bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expansion of a frontostriatal salience network in individuals with depression
Authors: Lynch Charles J. , Elbau Immanuel , Ng Tommy , Ayaz Aliza , Zhu Shasha , Manfredi Nicola , Johnson Megan , Wolk Danielle , Power Jonathan D. , Gordon Evan M. , Kay Kendrick , Aloysi Amy , Moia Stefano , Caballero-Gaudes Cesar , Victoria Lindsay W. , Solomonov Nili , Goldwaser Eric , Zebley Benjamin , Grosenick Logan , Downar Jonathan , Vila-Rodriguez Fidel , Daskalakis Zafiris J. , Blumberger Daniel M. , Williams Nolan , Gunning Faith M. , Liston Conor 
Published: August 2023

SUMMARYHundreds of neuroimaging studies spanning two decades have revealed differences in brain structure and functional connectivity in depression, but with modest effect sizes, complicating efforts to derive mechanistic pathophysiologic insights or develop biomarkers.1Furthermore, although depression is a fundamentally episodic condition, few neuroimaging studies have taken a longitudinal approach, which is critical for understanding cause and effect and delineating mechanisms that drive mood state transitions over time. The emerging field of precision functional mapping using densely-sampled longitudinal neuroimaging data has revealed unexpected, functionally meaningful individual differences in brain network topology in healthy individuals,2–5but these approaches have never been applied to individuals with depression. Here, using precision functional mapping techniques and 11 datasets comprising n=187 repeatedly sampled individuals and >21,000 minutes of fMRI data, we show that the frontostriatal salience network is expanded two-fold in most individuals with depression. This effect was replicable in multiple samples, including large-scale, group-average data (N=1,231 subjects), and caused primarily by network border shifts affecting specific functional systems, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was unexpectedly stable over time, unaffected by changes in mood state, and detectable in children before the subsequent onset of depressive symptoms in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in specific frontostriatal circuits that tracked fluctuations in specific symptom domains and predicted future anhedonia symptoms before they emerged. Together, these findings identify a stable trait-like brain network topology that may confer risk for depression and mood-state dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.
YiNet: An Integrated Traditional Chinese and Western Medicine Platform for Viral Infectious Diseases
Authors: Dong Fei , Guo Jincheng , Liu Liu , Han Aiqing , Zhang Jian , He Zihao , Qu Xinchi , Lei Shuangshuang , Wang Zhaoxin , Zhou Liwei , Wang Yifan , He Haoyang , Bu Dechao , Zhao Yi , Gu Xiaohong 
Published: August 2023

AbstractViral infectious diseases (VIDs) impose a heavy burden on global public health. Traditional Chinese medicine (TCM) has previously and is currently contributing to the prevention and treatment of infectious diseases. Omics and information technology enable the precise identification of virus characteristics, virus‒host interactions and TCM mechanisms. In this study, we constructed the YiNet platform to better integrate the novel techniques and historical experience of TCM in infectious diseases. YiNet comprises three modules: knowledge base, database and toolkit. The YiNet knowledge base involves 43 VIDs, thereby systematically integrating the knowledge regarding viruses, host symptoms and TCM and Western medicine (commonly used chemical drugs, 6,899 herbs and 2,481 formulas). The YiNet database module includes multiple databases, comprising 57,340 genome sequences of 45,791 viral strains and 5,726 multi-omics datasets such as RNA-seq, ChIP-seq and ATAC-seq from different tissues and cell models. It also integrates 1,105 real-world TCM clinical cases. We adopted visual analysis tool to investigate pathogen–host–herb relationships. To explore pharmacological mechanisms for the core herbs, we added formula data mining and network pharmacology analysis pipelines and visualisation tools. YiNet can facilitate the mechanistic study of TCM and drug development for VIDs. The YiNet platform is publicly available athttp://yinet.gene.ac/.
Napping and circadian sleep-wake regulation during healthy aging
Authors: Deantoni Michele , Reyt Mathilde , Baillet Marion , Dourte Marine , De Haan Stella , Lesoinne Alexia , Vandewalle Gilles , Maquet Pierre , Berthomier Christian , Muto Vincenzo , Hammad Gregory , Schmidt Christina 
Published: August 2023

