bluuebunny/crossref_metadata_2025_split huggingface dataset:
A ML Framework for Genetic Sequence Identification using 2D Electrical Conductance Probability Distributions from Mixed Data Sets
Authors: Wang Yiren , Wang Hongning , Das Arindam K. , Anantram M. P. 
Published: December 2024

AbstractGenetic sequence identification from electrical characterization of single molecules has emerged as a promising alternative to traditional approaches. Since electrical data on single molecules is extremely noisy due to the limitations of even state-of-the-art approaches, achieving high detection rates is challenging, particularly when the task involves being able to distinguish a sequence from its single base-pair mismatches. To address this issue, we propose an architecture based on combining a convolutional neural network with an ensemble learning method, XGBoost. In addition, four different input feature representations are considered, 1D conductance probability distributions and 2D conductance versus distance probability distributions which can be viewed as images, with or without averaging over the experimental parameters. The with averaging case corresponds to feature matrices derived from mixed datasets. We find that 2D probability distributions are helpful with respect to classifier accuracy, but averaged conductance probability distributions are much more impactful and significantly enhance prediction accuracy. Our quantitative analysis of multiple sequences shows an impressive performance increase of approximately 10% for all sequences. While the basis of our analysis is conductance data of DNA strands for COVID-19 Alpha, Beta, and Delta variants and their single base-pair mismatches, our method is generally applicable to other single-molecule identification based on their conductance.
A model of inborn metabolism errors associated with adenine amyloid-like fiber formation reduces TDP-43 aggregation and toxicity in yeast
Authors: Park Sangeun , Park Sei-Kyoung , Liebman Susan W. 
Published: December 2024

AbstractTDP-43 is linked to human diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Expression of TDP-43 in yeast is known to be toxic, cause cells to elongate, form liquid-like aggregates, and inhibit autophagy and TOROID formation. Here, we used theapt1Δ aah1Δyeast model of disorders of inborn errors of metabolism, previously shown to lead to intracellular adenine accumulation and adenine amyloid-like fiber formation, to explore interactions with TDP-43. Results show that the double deletion shifts the TDP-43 aggregates from a liquid-like, toward a more amyloid-like, state. At the same time the deletions reduce TDP-43’s effects on toxicity, cell morphology, autophagy, and TOROID formation without affecting the level of TDP-43. This suggests that the liquid-like and not amyloid-like TDP-43 aggregates are responsible for the deleterious effects in yeast. How theapt1Δ aah1Δdeletions alter TDP-43 aggregate formation is not clear. Possibly, it results from adenine/TDP-43 fiber interactions as seen for other heterologous fibers. The work offers new insights into the potential interactions between metabolite-based amyloids and pathological protein aggregates, with broad implications for understanding protein misfolding diseases.
Serum lipid reference intervals of high-density and low-density lipoprotein cholesterols and their association with atherosclerosis and other factors in Psittaciformes
Authors: Janeczek Matthias , Korbel Rüdiger , Janeczek Friedrich , Alber Helen , Küchenhoff Helmut , Rinder Monika 
Published: December 2024

