bluuebunny/crossref_metadata_2025_split huggingface dataset:
Continuous dynamic modeling of regulated cell adhesion
Authors: Ko J. M. , Lobo D. 
Published: March 2019

AbstractCell-cell adhesion is essential for tissue growth and multicellular pattern formation, and crucial for the cellular dynamics during embryogenesis and cancer progression. Understanding the dynamical gene regulation of cell adhesion molecules (CAMs) responsible for the emerging spatial tissue behaviors is a current challenge due to the complexity of these non-linear interactions and feedback loops at different levels of abstraction—from genetic regulation to whole-organism shape formation. Continuous mathematical models of cell adhesion are ideal for the modeling of the spatial dynamics of large cell populations, where different cell types define inherent adhesion strengths. However, biologically the adhesive properties of the cell arise dynamically from differential expression of CAMs, which are precisely regulated during development and cancer progression. To extend our understanding of cell and tissue behaviors due to the regulation of adhesion molecules, here we present a novel model for the spatial dynamics of cellular patterning, growth, and shape formation due to the differential expression of CAMs and their regulation. Capturing the dynamic interplay between genetic regulation, CAM expression, and differential cell adhesion, the proposed continuous model can recapitulate the complex and emergent spatial behaviors of cell populations that change their adhesion properties dynamically due to inter- and intracellular genetic regulation. This approach can demonstrate the mechanisms responsible for classical cell sorting behaviors, cell intercalation in proliferating populations, and the involution of germ layer cells induced by a diffusing morphogen during gastrulation. Integrating the emergent spatial tissue behaviors with the regulation of genes responsible for essential cellular properties such as adhesion will pave the way towards understanding the genetic regulation of large-scale complex patterns and shapes formation in developmental, regenerative, and cancer biology.
Tissue-specific MicroRNA Expression Alters Cancer Susceptibility Conferred by aTP53Noncoding Variant
Authors: Deng Qipan , Hu Hui , Yu Xinfang , Liu Shuanglin , Wang Lei , Chen Weiqun , Zhang Chi , Zeng Zhaoyang , Cao Ya , Li Ling , Zhang Mingzhi , Rosenfeld Steven , Bao Shideng , Hsi Eric , Young Ken H , Lu Zhongxin , Li Yong 
Published: March 2019

ABSTRACTPatients carryingTP53germline mutations develop Li-Fraumeni syndrome (LFS), a rare genetic disorder with high risk of several cancers, most notably breast cancer, sarcoma, and brain tumors. A noncoding polymorphism (rs78378222) inTP53, carried by scores of millions of people, was associated with moderate risk of brain, colon, and prostate tumors, and other neoplasms. We found a positive association between this variant and soft tissue sarcoma (odds ratio [OR] = 4.55,P= 3.3 x 10−5). In sharp contrast, this variant was protective against breast cancer (OR = 0.573,P= 0.0078). We generated a mouse line carrying this variant and found that this variant accelerated spontaneous tumorigenesis and tumor development at the brain, prostate, colon, and skeletal muscle, but strikingly, it significantly delayed mammary tumorigenesis. The variant created a miR-382 targeting site and compromised a miR-325 targeting site. Their differential expression resulted in p53 downregulation in the brain and several other tissues, but p53 upregulation in the mammary gland of the mutant mice compared to that of wild-type littermates. Thus, thisTP53variant is at odds with LFS mutants in breast cancer predisposition yet consistent with LFS mutants in susceptibility to soft tissue sarcoma and glioma. Our findings elucidate an underlying mechanism of cancer susceptibility that is conferred by genetic variation and yet altered by microRNA expression.
Patterns of diverse gene functions in genomic neighborhoods predict gene function and phenotype
Authors: Mihelčić Matej , Šmuc Tomislav , Supek Fran 
Published: March 2019

