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https://www.readbyqxmd.com/read/28107672/a-computational-model-of-conditioning-inspired-by-drosophila-olfactory-system
#1
Faramarz Faghihi, Ahmed A Moustafa, Ralf Heinrich, Florentin Wörgötter
Recent studies have demonstrated that Drosophila melanogaster (briefly Drosophila) can successfully perform higher cognitive processes including second order olfactory conditioning. Understanding the neural mechanism of this behavior can help neuroscientists to unravel the principles of information processing in complex neural systems (e.g. the human brain) and to create efficient and robust robotic systems. In this work, we have developed a biologically-inspired spiking neural network which is able to execute both first and second order conditioning...
November 23, 2016: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/28107624/tocilizumab-alendronate-conjugate-for-treatment-of-rheumatoid-arthritis
#2
Hwiwon Lee, Suk Ho Bhang, Jeong Ho Lee, Hyemin Kim, Sei Kwang Hahn
An autoimmune disease of rheumatoid arthritis (RA) causes severe inflammation on the synovial membrane, which results in the destruction of articular cartilage and bone. Here, Tocilizumab (TCZ) - Alendronate (ALD) conjugate is synthesized for the early intervention of RA. A humanized monoclonal antibody of TCZ shows an immunosuppressive effect, targeting interleukin-6 (IL-6) receptor in the RA pathogenesis. ALD is an anti-inflammatory bisphosphonate drug which can bind to the exposed bone surface. ALD is conjugated selectively to N-glycan on Fc region of TCZ using a chemical linker of 3-(2-pyridyldithio) propionyl hydrazide (PDPH) - poly(ethylene glycol) - N-hydroxysuccinimide (PDPH-PEG-NHS)...
January 20, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28107392/upon-accounting-for-the-impact-of-isoenzyme-loss-gene-deletion-costs-anticorrelate-with-their-evolutionary-rates
#3
Christopher Jacobs, Luke Lambourne, Yu Xia, Daniel Segrè
System-level metabolic network models enable the computation of growth and metabolic phenotypes from an organism's genome. In particular, flux balance approaches have been used to estimate the contribution of individual metabolic genes to organismal fitness, offering the opportunity to test whether such contributions carry information about the evolutionary pressure on the corresponding genes. Previous failure to identify the expected negative correlation between such computed gene-loss cost and sequence-derived evolutionary rates in Saccharomyces cerevisiae has been ascribed to a real biological gap between a gene's fitness contribution to an organism "here and now" and the same gene's historical importance as evidenced by its accumulated mutations over millions of years of evolution...
2017: PloS One
https://www.readbyqxmd.com/read/28107341/complex-dynamics-of-virus-spread-from-low-infection-multiplicities-implications-for-the-spread-of-oncolytic-viruses
#4
Ignacio A Rodriguez-Brenes, Andrew Hofacre, Hung Fan, Dominik Wodarz
While virus growth dynamics have been well-characterized in several infections, data are typically collected once the virus population becomes easily detectable. Earlier dynamics, however, remain less understood. We recently reported unusual early dynamics in an experimental system using adenovirus infection of human embryonic kidney (293) cells. Under identical experimental conditions, inoculation at low infection multiplicities resulted in either robust spread, or in limited spread that eventually stalled, with both outcomes occurring with approximately equal frequencies...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28106223/next-generation-of-network-medicine-interdisciplinary-signaling-approaches
#5
REVIEW
Tamas Korcsmaros, Maria Victoria Schneider, Giulio Superti-Furga
In the last decade, network approaches have transformed our understanding of biological systems. Network analyses and visualizations have allowed us to identify essential molecules and modules in biological systems, and improved our understanding of how changes in cellular processes can lead to complex diseases, such as cancer, infectious and neurodegenerative diseases. "Network medicine" involves unbiased large-scale network-based analyses of diverse data describing interactions between genes, diseases, phenotypes, drug targets, drug transport, drug side-effects, disease trajectories and more...
