bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving Deceased Donor Kidney Utilization: Predicting Risk of Nonuse with Interpretable Models
Authors: Li Ruoting , Tunc Sait , Ozaltin Osman , Ellis Matthew J. 
Published: September 2024

AbstractBackgroundDespite the increasing disparity between the number of patients awaiting kidney transplants and the availability of deceased donor kidneys, a significant number of donated kidneys go unused. Early identification of organs at high risk of nonuse can facilitate effective allocation interventions, ensuring these organs are offered to patients who could potentially benefit from them. While several machine learning models have been developed to predict nonuse risk, the complexity of these models compromises their practical implementation.MethodsWe propose implementable nonuse risk prediction models that consist of a minimal set of variables, including the Kidney Donor Risk Index (KDRI), along with factors selected by machine learning models or transplantation experts. Our approach takes into account the influence of Organ Procurement Organization (OPO) behavior on kidney disposition.ResultsThe proposed models demonstrate competitive performance compared to more complex models that involve a large number of variables. Importantly, they maintain simplicity and interpretability.ConclusionsOur results provide accurate risk predictions, offer valuable insights into key factors contributing to kidney nonuse, and underscore significant variations among OPOs in the allocation of hard-to-place kidneys. These findings can inform the design of effective organ allocation interventions, increasing the likelihood of transplantation for hard-to-place kidneys.
Identification of Proteins Influencing CRISPR-Associated Transposases for Enhanced Genome Editing
Authors: Song Leo C.T. , Alker Amanda T.P. , Oromí-Bosch Agnès , Swartz Sophia E. , Martinson Jonathan N.V. , Arora Jigyasa , Wang Abby M. , Rovinsky Rachel , Smith Sara J. , Pierce Emily C. , Deutschbauer Adam M. , Doudna Jennifer A. , Cress Brady F. , Rubin Benjamin E. 
Published: September 2024

ABSTRACTCRISPR-Associated Transposases (CASTs) hold tremendous potential for microbial genome editing due to their ability to integrate large DNA cargos in a programmable and site-specific manner. However, the widespread application of CASTs has been hindered by their low efficiency in diverse, non-model bacteria. In an effort to address this shortcoming, we conducted the first genome-wide screen for host factors impactingVibrio choleraeCAST (VchCAST) activity and used the findings to increaseVchCAST editing efficiency. A genome-wide loss-of-function mutant library inE. coliwas screened to identify 15 genes that impact typeVchCAST transposition. Of these, seven factors were validated to improveVchCAST activity and two were found to be inhibitory. Informed by homologous recombination involved effectors, RecD and RecA, we tested the λ-Red recombineering system in ourVchCAST editing vectors, which increased its insertion meditated-editing efficiency by 25.7-fold inE. coliwhile maintaining high target specificity and similar insertion arrangements. Furthermore, λ-Red-enhancedVchCAST achieved increased editing efficiency in the industrially important bacteriaPseudomonas putidaand the emerging pathogenKlebsiella michiganensis. This study improves understanding of factors impactingVchCAST activity and enhances its efficiency as a bacterial genome editor.GRAPHICAL ABSTRACT
ABHD11 mediated deglutarylation regulates the TCA cycle and T cell metabolism
Authors: Grice Guinevere L , Minogue Eleanor , Coates Hudson W , Debela Mekdes , Kaneider-Kaser Nicole , Antrobus P Robin , Johnson Randall S , Nathan James A 
Published: September 2024

SummaryGlutarate is an intermediate of amino acid catabolism and an important metabolite for reprogramming T cell immunity, exerting its effects by inhibition of histone demethylase enzymes or through glutarylation. However, how distinct glutarate modifications are regulated is unclear. Here, we uncover a deglutarylation pathway that couples amino acid catabolism to tricarboxylic acid (TCA) cycle function. By examining how glutarate can form conjugates with lipoate, an essential mitochondrial modification for the TCA cycle, we find that Alpha Beta Hydrolase Domain 11 (ABHD11) protects against the formation of glutaryl-lipoyl adducts. Mechanistically, ABHD11 acts as a thioesterase to selectively remove glutaryl adducts from lipoate, maintaining integrity of the TCA cycle. Functionally, ABHD11 influences the metabolic reprogramming of human T cells, increasing central memory T cell formation and attenuating oxidative phosphorylation. These results uncover ABHD11 as a selective deglutarylating enzyme and highlight that targeting ABHD11 offers a potential approach to metabolically reprogramme cytotoxic T cells.
Essential and dual effects of Notch activity on a natural transdifferentiation event
Authors: Daniele Thomas , Cury Jeanne , Morin Marie-Charlotte , Ahier Arnaud , Isaia Davide , Jarriault Sophie 
Published: September 2024

