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Τετάρτη 25 Ιανουαρίου 2017

Evidence accumulation detected in BOLD signal using slow perceptual decision making

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Publication date: Available online 25 January 2017
Source:Journal of Neuroscience Methods
Author(s): Paul M. Krueger, Marieke K. van Vugt, Patrick Simen, Leigh Nystrom, Philip Holmes, Jonathan D. Cohen
BackgroundWe assessed whether evidence accumulation could be observed in the BOLD signal during perceptual decision making. This presents a challenge since the hemodynamic response is slow, while perceptual decisions are typically fast.New MethodGuided by theoretical predictions of the drift diffusion model, we slowed down decisions by penalizing participants for incorrect responses. Second, we distinguished BOLD activity related to stimulus detection (modeled using a boxcar) from activity related to integration (modeled using a ramp) by minimizing the collinearity of GLM regressors. This was achieved by dissecting a boxcar into its two most orthogonal components: an "up-ramp" and a "down-ramp." Third, we used a control condition in which stimuli and responses were similar to the experimental condition, but that did not engage evidence accumulation of the stimuli.ResultsThe results revealed an absence of areas in parietal cortex that have been proposed to drive perceptual decision making but have recently come into question; and newly identified regions that are candidates for involvement in evidence accumulation.Comparison with Existing MethodsPrevious fMRI studies have either used fast perceptual decision making, which precludes the measurement of evidence accumulation, or slowed down responses by gradually revealing stimuli. The latter approach confounds perceptual detection with evidence accumulation because accumulation is constrained by perceptual input.ConclusionsWe slowed down the decision making process itself while leaving perceptual information intact. This provided a more sensitive and selective observation of brain regions associated with the evidence accumulation processes underlying perceptual decision making than previous



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Identification of the major yeasts isolated from high moisture corn and corn silages in the United States using genetic and biochemical methods

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): M.C. Santos, C. Golt, R.D. Joerger, G.D. Mechor, Gerson B. Mourão, L. Kung
The objective of this study was to identify species of yeasts in samples of high moisture corn (HMC) and corn silage (CS) collected from farms throughout the United States. Samples were plated and colonies were isolated for identification using DNA analysis. Randomly selected colonies were also identified by fatty acid methyl esters (FAME) and by physiological substrate profiling (ID 32C). For CS, Candida ethanolica, Saccharomyces bulderi, Pichia anomala, Kazachstania unispora, and Saccharomyces cerevisiae were the predominant yeasts. Pichia anomala, Issatchenkia orientalis, S. cerevisiae, and Pichia fermentans were the prevalent species in HMC. The 3 identification methods were in agreement at the species level for 16.6% of the isolates and showed no agreement for 25.7%. Agreement in species identification between ID 32C and DNA analysis, FAME and ID 32C, and FAME and DNA analysis was 41.1, 14.4, and 2.2%, respectively. Pichia anomala and I. orientalis were able to grow on lactic acid, whereas S. cerevisiae metabolized sugars (galactose, sucrose, and glucose) but failed to use lactic acid. The yeast diversity in CS and HMC varied due to type of feed and location. Differences in species assignments were seen among methods, but identification using substrate profiling generally corresponded with that based on DNA analysis. These findings provide information about the species that may be expected in silages, and this knowledge may lead to interventions that control unwanted yeasts.



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Antimicrobial resistance patterns of bovine Salmonella enterica isolates submitted to the Wisconsin Veterinary Diagnostic Laboratory: 2006–2015

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): J.R. Valenzuela, A.K. Sethi, N.A. Aulik, K.P. Poulsen
Salmonellosis on the dairy continues to have a significant effect on animal health and productivity and in the United States. Additionally, Salmonella enterica ssp. enterica causes an estimated 1.2 million cases of human illness annually. Contributing to the morbidity and mortality in both human and domestic animal species is emergence of antimicrobial resistance by Salmonella species and increased incidence of multidrug-resistant isolates. This study describes serotype distribution and the antimicrobial resistance patterns for various Salmonella serotypes isolated from bovine samples submitted to the Wisconsin Veterinary Diagnostic Laboratory (WVDL) over the past 10 yr. Salmonella serotyping and antimicrobial susceptibility testing data were obtained from the laboratory information management system at WVDL. Data from accessions were limited to bovine samples submitted to the WVDL between January 2006 and June 2015 and those that had both a definitive serotype and complete results for antimicrobial susceptibility testing. A total of 4,976 isolates were identified. Salmonella enterica ser. Dublin was the most prevalent serotype identified among bovine samples submitted to the WVDL, accounting for a total of 1,153 isolates (23% of total isolates) over the study period. Along with Dublin, Salmonella enterica ser. Cerro (795, 16%), Newport (720, 14%), Montevideo (421, 8%), Kentucky (419, 8%), and Typhimurium (202, 4%) comprised the top 6 most commonly isolated serotypes during that time. Overall, resistance of bovine Salmonella isolates in the study population remained stable, although decreases in resistance were noted for gentamicin, neomycin, and trimethoprim sulfamethoxazole during the study period. All isolates remained susceptible to enrofloxacin. These data show that antimicrobial susceptibility for bovine Salmonella has changed in the population served by WVDL in the past 10 yr. This information is important for understanding Salmonella disease ecology in Wisconsin. Our findings are also relevant for animal and public health by improving informed antimicrobial use, new drug development, and regulation of their use in food animals.



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Letter to the Editor: A response to Kertz (2017): Extension and clarification of a call for more complete reporting and evaluation of experimental methods, physical forms of starters, and results in calf research

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): A. Bach, M. Terré, M.A. Khan




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Analysis of pasture supplementation strategies by means of a mechanistic model of ruminal digestion and metabolism in the dairy cow

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): J.P. McNamara, M.J. Auldist, L.C. Marett, P.J. Moate, W.J. Wales
Effective pasture supplementation is critical to the efficiency of resource management in milk production. We understand a great deal about ruminal and metabolic processes in dairy cattle that control efficiency but we need to improve our ability to predict effects of practical feeding strategies based on the basic biological processes of the cow. Therefore, a large-scale pasture supplementation study was used to explore the details of both practical management and the underlying biological principles and processes involved. This included a multiple lactation study coupled with shorter-term experiments that tested the type and rate of supplementation. Basal supplementation strategies were (1) pasture allowance [14 kg of dry matter (DM)/d per cow] supplemented with milled barley grain fed twice daily in the milking parlor and pasture silage provided in the paddock; the ratio of grain:forage fed as supplement was 0.75:0.25 (control; DM basis); (2) the same pasture allowance plus the same amounts of milled barley grain and pasture silage, but the supplements were mixed and chopped before being fed immediately after each milking; and (3) the same pasture allowance and offered a partial mixed ration comprising barley (25%) and corn grain (30% of DM), corn silage (20% of DM), and alfalfa hay (25% of DM) after each milking. In late lactation (227 d in milk), a short-term experiment was done feeding the same pasture allowances but with the 3 supplements offered at 6, 8, 10, and 12 kg of DM/d for an 11-d measurement period following adaptation to the diet to each of the 3 long-term supplementation groups. Production responses were recorded and ruminal volatile fatty acids (VFA) and pH were measured in a subset of animals. Model descriptions of yields of milk and milk constituents as well as mean concentrations of ruminal fluid VFA and ruminal fluid pH were compared with measured values resulting when dairy cows were fed 12 different pasture-based diets with different levels and types of dietary supplement. Inputs into the model were measured dry matter intake and feed composition on the 12 combined treatments as well as initial body weight and composition. The model described milk and milk component production within 1 standard deviation of the treatment means (less than 5% of the mean as measured in the root mean square error). The simulated proportions of ruminal acetate, propionate, and butyrate were consistent with observed effects of supplemental treatments and rate of supplementation; however, the error analysis showed room for improvement. The model described, to a general extent, the changes in ruminal pH; however, this investigation showed that the equations that describe ruminal pH need to be improved or modified. These results show that the fundamental knowledge of ruminal and organ metabolism in this mechanistic model is sufficient to describe the qualitative responses to complicated dietary strategies, but our quantitative understanding of the parameters involved such as degradation and absorption kinetics and ruminal pH still demands more specific research.



