provided unique information independent of BP for task prediction which was not explained by volume conduction and was significantly decreased when a large Laplacian was applied. In other words, the large Laplacian eliminated the useful information in zero-phase PLV for task prediction suggesting that it contains effects of both amplitude and phase. Therefore, zero-phase PLV may have functional significance beyond volume conduction. The interpretation of spatial filtering may be complicated by effects of phase.



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Temporal and diurnal variations of carbonaceous aerosols and major ions in biomass burning influenced aerosols over Mt. Tai in the North China Plain during MTX2006

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Suresh K.R. Boreddy, Kimitaka Kawamura, Kazuhiro Okuzawa, Yugo Kanaya, Zifa Wang
To better understand the impact of agricultural waste burning on the air quality of free troposphere over the North China Plain (NCP), we collected total suspended particles (TSP) at the summit of Mt. Tai, located in the NCP using a high volume air sampler during 29 May to 28 June 2006, when the field burning of agricultural residue was intense. Temporal variations of all measured species showed that their concentration increases from late May to mid June (major BB period), peaking during 12–14 June, and then significantly decreased towards late June (minor BB period). We noticed that a significant reduction in the concentrations of carbonaceous aerosols during the period of 8–11 June, when the wind direction shifted from southerly to northerly. We found that concentrations of carbonaceous aerosols and some major ions showed several times higher during major BB period than those of minor BB period. We also found that nighttime concentrations are higher than daytime during major BB period, suggesting that a long-range atmospheric transport of biomass burning plumes in the free troposphere, which arrived at the summit of Mt. Tai. In contrast, daytime concentrations are higher than nighttime during minor BB period. We found higher concentrations of secondary organic carbon (SOC) during major BB period, suggesting that formation of secondary organic aerosols through aqueous phase chemistry under high NOx conditions during a long-range atmospheric transport. nss-K⁺ showed about four times higher concentrations during major BB than those of minor BB. Concentrations of nss-Ca²⁺ are higher in nighttime during major BB period, implying that a significant long-range atmospheric transport of mineral dust over the sampling site. These results are further supported by the positive matrix factorization (PMF) analysis, which showed that biomass burning was a major source for the carbonaceous aerosols followed by mineral dust sources over the summit of Mt. Tai.

Graphical abstract

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In-flight monitoring of particle deposition in the environmental control systems of commercial airliners in China

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Qing Cao, Qiuyu Xu, Wei Liu, Chao-Hsin Lin, Daniel Wei, Steven Baughcum, Sharon Norris, Qingyan Chen
Severe air pollution and low on-time performance of commercial flights in China could increase particle deposition in the environmental control systems (ECSs) of commercial airliners. The particles deposited in the ECSs could negatively affect the performance of the airplanes. In addition, particles that penetrate into the aircraft cabin could adversely impact the health of passengers and crew members. This investigation conducted simultaneous measurements of particle mass concentration and size distribution inside and outside the cabin during 64 commercial flights of Boeing 737 and Airbus 320 aircraft departing from or arriving at Tianjin Airport in China. The results showed that the PM2.5 mass concentration deposition in the ECSs of these airplanes ranged from 50% to 90%, which was much higher than that measured in an airplane with a ground air-conditioning unit. The average deposition rates of particles with diameters of 0.5–1 μm, 1–2 μm, 2–5 μm, 5–10 μm, and >10 μm were 89 ± 8%, 85 ± 13%, 80 ± 13%, 73 ± 15%, and 80 ± 14%, respectively. The in-flight measurement results indicated that the particle concentration in the breathing zone was higher than that in the air-supply zone, which implies a significant contribution by particles in the interior of the cabin. Such particles come from human emissions or particle resuspension from interior surfaces.