AbstractCell identity can be reprogrammed, naturally or experimentally, albeit with low frequency. Why given cells, but not their neighbours, undergo a cell identity conversion remains unclear. We find that Notch signalling plays a key role to promote natural transdifferentiation inC. elegans. Endogenous Notch signal endows a cell with the competence to transdifferentiate by promoting plasticity factors expression (hlh-16/Oligandsem-4/Sall). Strikingly, exogenous Notch can trigger ectopic transdifferentiationin vivo. However, Notch signalling can both promote and block transdifferentiation depending on its activation timing. Notch only promotes transdifferentiation during an early precise window of opportunity and signal duration must be tightly controlled in time. Our findings emphasise the importance of temporality and dynamics of the underlying molecular events preceding the initiation of natural cell reprogramming. Finally, our results support a model where both an extrinsic signal and the intrinsic cellular context combine to empower a cell with the competence to transdifferentiate.
The histone methyltransferase DOT1B is dispensable for stage differentiation and macrophage infection inLeishmania mexicana
Authors: Eisenhuth Nicole , Rauh Elisa Theres , Mitnacht Melina , Debus Andrea , Butter Falk , Schleicher Ulrike , Pruzinova Katerina , Volf Petr , Janzen Christian J. 
Published: September 2024

ABSTRACTConserved histone methyltransferases of the DOT1 family are involved in replication regulation, cell cycle progression, stage differentiation and gene regulation in trypanosomatids. However, the specific functions of these enzymes depend on the host evasion strategies of the parasites. In his study, we investigated the role of DOT1B inLeishmania mexicana, focusing on life cycle progression and infectivity. In contrast toTrypanosoma brucei, in which DOT1B is essential for the differentiation of mammal-infective bloodstream forms to insect procyclic forms,L. mexicanaDOT1B (LmxDOT1B) is not critical for the differentiation of promastigotes to amastigotesin vitro. Additionally, there are no significant differences in the ability to infect or differentiate in macrophages or sand fly vectors between theLmxDOT1B-depleted and control strains. These findings highlight the divergency of the function of DOT1B in these related parasites, suggesting genus-specific adaptations in the use of histone modifications for life cycle progression and host adaptation processes.
Integrated single-cell atlas of human atherosclerotic plaques
Authors: Traeuble K. , Munz M. , Pauli J. , Sachs N. , Vafadarnejad E. , Carrillo-Roa T. , Maegdefessel L. , Kastner P. , Heinig M. 
Published: September 2024

AbstractAtherosclerosis, a major cause of cardiovascular diseases, is characterized by the buildup of lipids and chronic inflammation in the arteries, leading to plaque formation and potential rupture. The underlying causal immune mechanisms and alterations in structural cell composition and plasticity driving plaque progression remain incompletely defined. Recent advances in single-cell transcriptomics (scRNA-seq) have provided deeper insights into the roles of immune and non-immune cells in atherosclerosis. However, existing public scRNA-seq datasets often lack comprehensive cell type coverage and consistent annotations, posing challenges for downstream analyses. In this study, we present an integrated single-cell atlas of human atherosclerotic plaques, encompassing 261,747 high-quality annotated cells from carotid, coronary, and femoral arteries. By benchmarking and applying the best-performing data integration method, scPoli, we achieved robust cell type annotations validated by expert consensus and surface protein measurements. This comprehensive atlas enables accurate automatic cell type annotation of new datasets, optimal experimental design, and deconvolution of existing as well as novel bulk RNA-seq data to comprehensively determine cell type proportions in human atherosclerotic lesions. It facilitates future studies by providing an interactive WebUI for easy data annotation and experimental design, while supporting various downstream applications, including integration of genetic association studies and experimental planning.
Multiplexed nanopore amplicon sequencing to distinguish recrudescence from new infection in antimalarial drug trials
Authors: Holzschuh Aurel , Lerch Anita , Nsanzabana Christian 
Published: September 2024

