Primary and acquired resistance to PD-1/PD-L1 blockade in cancer treatment

Publication date: May 2017
Source:International Immunopharmacology, Volume 46
Author(s): Qiaohong Wang, Xia Wu
PD-1/PD-L1 blockade appears to be a very promising immunotherapy with significant clinical benefits and durable responses in multiple tumor types. However, the effectual clinical benefits of PD-1/PD-L1 blockade are hampered by a high rate of primary resistance, where patients do not respond to PD-1/PD-L1 blockade initially. And more distressingly, most patients eventually develop acquired resistance after an initial response to PD-1/PD-L1 blockade. The mechanisms underlying primary and acquired resistance to PD-1/PD-L1 blockade have remained ambiguous. This review documents in detail the current understanding of the mechanisms through which resistance to anti-PD1/PD-L1 therapy occurs. The mechanisms underlying primary resistance to PD-1/PD-L1 blockade contain several immunoregulatory factors affecting tumor-specific immune responses within the immune microenvironment, co-enrichment of a group of 26 transcriptomic signatures (named innate anti-PD-1 resistance (IPRES) signatures) and cancer-cell-autonomous cues. The mechanism attributable to acquired resistance harbors evolution of neoantigen landscape, mutations of JAK and β-2-microglobulin, and epigenetic stability of exhausted T cells. At last, the promising therapeutic strategies to sensitize the resistant patients are also briefly discussed.



http://ift.tt/2n3ezFQ

An Unusual Cause of First Time Seizure in an Adult

Publication date: Available online 18 March 2017
Source:The Journal of Emergency Medicine
Author(s): Andrew Eyre, C. Eduardo Corrales, David Silvestri, Emily S. Miller, Kriti Bhatia




http://ift.tt/2mIPgpQ

Alpha cells, the main source of IL-1β in human pancreas

Publication date: Available online 18 March 2017
Source:Journal of Autoimmunity
Author(s): Florence Anquetil, Somayeh Sabouri, Charles Thivolet, Teresa Rodriguez-Calvo, Jose Zapardiel-Gonzalo, Natalie Amirian, Darius Schneider, Ericka Castillo, Yasaman Lajevardi, Matthias G. von Herrath
Interleukin-1β (IL-1β) is known to trigger beta cell dysfunction in vitro and could potentially play a role during the pathogenesis of type 1 diabetes and type 2 diabetes. However, several clinical trials attempting to block IL-1β function have had minimal success. We therefore re-investigated local expression of IL-1β in human diabetic and non-diabetic pancreata.We obtained pancreatic tissue sections from the Network for Pancreatic Organ Donors with Diabetes (nPOD) including non-diabetic (n = 9), non-diabetic auto-antibody positive (AAb+, n = 5), type 1 diabetes (n = 6), and type 2 diabetes (n = 6) donors. Islets were systematically investigated for the presence of IL-1β mRNA by in situ hybridization and IL-1β protein by indirect immunofluorescence. We found that intra-islet IL-1β was produced at comparable level in both non-diabetic and diabetic donors. Interestingly, the main source for IL-1β was alpha cells but not beta cells.Our findings call into question the role of IL-1β in the diabetic pancreas as it has been proposed in previous literature. Additionally, our results regarding the localization of IL-1β should lead to further investigation into the role of IL-1β in the physiology of pancreatic alpha cells.



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DNase-active TREX1 frame-shift mutants induce serologic autoimmunity in mice

Publication date: Available online 18 March 2017
Source:Journal of Autoimmunity
Author(s): Tomomi Sakai, Takuya Miyazaki, Dong-Mi Shin, Yong-Soo Kim, Chen-Feng Qi, Robert Fariss, Jeeva Munasinghe, Hongsheng Wang, Alexander L. Kovalchuk, Parul H. Kothari, Charles S. Fermaintt, John P. Atkinson, Fred W. Perrino, Nan Yan, Herbert C. Morse
TREX1/DNASE III, the most abundant 3′-5′ DNA exonuclease in mammalian cells, is tail-anchored on the endoplasmic reticulum (ER). Mutations at the N-terminus affecting TREX1 DNase activity are associated with autoimmune and inflammatory conditions such as Aicardi-Goutières syndrome (AGS). Mutations in the C-terminus of TREX1 cause loss of localization to the ER and dysregulation of oligosacchryltransferase (OST) activity, and are associated with retinal vasculopathy with cerebral leukodystrophy (RVCL) and in some cases with systemic lupus erythematosus (SLE). Here we investigate mice with conditional expression of the most common RVCL mutation, V235fs, and another mouse expressing a conditional C-terminal mutation, D272fs, associated with a case of human SLE. Mice homozygous for either mutant allele express the encoded human TREX1 truncations without endogenous mouse TREX1, and both remain DNase active in tissues. The two mouse strains are similar phenotypically without major signs of retinal, cerebral or renal disease but exhibit striking elevations of autoantibodies in the serum. The broad range of autoantibodies is primarily against non-nuclear antigens, in sharp contrast to the predominantly DNA-related autoantibodies produced by a TREX1-D18N mouse that specifically lacks DNase activity. We also found that treatment with an OST inhibitor, aclacinomycin, rapidly suppressed autoantibody production in the TREX1 frame-shift mutant mice. Together, our study presents two new mouse models based on TREX1 frame-shift mutations with a unique set of serologic autoimmune-like phenotypes.



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T cell receptor assessment in autoimmune disease requires access to the most adjacent immunologically active organ

Publication date: Available online 18 March 2017
Source:Journal of Autoimmunity
Author(s): Bergithe E. Oftedal, Brita Ardesjö Lundgren, David Hamm, Poh-Yi Gan, Stephen R. Holdsworth, Christopher N. Hahn, Andreas W. Schreiber, Hamish S. Scott
Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs. Here, we have utilized next generation sequencing technology to investigate the T cell receptor repertoire in autoimmunity induced by immunization of mice with a self-antigen, myeloperoxidase. By investigating the T cell receptor repertoire in peripheral blood, spleen and lumbar lymph nodes from naïve and immunized Aire −/− mice and wild type littermates, changes in the usage of V and J genes were evident. Our results identify TCR clonotypes which could be potential targets for immune therapy. Also, Aire −/− autoimmunity is driven by a variety of autoantigens where the autoimmune response is highly polyclonal, and access to the most adjacent immunologically active tissue is required to identify T cell receptor sequences that are potentially unique to the antigen in Aire−/− immunized mice.



http://ift.tt/2mgJOyh

Regulation of type I interferon signaling in immunity and inflammation: A comprehensive review

Publication date: Available online 19 March 2017
Source:Journal of Autoimmunity
Author(s): Kun Chen, Juan Liu, Xuetao Cao
Type I interferons (IFNs) play essential roles in establishing and modulating host defense against microbial infection via induction of IFN-stimulated genes (ISGs) through Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling pathway. However, dysregulation of IFNs production and function could also mediate immune pathogenesis such as inflammatory autoimmune diseases and infectious diseases via aberrantly activating inflammatory responses or improperly suppressing microbial controls. Thus, IFN responses need to be tightly regulated to achieve protective immunity against microbial infection while avoiding harmful toxicity caused by improper or prolonged IFN signaling. Multiple levels of cellular and molecular events act in a cooperated manner to regulate IFN responses, in especial, post-translational modification (PTMs) of signaling molecules and epigenetic modification of gene expression programs are two important mechanisms for regulation of IFN signaling and thus critical for orchestrating IFN-mediated host immune response to the complex pathogenic or environmental stimuli. Conventional PTMs such as phosphorylation and polyubiquitylation, as well as numerous other PTMs including acetylation, ISGylation, SUMOylation and methylation have been shown to potently modulate type I IFN signaling transduction via targeting distinct signaling steps or components. Moreover, epigenetic mechanisms, such as histone modification, DNA methylation, non-coding RNAs play critical roles in regulating chromatin structure and function, leading to flexible and dynamic gene expression patterns downstream type I IFN signaling. Herein, we summarize the recent advances in the PTMs and epigenetic mechanisms in regulation of type I IFN signaling and responses. The involvement of dysregulated IFN signaling in inflammatory and autoimmune diseases are also discussed.



http://ift.tt/2nRDr0H

Biosorption of the strontium ion by irradiated Saccharomyces cerevisiae under culture conditions

Publication date: June 2017
Source:Journal of Environmental Radioactivity, Volume 172
Author(s): Liang Qiu, Jundong Feng, Yaodong Dai, Shuquan Chang
As a new-emerging method for strontium disposal, biosorption has shown advantages such as high sorption capacity; low cost. In this study, we investigated the potential of Saccharomyces cerevisiae (S. cerevisiae) in strontium disposal under culture conditions and the effects of irradiation on their biosorption capabilities. We found that S. cerevisiae can survive irradiation and grow. Pre-exposure to irradiation rendered S. cerevisiae resistant to further irradiation. Surprisingly, the pre-exposure to irradiation can increase the biosorption capability of S. cerevisiae. We further investigated the factors that influenced the biosorption efficiency, which were (strongest to weakest): pH > strontium concentration > time > temperature. In our orthogonal experiment, the optimal conditions for strontium biosorption by irradiated S. cerevisiae were: pH 7, 150 mg L^-1 strontium at the temperature of 32 °C with 30 h. The equilibrium of strontium biosorption was analyzed by Langmuir and Freundlich models, from which the formal model is found to provide a better fit for the experimental results. The kinetics of strontium biosorption by living irradiated S. cerevisiae was found to be comprised of three phases: dramatically increased during 0–9 h, decreased during 12–24 h, and increased during 30–50 h. These results provide a systematic understanding of the biosorption capabilities of irradiated S. cerevisiae, which can contribute to the development of remediating nuclear waste water.



http://ift.tt/2mInDgU

Estimating doses from Aboriginal bush foods post-remediation of a uranium mine

Publication date: June 2017
Source:Journal of Environmental Radioactivity, Volume 172
Author(s): Che Doering, Andreas Bollhöfer, Peter Medley
This paper presents a calculator to facilitate assessments of ingestion doses from Aboriginal bush foods. The calculator combines information on traditional diet and land use with radionuclide concentration ratios and ingestion dose coefficients to estimate doses. The calculator was applied to the planned remediation of Ranger uranium mine to derive a set of scaling factors between radionuclide activity concentrations in environmental media and ingestion dose from bush foods. The scaling factors can be used to estimate doses from bush foods once the post-remediation radiological conditions of the mine and surrounding environment are known.



http://ift.tt/2n346ua

Frontiers of on-surface synthesis: From principles to applications

Publication date: Available online 18 March 2017
Source:Nano Today
Author(s): Qian Shen, Hong-Ying Gao, Harald Fuchs
On-surface synthesis is the bottom-up construction of covalent bonds between molecular building blocks, which has been greatly developed during the past decade. Dozens of reactions have been successfully realized and scrutinized on various surfaces with the help of surface science techniques combined with theoretical calculations. Functional nanoarchitectures such as one-dimensional nanowires, nanoribbons and two-dimensional nanonetworks have been constructed on surfaces and explored in several potential applications. In fact, the generation of multilevel nanostructures will play a key role in future soft nanoscience and technologies due to their emergent properties ranging far beyond those of the individual molecules building them up. In this review, we discuss selected examples of important processes in on-surface synthesis developed in recent years and summarize them under the following aspects: (1) on-surface reactions in a category of different carbon types; (2) techniques applied in on-surface synthesis; (3) on-surface synthesized functional nanostructures; and (4) potential applications of on-surface synthesized nano-materials. The review concludes with a perspective of the future development of on-surface synthesis.