ABSTRACTStudy objectivesDaytime napping is frequently reported among the older population and has attracted increasing attention due to its association with multiple health conditions. Here, we tested whether napping in the aged is associated with altered circadian regulation of sleep, sleepiness and vigilance performance.MethodsSixty healthy older individuals (mean age: 69y., 39 women) were recruited with respect to their napping habits (30 nappers, 30 non-nappers). All participants underwent an in-lab 40-h multiple nap protocol (10 cycles of 80 mins of sleep opportunity alternating with 160 mins of wakefulness), preceded and followed by a baseline and recovery sleep period. Saliva samples for melatonin assessment, sleepiness and vigilance performance were collected during wakefulness and electrophysiological data were recorded to derive sleep parameters during scheduled sleep opportunities.ResultsThe circadian amplitude of melatonin secretion was reduced in nappers, compared to non-nappers. Furthermore, nappers were characterized by higher sleep efficiencies and REM sleep proportion during day-compared to night-time naps. The nap group also presented altered modulation in sleepiness and vigilance performance at specific circadian phases.DiscussionOur data indicate that napping is associated with an altered circadian sleep-wake propensity rhythm and thereby contribute to the understanding of the biological correlates underlying napping and/or sleep-wake cycle fragmentation during healthy aging. Altered circadian sleep-wake promotion can lead to a less distinct allocation of sleep into night-time and/or a reduced wakefulness drive during the day, thereby potentially triggering the need to sleep at adverse circadian phase.SIGNIFICANCE STATEMENTWhile napping has raised increasing interest as a health risk factor in epidemiological studies, its underlying regulation processes in the aged remain largely elusive. Here we assessed whether napping in the older population is associated with physiological and behavioral changes in circadian sleep-wake characteristics. Our data indicate that, concomitant to a reduced circadian amplitude in melatonin secretion, healthy older nappers are characterized by reduced day-night differences in sleep efficiency and more particularly in REM sleep, compared to their non-napping counterparts. These results suggest altered circadian response as a cause or consequence of chronic napping in the aged and thereby contribute to the understanding of nap regulation during healthy aging.
Modulation of Recovery from Neonatal Hyperoxic Lung Injury by Sex as a Biological Variable
Authors: Cantu Abiud , Gutierrez Manuel Cantu , Dong Xiaoyu , Leek Connor , Anguera Montserrat , Lingappan Krithika 
Published: August 2023

ABSTRACTRecovery from lung injury during the neonatal period requires the orchestration of many biological pathways. The modulation of such pathways can drive the developing lung towards proper repair or persistent maldevelopment that can lead to a disease phenotype. Sex as a biological variable can regulate these pathways differently in the male and female lung exposed to neonatal hyperoxia. In this study, we assessed the contribution of cellular diversity in the male and female neonatal lung following injury. Our objective was to investigate sex and cell-type specific transcriptional changes that drive repair or persistent injury in the neonatal lung and delineate the alterations in the immune-endothelial cell communication networks using single cell RNA sequencing (sc-RNAseq) in a murine model of hyperoxic injury. We generated transcriptional profiles of >55,000 cells isolated from the lungs of postnatal day 1 (PND 1) and postnatal day 21 (PND 21) neonatal male and female C57BL/6 mice exposed to 95% FiO2between PND 1-5 (saccular stage of lung development). We show the presence of sex-based differences in the transcriptional states of lung endothelial and immune cells at PND 1 and PND 21. Furthermore, we demonstrate that biological sex significantly influences the response to injury, with a greater number of differentially expressed genes showing sex-specific patterns than those shared between male and female lungs. Pseudotime trajectory analysis highlighted genes needed for lung development that were altered by hyperoxia. Finally, we show intercellular communication between endothelial and immune cells at saccular and alveolar stages of lung development with sex-based biases in the crosstalk and identify novel ligand-receptor pairs. Our findings provide valuable insights into the cell diversity, transcriptional state, developmental trajectory, and cell-cell communication underlying neonatal lung injury, with implications for understanding lung development and possible therapeutic interventions while highlighting the crucial role of sex as a biological variable.
Dabrafenib alters MDSC differentiation and function by activation of GCN2
Authors: Ciudad M. Teresa , Quevedo Rene , Lamorte Sara , Jin Robbie , Nzirorera Nadine , Koritzinsky Marianne , McGaha Tracy L. 
Published: August 2023