AbstractThe prevalence of atherosclerosis is high in captive psittacine populations and the disease and subsequent heart problems have become a common reason for consultations in avian veterinary practices. To this day, ante-mortem diagnosis in birds remains challenging, however the serum lipoprotein-panel has been suggested to potentially aid in the diagnosis of the disease and provide better understanding of the pathogenesis. In parrots, unlike in humans, an association between serum lipoproteins and atherosclerosis has not been proven so far. The present retrospective cohort study aimed to establish multi-genera serum reference intervals for high-density-lipoprotein cholesterol (HDL-C) and low-density-lipoprotein cholesterol (LDL-C) in various parrot species. In addition, an evaluation on the changes of HDL-C and LDL-C depending on intrinsic and extrinsic factors of genus, age, sex, diet, prevalence of atherosclerosis, reproductive activity and body condition score was performed. An analysis of 1199 blood samples originating from 694 birds of multiple parrot genera revealed genus-specific variations in lipoprotein levels. Lipoproteins were studied for their association with independent variables of diet, age, sex, reproductive and breeding status, atherosclerosis and body conditioning score. A significant association between LDL-C levels and the prevalence of atherosclerosis could be observed, similar to findings in humans. Diet was found to be influencing both lipoprotein levels and risk for the development of atherosclerotic disease. Results showed, that LDL-C appears to be a potential predictor of atherosclerosis, while the role of HDL-C remained less conclusively defined. The results of the study provide a foundational framework for the future use of lipoprotein analysis in parrot medicine, offering novel insights into the management of cardiovascular health in pet parrots.
The complex development of psoralen-interstrand crosslink resistance inEscherichia colirequires AcrR inactivation, retention of amarboxsequence, and one of three MarA, SoxS, or Rob global regulators
Authors: Worley Travis K , Asal Ayah H , Cooper Lo , Courcelle Charmain T , Courcelle Justin 
Published: December 2024

AbstractCrosslinking agents, such as psoralen and UVA radiation, can be effectively used as antimicrobials and for treating several dysplastic conditions in humans, including some cancers. Yet, both cancer cells and bacteria can become resistant to these compounds, making it important to understand how resistance develops. Recently, several mutants were isolated that developed high-levels of resistance to these compounds through upregulation of components of the AcrAB-TolC-efflux pump. Here, we characterized these mutants and found that resistance specifically requires inactivating mutations of theacrRtranscriptional repressor which also retain themarboxsequence found within this coding region. In addition, the presence of any one of three global regulators, MarA, SoxS, or Rob, is necessary and sufficient to bind to themarboxsequence and activate resistance. Notably, although psoralen is a substrate for the efflux pump, these regulators are not naturally responsive to this stress as neither psoralen, UVA, nor crosslink induction upregulatesacrABexpression in the absence of mutation.HighlightsPsoralen crosslink resistance requires AcrR inactivation and MarA/SoxS/Rob activationPsoralen crosslink resistance is mediated by upregulating the AcrAB-TolC efflux pumpAcrAB-TolC can utilize psoralen as a substrate but not upregulated by this stressAcquiring resistance to DNA interstrand crosslinks requires mutation
CAFE: An Integrated Web App for High-Dimensional Analysis and Visualization in Spectral Flow Cytometry
Authors: Siam Md Hasanul Banna , Ali Md Akkas , Vardaman Donald , Acharyya Satwik , Patil Mallikarjun , Tyrrell Daniel J. 
Published: December 2024

AbstractSpectral flow cytometry provides greater insights into cellular heterogeneity by simultaneous measurement of up to 50 markers. However, analyzing such high-dimensional (HD) data is complex through traditional manual gating strategy. To address this gap, we developed CAFE as an open-source Python-based web application with a graphical user interface. Built with Streamlit, CAFE incorporates libraries such as Scanpy for single-cell analysis, Pandas and PyArrow for efficient data handling, and Matplotlib, Seaborn, Plotly for creating customizable figures. Its robust toolset includes density-based down-sampling, dimensionality reduction, batch correction, Leiden-based clustering, cluster merging and annotation. Using CAFE, we demonstrated analysis of a human PBMC dataset of 350,000 cells identifying 16 distinct cell clusters. CAFE can generate publication-ready figures in real time via interactive slider controls and dropdown menus, eliminating the need for coding expertise and making HD data analysis accessible to all. CAFE is licensed under MIT and is freely available athttps://github.com/mhbsiam/cafe.
TurboID-based proximity labeling identifies novel germline proteins that maintain E granule integrity and small RNA homeostasis inC. elegans
Authors: Li Kun , Feng Xuezhu , Wang Ke , Huang Xiaona , Zhu Chengming , Huang Xinya , Wen Quan , Guang Shouhong , Chen Xiangyang 
Published: December 2024