Graphical abstract

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Histidine deficiency has a negative effect on lactational performance of dairy cows

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): F. Giallongo, M.T. Harper, J. Oh, C. Parys, I. Shinzato, A.N. Hristov
A 10-wk randomized complete block design experiment with 24 Holstein cows was conducted to investigate the long-term effects of feeding a His-deficient diet on lactational performance of dairy cows. Cows were blocked by days in milk, milk yield, and parity, and randomly assigned to 1 of the following 2 treatments: (1) His-adequate diet [HAD; providing +166 g/d over metabolizable protein (MP) requirements, according to the National Research Council (2001) and digestible His (dHis) supply of 68 g/d, or 2.5% of MP requirements] and (2) His-deficient diet (HDD; +37 g/d over MP requirements and dHis supply of 49 g/d, or 1.9% of MP requirements). Both HAD and HDD were supplemented with rumen-protected (RP) Met and Lys supplying digestible Met and digestible Lys at 2.4 and 2.4% and 7.2 and 7.1% of MP requirements, respectively. At the end of the 10-wk experiment, HDD was supplemented with RPHis (HDD+RPHis; total dHis supply of 61 g/d, or 2.4% of MP requirements) for an additional 9 d. Dry matter intake (DMI; 25.4 and 27.1 kg/d, standard error of the mean = 0.41), yields of milk (37.6 and 40.5 kg/d, standard error of the mean = 0.62), protein and lactose, energy-corrected milk, and milk and plasma urea-N were decreased by HDD compared with HAD. Feed and energy-corrected milk feed efficiencies, milk fat, protein and lactose concentrations, body weight, and body condition score of the cows were not affected by treatment. Apparent total-tract digestibility of dry and organic matter, crude protein, and neutral detergent fiber, and excretion of urinary N and urea-N were decreased by HDD compared with HAD. Concentration of plasma leptin tended to be decreased for HDD compared with HAD. Plasma concentrations of EAA (His, Leu, Lys, Val) and carnosine decreased and total EAA tended to be decreased in cows fed HDD compared with HAD. Muscle concentrations of free His, Leu, and Val decreased and Gly and β-alanine tended to be increased by HDD compared with HAD. Cows fed HDD had a lower blood hemoglobin concentration than cows fed HAD. At the end of the 10-wk study, the 9-d supplementation of HDD with RPHis (i.e., HDD+RPHis) increased DMI and plasma His, and tended to increase energy-corrected milk yield and plasma carnosine, compared with HDD. In conclusion, feeding a diet deficient in dHis supplying adequate MP, digestible Met, and digestible Lys affected negatively lactational performance of dairy cows. These results confirm our previous findings that low dietary His supply can impair DMI, yields of milk and milk protein, and blood hemoglobin in dairy cows.



http://ift.tt/2mIwsHs

Evaluation of genetic components in traits related to superovulation, in vitro fertilization, and embryo transfer in Holstein cattle

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): K.L. Parker Gaddis, S. Dikmen, D.J. Null, J.B. Cole, P.J. Hansen
The objectives of this study were to estimate variance components and identify regions of the genome associated with traits related to embryo transfer in Holsteins. Reproductive technologies are used in the dairy industry to increase the reproductive rate of superior females. A drawback of these methods remains the variability of animal responses to the procedures. If some variability can be explained genetically, selection can be used to improve animal response. Data collected from a Holstein dairy farm in Florida from 2008 to 2015 included 926 superovulation records (number of structures recovered and number of good embryos), 628 in vitro fertilization records (number of oocytes collected, number of cleaved embryos, number of high- and low-quality embryos, and number of transferrable embryos), and 12,089 embryo transfer records (pregnancy success). Two methods of transformation (logarithmic and Anscombe) were applied to count variables and results were compared. Univariate animal models were fitted for each trait with the exception of pregnancy success after embryo transfer. Due to the binary nature of the latter trait, a threshold liability model was fitted that accounted for the genetic effect of both the recipient and the embryo. Both transformation methods produced similar results. Single-step genomic BLUP analyses were performed and SNP effects estimated for traits with a significant genetic component. Heritability of number of structures recovered and number of good embryos when log-transformed were 0.27 ± 0.08 and 0.15 ± 0.07, respectively. Heritability estimates from the in vitro fertilization data ranged from 0.01 ± 0.08 to 0.21 ± 0.15, but were not significantly different from zero. Recipient and embryo heritability (standard deviation) of pregnancy success after embryo transfer was 0.03 (0.01) and 0.02 (0.01), respectively. The 10-SNP window explaining the largest proportion of variance (0.37%) for total structures collected was located on chromosome 8 beginning at 55,663,248 bp. Similar regions were identified for number of good embryos, with the largest proportion of variance (0.43%) explained by a 10-SNP window on chromosome 14 beginning at 26,713,734 bp. Results indicate that there is a genetic component for some traits related to superovulation and that selection should be possible. Moreover, the genetic component for superovulation traits involves some genomic regions that are similar to those for other fertility traits currently evaluated.



http://ift.tt/2naaU9D

Invited review: Large-scale indirect measurements for enteric methane emissions in dairy cattle: A review of proxies and their potential for use in management and breeding decisions

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): E. Negussie, Y. de Haas, F. Dehareng, R.J. Dewhurst, J. Dijkstra, N. Gengler, D.P. Morgavi, H. Soyeurt, S. van Gastelen, T. Yan, F. Biscarini
Efforts to reduce the carbon footprint of milk production through selection and management of low-emitting cows require accurate and large-scale measurements of methane (CH4) emissions from individual cows. Several techniques have been developed to measure CH4 in a research setting but most are not suitable for large-scale recording on farm. Several groups have explored proxies (i.e., indicators or indirect traits) for CH4; ideally these should be accurate, inexpensive, and amenable to being recorded individually on a large scale. This review (1) systematically describes the biological basis of current potential CH4 proxies for dairy cattle; (2) assesses the accuracy and predictive power of single proxies and determines the added value of combining proxies; (3) provides a critical evaluation of the relative merit of the main proxies in terms of their simplicity, cost, accuracy, invasiveness, and throughput; and (4) discusses their suitability as selection traits. The proxies range from simple and low-cost measurements such as body weight and high-throughput milk mid-infrared spectroscopy (MIR) to more challenging measures such as rumen morphology, rumen metabolites, or microbiome profiling. Proxies based on rumen samples are generally poor to moderately accurate predictors of CH4, and are costly and difficult to measure routinely on-farm. Proxies related to body weight or milk yield and composition, on the other hand, are relatively simple, inexpensive, and high throughput, and are easier to implement in practice. In particular, milk MIR, along with covariates such as lactation stage, are a promising option for prediction of CH4 emission in dairy cows. No single proxy was found to accurately predict CH4, and combinations of 2 or more proxies are likely to be a better solution. Combining proxies can increase the accuracy of predictions by 15 to 35%, mainly because different proxies describe independent sources of variation in CH4 and one proxy can correct for shortcomings in the other(s). The most important applications of CH4 proxies are in dairy cattle management and breeding for lower environmental impact. When breeding for traits of lower environmental impact, single or multiple proxies can be used as indirect criteria for the breeding objective, but care should be taken to avoid unfavorable correlated responses. Finally, although combinations of proxies appear to provide the most accurate estimates of CH4, the greatest limitation today is the lack of robustness in their general applicability. Future efforts should therefore be directed toward developing combinations of proxies that are robust and applicable across diverse production systems and environments.



http://ift.tt/2mIGl83

Milk production and nutrient digestibility responses to increasing levels of stearic acid supplementation of dairy cows

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): J.P. Boerman, J. de Souza, A.L. Lock
The objective of our study was to evaluate the dose-response effects of a stearic acid (C18:0)-enriched supplement on nutrient digestibility, production responses, and the maximum amount of C18:0 that can be incorporated into the milk fat of dairy cows. Multiparous Holstein cows (n = 32; 145 ± 66 d in milk) with a wide range in milk yield (30 to 70 kg/d) were blocked by milk yield and assigned to replicated 4 × 4 Latin squares. Treatments were diets supplemented with a C18:0-enriched supplement (SA; 93% C18:0) at 0, 0.80, 1.50, or 2.30% of diet dry matter (DM). Periods were 21 d with the final 5 d used for data and sample collection. Dry matter intake increased linearly as SA supplementation increased. Supplementation of SA had no effect on the yield of milk or milk components. Due to the increase in DM intake, SA linearly reduced the ratio of energy-corrected milk to DM intake. Supplementation of SA did not affect body weight. Increasing SA reduced digestibility of 16-carbon, 18-carbon, and total fatty acids (FA), with the reduction in digestibility of 18-carbon FA being approximately 30 percentage units from the 0.0 to 2.30% SA supplemented diets. Supplementation of SA linearly increased concentrations of preformed milk fatty acids (FA) but did not affect the yield of preformed milk FA. Yields of C18:0 plus cis-9 C18:1 were increased by SA supplementation; however, the increase from 0 to 2.3% SA was only 16 g/d. The concentration and yield of de novo and 16-carbon milk FA were unaffected by SA supplementation. In conclusion, increasing doses of SA decreased FA digestibility and had little effect on production parameters. Although SA increased the yield of C18:0 and cis-9 C18:1 in milk fat, it had no overall effect on milk fat yield. The lack of production responses to a C18:0-enriched fat supplement was most likely associated with the marked decrease in FA digestibility.



http://ift.tt/2naiiBY

Genetic parameters for hoof health traits estimated with linear and threshold models using alternative cohorts

