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Taro Tezuka
A spike train kernel provides an effective way of decoding information represented by a spike train. Some spike train kernels have been extended to multineuron spike trains, which are simultaneously recorded spike trains obtained from multiple neurons. However, most of these multineuron extensions were carried out in a kernel-specific manner. In this paper, a general framework is proposed for extending any single-neuron spike train kernel to multineuron spike trains, based on the R-convolution kernel. Special subclasses of the proposed R-convolution linear combination kernel are explored...
March 6, 2018: Neural Networks: the Official Journal of the International Neural Network Society
I S Lvov, A A Grin', M A Nekrasov, A Yu Kordonskiy, A V Sytnik
Compression of the caudal medulla oblongata and ventral portions of the spinal cord is the most dangerous complication of atlanto-axial dislocation (AAD). AIM: The study objective was to improve surgical management of patients with ventral compression of the spinal cord in the setting of AAD of various genesis. MATERIAL AND METHODS: We analyzed treatment outcomes in 250 patients with C1 and C2 injuries and diseases for the period between 2002 and 2016. Persistent ventral compression of the neural structures in the setting of AAD was detected in 34 (13...
2018: Zhurnal Voprosy Neĭrokhirurgii Imeni N. N. Burdenko
Christina D Cota
Ascidians are increasingly being used as a system for investigating cell biology during development. The extreme genetic and cellular simplicity of ascidian embryos in combination with superior experimental tractability make this an ideal system for in vivo analysis of dynamic cellular processes. Transgenic approaches to cellular and sub-cellular analysis of ascidian development have begun to yield new insights into the mechanisms regulating developmental signaling and morphogenesis. This chapter focuses on the targeted expression of fusion proteins in ascidian embryos and how this technique is being deployed to garner new insights into the cell biology of development...
2018: Advances in Experimental Medicine and Biology
Stephen Smith, Neil Dalchau
Synthesizing a genetic network which generates stable Turing patterns is one of the great challenges of synthetic biology, but a significant obstacle is the disconnect between the mathematical theory and the biological reality. Current mathematical understanding of patterning is typically restricted to systems of two or three chemical species, for which equations are tractable. However, when models seek to combine descriptions of intercellular signal diffusion and intracellular biochemistry, plausible genetic networks can consist of dozens of interacting species...
March 2018: Journal of the Royal Society, Interface
Steven R Dolly, Yang Lou, Mark A Anastasio, Hua Li
It is widely known that the optimization of imaging systems based on objective, task-based measures of image quality via computer-simulation requires the use of a stochastic object model (SOM). However, the development of computationally tractable SOMs that can accurately model the statistical variations in human anatomy within a specified ensemble of patients remains a challenging task. Previously reported numerical anatomic models lack the ability to accurately model inter-patient and inter-organ variations in human anatomy among a broad patient population, mainly because they are established on image data corresponding to a few of patients and individual anatomic organs...
March 14, 2018: Physics in Medicine and Biology
Miri Shnayder, Aharon Nachshon, Benjamin Krishna, Emma Poole, Alina Boshkov, Amit Binyamin, Itay Maza, John Sinclair, Michal Schwartz, Noam Stern-Ginossar
Primary infection with human cytomegalovirus (HCMV) results in a lifelong infection due to its ability to establish latent infection, with one characterized viral reservoir being hematopoietic cells. Although reactivation from latency causes serious disease in immunocompromised individuals, our molecular understanding of latency is limited. Here, we delineate viral gene expression during natural HCMV persistent infection by analyzing the massive transcriptome RNA sequencing (RNA-seq) atlas generated by the Genotype-Tissue Expression (GTEx) project...
March 13, 2018: MBio
Rémi Patouret, Christelle Doebelin, Ruben D Garcia-Ordonez, Mi Ra Chang, Claudia Ruiz, Michael D Cameron, Patrick R Griffin, Theodore M Kamenecka
Crystallography has identified stearic acid, ALRT 1550 and ATRA as ligands that bind RORβ, however, none of these molecules represent good starting points to develop optimized small molecule modulators. Recently, Compound 1 was identified as a potent dual RORβ and RORγ inverse agonist with no activity towards RORα (Fig. 1). To our knowledge, this is one of only two small molecule RORβ inverse agonists identified in the primary literature from a tractable chemical series and represents an ideal starting point from which to design RORβ-selective modulators...
