bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring gene expression models from snapshot RNA data
Authors: Moyer Camille , Kilic Zeliha , Schweiger Max , Shepherd Douglas , Pressé Steve 
Published: May 2022

1AbstractGene networks, key toward understanding a cell’s regulatory response, underlie experimental observations of single cell transcriptional dynamics. While information on the gene network is encoded in RNA expression data, existing computational frameworks cannot currently infer gene networks from such data. Rather, gene networks—composed of gene states, their connectivities, and associated parameters—are currently deduced by pre-specifying gene state numbers and connectivity prior to learning associated rate parameters. As such, the correctness of gene networks cannot be independently assessed which can lead to strong biases. By contrast, here we propose a method to learn full distributions over gene states, state connectivities, and associated rate parameters, simultaneously and self-consistently from single molecule level RNA counts. Notably, our method propagates noise originating from fluctuating RNA counts over networks warranted by the data by treating networks themselves as random variables. We achieve this by operating within a Bayesian nonparametric paradigm. We demonstrate our method on thelacZpathway inEscherichia colicells, theSTL1pathway inSaccharomyces cerevisiaeyeast cells, and verify its robustness on synthetic data.
SNV-FEAST: microbial source tracking with single nucleotide variants
Authors: Briscoe Leah , Halperin Eran , Garud Nandita R. 
Published: May 2022

ABSTRACTElucidating the sources of a microbiome can provide insight into the ecological dynamics responsible for the formation of these communities. “Source tracking” approaches to date leverage species abundance information, however, single nucleotide variants (SNVs) may be more informative because of their high specificity to certain sources. To overcome the computational burden of utilizing all SNVs for a given sample, we introduce a novel method to identify signature SNVs for source tracking. We show that signature SNVs used as input into a previously designed source tracking algorithm, FEAST, can more accurately estimate contributions than species and provide novel insights, demonstrated in three case studies.
Not just the sum of its parts: geographic variation and non-additive effects of pyrazines in the chemical defence of an aposematic moth
Authors: Ottocento Cristina , Winters Anne E. , Rojas Bibiana , Mappes Johanna , Burdfield-Steel Emily 
Published: May 2022

AbstractChemical defences often vary within and between populations both in quantity and quality, which is puzzling if prey survival is dependent on the strength of the defence. We investigated the within-and between-population variability in chemical defence of the wood tiger moth (Arctia plantaginis). The major components of its defences, SBMP (2-sec-butyl-3-methoxypyrazine) and IBMP (2-isobutyl-3-methoxypyrazine) are volatiles that deter bird attacks. We expected the variation to reflect populations’ predation pressures and early-life conditions. To understand the role of the methoxypyrazines, we experimentally manipulated synthetic SBMP and IBMP and tested the birds’ reactions. We found a considerable variation in methoxypyrazine amounts and composition, both from wild-caught and laboratory-raised male moths. In agreement with the “cost of defence” hypothesis, the moths raised in the laboratory had a higher amount of pyrazines. We found that SBMP is more effective at higher concentrations and that IBMP is more effective only in combination with SBMP and at lower concentrations. Our results fit findings from the wild: the amount of SBMP was higher in the populations with higher predation pressure. Altogether, this suggests that, regarding pyrazine concentration, more is not always better, and highlights the importance of testing the efficacy of chemical defence and its components with relevant predators, rather than relying only on results from chemical analyses.
Trade-offs in telemetry tag programming for deep-diving cetaceans: data longevity, resolution, and continuity
Authors: Cioffi William R , Quick Nicola J , Swaim Zachary T , Foley Heather J , Waples Danielle M , Webster Daniel L , Baird Robin W , Southall Brandon L , Nowacek Douglas P , Read Andrew J 
Published: May 2022

