bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbes as manipulators of developmental life-history
Authors: Kustra Matthew C. , Carrier Tyler J. 
Published: February 2024

ABSTRACTMarine invertebrates mainly reproduce by energy-poor eggs that develop into feeding larvae or energy-rich eggs that develop into non-feeding larvae1–4. Transitions between these reproductive strategies have been studied in detail5–7, yet the evolutionary factor(s) responsible for these switches remains elusive. Here, we use theoretical models to show that microbes with the capacity to manipulate host reproduction are one possible factor. We report that microbial manipulators create a sperm-limited environment that selects for larger eggs by shifting the host’s sex ratio towards female dominance and, as a result, serve as the evolutionary driver of transitions in the developmental life-history for marine invertebrates. Loss of a microbial manipulator can then recover the ancestral developmental life-history. We also document more than a dozen genera of marine invertebrates from throughout the world’s oceans that fit the framework of a microbe-induced switch between these predominate reproductive strategies. We anticipate that microbial manipulators have a yet-to-be appreciated influence on the life-history strategies of marine invertebrates. We find it paramount to understand if transitions in developmental life-history also occur without microbial manipulators as well as if the underlying mechanisms of these manipulations are convergent with terrestrial systems.
Directing Cell Delivery to Murine Atherosclerotic Aortic Lesions via Targeting Inflamed Circulatory Interface using Nanocarriers
Authors: Huerta Carlos Theodore , Zhang Leiming , Ortiz Yulexi Y. , Li Yan , Zeynaloo Elnaz , Dikici Emre , Siahaan Teruna J. , Deo Sapna K. , Daunert Sylvia , Liu Zhao-Jun , Velazquez Omaida C. 
Published: February 2024

ABSTRACTStem cell therapy holds significant potential for many inflammatory diseases and regenerative medicine applications. However, delivery of therapeutic cells to specific disease sites after systemic administration without indiscriminate trafficking to other non-target tissues is a major limitation of current cell therapies. Here, we describe a novel nanocarrier-directed targeted cell delivery system that enables cell surface coating with dendrimer nanocarriers containing adhesion moieties to serve as a global positioning system “GPS” to guide circulating cells to targeted lesions and mediate the anchoring of cells at the inflammation site. By exploiting cell surface ligands/receptors selectively and/or molecular moieties that are highly expressed on activated endothelium in pathologic disease states, nanocarrier-coated cells containing the counterpart binding receptors/ligands can be enabled to specifically traffic to and dock at vasculature within target lesions. We demonstrate the efficacy of the I-domain fragment of LFA-1 (idLFA-1) complexed to modified nanocarriers to facilitate homing of mesenchymal stem cells (MSCs) to inflamed luminal endothelial cells on which ICAM-1 is highly expressed in a murine model of aortic atherosclerosis. Our method can overcome challenges imposed by the high velocity and dynamic circulatory flow of the aorta to successfully deliver MSCs to atherosclerotic regions and allow for docking of the potentially therapeutic and immunomodulating cells. This targeted cell-delivery platform can be tailored for selective systemic delivery of various types of therapeutic cells to different disease areas.
BiaPy: Accessible deep learning on bioimages
Authors: Franco-Barranco Daniel , Andrés-San Román Jesús A. , Hidalgo-Cenalmor Ivan , Backová Lenka , González-Marfil Aitor , Caporal Clément , Chessel Anatole , Gómez-Gálvez Pedro , Escudero Luis M. , Wei Donglai , Muñoz-Barrutia Arrate , Arganda-Carreras Ignacio 
Published: February 2024

