Editorial Board

Publication date: 1 March 2018
Source:Journal of Neuroscience Methods, Volume 297





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Essential Tremor Quantification Based on the Combined Use of a Smartphone and a Smartwatch: the NetMD study

Publication date: Available online 23 February 2018
Source:Journal of Neuroscience Methods
Author(s): Roberto López-Blanco, Miguel A. Velasco, Antonio Méndez-Guerrero, Juan Pablo Romero, María Dolores del Castillo, J. Ignacio Serrano, Julián Benito-León, Félix Bermejo-Pareja, Eduardo Rocon
BackgroundThe use of wearable technology is an emerging field of research in movement disorders. This paper introduces a clinical study to evaluate the feasibility, clinical correlation and reliability of using a system based in smartwatches to quantify tremor in essential tremor (ET) patients and check its acceptance as clinical monitoring tool.New MethodThe system is based on a commercial smartwatch and an Android smartphone. An investigational Android application controls the process of recording raw data from the smartwatch three-dimensional gyroscopes. Thirty-four ET patients were consecutively enrolled in the experiments and assessed along one year. Arm tremor was videofilmed and scored using the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). Tremor intensity was quantified with the root mean square of angular velocity measured in the patients' wrists.ResultsEighty-two assessments with smartwatches were performed. Spearman's correlation coefficients (ρ) between clinical tremor (FTM-TRS) scores and smartwatch measures for tremor intensity were 0.590 at rest; ρ = 0.738 in steady posture; ρ = 0.189 in finger-to-nose maneuvers; and ρ = 0.652 in pouring water task. Smartwatch reliability was checked by intraclass realiability coefficients: 0.85, 0.95, 0.91, 0.95 respectively. Most of patients showed good acceptance of the system.Comparison with Existing Method(s)This commodity hardware contributes to quantify tremor objectively in a consulting-room by customized Android smart devices as clinical monitoring tool.ConclusionsThe NetMD system for tremor analysis is feasible, well-correlated with clinical scores, reliable and well-accepted by patients to tremor follow-up. Therefore, it could be an option to objectively quantify tremor in ET patients during their regular follow-up.

Graphical abstract

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Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Aβ)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells

Publication date: 10 May 2018
Source:Journal of Ethnopharmacology, Volume 217
Author(s): Emilia Tze Ying Yeo, Kelly Wang Ling Wong, Mun Ling See, Ka Yan Wong, Sook Yee Gan, Elaine Wan Ling Chan
Ethnopharmacological relevancePiper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aβ)-induced microglia-mediated neurotoxicity.Materials and methodsThe inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aβ-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits.ResultsPolar extracts of PS leaves (LEA and LMEOH) reduced the Aβ-induced secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aβ-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins.ConclusionsThe present study suggests that polar extracts of PS leaves confer neuroprotection against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.

Graphical abstract

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Determination of cesium transfer factors by instrumental neutron activation analysis

Publication date: July 2018
Source:Journal of Environmental Radioactivity, Volume 187
Author(s): G. Bátor, A. Bednár, T.J. Glover, T. Kovács, S. Landsberger
Food-chain models are used to predict radionuclide ingestion after fallout deposition. These models include those transfer processes (soil-to-plant transfer factor(s) [TF], plant-to-animal transfer coefficient(s) [TC] and concentration ratio [CR]) that are likely to be important for radiological assessment. The range of variability for transfer factors for the same plant groups is great, about 4–5 orders of magnitude, which limits their applicability. A better way to determine the best estimate the factors for radiocaesium and other important radionuclides is if the site-specific data are available. Soil, plant and animal samples were collected from a pasture area in Hungary during the vegetation period in 2016. Stable ¹³³Cs concentration was analysed by comparative method with neutron activation analysis (NAA). The comparator and the samples were irradiated in thermal neutron flux 2.55 × 10¹² ncm⁻²s⁻¹ for 2 h (soil) and 6 h (vegetation, animal samples) in the TRIGA Mark II research reactor at the Nuclear Engineering Teaching Laboratory. After an appropriate decay time (12 days) the samples were measured by gamma-spectrometry and analysed. The observed stable caesium TCpm (0.48–0.53) and CRpm (0.41–0.45) were very close to ¹³⁷Cs factors in the IAEA 2009 Report of 0.49 and 0.54, respectively. This methodology is particularly suitable for the simultaneous study of natural caesium in ecosystem compartments. Consequently, the transfer of stable caesium in a pasture field may be regarded as a useful analogy in predicting the long-term changes of ¹³⁷Cs affected by site-specific environmental factors.



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Dentoalveolar characteristics in children with juvenile idiopathic arthritis

Abstract

Purpose

Juvenile idiopathic arthritis (JIA) is an autoimmune disease with multiple potential causal factors. In case of temporomandibular joint (TMJ) affection, the inflammatory reaction can result in restricted mandibular growth with implied skeletal and facial deformities. Aim of the present study was to examine dentoalveolar and occlusion characteristics in children with JIA.

Patients and methods

The sample consisted of 66 children (27 boys, 39 girls) with JIA. Thirty-three of them showed unilateral or bilateral condylar destruction, while the other half did not manifest any TMJ involvement. Corresponding dental casts of these patients were evaluated and Angle classification, overjet, overbite, crossbite, crowding, and ectopic teeth were registered. All dental casts were subsequently scanned and digitized to analyze 26 additional variables. Subgroups according to sex and condylar affection were formed. Statistical analysis was performed using Fisher's least significant difference (LSD) post hoc test of analysis of variance (ANOVA).

Results

The prevalence of Class II, division 1 malocclusion in this JIA sample was high (28.8%). Compared to girls, boys had significantly greater dental arch widths and lengths. The group with bilateral condylar affection had significantly decreased lower arch length and increased irregularity index (p < 0.035) compared to the non-affected group.

Conclusions

Bilateral condylar involvement in children with JIA seems to reduce the lower arch length, while increasing the irregularity index of the lower front teeth.

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Letter to the editor

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Does orthodontic treatment have a permanent effect on tooth color?

Abstract

Objectives

Aim of this systematic review was to assess the effect of orthodontic treatment with fixed appliances on the tooth color of patients.

Methods

Nine databases were searched up to May 2017 for clinical cohort studies on the effect of fixed appliance treatment on tooth color. After elimination of duplicate studies, data extraction, and risk of bias assessment according to the Cochrane guidelines, random effects meta-analyses of mean differences (MD) or means and their 95% confidence intervals (CIs) were performed, followed by GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment of the quality of evidence.

Results

Three nonrandomized and one randomized study with a total of 138 patients (46% male, 54% female) with average age of 15.7 years were included. Tooth color of treated patients was significantly altered during or after orthodontic treatment (4 studies; average of 3.2 ∆E units; 95% CI = 2.0–4.4 ∆E units), which was more than the variation among controls (1 study; MD = 1.9 ∆E units; 95% CI = 1.7–2.2 ∆E units). However, the quality of evidence was very low, due to the inclusion of nonrandomized studies, bias, and imprecision. Re-analysis of raw study data indicated that significant differences in clinically discernable treatment-induced color changes were seen between chemically and light-cured adhesives and among the various tooth categories.

Conclusion

Existing evidence of very low quality indicates that orthodontic treatment might be associated with alterations of tooth color, which are however not consistently clinically discernible. Treatment-induced color alterations might be dependent on bonding material and tooth type, but evidence supporting this is weak.

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Long-term effects of Class II orthodontic treatment on oral health

Abstract

Aim

To investigate the long-term (≥15 years) benefit of orthodontic Class II treatment (Tx) on oral health (OH).

Subjects and methods

All patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who underwent Class II correction (Herbst-multibracket Tx, end of active Tx ≥ 15 years ago) and agreed to participate in a recall (clinical examination, interview, impressions, and photographs) were included. Records after active Tx were used to assess the long-term OH effects. Data were compared to corresponding population-representative age-cohorts as well as to untreated Class I controls without orthodontic Tx need during adolescence.

Results

Of 152 treated Class II patients, 75 could be located and agreed to participate at 33.7 ± 3.0 years of age (pre-Tx age: 14.0 ± 2.7 years). The majority (70.8%) were fully satisfied with their teeth and with their masticatory system. The Decayed, Missing, Filled Teeth Index (DMFT) was 7.1 ± 4.8 and, thus, almost identical to that of the untreated Class I controls (7.9 ± 3.6). In contrast, the DMFT in the population-representative age-cohort was 56% higher. The determined mean Community Periodontal Index (CPI) maximum score (1.6 ± 0.6) was also comparable to the untreated Class I controls (1.7 ± 0.9) but in the corresponding population-representative age-cohort it was 19–44% higher. The extent of lower incisor gingival recessions did not differ significantly between the treated Class II participants and the untreated Class I controls (0.1 ± 0.2 vs. 0.0 ± 0.1 mm).

Conclusion

Patients with orthodontically treated severe Class II malocclusions had a lower risk for oral health impairment than the general population. The risk corresponded to that of untreated Class I controls (without orthodontic Tx need during adolescence).

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Insertion torque values and success rates for paramedian insertion of orthodontic mini-implants

Abstract

Objectives

Orthodontic mini-implants (OMIs) are a reliable method to provide temporary orthodontic anchorage. We hypothesized that there is an optimal insertion torque (<10 Ncm) that can be used to ensure the success of self-drilling OMIs in the paramedian region.

Patients and methods

Included were 40 (26 females, 14 males) consecutive patients requiring palatal skeletal anchorage. Mean age was 17.3 years (range 11.0–44.6 years) for female patients and 15.7 years (range 10.6–36.9 years) for male patients. A total of 22 patients received a Beneslider according to Wilmes for the distalization of maxillary first molars, 10 patients received a Mesialslider for the mesialization of maxillary first molars, and 8 patients received a bone-borne rapid palatal expansion (RPE) appliance. Torque values of 10–15 Ncm were recorded in 46.3% of the OMIs and 15–20 Ncm in 35% of OMIs. OMIs that endured the orthodontic force applied for ≥6 months were considered as success.

Results

The overall success rate was 98.8%. No significant differences were found between insertion torque values with respect to the right and left sides, Jarabak's ratio, facial axis, and Frankfort to mandibular plane angle. There were no significant differences in the OMIs insertion torques with regard to the different appliances. No association was found between insertion torque and vertical skeletal morphology.

Conclusion

With an overall success rate of 98.8%, the study hypothesis that greater insertion torque (>10 Ncm) will decrease the success rate and increase palatal OMI failure was rejected.

