bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short loop motif profiling of protein interaction networks in acute myeloid leukaemia
Authors: Chung Sun Sook , Laddach Anna , Thomas N. Shaun B. , Fraternali Franca 
Published: April 2018

AbstractRecent advances in biotechnologies for genomics and proteomics have expanded our understanding of biological components which play crucial roles in complex mechanisms related to cancer. However, it is still challenging to extract from the available knowledge reliable targets to use in a translational setting. The reasons for this are manifold, but essentially distilling real biological signal from heterogeneous “big data” collections is the major hurdle. Here, we aim to establish an in-silico pipeline to explore mutations and their effects on protein-protein interactions, with a focus on acute myeloid leukaemia (AML), one of the most common blood cancers with the highest mortality rate. Our method, based on cyclic interactions of a small number of proteins topologically linked in the network (short loop network motifs), highlights specific protein-protein interactions (PPIs) and their functions in AML when compared with other leukaemias. We also developed a new property named ‘short loop commonality’ to measure indirect PPIs occurringviacommon short loop interactions. This new method detects “modules” of PPI networks (PPINs) enriched with common biological functions which have proteins that contain mutation hotspots. We further perform 3D structural modelling to extract atomistic details, which shows that such hotspots map to PPI interfaces as well as active sites. Thus, our study proposes a framework for the macroscopic and microscopic investigation of PPINs, their relation to cancers, and highlights important functional modules in the network to be exploited in targeted drug screening.
Host sexual dimorphism affects the outcome of within-host pathogen competition
Authors: Gipson Stephen A.Y. , Jimenez Luis , Hall Matthew D. 
Published: April 2018

AbstractNatural infections often consist multiple pathogens of the same or different species. In multiple infections, pathogens compete for access to host resources and fitness is determined by how well a pathogen can reproduce compared to its competitors. Given the propensity for males and females to exhibit variation in pathogen-induced reduction in lifespan or fecundity, we explore how host sex may modulate the competitive ability of pathogens, potentially favouring the transmission of different pathogen genotypes. Using the Daphnia magna - Pasteuria ramosa model system, we exposed male and female hosts to either a single genotype infection or coinfections consisting of two pathogen genotypes of varying levels of virulence, measured as pathogen-induced reduction in host lifespan. We found that co-infections within females generally favoured the transmission of the more virulent pathogen genotype. Conversely, co-infections within male hosts resulted in equal transmission of competing genotypes, or favoured the transmission of the less virulent pathogen genotype in treatments where it established prior to the more virulent competitor. These results suggest that sex is a form of host heterogeneity which may influence the evolution of virulence within co-infection contexts and that one sex may be a reservoir for pathogen genetic diversity in nature.
Distinct prefrontal top-down circuits differentially modulate sensorimotor behavior
Authors: Huda Rafiq , Sipe Grayson O. , Breton-Provencher Vincent , Cruz K. Guadalupe , Pho Gerald N. , Adam Elie , Gunter Liadan M. , Sullins Austin , Wickersham Ian R. , Sur Mriganka 
Published: April 2018

AbstractSensorimotor behaviors require processing of behaviorally relevant sensory cues and the ability to select appropriate responses from a vast behavioral repertoire. Top-down modulation by the prefrontal cortex (PFC) is thought to be key for both processes but the precise role of specific circuits remains unclear. We examined the sensorimotor function of anatomically distinct outputs from a subdivision of the mouse PFC, the anterior cingulate cortex (ACC). Using a visually guided two-choice behavioral paradigm with multiple cue-response mappings, we dissociated the sensory and motor response components of sensorimotor control. Projection-specific two-photon calcium imaging and optogenetic manipulations show that ACC outputs to the superior colliculus, a key midbrain structure for response selection, principally coordinate specific motor responses. Importantly, ACC outputs exert top-down control by reducing the innate response bias of the superior colliculus. In contrast, ACC outputs to the visual cortex facilitate sensory processing of visual cues. Our results ascribe motor and sensory roles to ACC projections to the superior colliculus and the visual cortex and demonstrate for the first time a circuit motif for PFC function wherein anatomically non-overlapping output pathways coordinate complementary but distinct aspects of visual sensorimotor behavior.
Leucocyte integrins but not caspases or NLR inflammasome are associated with lipopolysaccharide recognition and response in barramundi (Lates calcarifer)
Authors: Zoccola Emmanuelle C. , Kellie Stuart , Barnes Andrew C. 
Published: April 2018