ABSTRACTBackgroundThe assessment of antimalarial drug efficacy againstPlasmodium falciparumrequires PCR correction to distinguish recrudescence from new infections by comparing parasite genotypes before treatment and in recurrent infections. Nanopore sequencing offers a low-cost, portable, scalable, and rapid alternative to traditional methods, supporting the expansion and decentralization of sequencing in endemic, resource-limited settings, potentially providing rapid PCR-corrected drug failure estimates.MethodsWe optimized a multiplexed AmpSeq panel targeting six microhaplotypes for high and uniform coverage. We assessed sensitivity and specificity for detecting minority clones in polyclonal infections and evaluated genetic diversity across the microhaplotype markers. We used mixtures of fourP. falciparumlaboratory strains at different ratios and 20 paired patient samples from a clinical trial. A custom bioinformatics workflow was used to infer haplotypes from polyclonal infections, including minority clones, with defined cut-off criteria for accurate haplotype calling.FindingsThe nanopore AmpSeq assay achieved uniform and high read coverage across all six microhaplotype markers (median coverage: 12,989× to 15,440× for laboratory strain mixtures and 7,011× to 11,600× for patients’ samples, respectively). We found high sensitivity in detecting minority clones (up to 50:1:1:1 in the 3D7:K1:HB3:FCB1 laboratory strain mixtures) and high specificity with less than 0.01% of all reads being false-positive haplotypes. Genetic diversity in the markers used was high (HE≥ 0.98 and up to 31 unique haplotypes in 20 paired samples withcpmp), and concordant results in classifying new infections and recrudescence across all markers used were observed in 18 (90%) of 20 paired samples.InterpretationOur study demonstrates the feasibility of nanopore AmpSeq for distinguishing recrudescence from new infections in clinical trials.FundingSwiss Tropical and Public Health Institute.
Elongation factor P controls ribosomal frameshift of aSalmonellaantimicrobial resistance gene
Authors: Baek Seungwoo , Cho Yong-Joon , Choi Eunna , Choi Soomin , Lee Eun-Jin 
Published: September 2024

AbstractRibosomes translate mRNAs by matching every 3-nucleotide sequence in mRNA, producing the corresponding proteins. As the amino acid sequence directly dictates the activity of the protein, frameshifts often lead to unexpected effects. Here, ribosome profiling reveals that the intracellular pathogenSalmonellaTyphimurium suppresses frameshift in theugtLantimicrobial resistance gene during translation. This suppression of frameshift is mediated by a ribosome pause occurring in a newly-identified overlapping gene, serving as a non-slip bump. Given that the pause site contains a poly-proline motif and can be resolved by elongation factor P, the removal of the ribosome pause by substituting the motif induces ribosome slippage inugtL, resulting in UgtL frameshifted protein production. This rendersSalmonellasensitive to antimicrobial peptides but, in turn, protects the MgtC virulence factor from the FtsH-mediated proteolysis, indicating that elongation factor P-dependent ribosome pause is required for controlling both full antimicrobial resistance and mouse virulence. These findings reveal a new regulatory mechanism in which ribosome pause controls the production of two different protein isoforms by suppressing ribosome slippage-mediated frameshift.
Effects of parental care on skin microbial community composition in poison frogs
Authors: Fischer Marie-Therese , Xue Katherine S. , Costello Elizabeth K. , Dvorak Mai , Raboisson Gaëlle , Robaczewska Anna , Caty Stephanie N. , Relman David A. , O’Connell Lauren A. 
Published: September 2024

