bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sea‐Level Rise Impacts on Tidal Marshes and Estuarine Biogeochemical Processes
Authors: Cai Xun , Shen Jian , Zhang Yinglong J. , Qin Qubin , Linker Lewis 
Published: August 2023

AbstractWe used a numerical model to investigate the effects of sea‐level rise (SLR) on the biogeochemical processes in the York River Estuary with extensive tidal marshes. The fully‐coupled hydrodynamic‐water quality‐marsh model accounts for the spatial and temporal variations of physical‐biogeochemical interactions between the tidal marshes and surrounding waters. This study focuses on an SLR scenario where the vertical accretion of tidal marshes keeps pace with the rising sea levels. Results show that SLR amplifies the tidal range and prolongs flooding duration, which results in enhanced porewater exchanges of materials between the tidal marshes and the surrounding waters. The increased availability of shallow‐water habitats and enhanced light utilization in the shallow areas under SLR promote phytoplankton production (PP) in the shallow‐water regions of the York River. Consequently, the organic carbon in the open water is fueled by the contributions from shallow waters and the enhanced export of organic carbon from the marshes. The change in the dissolved oxygen (DO) budget in the York River Estuary is attributed to changes in water column respiration, net metabolism of the benthic layer, reaeration, PP, and increased stratification under SLR. The net DO flux out of the York River increases at the York River mouth. Diel DO variation, especially in the marshes in the upper estuary, promotes phosphorus release from the sediment. The changes in dissolved nitrogen under SLR are relatively minimal.
α-parvin controls chondrocyte column formation and regulates long bone development
Authors: Yuan Jifan , Guo Ling , Wang Jiaxin , Zhou Zhongjun , Wu Chuanyue 
Published: August 2023

AbstractEndochondral ossification requires proper control of chondrocyte proliferation, differentiation, survival, and organization. Here we show that knockout of α-parvin, an integrin-associated focal adhesion protein, from murine limbs causes defects in endochondral ossification and dwarfism. The mutant long bones were shorter but wider, and the growth plates became disorganized, especially in the proliferative zone. With two-photon time-lapse imaging of bone explant culture, we provide direct evidence showing that α-parvin regulates chondrocyte rotation, a process essential for chondrocytes to form columnar structure. Furthermore, loss of α-parvin increased binucleation, elevated cell death, and caused dilation of the resting zones of mature growth plates. Single-cell RNA-seq analyses revealed alterations of transcriptome in all three zones (i.e., resting, proliferative, and hypertrophic zones) of the growth plates. Our results demonstrate a crucial role of α-parvin in long bone development and shed light on the cellular mechanism through which α-parvin regulates the longitudinal growth of long bones.
Cancer-associated fibroblasts: tumor defenders in radiation therapy
Authors: Zhang Yalin , Lv Na , Li Manshi , Liu Ming , Wu Chunli 
Published: August 2023

AbstractCancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment that are involved in multiple aspects of cancer progression and considered contributors to tumor immune escape. CAFs exhibit a unique radiation resistance phenotype, and can survive clinical radiation doses; however, ionizing radiation can induce changes in their secretions and influence tumor progression by acting on tumor and immune cells. In this review, we describe current knowledge of the effects of radiation therapies on CAFs, as well as summarizing understanding of crosstalk among CAFs, tumor cells, and immune cells. We highlight the important role of CAFs in radiotherapy resistance, and discuss current and future radiotherapy strategies for targeting CAFs.
The deubiquitinase Leon/USP5 interacts with Atg1/ULK1 and antagonizes autophagy
Authors: Pai Yueh-Ling , Lin Yuchieh Jay , Peng Wen-Hsin , Huang Li-Ting , Chou He-Yen , Wang Chien-Hsiang , Chien Cheng-Ting , Chen Guang-Chao 
Published: August 2023

AbstractAccumulating evidence has shown that the quality of proteins must be tightly monitored and controlled to maintain cellular proteostasis. Misfolded proteins and protein aggregates are targeted for degradation through the ubiquitin proteasome (UPS) and autophagy-lysosome systems. The ubiquitination and deubiquitinating enzymes (DUBs) have been reported to play pivotal roles in the regulation of the UPS system. However, the function of DUBs in the regulation of autophagy remain to be elucidated. In this study, we found that knockdown of Leon/USP5 caused a marked increase in the formation of autophagosomes and autophagic flux under well-fed conditions. Genetic analysis revealed that overexpression of Leon suppressed Atg1-induced cell death inDrosophila. Immunoblotting assays further showed a strong interaction between Leon/USP5 and the autophagy initiating kinase Atg1/ULK1. Depletion of Leon/USP5 led to increased levels of Atg1/ULK1. Our findings indicate that Leon/USP5 is an autophagic DUB that interacts with Atg1/ULK1, negatively regulating the autophagic process.
Storylines for unprecedented heatwaves based on ensemble boosting
Authors: Fischer E. M. , Beyerle U. , Bloin-Wibe L. , Gessner C. , Humphrey V. , Lehner F. , Pendergrass A. G. , Sippel S. , Zeder J. , Knutti R. 
Published: August 2023

