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https://www.readbyqxmd.com/read/29331353/mechanisms-of-sex-differences-in-fear-and-posttraumatic-stress-disorder
#1
REVIEW
Teniel Sonya Ramikie, Kerry James Ressler
Following sexual maturity, females disproportionately have higher rates of posttraumatic stress disorder (PTSD) and experience greater symptom severity and chronicity as compared with males. This observation has led many to examine sex differences in PTSD risk factors. Though relatively few, these studies reveal that the root causes of PTSD sex differences are complex, and partly represent interactions between sex-specific nonbiological and biological risk factors, which differentially shape PTSD vulnerability...
November 21, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29330054/deterministic-stability-regimes-and-noise-induced-quasistable-behavior-in-a-pair-of-reciprocally-inhibitory-neurons
#2
Mainak Patel, Badal Joshi
Reciprocal inhibition is a common motif exploited by neuronal networks; an intuitive and tractable way to examine the behaviors produced by reciprocal inhibition is to consider a pair of neurons that synaptically inhibit each other and receive constant or noisy excitatory driving currents. In this work, we examine reciprocal inhibition using two models (a voltage-based and a current-based integrate-and-fire model with instantaneous or temporally structured input), and we use analytic and computational tools to examine the bifurcations that occur and study the various possible monostable, bistable, and tristable regimes that can exist; we find that, depending on system parameters (and on choice of neuron model), there can exist up to 3 distinct monostable regimes (denoted M0, M1, M2), 3 distinct bistable regimes (denoted B, B1, B2), and a single tristable regime (denoted T)...
January 9, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29324850/generalization-of-the-ewens-sampling-formula-to-arbitrary-fitness-landscapes
#3
Pavel Khromov, Constantin D Malliaris, Alexandre V Morozov
In considering evolution of transcribed regions, regulatory sequences, and other genomic loci, we are often faced with a situation in which the number of allelic states greatly exceeds the size of the population. In this limit, the population eventually adopts a steady state characterized by mutation-selection-drift balance. Although new alleles continue to be explored through mutation, the statistics of the population, and in particular the probabilities of seeing specific allelic configurations in samples taken from the population, do not change with time...
2018: PloS One
https://www.readbyqxmd.com/read/29324456/targeted-knockdown-of-bone-morphogenetic-protein-signaling-within-neural-progenitors-protects-the-brain-and-improves-motor-function-following-postnatal-hypoxia-ischemia
#4
Robert W Dettman, Derin Birch, Augusta Fernando, John A Kessler, Maria L V Dizon
Hypoxic-ischemic injury (HI) to the neonatal human brain results in myelin loss that, in some children, can manifest as cerebral palsy. Previously, we had found that neuronal overexpression of the bone morphogenic protein (BMP) inhibitor noggin during development increased oligodendroglia and improved motor function in an experimental model of HI utilizing unilateral common carotid artery ligation followed by hypoxia. As BMPs are known to negatively regulate oligodendroglial fate specification of neural stem cells and alter differentiation of committed oligodendroglia, BMP signaling is likely an important mechanism leading to myelin loss...
January 12, 2018: Developmental Neuroscience
https://www.readbyqxmd.com/read/29322557/veni-vidi-vici-the-success-of-wtf-meiotic-drivers-in-fission-yeast
#5
José Fabricio López Hernández, Sarah E Zanders
Meiotic drivers are selfish DNA loci that can bias their own transmission into gametes. Due to their transmission advantages, meiotic drivers can spread in populations even if the drivers or linked variants decrease organismal fitness. Meiotic drive was first formally described in the 1950s and is thought to be a powerful force shaping eukaryotic genomes. Classic genetic analyses have detected the action of meiotic drivers in plants, filamentous fungi, insects, and vertebrates. Several of these drive systems have limited experimental tractability and relatively little is known about the molecular mechanisms of meiotic drive...
