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https://www.readbyqxmd.com/read/28440342/significant-variation-between-snp-based-hla-imputations-in-diverse-populations-the-last-mile-is-the-hardest
#1
D J Pappas, A Lizee, V Paunic, K R Beutner, A Motyer, D Vukcevic, S Leslie, J Biesiada, J Meller, K D Taylor, X Zheng, L P Zhao, P-A Gourraud, J A Hollenbach, S J Mack, M Maiers
Four single nucleotide polymorphism (SNP)-based human leukocyte antigen (HLA) imputation methods (e-HLA, HIBAG, HLA*IMP:02 and MAGPrediction) were trained using 1000 Genomes SNP and HLA genotypes and assessed for their ability to accurately impute molecular HLA-A, -B, -C and -DRB1 genotypes in the Human Genome Diversity Project cell panel. Imputation concordance was high (>89%) across all methods for both HLA-A and HLA-C, but HLA-B and HLA-DRB1 proved generally difficult to impute. Overall, <27.8% of subjects were correctly imputed for all HLA loci by any method...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28440278/an-insider-s-perspective-bacteroides-as-a-window-into-the-microbiome
#2
REVIEW
Aaron G Wexler, Andrew L Goodman
Over the last decade, our appreciation for the contribution of resident gut microorganisms-the gut microbiota-to human health has surged. However, progress is limited by the sheer diversity and complexity of these microbial communities. Compounding the challenge, the majority of our commensal microorganisms are not close relatives of Escherichia coli or other model organisms and have eluded culturing and manipulation in the laboratory. In this Review, we discuss how over a century of study of the readily cultured, genetically tractable human gut Bacteroides has revealed important insights into the biochemistry, genomics and ecology that make a gut bacterium a gut bacterium...
April 25, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28439228/from-engrams-to-pathologies-of-the-brain
#3
REVIEW
Christine A Denny, Evan Lebois, Steve Ramirez
Memories are the experiential threads that tie our past to the present. The biological realization of a memory is termed an engram-the enduring biochemical and physiological processes that enable learning and retrieval. The past decade has witnessed an explosion of engram research that suggests we are closing in on boundary conditions for what qualifies as the physical manifestation of memory. In this review, we provide a brief history of engram research, followed by an overview of the many rodent models available to probe memory with intersectional strategies that have yielded unprecedented spatial and temporal resolution over defined sets of cells...
2017: Frontiers in Neural Circuits
https://www.readbyqxmd.com/read/28437436/intrinsically-generated-fluctuating-activity-in-excitatory-inhibitory-networks
#4
Francesca Mastrogiuseppe, Srdjan Ostojic
Recurrent networks of non-linear units display a variety of dynamical regimes depending on the structure of their synaptic connectivity. A particularly remarkable phenomenon is the appearance of strongly fluctuating, chaotic activity in networks of deterministic, but randomly connected rate units. How this type of intrinsically generated fluctuations appears in more realistic networks of spiking neurons has been a long standing question. To ease the comparison between rate and spiking networks, recent works investigated the dynamical regimes of randomly-connected rate networks with segregated excitatory and inhibitory populations, and firing rates constrained to be positive...
April 24, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28435104/drosophila-pink1-and-parkin-loss-of-function-mutants-display-a-range-of-non-motor-parkinson-s-disease-phenotypes
#5
Hannah Julienne, Edgar Buhl, David S Leslie, James J L Hodge
Parkinson's disease (PD) is more commonly associated with its motor symptoms and the related degeneration of dopamine (DA) neurons. However, it is becoming increasingly clear that PD patients also display a wide range of non-motor symptoms, including memory deficits and disruptions of their sleep-wake cycles. These have a large impact on their quality of life, and often precede the onset of motor symptoms, but their etiology is poorly understood. The fruit fly Drosophila has already been successfully used to model PD, and has been used extensively to study relevant non-motor behaviours in other contexts, but little attention has yet been paid to modelling non-motor symptoms of PD in this genetically tractable organism...
