bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Early Pregnancy Human Placenta Shares Hypomethylation Patterns Characteristic of Solid Tumors
Authors: Nordor Akpéli V. , Nehar-Belaid Djamel , Richon Sophie , Klatzmann David , Bellet Dominique , Dangles-Marie Virginie , Fournier Thierry , Aryee Martin J. 
Published: January 2017

ABSTRACTBackgroundThe placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis, while surviving hypoxia, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors.ResultsWe show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues. We confirmed these findings in villous cytotrophoblasts isolated from the placenta and identified a time window at the end of the first trimester, when these cells come into contact with maternal blood as the likely time period for the methylome alterations. Furthermore, the large genomic regions affected by these patterns of hypomethylation encompass genes involved in pathways related to epithelial-mesenchymal transition (EMT), immune response and inflammation. Analyses of expression profiles corresponding to genes in these hypomethylated regions in colon adenocarcinoma tumors point to networks of differentially expressed genes previously implicated in carcinogenesis and placentogenesis, where nuclear factor kappa B (NF-kB) is a key hub.ConclusionTaken together, our results suggest the existence of epigenetic switches involving large-scale changes of methylation in the placenta during pregnancy and in tumors during neoplastic transformation. The characterization of such epigenetic switches might lead to the identification of biomarkers and drug targets in oncology as well as in obstetrics and gynecology.
Local differentiation in the defensive morphology of an invasive zooplankton species is not genetically based
Authors: Fiorino Giuseppe E. , McAdam Andrew G. 
Published: January 2017

AbstractEvolutionary changes in functional traits represent one possible reason why exotic species spread to become invasive, but empirical studies of the mechanisms driving phenotypic differentiation between populations of invasive species are rare. This study tested whether differences in distal spine length among populations of the invasive cladoceran,Bythotrephes longimanus, could be explained by local adaptation or phenotypic plasticity. We collectedBythotrephesfrom six lakes and found that distal spine lengths and natural selection on distal spine length differed among populations, but were unrelated to the gape-limitation of the dominant fish predator in the lake from which they were collected. A common garden experiment revealed significant genetic and maternal variation for distal spine length, but phenotypic differences among populations were not genetically based. Phenotypic differences among lakes in this ecologically important trait are, therefore, the result of plasticity and not local adaptation, despite spatially variable selection on this heritable trait. The ability ofBythotrephesto plastically adjust distal spine length may explain the success of this species at invading lake ecosystems with diverse biotic environments.
Reverse Watson-Crick purine-purine base pairs — the Sharp-turn motif and other structural consequences in functional RNAs
Authors: Mittal Abhinav , Halder Antarip , Bhattacharya Sohini , Bhattacharyya Dhananjay , Mitra Abhijit 
Published: January 2017

AbstractIdentification of static and/or dynamic roles of different noncanonical base pairs is essential for a comprehensive understanding of the sequence-structure-function space of RNA. In this context, reverse Watson-Crick purine-purine base pairs (A:A, G:G&A:GW:W Trans) constitute an interesting class of noncanonical base pairs in RNA due to their characteristic C1′–C1′ distance (highest among all base pairing geometries) and parallel local strand orientation. Structural alignment of the RNA stretches containing these W:W Trans base pairs with their corresponding homologous sites in a non-redundant set of RNA crystal structures show that, as expected, these base pairs are associated with specific structural folds or functional roles. Detailed analysis of these contexts further revealed a bimodal distribution in the local backbone geometry parameters associated with these base pairs. One mode, populated by both A:A and G:G W:W Trans pairs, manifests itself as a characteristic backbone fold. We call this fold a ‘Sharp-turn’ motif. The other mode is exclusively associated with A:A W:W Trans pairs involved in mediating higher order interactions. The same trend is also observed in available solution NMR structures. We have also characterized the importance of recurrent hydrogen bonding interactions between adenine and guanine in W:W Trans geometry. Quantum chemical calculations performed at M05-2X/6-31++(2d,2p) level explain how the characteristic electronic properties of these W:W Trans base pairs facilitate their occurrence in such exclusive structural folds that are important for RNA functionalities.
MinorityReport, software for generalized analysis of causal genetic variants
Authors: Horst Jeremy A , Wu Wesley , DeRisi Joseph L 
Published: January 2017