AbstractGerm granules are biomolecular condensates composed of RNA and proteins that play crucial roles in RNA metabolism and posttranscriptional gene regulation.C. elegansgerm granules consist of at least seven distinct subcompartments, including P granules, Z granules, Mutator foci, SIMR foci, P-bodies, D granules and E granules. Among these condensates, the E granule, which is nonrandomly positioned within the germ granule, is required for the production of a specialized class of small interfering RNAs (siRNAs). However, the mechanisms underlying E granule formation and its functional significance remain largely unexplored. In this study, via the use of TurboID- based proximity labeling technology combined with an RNAi-based reverse genetic screen, we identified two novel components of the E granule, EGC-2/C27B7.5 and EGC-3/F59G1.8, which initiate E granule assembly. The depletion of EGC-2 or EGC- 3 disrupts the perinuclear localization of the EGO and PICS complexes, both of which are enriched in E granules and are required for E-class siRNA and piRNA biogenesis, respectively. Small RNAomic analyses revealed that both EGC-2 and EGC-3 promote the production of 5’E-class siRNA, whereas prohibiting piRNA maturation. Taken together, our results elucidate the roles of EGC-2 and EGC-3 in maintaining E granule integrity and small RNA homeostasis, and suggest that intracellular condensation may exert distinct regulatory effects on different biological processes. Additionally, the combination of proximity labeling technology and reverse genetic screening provides a robust strategy for studying the assembly of biomolecular condensates.
A neural circuit for context-dependent multimodal signaling inDrosophila
Authors: Steinfath Elsa , Khalili Afshin , Stenger Melanie , Schultze Bjarne L. , Ravindran Sarath Nair , Alizadeh Kimia , Clemens Jan 
Published: December 2024

AbstractMany animals, including humans, produce multimodal displays by combining acoustic with visual or vibratory signals [1–4]. However, the neural circuits that coordinate the production of multiple signals in a context-dependent manner are unknown. Multimodal behaviors could be produced by parallel circuits that independently integrate the external cues that trigger each signal. We find that multimodal signals inDrosophilaare driven by a single circuit that integrates external sensory cues with internal motivational state and circuit dynamics.Drosophilamales produce air-borne song and substrate-borne vibration during courtship and previous studies have identified neurons that drive courtship and singing, but the contexts and circuits that drive vibrations and coordinate multimodal signaling were not known [5–11]. We show that males produce song and vibration in distinct, largely non-overlapping contexts and that brain neurons that drive song also drive vibrations with cell-type specific dynamics and via separate pre-motor pathways. This circuit also coordinates multimodal signaling with ongoing behavior, namely locomotion, to drive vibrations only when the male’s vibrations can reach the female. A shared circuit facilitates the control of signal dynamics by external cues and motivational state through shared mechanisms like recurrence and mutual inhibition. A proof-of-concept circuit model shows that these motifs are sufficient to explain the behavioral dynamics. Our work shows how simple motifs can be combined in a single neural circuit to select and coordinate multiple behaviors.
Estimating survival of an anadromous salmonid using Bayesian hierarchical models applied to acoustic telemetry, biological, and environmental data
Authors: Munaweera Inesh , Harris Les N. , Moore Jean-Sébastien , Tallman Ross F. , Gilbert Matthew J.H. , Fisk Aaron T. , Else Brent G. T. , Ahmed Mohamed M. M. , Gillis Darren M. , Muthukumarana Saman 
Published: December 2024