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Particulate matter air pollution in Europe in a +2 °C warming world

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Gwendoline Lacressonnière, Laura Watson, Michael Gauss, Magnuz Engardt, Camilla Andersson, Matthias Beekmann, Augustin Colette, Gilles Foret, Béatrice Josse, Virginie Marécal, Agnes Nyiri, Guillaume Siour, Stefan Sobolowski, Robert Vautard
In the framework of the IMPACT2C project, we have evaluated the future European particulate matter concentrations under the influence of climate change and anthropogenic emission reductions. To do so, 30-year simulations for present and future scenarios were performed with an ensemble of four regional Chemical Transport Models. +2 °C scenarios were issued from different regional climate simulations belonging to the CORDEX experiment (RCP4.5 scenario). Comparing present day simulations to observations shows that these simulations meet the requested quality criteria even if some biases do exist. Also, we showed that using regional climate models instead of meteorological reanalysis was not critical for the quality of our simulations. Present day as well as future scenarios show the large variability between models associated with different meteorology and process parameterizations. Future projections of PM concentrations show a large reduction of PM10 and PM2.5 concentrations in a +2 °C climate over the European continent (especially over Benelux), which can be mostly attributed to emission reduction policies. Under a current legislation scenario, annual PM10 could be reduced by between 1.8 and 2.9 μg m⁻³ (14.1–20.4%). If maximum technologically feasible emission reductions were implemented, further reductions of 1.4–1.9 μg m⁻³ (18.6–20.9%) are highlighted. Changes due to a +2 °C warming, in isolation from emission changes, are in general much weaker (−1.1 to +0.4 μg m⁻³,-0.3 to +5.1% for annual PM10 averaged over the European domain). Even if large differences exist between models, we have determined that the decrease of PM over Europe associated with emission reduction is a robust result. The patterns of PM changes resulting from climate change (for example the increase of PM over Spain and southern France and the decrease of PM10 over eastern Europe) are also robustly predicted even if its amplitude remains weak compared to changes associated with emission reductions.



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Tethered balloon-based particle number concentration, and size distribution vertical profiles within the lower troposphere of Shanghai

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Kun Zhang, Dongfang Wang, Qinggen Bian, Yusen Duan, Mengfei Zhao, Dongnian Fei, Guangli Xiu, Qingyan Fu
A tethered balloon-based measurement campaign of particle number concentration (PNC) and particle number size distribution (PNSD) in the size range of 15.7–661.2 nm was conducted within the lower troposphere of 1000 m in Shanghai, a Chinese megacity, during December of 2015. The meteorological conditions, PNC, and PNSD were synchronously measured at the ground-based station as well as by the tethered balloon. On ground level, the 88.2 nm particles were found to have the highest PNC. The Pearson correlation analysis based on the ground level data showed NO2 had a strong correlation with PNC. The synchronous measurement of PNC and PNSD at the ground station and on the tethered balloon showed that the 15.7–200 nm particles had higher PNC on ground level, but the PNC of 200–661.2 nm particles was higher at 400 m. One haze event (Dec 22nd-Dec 23rd) was selected for detailed discussion on the variation of vertical profiles of PNSD and PNC. The vertical distribution of characteristics of PNC and PNSD were observed and compared. Results indicated that the highest MaxDm (the diameter with the highest PNC) during those three launches all appeared at a high altitude, usually above 300 m. Compared to the clean days, the relatively bigger MaxDm at each height in the haze days also indicated regional transport of pollutants might contribute to more to that haze event.



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Spatial and temporal evaluation of long term trend (2005–2014) of OMI retrieved NO2 and SO2 concentrations in Henan Province, China

