bluuebunny/crossref_metadata_2025 huggingface dataset:
The Irrational Health Beliefs Scale and Health Behaviors in a	Non-Clinical Population
Authors: Pitel Lukáš , Ballová Mikušková Eva
Published: March 2021

Abstract. To date, there has been inconclusive evidence on the predictive ability of health-related cognitive distortion, as measured by the Irrational Health Belief Scale (IHBS), regarding health behaviors (HBs). The aims of our study were to provide a validation of the Slovak translation of the IHBS and to assess the relationship of the IHBS with a wide range of HBs, as well as the predictive ability of the IHBS regarding HBs over and above other health-related psychological constructs. A total of 448 students attending mostly Slovak universities completed the IHBS, the Multidimensional Health Locus of Control Scale, the Big Five Inventory – 2, the Positive and Negative Affect Scale, and the Bratislava Health Behaviors Questionnaire. The internal consistency and temporal stability of the Slovak version of the IHBS were confirmed. The IHBS correlated moderately with medical adherence but was unrelated to substance use and an unhealthy diet. The association of cognitive distortion with the sum score of HBs was only weak, albeit statistically significant. The IHBS had weak but significant incremental power. However, two health locus of control dimensions as well as negative emotionality were more strongly related to HBs than cognitive distortion in that multivariate model.
Do Multi‐Model Ensembles Improve Reconstruction Skill in Paleoclimate Data Assimilation?
Authors: Parsons Luke A. , Amrhein Daniel E. , Sanchez Sara C. , Tardif Robert , Brennan M. Kathleen , Hakim Gregory J.
Published: March 2021

Reconstructing past climates remains a difficult task because pre‐instrumental observational networks are composed of geographically sparse and noisy paleoclimate proxy records that require statistical techniques to inform complete climate fields. Traditionally, instrumental or climate model statistical relationships are used to spread information from proxy measurements to other locations and to other climate variables. Here ensembles drawn from single climate models and from combinations of multiple climate models are used to reconstruct temperature variability over the last millennium in idealized experiments. We find that reconstructions derived from multi‐model ensembles produce lower error than reconstructions from single‐model ensembles when reconstructing independent model and instrumental data. Specifically, we find the largest decreases in error over regions far from proxy locations that are often associated with large uncertainties in model physics, such as mid‐ and high‐latitude ocean and sea‐ice regions. Furthermore, we find that multi‐model ensemble reconstructions outperform single‐model reconstructions that use covariance localization. We propose that multi‐model ensembles could be used to improve paleoclimate reconstructions in time periods beyond the last millennium and for climate variables other than air temperature, such as drought metrics or sea ice variables.
Jupiter’s Great Red Spot: Strong Interactions With Incoming Anticyclones in 2019
Authors: Sánchez‐Lavega A. , Anguiano‐Arteaga A. , Iñurrigarro P. , Garcia‐Melendo E. , Legarreta J. , Hueso R. , Sanz‐Requena J. F. , Pérez‐Hoyos S. , Mendikoa I. , Soria M. , Rojas J. F. , Andrés‐Carcasona M. , Prat‐Gasull A. , Ordoñez‐Extebarria I. , Rogers J. H. , Foster C. , Mizumoto S. , Casely A. , Hansen C. J. , Orton G. S. , Momary T. , Eichstädt G.
Published: March 2021

Jupiter’s Great Red Spot (GRS), a giant anticyclone, is the largest and longest‐lived of all the vortices observed in planetary atmospheres. During its history, the GRS has shrunk to half its size since 1879, and encountered many smaller anticyclones and other dynamical features that interacted in a complex way. In 2018–2020, while having a historically small size, its structure and even its survival appeared to be threatened when a series of anticyclones moving in from the east tore off large fragments of the red area and distorted its shape. In this work, we report observations of the dynamics of these interactions and show that as a result the GRS increased its internal rotation velocity, maintaining its vorticity but decreasing its visible area, and suffering a transient change in its otherwise steady 90‐day oscillation in longitude. From a radiative transfer analysis and numerical simulations of the dynamics we show that the interactions affected the upper cloud tops of the GRS. We argue that the intense vorticity of the GRS, together with its larger size and depth compared to the interacting vortices, guarantees its long lifetime.
Glimpsing the Ins and Outs of the Arctic Atmospheric Cauldron
Authors: Wendisch Manfred , Handorf D�rthe , Tegen Ina , Neggers Roel , Spreen Gunnar
Published: March 2021

Specially equipped aircraft will follow air masses into and out of the Arctic, observing their transformations and improving our knowledge of the Arctic climate and its global influence.
Evaluation of Sedimentary Organic Carbon Reactivity and Burial in the Eastern China Marginal Seas
Authors: Guo Jinqiang , Yuan Huamao , Song Jinming , Li Xuegang , Duan Liqin , Li Ning , Wang Yingxia
Published: March 2021

