bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing Insights into Large-Artery Stiffening in Humans Through the Application of Multi-omics
Authors: Dib Marie-Joe 
Published: July 2024

Abstract
A healthy aorta limits excess arterial pulsatility and protects the microvasculature from the effects of fluctuating blood flow and pressure. Aging and various pathologic states impair this cushioning function, a phenomenon known as large-artery stiffening (LAS). LAS is a common risk factor for a plethora of chronic diseases, and an important contributor to the conundrum of vascular morbidity. Importantly, LAS is pathologically different from atherosclerosis as it rather occurs primarily from changes in the medial aortic layer, and can manifest itself in the absence of plaque formation. Clinically, LAS is one of the few biological parameters that more than doubles with aging. With the advent of novel highly effective therapies for atherosclerosis, and the likely decline of other causes of death in the next few decades, prevention and treatment of increased LAS may be one of the most relevant strategies for preventing multimorbidity in aging populations in upcoming decades. LAS characterizes a high-priority therapeutic target to improve cardiovascular disease burden and associated comorbidities. This review aims to (i) provide an overview of insights from genetic research on LAS pathophysiology, and explore the scope of next-generation sequencing methods in the field arterial research; (ii) shed light on the utility of emerging state-of-the-art multi-omics approaches to unravel mechanisms underlying LAS to identify candidate therapeutic targets; (iii) highlight the potential of emerging state-of-the-art integrative multi-omics, motivating their use to address current gaps in understanding sex- and ancestry-specific mechanisms of LAS.
Role of Salinity Barrier Layers and Westerly Wind Anomalies on Atlantic Niño Events
Authors: Ma Xiao , Liu Hailong 
Published: July 2024

AbstractPrevious studies have confirmed the diverse spatiotemporal characteristics of Atlantic Niño events. Our research further reveals the crucial preparatory role of equatorial western Atlantic barrier layers (BL) and the triggering effect of westerly wind bursts (WWB) on different varieties of Atlantic Niño. Strong easterly winds typically facilitate the formation of thick BL by deepening isothermal layer depth in the western Atlantic through horizontal transport. The existence of BL accumulates the necessary heat for the onset of Atlantic Niño. Additionally, the timing of BL occurrences, the presence of easterly wind anomalies preceding WWB, and the duration of westerly wind anomalies jointly contribute to Atlantic Niño diversity. Persistent westerly wind anomalies following strong easterly winds often lead to Atlantic Niño events lasting over 6 months, while short‐lived events occur when westerly wind anomalies cease shortly after their onset.
Quantifying the Diversity of an Atmospheric Aerosol Population in an Arctic Oil Field on a Single‐Particle Level
Authors: Wu J. , Liu J. , Gunsch M. J. , Mirrielees J. A. , Moffett C. E. , Zhang Q. , Sheesley R. J. , Pratt K. A. 
Published: July 2024

AbstractAs the Arctic rapidly warms, sea ice extent is decreasing and oil and gas extraction activities are expanding. Local combustion emissions affect the Arctic atmospheric aerosol chemical mixing state (the distribution of chemical species across the aerosol population), which impacts climate‐relevant properties. Bulk and single‐particle measurements of submicron aerosols were conducted at Oliktok Point, Alaska within the North Slope of Alaska oil fields. In this work, we quantify aerosol diversity using online single‐particle mass spectrometry data (32,880 individual particles), offline single‐particle microscopy data (20,912 individual particles), and online bulk aerosol mass spectrometry and aethalometer data. This method was used to derive individual particle mass fractions for both refractory and non‐refractory material within distinct particle types. Single‐particle, average single‐particle, and bulk population diversities (Di, Dα, Dγ, respectively) and mixing state indices (χ) were calculated for the data set. Calculated Di values were generally low (2.2 ± 0.6), as individual particle masses were dominated by a few chemical species of interest. Aged aerosol particles (those internally mixed with nitrate and/or sulfate) exhibited higher Di values (>3) compared to recently emitted (fresh) aerosol particles. During oil field plume periods, Dα values approached three due to the abundance of diesel combustion particles, which were rich in sulfate, black carbon, and organic aerosol. Overall, the submicron aerosol population within the Arctic oil fields was found to be relatively externally mixed (χ < 50%), due to the constant local emissions within oil fields combining with background aerosol and locally emitted sea spray aerosol at the coastal site.
Characterizing Mesoscale Cellular Convection in Marine Cold Air Outbreaks With a Machine Learning Approach
Authors: Lackner Christian P. , Geerts Bart , Juliano Timothy W. , Kosovic Branko , Xue Lulin 
Published: July 2024

