bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational control of Bcl-2 promotes apoptosis of gastric carcinoma cells
Authors: Tao Shuangfen , Gu Jianchun , Wang Qing , Zheng Leizhen 
Published: April 2019

AbstractAberrantly expressed microRNAs (miRNAs) are essential for the tumorigenesis of gastric carcinoma (GC). Nevertheless, an effect of miR-383 on GC cells apoptosis has not been acknowledged previously. Here, we investigated the miR-383 level and anti-apoptotic protein Bcl-2 level in specimens of GC. Bioinformatics analyses was performed, and assay of luciferase-reporter was used for analyzing the relationship between Bcl-2 and miR-383. We analyzed survival of GC cells upon Fluorouracil treatment in an assay of CCK, and measured apoptosis of cells using flow cytometric FITC Annexin V apoptosis detection assay. The level of miR-383 was found extremely lower while the level of Bcl-2 levels was found extremely higher in GC specimens, in comparison with tissue from the adjacent non-tumor region. Additionally, the miR-383 level and Bcl-2 level inversely correlated in specimens of GC. In comparison with miR-383-high subjects, MiR-383-low subjects showed overall lower survival. Bioinformatics analyses revealed that miR-383 targeted the 3’-UTR of Bcl-2 mRNA to restrain its translation, demonstrated in a luciferase reporter assay. MiR-383 overexpression inhibited the Bcl-2-mediated survival of cell against apoptosis induced by Fluorouracil, while miR-383 depletion enhanced the cell survival. Together, these data indicate that suppression of miR-383 in GC improves the Bcl-2-mediated cell survival of GC against the chemotherapy-induced cell death. MiR-383 re-expression in cells of GC might augment apoptosis of GC cells during chemotherapy.
Genomics, Molecular and Evolutionary Perspective of NAC Transcription Factors
Authors: Mohanta Tapan Kumar , Yadav Dhananjay , Khan Adil , Hashem Abeer , Tabassum Baby , Khan Abdul Latif , Abda_Allah Eslayed Fathi , Al-Harrasi Ahmed 
Published: April 2019

AbstractNAC (NAM, ATAF1,2, and CUC2) transcription factors are one of the largest transcription factor families found in plants and are involved in diverse developmental and signalling events. Despite the availability of comprehensive genomic information from diverse plant species, the basic genomic, biochemical, and evolutionary details of NAC TFs have not been established. Therefore, NAC TFs family proteins from 160 plant species were analyzed in the current study. The analysis, among other things, identified the first algal NAC TF in the Charophyte, Klebsormidium flaccidum. Furthermore, our analysis revealed that NAC TFs are membrane bound and contain monopartite, bipartite, and multipartite nuclear localization signals. NAC TFs were also found to encode a novel chimeric protein domain and are part of a complex interactome network. Synonymous codon usage is absent in NAC TFs and it appears that they have evolved from orthologous ancestors and undergone significant duplication events to give rise to paralogous NAC TFs.
The Anticipation of Events in Time
Authors: Grabenhorst Matthias , Michalareas Georgios , Maloney Laurence T. , Poeppel David 
Published: April 2019

AbstractHumans use sensory input to anticipate events. The brain’s capacity to predict cues in time is commonly assumed to be modulated by two uncertainty parameters, the hazard rate (HR) of event probability and the uncertainty in time estimation, which increases with elapsed time. We investigate both assumptions by manipulating event probability density functions (PDF) in three sensory modalities. First we show, contrary to expectation, that perceptual systems use the reciprocal PDF – and not the HR – to model event probability density. Next we demonstrate that temporal uncertainty does not necessarily grow with elapsed time but also diminishes, depending on the event PDF. Finally we show that reaction time (RT) distributions comprise modality-specific and modality-independent components, the latter likely reflecting similarity in processing of probability density across sensory modalities. The results are consistent across vision, audition, and somatosensation, indicating that probability density is more fundamental than hazard rate in terms of the neural operations determining event anticipation and temporal uncertainty. Previous research identified neuronal activitity related to event probability in multiple levels of the cortical hierarchy such as early and higher sensory (V1, V4), association (LIP), motor and other areas. This work proposed that the elementary neuronal computation in estimation of probability across time is the HR. In contrast, our results suggest that the neurobiological implementation of probability estimation is based on a different, much simpler and more stable computation than HR: the reciprocal PDF of events in time.
In Silico Genetics Revealing Novel Mutations inCEBPAGene Associated with Acute Myeloid Leukemia
Authors: Mustafa Mujahed I. , Mohammed Zainab O. , Murshed Naseem S. , Elfadol Nafisa M. , Abdelmoneim Abdelrahman H. , Hassan Mohamed A. 
Published: April 2019