Dynamic physicochemical interactions along continental margins create complex organic carbon (OC) cycles that have a significant impact on the global climate but remain enigmatic; in particular, the OC burial behaviors in mud areas are still unclear. Herein, the molecular and bulk properties of sedimentary OC (SOC) were investigated in eastern China marginal seas to better understand the fate of SOC. The source discrimination analysis showed that SOC was mainly derived from indigenous production and experienced strong heterotrophic alteration, as indicated by low glucosamine/galactosamine ratios (<3) and the relatively high contribution of bacterial OC (∼25%). The South Yellow Sea mud area (SYSMA) and East China Sea mud area (ECSMA) both represented hot spots for SOC burial, but the SYSMA exhibited lower SOC reactivity than the ECSMA because of intense degradation in the water column. Although the net particulate OC deposition flux in the ECSMA was approximately 5 times that of the SYSMA, the SOC burial efficiencies (∼35%) of these two areas were similar due to the presence of cold water masses and cyclonic eddies in the SYSMA (which are beneficial for the storage of SOC) and the active remineralization driven by the priming effect and intense physical reworking in the ECSMA. As human disturbance and global climate change intensify, the role of distal mud areas (represented by the SYSMA) in SOC burial may become increasingly prominent, while the SOC burial in inner shelf mobile mud areas (such as the ECSMA) affected by large rivers may be significantly reduced.
Pediatric MDS and bone marrow failure-associated germline mutations in SAMD9 and SAMD9L impair multiple pathways in primary hematopoietic cells
Authors: Thomas Melvin E. , Abdelhamed Sherif , Hiltenbrand Ryan , Schwartz Jason R. , Sakurada Sadie Miki , Walsh Michael , Song Guangchun , Ma Jing , Pruett-Miller Shondra M. , Klco Jeffery M.
Published: March 2021

Pediatric myelodysplastic syndromes (MDS) are a heterogeneous disease group associated with impaired hematopoiesis, bone marrow hypocellularity, and frequently have deletions involving chromosome 7 (monosomy 7). We and others recently identified heterozygous germline mutations inSAMD9andSAMD9Lin children with monosomy 7 and MDS. We previously demonstrated an antiproliferative effect of these gene products in non-hematopoietic cells, which was exacerbated by their patient-associated mutations. Here, we used a lentiviral overexpression approach to assess the functional impact and underlying cellular processes of wild-type and mutantSAMD9orSAMD9Lin primary mouse or human hematopoietic stem and progenitor cells (HSPC). Using a combination of protein interactome analyses, transcriptional profiling, and functional validation, we show that SAMD9 and SAMD9L are multifunctional proteins that cause profound alterations in cell cycle, cell proliferation, and protein translation in HSPCs. Importantly, our molecular and functional studies also demonstrated that expression of these genes and their mutations leads to a cellular environment that promotes DNA damage repair defects and ultimately apoptosis in hematopoietic cells. This study provides novel functional insights into SAMD9 and SAMD9L and how their mutations can potentially alter hematopoietic function and lead to bone marrow hypocellularity, a hallmark of pediatric MDS.
The age of adult pilocytic astrocytoma cells
Authors: Voronina Natalia , Aichmüller Christian , Kolb Thorsten , Korshunov Andrey , Ryzhova Marina , Barnholtz-Sloan Jill , Cioffi Gino , Sill Martin , von Deimling Andreas , Pfister Stefan M. , Gronych Jan , Jones David T. W. , Frisén Jonas , Zapatka Marc , Ernst Aurélie
Published: March 2021

Adult pilocytic astrocytomas (PAs) have been regarded as indistinguishable from pediatric PAs in terms of genome-wide expression and methylation patterns. It has been unclear whether adult PAs arise early in life and remain asymptomatic until adulthood, or whether they develop during adulthood. We sought to determine the age and origin of adult human PAs using two types of “marks” in the genomic DNA. First, we analyzed the DNA methylation patterns of adult and pediatric PAs to distinguish between PAs of different anatomic locations (n = 257 PA and control brain tissues). Second, we measured the concentration of nuclear bomb test-derived 14C in genomic DNA (n = 14 cases), which indicates the time point of the formation of human cell populations. Our data suggest that adult and pediatric PAs developing in the infratentorial brain are closely related and potentially develop from precursor cells early in life, whereas supratentorial PAs might show age and location-specific differences.
The additive effect of late-life depression and olfactory dysfunction on the risk of dementia was mediated by hypersynchronization of the hippocampus/fusiform gyrus
Authors: Chen Ben , Zhong Xiaomei , Zhang Min , Mai Naikeng , Wu Zhangying , Chen Xinru , Peng Qi , Zhou Huarong , Wang Qiang , Yang Mingfeng , Zhang Si , Auber Lavinia Alberi , Croy Ilona , Hummel Thomas , Ning Yuping
Published: March 2021

Early detection of patients with late-life depression (LLD) with a high risk of developing dementia contributes to early intervention. Odor identification (OI) dysfunction serves as a marker for predicting dementia, but whether OI dysfunction increases the risk of dementia in LLD patients remains unclear. The present study aimed to explore the interactive effect of LLD and OI dysfunction on the risk of dementia and its underlying neuroimaging changes. One hundred and fifty-seven LLD patients and 101 normal controls were recruited, and data on their OI, cognition, activity of daily living (ADL), and resting-state functional magnetic resonance imaging were collected. Two × two factorial analyses were used to analyze the interactive effects of LLD and OI dysfunction on neuropsychological and neuroimaging abnormalities. Mediation analyses were used to explore whether abnormalities detected by neuroimaging mediated the the associations between OI and cognition/ADL. The results suggested that LLD and OI dysfunction exhibited additive effects on reduced ADL, global cognition and memory scores, as well as neuroimaging variables including (i) increased fractional amplitude of low-frequency fluctuation (fALFF) in the right orbitofrontal cortex and right precentral cortex, and (ii) increased regional homogeneity (ReHo) in the left hippocampus/fusiform gyrus, etc. In addition, these increased fALFF and ReHo values were associated with reduced neuropsychological scores (ADL, global cognition, memory, and language). Moreover, ReHo of the left hippocampus/fusiform gyrus completely mediated the relationship between OI and ADL, and partially mediated the relationship between OI and global cognition. Overall, mediated by the hypersynchronization of the left hippocampus/fusiform gyrus, OI dysfunction may increase the risk of dementia in LLD patients.
Decreased defensive reactivity to interoceptive threat after successful exposure-based psychotherapy in patients with panic disorder
Authors: Benke Christoph , Alius Manuela G. , Hamm Alfons O. , Pané-Farré Christiane A.
Published: March 2021