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Mandibular fossa morphology during therapy with a fixed functional orthodontic appliance

Abstract

Objective

During therapy of distoclusion entailing a rigid, fixed orthodontic appliance, the mandibular fossa and condyle are ideally remodeled, while dentoalveolar effects occur through adaptive mechanisms. Adaptive processes, especially in the fossa region, have not been adequately investigated. Our magnetic resonance imaging (MRI) investigation aimed to assess the effects of therapy with a functional mandibular advancer (FMA) on mandibular fossa morphology.

Patients and methods

We monitored via MRI the therapeutic course of 25 patients at three time points. Visual findings and metric assessments were carried out in the sagittal plane. Three-dimensional (3D) reconstructions of the joint structure of two exemplary patients were also made.

Results

Visual examinations of the MRI slices at the three time points revealed no changes in fossa shape in any of the 50 temporomandibular joints. Lateral comparisons showed that the morphology of the fossae of all 25 patients was identical. Metric analysis demonstrated no significant alterations in width, depth, or in their ratio, not even laterally. Nine measurements of the distances between the porion, mandibular fossa, and articular eminence revealed no significant changes in total or on the left and right sides, or intralaterally.

Conclusion

The visual findings and metric analyses of parasagittal MRI slices did not indicate any morphological changes in the mandibular fossa or articular eminence in patients with distoclusion treated via a rigid, fixed orthodontic appliance. However, special reworking of the MRI data facilitated reconstruction of the surfaces of joint structures in 3D. This new method makes it possible to depict more accurately and noninvasively the adaptive mechanisms not ascertainable via metric methods and to assess them as 3D structures.

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Effect of EMD on the orthodontically induced root resorption repair process in rats

Abstract

Background

While different levels of root resorption may occur in orthodontic treatment, several preventive approaches have been reported. Nevertheless, little is known about the effect of enamel matrix derivative (EMD) on root repair during orthodontic tooth movement.

Objective

To evaluate the effect of EMD on root resorption repair following the application of orthodontic force.

Materials and methods

A force of 100 g was exerted for 14 days on the left maxillary first molars of twenty 10-week-old Sprague-Dawley rats divided into the EMD and control groups (n = 10 per group). In the EMD group, repeatedly injection of Emdogain® was administered after the appliance was removed, while phosphate-buffered saline was administered in the control group. In vivo microcomputed tomography (CT), haematoxylin and eosin (H&E) staining, and immunohistochemistry were then used to evaluate the effect of EMD on the process of root repair.

Results

In the EMD group, the observed decrease in root resorption crater volume and increase in both the bone volume fraction and trabecular thickness were significantly greater than those in the control group. H&E staining showed that the periodontal fibres were relatively regular in arrangement and that the surface of the cementum was smooth in the EMD group. Immunohistochemical analysis showed higher bone morphogenetic protein 2 (BMP-2) and bone sialoprotein (BSP) expression levels in the EMD group than in the control group. In addition, the osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) expression levels were similar in both groups.

Conclusion

EMD enhanced the repair process following orthodontically induced root resorption in rats.

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Molecular characterization, tissue distribution, localization and mRNA expression of the bucky ball gene in the Dabry's sturgeon (Acipenser dabryanus) during oogenesis

Publication date: Available online 23 February 2018
Source:Gene Expression Patterns
Author(s): Huan Ye, Huamei Yue, Xiaoge Yang, Chuangju Li, Qiwei Wei
In many organisms, germ cells are specified during embryogenesis by the inheritance of maternally deposited RNAs and proteins termed germ plasm. In vertebrates, the bucky ball (buc) gene plays an essential role in the germ plasm aggregation. In this study, the full-length cDNA of buc homologue in Dabry's sturgeon, Adbuc, was isolated and characterized. Multiple sequence alignments showed that the BUVE domain of Buc was highly conserved in vertebrates, despite exhibiting low identities with each other across the whole protein. By quantitative real-time PCR analysis, we found that Adbuc RNAs were only detected in the gonad with a high level in the ovary and a very low level in the testis. During embryogenesis, these RNAs were highly expressed from the unfertilized eggs to blastula, declined dramatically from the gastrula stage, and hardly found after the neurula stage. Moreover, with the development of ovary, the expression level of Adbuc was increasing. By in situ hybridization, the signal of Adbuc was not found in the oogonia, increased slightly in the stage I oocytes, and extremely strong in the stage II oocytes, suggesting that the signal became much stronger with increasing size of oocytes. Additionally, Adbuc co-localized with the mitochondrial cloud. Thus, we conclude that Dabry's sturgeon buc gene might also function in germplasm formation.



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The impact of polyunsaturated fatty acids on DNA methylation and expression of DNMTs in human colorectal cancer cells

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Mostafa Moradi Sarabi, Fakhraddin Naghibalhossaini
Growing evidence suggests a role of polyunsaturated fatty acids (PUFA) in the prevention of various types of malignancy, including colorectal cancer (CRC). No published studies have yet examined the direct effect of PUFA treatment on DNA methylation in CRC cells. In this study, 5 human CRC cells were treated with 100 μM DHA, EPA, and LA for 6 days and changes in their global- and gene-specific DNA methylation status as well as expression of DNA methyl transferases (DNMT) were investigated. Cell-type specific differences in DNA methylation and expression of DNMTs were observed in PUFA-treated cells. DHA and EPA treatment induced global hypermethylation in HT29/219 and HCT116 cells, but reduced methylation in Caco2 cells (p < 0.05). Among 10 tumor related genes tested in 5 CRC cell lines, DHA and EPA induced promoter demethylation of Cox2 in HT29/219, p14 and PPARγ in HCT116, and ECAD in SW742 cells. Cell-type specific differences in expression of DNMT1, DNMT3a, and 3b genes were also observed between PUFA-treated and control cells (p < 0.05). Overall, treatment of PUFAs coordinately induced the expression of DNMTs in HT29/219, but suppressed in other 4 cell lines investigated in this study.

Graphical abstract

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Biological effects of kojic acid on human monocytes in vitro

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Josineide P. Da Costa, Ana Paula D. Rodrigues, Luis Henrique S. Farias, Paula Cristina R. Frade, Bruno José Martins Da Silva, Jose Luiz M. Do Nascimento, Edilene O. Silva
Monocytes are mononuclear phagocytes in peripheral blood that can differentiate into macrophages and dendritic cells. Macrophages play a specific role in the inflammatory process and are essential for the innate response. Given the important role of monocytes/macrophages in the immune response, this study aimed to evaluate the activity of kojic acid (KA), a natural product of certain fungal species, on human peripheral blood monocytes in vitro. Purified monocytes isolated from human blood were incubated with KA (50 μg/mL for 48 h) and analyzed by light microscopy, scanning electron microscopy, transmission electron microscopy and flow cytometry. Host cell cytotoxicity was measured by the colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. KA treatment induced morphological alterations in monocytes, such as increased cell size, as well as numerous cellular projections. Furthermore, flow cytometry revealed increased labeling of cell surface EMR1-F4/80 but decreased labeling of CD11b and CD14. KA also promoted increased IL-6 cytokine production but did not cause cytotoxic effects in monocytes. In conclusion, our results show that KA promotes the differentiation of monocytes into macrophages and can act as an immunomodulatory agent.

Graphical abstract

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Ruscogenin suppressed the hepatocellular carcinoma metastasis via PI3K/Akt/mTOR signaling pathway

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Hui Hua, Yu Zhu, Yu-He Song
BackgroundHepatocellular carcinoma (HCC) is the third-leading cause of cancer-related mortality with poor prognosis and treatment. More effective strategies should be studied in HCC.MethodsAfter treated with ruscogenin, the cell proliferation was assessed by CCK-8 method. Cell migration and invasion were estimated using wound healing and transwell assays. Pathological changes of lung tissue were observed by HE staining and IHC methods. MMP-2, MMP-9, uPA, VEGF and HIF-1α levels were measured using ELISA, RT-qPCR and WB tests. PI3K/Akt/mTOR pathway related molecules were detected using WB analysis.ResultsThe results indicated the hypotoxicity of ruscogenin. Meanwhile, ruscogenin showed obvious interruption on the cancer cell migration and invasion, and inhibition on the metastatic foci in pulmonary tissue. Significantly, ruscogenin decreased the levels of MMP-2, MMP-9, uPA, VEGF and HIF-1α, down-regulated the phosphorylation of Akt, mTOR.ConclusionThe present study indicated a novel use of ruscogenin in suppressing HCC metastasis by reducing the expression of MMP-2, MMP-9, uPA, VEGF and HIF-1α via regulating the PI3K/Akt/mTOR signaling pathway.

Graphical abstract

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α-Hederin inhibits interleukin 6-induced epithelial-to-mesenchymal transition associated with disruption of JAK2/STAT3 signaling in colon cancer cells

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Dongdong Sun, Weixing Shen, Feng Zhang, Huisen Fan, Changliang Xu, Liu Li, Jiani Tan, Yunjie Miao, Haibin Zhang, Ye Yang, Haibo Cheng
Colon cancer is the third most frequently diagnosed malignancy and has high morbidity worldwide. Epithelial-mesenchymal transition (EMT) has been increasingly implicated in colon cancer progression and metastasis. The present study was aimed to evaluate the potential antitumor activity of α-hederin, a monodesmosidic triterpenoid saponin isolated from Hedera helix, in human SW620 colon cancer cells stimulated with interleukin 6 (IL-6) for mimicking the tumor inflammatory microenvironment in vivo. Cell viability assay showed that IL-6 at 6.25 ng/ml significantly enhanced viability of SW620 cells, and thus this concentration was used to stimulate SW620 cells throughout this study. We observed that α-hederin concentration-dependently inhibited cell viability, migration and invasion in IL-6-treated SW620 cells. Moreover, α-hederin significantly restored IL-6-induced decrease in E-cadherin expression and abolished IL-6-induced increase in N-cadherin, vimentin, fibronectin, twist and snail at both mRNA and protein levels in SW620 cells. These data suggested that α-hederin suppressed IL-6-indcued EMT in colon cancer cells. Further molecular examinations showed that α-hederin inhibited phosphorylation of Janus Kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3(STAT3), and halted the nuclear translocation of phosphorylated STAT3 in IL-6-treated SW620 cells. In addition, JAK2/STAT3 signaling inhibitor AG490 not only produced similar inhibitory effects on EMT markers as α-hederin, but also synergistically enhanced α-hederin's inhibitory effects on EMT markers in IL-6-treated SW620 cells. Altogether, we demonstrated that α-hederin suppressed IL-6-induced EMT associated with disruption of JAK2/STAT3 signaling in colon cancer cells. Our data strongly suggested α-hederin as a promising candidate for intervention of colon cancer and metastasis.



