bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Smurf1 E3 ligase inhibitors that prevent transthiolation
Authors: Chuong Patrick , Statsyuk Alexander 
Published: October 2023

AbstractSmurf1 is a HECT E3 ligase that is genetically micro-duplicated in human patients and is associated with osteoporosis. Smurf1-/-mice on the other hand show an increase in bone density as they age, while being viable and fertile. Therefore, Smurf1 is a promising drug target to treat osteoporosis. This paper reports the discovery, synthesis, and biochemical characterization of highly selective Smurf1 inhibitors. We show that these compounds inhibit the catalytic HECT domain of Smurf1 with 500 nM IC50, but they do not inhibit closely related Smurf2 ligase, which is 80% identical to Smurf1. We show that Smurf1 inhibitors act by preventing the trans-thiolation reaction between Smurf1 and E2∼Ub thioesters. Our preliminary studies show that the C-lobe of Smurf1 alone does not contribute to the observed high selectivity of Smurf1 inhibitors.
Temporal restriction of RNAi reveals breakdown of the segmentation clock is reversible after knock down of primary pair rule genes but not Wnt-signaling in the red flour beetle
Authors: Kaufholz Felix , Ulrich Julia , Hakeemi Muhammad Salim , Bucher Gregor 
Published: October 2023

AbstractAnimals from all major clades have evolved a segmented trunk, reflected for instance in the repetitive organization of the human spine or the insect segments. These units emerge during embryonic segmentation from a posterior segment addition zone, where repetitive gene activity is regulated in a spatiotemporal dynamic described by the clock and wavefront/speed gradient model. This model has been tested in the red flour beetleTribolium castaneumand other insects by studying the effect of the RNAi knockdown of segmentation genes. For upstream components such as primary pair rule genes, caudal or Wnt pathway components, this treatment often led to the breakdown of segmentation. However, it has remained untested, how the system would react to a temporally limited interruption of gene function. In order to ask such questions, we established a novel experimental system inT. castaneum, which allows blocking an ongoing RNAi effect with temporal control by expressing a viral inhibitor of RNAi. We show that theT. castaneumsegmentation machinery re-established after we blocked an ongoing RNAi response targeting the primary pair rule genesTc-eve, Tc-oddandTc-runt. However, we observed no rescue after blocking RNAi responses targeting Wnt pathway components. We conclude that the insect segmentation system contains both, robust feedback-loops that can re-establish and labile feedback loops that can breakdown irreversibly. This combination may reconcile two partially conflicting needs of the embryonic regulation of segmentation: A tightly controlled initiation and maintenance of the SAZ by labile feedback-loops ensures that only one segment addition zone is formed. Conversely, robust feedback-loops confer developmental robustness required for proper segmentation, which may be challenged by internal or external disturbances. Our results ponder the insect segmentation machinery from a different angle and introduce a new experimental tool for temporal control on RNAi.Significance statementThe generation of repetitive body parts during embryonic segmentation has been of key interest to developmental biologists, who usually used permanent knock-down of gene function for their studies. Using a new tool to temporally stop a gene knock-down effect, we find both robust and labile feedback-loops within the segmentation machinery. Thereby, the embryo may ensure that only one trunk is formed but that trunk formation is robust against external disturbance.
Sex-specific gut bacteria manipulation impacts offspring production in the honeybee parasite small hive beetle,Aethina tumidaMurray
Authors: Biswas Md Jamil , Khan Md Kawsar , Bashiribod Sahareh , Ponton Fleur 
Published: October 2023

AbstractSymbiotic bacteria play crucial roles in growth, development, behaviour, immunity, and metabolism of insects. Most of the research until now has explored the role of gut bacteria in insect model systems. The extent to which gut bacteria affect mating behaviour and reproduction of insect pest species still needs, however, to be fully comprehended. In this study, we aimed to investigate the effects of gut bacteria manipulation on mating behaviour and fecundity of a major beehive pest, the small hive beetleAethina tumida(Murray). We manipulated gut bacteria of both sexes and determined the effects on mating behaviour and reproductive output. Our results provided evidence that manipulation of the gut bacteria influences reproduction in both sexes, negatively affecting mating latency, mating number, mating duration and offspring number (larvae). These results highlight the role of gut bacteria on the reproduction of insect pests, which might help in designing new pest control methods.
Beyond six feet: The collective behavior of social distancing
Authors: Wu Zhijun 
Published: October 2023