March 3, 2018: Bioorganic & Medicinal Chemistry Letters
Benjamin Kleeman, Andre Olsson, Tess Newkold, Matt Kofron, Monica DeLay, David Hildeman, H Leighton Grimes
The advent of facile genome engineering technologies has made the generation of knock-in gene-expression or fusion-protein reporters more tractable. Fluorescent protein labeling of specific genes combined with surface marker profiling can more specifically identify a cell population. However, the question of which fluorescent proteins to utilize to generate reporter constructs is made difficult by the number of candidate proteins and the lack of updated experimental data on newer fluorescent proteins. Compounding this problem, most fluorescent proteins are designed and tested for use in microscopy...
March 13, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Sathvik X Palakurty, John R Stinchcombe, Michelle E Afkhami
A mechanistic understanding of community ecology requires tackling the nonadditive effects of multispecies interactions, a challenge that necessitates integration of ecological and molecular complexity- namely moving beyond pairwise ecological interaction studies and the 'gene at a time' approach to mechanism. Here, we investigate the consequences of multispecies mutualisms for the structure and function of genome-wide differential coexpression networks for the first time, using the tractable and ecologically-important interaction between legume Medicago truncatula, rhizobia, and mycorrhizal fungi...
March 13, 2018: Molecular Ecology
Godwin Sokpor, Eman Abbas, Joachim Rosenbusch, Jochen F Staiger, Tran Tuoc
The postnatal mammalian olfactory epithelium (OE) represents a major aspect of the peripheral olfactory system. It is a pseudostratified tissue that originates from the olfactory placode and is composed of diverse cells, some of which are specialized receptor neurons capable of transducing odorant stimuli to afford the perception of smell (olfaction). The OE is known to offer a tractable miniature model for studying the systematic generation of neurons and glia that typify neural tissue development. During OE development, stem/progenitor cells that will become olfactory sensory neurons and/or non-neuronal cell types display fine spatiotemporal expression of neuronal and non-neuronal genes that ensures their proper proliferation, differentiation, survival, and regeneration...
March 12, 2018: Molecular Neurobiology
Radhika Bartaula, Arthur T O Melo, Bryan A Connolly, Yue Jin, Iago Hale
Stem rust, caused by Puccinia graminis (Pg), remains a devastating disease of wheat; and the emergence of new Pg races virulent on deployed resistance genes fuels the ongoing search for sources of durable resistance. Despite its intrinsic durability, non-host resistance (NHR) is largely unexplored as a protection strategy against Pg, partly due to the inherent challenge of developing a genetically tractable system within which NHR segregates. Here we demonstrate that Pg's far less-studied ancestral host, barberry (Berberis spp...
February 26, 2018: Journal of Experimental Botany
Christina Zarouchlioti, Beatriz Sanchez-Pintado, Nathaniel J Hafford Tear, Pontus Klein, Petra Liskova, Kalyan Dulla, Ma'ayan Semo, Anthony A Vugler, Kirithika Muthusamy, Lubica Dudakova, Hannah J Levis, Pavlina Skalicka, Pirro Hysi, Michael E Cheetham, Stephen J Tuft, Peter Adamson, Alison J Hardcastle, Alice E Davidson
Fuchs endothelial corneal dystrophy (FECD) is a common disease for which corneal transplantation is the only treatment option in advanced stages, and alternative treatment strategies are urgently required. Expansion (≥50 copies) of a non-coding trinucleotide repeat in TCF4 confers >76-fold risk for FECD in our large cohort of affected individuals. An FECD subject-derived corneal endothelial cell (CEC) model was developed to probe disease mechanism and investigate therapeutic approaches. The CEC model demonstrated that the repeat expansion leads to nuclear RNA foci, with the sequestration of splicing factor proteins (MBNL1 and MBNL2) to the foci and altered mRNA processing...
March 1, 2018: American Journal of Human Genetics
Orlando Contreras-López, Tomás C Moyano, Daniela C Soto, Rodrigo A Gutiérrez
The rapid increase in the availability of transcriptomics data generated by RNA sequencing represents both a challenge and an opportunity for biologists without bioinformatics training. The challenge is handling, integrating, and interpreting these data sets. The opportunity is to use this information to generate testable hypothesis to understand molecular mechanisms controlling gene expression and biological processes (Fig. 1). A successful strategy to generate tractable hypotheses from transcriptomics data has been to build undirected network graphs based on patterns of gene co-expression...