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Effects of Saccharomyces cerevisiae fermentation products on dairy calves: Performance and health

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): G.M. Alugongo, J.X. Xiao, Y.H. Chung, S.Z. Dong, S.L. Li, I. Yoon, Z.H. Wu, Z.J. Cao
The aim of the study was to evaluate the effects of Saccharomyces cerevisiae fermentation products (SCFP) on performance and health of calves during the first 63 d of age. Sixty Holstein calves (30 males and 30 females) at 2 d of age were blocked by sex and date of birth then randomly assigned within blocks to 1 of 3 treatments. A texturized calf starter was fed ad libitum containing 0 (control), 0.5, or 1% SCFP (Original XPC, Diamond V, Cedar Rapids, IA) of DM. In addition, the supplemented calves were fed 1 g/d SCFP (SmartCare, Diamond V) in milk until d 30. All calves were fed 4 L of colostrum within 1 h of birth and were subsequently fed milk twice daily until weaned at 56 d of age. Male calves were harvested on d 56. Performance and health of weaned female calves were monitored until 63 d of age to determine the effect of preweaning treatment of SCFP on weaning stress. Starter intake, fecal scores, and medical treatments were recorded daily. Body weight measures and blood samples were collected on d 2, 28, 56, and 63. Serum was analyzed for blood urea nitrogen, fatty acids, insulin-like growth factor-1, glucose, and total protein. Oxidative biomarkers and total antioxidant capacity were also evaluated in the serum. Body weight, DMI, blood parameters, and oxidative biomarkers did not differ among treatments. Supplementation of SCFP lowered fecal scores in the pre- and postweaning periods. Saccharomyces cerevisiae fermentation products can be used to reduce the diarrhea in calves grown under normal commercial conditions.



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Letter to the Editor: A call for more complete reporting and evaluation of experimental methods, physical forms of starters, and results in calf research

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): A.F. Kertz




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Syneresis and rheological behaviors of set yogurt containing green tea and green coffee powders

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): Özge Dönmez, Burçe Ataç Mogol, Vural Gökmen
This study aimed to investigate the effect of added green coffee powder (GCP) and green tea powder (GTP) on syneresis behavior and consistency of set yogurts. Adding GCP (1 or 2%) decreased syneresis rate. The effect of GTP on the syneresis rate was concentration dependent. In comparison to the control, GTP decreased syneresis rate when it was added at 0.02%, but it caused an increase when added at 2%. No significant difference was observed in the syneresis rates when GTP was added at 1 and 0.01%, until 14 and 7 d of storage, respectively. The Herschel-Bulkley model parameters indicated that the consistency of control was considerably lower than that of GCP yogurts during 14 d, whereas it was higher at the end of storage. The GTP yogurt results showed that the consistency coefficients of GTP yogurts were different from those of control samples until 14 d of storage. In conclusion, GTP and GCP behaved differently in acidified gel networks of set yogurt, modifying its rheological behavior, as they have different profiles and concentrations of polyphenols.



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Genome-wide association study for cheese yield and curd nutrient recovery in dairy cows

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): C. Dadousis, S. Biffani, C. Cipolat-Gotet, E.L. Nicolazzi, G.J.M. Rosa, D. Gianola, A. Rossoni, E. Santus, G. Bittante, A. Cecchinato
Cheese production and consumption are increasing in many countries worldwide. As a result, interest has increased in strategies for genetic selection of individuals for technological traits of milk related to cheese yield (CY) in dairy cattle breeding. However, little is known about the genetic background of a cow's ability to produce cheese. Recently, a relatively large panel (1,264 cows) of different measures of individual cow CY and milk nutrient and energy recoveries in the cheese (REC) became available. Genetic analyses showed considerable variation for CY and for aptitude to retain high proportions of fat, protein, and water in the coagulum. For the dairy industry, these characteristics are of major economic importance. Nevertheless, use of this knowledge in dairy breeding is hampered by high costs, intense labor requirement, and lack of appropriate technology. However, in the era of genomics, new possibilities are available for animal breeding and genetic improvement. For example, identification of genomic regions involved in cow CY might provide potential for marker-assisted selection. The objective of this study was to perform genome-wide association studies on different CY and REC measures. Milk and DNA samples from 1,152 Italian Brown Swiss cows were used. Three CY traits expressing the weight (wt) of fresh curd (%CYCURD), curd solids (%CYSOLIDS), and curd moisture (%CYWATER) as a percentage of weight of milk processed, and 4 REC (RECFAT, RECPROTEIN, RECSOLIDS, and RECENERGY, calculated as the % ratio between the nutrient in curd and the corresponding nutrient in processed milk) were analyzed. Animals were genotyped with the Illumina BovineSNP50 Bead Chip v.2. Single marker regressions were fitted using the GenABEL R package (genome-wide association using mixed model and regression–genomic control). In total, 103 significant associations (88 single nucleotide polymorphisms) were identified in 10 chromosomes (2, 6, 9, 11, 12, 14, 18, 19, 27, 28). For RECFAT and RECPROTEIN, high significance peaks were identified in Bos taurus autosome (BTA) 6 and BTA11, respectively. Marker ARS-BFGL-NGS-104610 (∼104.3 Mbp) was highly associated with RECPROTEIN and Hapmap52348-rs29024684 (∼87.4 Mbp), closely located to the casein genes on BTA6, with RECFAT. Genomic regions identified may enhance marker-assisted selection in bovine cheese breeding beyond the use of protein (casein) and fat contents, whereas new knowledge will help to unravel the genomic background of a cow's ability for cheese production.



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Short communication: Interaction of the isomers carvacrol and thymol with the antibiotics doxycycline and tilmicosin: In vitro effects against pathogenic bacteria commonly found in the respiratory tract of calves

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): W. Kissels, X. Wu, R.R. Santos
Bovine respiratory disease is the major problem faced by cattle, specially calves, leading to reduced animal performance and increased mortality, consequently causing important economic losses. Hence, calves must be submitted to antibiotic therapy to counteract this infection usually initiated by the combination of environmental stress factors and viral infection, altering the animal's defense mechanism, and thus allowing lung colonization by the opportunistic bacteria Mannheimia haemolytica and Pasteurella multocida. Essential oils appear to be candidates to replace antibiotics or to act as antibiotic adjuvants due to their antimicrobial properties. In the present study, we aimed to evaluate the 4 essential oil components carvacrol, thymol, trans-anethole, and 1,8 cineole as antibacterial agents or as adjuvants for the antibiotics doxycycline and tilmicosin against M. haemolytica and P. multocida. Bacteria were cultured according to standard protocols, followed by the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration. A checkerboard assay was applied to detect possible interactions between components, between antibiotics, and between components and antibiotics. Doxycycline at 0.25 and 0.125 μg/mL inhibited the growth of P. multocida and M. haemolytica, respectively, whereas tilmicosin MIC values were 1.0 and 4.0 μg/mL for P. multocida and M. haemolytica, respectively. Carvacrol MIC values were 2.5 and 1.25 mM for P. multocida and M. haemolytica, respectively, whereas thymol MIC values were 1.25 and 0.625 mM for P. multocida and M. haemolytica, respectively. Trans-anethole and 1,8 cineole did not present any antibacterial effect even at 40 mM against the investigated pathogens. All minimum bactericidal concentration values were the same as MIC, except when thymol was tested against M. haemolytica, being twice the MIC data (i.e., 1.25 mM thymol). Based on fractional inhibitory concentration checkerboard assay, no interaction was observed between doxycycline and tilmicosin. Carvacrol and thymol presented an additive effect when one of them was combined with tilmicosin. Additive effect was also observed when doxycycline was combined with thymol. Synergism was observed when carvacrol was combined with doxycycline or with thymol. Although the antibacterial effects of the tested essential oil components were observed at high concentrations for in vitro conditions, the additive and synergic effects of carvacrol and thymol with antibiotics suggest the option to apply them as antibiotic adjuvants.



