bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wild yeast isolation by middle school students reveals features of North American oak populations ofSaccharomyces cerevisiaeandKluyveromyces lactis
Authors: Yeager Randi , Heasley Lydia , Baker Nolan , Shrivastava Vatsal , Woodman Julie , McMurray Michael 
Published: July 2024

ABSTRACTFeatures of the natural life cycle of the budding yeastSaccharomyces cerevisiaewere crucial to its domestication as a laboratory experimental model, especially the ability to maintain stable haploid clones and cross them at will to combine alleles via meiosis. Stable haploidy results from mutations inHO, which encodes an endonuclease required for haploid-specific mating-type switching. Previous studies found an unexpected diversity ofHOalleles among natural isolates within a small geographic area. We developed a hands-on field and laboratory activity for middle school students in Denver, Colorado, USA to isolate wild yeast from oak bark, identify species via DNA sequencing, and sequenceHOfromS. cerevisiaeisolates. We find limitedHOdiversity in North American oak isolates, pointing to efficient, continuous dispersal across the continent. By contrast, we isolated the “dairy yeast”,Kluyveromyces lactis, from a tree <10 m away and found that it represents a new population distinct from an oak population in an adjacent state, pointing to high genetic diversity. The outreach activity partnered middle school, high school, and university students in making scientific discoveries and can be adapted to other locations and natural yeast habitats. Indeed, a pilot sampling activity in southeast Texas yieldedS. cerevisiaeoak isolates with a new allele ofHOand, from a nearby prickly pear cactus, a heat-tolerant isolate ofSaccharomyces paradoxus.
Integrin-deficient T cell leukemia accumulates in the central nervous system
Authors: Lux Samantha Y. , Chen Cynthia , Subhan Bibi S. , Okuniewska Martyna , Chung Hyunsoo , Vernejoul Jonah B. , Martin Kathleen A. , Caslin Asha Y. , Schiavo Jennifer K. , Froemke Robert C. , Cammer Michael , Schwab Susan R. 
Published: July 2024

SummaryT cell acute lymphoblastic leukemia (T-ALL), a devastating childhood cancer, rapidly invades the central nervous system (CNS) and localizes to the meninges. T-ALL is aggressively treated with high-dose, CNS-directed chemotherapy; this regime results in lasting neurotoxicity and in some cases ultimately fails to protect from meningeal relapse. The paucity of knowledge about T-ALL entry and persistence in the CNS has limited the development of targeted therapies for decades. Here, we addressed whether VLA-4 and LFA-1, two integrins that mediate normal T cell entry to the CNS and that have been successfully targeted in patients for treatment of autoimmune disease, were similarly required in T-ALL. In the process, we uncovered an entirely unexpected role for these integrins in CNS disease. Not only were these integrins dispensable for T-ALL to reach the CNS, integrin-deficient T-ALL accumulated in the CNS compared to control T-ALL. Mechanistically, loss of integrins accelerated T-ALL proliferation in the CNS, suggesting that integrin-mediated interactions may promote quiescence in this space and highlighting the importance of niche-specific regulation of disease. Integrin blockade strongly synergized with anti-proliferative chemotherapy to treat CNS disease, indicating that combination therapy might be a powerful therapeutic strategy.
Modeling Mountain Pine Beetle Abundance and Distribution in a Changing Climate
Authors: Xie Xiaoqi , Brush Micah , Lewis Mark A. 
Published: July 2024

AbstractThe range of mountain pine beetle (Dendroctonus ponderosaeHopkins) is primarily constrained by climate, with winter temperatures playing a crucial role. Climate change is likely to increase the number of warm days and decrease cold days compared to historical norms, making higher latitudes more suitable habitats. In this work, we explore the potential impacts of environmental covariates on outbreaks of mountain pine beetle under climate change in a selected lodgepole pine area in Alberta. We employ a hierarchical model to examine mountain pine beetle dynamics approaching the end of the century. Our analysis assesses the impact of various climatic covariates and estimates the probability and expected number of infestations across different climate change scenarios. Our results from the hierarchical model underscore the critical role of degree days and overwinter survival probability, displaying an overall trend towards a higher probability and a greater number of outbreaks with increasing temperature. Our results indicate that Alberta is likely to experience widespread infestations in the future.
Dynamic Localization of Leukemia Stem Cells via CXCL12 Regulates Leukemia Progression
Authors: Wang Chen , Pan Yi , Dong Ruochen , Zhou WenXuan , Meng XiaDuo , Shi Yao , Nistala Ravi , Hammer Richard D. , Li Linheng , Kang XunLei 
Published: July 2024