AbstractHierarchical modelling is frequently used to model ecological processes because of its ability to handle complex ecological phenomena by decomposing them into naturally explainable sub-models. Hierarchical Bayesian approaches have gained widespread use in health, social, and environmental sciences, including in the estimation of demo-graphic parameters such as survival. In this study, we combine Bayesian hierarchical models with acoustic telemetry data to estimate survival probabilities for high-latitude populations of an anadromous salmonid, the Arctic char(Salvelinus alpinus), while in-corporating environmental and biological covariates to assess their impact on survival. The model we present here can also account for temporally varying detection probabilities due to changes to the acoustic receiver array design and seasonal variation in the detection probabilities related to environmental conditions (e.g., ice vs. no ice). As previously documented in this species, survival was high (>0.87) and we found that the covariates pertaining to sea ice coverage and Fulton’s condition factor impacted the survival probabilities. Contrary to our expectations, high-condition fish had lower survival rates. Survival was also considerably lower during the summer (open-water) compared to winter (ice-covered) seasons. While the biological explanations and implications of these findings require further exploration, they nonetheless demonstrate the utility of this approach. Specifically, we present a hierarchical Bayesian model that can consider environmental and biological covariates while accounting for varying detection probabilities, a major concern of acoustic telemetry studies. The model can be easily adapted for other taxa with similar life histories where mark recapture data are available and can be extended to include additional environmental (e.g., salinity) and biological parameters (e.g., sex).
Lymphatic activation of ACKR3 signaling regulates lymphatic response after ischemic heart injury
Authors: Balint Laszlo , Patel Shubhangi , Serafin D. Stephen , Zhang Hua , Quinn Kelsey E. , Aghajanian Amir , Kistner Bryan M. , Caron Kathleen M. 
Published: December 2024

2.AbstractBackgroundIschemic heart disease is a prevalent cause of death and disability worldwide. Recent studies reported a rapid expansion of the cardiac lymphatic network upon ischemic heart injury and proposed that cardiac lymphatics may attenuate tissue edema and inflammatory mechanisms after ischemic heart injury. Nevertheless, the mechanisms through which hypoxic conditions affect cardiac lymphangiogenesis and function remain unclear. Here, we aimed to characterize the role of the adrenomedullin decoy receptor atypical chemokine receptor 3 (ACKR3) in the lymphatic response following ischemic heart injury.MethodsSpatial assessment of ACKR3 signaling in the heart after ischemic heart injury was conducted using ACKR3-TangoGFP reporter mice. Roles of ACKR3 after ischemic heart injury were characterized inAckr3ΔLyve1mice and in cultured human lymphatic endothelial cells (LECs) exposed to hypoxia.ResultsUsing the novel ACKR3-Tango-GFP reporter mice, we detected activation of ACKR3 signaling in cardiac lymphatics adjacent to the site of ischemic injury of left anterior descending artery (LAD) ligation.Ackr3ΔLyve1mice exhibited better survival and were protected from the formation of acute tissue edema after ischemic cardiac injury.Ackr3ΔLyve1mice exhibited a denser cardiac lymphatic network after LAD ligation, especially in the injured tissues. Transcriptomic analysis revealed changes in cardiac lymphatic gene expression patterns that have been associated with extracellular matrix remodeling and immune activation. We also found that ACKR3 plays a critical role in the regulating continuous cell-cell junction dynamics in LECs under hypoxic conditions.ConclusionsLymphatic expression of ACKR3 governs numerous processes following ischemic heart injury, including the lymphangiogenic response, edema protection and overall survival. These results expand our understanding of how the heart failure biomarker adrenomedullin, regulated by lymphatic ACKR3, may exert its cardioprotective roles after ischemic cardiac injury.
Prediction and annotation of alternative transcription starts and promoter shift in the chicken genome
Authors: Grushina Valentina A , Yevshin Ivan S , Gusev Oleg A , Kolpakov Fedor A , Pintus Sergey S 
Published: December 2024