Publication date: April 2017
Source:Atmospheric Environment, Volume 154
Author(s): Leishi Zhang, Chih Sheng Lee, Ruiqin Zhang, Liangfu Chen
Tropospheric NO2 and SO2 concentrations are of great importance with regard to air quality, atmospheric chemistry, and climate change. Due to lack of surface monitoring stations, this study analyzes long term trend of NO2 and SO2 levels (2005–2014), retrieved from Ozone Monitoring Instrument (OMI) board on the NASA's Aura satellite, in an important region of China – Henan Province. Henan Province, located in North China Plain, has encountered serious air pollution problems including extremely high PM2.5 concentrations and as one of the most polluted region in China. The satellite spatial images clearly show that high levels of both NO2 and SO2 are concentrated in north and northeastern regions with much lower levels observed in other parts of Henan. Both pollutants exhibit the highest levels in winter with the least in summer/spring. The temporal trend analysis based on moving average of deseasonalized and decyclic data indicates that for NO2, there is a continuous increasing pattern from 2005 to 2011 at 6.4% per year, thereafter, it shows a decreasing trend (10.6% per year). As for SO2, the increasing trend is about 16% per year from 2005 to 2007 with decreasing rate 7% per year from 2007 to 2014. The economic development with incredible annual 11% GDP growth in Henan is responsible for increasing levels of NO2 and SO2. The observed decreasing SO2 level starting in 2007 is due to reduced SO2 emission, utilization of flue gas desulfurization (FGD) devices and to some extent, in preparation of Beijing 2008 Olympic Games. On the other hand, increasing vehicle numbers (155% from 2006 to 2012) and coal consumption (37% during the same span), along with the lack of denitration process for removing flue/exhaust gas NOx are responsible for increasing NO2 trend until 2011. The ratio of SO2/NO2 started decreasing in 2007 and dropped significantly from 2011 to 2013 indicating good performance of FGD and ever increasing NOx contribution from mobile sources. Unlike those observed in developed countries (US, EU and Japan) where a decreasing trend for both SO2 and NO2 has been observed since 1990s, the observed upward and downward trend found in Henan is similar to those found in North China Plain and other parts of China. The spatial and temporal trend analyses of SO2 and NO2 in four other regions in Henan further indicate a similar trend to those observed in Henan Province, albeit with different increasing and decreasing rate. The results provide regulatory agency to develop action plans to combat air pollution problem in general and SO2 and NO2 problems in particular in Henan. The implications of our findings and recommendations for decision makers are discussed in the paper.

Graphical abstract

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Randomized comparison of virtual microscopy and glass microscopy among dermatology and pathology residents during a simulated in-training examination

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Special Issue on Systematic Reviews in Criminology

Publication date: Available online 2 February 2017
Source:Aggression and Violent Behavior
Author(s): Darrick Jolliffe, David P. Farrington
This article introduces the special issue on systematic reviews in criminology. It explains what a systematic review is, and how it is superior to the more usual narrative reviews. It also defines a meta-analysis. This article then summarizes the eight systematic reviews and two reviews of systematic reviews that are published in this special issue, advancing knowledge about epidemiology, risk factors, and the effectiveness of interventions for offending and violence.



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The unique needs of pregnant, violence-exposed women: A systematic review of current interventions and directions for translational research

Publication date: Available online 2 February 2017
Source:Aggression and Violent Behavior
Author(s): Kathryn H. Howell, Laura E. Miller-Graff, Amanda J. Hasselle, Kathryn E. Scrafford
Intimate partner violence (IPV) is, unfortunately, a common lifetime experience for women, with heightened risk of exposure during pregnancy. IPV exposure in pregnancy is associated with serious physical and mental health problems in the perinatal period, as well as detrimental effects on the health and well-being of the developing infant. The objectives of the current review are to: (1) present representative literature on the effects of IPV in pregnancy, (2) conduct a systematic review of existing interventions for IPV-exposed pregnant women and (3) provide recommendations for future translational research in this area. The review indicated that despite the broad range of negative effects associated with IPV exposure during pregnancy, interventions are scarce and largely limited to crisis intervention approaches. Available interventions seeking to address broader or intergenerational effects of violence are limited in scope, and effectiveness data are preliminary in nature. As such, there is a great need for theory-based interventions that address women's complex needs, including specific developmental necessities of both the pregnant woman and her child (e.g., breastfeeding, early parenting, infant care). Incorporating these elements within a strengths-based paradigm may also decrease stigma related to IPV and facilitate empowerment and self-efficacy for this at-risk group.