AbstractBackgroundMyelodysplastic syndrome/Acute myeloid leukemia (MDS/AML) is a highly heterogeneous malignant disease; affects children and adults of all ages. AML is one of the main causes of death in children with cancer. However, It is the most common acute leukemia in adults, with a frequency of over 20 000 cases per year in the United States of America alone.MethodsThe SNPs were retrieved from the dbSNP database. this SNPs were submitted into various functional analysis tools that done by SIFT, PolyPhen-2, PROVEAN, SNAP2, SNPs&GO, PhD-SNP and PANTHER, while structural analysis were done by I-mutant3 and MUPro. The most damaging SNPs were selected for further analysis by Mutation3D, Project hope, ConSurf and BioEdit softwares.ResultsA total of five novel nsSNPs out of 248 missense mutations were predicted to be responsible for the structural and functional variations of CEBPA protein.ConclusionIn this study the impact of functional SNPs in the CEBPA gene was investigated through different computational methods, which determined that (R339W, R288P, N292S N292T and D63N) are novel SNPs have a potential functional effect and can thus be used as diagnostic markers and may facilitate in genetic studies with a special consideration of the large heterogeneity of AML among the different populations.
Microbial species coexistence depends on the host environment
Authors: Deines Peter , Hammerschmidt Katrin , Bosch Thomas CG 
Published: April 2019

AbstractOrganisms and their resident microbial communities form a complex and mostly stable ecosystem. It is known that the specific composition and abundance of certain bacterial species affect host health and fitness, but the processes that lead to these microbial patterns are unknown. We investigate this by deconstructing the simple microbiome of the freshwater polyp Hydra. We contrast the performance of its two main bacterial associates, Curvibacter and Duganella, on germ free hosts with two in vitro environments over time. We show that interactions within the microbiome but also the host environment lead to the observed species frequencies and abundances. More specifically, we find that both microbial species can only stably coexist in the host environment, whereas Duganella outcompetes Curvibacter in both in vitro environments irrespective of initial starting frequencies. While Duganella seems to benefit through secretions of Curvibacter, its competitive effect on Curvibacter depends upon direct contact. The competition might potentially be mitigated through the spatial structure of the two microbial species on the host, which would explain why both species stably coexist on the host. Interestingly, the fractions of both species on the host do not match the fractions reported previously nor the overall microbiome carrying capacity as reported in this study. Both observations indicate that the rare microbial community members might be relevant for achieving the native community composition and carrying capacity. Our study highlights that for dissecting microbial interactions the specific environmental conditions need to be replicated, a goal difficult to achieve with in vitro systems.ImportanceThis work studies microbial interactions within the microbiome of the simple cnidarian, Hydra, and investigates whether microbial species coexistence and community stability depends on the host environment. We find that the outcome of the interaction between the two most dominant bacterial species in Hydra’s microbiome differs depending on the environment and only results in a stable coexistence in the host context. The interactive ecology between the host, the two most dominant microbes, but also the less abundant members of the microbiome, are critically important for achieving the native community composition. This indicates that the metaorganism environment needs to be taken into account when studying microbial interactions.
Large-scale functional integration, rather than functional dissociation along dorsal and ventral streams, underlies visual perception and action
Authors: Ray Dipanjan , Hajare Nilambari , Roy Dipanjan , Banerjee Arpan 
Published: April 2019