AbstractIn a severe epidemic such as the COVID-19 pandemic, social distancing can be a vital tool to stop the spread of the disease and save lives. However, social distancing may induce profound negative social/economic impacts as well. How to optimize social distancing is a serious social, political, as well as public health issue yet to be resolved. This work investigates social distancing with a focus on how every individual reacts to an epidemic, what role he/she plays in social distancing, and how every individual’s decision contributes to the action of the population and vice versa. Social distancing is thus modeled as a population game, where every individual makes decision on how to participate in a set of social activities, some with higher frequencies while others lower or completely avoided, to minimize his/her social contacts with least possible social/economic costs. An optimal distancing strategy is then obtained when the game reaches an equilibrium. The game is simulated with various realistic restraints including (i) when the population is distributed over a social network, and the decision of each individual is made through the interactions with his/her social neighbors; (ii) when the individuals in different social groups such as children vs. adults or the vaccinated vs. unprotected have different distancing preferences; (iii) when leadership plays a role in decision making, with a few leaders making decisions while the rest of the population just follow. The simulation results show how the distancing game is played out in each of these scenarios, reveal the conflicting yet cooperative nature of social distancing, and shed lights on a self-organizing, bottom-up perspective of distancing practices.
Transcriptome-wide analysis of the function of Ded1 in translation preinitiation complex assembly in a reconstituted in vitro system
Authors: Zhou Fujun , Bocetti Julie M. , Hou Meizhen , Qin Daoming , Hinnebusch Alan G. , Lorsch Jon R. 
Published: October 2023

ABSTRACTWe have developed a deep sequencing-based approach, Rec-Seq, that allows simultaneous monitoring of ribosomal 48S pre-initiation complex (PIC) formation on every mRNA in the translatome in an in vitro reconstituted system. Rec-Seq isolates key early steps in translation initiation in the absence of all other cellular components and processes. Using this approach we show that the DEAD-box ATPase Ded1 promotes 48S PIC formation on the start codons of >1000 native mRNAs, most of which have long, structured 5’-untranslated regions (5’UTRs). Remarkably, initiation measured in Rec-Seq was enhanced by Ded1 for most mRNAs previously shown to be highly Ded1-dependent by ribosome profiling ofded1mutants in vivo, demonstrating that the core translation functions of the factor are recapitulated in the purified system. Our data do not support a model in which Ded1acts by reducing initiation at alternative start codons in 5’UTRs and instead indicate it functions by directly promoting mRNA recruitment to the 43S PIC and scanning to locate the main start codon. We also provide evidence that eIF4A, another essential DEAD-box initiation factor, is required for efficient PIC assembly on almost all mRNAs, regardless of their structural complexity, in contrast to the preferential stimulation by Ded1 of initiation on mRNAs with long, structured 5’UTRs.
ListiWiki: a database for the foodborne pathogenListeria monocytogenes
Authors: Elfmann Christoph , Zhu Bingyao , Stülke Jörg , Halbedel Sven 
Published: October 2023

