bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution and Preservation of Root‐ and Shoot‐Derived Carbon Components in Soils Across the Chinese‐Mongolian Grasslands
Authors: Ma Tian , Dai Guohua , Zhu Shanshan , Chen Dima , Chen Litong , Lü Xiaotao , Wang Xiaobo , Zhu Juntao , Zhang Yangjian , Ma Wenhong , He Jin‐Sheng , Bai Yongfei , Han Xingguo , Feng Xiaojuan 
Published: February 2019

AbstractThe relative contribution of roots versus shoots to soil organic carbon (SOC) is a long‐debated topic related to soil carbon formation and dynamics. However, the variation of root‐ and shoot‐derived carbon in natural soils remains poorly constrained due to limited tools to separate them. Here we overcome the difficulty by analyzing biomarkers for root (suberin) and shoot (cutin) in grassland soils spanning >7,000 km on the Qinghai‐Tibetan and Mongolian Plateaus. Coupled with a comprehensive list of climatic, edaphic, and vegetation variables, we assess their inputs, distribution, and preservation patterns. We find that while suberin was a root‐specific tracer, cutin biomarkers that occurred only in trace amount in roots also had a minor but nonnegligible contribution from belowground sources due to the massive root mass in the alpine grasslands. Both components had higher SOC‐normalized concentrations in the alpine than temperate grasslands, along with a higher preservation percentage against net primary productivity and a lower degradation parameter, suggesting a better preservation of these plant‐derived lipid components in the alpine region. Moreover, while cutin and suberin abundances were affected by plant inputs and other SOC constituents, the root mass normalized incorporation efficiency of suberin was only positively correlated to SOC in both regions with a steeper slope in the alpine grasslands and also negatively correlated to root mass in the alpine soils. These results imply that root carbon incorporation is sensitive to environmental variations in the cold region, suggesting potentially more dynamic alterations to root carbon sequestration with environmental changes.
Thermomechanical Implications of Sediment Transport for the Architecture and Evolution of Continental Rifts and Margins
Authors: Andrés‐Martínez Miguel , Pérez‐Gussinyé Marta , Armitage John , Morgan Jason P. 
Published: February 2019

AbstractErosion and deposition redistribute mass as a continental rift evolves, which modifies crustal loads and influences subsequent deformation. Surface processes therefore impact both the architecture and the evolution of passive margins. Here we use coupled numerical models to explore the interactions between the surface, crust, and lithosphere. This interaction is primarily sensitive to the efficiency of the surface processes in transporting mass from source to sink. If transport is efficient, there are two possible outcomes: (1) Faulting within the zone of extension is longer lived and has larger offsets. This implies a reduction of the number of faults and the width of the proximal domain. (2) Efficient transport of sediment leads to significant deposition and hence thermal blanketing. This will induce a switch from brittle to ductile deformation of the upper crust in the distal domains. The feedbacks between these two outcomes depend on the extension history, the underlying lithospheric rheology, and the influence of submarine deposition on sediment transport. High erosion/sedimentation during early faulting leads to abrupt crustal necking, while intermediate syntectonic sedimentation rates over distal deep submarine hotter crust leads to unstructured wide distal domains. In models where rheological conditions favor the formation of asymmetric conjugate margins, only subaerial transport of sediments into the distal domains can increase conjugate symmetry by plastic localization. These models suggest that passive margin architecture can be strongly shaped by the solid Earth structure, sea level, and climatic conditions during breakup.
Cobaviruses – a new globally distributed phage group infecting Rhodobacteraceae in marine ecosystems
Authors: Bischoff Vera , Bunk Boyke , Meier-Kolthoff Jan P , Spröer Cathrin , Poehlein Anja , Dogs Marco , Nguyen Mary , Petersen Jörn , Daniel Rolf , Overmann Jörg , Göker Markus , Simon Meinhard , Brinkhoff Thorsten , Moraru Cristina 
Published: February 2019