Panic disorder (PD) is characterized by a dysfunctional defensive responding to panic-related body symptoms that is assumed to contribute to the persistence of panic symptomatology. The present study aimed at examining whether this dysfunctional defensive reactivity to panic-related body symptoms would no longer be present following successful cognitive behavior therapy (CBT) but would persist when patients show insufficient symptom improvement. Therefore, in the present study, effects of CBT on reported symptoms and defensive response mobilization during interoceptive challenge were investigated using hyperventilation as a respiratory symptom provocation procedure. Changes in defensive mobilization to body symptoms in the course of CBT were investigated in patients with a primary diagnosis of PD with or without agoraphobia by applying a highly standardized hyperventilation task prior to and after a manual-based CBT (n = 38) or a waiting period (wait-list controls:n = 20). Defensive activation was indexed by the potentiation of the amygdala-dependent startle eyeblink response. All patients showed a pronounced defensive response mobilization to body symptoms at baseline. After treatment, no startle reflex potentiation was found in those patients who showed a clinically significant improvement. However, wait-list controls and treatment non-responders continued to show increased defensive responses to actually innocuous body symptoms after the treatment/waiting period. The present results indicate that the elimination of defensive reactivity to actually innocuous body symptoms might be a neurobiological correlate and indicator of successful CBT in patients with PD, which may help to monitor and optimize CBT outcomes.
Reduced SKP1 and CUL1 expression underlies increases in Cyclin E1 and chromosome instability in cellular precursors of high-grade serous ovarian cancer
Authors: Lepage Chloe Camille , Palmer Michaela Cora Lynn , Farrell Ally Catherina , Neudorf Nicole Marie , Lichtensztejn Zelda , Nachtigal Mark William , McManus Kirk James
Published: March 2021

Background

High-grade serous ovarian cancer (HGSOC) is the most common and lethal ovarian cancer histotype. Chromosome instability (CIN, an increased rate of chromosome gains and losses) is believed to play a fundamental role in the development and evolution of HGSOC. Importantly, overexpression of Cyclin E1 protein induces CIN, and genomic amplification of CCNE1 contributes to HGSOC pathogenesis in ~20% of patients. Cyclin E1 levels are normally regulated in a cell cycle-dependent manner by the SCF (SKP1–CUL1–FBOX) complex, an E3 ubiquitin ligase that includes the proteins SKP1 and CUL1. Conceptually, diminished SKP1 or CUL1 expression is predicted to underlie increases in Cyclin E1 levels and induce CIN.

Methods

This study employs fallopian tube secretory epithelial cell models to evaluate the impact diminished SKP1 or CUL1 expression has on Cyclin E1 and CIN in both short-term (siRNA) and long-term (CRISPR/Cas9) studies.

Results

Single-cell quantitative imaging microscopy approaches revealed changes in CIN-associated phenotypes and chromosome numbers and increased Cyclin E1 in response to diminished SKP1 or CUL1 expression.

Conclusions

These data identify SKP1 and CUL1 as novel CIN genes in HGSOC precursor cells that may drive early aetiological events contributing to HGSOC development.
Histone H2Bub1 deubiquitylation is essential for mouse development, but does not regulate global RNA polymerase II transcription
Authors: Wang Fang , El-Saafin Farrah , Ye Tao , Stierle Matthieu , Negroni Luc , Durik Matej , Fischer Veronique , Devys Didier , Vincent Stéphane D. , Tora László
Published: March 2021

Co-activator complexes dynamically deposit post-translational modifications (PTMs) on histones, or remove them, to regulate chromatin accessibility and/or to create/erase docking surfaces for proteins that recognize histone PTMs. SAGA (Spt-Ada-Gcn5 Acetyltransferase) is an evolutionary conserved multisubunit co-activator complex with modular organization. The deubiquitylation module (DUB) of mammalian SAGA complex is composed of the ubiquitin-specific protease 22 (USP22) and three adaptor proteins, ATXN7, ATXN7L3 and ENY2, which are all needed for the full activity of the USP22 enzyme to remove monoubiquitin (ub1) from histone H2B. Two additional USP22-related ubiquitin hydrolases (called USP27X or USP51) have been described to form alternative DUBs with ATXN7L3 and ENY2, which can also deubiquitylate H2Bub1. Here we report that USP22 and ATXN7L3 are essential for normal embryonic development of mice, however their requirements are not identical during this process, as Atxn7l3−/− embryos show developmental delay already at embryonic day (E) 7.5, while Usp22−/− embryos are normal at this stage, but die at E14.5. Global histone H2Bub1 levels were only slightly affected in Usp22 null embryos, in contrast H2Bub1 levels were strongly increased in Atxn7l3 null embryos and derived cell lines. Our transcriptomic analyses carried out from wild type and Atxn7l3−/− mouse embryonic stem cells (mESCs), or primary mouse embryonic fibroblasts (MEFs) suggest that the ATXN7L3-related DUB activity regulates only a subset of genes in both cell types. However, the gene sets and the extent of their deregulation were different in mESCs and MEFs. Interestingly, the strong increase of H2Bub1 levels observed in the Atxn7l3−/− mESCs, or Atxn7l3−/− MEFs, does not correlate with the modest changes in RNA Polymerase II (Pol II) occupancy and lack of changes in Pol II elongation observed in the two Atxn7l3−/− cellular systems. These observations together indicate that deubiquitylation of histone H2Bub1 does not directly regulate global Pol II transcription elongation.
Peroxisome-driven ether-linked phospholipids biosynthesis is essential for ferroptosis
Authors: Cui Weiwei , Liu Dong , Gu Wei , Chu Bo
Published: March 2021