AbstractParent-offspring interactions constitute the first contact of many newborns with their environment, priming community assembly of microbes through priority effects. Early exposure to microbes can have lasting influences on the assembly and functionality of the host’s microbiota, leaving a life-long imprint on host health and disease. Studies of the role played by parental care in microbial acquisition have primarily focused on humans and hosts with agricultural relevance. Anuran vertebrates offer the opportunity to examine microbial community composition across life stages as a function of parental investment. In this study, we investigate vertical transmission of microbiota during parental care in a poison frog (FamilyDendrobatidae), where fathers transport their offspring piggyback-style from terrestrial clutches to aquatic nurseries. We found that substantial bacterial colonization of the embryo begins after hatching from the vitelline envelope, emphasizing its potential role as microbial barrier during early development. Using a laboratory cross-foster experiment, we demonstrated that poison frogs performing tadpole transport serve as a source of skin microbes for tadpoles on their back. To study how transport impacts the microbial skin communities of tadpoles in an ecologically relevant setting, we sampled frogs and tadpoles of sympatric species that do or do not exhibit tadpole transport in their natural habitat. We found more diverse microbial communities associated with tadpoles of transporting species compared to a non-transporting frog. However, we detected no difference in the degree of similarity between adult and tadpole skin microbiotas, based on whether the frog species exhibits transporting behavior or not. Using a field experiment, we confirmed that tadpole transport can result in the persistent colonization of tadpoles by isolated microbial taxa associated with the caregiver’s skin, albeit often at low prevalence. This is the first study to describe vertical transmission of skin microbes in anuran amphibians, showing that offspring transport may serve as a mechanism for transmission of parental skin microbes. Overall, these findings provide a foundation for further research on how vertical transmission in this order impacts host-associated microbiota and physiology.
Electrophoresis-Correlative Ion Mobility Deepens Single-cell Proteomics in Capillary Electrophoresis Mass Spectrometry
Authors: Shen Bowen , Zhou Fei , Nemes Peter 
Published: September 2024

ABSTRACTDetection of trace-sensitive signals is a current challenge is single-cell mass spectrometry (MS) proteomics. Separation prior to detection improves the fidelity and depth of proteome identification and quantification. We recently recognized capillary electrophoresis (CE) electrospray ionization (ESI) for ordering peptides into mass-to-charge (m/z)-dependent series, introducing electrophoresis-correlative (Eco) data-independent acquisition. Here, we demonstrate that these correlations based on electrophoretic mobility (µef) in the liquid phase are transferred into the gas phase, essentially temporally ordering the peptide ions into charge-dependent ion mobility (IM, 1/K0) trends (ρ > 0.97). Rather than sampling the entire IM region broadly, we pursued these predictable correlations to schedule narrower frames. Compared to classical ddaPASEF, Eco-framing significantly enhanced the resolution of IM on a trapped ion mobility mass spectrometer (timsTOF PRO). This approach returned ∼50% more proteins from HeLa proteome digests approximating to one-to-two cells, identifying ∼962 proteins from ∼200 pg in <20 min of effective electrophoresis, without match-between-runs. As a proof of principle, we deployed Eco-ddaPASEF on 1,157 proteins by analyzing <4% of the total proteome in single, yolk-laden embryonic stem cells (∼80-µm) that were isolated from the animal cap of the South African clawed frog (Xenopus laevis). Quantitative profiling of 9 different blastomeres revealed detectable differences among these cells, which are normally fated to form the ectoderm but retain pluripotentiality. Eco-framing effectively deepens the proteome sensitivity in IMS using ddaPASEF, raising the possibility of a proteome-driven classification of embryonic cell differentiation.
A high-throughput, microplate reader-based method to monitorin vitroHIV latency reversal in the absence of flow cytometry
Authors: Nkwelle Chantal Emade , Stephens Unique , Liang Kimberly , Cassel Joel , Salvino Joseph M. , Montaner Luis J. , Ndip Roland N. , Esemu Seraphine N. , Ntie-Kang Fidele , Tietjen Ian 
Published: September 2024