AbstractBackgroundAnimal-borne telemetry instruments (tags) have greatly advanced our understanding of species that are challenging to observe. Recently, non-recoverable instruments attached to cetaceans have increased in use, but these devices have limitations in data transmission bandwidth. We analyze trade-offs in the longevity, resolution, and continuity of data records from non-recoverable satellite-linked tags on deep-diving Ziphius cavirostris in the context of a behavioral response study of acute noise exposure. We present a strategic data collection programming scheme that balances resolution and continuity against longevity to address specific questions about the behavioral responses of animals to noise exposure in experimental contexts. We compare accuracy and precision between two programming regimes on a commercially available satellite-linked tag: (1) dive behavior summary defined by conductivity thresholds and (2) depth time-series at various temporal resolutions.ResultsWe found that time-series data could faithfully replicate the more precisely defined dives from a dive summary record data stream to an acceptable error range for our application. We determined a 5-minute time-series data stream collected for 14 days balanced resolution with longevity, achieving complete or nearly complete diving records in 6 out of 8 deployments. We increased our data reception rate several fold by employing a boat based data capture system. Finally, a tag deployed in a group concurrently with a high resolution depth recorder showed high depth concordance.ConclusionsWe present the conceptual framework and iterative process for matching telemetry tag programming to research questions that we used and which should be applicable to a wide range of studies. Although designing new hardware for our specific questions was not feasible at the time, we were able to optimize the sampling regime of a commercially available instrument to meet the needs of our research questions and proposed analyses. Nevertheless, for other study species or designs, the complicated intersection between animal behavior and bandwidth of telemetry systems can often create a severe mismatch among research questions, data collection, and analysis tools. More flexible programming and purpose built instruments will increase the efficacy of these studies and increase the scientific yield relative to the inherently higher risk of invasive studies.
Parallel adaptation to lower altitudes is associated with enhanced plasticity in Heliosperma pusillum (Caryophyllaceae)
Authors: Szukala Aglaia , Bertel Clara , Frajman Božo , Schönswetter Peter , Paun Ovidiu 
Published: May 2022

AbstractHigh levels of phenotypic plasticity are thought to be inherently costly in stable or extreme environments, but enhanced plasticity may evolve as a response to novel environments and foster adaptation. Heliosperma pusillum forms pubescent montane and glabrous alpine ecotypes that diverged recurrently and polytopically (parallel evolution). The specific montane and alpine localities are characterized by distinct temperature conditions, available moisture and light. To disentangle the relative contribution of constitutive versus plastic gene expression to altitudinal divergence, we analyze the transcriptomic profiles of two parallely evolved ecotype pairs, grown in reciprocal transplantations at native altitudinal sites. In both ecotype pairs, only a minor proportion of genes appear constitutively differentially expressed between the ecotypes regardless of the growing environment. Both derived, montane populations bear comparatively higher plasticity of gene expression than the alpine populations that can be considered in this system as ‘ancestor-proxies’. Genes that change expression plastically and constitutively underlie similar ecologically relevant pathways, related to response to drought and trichome formation. Other relevant processes, such as photosynthesis, seem to rely mainly on plastic changes. The enhanced plasticity consistently observed in the montane ecotype likely evolved as a response to the newly colonized niche. Our findings confirm that directional changes in gene expression plasticity can shape initial stages of phenotypic evolution, likely fostering adaptation to novel environments.Significance StatementUnderstanding the importance of phenotypic plasticity for fast adaptation to stress is very timely for breeding and current environmental challenges. Our study of an alpine plant in the carnation family evidences an increased level of expression plasticity in early stages of adaptation to hotter and drier habitats.
PHYSIOLOGICAL CHARACTERISTICS OF BACTERIAL DROPLETS INDICATE A CATASTROPHIC CONSEQUENCE WITH AN INCREASE IN IMPACT VELOCITY
Authors: Hariharan Vishnu , Chowdhury Atish Roy , Rao S Srinivas , Chakravortty Dipshikha , Basu Saptarshi 
Published: May 2022