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Development and application of a sensitive, rapid, and reliable immunomagnetic separation-PCR detection method for Cronobacter spp.

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): Qiming Chen, Yuanhong Li, Tingting Tao, Xiaomei Bie, Fengxia Lu, Zhaoxin Lu
Cronobacter spp. have been linked to clinical cases of infection in both adults and infants. Enrichment of Cronobacter spp. before detection has been necessary but is quite time consuming. Hence, we sought to develop an immunomagnetic separation (IMS) PCR method that could shorten the time of enrichment before the detection of Cronobacter spp. The polyclonal antibody used in this immunomagnetic separation was prepared based on the outer membrane protein A of Cronobacter sakazakii China Center of Industrial Culture Collection 21560 and had high specificity to the target. The primers used in the IMS-PCR method also showed high specificity. The detection limit of IMS-PCR for pure C. sakazakii culture was 5.2 × 102 cfu/mL. Cronobacter sakazakii in artificially contaminated powdered infant formula (PIF) was also detected at a detection limit of 5.2 × 102 cfu/mL. After 8 h of enrichment, the detection limit in PIF was lower than 5.2 × 101 cfu/mL. An interference test using Escherichia coli in artificially contaminated PIF showed that the IMS-PCR method developed in this study had a good ability to resist interference. Finally, the IMS-PCR method was applied to the detection of Cronobacter in food samples and was shown to be reliable. Thus, this newly developed IMS-PCR detection method was quite sensitive, rapid, and reliable and could be applied to the detection of Cronobacter in foods.



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Growth performance, feeding behavior, and selected blood metabolites of Holstein dairy calves fed restricted amounts of milk: No interactions between sources of finely ground grain and forage provision

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): M. Mirzaei, M. Khorvash, G.R. Ghorbani, M. Kazemi-Bonchenari, M.H. Ghaffari
The objective of this study was to investigate the effects of grain sources and forage provision on growth performance, blood metabolites, and feeding behaviors of dairy calves. Sixty 3-d-old Holstein dairy calves (42.2 ± 2.5 kg of body weight) were used in a 2 × 3 factorial arrangement with the factors being grain sources (barley and corn) and forage provision (no forage, alfalfa hay, and corn silage). Individually housed calves were randomly assigned (n = 10 calves per treatment: 5 males and 5 females) to 6 treatments: (1) barley grain (BG) without forage supplement, (2) BG with alfalfa hay (AH) supplementation, (3) BG with corn silage (CS) supplementation, (4) corn grain (CG) without forage supplement, (5) CG with AH supplementation, and (6) CG with CS supplementation. All calves had ad libitum access to water and starter feed throughout the experiment. All calves were weaned on d 49 and remained in the study until d 63. Starter feed intake and average daily gain (ADG) was greater for calves fed barley than those fed corn during the preweaning and overall periods. Calves supplemented with CS had greater final body weight and postweaning as well as overall starter feed intake than AH and non-forage-supplemented calves. During the preweaning and overall periods, feeding of CS was found to increase ADG compared with feeding AH and nonforage diets. However, feed efficiency was not affected by dietary treatments. Calves supplemented with CS spent more time ruminating compared with AH and control groups; nonnutritive oral behaviors were the greatest in non-forage-supplemented calves. Regardless of the grain sources, the rumen pH value was greater for AH calves compared with CS and non-forage-supplemented calves. Blood concentration of BHB was greater for CS-supplemented calves compared with AH and non-forage-supplemented calves. Furthermore, body length and heart girth were greater for calves fed barley compared with those fed corn, and also in forage-supplemented calves compared with non-forage-supplemented calves. These results showed no interactions between grain sources and forage provision on calf performance; however, the inclusion of CS and barley in starter diets could enhance the growth performance of Holstein calves during the transition from liquid to solid feed.



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Short communication: Improving the activity of bile salt hydrolases in Lactobacillus casei based on in silico molecular docking and heterologous expression

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): Zhi-Qiang Xiong, Qiao-Hui Wang, Ling-Hui Kong, Xin Song, Guang-Qiang Wang, Yong-Jun Xia, Hui Zhang, Yong Sun, Lian-Zhong Ai
Bile salt hydrolase (BSH) plays an essential role in the cholesterol-removing effect of lactic acid bacteria, which hydrolyze conjugated bile salts to amino acid and deconjugated bile salts. However, Lactobacillus casei lacks the bsh gene, which may make it highly sensitive to bile salt stress. We wanted to improve the BSH activity of L. casei for various food-industry applications (e.g., milk fermentation). Plate assay testing indicated that Lactobacillus plantarum AR113 has the highest BSH activity. We cloned and sequenced 4 bsh genes from the genome of L. plantarum AR113. Structure modeling and molecular docking of BSH indicated that BSH1 and BSH3 could react efficiently with bile salts, so we selected BSH1 and BSH3 for heterologous expression in L. casei. Compared with single expression of BSH1 or BSH3, co-expression of both protein sequences showed the highest hydrolysis activity by HPLC analysis. Our results suggested that heterologous expression of BSH in L. casei can significantly improve host activity against bile salts, and in silico molecular docking could be an efficient method of rapid screening for BSH with high activity.



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Biofouling of ultrafiltration membrane by dairy fluids: Characterization of pioneer colonizer bacteria using a DNA metabarcoding approach

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): Julien Chamberland, Marie-Hélène Lessard, Alain Doyen, Steve Labrie, Yves Pouliot
Biofouling of filtration membranes is a major quality and performance issue for the dairy industry. Because biofilms that survive cleaning cycles become resistant over time, prevention strategies limiting the adhesion of bacteria to membranes should be prioritized for sustainable control of biofouling. However, this cannot be achieved because the pioneer bacteria colonizing these membranes are still unknown. Consequently, the objective of this study was to characterize pioneer bacteria on the filtration membrane surface and to measure the effect of filtration operational parameters on their diversity. Thus, milk and cheese whey were filtered for 5 h in concentration mode at 10 and 40°C using a laboratory-scale crossflow filtration system equipped with flat-sheet ultrafiltration membranes. Pioneer colonizer bacteria found on membranes after a chlorinated alkaline cleaning cycle were identified using a metabarcoding approach targeting the 16S ribosomal RNA genes. Our results suggested that prevention strategies targeting biofouling should consider the nature of the filtered fluid and the feed temperature (36.15 and 5.09% of the variances observed on membranes, respectively), as well as the microbial environment of the dairy processing plant. In the future, it is hypothesized that cleaning prevention strategies will be specific to each dairy processor and their operational parameters.



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Short communication: Influence of pulsed light treatment on the quality and sensory characteristics of Cheddar cheese

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): J. Proulx, M. Agustin, G. Sullivan, S. VanWees, J. Jian, S.T. Hilton, C.I. Moraru
The objective of this study was to examine the effect of pulsed light (PL) treatment on the color, oxidative stability, and onset of molding of Cheddar cheese. Slices of sharp white Cheddar cheese of 2.5 × 5 cm were treated on one side with PL doses from 1.02 to 12.29 J/cm2, sealed in polyethylene bags, and stored at 6°C for up to 1 mo. Peroxide value, color parameters, and the onset of molding were evaluated. No significant changes in color or peroxide value were observed for PL-treated samples compared with the untreated controls. Pulsed light was able to significantly delay surface molding during refrigerated storage, with a PL dose of 9.22 J/cm2 delaying the onset of molding by 7 d. The effect of PL on the taste, appearance, and acceptability of Cheddar cheese slices treated with a PL dose of 9.22 J/cm2 on each side was assessed. In triangle tests, 60 untrained panelists were unable to detect significant differences between the control and PL-treated samples, although PL had a significant effect on overall liking, flavor, and appearance. These findings suggest that although PL can be effective for surface decontamination of cheese, it may have some detrimental effects on sensory properties.



