bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interpretable deep generative models for genomics
Authors: Choi Yongin , Li Ruoxin , Quon Gerald 
Published: September 2021

ABSTRACTDeep neural networks implementing generative models for dimensionality reduction have been extensively used for the visualization and analysis of genomic data. One of their key limitations is lack of interpretability: it is challenging to quantitatively identify which input features are used to construct the embedding dimensions, thus preventing insight into why cells are organized in a particular data visualization, for example. Here we present a scalable, interpretable variational autoencoder (siVAE) that is interpretable by design: it learns feature embeddings that guide the interpretation of the cell embeddings in a manner analogous to factor loadings of factor analysis. siVAE is as powerful and nearly as fast to train as the standard VAE but achieves full interpretability of the embedding dimensions. Using siVAE, we exploit a number of connections between dimensionality reduction and gene network inference to identify gene neighborhoods and gene hubs, without the explicit need for gene network inference. We observe a systematic difference in the gene neighborhoods identified by dimensionality reduction methods and gene network inference algorithms in general, suggesting they provide complementary information about the underlying structure of the gene co-expression network. Finally, we apply siVAE to implicitly learn gene networks for individual iPSC lines and uncover a correlation between neuronal differentiation efficiency and loss of co-expression of several mitochondrial complexes, including NADH dehydrogenase, cytochrome C oxidase, and cytochrome b.
Acidity and sulfur oxidation intermediate concentrations controlled by O2-driven partitioning of sulfur oxidizing bacteria in a mine tailings impoundment
Authors: Whaley-Martin Kelly J. , Chen Lin-Xing , Nelson Tara Colenbrander , Gordon Jennifer , Kantor Rose , Twible Lauren E. , Marshall Stephanie , Rossi Laura , Bessette Benoit , Baron Christian , Apte Simon , Banfield Jillian F. , Warren Lesley A. 
Published: September 2021

AbstractAcidification of freshwater in mining impacted areas is a major global environmental problem catalyzed by sulfur-oxidizing bacteria (SOB). To date, little is known about the active bacteria in mine tailings impoundments and their environmental niches. Here, biological sulfur oxidation was investigated over four years in a mine tailings impoundment, integrating sulfur geochemistry, genome-resolved metagenomics and metatranscriptomics. We demonstrated oxygen driven niche partitioning of SOB and their metabolic pathways that explain acidity generation and thiosulfate persistence. Four chemolithoautotrophic SOB, Halothiobacillus, Thiobacillus, Sulfuricurvum and Sediminibacterium comprised 37% to 73% of the analyzed communities. The impoundment waters alternated between the dominance of Halothiobacillus versus a Thiobacillus, Halothiobacillus, Sulfuricurvum and Sediminibacterium consortia. Halothiobacillus dominance was associated with lower pH values (∼4.3), higher [H+]/[SO42-] and lower [S2O32-], collectively indicative of extensive sulfur oxidation. Halothiobacillus, which couple sulfur oxidation via the Sox pathway to aerobic respiration or NO2- reduction, were present throughout the depth profile, yet their expression of sox genes occurred only in upper highly oxygenated waters. Conversely, when consortia of Thiobacillus, Halothiobacillus, Sulfuricurvum and Sediminibacterium dominated, recycling/disproportionating reactions were more prevalent. Thiobacillus, which dominated deeper micro-oxic/anoxic waters, oxidized sulfur primarily through the rDSR pathway, coupled to NO3-/NO2- reduction, resulting in lower [H+]/[SO42-] and higher [S2O32-] relative to upper waters. These field results mirror the Sox/rDSR-geochemical patterns of experimental SOB enrichments and reveal opportunities for biological treatments of recalcitrant reduced sulfur compounds, as well as gene-based monitoring and in situ RNA detection to predict the onset of problematic geochemistry.
Photoinduced Isomerization Sampling of Retinal in Bacteriorhodopsin
Authors: Ren Zhong 
Published: September 2021