It is well established that ferroptosis is primarily induced by peroxidation of long-chain poly-unsaturated fatty acid (PUFA) through nonenzymatic oxidation by free radicals or enzymatic stimulation of lipoxygenase. Although there is emerging evidence that long-chain saturated fatty acid (SFA) might be implicated in ferroptosis, it remains unclear whether and how SFA participates in the process of ferroptosis. Using endogenous metabolites and genome-wide CRISPR screening, we have identified FAR1 as a critical factor for SFA-mediated ferroptosis. FAR1 catalyzes the reduction of C16 or C18 saturated fatty acid to fatty alcohol, which is required for the synthesis of alkyl-ether lipids and plasmalogens. Inactivation of FAR1 diminishes SFA-dependent ferroptosis. Furthermore, FAR1-mediated ferroptosis is dependent on peroxisome-driven ether phospholipid biosynthesis. Strikingly, TMEM189, a newly identified gene which introduces vinyl-ether double bond into alkyl-ether lipids to generate plasmalogens abrogates FAR1-alkyl-ether lipids axis induced ferroptosis. Our study reveals a new FAR1-ether lipids-TMEM189 axis dependent ferroptosis pathway and suggests TMEM189 as a promising druggable target for anticancer therapy.
p97/VCP is highly expressed in the stem-like cells of breast cancer and controls cancer stemness partly through the unfolded protein response
Authors: Li Chuang , Huang Yongsheng , Fan Qianqian , Quan Hongyang , Dong Yeqing , Nie Meng , Wang Jiaqi , Xie Fucun , Ji Jiang , Zhou Lan , Zheng Zhi , Wang Lin
Published: March 2021

p97/VCP, an evolutionarily concerned ATPase, partakes in multiple cellular proteostatic processes, including the endoplasmic reticulum (ER)-associated protein degradation (ERAD). Elevated expression of p97 is common in many cancers and is often associated with poor survival. Here we report that the levels of p97 positively correlated with the histological grade, tumor size, and lymph node metastasis in breast cancers. We further examined p97 expression in the stem-like cancer cells or cancer stem cells (CSCs), a cell population that purportedly underscores cancer initiation, therapeutic resistance, and recurrence. We found that p97 was consistently at a higher level in the CD44+/CD24−, ALDH+, or PKH26+ CSC populations than the respective non-CSC populations in human breast cancer tissues and cancer cell lines and p97 expression also positively correlated with that of SOX2, another CSC marker. To assess the role of p97 in breast cancers, cancer proliferation, mammosphere, and orthotopic growth were analyzed. Similarly as p97 depletion, two pharmacological inhibitors, which targets the ER-associated p97 or globally inhibits p97’s ATPase activity, markedly reduced cancer growth and the CSC population. Importantly, depletion or inhibition of p97 greatly suppressed the proliferation of the ALDH+ CSCs and the CSC-enriched mammospheres, while exhibiting much less or insignificant inhibitory effects on the non-CSC cancer cells. Comparable phenotypes produced by blocking ERAD suggest that ER proteostasis is essential for the CSC integrity. Loss of p97 gravely activated the unfolded protein response (UPR) and modulated the expression of multiple stemness and pluripotency regulators, including C/EBPδ, c-MYC, SOX2, and SKP2, which collectively contributed to the demise of CSCs. In summary, p97 controls the breast CSC integrity through multiple targets, many of which directly affect cancer stemness and are induced by UPR activation. Our findings highlight the importance of p97 and ER proteostasis in CSC biology and anticancer therapy.
Rab26 suppresses migration and invasion of breast cancer cells through mediating autophagic degradation of phosphorylated Src
Authors: Liu Huiying , Zhou Yuxia , Qiu Hantian , Zhuang Ruijuan , Han Yang , Liu Xiaoqing , Qiu Xi , Wang Ziyan , Xu Liju , Tan Ran , Hong Wanjin , Wang Tuanlao
Published: March 2021

Rab proteins play crucial roles in membrane trafficking. Some Rab proteins are implicated in cancer development through regulating protein sorting or degradation. In this study, we found that the expression of Rab26 is suppressed in the aggressive breast cancer cells as compared to the levels in non-invasive breast cancer cells. Over-expression of Rab26 inhibits cell migration and invasion, while Rab26 knockdown significantly promotes the migration and invasion of breast cancer cells. Rab26 reduces focal adhesion association of Src kinase and induces endosomal translocation of Src. Further experiments revealed that Rab26 mediates the autophagic degradation of phosphorylated Src through interacting with ATG16L1, consequently, resulting in the suppression of the migration and invasion ability of breast cancer cells.
PEDF inhibits lymphatic metastasis of nasopharyngeal carcinoma as a new lymphangiogenesis inhibitor
Authors: Luo Chuanghua , Yin Haofan , Gao Tianxiao , Ma Caiqi , Liu Junxi , Zhang Ting , Xu Zumin , Wang Xi , Zhang Danrui , Qi Weiwei , Yang Zhonghan , Gao Guoquan , Yang Xia , Zhou Ti
Published: March 2021