AbstractRecent temperature extremes have shattered previously observed records, reaching intensities that were inconceivable before the events. Could the possibility of an event with such unprecedented intensity as the 2021 Pacific Northwest heatwave have been foreseen, based on climate model information available before the event? Could the scientific community have quantified its potential intensity based on the current generation of climate models? Here, we demonstrate how an ensemble boosting approach can be used to generate physically plausible storylines of a heatwave hotter than observed in the Pacific Northwest. We also show that heatwaves of much greater intensities than ever observed are possible in other locations like the Greater Chicago and Paris regions. In order to establish confidence in storylines of ‘black swan’-type events, different lines of evidence need to be combined along with process understanding to make this information robust and actionable for stakeholders.
Bat teeth illuminate the diversification of mammalian tooth classes
Authors: Sadier Alexa , Anthwal Neal , Krause Andrew L. , Dessalles Renaud , Lake Michael , Bentolila Laurent A. , Haase Robert , Nieves Natalie A. , Santana Sharlene E. , Sears Karen E. 
Published: August 2023

AbstractTooth classes are an innovation that has contributed to the evolutionary success of mammals. However, our understanding of the mechanisms by which tooth classes diversified remain limited. We use the evolutionary radiation of noctilionoid bats to show how the tooth developmental program evolved during the adaptation to new diet types. Combining morphological, developmental and mathematical modeling approaches, we demonstrate that tooth classes develop through independent developmental cascades that deviate from classical models. We show that the diversification of tooth number and size is driven by jaw growth rate modulation, explaining the rapid gain/loss of teeth in this clade. Finally, we mathematically model the successive appearance of tooth buds, supporting the hypothesis that growth acts as a key driver of the evolution of tooth number and size. Our work reveal how growth, by tinkering with reaction/diffusion processes, drives the diversification of tooth classes and other repeated structure during adaptive radiations.
TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation
Authors: Suzuki Miho M. , Iijima Kenta , Ogami Koichi , Shinjo Keiko , Murofushi Yoshiteru , Xie Jingqi , Wang Xuebing , Kitano Yotaro , Mamiya Akira , Kibe Yuji , Nishimura Tatsunori , Ohka Fumiharu , Saito Ryuta , Sato Shinya , Kobayashi Junya , Yao Ryoji , Miyata Kanjiro , Kataoka Kazunori , Suzuki Hiroshi I. , Kondo Yutaka 
Published: August 2023

AbstractOncogene-induced DNA replication stress (RS) and consequent pathogenic R-loop formation are known to impede S phase progression. Nonetheless, cancer cells continuously proliferate under such high-stressed conditions through incompletely understood mechanisms. Here, we report taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA), which is highly expressed in many types of cancers, as an important regulator of intrinsic R-loop in cancer cells. Under RS conditions, TUG1 is rapidly upregulated via activation of the ATR-CHK1 signaling pathway, interacts with RPA and DHX9, and engages in resolving R-loops at certain loci, particularly at the CA repeat microsatellite loci. Depletion of TUG1 leads to overabundant R-loops and enhanced RS, leading to substantial inhibition of tumor growth. Our data reveal a role of TUG1 as molecule important for resolving R-loop accumulation in cancer cells and suggest targeting TUG1 as a potent therapeutic approach for cancer treatment.
Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence
Authors: Lluch Aina , Latorre Jessica , Serena-Maione Angela , Espadas Isabel , Caballano-Infantes Estefanía , Moreno-Navarrete José M. , Oliveras-Cañellas Núria , Ricart Wifredo , Malagón María M. , Martin-Montalvo Alejandro , Birchmeier Walter , Szymanski Witold , Graumann Johannes , Gómez-Serrano María , Sommariva Elena , Fernández-Real José M. , Ortega Francisco J. 
Published: August 2023