January 11, 2018: Yeast
https://www.readbyqxmd.com/read/29321270/phenotypes-can-be-robust-and-evolvable-if-mutations-have-non-local-effects-on-sequence-constraints
#6
Marcel Weiß, Sebastian E Ahnert
The mapping between biological genotypes and phenotypes plays an important role in evolution, and understanding the properties of this mapping is crucial to determine the outcome of evolutionary processes. One of the most striking properties observed in several genotype-phenotype (GP) maps is the positive correlation between the robustness and evolvability of phenotypes. This implies that a phenotype can be strongly robust against mutations and at the same time evolvable to a diverse range of alternative phenotypes...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29321164/kras-oncoprotein-expression-is-regulated-by-a-self-governing-eif5a-peak1-feed-forward-regulatory-loop
#7
Ken Fujimura, Huawei Wang, Felicia Watson, Richard L Klemke
There remains intense interest in tractable approaches to target or silence the KRAS oncoprotein as a rational therapeutic strategy to attack pancreatic adenocarcinoma (PDAC) and other cancers which overexpress it. Here we provide evidence that accumulation of the KRAS oncoprotein is controlled by a self-regulating feed-forward regulatory loop that utilizes a unique hypusinated isoform of the translation elongation factor eIF5A and the tyrosine kinase PEAK1. Oncogenic activation of KRAS increased eIF5A-PEAK1 translational signaling, which in turn facilitated increased KRAS protein synthesis...
January 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29320478/an-extracellular-network-of-arabidopsis-leucine-rich-repeat-receptor-kinases
#8
Elwira Smakowska-Luzan, G Adam Mott, Katarzyna Parys, Martin Stegmann, Timothy C Howton, Mehdi Layeghifard, Jana Neuhold, Anita Lehner, Jixiang Kong, Karin Grünwald, Natascha Weinberger, Santosh B Satbhai, Dominik Mayer, Wolfgang Busch, Mathias Madalinski, Peggy Stolt-Bergner, Nicholas J Provart, M Shahid Mukhtar, Cyril Zipfel, Darrell Desveaux, David S Guttman, Youssef Belkhadir
The cells of multicellular organisms receive extracellular signals using surface receptors. The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability. In plants, the discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions...
January 10, 2018: Nature
https://www.readbyqxmd.com/read/29320160/efforts-aimed-to-reduce-attrition-in-antimalarial-drug-discovery-a-systematic-evaluation-of-current-antimalarial-targets-portfolio
#9
María Jesus Chaparro, Felix Calderon, Pablo Castañeda, Elena Fernandez Alvaro, Raquel Gabarro, Francisco-Javier Gamo, María G Gómez-Lorenzo, Julio Martín, Esther Fernandez
Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (Artemisinin Combination Therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits...
January 10, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29318727/transformation-of-diplonema-papillatum-the-type-species-of-the-highly-diverse-and-abundant-marine-micro-eukaryotes-diplonemida-euglenozoa
#10
Binnypreet Kaur, Matus Valach, Priscila Peña-Diaz, Sandrine Moreira, Patrick J Keeling, Gertraud Burger, Julius Lukeš, Drahomíra Faktorová
Diplonema papillatum is the type species of diplonemids, which are among the most abundant and diverse heterotrophic micro-eukaryotes in the world's oceans. Diplonemids are also known for a unique form of post-transcriptional processing in mitochondria. However, the lack of reverse genetics methodologies in these protists has hampered elucidation of their cell and molecular biology. Here we report a protocol for D. papillatum transformation. We have identified several antibiotics to which D. papillatum is sensitive and thus are suitable selectable markers, and focus in particular on puromycin...