Droplet impacts on various surfaces play a profound role in different bio-physiological processes and engineering applications. The current study opens a new realm that investigates the plausible effect of impact velocities on bacteria-laden droplets against a solid surface. We unveiled the alarming consequences of Salmonella Typhimurium (STM) laden drop, carrying out the in vitro and intracellular viability of STM to the impact Weber numbers ranging from 100-750. The specified Weber number range mimics the velocity range occurring during the respiratory processes, especially the airborne dispersion of drops during cough. A thick ring of bacterial deposition was observed in all cases irrespective of impacting velocity and the nutrient content of the bacterial medium. The mechanical properties of the bacterial deposit examined using Atomic Force Microscopy reveals the deformation of bacterial morphology, cushioning effect and adhesion energy to determine the cell-cell interactions. The impact velocity induces the shear stress onto the cell walls of STM, thereby deteriorating the in vitro viability. However, we found that even with compromised in vitro viability, Salmonella retrieved from deposited patterns impacted at higher velocity revealed an increased expression of phoP (the response regulator of the PhopQ two-component system) and uninterrupted intracellular proliferation in macrophages. The inability of STM ΔphoP growth in nutrient-rich dried droplets to the subjected impact velocities signifies the predominant role of phoP in maintaining the virulence of Salmonella during desiccation stress. Our findings open a promising avenue for understating the effect of bacteria-laden drop impact and its role in disease spread.Abstract Figure
Joint Instability Causes Catabolic Enzyme Production in Chondrocytes prior to Synovial Cells in Novel Non-Invasive ACL ruptured Mouse Model
Authors: Takahata Kei , Arakawa Kohei , Enomoto Saaya , Usami Yuna , Nogi Koyo , Saitou Riku , Ozone Kaichi , Takahashi Haruna , Yoneno Moe , Kokubun Takanori 
Published: May 2022

AbstractObjectiveThe ACL-deficient model helps to clarify the mechanism of knee OA; however, the conventional ACL injury model could have included concurrent onset factors such as direct compression stress to cartilage and subchondral bone. In this study, we established a novel Non-invasive ACL-Ruptured mouse model without concurrent injuries and elucidated the relationship between OA progression and joint instability.DesignWe induced the ACL-Rupture non-invasively in twelve-week-old C57BL/6 male mice and evaluated histological, macroscopical, and morphological analysis at 0 days. Next, we created the ACL-R, controlled abnormal tibial translation (CATT), and Sham groups. Then, the joint stability and OA pathophysiology were analyzed at 2, 4, and 8 weeks.ResultsNo intra-articular injuries, except for ACL rupture, were observed in the ACL-R model. ACL-R mice increased anterior tibial displacement compared to the Sham group (p<0.001, 95% CI [-1.509 to -0.966]) and CATT group (p<0.001, 95% CI [-0.841 to -0.298]) at 8 weeks. All mice in the ACL-R group caused cartilage degeneration. The degree of cartilage degeneration in the ACL-R group was higher than in the CATT group (p=0.006) at 8 weeks. The MMP-3-positive cell rate of chondrocytes increased in the ACL-R group than CATT group from 4 weeks (p=0.043; 95% CI [-28.32 to -0.364]) while that of synovial cells increased at 8 weeks (p=0.031; 95% CI [-23.398 to -1.021]).ConclusionWe successfully established a Non-invasive ACL-R model without intra-articular damage. Our model revealed that chondrocytes might react to abnormal mechanical stress prior to synovial cells while the knee OA onset.
An autoactive NB-LRR gene causes Rht13 dwarfism in wheat
Authors: Borrill Philippa , Mago Rohit , Xu Tianyuan , Ford Brett , Williams Simon J , Derkx Adinda , Bovill William D , Hyles Jessica , Bhatt Dhara , Xia Xiaodi , MacMillan Colleen , White Rosemary , Buss Wolfram , Molnár István , Walkowiak Sean , Olsen Odd-Arne , Doležel Jaroslav , Pozniak Curtis J , Spielmeyer Wolfgang 
Published: May 2022

AbstractSemidwarfing genes have greatly increased wheat yields globally, yet the widely used gibberellin (GA) insensitive genes Rht-B1b and Rht-D1b have disadvantages for seedling emergence. Use of the GA sensitive semidwarfing gene Rht13 avoids this pleiotropic effect. Here we show that Rht13 encodes a nucleotide-binding site/leucine-rich repeat (NB-LRR) gene. A point mutation in the semidwarf Rht-B13b allele autoactivates the NB-LRR gene and causes a height reduction comparable to Rht-B1b and Rht-D1b in diverse genetic backgrounds. The autoactive Rht-B13b allele leads to transcriptional upregulation of pathogenesis-related genes including class III peroxidases associated with cell wall remodelling. Rht13 represents a new class of reduced height (Rht) gene, unlike other Rht genes which encode components of the GA signalling or metabolic pathways. This discovery opens new avenues to use autoactive NB-LRR genes as semidwarfing genes in a range of crop species, and to apply Rht13 in wheat breeding programmes using a perfect genetic marker.
A Diabetic Mice Model For Studying Skin Wound Healing
Authors: Poblete Jara Carlos , Nogueira Guilherme , Morari Joseane , Paulino do Prado Thaís , de Medeiros Bezerra Renan , Bombassaro Bruna , Velloso Lício A. , Velander William , de Araújo Eliana Pereira 
Published: May 2022

