bluuebunny/crossref_metadata_2025_split huggingface dataset:
Connectome-based predictive modeling of early and chronic psychosis symptoms
Authors: Foster Maya L. , Ye Jean , Powers Albert , Dvornek Nicha , Scheinost Dustin 
Published: May 2024

AbstractThe symptoms of psychosis-spectrum disorders, which include positive symptoms (e.g., hallucinations and delusions) and negative symptoms (e.g., memory impairment and disorganized thinking), can cause significant distress and disability. Despite shared symptomatology and converging brain correlates, early (EP) and chronic (CP) psychosis differ in their symptom-related treatment response. At present, the mechanism underlying these differences is unknown, in large part because EP and CP have predominantly been studied and characterized independently or in comparison to control populations. To answer this question, we use connectome-based predictive modeling (CPM) and resting-state functional magnetic resonance imaging to identify biologically-based early (EP, n=107) and chronic (CP, n=123) psychosis symptom networks. We predicted both samples’ total, positive, and negative symptoms from the PANSS. Virtual lesioning analyses highlight the frontoparietal network as a critical component of EP and CP symptom networks, but the specific functional connections used for prediction differ. Finally, group differences compared to healthy controls (n=150) were observed for CP but not EP. These differences broadly overlapped with the symptom model for both EP and CP. Our results encourage using longitudinal studies to track connectivity changes in putative symptom networks during the progression of psychosis, as they may be explicative of EP-CP treatment differences.
Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes
Authors: Moll Matthew , Hecker Julian , Platig John , Zhang Jingzhou , Ghosh Auyon J. , Pratte Katherine A. , Wang Rui-Sheng , Hill Davin , Konigsberg Iain R. , Chiles Joe W. , Hersh Craig P. , Castaldi Peter J. , Glass Kimberly , Dy Jennifer G. , Sin Don D. , Tal-Singer Ruth , Mouded Majd , Rennard Stephen I. , Anderson Gary P. , Kinney Gregory L. , Bowler Russell P. , Curtis Jeffrey L. , McDonald Merry-Lynn , Silverman Edwin K. , Hobbs Brian D. , Cho Michael H. 
Published: May 2024

ABSTRACTRationaleGenetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear.ObjectivesDefine high-risk COPD subtypes using both genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.MethodsWe defined high-risk groups based on PRS and TRS quantiles by maximizing differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing analyses between high-risk groups.Measurements and Main ResultsWe examined two high-risk omics-defined groups in non-overlapping test sets (n=1,133 NHW COPDGene, n=299 African American (AA) COPDGene, n=468 ECLIPSE). We defined “High activity” (low PRS/high TRS) and “severe risk” (high PRS/high TRS) subgroups. Participants in both subgroups had lower body-mass index (BMI), lower lung function, and alterations in metabolic, growth, and immune signaling processes compared to a low-risk (low PRS, low TRS) reference subgroup. “High activity” but not “severe risk” participants had greater prospective FEV1decline (COPDGene: -51 mL/year; ECLIPSE: - 40 mL/year) and their proteomic profiles were enriched in gene sets perturbed by treatment with 5-lipoxygenase inhibitors and angiotensin-converting enzyme (ACE) inhibitors.ConclusionsConcomitant use of polygenic and transcriptional risk scores identified clinical and molecular heterogeneity amongst high-risk individuals. Proteomic and drug repurposing analysis identified subtype-specific enrichment for therapies and suggest prior drug repurposing failures may be explained by patient selection.
Competitor Displacement by an Herbivore that Manipulates Plant Defences
Authors: Chafi Rachid , Ataide Livia M. S. , Scala Alessandra , Villacis-Perez Ernesto , Alba Juan M. , Schimmel Bernardus C. J. , Kant Merijn R. 
Published: May 2024