AbstractVisual dual stream theory posits that two distinct neural pathways of specific functional significance originate from primary visual areas and reach the inferior temporal (ventral) and posterior parietal areas (dorsal). However, there are several unresolved questions concerning the fundamental aspects of this theory. For example, is the functional dissociation between ventral and dorsal stream driven by features in input stimuli or is it driven by categorical differences between visuo-perceptual and visuo-motor functions? Is the dual stream rigid or flexible? What is the nature of the interactions between two streams? We addressed these questions using fMRI recordings on healthy human volunteers and employing stimuli and tasks that can tease out the divergence between visuo-perceptual and visuo-motor models of dual stream theory. fMRI scans were repeated after seven practice sessions that were conducted in a non-MRI environment to investigate the effects of neuroplasticity. Brain activation analysis supports an input-based functional dissociation and existence of context-dependent neuroplasticity in dual stream areas. Intriguingly, premotor cortex activation was observed in the position perception task and distributed deactivated regions were observed in all perception tasks thus, warranting a network level analysis. Dynamic causal modelling (DCM) analysis incorporating activated and deactivated brain areas during perception tasks indicates that the brain dynamics during visual perception and actions could be interpreted within the framework of predictive coding. Effectively, the network level findings point towards the existence of more intricate context-driven functional networks selective of “what” and “where” information rather than segregated streams of processing along ventral and dorsal brain regions.
Maturation of the human B-cell receptor repertoire with age
Authors: Ghraichy Marie , Galson Jacob D. , Kovaltsuk Aleksandr , Niederhäusern Valentin von , Schmid Jana Pachlopnik , Recher Mike , Jauch Annaïse J , Miho Enkelejda , Kelly Dominic F. , Deane Charlotte M. , Trück Johannes 
Published: April 2019

AbstractB cells play a central role in adaptive immune processes, mainly through the production of antibodies. The maturation of the B-cell system with age is poorly studied. We extensively investigated age-related alterations of naïve and antigen-experienced B-cell receptor (BCR) repertoires. The most significant changes were observed in the first 10 years of life, and were characterized by altered immunoglobulin gene usage and an increased frequency of mutated antibodies structurally diverging from their germline precursors. Older age was associated with an increased usage of downstream constant region genes and fewer antibodies with self-reactive properties. As mutations accumulated with age, the frequency of germline-encoded self-reactive antibodies decreased, indicating a possible beneficial role of self-reactive B-cells in the developing immune system. Our results suggest a continuous process of change through childhood across a broad range of parameters characterizing BCR repertoires and stress the importance of using well-selected, age-appropriate controls in BCR studies.
Foundress Number, But Not Queen Size or Boldness, Predicts Colony Life-History in Wild Paper Wasps
Authors: Wright Colin M. , Fisher David N. , Nerone Wayne V. , Lichtenstein James L.L. , Tibbetts Elizabeth A. , Pruitt Jonathan N. 
Published: April 2019

AbstractColonies of social insects exhibit a spectacular variety of life histories. Here we documented the degree of variation in colony life-history traits, mostly related to productivity, in two species of wild paper wasps. We then tested for associations between colony life-history traits to look for trade-offs or positively associated syndromes, and examined whether individual differences in the behavioral tendencies of foundresses (Polistes metricus) or the number of cofoundresses (P. fuscatus) influenced colony life-history. The majority of our measures of colony life-history were positively related, indicating no obvious resource allocation trade-offs. Instead, the positive association of traits into a productivity syndrome appears to be driven by differences in queen or microhabitat quality. Syndrome structure differed only marginally between species. Queen boldness and body size were not associated with colony life-history inP. metricus. Colonies initiated by multipleP. fuscatusfoundresses were generally more productive, and this advantage was approximately proportional to the number of cofoundresses. These findings demonstrate that colony life-history traits can be associated together much like individual life-history traits, and the associations seen here convey that differences in overall productivity drive between-colony differences in life-history.
Imperfect strategy transmission can reverse the role of population viscosity on the evolution of altruism
Authors: Débarre F. 
Published: April 2019