AbstractGenes with similar roles in the cell are known to cluster on chromosomes, thus benefiting from coordinated regulation. This allows gene function to be inferred by transferring annotations from genomic neighbors, following the guilt-by-association principle. We performed a systematic search for co-occurrence of >1000 gene functions in genomic neighborhoods across 1669 prokaryotic, 49 fungal and 80 metazoan genomes, revealing prevalent patterns that cannot be explained by clustering of functionally similar genes. It is a very common occurrence that pairs of dissimilar gene functions – corresponding to semantically distant Gene Ontology terms – are significantly co-located on chromosomes. These neighborhood associations are often as conserved across genomes as the known associations between similar functions, suggesting selective benefits from clustering of certain diverse functions, which may conceivably play complementary roles in the cell. We propose a simple encoding of chromosomal gene order, the neighborhood function profiles (NFP), which draws on diverse gene clustering patterns to predict gene function and phenotype. NFPs yield a 26-46% increase in predictive power over state-of-the-art approaches that propagate function across neighborhoods, thus providing hundreds of novel, high-confidence gene function inferences per genome. Furthermore, we demonstrate that the effect of structural variation on gene function distribution across chromosomes may be used to predict phenotype of individuals from their genome sequence.
Nuclear pores as versatile reference standards for quantitative superresolution microscopy
Authors: Thevathasan Jervis Vermal , Kahnwald Maurice , Cieśliński Konstanty , Hoess Philipp , Peneti Sudheer Kumar , Reitberger Manuel , Heid Daniel , Kasuba Krishna Chaitanya , Hoerner Sarah Janice , Li Yiming , Wu Yu-Le , Mund Markus , Matti Ulf , Pereira Pedro Matos , Henriques Ricardo , Nijmeijer Bianca , Kueblbeck Moritz , Sabinina Vilma Jimenez , Ellenberg Jan , Ries Jonas 
Published: March 2019

AbstractQuantitative fluorescence and superresolution microscopy are often limited by insufficient data quality or artifacts. In this context, it is essential to have biologically relevant control samples to benchmark and optimize the quality of microscopes, labels and imaging conditions.Here we exploit the stereotypic arrangement of proteins in the nuclear pore complex as in situ reference structures to characterize the performance of a variety of microscopy modalities. We created four genome edited cell lines in which we endogenously labeled the nucleoporin Nup96 with mEGFP, SNAP-tag or HaloTag or the photoconvertible fluorescent protein mMaple. We demonstrate their use a) as 3D resolution standards for calibration and quality control, b) to quantify absolute labeling efficiencies and c) as precise reference standards for molecular counting.These cell lines will enable the broad community to assess the quality of their microscopes and labels, and to perform quantitative, absolute measurements.
Trans-generational effects on diapause and life-history-traits of an aphid parasitoid
Authors: K. Tougeron , M. Devogel , J. van Baaren , C. Le Lann , T. Hance 
Published: March 2019

SummaryTransgenerational effects act on a wide range of insects’ life-history traits and can be involved in the control of developmental plasticity, such as diapause expression. Decrease in or total loss of winter diapause expression recently observed in some species could arise from inhibiting maternal effects. In this study, we explored transgenerational effects on diapause expression and traits in one industrial and one wild strain of the aphid parasitoidAphidius ervi. These strains were reared under short photoperiod (8:16 h LD) and low temperature (14 °C) conditions over two generations. Diapause levels, developmental times, physiological and morphological traits were measured. Diapause levels increased after one generation in the wild but not in the industrial strain. For both strains, the second generation took longer to develop than the first one. Tibia length and wing surface decreased over generations while fat content increased. A crossed-generations experiment focusing on the industrial parasitoid strain showed that offspring from mothers reared at 14 °C took longer to develop, were heavier, taller with wider wings and with more fat reserves than those from mothers reared at 20 °C (8:16 h LD). No effect of the mother rearing conditions was shown on diapause expression. Additionally to direct plasticity of the offspring, results suggest transgenerational plasticity effects on diapause expression, development time, and on the values of life-history traits. We demonstrated that populations showing low diapause levels may recover higher levels through transgenerational plasticity in response to diapause-induction cues, provided that environmental conditions are reaching the induction-thresholds specific to each population. Transgenerational plasticity is thus important to consider when evaluating how insects adapt to changing environments.
The use of a virus-derived targeting peptide to selectively kill staphylococcus bacteria with antimicrobial peptides
Authors: Ashiqul Islam S M , Choudhury Ankan , Ghidey Meron R. , Kearney Christopher Michel 
Published: March 2019