January 20, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28105958/dmirnet-inferring-direct-microrna-mrna-association-networks
#6
Minsu Lee, HyungJune Lee
BACKGROUND: MicroRNAs (miRNAs) play important regulatory roles in the wide range of biological processes by inducing target mRNA degradation or translational repression. Based on the correlation between expression profiles of a miRNA and its target mRNA, various computational methods have previously been proposed to identify miRNA-mRNA association networks by incorporating the matched miRNA and mRNA expression profiles. However, there remain three major issues to be resolved in the conventional computation approaches for inferring miRNA-mRNA association networks from expression profiles...
December 5, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/28105918/mirnacle-machine-learning-with-smote-and-random-forest-for-improving-selectivity-in-pre-mirna-ab-initio-prediction
#7
Yuri Bento Marques, Alcione de Paiva Oliveira, Ana Tereza Ribeiro Vasconcelos, Fabio Ribeiro Cerqueira
BACKGROUND: MicroRNAs (miRNAs) are key gene expression regulators in plants and animals. Therefore, miRNAs are involved in several biological processes, making the study of these molecules one of the most relevant topics of molecular biology nowadays. However, characterizing miRNAs in vivo is still a complex task. As a consequence, in silico methods have been developed to predict miRNA loci. A common ab initio strategy to find miRNAs in genomic data is to search for sequences that can fold into the typical hairpin structure of miRNA precursors (pre-miRNAs)...
December 15, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28105915/spectral-consensus-strategy-for-accurate-reconstruction-of-large-biological-networks
#8
Séverine Affeldt, Nataliya Sokolovska, Edi Prifti, Jean-Daniel Zucker
BACKGROUND: The last decades witnessed an explosion of large-scale biological datasets whose analyses require the continuous development of innovative algorithms. Many of these high-dimensional datasets are related to large biological networks with few or no experimentally proven interactions. A striking example lies in the recent gut bacterial studies that provided researchers with a plethora of information sources. Despite a deeper knowledge of microbiome composition, inferring bacterial interactions remains a critical step that encounters significant issues, due in particular to high-dimensional settings, unknown gut bacterial taxa and unavoidable noise in sparse datasets...
December 13, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28103917/a-fast-and-robust-protocol-for-metataxonomic-analysis-using-rnaseq-data
#9
Jeremy W Cox, Richard A Ballweg, Diana H Taft, Prakash Velayutham, David B Haslam, Aleksey Porollo
BACKGROUND: Metagenomics is a rapidly emerging field aimed to analyze microbial diversity and dynamics by studying the genomic content of the microbiota. Metataxonomics tools analyze high-throughput sequencing data, primarily from 16S rRNA gene sequencing and DNAseq, to identify microorganisms and viruses within a complex mixture. With the growing demand for analysis of the functional microbiome, metatranscriptome studies attract more interest. To make metatranscriptomic data sufficient for metataxonomics, new analytical workflows are needed to deal with sparse and taxonomically less informative sequencing data...
January 19, 2017: Microbiome
https://www.readbyqxmd.com/read/28103880/the-use-of-genome-scale-metabolic-network-reconstruction-to-predict-fluxes-and-equilibrium-composition-of-n-fixing-versus-c-fixing-cells-in-a-diazotrophic-cyanobacterium-trichodesmium-erythraeum
#10
Joseph J Gardner, Nanette R Boyle
BACKGROUND: Computational, genome based predictions of organism phenotypes has enhanced the ability to investigate the biological phenomena that help organisms survive and respond to their environments. In this study, we have created the first genome-scale metabolic network reconstruction of the nitrogen fixing cyanobacterium T. erythraeum and used genome-scale modeling approaches to investigate carbon and nitrogen fluxes as well as growth and equilibrium population composition. RESULTS: We created a genome-scale reconstruction of T...