AbstractThe effect of targeted therapeutics on anti-cancer immune responses is poorly understood. The BRAF inhibitor dabrafenib has been reported to activate the integrated stress response (ISR) kinase GCN2, and the therapeutic effect has been partially attributed to GCN2 activation. Since ISR signaling is a key component of myeloid-derived suppressor cell (MDSC) development and function, we measured the effect of dabrafenib on MDSC differentiation and suppressive activity. Our data showed that dabrafenib attenuated MDSC ability to suppress T cell activity, which was associated with a GCN2-dependent block of the transition from monocytic progenitor to polymorphonuclear (PMN)-MDSCs and proliferative arrest resulting in PMN-MDSC loss. Transcriptional profiling revealed that dabrafenib-driven GCN2 activation altered metabolic features in MDSCs enhancing oxidative respiration, and attenuated transcriptional programs required for PMN development. Moreover, we observed a broad downregulation of transcriptional networks associated with PMN developmental pathways, and increased activity of transcriptional regulons driven byAtf5,Mafg, andZbtb7a. This transcriptional program alteration underlies the basis for PMN-MDSC developmental arrest, skewing immature MDSC development towards monocytic lineage cells.In vivo, we observed a pronounced reduction in PMN-MDSCs in dabrafenib-treated tumor-bearing mice suggesting that dabrafenib impacts MDSC populations systemically and locally, in the tumor immune infiltrate. Thus, our data reveals transcriptional networks that govern MDSC developmental programs, and the impact of GCN2 stress signaling on the innate immune landscape in tumors, providing novel insight into potentially beneficial off target effects of dabrafenib.
Vitamin D deficiency induces erectile dysfunction: role of superoxide
Authors: Olivencia Miguel A. , Climent Belen , Barreira Bianca , Morales-Cano Daniel , Sánchez Ana , Fernández Argentina , García-Gómez Borja , Romero-Otero Javier , Rodríguez Claudia , Moreno Laura , Prieto Dolores , Larriba María Jesús , Cogolludo Angel , Angulo Javier , Perez-Vizcaino Francisco 
Published: August 2023

ABSTRACTEpidemiological studies suggest a relationship between vitamin D deficiency and erectile dysfunction (ED) but its causal relationship and the mechanism involved are unclear. Here we demonstrate that isolated corpora cavernosa (CC) from human donors with low vitamin D levels show reduced NO-dependent erectile function. This ED is also reproduced in vitamin D deficient rats and vitamin D receptor knockout micein vivoandex vivoand is associated with penile fibrosis. Vitamin D deficiency also blunts the response of CC to the phosphodiesterase 5 inhibitor sildenafil. CC from deficient rats show increased superoxide and their impaired erectile function is restored by superoxide scavengers. These results suggest that vitamin D deficiency induces ED via increased superoxide production.
Quantum machine learning for untangling the real-world problem of cancers classification based on gene expressions
Authors: Ghoabdi Mohadeseh Zarei , Afsaneh Elaheh 
Published: August 2023

AbstractQuantum machine learning algorithms using the power of quantum computing provide fast- developing approaches for solving complicated problems and speeding-up calculations for big data. As such, they could effectively operate better than the classical algorithms. Herein, we demonstrate for the first time the classification of eleven cancers based on the gene expression values with 4495 samples using quantum machine learning. In addition, we compare the obtained quantum classification results with the classical outcomes. By implementing a dimensional reduction method, we introduce significant biomarkers for each cancer. In this research, we express that some of the identified gene biomarkers are consistent with DNA promotor methylation, and some other ones can be applied for the survival determination of patients.
Accessory genes define species-specific pathways to antibiotic resistance
Authors: Dillon L. , Dimonaco NJ. , Creevey CJ. 
Published: August 2023