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): F. Malchiodi, A. Koeck, S. Mason, A.M. Christen, D.F. Kelton, F.S. Schenkel, F. Miglior
A national genetic evaluation program for hoof health could be achieved by using hoof lesion data collected directly by hoof trimmers. However, not all cows in the herds during the trimming period are always presented to the hoof trimmer. This preselection process may not be completely random, leading to erroneous estimations of the prevalence of hoof lesions in the herd and inaccuracies in the genetic evaluation. The main objective of this study was to estimate genetic parameters for individual hoof lesions in Canadian Holsteins by using an alternative cohort to consider all cows in the herd during the period of the hoof trimming sessions, including those that were not examined by the trimmer over the entire lactation. A second objective was to compare the estimated heritabilities and breeding values for resistance to hoof lesions obtained with threshold and linear models. Data were recorded by 23 hoof trimmers serving 521 herds located in Alberta, British Columbia, and Ontario. A total of 73,559 hoof-trimming records from 53,654 cows were collected between 2009 and 2012. Hoof lesions included in the analysis were digital dermatitis, interdigital dermatitis, interdigital hyperplasia, sole hemorrhage, sole ulcer, toe ulcer, and white line disease. All variables were analyzed as binary traits, as the presence or the absence of the lesions, using a threshold and a linear animal model. Two different cohorts were created: Cohort 1, which included only cows presented to hoof trimmers, and Cohort 2, which included all cows present in the herd at the time of hoof trimmer visit. Using a threshold model, heritabilities on the observed scale ranged from 0.01 to 0.08 for Cohort 1 and from 0.01 to 0.06 for Cohort 2. Heritabilities estimated with the linear model ranged from 0.01 to 0.07 for Cohort 1 and from 0.01 to 0.05 for Cohort 2. Despite a low heritability, the distribution of the sire breeding values showed large and exploitable variation among sires. Higher breeding values for hoof lesion resistance corresponded to sires with a higher prevalence of healthy daughters. The rank correlations between estimated breeding values ranged from 0.96 to 0.99 when predicted using either one of the 2 cohorts and from 0.94 to 0.99 when predicted using either a threshold or a linear model.



http://ift.tt/2mIEDUc

Bovine milk oligosaccharides decrease gut permeability and improve inflammation and microbial dysbiosis in diet-induced obese mice

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Gaëlle Boudry, M. Kristina Hamilton, Maciej Chichlowski, Saumya Wickramasinghe, Daniela Barile, Karen M. Kalanetra, David A. Mills, Helen E. Raybould
Obesity is characterized by altered gut homeostasis, including dysbiosis and increased gut permeability closely linked to the development of metabolic disorders. Milk oligosaccharides are complex sugars that selectively enhance the growth of specific beneficial bacteria in the gastrointestinal tract and could be used as prebiotics. The aim of the study was to demonstrate the effects of bovine milk oligosaccharides (BMO) and Bifidobacterium longum ssp. infantis (B. infantis) on restoring diet-induced obesity intestinal microbiota and barrier function defects in mice. Male C57/BL6 mice were fed a Western diet (WD, 40% fat/kcal) or normal chow (C, 14% fat/kcal) for 7 wk. During the final 2 wk of the study, the diet of a subgroup of WD-fed mice was supplemented with BMO (7% wt/wt). Weekly gavage of B. infantis was performed in all mice starting at wk 3, yet B. infantis could not be detected in any luminal contents when mice were killed. Supplementation of the WD with BMO normalized the cecal and colonic microbiota with increased abundance of Lactobacillus compared with both WD and C mice and restoration of Allobaculum and Ruminococcus levels to that of C mice. The BMO supplementation reduced WD-induced increase in paracellular and transcellular flux in the large intestine as well as mRNA levels of the inflammatory marker tumor necrosis factor α. In conclusion, BMO are promising prebiotics to modulate gut microbiota and intestinal barrier function for enhanced health.



http://ift.tt/2naf8Op

Hot topic: Antilisterial activity by endolysin PlyP100 in fresh cheese

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Maxwell L. Van Tassell, Luis A. Ibarra-Sánchez, Garrett P. Hoepker, Michael J. Miller
Our objective was to assess the antimicrobial efficacy of a Listeria bacteriophage endolysin that may address limitations of current antilisterial processes for fresh cheeses. Listeria monocytogenes is highly problematic in the manufacture and processing of ready-to-eat foods due to its environmental persistence and its ability to grow under refrigerated storage. Special care must be taken to prevent listerial contamination during the production of fresh cheeses, as their delicate flavor and texture are incompatible with many of the antimicrobial processes and additives commonly used for other foods. Bacteriophage-derived cell wall hydrolytic enzymes, known as endolysins, comprise one possible intervention that may not suffer from the high strain specificity of their parent bacteriophages or the development of resistant strains. We recombinantly expressed endolysin PlyP100 and compared its lytic activity in vitro across several environmental parameters and target organisms, then incorporated it into a fresh cheese model challenged with a cocktail of L. monocytogenes. We show that PlyP100 demonstrates optimal activity under pH and salt concentrations consistent with a low-acid food matrix such as fresh cheese. Furthermore, we show that PlyP100 exhibits target specificity for gram-positive organisms with directly crosslinked peptidoglycan and displays considerable inhibitory activity against L. monocytogenes in fresh cheese for at least 4 wk under refrigerated storage. As PlyP100 demonstrates considerable promise for preventing the propagation of L. monocytogenes in fresh cheeses, this novel preservation method could help safeguard consumer health and the market expansion of an otherwise high-risk food with few other viable preservatives.



http://ift.tt/2mIDtIc

Journal of Dairy Science® 2016 Editorial Report

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Matthew Lucy




http://ift.tt/2na4cQW

Characterization of volatile compounds in fermented milk using solid-phase microextraction methods coupled with gas chromatography-mass spectrometry

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): T. Dan, D. Wang, R.L. Jin, H.P. Zhang, T.T. Zhou, T.S. Sun
Lactic acid bacteria (LAB) are industrially important bacteria that are widely used in the fermented food industry, especially in the manufacture of yogurt. Characteristic flavors are produced by LAB during fermentation and storage that affect the quality and acceptability of fermented milk products. In this study, the volatile compounds in milk fermented by Streptococcus thermophilus IMAU80842 alone, Lactobacillus delbrueckii ssp. bulgaricus IMAU20401 alone, or both species together were identified using solid-phase microextraction methods coupled with gas chromatography-mass spectrometry. A total of 53, 43, and 32 volatile compounds were identified in milk fermented by S. thermophilus alone, L. delbrueckii ssp. bulgaricus alone, or both species together, respectively. The presence of some important flavor compounds was confirmed: acetic acid, acetaldehyde, acetoin, 2,3-butanedione, ethanol, and 1-heptanol. Our results demonstrate that the composition of the volatile compounds in fermented milk depends on the species of LAB used and whether they are used alone or in combination. This is important for the selection of appropriate starter cultures for the production of different types of fermented milk product with particular flavors.



http://ift.tt/2nabWCn

Comparison of immunochromatographic assays based on fluorescent microsphere and quantum-dot submicrobead for quantitative detection of aflatoxin M1 in milk

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Chenghui Wu, Liming Hu, Jun Xia, Guomao Xu, Kai Luo, Daofeng Liu, Hong Duan, Song Cheng, Yonghua Xiong, Weihua Lai
The performance of fluorescent microsphere immunochromatographic assay (FM-ICA) and quantum-dot submicrobead immunochromatographic assay (QB-ICA) was systematically and comprehensively compared in quantitative detection of aflatoxin M1 in milk. Under optimum conditions, the advantages of FM-ICA include lower limit of detection of 42.3 pg/mL with better accuracy, precision, reliability, and practicability. The advantages of QB-ICA include shorter detection time and lower monoclonal antibody consumption. The 2 ICA were consistent with liquid chromatography-tandem mass spectrometry. This study serves as a reference for selecting appropriate fluorescent labels for the immunochromatographic assay of aflatoxin M1.



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Technical note: Evaluating nuclear magnetic resonance spectroscopy for determining body composition in Holstein dairy calves using deuterium oxide dilution methods

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): C.E. Chapman, P. Stone Wilkinson, M.R. Murphy, P.S. Erickson
Deuterium oxide (D2O) dilution methods have been used to assess body composition in live animals. Estimated body water content can be used to predict body fat and protein, and thus, the amount of energy reserves. It is an alternative method to direct chemical analysis and considered a noninvasive technique that is economical and repeatable. Deuterium oxide use is considered easy, safe, and accurate; however, the traditional methods of analyzing D2O are expensive, tedious, and time consuming. The objective of this study was to evaluate the potential for using nuclear magnetic resonance spectroscopy (NMR) to determine body composition in Holstein dairy heifers. Nuclear magnetic resonance is less expensive and requires minutes to calculate the percentage of D2O in the blood. This study used 24 newborn dairy heifer calves blocked by birth and randomly assigned to 1 of 3 treatments: (1) 446 g dry matter (DM) of a conventional milk replacer (MR) [CON; 20% crude protein (CP), 20% fat], (2) 669 g DM of a moderately high protein MR (MOD; 26% CP, 18% fat), or (3) 892 g DM of a moderately high protein MR (aggressive, AGG; 26% CP, 18% fat). All calves had free-choice access to starter and water. Both MR and starter were medicated with decoquinate. During weaning (d 43 to 49), the morning MR feeding ceased. On d 50, all MR feedings ended but starter and water intakes were continuously recorded until d 56. When calves were 50 d of age, a baseline blood sample was taken followed by injection of 300 mg of D2O/kg of body weight in sterile physiological saline (0.9%). The syringes containing the D2O in physiological saline were weighed before and after administration to record the actual dose of D2O injected gravimetrically. After injection, the D2O was allowed to equilibrate with body water for 1 h. Six blood samples were taken over 6 d (1/d) at 1630 h to estimate the dilution of the tracer. The plasma was aspirated and stored at −20°C until further D2O analysis. This new method was validated using 4 calf plasma samples that were sent to an outside laboratory for measurement using an independent validation method. We detected no differences in total body water, protein, fat, or mineral content in calves fed CON, MOD, or AGG; however, results demonstrated that the D2O dilution technique and analysis by NMR is an appropriate and easy method to estimate water, protein, ash, and fat in young heifers.



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Estimating genetic and phenotypic parameters of cellular immune-associated traits in dairy cows

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Scott J. Denholm, Tom N. McNeilly, Georgios Banos, Mike P. Coffey, George C. Russell, Ainsley Bagnall, Mairi C. Mitchell, Eileen Wall
Data collected from an experimental Holstein-Friesian research herd were used to determine genetic and phenotypic parameters of innate and adaptive cellular immune-associated traits. Relationships between immune-associated traits and production, health, and fertility traits were also investigated. Repeated blood leukocyte records were analyzed in 546 cows for 9 cellular immune-associated traits, including percent T cell subsets, B cells, NK cells, and granulocytes. Variance components were estimated by univariate analysis. Heritability estimates were obtained for all 9 traits, the highest of which were observed in the T cell subsets percent CD4⁺, percent CD8⁺, CD4⁺:CD8⁺ ratio, and percent NKp46⁺ cells (0.46, 0.41, 0.43 and 0.42, respectively), with between-individual variation accounting for 59 to 81% of total phenotypic variance. Associations between immune-associated traits and production, health, and fertility traits were investigated with bivariate analyses. Strong genetic correlations were observed between percent NKp46⁺ and stillbirth rate (0.61), and lameness episodes and percent CD8⁺ (−0.51). Regarding production traits, the strongest relationships were between CD4⁺:CD8⁺ ratio and weight phenotypes (−0.52 for live weight; −0.51 for empty body weight). Associations between feed conversion traits and immune-associated traits were also observed. Our results provide evidence that cellular immune-associated traits are heritable and repeatable, and the noticeable variation between animals would permit selection for altered trait values, particularly in the case of the T cell subsets. The associations we observed between immune-associated, health, fertility, and production traits suggest that genetic selection for cellular immune-associated traits could provide a useful tool in improving animal health, fitness, and fertility.