AbstractPopulation viscosity,i.e., low emigration out of the natal deme, leads to high within-deme relatedness, which is beneficial to the evolution of altruistic behavior when social interactions take place among deme-mates. However, a detrimental side-effect of low emigration is the increase in competition among related individuals. The evolution of altruism depends on the balance between these opposite effects. This balance is already known to be affected by details of the life cycle; we show here that it further depends on the fidelity of strategy transmission from parents to their offspring. We consider different life cycles and identify thresholds of parent-offspring strategy transmission inaccuracy, above which higher emigration can increase the frequency of altruists maintained in the population. Predictions were first obtained analytically assuming weak selection and equal deme sizes, then confirmed with stochastic simulations relaxing these assumptions. Contrary to what happens with perfect strategy transmission from parent to off-spring, our results show that higher emigration can be favorable to the evolution of altruism.
Extensive impact of low-frequency variants on the phenotypic landscape at population-scale
Authors: Fournier T. , Saada O. Abou , Hou J. , Peter J. , Caudal E. , Schacherer J. 
Published: April 2019

AbstractGenome-wide association studies (GWAS) allows to dissect the genetic basis of complex traits at the population level1. However, despite the extensive number of trait-associated loci found, they often fail to explain a large part of the observed phenotypic variance2–4. One potential source of this discrepancy could be the preponderance of undetected low-frequency genetic variants in natural populations5,6. To increase the allele frequency of those variants and assess their phenotypic effects at the population level, we generated a diallel panel consisting of 3,025 hybrids, derived from pairwise crosses between a subset of natural isolates from a completely sequenced 1,011 Saccharomyces cerevisiae population. We examined each hybrid across a large number of growth traits, resulting in a total of 148,225 cross/trait combinations. Parental versus hybrid regression analysis showed that while most phenotypic variance is explained by additivity, a significant proportion (29%) is governed by non-additive effects. This is confirmed by the fact that a majority of complete dominance is observed in 25% of the traits. By performing GWAS on the diallel panel, we detected 1,723 significantly associated genetic variants, with 16.3% of them being low-frequency variants in the initial population. These variants, which would not be detected using classical GWAS, explain 21% of the phenotypic variance on average. Altogether, our results demonstrate that low-frequency variants should be accounted for as they contribute to a large part of the phenotypic variation observed in a population.
Accelerated trans-sulfuration metabolically defines a discrete subclass of ALS patients
Authors: Chen Qiuying , Sandhu Davinder , Konrad Csaba , Roychoudhury Dipa , Schwartz Benjamin I. , Cheng Roger R. , Bredvik Kirsten , Kawamata Hibiki , Calder Elizabeth L. , Studer Lorenz , Fischer Steven. M. , Manfredi Giovanni , Gross Steven. S. 
Published: April 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a disease characterized by progressive paralysis and death. Most ALS cases are sporadic (sALS) and patient heterogeneity poses a formidable challenge for the development of viable biomarkers and effective therapies. Applying untargeted metabolite profiling on 77 sALS patient-derived primary dermal fibroblast lines and 45 sex/age matched controls, we found that ∼25% of cell lines (termed sALS-1) are characterized by upregulated trans-sulfuration, where methionine-derived homocysteine is channeled into cysteine and glutathione synthesis. sALS-1 fibroblasts exhibit a growth defect when grown under oxidative conditions, that can be fully-rescued by N-acetylcysteine. [U-13C]-glucose tracing shows that activation of the trans-sulfuration pathway is associated with accelerated glucose flux into the TCA cycle. Based on four metabolites, we developed a support vector machine model capable of distinguishing sALS-1 with 97.5% accuracy. Importantly, plasma metabolite profiling identifies a systemic perturbation of cysteine metabolism as a hallmark of sALS-1. These results indicate that sALS patients can be stratified into distinct metabotypes, differently sensitive to metabolic stress, and provides new insights into metabolic biomarkers for personalized sALS therapy.
Bottom trawl catch comparison in the Mediterranean Sea: Flexible Turtle Excluder Device (TED)vstraditional gear
Authors: Vasapollo Claudio , Virgili Massimo , Petetta Andrea , Bargione Giada , Sala Antonello , Lucchetti Alessandro 
Published: April 2019