ABSTRACTListeria monocytogenesis a Gram positive foodborne pathogen that regularly causes outbreaks of systemic infectious diseases. The bacterium maintains a facultative intracellular lifestyle; it thrives under a variety of environmental conditions and is able to infect human host cells.L. monocytogenesis genetically tractable and therefore has become an attractive model system to study the mechanisms employed by facultative intracellular bacteria to invade eukaryotic host cells and to replicate in their cytoplasm. Besides its importance for basic research,L. monocytogenesalso serves as a paradigmatic pathogen in genomic epidemiology, where the relative stability of its genome facilitates successful outbreak detection and elucidation of transmission chains in genomic pathogen surveillance systems. In both terms, it is necessary to keep the annotation of theL. monocytogenesgenome up to date. Therefore, we have created the databaseListiWiki (http://listiwiki.uni-goettingen.de/) which stores comprehensive information on the widely usedL. monocytogenesreference strain EDG-e.ListiWiki is designed to collect information on genes, proteins and RNAs and their relevant functional characteristics, but also further information such as mutant phenotypes, available biological material, and publications. In its present form,ListiWiki combines the most recent annotation of the EDG-e genome with published data on gene essentiality, gene expression and subcellular protein localization.ListiWiki also predicts protein-protein interactions networks based on protein homology toBacillus subtilisproteins, for which detailed interaction maps have been compiled in the sibling databaseSubtiWiki. Furthermore, crystallographic information of proteins is made accessible through integration of Protein Structure Database codes and AlphaFold structure predictions.ListiWiki is an easy-to-use web interface that has been developed with a focus on an intuitive access to all information. Use ofListiWiki is free of charge and its content can be edited by all members of the scientific community after registration. In our labs,ListiWiki has already become an important and easy to use tool to quickly access genome annotation details that we can keep updated with advancing knowledge. It also might be useful to promote the comprehensive understanding of the physiology and virulence of an important human pathogen.
Microbial communities from lean or obese are differently shaped after apple fibres supplementation
Authors: Dell’Olio Andrea , Scott William T. , Taroncher-Ferrer Silvia , San Onofre Nadia , Soriano Jose , Rubert Josep 
Published: October 2023

AbstractBackgroundObese microbial communities differ from lean ones. Previous studies have shown how dietary fiber interventions target the gut microbiome and effectively attenuate obesity-related conditions. Nevertheless, the mechanisms by which dietary fibres shape the gut microbiota are not elucidated yet. Thisin-vitrostudy investigated the differences between lean and obese microbiota and how they responded to dietary interventions using a multi-omics approach.ResultsBy employingin vitrodigestion followed by microcolonic fermentations, we exposed obese and lean microbial communities to apple as a representative complex food matrix, apple pectin as a soluble fiber, and cellulose as an insoluble fibe. Metagenomics and metabolomics data indicated that obese and lean individuals had distinct starting microbial communities and functions. After 24 hours of exposure to different feeding conditions, the diet-responsive bacteria modulated the composition and functionality of lean and obese microbial communities. In the obese, the results suggested different mechanisms among gut commensals with an opportunistic lifestyle, allowing them to maximize their energy production from substrates breakdown and produce a specific profile of gut microbial metabolites (GMMs).ConclusionAt the taxonomical and functional level, our results underscore that dietary fibres shape bacterial communities differently depending on their initial microbial composition. This modulation affects the production of GMMs. Eating foods high in fiber is recognised to promotes a healthy gut microbiome. However, the same intervention can result in varying metabolic profiles depending on the microbial communities, which may affect the host differently.
Dynamic changes in subplate and cortical plate microstructure at the onset of cortical folding in vivo
Authors: Wilson Siân , Christiaens Daan , Yun Hyukjin , Uus Alena , Cordero-Grande Lucilio , Karolis Vyacheslav , Price Anthony , Deprez Maria , Tournier Jacques-Donald , Rutherford Mary , Grant Ellen , Hajnal Joseph V. , Edwards A David , Arichi Tomoki , O’Muircheartaigh Jonathan , Im Kiho 
Published: October 2023

