bluuebunny/crossref_metadata_2025_split huggingface dataset:
A scalable and robust variance components method reveals insights into the architecture of gene-environment interactions underlying complex traits
Authors: Pazokitoroudi Ali , Dahl Andrew , Zaitlen Noah , Rosset Saharon , Sankararaman Sriram 
Published: December 2023

AbstractUnderstanding the contribution of gene-environment interactions (GxE) to complex trait variation can provide insights into mechanisms underlying disease risk, explain sources of heritability, and improve the accuracy of genetic risk prediction. While biobanks that collect genetic and deep phenotypic data over large numbers of individuals offer the promise of obtaining novel insights into GxE, our understanding of the architecture of GxE in complex traits remains limited. We introduce a method that can estimate the proportion of trait variance explained by GxE (GxE heritability) and additive genetic effects (additive heritability) across the genome and within specific genomic annotations. We show that our method is accurate in simulations and computationally efficient for biobank-scale datasets.We applied our method to≈500, 000 common array SNPs (MAF≥1%), fifty quantitative traits, and four environmental variables (smoking, sex, age, and statin usage) measured across≈300, 000 unrelated white British individuals in the UK Biobank. We found 69 trait-environmental variable pairs with significant genome-wide GxE heritability (p <0.05/200 correcting for the number of trait-E pairs tested) with an average ratio of GxE to additive heritability≈6.8% that include BMI with smoking (ratio of GxE to additive heritability = 6.3±1.1%), WHR (waist-to-hip ratio adjusted for BMI) with sex (ratio = 19.6±2%), LDL cholesterol with age (ratio = 9.8±3.9%), and HbA1c with statin usage (ratio = 11±2%). Analyzing nearly 8 million common and low-frequency imputed SNPs (MAF≥0.1%), we document an increase in genome-wide GxE heritability of about 28% on average over array SNPs. We partitioned GxE heritability across minor allele frequency (MAF) and local linkage disequilibrium values (LD score) of each SNP to observe that analogous to the relationship that has been observed for additive allelic effects, the magnitude of GxE allelic effects tends to increase with decreasing MAF and LD. Testing whether GxE heritability is enriched around genes that are highly expressed in specific tissues, we find significant tissue-specific enrichments that include brain-specific enrichment for BMI and Basal Metabolic Rate in the context of smoking, adipose-specific enrichment for WHR in the context of sex, and cardiovascular tissue-specific enrichment for total cholesterol in the context of age. Our analyses provide detailed insights into the architecture of GxE underlying complex traits.
Cortical ripples mediate top-down suppression of hippocampal reactivation during sleep memory consolidation
Authors: Shin Justin D. , Jadhav Shantanu P. 
Published: December 2023

AbstractConsolidation of initially encoded hippocampal representations in the neocortex through reactivation is crucial for long-term memory formation, and is facilitated by the coordination of hippocampal sharp-wave ripples (SWRs) with cortical oscillations during non-REM sleep. However, the contribution of high-frequency cortical ripples to consolidation is still unclear. We used continuous recordings in the hippocampus and prefrontal cortex (PFC) over the course of spatial learning and show that independent PFC ripples, when dissociated from SWRs, predominantly suppress hippocampal activity in non-REM sleep. PFC ripples paradoxically mediate top-down suppression of hippocampal reactivation, which is inversely related to reactivation strength during coordinated CA1-PFC ripples. Further, we show non-canonical, serial coordination of ripples with cortical slow and spindle oscillations. These results establish a role for cortical ripples in regulating consolidation.
scHiCyclePred: a deep learning framework for predicting cell cycle phases from single-cell Hi-C data using multi-scale interaction information
Authors: Wu Yingfu , Shi Zhenqi , Zhou Xiangfei , Zhang Pengyu , Yang Xiuhui , Ding Jun , Wu Hao 
Published: December 2023