SummaryJ-Lat cells are derivatives of the Jurkat CD4+ T cell line that contain a non-infectious, inducible HIV provirus with a GFP tag. While these cells have substantially advanced our understanding of HIV latency, their use by many laboratories in low and middle-income countries is restricted by limited access to flow cytometry. To overcome this barrier, we describe a modified J-Lat assay using a standard microplate reader that detects HIV-GFP expression following treatment with latency-reversing agents (LRAs). We show that HIV reactivation by control LRAs like prostratin and romidepsin is readily detected with dose dependence and with significant correlation and sensitivity to standard flow cytometry. For example, 10 µM prostratin induced a 20.1 ± 3.3-fold increase in GFP fluorescence in the microplate reader assay, which corresponded to 64.2 ± 5.0% GFP-positive cells detected by flow cytometery. Similarly, 0.3 µM prostratin induced a 1.7 ± 1.2-fold increase compared to 8.7 ± 5.7% GFP-positive cells detected. Using this method, we screen 79 epigenetic modifiers and identify molibresib, quisinostat, and CUDC-101 as novel LRAs. This microplate reader-based method offers accessibility to researchers in resource-limited regions to work with J-Lat cells and more actively participate in global HIV cure research efforts.HighlightsJ-Lat T-cell lines are important to HIV cure research but require flow cytometryWe describe a method to work with J-Lat cells using a standard microplate readerThis assay can detect control LRAs similar to flow cytometry and discover new LRAsThis assay allows low-resourced laboratories to contribute to HIV cure research
Vesicle docking and fusion pore modulation by the neuronal calcium sensor Synaptotagmin-1
Authors: Tsemperouli Maria , Kumar Cheppali Sudheer , Rivera Molina Felix , Chetrit David , Landajuela Ane , Toomre Derek , Karatekin Erdem 
Published: September 2024

ABSTRACTSynaptotagmin-1 (Syt1) is a major calcium sensor for rapid neurotransmitter release in neurons and hormone release in many neuroendocrine cells. It possesses two tandem cytosolic C2 domains that bind calcium, negatively charged phospholipids, and the neuronal SNARE complex. Calcium binding to Syt1 triggers exocytosis, but how this occurs is not well understood. Syt1 has additional roles in docking dense core vesicles (DCV) and synaptic vesicles (SV) to the plasma membrane (PM) and in regulating fusion pore dynamics. Thus, Syt1 perturbations could affect release through vesicle docking, fusion triggering, fusion pore regulation, or a combination of these. Here, using a human neuroendocrine cell line, we show that neutralization of highly conserved polybasic patches in either C2 domain of Syt1 impairs both DCV docking and efficient release of serotonin from DCVs. Interestingly, the same mutations resulted in larger fusion pores and faster release of serotonin during individual fusion events. Thus, Syt1’s roles in vesicle docking, fusion triggering, and fusion pore control may be functionally related.
Learning opportunity as a critical attribute to attract employees in the context of startups: a text-mining approach
Authors: Seo Jaekyo , Leach Raymond , Lee Suhyung 
Published: September 2024

Purpose
While founder characteristics have been studied extensively as a factor in attracting employees, organizational attributes of startups have received little attention. To fill the void, this study aims to examine organizational attributes of startups to attract employees.

Design/methodology/approach
This research collected 8,817 online employer reviews of 117 startups from Glassdoor.com. This research conducted two studies. In Study 1, a topic modeling approach was applied to identify startup attributes to attract employees having actual employer experience and to examine the importance and relationship of the attributes, drawing the person–organization fit theory. Study 2 used logistic regression analysis to explore the effect of identified attributes on employer attractiveness based on the signaling theory.

Findings
Study 1 found six attributes: high-quality coworkers, entrepreneurial culture, development, company outlook, physical office and stereotypical startup perks. This study also found high-quality coworkers, entrepreneurial culture and development are not only related to each other but also more critical attributes than other attributes. The core value of the three attributes can be conceptualized as “learning opportunity.” Study 2 found that employees attracted to “learning opportunity” are more likely to recommend their employers than instrumental attributes, including physical office and stereotypical startup perks.

Originality/value
This research elaborates on employer attributes to attract employees in the context of startup based on the real voices of employees having actual employer experience. Furthermore, this research extends the understanding of employer attributes contributing to employer attractiveness by combining qualitative review data with quantitative rating data.