AbstractCortical gyrification takes place predominantly during the second to third trimester, alongside other fundamental developmental processes, such as the development of white matter connections, lamination of the cortex and formation of neural circuits. The mechanistic biology that drives the formation cortical folding patterns remains an open question in neuroscience. In our previous work, we modelled the in utero diffusion signal to quantify the maturation of microstructure in transient fetal compartments, identifying patterns of change in diffusion metrics that reflect critical neurobiological transitions occurring in the second to third trimester. In this work, we apply the same modelling approach to explore whether microstructural maturation of these compartments is correlated with the process of gyrification. We quantify the relationship between sulcal depth and tissue anisotropy within the cortical plate (CP) and underlying subplate (SP), key transient fetal compartments often implicated in mechanistic hypotheses about the onset of gyrification. Using in utero high angular resolution multi-shell diffusion-weighted imaging (HARDI) from the Developing Human Connectome Project (dHCP), our analysis reveals that the anisotropic, tissue component of the diffusion signal in the SP and CP decreases immediately prior to the formation of sulcal pits in the fetal brain. By back-projecting a map of folded brain regions onto the unfolded brain, we find evidence for cytoarchitectural differences between gyral and sulcal areas in the late second trimester, suggesting that regional variation in the microstructure of transient fetal compartments precedes, and thus may have a mechanistic function, in the onset of cortical folding in the developing human brain.
Chronic Interferon Stimulated Gene Transcription Promotes Oncogene Induced Breast Cancer
Authors: Wang Hexiao , Canasto-Chibuque Claudia , Kim Jun Hyun , Hohl Marcel , Leslie Christina , Reis-Filho Jorge S , Petrini John HJ 
Published: October 2023

AbstractThe Mre11 complex (comprising Mre11, Rad50, Nbs1) is integral to the maintenance of genome stability. We previously showed that a hypomorphicMre11mutant mouse strain (Mre11ATLD1/ATLD1) was highly susceptible to oncogene induced breast cancer. Here we used a mammary organoid system to examine which Mre11 dependent responses are tumor suppressive. We found thatMre11ATLD1/ATLD1organoids exhibited an elevated interferon stimulated gene (ISG) signature and sustained changes in chromatin accessibility. ThisMre11ATLD1/ATLD1phenotype depended on DNA binding of a nuclear innate immune sensor, IFI205. Ablation ofIfi205inMre11ATLD1/ATLD1organoids restored baseline and oncogene-induced chromatin accessibility patterns to those observed inWT. Implantation ofMre11ATLD1/ATLD1organoids and activation of oncogene led to aggressive metastatic breast cancer. This outcome was reversed in implantedIfi205-/-Mre11ATLD1/ATLD1organoids. These data reveal a connection between innate immune signaling and tumor suppression in mammary epithelium. Given the abundance of aberrant DNA structures that arise in the context of genome instability syndromes, the data further suggest that cancer predisposition in those contexts may be partially attributable to tonic innate immune transcriptional programs.
Assessing three soil removal methods for environmental DNA analysis of mock forensic geology evidence
Authors: Tiedge Teresa M. , Meiklejohn Kelly A. 
Published: October 2023

AbstractSoil is useful in criminal investigations as it is highly variable and readily transferred. Forensic geologists use several different techniques to removal soil from evidence prior to the analysis of inorganic components. There has been recent interest from the forensic science community to analyze environmental deoxyribonucleic acid (eDNA) associated with soil to augment existing forensic analyses. Notably however, limited research has been conducted to compare commonly used soil removal methods for downstream eDNA analysis. In this study, three soil removal methods were assessed: picking/scraping, sonication, and swabbing. Three mock evidence types (t‐shirts, boot soles, and trowels) were sampled in triplicate with each removal method (n = 27). Soil samples underwent DNA isolation, quantification, and amplification of four genomic barcode regions: 16S for bacteria, ITS1 for fungi, ITS2 for plants, and COI for arthropods. Amplicons were prepared into libraries for DNA sequencing on an Illumina® MiniSeq. DNA concentrations were highest in picked/scraped samples and were statistically significant compared with swabbed and sonicated samples. Amplicon sequence variants (ASVs) were identified, and removal methods had no impact on the recovery of the total number of target ASVs. Additionally, when assessing each sample in multidimensional space, picked/scraped samples tended to cluster separately from swabbed and sonicated samples. The soil core used a reference in this study also clustered with the picked/scraped samples, indicating that these samples may be more reflective of the communities collected from soil cores. Based on these data, we identified that picking/scraping is an acceptable soil removal method for eDNA analysis.
Non‐abstinent recovery in alcohol use disorder is associated with greater regional cortical volumes than heavy drinking
Authors: May A. C. , Meyerhoff D. J. , Durazzo T. C. 
Published: October 2023