Abstract
Bacteriophages are widely considered to influence bacterial communities, however most phages are still unknown or not studied well enough to understand their ecological roles. We have isolated two phages infecting Lentibacter sp. SH36, affiliated with the marine Roseobacter group, and retrieved similar phage genomes from publicly available metagenomics databases. Phylogenetic analysis placed the new phages within the Cobavirus group, in the here newly proposed genus Siovirus and subfamily Riovirinae of the Podoviridae. Gene composition and presence of direct terminal repeats in cultivated cobaviruses point toward a genome replication and packaging strategy similar to the T7 phage. Investigation of the genomes suggests that viral lysis of the cell proceeds via the canonical holin-endolysin pathway. Cobaviral hosts include members of the genera Lentibacter, Sulfitobacter and Celeribacter of the Roseobacter group within the family Rhodobacteraceae (Alphaproteobacteria). Screening more than 5,000 marine metagenomes, we found cobaviruses worldwide from temperate to tropical waters, in the euphotic zone, mainly in bays and estuaries, but also in the open ocean. The presence of cobaviruses in protist metagenomes as well as the phylogenetic neighborhood of cobaviruses in glutaredoxin and ribonucleotide reductase trees suggest that cobaviruses could infect bacteria associated with phototrophic or grazing protists. With this study, we expand the understanding of the phylogeny, classification, genomic organization, biogeography and ecology of this phage group infecting marine Rhodobacteraceae.
Functional EEG connectivity in infants associates with later restricted and repetitive behaviours in autism; a replication study
Authors: Haartsen Rianne , Jones Emily J. H. , Orekhova Elena V. , Charman Tony , Johnson Mark H. ,   The BASIS team, Baron-Cohen S. , Bedford R. , Blasi A. , Bolton P. , Chandler S. , Cheung C. , Davies K. , Elsabbagh M. , Fernandes J. , Gammer I. , Garwood H. , Gliga T. , Guiraud J. , Hudry K. , Liew M. , Lloyd-Fox S. , Maris H. , O’Hara L. , Pasco G. , Pickles A. , Ribeiro H. , Salomone E. , Tucker L. , Volein A. 
Published: February 2019

AbstractWe conducted a replication study of our prior report that increased alpha EEG connectivity at 14-months associates with later autism spectrum disorder (ASD) diagnosis, and dimensional variation in restricted interests/repetitive behaviours. 143 infants at high and low familial risk for ASD watched dynamic videos of spinning toys and women singing nursery rhymes while high-density EEG was recorded. Alpha functional connectivity (7–8 Hz) was calculated using the debiased weighted phase lag index. The final sample with clean data included low-risk infants (N = 20), and high-risk infants who at 36 months showed either typical development (N = 47), atypical development (N = 21), or met criteria for ASD (N = 13). While we did not replicate the finding that global EEG connectivity associated with ASD diagnosis, we did replicate the association between higher functional connectivity at 14 months and greater severity of restricted and repetitive behaviours at 36 months in infants who met criteria for ASD. We further showed that this association is strongest for the circumscribed interests subdomain. We propose that structural and/or functional abnormalities in frontal-striatal circuits underlie the observed association. This is the first replicated infant neural predictor of dimensional variation in later ASD symptoms.
Neurodevelopmental heterogeneity and computational approaches for understanding autism
Authors: Jacob Suma , Wolff Jason J. , Steinbach Michael S. , Doyle Colleen B. , Kumar Vipan , Elison Jed T. 
Published: February 2019