AbstractBiaPy is an open-source library and application that streamlines the use of common deep learning approaches for bioimage analysis. Designed to simplify technical complexities, it offers an intuitive interface, zero-code notebooks, and Docker integration, catering to both users and developers. While focused on deep learning workflows for 2D and 3D image data, it enhances performance with multi-GPU capabilities, memory optimization, and scalability for large datasets. Although BiaPy does not encompass all aspects of bioimage analysis, such as visualization and manual annotation tools, it empowers researchers by providing a ready-to-use environment with customizable templates that facilitate sophisticated bioimage analysis workflows.
Enzyme Bioink for the 3D Printing of Biocatalytic Materials
Authors: Altevogt Luca A. , Sheikh Rakib H. , Molley Thomas G. , Yong Joel , Liang Kang , Spicer Patrick , Kilian Kristopher A. , Wich Peter R. 
Published: February 2024

AbstractThe field of 3D biofabrication faces major challenges on the road to printing fully functional tissues and organs. One of them is adding functionality to the newly formed tissue for replicating an active biochemical environment. Native extracellular matrices sequester numerous bioactive species, making the microenvironment biochemically active. On the other hand, most 3D-printed constructs have limited activity, serving merely as mechanical scaffolding. Here we demonstrate active scaffolding through the integration of biocatalytic enzymes within the bioink. Enzymes are an attractive class of biocompatible and substrate-specific bioactive agents that can improve tissue regeneration outcomes. However, the difficulty in the application remains in providing enzymes at the targeted site in adequate amounts over an extended time.In this work, a durable biocatalytic active enzyme bioink for 3D extrusion-based bioprinting is developed by covalently attaching the globular enzyme horseradish peroxidase (HRP) to a gelatin methacrylate (Gel-MA) biopolymer scaffold. Upon introducing methacrylate groups on the surface of the enzyme, it undergoes photo-crosslinking in a post-printing step with the methacrylate groups of Gel-MA without compromising its activity. As a result, HRP becomes a fixed part of the hydrogel network and achieves higher stability inside the gel which results in a higher concentration and catalytic activity for a longer time than solely entrapping the protein inside the hydrogel. We also demonstrate the cytocompatibility of this enzyme bioink and show its printing capabilities for precise applications in the field of tissue engineering. Our approach offers a promising solution to enhance the bioactive properties of 3D-printed constructs, representing a critical step towards achieving functional biofabricated tissues.
Multi-class Modeling Identifies Shared Genetic Risk for Late-onset Epilepsy and Alzheimer’s Disease
Authors: Fu Mingzhou , Tran Thai , Eskin Eleazar , Lajonchere Clara , Pasaniuc Bogdan , Geschwind Daniel H. , Vossel Keith , Chang Timothy S 
Published: February 2024

AbstractBackgroundPrevious studies have established a strong link between late-onset epilepsy (LOE) and Alzheimer’s disease (AD). However, their shared genetic risk beyond theAPOEgene remains unclear. Our study sought to examine the shared genetic factors of AD and LOE, interpret the biological pathways involved, and evaluate how AD onset may be mediated by LOE and shared genetic risks.MethodsWe defined phenotypes using phecodes mapped from diagnosis codes, with patients’ records aged 60-90. A two-step Least Absolute Shrinkage and Selection Operator (LASSO) workflow was used to identify shared genetic variants based on prior AD GWAS integrated with functional genomic data. We calculated an AD-LOE shared risk score and used it as a proxy in a causal mediation analysis. We used electronic health records from an academic health center (UCLA Health) for discovery analyses and validated our findings in a multi-institutional EHR database (All of Us).ResultsThe two-step LASSO method identified 34 shared genetic loci between AD and LOE, including theAPOEregion. These loci were mapped to 65 genes, which showed enrichment in molecular functions and pathways such as tau protein binding and lipoprotein metabolism. Individuals with high predicted shared risk scores have a higher risk of developing AD, LOE, or both in their later life compared to those with low-risk scores. LOE partially mediates the effect of AD-LOE shared genetic risk on AD (15% proportion mediated on average). Validation results from All of Us were consistent with findings from the UCLA sample.ConclusionsWe employed a machine learning approach to identify shared genetic risks of AD and LOE. In addition to providing substantial evidence for the significant contribution of theAPOE-TOMM40-APOC1gene cluster to shared risk, we uncovered novel genes that may contribute. Our study is one of the first to utilize All of Us genetic data to investigate AD, and provides valuable insights into the potential common and disease-specific mechanisms underlying AD and LOE, which could have profound implications for the future of disease prevention and the development of targeted treatment strategies to combat the co-occurrence of these two diseases.
Associations between genetically predicted iron status and cardiovascular disease risk: A Mendelian randomization study
Authors: Barad Alexa , Clark Andrew G. , O’Brien Kimberly O. , Pressman Eva K. 
Published: February 2024