Nasopharyngeal carcinoma (NPC) is one of the most malignant tumors in southern China and Asia, and lymph node metastasis is an important cause for treatment failure. Lymphangiogenesis is a crucial step in lymphatic metastasis of NPC, while little is known about lymphangiogenesis in NPC. Similar to angiogenesis, lymphangitic neovascularization is a process of balance between pro-lymphangiogenesis and anti-lymphangiogenesis factors, but there are few studies on endogenous lymphangiogenesis inhibitors. Pigment epithelium-derived factor (PEDF) is a well-known effective endogenous angiogenesis inhibitor. However, the relationship between PEDF and lymphangiogenesis remains unknown. Our present study reveals that PEDF is lowly expressed in human NPC tissues with poor prognosis and is negatively correlated with lymphatic vessel density (LVD). Consistently, PEDF inhibits lymphangiogenesis and lymphatic metastasis of NPC in vivo experiments. Mechanistically, PEDF inhibits the proliferation, migration, and tube formation of lymphatic endothelial cells and promotes cell apoptosis. On the other hand, PEDF reduces the expression and secretion of vascular endothelial growth factor C (VEGF-C) of NPC cells through the nuclear factor-κB (NF-κB) signaling pathway. Our findings indicate that PEDF plays a vital role in lymphatic metastasis by targeting both lymphatic endothelial cells and NPC cells, and PEDF may represent a novel therapeutic target for NPC.
Isolation and characterization of a covalent CeIV-Aryl complex with an anomalous 13C chemical shift
Authors: Panetti Grace B. , Sergentu Dumitru-Claudiu , Gau Michael R. , Carroll Patrick J. , Autschbach Jochen , Walsh Patrick J. , Schelter Eric J.
Published: March 2021

The synthesis of bona fide organometallic CeIVcomplexes is a formidable challenge given the typically oxidizing properties of the CeIVcation and reducing tendencies of carbanions. Herein, we report a pair of compounds comprising a CeIV − Carylbond [Li(THF)4][CeIV(κ2-ortho-oxa)(MBP)2] (3-THF) and [Li(DME)3][CeIV(κ2-ortho-oxa)(MBP)2] (3-DME),ortho-oxa = dihydro-dimethyl-2-[4-(trifluoromethyl)phenyl]-oxazolide, MBP2– = 2,2′-methylenebis(6-tert-butyl-4-methylphenolate), which exhibit CeIV − Carylbond lengths of 2.571(7) – 2.5806(19) Å and strongly-deshielded, CeIV − Cipso13C{1H} NMR resonances at 255.6 ppm. Computational analyses reveal the Ce contribution to the CeIV − Carylbond of3-THFis ~12%, indicating appreciable metal-ligand covalency. Computations also reproduce the characteristic13C{1H} resonance, and show a strong influence from spin-orbit coupling (SOC) effects on the chemical shift. The results demonstrate that SOC-driven deshielding is present for CeIV − Cipso13C{1H} resonances and not just for diamagnetic actinide compounds.
Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice
Authors: Bang Sangsu , Donnelly Christopher R. , Luo Xin , Toro-Moreno Maria , Tao Xueshu , Wang Zilong , Chandra Sharat , Bortsov Andrey V. , Derbyshire Emily R. , Ji Ru-Rong
Published: March 2021

GPR37 was discovered more than two decades ago, but its biological functions remain poorly understood. Here we report a protective role of GPR37 in multiple models of infection and sepsis. Mice lacking Gpr37 exhibited increased death and/or hypothermia following challenge by lipopolysaccharide (LPS), Listeria bacteria, and the mouse malaria parasite Plasmodium berghei. Sepsis induced by LPS and Listeria in wild-type mice is protected by artesunate (ARU) and neuroprotectin D1 (NPD1), but the protective actions of these agents are lost in Gpr37−/− mice. Notably, we found that ARU binds to GPR37 in macrophages and promotes phagocytosis and clearance of pathogens. Moreover, ablation of macrophages potentiated infection, sepsis, and their sequelae, whereas adoptive transfer of NPD1- or ARU-primed macrophages reduced infection, sepsis, and pain-like behaviors. Our findings reveal physiological actions of ARU in host cells by activating macrophages and suggest that GPR37 agonists may help to treat sepsis, bacterial infections, and malaria.
A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies
Authors: Wang Chunyan , van Haperen Rien , Gutiérrez-Álvarez Javier , Li Wentao , Okba Nisreen M. A. , Albulescu Irina , Widjaja Ivy , van Dieren Brenda , Fernandez-Delgado Raul , Sola Isabel , Hurdiss Daniel L. , Daramola Olalekan , Grosveld Frank , van Kuppeveld Frank J. M. , Haagmans Bart L. , Enjuanes Luis , Drabek Dubravka , Bosch Berend-Jan
Published: March 2021