AbstractThe inflammatory response of fish to LPS is subdued, attributed to absence of TLR4, a key pro-inflammatory receptor for LPS in mammals. Nevertheless, LPS is processed in fish in a T-independent manner and is a protective antigen in fish vaccines, yet pathways for processing LPS in fish remain to be elucidated. Here, we report that caspases and NOD-like receptor inflammasomes typically responsible for LPS recognition and processing in mammals lack critical domains or are absent in barramundi (Lates calcarifer). However, leucocyte integrins MAC-1 and LFA-1 induce pro-inflammatory cytokine expression poststimulation with LPS. Moreover, MAC-1 and LFA-1 were detected on the surface of neutrophil- and lymphocyte-like cells respectively in the barramundi spleen by immunocytochemistry, and leucocytes displaying MAC-1 or LFA-1 bound to Factor X and ESM-1 respectively. Our results implicate MAC-1 and LFA-1 in immune processing of LPS in barramundi and potentially in antigen processing in fish.
Characterization of genomic DNA of lactic acid bacteria for activation of plasmacytoid dendritic cells
Authors: Horie Akira , Tomita Yasuyuki , Oshio Konomi , Fujiwara Daisuke , Fujii Toshio 
Published: April 2018

AbstractLactococcus lactisstrain Plasma (LC-Plasma) possesses strong activity of stimulating plasmacytoid dendritic cells (pDCs) via the TLR9-Myd88 pathway. To reveal the effective genome structure for pDCs stimulatory activity, we performed anin vitroscreening, using randomly selected DNA fragments from the LC-Plasma genome. The results showed that CpG motifs are necessary factor for active DNA fragment, but the copy number of CpG motifs did not show strong correlation to the pDCs stimulatory activity of DNA fragment. We also found that the G+C contents of DNA fragments have significant negative effects on pDCs stimulatory activity. We also performed bioinformatics analysis of genome of lactic acid bacteria (LAB) and investigated the relation between CpG copy number in the genome and pDCs stimulatory activity. We found that strains of lactic acid bacteria (LAB) with high copy number of CpG motifs in the low-G+C region of the genome had higher probability of having high pDCs stimulatory activity. Three species,L.lactissubsp.lactis, Leuconostoc mesenteroides, andPediococcus pentosaceuswere the typical examples of high pDCs stimulatory activity LAB.ImportanceThis study provides a new perspective on the structure of DNA fragments that are able to activate pDCs via the TLR9-Myd88 pathway. The information from this study should be useful for designing new DNA fragments, including phosphodiesterbond-DNA oligomers containing CpG motifs and DNA-containing vaccines. This work also presented anin silicoscreening method for identifying bacterial species that are able to activate pDCs. Therefore, this study should be useful for providing data for the development of vaccine adjuvants and therapeutics for infectious and allergic diseases.
Machine learning based prediction of functional capabilities in metagenomically assembled microbial genomes
Authors: Farrell Fred , Soyer Orkun S. , Quince Christopher 
Published: April 2018

AbstractThe increasing popularity of genome resolved meta genomics - the binning of genomes of potentially uncultured organisms direct from the environmental DNA - has resulted in a deluge of draft genomes. There is a pressing need to develop methods to interpret this data. Here, we used machine learning to predict functional and metabolic traits of microbes from their genomes. We collated an extensive database of 84 phenotypic traits associated with 9407 prokaryotic genomes and trained different machine learning models on this data. We found that a lasso logistic regression based on the frequency of gene orthologs had the best combination of functional prediction performance and interpretability. This model was able to classify 65 phenotypic traits with greater than 90
Asymmetrical template-DNA strand segregation can explain density-associated mutation-rate plasticity
Authors: Aanen Duur K. , Debets Alfons J.M. 
Published: April 2018