AbstractBackgroundMendelian randomization (MR) studies suggest a causal effect of iron (Fe) status on cardiovascular disease (CVD) risk, but it is unknown if these associations are confounded by pleiotropic effects of the instrumental variables (IV) on CVD risk factors. We aimed to investigate the effect of Fe status on CVD risk controlling for CVD risk factors.MethodsFe biomarker IVs (total Fe binding capacity (TIBC,n=208,422), transferrin saturation (TSAT,n=198,516), serum Fe (SI,n=236,612), ferritin (n=257,953)) were selected from a European GWAS meta-analysis. We performed two-sample univariate (UV) MR of each Fe trait on CVD outcomes (all-cause ischemic stroke (IS), cardioembolic IS (CES), large artery IS (LAS), small vessel IS (SVS), and coronary heart disease (CHD)) from MEGASTROKE (n=440,328) and CARDIoGRAMplusC4D (n=183,305). We then implemented multivariate (MV) MR conditioning on six CVD risk factors from independent European samples to evaluate their potential confounding and/or mediating effects on the observed Fe-CVD associations.ResultsWith UVMR analyses, we found higher genetically predicted Fe status to be associated with a greater risk of CES (TSAT: OR 1.17 [95%CI 1.03, 1.33], SI: OR 1.21 [ 95%CI 1.02, 1.44]; TIBC: OR 0.81 [95%CI 0.69, 0.94]). The detrimental effects of Fe status on CES risk remained unaffected when adjusting for CVD risk factors (allP<0.05). Additionally, we found diastolic blood pressure (DBP) to mediate between 7.1-8.8% of the total effect of Fe status on CES incidence. While UVMR initially suggested a protective effect of Fe status on LAS and CHD, MVMR analyses factoring CVD risk factors revealed a complete annulment of this perceived protective effect (allP>0.05).DiscussionHigher Fe status was associated with a greater risk of CES independent of CVD risk factors, and this effect was partly mediated by DBP. These findings support a role of Fe status as a modifiable risk factor for CES.
Quantifying internal conflicts and their threats to organismal form and fitness
Authors: Schenkel Martijn A. , Patten Manus M. , Ågren J. Arvid 
Published: February 2024

AbstractEvolutionary biologists often treat organisms as both fitness-maximizing agents and as the primary level at which adaptation manifests. Yet, genes and cells may also seek to optimize their fitness by distorting the Mendelian rules of transmission or by influencing organismal traits for their own benefit. Organismal form and fitness are therefore threatened from within by selfish genes and cells. However, to what extent such internal conflicts actually harm individual organisms and threaten our concept of the organism as the sole bearer of adaptation remains unclear. We introduce a mathematical framework to capture the threat posed by internal conflicts and develop two metrics to measure their various forms of harm. We name these metrics fitness unity and trait unity, and use them to refer to the threats posed by internal conflicts to an organism’s role as the optimizing agent and the strategy wielded to achieve that optimization, respectively. We apply our framework to two examples of internal conflicts, genomic imprinting and sex ratio distortion, to illustrate how such harms from internal conflict may be quantified. We conclude by discussing the conditions under which internal conflict becomes sufficiently disruptive to organisms that it no longer makes sense to think of them as unified fitness-maximizing agents, but instead as adaptive compromises of multiple competing sub-agents.
TAF2 condensation in nuclear speckles links basal transcription factor TFIID to RNA splicing
Authors: Bhuiyan Tanja , Mendoza Sanchez Paulina K. , Arecco Niccolò , Kim Juhyeong , Nizamuddin Sheikh , Prunotto Andrea , Tekman Mehmet , Biniossek Martin L. , Koidl Stefanie , Hugel Thorsten , Arnold Sebastian J. 
Published: February 2024