ABSTRACTAdvances in wound treatment depend on the availability of suitable animal models. All animal models try to reflect human wound healing problems. For acute wounds, it is easier to obtain adequate animal models, however, for chronic wounds such as those found in individuals with diabetic foot ulcer, approximations of the clinical picture become a challenge. Nowadays, the key points of wound healing processes are better understood, and therefore, therapeutic strategies can be developed to manipulate wound repair. Research efforts involves the development of therapies to aid in the treatment of impaired wound healing and, to improving normal wound healing to drive a process close to regenerative. To achieve a better animal model that is more appropriate for studying wound healing, six-week- old male C57BL/6 mice were separated into groups fed a Chow and High-Fat Diet for 0.5, 3, and 6 months, when part of the animals were induced to diabetes by streptozotocin. Then, mice were submitted to metabolic, molecular, and morphological analyses. We show that this model results in a severe metabolic phenotype with insulin resistance, reduced insulin expression, and glucose intolerance associated with obesity and, more importantly, skin changes. Furthermore, the skin phenotype, both structurally and transcriptionally, overlapped with conditions found in elderly patients with DM that reproduce the phenotype of most patients who develop diabetic foot ulcers.
scMinerva: an Unsupervised Graph Learning Framework with Label-efficient Fine-tuning for Single-cell Multi-omics Integrated Analysis
Authors: Yu Tingyang , Zong Yongshuo , Wang Yixuan , Wang Xuesong , Li Yu 
Published: May 2022

AbstractSingle-cell multi-omics is a rapidly growing field in biomedicine, where multiple biological contents, such as the epigenome, genome, and transcriptome, can be measured simultaneously. Despite its potential, the integrated analysis and prediction of cellular states based on this complex multi-omics data pose significant challenges due to data sparsity, high noise, and computational overhead. To address these challenges, we developedscMinerva, an unsupervised framework for single-cell multi-omics integrated analysis. The learned embeddings from the multi-omics data enable accurate integrated classification of cell types and stages. Specifically, we construct a heterogeneous graph from multiple omics and propose a novel biased random walk algorithmomics2vec, which can learn the heterogeneous biological graph in a way that balances both local and global network structures. scMinerva successfully outperforms existing unsupervised methods on various simulated and real-world datasets when fine-tuned by very few labels. Additionally, scMinerva demonstrates strong label efficiency, is robust to fluctuation in data quality, allows one omics to compensate for weakness in others and could effectively classify cells with different annotation granularities. Furthermore, we showcase scMinerva’s ability to accurately provide prospective biomarkers and predict cell differentiation trends for COVID-19-infected cells, through the joint analysis of multi-omics data.
Dityrosine cross-links are present in Alzheimer’s disease-derived tau oligomers and paired helical filaments (PHF) which promotes the stability of the PHF-core tau (297-391) in vitro
Authors: Maina Mahmoud B. , Al-Hilaly Youssra K. , Oakley Sebastian , Burra Gunashekar , Khanon Tahmida , Biasetti Luca , Mengham Kurtis , Marshall Karen , Rickard Janet E. , Harrington Charles R. , Wischik Claude M. , Serpell Louise C. 
Published: May 2022

