bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary potassium and cold acclimation additively increase cold tolerance inDrosophila melanogaster
Authors: Helou Bassam , Ritchie Marshall W. , MacMillan Heath A. , Andersen Mads Kuhlmann 
Published: May 2024

AbstractIn the cold, chill susceptible insects lose the ability to regulate ionic and osmotic gradients. This leads to hemolymph hyperkalemia that drives a debilitating loss of cell membrane polarization, triggering cell death pathways and causing organismal injury. Biotic and abiotic factors can modulate insect cold tolerance by impacting the ability to mitigate or prevent this cascade of events. In the present study, we test the combined and isolated effects of dietary manipulations and thermal acclimation on cold tolerance in fruit flies. Specifically, we acclimated adultDrosophila melanogasterto 15 or 25°C and fed them either a K+-loaded diet or a control diet. We then tested the ability of these flies to recover from and survive a cold exposure, as well as their capacity to protect transmembrane K+gradients, and intracellular Na+concentration. As predicted, cold-exposed flies experienced hemolymph hyperkalemia and cold-acclimated flies had improved cold tolerance due to an improved maintenance of the hemolymph K+concentration at low temperature. Feeding on a high-K+diet improved cold tolerance additively, but paradoxically reduced the ability to maintain extracellular K+concentrations. Cold-acclimation and K+-feeding additively increased the intracellular K+concentration, aiding in maintenance of the transmembrane K+gradient during cold exposure despite cold-induced hemolymph hyperkalemia. There was no effect of acclimation of diet on intracellular Na+concentration. These findings suggest intracellular K+loading and reduced muscle membrane K+sensitivity as mechanisms through which cold-acclimated and K+-fed flies are able to tolerate hemolymph hyperkalemia.Highlights-Insect cold tolerance varies in relation to ionoregulatory capacity-Cold acclimation improves cold tolerance and K+handling during cold exposure-A high K+diet also improves cold tolerance, but reduces the K+-handling capacity-We highlight a novel mechanism for preventing K+gradient disruption
Sequence alignment using large protein structure alphabets improves sensitivity to remote homologs
Authors: Edgar Robert C. 
Published: May 2024

ABSTRACTRecent breakthroughs in protein fold prediction from amino acid sequences have unleashed a deluge of new structures, raising new opportunities for expanding insights into the universe of proteins and pursuing practical applications in bio-engineering and therapeutics while also presenting new challenges to protein search and analysis algorithms. Here, I describe Reseek, a protein alignment algorithm which improves sensitivity in protein homolog detection compared to state-of-the-art methods including DALI, TM-align and Foldseek, with improved speed over Foldseek, the fastest previous method. Reseek is based on alignment of sequences where each residue in the protein backbone is represented by a letter in a novel “mega-alphabet” of 85,899,345,920 (∼1011) distinct states. Code is available athttps://github.com/rcedgar/reseek.
Interpretable Protein-DNA Interactions Captured by Structure-Sequence Optimization
Authors: Zhang Yafan , Silvernail Irene , Lin Zhuyang , Lin Xingcheng 
Published: May 2024

AbstractSequence-specific DNA recognition underlies essential processes in gene regulation, yet methods for simultaneous prediction of genomic DNA recognition sites and their binding affinity remain lacking. Here, we present the Interpretable protein-DNA Energy Associative (IDEA) model, a residue-level, interpretable biophysical model capable of predicting binding sites and affinities of DNA-binding proteins. By fusing structures and sequences of known protein-DNA complexes into an optimized energy model, IDEA enables direct interpretation of physicochemical interactions among individual amino acids and nucleotides. We demonstrate that this energy model can accurately predict DNA recognition sites and their binding strengths across various protein families. Additionally, the IDEA model is integrated into a coarse-grained simulation framework that quantitatively captures the absolute protein-DNA binding free energies. Overall, IDEA provides an integrated computational platform alleviating experimental costs and biases in assessing DNA recognition and can be utilized for mechanistic studies of various DNA-recognition processes.
Molecular Signatures for Microbe-Associated Colorectal Cancers
Authors: Sayed Ibrahim M , Vo Daniella T , Alcantara Joshua , Inouye Kaili M , Pranadinata Rama F , Luo Linda , Boland C Richard , Goyal Nidhi P. , Kuo Dennis John , Huang Sherry C. , Sahoo Debashis , Ghosh Pradipta , Das Soumita 
Published: May 2024

AbstractBackgroundGenetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood. While bioinformatic approaches offer valuable insights, the rising incidence of CRCs creates a pressing need to precisely identify early CRC events. We constructed a network model to identify continuum states during CRC initiation spanning normal colonic tissue to pre-cancer lesions (adenomatous polyps) and examined the influence of microbes and host genetics.MethodsA Boolean network was built using a publicly available transcriptomic dataset from healthy and adenoma affected patients to identify an invariant Microbe-Associated Colorectal Cancer Signature (MACS). We focused onFusobacterium nucleatum(Fn), a CRC-associated microbe, as a model bacterium. MACS-associated genes and proteins were validated by RT-qPCR, RNA seq, ELISA, IF and IHCs in tissues and colon-derived organoids from genetically predisposed mice (CPC-APCMin+/-) and patients (FAP, Lynch Syndrome, PJS, and JPS).ResultsThe MACS that is upregulated in adenomas consists of four core genes/proteins: CLDN2/Claudin-2 (leakiness), LGR5/leucine-rich repeat-containing receptor (stemness), CEMIP/cell migration-inducing and hyaluronan-binding protein (epithelial-mesenchymal transition) and IL8/Interleukin-8 (inflammation). MACS was induced uponFninfection, but not in response to infection with other enteric bacteria or probiotics. MACS induction uponFninfection was higher inCPC-APCMin+/-organoids compared to WT controls. The degree of MACS expression in the patient-derived organoids (PDOs) generally corresponded with the known lifetime risk of CRCs.ConclusionsComputational prediction followed by validation in the organoid-based disease model identified the early events in CRC initiation. MACS reveals that the CRC-associated microbes induce a greater risk in the genetically predisposed hosts, suggesting its potential use for risk prediction and targeted cancer prevention.
Intersex/Differences of Sex Development (I/DSD) Traits: Exploring Their Association with 15% of Phenotypically Detailed Genetic Disorders
Authors: Ragno Leah , Pyle Louise C. 
Published: May 2024

AbstractThe study of Intersex traits or Differences of Sex Development (I/DSD) is an imperative area within medical genetics that confronts a long-standing problem: the prevalence of these conditions in the population is not fully clear, likely undercounted, and therefore no universally agreed upon numbers exist. Proportions among rare differences are not fully understood. While each specific I/DSD condition is individually rare, together they are estimated to affect about 0.7-1.7% of people worldwide (Fausto-Sterling, 1993). Over 10% of individuals with I/DSD traits exhibit comorbidities affecting other bodily systems, suggesting a broader, systemic impact of these conditions. The comprehensive phenotypic spectrum and systemic implications of I/DSD traits are not well-documented, likely due to social, cultural, and privacy concerns that may contribute to the under-phenotyping of genital variations. This research aims to delineate the disease landscape associated with I/DSD traits. By using the Online Mendelian Inherit ance in Man (OMIM) database, a comprehensive resource for human genes and genetic disorders, we compiled an expert list of 155 Human Phenotype Ontology (HPO) terms that encompass the entirety of the medically defined I/DSD space. These terms were cross-referenced with the OMIM database to pinpoint diseases annotated with these HPO terms. Out of 8,181 phenotypically detailed diseases listed in OMIM and included in the HPO database, we discovered that 1,264 (15.5%) have associations with I/DSD-related HPO terms, signifying their presence in I/DSD traits. This substantial overlap underscores the need to rethink I/DSD not just as isolated anomalies but as a continuum of conditions that are crucial for a broader understanding of health issues. It also highlights that I/DSD traits are relatively common within the realm of rare differences, emphasizing the necessity for specialists, such as clinical geneticists, to be well-versed in I/DSD. Our findings call for a shift in the medical community’s perception and approach to studying I/DSD traits. Further research is required to confirm these associations and to explore the relationship between I/DSD traits and overall health.
Adaptive loss of shortwave cone opsins during genomic evolution in cartilaginous fish
Authors: Zhang Bo , Feng Yidong , Lv Meiqi , Jia Lei , Liao Yongguan , Xu Xiaoyan , Meyer Axel , Sun Jinsheng , Li Yumin , Zhang Yaolei , Zhao Na , Li Yunkai , Bao Baolong 
Published: May 2024