January 10, 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29315477/enrichment-of-high-affinity-subclasses-and-glycoforms-from-serum-derived-igg-using-fc%C3%AE-rs-as-affinity-ligands
#11
Boesch Aw, Kappel Jh, Mahan Ae, Chu Th, Crowley Ar, Osei-Owusu Ny, Alter G, Ackerman Me
As antibodies continue to gain predominance in drug discovery and development pipelines, efforts to control and optimize their activity in vivo have matured to incorporate sophisticated abilities to manipulate engagement of specific Fc binding partners. Such efforts to promote diverse functional outcomes include modulating IgG-Fc affinity for FcγRs to alternatively potentiate or reduce effector functions, such as antibody-dependent cellular cytotoxicity and phagocytosis. While a number of natural and engineered Fc features capable of eliciting variable effector functions have been demonstrated in vitro and in vivo, elucidation of these important functional relationships has taken significant effort through use of diverse genetic, cellular and enzymatic techniques...
January 8, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29314742/the-role-of-mass-spectrometry-and-proteogenomics-in-the-advancement-of-hla-epitope-prediction
#12
REVIEW
Amanda L Creech, Ying S Ting, Scott P Goulding, John Fk Sauld, Dominik Barthelme, Michael S Rooney, Terri A Addona, Jennifer G Abelin
A challenge in developing personalized cancer immunotherapies is the prediction of putative cancer-specific antigens. Currently, predictive algorithms are used to infer binding of peptides to human leukocyte antigen (HLA) heterodimers to aid in the selection of putative epitope targets. One drawback of current epitope prediction algorithms is that they are trained on datasets containing biochemical HLA-peptide binding data that may not completely capture the rules associated with endogenous processing and presentation...
January 3, 2018: Proteomics
https://www.readbyqxmd.com/read/29311327/functional-characterization-of-the-mucus-barrier-on-the-xenopus-tropicalis-skin-surface
#13
Eamon Dubaissi, Karine Rousseau, Gareth W Hughes, Caroline Ridley, Richard K Grencis, Ian S Roberts, David J Thornton
Mucosal surfaces represent critical routes for entry and exit of pathogens. As such, animals have evolved strategies to combat infection at these sites, in particular the production of mucus to prevent attachment and to promote subsequent movement of the mucus/microbe away from the underlying epithelial surface. Using biochemical, biophysical, and infection studies, we have investigated the host protective properties of the skin mucus barrier of the Xenopus tropicalis tadpole. Specifically, we have characterized the major structural component of the barrier and shown that it is a mucin glycoprotein (Otogelin-like or Otogl) with similar sequence, domain organization, and structural properties to human gel-forming mucins...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29303513/in-vitro-modeling-of-hepatocellular-carcinoma-molecular-subtypes-for-anti-cancer-drug-assessment
#14
Hadassa Hirschfield, C Billie Bian, Takaaki Higashi, Shigeki Nakagawa, Tizita Z Zeleke, Venugopalan D Nair, Bryan C Fuchs, Yujin Hoshida
Tractable experimental model that accounts for inter-tumor molecular heterogeneity is a key element of anti-cancer drug development. Hepatocellular carcinoma is known to exhibit highly heterogeneous molecular aberrations across the tumors, including somatic genetic and epigenetic alterations. Previous studies showed that molecular tumor subtypes determined by transcriptome, as a comprehensive functional readout, are reproducibly observed across global patient populations irrespective of geographic and etiological variations...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29297814/coagulation-assessment-underutilized-diagnostic-tools-in-zoo-and-aquatic-animal-medicine
#15
Trevor J Gerlach, Ashley Barratclough, Bobbi Conner
Veterinarians specializing in nondomestic species are faced with unique challenges regarding research and diagnostic capabilities given the wild and frequently dangerous nature of their patients. Standard diagnostic techniques used in small or large animal practice are not always possible due to anatomical constraints, size, tractability, or the inherent risk of anesthesia in highly valued, rare species. Diagnostic modalities that utilize simple, relatively noninvasive techniques show promise in evaluating nondomestic species and elucidating the pathophysiology behind poorly characterized disease processes in both wild and captive populations...