AbstractThe Mediterranean Sea is a hotspot of biodiversity, but the high fishing pressure results in high bycatch rates of protected (sea turtles and cetaceans) and top predator species (sharks). The reduction of bycatch is challenging for fishery scientists, as conservation of these species has become a priority. Among the animals threatened by fishing activities, the loggerhead (Caretta caretta) represents a charismatic species considered as “vulnerable” at the global scale by IUCN.In the Mediterranean Sea, trawl nets show the highest probabilities of bycatch of protected species, with high rates of mortality. A new flexible Turtle Excluder Device (TED) has been tested for the first time on a commercial scale in the Mediterranean Sea to assess its effectiveness in reducing bycatch. The results did not show any significant (α = 0.05) loss in terms of commercial weight, but a significant reduction of debris in the codend of the nets mounting the TED respect to traditional nets. The catch comparison of the main commercial species showed similar rates without any significant loss of sizes, with the only exception of anglerfishes (Lophiusspp.) that showed a loss of the largest individuals by TED. In terms of bycatch, the traditional nets captured mostly rays and sharks, while no turtles were captured, at all. In this regard, the authors were informed by other vessels operating in the same areas at the time of the trials about some accidental catches of loggerhead turtles. Our results demonstrated that the flexible TED represents a practical and effective solution to reduce the bycatch of endangered species in coastal Mediterranean demersal multispecies fisheries, as demonstrated experimentally also in other areas of the world. The measures involving technical modifications of fishing gears require significant investments but are technically feasible and could guarantee the success of the conservation.
TLR4-dependent signaling drives extracellular catabolism of low-density lipoprotein aggregates
Authors: Singh Rajesh K. , Haka Abigail S. , Asmal Arky , Barbosa-Lorenzi Valéria C. , Grosheva Inna , Chin Harvey F. , Xiong Yuquan , Hla Timothy , Maxfield Frederick R. 
Published: April 2019

ABSTRACTObjectiveAggregation and modification of low-density lipoproteins (LDL) promotes their retention and accumulation in the arteries. This is a critical initiating factor during atherosclerosis. Macrophage catabolism of aggregated LDL (agLDL) occurs using a specialized extracellular, hydrolytic compartment, the lysosomal synapse (LS). Compartment formation by local actin polymerization and delivery of lysosomal contents by exocytosis promotes acidification of the compartment and degradation of agLDL. Internalization of metabolites such as cholesterol promotes foam cell formation, a process that drives atherogenesis. Further, there is accumulating evidence for the involvement of TLR4 and its adaptor protein MyD88 in atherosclerosis. Here, we investigated the role of TLR4 in catabolism of agLDL using the LS and foam cell formation.Approach and ResultsUsing bone marrow-derived macrophages (BMMs) from knockout mice, we find that TLR4 and MyD88 regulate compartment formation, lysosome exocytosis, acidification of the compartment and foam cell formation. Using siRNA, pharmacological inhibition and knockout BMMs, we implicate SYK, PI3 kinase and Akt in agLDL catabolism using the LS. Using bone marrow transplantation of LDL receptor knockout mice with TLR4KO bone marrow, we show that deficiency of TLR4 protects macrophages from lipid accumulation during atherosclerosis. Finally, we demonstrate that macrophagesin vivoform an extracellular compartment and exocytose lysosome contents similar to that observedin vitrofor degradation of agLDL.ConclusionsWe present a mechanism in which interaction of macrophages with agLDL initiates a TLR4 signaling pathway, resulting in formation of the LS, catabolism of agLDL and lipid accumulationin vitroandin vivo.