April 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28433665/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#6
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart Lung Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
April 19, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28431245/host-microbe-co-metabolism-dictates-cancer-drug-efficacy-in-c-%C3%A2-elegans
#7
Timothy A Scott, Leonor M Quintaneiro, Povilas Norvaisas, Prudence P Lui, Matthew P Wilson, Kit-Yi Leung, Lucia Herrera-Dominguez, Sonia Sudiwala, Alberto Pessia, Peter T Clayton, Kevin Bryson, Vidya Velagapudi, Philippa B Mills, Athanasios Typas, Nicholas D E Greene, Filipe Cabreiro
Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed three-way high-throughput screens that unraveled the complexity underlying host-microbe-drug interactions. We report that microbes can bolster or suppress the effects of fluoropyrimidines through metabolic drug interconversion involving bacterial vitamin B6, B9, and ribonucleotide metabolism...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28429742/crossing-lines-a-multidisciplinary-framework-for-assessing-connectivity-of-hammerhead-sharks-across-jurisdictional-boundaries
#8
A Chin, C A Simpfendorfer, W T White, G J Johnson, R B McAuley, M R Heupel
Conservation and management of migratory species can be complex and challenging. International agreements such as the Convention on Migratory Species (CMS) provide policy frameworks, but assessments and management can be hampered by lack of data and tractable mechanisms to integrate disparate datasets. An assessment of scalloped (Sphyrna lewini) and great (Sphyrna mokarran) hammerhead population structure and connectivity across northern Australia, Indonesia and Papua New Guinea (PNG) was conducted to inform management responses to CMS and Convention on International Trade in Endangered Species listings of these species...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428271/master-transcriptional-regulators-in-cancer-discovery-via-reverse-engineering-approaches-and-subsequent-validation
#9
REVIEW
Bruce Moran, Arman Rahman, Katja Palonen, Fiona T Lanigan, William M Gallagher
Reverse engineering of transcriptional networks using gene expression data enables identification of genes that underpin the development and progression of different cancers. Methods to this end have been available for over a decade and, with a critical mass of transcriptomic data in the oncology arena having been reached, they are ever more applicable. Extensive and complex networks can be distilled into a small set of key master transcriptional regulators (MTR), genes that are very highly connected and have been shown to be involved in processes of known importance in disease...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28422687/theoretical-limits-on-multiuser-molecular-communication-in-internet-of-nano-bio-things
#10
Ergin Dinc, Ozgur B Akan
In nano-bio networks, multiple transmitter-receiver pairs will operate in the same medium. Both inter-symbol interference and multi-user interference can cause saturation at the receiver side, and this effect may cause an outage. Thus, we propose a tractable framework to calculate the theoretical operating points for fully absorbing receiver.
April 12, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28419219/dna-remodelling-by-strict-partial-endoreplication-in-orchids-an-original-process-in-the-plant-kingdom
#11
Spencer C Brown, Mickaël Bourge, Nicolas Maunoury, Maurice Wong, Michele Wolfe Bianchi, Sandra Lepers-Andrzejewski, Pascale Besse, Sonja Siljak-Yakovlev, Michel Dron, Béatrice Satiat-Jeunemaître
DNA remodelling during endoreplication appears to be a strong developmental characteristic in orchids. In this study, we analysed DNA content and nuclei in 41 species of orchids to further map the genome evolution in this plant family. We demonstrate that the DNA remodelling observed in 36 out of 41 orchids studied corresponds to strict partial endoreplication. Such process is developmentally regulated in each wild species studied. Cytometry data analyses allowed us to propose a model where nuclear states 2C, 4E, 8E, etc...
April 13, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28418626/degradation-of-the-baf-complex-factor-brd9-by-heterobifunctional-ligands
#12
David Remillard, Dennis L Buckley, Joshiawa Paulk, Gerard L Brien, Matthew Sonnett, Hyuk-Soo Seo, Shiva Dastierdi, Martin Wühr, Sirano Dhe-Paganon, Scott A Armstrong, James E Bradner
The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex...
April 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28416630/common-microbehavioral-footprint-of-two-distinct-classes-of-conditioned-aversion
#13
Emmanouil Paisios, Annabell Rjosk, Evren Pamir, Michael Schleyer
Avoiding unfavorable situations is a vital skill and a constant task for any animal. Situations can be unfavorable because they feature something that the animal wants to escape from, or because they do not feature something that it seeks to obtain. We investigate whether the microbehavioral mechanisms by which these two classes of aversion come about are shared or distinct. We find that larval Drosophila avoid odors either previously associated with a punishment, or previously associated with the lack of a reward...
May 2017: Learning & Memory
https://www.readbyqxmd.com/read/28415348/delineating-parameter-unidentifiabilities-in-complex-models
#14
Dhruva V Raman, James Anderson, Antonis Papachristodoulou
Scientists use mathematical modeling as a tool for understanding and predicting the properties of complex physical systems. In highly parametrized models there often exist relationships between parameters over which model predictions are identical, or nearly identical. These are known as structural or practical unidentifiabilities, respectively. They are hard to diagnose and make reliable parameter estimation from data impossible. They furthermore imply the existence of an underlying model simplification. We describe a scalable method for detecting unidentifiabilities, as well as the functional relations defining them, for generic models...