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Hepatic expression of aminoadipate semialdehyde synthase is unchanged by postruminal lysine supply in lactating dairy cows

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): H.A. Tucker, M.D. Hanigan, J. Escobar, P.H. Doane, S.S. Donkin
Lysine supply is potentially limiting for milk production in dairy cows. The availability of Lys to the mammary gland and other tissues is a function of the quantity of metabolizable Lys supplied and Lys catabolism by the liver. Likewise, Lys catabolism may be influenced by Lys supply. This study evaluated the effect of increased postruminal Lys supply on the expression of aminoadipate semialdehyde synthase (AASS, a committing step in Lys catabolism in the liver) and ornithine transcarbamoylase and argininosuccinate synthase (key urea cycle enzymes that are responsive to protein supply). Eight multiparous peak Holstein cows were used in a replicated 4 × 4 Latin square. Cows were fed a Lys-limiting ration and infused postruminally with 0, 9, 27, or 63 g/d of Lys. The study consisted of 10 d of pretreatment followed by 10 d of Lys infusion. On the last day of each period, liver and milk samples were collected for mRNA analysis, and blood samples were collected for analysis of amino acids and Lys metabolites. Milk protein percent increased by 5.9%, plasma Lys increased by 74%, and α-aminoadipic acid increased by 51% with postruminal infusion of 63 g/d Lys compared with 0 g/d. Expression of AASS, ornithine transcarbamoylase, and argininosuccinate synthase mRNA in liver did not differ with postruminal infusion of Lys. Milk fat globule mRNA for major milk proteins and AASS were not affected by Lys infusion. Postruminal infusion of Lys resulted in an 86% greater increase in AASS mRNA in the liver compared with mammary mRNA. These changes suggest that hepatic Lys metabolism is not responsive to Lys supply at the transcription level, and that the availability of Lys to extrahepatic tissue may be determined by hepatic Lys metabolism.



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Genome-wide association study for lactation persistency, female fertility, longevity, and lifetime profit index traits in Holstein dairy cattle

Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): S. Nayeri, M. Sargolzaei, M.K. Abo-Ismail, S. Miller, F. Schenkel, S.S. Moore, P. Stothard
Female fertility in Holstein cattle can decline when intense genetic selection is placed on milk production. One approach to improving fertility is to identify the genomic regions and variants affecting fertility traits and then incorporate this knowledge into selection decisions. The objectives of this study were to identify or refine the positions of the genomic regions associated with lactation persistency, female fertility traits (age at first service, cow first service to conception, heifer and cow nonreturn rates), longevity traits (herd life, indirect herd life, and direct herd life), and lifetime profit index in the North American Holstein dairy cattle population. A genome-wide association study was performed for each trait, using a single SNP (single nucleotide polymorphism) regression mixed linear model and imputed high-density panel (777k) genotypes. No associations were identified for fertility traits. Several peak regions were detected for lifetime profit index, lactation persistency, and longevity. The results overlap with previous findings and identify some novel regions for lactation persistency. Previously proposed causative and candidate genes supported by this work include DGAT1, GRINA, and CPSF1, whereas new candidate genes are SLC2A4RG and THRB. Thus, the chromosomal regions identified in this study not only confirm several previous findings but also highlight new regions that may contribute to genetic variation in lactation persistency and longevity-associated traits in dairy cattle.



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Short communication: Identification of variation in the ovine prolactin gene of Chios sheep with a cost-effective sequence-based typing assay

Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): D. Miltiadou, M. Orford, S. Symeou, G. Banos
The present study identified single nucleotide polymorphisms (SNP) in the coding and untranslated regions of the ovine prolactin gene of Chios sheep. By developing a cost-effective direct sequence-based typing assay, around 600 bp of reliable sequencing data and clear identification of heterozygous positions was achieved. Five SNP were found, located in exons 2 (KC764410:g.567G>A, g.625C>T, g.683C>A) and 3 (KC764410:g.2015C>A, g.2101G>A), whereas the remaining exons were monomorphic. The identified SNP were synonymous, with the exception of the g.567G>A SNP, which results in an Arg to His amino acid change. As the sequencing cost of the sequence-based typing assay was 20 orders of magnitude lower compared with a standard Sanger method, the assay was also used as a genotyping tool. The identified polymorphism was genotyped for 247 ewes and was subsequently used in mixed model association analyses of milk yield, milk fat content, and litter size at birth. The association analysis revealed a significant dominance effect of 0.17 ± 0.07 of the g.2015C>A SNP on milk fat percentage, whereas a dominance effect of −21.33 ± 10.51 of the same SNP on total lactation milk yield was also estimated. The g.2015C>A SNP explained 2.47 and 3.68% of the total phenotypic variance of milk yield and milk fat percentage, respectively, whereas the corresponding values for the animal variance were 7.14 and 11.75%. A suggestive association of the nonsynonymous g.567G>A SNP with litter size at birth was also detected.



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Investigating the within-herd prevalence and risk factors for ketosis in dairy cattle in Ontario as diagnosed by the test-day concentration of β-hydroxybutyrate in milk

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): Elise H. Tatone, Todd F. Duffield, Stephen J. LeBlanc, Trevor J. DeVries, Jessica L. Gordon
An observational study of 790 to over 3,000 herds was conducted to estimate the within-herd prevalence and cow-level risk factors for ketosis in dairy cattle in herds that participate in a Dairy Herd Improvement Association (DHIA) program. Ketosis or hyperketolactia (KET) was diagnosed as milk β-hydroxybutyrate ≥0.15 mmol/L at first DHIA test when tested within the first 30 d in milk. Seven hundred ninety-five herds providing at least 61 first milk tests from June 2014 to December 2015 were used to estimate the provincial within-herd prevalence of KET. All herds on DHIA in Ontario (n = 3,042) were used to construct cow-level multilevel logistic regression models to investigate the association of DHIA collected variables with the odds of KET at first DHIA milk test. Primiparous and multiparous animals were modeled independently. The cow-level KET prevalence in Ontario was 21%, with an average within-herd prevalence of 21% (standard deviation = 10.6) for dairy herds enrolled in a DHIA program. The prevalence of KET had a distinct seasonality with the lowest prevalence occurring from July to November. Automatic milking systems (AMS) were associated with increased within-herd prevalence, as well as increased odds of KET in multiparous animals at first test (odds ratio: 1.45; 95% confidence interval: 1.30 to 1.63). Jersey cattle had over 1.46 times higher odds of KET than Holstein cattle. Milk fat yield ≥1.12 kg/d at the last test of the previous lactation was associated with decreased odds of KET in the current lactation (odds ratio: 0.56; 95% confidence interval: 0.53 to 0.59). Increased days dry and longer calving intervals, for multiparous animals, and older age at first calving for primiparous animals increased the odds of KET at first test. This study confirms previous findings that increased days dry, longer calving intervals, and increased age at first calving are associated with increased odds of KET and is the first report of increased KET in herds with AMS and in relation to milk fat yield at the final test of the previous lactation. Feeding management on AMS herds likely contributes to the increased prevalence of KET and further work is required to investigate modifications to current management to minimize risk. Milk fat yield during the previous lactation may be representative of energy partitioning.