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Short communication: The combined use of linkage disequilibrium–based haploblocks and allele frequency–based haplotype selection methods enhances genomic evaluation accuracy in dairy cattle

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Dávid Jónás, Vincent Ducrocq, Pascal Croiseau
The construction and use of haploblocks [adjacent single nucleotide polymorphisms (SNP) in strong linkage disequilibrium] for genomic evaluation is advantageous, because the number of effects to be estimated can be reduced without discarding relevant genomic information. Furthermore, haplotypes (the combination of 2 or more SNP) can increase the probability of capturing the quantitative trait loci effect compared with individual SNP markers. With regards to haplotypes, the allele frequency parameter is also of interest, because as a selection criterion, it allows the number of rare alleles to be reduced, and the effects of those alleles are usually difficult to estimate. We have proposed a simple pipeline that simultaneously incorporates linkage disequilibrium and allele frequency information in genomic evaluation, and here we present the first results obtained with this procedure. We used a population of 2,235 progeny-tested bulls from the Montbéliarde breed for the tests. Phenotype data were available in the form of daughter yield deviations on 5 production traits, and genotype data were available from the 50K SNP chip. We conducted a classical validation study by splitting the population into training (80% oldest animals) and validation (20% youngest animals) sets to emulate a real-life scenario in which the selection candidates had no available phenotype data. We measured all reported parameters for the validation set. Our results proved that the proposed method was indeed advantageous, and that the accuracy of genomic evaluation could be improved. Compared with results from a genomic BLUP analysis, correlations between daughter yield deviations (a proxy for true) and genomic estimated breeding values increased by an average of 2.7 percentage points for the 5 traits. Inflation of the genomic evaluation of the selection candidates was also significantly reduced. The proposed method outperformed the other SNP and haplotype-based tests we had evaluated in a previous study. The combination of linkage disequilibrium–based haploblocks and allele frequency–based haplotype selection methods is a promising way to improve the efficiency of genomic evaluation. Further work is needed to optimize each step in the proposed analysis pipeline.



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In utero exposure to heat stress during late gestation has prolonged effects on the activity patterns and growth of dairy calves

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): J. Laporta, T.F. Fabris, A.L. Skibiel, J.L. Powell, M.J. Hayen, K. Horvath, E.K. Miller-Cushon, G.E. Dahl
Exposure to heat stress during late gestation exerts negative carryover effects on the postnatal performance of the calf. In this study, we evaluated the health, growth, and activity patterns of calves born to cows exposed to heat stress (HT, provided only shade, n = 31) or cooling (CL, fans, soakers, and shade, n = 29) during late gestation (∼46 d, maternal dry period). Calves' body weight, rectal temperature, suckling reflex, and movement scores were recorded at birth, and calves were fed 6.6 L of maternal colostrum in 2 meals. Blood samples were collected at birth (before feeding), 24 h after birth, and at d 10 and 28 of age. Calves were housed in individual pens, fed pasteurized milk (6 L/d), and had ad libitum access to grain and water until weaning (49 d). Activity was assessed during the first week of life (wk 1), at weaning (wk 7), and in the first week postweaning (wk 8) using electronic data loggers. Health and body weight were monitored weekly. At birth, calves born to CL cows were heavier (41.9 vs. 39.1 ± 0.8 kg), their temperature was lower (38.9 vs. 39.3 ± 0.08°C), and they were more efficient at absorbing IgG than HT calves. Suckling reflex and movement score at birth were not different between groups, but calves born to CL cows spent more time (50 min/d) standing in the first week of life as a result of longer standing bouts. In wk 7 and 8, calves born to CL cows had less frequent standing bouts than HT heifers, but CL heifers maintained greater total daily standing time (36 min/d) due to longer (7 min/bout) standing bouts. All calves were healthy, but HT heifers tended to have higher (looser) fecal scores on d 10. Heifers born from CL cows gained 0.2 kg/d more from birth to weaning, weighed 4 kg more at weaning, and had greater concentrations of IGF-1 than HT calves, particularly on d 28. In utero heat stress during late gestation had immediate and prolonged effects on passive immunity, growth, and activity patterns in dairy calves.



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Short communication: Evaluation of a sol-gel–based stainless steel surface modification to reduce fouling and biofilm formation during pasteurization of milk

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Dylan Zhe Liu, Shivali Jindal, Jayendra Amamcharla, Sanjeev Anand, Lloyd Metzger
Milk fouling and biofilms are common problems in the dairy industry across many types of processing equipment. One way to reduce milk fouling and biofilms is to modify the characteristics of milk contact surfaces. This study examines the viability of using Thermolon (Porcelain Industries Inc., Dickson, TN), a sol-gel-based surface modification of stainless steel, during thermal processing of milk. We used stainless steel 316L (control) and sol-gel-modified coupons in this study to evaluate fouling behavior and bacterial adhesion. The surface roughness as measured by an optical profiler indicated that the control coupons had a slightly smoother finish. Contact angle measurements showed that the modified surface led to a higher water contact angle, suggesting a more hydrophobic surface. The modified surface also had a lower surface energy (32.4 ± 1.4 mN/m) than the control surface (41.36 ± 2.7 mN/m). We evaluated the susceptibility of control and modified stainless steel coupons to fouling in a benchtop plate heat exchanger. We observed a significant reduction in the amount of fouled layer on modified surfaces. We found an average fouling weight of 19.21 mg/cm² and 0.37 mg/cm² on the control and modified stainless steel coupons, respectively. We also examined the adhesion of Bacillus and biofilm formation, and observed that the modified stainless steel surface offered greater resistance to biofilm formation. Overall, the Thermolon-modified surface showed potential in the thermal processing of milk, offering significantly lower fouling and bacterial attachment than the control surface.



http://ift.tt/2naqCl3

Differential effects of monensin and a blend of essential oils on rumen microbiota composition of transition dairy cows

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): M. Schären, C. Drong, K. Kiri, S. Riede, M. Gardener, U. Meyer, J. Hummel, T. Urich, G. Breves, S. Dänicke
In response to oral application, monensin alters the rumen microbiota, increasing ruminal propionate production and energy availability in the animal. Data from different studies indicate that the susceptibility of rumen bacteria to monensin is mainly cell-wall dependent but tracing its activity to specific microbial groups has been challenging. Several studies have shown a similar effect for essential oils but results are inconsistent. To investigate the influence of monensin and a blend of essential oils (BEO, containing thymol, guaiacol, eugenol, vanillin, salicylaldehyde, and limonene) on the rumen microbiome, rumen liquid samples were collected orally on d 56 postpartum from cows that had either received a monensin controlled-release capsule 3 wk antepartum, a diet containing a BEO from 3 wk antepartum onward, or a control diet (n = 12). The samples were analyzed for pH, volatile fatty acid, ammonia, and lipopolysaccharide concentrations and protozoal counts. A 16S rRNA gene fingerprinting analysis (PCR–single-strand conformation polymorphism) and sequencing revealed that the BEO treatment had no effect on the rumen microbiota, whereas monensin decreased bacterial diversity. Twenty-three bacterial species-level operational taxonomic units were identified for which monensin caused a significant decrease in their relative abundance, all belonging to the phyla Bacteroidetes (uncultured BS11 gut group and BS9 gut group) and Firmicutes (Lachnospiraceae, Ruminococcaceae, and Erysipelotrichaceae). Ten bacterial operational taxonomic units belonging to the phyla Actinobacteria (Coriobacteriaceae), Bacteroidetes (Prevotella), Cyanobacteria (SHA-109), and Firmicutes (Lachnospiraceae and Ruminococcaceae) increased in relative abundance due to the monensin treatment. These results confirm the hypothesis that varying effects depending on cell-wall constitution and thickness might apply for monensin sensitivity rather than a clear-cut difference between gram-negative and gram-positive bacteria. No effect of monensin on the archaea population was observed, confirming the assumption that reported inhibition of methanogenesis is most likely caused through a decrease in substrate availability, rather than by a direct effect on the methanogens. The data support the hypothesis that the observed increase in ruminal molar propionate proportions due to monensin may be caused by a decrease in abundance of non-producers and moderate producers of propionate and an increase in abundance of succinate and propionate producers.



http://ift.tt/2mIASOv

Short communication: Evaluation of the PREP10 energy-, protein-, and amino acid-allowable milk equations in comparison with the National Research Council model

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Robin R. White, Tyler McGill, Rebecca Garnett, Robert J. Patterson, Mark D. Hanigan
The objective of this work was to evaluate the precision and accuracy of the milk yield predictions made by the PREP10 model in comparison to those from the National Research Council (NRC) Nutrient Requirements of Dairy Cattle. The PREP10 model is a ration-balancing system that allows protein use efficiency to vary with production level. The model also has advanced AA supply and requirement calculations that enable estimation of AA-allowable milk (MilkAA) based on 10 essential AA. A literature data set of 374 treatment means was collected and used to quantitatively evaluate the estimates of protein-allowable milk (MilkMP) and energy-allowable milk yields from the NRC and PREP10 models. The PREP10 MilkAA prediction was also evaluated, as were both models' estimates of milk based on the most-limiting nutrient or the mean of the estimated milk yields. For most milk estimates compared, the PREP10 model had reduced root mean squared prediction error (RMSPE), improved concordance correlation coefficient, and reduced mean and slope bias in comparison to the NRC model. In particular, utilizing the variable protein use efficiency for milk production notably improved the estimate of MilkMP when compared with NRC. The PREP10 MilkMP estimate had an RMSPE of 18.2% (NRC = 25.7%), concordance correlation coefficient of 0.82% (NRC = 0.64), slope bias of −0.14 kg/kg of predicted milk (NRC = −0.34 kg/kg), and mean bias of −0.63 kg (NRC = −2.85 kg). The PREP10 estimate of MilkAA had slightly elevated RMSPE and mean and slope bias when compared with MilkMP. The PREP10 estimate of MilkAA was not advantageous when compared with MilkMP, likely because AA use efficiency for milk was constant whereas MP use was variable. Future work evaluating variable AA use efficiencies for milk production is likely to improve accuracy and precision of models of allowable milk.