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Grape seed proanthocyanidin reverses pulmonary vascular remodeling in monocrotaline-induced pulmonary arterial hypertension by down-regulating HSP70

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Fangzheng Chen, Heng Wang, Junjie Yan, Jiadan Lai, Shujing Cai, Linbo Yuan, Situo Zheng
Heat shock protein 70 (HSP70) is a molecular chaperone which has a low content in cytoplasm under normal physiological conditions. A higher intracytoplasmic HSP70 level can be observed in pulmonary arterial smooth muscle cell (PASMC) in pulmonary arterial hypertension (PAH), and this up-regulation can promote pho-IκBα expression, which is an NF-κB signaling pathway inhibitor. NF-κB signaling pathway up-regulation can promote PASMC proliferation and pulmonary vascular remodeling in PAH, resulting in elevation of pulmonary pressure and the subsequent right heart failure caused by right ventricular hypertrophy. Grape seed proanthocyanidin (GSP) is effective in vascular protection and several tumor treatments, and its effect on PAH treatment remains to be elucidated. In this study, we made observations and contrasts in monocrotaline(MCT) -induced PAH rats, and found decrease in mPAP, PVR and RVHI after GSP administration. Our study also proved GSP's effect on down-regulating the intracytoplasmic HSP70 content both in cellular and animal levels. The results indicate a possible mechanism of GSP reversing pulmonary vascular remodeling by down-regulating HSP70, and this change may influence pho-IκBα expression. Therefore, inhibition of NF-κB signaling pathway caused by GSP can lead to inhibition of PASMC proliferation in PAH.



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Evaluation of cell toxicity and DNA and protein binding of green synthesized silver nanoparticles

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): A.P.C. Ribeiro, S. Anbu, E.C.B.A. Alegria, A.R. Fernandes, P.V. Baptista, R. Mendes, A.S. Matias, M. Mendes, M.F.C. Guedes da Silva, A.J.L. Pombeiro
Silver nanoparticles (AgNPs) were prepared by GREEN chemistry relying on the reduction of AgNO3 by phytochemicals present in black tea extract. AgNPs were fully characterized by transmission electron microscopy (TEM), ultraviolet-visible spectroscopy ((UV–vis)), X-ray diffraction (XRD) and energy dispersive absorption spectroscopy (EDS). The synthesized AgNPs induced a decrease of the cell viability in a dose-dependent manner with a low IC50 (0.5 ± 0.1 μM) for an ovarian carcinoma cell line (A2780) compared to primary human fibroblasts (IC50 5.0 ± 0.1 μM). The DNA binding capability of CT (calf thymus) DNA was investigated using electronic absorption and fluorescence spectroscopies, circular dichroism and viscosity titration methods. Additionally, the AgNPs strongly quench the intrinsic fluorescence of BSA, as determined by synchronous fluorescence spectra.

Graphical abstract

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Inhibition of class IIa histone deacetylase activity by gallic acid, sulforaphane, TMP269, and panobinostat

Publication date: May 2018
Source:Biomedicine & Pharmacotherapy, Volume 101
Author(s): Sin Young Choi, Hae Jin Kee, Li Jin, Yuhee Ryu, Simei Sun, Gwi Ran Kim, Myung Ho Jeong
Histone deacetylase (HDAC) inhibitors are gaining increasing attention as potential therapeutics for cardiovascular diseases as well as cancer.We recently reported that the class II HDAC inhibitor, MC1568, and the phytochemical, gallic acid, lowered high blood pressure in mouse models of hypertension. We hypothesized that class II HDACs may be involved in the regulation of hypertension. The aim of this study was to determine and compare the effects of well-known HDAC inhibitors (TMP269, panobinostat, and MC1568), phytochemicals (gallic acid, sulforaphane, and piceatannol), and anti-hypertensive drugs (losartan, carvedilol, and furosemide) on activities of class IIa HDACs (HDAC4, 5, 7, and 9).The selective class IIa HDAC inhibitor, TMP269, and the pan-HDAC inhibitor, panobinostat, but not MC1568, clearly inhibited class IIa HDAC activities. Among the three phytochemicals, gallic acid showed remarkable inhibition, whereas sulforaphane presented mild inhibition of class IIa HDACs. Piceatannol inhibited only HDAC7 activity. As expected, the anti-hypertensive drugs losartan, carvedilol, and furosemide did not affect the activity of any class IIa HDAC.In addition, we evaluated the inhibitory effect of several compounds on the activity of class l HDACs (HDAC1, 2, 3, and 8) and class IIb HDAC (HDAC6). MC1568 did not affect the activities of HDAC1, HDAC2, and HDAC3, but it reduced the activity of HDAC8 at concentrations of 1 and 10 μM. Gallic acid weakly inhibited HDAC1 and HDAC6 activities, but strongly inhibited HDAC8 activity with effectiveness comparable to that of trichostatin A. Inhibition of HDAC2 activity by sulforaphane was stronger than that by piceatnnaol.These results indicated that gallic acid is a powerful dietary inhibitor of HDAC8 and class IIa/b HDAC activities. Sulforaphane may also be used as a dietary inhibitor of HDAC2 and class IIa HDAC. Our findings suggest that the class II HDAC inhibitor, MC1568, does not inhibit class IIa HDAC, but inhibits HDAC8.



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Pharmacological values and therapeutic properties of black tea (Camellia sinensis): A comprehensive overview

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Muhammad Naveed, Jannat BiBi, Asghar Ali Kamboh, Imran Suheryani, Ihsanullah Kakar, Sarfaraz Ali Fazlani, Xia FangFang, Shahmir Ali kalhoro, Liang Yunjuan, Mohib Ullah Kakar, Mohamed E. Abd El-Hack, Ahmed E. Noreldin, Shi Zhixiang, Chen LiXia, Zhou XiaoHui
Medicinal plants are essential parts of traditional medicine due to their phytochemical constituents having pharmacological values and therapeutic applications. Black tea have thousands of various biological compounds such as flavonoids (Thearubigins (TRs) and theaflavins (TFs) and catechins), amino acids (L.theanine), vitamins (A, C, K), phenolic acids (caffeic acid (CA), gallic acid (GA), chlorogenic acids (CGA) and cauramic acid), lipids, proteins, volatile compounds carbohydrates, β-carotene and fluoride that illustrated many promising pharmacological effects regarded as growth promoter, cardioprotector, potent cholesterol-lowering effect, antioxidant and antimicrobial, etc inhuman. Although there is an exponential growth in molecular evidence of cholesterol-lowering and antioxidant effect in human, there is still a lack of information of the pharmacological effects of black tea. To fill this information gap, therefore, this review article underscores broadening the new insight pertaining to black tea that could be used as safe food additive. This article also illuminates the interesting role of black tea as an herbal medicine that is the future demand to get rid of synthetic health promoters in the human health practice. Moreover, this information would be useful in terms of the low-cost practice of natural medicines with no residual effects, and a natural protection of the human being. In addition, further studies at a molecular level are needed to reveal its mechanism of action particularly for the hypocholesterolemic effect of black tea to overcome the heart-related diseases, fewer side effects and being a natural safeguard of human health.



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Clinicopathological and Ultrasonic Features of Triple-Negative Breast Cancers: A Comparison with Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-2-Negative Breast Cancers

Publication date: Available online 23 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): Dongmo Wang, Kai Zhu, Jiawei Tian, Ziyao Li, Guoqing Du, Qiang Guo, Tong Wu, Juan Li
The purpose of this study was to analyze the clinicopathological and ultrasound characteristics of triple-negative breast cancers (TNBCs) and compare these findings with those for hormone receptor-positive (HR-positive)/human epidermal growth factor receptor-2-negative (HER-2-negative) tumors. Seventy-five TNBCs and 135 HR-positive/HER-2-negative breast cancers were reviewed. Data from conventional ultrasound, Doppler vascularity and elastography were included in the analysis. TNBCs had a higher histologic grade and Ki-67 level. On ultrasound, TNBCs often appeared as microlobulated, markedly hypo-echoic masses with an abrupt interface boundary, posterior acoustic enhancement, absence of calcifications and more characteristics of surrounding tissue. Results from multivariate regression analysis revealed that margin, posterior acoustic features and surrounding tissue features of tumors were independent predictive factors in differentiating TNBCs from HR-positive/HER-2-negative tumors. Our results suggest that a thorough evaluation of sonographic findings might be useful in discriminating between TNBCs and HR-positive/HER-2-negative tumors, which may provide accurate evidence for clinical early diagnosis.



http://ift.tt/2ESaACj

Measuring the Absolute Concentration of Microparticles in Suspension Using High-Frequency B-Mode Ultrasound Imaging

Publication date: Available online 23 February 2018
Source:Ultrasound in Medicine & Biology
Author(s): John H. Lee, Duane S. Boning, Brian W. Anthony
Concentration measurement of particles in suspension is an important procedure performed in biological and clinical laboratories. Existing methods based on instruments such as hemocytometers, Coulter counters and flow cytometers are often laborious, destructive and incapable of in vivo measurements. On the other hand, an ultrasound-based method can be non-destructive and non-invasive and have the potential for in vivo measurement. In this work, a method is presented that estimates absolute particle concentration from high-frequency B-mode ultrasound images of a sample. The method is based on the detection and characterization of the echoes from individual particles to estimate the effective slice thickness of the image. Calibration using a reference sample is not required because the estimation is entirely image based. The particle type differential is also performed by using the backscatter coefficient of each detected echoes. The method is demonstrated by measuring microsphere suspensions as well as human T-cell suspensions. The proposed method has a wide range of potential clinical applications including non-invasive measurement of cell concentration in biological fluids such as cerebrospinal fluid.



http://ift.tt/2Fsw4qI

Characterization of halotolerant, pigmented, plant growth promoting bacteria of groundnut rhizosphere and its in-vitro evaluation of plant-microbe protocooperation to withstand salinity and metal stress

Publication date: 15 July 2018
Source:Science of The Total Environment, Volume 630
Author(s): Avishek Banik, Pooja Pandya, Bhoomi Patel, Chirag Rathod, Maya Dangar
The use of plant associated, indigenous beneficial microbes for sustainable agriculture is getting worldwide acceptance as they successfully colonize at different plant niche under stress conditions to enhance the crop productivity. They also generate several plant growth regulators and protect plants from adversity like presence of salts and metals. In the present study, indigenous, halotolerant, plant growth promoting (PGP) bacterial isolates were isolated from the saline rhizospheric soil of groundnut plants aiming to investigate its in-vitro metal remediation capabilities under saline stress condition. Two pigmented bacteria were selected based on their phenotypic, biochemical, physiological and PGP characters and identified as members of family Bacillaceae (Bacillus and Halobacillus) based on 16S rRNA gene sequence similarity. The pigments were extracted, tested for different antioxidant properties and identified by GC–MS and FT-IR spectra. Simultaneously, both strains exhibited a wide range of salinity (NaCl≥25%), metal resistance (Zinc≈1700mgkg⁻¹, Aluminium≈1800mgkg⁻¹, Lead≈1800mgkg⁻¹), pH (6–10), PGP attributes (indole - 1.05–3.15μgml⁻¹, ammonia - 0.13–19.95mmolml⁻¹, nitrite - 0.07–0.26mmolml⁻¹) and antibiotics sensitivity revealing their wide range of metabolic diversity. In-vitro inoculation of groundnut seedlings with selected isolates under salinity (1% NaCl) and metal (Zn, Al and Pb) stress had a positive impact on different plant physiological parameters (lesser lignification, intact proto xylem and cortical parenchyma) which was correlated with PGP attributes. Microwave plasma atomic emission spectroscopy analysis of seedling samples also detected less amount of metals in plants treated with bacteria indicating, an establishment of plant-microbe protocooperation to withstand salinity and metal stress. This strategy can be implemented to improve crop production in saline metal polluted agriculture fields.

