bluuebunny/crossref_metadata_2025_split huggingface dataset:
Switching the left and the right hearts: A novel bi-ventricle mechanical support strategy with spared native single-ventricle
Authors: Şişli Emrah , Yıldırım Canberk , Başar Aka İbrahim , Tuncer Osman Nuri , Atay Yüksel , Özbaran Mustafa , Pekkan Kerem 
Published: December 2022

AbstractMechanical circulatory support (MCS) is used as a bridge-to-heart transplantation for end-stage failing Fontan patients with single-ventricle (SV) circulation. Donor shortage and complexity of the single-ventricle circulation physiology demands novel circulatory support systems and alternative solutions. An out-of-the-box circulation concept in which the left and right ventricles are switched with each other inspired a novel bi-ventricle MCS configuration for the “failing” Fontan patients. In the proposed configuration, the systemic circulation is maintained by a conventional mechanical ventricle assist device while the venous circulation is delegated to the native SV. This approach spares the SV and puts it to a new use at the right-side providing the most needed venous flow pulsatility. To analyze its feasibility and performance, 8 realistic Fontan circulation scenarios have been studied via a multi-compartmental lumped parameter cardiovascular model (LPM). Model is developed specifically for simulating the SV circulation and validated against pulsatile mock-up flow loop measurements for the ideal (Fontan), failed (VD) and assisted Fontan (PVR-cmcs) scenarios. The proposed surgical configuration maintained the cardiac index (3-3.5 l/min/m2) providing a normal mean systemic arterial pressure. For a failed SV with low ejection fraction (EF=26%), representing a typical systemic failure, proposed configuration introduced a venous/pulmonary pulsatility of ∼28 mmHg and a drop of 2 mmHg in central venous pressure (CVP) with acceptable pulmonary artery pressures (17.5 mmHg). In the pulmonary vascular resistance (PVR) failure model, it provided approximately 5 mmHg drop in CVP with venous/pulmonary pulsatility reaching ∼22 mmHg. For high PVR failure case with a healthy SV (EF = 44%) pulmonary hypertension is likely to occur, indicating a need for precise functional assessment of the failed-ventricle before it is considered for the proposed arrangement. Comprehensivein vitroandin silicoresults encourage this concept as an economical alternative to the conventional bi-ventricle MCS pending animal experiments.
Disparate roles forC. elegansDNA translocase paralogs RAD-54.L and RAD-54.B in meiotic prophase germ cells
Authors: Yamaya Kei , Wang Bin , Memar Nadin , Odiba Arome Solomon , Woglar Alexander , Gartner Anton , Villeneuve Anne M. 
Published: December 2022

AbstractRAD54 family DNA translocases partner with RAD51 recombinases to ensure stable genome inheritance, exhibiting biochemical activities both in promoting recombinase removal and in stabilizing recombinase association with DNA. Understanding how such disparate activities of RAD54 paralogs align with their biological roles is an ongoing challenge. Here we investigate thein vivofunctions ofC. elegansRAD54 paralogs RAD-54.L and RAD-54.B during meiotic prophase, revealing distinct contributions to the dynamics of RAD-51 association with DNA and to the progression of meiotic double-strand break repair (DSBR). While RAD-54.L is essential for RAD-51 removal from meiotic DSBR sites to enable recombination progression, RAD-54.B is largely dispensable for meiotic DSBR. However, RAD-54.B is required to prevent hyperaccumulation of RAD-51 on unbroken DNA during a key meiotic sub-stage when protein kinase CHK-2 is active. Moreover, DSB-independent hyperaccumulation of RAD-51 foci in the absence of RAD-54.B is RAD-54.L-dependent, revealing a hidden activity of RAD-54.L in promoting promiscuous RAD-51 association that is antagonized by RAD-54.B. We propose a model wherein a division of labor among RAD-54 paralogs allows germ cells to ramp up their capacity for efficient homologous recombination that is crucial to successful meiosis while counteracting potentially deleterious effects of unproductive RAD-51 association with unbroken DNA.
Structural screens identify candidate human homologs of insect chemoreceptors and crypticDrosophilagustatory receptor-like proteins
Authors: Benton Richard , Himmel Nathaniel J. 
Published: December 2022