AbstractWhile scRNA-seq offers gene expression snapshots, it misses the spatial context of chromatin organization crucial for cell cycle regulation. Single-cell Hi-C, capturing chromatin’s three-dimensional (3D) architecture, fills this void, revealing interactions between genomic regions that transcript-only data might overlook. We introduce scHiCyclePred, a model that utilizes single-cell Hi-C’s multi-scale interaction data to predict cell cycle phases by extracting chromatin’s 3D features. This fusion-prediction model integrates three feature sets into a unified vector. Remarkably, scHiCyclePred outperforms methods like NAGANO and CIRCLET and traditional machine learning techniques across various metrics. Our insights into 3D chromatin dynamics during the cell cycle further underscore its utility. By offering a more comprehensive view of cell cycle dynamics through chromatin structure, scHiCyclePred stands to significantly advance our understanding in cellular biology and holds potential to catalyze breakthroughs in disease research. Access scHiCyclePred atgithub.com/HaoWuLab-Bioinformatics/scHiCyclePred.
Identification of Clonal Hematopoiesis Driver Mutations through In Silico Saturation Mutagenesis
Authors: Demajo Santiago , Ramis-Zaldivar Joan Enric , Muiños Ferran , Grau Miguel L , Andrianova Maria , López-Bigas Núria , González-Pérez Abel 
Published: December 2023

AbstractClonal hematopoiesis (CH) is a phenomenon of clonal expansion of hematopoietic stem cells driven by somatic mutations affecting certain genes. Recently, CH has been linked to the development of a number of hematologic malignancies, cardiovascular diseases and other conditions. Although the most frequently mutated CH driver genes have been identified, a systematic landscape of the mutations capable of initiating this phenomenon is still lacking. Here, we train high-quality machine-learning models for 12 of the most recurrent CH driver genes to identify their driver mutations. These models outperform an experimental base-editing approach and expert-curated rules based on prior knowledge of the function of these genes. Moreover, their application to identify CH driver mutations across almost half a million donors of the UK Biobank reproduces known associations between CH driver mutations and age, and the prevalence of several diseases and conditions. We thus propose that these models support the accurate identification of CH across healthy individualsSignificanceWe developed and validated 12 gene-specific machine learning models to identify CH driver mutations, showing their advantage with respect to expert-curated rules. These models can support the identification and clinical interpretation of CH mutations in newly sequenced individuals.
Hummingbirds rapidly respond to the removal of vision and control a sequence of rate-commanded maneuvers in milliseconds
Authors: Anwar Md Zafar , Tobalske Bret W. , Agrawal Suyash , Mongeau Jean-Michel , Luo Haoxiang , Cheng Bo 
Published: December 2023

AbstractHummingbird flight is the epitome of extreme aerial agility and controlled stability, as hummingbirds routinely exercise a variety of stunning aerobatic feats. Yet, the control of these amazing maneuvers is not well understood. Here we examined how hummingbirds control a sequence of maneuvers within milliseconds and tested whether and when their vision is active during this rapid process. We elicited escape flight in calliope hummingbirds and removed visible light at various instants during the maneuvers and quantified their flight kinematics and responses. We show that the escape maneuvers were composed of rapidly-controlled sequential modules, including evasion, reorientation, nose-down dive, forward flight, and nose-up to hover. The hummingbirds did not respond to the light removal during evasion and reorientation until a critical light-removal time; afterward they showed two categories of luminance-based responses that rapidly altered maneuvering modules to terminate the escape. We also show that hummingbird maneuvers are rate-commanded and require no active braking, i.e., their body angular velocities were proportional to the change of wing motion patterns, a trait that likely alleviates the computational demand on flight control. Together, this work uncovers the key traits of hummingbird agility, which can also inform and inspire designs for next-generation agile aerial systems.
Sysrecon: A systematic data-driven tool for genome-scale metabolic reconstructions
Authors: Ouyang Shilin , Li Zihao , Hu Jiamin , Cao Miyuan , Wang Xiting , Sun Hongxia , Yu Feng , Mao Longfei 
Published: December 2023