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Determining suitable dimensions for dairy goat feeding places by evaluating body posture and feeding reach

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Publication date: February 2017
Source:Journal of Dairy Science, Volume 100, Issue 2
Author(s): Nina M. Keil, Marc Pommereau, Antonia Patt, Beat Wechsler, Lorenz Gygax
Confined goats spend a substantial part of the day feeding. A poorly designed feeding place increases the risk of feeding in nonphysiological body postures, and even injury. Scientifically validated information on suitable dimensions of feeding places for loose-housed goats is almost absent from the literature. The aim of the present study was, therefore, to determine feeding place dimensions that would allow goats to feed in a species-appropriate, relaxed body posture. A total of 27 goats with a height at the withers of 62 to 80 cm were included in the study. Goats were tested individually in an experimental feeding stall that allowed the height difference between the feed table, the standing area of the forelegs, and a feeding area step (difference in height between forelegs and hind legs) to be varied. The goats accessed the feed table via a palisade feeding barrier. The feed table was equipped with recesses at varying distances to the feeding barrier (5–55 cm in 5-cm steps) at angles of 30°, 60°, 90°, 120°, or 150° (feeding angle), which were filled with the goats' preferred food. In 18 trials, balanced for order across animals, each animal underwent all possible combinations of feeding area step (3 levels: 0, 10, and 20 cm) and of difference in height between feed table and standing area of forelegs (6 levels: 0, 5, 10, 15, 20, and 25 cm). The minimum and maximum reach at which the animals could reach feed on the table with a relaxed body posture was determined for each combination. Statistical analysis was performed using mixed-effects models. The animals were able to feed with a relaxed posture when the feed table was at least 10 cm higher than the standing height of the goats' forelegs. Larger goats achieved smaller minimum reaches and minimum reach increased if the goats' head and neck were angled. Maximum reach increased with increasing height at withers and height of the feed table. The presence of a feeding area step had no influence on minimum and maximum reach. Based on these results, the goats' feeding place can be designed to ensure that the animals are able to reach all of the feed in the manger or on the feed table with a relaxed posture, thus avoiding injuries and nonphysiological stress on joints and hooves. A feeding area step up to a maximum of 20 cm need not be taken into account in terms of feeding reach. However, the feed table must be raised at least 10 cm above the standing area to allow the goats to feed in a species-appropriate, relaxed posture.



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Domestic violence offending behaviors: A review of the literature examining childhood exposure, implicit theories, trait aggression and anger rumination as predictive factors

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Publication date: Available online 25 January 2017
Source:Aggression and Violent Behavior
Author(s): Anita Ruddle, Afroditi Pina, Eduardo Vasquez
The prevalence of domestic violence (DV) is an increasing public health concern globally. This paper outlines the current literature on what is known about DV proclivity, with particular attention to predictors for DV perpetration from childhood. We begin by reviewing key methodological issues that are inherent within DV literature and hinder the development of interventions and treatments for DV offenders. The main body of this article provides an overview of four main predictive components for DV perpetration: (1) developmental risk factors for DV offending (e.g. childhood exposure to DV); (2) specific implicit theories related to sexual, violent and DV offenders; (3) the role of anger rumination as a psychological process of DV offending; and (4) an exploration of the role of trait aggression in increasing DV Proclivity. Finally, it was concluded that there is a need for the development of a psychometric measure to encompass these four key predictors of DV Proclivity and future offending.



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Evaluation of seclusion and restraint reduction programs in mental health: A systematic review

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Publication date: Available online 26 January 2017
Source:Aggression and Violent Behavior
Author(s): Marie-Hélène Goulet, Caroline Larue, Alexandre Dumais
ContextThe effectiveness of seclusion and restraint (SR) reduction programs has not been well established.ObjectiveTo examine the effectiveness of SR reduction programs in mental health settings.Data sourcesA systematic review of English and French articles, using CINALH, Web of Science, PubMed, Medline, Embase, and the Cochrane Library. Additional studies were added by searching the references of identified papers.Study selectionAll evaluative studies on SR reduction programs in mental health were included based on predefined criteria (n=23 articles).Data extractionData extraction of articles was performed using predefined data fields. The three authors conducted quality assessments independently.Data synthesisIn the 23 articles analyzed, six key components were predominant in SR reduction programs: 1) leadership, 2) training, 3) post-seclusion and/or restraint review, 4) patient involvement, 5) prevention tools, and 6) the therapeutic environment.ConclusionDespite wide variability in SR indicators and methodological rigor, it remains that the outcomes argue in favor of SR reduction program implementation.



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Thermal characterization of natural and synthetic spider silks by both the 3ω and transient electrothermal methods

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Changhu Xing, Troy Munro, Colby Jensen, Heng Ban, Cameron G. Copeland, Randolph V. Lewis
Thermal conductivity, thermal diffusivity, and volumetric heat capacity of three spider silks are measured in this paper as a benchmark for further studies. These silks include the major and minor ampullate silks of the Nephila clavipes spider, and a synthetic spider silk fiber made from recombinant dragline silk proteins purified from transgenic goats' milk. Two complementary measurement techniques are employed in the thermal characterization of these microscale single fibers for self-verification. One is the transient electrothermal technique (TET) and the other is the 3ω method. Experimental measurements indicate that thermal properties of the dragline silk are very close to those of the minor ampullate silk, whereas the ones for the synthetic silk are much lower due in part to its low crystallinity. The directly measured thermal conductivity, thermal diffusivity, and volumetric heat capacity of the major and minor ampullate silks are 1.2–1.26Wm−1K−1, 5.7–6×10−7m2s−1, and 2–2.17 MJm−3K−1, respectively. The thermal conductivity and thermal diffusivity of the as-spun synthetic silk are 0.24Wm−1K−1 and 1.6×10−7m2s−1 respectively. As part of this study, a detailed comparison of the TET and 3ω methods is provided showing the complementary nature of the techniques and illustrating the strengths and weaknesses of each.

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Effects of vacancies on the mechanical properties of zirconium: An ab initio investigation

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Xueyan Zhu, Xingyu Gao, Haifeng Song, Guomin Han, De-Ye Lin
The irradiation-induced defects strongly influence the mechanical behaviors of zirconium (Zr) and its alloys in nuclear reactors. In this work, we focus on how the vacancies change the mechanical properties of α-Zr through density functional theory (DFT) calculations. Both uniformly distributed vacancies and vacancy clusters were considered. And a wide range of vacancy concentrations from 0.005 to 0.063 (molar fraction) was modeled. The most stable configurations of di- and trivacancy clusters were predicted, which correspond to the most compact distribution of vacancies. Mechanical properties were explored in terms of single-crystal elastic constants, based on which the polycrystalline elastic moduli, Pugh's ratio for ductility and Vickers hardness were derived. Our results show that the existence of uniformly distributed vacancies can reduce the ductility, while enhance the hardness in general. However, when the vacancy concentration is larger than a critical value, a rise in the ductility and a reduction in the hardness occur, which may contribute to the degeneration of the material. Compared with the uniform distribution of vacancies, clustering of vacancies strengthens the above changes of ductility and hardness. Moreover, it was found that the anisotropy of Young's modulus decreases with increasing vacancy concentration.

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Synergistic effects of CNT and GO on enhancing mechanical properties and separation performance of polyelectrolyte complex membranes

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Jia-Kai Wu, Chun-Chun Ye, Tao Liu, Quan-Fu An, Yi-Hu Song, Kueir-Rarn Lee, Wei-Song Hung, Cong-Jie Gao
High strength polyelectrolyte complex (PEC) nanocomposite membranes were prepared via synergistic ionic complexation between graphene oxide/carbon nanotubes nanofillers (GO/CNT) and oppositely charged polyelectrolytes of sodium carboxymethyl cellulose (CMC) and poly(2-methacryloyloxy ethyl trimethylammonium chloride) (PDMC). Ultraviolet-visible, Raman spectroscopy and microscopies results demonstrated that the combination of one-dimensional CNTs and two-dimensional GO nanosheets lead to an integrated three-dimensional network through π-π interaction with GO distributed parallel to the surface of PEC membranes. Besides, CNTs and GO nanosheets are tightly encapsulated by PEC matrix through electrostatic interactions. The tensile strength of PEC/GO-CNT nanocomposite membrane containing 3wt% GO-CNT (1:1, w/w) was 155.4MPa, showing 2.3 and 1.6 times as high as that of PEC/CNT and PEC/GO membranes, respectively. Moreover, PEC/GO-CNT membranes showed improved separation performance and operation stability with introduction of the three-dimensional network constructed by GO and CNT.