AbstractDuring marine cold‐air outbreaks (MCAOs), when cold polar air moves over warmer ocean, a well‐recognized cloud pattern develops, with open or closed mesoscale cellular convection (MCC) at larger fetch over open water. The Cold‐Air Outbreaks in the Marine Boundary Layer Experiment provided a comprehensive set of ground‐based in situ and remote sensing observations of MCAOs at a coastal location in northern Norway. MCAO periods that unambiguously exhibit open or closed MCC are determined. Individual cells observed with a profiling Ka‐band radar are identified using a watershed segmentation method. Using self‐organizing maps (SOMs), these cells are then objectively classified based on the variability in their vertical structure. The SOM nodes contain some information about the location of the cell transect relative to the center of the MCC. This adds classification noise, requiring numerous cell transects to isolate cell dynamical information. The SOM‐based classification shows that comparatively intense convection occurs only in open MCC. This convection undergoes an apparent lifecycle. Developing cells are associated with stronger updrafts, large spectrum width, larger amounts of liquid water, lower surface precipitation rates, and lower cloud tops than mature and weakening cells. The weakening of these cells is associated with the development of precipitation‐induced cold pools. The SOM classification also reveals less intense convection, with a similar lifecycle. More stratiform vertical cloud structures with weak vertical motions are common during closed MCC periods and are separated into precipitating and non‐precipitating stratiform cores. Convection is observed only occasionally in the closed MCC environment.
HIF-1 inactivation empowers HIF-2 to drive hypoxia adaptation in aggressive forms of medulloblastoma
Authors: Contenti J. , Guo Y. , Larcher M. , Mirabal-Ortega L. , Rouleau M. , Irondelle M. , Tiroille V. , Mazzu A. , Duranton-Tanneur V. , Pedeutour F. , Ben-Sahra I. , Lago C. , Leva G. , Tiberi L. , Robert G. , Pouponnot C. , Bost F. , Mazure N. M. 
Published: July 2024

AbstractMedulloblastoma (MB) is the most prevalent brain cancer in children. Four subgroups of MB have been identified; of these, Group 3 is the most metastatic. Its genetics and biology remain less clear than the other groups, and it has a poor prognosis and few effective treatments available. Tumor hypoxia and the resulting metabolism are known to be important in the growth and survival of tumors but, to date, have been only minimally explored in MB. Here we show that Group 3 MB tumors do not depend on the canonical transcription factor hypoxia-inducible factor-1α (HIF-1α) to mount an adaptive response to hypoxia. We discovered that HIF-1α is rendered inactive either through post-translational methylation, preventing its nuclear localization specifically in Group 3 MB, or by a low expression that prevents modulation of HIF-target genes. Strikingly, we found that HIF-2 takes over the role of HIF-1 in the nucleus and promotes the activation of hypoxia-dependent anabolic pathways. The exclusion of HIF-1 from the nucleus in Group 3 MB cells enhances the reliance on HIF-2’s transcriptional role, making it a viable target for potential anticancer strategies. By combining pharmacological inhibition of HIF-2α with the use of metformin, a mitochondrial complex I inhibitor to block respiration, we effectively induced Group 3 MB cell death, surpassing the effectiveness observed in Non-Group 3 MB cells. Overall, the unique dependence of MB cells, but not normal cells, on HIF-2-mediated anabolic metabolism presents an appealing therapeutic opportunity for treating Group 3 MB patients with minimal toxicity.
Exploring high corrosion-resistant refractory high-entropy alloy via a combined experimental and simulation study
Authors: Zhao Xinpeng , Huang Haiyou , Su Yanjing , Qiao Lijie , Yan Yu 
Published: July 2024