SummaryTFIID is an essential basal transcription factor, crucial for RNA polymerase II (pol II) promoter recognition and transcription initiation. The TFIID complex consists of the TATA-binding protein (TBP) and 13 TBP-associated factors (TAFs) that contain intrinsically disordered regions (IDRs) with currently unknown functions. Here, we show that a conserved IDR drives TAF2 condensation in nuclear speckles, independently of other TFIID subunits. Quantitative mass spectrometry analyses reveal that the TAF2 IDR specifically interacts with the nuclear speckle and spliceosome-associated protein SRRM2. Consequently, TAF2 recruits SRRM2 to TFIID to form non-canonical TFIID-SRRM2 complexes. Reduced SRRM2 recruitment elicits alternative splicing events in RNAs coding for proteins involved in transcription and transmembrane transport. Further, genome-wide binding analyses suggest TAF2 shuttling between nuclear speckles and pol II promoters. This study identifies an IDR of the basal transcription machinery as a molecular guide for protein partitioning into nuclear compartments, controlling protein complex composition and pre-mRNA splicing.
Examining the relationship between psychosocial adversity and inhibitory control: an fMRI study of children growing up in extreme poverty
Authors: Surani Zoya , Turesky Ted K , Sullivan Eileen , Shama Talat , Haque Rashidul , Islam Nazrul , Kakon Shahria Hafiz , Yu Xi , Petri William A , Nelson Charles , Gaab Nadine 
Published: February 2024

ABSTRACTExposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. As these outcomes are related to alterations in developmental processes, growing evidence suggests that deficits in executive functions–inhibitory control in particular–may, in part, explain this relationship. However, literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how low resource settings might exacerbate the link between inhibitory control and health outcomes. In this context, we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children’s mothers completed behavioral questionnaires to assess the child’s PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyri, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.
The role of prospective contingency in the control of behavior and dopamine signals during associative learning
Authors: Qian Lechen , Burrell Mark , Hennig Jay A. , Matias Sara , Murthy Venkatesh. N. , Gershman Samuel J. , Uchida Naoshige 
Published: February 2024

AbstractAssociative learning depends on contingency, the degree to which a stimulus predicts an outcome. Despite its importance, the neural mechanisms linking contingency to behavior remain elusive. Here we examined the dopamine activity in the ventral striatum – a signal implicated in associative learning – in a Pavlovian contingency degradation task in mice. We show that both anticipatory licking and dopamine responses to a conditioned stimulus decreased when additional rewards were delivered uncued, but remained unchanged if additional rewards were cued. These results conflict with contingency-based accounts using a traditional definition of contingency or a novel causal learning model (ANCCR), but can be explained by temporal difference (TD) learning models equipped with an appropriate inter-trial-interval (ITI) state representation. Recurrent neural networks trained within a TD framework develop state representations like our best ‘handcrafted’ model. Our findings suggest that the TD error can be a measure that describes both contingency and dopaminergic activity.
Sparse CBX2 nucleates many Polycomb proteins to promote facultative heterochromatinization of Polycomb target genes
Authors: Ingersoll Steven , Trouth Abby , Luo Xinlong , Espinoza Axel , Wen Joey , Tucker Joseph , Astatike Kalkidan , Phiel Christopher J. , Kutateladze Tatiana G. , Wu Tao P. , Ramachandran Srinivas , Ren Xiaojun 
Published: February 2024