ABSTRACTBackgroundThe widespread availability of next generation genome sequencing technologies has enabled a wide range of variant detection applications, especially in cancer and inborn genetic disorders. For model systems and microorganisms, the same technology may be used to discover the causative mutations for any phenotype, including those generated in response to chemical perturbation. In the case of pathogenic organisms, these approaches have allowed the determination of drug targets by means of resistance selection followed by genome sequencing.ResultsHere, we present open source software written in python, MinorityReport, to facilitate the comparison of any two sets of genome alignments for the purpose of rapidly identifying the spectrum of nonsynonymous changes, insertions or deletions, and copy number variations in a presumed mutant relative to its parent. Specifically, MinorityReport relates mapped sequence reads in SAM format output from any alignment tool for both the mutant and parent genome, relative to a reference genome, and produces the set of variants that distinguishes the mutant from the parent, all presented in an intuitive, straightforward report format. MinorityReport features tunable parameters for evaluating evidence and a scoring system that prioritizes reported variants based on relative proportions of read counts supporting the variant in the mutant versus parent data sets. We demonstrate the utility of MinorityReport using publicly available data sets that we previously published to find the determinants of resistance for novel anti-malarial drugs.ConclusionsMinorityReport is readily available (github: xxxxxxx) to identify the genetic mechanisms of drug resistance in plasmodium, genotype-phenotype relationships in human diads, or genomic variations between any two related organisms.
Cyclic-di-GMP is required for corneal infection byPseudomonas aeruginosaand modulates host immunity
Authors: Yam Joey Kuok Hoong , Aung Thet Tun , Chua Song Lin , Cheng Yingying , Kohli Gurjeet Singh , Zhou Jianuan , Constancias Florentin , Liu Yang , Cai Zhao , Salido May Margarette Santillan , Drautz-Moses Daniela I. , Rice Scott A. , Schuster Stephan Christoph , Wu Bin , Kjelleberg Staffan , Tolker-Nielsen Tim , Beuerman Roger W. , Givskov Michael , Yang Liang 
Published: January 2017

AbstractBiofilms are extremely tolerant toward antimicrobial treatment and host immune clearance due to their distinct physiology and protection by extracellular polymeric substances. Bis-(3´-5´)-cyclic dimeric guanosine monophosphate (c-di-GMP) is an essential messenger that regulates biofilm formation by a wide range of bacteria. However, there is a lack of physiological characterization of biofilmsin vivoas well as the roles of c-di-GMP signaling in mediating host-biofilm interactions. Here, we employed dual RNA-Seq to characterize the host and pathogen transcriptomes duringPseudomonas aeruginosainfection using a mouse keratitis model.In vivo P. aeruginosabiofilms maintained a distinct physiology compared within vitro P. aeruginosabiofilms, with enhanced virulence and iron uptake capacity. C-di-GMP synthesis was enhanced inP. aeruginosacellsin vivo,potentially due to down-regulation of the expression of several phosphodiesterases (e.g., DipA, NbdA). Increased intracellular c-di-GMP levels were required for long-term ocular colonization ofP. aeruginosaand impaired host innate immunity.
Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity
Authors: Bassani-Sternberg Michal , Chong Chloé , Guillaume Philippe , Solleder Marthe , Pak HuiSong , Gannon Philippe O , Kandalaft Lana E , Coukos George , Gfeller David 
Published: January 2017