http://ift.tt/2naifGi

Ability of dairy cows to ensure pregnancy according to breed and genetic merit for production traits under contrasted pasture-based systems

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): N. Bedere, C. Disenhaus, V. Ducrocq, S. Leurent-Colette, L. Delaby
The present study aimed to assess and measure the effects of breed, genetic merit for production traits, and feeding systems (FS) on the ability of dairy cows to ensure pregnancy through its components (fertilization, embryonic losses, recalving). An experiment was conducted over 9 yr on Normande and Holstein cows assigned to contrasted FS. Diets were based on maize silage in winter and grazing plus concentrate in spring in the high FS group, and on grass silage in winter and grazing with no concentrate during spring in the low FS group. Within breeds, cows were classified into 2 groups with similar estimated breeding values (EBV) for milk solids: cows with high EBV for milk yield were included in a milk group and those with high EBV for fat and protein contents were included in a content group. Holstein cows produced more milk throughout lactation than Normande cows (the differential was greater in the high FS group, +2,294 kg, compared with +1,280 kg in the low FS group) and lost more body condition to nadir (the differential was greater in the high FS group, −1.00 point, compared with −0.80 point in the low FS group). Within breeds, milk solids production was similar between genetic groups. Cows in the high FS group produced more milk (+2,495 kg for Holstein and +1,481 kg for Normande cows) and had a higher body condition score at nadir (+0.40 point for Holstein and +0.60 point for Normande) than cows in the low FS group. Holstein cows had a lower recalving rate than Normande cows (−19 percentage units). We found no effect of genetic group and FS on fertility of Normande cows. However, according to FS, Holstein cows in the content group exhibited different fertility failure patterns. In the low FS group, Holstein cows in the content group had more nonfertilizations or early embryo mortality (+26 percentage units at first and second services) than Holstein cows in the milk group. In the high FS group, Holstein cows in the content group had a higher proportion of late embryo mortality than in the milk group (+10 percentage units at first and second services). We observed no effect of FS on recalving rate; however, indicators of energy balance (protein content or body condition score) were positively associated with successful conception and pregnancy. This suggested a link between genetic merit for fat and protein content and lower ability of dairy cows to ensure pregnancy because of more nonfertilizations and early or late embryo mortality.



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A comparison of different algorithms for phasing haplotypes using Holstein cattle genotypes and pedigree data

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): Younes Miar, Mehdi Sargolzaei, Flavio S. Schenkel
Phasing genotypes to haplotypes is becoming increasingly important due to its applications in the study of diseases, population and evolutionary genetics, imputation, and so on. Several studies have focused on the development of computational methods that infer haplotype phase from population genotype data. The aim of this study was to compare phasing algorithms implemented in Beagle, Findhap, FImpute, Impute2, and ShapeIt2 software using 50k and 777k (HD) genotyping data. Six scenarios were considered: no-parents, sire-progeny pairs, sire-dam-progeny trios, each with and without pedigree information in Holstein cattle. Algorithms were compared with respect to their phasing accuracy and computational efficiency. In the studied population, Beagle and FImpute were more accurate than other phasing algorithms. Across scenarios, phasing accuracies for Beagle and FImpute were 99.49–99.90% and 99.44–99.99% for 50k, respectively, and 99.90–99.99% and 99.87–99.99% for HD, respectively. Generally, FImpute resulted in higher accuracy when genotypic information of at least one parent was available. In the absence of parental genotypes and pedigree information, Beagle and Impute2 (with double the default number of states) were slightly more accurate than FImpute. Findhap gave high phasing accuracy when parents' genotypes and pedigree information were available. In terms of computing time, Findhap was the fastest algorithm followed by FImpute. FImpute was 30 to 131, 87 to 786, and 353 to 1,400 times faster across scenarios than Beagle, ShapeIt2, and Impute2, respectively. In summary, FImpute and Beagle were the most accurate phasing algorithms. Moreover, the low computational requirement of FImpute makes it an attractive algorithm for phasing genotypes of large livestock populations.



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Methane production, ruminal fermentation characteristics, nutrient digestibility, nitrogen excretion, and milk production of dairy cows fed conventional or brown midrib corn silage

Publication date: April 2017
Source:Journal of Dairy Science, Volume 100, Issue 4
Author(s): F. Hassanat, R. Gervais, C. Benchaar
The objective of this study was to examine the effect of replacing conventional corn silage (CCS) with brown midrib corn silage (BMCS) in dairy cow diets on enteric CH4 emission, nutrient intake, digestibility, ruminal fermentation characteristics, milk production, and N excretion. Sixteen rumen-cannulated lactating cows used in a crossover design (35-d periods) were fed (ad libitum) a total mixed ration (forage:concentrate ratio = 65:35, dry matter basis) based (59% dry matter) on either CCS or BMCS. Dry matter intake and milk yield increased when cows were fed BMCS instead of CCS. Of the milk components, only milk fat content slightly decreased when cows were fed the BMCS-based diet compared with when fed the CCS-based diet (3.81 vs. 3.92%). Compared with CCS, feeding BMCS to cows increased yields of milk protein and milk fat. Ruminal pH, protozoa numbers, total VFA concentration, and molar proportions of acetate and propionate were similar between cows fed BMCS and those fed CCS. Daily enteric CH4 emission (g/d) was unaffected by dietary treatments, but CH4 production expressed as a proportion of gross energy intake or on milk yield basis was lower for cows fed the BMCS-based diet than for cows fed the CCS-based diet. A decline in manure N excretion and a shift in N excretion from urine to feces were observed when BMCS replaced CCS in the diet, suggesting reduced potential of manure N volatilization. Results from this study show that improving fiber quality of corn silage in dairy cow diets through using brown midrib trait cultivar can reduce enteric CH4 emissions as well as potential emissions of NH3 and N2O from manure. However, CH4 emissions during manure storage may increase due to excretion of degradable OM when BMCS diet is fed, which merits further investigation.



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Increase of circulating α4β7+ conventional memory CD4 and regulatory T cells in patients with common variable immunodeficiency (CVID)

Publication date: Available online 18 March 2017
Source:Clinical Immunology
Author(s): Karina Mescouto de Melo, Susanne Unger, Baerbel Keller, Sylvia Gutenberger, Ina Stumpf, Sigune Goldacker, Klaus Warnatz
This study investigated whether circulating α4β7⁺ expressing T cells could serve as a potential marker for gastrointestinal (GI) disease activity in patients with CVID. The analysis of α4β7⁺ T cells in the peripheral blood of 36 patients and 22 healthy donors (HD) revealed increased percentages of α4β7⁺ conventional memory CD4 T cells and Tregs, but not among CD8 T-cell populations in patients with CVID compared to HD. No differences between patients with and without chronic or acute GI symptoms were observed. EUROClass smB− and 21lo patients, had higher percentages of α4β7⁺ memory CD4 T cells compared to HD and smB+ or 21norm patients, respectively. In summary, the detection of α4β7⁺ T cells in the peripheral blood did not correlate with active or chronic gastrointestinal disease. The increase of these cells in smB− and 21lo patients adds another piece to the immune dysregulation observed in these patients.



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Physiological arousal accompanying postural responses to external perturbations after stroke

Publication date: Available online 18 March 2017
Source:Clinical Neurophysiology
Author(s): C.L. Pollock, M.G. Carpenter, M.A. Hunt, A. Gallina, T.M. Vieira, T.D. Ivanova, Garland SJ
ObjectiveThe purpose of this study was to examine simultaneously the level of physiological arousal and the postural response to external perturbations in people post-stroke compared to age-matched controls to build a more comprehensive understanding of the effect of stroke on postural control and balance self-efficacy.MethodsParticipants stood with each foot on separate force platforms. Ten applications of loads of 2% body weight at the hips perturbed the participant anteriorly under two conditions: investigator-triggered or self-triggered (total 20). Electrodermal activity (EDA; measurement of physiological arousal), electromyography (EMG) of the ankle plantarflexor muscles and anterior-posterior center of pressure measurements were taken pre-perturbation (anticipatory) and post-perturbation (response) and compared between the initial (first two) and final (last two) perturbations.ResultsParticipants post-stroke demonstrated significantly higher levels of anticipatory EDA and anticipatory paretic plantarflexor EMG during both self- and investigator-triggered conditions compared to controls. Anticipatory EDA levels were higher in the final perturbations in participants post-stroke in both conditions, but not in controls. Habituation of the EDA responses post-perturbation was exhibited in the self-triggered perturbations in controls, but not in participants post-stroke.ConclusionsPhysiological arousal and postural control strategies of controls revealed habituation in response to self-triggered perturbations, whereas this was not seen in participants post-stroke.SignificanceUnderstanding the physiological arousal response to challenges to standing balance post-stroke furthers our understanding of postural control mechanisms post-stroke.



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Olfactory dysfunction in early Parkinson’s disease is associated with short latency afferent inhibition reflecting central cholinergic dysfunction

Publication date: Available online 18 March 2017
Source:Clinical Neurophysiology
Author(s): Eungseok Oh, Jinse Park, Jinyoung Youn, Ji Sun Kim, Suyeon Park, Wooyoung Jang
ObjectiveOur study aimed to determine whether the short latency afferent inhibition (SAI) response could be associated with the severity of olfactory dysfunction in PD patients.MethodsA total of 71 PD patients and 20 controls were enrolled. All PD patients were classified into 3 groups by the severity of the olfactory deficit. Single-pulse transmagnetic stimulation (TMS) parameters and SAI were assessed.ResultsThe integrated SAI in the PD with anosmia and PD with hyposomia groups was significantly less inhibited than that in the PD with normosmia and control groups [64.79 {Interquartile range(IQR): 59.96, 71.33}, 84.79 {IQR: 75.03, 90.63} versus 36.72 {IQR: 32.28, 48.33}, 42.15 {IQR: 34.60, 44.96}, respectively]. In PD subjects, the severity of olfactory dysfunction also showed a significant negative correlation with the SAI response (r = -0.829, p < 0.001).ConclusionsConsidering that the SAI response partly reflects central cholinergic dysfunction and that our study shows a relationship between the SAI response and the severity of olfactory dysfunction in PD, our findings indicate that cholinergic dysfunction could possibly contribute to the pathogenesis of olfactory dysfunction in early PD.SignificanceSAI could be a useful marker to detect severe olfactory dysfunction in PD.