AbstractGenome-scale metabolic reconstructions contain the information about metabolism, which understands organisms’ molecular mechanisms better. Different reconstruction procedures are developed to achieve high-quality GSMRs of organisms; however, the descriptions of procedures are vague, meaning that they cannot be qualitatively reproduced, even contradictory, and different published reconstructions may involve different steps. This indicates that there is no unified strategy to quantify the steps in GSMRs. To resolve the problem, we created a R package, Sysrecon, to quantitatively and qualitatively describe the steps of GSMRs in the literature. Sysrecon disassembles GSMR into 93 steps, which are compiled after the comprehensive textual analysis of metabolic reconstructions. Then, Sysrecon decomposes each step of the reconstruction procedure into three components: step content, step conversion, and database and tools. When building a GSMR, Sysrecon creates a template procedure that includes a list of pipeline steps, the description of the information conversion in the steps, and the database and tools that may be used to facilitate the conversion. Because each step’s conversion is defined by a formula, the entire GSMR can be dismantled into many ‘step’ blocks. The reconstruction procedure is therefore transformed into an adaptable automated assembly line that can be customized and tailored to settings of different organisms. To the best of our knowledge, Sysrecon is the first computational tool that dynamically constructs the GSMRs pipeline and provides a framework for defining reconstruction steps and can be used as a basis for the development of high-quality GSMRs.
Java sparrow song conforms to Menzerath’s Law but not Zipf’s Law of Abbreviation
Authors: Lewis Rebecca N , Kwong Anthony , Soma Masayo , de Kort Selvino R , Gilman R Tucker 
Published: December 2023

AbstractLinguistic laws, which describe common statistical patterns in human language, are often studied in animal communication systems. Despite good evidence for the existence of these laws in non-human primates, data is still limited for other taxa. Birdsong is often used as a model for human language development due to similarities in vocal learning and production. Therefore, it is useful to explore features of human language in birdsong to determine the value and limitations of such comparisons. Here, we looked for patterns consistent with Menzerath’s law, the tendency for longer sequences to be made up of smaller constituent parts, and Zipf’s Law of Abbreviation, the tendency for more frequently used elements to be shorter in length, in the songs of Java sparrows (Padda oryzivora). We found that songs conformed to Menzerath’s law at both the population and individual level; longer sequences were made up of shorter notes, and this pattern was achieved through note selection, rather than shortening existing notes. This adherence to Menzerath’s law may reflect species-specific constraints on song durations. However, we found no evidence to support adherence to Zipf’s Law of Abbreviation, either at population or individual level; more frequently used notes were not shorter in length. As they are used in courtship, songs may experience different selection pressure to other parts of the vocal repertoire, which could act against compression. Whilst there may be some limitations in applying linguistic laws designed for human language to birdsong, especially Zipf’s Law of Abbreviation, these laws may still provide insights into animal and human communication systems.
Most azole antifungal resistance mutations in the drug target provide cross-resistance and carry no intrinsic fitness cost
Authors: Bédard Camille , Gagnon-Arsenault Isabelle , Boisvert Jonathan , Plante Samuel , Dubé Alexandre K. , Pageau Alicia , Fijarczyk Anna , Sharma Jehoshua , Maroc Laetitia , Shapiro Rebecca S. , Landry Christian R. 
Published: December 2023

AbstractAzole antifungals are among the most frequently used drugs to treat fungal infections. Amino acid substitutions in and around the binding site of the azole target Erg11 (Cyp51) are a common resistance mechanism in pathogenic yeasts such asCandida albicans. How many and which mutations confer resistance, and at what cost, is however largely unknown. Here, we measure the impact of nearly 4,000 amino acid variants of the Erg11 ligand binding pocket on the susceptibility to six medical azoles. We find that a large fraction of amino acid substitutions lead to resistance (33%), most resistance mutations confer cross-resistance to two or more azoles (88%) and most importantly, only a handful of resistance mutations show a significant fitness cost in the absence of drug (9%). Our results reveal that resistance to azoles can arise through a large set of mutations and this will likely lead to azole pan-resistance, with very little evolutionary compromise. Such a resource will help inform treatment choices in clinical settings and guide the development of new drugs.
Thermo-optoplasmonic single-molecule sensing on optical microcavities
Authors: Toropov Nikita A. , Houghton Matthew C. , Yu Deshui , Vollmer Frank 
Published: December 2023

