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Biology Direct

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https://www.readbyqxmd.com/read/28103906/thermodynamic-and-kinetic-stability-of-the-josephin-domain-closed-arrangement-evidences-from-replica-exchange-molecular-dynamics
#1
Gianvito Grasso, Jack A Tuszynski, Umberto Morbiducci, Ginevra Licandro, Andrea Danani, Marco A Deriu
BACKGROUND: Molecular phenomena driving pathological aggregation in neurodegenerative diseases are not completely understood yet. Peculiar is the case of Spinocerebellar Ataxia 3 (SCA3) where the conformational properties of the AT-3 N-terminal region, also called Josephin Domain (JD), play a key role in the first step of aggregation, having the JD an amyloidogenic propensity itself. For this reason, unraveling the intimate relationship between JD structural features and aggregation tendency may lead to a step forward in understanding the pathology and rationally design a cure...
January 19, 2017: Biology Direct
https://www.readbyqxmd.com/read/28095902/identification-of-positive-selection-in-genes-is-greatly-improved-by-using-experimentally-informed-site-specific-models
#2
Jesse D Bloom
BACKGROUND: Sites of positive selection are identified by comparing observed evolutionary patterns to those expected under a null model for evolution in the absence of such selection. For protein-coding genes, the most common null model is that nonsynonymous and synonymous mutations fix at equal rates; this unrealistic model has limited power to detect many interesting forms of selection. RESULTS: I describe a new approach that uses a null model based on experimental measurements of a gene's site-specific amino-acid preferences generated by deep mutational scanning in the lab...
January 17, 2017: Biology Direct
https://www.readbyqxmd.com/read/28031045/expansion-of-the-molecular-and-morphological-diversity-of-acanthamoebidae-centramoebida-amoebozoa-and-identification-of-a-novel-life-cycle-type-within-the-group
#3
Alexander K Tice, Lora L Shadwick, Anna Maria Fiore-Donno, Stefan Geisen, Seungho Kang, Gabriel A Schuler, Frederick W Spiegel, Katherine A Wilkinson, Michael Bonkowski, Kenneth Dumack, Daniel J G Lahr, Eckhard Voelcker, Steffen Clauß, Junling Zhang, Matthew W Brown
BACKGROUND: Acanthamoebidae is a "family" level amoebozoan group composed of the genera Acanthamoeba, Protacanthamoeba, and very recently Luapeleamoeba. This clade of amoebozoans has received considerable attention from the broader scientific community as Acanthamoeba spp. represent both model organisms and human pathogens. While the classical composition of the group (Acanthamoeba + Protacanthamoeba) has been well accepted due to the morphological and ultrastructural similarities of its members, the Acanthamoebidae has never been highly statistically supported in single gene phylogenetic reconstructions of Amoebozoa either by maximum likelihood (ML) or Bayesian analyses...
December 28, 2016: Biology Direct
https://www.readbyqxmd.com/read/27993167/prognostic-value-of-cross-omics-screening-for-kidney-clear-cell-renal-cancer-survival
#4
Slavica Dimitrieva, Ralph Schlapbach, Hubert Rehrauer
BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is a type of cancer that is resistant to chemotherapy and radiotherapy and has limited treatment possibilities. Large-scale molecular profiling of KIRC tumors offers a great potential to uncover the genetic and epigenetic changes underlying this disease and to improve the clinical management of KIRC patients. However, in practice the clinicians and researchers typically focus on single-platform molecular data or on a small set of genes...
December 20, 2016: Biology Direct
https://www.readbyqxmd.com/read/27993158/inter-platform-concordance-of-gene-expression-data-for-the-prediction-of-chemical-mode-of-action
#5
Chathura Siriwardhana, Susmita Datta, Somnath Datta
BACKGROUND: It is interesting to study the consistency of outcomes arising from two genomic platforms: Microarray and RNAseq, which are established on fundamentally different technologies. This topic has been frequently discussed from the prospect of comparing differentially expressed genes (DEGs). In this study, we explore the inter-platform concordance between microarray and RNASeq in their ability to classify samples based on genomic information. We use a set of 7 standard multi-class classifiers and an adaptive ensemble classifier developed around them to predict Chemical Modes of Actions (MOA) of data profiled by microarray and RNASeq platforms from Rat Liver samples exposed to a variety of chemical compounds...