ABSTRACTBackgroundThe rise of antimicrobial resistance (AMR) is a growing concern globally and a deeper understanding of AMR gene carriage vs usage is vital for future responses to reduce the spread of AMR. Identification of AMR phenotype by laboratory-based assays are often hindered by difficulties in establishing cultures. This issue could be resolved by rapid computational assessment of an organism’s genome, however, AMR gene finder tools are not intended to infer AMR phenotype which is likely to be a product of multiple gene interactions.MethodsTo understand the importance of multi-gene interactions to the relationship between AMR genotype and AMR phenotype, we applied machine learning approaches to 16,950 genomes from microbial isolates representing 28 different genera with 1.2 million corresponding laboratory-determined MICs for 23 different antibiotics. We then elucidated the genomic paths to phenotypic antimicrobial resistance with the aim of allowing for the development of rapid determination of AMR phenotype from genomes or even whole microbiomes.ResultsThe application of machine learning models resulted in a >1.5-fold increase in average prediction accuracy of AMR phenotype across the 23 antibiotic models. Interpretation of these models revealed 528 distinct genomic pathways to phenotypic resistance, many of which were species-specific and involved genes which have not previously been associated with AMR phenotype. This is the first study to demonstrate the utility of machine learning models in the prediction of AMR phenotype for a wide range of clinically relevant organisms and antibiotics. This could be applied as a rapid and affordable alternative to culture-based techniques, estimating taxonomy in addition to AMR phenotype, and providing real-time monitoring of multi-drug resistant pathogens.Availability and implementationContactldillon05@qub.ac.ukView supplementary information at this linkhttps://osf.io/cj4bq/?view_only=c0ee87b7609543b688953089be4c376fSee Code Availability for scripts used.
Microcystin-RR is a biliary toxin selective for neonatal cholangiocytes
Authors: Gupta Kapish , Chen Dongning , Wells Rebecca G. 
Published: August 2023

AbstractBACKGROUND AND AIMSBiliary atresia is a fibrosing cholangiopathy affecting neonates that is thought to be caused by a prenatal environmental insult to the bile duct. Biliatresone, a plant toxin with an α-methylene ketone group, was previously implicated in toxin-induced biliary atresia in Australian livestock, but is found in a limited location and is highly unlikely to be a significant human toxin. We hypothesized that other molecules with α-methylene ketone groups, some with the potential for significant human exposure, might also be biliary toxins.APPROACH AND RESULTSWe focused on the family of microcystins, cyclic peptide toxins from blue-green algae that have an α-methylene ketone group and are found worldwide, particularly during harmful algal blooms. We found that microcystin-RR, but not 6 other microcystins, caused damage to cell spheroids made using cholangiocytes isolated from 2-3-day-old mice, but not from adult mice. We also found that microcystin- RR caused occlusion of extrahepatic bile duct explants from 2-day-old mice, but not 18-day-old mice. Microcystin-RR caused elevated reactive oxygen species in neonatal cholangiocytes, and treatment with N-acetyl cysteine partially prevented microcystin-RR- induced lumen closure, suggesting a role for redox homeostasis in its mechanism of action.CONCLUSIONSThis study highlights the potential for environmental toxins to cause neonatal biliary disease and identifies microcystin-RR acting via increased redox stress as a possible neonatal bile duct toxin.
Brain Specific Estrogen Ameliorates Cognitive Effects of Surgical Menopause in Mice
Authors: Salinero Abigail E. , Abi-Ghanem Charly , Venkataganesh Harini , Sura Avi , Smith Rachel M. , Thrasher Christina A. , Kelly Richard D. , Hatcher Katherine M. , NyBlom Vanessa , Shamlian Victoria , Kyaw Nyi-Rein , Belanger Kasey M. , Gannon Olivia J. , Stephens Shannon B.Z. , Zuloaga Damian G. , Zuloaga Kristen L. 
Published: August 2023