AbstractThe promoter shift is a long known phenomenon which implies changes in the coordinates of a transcription start site (TSS). Analysis of CAGE experiments allows one to assess the impact and statistical significance of the shift. The promoter shift can be associated not only with the change of stages in early development or tissue differentiation, but also with the environmental influence on the cells. Differential promoter usage suggests non-constitutive expression activity of the regulated gene, which, in turn, suggests the usage of few sharp promoters. On the other hand, the housekeeping genes are assumed to demonstrate stable levels of expression while using multiple broad promoters. Additionally, the housekeeping genes are assumed to be normally expressed in most of the tissues. Our results show that many ubiquitously expressed genes use single sharp promoters and are subject to the significant promoter shift, which implies an additional level of complexity to the problem of definition of a housekeeping gene.The reaction of genes in cells and tissues to external stimuli is often studied in the context of differential gene expression. Our study employs a different approach of differential promoter usage, which takes the genes whose promoters undergo significant promoter shifting as the signatures of tissue response and phenotypic effect. Our results suggest that the difference in growth rate of chickens is controlled by the rate of metabolism of nutrients via the differential usage of promoters of the relevant genes.
Cortical dynamics underlying initiation of rapid steps with contrasting postural demands
Authors: Giesbers Ilse , Billen Lucas , van der Cruijsen Joris , Corneil Brian D. , Weerdesteyn Vivian 
Published: December 2024

AbstractOur ability to flexibly initiate rapid visually-guided stepping movements can be measured in the form of express visuomotor responses (EVRs), which are short-latency (∼100ms), goal-directed bursts of lower-limb muscle activity. Interestingly, we previously demonstrated that recruitment of anticipatory postural adjustments (APAs) interacted with the subcortically-generated EVRs in the lower limb, suggesting context-dependent top-down modulation.We investigated the associated cortical dynamics prior to and during rapid step initiation towards a salient visual target in twenty-one young, healthy individuals. We adopted two contrasting postural conditions by manipulating the stepping direction. Anterolateral steps involved low postural demands, whereas anteromedial stepping involved high postural demands. We recorded high-density EEG, surface electromyography from gluteus medius and ground-reaction forces.Independent component analysis and time-frequency statistics revealed significant, yet relatively modest differences between conditions in preparatory cortical dynamics, most evidently in primary motor areas. Following target presentation, we observed stronger theta and alpha power enhancement in the supplementary motor area, and stronger alpha and beta power decrease in primary motor, parietal and occipital clusters during APA recruitment that preceded steps under high postural demands. We found no differences in (pre)frontal areas associated with the observed EVR suppression in the high postural demand condition.Together, our findings point towards greater cortical involvement in step initiation under high postural demands as compared to more reflexive, stimulus-driven steps. This notion may be particularly relevant for populations where postural control is impaired by age or disease, as more cortical resources may need to be allocated during stepping.
TRPM7 activity drives human CD4 T-cell activation and differentiation in a magnesium dependent manner
Authors: Hoelting Kilian , Madlmayr Anna , Hoeger Birgit , Lewitz Dorothea , Weng Marius , Haider Tanja , Duggan Michelle , Ross Rylee , Horgen F. David , Sperandio Markus , Dietrich Alexander , Gudermann Thomas , Zierler Susanna 
Published: December 2024

AbstractT lymphocyte activation is a crucial process in the regulation of innate and adaptive immune responses. The ion channel-kinase TRPM7 has previously been implicated in cellular Mg2+homeostasis, proliferation, and immune cell modulation. Here, we show that pharmacological and genetic silencing of TRPM7 leads to diminished human CD4 T-cell activation and proliferation following TCR mediated stimulation. In both primary human CD4 T cells and CRISPR/Cas-9 engineered Jurkat T cells, loss of TRPM7 led to altered Mg2+homeostasis, Ca2+signaling, reduced NFAT translocation, decreased IL-2 secretion and ultimately diminished proliferation and differentiation. While the activation of primary human CD4 T cells was dependent on TRPM7, polarization of naïve CD4 T cells into regulatory T cells (Treg) was not. Taken together, these results highlight TRPM7 as a key protein of cellular Mg2+homeostasis and CD4 T-cell activation. Its role in lymphocyte activation suggests therapeutic potential for TRPM7 in numerous T-cell mediated diseases.SummaryTRPM7 is crucial to maintaining cellular Mg2+homeostasis and regulates human CD4 T-cell activation by modulating early Ca2+signaling events in response to TCR-mediated stimulation subsequently, influencing T-cell differentiation in a Mg2+dependent manner.