AbstractInsect Odorant receptors and Gustatory receptors define a superfamily of seven-transmembrane domain ligand-gated ion channels (termed here 7TMICs), with homologs identified across Animalia except Chordata. Previously, we used sequence-based screening methods to reveal conservation of this family in unicellular eukaryotes and plants (DUF3537 proteins) (Bentonet al., 2020). Here we combine three-dimensional structure-based screening,ab initioprotein folding predictions, phylogenetics and expression analyses to characterize additional candidate homologs with tertiary but little or no primary structural similarity to known 7TMICs, including proteins in disease-causing Trypanosoma. Unexpectedly, we identify structural similarity between 7TMICs and PHTF proteins, a deeply-conserved family of unknown function, whose human orthologs display enriched expression in testis, cerebellum and muscle. We also discover divergent groups of 7TMICs in insects, which we term the Gustatory receptor-like (Grl) proteins. SeveralDrosophila melanogaster Grls display selective expression in subsets of taste neurons, suggesting that they are previously-unrecognized insect chemoreceptors. Although we cannot exclude the possibility of remarkable structural convergence, our findings support the origin of 7TMICs in a eukaryotic common ancestor, counter previous assumptions of complete loss of 7TMICs in Chordata, and highlight the extreme evolvability of this protein fold, which likely underlies its functional diversification in different cellular contexts.
Maternal control of spontaneous dormancy termination inDaphnia pulex
Authors: Porter Robert J. , Gutierrez Grace M. , Barnard-Kubow Karen B. , Bergland Alan O. 
Published: December 2022

AbstractThis study examined maternal influence and life-history consequences of diapause termination timing inDaphnia pulex. We raised clonal isolates ofD. pulexin mesocosms and observed hatching rates prior to and after exposing embryos to a cold shock. A substantial proportion of individuals hatched early, prior to the cold shock. We found that siblings from the same ephippium were more likely than expected by chance to emerge at the same time, even after dissection and separation, suggesting the presence of a maternal effect that influences diapause duration. We also found that for individuals who emerged early, the time to first reproduction was significantly delayed, and individuals produced fewer resting embryos in subsequent generations. We suggest that early diapause termination may be driven by maternal effects to generate offspring that emerge from dormancy at different times.
Multiparametric sensing of outer membrane vesicle-derived supported lipid bilayers demonstrates the specificity of bacteriophage interactions
Authors: Bali Karan , Lu Zixuan , McCoy Reece , Treiber Jeremy , Savva Achilleas , Kaminski Clemens F. , Salmond George , Salleo Alberto , Mela Ioanna , Monson Rita , Owens Róisín M. 
Published: December 2022

ABSTRACTThe use of bacteriophage, viruses that specifically infect bacteria, as antibiotics has become an area of great interest in recent years as the effectiveness of conventional antibiotics recedes. The detection of phage interactions with specific bacteria in a rapid and quantitative way is key for identifying phage of interest for novel antimicrobials. Outer membrane vesicles (OMVs) derived from gram-negative bacteria can be used to make supported lipid bilayers (SLBs) and thereforein vitromembrane models that contain naturally occurring components of the bacterial outer membrane. In this study, we usedEscherichia coliOMV derived SLBs and use both fluorescent imaging and surface sensitive techniques to show their interactions with T4 phage. We also integrate these bilayers with microelectrode arrays (MEAs) functionalised with the conducting polymer PEDOT:PSS and show that the pore forming interactions of the phage with the SLBs can be monitored using electrical impedance spectroscopy. To highlight our ability to detect specific phage interactions, we also generate SLBs using OMVs derived fromCitrobacter rodentium, which is resistant to T4 phage infection, and identify their lack of interaction with phage. The work presented here shows how interactions occurring between phage and these complex SLB systems can be monitored using a range of experimental techniques. We believe this approach can be used to identify phage against bacterial strains of interest, as well as more generally to monitor any pore forming structure (such as defensins) interacting with bacterial outer membranes, and thus aid in the development of next generation antimicrobials.
Optimizing the delivery of self-disseminating vaccines in fluctuating wildlife populations
Authors: Schreiner Courtney L. , Basinski Andrew J. , Remien Christopher H. , Nuismer Scott L. 
Published: December 2022