January 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28103803/variational-inference-for-rare-variant-detection-in-deep-heterogeneous-next-generation-sequencing-data
#11
Fan Zhang, Patrick Flaherty
BACKGROUND: The detection of rare single nucleotide variants (SNVs) is important for understanding genetic heterogeneity using next-generation sequencing (NGS) data. Various computational algorithms have been proposed to detect variants at the single nucleotide level in mixed samples. Yet, the noise inherent in the biological processes involved in NGS technology necessitates the development of statistically accurate methods to identify true rare variants. RESULTS: We propose a Bayesian statistical model and a variational expectation maximization (EM) algorithm to estimate non-reference allele frequency (NRAF) and identify SNVs in heterogeneous cell populations...
January 19, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28103780/a-random-forest-induced-distance-based-measure-of-physiological-dysregulation
#12
Ghalib Ayodeji Bello, Gerard Dumancas
Aging involves gradual, multisystemic physiological dysregulation and over time, this degenerative process increases an individual's risk for multiple age-related comorbidities. The ability to quantify age-related physiological dysregulation can provide key insights into the biological mechanisms underlying the aging process and facilitate the development of clinical interventions. Recent studies have introduced and validated a measure of physiological dysregulation based on statistical distance. This measure quantifies the extent of physiological dysregulation in an individual by measuring how much the individual's biomarker profile deviates from the expected average...
January 17, 2017: Current Aging Science
https://www.readbyqxmd.com/read/28103710/radiography-and-abdominal-ct-compared-with-sacroiliac-joint-ct-in-the-diagnosis-of-sacroiliitis
#13
Julian Melchior, Yusef Azraq, Isabelle Chary-Valckenaere, Anne-Christine Rat, Pedro Texeira, Alain Blum, Damien Loeuille
Background The presence of structural sacroiliitis is strong evidence for the diagnosis of spondyloarthritis (SpA). Purpose To assess the performance of abdominal computed tomography (CT) and pelvic plain radiography for the diagnosis of structural sacroiliitis compared with sacroiliac CT (SI joint CT) considered the reference technique in patients with SpA. Material and Methods All SpA patients eligible for biologic treatment were selected from 2005 to 2012. An assessment of sacroiliitis was based on radiography according to the modified New York criteria and on abdominal CT and SI joint CT scans depending on the presence of erosion on at least two consecutive slices...
January 1, 2017: Acta Radiologica
https://www.readbyqxmd.com/read/28103228/human-specific-cortical-synaptic-connections-and-their-plasticity-is-that-what-makes-us-human
#14
Joana Lourenço, Alberto Bacci
One outstanding difference between Homo sapiens and other mammals is the ability to perform highly complex cognitive tasks and behaviors, such as language, abstract thinking, and cultural diversity. How is this accomplished? According to one prominent theory, cognitive complexity is proportional to the repetition of specific computational modules over a large surface expansion of the cerebral cortex (neocortex). However, the human neocortex was shown to also possess unique features at the cellular and synaptic levels, raising the possibility that expanding the computational module is not the only mechanism underlying complex thinking...
January 2017: PLoS Biology
https://www.readbyqxmd.com/read/28102759/antisense-transcription-of-the-myotonic-dystrophy-locus-yields-low-abundant-rnas-with-and-without-cag-n-repeat
#15
Anke E E G Gudde, Simon J van Heeringen, Amanda I de Oude, Ingeborg D G van Kessel, Joseph Estabrook, Eric T Wang, Bé Wieringa, Derick G Wansink
The unstable (CTG·CAG)n trinucleotide repeat in the myotonic dystrophy type 1 (DM1) locus is bidirectionally transcribed from genes with terminal overlap. By transcription in the sense direction, the DMPK gene produces various alternatively spliced mRNAs with a (CUG)n repeat in their 3' UTR. Expression in opposite orientation reportedly yields (CAG)n-repeat containing RNA, but both structure and biological significance of this antisense gene (DM1-AS) are largely unknown. Via a combinatorial approach of computational and experimental analyses of RNA from unaffected individuals and DM1 patients we discovered that DM1-AS spans >6 kb, contains alternative transcription start sites and uses alternative polyadenylation sites up- and downstream of the (CAG)n repeat...