AbstractTetranychus evansiis an herbivorous mite specialised on solanaceous hosts, although it has also been observed to colonise non-solanaceous species. It has the ability to suppress the defences of tomato (Solanum lycopersicum), and it can displace competitors from this host using a diverse array of traits.T. evansiis an invasive species in Africa and Europe, where it often displaces native species. While recent evidence suggests thatT. evansican also suppress defences of non-solanaceous hosts, there is a lack of understanding of the molecular changes induced upon mite infestation on hosts other than tomato, as well as how these changes may impact populations of competing herbivores. Here, we investigate the transcriptomic and metabolomic responses of bean (Phaseolus vulgaris) toT. evansiinfestation and toT. urticaeinfestation, a cosmopolitan congeneric that often competes withT. evansifor hosts in areas of co-occurrence. We ask whether the presence ofT. evansifacilitates bean colonization forT. urticae,and whether the spatial distribution of mite feeding sites depends on the presence of competitors on bean leaves. We examine whether this facilitation is attributed to jasmonic acid (JA) or salicylic acid (SA) defences by treating plants with exogenous SA and JA and comparing the transcriptomes and metabolomes of bean exposed to either phytohormones or to mite feeding. Finally, we measure phytohormone concentrations and the expression of JA- and SA-responsive genes in plants infested with either mite species or co-infested with both, at different spatial scales. We found that, as previously observed on tomato,T. urticaebenefits from the suppression of bean defences when sharing a leaf withT. evansi.Phytohormone treatments revealed that the reproductive performance of both species decreases with artificially induced JA defences, irrespective of the presence of SA. We found that the molecular suppression and induction of defences is mostly, but not exclusively restricted to the leaf area from where the mites feed. In full leaves co-infested with both mites, levels of marker gene induction were comparable to the inducer miteT. urticae, although not as prominent, while in smaller feeding arenas where both species fed closely to each other, the expression of a JA-responsive proteinase inhibitor was suppressed. When residing alone on a leaf, both mites had distinct preferred feeding sites with only partial overlap, but when sharing a leaf,T. evansiretained its preferred feeding site andT. urticaemoved away from its own. We argue that the suppression of defences byT. evansiis mostly, although not exclusively, locally restricted, and thus the spatial distribution of individuals on the leaf is a strong determinant of competitor facilitation. This suggests that traits that displace competitors from plant tissues with suppressed defences would be under selection to co-evolve together with defence suppression.
The ontogeny of immune tolerance: a model of early-life secretory IgA - gut microbiome interactions
Authors: Tepekule Burcu , Lim Ai Ing , Metcalf C. Jessica E. 
Published: May 2024

AbstractTo achieve immune and microbial homeostasis during adulthood, the developing immune system must learn to identify which microbes to tolerate and which to defend against. How such ‘immune education’ unfolds remains a major knowledge gap. We address this gap by synthesizing existing literature to develop a mechanistic mathematical model representing the interplay between gut ecology and adaptive immunity in early life. Our results indicate that the inflammatory tone of the microenvironment is the mediator of information flow from pre- to post- weaning periods. We evaluate the power of postnatal fecal samples for predicting immunological trajectories, and explore breastfeeding scenarios when maternal immunological conditions affect breastmilk composition. Our work establishes a quantitative basis for ’immune education’, yielding insights into questions of applied relevance.
Control of Physiologic Glucose Homeostasis via the Hypothalamic Modulation of Gluconeogenic Substrate Availability
Authors: Hashsham Abdullah , Kodur Nandan , Su Jiaao , Tomlinson Abigail J. , Yacawych Warren T. , Flak Jon N. , Lewis Kenneth T. , Oles Lily R. , Mori Hiroyuki , Bozadjieva-Kramer Nadejda , Turcu Adina F. , MacDougald Ormond A. , Myers Martin G. , Affinati Alison H. 
Published: May 2024

AbstractThe brain augments glucose production during fasting, but the mechanisms are poorly understood. Here, we show thatCckbr-expressing neurons in the ventromedial hypothalamic nucleus (VMNCckbrcells) prevent low blood glucose during fasting through sympathetic nervous system (SNS)-mediated augmentation of adipose tissue lipolysis and substrate release. Activating VMNCckbrneurons mobilized gluconeogenic substrates without altering glycogenolysis or gluconeogenic enzyme expression. Silencing these cells (CckbrTetToxanimals) reduced fasting blood glucose, impaired lipolysis, and decreased circulating glycerol (but not other gluconeogenic substrates) despite normal insulin, counterregulatory hormones, liver glycogen, and liver gluconeogenic gene expression. Furthermore, β3-adrenergic adipose tissue stimulation in CckbrTetToxanimals restored lipolysis and blood glucose. Hence, VMNCckbrneurons impact blood glucose not by controlling islet or liver physiology, but rather by mobilizing gluconeogenic substrates. These findings establish a central role for hypothalamic and SNS signaling during normal glucose homeostasis and highlight the importance of gluconeogenic substrate mobilization during physiologic fasting.
Live-cell imaging and CLEM reveal the existence of ACTN4-dependent ruffle-edge lamellipodia acting as a novel mode of cell migration
Authors: Morishita Haruka , Kawai Katsuhisa , Egami Youhei , Honda Kazufumi , Araki Nobukazu 
Published: May 2024