AbstractBackgroundHarm‐reduction (i.e., non‐abstinent recovery) approaches to substance use treatment have garnered increasing attention. Reduced levels of alcohol consumption post‐treatment have been associated with better psychosocial functioning and physical health, yet less is known regarding differences in brain structures associated with varying levels of alcohol consumption. This study investigated regional cortical volumes after alcohol use disorder (AUD) treatment among individuals who achieved complete abstinence and those who returned to lower and higher levels of consumption.MethodsData were collected from individuals with AUD (n = 68) approximately 8 months after the initiation of treatment. Using risk drinking levels defined by the World Health Organization, participants were classified as abstaining (AB) or relapsing with low (RL) or higher (RH) levels. Data were also obtained from 34 age‐matched light/non‐drinking controls (LN). All participants completed a 1.5 T magnetic resonance imaging session and volumes for 34 bilateral cortical regions of interest were quantitated with FreeSurfer. Generalized linear models were used to examine group differences in cortical volume. All group findings are significant at an FDR‐corrected value of 0.018.ResultsAdjusting for age and intracranial volume, significant group differences were found in 13/34 cortical regions. AB showed greater volumes than RL in 2/13 regions and RH in 6/13 regions. RH demonstrated significantly smaller volumes than LN in 12/13 ROIs, whereas RL differed from LN in 9/13 regions. RH and RL differed in only two cortical regions.ConclusionsIndividuals who consumed low‐risk levels of alcohol post‐treatment exhibited regional cortical volumes more similar to abstainers than individuals who returned to higher‐risk levels. This suggests that low‐risk levels of alcohol consumption are associated with brain integrity that is comparable to that seen with complete abstinence. Given the previously demonstrated improvement in psychosocial and physical health with reduced levels of alcohol consumption post‐treatment, harm reduction may be a beneficial and more attainable goal for some individuals with AUD who are seeking treatment.
Comparison of chemical and enzymatic maceration processes for soft tissue removal from arterial silicone casts on skull scaffolds
Authors: Granroth Janne , Laakkonen Juha 
Published: October 2023

AbstractThe various models used in gross anatomical studies to improve the visualization of blood vessels differ in the amount of manual labour, cost, equipment and time involved. This study aimed to compare chemical and enzymatic maceration processes for soft‐tissue removal from arterial silicone casts on skull scaffolds using ringed seal (Pusa hispida) skull specimens. Both processes produced specimens that covered all anatomical aspects required to visualize the intracranial arterial arrangement on a bone scaffold. Overall, the enzyme maceration process was better for production of such specimens, as this process is easy and safe to perform, is less harmful to the bony parts of the specimen, and the resulting specimens are visually more appealing for display and teaching. Compared with previously published models, the end result varied in the amount of dissolved bone tissue and the visual presentation of the model.
How open innovation specialists contribute to corporate sustainability and responsibility: A latent Dirichlet allocation approach
Authors: Culasso Francesca , Giacosa Elisa , Giordino Daniele , Crocco Edoardo 
Published: October 2023

AbstractThis study examines the job postings for open innovation (OI) specialists to determine a universal archetype of what competencies and tasks are requested from said professionals and their implications for corporate sustainability and responsibility. This research uses Bayesian statistics and latent Dirichlet allocation (LDA) topic modeling to measure multiple dimensions of the 341 sampled job postings. Our empirical findings unveil the pivotal role that OI specialists have in engaging with stakeholders and monitoring OI dynamics. Multiple dimensions are expected from OI specialists, addressing a multitude of concerns, such as the environment and technologies. Moreover, this study underlines the need for OI specialists to comprehend both internal and external stakeholders' needs. This research contributes to the literature as follows. First, it underlines the value of topic modeling analysis in job profiling research. Second, it bridges existing knowledge gaps on OI specialists' competencies and roles with empirical evidence obtained from a global dataset. Third, it outlines the current market expectations and requirements for OI specialists, which is useful to both candidates and companies.