AbstractWhispering-gallery-mode (WGM) resonators are powerful instruments for single-molecule sensing in biological and biochemical investigations. WGM sensors leveraged by plasmonic nanostructures, known as optoplasmonic sensors, provide unprecedented sensitivity down to single atomic ions. In this article, we describe that the response of optoplasmonic sensors upon the attachment of single protein molecules strongly depends on the intensity of WGM. At low intensity, protein binding causes red shifts of WGM resonance wavelengths, known as the reactive sensing mechanism. By contrast, blue shifts are obtained at high intensities, which we explain as thermo-optoplasmonic (TOP) sensing, where molecules transform absorbed WGM radiation into heat. To support our conclusions, we experimentally investigated seven molecules and complexes; we observed blue shifts for dye molecules, amino acids and anomalous absorption of enzymes in the near-infrared spectral region. As an example of application, we propose a physical model of TOP sensing that can be used for the development of single-molecule absorption spectrometers.Significance StatementA notable contribution to the optical detection of single molecules has been brought about by using optical microcavities, specifically whispering-gallery-mode resonators that combine optical and plasmon resonances for the most sensitive single-molecule and ion detection. Adding absorption measurements to a single-molecule technique that operates in an aqueous solution would provide powerful new detection capabilities for sensing the properties of single molecules. We demonstrate here, for the first time, the detection of absorption cross-sections of protein molecules on optoplasmonic microcavities and validate the technique with seven different molecules and complexes. A proof-of-concept for single-molecule optoplasmonic absorption spectrometers is presented, based on a thermo-optoplasmonic sensing mechanism.
Quorum Sensing Positively Regulates CPS-dependentAutographiviridaePhages Infection inVibrio alginolyticus
Authors: Li Xixi , Zhang Chen , Li Shenao , Liang Sixuan , Xu Xuefei , Zhao Zhe 
Published: December 2023

ABSTRACTQuorum sensing (QS) orchestrates many bacterial behaviors, such as virulence and biofilm formation, across bacterial populations. Nevertheless, the underlying mechanism of QS regulating CPS-dependent phage-bacterium interactions remains unclear. In the present study, we report that QS upregulated the expression of CPS-dependent phage receptors, thus increasing phage adsorption and infection rates inV. alginolyticus. We found that QS upregulated the expression of theugdgene, leading to increased synthesis ofAutographiviridaephage receptor capsular polysaccharide (CPS) synthesis inV. alginolyticus. The signal molecule autoinducer-2 (AI-2) released byV. alginolyticusfrom different sources can potentially enhance CPS-dependent phage infection. Therefore, our data suggest that inhibiting quorum sensing may reduce rather than improve the therapeutic efficacy of CPS-specific phages.IMPORTANCEPhage resistance is a direct threat to phage therapy, and understanding phage-host interactions, especially bacteria block phage infection, is essential for developing successful phage therapy. In the present study, we demonstrate for the first time thatV. alginolyticususes QS to promote CPS-specific phage infection by upregulating the expression ofugd, which is necessary for the synthesis ofAutographiviridaephage receptor capsular polysaccharide (CPS). Although increased CPS-specific phage susceptibility is a novel trade-off mediated by QS, it results in the upregulation of virulence factors, promoting biofilm development and enhanced capsular polysaccharide production inV. alginolyticus. This suggests that inhibiting QS may improve the effectiveness of antibiotic treatment, but it may also reduce the efficacy of phage therapy.
Age-dependent decline in sperm quality and function in a naturally short-lived vertebrate
Authors: Cattelan Silvia , Valenzano Dario Riccardo 
Published: December 2023