AbstractPhotoisomerization of retinoids inside a confined protein pocket represents a critical chemical event in many important biological processes from animal vision, non-visual light effects, to bacterial light sensing and harvesting. Light driven proton pumping in bacteriorhodopsin entails exquisite electronic and conformational reconfigurations during its photocycle. However, it has been a major challenge to delineate transient molecular events preceding and following the photoisomerization of the retinal from noisy electron density maps when varying populations of intermediates coexist and evolve as a function of time. Here I report several distinct early photoproducts deconvoluted from the recently observed mixtures in time-resolved serial crystallography. This deconvolution substantially improves the quality of the electron density maps hence demonstrates that the all-trans retinal undergoes extensive isomerization sampling before it proceeds to the productive 13-cis configuration. Upon light absorption, the chromophore attempts to perform trans-to-cis isomerization at every double bond together with the stalled anti-to-syn rotations at multiple single bonds along its polyene chain. Such isomerization sampling pushes all seven transmembrane helices to bend outward, resulting in a transient expansion of the retinal binding pocket, and later, a contraction due to recoiling. These ultrafast responses observed at the atomic resolution support that the productive photoreaction in bacteriorhodopsin is initiated by light-induced charge separation in the prosthetic chromophore yet governed by stereoselectivity of its protein pocket. The method of a numerical resolution of concurrent events from mixed observations is also generally applicable.Significance StatementPhotoisomerization of retinal is a critical rearrangement reaction in many important biological processes from animal vision, non-visual light effects, to bacterial light sensing and harvesting. It has been a major challenge to visualize rapid molecular events preceding and following photoisomerization so that many protein functions depending on such reaction remain vaguely understood. Here I report a direct observation of the stereoselectivity of bacteriorhodopsin hence delineate the structural mechanism of isomerization. Upon a light-induced charge separation, the retinal in a flat conformation attempts to perform double bond isomerization and single bond rotation everywhere along its polyene chain before it proceeds to the specific, productive configuration. This observation improves our understanding on how a non-specific attraction force could drive a specific isomerization.
The landscape of nucleotide diversity inDrosophila melanogasteris shaped by mutation rate variation
Authors: Barroso Gustavo V. , Dutheil Julien Y. 
Published: September 2021

ABSTRACTWhat shapes the distribution of nucleotide diversity along the genome? Attempts to answer this question have sparked debate about the roles of neutral stochastic processes and natural selection in molecular evolution. However, the mechanisms of evolution do not act in isolation, and integrative models that simultaneously consider the influence of multiple factors on diversity are lacking; without them, confounding factors lurk in the estimates. Here we present a new statistical method that jointly infers the genomic landscapes of genealogies, recombination rates and mutation rates. In doing so, our model captures the effects of genetic drift, linked selection and local mutation rates on patterns of genomic variation. We then formalize a causal model of how these microevolutionary mechanisms interact, and cast it as a linear regression to estimate their individual contributions to levels of diversity along the genome. Our analyses reclaim the well-established signature of linked selection inDrosophila melanogaster,but we estimate that the mutation landscape is the major driver of the genome-wide distribution of diversity in this species. Furthermore, our simulation results suggest that in many evolutionary scenarios the mutation landscape will be a crucial factor shaping diversity, depending notably on the genomic window size. We argue that incorporating mutation rate variation into the null model of molecular evolution will lead to more realistic inferences in population genomics.
CRISPR-Cas Inhibits Natural Transformation Through Altruistic Group Defense and Self-Sacrifice
Authors: Cooper Robert M. , Hasty Jeff 
Published: September 2021

SummaryCRISPR-Cas systems present an evolutionary tradeoff: does defense against phages and other parasitic DNA also prevent cells from acquiring potentially helpful new genes? Genomic analyses of this conundrum have arrived at often contradictory conclusions. Meanwhile, experimental studies have focused mainly on phages, conjugation, or artificial transformation, but less work has examined natural competence, a major driver of evolution and antibiotic resistance. Here, we use Acinetobacter baylyi, which combines high natural competence with a functional CRISPR-Cas system, to experimentally probe the interactions between CRISPR-Cas and natural competence. In these bacteria, the endogenous CRISPR array largely allows natural transformation by targeted DNA. However, CRISPR-Cas then kills the newly autoimmune cells in a form of programmed cell death. CRISPR-Cas often allows self-targeting cells to form colonies, albeit with fitness costs. Thus CRISPR-Cas appears to block natural transformation in a process more akin to altruistic group defense than an individual immune system.
Kinetics of the inflammatory response during experimentalBabesia rossiinfection of beagle dogs
Authors: Atkinson B.K. , Thompson P. , Van Zyl E. , Goddard A. , Rautenbach Y. , Schoeman J.P. , Mukorera V. , Leisewitz A. 
Published: September 2021