AbstractThere is ample evidence of the loss of the shortwave visual protein gene in cartilaginous fish. However, the underlying logic and mechanisms by which organisms need to adapt to the environment behind the opsin loss are still unclear. Here, we report the assembly structure of the whole genome ofOkamejei kenojeiandPrionace glauca, identify TcMar difference between skates/rays and sharks/chimaeras, and analyze the distribution characteristics and intra group differentiation of opsin-related genes in cartilaginous fish. By establishing a zebrafish model with short wave opsin gene deletion, we find blue or violet lightviashort-wave sensitive opsins SWS1 or SWS2 can cause the photoreceptor layer thinning (the biomarker for age-related macular degeneration in human eye) through enactive the cell aging. The loss ofswsis helpful for alleviating the short-wave light damage on the eye. Since the tapetum lucidum in the eye is found broad existence in various cartilaginous fish, a logical hypothesis was creatively proposed that the existence of tapetum lucidum on the retina of cartilaginous fish is interdependent with the loss of shortwave visual protein gene, providing a new perspective and explanatory path for further understanding of the evolution of visual genes in cartilaginous fish.
Mitochondrial inner membrane remodeling as a driving force of organelle shaping
Authors: Preminger Noga , Zucker Ben , Hassdenteufel Sarah , Stephan Till , Jakobs Stefan , Kozlov Michael M , Schuldiner Maya 
Published: May 2024

AbstractMitochondria are dynamic organelles exhibiting diverse shapes. While the variation of shapes, ranging from spheres to elongated tubules, and the transition between them, are clearly seen in many cell types, the molecular mechanisms governing this morphological variability remain poorly understood. Here, we propose a novel shaping mechanism based on the interplay between the inner and outer mitochondrial membranes. Our biophysical model suggests that the difference in surface area, arising from the pulling of the inner membrane into cristae, correlates with mitochondrial elongation. Analysis of live cell super-resolution microscopy data supports this correlation, linking elongated shapes to the extent of cristae in the inner membrane. Knocking down cristae shaping proteins further confirms the impact on mitochondrial shape, demonstrating that defects in cristae formation correlate with mitochondrial sphericity. Our results suggest that the dynamics of the inner mitochondrial membrane are important not only for simply creating surface area required for respiratory capacity, but go beyond that to affect the whole organelle morphology. This work explores the biophysical foundations of individual mitochondrial shape, suggesting potential links between mitochondrial structure and function. This should be of profound significance, particularly in the context of disrupted cristae shaping proteins and their implications in mitochondrial diseases.
Molecular Display of the Animal Meta-Venome for Discovery of Novel Therapeutic Peptides
Authors: Hsiao Meng-Hsuan , Miao Yang , Liu Zixing , Schütze Konstantin , Limjunyawong Nathachit , Chien Daphne Chun-Che , Monteiro Wayne Denis , Chu Lee-Shin , Morgenlander William , Jayaraman Sahana , Jang Sung-eun , Gray Jeffrey J. , Zhu Heng , Dong Xinzhong , Steinegger Martin , Larman H. Benjamin 
Published: May 2024

AbstractAnimal venoms, distinguished by their unique structural features and potent bioactivities, represent a vast and relatively untapped reservoir of therapeutic molecules. However, limitations associated with extracting or expressing large numbers of individual venoms and venom-like molecules have precluded their therapeutic evaluation via high throughput screening. Here, we developed an innovative computational approach to design a highly diverse library of animal venoms and “metavenoms”. We employed programmable M13 hyperphage display to preserve critical disulfide-bonded structures for highly parallelized single-round biopanning with quantitation via high-throughput DNA sequencing. Our approach led to the discovery of Kunitz type domain containing proteins that target the human itch receptor Mas-related G protein-coupled receptor X4 (MRGPRX4), which plays a crucial role in itch perception. Deep learning-based structural homology mining identified two endogenous human homologs, tissue factor pathway inhibitor (TFPI) and serine peptidase inhibitor, Kunitz type 2 (SPINT2), which exhibit agonist-dependent potentiation of MRGPRX4. Highly multiplexed screening of animal venoms and metavenoms is therefore a promising approach to uncover new drug candidates.
Detection of a reassortant swine- and human-origin H3N2 influenza A virus in farmed mink in British Columbia, Canada
Authors: Kuchinski Kevin S. , Tyson John , Lee Tracy , Detmer Susan , Berhane Yohannes , Burns Theresa , Prystajecky Natalie A. , Himsworth Chelsea G. 
Published: May 2024