AbstractMaximizing the life-long reproductive output would lead to the prediction that short-lived and fast aging species would undergo no – if any – reproductive senescence. Turquoise killifish (Nothobranchius furzeri) are naturally short-lived teleosts, and undergo extensive somatic aging, characterized by molecular, cellular, and organ dysfunction following the onset of sexual maturation. Here, we tested whether naturally short-lived and fast aging turquoise killifish males maximize reproduction and display minimal – if any, reproductive senescence. We analysed age-related changes in sperm traits, the proportion of fertilized eggs, as well as embryo survival. Contrary to the expectation of no reproductive aging, we found that turquoise killifish males undergo extensive reproductive aging, consisting in the age-dependent decline in sperm quality, decreased proportion of fertilized eggs and lower embryo survival. Our results indicate that male turquoise killifish do not trade-off age-dependent soma decline with life-long sustained reproductive fitness. Instead, somatic and reproductive aging appear to occur simultaneously. Our findings question generalized soma vs. reproductive senescence trade-off models and highlight the importance of integrating species-specific ecological and demographic constraints to explain observed life history traits.
Temporal resolution trumps spectral resolution in UAV-based monitoring of canopy senescence dynamics
Authors: Tschurr Flavian , Roth Lukas , Storni Nicola , Zumsteg Olivia , Walter Achim , Anderegg Jonas 
Published: December 2023

AbstractSenescence is a dynamic process that is affected by many environmental, genetic, and physiological factors. Quantifying this process is important for breeding wheat varieties with high yield and of high quality. We present a method that allows up-scaling of the state of the art method - visual scoring - by using image sequences acquired from Unmanned Aerial Vehicles (UAV). This reduces measurement time and environmental changes during the measurement as well as rater bias. We compared the potential of a widely used multispectral sensor and a cheaper high-resolution RGB camera to track the dynamics of senescence. A UAV each was equipped with one of these sensors and used to measure canopy reflectance throughout the senescence process that lasted several weeks, for more than 400 winter wheat cultivars across three field seasons. Multiple spectral and RGB indices were calculated at the experimental plot level and used to model the dynamics of senescence. Model fits were further processed to extract key time points of the senescence phase. By comparing the results of the two sensors with each other and with the visual evaluation, respectively, we show that both sensors allow monitoring of senescence dynamics and measure key time points of the phase with a precision close to that of more sophisticated proximal sensing approaches. Optimal timing of measurements proved to be more important than the choice of sensor, confirming that timely and frequent measurements should be prioritized over more expensive sensors that provide a higher spectral resolution.
Conditioner application improves bedding quality and bacterial composition with potential beneficial impacts for dairy cow’s health
Authors: Duniere Lysiane , Frayssinet Bastien , Achard Caroline , Chevaux Eric , Plateau Julia 
Published: December 2023

AbstractRecycled Manure Solid is used as bedding material in cow housing but can be at risk for pathogens development. Cows spend several hours per day lying, contributing to the transfer of potential mastitis pathogens from the bedding to the udder. The effect of a bacterial conditioner (Manure Pro, MP) application was studied on RMS-bedding and milk qualities and on animal health.MP product was applied on bedding once a week for 3 months. Bedding and teat skin samples were collected from Control and MP groups at D01, D51 and D90 and analyzed through 16S rDNA amplicon sequencing. MP application modified bacterial profiles and diversity. Control bedding was significantly associated with potential mastitis pathogens while no taxa of potential health risk was significantly detected in MP beddings. Functional prediction identified enrichment of metabolic pathways of agronomic interest in MP beddings. Significant associations with potential mastitis pathogens were mainly observed in Control teat skin samples. Finally, significantly better hygiene and lower Somatic Cell Counts in milk were observed for cows from MP group while no group impact was observed on milk quality and microflora. No dissemination of MP strains was observed from bedding to teats or milk.ImportanceThe use of MP conditioner improved RMS-bedding quality and this higher sanitary condition had further impacts on dairy cows’ health with less potential mastitis pathogens significantly associated to bedding and teat skin samples of animals from MP group. The animals also presented an improved inflammation status, while milk quality was not modified. The use of MP conditioner on bedding may be of interest in controlling the risk of mastitis onset for dairy cows and further associated costs.