bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agreement of Analytical and Simulation‐Based Estimates of the Required Land Depth in Climate Models
Authors: Steinert N. J. , González‐Rouco J. F. , Melo Aguilar C. A. , García Pereira F. , García‐Bustamante E. , de Vrese P. , Alexeev V. , Jungclaus J. H. , Lorenz S. J. , Hagemann S. 
Published: September 2021

AbstractPrevious analytical and simulation‐based analyses suggest that deeper land surface models are needed to realistically simulate the terrestrial thermal state in climate models, with implications for land‐atmosphere interactions. Analytical approaches mainly focused on the subsurface propagation of harmonics such as the annual temperature signal, and a direct comparison with climate‐change model output has been elusive. This study addresses the propagation of a harmonic pulse fitted to represent the timescale and amplitude of anthropogenic warming. Its comparison to land model simulations with stepwise increased bottom boundary depth leads to an agreement between the simulation‐based and analytical frameworks for long‐term climate trends. Any depth increase gradually decreases the relative error in the subsurface thermodynamics, and a minimum depth of 170 m is recommended to simulate the ground climate adequately. The approach provides an accurate estimate of the required land‐model depth for climate‐change simulations and assesses the relative bias in insufficiently deep land models.
Climatology of Cloud‐Top Radiative Cooling in Marine Shallow Clouds
Authors: Zheng Youtong , Zhu Yannian , Rosenfeld Daniel , Li Zhanqing 
Published: September 2021

AbstractA one‐year’s worth of near‐global marine shallow single‐layer cloud top radiative cooling (CTRC) is derived from a radiative transfer model with inputs from the satellite cloud retrievals and reanalysis sounding. The mean cloud top radiative flux divergence is 61 Wm−2, decomposed into the longwave and shortwave components of 73 and −11 W m−2, respectively. Equatorward of 30°N/S, the CTRC is largely a reflection of free‐atmospheric specific humidity distribution: a dry atmosphere enhances CTRC by reducing downward thermal radiation. Consequently, the cooling minimizes in the “wet” tropics and maximizes in the “dry” eastern subtropics. Poleward of 30°N/S, the CTRC decreases slightly due to the colder clouds that emit less effectively. The CTRC exhibits distinctive seasonal cycles with stronger cooling in the winter and has amplitudes of order 10–20 Wm−2 in stratocumulus‐rich regions. The datasets were used to train a machine‐learning model that substantially speeds up the retrieval.
Mammatus‐Like Echo Structures Along the Base of Upper‐Tropospheric Outflow‐Layer Clouds of Typhoons Observed by Cloud Radar
Authors: Ohigashi Tadayasu , Tsuboki Kazuhisa , Shinoda Taro , Minda Haruya , Kyushima Moeto , Yamada Hiroyuki , Iwai Hironori 
Published: September 2021

AbstractUpper‐tropospheric clouds in the outflow layer of typhoons can affect the track of typhoons (tropical cyclones) through radiation effects. In this study, the microstructure of the outflow‐layer clouds of several typhoons was examined. Cloud radar observations of three typhoons around Japan revealed numerous protuberances in echoes along the base of the upper‐level clouds, which are referred to as mammatus‐like echoes. The horizontal and vertical scales of these mammatus‐like echoes were 0.5–3.0 and 0.3–1.5 km, respectively. Vertical observations revealed downward (upward) Doppler velocities in (between) the hanging echo regions. Upward and downward velocity maxima were estimated at 3 m s−1 around the mammatus‐like echoes. Neutral stratification developed in the dry layer beneath the cloud base in which the mammatus‐like echoes formed. These mammatus‐like structures may promote mixing along the cloud base that contributes to dissipation of the outflow‐layer clouds.
The Influence of Ocean Topography on the Upwelling of Carbon in the Southern Ocean
Authors: Brady Riley X. , Maltrud Mathew E. , Wolfram Phillip J. , Drake Henri F. , Lovenduski Nicole S. 
Published: September 2021