ABSTRACTMenopause is a major endocrinological shift that leads to an increased vulnerability to the risk factors for cognitive impairment and dementia. This is thought to be due to the loss of circulating estrogens, which exert many potent neuroprotective effects in the brain. Systemic replacement of estrogen post-menopause has many limitations, including increased risk for estrogen-sensitive cancers. A more promising therapeutic approach therefore might be to deliver estrogen only to the brain thus limiting adverse peripheral side effects. We examined whether we could enhance cognitive performance by delivering estrogen exclusively to the brain in post-menopausal mice. We modeled surgical menopause via bilateral ovariectomy (OVX). We treated mice with the pro-drug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), which can be administered systemically but is converted to 17β-estradiol only in the brain. Young (2.5-month) and middle-aged (11-month-old) female C57BL/6J mice received ovariectomy and a subcutaneous implant containing vehicle (cholesterol) or DHED. At 3.5 months old (young group) and 14.5 months old (middle-aged group), mice underwent behavior testing to assess memory. DHED did not significantly alter metabolic status in middle-aged, post-menopausal mice. In both young and middle-aged mice, the brain-specific estrogen DHED improved spatial memory. Additional testing in middle-aged mice also showed that DHED improved working and recognition memory. These promising results lay the foundation for future studies aimed at determining if this intervention is as efficacious in models of dementia that have comorbid risk factors.
Sclerotome-derived vascular smooth muscle progenitors contribute to the haematopoietic stem cell specification niche
Authors: Kelley Clair M. , Glenn Nicole O. , Gays Dafne , Santoro Massimo M. , Clements Wilson K. 
Published: August 2023

AbstractHaematopoietic stem cells (HSCs) are the self-renewing progenitors that continuously populate the haemato-immune cell lineages throughout life, and constitute the therapeutic component of bone marrow transplants. A major biomedical goal has been to understand the native specification of HSCs during embryonic development as a means to informin vitrodirected differentiation of pluripotent stem cells. Across vertebrate phyla, HSCs derive from haemogenic endothelium in the ventral floor of the primitive dorsal aorta (DA), also known as the descending aorta in mammals. Competent HSC-fated cells in the endothelium likely receive instructive signaling from neighbouring cells that constitute a “specification niche.” We previously showed that experimental manipulations leading to defects in the most ventral compartment of the somite, the sclerotome, are correlated with HSC defects, raising the possibility that sclerotome patterning is required for HSC specification. Here we show that in zebrafish, specific sclerotome-derived cells contact the DA immediately prior to the emergence of HSCs. These cells subsequently give rise to vascular smooth muscle cells (VSMCs). When sclerotome patterning is disrupted, VSMCs are diminished, and HSC specification fails. We conclude that sclerotome-derived VSMC progenitors contribute to the embryonic HSC specification niche, most likely by providing unknown HSC inductive signals.
Spontaneous and double-strand break repair-associated quasipalindrome and frameshift mutagenesis in budding yeast: role of mismatch repair
Authors: Sugawara Neal , Towne Mason J. , Lovett Susan T. , Haber James E. 
Published: August 2023

ABSTRACTAlthough gene conversion (GC) inSaccharomyces cerevisiaeis the most error-free way to repair double-strand breaks (DSBs), the mutation rate during homologous recombination is 1000 times greater than during replication. Many mutations involve dissociating a partially-copied strand from its repair template and re-aligning with the same or another template, leading to -1 frameshifts in homonucleotide runs, quasipalindrome (QP)-associated mutations and microhomology-mediated interchromosomal template switches. We studied GC induced by HO endonuclease cleavage atMATα, repaired by anHMR::Kl-URA3donor. We inserted intoHMR::Kl-URA3an 18-bp inverted repeat where one arm had a 4-bp insertion. Most GCs yieldmat::Kl-ura3::QP+4(Ura-) outcomes, but template-switching produces Ura+colonies, losing the 4-bp insertion. If the QP arm without the insertion is first encountered by repair DNA polymerase and is then (mis)used as a template, the palindrome is perfected. When the QP+4 arm is encountered first, Ura+derivatives only occur after second-end capture and second-strand synthesis. QP+4 mutations are suppressed by mismatch repair (MMR) proteins Msh2, Msh3, and Mlh1, but not Msh6. Deleting Rdh54 significantly reduces QP mutations only when events creating Ura+occur in the context of a D-loop but not during second-strand synthesis. A similar bias is found with a proofreading-defective DNA polymerase mutation (pol3-01). DSB-induced mutations differed in several genetic requirements from spontaneous events. We also created a +1 frameshift in the donor, expanding a run of 4 Cs to 5 Cs. Again, Ura3+recombinants markedly increased by disabling MMR, suggesting that MMR acts during GC but favors the unbroken, template strand.