AbstractRefractory high-entropy alloys (HEAs) have attracted considerable attention due to their stable phase structure and excellent high-temperature properties. In this work, we performed first-principles calculations, coupled with experiments, to explore HEAs with high corrosion resistance. The results revealed that TiNbTa-based HEAs exhibited a lower tendency for corrosion. However, the appearance of local chemical fluctuations (LCFs) increased the corrosion tendency of TiNbTa-based HEAs. Comprehensive SHapley Additive exPlanations analyses uncovered that in a sample with configurational LCFs, the atomic order near the surface was altered. Therefore, corrosion behavior was affected. Based on experiments, the annealed samples exhibited typical chemical segregation and declined corrosion resistance.
Iron-coated Komodo dragon teeth and the complex dental enamel of carnivorous reptiles
Authors: LeBlanc Aaron R. H. , Morrell Alexander P. , Sirovica Slobodan , Al-Jawad Maisoon , Labonte David , D’Amore Domenic C. , Clemente Christofer , Wang Siyang , Giuliani Finn , McGilvery Catriona M. , Pittman Michael , Kaye Thomas G. , Stevenson Colin , Capon Joe , Tapley Benjamin , Spiro Simon , Addison Owen 
Published: July 2024

AbstractKomodo dragons (Varanus komodoensis) are the largest extant predatory lizards and their ziphodont (serrated, curved and blade-shaped) teeth make them valuable analogues for studying tooth structure, function and comparing with extinct ziphodont taxa, such as theropod dinosaurs. Like other ziphodont reptiles, V. komodoensis teeth possess only a thin coating of enamel that is nevertheless able to cope with the demands of their puncture–pull feeding. Using advanced chemical and structural imaging, we reveal that V. komodoensis teeth possess a unique adaptation for maintaining their cutting edges: orange, iron-enriched coatings on their tooth serrations and tips. Comparisons with other extant varanids and crocodylians revealed that iron sequestration is probably widespread in reptile enamels but it is most striking in V. komodoensis and closely related ziphodont species, suggesting a crucial role in supporting serrated teeth. Unfortunately, fossilization confounds our ability to consistently detect similar iron coatings in fossil teeth, including those of ziphodont dinosaurs. However, unlike V. komodoensis, some theropods possessed specialized enamel along their tooth serrations, resembling the wavy enamel found in herbivorous hadrosaurid dinosaurs. These discoveries illustrate unexpected and disparate specializations for maintaining ziphodont teeth in predatory reptiles.
AI models collapse when trained on recursively generated data
Authors: Shumailov Ilia , Shumaylov Zakhar , Zhao Yiren , Papernot Nicolas , Anderson Ross , Gal Yarin 
Published: July 2024

AbstractStable diffusion revolutionized image creation from descriptive text. GPT-2 (ref. 1), GPT-3(.5) (ref. 2) and GPT-4 (ref. 3) demonstrated high performance across a variety of language tasks. ChatGPT introduced such language models to the public. It is now clear that generative artificial intelligence (AI) such as large language models (LLMs) is here to stay and will substantially change the ecosystem of online text and images. Here we consider what may happen to GPT-{n} once LLMs contribute much of the text found online. We find that indiscriminate use of model-generated content in training causes irreversible defects in the resulting models, in which tails of the original content distribution disappear. We refer to this effect as ‘model collapse’ and show that it can occur in LLMs as well as in variational autoencoders (VAEs) and Gaussian mixture models (GMMs). We build theoretical intuition behind the phenomenon and portray its ubiquity among all learned generative models. We demonstrate that it must be taken seriously if we are to sustain the benefits of training from large-scale data scraped from the web. Indeed, the value of data collected about genuine human interactions with systems will be increasingly valuable in the presence of LLM-generated content in data crawled from the Internet.
Global atmospheric methane uptake by upland tree woody surfaces
Authors: Gauci Vincent , Pangala Sunitha Rao , Shenkin Alexander , Barba Josep , Bastviken David , Figueiredo Viviane , Gomez Carla , Enrich-Prast Alex , Sayer Emma , Stauffer Tainá , Welch Bertie , Elias Dafydd , McNamara Niall , Allen Myles , Malhi Yadvinder 
Published: July 2024