AbstractBabesia rossicauses severe morbidity and mortality in dogs in sub-Saharan Africa, and the complications associated with this disease are likely caused by an unfocused, excessive inflammatory response. During this experimentalB. rossistudy we investigated inflammatory marker and cytokine kinetics during infection and after treatment. We aimed to determine whether infectious dose and treatment would influence the progression of the inflammatory response and clinical disease. Five healthy male beagle dogs were infected withB. rossi, three with a high infectious dose (HD group) and two with a low infectious dose (LD group). Clinical examination, complete blood count (CBC) and C-reactive protein (CRP) were determined daily. Cytokines were quantified on stored plasma collected during the study, using a canine specific cytokine magnetic bead panel (Milliplex©). The experiment was terminated when predetermined endpoints were reached. Parasitemia occurred on day 1 and 3 in the HD group and LD group respectively. The rate of increase in parasitemia in the HD group was significantly faster than that seen in the LD group. Significant differences were found in heart rate, blood pressure, interferon gamma (INFγ), keratinocyte chemoattractant (KC), INFγ-induced protein 10 (IP10), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP1), tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), IL-6, IL-7, IL-8, IL-10 IL-15, IL-18, CRP, neutrophils and monocytes between groups at multiple time points during the course of the infection. Our findings suggest that the initiation of inflammation occurs before the onset of clinical disease inB. rossiinfection and infectious dose influences the onset of the inflammatory response. Treatment not only fails to curb the inflammatory response but may enhance it. Finally, we found that there is an imbalance in pro/anti-inflammatory cytokine concentrations during infection which may promote parasite replication.
Cytokine gene polymorphism and parasite susceptibility in free-living rodents: importance of non-coding variants
Authors: Kloch Agnieszka , Mierzejewska Ewa J , Welc-Falęciak Renata , Bajer Anna , Biedrzycka Aleksandra 
Published: September 2021

AbstractAssociations between genetic variants and susceptibility to infections have long been studied in free-living hosts to infer contemporary evolutionary forces shaping genetic polymorphisms of the immunity genes. Despite extensive studies of receptors, such as MHC or TLR, little is known about efferent arm of the immune system. Cytokines are signalling molecules that trigger and modulate the immune response, acting as a crucial link between innate and adaptive immunity. In the present study we investigated how genetic variation in cytokines affects susceptibility to parasitic diseases in bank voles. We focused on three cytokines: tumour necrosis factor (TNF), lymphotoxin alpha (LTα), and interferon beta (IFNβ1). Two SNPs in LTα and two in IFNβ1 significantly affected susceptibility to nematodes, and was of them was also associated with susceptibility to microbial pathogen Bartonella. All these variants displayed signatures of selection. One of the variants was synonymous, and one was located in an intron. Our study shows that cytokines are prone to parasite-driven selection, and non-coding variants may play an important role in susceptibility to infections in wild systems.
The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis
Authors: Roblek Marko , Bicher Julia , van Gogh Merel , György Attila , Seeböck Rita , Szulc Bozena , Damme Markus , Olczak Mariusz , Borsig Lubor , Siekhaus Daria 
Published: September 2021

AbstractSolute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in a mouse model. We identified an increased migratory potential in MFSD1-/-tumor cells which was mediated by increased focal adhesion turn-over, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, down-regulation of MFSD1 expression was observed during early steps of tumorigenesis and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread.
Change in brand attitude depending on fashion film type: the psychological mechanisms by engagement and consumer fantasy proneness
Authors: Park Hyun Hee 
Published: September 2021

PurposeThis study investigates the effect of consumers' brand attitude changes according to the fashion film type. Furthermore, it examines the psychological mechanism by engagement and consumer fantasy proneness. This study is meaningful because it provides a more in-depth understanding of the use of fashion film as a means of consumer-oriented persuasion communication.Design/methodology/approachThis research uses a 2(fashion film type: narrative vs non-narrative) × 2(consumer fantasy proneness: high vs low) mixed factorial design to test the hypotheses. ANOVA and the PROCESS macro mounted on SPSS was used to test hypotheses.FindingsThe group with high consumer fantasy proneness showed more changes in brand attitude when exposed to non-narrative than narrative fashion films, but the group with low consumer fantasy proneness showed no significant difference in brand attitude change according to the fashion film type. In addition, when consumer fantasy proneness is high, media and brand engagement for non-narrative fashion films increase sequentially, resulting in a greater change in brand attitude, whereas these psychological mechanisms do not work in groups with low consumer fantasy proneness.Practical implicationsFashion brands should identify their respective target group when producing fashion films and choose differentiated narrative forms. In the case of pursuing a fantastic aesthetic value, the non-narrative type induces more attention and curiosity from consumers than the narrative type, which affects the feeling of a special bond or relevance with the brand.Originality/valueThis study has value in that it demonstrates the rationale for why a fashion brand needs to select a differentiated content structure according to the aesthetic value pursued when making a fashion film in branding work.
Consumer adoption of online-to-offline food delivery services in China and New Zealand
Authors: Wang Ou , Scrimgeour Frank 
Published: September 2021