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Computational and Split-Hopkinson Pressure-Bar studies on the effect of the jacket during penetration of an AK47 bullet into ceramic armour

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): LB Brown, PJ Hazell, IG Crouch, JP Escobedo, AD Brown
In this paper we probe the effect of a bullet's jacket on its ability to enhance penetration of a bullet core into a ceramic-faced target. This is achieved through computational modelling using ANSYS AUTODYN® and by Split-Hopkinson Pressure-Bar compression testing of a core, with and without a jacket. The focus of this work was on an AK47 mild-steel-cored (MSC) bullet. The objective of this work was to investigate the role of the jacket in the penetration process and to better understand if there is any protective benefit of stripping a bullet's jacket prior to making contact with ceramic armour. Further, new Johnson-Cook parameters for the AK47 steel core are presented.

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Thermal stability of the lightweight 2099 Al-Cu-Li alloy: Tensile tests and microstructural investigations after overaging

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): E. Balducci, L. Ceschini, S. Messieri, S. Wenner, R. Holmestad
The thermal stability of the lightweight, T83 heat treated 2099 Al-Cu-Li alloy was assessed in the temperature range 200–305°C, through both hardness and tensile tests after overaging. After prolonged thermal exposure, the alloy exhibited a better performance compared to aluminium alloys specifically developed for high temperature applications, with the advantage of a considerable lower density. The tensile behaviour was modelled through Hollomon's equation as a function of residual hardness. The changes in the alloy performance were explained through both SEM and STEM investigations. Microstructural analyses gave evidence of Ostwald ripening, while fractographic analyses revealed a transition from an intergranular to a ductile fracture mechanism in the overaged alloy. STEM investigations highlighted the superior thermal stability of the T1 phase compared to ϑ and S strengthening phases, which dissolved during overaging at 245°C. The study underlines the need to enhance the formation of T1 precipitates when high temperature strength is required. The results of the present study suggest that the 2099 alloy is a very promising candidate for automotive engine components, which are extremely demanding in terms of both thermal resistance and lightweight.

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Enhancement of oxidation resistance of CoSb3 thermoelectric material by glass coating

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): K. Zawadzka, E. Godlewska, K. Mars, M. Nocun, A. Kryshtal, A. Czyrska-Filemonowicz
Materials based on CoSb3 are ranked among thermoelectrics with the highest conversion rate, however in service they tend to rapidly lose the useful properties as a result of oxidation or sublimation. Glass coatings were designed in this work to protect CoSb3 against degradation in air at elevated temperatures. The coatings were based on borosilicate glass with a high content of titania. Their chemical composition was tailored to match the coefficient of thermal expansion (CTE) of the substrate (9.2·10−6K−1) and to secure thermal stability and low softening point of glass. The coatings deposited by a simple dipping technique were fired in the temperature range 700–740°C. Evaluation of these coatings was based on accelerated oxidation tests at 600°C for 20h. The micro- and nanostructure of the CoSb3/glass coating interface were examined by means of advanced electron microscopy. The coating appeared to have good adherence and to effectively protect the thermoelectric substrate against antimony loss and oxidation up to 600°C.

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Green electrospun Manuka honey/silk fibroin fibrous matrices as potential wound dressing

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Xingxing Yang, Linpeng Fan, Linlin Ma, Yunyi Wang, Si Lin, Fan Yu, Xiaohan Pan, Gejie Luo, Dongdong Zhang, Hongsheng Wang
Wound dressing plays an irreplaceable role in preventing infection and accelerating healing of wounds, especially the chronic non-healing wounds. Recently, the electrospun silk fibroin (SF) fibrous matrices is regarded as an ideal candidate for wound healing in virtue of its excellent skin affinity and good permeability for air and water. Manuka honey (MH) has demonstrated its unique properties in wound healing, including anti-inflammatory and anti-bacterial function as well as promoting tissue growth and reducing pain of patients. Here we report the feasibility of developing MH/SF composite fibrous matrices as antimicrobial wound dressing. SF fibrous matrices loading different amount of MH were manufactured by green electrospinning. The FTIR spectra indicated that MH was successfully loaded into the SF fibers. The composite fibers show smooth morphology and their diameter increases with MH content increased. Interestingly, the incorporation of MH significantly improved the antimicrobial activity of SF fibrous matrices, without negative effect on the excellent biocompatibility of SF. Moreover, the MH/SF composite fibrous matrices showed good performance on improving wound healing according to the data of animal experiment. Our findings suggest as-prepared natural green composite matrices combining the merits of both SF and MH could be a promising candidate for wound dressing.

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Fibrous CaF2:Yb,Er@SiO2-PAA ‘tumor patch’ with NIR-triggered and trackable DOX release

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Zhen Xia, Yike Fu, Tongxu Gu, Yangyang Li, Heng Liu, Zhaohui Ren, Xiang Li, Gaorong Han
Smart localized drug delivery systems (LDDSs), with stimuli-responsive properties, offer tremendous opportunity for personalized cancer chemotherapy. In our work, an implantable 'tumor patch', consisting of upconversion (UC) photoluminescent CaF2:Yb,Er nanoparticles embedded within silica nanofibers (CaF2:Yb,Er@SiO2), was designed and synthesized for doxorubicin (DOX) delivery. DOX loading capacity of the fiber mesh was remarkably enhanced with assist of polyacrylic acid (PAA) functionalization. PAA modified CaF2:Yb,Er@SiO2 nanofibers presented highly corresponding optical response to DOX release kinetics. Accelerated drug release in acidic condition induced more rapid increase in the spectral intensity ratio of green to red emission (I550/I660), and vice versa. More importantly, under the irradiation of NIR (808nm) laser, DOX release kinetics and consequently the in-vitro anti-cancer efficacy were enhanced. This study has thus offered another new implantable LDDS with NIR-triggered and monitored DOX delivery for personalized protocols in tumor chemotherapy.

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Epidermolytic Ichthyosis Sine Epidermolysis.

Epidermolytic ichthyosis (EI) is a rare disorder of cornification caused by mutations in KRT1 and KRT10, encoding two suprabasal epidermal keratins. Because of the variable clinical features and severity of the disease, histopathology is often required to correctly direct the molecular analysis. EI is characterized by hyperkeratosis and vacuolar degeneration of the upper epidermis, also known as epidermolytic hyperkeratosis, hence the name of the disease. In the current report, the authors describe members of 2 families presenting with clinical features consistent with EI. The patients were shown to carry classical mutations in KRT1 or KRT10, but did not display epidermolytic changes on histology. These observations underscore the need to remain aware of the limitations of pathological features when considering a diagnosis of EI. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Tissue engineering the mechanosensory circuit of the stretch reflex arc with human stem cells: Sensory neuron innervation of intrafusal muscle fibers

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Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Xiufang Guo, Alisha Colon, Nesar Akanda, Severo Spradling, Maria Stancescu, Candace Martin, James J. Hickman
Muscle spindles are sensory organs embedded in the belly of skeletal muscles that serve as mechanoreceptors detecting static and dynamic information about muscle length and stretch. Through their connection with proprioceptive sensory neurons, sensation of axial body position and muscle movement are transmitted to the central nervous system. Impairment of this sensory circuit causes motor deficits and has been linked to a wide range of diseases. To date, no defined human-based in vitro model of the proprioceptive sensory circuit has been developed. The goal of this study was to develop a human-based in vitro muscle sensory circuit utilizing human stem cells. A serum-free medium was developed to drive the induction of intrafusal fibers from human satellite cells by actuation of a neuregulin signaling pathway. Both bag and chain intrafusal fibers were generated and subsequently validated by phase microscopy and immunocytochemistry. When co-cultured with proprioceptive sensory neurons derived from human neuroprogenitors, mechanosensory nerve terminal structural features with intrafusal fibers were demonstrated. Most importantly, patch-clamp electrophysiological analysis of the intrafusal fibers indicated repetitive firing of human intrafusal fibers, which has not been observed in human extrafusal fibers.