AbstractIn December 2021, influenza A viruses (IAV) were detected in a population of farmed mink in British Columbia, Canada. Based on genomic sequencing and phylogenetic analysis, these IAVs were subtyped as H3N2s that originated from reassortment of swine H3N2 (clade 1990.4h), human seasonal H1N1 (pdm09), and swine H1N2 (clade 1A.1.1.3). This reassortant has been subsequently observed in swine in several Midwest American states, as well as in swine and turkeys in Ontario, suggesting its spillover into farmed mink in British Columbia was incidental to its broader dissemination in North American swine populations. These detections reaffirm the need for extensive genomic surveillance of IAVs in swine populations to monitor reassortments that might become public health concerns. They also highlight the need for closer surveillance of IAVs in mink to preserve animal health, protect agricultural interests, and monitor potential zoonotic threats.
International medical graduates’ experiences of clinical competency assessment in postgraduate and licensing examinations: a scoping review protocol
Authors: Hynes Helen , Wiese Anél , McCarthy Nora , Sweeney Catherine , Foley Tony , Bennett Deirdre 
Published: May 2024

AbstractAn international medical graduate (IMG) is a doctor who has received their basic medical qualification from a medical school located in a different country from that in which they practice or intend to practice. IMGs are known to face difficulties in their working lives, including differential attainment in assessment.The objective of this review is to map key concepts and types of evidence in academic and gray literature relating to international medical graduates’ experiences of clinical competency assessment and to identify knowledge gaps on this topic by systematically searching, selecting, and synthesizing existing knowledge.All studies will relate to IMGs. The concept of interest will be IMGs’ experiences of assessment. The context will be postgraduate, licensing or credentialing medical assessments of clinical competence.This review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews. Seven electronic databases will be searched for literature published between 2009 and 2024: the Australian Education Index, British Education Index, ERIC, PubMed, PsycINFO, Scopus, and SocINDEX. Gray literature will be searched using Google, Google Scholar, and published reports from postgraduate training bodies and medical licensing organizations. Documents will be independently screened, selected, and extracted by two researchers using a piloted data-extraction tool. Data will be analyzed and presented in tables and in a narrative format.Scoping review registrationOpen Science Framework:https://osf.io/8gdm7
Converting dose-area product to effective dose in dental cone-beam computed tomography using organ-specific deep learning
Authors: Pauwels Ruben 
Published: May 2024

AbstractObjectiveTo develop an accurate method for converting dose-area product (DAP) to patient dose for dental cone-beam computed tomography (CBCT) using deep learning.Methods24,384 CBCT exposures of an adult phantom were simulated with PCXMC 2.0, using permutations of tube voltage, filtration, source-isocenter distance, beam width/height and isocenter position. Equivalent organ doses as well as DAP values were recorded. Next, using the aforementioned scan parameters as inputs, neural networks (NN) were trained using Keras for estimating the equivalent dose per DAP for each organ. Two methods were explored for positional input features: (1) ‘Coordinate’ mode, which uses the (continuous) XYZ-coordinates of the isocenter, and (2) ‘AP/JAW’ mode, which uses the (categorical) anteroposterior and craniocaudal position. Each network was trained, validated and tested using a 3/1/1 data split. Effective dose (ED) was calculated from the combination of NN outputs using ICRP 103 tissue weighting factors. The performance of the resulting NN models for estimating ED/DAP was compared with that of a multiple linear regression (MLR) model as well as direct conversion coefficients (CC).ResultsThe mean absolute error (MAE) for organ dose / DAP on the test data ranged from 0.18% (bone surface) to 2.90% (oesophagus) in ‘Coordinate’ mode and from 2.74% (red bone-marrow) to 14.13% (brain) in ‘AP/JAW’ mode. The MAE for ED was 0.23% and 4.30%, respectively, for the two modes, vs. 5.70% for the MLR model and 20.19%-32.67% for the CCs.ConclusionNNs allow for an accurate estimation of patient dose based on DAP in dental CBCT.
Prospect study for the measurement of the
Hbb¯
coupling at the LHC and FCC-hh
Authors: Abdy Zahra , Mohammadi Najafabadi Mojtaba 
Published: May 2024