AbstractThe physical circulation of the Southern Ocean sets the surface concentration and thus air‐sea exchange of . However, we have a limited understanding of the three‐dimensional circulation that brings deep carbon‐rich waters to the surface. Here, we introduce and analyze a novel high‐resolution ocean model simulation with active biogeochemistry and online Lagrangian particle tracking. We focus our attention on a subset of particles with high dissolved inorganic carbon (DIC) that originate below 1,000 m and eventually upwell into the near‐surface layer (upper 200 m). We find that 71% of the DIC‐enriched water upwelling across 1,000 m is concentrated near topographic features, which occupy just 33% of the Antarctic Circumpolar Current. Once particles upwell to the near‐surface layer, they exhibit relatively uniform levels and DIC decorrelation timescales, regardless of their origin. Our results show that Southern Ocean bathymetry plays a key role in delivering carbon‐rich waters to the surface.
Tenascin-C expression in the lymph node pre-metastatic niche in muscle-invasive bladder cancer
Authors: Silvers Christopher R. , Messing Edward M. , Miyamoto Hiroshi , Lee Yi-Fen 
Published: September 2021

Abstract
Background
Markers of stromal activation at future metastatic sites may have prognostic value and may allow clinicians to identify and abolish the pre-metastatic niche to prevent metastasis. In this study, we evaluate tenascin-C as a marker of pre-metastatic niche formation in bladder cancer patient lymph nodes.

Methods
Tenascin-C expression in benign lymph nodes was compared between metastatic (n = 20) and non-metastatic (n = 27) patients with muscle-invasive bladder cancer. Urinary extracellular vesicle (EV) cytokine levels were measured with an antibody array to examine potential correlation with lymph node inflammation. The ability of bladder cancer EVs to activate primary bladder fibroblasts was assessed in vitro.

Results
Lymph node tenascin-C expression was elevated in metastatic patients vs. non-metastatic patients, and high expression was associated with worse survival. Urinary EVs contained four cytokines that were positively correlated with lymph node tenascin-C expression. Bladder cancer EVs induced tenascin-C expression in fibroblasts in an NF-κB-dependent manner.

Conclusions
Tenascin-C expression in regional lymph nodes may be a good predictor of bladder cancer metastasis and an appropriate imaging target. It may be possible to interrupt pre-metastatic niche formation by targeting EV-borne tumour cytokines or by targeting tenascin-C directly.
The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness and radiotherapy resistance in glioblastoma
Authors: Ahmadov Ulvi , Picard Daniel , Bartl Jasmin , Silginer Manuela , Trajkovic-Arsic Marija , Qin Nan , Blümel Lena , Wolter Marietta , Lim Jonathan K. M. , Pauck David , Winkelkotte Alina Marie , Melcher Marlen , Langini Maike , Marquardt Viktoria , Sander Felix , Stefanski Anja , Steltgens Sascha , Hassiepen Christina , Kaufhold Anna , Meyer Frauke-Dorothee , Seibt Annette , Kleinesudeik Lara , Hain Anika , Münk Carsten , Knobbe-Thomsen Christiane Brigitte , Schramm Alexander , Fischer Ute , Leprivier Gabriel , Stühler Kai , Fulda Simone , Siveke Jens T. , Distelmaier Felix , Borkhardt Arndt , Weller Michael , Roth Patrick , Reifenberger Guido , Remke Marc 
Published: September 2021

AbstractGlioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could potentially serve as novel biomarkers. The clinical significance ofHOXATranscript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was determined by analyzingHOTAIRM1in multiple glioblastoma gene expression data sets for associations with prognosis, as well as, IDH mutation andMGMTpromoter methylation status. Finally, the role ofHOTAIRM1in glioblastoma biology and radiotherapy resistance was characterized in vitro and in vivo. We identifiedHOTAIRM1as a candidate lncRNA whose up-regulation is significantly associated with shorter survival of glioblastoma patients, independent from IDH mutation andMGMTpromoter methylation. Glioblastoma cell line models uniformly showed reduced cell viability, decreased invasive growth and diminished colony formation capacity uponHOTAIRM1down-regulation. Integrated proteogenomic analyses revealed impaired mitochondrial function and determination of reactive oxygen species (ROS) levels confirmed increased ROS levels uponHOTAIRM1knock-down.HOTAIRM1knock-down decreased expression of transglutaminase 2 (TGM2), a candidate protein implicated in mitochondrial function, and knock-down ofTGM2mimicked the phenotype ofHOTAIRM1down-regulation in glioblastoma cells. Moreover,HOTAIRM1modulates radiosensitivity of glioblastoma cells both in vitro and in vivo. Our data support a role forHOTAIRM1as a driver of biological aggressiveness, radioresistance and poor outcome in glioblastoma. TargetingHOTAIRM1may be a promising new therapeutic approach.
Inhibition of nuclear receptor RORα attenuates cartilage damage in osteoarthritis by modulating IL-6/STAT3 pathway
Authors: Liang Tongzhou , Chen Taiqiu , Qiu Jincheng , Gao Wenjie , Qiu Xianjian , Zhu Yuanxin , Wang Xudong , Chen Yanbo , Zhou Hang , Deng Zhihuai , Li Pengfei , Xu Caixia , Peng Yan , Liang Anjing , Su Peiqiang , Gao Bo , Huang Dongsheng 
Published: September 2021