Graphical abstract

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Structure and magnetic properties of iron-based soft magnetic composite with Ni-Cu-Zn ferrite–silicone insulation coating

Publication date: 15 June 2018
Source:Journal of Magnetism and Magnetic Materials, Volume 456
Author(s): Wangchang Li, Wei Wang, Junjun Lv, Yao Ying, Jing Yu, Jingwu Zheng, Liang Qiao, Shenglei Che
This paper investigates the structure and magnetic properties of Ni-Cu-Zn ferrite-silicone coated iron-based soft magnetic composites (SMCs). Scanning electron microscopy coupled with a energy-dispersive spectroscopy (EDS) analysis revealed that the Ni-Cu-Zn ferrite and silicone resin were uniformly coated on the surface of iron powders. By controlling the composition of the coating layer, low total core loss of 97.7 mW/cm³ (eddy current loss of 48 mW/cm³, hysteresis loss of 49.7 mW/cm³, measured at 100 kHz and 0.02 T) and relatively high effective permeability of 72.5 (measured at 100 kHz) were achieved. In addition, the as-prepared SMCs displayed higher electrical resistivity, good magnetic characteristics over a wide range of frequencies (20–200 kHz) and ideal the D-C bias properties (more than 75% at H = 50 Oe). Furthermore, higher elastic modulus and hardness of SMCs, which means that the coating layer has good mechanical properties and is not easily damaged during the pressing process, were obtained in this paper. The results of this work indicate that the Ni-Cu-Zn ferrite-silicone coated SMCs have desirable properties which would make them suitable for application in the fields of the electric-magnetic switching devices, such as inductance coils, transformer cores, synchronous electric motors and resonant inductors.



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Microstructure and mechanical performance of composite joints of sapphire by ultrasonic-assisted brazing

Publication date: July 2018
Source:Journal of Materials Processing Technology, Volume 257
Author(s): Wei Cui, Shuqi Li, Jiuchun Yan, Xing Zhang
A method of lowering the coefficient of thermal expansion (CTE) of a bond metal of sapphire joints was examined for inhibiting the interfacial cracking of joints. An interlayer with the sandwich structure of Zn-Al/(SiCp/A356)/Zn-Al was fabricated and the surface of sapphire blocks was coated with a Zn-Al alloy by assistance of ultrasound. The assembly of sapphire and interlayer was brazed under the action of ultrasound. A metallurgical bond is performed between the sapphire and interlayer, and the composite material of SiCp/A356 is dissolved by Zn-Al alloys during brazing, resulting in a joint consisting of a new composite material of SiCp/Zn-Al-Si. It was composed of Zn-Al-Si alloy matrix and SiC particles with ∼40 vol.%, and has a CTE of ∼7.4 × 10⁻⁶ /°C estimated by using Turner's model, approaching that of sapphire (∼5 × 10⁻⁶ /°C). The maximum shear strength of the composite joints reached ∼155 ± 10 MPa, an increase of ∼250% in comparison with that joined using the Zn-Al alloys.



http://ift.tt/2GHT2tn

Carbon nanotubes intercalated Co/N-doped porous carbon nanosheets as efficient electrocatalyst for oxygen reduction reaction and zinc–air batteries

Publication date: 15 June 2018
Source:Chemical Engineering Journal, Volume 342
Author(s): Shaojun Liu, Ibrahim Saana Amiinu, Xiaobo Liu, Jian Zhang, Mingjun Bao, Tian Meng, Shichun Mu
Earth abundant transition-metals and nitrogen co-doped carbon (M-N/C) materials are particularly attractive as the most viable alternative to precious metal catalysts. Herein, a high-performance catalyst is prepared by building a carbon nanotubes (CNTs) intercalated Co/N-doped few layered carbon nanosheet (CNTs-Co/NC) hybrid with a unique open-ended porous structure. To prepare the catalyst, polyaniline molecules are first polymerized on carbon nanotubes and subsequent thermal annealing, resulting in formation of CNTs-Co/NC. For the CNTs-Co/NC catalyst, its surface area and pore volume are as high as 1072 m²/g and 0.63 cm³/g, respectively. As expected, it displays high ORR performance with an onset and a half wave potential of 0.96 V and 0.84 V (vs. RHE), respectively, in alkaline media. Impressively, when used as a cathode catalyst for zinc-air batteries, CNTs-Co/NC also exhibits a peak power density up to 83 mWcm⁻² with long-term durability and high rate capacity. Such enhanced performance can be attributed to the synergistic effect of the abundant Co/N coupling centers, the high surface area with more exposed active sites, and the high porosity accessible to ion transport.

Graphical abstract

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Particulate matter concentrations and heavy metal contamination levels in the railway transport system of Sydney, Australia

Publication date: July 2018
Source:Transportation Research Part D: Transport and Environment, Volume 62
Author(s): Marwa Mohsen, Mohammad Boshir Ahmed, John L. Zhou
Sampling campaign was conducted over six weeks to determine particulate matter (PM) concentrations from Sydney Trains airport line (T2) at both underground and ground levels using DustTrak. Dust samples were collected and analysed for 12 metals (Fe, Ca, Mn, Cr, Zn, Cu, Pb, Al, Co, Ni, Ba and Na) by atomic emission spectroscopy. Average underground PM10 and PM2.5 concentrations from inside the trains were 2.8 and 2.5 times greater than at ground level. Similarly, PM10 and PM2.5 concentrations on underground platforms were 2.7 and 2.5 times greater than ground level platforms. Average underground PM concentrations exceeded the national air quality standards for both PM10 (50 µg/m³) and PM2.5 (25 µg/m³). Correlation analysis showed a strong to moderate association between PM concentrations at ground level and background PM concentrations (r² from 0.952 to 0.500). The findings suggested that underground PM concentrations were less influenced by the ambient background than at ground level. The metal concentrations decreased in the order of Fe, Cr, Ca, Al, Na, Ba, Mn, Zn, Cu, Ni, Co and Pb. The pollution index (PI) and enrichment factor (EF) values were calculated to identify the levels and sources of contamination in the underground railway microenvironments. PM was remarkably rich in Fe with a mean concentration of 73.51 mg/g and EF of 61.31, followed by Ni and Cr. These results noticeably indicated a high level of metal contamination in the underground environments, with the principal contribution from track abrasion and wear processes.

Graphical abstract

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Essential micronutrient and toxic trace element concentrations in gluten containing and gluten-free foods

Publication date: 30 June 2018
Source:Food Chemistry, Volume 252
Author(s): Tracy Punshon, Brian P. Jackson
For individuals following a gluten-free (GF) diet, rice is commonly the major grain. People following a GF diet have a higher arsenic burden than the general population. We conducted a multielemental market basket study of GF and gluten containing ingredients and prepared foods (Mn, Fe, Ni, Cu, Zn, Cr, Co, Se, Cd, Sb, Pb, total As, As species, total Hg and methylmercury). Foods containing rice were significantly higher in As, Hg and Pb and lower in Se, Fe, Cu and Zn. Wheat-based foods were higher in Cd. Mercury concentrations were low (<3.5 ng/g); speciation was predominantly methylmercury. Arsenic and mercury in rice were correlated. GF foods contained significantly more As and Hg. Eating a wide variety of GF grains may reduce contaminant exposure and increase micronutrient status compared to a rice-based GF diet.



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Fixation Reinstatement Supports Visuospatial Memory in Older Adults.

Author: Wynn, Jordana S.; Olsen, Rosanna K.; Binns, Malcolm A.; Buchsbaum, Bradley R.; Ryan, Jennifer D.

DOI: 10.1037/xhp0000522

Publication Date: POST AUTHOR CORRECTIONS, 22 February 2018

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Role of CTCF in DNA Damage Response

Publication date: Available online 23 February 2018
Source:Mutation Research/Reviews in Mutation Research
Author(s): Vinay Singh Tanwar, Cynthia C. Jose, Suresh Cuddapah
CCCTC-binding factor (CTCF) is a highly conserved, ubiquitously expressed zinc finger protein. CTCF is a multifunctional protein, associated with a number of vital cellular processes such as transcriptional activation, repression, insulation, imprinting and genome organization. Emerging evidence indicates that CTCF is also involved in DNA damage response. In this review, we focus on this newly identified role of CTCF in facilitating DNA double-strand break repair. Due to the large number of cellular processes in which CTCF is involved, factors that functionally affect CTCF could have serious implications on genomic stability. It is becoming increasingly clear that exposure to environmental toxicants could have adverse effects on CTCF functions. Here we discuss the various ways that the environmental toxicants could impact CTCF functions and the potential consequences on DNA damage response.



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DNA AND CHROMOSOME DAMAGE INDUCED BY BLEOMYCIN IN MAMMALIAN CELLS: AN UPDATE

Publication date: Available online 23 February 2018
Source:Mutation Research/Reviews in Mutation Research
Author(s): Alejandro D. Bolzán, Martha S. Bianchi
Bleomycin (BLM) is an antibiotic isolated from Streptomyces verticillus. It has radiomimetic actions on DNA thus it has been widely used in clinical chemotherapy for the treatment of different types of cancer, including head and neck tumors, lymphomas, squamous-cell carcinomas and germ-cell tumors. Because of this, the study of BLM genotoxicity is of practical interest. This antibiotic is an S-independent clastogen and an agent that generates free radicals and induces single- and double-strand breaks in DNA. In the present review, we will summarize our current knowledge concerning the DNA and chromosome damage induced by BLM in mammalian cells, with emphasis on new developments published since 1991.