AbstractIn recent years, the emerging field of computational psychiatry has impelled the use of machine learning models as a means to further understand the pathogenesis of multiple clinical disorders. In this paper, we discuss how autism spectrum disorder (ASD) was and continues to be diagnosed in the context of its complex neurodevelopmental heterogeneity. We review machine learning approaches to streamline ASD’s diagnostic methods, to discern similarities and differences from comorbid diagnoses, and to follow developmentally variable outcomes. Both supervised machine learning models for classification outcome and unsupervised approaches to identify new dimensions and subgroups are discussed. We provide an illustrative example of how computational analytic methods and a longitudinal design can improve our inferential ability to detect early dysfunctional behaviors that may or may not reach threshold levels for formal diagnoses. Specifically, an unsupervised machine learning approach of anomaly detection is used to illustrate how community samples may be utilized to investigate early autism risk, multidimensional features, and outcome variables. Because ASD symptoms and challenges are not static within individuals across development, computational approaches present a promising method to elucidate subgroups of etiological contributions to phenotype, alternative developmental courses, interactions with biomedical comorbidities, and to predict potential responses to therapeutic interventions.
Molecular underpinnings of clinical disparity patterns in African American vs. Caucasian American multiple myeloma patients
Authors: Kazandjian Dickran , Hill Elizabeth , Hultcrantz Malin , Rustad Evan H. , Yellapantula Venkata , Akhlaghi Theresia , Korde Neha , Mailankody Sham , Dew Alex , Papaemmanuil Elli , Maric Irina , Kwok Mary , Landgren Ola 
Published: February 2019

AbstractCaucasian Americans (CA) compared with African Americans (AA) have a twofold increased incidence of multiple myeloma (MM) and have an earlier age of diagnosis. However, there is sparse information regarding underlying biological differences across racial/ethnic groups. We characterized genetic alterations using a targeted next-generation sequencing assay called myTYPE, developed at MSKCC, allowing capture of somatic mutations, IgH translocations, gains/losses, and hyperdiploidy. Samples were obtained from the NIH Plasma Cell Dyscrasia Racial Disparity Cohort. In total, 68 patient samples were successfully sequenced and manually curated based on well-established databases. Of the 68 patient samples (47 CA, 21 AA), 84% had at least one type of genomic alteration. Importantly, the IgH translocation, t(11;14), was observed more frequently in the AA group (0 vs. 29%, p = 0.001). Known oncogenic somatic non-synonymous mutations were found in 18 genes and indels in 2 genes. KRAS mutations were the most common mutation found in 16% of patients followed by NRAS and BRAF mutations. TP53 somatic mutations appeared to be more common in CA but lacked significance. This proof-of-principle study indicates the presence of varying underlying tumor biology between racial groups and supports the need of future prospective trials to capture these molecular characteristics.
Pro-oncogenic action of LOX-1 and its splice variant LOX-1Δ4 in breast cancer phenotypes
Authors: Pucci Sabina , Polidoro Chiara , Greggi Chiara , Amati Francesca , Morini Elena , Murdocca Michela , Biancolella Michela , Orlandi Augusto , Sangiuolo Federica , Novelli Giuseppe 
Published: February 2019

AbstractThe identification of new predictive biomarkers and therapeutic target for tailored therapy in breast cancer onset and progression is an interesting challenge. OLR-1 gene encodes the cell membrane receptor LOX-1 (lectin-like oxidized low-density lipoprotein receptor). We have recently identified a novel alternative OLR-1 isoform, LOX-1Δ4, whose expression and functions are still not clarified. In the present paper, we demonstrated that LOX-1 is overexpressed in 70% of human breast cancer (n = 47) and positively correlated to the tumor stage and grade (p < 0.01). Observations on LOX-1 and its splice variant Δ4 pointed out a different expression pattern correlated to breast cancer phenotypes. Overexpressing LOX-1 and LOX-1Δ4 in vitro, we obtained a strong enhancement of proliferative rate and a downregulation of cell death-related proteins. In addition, we observed a strong modulation of histone H4 acetylation and Ku70, the limiting factor of DNA double-strand breaks repair machinery implied in apoptosis inhibition and drug resistance acquisition. Moreover, LOX-1Δ4 overexpression is able to increase proliferation in a non-tumorigenic epithelial cell line, MCF12-F, acting as an oncogene. Altogether, these results suggest that LOX-1 may acts as a molecular link among metabolism, inflammation and cancer, indicating its potential role as biomarker and new molecular target, representing an attractive and concrete opportunity to improve current strategies for breast cancer tailored therapy.
CBX8 exhibits oncogenic properties and serves as a prognostic factor in hepatocellular carcinoma
Authors: Tang Bo , Tian Yu , Liao Yong , Li Zeming , Yu Shuiping , Su Huizhao , Zhong Fudi , Yuan Guandou , Wang Yan , Yu Hongping , Tomlinson Stephen , Qiu Xiaoqiang , He Songqing 
Published: February 2019