Summaryα-Actinin-4 (ACTN4) expression levels are correlated with the invasive and metastatic potential of cancer cells; however, the underlying mechanism remains unclear. Here, we identified ACTN4-localized ruffle-edge lamellipodia using live-cell imaging and correlative light and electron microscopy (CLEM). BSC-1 cells expressing EGFP-ACTN4 showed that ACTN4 was most abundant in the leading edges of lamellipodia, although it was also present in stress fibers and focal adhesions. ACTN4 localization in lamellipodia was markedly diminished by phosphoinositide 3-kinase inhibition, whereas its localization in stress fibers and focal adhesions remained. Furthermore, overexpression of ACTN4, but not ACTN1, promoted lamellipodial formation. Live-cell analysis demonstrated that ACTN4-enriched lamellipodia are highly dynamic and associated with cell migration. CLEM revealed that ACTN4-enriched lamellipodia exhibit a characteristic morphology of multilayered ruffle-edges that differs from canonical flat lamellipodia. Similar ruffle-edge lamellipodia were observed in A549 and MBA-MD-231 invasive cancer cells. ACTN4 knockdown suppressed the formation of ruffle-edge lamellipodia and cell migration during wound healing in A549 monolayer cultures. Additionally, membrane-type 1 matrix metalloproteinase was observed in the membrane ruffles, suggesting that ruffle-edge lamellipodia have the ability to degrade the extracellular matrix and may contribute to active cell migration/invasion in certain cancer cell types.
IP3R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage
Authors: Zhang Chang , Sun Xiaoqing , Wu Deyi , Wang Guoxia , Lan Hainan , Zheng Xin , Li Suo 
Published: May 2024

AbstractCalcium ions (Ca2+) regulate cell proliferation and differentiation and participate in various physiological activities of cells. The calcium transfer protein inositol 1,4,5-triphosphate receptor (IP3R), located between the endoplasmic reticulum (ER) and mitochondria, plays an important role in regulating Ca2+levels. However, the mechanism by which IP3R1 affects porcine meiotic progression and embryonic development remains unclear. We established a model in porcine oocytes using siRNA-mediated knockdown of IP3R1 to investigate the effects of IP3R1 on porcine oocyte meiotic progression and embryonic development. The results indicated that a decrease in IP3R1 expression significantly enhanced the interaction between the ER and mitochondria. Additionally, the interaction between the ER and the mitochondrial Ca2+([Ca2+]m) transport network protein IP3R1-GRP75-VDAC1 was disrupted. PLA decreased IP3R1, weakened the pairwise interaction between IP3R1-GRP75 and VDAC1 and significantly enhanced the interaction between GRP75 and VDAC1, resulting in the accumulation of large amounts of [Ca2+]m. These changes led to mitochondrial oxidative stress and reduced ATP production, which hindered the maturation and late development of porcine oocytes and caused apoptosis.
Personalized stimulation therapies for disorders of consciousness: a computational approach to inducing healthy-like brain activity based on neural field theory
Authors: Polyakov Daniel , Robinson P.A. , Müller Eli J. , van der Lande Glenn , Nunez Pablo , Annen Jitka , Gosseries Olivia , Shriki Oren 
Published: May 2024

