bluuebunny/crossref_metadata_2025_split huggingface dataset:
A joint embedding of protein sequence and structure enables robust variant effect predictions
Authors: Blaabjerg Lasse M. , Jonsson Nicolas , Boomsma Wouter , Stein Amelie , Lindorff-Larsen Kresten 
Published: December 2023

AbstractThe ability to predict how amino acid changes may affect protein function has a wide range of applications including in disease variant classification and protein engineering. Many existing methods focus on learning from patterns found in either protein sequences or protein structures. Here, we present a method for integrating information from protein sequences and structures in a single model that we term SSEmb (Sequence Structure Embedding). SSEmb combines a graph representation for the protein structure with a transformer model for processing multiple sequence alignments, and we show that by integrating both types of information we obtain a variant effect prediction model that is more robust to cases where sequence information is scarce. Furthermore, we find that SSEmb learns embeddings of the sequence and structural properties that are useful for other downstream tasks. We exemplify this by training a downstream model to predict protein-protein binding sites at high accuracy using only the SSEmb embeddings as input. We envisage that SSEmb may be useful both for zero-shot predictions of variant effects and as a representation for predicting protein properties that depend on protein sequence and structure.
VoltRon: A Spatial Omics Analysis Platform for Multi-Resolution and Multi-omics Integration using Image Registration
Authors: Manukyan Artür , Bahry Ella , Wyler Emanuel , Becher Erik , Pascual-Reguant Anna , Plumbom Izabela , Dikmen Hasan Onur , Elezkurtaj Sefer , Conrad Thomas , Altmüller Janine , Hauser Anja E. , Hocke Andreas , Radbruch Helena , Schmidt Deborah , Landthaler Markus , Akalin Altuna 
Published: December 2023

AbstractThe growing number of spatial omic technologies have created a demand for computational tools capable of managing, storing, and analyzing spatial datasets with multiple modalities and spatial resolutions. Meanwhile, computer vision is becoming an integral part of processing spatial data readouts where image registration and spatial data alignment of tissue sections are essential prior to data integration. Hence, there is a need for computational platforms that analyze data across spatial datasets with diverse resolutions as well as those that manipulate and process images of microanatomical tissue structures. To this end, we have developed VoltRon, a novel R package for spatial omics analysis with a unique data structure that accommodates data readouts with many levels of spatial resolutions (i.e., multi-resolution) including regions of interest (ROIs), spots, single cells, and even subcellular entities such as molecules. To connect and integrate these spatially diverse omic profiles, VoltRon accounts for spatial organization of tissue blocks (samples), layers (sections) and assays given a multi-resolution collection of spatial data readouts. An easy-to-use computer vision toolbox, OpenCV, is fully embedded in VoltRon that allows users to both automatically and manually register spatial coordinates across adjacent layers for data transfer without the need for external software tools. VoltRon is implemented in the R programming language and is freely available athttps://github.com/BIMSBbioinfo/VoltRon.
Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies
Authors: Henderson Rory , Anasti Kara , Manne Kartik , Stalls Victoria , Saunders Carrie , Bililign Yishak , Williams Ashliegh , Bubphamala Pimthada , Montani Maya , Kachhap Sangita , Li Jingjing , Jaing Chuancang , Newman Amanda , Cain Derek , Lu Xiaozhi , Venkatayogi Sravani , Berry Madison , Wagh Kshitij , Korber Bette , Saunders Kevin O. , Tian Ming , Alt Fred , Wiehe Kevin , Acharya Priyamvada , Alam S. Munir , Haynes Barton F. 
Published: December 2023

AbstractVaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and, in some cases, the same Ig-heavy chains. The current trial-and-error search for immunogen modifications that improve selection for specific bnAb mutations is imprecise. To precisely engineer bnAb boosting immunogens, we used molecular dynamics simulations to examine encounter states that form when antibodies collide with the HIV-1 Envelope (Env). By mapping how bnAbs use encounter states to find their bound states, we identified Env mutations that were predicted to select for specific antibody mutations in two HIV-1 bnAb B cell lineages. The Env mutations encoded antibody affinity gains and selected for desired antibody mutationsin vivo. These results demonstrate proof-of-concept that Env immunogens can be designed to directly select for specific antibody mutations at residue-level precision by vaccination, thus demonstrating the feasibility of sequential bnAb-inducing HIV-1 vaccine design.
Characterizing the viscoelastic properties of different fibroblasts in 2D and 3D collagen gels
Authors: Pérez-Domínguez Sandra , Sanz-Fraile Héctor , Vidal Laura Martínez , Alfano Massimo , Otero Jorge , Radmacher Manfred 
Published: December 2023