AbstractPolycomb group family is a class of proteins that have important roles in both physiological and pathological processes, and its family member Chromobox homolog 8 (CBX8) regulates cell differentiation, aging, and cell cycle progression in numerous carcinomas; however, the effects and underlying mechanisms of CBX8 in hepatocellular carcinoma (HCC) are rarely reported. We found that CBX8 expression in clinical HCC specimens correlates inversely with patient survival. In HCC cells, we found that enforced overexpression of CBX8 induces epithelial–mesenchymal transition, invasive migration, and stem cell-like traits, which are associated with increased tumor growth and metastasis in mice. Conversely, CBX8 silencing inhibits the aggressive phenotype of HCC cells that have high CBX8 expression. Mechanistically, CBX8 modulates H3K27me3 in the gene promoter of bone morphogenetic protein 4 (BMP4), which is associated with active BMP4 transcription and, consequently, the activation of Smads and mitogen-activated protein kinases. BMP4 expression reverses the effects of CBX8 silencing in inhibiting epithelial–mesenchymal transition, stemness, and metastasis. Our results establish CBX8 as a critical driver of HCC stem cell-like and metastatic behaviors and characterize its role in modulating BMP4 expression. These findings have implications for the targeting of CBX8 as an approach to HCC prognosis and treatment.
miR-34a: a new player in the regulation of T cell function by modulation of NF-κB signaling
Authors: Hart Martin , Walch-Rückheim Barbara , Friedmann Kim S. , Rheinheimer Stefanie , Tänzer Tanja , Glombitza Birgit , Sester Martina , Lenhof Hans-Peter , Hoth Markus , Schwarz Eva C. , Keller Andreas , Meese Eckart 
Published: February 2019

AbstractNF-κB functions as modulator of T cell receptor-mediated signaling and transcriptional regulator of miR-34a. Our in silico analysis revealed that miR-34a impacts the NF-κB signalosome with miR-34a binding sites in 14 key members of the NF-κB signaling pathway. Functional analysis identified five target genes of miR-34a including PLCG1, CD3E, PIK3CB, TAB2, and NFΚBIA. Overexpression of miR-34a in CD4+ and CD8+ T cells led to a significant decrease of NFΚBIA as the most downstream cytoplasmic NF-κB member, a reduced cell surface abundance of TCRA and CD3E, and to a reduction of T cell killing capacity. Inhibition of miR-34a caused an increase of NFΚBIA, TCRA, and CD3E. Notably, activation of CD4+ and CD8+ T cells entrails a gradual increase of miR-34a. Our results lend further support to a model with miR-34a as a central NF-κB regulator in T cells.
Sphingosine 1 phosphate receptor-1 (S1P1) promotes tumor-associated regulatory T cell expansion: leading to poor survival in bladder cancer
Authors: Liu Yi-Na , Zhang Han , Zhang Lin , Cai Ting-Ting , Huang Dai-Jia , He Jia , Ni Huan-He , Zhou Fang-Jian , Zhang Xiao-Shi , Li Jiang 
Published: February 2019