AbstractPlakophilin-2 (PKP2) is a key component of desmosomes, which, when defective, is known to promote the fibro-fatty infiltration of heart muscle. Less attention has been given to its role in adipose tissue. We report here that levels of PKP2 steadily increase during fat cell differentiation, and are compromised if adipocytes are exposed to a pro-inflammatory milieu. Accordingly, expression of PKP2 in subcutaneous adipose tissue diminishes in patients with obesity, and normalizes upon mild-to-intense weight loss. We further show defective PKP2 in adipocytes to break cell cycle dynamics and yield premature senescence, a key rheostat for stress-induced adipose tissue dysfunction. Conversely, restoring PKP2 in inflamed adipocytes rewires E2F signaling towards the re-activation of cell cycle and decreased senescence. Our findings connect the expression of PKP2 in fat cells to the physiopathology of obesity, as well as uncover a previously unknown defect in cell cycle and adipocyte senescence due to impaired PKP2.
Demethylase-independent roles of LSD1 in regulating enhancers and cell fate transition
Authors: Zeng Cheng , Chen Jiwei , Cooke Emmalee W. , Subuddhi Arijita , Roodman Eliana T. , Chen Fei Xavier , Cao Kaixiang 
Published: August 2023

AbstractThe major enhancer regulator lysine-specific histone demethylase 1A (LSD1) is required for mammalian embryogenesis and is implicated in human congenital diseases and multiple types of cancer; however, the underlying mechanisms remain enigmatic. Here, we dissect the role of LSD1 and its demethylase activity in gene regulation and cell fate transition. Surprisingly, the catalytic inactivation of LSD1 has a mild impact on gene expression and cellular differentiation whereas the loss of LSD1 protein de-represses enhancers globally and impairs cell fate transition. LSD1 deletion increases H3K27ac levels and P300 occupancy at LSD1-targeted enhancers. The gain of H3K27ac catalyzed by P300/CBP, not the loss of CoREST complex components from chromatin, contributes to the transcription de-repression of LSD1 targets and differentiation defects caused by LSD1 loss. Together, our study demonstrates a demethylase-independent role of LSD1 in regulating enhancers and cell fate transition, providing insight into treating diseases driven by LSD1 mutations and misregulation.
Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy
Authors: Leung Elaine Lai-Han , Li Run-Ze , Fan Xing-Xing , Wang Lily Yan , Wang Yan , Jiang Zebo , Huang Jumin , Pan Hu-Dan , Fan Yue , Xu Hongmei , Wang Feng , Rui Haopeng , Wong Piu , Sumatoh Hermi , Fehlings Michael , Nardin Alessandra , Gavine Paul , Zhou Longen , Cao Yabing , Liu Liang 
Published: August 2023

AbstractResponse to immunotherapy widely varies among cancer patients and identification of parameters associating with favourable outcome is of great interest. Here we show longitudinal monitoring of peripheral blood samples of non-small cell lung cancer (NSCLC) patients undergoing anti-PD1 therapy by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines measurements. We find that higher proportions of circulating CD8+ and of CD8+CD101hiTIM3+ (CCT T) subsets significantly correlate with poor clinical response to immune therapy. Consistently, CD8+ T cells and CCT T cell frequencies remain low in most responders during the entire multi-cycle treatment regimen; and higher killer cell lectin-like receptor subfamily G, member 1 (KLRG1) expression in CCT T cells at baseline associates with prolonged progression free survival. Upon in vitro stimulation, CCT T cells of responders produce significantly higher levels of cytokines, including IL-1β, IL-2, IL-8, IL-22 and MCP-1, than of non-responders. Overall, our results provide insights into the longitudinal immunological landscape underpinning favourable response to immune checkpoint blockade therapy in lung cancer patients.
Direction-dependent dynamics of colloidal particle pairs and the Stokes-Einstein relation in quasi-two-dimensional fluids
Authors: Barbhuiya Noman Hanif , Yodh A. G. , Mishra Chandan K. 
Published: August 2023