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Dendritic spine density and EphrinB2 levels of hippocampal and anterior cingulate cortex neurons increase sequentially during formation of recent and remote fear memory in the mouse

Publication date: 15 May 2018
Source:Behavioural Brain Research, Volume 344
Author(s): Georgia Abate, Sandra Colazingari, Alessandra Accoto, David Conversi, Arturo Bevilacqua
Memory consolidation is a dynamic process that involves a sequential remodeling of hippocampal–cortical circuits. Although synaptic events underlying memory consolidation are well assessed, fine molecular events controlling this process deserve further characterization.To this aim, we challenged male C57BL/6N mice in a contextual fear conditioning (CFC) paradigm and tested their memory 24 h, 7 days or 36 days later. Mice displayed a strong fear response at all time points with an increase in dendritic spine density and protein levels of the cell adhesion factor EphrinB2 in CA1 hippocampal neurons 24 h and 7 days post conditioning (p.c.), and in anterior cingulate cortex (ACC) neurons 36 days p.c. We then investigated whether the formation of remote memory and neuronal modifications in the ACC would depend on p.c. protein synthesis in hippocampal neurons. Bilateral intrahippocampal infusions with the protein synthesis inhibitor anisomycin administered immediately p.c. decreased fear response, neuronal spine growth and EphrinB2 protein levels of hippocampal and ACC neurons 24 h and 36 days p.c., respectively. Anisomycin infusion 24 h p.c. had no effects on fear response, increase in spine density and in EphrinB2 protein levels in ACC neurons 36 days p.c. Our results thus confirm that early but not late p.c. hippocampal protein synthesis is necessary for the formation of remote memory and provide the first evidence of a possible involvement of EphrinB2 in neuronal plasticity in the ACC.



http://ift.tt/2CgrwVI

Assessment of impulsivity in adolescent mice: A new training procedure for a 3-choice serial reaction time task

Publication date: 2 May 2018
Source:Behavioural Brain Research, Volume 343
Author(s): Hitomi Sasamori, Yu Ohmura, Takuya Kubo, Takayuki Yoshida, Mitsuhiro Yoshioka
Immaturity in impulse control among adolescents could result in substance abuse, criminal involvement, and suicide. The brains of adolescents and adults are anatomically, neurophysiologically, and pharmacologically different. Therefore, preclinical models of adolescent impulsivity are required to screen drugs for adolescents and elucidate the neural mechanisms underlying age-related differences in impulsivity. The conventional 3- or 5-choice serial reaction time task, which is a widely used task to assess impulsivity in adult rodents, cannot be used for young mice because of two technical problems: impaired growth caused by food restriction and the very long training duration. To overcome these problems, we altered the conventional training process, optimizing the degree of food restriction for young animals and shortening the training duration. We found that almost all basal performance levels were similar between the novel and conventional procedures. We also confirmed the pharmacological validity of our results: the 5-hydroxytryptamine 2C (5-HT2C) receptor agonist Ro60-0175 (0.6 mg/kg, subcutaneous) reduced the occurrence of premature responses, whereas the 5-HT2C receptor antagonist SB242084 (0.5 mg/kg intraperitoneal) increased their occurrence, consistent with results of previous studies using conventional procedures. Furthermore, we detected age-related differences in impulsivity using the novel procedure: adolescent mice were found to be more impulsive than adult mice, congruent with the results of human studies. Thus, the new procedure enables the assessment of impulsivity in adolescent mice and facilitates a better understanding of the neurophysiological/pharmacological properties of adolescents.



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Incorporation of new neurons in the olfactory bulb after paced mating in the female rat

Publication date: 2 May 2018
Source:Behavioural Brain Research, Volume 343
Author(s): R. Alvarado-Martínez, R.G. Paredes
One of the regions that constantly produces neurogenesis in the adult brain is the subventricular zone (SVZ), whose new cells migrate to the olfactory bulbs (OB). When the females regulate the copulatory events (paced mating) the number of new cells in the SVZ increases, as well as those observed in the OB 15 days later. However, no changes were observed in the number of cells 45 days after the females paced the sexual interaction. Constant sensory stimulation is an important promoter of cell survival in the OB circuit. Hence, we increased the number of mating sessions in this study to cover the period where stimulation of the new cells is critical for their incorporation into pre-existing circuits in the OB. Ovariectomized female Wistar rats, were injected with the mitotic marker 5-bromo-2′-deoxyuridine (BrdU, 100 mg/kg, per injection) before, at the end and one hour after mating. Sexual behavior was recorded for 1 h in 10 weekly sessions. After the last mating session, brain sections were processed to determine BrdU immunoreactivity. Our results indicate that females that paced the sexual interaction for 10 sessions had a higher number of cells in the glomerular layer (GL) of the accessory olfactory bulb (AOB) and a higher number of neurons in the granular layer (GrL) of the main olfactory bulb (MOB) in comparison to the control group. These results indicate that continued sexual interaction contributes to the integration of new cells and neurons, induced in the first sexual experience, into pre-exiting circuits of the OB.



http://ift.tt/2onvsex

Genetically defined fear-induced aggression: Focus on BDNF and its receptors

Publication date: 2 May 2018
Source:Behavioural Brain Research, Volume 343
Author(s): Tatiana V. Ilchibaeva, Anton S. Tsybko, Rimma V. Kozhemyakina, Elena M. Kondaurova, Nina K. Popova, Vladimir S. Naumenko
Brain-derived neurotrophic factor (BDNF), its precursor proBDNF, BDNF pro-peptide, BDNF mRNA levels, as well as TrkB and p75^NTR receptors mRNA and protein levels, were studied in the brain of rats, selectively bred for more than 85 generations for either the high level or the lack of fear-induced aggressive behavior. Furthermore, we have found that rats of aggressive strain demonstrated both high level of aggression toward humans and increased amplitude of acoustic startle response compared to rats selectively bred for the lack of fear-induced aggression. Significant increase in the BDNF mRNA, mature BDNF and proBDNF protein levels in the raphe nuclei (RN), hippocampus (Hc), nucleus accumbens (NAcc), amygdala, striatum and hypothalamus (Ht) of aggressive rats was revealed. The BDNF/proBDNF ratio was significantly reduced in the Hc and NAcc of highly aggressive rats suggesting prevalence of the proBDNF in these structures. In the Hc and frontal cortex (FC) of aggressive rats, the level of the full-length TrkB (TrkB-FL) receptor form was decreased, whereas the truncated TrkB (TrkB-T) protein level was increased in the RN, FC, substantia nigra and Ht. The TrkB-FL/TrkB-T ratio was significantly decreased in highly aggressive rats suggesting TrkB-T is predominant in highly aggressive rats. The p75^NTR expression was slightly changed in majority of studied brain structures of aggressive rats. The data indicate the BDNF system in the brain of aggressive and nonaggressive animals is extremely different at all levels, from transcription to reception, suggesting significant role of BDNF system in the development of highly aggressive phenotype.



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The evolution of methods for urinary steroid metabolomics in clinical investigations particularly in childhood

Publication date: Available online 23 February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): John W. Honour, E. Conway, R. Hodkinson, F. Lam
The metabolites of cortisol, and the intermediates in the pathways from cholesterol to cortisol and the adrenal sex steroids can be analysed in a single separation of steroids by gas chromatography (GC) coupled to MS to give a urinary steroid profile (USP). Steroids individually and in profile are now commonly measured in plasma by liquid chromatography (LC) coupled with MS/MS. The steroid conjugates in urine can be determined after hydrolysis and derivative formation and for the first time without hydrolysis using GC–MS, GC–MS/MS and liquid chromatography with mass spectrometry (LC–MS/MS). The evolution of the technology, practicalities and clinical applications are examined in this review. The patterns and quantities of steroids changes through childhood. Information can be obtained on production rates, from which children with steroid excess and deficiency states can be recognised when presenting with obesity, adrenarche, adrenal suppression, hypertension, adrenal tumours, intersex condition and early puberty, as examples. Genetic defects in steroid production and action can be detected by abnormalities from the GC–MS of steroids in urine. New mechanisms of steroid synthesis and metabolism have been recognised through steroid profiling. GC with tandem mass spectrometry (GC–MS/MS) has been used for the tentative identification of unknown steroids in urine from newborn infants with congenital adrenal hyperplasia. Suggestions are made as to areas for future research and for future applications of steroid profiling. As routine hospital laboratories become more familiar with the problems of chromatographic and MS analysis they can consider steroid profiling in their test repertoire although with LC–MS/MS of urinary steroids this is unlikely to become a routine test because of the availability, cost and purity of the internal standards and the complexity of data interpretation. Steroid profiling with quantitative analysis by mass spectrometry (MS) after chromatography now provides the most versatile of tests of adrenal function in childhood.



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A possible principal function of corticosteroid signaling that is conserved in vertebrate evolution: lessons from receptor-knockout small fish

Publication date: Available online 23 February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Tatsuya Sakamoto, Susumu Hyodo, Wataru Takagi
Corticosteroid receptors are critical for homeostasis maintenance, but understanding of the principal roles of the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) throughout vertebrates is limited. Lines of constitutive GR-knockout zebrafish and MR-knockout medaka have recently been generated as the first adult-viable corticosteroid receptor-knockout animals, in contrast to the lethality of these receptor knockouts in mice. Here, we describe behavioral and physiological modifications following disruption of corticosteroid receptor function in these animal models. We suggest these data point toward a potentially conserved function of corticosteroid receptors in integrating brain-behavior and visual responses in vertebrates. Finally, we discuss how future work in cartilaginous fishes (Chondrichthyes) will further advance understanding of the unity and diversity of corticosteroid receptor function, since distinct orthologs of GR and MR derived from an ancestral corticoid receptor appear in these basal jawed vertebrates.



http://ift.tt/2CFfyAB

Method for identifying outliers of soil heavy metal data

Abstract

Artificial errors in the experimental process may lead to some outliers, which reduce data quality and cause erroneous judgment in soil pollution assessment. Based on this, a method for detecting outliers of soil heavy metal data was proposed in this study. The As, Cd, and Pb concentrations of the soil in Beijing, China, were taken as samples to verify the validity of the method. Results showed that there were 8, 34, and 38 outliers for the As, Cd, and Pb concentrations in the Beijing soil, respectively. The result of re-analyzed revealed that 75.0, 76.5, and 92.1% of the As, Cd, and Pb outliers, respectively, were caused by artificial errors. After correcting, the interpolation accuracy for data was improved significantly. The mean relative error (MRE) of the As, Cd, and Pb outliers decreased by 48.0, 44.6, and 54.7%, while the mean square error of these outliers decreased by 34.2, 33.3, and 46.4%, respectively. The MRE values of the nearest neighboring points which were influenced by the outliers decreased by 5.2, 20.6, and 27.6%, while the mean square error of these points decreased by 5.3, 17.3, and 33.2%, respectively. To our knowledge, this is the first study on detecting outliers of soil heavy metal data. The method considers both spatial and numerical outliers, which avoids the limitation of single method, and can effectively improve the data quality of soil heavy metal concentrations with a finite sample size and analysis time.