AbstractMethane is an important greenhouse gas1, but the role of trees in the methane budget remains uncertain2. Although it has been shown that wetland and some upland trees can emit soil-derived methane at the stem base3,4, it has also been suggested that upland trees can serve as a net sink for atmospheric methane5,6. Here we examine in situ woody surface methane exchange of upland tropical, temperate and boreal forest trees. We find that methane uptake on woody surfaces, in particular at and above about 2 m above the forest floor, can dominate the net ecosystem contribution of trees, resulting in a net tree methane sink. Stable carbon isotope measurement of methane in woody surface chamber air and process-level investigations on extracted wood cores are consistent with methanotrophy, suggesting a microbially mediated drawdown of methane on and in tree woody surfaces and tissues. By applying terrestrial laser scanning-derived allometry to quantify global forest tree woody surface area, a preliminary first estimate suggests that trees may contribute 24.6–49.9 Tg of atmospheric methane uptake globally. Our findings indicate that the climate benefits of tropical and temperate forest protection and reforestation may be greater than previously assumed.
Single-cell multiregion dissection of Alzheimer’s disease
Authors: Mathys Hansruedi , Boix Carles A. , Akay Leyla Anne , Xia Ziting , Davila-Velderrain Jose , Ng Ayesha P. , Jiang Xueqiao , Abdelhady Ghada , Galani Kyriaki , Mantero Julio , Band Neil , James Benjamin T. , Babu Sudhagar , Galiana-Melendez Fabiola , Louderback Kate , Prokopenko Dmitry , Tanzi Rudolph E. , Bennett David A. , Tsai Li-Huei , Kellis Manolis 
Published: July 2024

AbstractAlzheimer’s disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood1–3. Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer’s disease. We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses. We identify vulnerable populations of excitatory and inhibitory neurons that are depleted in specific brain regions in Alzheimer’s disease, and provide evidence that the Reelin signalling pathway is involved in modulating the vulnerability of these neurons. We develop a scalable method for discovering gene modules, which we use to identify cell-type-specific and region-specific modules that are altered in Alzheimer’s disease and to annotate transcriptomic differences associated with diverse pathological variables. We identify an astrocyte program that is associated with cognitive resilience to Alzheimer’s disease pathology, tying choline metabolism and polyamine biosynthesis in astrocytes to preserved cognitive function late in life. Together, our study develops a regional atlas of the ageing human brain and provides insights into cellular vulnerability, response and resilience to Alzheimer’s disease pathology.
Cryo-EM architecture of a near-native stretch-sensitive membrane microdomain
Authors: Kefauver Jennifer M. , Hakala Markku , Zou Luoming , Alba Josephine , Espadas Javier , Tettamanti Maria G. , Gajić Jelena , Gabus Caroline , Campomanes Pablo , Estrozi Leandro F. , Sen Nesli E. , Vanni Stefano , Roux Aurélien , Desfosses Ambroise , Loewith Robbie 
Published: July 2024

AbstractBiological membranes are partitioned into functional zones termed membrane microdomains, which contain specific lipids and proteins1–3. The composition and organization of membrane microdomains remain controversial because few techniques are available that allow the visualization of lipids in situ without disrupting their native behaviour3,4. The yeast eisosome, composed of the BAR-domain proteins Pil1 and Lsp1 (hereafter, Pil1/Lsp1), scaffolds a membrane compartment that senses and responds to mechanical stress by flattening and releasing sequestered factors5–9. Here we isolated near-native eisosomes as helical tubules made up of a lattice of Pil1/Lsp1 bound to plasma membrane lipids, and solved their structures by helical reconstruction. Our structures reveal a striking organization of membrane lipids, and, using in vitro reconstitutions and molecular dynamics simulations, we confirmed the positioning of individual PI(4,5)P2, phosphatidylserine and sterol molecules sequestered beneath the Pil1/Lsp1 coat. Three-dimensional variability analysis of the native-source eisosomes revealed a dynamic stretching of the Pil1/Lsp1 lattice that affects the sequestration of these lipids. Collectively, our results support a mechanism in which stretching of the Pil1/Lsp1 lattice liberates lipids that would otherwise be anchored by the Pil1/Lsp1 coat, and thus provide mechanistic insight into how eisosome BAR-domain proteins create a mechanosensitive membrane microdomain.
Shifts in receptors during submergence of an encephalitic arbovirus
Authors: Li Wanyu , Plante Jessica A. , Lin ChieYu , Basu Himanish , Plung Jesse S. , Fan Xiaoyi , Boeckers Joshua M. , Oros Jessica , Buck Tierra K. , Anekal Praju V. , Hanson Wesley A. , Varnum Haley , Wells Adrienne , Mann Colin J. , Tjang Laurentia V. , Yang Pan , Reyna Rachel A. , Mitchell Brooke M. , Shinde Divya P. , Walker Jordyn L. , Choi So Yoen , Brusic Vesna , Llopis Paula Montero , Weaver Scott C. , Umemori Hisashi , Chiu Isaac M. , Plante Kenneth S. , Abraham Jonathan 
Published: July 2024