SUMMARYFacultative heterochromatinization of genomic regulators by Polycomb repressive complex (PRC) 1 and 2 is essential in development and differentiation; however, the underlying molecular mechanisms remain obscure. Using genetic engineering, molecular approaches, and live-cell single-molecule imaging, we quantify the number of proteins within condensates formed through liquid-liquid phase separation (LLPS) and find that in mouse embryonic stem cells (mESCs), approximately 3 CBX2 proteins nucleate many PRC1 and PRC2 subunits to form one non-stoichiometric condensate. We demonstrate that sparse CBX2 prevents Polycomb proteins from migrating to constitutive heterochromatin, demarcates the spatial boundaries of facultative heterochromatin, controls the deposition of H3K27me3, regulates transcription, and impacts cellular differentiation. Furthermore, we show that LLPS of CBX2 is required for the demarcation and deposition of H3K27me3 and is essential for cellular differentiation. Our findings uncover new functional roles of LLPS in the formation of facultative heterochromatin and unravel a new mechanism by which low-abundant proteins nucleate many other proteins to form compartments that enable them to execute their functions.
A disrupted compartment boundary underlies abnormal cardiac patterning and congenital heart defects
Authors: Kathiriya Irfan S. , Dominguez Martin H. , Rao Kavitha S. , Muncie-Vasic Jonathon M. , Devine W. Patrick , Hu Kevin M. , Hota Swetansu K. , Garay Bayardo I. , Quintero Diego , Goyal Piyush , Matthews Megan N. , Thomas Reuben , Sukonnik Tatyana , Perez Dario Miguel- , Winchester Sarah , Brower Emily F. , Forjaz André , Wu Pei-Hsun , Wirtz Denis , Kiemen Ashley L. , Bruneau Benoit G. 
Published: February 2024

AbstractFailure of septation of the interventricular septum (IVS) is the most common congenital heart defect (CHD), but mechanisms for patterning the IVS are largely unknown. We show that aTbx5+/Mef2cAHF+progenitor lineage forms a compartment boundary bisecting the IVS. This coordinated population originates at a first- and second heart field interface, subsequently forming a morphogenetic nexus. Ablation ofTbx5+/Mef2cAHF+progenitors cause IVS disorganization, right ventricular hypoplasia and mixing of IVS lineages. Reduced dosage of the CHD transcription factor TBX5 disrupts boundary position and integrity, resulting in ventricular septation defects (VSDs) and patterning defects, includingSlit2andNtn1misexpression. Reducing NTN1 dosage partly rescues cardiac defects inTbx5mutant embryos. Loss ofSlit2orNtn1causes VSDs and perturbed septal lineage distributions. Thus, we identify essential cues that direct progenitors to pattern a compartment boundary for proper cardiac septation, revealing new mechanisms for cardiac birth defects.
Age Estimation from Blood Test Results Using a Random Forest Model
Authors: Kodera Satomi , Yokoi Osamu , Kaneko Masaki , Sato Yuka , Ito Susumu , Hata Katsuhiko 
Published: February 2024

AbstractBackground and ObjectivesFrom the perspective of preventive medicine, in situations where screening tests are widely used, this study aims to clarify the role of screening data on ageing and health problems by estimating age from screening data with verifying the number of data items required.Materials and MethodsA Python random forest model was generated using Chat GPT and tested.ResultsWhen using all 71 items, including gender, for the test results, a high accuracy of R2= 0.7010 was obtained when there were 9243 training data sets (80% of the total number of data sets). The R2 decreased slightly to 0.6937 when the number of data items was reduced to 15 by discarding lesser importance items. When the number of data sets were less than 800 or when the number of data items were less than 7, the R2value fell below 0.6. Interestingly, a higher age was tended to be estimated for post-menopausal women compared to pre-menopausal women.ConclusionsThe age estimated from blood data by the random forest model (blood age, so to speak) is so precise that it can be useful for assessing physical ageing state. However, the specific relationship between blood age and health status is still unclear, waiting for future research in order to deepen our understanding of this area.