2018: Methods in Molecular Biology
Divya Sharma, Mahendra Pratap Singh, Divya Vimal, Saurabh Kumar, Rakesh Roshan Jha, D Kar Chowdhuri
Adaptive behaviour of an organism has relevance towards developing better resistance in subsequent generations following xenobiotic exposures. Using a genetically tractable and functional insect model, Drosophila melanogaster, we aimed to examine the resistance of the organism against repeated exposures of benzene, an industrial and environmental-chemical and a class I human carcinogen. While 100 mM benzene exposure to one-day old flies for seven days caused ∼95% mortality (F0), its exposure to subsequent generations of flies led a significant decrease in mortality with maximum survival (∼85%) as evident at F28 generation...
February 23, 2018: Chemosphere
Sinisa Vukovic, David J Huggins
Ligandability is a prerequisite for druggability and is a much easier concept to understand, model and predict because it does not depend on the complex pharmacodynamic and pharmacokinetic mechanisms in the human body. In this review, we consider a metric for quantifying ligandability from experimental data. We discuss ligandability in terms of the balance between effort and reward. The metric is evaluated for a standard set of well-studied drug targets - some traditionally considered to be ligandable and some regarded as difficult...
March 6, 2018: Drug Discovery Today
John W Hargrove, M Odwell Muzari, Sinead English
Theory suggests females should optimize resource allocation across reproductive bouts to maximize lifetime reproduction, balancing current and future reproductive efforts according to physiological state and projected survival and reproduction. Tests of these ideas focus on long-lived vertebrates: few measure age-related reproductive output in iteroparous invertebrates, or partition reserves between those allocated to offspring versus mothers. We investigated how maternal age, and environmental and physiological factors influence reproductive investment in wild tsetse, Glossina pallidipes Austen and G...
February 2018: Royal Society Open Science
Moritz Horn, Virginia Kroef, Kira Allmeroth, Nicole Schuller, Stephan Miethe, Martin Peifer, Josef M Penninger, Ulrich Elling, Martin S Denzel
Forward genetic screens in haploid mammalian cells have recently emerged as powerful tools for the discovery and investigation of recessive traits. Use of the haploid system provides unique genetic tractability and resolution. Upon positive selection, these screens typically employ analysis of loss-of-function (LOF) alleles and are thus limited to non-essential genes. Many relevant compounds, including anti-cancer therapeutics, however, target essential genes, precluding positive selection of LOF alleles. Here, we asked whether the use of random and saturating chemical mutagenesis might enable screens that identify essential biological targets of toxic compounds...
February 9, 2018: Oncotarget
Jessica Needham, Cory Merow, Chia-Hao Chang-Yang, Hal Caswell, Sean M McMahon
As population-level patterns of interest in forests emerge from individual vital rates, modelling forest dynamics requires making the link between the scales at which data are collected (individual stems) and the scales at which questions are asked (e.g. populations and communities). Structured population models (e.g. integral projection models (IPMs)) are useful tools for linking vital rates to population dynamics. However, the application of such models to forest trees remains challenging owing to features of tree life cycles, such as slow growth, long lifespan and lack of data on crucial ontogenic stages...
March 14, 2018: Proceedings. Biological Sciences
Michael D Deel, Katherine K Slemmons, Ashley R Hinson, Katia C Genadry, Breanne A Burgess, Lisa E S Crose, Nina Kuprasertkul, Kristianne M Oristian, Rex C Bentley, Corinne M Linardic
PURPOSE: Alveolar rhabdomyosarcoma (aRMS) is a childhood soft tissue sarcoma driven by the signature PAX3-FOXO1 (P3F) fusion gene. 5-year survival for aRMS is <50%, with no improvement in over four decades. Although the transcriptional co-activator TAZ is oncogenic in carcinomas, the role of TAZ in sarcomas is poorly understood. The aim of this study was to investigate the role of TAZ in P3F-aRMS tumorigenesis. EXPERIMENTAL DESIGN: After determining from public datasets that TAZ is upregulated in human aRMS transcriptomes, we evaluated whether TAZ is also upregulated in our myoblast-based model of P3F-initiated tumorigenesis, and performed IHC staining of 63 human aRMS samples from tissue microarrays...
March 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Katarína Bod'ová, Gabriel J Mitchell, Roy Harpaz, Elad Schneidman, Gašper Tkačik
Recent developments in automated tracking allow uninterrupted, high-resolution recording of animal trajectories, sometimes coupled with the identification of stereotyped changes of body pose or other behaviors of interest. Analysis and interpretation of such data represents a challenge: the timing of animal behaviors may be stochastic and modulated by kinematic variables, by the interaction with the environment or with the conspecifics within the animal group, and dependent on internal cognitive or behavioral state of the individual...
2018: PloS One
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