AbstractBackgroundTargeted therapies seek to selectively eliminate a pathogen without disrupting the microbiome community. Bacteriophages provide a rich, well-documented source of bacterium-specific binding proteins for use as targeting peptides fused to antimicrobial peptides. Though resistance may develop as with any antibiotic, the wealth of variants available in natural bacteriophage populations adds to the robustness of this system.ResultsHere, we target two cationic antimicrobial peptides (AMPs), plectasin and eurocin, by genetically fusing their coding sequence to that of the host-binding protein of bacteriophage A12C, which selectively infectsStaphylococcus. Surprisingly, we noted that targeting brought no change in the toxicity of the AMP when applied to two different staphylococci,S. aureusandS. epidermidis, but found a drastic decrease in toxicity against the negative controls,Enterococcus faecalisandBacillus subtilis. Thus, the differential selectivity in this case is a loss of toxicity against the non-target species rather than the gain of toxicity against the target species which was reported in previous studies with other types of targeting antimicrobial peptides.ConclusionThis is the first report of the use of virus-derived peptide sequences to target antimicrobial peptides. Considering the very large databank of bacteriophages and their bacterial hosts, this targeting approach should be generally applicable to a wide range of bacterial pathogens.
Scalable generalized linear mixed model for region-based association tests in large biobanks and cohorts
Authors: Zhou Wei , Zhao Zhangchen , Nielsen Jonas B. , Fritsche Lars G. , LeFaive Jonathon , Gagliano Taliun Sarah A. , Bi Wenjian , Gabrielsen Maiken E. , Daly Mark J. , Neale Benjamin M. , Hveem Kristian , Abecasis Goncalo R. , Willer Cristen J. , Lee Seunggeun 
Published: March 2019

AbstractWith very large sample sizes, population-based cohorts and biobanks provide an exciting opportunity to identify genetic components of complex traits. To analyze rare variants, gene or region-based multiple variant aggregate tests are commonly used to increase association test power. However, due to the substantial computation cost, existing region-based rare variant tests cannot analyze hundreds of thousands of samples while accounting for confounders, such as population stratification and sample relatedness. Here we propose a scalable generalized mixed model region-based association test that can handle large sample sizes and accounts for unbalanced case-control ratios for binary traits. This method, SAIGE-GENE, utilizes state-of-the-art optimization strategies to reduce computational and memory cost, and hence is applicable to exome-wide and genome-wide region-based analysis for hundreds of thousands of samples. Through the analysis of the HUNT study of 69,716 Norwegian samples and the UK Biobank data of 408,910 White British samples, we show that SAIGE-GENE can efficiently analyze large sample data (N > 400,000) with type I error rates well controlled.
The TMEM106B rs1990621 protective variant is also associated with increased neuronal proportion
Authors: Li Zeran , Farias Fabiana G. , Dube Umber , Del-Aguila Jorge L. , Mihindukulasuriya Kathie A. , Fernandez Maria Victoria , Ibanez Laura , Budde John P. , Wang Fengxian , Lake Allison M. , Deming Yuetiva , Perez James , Yang Chengran , Bradley Joseph , Davenport Richard , Bergmann Kristy , Benitez Bruno A. , Dougherty Joseph D. , Harari Oscar , Cruchaga Carlos 
Published: March 2019