1AbstractZoonotic pathogens spread by wildlife continue to spill into human populations and threaten human lives. A potential way to reduce this threat is by vaccinating wildlife species that harbor pathogens that are infectious to humans. Unfortunately, even in cases where vaccines can be distributed en masse as edible baits, achieving levels of vaccine coverage sufficient for pathogen elimination is rare. Developing vaccines that self-disseminate may help solve this problem by magnifying the impact of limited direct vaccination. Although models exist that quantify how well these self-disseminating vaccines will work when introduced into temporally stable wildlife populations, how well they will perform when introduced into populations with pronounced seasonal population dynamics remains unknown. Here we develop and analyze mathematical models of fluctuating wildlife populations that allow us to study how reservoir ecology, vaccine design, and vaccine delivery interact to influence vaccine coverage and opportunities for pathogen elimination. Our results demonstrate that the timing of vaccine delivery can make or break the success of vaccination programs. As a general rule, the effectiveness of self-disseminating vaccines is optimized by introducing after the peak of seasonal reproduction when the number of susceptible animals is near its maximum.
NanopoReaTA: a user-friendly tool for nanopore-seq real-time transcriptional analysis
Authors: Wierczeiko Anna , Pastore Stefan , Mündnich Stefan , Busch Anne M. , Dietrich Vincent , Helm Mark , Butto Tamer , Gerber Susanne 
Published: December 2022

AbstractSummaryOxford Nanopore Technologies’ (ONT) sequencing platform offers an excellent opportunity to perform real-time analysis during sequencing. This feature allows for early insights into experimental data and accelerates a potential decision-making process for further analysis, which can be particularly relevant in the clinical context. Although some tools for the real-time analysis of DNA-sequencing data already exist, there is currently no application available for differential transcriptome data analysis designed for scientists or physicians with limited bioinformatics knowledge. Here we introduce NanopoReaTA, a user-friendly real-time analysis toolbox for RNA sequencing data from ONT. Sequencing results from a running or finished experiment are processed through an R Shiny-based graphical user interface (GUI) with an integratedNextflowpipeline for whole transcriptome or gene-specific analyses. NanopoReaTA provides visual snapshots of a sequencing run in progress, thus enabling interactive sequencing and rapid decision-making that could also be applied to clinical cases.Availabilityhttps://github.com/AnWiercze/NanopoReaTAContactbuttamer@uni-mainz.deandsugerber@uni-mainz.de
A multi-omics analysis identifies molecular features associated with heifer fertility in a case-control design including Angus and Holstein cattle
Authors: Marrella Mackenzie A. , Biase Fernando H. 
Published: December 2022

AbstractBackgroundInfertility or subfertility is a critical barrier to sustainable cattle production, including in heifers. The development of heifers that do not produce a calf within an optimum window of time is a critical factor for the profitability and sustainability of the cattle industry. The early identification of heifers with optimum fertility using molecular phenotyping is a promising approach to improving sustainability in beef and dairy cattle production.ResultsUsing a high-density single nucleotide polymorphism (SNP) chip, we collected genotypic data from 575,053 SNPs. We also produced quantitative transcriptome data for 12,445 genes (12,105 protein-coding genes, 228 long non-coding RNAs, and 112 pseudogenes) and proteome data for 213 proteins. We identified two SNPs significantly associated with heifer fertility (rs110918927, chr12: 85648422, P = 6.7×10-7; and rs109366560, chr11:37666527, P = 2.6×10-5). We identified two genes with differential transcript abundance (eFDR ≤ 0.002) between the two groups (Fertile and Sub-Fertile): Adipocyte Plasma Membrane Associated Protein (APMAP, 1.16 greater abundance in the Fertile group) and Dynein Axonemal Intermediate Chain 7 (DNAI7, 1.23 greater abundance in the Sub-Fertile group). Our analysis revealed that the protein Alpha-ketoglutarate-dependent dioxygenase FTO was more abundant in the plasma collected from Fertile heifers relative to their Sub-Fertile counterparts (FDR < 0.05). Interestingly, two proteins did not reach the significance threshold in the model accounting for all samples (Apolipoprotein C-II, APOC2 (FDRglmm= 0.06) and Lymphocyte cytosolic protein 1, LCP1 (FDRglmm= 0.06)), but both proteins were less abundant in the plasma of Fertile Holstein heifers (P < 0.05). Lastly, an integrative analysis of the three datasets identified a series of features (SNPs, gene transcripts, and proteins) that can be useful for the discrimination of heifers based on their fertility. When all features were utilized together, 21 out of 22 heifers were classified correctly based on their fertility category.ConclusionsOur multi-omics analyses confirm the complex nature of female fertility. Very importantly, our results also highlight differences in the molecular profile of heifers associated with fertility that transcend the constraints of breed-specific genetic background.
Exact Probability Distribution for the ROC Area Under Curve
Authors: Ekström Joakim , Ögren Jim , Sjöblom Tobias 
Published: December 2022