AbstractThe processes that govern leukemia progression and remission are poorly understood. Our research reveals that the CXCL12 gradient, traditionally associated with LSC quiescence and survival, critically determines LSC localization and associated behavior. Specifically, CXCL12 guides LSCs to either the quiescent niche in the metaphysis, characterized by N-cadherin-expressing mesenchymal stromal cells (N-cad+MSCs), or the proliferative niche in the central marrow (CM), marked by sinusoidal endothelial cells and associated stromal cells. We identified that the CXCL12 gradient is finely regulated by the interplay between dipeptidyl peptidase 4 (DPP4) on LSCs and glypican-3 (GPC3) on N-cad+MSCs. DPP4 deactivates CXCL12, while GPC3 inhibits DPP4, resulting in a higher CXCL12 concentration in the metaphysis and a lower concentration in the CM. This differential gradient facilitates leukemia progression by promoting LSC quiescence and survival in the metaphysis versus relative proliferation and apoptosis in the CM. Depletion ofDpp4from LSCs orCxcl12from N-cad+MSCs disrupts this gradient, mobilizing LSCs from the metaphysis to the CM and significantly hindering leukemia development. Our findings redefine the role of CXCL12 in LSC behavior and provide a clearer understanding of leukemia progression. This novel insight highlights the potential for targeted therapeutic strategies that disrupt the CXCL12 gradient to treat minimal residual LSCs, offering a promising path toward a lasting cure for acute myeloid leukemia (AML).
Evolution into chaos – implications of the trade-off between transmissibility and immune evasion
Authors: Sayyar Golsa , Garab Ábel , Röst Gergely 
Published: July 2024

AbstractPredicting viral evolution presents a significant challenge and is a critical public health priority. In response to this challenge, we develop a novel model for viral evolution that considers a trade-off between immunity evasion and transmissibility. The model selects for a new strain with the highest invasion fitness, taking into account this trade-off. When the dominant strain of the pathogen is highly transmissible, evolution tends to favor immune evasion, whereas for less contagious strains the direction of evolution leads toward increasing transmissibility. Assuming a linear functional form of this trade-off, we can express the long-term evolutionary patterns following the emergence of subsequent strains by a non-linear difference equation. We provide sufficient criteria for when evolution converges, and successive strains exhibit similar transmissibility. We also identify scenarios characterized by a two-periodic pattern in upcoming strains, indicating a situation where a highly transmissible but not immune-evasive strain is replaced by a less transmissible but highly immune-evasive strain, and vice versa, creating a cyclic pattern. Finally, we show that under certain conditions, viral evolution becomes chaotic and thus future transmissibilites become unpredictable in the long run. Visualization via bifurcation diagrams elucidates our analytical findings, revealing complex dynamic behaviors that include the presence of multiple periodic solutions and extend to chaotic regimes. Our analysis provides valuable insights into the complexities of viral evolution in the light of the trade-off between immune evasion and transmissibility.
Attention-based frontal-posterior coupling for visual consciousness in the human brain
Authors: Zhang Xilei , Zhang Chao , Wu Xiqian , Zhou Wenjing , He Sheng , Jiang Yi , Zhang Kai , Wang Liang 
Published: July 2024

AbstractWe usually perceive what we are attending to. How goal-directed attention contributes to conscious perception remains yet elusive. Here we combined a novel psychophysical paradigm with intracranial electroencephalography data to investigate this issue in the human brain. Relative to unattended conditions, goal-directed attention modulated early activity and inter-regional connectivity, even though this part of attention failed to predict image detectability. Later, the coupling between the frontal and posterior brain got established and maintained but the signals exchanged did not inform fine-grained image contents but instead reflect success or failure of attentional capture. This part of captured attention proportionally predicted image detectability. These results attribute consciousness to attention-based coupling between the frontal and posterior brain as a whole, rather than activity of either part alone.
Bird population trend analyses for a monitoring scheme with a highly structured sampling design
Authors: Rieger Mirjam R. , Grüneberg Christoph , Oberhaus Michael , Trautmann Sven , Parepa Madalin , Anthes Nils 
Published: July 2024