SummaryThe mutation rate is a fundamental factor in evolutionary genetics. Recently, mutation rates were found to be strongly reduced at high density in a wide range of unicellular organisms, prokaryotic and eukaryotic. Independently, cell division was found to become more asymmetrical at increasing density in diverse organisms; in yeast, some ‘mother’ cells continue dividing, while their ‘offspring’ cells do not divide further. Here, we investigate how this increased asymmetry in cell division at high density can be reconciled with reduced mutation-rate estimates. We calculated the expected number of mutant cells due to replication errors under various modes of segregation of template-DNA strands and copy-DNA strands, both under exponential and under linear growth. We show that the observed reduction in the mutation rate at high density can be explained if mother cells preferentially retain the template-DNA strands, since new mutations are then confined to non-dividing daughter cells thus reducing the spread of mutant cells. Any other inheritance mode results in anincreasein the number of mutant cells at higher density. The proposed hypothesis that patterns of DNA-strand segregation are density dependent fundamentally challenges our current understanding of mutation-rate estimates and extends the distinction between germline and soma to unicellular organisms.
Filamin-A susceptibility to calpain-mediated cleavage as a marker of dynamic conformational changes in intact platelets
Authors: Buitrago Lorena , Coller Barry S. 
Published: April 2018

ABSTRACTFilamin-A (FlnA), an actin-binding protein that organizes the actin cytoskeleton and mechanically links transmembrane glycoproteins to the cytoskeleton, associates with platelet receptors integrin αIIbβ3, glycoprotein-Ib (GPIb), and integrin α2β1. Fibrinogen, von Willebrand Factor (vWF) and collagen, binding to these receptors mechanically connect the extracellular matrix to the cytoskeleton. Here we identified that under standardized conditions, platelet activation and ligand binding to αIIbβ3, GPIb, or α2β1, generates reproducible patterns of FlnA cleavage after platelet lysis. We exploited this novel assay to study the impact of ligand binding and receptor activation on the platelet cytoskeleton. We identified that: i) the FlnA modification that renders it cleavable by calpain after platelet lysis, requires both ligand binding and either internal force (e.g; clot retraction) or external forces (e.g; stirring and aggregating), ii) FlnA modification depends on actin polymerization downstream of integrin αIIbβ3 and integrin α2β1, but not downstream of GPIb signaling, iii) FlnA modification is reversible in time when platelets are activated with convulxin (Cvx), collagen, von Willebrand factor (vWF) or thrombin receptor activating peptide (T6), and this reversibility correlates with platelet dissagregation, iv) in contrast to the reversible nature of platelet aggregation and FlnA modification by activation with Cvx, collagen, ristocetin or T6, when platelets are activated by thrombin the platelet do not disaggregate and FlnA remains cleavable. Our data demonstrate that αIIbβ3, α2β1 and GPIb can each exert tension on the cytoskeleton by virtue of binding ligand under conditions of shear. We further identified a unique role for αIIbβ3-fibrin interactions in creating sustained cytoskeletal tension, with implications for thrombus stability and clot retraction.
Colonic Epithelial miR-31 Associates with the Development of Crohn’s Phenotypes
Authors: Keith Benjamin P. , Barrow Jasmine B. , Toyonaga Takahiko , Kazgan Nevzat , O’Connor Michelle Hoffner , Shah Neil D. , Schaner Matthew S. , Wolber Elisabeth A. , Trad Omar K. , Gipson Greg R. , Pitman Wendy A. , Kanke Matthew , Saxena Shruti J. , Chaumont Nicole , Sadiq Timothy S. , Koruda Mark J. , Cotney Paul A. , Allbritton Nancy , Trembath Dimitri G. , Sylvester Francisco , Furey Terrence S. , Sethupathy Praveen , Sheikh Shehzad Z. 
Published: April 2018