AbstractOsteoarthritis (OA) is characterized by cartilage destruction, chronic inflammation, and local pain. Evidence showed that retinoic acid receptor-related orphan receptor-α (RORα) is crucial in cartilage development and OA pathogenesis. Here, we investigated the role and molecular mechanism of RORα, an important member of the nuclear receptor family, in regulating the development of OA pathologic features. Investigation into clinical cartilage specimens showed that RORα expression level is positively correlated with the severity of OA and cartilage damage. In an in vivo OA model induced by anterior crucial ligament transaction, intra-articular injection of si-Rora adenovirus reversed the cartilage damage. The expression of cartilage matrix components type II collagen and aggrecan were elevated upon RORα blockade. RNA-seq data suggested that the IL-6/STAT3 pathway is significantly downregulated, manifesting the reduced expression level of both IL-6 and phosphorylated STAT3. RORα exerted its effect on IL-6/STAT3 signaling in two different ways, including interaction with STAT3 and IL-6 promoter. Taken together, our findings indicated the pivotal role of the RORα/IL-6/STAT3 axis in OA progression and confirmed that RORα blockade improved the matrix catabolism in OA chondrocytes. These results may provide a potential treatment target in OA therapy.
Signaling through TLR5 mitigates lethal radiation damage by neutrophil-dependent release of MMP-9
Authors: Brackett Craig M. , Greene Kellee F. , Aldrich Alyssa R. , Trageser Nicholas H. , Pal Srabani , Molodtsov Ivan , Kandar Bojidar M. , Burdelya Lyudmila G. , Abrams Scott I. , Gudkov Andrei V. 
Published: September 2021

AbstractAcute radiation syndrome (ARS) is a major cause of lethality following radiation disasters. A TLR5 agonist, entolimod, is among the most powerful experimental radiation countermeasures and shows efficacy in rodents and non-human primates as a prophylactic (radioprotection) and treatment (radiomitigation) modality. While the prophylactic activity of entolimod has been connected to the suppression of radiation-induced apoptosis, the mechanism by which entolimod functions as a radiomitigator remains poorly understood. Uncovering this mechanism has significant and broad-reaching implications for the clinical development and improvement of TLR5 agonists for use as an effective radiation countermeasure in scenarios of mass casualty resulting from accidental exposure to ionizing radiation. Here, we demonstrate that in contrast to radioprotection, neutrophils are essential for the radiomitigative activity of entolimod in a mouse model of lethal ARS. Neutrophils express functional TLR5 and rapidly exit the bone marrow (BM), accumulate in solid tissues, and release MMP-9 following TLR5 stimulation which is accompanied by an increase in the number of active hematopoietic pluripotent precursors (HPPs) in the BM. Importantly, recombinant MMP-9 by itself has radiomitigative activity and, in the absence of neutrophils, accelerates the recovery of the hematopoietic system. Unveiling this novel TLR5-neutrophil-MMP-9 axis of radiomitigation opens new opportunities for the development of efficacious radiation countermeasures to treat ARS following accidental radiation disasters.
Superlubric polycrystalline graphene interfaces
Authors: Gao Xiang , Ouyang Wengen , Urbakh Michael , Hod Oded 
Published: September 2021

AbstractThe effects of corrugated grain boundaries on the frictional properties of extended planar graphitic contacts incorporating a polycrystalline surface are investigated via molecular dynamics simulations. The kinetic friction is found to be dominated by shear induced buckling and unbuckling of corrugated grain boundary dislocations, leading to a nonmonotonic behavior of the friction with normal load and temperature. The underlying mechanism involves two effects, where an increase of dislocation buckling probability competes with a decrease of the dissipated energy per buckling event. These effects are well captured by a phenomenological two-state model, that allows for characterizing the tribological properties of any large-scale polycrystalline layered interface, while circumventing the need for demanding atomistic simulations. The resulting negative differential friction coefficients obtained in the high-load regime can reduce the expected linear scaling of grain-boundary friction with surface area and restore structural superlubricity at increasing length-scales.
Assembly defects of human tRNA splicing endonuclease contribute to impaired pre-tRNA processing in pontocerebellar hypoplasia
Authors: Sekulovski Samoil , Devant Pascal , Panizza Silvia , Gogakos Tasos , Pitiriciu Anda , Heitmeier Katharina , Ramsay Ewan Phillip , Barth Marie , Schmidt Carla , Tuschl Thomas , Baas Frank , Weitzer Stefan , Martinez Javier , Trowitzsch Simon 
Published: September 2021