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Editorial Board

Publication date: March 2018
Source:Peptides, Volume 101





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Corrigendum to “Structure, folding and stability of a minimal homologue from Anemonia sulcata of the sea anemone potassium channel blocker ShK” [Peptides 99 (2018) 169–178]

Publication date: March 2018
Source:Peptides, Volume 101
Author(s): Bankala Krishnarjuna, Christopher A. MacRaild, Punnepalli Sunanda, Rodrigo A.V. Morales, Steve Peigneur, Jason Macrander, Heidi H. Yu, Marymegan Daly, Srinivasarao Raghothama, Vikas Dhawan, Satendra Chauhan, Jan Tytgat, Michael W. Pennington, Raymond S. Norton




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Enhancement of nitrogen and phosphorus removal in landscape water using polymeric ferric sulfate as well as the synergistic effect of four kinds of natural rocks as promoter

Abstract

Eutrophication in lakes and rivers caused by the nitrogen (N) and phosphorus (P) is urgent since the accumulation of N and P can possibly cause the algal blooms and devastation to the water ecological system. The removal of N and P in the landscape water would be an efficient way to reduce the enrichment of nutrition before they reach the large water system. The N and P removal efficiency of PFS as well as the synergistic effect of natural rocks (four types of purple parent rock (J₃p, J₂s, T₁f, and J₃s)) as promoter was examined under laboratory conditions. The results indicated that TN and TP removal efficiency of the composite coagulant was significantly better than that of PFS or purple parent rock alone and J₃p + PFS (combination of PFS and J₃p purple parent rock) showed the best TN and TP removal efficiency. TN and TP removal efficiency of 53.53 and 86.48%, respectively, were achieved with coagulant dosage of 6 g L⁻¹ J₃p and 30 mg L⁻¹ PFS, water temperature of 30 °C, and wastewater initial pH of 9. In addition, Fourier transformed infrared (FTIR) spectrophotometer, X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive analysis (EDX), and the water quality index analysis revealed that the treatment of TN and TP by using J₃p + PFS was taking advantage of the flocculation function of PFS and the adsorption function of PFS and J₃p. In which, the flocculation mechanism was mainly charge neutralization; adsorption mechanism was mainly physical and chemical adsorption.

http://ift.tt/2osmGuU

Humoral immune responses to infection: common mechanisms and unique strategies to combat pathogen immune evasion tactics

Publication date: April 2018
Source:Current Opinion in Immunology, Volume 51
Author(s): Ismail Sebina, Marion Pepper
Humoral immune responses are crucial for protection against invading pathogens and are the underlying mechanism of protection for most successful vaccines. Our understanding of how humoral immunity develops is largely based on animal models utilizing experimental immunization systems. While these studies have made enormous progress for the field and have defined many of the fundamental principles of B cell differentiation and function, we are only now beginning to appreciate the complexities of humoral immune responses induced by infection. Co-evolution of the adaptive immune system and the pathogenic world has created a diverse array of B cell responses to infections, with both shared and unique strategies. In this review, we consider the common mechanisms that regulate the development of humoral immune responses during infection and highlight recent findings demonstrating the evolution of unique strategies used by either host or pathogen for survival.



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Effects of bisphenol A on metabolism and evidences of a mode of action mediated through endocrine disruption

Publication date: Available online 23 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Brigitte Le Magueresse-Battistoni, Luc Multigner, Claire Beausoleil, Christophe Rousselle
Based on rodent studies after prenatal and/or perinatal or adult exposure, there is now evidence that BPA may increase metabolic disturbances eventually leading to type-2 diabetes development via an ED MoA. In particular, BPA has been shown to alter insulin synthesis and/or release by pancreatic β-cells, and insulin signaling within insulin-sensitive organs (i.e., liver, muscle, adipose tissues). This resulted in variations in the expression of specific hepatic or adipose tissue markers, which are indicative of a state of insulin resistance. These effects are considered by experts to be hallmarks of adverse hormonal effects, each leading to insulin resistance within the different insulin-sensitive tissues.Although epidemiological studies are inconclusive, these effects are considered relevant for humans, because similarities exist in homeostatic regulation of insulin production and sensitivity between rodents and humans and because evidence was also shown through in vitro experimental data using human cells or tissues.



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Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation

Publication date: Available online 7 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Sofia Christakoudi, Manohursingh Runglall, Paula Mobillo, Irene Rebollo-Mesa, Tjir-Li Tsui, Estefania Nova-Lamperti, Sonia Norris, Yogesh Kamra, Rachel Hilton, Sunil Bhandari, Richard Baker, David Berglund, Sue Carr, David Game, Sian Griffin, Philip A. Kalra, Robert Lewis, Patrick B. Mark, Stephen D. Marks, Iain Macphee, William McKane, Markus G. Mohaupt, Ravi Pararajasingam, Sui Phin Kon, Daniel Serón, Manish Sinha, Beatriz Tucker, Ondrej Viklický, Robert I. Lechler, Graham M. Lord, Daniel Stahl, Maria P. Hernandez-Fuentes
Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n = 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.



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A review on Drug-induced Sedation Endoscopy – Technique, Grading Systems and Controversies

Sleep disordered breathing (SDB) comprises a spectrum of disorders, ranging from simple snoring to severe obstructive sleep apnoea (OSA), with a significant burden to health care systems in the developed world. If left untreated, obstructive sleep apnoea has significant cumulative, long-term health consequences. In the 1990s drug induced sedation endoscopy (DISE) has been developed to become a primary tool in the diagnosis and management of obstructive sleep apnoea (OSA). It allows meticulous endoscopic evaluation of the airway and identifies areas of collapse, thereby informing both on the selection of surgical techniques, where efficacy depends entirely on success at relieving obstruction at a certain level and on the usefulness of conservative measures, such as mandibular advancement splints.

http://ift.tt/2BMPmXR

Dampened STING-Dependent Interferon Activation in Bats

Publication date: Available online 22 February 2018
Source:Cell Host & Microbe
Author(s): Jiazheng Xie, Yang Li, Xurui Shen, Geraldine Goh, Yan Zhu, Jie Cui, Lin-Fa Wang, Zheng-Li Shi, Peng Zhou
Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir.

Graphical abstract

Teaser

Bats co-exist with a large variety of viruses, and infection-derived cytosolic DNA could result in heightened DNA sensing and overactivation. Xie et al. show that STING-dependent IFN activation is dampened in bats due to the replacement of the highly conserved and functionally important serine residue S358.


http://ift.tt/2CFGyQF

Getting the “Kill” into “Shock and Kill”: Strategies to Eliminate Latent HIV

Publication date: 10 January 2018
Source:Cell Host & Microbe, Volume 23, Issue 1
Author(s): Youry Kim, Jenny L. Anderson, Sharon R. Lewin
Despite the success of antiretroviral therapy (ART), there is currently no HIV cure and treatment is life long. HIV persists during ART due to long-lived and proliferating latently infected CD4+ T cells. One strategy to eliminate latency is to activate virus production using latency reversing agents (LRAs) with the goal of triggering cell death through virus-induced cytolysis or immune-mediated clearance. However, multiple studies have demonstrated that activation of viral transcription alone is insufficient to induce cell death and some LRAs may counteract cell death by promoting cell survival. Here, we review new approaches to induce death of latently infected cells through apoptosis and inhibition of pathways critical for cell survival, which are often hijacked by HIV proteins. Given advances in the commercial development of compounds that induce apoptosis in cancer chemotherapy, these agents could move rapidly into clinical trials, either alone or in combination with LRAs, to eliminate latent HIV infection.

Teaser

The major barrier to a cure for HIV is the persistence of latently infected T cells. One strategy being pursued to eliminate HIV latency involves the activation of virus transcription to induce cell death. Kim et al. review approaches that aim to enhance HIV-specific cell death following virus activation.


http://ift.tt/2F1uUo5

Botulinum Neurotoxins: Still a Privilege of Clostridia?

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Michel R. Popoff
Botulinum neurotoxins (BoNTs) are potent bacterial toxins mostly produced by genetically diverse clostridial strains. Recently, BoNT variants have been reported in non-clostridial strains. In this issue of Cell Host & Microbe, Zhang et al. (2018) describe a novel BoNT in Entecoccus faecium.

Teaser

Botulinum neurotoxins (BoNTs) are potent bacterial toxins mostly produced by genetically diverse clostridial strains. Recently, BoNT variants have been reported in non-clostridial strains. In this issue of Cell Host & Microbe, Zhang et al. (2018) describe a novel BoNT in Entecoccus faecium.


http://ift.tt/2CEiJsn

Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical for Efficient Early HIV-1 Replication In Vivo

Publication date: 10 January 2018
Source:Cell Host & Microbe, Volume 23, Issue 1
Author(s): Eri Yamada, Shinji Nakaoka, Lukas Klein, Elisabeth Reith, Simon Langer, Kristina Hopfensperger, Shingo Iwami, Gideon Schreiber, Frank Kirchhoff, Yoshio Koyanagi, Daniel Sauter, Kei Sato
The HIV-1-encoded accessory protein Vpu exerts several immunomodulatory functions, including counteraction of the host restriction factor tetherin, downmodulation of CD4, and inhibition of NF-κB activity to facilitate HIV-1 infection. However, the relative contribution of individual Vpu functions to HIV-1 infection in vivo remained unclear. Here, we used a humanized mouse model and HIV-1 strains with selective mutations in vpu to demonstrate that the anti-tetherin activity of Vpu is a prerequisite for efficient viral spread during the early phase of infection. Mathematical modeling and gain-of-function mutations in SIVcpz, the simian precursor of pandemic HIV-1, corroborate this finding. Blockage of interferon signaling combined with transcriptome analyses revealed that basal tetherin levels are sufficient to control viral replication. These results establish tetherin as a key effector of the intrinsic immune defense against HIV-1, and they demonstrate that Vpu-mediated tetherin antagonism is critical for efficient viral spread during the initial phase of HIV-1 replication.