This paper employs the H+b+jets signature in proton-proton collisions to explore the structure of the Hbb¯ couplings. The focus of the analysis lies in the decay of the Higgs boson into a photon pair, taking into account both reducible and irreducible backgrounds and a realistic simulation of the detector effects. To enhance the discrimination between signal and background, a multivariate analysis is employed to analyze the kinematic variables and optimise the signal-to-background ratio. The results indicate that the H+b+jets process can significantly contribute to the precise measurement of CP-even and CP-odd couplings between the bottom quark and the Higgs boson at the LHC and FCC-hh. Finally, a novel asymmetry is introduced for the purpose of probing CP violation within the Hbb¯ coupling, formulated exclusively based on lab-frame momenta.

Published by the American Physical Society
2024
Can Supercooled Phase Transitions Explain the Gravitational Wave Background Observed by Pulsar Timing Arrays?
Authors: Athron Peter , Fowlie Andrew , Lu Chih-Ting , Morris Lachlan , Wu Lei , Wu Yongcheng , Xu Zhongxiu 
Published: May 2024

Several pulsar timing array collaborations recently reported evidence of a stochastic gravitational wave background (SGWB) at nHz frequencies. While the SGWB could originate from the merger of supermassive black holes, it could be a signature of new physics near the 100 MeV scale. Supercooled first-order phase transitions (FOPTs) that end at the 100 MeV scale are intriguing explanations, because they could connect the nHz signal to new physics at the electroweak scale or beyond. Here, however, we provide a clear demonstration that it is not simple to create a nHz signal from a supercooled phase transition, due to two crucial issues that could rule out many proposed supercooled explanations and should be checked. As an example, we use a model based on nonlinearly realized electroweak symmetry that has been cited as evidence for a supercooled explanation. First, we show that a FOPT cannot complete for the required transition temperature of around 100 MeV. Such supercooling implies a period of vacuum domination that hinders bubble percolation and transition completion. Second, we show that even if completion is not required or if this constraint is evaded, the Universe typically reheats to the scale of any physics driving the FOPT. The hierarchy between the transition and reheating temperature makes it challenging to compute the spectrum of the SGWB.

Published by the American Physical Society
2024
Unleashing the mechanism to promote psychological ownership: a comparative study of generation X, Y, and Z
Authors: Bhushan Balram 
Published: May 2024

Purpose
With the increasing turnover intention worldwide, psychological ownership is gaining traction. Considering the significance of the same for the development and growth of an organization, this paper explores the mechanism to promote psychological ownership and how generational differences contribute to the same.

Design/methodology/approach
A questionnaire was designed and circulated to 1450 employees covering Generation X, Y, and Z. A total of 378 usable responses were received and subjected to Process Macro Model 7 to test seven hypotheses. SPSS was used to test the reliability and validity of the dataset, and RStudio was used for the Confirmatory Factor Analysis.

Findings
The findings supported the moderated mediation model between psychological ownership (PO) and psychological availability (PA). Here, meaningfulness (MN) was the mediator, and age was the moderator. The paper suggests that Generation Z experiences significantly lower psychological ownership (PO) and psychological availability (PA) compared to their elder colleagues. The indirect effect of PA on PO through meaningfulness was significant for all generations, and the generational transition also introduced significant changes.

Originality/value
This is the first study to examine the generational differences in psychological ownership among employees. Accordingly, this research adds to the organizational development literature and suggests that human resource managers design customized interventions for promoting psychological availability. Also, the organization needs to maintain demographic diversity to facilitate learning and development.