AbstractWe assessed cell mechanical properties in both 2D and 3D environments employing compliant type I collagen matrices. Firstly, collagen gels of varying stiffness were prepared using a photocrosslinker to increase gel stiffness. Using methacrylic anhydride and UV light, a 10-fold increase in apparent Young’s modulus with respect to the soft collagen gel was achieved (0.2 kPa to 2 kPa). In addition, cells were plated onto the different collagen gels and hard Petri dishes (as a super stiff substrate) and their mechanical properties were evaluated. An increase in apparent Young’s modulus was observed in Dupuytren fibroblasts behavior when increasing substrate stiffness, supporting its myofibroblast phenotype (3.8 kPa to 5.2 kPa from soft collagen gels to hard Petri dishes). Secondly, gel’s mechanics, in which fibroblasts were embedded, were evaluated over time to assess cells contraction properties. Gel’s apparent Young’s modulus increased over time regardless of fibroblasts type and cells presented dendritic protrusions. Rheological properties of both cells and gels were extracted using AFM sweep frequency scheme and power law structural damping model for data analysis. As a summary, we have found that fibroblasts contractile properties, related to myofibroblast differentiation and development are highly influenced on the mechanical properties of the surrounding environment, being stiffer environments those that favor the increase in fibroblast mechanical tension.
Functional implication of the homotrimeric multidomain vacuolar sorting receptor 1 (VSR1) fromArabidopsis thaliana
Authors: Park HaJeung , Youn BuHyun , Park Daniel J. , Puthanveettil Sathyanarayanan V. , Kang ChulHee 
Published: December 2023

SummaryThe vacuolar sorting receptors (VSRs) are specific to plants and are responsible for sorting and transporting particular proteins from thetrans-Golgi network to the vacuole. This process is critically important for various cellular functions, including storing nutrients during seed development. Despite many years of intense studies on VSRs, a complete relation between function and structure has not yet been revealed. For the first time, the crystal structure of the full-length luminal part of glycosylated VSR1 fromArabidopsis thaliana(AtVSR1) has been determined. The structure provides insights into the tertiary and quaternary structures of VSR1, which are composed of an N-terminal protease-associated (PA) domain, a unique central region, and one epidermal growth factor (EGF) domain followed by two disordered EGF domains. The structure of VSR1 exhibits unique characteristics, the significance of which is yet to be fully understood.
Downscaling global reference points to assess the sustainability of local fisheries
Authors: Zamborain-Mason Jessica , Connolly Sean R. , MacNeil M. Aaron , Barnes Michele L. , Bauman Andrew G. , Feary David A. , Huertas Victor , Januchowski-Hartley Fraser A. , Lau Jacqueline D. , Mihalitsis Michalis , Cinner Joshua E. 
Published: December 2023