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The Role of Histopathologic Subtype in the Setting of Hippocampal Sclerosis-Associated Mesial Temporal Lobe Epilepsy

Publication date: Available online 18 March 2017
Source:Human Pathology
Author(s): Jordan M. Gales, Lara Jehi, Amy Nowacki, Richard A. Prayson
Hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) are among the most common neuropathological findings in those undergoing surgery for refractory mesial temporal lobe epilepsy (MTLE). Existing data regarding differences among the most recent International League Against Epilepsy (ILAE) HS subtypes remains limited. This study sought to characterize the roles of HS subtype and coexistent FCD. Epilepsy surgery pathologic specimens in 307 cases of temporal lobe epilepsy with HS were reviewed (mean age ± SD, 37 ± 15 years, 56% women). HS and coexistent FCD were classified according to ILAE guidelines. Medical records were reviewed for data on seizure recurrence and seizure burden (clinical follow-up mean duration ± SD, 5±4 years). Cases of typical HS (ILAE type I) predominated [ILAE type Ia: 41%, Ib: 47%, II: 11%, III: 0.7%]. The HS subtypes shared similar demographic and etiologic characteristics, as well as associated pathology and post-operative seizure outcomes. Individuals with type Ib HS were more likely to remain seizure free at long term follow-up when compared to other subtypes, and they had a later age of seizure onset. Two hundred-forty-three cases (79%) demonstrated FCD within the adjacent temporal lobe. Its presence was associated with a significantly decreased risk of seizure recurrence (p=.02). When present, FCD was predominantly Type I (98%). HS subtype does not appear to affect epilepsy surgery outcomes, despite some clinical differences between the subgroups. FCD is often observed in association with HS in MTLE; the finding of FCD was associated with better post-operative outcomes.



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Effects of chemical stimulation of the lateral wings of the dorsal raphe nucleus on panic-like defensive behaviors and Fos protein expression in rats

Publication date: 30 May 2017
Source:Behavioural Brain Research, Volume 326
Author(s): Melina Matthiesen, Ailton Spiacci, Hélio Zangrossi
The lateral wings subnucleus of the dorsal raphe nucleus (lwDR) has been implicated in the modulation of panic-like behaviors, such as escape. Infusion of non- excitotoxic doses of the excitatory amino acid kainic acid into this subnucleus promptly evokes a vigorous escape response. In addition, rats exposed to panic-inducing situations show an increase in Fos protein expression in neurons within the lwDR. In the present study, we first investigated whether key structures associated with the mediation of escape behavior are recruited after chemical stimulation of the lwDR with kainic acid. We next investigated whether the infusion of the GABAA receptor antagonist bicuculline into the lwDR also evoked escape responses measured both in a circular arena and in the rat elevated T-maze. The effects of bicuculline in the circular arena were compared to those caused by the infusion of this antagonist into the ventrolateral periaqueductal gray (vlPAG), an area in close vicinity to the lwDR. The results showed that kainic acid infusion into the lwDR increased Fos protein immunostaining in brain structures deeply involved in panic-like defensive behaviors, such as the periaqueductal gray and hypothalamus, but not the amygdala. As observed with kainic acid, bicuculline evoked a pronounced escape response in the circular arena when microinjected in the lwDR, but not in the vlPAG. The escape-promoting effect of bicuculline in the lwDR was also evidenced in the elevated T-maze. These findings strength the view that dysfunction in mechanisms controlling escape in the lwDR is critically implicated in the pathophysiology of panic disorder.



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The role of nidopallium caudolaterale in the goal-directed behavior of pigeons

Publication date: 30 May 2017
Source:Behavioural Brain Research, Volume 326
Author(s): Xinyu Liu, Hong Wan, Shan Li, Zhigang Shang, Li Shi
Avian nidopallium caudolaterale (NCL) is believed to be analogue to the mammalian prefrontal cortex (PFC), a key brain region for guiding goal-directed behavior. But the role of NCL during goal-directed behavior remains unclear. To investigate whether the pigeon NCL participate in the goal-directed behavior, we recorded single-units from the NCL of four pigeons as they performing goal-directed decision-making task in a plus-maze. During the decision-making process, the firing rates of NCL neurons significantly increased and they are associated with the choice of the upcoming movement. Moreover, both the firing rates and the decoding performance in the correct trials are significantly higher both of that in the error trials. These suggest that the NCL neurons indeed participate in the goal-directed behavior of pigeon and the neural activities may be induced by the rewards. However, the NCL neurons are depend on the rewards received to produce firing patterns discriminating the features of goal-directed behaviors, rather than encode the reward itself. In addition, we found that the functional components of goal-directed behavior are lateralized in the NCL, both the firing rates and the decoding performance in left NCL are significantly higher than both of that in right NCL.



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Repeated corticosterone injections in adult mice alter stress hormonal receptor expression in the cerebellum and motor coordination without affecting spatial learning

Publication date: 30 May 2017
Source:Behavioural Brain Research, Volume 326
Author(s): Guillaume Harlé, Robert Lalonde, Coralie Fonte, Armelle Ropars, Jean-Pol Frippiat, Catherine Strazielle
Receptors for glucocorticoid (GR) and corticotropin-releasing hormone (CRH) are largely found in brain sensorimotor structures, particularly in cerebellum, underlining a potential role of stress hormones in the regulation of motor function. Since CRH is involved in neuroplasticity, known for its trophic effect on synapses, we investigated how manipulations in corticosterone serum levels can modulate the CRH system in the cerebellum and affect motor coordination. Corticosterone at doses of either 15 or 30mg/kg was injected in mice and the status of hormonal expression evaluated in cerebellum, hippocampus, and hypothalamus in undisturbed housing conditions or after different behavioral tests. Under both conditions, metabolic activity in numerous brain regions involved in motor functions and emotion was measured by means of cytochrome oxidase (COX) activity labeling. After six consecutive days of corticosterone administration, CRH-R1 transcription was downregulated in hypothalamic and cerebellar regions and hypometabolic changes were observed in mice treated with the higher dose for several limbic and sensorimotor circuitries, notably basal ganglia, deep cerebellar nuclei, and red nucleus. Corticosterone did not modify motor activity, anxiety, and spatial orientation, but decreased latencies before falling from the rotorod and prevented mice from reaching targets in the coat-hanger test. In addition, COX activities were similar to control mice except in ventromedial thalamus and dorsal neostriatum, possibly indicating that physical activity protected brain energy metabolism against the stress hormone. The present findings showed that the CRH/CRH-R1 system might play a role in mediating the effects of stress on cerebellar function, affecting especially motor learning tasks.

Graphical abstract

http://ift.tt/2nRraJS

Decreased functional connectivity between the dorsal anterior cingulate cortex and lingual gyrus in Alzheimer's disease patients with depression

Publication date: 30 May 2017
Source:Behavioural Brain Research, Volume 326
Author(s): Xiaozheng Liu, Wei Chen, Hongtao Hou, Xingli Chen, Jiangtao Zhang, Jian Liu, Zhongwei Guo, Guanghui Bai
BackgroundDepression is one of the most common psychiatric symptoms in Alzheimer's disease (AD), occurring in up to 40% of AD patients. It influences the cognitive function of patients and increases the burden on their caregivers. Currently, there are few effective medical treatments for reducing the symptoms of depression in AD patients. Understanding the underlying neurobiological mechanisms in AD patients with depression (D-AD) is crucial for developing effective interventions. The anterior cingulate cortex (ACC) is an important brain region involved in emotional and cognitive processing. Several functional magnetic resonance imaging studies have shown that patients with major depressive disorder have structural, functional, and metabolic abnormalities in the ACC.MethodsWe investigated the resting-state functional connectivity (FC) of ACC subregions in 15 D-AD patients and 17 non-depressed AD (nD-AD) patients, by parcellating the ACC into the rostral and dorsal ACC (dACC).ResultsOur results revealed that D-AD patients have decreased FC between the dACC and the right occipital lobe and right lingual gyrus, compared with nD-AD patients.ConclusionsDecreased FC between the dACC and the right occipital lobe and right lingual gyrus may play an important role in the neuropathophysiology of depression in AD.



http://ift.tt/2nRGOox

Behavioral characterization of blocking the ErbB signaling during adolescent and adulthood in reward-liking (preference) and reward-related learning

Publication date: 30 May 2017
Source:Behavioural Brain Research, Volume 326
Author(s): Hagar Tadmor, Idit Golani, Eshkar Dvir, Ilana Kremer, Alon Shamir
Adolescence is a critical period in brain development. During this critical period the seeking for hedonic activities is increased, and their activity signals are stronger than the regulatory signals of judgment and reasoning. We recently reported that alteration of ErbB signaling during this period led to elevated striatal dopamine levels and reduced preference for sweetness without affecting locomotor activity and exploratory behavior. In the current study, we extend our findings and explore whether inhibition of the ErbB pathway during adolescence or adulthood also affects alcohol preference (hedonic "liking"), avoidance learning, and motivational reward "wanting". We demonstrated that chronic administration of the pan-ErbB kinase inhibitor JNJ28871063 (JNJ) to adolescent mice, but not to adult mice, reduced alcohol preference compared with the saline-injected group, without affecting avoidance learning as measured by increasing concentrations of quinine in the bitter avoidance test. Adolescent JNJ-treated mice continue to demonstrate less alcohol preference in adulthood compared with their saline-injected controls. In addition, adolescent JNJ-treated mice and their saline-injected controls did not differ in the time they spent in the food-condition chamber, and in their preference for social odor. In contrast to adolescent JNJ- treated mice, blocking the pathway during adulthood alter the preference to natural reward. These data support our initial findings that interruption of the ErbB pathway during adolescence emerges in a reduced hedonic capacity that persists into adulthood, without disturbing avoidance and reward learning. In addition, this paper provides a further behavioral role of the ErbB signaling pathway in the reward system, and suggests a different time period for the involvement of the pathway in the "liking" and the "wanting" components of the system.



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Social experiences during adolescence affect anxiety-like behavior but not aggressiveness in male mice

Publication date: 30 May 2017
Source:Behavioural Brain Research, Volume 326
Author(s): Neele Meyer, Julia Jenikejew, S. Helene Richter, Sylvia Kaiser, Norbert Sachser
Adolescence has lately been recognized as a key developmental phase during which an individual's behavior can be shaped. In a recent study with male mice varying in the expression of the serotonin transporter, escapable adverse social experiences during adolescence led to decreased anxiety-like behavior and increased exploratory and aggressive behavior compared to throughout beneficial experiences. Since in this study some behavioral tests took place with a delay of one week after the last social experiences have been made, it was not clear whether the observed effects really reflected the consequences of the experienced different social environments. To test this, the present study focused on the direct effects of beneficial and adverse social experiences on aggressiveness and anxiety-like behavior in C57BL/6J mice. In contrast to the previous study, behavioral testing took place immediately after the last social experiences had been made. Interestingly, whereas individuals from an escapable adverse environment showed significantly lower levels of anxiety-like and higher levels of exploratory behavior than animals from a beneficial environment, aggressive behavior was not affected. From this, we conclude that different social experiences during adolescence exert immediate effects on anxiety-like but not aggressive behavior in male mice.



http://ift.tt/2nRxXmz

Synthesis and carbonic anhydrase inhibition of a series of SLC-0111 analogs

Publication date: Available online 18 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Fabrizio Carta, Daniela Vullo, Sameh M. Osman, Zeid AlOthman, Claudiu T. Supuran
SLC-0111 is a sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor (CAI) in Phase I/II clinical trials for the treatment of advanced hypoxic tumors complicated with metastases. Its antitumor effects are due to inhibition of the enzymatic activity of CA IX, an isoform predominantly found in tumors/metastases, but it also reduces the cancer stem cells population. Here we report the synthesis of analogs of SLC-0111, both of the sulfanilamide and metanilamide series, which possess diverse substitution patterns at the terminal ureido-phenyl moiety, thus including one or more halogens, trifluoromethyl, perchloro-/perfluorophenyl groups instead of the 4-fluorophenyl present in SLC-0111. Most of the sulfanilamide ureido derivatives were highly effective inhibitors of the tumor associated isoform and some showed selective CA IX/XII inhibitory profiles. Most of the sulfanilamide ureido derivatives were highly effective and in some cases selective CA IX/XII inhibitors, whereas the metanilamide ureido derivatives were less effective as transmembrane CA isoforms inhibitors. Structure activity relationship for this class of sulfonamides is discussed in detail.