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Effects of maize stover and its derived biochar on greenhouse gases emissions and C-budget of brown earth in Northeast China

Abstract

Concerns regarding rising population levels and the impacts of atmospheric greenhouse gas (GHG) emissions on world climate have encouraged effective alternative methods to increase agricultural production while mitigating climate change. Soil GHG emissions from maize (Zea mays L.) fields treated with stover and a stover-derived biochar amendment during two consecutive maize growing seasons were studied in a brown earth soil type in Liaoning, China. We considered three treatments: CK (basal application of mineral NPK fertilizer; 120 kg N ha⁻¹, 60 kg P₂O₅ ha⁻¹, and 60 kg K₂O ha⁻¹, respectively), ST (maize stover application; 7.5 t ha⁻¹), and BC (7.5 t ha⁻¹ of maize stover was charred, with a yield of 35% of the original biomass; 2.63 t ha⁻¹). Both ST and BC treatments received the same fertilization as CK. Soil GHG emissions were monitored using the static chamber-gas chromatography method. The mean CO₂ emissions of the two-year experiment indicated that ST and BC were significantly higher than CK by 131.0 and by 21.3%, respectively, and there was a striking difference between ST and BC treatments. The N₂O-N emissions decreased in the following order, BC < ST < CK, and cumulative reduced CH₄ emissions in BC and ST were 1.58 and 2.21 times higher than observations in CK, respectively. The total global warming potential (GWP) in 2013 and 2014 decreased in the following order: BC < ST < CK. For the yield average data of two-year experiment, compared to CK and BC treatments, ST treatment showed 7.9 and 4.5% reduction, respectively. The C gains in BC treatment were significantly higher than that observed in ST treatment by 7.3%. Compared with the stover incorporating, biochar application significantly decreased the total CO₂ emissions and GHG intensity (GHGI), and it enhanced C-sequestration.

http://ift.tt/2k2CS5n

Effect of organic manure on Cd and As accumulation in brown rice and grain yield in Cd-As-contaminated paddy fields

Abstract

Large areas of paddy fields in mining areas in south China have been contaminated by mixed Cd and As. To test the possibility of using organic manure (OM) as a method of reducing Cd and As accumulation in brown rice and increase the grain yield in such paddy fields, two rice cultivars [Jianyou G2 (JY) and Fengyousimiao (FY)] and three amounts of OM (0, 0.5, 1.5 kg/m²) were examined in three Cd-As-contaminated paddy fields (Fogang, Dabaoshan, Fankou) in Guangdong Province. The results show that the application of OM can effectively increase the grain yield and reduce Cd. However, the As concentration was found to increase in brown rice, especially when high levels of OM were used. The addition of OM increased the soil pH and organic matter content in the soils and enhanced the activities of superoxide dismutase (SOD) and catalase (CAT) in plant tissues. Our results suggest that OM can be used as an amendment to effectively decrease Cd accumulation in brown rice in Cd-contaminated paddy fields. However, it is necessary to consider the negative effects of OM amendments when adding OM to As-contaminated paddy fields.

http://ift.tt/2kZ45U2

The Depressed Brain: An Evolutionary Systems Theory

Publication date: Available online 1 February 2017
Source:Trends in Cognitive Sciences
Author(s): Paul B. Badcock, Christopher G. Davey, Sarah Whittle, Nicholas B. Allen, Karl J. Friston
Major depression is a debilitating condition characterised by diverse neurocognitive and behavioural deficits. Nevertheless, our species-typical capacity for depressed mood implies that it serves an adaptive function. Here we apply an interdisciplinary theory of brain function to explain depressed mood and its clinical manifestations. Combining insights from the free-energy principle (FEP) with evolutionary theorising in psychology, we argue that depression reflects an adaptive response to perceived threats of aversive social outcomes (e.g., exclusion) that minimises the likelihood of surprising interpersonal exchanges (i.e., those with unpredictable outcomes). We suggest that psychopathology typically arises from ineffectual attempts to alleviate interpersonal difficulties and/or hyper-reactive neurobiological responses to social stress (i.e., uncertainty), which often stems from early experience that social uncertainty is difficult to resolve.