The coronavirus spike glycoprotein, located on the virion surface, is the key mediator of cell entry and the focus for development of protective antibodies and vaccines. Structural studies show exposed sites on the spike trimer that might be targeted by antibodies with cross-species specificity. Here we isolated two human monoclonal antibodies from immunized humanized mice that display a remarkable cross-reactivity against distinct spike proteins of betacoronaviruses including SARS-CoV, SARS-CoV-2, MERS-CoV and the endemic human coronavirus HCoV-OC43. Both cross-reactive antibodies target the stem helix in the spike S2 fusion subunit which, in the prefusion conformation of trimeric spike, forms a surface exposed membrane-proximal helical bundle. Both antibodies block MERS-CoV infection in cells and provide protection to mice from lethal MERS-CoV challenge in prophylactic and/or therapeutic models. Our work highlights an immunogenic and vulnerable site on the betacoronavirus spike protein enabling elicitation of antibodies with unusual binding breadth.
Author Correction: Lkb1 suppresses amino acid-driven gluconeogenesis in the liver
Authors: Just Pierre-Alexandre , Charawi Sara , Denis Raphaël G. P. , Savall Mathilde , Traore Massiré , Foretz Marc , Bastu Sultan , Magassa Salimata , Senni Nadia , Sohier Pierre , Wursmer Maud , Vasseur-Cognet Mireille , Schmitt Alain , Le Gall Morgane , Leduc Marjorie , Guillonneau François , De Bandt Jean-Pascal , Mayeux Patrick , Romagnolo Béatrice , Luquet Serge , Bossard Pascale , Perret Christine
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22104-4
Author Correction: Metabolite signatures of diverse Camellia sinensis tea populations
Authors: Yu Xiaomin , Xiao Jiajing , Chen Si , Yu Yuan , Ma Jianqiang , Lin Yuzhen , Li Ruizi , Lin Jun , Fu Zhijun , Zhou Qiongqiong , Chao Qianlin , Chen Liang , Yang Zhenbiao , Liu Renyi
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22150-y
Bursting out: linking changes in nanotopography and biomechanical properties of biofilm-forming Escherichia coli to the T4 lytic cycle
Authors: Abraham Shiju , Kaufman Yair , Perreault François , Young Ry , Bar-Zeev Edo
Published: March 2021

The bacteriophage infection cycle has been extensively studied, yet little is known about the nanostructure and mechanical changes that lead to bacterial lysis. Here, atomic force microscopy was used to study in real time and in situ the impact of the canonical phage T4 on the nanotopography and biomechanics of irreversibly attached, biofilm-forming E. coli cells. The results show that in contrast to the lytic cycle in planktonic cells, which ends explosively, anchored cells that are in the process of forming a biofilm undergo a more gradual lysis, developing distinct nanoscale lesions (~300 nm in diameter) within the cell envelope. Furthermore, it is shown that the envelope rigidity and cell elasticity decrease (>50% and >40%, respectively) following T4 infection, a process likely linked to changes in the nanostructure of infected cells. These insights show that the well-established lytic pathway of planktonic cells may be significantly different from that of biofilm-forming cells. Elucidating the lysis paradigm of these cells may advance biofilm removal and phage therapeutics.
PRISMS-Fatigue computational framework for fatigue analysis in polycrystalline metals and alloys
Authors: Yaghoobi Mohammadreza , Stopka Krzysztof S. , Lakshmanan Aaditya , Sundararaghavan Veera , Allison John E. , McDowell David L.
Published: March 2021

The PRISMS-Fatigue open-source framework for simulation-based analysis of microstructural influences on fatigue resistance for polycrystalline metals and alloys is presented here. The framework uses the crystal plasticity finite element method as its microstructure analysis tool and provides a highly efficient, scalable, flexible, and easy-to-use ICME community platform. The PRISMS-Fatigue framework is linked to different open-source software to instantiate microstructures, compute the material response, and assess fatigue indicator parameters. The performance of PRISMS-Fatigue is benchmarked against a similar framework implemented using ABAQUS. Results indicate that the multilevel parallelism scheme of PRISMS-Fatigue is more efficient and scalable than ABAQUS for large-scale fatigue simulations. The performance and flexibility of this framework is demonstrated with various examples that assess the driving force for fatigue crack formation of microstructures with different crystallographic textures, grain morphologies, and grain numbers, and under different multiaxial strain states, strain magnitudes, and boundary conditions.
Structural and biochemical mechanisms of NLRP1 inhibition by DPP9
Authors: Huang Menghang , Zhang Xiaoxiao , Toh Gee Ann , Gong Qin , Wang Jia , Han Zhifu , Wu Bin , Zhong Franklin , Chai Jijie
Published: March 2021

Nucleotide-binding domain, leucine-rich repeat receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires autocleavage within its function-to-find domain (FIIND)1–7. In resting cells, the dipeptidyl peptidases DPP8 and DPP9 interact with the FIIND of NLRP1 and suppress spontaneous NLRP1 activation8,9; however, the mechanisms through which this occurs remain unknown. Here we present structural and biochemical evidence that full-length rat NLRP1 (rNLRP1) and rat DPP9 (rDPP9) form a 2:1 complex that contains an autoinhibited rNLRP1 molecule and an active UPA–CARD fragment of rNLRP1. The ZU5 domain is required not only for autoinhibition of rNLRP1 but also for assembly of the 2:1 complex. Formation of the complex prevents UPA-mediated higher-order oligomerization of UPA–CARD fragments and strengthens ZU5-mediated NLRP1 autoinhibition. Structure-guided biochemical and functional assays show that both NLRP1 binding and enzymatic activity are required for DPP9 to suppress NLRP1 in human cells. Together, our data reveal the mechanism of DPP9-mediated inhibition of NLRP1 and shed light on the activation of the NLRP1 inflammasome.
Identification of nodes influence based on global structure model in complex networks
Authors: Ullah Aman , Wang Bin , Sheng JinFang , Long Jun , Khan Nasrullah , Sun ZeJun
Published: March 2021