AbstractBackgroundIn previous studies, we observed decreased neuronal and increased astrocyte proportions in AD cases in parietal brain cortex by using a deconvolution method for bulk RNA-seq. These findings suggested that genetic risk factors associated with AD etiology have a specific effect in the cellular composition of AD brains. The goal of this study is to investigate if there are genetic determinants for brain cell compositions.MethodsUsing cell type composition inferred from transcriptome as a disease status proxy, we performed cell type association analysis to identify novel loci related to cellular population changes in disease cohort. We imputed and merged genotyping data from seven studies in total of 1,669 samples and derived major CNS cell type proportions from cortical RNAseq data. We also inferred RNA transcript integrity number (TIN) to account for RNA quality variances. The model we performed in the analysis was: normalized neuronal proportion ∼ SNP + Age + Gender + PC1 + PC2 + median TIN.ResultsA variant rs1990621 located in the TMEM106B gene region was significantly associated with neuronal proportion (p=6.40×10−07) and replicated in an independent dataset. The association became more significant as we combined both discovery and replication datasets in multi-tissue meta-analysis (p=9.42×10−09) and joint analysis (p=7.66×10−10). This variant is in high LD with rs1990622 (r2 = 0.98) which was previously identified as a protective variant in FTD cohorts. Further analyses indicated that this variant is associated with increased neuronal proportion in participants with neurodegenerative disorders, not only in AD cohort but also in cognitive normal elderly cohort. However, this effect was not observed in a younger schizophrenia cohort with a mean age of death < 65. The second most significant loci for neuron proportion was APOE, which suggested that using neuronal proportion as an informative endophenotype could help identify loci associated with neurodegeneration.ConclusionThis result suggested a common pathway involving TMEM106B shared by aging groups in the present or absence of neurodegenerative pathology may contribute to cognitive preservation and neuronal protection.
Comparative thermal performance ofOrbicella franksiat its latitudinal range limits
Authors: Silbiger Nyssa J. , Goodbody-Gringley Gretchen , Bruno John F. , Putnam Hollie M. 
Published: March 2019

AbstractTemperature drives biological responses that scale from the cellular to ecosystem levels and thermal sensitivity will shape organismal functions and population dynamics as the world warms. Reef building corals are sensitive to temperature due to their endosymbiotic relationship with single celled dinoflagellates, with mass mortality events increasing in frequency and magnitude. The purpose of this study was to quantify the thermal sensitivity of important physiological functions of a Caribbean reef-building coral,Orbicella franksithrough the measurement of thermal performance curves (TPCs). We compared TPC metrics (thermal optimum, critical maximum, activation energy, deactivation energy, and rate at a standardized temperature) between two populations at the northern and southern extent of the geographic range of this species. We further compared essential coral organismal processes (gross photosynthesis, respiration, and calcification) within a site to determine which function is most sensitive to thermal stress using a hierarchical Bayesian modeling approach. We found evidence for differences in thermal performance, which could be due to thermal adaptation or acclimatization, with higher TPC metrics (thermal optimum and critical maximum) in warmer Panama, compared to cooler Bermuda. We also documented the hierarchy in thermal sensitivity of essential organismal functions within a population, with respiration less sensitive than photosynthesis, which was less sensitive than calcification. Understanding thermal performance of corals is essential for projecting coral reef futures, given that key biological functions necessary to sustain coral reef ecosystems are thermally-mediated.Summary statementWe apply a thermal performance curve approach to a variety of fitness related parameters in a reef building coral across its geographic range and various functions to improve our understanding of the inherent variability in thermal tolerance.
SULTA4A1 modulates synaptic development and function by promoting the formation of PSD-95/NMDAR complex
Authors: Culotta Lorenza , Terragni Benedetta , Vinci Ersilia , Sessa Alessandro , Broccoli Vania , Mantegazza Massimo , Verpelli Chiara 
Published: March 2019

AbstractSulfotransferase 4A1 (SULT4A1) is a cytosolic sulfotransferase, that is highly conserved across species and extensively expressed in the brain. However, the biological function of SULT4A1 is unclear. SULT4A1 has been implicated in several neuropsychiatric disorders, such as Phelan-McDermid Syndrome and schizophrenia. Here, we investigate the role of SULT4A1 within neuron development and function. Our data demonstrate that SULT4A1 modulates neuronal branching complexity and dendritic spines formation. Moreover, we show that SULT4A1, by negatively regulating the catalytic activity of Pin1 towards PSD-95, facilitates NMDAR synaptic expression and function. Finally, we demonstrate that the pharmacological inhibition of Pin1 reverses the pathological phenotypes of SULT4A1 knockdown neurons by specifically restoring dendritic spine density and rescuing NMDAR-mediated synaptic transmission. Together, these findings identify SULT4A1 as a novel player in neuron development and function by modulating dendritic morphology and synaptic activity.
Chemical degumming increases larvae size and facilitates the commercial production of Lumpfish (Cyclopterus lumpus) eggs
Authors: Pooley Craig , Berwick Mia , Leaniz Carlos Garcia de 
Published: March 2019