March 2017: Physical Review. E
https://www.readbyqxmd.com/read/28414310/autophagy-supports-generation-of-cells-with-high-cd44-expression-via-modulation-of-oxidative-stress-and-parkin-mediated-mitochondrial-clearance
#15
K A Whelan, P M Chandramouleeswaran, K Tanaka, M Natsuizaka, M Guha, S Srinivasan, D S Darling, Y Kita, S Natsugoe, J D Winkler, A J Klein-Szanto, R K Amaravadi, N G Avadhani, A K Rustgi, H Nakagawa
High CD44 expression is associated with enhanced malignant potential in esophageal squamous cell carcinoma (ESCC), among the deadliest of all human carcinomas. Although alterations in autophagy and CD44 expression are associated with poor patient outcomes in various cancer types, the relationship between autophagy and cells with high CD44 expression remains incompletely understood. In transformed oesophageal keratinocytes, CD44(Low)-CD24(High) (CD44L) cells give rise to CD44(High)-CD24(-/Low) (CD44H) cells via epithelial-mesenchymal transition (EMT) in response to transforming growth factor (TGF)-β...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28413160/interaction-between-familial-transmission-and-a-constitutively-active-immune-system-shapes-gut-microbiota-in-drosophila-melanogaster
#16
Rupal Mistry, Ilias Kounatidis, Petros Ligoxygakis
Resident gut bacteria are constantly influencing the immune system. Yet the role of the immune system in shaping microbiota composition during an organism's lifespan has remained unclear. Experiments in mice have been inconclusive due to differences in husbandry schemes that led to conflicting results. We used Drosophila as a genetically tractable system with simpler gut bacterial population structure and streamlined genetic backgrounds and established cross schemes to address this issue. We found that depending on their genetic background, young flies had microbiota of different diversities that converged with age to the same Acetobacteraceae-dominated pattern in healthy flies...
April 16, 2017: Genetics
https://www.readbyqxmd.com/read/28412935/fitness-costs-of-symbiont-switching-using-entomopathogenic-nematodes-as-a-model
#17
John G McMullen, Brittany F Peterson, Steven Forst, Heidi Goodrich Blair, S Patricia Stock
BACKGROUND: Steinernematid nematodes form obligate symbioses with bacteria from the genus Xenorhabdus. Together Steinernema nematodes and their bacterial symbionts successfully infect, kill, utilize, and exit their insect hosts. During this process the nematodes and bacteria disassociate requiring them to re-associate before emerging from the host. This interaction can be complicated when two different nematodes co-infect an insect host. RESULTS: Non-cognate nematode-bacteria pairings result in reductions for multiple measures of success, including total progeny production and virulence...
April 17, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28411849/the-molecular-revolution-in-cutaneous-biology-keratin-genes-and-their-associated-disease-diversity-opportunities-and-challenges
#18
REVIEW
Pierre A Coulombe
The abundance of keratin proteins and the filaments they form in surface epithelia has long been appreciated. This said, the remarkable diversity of keratin proteins and the notion that they are encoded by one of the largest gene families in the human genome has come to the fore relatively recently, coinciding with the sequencing of whole genomes. This complexity has generated some practical challenges, notably in terms of nomenclature and tractability. More importantly, however, studies of keratin have seeded the discovery of the genetic basis for a large number of genodermatoses and continue to provide a unique perspective on and insight into epithelial cells and tissues, whether normal or diseased...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28411024/epcam-controls-morphogenetic-programs-during-zebrafish-pronephros-development
#19
Sebastian Kuechlin, Maximilian Schoels, Krasimir Slanchev, Silke Lassmann, Gerd Walz, Toma A Yakulov
Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is dynamically expressed in human and murine renal epithelia during development. The levels of EpCAM in the renal epithelium are upregulated both during regeneration after ischemia/reperfusion injury and in renal-derived carcinomas. The role of EpCAM in early kidney development, however, has remained unclear. The zebrafish pronephros shows a similar segmentation pattern to the mammalian metanephric nephron, and has recently emerged as a tractable model to study the regulatory programs governing early nephrogenesis...
April 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28408787/isotropy-of-angular-frequencies-and-weak-chimeras-with-broken-symmetry
#20
Christian Bick
The notion of a weak chimeras provides a tractable definition for chimera states in networks of finitely many phase oscillators. Here, we generalize the definition of a weak chimera to a more general class of equivariant dynamical systems by characterizing solutions in terms of the isotropy of their angular frequency vector-for coupled phase oscillators the angular frequency vector is given by the average of the vector field along a trajectory. Symmetries of solutions automatically imply angular frequency synchronization...
2017: J Nonlinear Sci
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