AbstractHydrodynamic interactions are important for diverse fluids, especially those with low Reynolds number such as microbial and particle-laden suspensions, and proteins diffusing in membranes. Unfortunately, while far-field (asymptotic) hydrodynamic interactions are fully understood in two- and three-dimensions, near-field interactions are not, and thus our understanding of motions in dense fluid suspensions is still lacking. In this contribution, we experimentally explore the hydrodynamic correlations between particles in quasi-two-dimensional colloidal fluids in the near-field. Surprisingly, the measured displacement and relaxation of particle pairs in the body frame exhibit direction-dependent dynamics that can be connected quantitatively to the measured near-field hydrodynamic interactions. These findings, in turn, suggest a mechanism for how and when hydrodynamics can lead to a breakdown of the ubiquitous Stokes-Einstein relation (SER). We observe this breakdown, and we show that the direction-dependent breakdown of the SER is ameliorated along directions where hydrodynamic correlations are smallest. In total, the work uncovers significant ramifications of near-field hydrodynamics on transport and dynamic restructuring of fluids in two-dimensions.
A ferroptosis-targeting ceria anchored halloysite as orally drug delivery system for radiation colitis therapy
Authors: Feng Yue , Luo Xiang , Li Zichun , Fan Xinjuan , Wang Yiting , He Rong-Rong , Liu Mingxian 
Published: August 2023

AbstractRadiation colitis is the leading cause of diarrhea and hematochezia in pelvic radiotherapy patients. This work advances the pathogenesis of radiation colitis from the perspective of ferroptosis. An oral Pickering emulsion is stabilized with halloysite clay nanotubes to alleviate radiation colitis by inhibiting ferroptosis. Ceria nanozyme grown in situ on nanotubes can scavenge reactive oxygen species, and deferiprone was loaded into the lumen of nanotubes to relieve iron stress. These two strategies effectively inhibit lipid peroxidation and rescue ferroptosis in the intestinal microenvironment. The clay nanotubes play a critical role as either a medicine to alleviate colitis, a nanocarrier that targets the inflamed colon by electrostatic adsorption, or an interfacial stabilizer for emulsions. This ferroptosis-based strategy was effective in vitro and in vivo, providing a prospective candidate for radiotherapy protection via rational regulation of specific oxidative stress.
Structural insights into opposing actions of neurosteroids on GABAA receptors
Authors: Legesse Dagimhiwat H. , Fan Chen , Teng Jinfeng , Zhuang Yuxuan , Howard Rebecca J. , Noviello Colleen M. , Lindahl Erik , Hibbs Ryan E. 
Published: August 2023

Abstractγ-Aminobutyric acid type A (GABAA) receptors mediate fast inhibitory signaling in the brain and are targets of numerous drugs and endogenous neurosteroids. A subset of neurosteroids are GABAA receptor positive allosteric modulators; one of these, allopregnanolone, is the only drug approved specifically for treating postpartum depression. There is a consensus emerging from structural, physiological and photolabeling studies as to where positive modulators bind, but how they potentiate GABA activation remains unclear. Other neurosteroids are negative modulators of GABAA receptors, but their binding sites remain debated. Here we present structures of a synaptic GABAA receptor bound to allopregnanolone and two inhibitory sulfated neurosteroids. Allopregnanolone binds at the receptor-bilayer interface, in the consensus potentiator site. In contrast, inhibitory neurosteroids bind in the pore. MD simulations and electrophysiology support a mechanism by which allopregnanolone potentiates channel activity and suggest the dominant mechanism for sulfated neurosteroid inhibition is through pore block.
Acidification suppresses the natural capacity of soil microbiome to fight pathogenic Fusarium infections
Authors: Li Xiaogang , Chen Dele , Carrión Víctor J. , Revillini Daniel , Yin Shan , Dong Yuanhua , Zhang Taolin , Wang Xingxiang , Delgado-Baquerizo Manuel 
Published: August 2023

AbstractSoil-borne pathogens pose a major threat to food production worldwide, particularly under global change and with growing populations. Yet, we still know very little about how the soil microbiome regulates the abundance of soil pathogens and their impact on plant health. Here we combined field surveys with experiments to investigate the relationships of soil properties and the structure and function of the soil microbiome with contrasting plant health outcomes. We find that soil acidification largely impacts bacterial communities and reduces the capacity of soils to combat fungal pathogens. In vitro assays with microbiomes from acidified soils further highlight a declined ability to suppress Fusarium, a globally important plant pathogen. Similarly, when we inoculate healthy plants with an acidified soil microbiome, we show a greatly reduced capacity to prevent pathogen invasion. Finally, metagenome sequencing of the soil microbiome and untargeted metabolomics reveals a down regulation of genes associated with the synthesis of sulfur compounds and reduction of key traits related to sulfur metabolism in acidic soils. Our findings suggest that changes in the soil microbiome and disruption of specific microbial processes induced by soil acidification can play a critical role for plant health.
Topological soliton molecule in quasi 1D charge density wave
Authors: Im Taehwan , Song Sun Kyu , Park Jae Whan , Yeom Han Woong 
Published: August 2023