Graphical abstract

Teaser

The HIV-1-encoded accessory protein Vpu exerts several functions. Using a humanized mouse model and HIV-1 Vpu mutant viruses, Yamada et al. demonstrate that Vpu-mediated antagonism of the interferon-induced antiviral protein tetherin is critical for efficient viral spread during the initial phase of HIV-1 replication in vivo.


http://ift.tt/2F3Ckrc

In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium Vivax Hypnozoites

Publication date: Available online 22 February 2018
Source:Cell Host & Microbe
Author(s): Nil Gural, Liliana Mancio-Silva, Alex B. Miller, Ani Galstian, Vincent L. Butty, Stuart S. Levine, Rapatbhorn Patrapuvich, Salil P. Desai, Sebastian A. Mikolajczak, Stefan H.I. Kappe, Heather E. Fleming, Sandra March, Jetsumon Sattabongkot, Sangeeta N. Bhatia
The unique relapsing nature of Plasmodium vivax infection is a major barrier to malaria eradication. Upon infection, dormant liver-stage forms, hypnozoites, linger for weeks to months and then relapse to cause recurrent blood-stage infection. Very little is known about hypnozoite biology; definitive biomarkers are lacking and in vitro platforms that support phenotypic studies are needed. Here, we recapitulate the entire liver stage of P. vivax in vitro, using a multiwell format that incorporates micropatterned primary human hepatocyte co-cultures (MPCCs). MPCCs feature key aspects of P. vivax biology, including establishment of persistent small forms and growing schizonts, merosome release, and subsequent infection of reticulocytes. We find that the small forms exhibit previously described hallmarks of hypnozoites, and we pilot MPCCs as a tool for testing candidate anti-hypnozoite drugs. Finally, we employ a hybrid capture strategy and RNA sequencing to describe the hypnozoite transcriptome and gain insight into its biology.

Graphical abstract

Teaser

Plasmodium vivax hypnozoites are difficult to study due to the lack of human liver platforms. Gural et al. recapitulated the entire liver stage of P. vivax in vitro, including formation and reactivation of hypnozoites and release of merosomes. Hybrid capture followed by RNA-seq revealed a first look into the hypnozoite transcriptome.


http://ift.tt/2CFjTE0

Less Is Best in the Convergent Evolution of Typhoidal Salmonella

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Andrés Vázquez-Torres
Related works in this issue of Cell Host & Microbe (Bronner et al., 2018) and in a recent issue of Cell Reports (Hiyoshi et al., 2018) demonstrate how loss-of-function mutations in butyrate utilization and lipopolysaccharide O-antigen processing contribute to evasion of innate host defenses and the convergent evolution of distinct typhoidal Salmonella lineages.

Teaser

Related works in this issue of Cell Host & Microbe (Bronner et al., 2018) and in a recent issue of Cell Reports (Hiyoshi et al., 2018) demonstrate how loss-of-function mutations in butyrate utilization and lipopolysaccharide O-antigen processing contribute to evasion of innate host defenses and the convergent evolution of distinct typhoidal Salmonella lineages.


http://ift.tt/2ELSWEk

Infectious Scarring: Setting the Trigger for Intestinal Inflammation

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Andrew M.F. Johnson, R. William DePaolo
The initiating factors that trigger inflammatory bowel disease (IBD) are poorly understood. In a recent paper, Yang et al. (2017) demonstrate that IBD-like syndrome in mice can develop as a consequence of recurrent pathogen infection. Pathogenic triggering of inflammatory disease is a re-emerging concept that has significant therapeutic implications.

Teaser

The initiating factors that trigger inflammatory bowel disease (IBD) are poorly understood. In a recent paper, Yang et al. (2017) demonstrate that IBD-like syndrome in mice can develop as a consequence of recurrent pathogen infection. Pathogenic triggering of inflammatory disease is a re-emerging concept that has significant therapeutic implications.


http://ift.tt/2CG5CXq

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

Publication date: 10 January 2018
Source:Cell Host & Microbe, Volume 23, Issue 1
Author(s): Rob J.W. Arts, Simone J.C.F.M. Moorlag, Boris Novakovic, Yang Li, Shuang-Yin Wang, Marije Oosting, Vinod Kumar, Ramnik J. Xavier, Cisca Wijmenga, Leo A.B. Joosten, Chantal B.E.M. Reusken, Christine S. Benn, Peter Aaby, Marion P. Koopmans, Hendrik G. Stunnenberg, Reinout van Crevel, Mihai G. Netea
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1β, a heterologous cytokine associated with the induction of trained immunity, but not with the specific IFNγ response. The importance of IL-1β for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1β as a mediator of trained immunity responses.

Graphical abstract

Teaser

In this paper, Arts et al. describe that BCG vaccination induces genome-wide epigenetic reprogramming of human monocytes that correlates with protection against experimental viral infection. Reduction of viremia correlated with upregulation of non-specific IL-1β production, and genetic polymorphisms in the IL-1 pathway affect the induction of trained immunity by BCG.


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An Additive Sugar Helps the C. diff Go Round

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Michael C. Abt
Outbreaks of hypervirulent strains of Clostridium difficile began to be reported in healthcare facilities worldwide around 20 years ago. Concurrently, trehalose became a common additive used by the global food industry. A new study provides evidence that these two observations are a linked phenomenon (Collins et al., 2018).

Teaser

Outbreaks of hypervirulent strains of Clostridium difficile began to be reported in healthcare facilities worldwide around 20 years ago. Concurrently, trehalose became a common additive used by the global food industry. A new study provides evidence that these two observations are a linked phenomenon (Collins et al., 2018).


http://ift.tt/2CG5wiw

Identification of a Botulinum Neurotoxin-like Toxin in a Commensal Strain of Enterococcus faecium

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Sicai Zhang, Francois Lebreton, Michael J. Mansfield, Shin-Ichiro Miyashita, Jie Zhang, Julia A. Schwartzman, Liang Tao, Geoffrey Masuyer, Markel Martínez-Carranza, Pål Stenmark, Michael S. Gilmore, Andrew C. Doxey, Min Dong
Botulinum neurotoxins (BoNTs), produced by various Clostridium strains, are a family of potent bacterial toxins and potential bioterrorism agents. Here we report that an Enterococcus faecium strain isolated from cow feces carries a BoNT-like toxin, designated BoNT/En. It cleaves both VAMP2 and SNAP-25, proteins that mediate synaptic vesicle exocytosis in neurons, at sites distinct from known BoNT cleavage sites on these two proteins. Comparative genomic analysis determines that the E. faecium strain carrying BoNT/En is a commensal type and that the BoNT/En gene is located within a typical BoNT gene cluster on a 206 kb putatively conjugative plasmid. Although the host species targeted by BoNT/En remains to be determined, these findings establish an extended member of BoNTs and demonstrate the capability of E. faecium, a commensal organism ubiquitous in humans and animals and a leading cause of hospital-acquired multi-drug-resistant (MDR) infections, to horizontally acquire, and possibly disseminate, a unique BoNT gene cluster.

Graphical abstract

Teaser

Botulinum neurotoxins (BoNTs) are potent toxins produced by diverse bacteria in the Clostridium genus. Zhang et al. report that a commensal strain of Enterococcus faecium carries a conjugative plasmid encoding a BoNT-like toxin gene. Thus, a commensal organism can acquire and possibly disseminate BoNT genes.


http://ift.tt/2CE3Feh

Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii-Mediated Inflammation

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Elise Burger, Alessandra Araujo, Américo López-Yglesias, Michael W. Rajala, Linda Geng, Beth Levine, Lora V. Hooper, Ezra Burstein, Felix Yarovinsky
The protozoan parasite Toxoplasma gondii triggers severe small intestinal immunopathology characterized by IFN-γ- and intestinal microbiota-mediated inflammation, Paneth cell loss, and bacterial dysbiosis. Paneth cells are a prominent secretory epithelial cell type that resides at the base of intestinal crypts and releases antimicrobial peptides. We demonstrate that the microbiota triggers basal Paneth cell-specific autophagy via induction of IFN-γ, a known trigger of autophagy, to maintain intestinal homeostasis. Deletion of the autophagy protein Atg5 specifically in Paneth cells results in exaggerated intestinal inflammation characterized by complete destruction of the intestinal crypts resembling that seen in pan-epithelial Atg5-deficient mice. Additionally, lack of functional autophagy in Paneth cells within intestinal organoids and T. gondii-infected mice causes increased sensitivity to the proinflammatory cytokine TNF along with increased intestinal permeability, leading to exaggerated microbiota- and IFN-γ-dependent intestinal immunopathology. Thus, Atg5 expression in Paneth cells is essential for tissue protection against cytokine-mediated immunopathology during acute gastrointestinal infection.

Graphical abstract

Teaser

Autophagy is an essential cellular process in all cells. Burger et al. show that the microbiota drives autophagy predominantly in Paneth cells via basal induction of IFN-γ. A Paneth cell-restricted deficiency in autophagy results in the inability to control intestinal inflammation and acute mortality during T. gondii infection.


http://ift.tt/2EOqhOW

Intestinal Epithelial Cell Autophagy Is Required to Protect against TNF-Induced Apoptosis during Chronic Colitis in Mice

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Johanna Pott, Agnieszka Martyna Kabat, Kevin Joseph Maloy
Genome-wide association studies have linked polymorphisms in the autophagy gene ATG16L1 with susceptibility to inflammatory bowel disease (IBD). However, the cell-type-specific effects of autophagy on the regulation of chronic intestinal inflammation have not been investigated. Here, we assessed the effect of myeloid-specific or intestinal epithelial cell (IEC)-specific deletion of Atg16l1 on chronic colitis triggered by the intestinal opportunistic pathogen Helicobacter hepaticus in mice. Although Atg16l1 deficiency in myeloid cells had little effect on disease, mice selectively lacking Atg16l1 in IECs (Atg16l1^VC) developed severely exacerbated pathology, accompanied by elevated pro-inflammatory cytokine secretion and increased IEC apoptosis. Using ex vivo IEC organoids, we demonstrate that autophagy intrinsically controls TNF-induced apoptosis and in vivo blockade of TNF attenuated the exacerbated pathology in Atg16l1^VC mice. These findings suggest that the IBD susceptibility gene ATG16L1 and the process of autophagy within the epithelium control inflammation-induced apoptosis and barrier integrity to limit chronic intestinal inflammation.

Graphical abstract

Teaser

Autophagy is genetically linked with inflammatory bowel disease. Using tissue-specific Atg16l1 knockout mice, Pott et al. demonstrate that autophagy within the intestinal epithelium maintains barrier integrity and limits inflammation by protecting the cells from TNF-induced apoptosis in a model of chronic colitis.


http://ift.tt/2CFs9DQ

Good Bug, Bad Bug: Breaking through Microbial Stereotypes

Publication date: 10 January 2018
Source:Cell Host & Microbe, Volume 23, Issue 1
Author(s): Mihai Cirstea, Nina Radisavljevic, B. Brett Finlay
Our expanding knowledge of microbial mechanisms is challenging the notion of "good" versus "bad" microbes and encouraging a better understanding of their roles in various contexts before their widespread therapeutic and clinical application. The intestinal microbe Akkermansia muciniphila, a promising probiotic with an emerging cautionary tale, best highlights this challenge.