AbstractCrohn’s disease (CD) is highly heterogeneous, due in large part to variability in cellular processes that underlie the natural history of CD, thereby confounding effective therapy. There is a critical need to advance understanding of the cellular mechanisms that drive CD heterogeneity. In this study, small RNA-sequencing and microRNA profiling in the colon revealed two distinct molecular subtypes, each with different clinical associations, in both adult and treatment-naïve pediatric CD patients. Notably, we found that microRNA-31 (miR-31) expression by itself can stratify patients into these two subtypes. Through detailed analysis of several colonic mucosa cell types from adult patients, we found that differential levels of miR-31 are particularly pronounced in epithelial cells. We generated patient crypt-derived epithelial colonoids and showed that miR-31 expression differences preserved in this ex-vivo system. In adult patients, low colonic miR-31 expression levels at the time of surgery are associated with post-operative recurrence of ileal disease. In pediatric patients, lower miR-31 expression at the time of diagnosis is associated with the future development of fibrostenotic ileal CD requiring surgery. These findings represent an important step forward in designing more effective clinical trials and developing personalized therapies for CD.
Patterning of a telencephalon-like region in the adult brain of amphioxus
Authors: Benito-Gutiérrez Èlia , Stemmer Manuel , Rohr Silvia D , Schuhmacher Laura N , Tang Jocelyn , Marconi Aleksandra , Jékely Gáspár , Arendt Detlev 
Published: April 2018

ABSTRACTThe evolutionary origin of the vertebrate telencephalon remains unsolved. A major challenge has been the identification of homologous brain parts in invertebrate chordates. Here we report evidence for a telencephalic region in the brain of amphioxus, the most basally branching invertebrate chordate. This region is characterised, like its vertebrate counterpart, by the combined expression of the telencephalic markers FoxG1, Emx and Lhx2/9. It is located at the anterior neural border and dorsal-ventrally patterned, as in vertebrates, by the antagonistic expression of Pax4/6 and Nkx2.1, and a ventral Hh signal. This part of the brain develops only after metamorphosis via sustained proliferation of neuronal progenitors at the ventricular zone. This is concomitant with a massive expansion of late differentiating neuronal types as revealed by neuropeptide and neurotransmitter profiling. Overall, our results suggest that the adult amphioxus brain shows remarkable similarities to the vertebrate embryonic brain, thus providing a key missing link in understanding the invertebrate-to-vertebrate transition in chordate brain evolution.
Comparison of single gene and module-based methods for modeling gene regulatory networks
Authors: Hernaez Mikel , Gevaert Olivier 
Published: April 2018

AbstractGene regulatory networks describe the regulatory relationships among genes, and developing methods for reverse engineering these networks are an ongoing challenge in computational biology. The majority of the initially proposed methods for gene regulatory network discovery create a network of genes and then mine it in order to uncover previously unknown regulatory processes. More recent approaches have focused on inferring modules of co-regulated genes, linking these modules with regulator genes and then mining them to discover new molecular biology.In this work we analyze module-based network approaches to build gene regulatory networks, and compare their performance to the well-established single gene network approaches. In particular, we focus on the problem of linking genes with known regulatory genes. First, modules are created iteratively using a regression approach that links co-expressed genes with few regulatory genes. After the modules are built, we create bipartite graphs to identify a set of target genes for each regulatory gene. We analyze several methods for uncovering these modules and show that a variational Bayes approach achieves significant improvement with respect to previously used methods for module creation on both simulated and real data. We also perform a topological and gene set enrichment analysis and compare several module-based approaches to single gene network approaches where a graph is built from the gene expression profiles without clustering genes in modules. We show that the module-based approach with variational Bayes outperforms all other methods and creates regulatory networks with a significantly higher rate of enriched molecular pathways.The code is written in R and can be downloaded from https://github.com/mikelhernaez/linker.
TSA-Seq Mapping of Nuclear Genome Organization
Authors: Chen Yu , Zhang Yang , Wang Yuchuan , Zhang Liguo , Brinkman Eva K. , Adam Stephen A. , Goldman Robert , van Steensel Bas , Ma Jian , Belmont Andrew S. 
Published: April 2018