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miRNases: Novel peptide-oligonucleotide bioconjugates that silence miR-21 in lymphosarcoma cells

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Olga A. Patutina, Elena V. Bichenkova, Svetlana K. Miroshnichenko, Nadezhda L. Mironova, Linda T. Trivoluzzi, Kepa K. Burusco, Richard A. Bryce, Valentin V. Vlassov, Marina A. Zenkova
MicroRNAs (miRNAs) are active regulators in malignant growth and constitute potential targets for anticancer therapy. Consequently, considerable effort has focused on identifying effective ways to modulate aberrant miRNA expression. Here we introduce and assess a novel type of chemically engineered biomaterial capable of cleaving specific miRNA sequences, i.e. miRNA-specific artificial ribonucleases (hereafter 'miRNase'). The miRNase template presented here consists of the catalytic peptide Acetyl-[(LeuArg)2Gly]2 covalently attached to a miRNA-targeting oligonucleotide, which can be linear or hairpin. The peptide C-terminus is conjugated to an aminohexyl linker located at either the 3′- or 5′-end of the oligonucleotide. The cleavage efficacy, structural aspects of cleavage and biological relevance of a set of these designed miRNases was assayed with respect to highly oncogenic miR-21. Several miRNases demonstrated effective site-selective cleavage of miR-21 exclusively at G-X bonds. One of the most efficient miRNase was shown to specifically inhibit miR-21 in lymphosarcoma cells and lead to a reduction in their proliferative activity. This report provides the first experimental evidence that metallo-independent peptide-oligonucleotide chemical ribonucleases are able to effectively and selectively down-regulate oncogenic miRNA in tumour cells, thus suggesting their potential in development of novel therapeutics aimed at overcoming overexpression of disease-related miRNAs.

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Policy Priorities for 2017—and Beyond

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2
Author(s): Lucille Beseler




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Assessing the Reach of MyPlate using National Health and Nutrition Examination Survey Data

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2
Author(s): Angie Tagtow, Ramkripa Raghavan




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Table of Contents

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2





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Position and Practice Paper Update for 2017

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2
Author(s): The Academy of Nutrition and Dietetics




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2016 Journal Reader Survey Results

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2
Author(s): Dan Carroll




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February 2017 People & Events

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2





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Erratum

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2





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Erratum

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2





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Erratum

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2





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THE HUDDLESON AWARD 2016: Recognize research excellence—Nominate an article published in the 2016 Journal for the Huddleson

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2





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February 2017 New in Review

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2





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February 2017 Classified Advertisements

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2





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What Are Endoscopic Bariatric Therapies?

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Publication date: February 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 2
Author(s): Wendy Marcason




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A Novel Reconstructive Procedure for the Divided Nevus of the Eyelids Using a Tissue Expander

imageSummary: Expanded local flaps and skin grafts (expanded/nonexpanded) are a common approach for reconstructing medium (1.5–20 cm) and large (>20 cm) divided nevi of the eyelids. However, this approach does not often provide a satisfactory cosmetic result, particularly in Asian patients, because of different skin types. We recently devised a new surgical procedure using an extended cheek flap and tissue expander for the medium-sized divided nevus of the eyelids. The upper and lower eyelids are concurrently reconstructed by divided flaps. This method is an effective treatment method for the medium-sized divided nevus of the eyelids and can be applied in total reconstruction of the eyelids in the future. This article presents our novel technique and is illustrated using a brief case report.

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An Easy Method for Drainage of Fluid in Cases of Continuous Irrigation of the Hand

imageSummary: Description of a novel method to perform continuous irrigation for flexor tenosynovitis in a way that is comfortable for the patient and convenient for nursing staff by placing the hand in the suction pouch of a lithotomy style drape attached to wall suction.

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Metacognitive Unawareness of the Errorful Generation Benefit and Its Effects on Self-Regulated Learning.

Author: Yang, Chunliang; Potts, Rosalind; Shanks, David R.
DOI: 10.1037/xlm0000363
Publication Date: POST AUTHOR CORRECTIONS, 23 January 2017


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Short-Term Upper Limb Immobilization Affects Action-Word Understanding.

Author: Bidet-Ildei, Christel; Meugnot, Aurore; Beauprez, Sophie-Anne; Gimenes, Manuel; Toussaint, Lucette
DOI: 10.1037/xlm0000373
Publication Date: POST AUTHOR CORRECTIONS, 23 January 2017


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Reduced Interference From Memory Testing: A Postretrieval Monitoring Account.

Author: Pierce, Benton H.; Gallo, David A.; McCain, Jason L.
DOI: 10.1037/xlm0000377
Publication Date: POST AUTHOR CORRECTIONS, 23 January 2017


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A Task-Dependent Causal Role for Low-Level Visual Processes in Spoken Word Comprehension.

Author: Ostarek, Markus; Huettig, Falk
DOI: 10.1037/xlm0000375
Publication Date: POST AUTHOR CORRECTIONS, 23 January 2017


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Angles No Longer Weigh In: The Effect of Geometric Cue Directness on Reorientation.

Author: Huang, Zhenzhen; Hu, Qingfen; Shao, Yi
DOI: 10.1037/xlm0000361
Publication Date: POST AUTHOR CORRECTIONS, 23 January 2017


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Alternating-Script Priming in Japanese: Are Katakana and Hiragana Characters Interchangeable?.

Author: Perea, Manuel; Nakayama, Mariko; Lupker, Stephen J.
DOI: 10.1037/xlm0000365
Publication Date: POST AUTHOR CORRECTIONS, 23 January 2017


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Myoblast replication is reduced in the IUGR fetus despite maintained proliferative capacity in vitro

Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass and insulin resistance, suggesting muscle growth may be restricted by molecular events that occur during fetal development. To explore the basis of restricted fetal muscle growth, we used a sheep model of progressive placental insufficiency-induced IUGR to assess myoblast proliferation within intact skeletal muscle in vivo and isolated myoblasts stimulated with insulin in vitro. Gastrocnemius and soleus muscle weights were reduced by 25% in IUGR fetuses compared to those in controls (CON). The ratio of PAX7+ nuclei (a marker of myoblasts) to total nuclei was maintained in IUGR muscle compared to CON, but the fraction of PAX7+ myoblasts that also expressed Ki-67 (a marker of cellular proliferation) was reduced by 23%. Despite reduced proliferation in vivo, fetal myoblasts isolated from IUGR biceps femoris and cultured in enriched media in vitro responded robustly to insulin in a dose- and time-dependent manner to increase proliferation. Similarly, insulin stimulation of IUGR myoblasts upregulated key cell cycle genes and DNA replication. There were no differences in the expression of myogenic regulatory transcription factors that drive commitment to muscle differentiation between CON and IUGR groups. These results demonstrate that the molecular machinery necessary for transcriptional control of proliferation remains intact in IUGR fetal myoblasts, indicating that in vivo factors such as reduced insulin and IGF1, hypoxia and/or elevated counter-regulatory hormones may be inhibiting muscle growth in IUGR fetuses.