AbstractWestern equine encephalitis virus (WEEV) is an arthropod-borne virus (arbovirus) that frequently caused major outbreaks of encephalitis in humans and horses in the early twentieth century, but the frequency of outbreaks has since decreased markedly, and strains of this alphavirus isolated in the past two decades are less virulent in mammals than strains isolated in the 1930s and 1940s1–3. The basis for this phenotypic change in WEEV strains and coincident decrease in epizootic activity (known as viral submergence3) is unclear, as is the possibility of re-emergence of highly virulent strains. Here we identify protocadherin 10 (PCDH10) as a cellular receptor for WEEV. We show that multiple highly virulent ancestral WEEV strains isolated in the 1930s and 1940s, in addition to binding human PCDH10, could also bind very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), which are recognized by another encephalitic alphavirus as receptors4. However, whereas most of the WEEV strains that we examined bind to PCDH10, a contemporary strain has lost the ability to recognize mammalian PCDH10 while retaining the ability to bind avian receptors, suggesting WEEV adaptation to a main reservoir host during enzootic circulation. PCDH10 supports WEEV E2–E1 glycoprotein-mediated infection of primary mouse cortical neurons, and administration of a soluble form of PCDH10 protects mice from lethal WEEV challenge. Our results have implications for the development of medical countermeasures and for risk assessment for re-emerging WEEV strains.
The correlation between CpG methylation and gene expression is driven by sequence variants
Authors: Stefansson Olafur Andri , Sigurpalsdottir Brynja Dogg , Rognvaldsson Solvi , Halldorsson Gisli Hreinn , Juliusson Kristinn , Sveinbjornsson Gardar , Gunnarsson Bjarni , Beyter Doruk , Jonsson Hakon , Gudjonsson Sigurjon Axel , Olafsdottir Thorunn Asta , Saevarsdottir Saedis , Magnusson Magnus Karl , Lund Sigrun Helga , Tragante Vinicius , Oddsson Asmundur , Hardarson Marteinn Thor , Eggertsson Hannes Petur , Gudmundsson Reynir L. , Sverrisson Sverrir , Frigge Michael L. , Zink Florian , Holm Hilma , Stefansson Hreinn , Rafnar Thorunn , Jonsdottir Ingileif , Sulem Patrick , Helgason Agnar , Gudbjartsson Daniel F. , Halldorsson Bjarni V. , Thorsteinsdottir Unnur , Stefansson Kari 
Published: July 2024

AbstractGene promoter and enhancer sequences are bound by transcription factors and are depleted of methylated CpG sites (cytosines preceding guanines in DNA). The absence of methylated CpGs in these sequences typically correlates with increased gene expression, indicating a regulatory role for methylation. We used nanopore sequencing to determine haplotype-specific methylation rates of 15.3 million CpG units in 7,179 whole-blood genomes. We identified 189,178 methylation depleted sequences where three or more proximal CpGs were unmethylated on at least one haplotype. A total of 77,789 methylation depleted sequences (~41%) associated with 80,503 cis-acting sequence variants, which we termed allele-specific methylation quantitative trait loci (ASM-QTLs). RNA sequencing of 896 samples from the same blood draws used to perform nanopore sequencing showed that the ASM-QTL, that is, DNA sequence variability, drives most of the correlation found between gene expression and CpG methylation. ASM-QTLs were enriched 40.2-fold (95% confidence interval 32.2, 49.9) among sequence variants associating with hematological traits, demonstrating that ASM-QTLs are important functional units in the noncoding genome.
Cohesin prevents cross-domain gene coactivation
Authors: Dong Peng , Zhang Shu , Gandin Valentina , Xie Liangqi , Wang Lihua , Lemire Andrew L. , Li Wenhong , Otsuna Hideo , Kawase Takashi , Lander Arthur D. , Chang Howard Y. , Liu Zhe J. 
Published: July 2024

AbstractThe contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure–function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis-linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis. Spatial genome and protein imaging reveals that cohesin prevents gene co-bursting along the chromosome and blocks spatial mixing of transcriptional hubs. Single-molecule imaging shows that cohesin confines the exploration of diverse enhancer and core promoter binding transcriptional regulators. Together, these results support that cohesin arranges nuclear topology to control gene coexpression in single cells.