AbstractThe precise identification of Human Leukocyte Antigen class I (HLA-I) binding motifs plays a central role in our ability to understand and predict (neo-)antigen presentation in infectious diseases and cancer. Here, by exploiting co-occurrence of HLA-I alleles across ten newly generated as well as forty public HLA peptidomics datasets comprising more than 115,000 unique peptides, we show that we can rapidly and accurately identify many HLA-I binding motifs and map them to their corresponding alleles without anya prioriknowledge of HLA-I binding specificity. Our approach recapitulates and refines known motifs for 43 of the most frequent alleles, uncovers new motifs for 9 alleles that up to now had less than five known ligands and provides a scalable framework to incorporate additional HLA peptidomics studies in the future. The refined motifs improve neo-antigen and cancer testis antigen predictions, indicating that unbiased HLA peptidomics data are ideal forin silicopredictions of neo-antigens from tumor exome sequencing data. The new motifs further reveal allosteric modulation of the binding specificity of HLA-I alleles and we unravel the underlying mechanisms by protein structure analysis, mutagenesis andin vitrobinding assays.
Integration of visual information in auditory cortex promotes auditory scene analysis through multisensory binding
Authors: Atilgan Huriye , Town Stephen M. , Wood Katherine C. , Jones Gareth P. , Maddox Ross K. , Lee Adrian K.C. , Bizley Jennifer K. 
Published: January 2017

SummaryHow and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a mechanism for binding stimulus features across sensory modalities. Here we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex, via the phase of the local field potential is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.
Time-resolved dual root-microbe transcriptomics reveals early induced Nicotiana benthamiana genes and conserved infection-promoting Phytophthora palmivora effectors
Authors: Evangelisti Edouard , Gogleva Anna , Hainaux Thomas , Doumane Mehdi , Tulin Frej , Quan Clément , Yunusov Temur , Floch Kevin , Schornack Sebastian 
Published: January 2017

AbstractBackgroundPlant-pathogenic oomycetes are responsible for economically important losses on crops worldwide. Phytophthora palmivora, a broad-host-range tropical relative of the potato late blight pathogen, causes rotting diseases in many important tropical crops including papaya, cocoa, oil palm, black pepper, rubber, coconut, durian, mango, cassava and citrus.Transcriptomics have helped to identify repertoires of host-translocated microbial effector proteins which counteract defenses and reprogram the host in support of infection. As such, these studies have helped understanding of how pathogens cause diseases. Despite the importance of P. palmivora diseases, genetic resources to allow for disease resistance breeding and identification of microbial effectors are scarce.ResultsWe employed the model plant N. benthamiana to study the P. palmivora root infections at the cellular and molecular level. Time-resolved dual transcriptomics revealed different pathogen and host transcriptome dynamics. De novo assembly of P. palmivora transcriptome and semi-automated prediction and annotation of the secretome enabled robust identification of conserved infection-promoting effectors. We show that one of them, REX3, suppresses plant secretion processes. In a survey for early transcriptionally activated plant genes we identified a N. benthamiana gene specifically induced at infected root tips that encodes a peptide with danger-associated molecular features.ConclusionsThese results constitute a major advance in our understanding of P. palmivora diseases and establish extensive resources for P. palmivora pathogenomics, effector-aided resistance breeding and the generation of induced resistance to Phytophthora root infections. Furthermore, our approach to find infection relevant secreted genes is transferable to other pathogen-host interactions and not restricted to plants.
Evolution of the Mineralocorticoid Receptor: Sequence, Structure and Function
Authors: Baker Michael E. , Katsu Yoshinao 
Published: January 2017