Identification of Influential nodes in complex networks is challenging due to the largely scaled data and network sizes, and frequently changing behaviors of the current topologies. Various application scenarios like disease transmission and immunization, software virus infection and disinfection, increased product exposure and rumor suppression, etc., are applicable domains in the corresponding networks where identification of influential nodes is crucial. Though a lot of approaches are proposed to address the challenges, most of the relevant research concentrates only on single and limited aspects of the problem. Therefore, we propose Global Structure Model (GSM) for influential nodes identification that considers self-influence as well as emphasizes on global influence of the node in the network. We applied GSM and utilized Susceptible Infected Recovered model to evaluate its efficiency. Moreover, various standard algorithms such as Betweenness Centrality, Profit Leader, H-Index, Closeness Centrality, Hyperlink Induced Topic Search, Improved K-shell Hybrid, Density Centrality, Extended Cluster Coefficient Ranking Measure, and Gravity Index Centrality are employed as baseline benchmarks to evaluate the performance of GSM. Similarly, we used seven real-world and two synthetic multi-typed complex networks along-with different well-known datasets for experiments. Results analysis indicates that GSM outperformed the baseline algorithms in identification of influential node(s).
Measurement of the sound velocity of shock compressed water
Authors: Shu Hua , Li Jiangtao , Tu Yucheng , Ye Junjian , Wang Junyue , Zhang Qili , Tian Huiru , Jia Guo , He Zhiyu , Zhang Fan , Xie Zhiyong , Huang Xiuguang , Pei Wenbin , Fu Sizu
Published: March 2021

The sound velocities of water in the Hugoniot states are investigated by laser shock compression of precompressed water in a diamond anvil cell. The obtained sound velocities in the off-Hugoniot region of liquid water at precompressed conditions are used to test the predictions of quantum molecular dynamics (QMD) simulations and the SESAME equation-of-state (EOS) library. It is found that the prediction of QMD simulations agrees with the experimental data while the prediction of SESAME EOS library underestimates the sound velocities probably due to its improper accounting for the ionization processes.
Catalytic hydrotreating of bio-oil and evaluation of main noxious emissions of gaseous phase
Authors: Doukeh Rami , Bombos Dorin , Bombos Mihaela , Oprescu Elena-Emilia , Dumitrascu Gheorghe , Vasilievici Gabriel , Calin Catalina
Published: March 2021

Bio-oil produced from biomass pyrolysis has the potential to become an alternative renewable fuel. However due to the high content of oxygenated compounds is unsuitable as transportation fuel. The objective of this work is to evaluate the catalytic activity of CoMo /γ-Al2O3-HMS in the hydrotreating process of biomass pyrolysis bio-oil. The prepared catalyst was characterized by different techniques (X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS)) analysis. The experiments were carried out in a flow fixed-bed reactor at the temperature range of 250–320 °C, pressure between 20–40 bar, and LHSV of 3 h-1. The results showed that at mild conditions of 320 °C and 40 bar, the catalyst is very active in the hydrotreating process leading to a decrease of total acid number of hydrotreated bio-oil with almost 89% and bio-oil conversion of 87.23%. In addition, in order to evaluate the harmful emissions resulted from combustion of gaseous phase obtained in the hydrotreating process a chemical modelling algorithm was developed.
MgO surface lattice phonons observation during interstellar ice transition
Authors: Chavarría-Sibaja A. , Marín-Sosa S. , Bolaños-Jiménez E. , Hernández-Calderón M. , Herrera-Sancho O. A.
Published: March 2021

Relevant information on the origins of the solar system and the early evolution of life itself can be derive from systematic and controlled exploration of water ice here on Earth. Therefore, over the last decades, a huge effort on experimental methodologies has been made to study the multiple crystal ice phases, which are observed outside our home–gravitational–potential. By employing (100)–oriented MgO lattice surface as a microcantilever sensor, we conducted the first ever study on the dynamics of the Structural Phase Transition at 185 K in water ice by means of coherent elastic scattering of electron diffraction. We estimate the amount of phonons caused by this transition applying precise quantum computing key tools, and resulting in a maximum value of 1.23 ± 0.02. Further applications of our microcantilever sensor were assessed using unambiguous mapping of the surface stress induced by the c($$4 \times 2$$

4
×
2

) → p($$3 \times 2$$

3
×
2

) Structural Phase Transition of the interstellar ice formulated on the Williamsom–Hall model. This development paves the way and thus establishes an efficient characterization tool of the surface mechanical strains of materials with potential applications arising from interstellar ice inclusive glaciers to the wide spectrum of solid–state physics.
IgGFc-binding protein in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study
Authors: Stranik Jaroslav , Kacerovsky Marian , Soucek Ondrej , Kolackova Martina , Musilova Ivana , Pliskova Lenka , Bolehovska Radka , Bostik Pavel , Matulova Jana , Jacobsson Bo , Andrys Ctirad
Published: March 2021

To determine the IgGFc-binding protein (FcgammaBP) concentration in amniotic and cervical fluids in preterm prelabor rupture of membranes (PPROM) and preterm labor with intact membranes (PTL) and to assess the diagnostic indices of FcgammaBP to predict intra-amniotic infection (the presence of both microbial invasion of the amniotic cavity and intra-amniotic inflammation). In this study, we included 170 and 79 women with PPROM and PTL, respectively. Paired cervical and amniotic fluid samples were obtained using a Dacron polyester swab and transabdominal amniocentesis, respectively. The FcgammaBP concentrations in the samples were assessed using an enzyme-linked immunosorbent assay. The presence of intra-amniotic infection was associated with elevated FcgammaBP concentrations in pregnancies with PPROM and PTL [PPROM—presence: 86 ng/mL vs. absence: 13 ng/mL,p < 0.0001, area under receiver operating characteristic curve (AUC) = 0.94; PTL—presence: 140 ng/mL vs. absence: 22 ng/mL,p < 0.0001, AUC = 0.86]. In cervical fluid, the concentrations of FcgammaBP were elevated in the presence of intra-amniotic infection in pregnancies with PPROM only (presence: 345 ng/mL vs. absence: 60 ng/mL,p < 0.0001, AUC = 0.93). FcgammaBP in amniotic fluid might be a marker of intra-amniotic infection in women with both PPROM and PTL However, in cervical fluid, it is only observed in women with PPROM.
Antibiotic tolerance is associated with a broad and complex transcriptional response in E. coli
Authors: Deter Heather S. , Hossain Tahmina , Butzin Nicholas C.
Published: March 2021