AbstractMultispecies coral reef fisheries are typically managed by local communities who often lack research and monitoring capacity, which prevents estimation of well-defined sustainable reference points to perform locally relevant fishery assessments. Recent global advances in modelling coral reef fisheries have developed pathways to use environmental indicators to estimate multispecies sustainable reference points. These global reference points are a promising tool for assessing data-poor reef fisheries but need to be downscaled to be relevant to resource practitioners. Here, using a small-scale multispecies reef fishery from Papua New Guinea, we estimate sustainable reference points and assess the sustainability of the fishery by integrating global-scale analyses with local-scale environmental conditions, fish catch, reef area, standing biomass estimates, and fishers’ perceptions. We found that assessment results from global models applied to the local context of our study location provided results consistent with local fishers’ perceptions. Specifically, our downscaled results suggest that the fishing community is overfishing their reef fish stocks (i.e., catching more than can be sustained) and stocks are below BMMSY(i.e., below biomass levels that maximize production), making the overall reef fishery unsustainable. These results were consistent with fisher perceptions that reef fish stocks were declining in abundance and mean fish length, and that they had to spend more time finding fish. Our downscaled site-level assessment reveals severe local resource exploitation, whose dynamics are masked in national-scale assessments, emphasizing the importance of matching assessments to the scale of management. More broadly, our study shows how global reference points can be applied locally when long-term data are not available, providing baseline assessments for sustainably managing previously un-assessed multispecies reef fisheries around the globe.
In vitro antimicrobial mechanism of diacerein and potential to reverse MRSE resistance to β-lactams
Authors: Fu Chunyan , Xu Yi , Mao Liping , Zheng Chengzhi , Shen Yangyang , Ling Xinyi , Zhou Yumei , Yin Yiling , Lou Yongliang , Zheng Meiqin 
Published: December 2023

AbstractStaphylococcus epidermidisis the most common pathogens causing ocular infection. With the increase of drug resistance rate, it poses a new challenge to anti-infection treatment. In this study, we analyzed the drug resistance ofS. epidermidisisolated from the eye in the past 5 years to guide empirical antibiotics treatment. Then, the MIC and MBC of diacerein against MRSE were detected, and continuous induced resistance experiments confirmed that MRSE not easily induce resistance to diacerein. In addition, it was observed that diacerein induced MRSE cell lysis, increased membrane permeability and resulted in intracellular ROS accumulation. Diacerein does not have toxic effects to HCEC at effective bacteriostatic concentrations. The results of checkerboard assay indicated that the combination of diacerein and β-lactams had additive effect on MRSE. We also observed that diacerein may reverse MRSE resistance to β-lactam drugs by affecting the active efflux system. In conclusion, our results provide strong evidence for the high therapeutic potential of diacerein against MRSE.
An RXLR effector targets ER-Golgi interface to induce ER stress and necrotic cell death
Authors: Kim Jihyun , Kaleku Jesse , Woo Jongchan , Jin Hongshi , Kang Hui Jeong , Kang Minji , Kim Haeun , Jung Seungmee , Segonzac Cecile , Park Eunsook , Choi Doil 
Published: December 2023

AbstractTo achieve successful colonization, the pathogen secretes hundreds of effectors into host cells to manipulate the host’s immune response. Despite numerous studies, the molecular mechanisms underlying effector-induced necrotic cell death remain elusive. In this study, we identified a novel virulent RXLR effector named Pc12 fromP. capsici.Pc12 induces necrosis by triggering a distinct ER stress response through its interaction with Rab13-2. Unlike conventional hypersensitive response cell death associated with effector-triggered immunity, Pc12-induced cell death does not coincide with defense gene expression. Instead, it induces the aggregation of ER-resident proteins and confines secretory proteins within the ER. Pc12 interacts with Rab13-2, exhibiting a specific affinity for the active form of Rab13-2. Thus, the complex of Pc12 and Rab13-2 mimics the conformation of the inactive state of Rab13-2, subsequently recruiting the Rab-escort protein (REP). This process results in disruptions in vesicle formation within the ER-Golgi trafficking pathway. Furthermore, the substitution of a single amino acid of Rab13-2 structurally predicted to be crucial for the Pc12 interaction decreased the interaction with Pc12 while maintaining the interaction with REP1. These findings offer valuable insights into the ER stress-mediated cell death as well as a potential strategy for enhancing resistance against pathogens.
The ICF syndrome protein CDCA7 harbors a unique DNA-binding domain that recognizes a CpG dyad in the context of a non-B DNA
Authors: Hardikar Swanand , Ren Ren , Ying Zhengzhou , Horton John R. , Bramble Matthew D. , Liu Bin , Lu Yue , Liu Bigang , Dan Jiameng , Zhang Xing , Cheng Xiaodong , Chen Taiping 
Published: December 2023