Abstract.The mineralocorticoid receptor (MR) is descended from a corticoid receptor (CR), which has descendants in lamprey and hagfish, cyclostomes (jawless fish), a taxon that evolved at the base of the vertebrate line. A distinct MR and GR first appear in cartilaginous fishes (Chondrichthyes), such as sharks, skates, rays and chimaeras. Skate MR has a strong response to corticosteroids that are mineralocorticoids and glucocorticoids in humans. The half-maximal responses (EC50s) for skate MR for the mineralocorticoids aldosterone and 11-deoxycorticosterone are 0.07 nM and 0.03 nM, respectively. EC50s for the glucocorticoids cortisol and corticosterone are 1 nM and 0.09 nM, respectively. The physiological mineralocorticoid in ray-finned fish, which do not synthesize aldosterone, is not fully understood because several 3-ketosteroids, including cortisol, 11-deoxycortisol, corticosterone, 11-deoxycorticosterone and progesterone are transcriptional activators of fish MR. Divergence of the MR and GR in terrestrial vertebrates, which synthesize aldosterone, led to increased selectivity of the MR for aldosterone, coupled with a diminished response to cortisol and corticosterone. Here, we combine sequence analysis of the CR and vertebrate MRs and GRs, analysis of crystal structures of human MR and GR and data on transcriptional activation by 3-ketosteroids of wild-type and mutant MRs and GRs to investigate the evolution of selectivity for 3-ketosteroids by the MR in terrestrial vertebrates and ray-finned fish, as well as the basis for binding of some glucocorticoids by human MR and other vertebrate MRs.
Chunking as a rational strategy for lossy data compression in visual working memory
Authors: Nassar Matthew R. , Helmers Julie C. , Frank Michael J. 
Published: January 2017

AbstractThe nature of capacity limits for visual working memory has been the subject of an intense debate that has relied on models that assume items are encoded independently. Here we propose that instead, similar features are jointly encoded through a “chunking” process to optimize performance on visual working memory tasks. We show that such chunking can: 1) facilitate performance improvements for abstract capacity-limited systems, 2) be optimized through reinforcement, 3) be implemented by center-surround dynamics, and 4) increase effective storage capacity at the expense of recall precision. Human performance on a variant of a canonical working memory task demonstrated performance advantages, precision detriments, inter-item dependencies, and trial-to-trial behavioral adjustments diagnostic of performance optimization through center-surround chunking. Models incorporating center-surround chunking provided a better quantitative description of human performance in our study as well as in a meta-analytic dataset, and apparent differences in working memory capacity across individuals were attributable to individual differences in the implementation of chunking. Our results reveal a normative rationale for center-surround connectivity in working memory circuitry, call for re-evaluation of memory performance differences that have previously been attributed to differences in capacity, and support a more nuanced view of visual working memory capacity limitations: strategic tradeoff between storage capacity and memory precision through chunking contribute to flexible capacity limitations that include both discrete and continuous aspects.
fastBMA: Scalable Network Inference and Transitive Reduction
Authors: Hung Ling-Hong , Shi Kaiyuan , Wu Migao , Young William Chad , Raftery Adrian E. , Yeung Ka Yee 
Published: January 2017

AbstractBACKGROUND:Inferring genetic networks from genome-wide expression data is extremely demanding computationally. We have developed fastBMA, a distributed, parallel and scalable implementation of Bayesian model averaging (BMA) for this purpose. fastBMA also includes a novel and computationally efficient method for eliminating redundant indirect edges in the network.FINDINGS:We evaluated the performance of fastBMA on synthetic data and experimental genome-wide yeast and human datasets. When using a single CPU core, fastBMA is up to 100 times faster than the next fastest method, LASSO, with increased accuracy. It is a memory efficient, parallel and distributed application that scales to human genome wide expression data. A 10,000-gene regulation network can be obtained in a matter of hours using a 32-core cloud cluster.CONCLUSIONS:fastBMA is a significant improvement over its predecessor ScanBMA. It is orders of magnitude faster and more accurate than other fast network inference methods such as LASSO. The improved scalability allows it to calculate networks from genome scale data in a reasonable timeframe. The transitive reduction method can improve accuracy in denser networks. fastBMA is available as code (M.I.T. license) from GitHub (https://github.com/lhhunghimself/fastBMA), as part of the updated networkBMA Bioconductor package (https://www.bioconductor.org/packages/release/bioc/html/networkBMA.html) and as ready-to-deploy Docker images (https://hub.docker.com/r/biodepot/fastbma/).
Prognostic value of the MicroRNA‐29 family in multiple human cancers: A meta‐analysis and systematic review
Authors: Qi Yan , Huang Yalan , Pang Lijuan , Gu Wenyi , Wang Ning , Hu Jianming , Cui Xiaobin , Zhang Jun , Zhao Jin , Liu Chunxia , Zhang Wenjie , Zou Hong , Li Feng 
Published: January 2017