SummaryWhile nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. Here we describe TSA-Seq, a new mapping method able to estimate mean chromosomal distances from nuclear speckles genome-wide and predict several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple, spatially separated nuclear domains, including two types of transcription “hot-zones”. Transcription hot-zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, house-keeping genes, genes with low transcriptional pausing, and super-enhancers. Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for nuclear spatial organization of transcription.
Host identity and functional traits determine the community composition of the arbuscular mycorrhizal fungi in facultative epiphytic plant species
Authors: Alguacil MM , Díaz G , Torres P , Rodríguez-Caballero G , Roldán A 
Published: April 2018

ABSTRACTThe epiphytic vascular flora is scarce and facultative in semiarid Mediterranean ecosystems, thus covering diverse taxonomic groups. However, differently to terrestrial conditions, little is known about the factors driving mycorrhizal communities in epiphytic environments. Here, we investigated the arbuscular mycorrhizal fungi (AMF) harboured by 31 plant species occurring in the trunks of Phoenix dactylifera. We wanted to ascertain if host identity and plant functional traits shape mycorrhizal communities. Specifically, we tested the plant life-cycle (perennial versus annual), the plant life-form (herbaceous versus woody), the plant origin (exotic versus native) and the plant species.The roots were examined by molecular and phylogenetic analysis of AMF community. The plant affiliation to species strongly influenced the AMF assemblages. Plant life-form and plant life-cycle also shaped AMF interactions. The AMF community differed between annual and perennial species and higher AMF richness was detected in perennial plants. The indicator species analysis revealed three Operational Taxonomic Units belonging to the Glomeraceae, associated with annual species. However, the epiphytic plants associated with AMF irrespective of whether they were native or not, probably because here no functional differences derive from plant origin.IMPORTANCEArbuscular mycorrhizal (AM) symbiosis has a decisive role in plant nutrient and water uptake by plants, with particular importance in stressful environments. Under semiarid conditions, the facultative epiphytic flora should cope with harsh conditions. While numerous studies have been conducted on factors driving terrestrial AM assemblages, the epiphytic environment remains unexplored. We offer new insights into composition of AM communities as shaped by epiphytic plant host identity and functional traits.
Antimicrobial susceptibility patterns of anaerobic bacteria in Victoria, Australia
Authors: Teng Jasmine C. , Linda Dreyer L 
Published: April 2018

AbstractMortality associated with anaerobic infections approximates 20%. Resistance of anaerobic bacteria to commonly used antimicrobials has been increasingly reported. The aim of this study was to describe antimicrobial susceptibility patterns of anaerobic bacteria isolated from clinical samples using a gradient diffusion method, E test (bioMérieux), in Victoria, Australia. Metronidazole, meropenem and amoxycillin-clavulanate were found to be active against almost all isolates tested. Most Gram positive anaerobic cocci (GPAC), exceptPeptostreptococcus anaerobius(64.6% penicillin-susceptible), remained susceptible to penicillin. AllClostridium perfringensisolates tested were penicillin, metronidazole and meropenem susceptible. OfB. fragilisisolates tested, 5% and 0.83% were meropenem and metronidazole non-susceptible, respectively. Clindamycin susceptibility in anaerobes other than the GPAC is approximately 75% and therefore should not be used as empirical treatment in the absence of susceptibility testing. Considering the global trend of antibiotic resistance among anaerobic bacteria, routine susceptibility testing of anaerobic bacteria, particularly when isolated from critical sites, as well as surveillance of local resistance trends is strongly encouraged. Gradient diffusion MIC determination of anaerobic bacteria is feasible in a clinical diagnostic laboratory and should be more widely utilised.