December 20, 2016: Biology Direct
https://www.readbyqxmd.com/read/27993156/sensitivity-specificity-and-reproducibility-of-rna-seq-differential-expression-calls
#6
Paweł P Łabaj, David P Kreil
BACKGROUND: The MAQC/SEQC consortium has recently compiled a key benchmark that can serve for testing the latest developments in analysis tools for microarray and RNA-seq expression profiling. Such objective benchmarks are required for basic and applied research, and can be critical for clinical and regulatory outcomes. Going beyond the first comparisons presented in the original SEQC study, we here present extended benchmarks including effect strengths typical of common experiments. RESULTS: With artefacts removed by factor analysis and additional filters, for genome scale surveys, the reproducibility of differential expression calls typically exceed 80% for all tool combinations examined...
December 20, 2016: Biology Direct
https://www.readbyqxmd.com/read/27993151/exploring-the-importance-of-cancer-pathways-by-meta-analysis-of-differential-protein-expression-networks-in-three-different-cancers
#7
Sinjini Sikdar, Somnath Datta, Susmita Datta
BACKGROUND: It is believed that all cancers occur due to the mutation or change in one or more genes. In order to investigate the significance of the biological pathways which are interrupted by these genetic mutations, we pursue an integrated analysis using multiple cancer datasets released by the International Cancer Genome Consortium (ICGC). This dataset consists of expression profiles for genes/proteins of patients receiving treatment, for three types of cancer - Head and Neck Squamous Cell Carcinoma (HNSC), Lung Adenocarcinoma (LUAD) and Kidney Renal Clear Cell Carcinoma (KIRC)...
December 20, 2016: Biology Direct
https://www.readbyqxmd.com/read/27906033/the-role-of-the-backbone-torsion-in-protein-folding
#8
EDITORIAL
Irina Sorokina, Arcady Mushegian
BACKGROUND: The set of forces and sequence of events that govern the transition from an unfolded polypeptide chain to a functional protein with correct spatial structure remain incompletely known, despite the importance of the problem and decades of theory development, computer simulations, and laboratory experiments. Information about the correctly folded state of most proteins is likely to be present in their sequences, and yet many proteins fail to attain native structure after overexpression in a non-native environment or upon experimental denaturation and refolding...
December 1, 2016: Biology Direct
https://www.readbyqxmd.com/read/27894340/xhmmer3x2-utilizing-hmmer3-s-speed-and-hmmer2-s-sensitivity-and-specificity-in-the-glocal-alignment-mode-for-improved-large-scale-protein-domain-annotation
#9
Choon-Kong Yap, Birgit Eisenhaber, Frank Eisenhaber, Wing-Cheong Wong
BACKGROUND: While the local-mode HMMER3 is notable for its massive speed improvement, the slower glocal-mode HMMER2 is more exact for domain annotation by enforcing full domain-to-sequence alignments. Since a unit of domain necessarily implies a unit of function, local-mode HMMER3 alone remains insufficient for precise function annotation tasks. In addition, the incomparable E-values for the same domain model by different HMMER builds create difficulty when checking for domain annotation consistency on a large-scale basis...
November 29, 2016: Biology Direct
https://www.readbyqxmd.com/read/27871336/zfas1-a-long-noncoding-rna-associated-with-ribosomes-in-breast-cancer-cells
#10
Herah Hansji, Euphemia Y Leung, Bruce C Baguley, Graeme J Finlay, David Cameron-Smith, Vandre C Figueiredo, Marjan E Askarian-Amiri
BACKGROUND: Most of the eukaryotic genome is transcribed, yielding a complex network of transcripts including thousands of lncRNAs that generally lack protein coding potential. However, only a small percentage of these molecules has been functionally characterised, and discoveries of specific functions demonstrate layers of complexity. A large percentage of lncRNAs is located in the cytoplasm, associated with ribosomes but the function of the majority of these transcripts is unclear. The current study analyses putative mechanisms of action of the lncRNA species member ZFAS1 that was initially discovered by microarray analysis of murine tissues undergoing mammary gland development...