SummaryThe Receiver Operating Characteristic (ROC) is ade factostandard for determining the accuracy ofin vitrodiagnostic (IVD) medical devices, and thus exactness in its probability distribution is crucial toward accurate statistical inference. We show the exact probability distribution of the ROC AUC-value, hence exact critical values and p-values are readily obtained. Because the exact calculations are computationally intense, we demonstrate a method of geometric interpolation which is exact in a special case but generally an approximation, vastly increasing computational speeds. The method is illustrated through open access data, demonstrating superiority of 26 composite biomarkers relative to a predicate device. Especially under correction for testing of multiple hypotheses, traditional asymptotic approximations are encumbered by considerable imprecision, adversely affecting IVD device development. The ability to obtain exact p-values will allow more efficient IVD device development.
Alignment-based protein mutational landscape prediction: doing more with less
Authors: Abakarova Marina , Marquet Ćeline , Rera Michael , Rost Burkhard , Laine Elodie 
Published: December 2022

AbstractThe wealth of genomic data has boosted the development of computational methods predicting the phenotypic outcomes of missense variants. The most accurate ones exploit multiple sequence alignments, which can be costly to generate. Recent efforts for democratizing protein structure prediction have overcome this bottleneck by leveraging the fast homology search of MMseqs2. Here, we show the usefulness of this strategy for mutational outcome prediction through a large-scale assessment of 1.5M missense variants across 72 protein families. Our study demonstrates the feasibility of producing alignment-based mutational landscape predictions that are both high-quality and compute-efficient for entire proteomes. We provide the community with the whole human proteome mutational landscape and simplified access to our predictive pipeline.Significant statementUnderstanding the implications of DNA alterations, particularly missense variants, on our health is paramount. This study introduces a faster and more efficient approach to predict these effects, harnessing vast genomic data resources. The speed-up is possible by establishing that resource-saving multiple sequence alignments suffice even as input to a method fitting few parameters given the alignment. Our results opens the door to discovering how tiny changes in our genes can impact our health. They provide valuable insights into the genotype-phenotype relationship that could lead to new treatments for genetic diseases.
Shifts in competitive structures can drive variation in species’ phenology
Authors: Dumandan Patricia Kaye T. , Yenni Glenda M. , Ernest S. K. Morgan 
Published: December 2022

ABSTRACTFor many species, a well-documented response to anthropogenic climate change is a shift in various aspects of its life-history, including its timing or phenology. Often, these phenological shifts are associated with changes in abiotic factors used as proxies for resource availability or other suitable conditions. Resource availability, however, can also be impacted by competition, but the impact of competition on phenology is less studied than abiotic drivers. We fit generalized additive models (GAMs) to a long-term experimental dataset on small mammals monitored in the southwestern United States and show that altered competitive landscapes can drive shifts in breeding timing and prevalence, and that, relative to a dominant competitor, other species exhibit less specific responses to environmental factors. These results suggest that plasticity of phenological responses, that is often described in the context of annual variation in abiotic factors, can occur in response to biotic context as well. Variation in phenological responses under different biotic conditions shown here further demonstrates that a more nuanced understanding of shifting biotic interactions is useful to better understand and predict biodiversity patterns in a changing world.
Game of full siblings in Mendelian populations
Authors: Garay József , Szilágyi András , Varga Tamás , Csiszár Villő , Móri Tamás F. 
Published: December 2022