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Cancer cachexia differentially regulates visceral adipose tissue turnover

Cancer cachexia (CC) is a progressive metabolic syndrome that is marked by severe body weight loss. Metabolic disarrangement of fat tissues is a very early event in CC, followed by adipose tissue (AT) atrophy and remodelling. However, there is little information regarding the possible involvement of cellular turnover in this process. Thus, in this study, we evaluated the effect of CC on AT turnover and fibrosis of mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue depots as possible factors that contribute to AT atrophy. CC was induced by a subcutaneous injection of Walker tumour cells (2 x 107) in Wistar rats, and control animals received only saline. The experimental rats were randomly divided into four experimental groups: 0 days, 4 days, 7 days and 14 days after injection. AT turnover was analysed according to the Pref1/Adiponectin ratio of gene expression from the stromal vascular fraction and pro-apoptotic CASPASE3 and CASPASE9 from MEAT and RPAT. Fibrosis was verified according to the total collagen levels and expression of extracellular matrix genes. AT turnover was verified by measurements of lipolytic protein expression. We found that the Pref1/Adiponectin ratio was decreased in RPAT (81.85%, P < 0.05) with no changes in MEAT compared with the respective controls. CASPASE3 and CASPASE9 were activated on day 14 only in RPAT. Collagen was increased on day 7 in RPAT (127%) and MEAT (4.3-fold). The Collagen1A1, Collagen3A1, Mmp2 and Mmp9 mRNA levels were upregulated only in MEAT in CC. Lipid turnover was verified in RPAT and was not modified in CC. We concluded that the results suggest that CC affects RPAT cellular turnover, which may be determinant for RPAT atrophy.



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Novel 6-Methoxycarbonyl Indolinones Bearing a Pyrrole Mannich Base Moiety as Angiokinase Inhibitors

Publication date: Available online 25 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Mingze Qin, Shuang Yan, Lei Wang, Haotian Zhang, Ye Tian, Yanfang Zhao, Ping Gong
Inhibition of tumor angiogenesis through simultaneously disturbing vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) mediated signaling pathways is a well-established approach in intervention of tumor. A series of 6-methoxycarbonyl indolinones bearing a pyrrole Mannich base moiety were synthesized and evaluated as potent angiokinase inhibitors. Compound 8a demonstrated favorable enzymatic activity against all subtypes of VEGFR and PDGFR. Also, it potently suppressed proliferation of HT-29 cells by inducing apoptosis. Compound 8a has emerged as a promising lead compound for development of angiokinase inhibitors targeting VEGFR and PDGFR.

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Synthesis and in vitro evaluation of 5-substituted benzovesamicol analogs containing N-substituted amides as potential positron emission tomography tracers for the Vesicular Acetylcholine Transporter

Publication date: Available online 25 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Sara Roslin, Maria De Rosa, Winnie Deuther-Conrad, Jonas Eriksson, Luke R. Odell, Gunnar Antoni, Peter Brust, Mats Larhed
Herein, new ligands for the vesicular acetylcholine transporter (VAChT), based on a benzovesamicol scaffold, are presented. VAChT is acknowledged as a marker for cholinergic neurons and a positron emission tomography tracer for VAChT could serve as a tool for quantitative analysis of cholinergic neuronal density. With an easily accessible triflate precursor, aminocarbonylations were utilized to evaluate the chemical space around the C5 position on the tetrahydronaphthol ring. Synthesized ligands were evaluated for their affinity and selectivity for VAChT. Small, preferably aromatic, N-substituents proved to be more potent than larger substituents. Of the fifteen compounds synthesized, benzyl derivatives (±)-7i and (±)-7l had the highest affinities for VAChT. Compound (±)-7i was chosen to investigate the importance of stereochemistry for binding to VAChT and selectivity towards the σ1 and σ2 receptor. Enantiomeric resolution gave (+)-7i and (-)-7i, and the eutomer showed seven times better affinity. Although racemate (±)-7i was initially promising, the affinity of (-)-7i for VAChT was not better than 56.7 nM which precludes further preclinical evaluation. However, the nanomolar binding together with the ready synthesis of [11C]-(±)-7i shows that (-)-7i can serve as a scaffold for future optimizations to provide improved 11C-labelled VAChT PET tracers.

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Discovery and Structure Activity Relationship of the First Potent Cryptosporidium FIKK Kinase Inhibitor

Publication date: Available online 24 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Khan T. Osman, Juntao Ye, Zhihao Shi, Christina Toker, Diogo Lovato, Rajiv S. Jumani, William Zuercher, Christopher D. Huston, Aled M Edwards, Mark Lautens, Vijayaratnam Santhakumar, Raymond Hui
FIKKs are parasite-specific protein kinases with distinctive sequence motifs and their biological roles have not been completely elucidated. Here, we report the first potent Cryptosporidium FIKK (CpFIKK) inhibitor. We identified 4b as a potent (IC50=0.2 nM) inhibitor of CpFIKK catalytic activity. In addition, we identified both CpCDPK1 selective as well as dually acting CpFIKK-CDPK1 inhibitors from the same structural class of compounds. We evaluated these CpFIKK inhibitors for inhibition of parasite growth in vitro. The observed effects on parasite growth did not correlate with CpFIKK inhibition, suggesting that CpFIKK may not be involved in parasite growth.

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Carbonic anhydrases activation with 3-amino-1H-1,2,4-triazole-1-carboxamides: Discovery of subnanomolar isoform II activators

Publication date: Available online 24 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yann Le Duc, Erol Licsandru, Daniela Vullo, Mihail Barboiu, Claudiu T. Supuran
A series of ureas was prepared by reacting mono- or di- isocyanates with 3-amino-1H-1,2,4-triazole derivatives. The new carboxamides were investigated as activators of two human (h) carbonic anhydrases (CAs, EC 4.2.1.1), the physiologically relevant isoforms hCA I and II, considering the fact that they have structural resemblance to histamine, a well-known CA activator. Highly effective activators were detected in the series, with potency in the low nanomolar and subnanomolar range, depending on the substitution pattern at the 1,2,4-triazole ring and the nature of the linker between the two heterocyclic rings, in the case of the diureas. The most effective hCA II activator (KA of 0.05 nM) ever reported has been evidenced in this study. Although CA activators do not have pharmacological applications for the moment, in animal models it has been shown that they enhance cognition, making them interesting for conditions in which CA activity is diminished, such as aging or Alzheimeŕs disease.

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Conjugates of phosphorylated zalcitabine and lamivudine with SiO2 nanoparticles: synthesis by CuAAC click chemistry and preliminary assessment of anti-HIV and antiproliferative activity

Publication date: Available online 25 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Svetlana V. Vasilyeva, Alexander A. Shtil, Albina S. Petrova, Sergei M. Balakhnin, Polina Y. Achigecheva, Dmitry A. Stetsenko, Vladimir N. Silnikov
Conjugates of phosphorylated dideoxynucleoside antiviral drugs dideoxycytidine (zalcitabine) and lamivudine with SiO2 nanoparticles were obtained via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry between a nucleoside triphosphate containing an alkynyl group at the γ-phosphate or azidothymidine triphosphate and SiO2 nanoparticles containing alkyl azide or alkynyl groups, respectively. 4-(Prop-2-yn-1-yloxy)butylamino group has been attached to the γ-phosphate group of dideoxycytidine (zalcitabine) and lamivudine 5'-triphosphates via the phosphoramidate linkage. New compounds were shown to be potent killers of human colon carcinoma cells. Anti-HIV activity of the conjugates was demonstrated as well. The conjugates of phosphorylated lamivudine and dideoxycytidine (zalcitabine) showed higher potency than the parent nucleosides. The conjugate of phosphorylated azidothymidine was less active againstHIV-1 than the parent nucleoside probably because of the replacement of its 3'-azido group by 1,2,3-triazole ring. These results show an opportunity for using SiO2 nanoparticles as a transport for delivering phosphorylated nucleosides to cells in order to increase their efficiency as antiviral and anticancer drugs.

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