December 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/29296679/foot-force-models-of-crowd-dynamics-on-a-wobbly-bridge
#16
Igor Belykh, Russell Jeter, Vladimir Belykh
Modern pedestrian and suspension bridges are designed using industry standard packages, yet disastrous resonant vibrations are observed, necessitating multimillion dollar repairs. Recent examples include pedestrian-induced vibrations during the opening of the Solférino Bridge in Paris in 1999 and the increased bouncing of the Squibb Park Bridge in Brooklyn in 2014. The most prominent example of an unstable lively bridge is the London Millennium Bridge, which started wobbling as a result of pedestrian-bridge interactions...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29290392/mlh1-is-required-for-female-fertility-in-drosophila-melanogaster-an-outcome-of-effects-on-meiotic-crossing-over-ovarian-follicles-and-egg-activation
#17
Divya Vimal, Saurabh Kumar, Ashutosh Pandey, Divya Sharma, Sanjay Saini, Snigdha Gupta, Kristipati Ravi Ram, Debapratim Kar Chowdhuri
Mismatch repair (MMR) system, a conserved DNA repair pathway, plays crucial role in DNA recombination and is involved in gametogenesis. The impact of alterations in MMR family of proteins (bacterial MutS and MutL homologues) on mammalian fertility is well documented. However, an insight to the role of MMR in reproduction of non-mammalian organisms is limited. Hence, in the present study, we analysed the impact of mlh1 (a MutL homologue) on meiotic crossing over/recombination and fertility in a genetically tractable model, Drosophila melanogaster...
December 16, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29290388/drosophila-perpetuates-nutritional-mutualism-by-promoting-the-fitness-of-its-intestinal-symbiont-lactobacillus-plantarum
#18
Gilles Storelli, Maura Strigini, Théodore Grenier, Loan Bozonnet, Martin Schwarzer, Catherine Daniel, Renata Matos, François Leulier
Facultative animal-bacteria symbioses, which are critical determinants of animal fitness, are largely assumed to be mutualistic. However, whether commensal bacteria benefit from the association has not been rigorously assessed. Using a simple and tractable gnotobiotic model- Drosophila mono-associated with one of its dominant commensals, Lactobacillus plantarum-we reveal that in addition to benefiting animal growth, this facultative symbiosis has a positive impact on commensal bacteria fitness. We find that bacteria encounter a strong cost during gut transit, yet larvae-derived maintenance factors override this cost and increase bacterial population fitness, thus perpetuating symbiosis...
December 26, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29288462/primary-characterization-of-small-rnas-in-symbiotic-nitrogen-fixing-bacteria
#19
Marta Robledo, Natalia I García-Tomsig, José I Jiménez-Zurdo
High-throughput transcriptome profiling (RNAseq) has uncovered large and heterogeneous populations of small noncoding RNA species (sRNAs) with potential regulatory roles in bacteria. A large fraction of sRNAs are differentially regulated and rely on protein-assisted antisense interactions to trans-encoded target mRNAs to fine-tune posttranscriptional reprogramming of gene expression in response to external cues. However, annotation and function of sRNAs are still largely overlooked in nonmodel bacteria with complex lifestyles...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29286374/optical-screening-of-novel-bacteria-specific-probes-on-ex-vivo-human-lung-tissue-by-confocal-laser-endomicroscopy
#20
Bethany Mills, Ahsan R Akram, Emma Scholefield, Mark Bradley, Kevin Dhaliwal
Improving the speed and accuracy of bacterial detection is important for patient stratification and to ensure the appropriate use of antimicrobials. To achieve this goal, the development of diagnostic techniques to recognize bacterial presence in real-time at the point-of-care is required. Optical imaging for direct identification of bacteria within the host is an attractive approach. Several attempts at chemical probe design and validation have been investigated, however none have yet been successfully translated into the clinic...
November 29, 2017: Journal of Visualized Experiments: JoVE
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