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Climbing Brain Levels of Organisation from Genes to Consciousness

Publication date: Available online 1 February 2017
Source:Trends in Cognitive Sciences
Author(s): Jean-Pierre Changeux
Given the tremendous complexity of brain organisation, here I propose a strategy that dynamically links stages of brain organisation from genes to consciousness, at four privileged structural levels: genes; transcription factors (TFs)–gene networks; synaptic epigenesis; and long-range connectivity. These structures are viewed as nested and reciprocally inter-regulated, with a hierarchical organisation that proceeds on different timescales during the course of evolution and development. Interlevel bridging mechanisms include intrinsic variation-selection mechanisms, which offer a community of bottom-up and top-down models linking genes to consciousness in a stepwise manner.



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Neural Perspectives on Cognitive Control Development during Childhood and Adolescence

Publication date: Available online 31 January 2017
Source:Trends in Cognitive Sciences
Author(s): Eveline A. Crone, Nikolaus Steinbeis
Since the discovery that patients with damage to the prefrontal cortex (PFC) show similar deficits in cognitive control as young children, the PFC model of cognitive control development has been a popular description of how cognitive control emerges over time. In this review, we show that not only do many studies support this model, but also that more specific models of PFC development can be formulated, according to the functional roles of subregions and by taking into account the distinctions within ventral–dorsal and lateral–medial PFC. We also reveal that the functional development of dorsolateral PFC supports the development of deliberative processes, whereas that of the medial PFC supports the development of internalized decisions. These new conceptualizations may provide better descriptions of the complexity of cognitive control development.



http://ift.tt/2kv6JUx

Working Memory Maintenance: Sustained Firing or Synaptic Mechanisms?

Publication date: Available online 31 January 2017
Source:Trends in Cognitive Sciences
Author(s): Juha Silvanto
According to conventional views, holding information in working memory (WM) involves elevated and persistent neuronal firing. This has been challenged by models in which WM maintenance is implemented by activity-silent synaptic mechanisms. A new study suggests that both have a role, consistent with cognitive models positing several states of WM. However, do these states reflect the operation of attention or awareness?



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The role of cross-group friendship and emotions in adolescents’ attitudes towards inclusion

Publication date: March 2017
Source:Research in Developmental Disabilities, Volume 62
Author(s): Jeanine Grütter, Luciano Gasser, Tina Malti
BackgroundMost countries have started to educate students with special educational needs (SEN) in mainstream schools, but it remains unclear how inclusive attitudes towards students with SEN can be promoted.AimsThis study investigated the role of adolescents' friendships and socio-moral competencies for their attitudes towards the inclusion of students with SEN. Specifically, we studied whether adolescents without SEN would develop more inclusive attitudes if they had close friendships with SEN students and if they expressed negative emotions about social exclusion.MethodsAdolescents' inclusive attitudes and their emotions were gathered from survey data of 1225 Swiss students aged 11–13. Social network data were collected to assess adolescents' friendship relationships.ResultsThe results indicated that adolescents' friendship closeness with SEN students positively related to their inclusive attitudes. However, this was only true for adolescents who anticipated more negative than positive emotions if a student with SEN was excluded.ImplicationsThese findings highlight the role of friendship relationships between adolescents with and without SEN and adolescents' socio-moral experiences for their attitudes towards the inclusion of peers with SEN. Thus, inclusive education may benefit from promoting friendships among students with and without SEN as well as adolescents' socio-moral competencies.