January 19, 2017: RNA Biology
https://www.readbyqxmd.com/read/28102262/scaling-single-cell-genomics-from-phenomenology-to-mechanism
#16
Amos Tanay, Aviv Regev
Three of the most fundamental questions in biology are how individual cells differentiate to form tissues, how tissues function in a coordinated and flexible fashion and which gene regulatory mechanisms support these processes. Single-cell genomics is opening up new ways to tackle these questions by combining the comprehensive nature of genomics with the microscopic resolution that is required to describe complex multicellular systems. Initial single-cell genomic studies provided a remarkably rich phenomenology of heterogeneous cellular states, but transforming observational studies into models of dynamics and causal mechanisms in tissues poses fresh challenges and requires stronger integration of theoretical, computational and experimental frameworks...
January 18, 2017: Nature
https://www.readbyqxmd.com/read/28101869/fibrin-formation-structure-and-properties
#17
John W Weisel, Rustem I Litvinov
Fibrinogen and fibrin are essential for hemostasis and are major factors in thrombosis, wound healing, and several other biological functions and pathological conditions. The X-ray crystallographic structure of major parts of fibrin(ogen), together with computational reconstructions of missing portions and numerous biochemical and biophysical studies, have provided a wealth of data to interpret molecular mechanisms of fibrin formation, its organization, and properties. On cleavage of fibrinopeptides by thrombin, fibrinogen is converted to fibrin monomers, which interact via knobs exposed by fibrinopeptide removal in the central region, with holes always exposed at the ends of the molecules...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101860/the-structure-and-topology-of-%C3%AE-helical-coiled-coils
#18
Andrei N Lupas, Jens Bassler, Stanislaw Dunin-Horkawicz
α-Helical coiled coils constitute one of the most diverse folds yet described. They range in length over two orders of magnitude; they form rods, segmented ropes, barrels, funnels, sheets, spirals, and rings, which encompass anywhere from two to more than 20 helices in parallel or antiparallel orientation; they assume different helix crossing angles, degrees of supercoiling, and packing geometries. This structural diversity supports a wide range of biological functions, allowing them to form mechanically rigid structures, provide levers for molecular motors, project domains across large distances, mediate oligomerization, transduce conformational changes and facilitate the transport of other molecules...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101858/coiled-coil-design-updated-and-upgraded
#19
Derek N Woolfson
α-Helical coiled coils are ubiquitous protein-folding and protein-interaction domains in which two or more α-helical chains come together to form bundles. Through a combination of bioinformatics analysis of many thousands of natural coiled-coil sequences and structures, plus empirical protein engineering and design studies, there is now a deep understanding of the sequence-to-structure relationships for this class of protein architecture. This has led to considerable success in rational design and what might be termed in biro de novo design of simple coiled coils, which include homo- and hetero-meric parallel dimers, trimers and tetramers...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28101733/3d-absorbed-dose-distribution-estimated-by-monte-carlo-simulation-in-radionuclide-therapy-with-a-monoclonal-antibody-targeting-synovial-sarcoma
#20
David Sarrut, Jean-Noël Badel, Adrien Halty, Gwenaelle Garin, David Perol, Philippe Cassier, Jean-Yves Blay, David Kryza, Anne-Laure Giraudet
BACKROUND: Radiolabeled OTSA101, a monoclonal antibody targeting synovial sarcoma (SS) developed by OncoTherapy Science, was used to treat relapsing SS metastases following a theranostic procedure: in case of significant (111)In-OTSA101 tumor uptake and favorable biodistribution, patient was randomly treated with 370/1110 MBq (90)Y-OTSA101. Monte Carlo-based 3D dosimetry integrating time-activity curves in VOI was performed on (111)In-OTSA101 repeated SPECT/CT. Estimated absorbed doses (AD) in normal tissues were compared to biological side effects and to the admitted maximal tolerated absorbed dose (MTD) in normal organs...
December 2017: EJNMMI Physics
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