AbstractDisorders of consciousness (DoC) pose significant challenges in neurology. Conventional neuromodulation therapies for DoC have exhibited limited success, with varying effectiveness among patients. In this study, we introduce a computational approach for constructing personalized stimulus signals capable of inducing healthy-like neural activity patterns in DoC patients.Leveraging a simplified brain model based on neural field theory, we fit this model to the power spectrum of a patient with DoC and derive a personalized stimulus time series to induce a healthy-like power spectrum. By applying this stimulus to brain regions typically targeted by stimulation therapies such as deep brain stimulation and repetitive transcranial magnetic stimulation, we demonstratein silicothe ability of our method to elicit EEG power spectra resembling those of healthy individuals.We speculate that in the course of a long-term treatment, when the brain produces healthy-like activity, it may trigger intrinsic plasticity mechanisms, potentially leading to sustained improvements in the patient’s condition. While further clinical adjustments and validation are needed, this novel approach offers promise in tailoring brain stimulation therapies for DoC patients. Moreover, it presents potential extensions to other conditions that could also benefit from brain stimulation therapies.Author summaryIn this research, we tackled a challenging issue in the field of neurology - disorders of consciousness (DoC). These conditions, which include states like coma and the minimally consciousness state, have been difficult to treat effectively. While traditional brain stimulation treatments have been tried, they do not always work well, and their effects can vary greatly from one person to another. Thus, we set out to find a new way to help these patients. Our approach involves using computer models of the brain to design personalized treatments. We designed a method to generate stimulation signals tailored to individual DoC patients. These signals aim to trigger healthier brain activity patterns, similar to those found in individuals without consciousness disorders. What is exciting is that if the brain begins to produce these healthy-like patterns, it could potentially lead to lasting improvements in the patient’s consciousness level. We show that this approach works in different simulations, and can be applied in multiple neuromodulation techniques like deep brain stimulation and transcranial magnetic stimulation. This research opens up new possibilities for more effective treatments for people dealing with these challenging disorders. Plus, it might work for other conditions treated with similar brain stimulation therapies.
Personality and MB-COMT gene: molecular-genetic and epigenetic associations with NEO-PI-R personality domains and facets in monozygotic twins
Authors: Mitrović Dušanka , Smederevac Snežana , Delgado-Cruzata Lissette , Sadiković Selka , Pajić Dejan , Prinz Mechthild , Budimlija Zoran , Oljača Milan , Kušić-Tišma Jelena , Vučinić Nataša , Milutinović Aleksandra 
Published: May 2024

AbstractThis study investigates the relationship betweenMB-COMTDNA methylation (DNAm) and the personality traits outlined in the NEO-PI-R model through an epigenetic study of monozygotic twins. DNAm, a critical epigenetic mechanism, regulates gene expression and has been linked to various biological processes and disorders. By leveraging the genetic similarities of monozygotic twins, this research explores how epigenetic variations influenced by environmental factors correlate with personality differences. The study utilized the Five-Factor Model (FFM) to categorize personality traits into five domains: Neuroticism, Extraversion, Conscientiousness, Agreeableness, and Openness to Experience. Each domain comprises six facets, providing a granular view of personality. The research centered on the catechol-O-methyltransferase (COMT) gene, focusing on its role in dopamine metabolism, which is hypothesized to influence personality traits through the dopaminergic system. DNAm status in the promoter region of theMB-COMTgene, was examined to determine its association with personality facets. Preliminary findings suggest a complex interaction betweenMB-COMTDNAm patterns and personality traits. Specific methylation patterns at different CpG sites were linked to varying expressions of traits such as impulsivity and aggression, highlighting the nuanced impact of epigenetics on personality. This study underscores the potential of integrating genetic, epigenetic, and environmental data to enhance our understanding of personality formation. The results contribute to a broader understanding of how genetic predispositions shaped by environmental factors manifest in complex trait differences, paving the way for future research in genetic psychiatry and personalized medicine.
The long-term effects of chemotherapy on normal blood cells
Authors: Mitchell Emily , Pham My H. , Clay Anna , Sanghvi Rashesh , Pietsch Sandra , Hsu Joanne I. , Jung Hyunchul , Vedi Aditi , Moody Sarah , Wang Jingwei , Leonganmornlert Daniel , Chapman Michael Spencer , Williams Nicholas , Dunstone Ellie , Santarsieri Anna , Cagan Alex , Machado Heather E. , Baxter Joanna , Follows George , Hodson Daniel J , McDermott Ultan , Doherty Gary J. , Martincorena Inigo , Humphreys Laura , Mahbubani Krishnaa , Parsy Kourosh Saeb , Takahashi Koichi , Goodell Margaret A. , Kent David , Laurenti Elisa , Campbell Peter J. , Rahbari Raheleh , Nangalia Jyoti , Stratton Michael R. 
Published: May 2024