PurposeThis study explores impacts of innovation-adoption characteristics, food choice motives, segmentation and socio-demographics on consumer adoption of online-to-offline food delivery services (O2O-FDS) in a Western developed country – New Zealand – and an Asian developing country – China.Design/methodology/approachAn online survey of 1,185 consumers provides data that the authors analyse using factor analyses, structural equation modelling and cluster analysis.FindingsThe following innovation-adoption characteristics and food choice motives have statistically significant effects on consumers' attitudes and/or purchase intentions towards O2O-FDS in the pooled sample and/or the samples of two countries: perceived incentive, perceived complexity, processed convenience, cheapness, taste appeal, safety-assured and purchase convenience. Three consumer segments are recognized: conservatives (26.6%), food-value seekers (40.8%) and pioneers (32.6%). Significant differences are found in marital status, age, household income, education level, household size, occupation, country and residential areas across the three segments.Originality/valueThis is the first study to systematically understand significant influencing factors for the O2O-FDS adoption by using a sample set composed of both Eastern and Western consumers.
A qualitative conceptual framework to tackle skill shortages in offsite construction industry: a scientometric approach
Authors: Saad Syed , Alaloul Wesam Salah , Ammad Syed , Qureshi Abdul Hannan 
Published: September 2021

PurposeThis study assessed the key construction technology trends and tracked the impact of these developments on labor influencing factors in an effort to alleviate the limitations posed by skilled labor scarcity in offsite construction (OSC).Design/methodology/approachThe study followed systematic literature review to acquisition initial data sets. The data retrieved form identified databases was then subjected to scientometric analysis. In next stage, disruptive factors were identified to produce a conceptual framework followed by its practical application for an OSC firm.FindingsThis study identified seven construction technologies with a potential to disrupt OSC in future. The study also developed a conceptual framework as a benchmark to help establish further frameworks for policy interns in OSC.Research limitations/implicationsThe review conducted only takes into account the literature from 2009 to March 2021. Any prior to the date and unpublished studies were not included in study.Practical implicationsA proper utilization of conceptual framework can contribute to technological adoption significantly lowering the need of labor in OSC industry. Moreover, the established discussion on understanding the purpose of deploying latest technology may reduce additional costs, management, time and allocation of labor resources.Social implicationsThis study provides a mechanism to intern OSC policymakers to impartially incorporate the latest technology in OSC.Originality/valueThis study fulfilled an identified need to study latest technological trends in OSC by utilizing bibliometric tools with SLR. The disruptive categories and factors highlighted by the study were not identified in a systematic manner in previous studies, which could further enhance the implementation of latest construction technology in OSC.
My future entrepreneurial self: antecedents of entrepreneurial identity aspiration
Authors: Gregori Patrick , Holzmann Patrick , Schwarz Erich J. 
Published: September 2021

PurposeEntrepreneurial identity aspiration refers to the desire to occupy an entrepreneurial role in the future and is an essential impetus for initially engaging in entrepreneurial activities. Building on identity theory, the article investigates the effects of personal attitudes, experiences and inclination towards specific practices on the strength of entrepreneurial identity aspiration.Design/methodology/approachThis article applies multiple linear regression analysis to test the developed hypotheses on an original sample of 127 vocational college students in Austria.FindingsResults show that risk-taking propensity, proactiveness, entrepreneurial self-efficacy and competitiveness drive entrepreneurial identity aspiration. The effects of innovativeness and need for achievement motivation are nonsignificant. Data further suggest that entrepreneurial identity aspiration is related to gender, while entrepreneurial exposure and previous entrepreneurship education show no or adverse effects.Practical implicationsBased on our findings, the authors argue that education should focus on teaching and discussing the identified attitudes and inclinations to foster the formation of entrepreneurial identities. Doing so increases students' aspirations and provides them with the necessary cognitive underpinnings for subsequent entrepreneurial action. The article suggests action-based teaching to achieve this goal.Originality/valueThis article is the first to investigate antecedents of entrepreneurial identity aspiration by connecting it to essential concepts of entrepreneurship research. The authors extend previous work on entrepreneurial identity and add to the theoretical approaches for research in entrepreneurship education. Furthermore, the article points out central aspects that should receive additional attention in educational settings.