Antibiotic treatment kills a large portion of a population, while a small, tolerant subpopulation survives. Tolerant bacteria disrupt antibiotic efficacy and increase the likelihood that a population gains antibiotic resistance, a growing health concern. We examined how E. coli transcriptional networks changed in response to lethal ampicillin concentrations. We are the first to apply transcriptional regulatory network (TRN) analysis to antibiotic tolerance by leveraging existing knowledge and our transcriptional data. TRN analysis shows that gene expression changes specific to ampicillin treatment are likely caused by specific sigma and transcription factors typically regulated by proteolysis. These results demonstrate that to survive lethal concentration of ampicillin specific regulatory proteins change activity and cause a coordinated transcriptional response that leverages multiple gene systems.
Systematic differences in effect estimates between observational studies and randomized control trials in meta-analyses in nephrology
Authors: Kimachi Miho , Onishi Akira , Tajika Aran , Kimachi Kimihiko , Furukawa Toshi A.
Published: March 2021

The limited availability of randomized controlled trials (RCTs) in nephrology undermines causal inferences in meta-analyses. Systematic reviews of observational studies have grown more common under such circumstances. We conducted systematic reviews of all comparative observational studies in nephrology from 2006 to 2016 to assess the trends in the past decade. We then focused on the meta-analyses combining observational studies and RCTs to evaluate the systematic differences in effect estimates between study designs using two statistical methods: by estimating the ratio of odds ratios (ROR) of the pooled OR obtained from observational studies versus those from RCTs and by examining the discrepancies in their statistical significance. The number of systematic reviews of observational studies in nephrology had grown by 11.7-fold in the past decade. Among 56 records combining observational studies and RCTs, ROR suggested that the estimates between study designs agreed well (ROR 1.05, 95% confidence interval 0.90–1.23). However, almost half of the reviews led to discrepant interpretations in terms of statistical significance. In conclusion, the findings based on ROR might encourage researchers to justify the inclusion of observational studies in meta-analyses. However, caution is needed, as the interpretations based on statistical significance were less concordant than those based on ROR.
Extracellular vesicles from human airway basal cells respond to cigarette smoke extract and affect vascular endothelial cells
Authors: Saxena Ashish , Walters Matthew S. , Shieh Jae-Hung , Shen Ling-Bo , Gomi Kazunori , Downey Robert J. , Crystal Ronald G. , Moore Malcolm A. S.
Published: March 2021

The human airway epithelium lining the bronchial tree contains basal cells that proliferate, differentiate, and communicate with other components of their microenvironment. One method that cells use for intercellular communication involves the secretion of exosomes and other extracellular vesicles (EVs). We isolated exosome-enriched EVs that were produced from an immortalized human airway basal cell line (BCi-NS1.1) and found that their secretion is increased by exposure to cigarette smoke extract, suggesting that this stress stimulates release of EVs which could affect signaling to other cells. We have previously shown that primary human airway basal cells secrete vascular endothelial growth factor A (VEGFA) which can activate MAPK signaling cascades in endothelial cells via VEGF receptor–2 (VEGFR2). Here, we show that exposure of endothelial cells to exosome-enriched airway basal cell EVs promotes the survival of these cells and that this effect also involves VEGFR2 activation and is, at least in part, mediated by VEGFA present in the EVs. These observations demonstrate that EVs are involved in the intercellular signaling between airway basal cells and the endothelium which we previously reported. The downstream signaling pathways involved may be distinct and specific to the EVs, however, as increased phosphorylation of Akt, STAT3, p44/42 MAPK, and p38 MAPK was not seen following exposure of endothelial cells to airway basal cell EVs.
Publisher Correction: Floquet-engineered quantum walks
Authors: Katayama Haruna , Hatakenaka Noriyuki , Fujii Toshiyuki
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Potential drug-drug interactions of antiretrovirals and antimicrobials detected by three databases
Authors: Vivithanaporn Pornpun , Kongratanapasert Teetat , Suriyapakorn Bovornpat , Songkunlertchai Pichayut , Mongkonariyawong Patpicha , Limpikirati Patanachai K. , Khemawoot Phisit
Published: March 2021

Standard treatment for HIV infection involves a combination of antiretrovirals. Additionally, opportunistic infections in HIV infected patients require further antimicrobial medications that might cause drug-drug interactions (DDIs). The objective of this study was to to compare the recognition of DDIs between antiretrovirals and antimicrobials by three proprietary databases and evaluate their concordance. 114 items of antiretrovirals and antimicrobials from the National List of Essential Medicines of Thailand 2018 were used in the study. However, 21 items were not recognised by Micromedex, Drugs.com, and Liverpool HIV interactions. Only 93 items were available for the detection of potential DDIs by the three databases. Potential DDIs detected from the three databases included 292 pairs. Liverpool showed the highest number of DDIs with 285 pairs compared with 259 pairs by drugs.com and 133 pairs by Micromedex. Regarding the severity classifications, Liverpool reported 10% Contraindicated; Micromedex reported 14% contraindicated and 59% major; Drugs.com reported 21% major. The Fleiss’ kappa agreements were fair to poor among the three databases, higher agreement was observed for DDIs classified as severe. This study highlights the need to harmonize the evaluation and interpretation of DDI risk in order to produce standardized information to support prescribers.