AbstractIn developed countries, ∼10% of individuals are exposed to systemic chemotherapy for cancer and other diseases. Many chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage to normal tissues. To investigate the impact of chemotherapy on mutation burdens and cell population structure of a normal tissue we sequenced blood cell genomes from 23 individuals, aged 3–80 years, treated with a range of chemotherapy regimens. Substantial additional mutation loads with characteristic mutational signatures were imposed by some chemotherapeutic agents, but there were differences in burden between different classes of agent, different agents of the same class and different blood cell types. Chemotherapy also induced premature changes in the cell population structure of normal blood, similar to those of normal ageing. The results constitute an initial survey of the long-term biological consequences of cytotoxic agents to which a substantial fraction of the population is exposed during the course of their disease management, raising mechanistic questions and highlighting opportunities for mitigation of adverse effects.
Spatial omics of acute myocardial infarction reveals a novel mode of immune cell infiltration
Authors: Wünnemann Florian , Sicklinger Florian , Bestak Kresimir , Nimo Jose , Thiemann Tobias , Amrute Junedh , Nordbeck Mathias , Hartmann Niklas , Ibarra-Arellano Miguel A. , Tanevski Jovan , Heine Clara , Frey Norbert , Lavine Kory J. , Coscia Fabian , Saez-Rodriguez Julio , Leuschner Florian , Schapiro Denis 
Published: May 2024

AbstractMyocardial infarction (MI) continues to be a leading cause of death worldwide. Even though it is well-established that the complex interplay between different cell types determines the overall healing response after MI, the precise changes in the tissue architecture are still poorly understood. Here we generated an integrative cellular map of the acute phase after murine MI using a combination of imaging-based transcriptomics (Molecular Cartography) and antibody-based highly multiplexed imaging (Sequential Immunofluorescence), which enabled us to evaluate cell-type compositions and changes at subcellular resolution over time. One striking finding of these analyses was the identification of a novel mode of leukocyte accumulation to the infarcted heart via the endocardium - the inner layer of the heart. To investigate the underlying mechanisms driving this previously unknown infiltration route, we performed unbiased spatial proteomic analysis using Deep Visual Proteomics (DVP). When comparing endocardial cells of homeostatic hearts and infarcted hearts, DVP identified von Willebrand Factor (vWF) as an upregulated mediator of inflammation 24 hours post-MI. To further explore the immune mediating capabilities of vWF and its effect on tissue repair, we performed functional blocking of vWF during acute murine MI. This resulted in a reduced amount of infiltration by CCR2+monocytes and worse cardiac function post-MI. Our study provides the first spatial map of acute murine MI with subcellular resolution and subsequently discovers a novel route of immune infiltration. Furthermore, we identified vWF as a critical immune mediating agent for endocardial immune cell infiltration.
Predicted Future Changes in the Mean Seasonal Carbon Cycle Due to Climate Change
Authors: Morichetti Mauro , Vangi Elia , Collalti Alessio 
Published: May 2024

AbstractThrough photosynthesis, forests absorb annually large amounts of atmospheric CO2. However, they also release CO2back through respiration. These two, opposite in sign, large fluxes determine, much of the carbon that is stored or released back to the atmosphere. The mean seasonal cycle (MSC) is an interesting metric that associates phenology and carbon (C) partitioning-allocation analysis within forest stands. Here we applied the 3D-CMCC-FEM model and analyzed its capability to represent the main C-fluxes, by validating the model against observed data, questioning if the sink/source mean seasonality is influenced under two scenarios of climate change, in five contrasting European forest sites. We found the model has, under current climate conditions, robust predictive abilities in estimating NEE. Model results also predict a consistent reduction of the forest’s capabilities to act as a C-sink under climate change and stand-ageing at all sites. Such a reduction is predicted despite the number of annual days of C-sink in evergreen forests increasing over the years, indicating a consistent downward trend. Similarly, deciduous forests, despite maintaining a relatively stable number of C-sink days throughout the year and over the century, show a reduction in their overall annual C-sink capacity. Overall, both types of forests at all sites show a consistent reduction in their future mitigating potential.