AbstractA characteristic hallmark of Alzheimer’s Disease (AD) is the pathological aggregation and deposition of tau into paired helical filaments (PHF) in neurofibrillary tangles (NFTs). Oxidative stress is an early event during AD pathogenesis and is associated with tau-mediated AD pathology. Oxidative environments can result in the formation of covalent dityrosine crosslinks that can increase protein stability and insolubility. Dityrosine cross-linking has been shown to occur in vivo in Aβ plaques and α-synuclein aggregates in Lewy bodies, and this modification may increase the insolubility of these aggregates and their resistance to degradation. Using the PHF-core tau fragment (residues 297 – 391) as a model, we have previously demonstrated that dityrosine formation traps tau assemblies to reduce further elongation. However, it is unknown whether dityrosine crosslinks are found in tau deposits in vivo in AD and its relevance to disease mechanism is unclear. Here, using transmission electron microscope (TEM) double immunogold-labelling, we reveal that neurofibrillary NFTs in AD are heavily decorated with dityrosine crosslinks alongside tau. Single immunogold-labelling TEM and fluorescence spectroscopy revealed the presence of dityrosine on AD brain-derived tau oligomers and fibrils. Using the tau (297-391) PHF-core fragment as a model, we further showed that prefibrillar tau species are more amenable to dityrosine crosslinking than tau fibrils. Dityrosine formation results in heat and SDS stability of oxidised prefibrillar and fibrillar tau assemblies. This finding has implications for understanding the mechanism governing the insolubility and toxicity of tau assemblies in vivo.
Charting a narrow course for direct electron uptake-facilitated electromicrobial production
Authors: Abel Anthony J. , Adams Jeremy D. , Hilzinger Jacob M. , Arkin Adam P. 
Published: May 2022

AbstractElectromicrobial production (EMP) processes based on CO2-fixing microbes that directly accept electrons from a cathode have received significant attention in the past decade. However, fundamental questions about the performance limits and viability of this strategy remain unanswered. Here, we sought to determine what would be necessary for such a system to compete with alternative sustainable production technologies based on H2-mediated EMP and traditional bioprocessing with crop feedstocks. Using global warming potential as the metric for comparison, we show that each EMP process can outperform sugarcane-based sucrose production. Following a stoichiometric and energetic analysis, direct electron uptake-based EMP would need to achieve a current density >48 mA/cm2to reach parity with the H2- mediated system. Because this is currently only practical with a gas diffusion electrode (GDE) architecture, we developed a physical model of the proposed bio-GDE and used it to determine the conditions that a microbial catalyst would experience in a reactor. Our analysis demonstrates that unavoidable inefficiencies in the reactor (e.g., kinetic overpotentials and Ohmic losses) require additional energy input, increasing the breakeven current density to ∼91 mA/cm2. At this current density, the microbial catalyst would need to withstand a pH >10.4 and a total salinity >18.8%. Because currently-known electroautotrophs are not adapted to such extreme conditions, we discuss potential improvements to reactor design that may alleviate these challenges, and consider the implications these results have on the engineerability and feasibility of direct electron uptake-based EMP.
Identification of epigenetic modulators as determinants of nuclear size and shape
Authors: Schibler Andria , Jevtic Predrag , Pegoraro Gianluca , Levy Daniel L. , Misteli Tom 
Published: May 2022

ABSTRACTThe shape and size of the human cell nucleus is highly variable amongst cell types and tissues. Changes in nuclear morphology are associated with disease, including cancer, as well as with premature and normal aging. Despite the very fundamental nature of nuclear morphology, the cellular factors that determine nuclear shape and size are not well understood. To identify regulators of nuclear architecture in a systematic and unbiased fashion, we performed a high-throughput imaging-based siRNA screen targeting 867 nuclear proteins including chromatin-associated proteins, epigenetic regulators, and nuclear envelope components. Using multiple morphometric parameters, we identified cell-type specific and general effectors of nuclear size and shape. Interestingly, most identified factors altered nuclear morphology without affecting the levels of lamin proteins, which are known prominent regulators of nuclear shape. In contrast, a major group of nuclear shape regulators were modifiers of repressive heterochromatin. Biochemical and molecular analysis uncovered a direct physical interaction of histone H3 with lamin A mediated via combinatorial histone modifications. Furthermore, disease-causing lamin A mutations that result in disruption of nuclear shape inhibited lamin A-histone H3 interactions. Finally, oncogenic histone H3.3 mutants defective for H3K27 methylation resulted in nuclear morphology abnormalities. Altogether, our results represent a systematic exploration of cellular factors involved in determining nuclear morphology and they identify the interaction of lamin A with histone H3 as an important contributor to nuclear morphology in human cells.