SummaryMicroRNAs (miRNAs) in cancer development have attracted much attention in recent years. miR‐29 is known to critically affect cancer progression by functioning as a tumor suppressor. However, it may also act as an oncogene under certain situations. The prognostic value of the miR‐29 family in cancer progression is still under debate and reported results are inconsistent. Therefore, we reported here a meta‐analysis and systematic review to analyze the prognostic role of the miR‐29 family in cancer. We screened 20 published studies and calculated pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS) or disease‐free survival/recurrence‐free survival (DFS/RFS). Our results showed that a low or absent expression of miR‐29 family was significantly associated with poor OS (HR, 1.57; 95%CI, 1.18‐2.08), and inferior to 5‐year DFS/RFS (HR, 1.89; 95%CI, 1.47‐2.44). Analysis of individual miR‐29 subtypes indicated that the low expression of miR‐29a/b/c subtypes correlated with poor 5‐year OS (miR‐29a: HR, 1.99; 95%CI, 1.41‐2.80; miR‐29b: HR, 1.60; 95%CI, 1.18‐2.17; miR‐29c: HR, 1.69; 95%CI, 1.00‐2.86), as well as poor 5‐year DFS/RFS (miR‐29b: HR, 1.70; 95%CI, 1.27‐2.27). Ethnicity analysis demonstrated Asian patients with low expression of miR‐29 were significantly correlated with poor OS (HR, 1.61; 95%CI, 1.16‐2.23) and 5‐year DFS/RFS (HR, 2.03; 95%CI, 1.50‐2.74). Taken together, our analysis indicates that the low expression of miR‐29 is associated with aggressiveness and poor prognosis of malignant neoplasms. More importantly, miR‐29 might serve as a key biomarker for predicting the recurrence and progression of human cancers.
Effects of electrical lesion of basolateral amygdala nucleus on rat anxiety‐like behaviour under acute, sub‐chronic, and chronic stresses
Authors: Ranjbar Hoda , Radahmadi Maryam , Reisi Parham , Alaei Hojjatallah 
Published: January 2017

SummaryStress contributes, as a risk factor, to such psychological disorders as anxiety. The effects of electrical lesions in the basolateral amygdala nucleus (BLA) were investigated on the locomotor activity and anxiety‐like behaviour in different stress durations. For this purpose, rats were randomly allocated to control, sham, and experimental groups, the latter including groups with and without BLA nucleus subjected to acute, sub‐chronic, and chronic stress conditions for 1, 7, and 21 days, respectively, applied 6 h/d. The induced anxiety behaviour was evaluated using the open field test (OFT) while other variables were measured. Findings revealed that sub‐chronic stress led to significantly reduced (P<.05) anxiety behaviours as measured by entries into and the time spent in the centre area while it also led to significant impairments in exploratory and locomotor activities, indicating intensified anxiety‐like behaviour. BLA lesion affected rat behaviour differently such that it significantly (P<.05) decreased fear under sub‐chronic and chronic stress conditions as evidenced by the subjects’ greater tendency to enter the centre area in the open field test and their increased number of rearing events (P<.01). However, BLA lesion led to no significant decrease in the locomotor activity of subjects exposed to sub‐chronic or chronic stress conditions as compared with those in similar groups but without BLA lesion. Finally, BLA lesion was found not only to decrease significantly (P<.01) adrenal gland and body weights, particularly under sub‐chronic stress, but also to play a critical role in modulating adrenal functions by decreasing adrenal gland weight, and thereby reducing depression‐like symptoms.