Teaser

Our expanding knowledge of microbial mechanisms is challenging the notion of "good" versus "bad" microbes and encouraging a better understanding of their roles in various contexts before their widespread therapeutic and clinical application. The intestinal microbe Akkermansia muciniphila, a promising probiotic with an emerging cautionary tale, best highlights this challenge.


http://ift.tt/2F3dvvk

Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Liam Chung, Erik Thiele Orberg, Abby L. Geis, June L. Chan, Kai Fu, Christina E. DeStefano Shields, Christine M. Dejea, Payam Fathi, Jie Chen, Benjamin B. Finard, Ada J. Tam, Florencia M. McAllister, Hongni Fan, Xinqun Wu, Sudipto Ganguly, Andriana Lebid, Paul Metz, Sara W. Van Meerbeke, David L. Huso, Elizabeth C. Wick, Drew M. Pardoll, Fengyi Wan, Shaoguang Wu, Cynthia L. Sears, Franck Housseau
Pro-carcinogenic bacteria have the potential to initiate and/or promote colon cancer, in part via immune mechanisms that are incompletely understood. Using Apc^Min mice colonized with the human pathobiont enterotoxigenic Bacteroides fragilis (ETBF) as a model of microbe-induced colon tumorigenesis, we show that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic, multi-step inflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling in colonic epithelial cells (CECs). Although necessary, Stat3 activation in CECs is not sufficient to trigger ETBF colon tumorigenesis. Notably, IL-17-dependent NF-κB activation in CECs induces a proximal to distal mucosal gradient of C-X-C chemokines, including CXCL1, that mediates the recruitment of CXCR2-expressing polymorphonuclear immature myeloid cells with parallel onset of ETBF-mediated distal colon tumorigenesis. Thus, BFT induces a pro-carcinogenic signaling relay from the CEC to a mucosal Th17 response that results in selective NF-κB activation in distal colon CECs, which collectively triggers myeloid-cell-dependent distal colon tumorigenesis.

Graphical abstract

Teaser

Chung et al. uncover a complex, microbe-driven carcinogenic mechanism whereby the Bacteroides fragilis toxin targets the colonic epithelium to trigger an IL-17 mucosal immune response that relays back to epithelial cells, inciting pro-tumoral myeloid cell infiltration, principally to the distal colon, corresponding to the region of tumorigenesis in Apc^Min/− mice.


http://ift.tt/2CF7mAf

Cytosolic and Secreted Peptidoglycan-Degrading Enzymes in Drosophila Respectively Control Local and Systemic Immune Responses to Microbiota

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Bernard Charroux, Florence Capo, C. Léopold Kurz, Sabine Peslier, Delphine Chaduli, Annelise Viallat-lieutaud, Julien Royet
Gut-associated bacteria produce metabolites that both have a local influence on the intestinal tract and act at a distance on remote organs. In Drosophila, bacteria-derived peptidoglycan (PGN) displays such a dual role. PGN triggers local antimicrobial peptide production by enterocytes; it also activates systemic immune responses in fat-body cells and modulates fly behavior by acting on neurons. How these responses to a single microbiota-derived compound are simultaneously coordinated is not understood. We show here that the PGRP-LB locus generates both cytosolic and secreted PGN-cleaving enzymes. Through genetic analysis, we demonstrate that the cytosolic PGRP-LB isoforms cell-autonomously control the intensity of NF-κB activation in enterocytes, whereas the secreted isoform prevents massive and detrimental gut-derived PGN dissemination throughout the organism. This study explains how Drosophila are able to uncouple the modulation of local versus systemic responses to a single gut-bacteria-derived product by using isoform-specific enzymes.

Graphical abstract

Teaser

Since microbiota-derived peptidoglycan activates NF-κB signaling in the gut and remote organs, its levels need to be controlled in vivo. Charroux et al. show how, by generating both secreted and cytosolic peptidoglycan-cleaving enzymes, Drosophila uncouple the modulation of local versus systemic responses to a single gut-bacteria-derived product.


http://ift.tt/2F14T8A

Ecotoxicity tests with Allium cepa to determine the efficiency of rice husk ash in the treatment of groundwater contaminated with benzene, toluene, ethylbenzene, and xylene

Abstract

The validation of adsorption treatment based on toxicity assays aims to assess the actual environmental impact caused by effluents after treatment. This study describes the use of rice husk ash as adsorbent and evaluates the efficiency of adsorption treatment to remediate groundwater contaminated with benzene, toluene, ethylbenzene, and xylene (BTEX). The synthetic effluent was prepared with standard benzene, toluene, ethylbenzene, and xylene solutions. Adsorption was assessed at treatment times 0, 60, 120, and 240 min. Compounds were quantified by gas chromatography with flame ionization detector. The treatment was validated based on ecotoxicity assays using Allium cepa as indicator organism. For the treatment times stipulated, samples containing 25, 50, and 100% of BTEX were used. The dilutions were carried out with drinking water according to Fiskesjö (1985). The relative growth index (RGI), root inhibition index (Ii), and germination index (GI) confirmed the efficiency of the treatment approach tested. The best adsorption time for an initial BTEX concentration of 3.378 mg/L was 60 min. Critical level (EC50) and critical concentration that induced phytotoxic effect on A. cepa germination was observed only for the undiluted effluent.

http://ift.tt/2sSeWrP

Wound irrigation and the lack of evidence-based-practice

Dear Editor,

http://ift.tt/2ERpyZq

Circadian Control of DRP1 Activity Regulates Mitochondrial Dynamics and Bioenergetics

Publication date: Available online 22 February 2018
Source:Cell Metabolism
Author(s): Karen Schmitt, Amandine Grimm, Robert Dallmann, Bjoern Oettinghaus, Lisa Michelle Restelli, Melissa Witzig, Naotada Ishihara, Katsuyoshi Mihara, Jürgen A. Ripperger, Urs Albrecht, Stephan Frank, Steven A. Brown, Anne Eckert
Mitochondrial fission-fusion dynamics and mitochondrial bioenergetics, including oxidative phosphorylation and generation of ATP, are strongly clock controlled. Here we show that these circadian oscillations depend on circadian modification of dynamin-related protein 1 (DRP1), a key mediator of mitochondrial fission. We used a combination of in vitro and in vivo models, including human skin fibroblasts and DRP1-deficient or clock-deficient mice, to show that these dynamics are clock controlled via circadian regulation of DRP1. Genetic or pharmacological abrogation of DRP1 activity abolished circadian network dynamics and mitochondrial respiratory activity and eliminated circadian ATP production. Pharmacological silencing of pathways regulating circadian metabolism and mitochondrial function (e.g., sirtuins, AMPK) also altered DRP1 phosphorylation, and abrogation of DRP1 activity impaired circadian function. Our findings provide new insight into the crosstalk between the mitochondrial network and circadian cycles.

Graphical abstract

Teaser

Schmitt et al. demonstrate that the circadian clock globally regulates mitochondrial morphology and energy metabolism. Even in non-dividing tissues, rhythmic control of DRP1 phosphorylation directs circadian mitochondrial morphology. This control is not only essential for circadian ATP production but also feeds back to influence the core circadian clock.


http://ift.tt/2CEzfZs

Structure activity relationship studies on rhodanines and derived enethiol inhibitors of metallo-β-lactamases

Publication date: Available online 23 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Dong Zhang, Marios S. Markoulides, Dmitrijs Stepanovs, Anna M. Rydzik, Ahmed El-Hussein, Corentin A.M. Bon, Jos J.A.G. Kamps, Klaus-Daniel Umland, Patrick M. Collins, Samuel T. Cahill, David Y. Wang, Timothy D.W. Claridge, Jürgen Brem, Michael A. McDonough, Christopher J. Schofield
Metallo-β-lactamases (MBLs) enable bacterial resistance to almost all classes of β-lactam antibiotics. We report studies on enethiol containing MBL inhibitors, which were prepared by rhodanine hydrolysis. The enethiols inhibit MBLs from different subclasses. Crystallographic analyses reveal that the enethiol sulphur displaces the di-Zn(II) ion bridging 'hydrolytic' water. In some, but not all, cases biophysical analyses provide evidence that rhodanine/enethiol inhibition involves formation of a ternary MBL enethiol rhodanine complex. The results demonstrate how low molecular weight active site Zn(II) chelating compounds can inhibit a range of clinically relevant MBLs and provide additional evidence for the potential of rhodanines to be hydrolysed to potent inhibitors of MBL protein fold and, maybe, other metallo-enzymes, perhaps contributing to the complex biological effects of rhodanines. The results imply that any medicinal chemistry studies employing rhodanines (and related scaffolds) as inhibitors should as a matter of course include testing of their hydrolysis products.

Graphical abstract

http://ift.tt/2Fw1Jrr

Aralkyl selenoglycosides and related selenosugars in acetylated form activate protein phosphatase-1 and -2A

Publication date: Available online 22 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Zoltán Kónya, Bálint Bécsi, Andrea Kiss, István Tamás, Beáta Lontay, László Szilágyi, Katalin E. Kövér, Ferenc Erdődi
Aralkyl and aryl selenoglycosides as well as glycosyl selenocarboxylate derivatives were assayed on the activity of protein phosphatase-1 (PP1) and -2A (PP2A) catalytic subunits (PP1c and PP2Ac) in search of compounds for PP1c and PP2Ac effectors. The majority of tested selenoglycosides activated both PP1c and PP2Ac by ∼2-4-fold in a phosphatase assay with phosphorylated myosin light chain substrate when the hydroxyl groups of the glycosyl moiety were acetylated, but they were without any effects in the non-acetylated forms. A peptide from the myosin phosphatase target subunit-1 (MYPT1^23-38) that included an RVxF PP1c-binding motif attenuated activation of PP1c by 2-Trifluoromethylbenzyl 2,3,4,6-tetra-O-acetyl-1-seleno-β-D-glucopyranoside (TFM-BASG) and 4-Bromobenzyl 2,3,4,6-tetra-O-acetyl-1-seleno-β-D-glucopyranoside (Br-BASG). MYPT1^23-38 stimulated PP2Ac and contributed to PP2Ac activation exerted by either Br-BASG or TFM-BASG. Br-BASG and TFM-BASG suppressed partially binding of PP1c to MYPT1 in surface plasmon resonance based binding experiments. Molecular docking predicted that the hydrophobic binding surfaces in PP1c for interaction with either the RVxF residues of PP1c-interactors or selenoglycosides are partially overlapped. Br-BASG and TFM-BASG caused a moderate increase in the phosphatase activity of HeLa cells in 1 hour, and suppressed cell viability in 24 hour incubations. In conclusion, our present study identified selenoglycosides as novel activators of PP1 and PP2A as well as provided insights into the structural background of their interactions establishing a molecular model for future design of more efficient phosphatase activator molecules.

Graphical abstract

http://ift.tt/2ESfHmk