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Editorial

Publication date: 20 January 2017
Source:Journal of Genetics and Genomics, Volume 44, Issue 1
Author(s): Yongbiao Xue




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Correlative analysis of dopaminergic and serotonergic metabolism across the brain to study monoaminergic function and interaction

Publication date: Available online 1 February 2017
Source:Journal of Neuroscience Methods
Author(s): Françoise Dellu-Hagedorn, Aurélie Fitoussi, Philippe De Deurwaerdère
BackgroundThe widespread innervation of dopamine (DA) and serotonin (5-HT) systems in cortical and subcortical regions suggests that their biochemical interactions can occur in multiple regions directly or indirectly via neurobiological networks.New MethodThe present study was aimed at validating a neurochemical approach of monoaminergic function based on inter-individual variability of monoamine tissue contents in various cortical and subcortical areas. We focused on monoamines metabolism and examined correlations within and between these monoaminergic systems in selected regions for the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and/or homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) alone or with respect to the turnover indexes DOPAC/DA, DOPAC+HVA/DA and 5-HIAA/5-HT.ResultsThe tissue content of metabolites and their parent drug correlated within a brain region. Conversely, a few specific relationships (10%) were observed for each turnover in paired brain regions and even less between the 5-HT and DA turnovers. The number of correlations was lower when looking at the metabolite tissue contents. In all cases, the 5-HT and DA turnover indexes or metabolites correlated positively within a brain region.Comparison with Existing Method(s)These data validate the inter-individual analysis of monoamine tissue content by providing evidence that the metabolite correlates with the parent neurotransmitter in the same region. The pattern of correlations of metabolisms reported here differs from that of the parent neurotransmitters, notably regarding the relationships of DA turnovers between striatal territories.ConclusionThe whole neurochemical approach is of interest for characterizing monoaminergic systems interaction in various genetic or pharmacological models of neuropsychiatric diseases.

Graphical abstract

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Cell Culture Chamber with Gas Supply for Prolonged Recording of Human Neuronal Cells on Microelectrode Array

Publication date: Available online 1 February 2017
Source:Journal of Neuroscience Methods
Author(s): Joose Kreutzer, Laura Ylä-Outinen, Antti-Juhana Mäki, Mervi Ristola, Susanna Narkilahti, Pasi Kallio
BackgroundTypically, live cell analyses are performed outside an incubator in an ambient air, where the lack of sufficient CO2 supply results in a fast change of pH and the high evaporation causes concentration drifts in the culture medium. That limits the experiment time for tens of minutes. In many applications, e.g. in neurotoxicity studies, a prolonged measurement of extracellular activity is, however, essential.New MethodWe demonstrate a simple cell culture chamber that enables stable culture conditions during prolonged extracellular recordings on a microelectrode array (MEA) outside an incubator. The proposed chamber consists of a gas permeable silicone structure that enables gas transfer into the chamber.ResultsWe show that the culture chamber supports the growth of the human embryonic stem cell (hESC)-derived neurons both inside and outside an incubator. The structure provides very low evaporation, stable pH and osmolarity, and maintains strong signaling of hESC-derived neuronal networks over three-day MEA experiments.Comparison with Existing MethodsExisting systems are typically complex including continuous perfusion of medium or relatively large amount of gas to supply. The proposed chamber requires only a supply of very low flow rate (1.5ml/min) of non-humidified 5% CO2 gas. Utilizing dry gas supply makes the proposed chamber simple to use.ConclusionUsing the proposed culture structure on top of MEA, we can maintain hESC-derived neural networks over three days outside an incubator. Technically, the structure requires very low flow rate of dry gas supporting, however, low evaporation and maintaining the pH of the culture.

Graphical abstract

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Biochemistry and neuroscience: the twain need to meet

Publication date: April 2017
Source:Current Opinion in Neurobiology, Volume 43
Author(s): Mary B Kennedy
Neuroscience has come to mean the study of electrophysiology of neurons and synapses, micro and macro-scale neuroanatomy, and the functional organization of brain areas. The molecular axis of the field, as reflected in textbooks, often includes only descriptions of the structure and function of individual channels and receptor proteins, and the extracellular signals that guide development and repair. Studies of cytosolic 'molecular machines', large assemblies of proteins that orchestrate regulation of neuronal functions, have been neglected. However, a complete understanding of brain function that will enable new strategies for treatment of the most intractable neural disorders will require that in vitro biochemical studies of molecular machines be reintegrated into the field of neuroscience.



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