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Do spiroindolines have the potential to replace vesamicol as lead compound for the development of radioligands targeting the vesicular acetylcholine transporter?

Publication date: Available online 18 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Marcel Lindemann, Winnie Deuther-Conrad, Rares Moldovan, Kondapalli Venkata Gowri Chandra Sekhar, Peter Brust, Barbara Wenzel
The vesicular acetylcholine transporter (VAChT) is an important target for in vivo imaging of neurodegenerative processes using positron-emission-tomography (PET). So far the development of VAChT PET radioligands is based on the single known lead compound vesamicol. In this study we investigated a recently published spiroindoline based compound class (Sluder et al. 2012), which was suggested to have potential in the development of VAChT ligands. Therefore, we synthesized a small series of N,N-substituted spiro[indoline-3,4'-piperidine] derivatives and determined their in vitro binding affinities toward the VAChT. In order to investigate the selectivity, the off-target binding toward σ1 and σ2 receptors were determined. The compounds possessed VAChT affinities with Ki values in the range of 39 to 376 nM. Binding affinities toward the σ1 and σ2 receptors are in a similar range indicating that the strong structural difference between the spiroindolines and vesamicol did not improve the selectivity. The observed potential to additionally bind to σ receptors let us assume that the herein investigated spiroindolines are not suitable to replace vesamicol as lead compound for the development of VAChT ligands.

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C-2 (E)-4-(Styryl)aniline Substituted Diphenylpyrimidine Derivatives (Sty-DPPYs) as Specific Kinase Inhibitors Targeting Clinical Resistance related EGFRT790M Mutant

Publication date: Available online 18 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Anran Song, Jianbin Zhang, Yang Ge, Changyuan Wang, Qiang Meng, Zeyao Tang, Jinyong Peng, Kexin Liu, Yanxia Li, Xiaodong Ma
With the aim to overcome the drug resistance induced by the EGFR T790M mutation (EGFR^T790M), herein, a family of diphenylpyrimidine derivatives (Sty-DPPYs) bearing a C-2 (E)-4-(styryl)aniline functionality were designed and synthesized as potential EGFR^T790M inhibitors. Among them, the compound 10e displayed strong potency against the EGFR^T790M enzyme, with the IC50 of 11.0 nM. Compound 10e also showed a higher SI value (SI = 49.0) than rociletinib (SI = 21.4), indicating its less side effect. In addition, compound 10e could effectively inhibit the proliferation of H1975 cells harboring the EGFR^T790M mutation, within the concentration of 2.91 μM. Significantly, compound 10e has low toxicity against the normal HBE cell (IC50 = 22.48 μM). This work provided new insights into the discovery of potent and selective inhibitor against EGFR^T790M over wild-type (EGFR^WT)

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Design and synthesis of bicyclic acetals as Beta Secretase (BACE1) inhibitors

Publication date: Available online 18 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Riccardo Innocenti, Elena Lenci, Gloria Menchi, Alberto Pupi, Andrea Trabocchi
Taking advantage of the structural similarity between aspartic proteases, small-molecule peptidomimetic inhibitors that already showed activity towards Secreted Aspartic Protease 2 as anti-Candida agents and HIV protease inhibitors were exploited as potential BACE1 inhibitors. A focused library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was synthesized and assayed towards BACE1 enzyme, resulting in the identification of a thiolactam-containing hit compound possessing IC50 in the low micromolar range, and confirming the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues

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Comparative assessment of a 99mTc labeled H1299.2-HYNIC peptide bearing two different co-ligands for tumor-targeted imaging

Publication date: Available online 18 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Seyedeh Atekeh Torabizadeh, Seyed Mohammad Abedi, Zoreh Noaparsat, Seyed Jalal Hosseinimehr
Peptides are a class of targeting agents that bind to cancer-specific cell surfaces. Since they specifically target cancer cells, they could be used as molecular imaging tools. In this study, the 15-mer peptide Ac-H1299.2 (YAAWPASGAWTGTAP) was conjugated with HYNIC via lysine amino acid on C-terminus and labeled with ^99mTc using tricine and EDDA/tricine as the co-ligands. These radiotracers were evaluated for potential utilization in diagnostic imaging of ovarian cancer cells (SKOV-3). The cell-specificity of these radiolabeled peptides was determined based on their binding on an ovarian cancer cell line (SKOV-3), and displaying a low affinity for lung adenocarcinoma cell line (A549) and breast cancer cell line (MCF7). Biodistribution studies were conducted in normal mice as well as in nude mice bearing SKOV-3 ovarian cancer xenografts. HYNIC-peptides was labeled with ^99mTc with more than 99% efficiency and showed high stability in buffer and serum. We observed nanomolar binding affinities for both radiolabeled peptides. The tumor uptakes were 3.27% ± 0.46% and 1.55% ± 0.20% for tricine and 2.34 ± 0.18% and 1.09% ± 0.18% for EDDA/tricine at 1 and 4 h after injection, respectively. A higher tumor to background ratio and lower radioactivity in the blood were observed for EDDA/tricine co-ligands, leading to clear tumor visualization in imaging with injection of this peptide. This new ^99mTc-labeled peptide selectively targeted ovarian cancer and introduction of a (EDDA/tricine) as a co-ligand improved the pharmacokinetics of ^99mTc-labeled H1299.2 for tumor imaging in animals.

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Inhibition of Malassezia globosa carbonic anhydrase with phenols

Publication date: Available online 18 March 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yeganeh Entezari Heravi, Silvia Bua, Alessio Nocentini, Sonia Del Prete, Ali Akbar Saboury, Hassan Sereshti, Clemente Capasso, Paola Gratteri, Claudiu T. Supuran
A panel of 22 phenols was investigated as inhibitors of the β-class carbonic anhydrase (CAs, EC 4.2.1.1) from the fungal parasite Malassezia globosa (MgCA), a validated anti-dandruff drug target. The displayed inhibitory activities were compared to the ones previously reported against the off-target widely distributed human (h) isoforms hCA I and II. All tested phenols possessed a better efficacy in inhibiting MgCA than the clinically used sulfonamide acetazolamide, with KIs in the range of 2.5 and 65.0 μM. A homology-built model of MgCA was also used for understanding the binding mode of phenols to the fungal enzyme. Indeed, a wide network of hydrogen bonds and hydrophobic interactions between the phenol and active site residues were evidenced. The OH moiety of the inhibitor was observed anchored to the zinc-coordinated water, also making hydrogen bonds with Ser48 and Asp49. The diverse substituents at the phenolic scaffold were observed to interact with different portions of the hydrophobic pocket according to their nature and position. Considering the effective MgCA inhibitory properties of phenols, beside to the rather low inhibition against the off-target hCA I and II, this class of compounds might be of considerable interest in the cosmetics field as potential anti-dandruff drugs.

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Importance of perceived naturalness for acceptance of food additives and cultured meat

Publication date: 1 June 2017
Source:Appetite, Volume 113
Author(s): Michael Siegrist, Bernadette Sütterlin
Four experiments examined some factors influencing the perceived naturalness of food products and their biasing effect on risk perception. The results of Experiment 1a showed that three food additives displaying their respective E-numbers (i.e., codes for food additives in the European Union and Switzerland) decreased perceived naturalness. Experiment 1b demonstrated that mentioning possible health effects decreased the perceived naturalness of a plant-based food additive. This experiment further showed that it would not matter for perceived naturalness whether the food was synthetic or nature-identical. Moreover, the results of Experiments 2 and 3 suggested that the same risk associated with meat consumption was much more acceptable for traditionally produced meat compared with in-vitro meat. Experiment 3 further indicated that the perceived naturalness of the meat (i.e., traditional or cultured meat) had a full mediation effect on participants' evaluation of the acceptability of the risk of colon cancer associated with the meat consumption. Even if the new production method (i.e., cultured meat) was more environmentally friendly and less harmful to animals, the perceived lack of naturalness might reduce the acceptability of the risk associated with such a product. The present study provides evidence that consumers rely on symbolic information when evaluating foods, which may lead to biased judgments and decisions.



http://ift.tt/2nRsooi

A review of instruments developed to measure food neophobia

Publication date: 1 June 2017
Source:Appetite, Volume 113
Author(s): Marie Damsbo-Svendsen, Michael Bom Frøst, Annemarie Olsen
BackgroundFood choices are influenced by an individual's attitude towards foods. Food neophobia may be associated with less variety of diets, inadequate nutrient intake and high product failure rate for new food products entering the market. To quantify the extent of these challenges, instruments to measure the food neophobia in different target groups are needed. Several such instruments with significantly different measurement outcomes and procedures have been developed. This review provides an overview and discusses strengths and weaknesses of these instruments.ObjectiveWe evaluate strengths and weaknesses of previously developed instruments to measure neophobia and willingness to try unfamiliar foods.DesignLiterature was searched through the databases Web of Science and Google Scholar. We identified 255 studies concerning neophobia and willingness to try unfamiliar foods. Of these, 13 studies encompassing 13 instruments to measure neophobia and willingness to try unfamiliar foods were included in the review. Results are summarized and evaluated with a narrative approach.ResultsIn the 13 instruments to assess neophobia and willingness to try unfamiliar foods, 113 to 16.644 subjects aged 2–65 years were involved, scales with 3–7 response categories were used and behavioral validation tests were included in 6 studies.ConclusionsSeveral instruments to measure neophobia and willingness to try unfamiliar foods exist. We recommend selecting one or more among the 13 instruments reviewed in this paper to assess relevant aspects of neophobia.



http://ift.tt/2n34GIh

Changing children's eating behaviour - A review of experimental research

Publication date: 1 June 2017
Source:Appetite, Volume 113
Author(s): Patricia DeCosta, Per Møller, Michael Bom Frøst, Annemarie Olsen
The interest in children's eating behaviours and how to change them has been growing in recent years. This review examines the following questions: What strategies have been used to change children's eating behaviours? Have their effects been experimentally demonstrated? And, are the effects transient or enduring? Medline and Cab abstract (Ovid) and Web of Science (Thomson Reuters) were used to identify the experimental studies. A total of 120 experimental studies were identified and they are presented grouped within these 11 topics; parental control, reward, social facilitation, cooking programs, school gardens, sensory education, availability and accessibility, choice architecture and nudging, branding and food packaging, preparation and serving style, and offering a choice. In conclusion, controlling strategies for changing children's eating behaviour in a positive direction appear to be counterproductive. Hands-on approaches such as gardening and cooking programs may encourage greater vegetable consumption and may have a larger effect compared to nutrition education. Providing children with free, accessible fruits and vegetables have been experimentally shown to positively affect long-term eating behaviour. The authors recommend future research to examine how taste and palatability can positively affect children's attitudes and eating behaviour.