AbstractCDCA7, encoding a protein with a C-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout the genome. At S phase, CDCA7, but not ICF mutants, is concentrated in constitutive heterochromatin foci, and the formation of such foci can be inhibited by exogenous hemi-methylated non-B DNA bound by the CRD. Binding of the non-B DNA formed in juxtacentromeric regions during DNA replication provides a mechanism by which CDCA7 controls the specificity of DNA methylation.
Data driven discovery and quantification of hyperspectral leaf reflectance phenotypes across a maize diversity panel
Authors: Tross Michael C. , Grzybowski Marcin W. , Jubery Talukder Z. , Grove Ryleigh J. , Nishimwe Aime V. , Torres-Rodriguez J Vladimir , Sun Guangchao , Ganapathysubramanian Baskar , Ge Yufeng , Schnable James C. 
Published: December 2023

AbstractHyperspectral reflectance data can be collected from large plant populations in a high-throughput manner in both controlled and field environments. The efficacy of using hyperspectral leaf reflectance as a proxy for traits that typically require significant labor and time to collect has been evaluated in a number of studies. Commonly, estimating plant traits using hyperspectral reflectance involves collecting substantial amounts of ground truth data from plant populations, which may not be feasible for many researchers. In this study, we explore the potential of data-driven approaches to analyze hyperspectral reflectance data with little to no ground truth phenotypic measurements. Evaluations were performed using data on the reflectance of 2,151 individual wavelengths of light from the leaves of maize plants harvested from 1,658 field plots of a replicated trial including representatives of 752 maize genotypes from the Wisconsin Diversity Panel. We reduced the dimensionality of this dataset using an autoencoder neural network and principal component analyses, producing 10 latent variables and principal components, respectively. A subset of these principal components and latent variables demonstrated significant repeatability, indicating that a substantial proportion of the total variance in these variables was explained by genetic factors. Moreover, correlations were observed between variables derived from the autoencoder network and principal components with molecular traits. Notably, the most relevant latent variable (LV8) showed a much stronger correlation with chlorophyll content (R2= 0.59) compared to the most correlated principal component (PC2;R2= 0.31). Furthermore, one latent variable exhibited modestly better performance than a partial least squares regression model in estimating leaf chlorophyll content (PLSR;R2= 0.58, LV8;R2= 0.59). A number of genetic markers in the maize genome were significantly correlated with variation in different latent variables in genome wide association studies. In a number of cases, significant signals in genome wide association studies were adjacent to genes with plausible links to traits expected to influence leaf hyperspectral reflectance patterns.
AVM: a manually curated database of aerosol-transmitted virus mutations, human diseases, and drugs
Authors: Mei Lan , Hou Yaopan , Zhou Jiajun , Chang Yetong , Liu Yuwei , Wang Di , Zhang Yunpeng , Ning Shangwei , Li Xia 
Published: December 2023

AbstractAerosol-transmitted viruses, with aerosol particles floating in the air to long distances, have the characteristics of strong infectivity and wide spread that is difficult to control. They cause various human diseases, posing a huge threat to human health. Some mutations can increase the transmissibility and virulence of the strain, which can reduce the protection of vaccines and weaken efficacy of antiviral drugs. Here, we established a manually curated database, AVM, to store this information. The current version of the AVM contains a total of 42,041 virus mutations, including 2613 immune escape mutations, 45 clinical information datasets, and 407 drugs, antibodies, or vaccines. In addition, we recorded 88 human diseases associated with viruses, and we found that the same virus can attack multiple target organs in the body and lead to diversified diseases. Further, the AVM database offers a straightforward user interface to expediently browse, retrieve, and download details. The AVM database is a comprehensive resource that provides timely and valuable assistance regarding the transmission, treatment, and related diseases of aerosol-transmitted viruses (http://bio-bigdata.hrbmu.edu.cn/AVMorhttp://www.bio-bigdata.center/AVM).
Proliferation in malaria parasites: how resource limitation can prevent evolution of greater virulence
Authors: Pak Damie , Kamiya Tsukushi , Greischar Megan A. 
Published: December 2023