AbstractSoliton molecules, bound states of two solitons, can be important for the informatics using solitons and the quest for exotic particles in a wide range of physical systems from unconventional superconductors to nuclear matter and Higgs field, but have been observed only in temporal dimension for classical wave optical systems. Here, we identify a topological soliton molecule formed spatially in an electronic system, a quasi 1D charge density wave of indium atomic wires. This system is composed of two coupled Peierls chains, which are endowed with a Z4 topology and three distinct, right-chiral, left-chiral, and non-chiral, solitons. Our scanning tunneling microscopy measurements identify a bound state of right- and left-chiral solitons with distinct in-gap states and net zero phase shift. Our density functional theory calculations reveal the attractive interaction of these solitons and the hybridization of their electronic states. This result initiates the study of the interaction between solitons in electronic systems, which can provide novel manybody electronic states and extra data-handling capacity beyond the given soliton topology.
Novel insights into the role of long non-coding RNA in the human malaria parasite, Plasmodium falciparum
Authors: Batugedara Gayani , Lu Xueqing M. , Hristov Borislav , Abel Steven , Chahine Zeinab , Hollin Thomas , Williams Desiree , Wang Tina , Cort Anthony , Lenz Todd , Thompson Trevor A. , Prudhomme Jacques , Tripathi Abhai K. , Xu Guoyue , Cudini Juliana , Dogga Sunil , Lawniczak Mara , Noble William Stafford , Sinnis Photini , Le Roch Karine G. 
Published: August 2023

AbstractThe complex life cycle of Plasmodium falciparum requires coordinated gene expression regulation to allow host cell invasion, transmission, and immune evasion. Increasing evidence now suggests a major role for epigenetic mechanisms in gene expression in the parasite. In eukaryotes, many lncRNAs have been identified to be pivotal regulators of genome structure and gene expression. To investigate the regulatory roles of lncRNAs in P. falciparum we explore the intergenic lncRNA distribution in nuclear and cytoplasmic subcellular locations. Using nascent RNA expression profiles, we identify a total of 1768 lncRNAs, of which 718 (~41%) are novels in P. falciparum. The subcellular localization and stage-specific expression of several putative lncRNAs are validated using RNA-FISH. Additionally, the genome-wide occupancy of several candidate nuclear lncRNAs is explored using ChIRP. The results reveal that lncRNA occupancy sites are focal and sequence-specific with a particular enrichment for several parasite-specific gene families, including those involved in pathogenesis and sexual differentiation. Genomic and phenotypic analysis of one specific lncRNA demonstrate its importance in sexual differentiation and reproduction. Our findings bring a new level of insight into the role of lncRNAs in pathogenicity, gene regulation and sexual differentiation, opening new avenues for targeted therapeutic strategies against the deadly malaria parasite.
Convergent somatic evolution commences in utero in a germline ribosomopathy
Authors: Machado Heather E. , Øbro Nina F. , Williams Nicholas , Tan Shengjiang , Boukerrou Ahmed Z. , Davies Megan , Belmonte Miriam , Mitchell Emily , Baxter E. Joanna , Mende Nicole , Clay Anna , Ancliff Philip , Köglmeier Jutta , Killick Sally B. , Kulasekararaj Austin , Meyer Stefan , Laurenti Elisa , Campbell Peter J. , Kent David G. , Nangalia Jyoti , Warren Alan J. 
Published: August 2023

AbstractClonal tracking of cells using somatic mutations permits exploration of clonal dynamics in human disease. Here, we perform whole genome sequencing of 323 haematopoietic colonies from 10 individuals with the inherited ribosomopathy Shwachman-Diamond syndrome to reconstruct haematopoietic phylogenies. In ~30% of colonies, we identify mutually exclusive mutations in TP53, EIF6, RPL5, RPL22, PRPF8, plus chromosome 7 and 15 aberrations that increase SBDS and EFL1 gene dosage, respectively. Target gene mutations commence in utero, resulting in a profusion of clonal expansions, with only a few haematopoietic stem cell lineages (mean 8, range 1-24) contributing ~50% of haematopoietic colonies across 8 individuals (range 4-100% clonality) by young adulthood. Rapid clonal expansion during disease transformation is associated with biallelic TP53 mutations and increased mutation burden. Our study highlights how convergent somatic mutation of the p53-dependent nucleolar surveillance pathway offsets the deleterious effects of germline ribosomopathy but increases opportunity for TP53-mutated cancer evolution.