AbstractIntrons of human transfer RNA precursors (pre-tRNAs) are excised by the tRNA splicing endonuclease TSEN in complex with the RNA kinase CLP1. Mutations in TSEN/CLP1 occur in patients with pontocerebellar hypoplasia (PCH), however, their role in the disease is unclear. Here, we show that intron excision is catalyzed by tetrameric TSEN assembled from inactive heterodimers independently of CLP1. Splice site recognition involves the mature domain and the anticodon-intron base pair of pre-tRNAs. The 2.1-Å resolution X-ray crystal structure of a TSEN15–34 heterodimer and differential scanning fluorimetry analyses show that PCH mutations cause thermal destabilization. While endonuclease activity in recombinant mutant TSEN is unaltered, we observe assembly defects and reduced pre-tRNA cleavage activity resulting in an imbalanced pre-tRNA pool in PCH patient-derived fibroblasts. Our work defines the molecular principles of intron excision in humans and provides evidence that modulation of TSEN stability may contribute to PCH phenotypes.
Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration
Authors: Law Ah-Lai , Jalal Shamsinar , Pallett Tommy , Mosis Fuad , Guni Ahmad , Brayford Simon , Yolland Lawrence , Marcotti Stefania , Levitt James A. , Poland Simon P. , Rowe-Sampson Maia , Jandke Anett , Köchl Robert , Pula Giordano , Ameer-Beg Simon M. , Stramer Brian Marc , Krause Matthias 
Published: September 2021

AbstractCell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. Here we identify Nance-Horan Syndrome-like 1 protein (NHSL1) as a direct binding partner of the Scar/WAVE complex, which co-localise at protruding lamellipodia. This interaction is mediated by the Abi SH3 domain and two binding sites in NHSL1. Furthermore, active Rac binds to NHSL1 at two regions that mediate leading edge targeting of NHSL1. Surprisingly, NHSL1 inhibits cell migration through its interaction with the Scar/WAVE complex. Mechanistically, NHSL1 may reduce cell migration efficiency by impeding Arp2/3 activity, as measured in cells using a Arp2/3 FRET-FLIM biosensor, resulting in reduced F-actin density of lamellipodia, and consequently impairing the stability of lamellipodia protrusions.
Design principles of collateral sensitivity-based dosing strategies
Authors: Aulin Linda B. S. , Liakopoulos Apostolos , van der Graaf Piet H. , Rozen Daniel E. , van Hasselt J. G. Coen 
Published: September 2021

AbstractCollateral sensitivity (CS)-based antibiotic treatments, where increased resistance to one antibiotic leads to increased sensitivity to a second antibiotic, may have the potential to limit the emergence of antimicrobial resistance. However, it remains unclear how to best design CS-based treatment schedules. To address this problem, we use mathematical modelling to study the effects of pathogen- and drug-specific characteristics for different treatment designs on bacterial population dynamics and resistance evolution. We confirm that simultaneous and one-day cycling treatments could supress resistance in the presence of CS. We show that the efficacy of CS-based cycling therapies depends critically on the order of drug administration. Finally, we find that reciprocal CS is not essential to suppress resistance, a result that significantly broadens treatment options given the ubiquity of one-way CS in pathogens. Overall, our analyses identify key design principles of CS-based treatment strategies and provide guidance to develop treatment schedules to suppress resistance.
Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion
Authors: Okumura Shintaro , Konishi Yusuke , Narukawa Megumi , Sugiura Yuki , Yoshimoto Shin , Arai Yuriko , Sato Shintaro , Yoshida Yasuo , Tsuji Shunya , Uemura Ken , Wakita Masahiro , Matsudaira Tatsuyuki , Matsumoto Tomonori , Kawamoto Shimpei , Takahashi Akiko , Itatani Yoshiro , Miki Hiroaki , Takamatsu Manabu , Obama Kazutaka , Takeuchi Kengo , Suematsu Makoto , Ohtani Naoko , Fukunaga Yosuke , Ueno Masashi , Sakai Yoshiharu , Nagayama Satoshi , Hara Eiji 
Published: September 2021

AbstractEmerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate. Notably, the invasion of these bacteria is observed in the CRC tissues, coinciding with the elevation of butyrate levels and signs of senescence-associated inflammatory phenotypes. Moreover, although the administration of these bacteria into ApcΔ14/+ mice accelerate the onset of colorectal tumours, this is not the case when bacterial butyrate-synthesis genes are disrupted. These results suggest a causal relationship between Porphyromonas species overgrowth and colorectal tumourigenesis which may be due to butyrate-induced senescence.
Multi-species single-cell transcriptomic analysis of ocular compartment regulons
Authors: Gautam Pradeep , Hamashima Kiyofumi , Chen Ying , Zeng Yingying , Makovoz Bar , Parikh Bhav Harshad , Lee Hsin Yee , Lau Katherine Anne , Su Xinyi , Wong Raymond C. B. , Chan Woon-Khiong , Li Hu , Blenkinsop Timothy A. , Loh Yuin-Han 
Published: September 2021

AbstractThe retina is a widely profiled tissue in multiple species by single-cell RNA sequencing studies. However, integrative research of the retina across species is lacking. Here, we construct the first single-cell atlas of the human and porcine ocular compartments and study inter-species differences in the retina. In addition to that, we identify putative adult stem cells present in the iris tissue. We also create a disease map of genes involved in eye disorders across compartments of the eye. Furthermore, we probe the regulons of different cell populations, which include transcription factors and receptor-ligand interactions and reveal unique directional signalling between ocular cell types. In addition, we study conservation of regulons across vertebrates and zebrafish to identify common core factors. Here, we show perturbation of KLF7 gene expression during retinal ganglion cells differentiation and conclude that it plays a significant role in the maturation of retinal ganglion cells.
Persistence of plant-mediated microbial soil legacy effects in soil and inside roots
Authors: Hannula S. Emilia , Heinen Robin , Huberty Martine , Steinauer Katja , De Long Jonathan R. , Jongen Renske , Bezemer T. Martijn 
Published: September 2021

AbstractPlant-soil feedbacks are shaped by microbial legacies that plants leave in the soil. We tested the persistence of these legacies after subsequent colonization by the same or other plant species using 6 typical grassland plant species. Soil fungal legacies were detectable for months, but the current plant effect on fungi amplified in time. By contrast, in bacterial communities, legacies faded away rapidly and bacteria communities were influenced strongly by the current plant. However, both fungal and bacterial legacies were conserved inside the roots of the current plant species and their composition significantly correlated with plant growth. Hence, microbial soil legacies present at the time of plant establishment play a vital role in shaping plant growth even when these legacies have faded away in the soil due the growth of the current plant species. We conclude that soil microbiome legacies are reversible and versatile, but that they can create plant-soil feedbacks via altering the endophytic community acquired during early ontogeny.
Strong intrinsic room-temperature ferromagnetism in freestanding non-van der Waals ultrathin 2D crystals
Authors: Wu Hao , Zhang Wenfeng , Yang Li , Wang Jun , Li Jie , Li Luying , Gao Yihua , Zhang Liang , Du Juan , Shu Haibo , Chang Haixin 
Published: September 2021

AbstractControl of ferromagnetism is of critical importance for a variety of proposed spintronic and topological quantum technologies. Inducing long-range ferromagnetic order in ultrathin 2D crystals will provide more functional possibility to combine their unique electronic, optical and mechanical properties to develop new multifunctional coupled applications. Recently discovered intrinsic 2D ferromagnetic crystals such as Cr2Ge2Te6, CrI3 and Fe3GeTe2 are intrinsically ferromagnetic only below room temperature, mostly far below room temperature (Curie temperature, ~20–207 K). Here we develop a scalable method to prepare freestanding non-van der Waals ultrathin 2D crystals down to mono- and few unit cells (UC) and report unexpected strong, intrinsic, ambient-air-robust, room-temperature ferromagnetism with TC up to ~367 K in freestanding non-van der Waals 2D CrTe crystals. Freestanding 2D CrTe crystals show comparable or better ferromagnetic properties to widely-used Fe, Co, Ni and BaFe12O19, promising as new platforms for room-temperature intrinsically-ferromagnetic 2D crystals and integrated 2D devices.