AbstractWe adapt the concept of evolutionary stability to familial selection when a game theoretic conflicts between siblings determines the survival rate of each sibling in monogamous, exogamous families in a diploid, panmictic population. Similarly to the classical evolutionary game theory, the static condition of evolutionary stability of mixed Nash equilibrium implies the local stability of the genotype dynamics, in spite of that the mating table based genotype dynamics is not a replicator dynamics.We apply our general result to the case where a matrix game determines the survival rate of siblings. In our numerical studies we consider the prisoner’s dilemma between siblings, when the cooperator and defector behaviour are unequally determined by a recessive-dominant allele pair at an autosomal locus. When the prisoner’s dilemma game is strict (cf. iterated one) and the cooperator phenotype is recessive resp. dominant, then the cooperator and defector phenotypes are the unique stable phenotypes, respectively. When the prisoner’s dilemma game is not strict, both phenotypes coexist, independently of the genotype-phenotype mapping. However, the frequencies of the phenotypes are different according to which phenotype is dominant.
GeneSegNet: a deep learning framework for cell segmentation by integrating gene expression and imaging
Authors: Wang Yuxing , Wang Wenguan , Liu Dongfang , Hou Wenpin , Zhou Tianfei , Ji Zhicheng 
Published: December 2022

AbstractWhen analyzing data from in situ RNA detection technologies, cell segmentation is an essential step in identifying cell boundaries, assigning RNA reads to cells, and studying the gene expression and morphological features of cells. We developed a deep-learning-based method, GeneSegNet, that integrates both gene expression and imaging information to perform cell segmentation. GeneSegNet also employs a recursive training strategy to deal with noisy training labels. We show that GeneSegNet significantly improves cell segmentation performances over existing methods that either ignore gene expression information or underutilize imaging information.
Genomic evaluation of a case ofLacticaseibacillus rhamnosusendocarditis: comparison with commercial yogurt isolates and examination of global population structure
Authors: Santoiemma Phillip P. , Cohn Susan E. , Gatesy Samuel W. M. , Hauser Alan R. , Agrawal Saaket , Theodorou Maria , Bachta Kelly E.R. , Ozer Egon A. 
Published: December 2022

ABSTRACTProbiotics, including yogurt commonly containing bacteria of theLactobacillusgroup, are widely used to promote microbiome health and to prevent gastrointestinal or other infections, especially in the setting of antibiotic use. Rarely, however,Lactobacillusbacteria have caused invasive or severe infections in patients. In this report, we present a patient with fatalLacticaseibacillusbacteremia and endocarditis who frequently consumed yogurt. Whole genome sequencing identified the patient’s bloodstream isolate asLacticaseibacillus(formerlyLactobacillus)rhamnosus, and sequencing ofLactobacillusisolates from selected commercial yogurt preparations revealed one isolate nearly identical to the patient’s isolate, differing by only one nucleotide (adenine to guanine substitution leading to a M1A amino acid change in the start codon of thenrdRgene). To place these sequences into broader context ofL. rhamnosusstrains, we compared them to 602L. rhamnosusgenome sequences publicly available through the National Center for Biotechnology Information repository. Both isolates belonged to a clade, identified in this report as clade YC, composed of mostly gastrointestinal isolates from healthy individuals, some of which also differed by only a single nucleotide from the patient’s isolate. Members of clade YC had only rarely been previously identified in invasive infections. In summary, theLacticaseibacillusstrain causing this patient’s infection may have originated from a commercial dairy product or from the commensal flora of his gastrointestinal tract. This study demonstrates that whole genome sequencing may be insufficient to reliably determine the source of invasive infections caused byL. rhamnosus.IMPORTANCEActive culture and probiotic foods and supplements are often used to promote gut health. Though largely considered safe for human consumption, there are rare reports of severe infections linked to bacterial species used in these products. Using whole genome sequencing, we examined a case of fatal infection withLacticaseibacillus rhamnosusin the patient’s blood. By comparing the bacterial genome sequence from the patient to strains cultured from 4 commercial yogurt samples and 602 publicly available sequences ofL. rhamnosusfrom around the world, we found that it was nearly identical to one of the yogurt strains and equally similar to other strains from both probiotics and healthy individuals’ gastrointestinal tracts. These findings show that even with whole genome sequencing it can be difficult to determine the source of an invasiveL. rhamnosusinfection, whether from recent consumption of a probiotic or dairy product versus from the gastrointestinal microbiome.