November 21, 2016: Biology Direct
https://www.readbyqxmd.com/read/27835978/importins-promote-high-frequency-nf-%C3%AE%C2%BAb-oscillations-increasing-information-channel-capacity
#11
Zbigniew Korwek, Karolina Tudelska, Paweł Nałęcz-Jawecki, Maciej Czerkies, Wiktor Prus, Joanna Markiewicz, Marek Kochańczyk, Tomasz Lipniacki
BACKGROUND: Importins and exportins influence gene expression by enabling nucleocytoplasmic shuttling of transcription factors. A key transcription factor of innate immunity, NF-κB, is sequestered in the cytoplasm by its inhibitor, IκBα, which masks nuclear localization sequence of NF-κB. In response to TNFα or LPS, IκBα is degraded, which allows importins to bind NF-κB and shepherd it across nuclear pores. NF-κB nuclear activity is terminated when newly synthesized IκBα enters the nucleus, binds NF-κB and exportin which directs the complex to the cytoplasm...
November 11, 2016: Biology Direct
https://www.readbyqxmd.com/read/27825385/neurogenomics-and-the-role-of-a-large-mutational-target-on-rapid-behavioral-change
#12
Craig E Stanley, Rob J Kulathinal
BACKGROUND: Behavior, while complex and dynamic, is among the most diverse, derived, and rapidly evolving traits in animals. The highly labile nature of heritable behavioral change is observed in such evolutionary phenomena as the emergence of converged behaviors in domesticated animals, the rapid evolution of preferences, and the routine development of ethological isolation between diverging populations and species. In fact, it is believed that nervous system development and its potential to evolve a seemingly infinite array of behavioral innovations played a major role in the successful diversification of metazoans, including our own human lineage...
November 8, 2016: Biology Direct
https://www.readbyqxmd.com/read/27809935/identification-of-micrornas-regulating-escherichia-coli-f18-infection-in-meishan-weaned-piglets
#13
Zhengchang Wu, Weiyun Qin, Seng Wu, Guoqiang Zhu, Wenbin Bao, Shenglong Wu
BACKGROUND: Escherichia coli F18 is mainly responsible for post-weaning diarrhea (PWD) in piglets. The molecular regulation of E. coli F18 resistance in Chinese domestic weaned piglets is still obscure. We used Meishan piglets as model animals to test their susceptibility to E. coli F18. Small RNA duodenal libraries were constructed for E. coli F18-sensitive and -resistant weaned piglets challenged with E. coli F18 and sequenced using Illumina Solexa high-throughput sequencing technology...
November 3, 2016: Biology Direct
https://www.readbyqxmd.com/read/27809888/the-struggle-by-caenorhabditis-elegans-to-maintain-proteostasis-during-aging-and-disease
#14
REVIEW
Elise A Kikis
: The presence of only small amounts of misfolded protein is an indication of a healthy proteome. Maintaining proteome health, or more specifically, "proteostasis," is the purview of the "proteostasis network." This network must respond to constant fluctuations in the amount of destabilized proteins caused by errors in protein synthesis and exposure to acute proteotoxic conditions. Aging is associated with a gradual increase in damaged and misfolded protein, which places additional stress on the machinery of the proteostasis network...