SummaryPopulation trends derived from systematic monitoring programmes are essential to identify species of conservation concern and to evaluate conservation measures. However, monitoring data pose several challenges for statistical analysis, including spatial bias due to an unbalanced sampling of landscapes or habitats, variation in observer expertise, frequent observer changes, and overdispersion or zero-inflation in the raw data. An additional challenge arises from so-called ‘rolling’ survey designs, where each site is only visited once within each multi-year rotation cycle. We developed a GAMM-based workflow that addresses these challenges and exemplify its application with the highly structured data from the Ecological Area Sampling (EAS) in the German federal state North-Rhine Westphalia (NRW). First, we derive a routine that allows informed decisions about the most appropriate combination of distribution family (Poisson or negative binomial), model covariates (e.g., habitat characteristics), and zero-inflation formulations to reflect species-specific data distributions. Second, we develop a correction factor that buffers population trend estimates for variation in observer expertise as reflected in variation in total bird abundance. Third, we integrate landscape-specific trends that adjust for between-year variation in the representation of habitat or landscape types within the yearly subset of sampled sites. In a consistency check, we found good match between our GAMM-based EAS trends and TRIM-based trends from the standard German common Bird monitoring scheme. The study provides a template script forRstatistical software so the workflow can be adapted to other monitoring programmes with comparable survey designs and data structures.
PIEZO1-Mediated Mechanotransduction Regulates Collagen Synthesis on Nanostructured 2D and 3D Models of Fibrosis
Authors: Rashidi Neda , Harasymowicz Natalia S. , Savadipour Alireza , Steward Nancy , Tang Ruhang , Oswald Sara , Guilak Farshid 
Published: July 2024

AbstractProgressive fibrosis causes tissue malfunction and organ failure due to the pathologic accumulation of a collagen-rich extracellular matrix. In vitro models provide useful tools for deconstructing the roles of specific biomechanical or biological mechanisms involved in these processes and identifying potential therapeutic targets. In particular, recent studies have implicated cellular mechanosensing of substrate micro- and nanoscale architecture as a regulator of fibrosis. In this study, we investigated how the mechanosensitive ion channel PIEZO1 and intracellular mechanotransduction pathways influence fibrotic gene and protein expression in adipose-derived stem cells (hASCs). Specifically, we examined the role of PIEZO1 and the mechano-sensitive transcription factors YAP/TAZ in sensing aligned or non-aligned substrate architecture to regulate collagen formation. We utilized both 2D microphotopatterned substrates and 3D electrospun polycaprolactone (PCL) substrates to study the role of culture dimensionality. We found that PIEZO1 regulates collagen production in hASCs in a manner that is sensitive to substrate architecture. Activation of PIEZO1 induced significant morphological changes in hASCs, particularly when they were cultured on aligned substrates. While YAP translocated to the cytoplasm following PIEZO1 activation, depleting YAP and TAZ did not change collagen expression significantly downstream of PIEZO1 activation, implying that YAP/TAZ translocation out of the nucleus and increased collagen production may be independent outputs of PIEZO1 activation. Our studies demonstrate a role for PIEZO1 in cellular mechanosensing of substrate architecture and provide targetable pathways for treating fibrosis as well as for enhancing tissue-engineered and regenerative approaches for fibrous tissue repair.
Predicting the physiological effects of multiple drugs using electronic health record
Authors: Jeon Junhyeok , Hong Eujin , Kim Jong-Yeup , Lee Suehyun , Kim Hyun Uk 
Published: July 2024

ABSTRACTVarious computational models have been developed to understand the physiological effects of drug-drug interactions, which can contribute to more effective drug treatments. However, they mostly focus on interactions of only two drugs, and do not consider the patient information. To address this challenge, we use publicly available electronic health record (EHR), MIMIC-IV, to develop machine learning models that predict the physiological effects of two or more drugs. This study involves extensive preprocessing of laboratory measurement data, prescription data and patient data. The resulting machine learning models predict potential abnormalities across 20 selected measurement items (e.g., concentrations of metabolites and blood cells) in the form of a sentence. The models showed an average AUROC of 0.75, and age, specific active pharmaceutical ingredients, and gender appeared to be the most influential features. The model development process showcased in this study can be extended to other measurement items for a target EHR.
Cerebral Microvascular Density, Permeability of the Blood-Brain Barrier, and Neuroinflammatory Responses Indicate Early Aging Characteristics in a Marfan Syndrome Mouse Model
Authors: Curry-Koski T , Curtin L , Esfandiarei M. , Currier Thomas T. 
Published: July 2024