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Higher BMI is associated with stronger effects of social cues on everyday snacking behaviour

Publication date: 1 July 2017
Source:Appetite, Volume 114
Author(s): Benjamin Schüz, Sarah Revell, Andrew P. Hills, Natalie Schüz, Stuart G. Ferguson
Discretionary food choices (snacks) contribute up to a third of the daily energy intake and potentially contribute to energy imbalance and weight gain. Individual snack intake behaviour is guided by internal and external cues, with social cues (seeing others eat, being alone) consistently showing large effects. A wide body of (mainly laboratory-based) research suggests marked differences in people's response to eating cues based on BMI. Here, we show that these BMI differences in cue responsiveness also pertain to everyday snacking behaviour. In two combined ecological momentary assessment studies, 122 participants with BMIs ranging from 18.34 to 45.71 kg/m² logged their everyday snacking behaviour in real-time over two weeks along with the presence or absence of social cues. Random-effects modelling showed that people with higher BMI were more likely to consume high-energy snacks when alone, and were more likely to consume low-energy snacks in the presence of others eating. This suggests BMI differences in cue responsiveness that are in line with impression management theory and underlines the importance of social cues for snacking behaviour and provides avenues for both theory and intervention development.



http://ift.tt/2n2Tnjb

Mechanistic Insights into the Bleaching of Melanin by Alkaline Hydrogen Peroxide

Publication date: Available online 18 March 2017
Source:Free Radical Biology and Medicine
Author(s): R.A.W. Smith, B. Garrett, K.R. Naqvi, A. Fülöp, S. Godfrey, J. Marsh, V. Chechik
This work aims to determine the roles of reactive oxygen species HO∙ and HO2^- in the bleaching of melanins by alkaline hydrogen peroxide. Experiments using melanosomes isolated from human hair indicated that the HO∙ radical generated in the outside solution does not contribute significantly to bleaching. However, studies using soluble Sepia melanin demonstrated that both HO2^- and HO∙ will individually bleach melanin. Additionally, when both oxidants are present, bleaching is increased dramatically in both rate and extent. Careful experimental design enabled the separation of the roles and effects of these key reactive species, HO∙ and HO2^-. Rationalisation of the results presented, and review of previous literature, allowed the postulation of a simplified general scheme whereby the strong oxidant HO∙ is able to pre-oxidise melanin units to o-quinones enabling more facile ring opening by the more nucleophilic HO2^-. In this manner the efficiency of the roles of both species is maximised.

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Direct participation of DNA in the formation of singlet oxygen and base damage under UVA irradiation

Publication date: Available online 18 March 2017
Source:Free Radical Biology and Medicine
Author(s): Teiti Yagura, André Passaglia Schuch, Camila Carrião Machado Garcia, Clarissa Ribeiro Reily Rocha, Natália Cestari Moreno, José Pedro Friedmann Angeli, Davi Mendes, Divinomar Severino, Angelica Bianchini Sanchez, Paolo Di Mascio, Marisa Helena Gennari de Medeiros, Carlos Frederico Martins Menck
UVA light is hardly absorbed by the DNA molecule, but recent works point to a direct mechanism of DNA lesion by these wavelengths. UVA light also excite endogenous chromophores, which causes DNA damage through ROS. In this study, DNA samples were irradiated with UVA light in different conditions to investigate possible mechanisms involved in the induction of DNA damage. The different types of DNA lesions formed after irradiation were determined through the use of endonucleases, which recognize and cleave sites containing oxidized bases and cyclobutane pyrimidine dimers (CPDs), as well as through antibody recognition. The formation of 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxodG) was also studied in more detail using electrochemical detection. The results show that high NaCl concentration and concentrated DNA are capable of reducing the induction of CPDs. Moreover, concerning damage caused by oxidative stress, the presence of sodium azide and metal chelators reduce their induction, while deuterated water increases the amounts of oxidized bases, confirming the involvement of singlet oxygen in the generation of these lesions. Curiously, however, high concentrations of DNA also enhanced the formation of oxidized bases, in a reaction that paralleled the increase in the formation of singlet oxygen in the solution. This was interpreted as being due to an intrinsic photosensitization mechanism, depending directly on the DNA molecule to absorb UVA and generate singlet oxygen. Therefore, the DNA molecule itself may act as a chromophore for UVA light, locally producing a damaging agent, which may lead to even greater concerns about the deleterious impact of sunlight.

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Peroxiredoxin 2 regulates PGF2α-induced corpus luteum regression in mice by inhibiting ROS-dependent JNK activation

Publication date: Available online 18 March 2017
Source:Free Radical Biology and Medicine
Author(s): Sun-Ji Park, Jung-Hak Kim, Tae-shin Kim, Sang-Rae Lee, Jeen-Woo Park, Seunghoon Lee, Jin-Man Kim, Dong-Seok Lee
Luteal regression is a natural and necessary event to regulate the reproductive process in all mammals. Prostaglandin F2α (PGF2α) is the main factor that causes functional and structural regression of the corpus luteum (CL). It is well known that PGF2α-mediated ROS generation is closely involved in luteal regression. Peroxiredoxin 2 (Prx2) as an antioxidant enzyme plays a protective role against oxidative stress-induced cell death. However, the effect of Prx2 on PGF2α-induced luteal regression has not been reported. Here, we investigated the role of Prx2 in functional and structural CL regression induced by PGF2α-mediated ROS using Prx2-deficient (-/-) mice. We found that PGF2α-induced ROS generation was significantly higher in Prx2-/- MEF cells compared with that in wild-type (WT) cells, which induced apoptosis by activating JNK-mediated apoptotic signaling pathway. Also, PGF2α treatment in the CL derived from Prx2-/- mice promoted the reduction of steroidogenic enzyme expression and the activation of JNK and caspase3. Compared to WT mice, serum progesterone levels and luteal expression of steroidogenic enzymes decreased more rapidly whereas JNK and caspase3 activations were significantly increased in Prx2-/- mice injected with PGF2α. However, the impaired steroidogenesis and PGF2α-induced JNK-dependent apoptosis were rescued by the addition of the antioxidant N-acetyl-L-cysteine (NAC).This is the first study to demonstrate that Prx2 deficiency ultimately accelerated the PGF2α-induced luteal regression through activation of the ROS-dependent JNK pathway. These findings suggest that Prx2 plays a crucial role in preventing accelerated luteal regression via inhibition of the ROS/JNK pathway.

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Monocyte activation drives preservation of membrane thiols by promoting release of oxidised membrane moieties via extracellular vesicles extracellular vesicles

Publication date: Available online 18 March 2017
Source:Free Radical Biology and Medicine
Author(s): K.É. Szabó-Taylor, E.Á. Tóth, A.M. Balogh, B.W. Sódar, L. Kádár, K. Pálóczi, N. Fekete, A. Németh, X. Osteikoetxea, K.V. Vukman, M. Holub, É. Pállinger, Gy. Nagy, P.G. Winyard, E.I. Buzás
The redox state of cellular exofacial molecules is reflected by the amount of available thiols. Furthermore, surface thiols can be considered as indicators of immune cell activation. One group of thiol containing proteins, peroxiredoxins, in particular, have been associated with inflammation.In this study, we assessed surface thiols of the U937 and THP1 monocyte cell lines and primary monocytes in vitro upon inflammatory stimulation by irreversibly labelling the cells with a fluorescent derivative of maleimide. We also investigated exofacial thiols on circulating blood mononuclear cells in patients with rheumatoid arthritis and healthy controls. When analysing extracellular vesicles, we combined thiol labelling with the use of antibodies to specific CD markers to exclude extracellular vesicle mimicking signals from thiol containing protein aggregates. Furthermore, differential detergent lysis was applied to confirm the vesicular nature of the detected extracellular events in blood plasma.We found an increase in exofacial thiols on monocytes upon in vitro stimulation by LPS or TNF, both in primary monocytes and monocytic cell lines (p<0.0005). At the same time, newly released extracellular vesicles showed a decrease in their exofacial thiols compared with those from unstimulated cells (p<0.05). We also found a significant elevation of surface thiols on circulating monocytes in rheumatoid arthritis patients (p<0.05) and newly released extracellular vesicles of isolated CD14⁺ cells from rheumatoid arthritis patients had decreased thiol levels compared with healthy subjects (p<0.01). Exofacial peroxiredoxin 1 was demonstrated on the surface of primary and cultured monocytes, and the number of peroxiredoxin 1 positive extracellular vesicles was increased in rheumatoid arthritis blood plasma (p<0.05). Furthermore, an overoxidised form of peroxiredoxin was detected in extracellular vesicle-enriched preparations from blood plasma.Our data show that cell surface thiols play a protective role and reflect oxidative stress resistance state in activated immune cells. Fsurthermore, they support a role of extracellular vesicles in the redox regulation of human monocytes, possibly representing an antioxidant mechanism.

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An in depth study of solvent effects on yield and average molecular weight in poly(3-hexylthiophene)

Publication date: 21 April 2017
Source:Polymer, Volume 115
Author(s): Jennifer Gadient, Rebecca Groch, Cora Lind
Poly(3-hexylthiophene) was synthesized by chemical oxidation using FeCl3 in chloroform, dichloromethane, acetonitrile, nitromethane, nitrobenzene and mixtures of these solvents. Comparative reactions for 1 day at room temperature were carried out to investigate solvent effects. Polymer samples and the remaining reaction solutions were analyzed by MALDI-MS and LDI-MS to determine Mw and reaction completeness, respectively. Solubilities of FeCl3, FeCl2, and P3HT in each pure solvent were measured and correlated to the results. Open circuit potentials of FeCl3 and mixtures of FeCl3 and FeCl2 in pure solvents were measured and compared to the experimentally determined oxidation potential of 3-hexylthiophene. An optimized solvent system for reproducible synthesis of high Mw P3HT with quantitative yields is proposed based on MS analysis results.

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