November 3, 2016: Biology Direct
https://www.readbyqxmd.com/read/27776539/clip-gene-a-web-service-of-the-condition-specific-context-laid-integrative-analysis-for-gene-prioritization-in-mouse-tf-knockout-experiments
#15
Benjamin Hur, Sangsoo Lim, Heejoon Chae, Seokjun Seo, Sunwon Lee, Jaewoo Kang, Sun Kim
MOTIVATION: Transcriptome data from the gene knockout experiment in mouse is widely used to investigate functions of genes and relationship to phenotypes. When a gene is knocked out, it is important to identify which genes are affected by the knockout gene. Existing methods, including differentially expressed gene (DEG) methods, can be used for the analysis. However, existing methods require cutoff values to select candidate genes, which can produce either too many false positives or false negatives...
October 24, 2016: Biology Direct
https://www.readbyqxmd.com/read/27770811/long-range-personalized-cancer-treatment-strategies-incorporating-evolutionary-dynamics
#16
Chen-Hsiang Yeang, Robert A Beckman
BACKGROUND: Current cancer precision medicine strategies match therapies to static consensus molecular properties of an individual's cancer, thus determining the next therapeutic maneuver. These strategies typically maintain a constant treatment while the cancer is not worsening. However, cancers feature complicated sub-clonal structure and dynamic evolution. We have recently shown, in a comprehensive simulation of two non-cross resistant therapies across a broad parameter space representing realistic tumors, that substantial improvement in cure rates and median survival can be obtained utilizing dynamic precision medicine strategies...
October 22, 2016: Biology Direct
https://www.readbyqxmd.com/read/27769290/ipc-isoelectric-point-calculator
#17
Lukasz P Kozlowski
BACKGROUND: Accurate estimation of the isoelectric point (pI) based on the amino acid sequence is useful for many analytical biochemistry and proteomics techniques such as 2-D polyacrylamide gel electrophoresis, or capillary isoelectric focusing used in combination with high-throughput mass spectrometry. Additionally, pI estimation can be helpful during protein crystallization trials. RESULTS: Here, I present the Isoelectric Point Calculator (IPC), a web service and a standalone program for the accurate estimation of protein and peptide pI using different sets of dissociation constant (pKa) values, including two new computationally optimized pKa sets...
October 21, 2016: Biology Direct
https://www.readbyqxmd.com/read/27760563/evolution-of-the-tim17-protein-family
#18
Vojtěch Žárský, Pavel Doležal
BACKGROUND: The Tim17 family of proteins plays a fundamental role in the biogenesis of mitochondria. Three Tim17 family proteins, Tim17, Tim22, and Tim23, are the central components of the widely conserved multi-subunit protein translocases, TIM23 and TIM22, which mediate protein transport across and into the inner mitochondrial membrane, respectively. In addition, several Tim17 family proteins occupy the inner and outer membranes of plastids. RESULTS: We have performed comprehensive sequence analyses on 5631 proteomes from all domains of life deposited in the Uniprot database...
October 19, 2016: Biology Direct
https://www.readbyqxmd.com/read/27737715/cancer-heterogeneity-and-multilayer-spatial-evolutionary-games
#19
Andrzej Świerniak, Michał Krześlak
BACKGROUND: Evolutionary game theory (EGT) has been widely used to simulate tumour processes. In almost all studies on EGT models analysis is limited to two or three phenotypes. Our model contains four main phenotypes. Moreover, in a standard approach only heterogeneity of populations is studied, while cancer cells remain homogeneous. A multilayer approach proposed in this paper enables to study heterogeneity of single cells. METHOD: In the extended model presented in this paper we consider four strategies (phenotypes) that can arise by mutations...
October 13, 2016: Biology Direct
https://www.readbyqxmd.com/read/27737689/unexpected-links-reflect-the-noise-in-networks
#20
Anatoly Yambartsev, Michael A Perlin, Yevgeniy Kovchegov, Natalia Shulzhenko, Karina L Mine, Xiaoxi Dong, Andrey Morgun
BACKGROUND: Gene covariation networks are commonly used to study biological processes. The inference of gene covariation networks from observational data can be challenging, especially considering the large number of players involved and the small number of biological replicates available for analysis. RESULTS: We propose a new statistical method for estimating the number of erroneous edges in reconstructed networks that strongly enhances commonly used inference approaches...
October 13, 2016: Biology Direct
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