AbstractMany fishes produce adhesive eggs that confer protection from currents and predators in the wild, but that are more difficult to disinfect and aerate under aquaculture conditions. Removing egg adhesiveness (‘degumming’) has proved beneficial in the culture of many fish, and a recent gap analysis identified this as a potential way of increasing hatching success and minimize the risk of infectious diseases in the culture of lumpfish (Cyclopteurs lumpus), a novel species to aquaculture. We tested the efficacy of the enzyme alcalase (0.02%, 0.2%, 2%) as a degumming agent for lumpfish eggs, and examined its effects on hatching success, survival, and larvae size under laboratory and commercial conditions. A five-minute exposure to 0.2% and 2% alcalase decreased chorion thickness by 14% and resulted in 61-75% degumming rates, without any negative effects on hatching rate, larval survival, or incidence of embryo malformations. Degummed eggs hatched earlier than controls and resulted in larger larvae, which may confer some benefits under aquaculture conditions. A cost-benefit analysis indicates that the benefits of egg degumming compensate the costs of chemical treatment under most conditions, and that the optimal alcalase concentration is around 0.2%. We therefore recommend egg degumming as a way of making the lumpfish industry more efficient and sustainable.Statement of relevanceImproving the commercial production of lumpfish
Inhibition of Osteoblast Proliferation and Migration by Exogenous and Endogenous Formaldehyde
Authors: Teng Xu , Huang Wei , Yu Hefeng , Wang Pei , Li Weishi , Chen Zhongqiang , Fan Dongwei 
Published: March 2019

AbstractExogenous and endogenous formaldehyde (FA) plays an important role in cell growth and migration; however, its potential role in osteoblasts remains largely unclear. Cell counting kit-8 (CCK-8) and wound healing assays revealed that FA exposure at naturally occurring concentrations inhibited the proliferation and migration of mouse preosteoblast MC3T3-E1 cells. Moreover, RNA sequencing (RNA-seq) analysis revealed that FoxO1 signaling pathway components displayed distinct expression patterns upon FA exposure, reflected through significant enrichment of cell migration. In particular, FoxO1 Sirt1 and FA-induced related protein expression which were closely with cell proliferation and migration were confirmed by western blotting. The present results indicate that the FoxO1 pathway is involved in FA-induced inhibition of cell growth and migration.
A normative study of modified spatial context memory test in middle and older individuals
Authors: Wang Hsuan-Min , Huang Yo-Ping , Kuo Hsun-Yu , Kuo Hung-Chou 
Published: March 2019

AbstractIn view of the spatial context memory function of hippocampus complex region, we designed a modified spatial context memory test (SCMT) and try to early identify amnesic mild cognitive impairment.All participants with non-dementia were recruited and divided 2 age groups (55-65 years and 66-75 years) and 3 education levels (6-9 years, 10-12 years and more than 12 years). The mini-mental state examination, visual associative memory test, visual construction retention test, and logical memory subtest of the Wechsler memory scale-III were used to evaluate the cognition state of the individuals. Spatial-context memory test version I with combination of a spatial memory paradigm and a real-life event included 3 subtests of navigation, scene-event association and people-object association.A total of 147 individuals were confirmed to be normal in cognition in the assessment of the neuropsychological test battery. Regardless of age or level of education, there was no significance in perseveration errors and the retrieval of learned-well navigation information. In the Scene-Event Association test, the subjects with a low level of education seemed to have relative difficulty to quickly classify new information and establish the effective cues to retrieval. The subjects with a high level of education, the performance of spatial-context memory were negative correlation to the age. In the People-Object association test, the subjects in all six groups made no perseveration errors, but older subjects required more time to retrieval, and this situation was more prominent in the subjects with high level education.We establish a normal age‐ and education‐adjusted SCMT score in the middle and elder individuals.