AbstractMarfan Syndrome (MFS) is a connective tissue disorder due to mutations in fibrillin-1 (Fbn1), where aFbn1missense mutation (Fbn1C1039G/+) can result in systemic increases in the bioavailability and signaling of transforming growth factor-β (TGF-β). In a well-established mouse model of MFS (Fbn1C1041G/+), pre-mature aging of the aortic wall and the progression of aortic root aneurysm are observed by 6-months-of-age. TGF-β signaling has been implicated in cerebrovascular dysfunction, loss of blood-brain barrier (BBB) integrity, and age-related neuroinflammation. We have reported that pre-mature vascular aging in MFS mice could extend to cerebrovasculature, where peak blood flow velocity in the posterior cerebral artery (PCA) of 6-month-old (6M) MFS mice was reduced, similarly to 12-month-old (12M) control mice. Case studies of MFS patients have documented neurovascular manifestations, including intracranial aneurysms, stroke, arterial tortuosity, as well as headaches and migraines, with reported incidence of pain and chronic fatigue. Despite these significant clinical observations, investigation into cerebrovascular dysfunction and neuropathology in MFS remains limited. Using 6M-control (C57BL/6) and 6M-MFS (Fbn1C1041G/+) and healthy 12M-control male and female mice, we test the hypothesis that abnormal Fbn1 protein expression is associated with altered cerebral microvascular density, BBB permeability, and neuroinflammation in the PCA-perfused hippocampus, all indicative of a pre-mature aging brain phenotype.Using Glut1 staining, 6M-MFS mice and 12M-CTRL similarly present decreased microvascular density in the dentate gyrus (DG), cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) regions of the hippocampus. 6M-MFS mice exhibit increased BBB permeability in the DG, CA1, and CA3 as evident by Immunoglobulin G (IgG) staining, which was more comparable to 12M-CTRL mice. 6M-MFS mice show a higher number of microglia in the hippocampus compared to age-matched control mice, a pattern resembling that of 12M-CTRL mice.This study represents the first known investigation into neuropathology in a mouse model of MFS and indicates that the pathophysiology underlying MFS leads to a systemic pre-mature aging phenotype. This study is crucial for identifying and understanding MFS-associated neurovascular and neurological abnormalities, underscoring the need for research aimed at improving the quality of life and managing pre-mature aging symptoms in MFS and related connective tissue disorders.
CoPR: Collective Pattern Recognition—a Framework for Microbial Community Activity Analysis
Authors: Vidanaarachchi Rajith , Tang Sen Lin , Halgamuge Saman 
Published: July 2024

AbstractBackgroundMicrobial community activities provide essential information on understanding bacterial communities. Unfortunately, they are generally not directly observable. We rely on longitudinal abundance profiles to get insight into microbial community activities. Often datasets do not have sufficient longitudinal sampling points to successfully apply our algorithms. Hence, in this paper, we are interested in analysing multiple datasets from similar environments to alleviate the aforementioned problem. Furthermore, we wish to see whether collective pattern recognition would enhance our understanding of microbial community activities.ResultsIn this paper, we present CoPR, a framework for collective microbial longitudinal abundance data. Our visualisation shows that a single pattern for temporal abundance variation does not exist. However, it also indicates that even complete individuality does not exist. Consequently, our visualisation highlights the individuality and conformity in the temporal variation of abundance profiles of similar host environments. We also identify different characteristics in the TVAP (Temporal Variation of Abundance Profile) patterns with regards to cohesion and separation.ConclusionsCoPR helps gain essential insights into the microbial communities and their heterogeneity through visualisation tools. This paper also highlights the choice between individuality and conformity in microbial community data analysis.
Somatic instability of theFGF14-SCA27B GAA•TTC repeat reveals a marked expansion bias in the cerebellum
Authors: Pellerin David , Méreaux Jean-Loup , Boluda Susana , Danzi Matt C. , Dicaire Marie-Josée , Davoine Claire-Sophie , Genis David , Spurdens Guinevere , Ashton Catherine , Hammond Jillian M. , Gerhart Brandon J. , Chelban Viorica , Le Phuong U. , Safisamghabadi Maryam , Yanick Christopher , Lee Hamin , Nageshwaran Sathiji K. , Matos-Rodrigues Gabriel , Jaunmuktane Zane , Petrecca Kevin , Akbarian Schahram , Nussenzweig André , Usdin Karen , Renaud Mathilde , Bonnet Céline , Ravenscroft Gianina , Saporta Mario A. , Napierala Jill S. , Houlden Henry , Deveson Ira W. , Napierala Marek , Brice Alexis , Molina Porcel Laura , Seilhean Danielle , Zuchner Stephan , Durr Alexandra , Brais Bernard 
Published: July 2024