AbstractFor parasites, robust proliferation within hosts is crucial for establishing the infection and creating opportunities for onward transmission. While faster proliferation enhances transmission rates, it is often assumed to curtail transmission duration by killing the host (virulence), a tradeoff constraining parasite evolution. Yet in many diseases, including malaria, the preponderance of infections with mild or absent symptoms suggests that host mortality is not a sufficient constraint, raising the question of what restrains evolution towards faster proliferation. In malaria infections, the maximum rate of proliferation is determined by the burst size, the number of daughter parasites produced per infected red blood cell. Larger burst sizes should expand the pool of infected red blood cells that can be used to produce the specialized transmission forms needed to infect mosquitoes. We use a within-host model parameterized for rodent malaria parasites (Plasmodium chabaudi) to project the transmission consequences of burst size, focusing on initial acute infection where re-source limitation and risk of host mortality are greatest. We find that resource limitation restricts evolution towards higher burst sizes below the level predicted by host mortality alone. Our results suggest resource limitation could represent a more general constraint than virulence-transmission tradeoffs, preventing evolution towards faster proliferation.
Sociodemographic correlates of parent and youth-reported eating disorder symptoms in the Adolescent Brain Cognitive Development Study
Authors: Makowski Carolina , Westwater Margaret L. , Rhee Kyung E. , Zou Jingjing , Bischoff-Grethe Amanda , Wierenga Christina E. 
Published: December 2023

ABSTRACTPurposeEating Disorders (EDs) often start in adolescence, though ED-related concerns in diverse youth samples remain understudied. We leveraged data from the Adolescent Brain Cognitive Development□(ABCD) Study to identify the prevalence of parent- and youth-reported ED symptoms and their sociodemographic characteristics.MethodsData were drawn from baseline (ages 9-11 years, n=11,868) and 2-year follow-up (ages 11-14 years; n=10,908) from the ABCD Study. A tetrachoric factor analysis summarized clusters of ED symptoms, which were compared between parent and youth reports and across sociodemographic variables.ResultsThree factors emerged reflecting “weight distress”, “weight control”, and “binge eating” (prevalence range: 1.5-7.3%). Symptoms loaded onto similar factors between reporters. Rates of symptom endorsement were similar between sexes, with disproportionately higher endorsement rates for youth who self-identified as sexual minority, Hispanic, Black, or Mixed race participants, and those from a disadvantaged socioeconomic background, compared to the reference ABCD sample. Youth and parent reports at 2-year showed ∼12% overlap.ConclusionsED-related concerns among historically understudied racial and sexual minority groups call for greater attention to the detection and treatment of these symptoms in these groups. Applying a transdiagnostic approach to ED symptoms can inform effective detection and intervention efforts.Public health statementOur work depicts the sociodemographic breadth of disordered eating behaviors in a large diverse sample of American youth, and underscores the importance of including multiple reporters when assessing ED symptoms in community samples of children and adolescents. Taking into consideration the diverse sociodemographic landscape of disordered eating behaviors is imperative to ensure access to care is equitable across the sexes, and racial, ethnic and socioeconomic groups.
Short-term and Mid-term Blood Pressure Variability and long-term Mortality: evidence from the Third National Health and Nutrition Examination Study
Authors: Steinsaltz David , Patten Hamish , Bester D W , Rehkopf David H. 
Published: December 2023

AbstractIn considering the impact of blood-pressure variability on health outcomes, two methodological challenges arise: The presence of multiple timescales of variability that may act independently and interactively, and the fairly large stochastic uncertainty that is inevitable in estimates of individual variability based on modest numbers of observations. Here we present an application of Bayesian hierarchical modeling to the problem of estimating the effect of blood pressure (BP) variability on all-cause and cardiovascular mortality with two timescales – short-term variation among multiple measures at one visit, and medium-term variation between the measures at two visits several months apart. We use data from the Third National Health and Nutrition Examination Survey linked with up to 27 years of mortality follow-up. We find that medium-term systolic BP variability had a very significant predictive value for CV and all-cause mortality, around one-third as large as the well-established impact of mean systolic BP. Medium-term diastolic variability had an additional, though smaller, predictive effect. Short-term variability, on the other hand, had little or no measurable predictive value. The medium-term variability effect persisted when controlling for Framingham risk score.