AbstractSpinocerebellar ataxia 27B (SCA27B) is a common autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion inFGF14. Neuropathological studies have shown that neuronal loss is largely restricted to the cerebellum. Although the repeat locus is highly unstable during intergenerational transmission, it remains unknown whether it exhibits cerebral mosaicism and progressive instability throughout life. We conducted an analysis of theFGF14GAA•TTC repeat somatic instability across 156 serial blood samples from 69 individuals, fibroblasts, induced pluripotent stem cells, and post-mortem brain tissues from six controls and six patients with SCA27B, alongside methylation profiling using targeted long-read sequencing. Peripheral tissues exhibited minimal somatic instability, which did not significantly change over periods of more than 20 years. In post-mortem brains, the GAA•TTC repeat was remarkably stable across all regions, except in the cerebellar hemispheres and vermis. The levels of somatic expansion in the cerebellar hemispheres and vermis were, on average, 3.15 and 2.72 times greater relative to other examined brain regions, respectively. Additionally, levels of somatic expansion in the brain increased with repeat length and tissue expression ofFGF14. We found no significant difference in methylation of wild-type and expandedFGF14alleles in post-mortem cerebellar hemispheres between patients and controls. In conclusion, our study revealed that theFGF14GAA•TTC repeat exhibits a cerebellar-specific expansion bias, which may explain the pure and late-onset cerebellar involvement in SCA27B.
Multicenter validation of artificial intelligence software predicting large vessel occlusion using noncontrast brain CT
Authors: Chung Jong-Won , Lee Myungjae , Ha Sue Young , Kim Pyeong Eun , Sunwoo Leonard , Kim Nakhoon , Park Kwang-Yeol , Yum Kyu Sun , Shin Dong-Ick , Park Hong-Kyun , Cho Yong-Jin , Hong Keun-Sik , Kim Jae Guk , Lee Soo Joo , Kim Joon-Tae , Seo Woo-Keun , Bang Oh Young , Kim Gyeong-Moon , Kim Dongmin , Bae Hee- Joon , Ryu Wi-Sun , Kim Beom Joon 
Published: July 2024

AbstractBackgroundTo validate JLK-CTL, an artificial intelligence (AI) software developed to predict large vessel occlusion (LVO) using non-contrast CT (NCCT) scans, and to investigate its clinical implications regarding both infarct volume and functional outcomes.MethodsBetween January-2021 and April-2023, a consecutive series of patients who concurrently underwent CT angiography and NCCT within 24 hours of last- known-well (LKW) were collected. LVO was confirmed through consensus among three experts reviewing CT angiography. Infarct volumes were quantified using diffusion-weighted imaging (DWI) conducted within seven days of the NCCT. The performance of the JLK-CTL was evaluated based on the area under the receiver operating characteristic curve (AUROC), as well as its sensitivity and specificity. The association of JLK-CTL LVO scores with infarct volumes and functional outcomes was assessed using Pearson correlation and logistic regression analyses, respectively.ResultsOf 1,391 screened patients, 774 (mean age 69.0 ± 13.6 years, 57.6% men) were included. The median time from LKW to NCCT was 3.1 hours (IQR 1.5–7.4), with 24.2% (n=187) presenting LVO. The JLK-CTL demonstrated AUROC of 0.832 (95% CI 0.804–0.858), with a sensitivity of 0.711 (95% CI 0.641–0.775) and a specificity of 0.830 (95% CI 0.797–0.859) at the predefined threshold. Incorporating the National Institute of Health Stroke Scale into the model increased the AUROC to 0.872 (95% CI 0.846–0.894; p<0.001). The LVO scores showed a significant correlation with infarct volumes on follow-up DWI (r=0.53; p<0.001). When JLK-CTL LVO scores were categorized based on observed frequency of LVO, the highest JLK-CTL LVO scores (51-100) group showed an independent association with unfavorable functional outcomes (adjusted odds ratio 9.48; 95% CI 3.98–22.55).ConclusionThe performance of the AI software in predicting LVO was validated across multiple centers. This tool has the potential to assist physicians in optimizing stroke management workflows, especially in resource-limited settings.