AbstractRegulatory T cells (Tregs) represent an important contributor to cancer immune escape, but the molecular mechanism responsible for Treg expansion in tumors is heterogeneous and unclear. Here, we investigated the role of S1P1, a receptor of the bioactive lipid sphingosine 1-phosphate (S1P), in regulating the crosstalk between tumor cells and tumor-associated Tregs in bladder cancer (BC). We found that the frequency of CD4+Foxp3+ Tregs was increased in circulating and tumor-infiltrating lymphocytes from BC patients. S1P1 expression was upregulated in BC tissues compared with tumor-adjacent tissues and was positively correlated with the density of tumor-infiltrated Foxp3+ Tregs. Both S1P1 and Treg predicted poor overall survival in BC patients. The in vitro data paralleled the in vivo data and suggested that the activation or overexpression of S1P1 in BC cells promoted the generation of BC-induced (i)Tregs from CD4+CD25−cells, and the generation of these cells was reversed by treatment with anti-IL-10 or anti-TGF-β. Moreover, S1P1 promoted Treg migration mediated by BC cells. Mechanistically, S1P1 activated the TGF-β signaling pathway, leading to the secretion of TGF-β and IL-10 from BC cells. In total, our findings suggest that S1P1 induces tumor-derived Treg expansion in a cell-specific manner and serves as a potent prognostic biomarker and therapeutic target in BC.
Stress-induced precocious aging in PD-patient iPSC-derived NSCs may underlie the pathophysiology of Parkinson’s disease
Authors: Zhu Liang , Sun Chenxi , Ren Jie , Wang Guangming , Ma Rongjie , Sun Lixin , Yang Danjing , Gao Shane , Ning Ke , Wang Zhigang , Chen Xu , Chen Shengdi , Zhu Hongwen , Gao Zhengliang , Xu Jun 
Published: February 2019

AbstractParkinson’s disease (PD) is an aging-related degenerative disorder arisen from the loss of dopaminergic neurons in substantia nigra. Although many genetic mutations have been implicated to be genetically linked to PD, the low incidence of familial PD carried with mutations suggests that there must be other factors such as oxidative stress, mitochondrial dysfunction, accumulation of misfolded proteins, and enhanced inflammation, which are contributable to the pathophysiology of PD. The major efforts of current research have been devoted to unravel the toxic effect of multiple factors, which directly cause the degeneration of dopaminergic neurons in adulthood. Until recently, several studies have demonstrated that NSCs had compromised proliferation and differentiation capacity in PD animal models or PD patient-derived iPS models, suggesting that the pathology of PD may be rooted in some cellular aberrations at early developmental stage but the mechanism remains to be elusive. Based on the early-onset PD patient-specific iPSCs, we found that PD-patient iPSC-derived NSCs were more susceptible to stress and became functionally compromised by radiation or oxidative insults. We further unraveled that stress-induced SIRT1 downregulation leading to autophagic dysfunction, which were responsible for these deficits in PD-NSCs. Mechanistically, we demonstrated that stress-induced activation of p38 MAPK suppressed SIRT1 expression, which in turn augmented the acetylation of multiple ATG proteins of autophagic complex and eventually led to autophagic deficits. Our studies suggest that early developmental deficits may, at least partially, contribute to the pathology of PD and provide a new avenue for developing better therapeutic interventions to PD.
Ser46 phosphorylation of p53 is an essential event in prolyl-isomerase Pin1-mediated p53-independent apoptosis in response to heat stress
Authors: Li Li , Su Zijun , Zou Zhimin , Tan Hongping , Cai Daozhang , Su Lei , Gu Zhengtao 
Published: February 2019

AbstractHeat stroke has increased in frequency worldwide in recent years and continues to have a high morbidity and mortality. Identification of the mechanisms mediating heat stoke is important and necessary. Our preliminary study revealed heat stress (HS)-induced apoptosis of vascular endothelial cells was associated with reactive oxygen species (ROS)-induced p53 translocation into mitochondria. Previous studies have suggested the prolyl-isomerase Pin1 regulates p53 functioning through specific binding to p53 phosphorylation sites. Based on these studies, we presumed Pin1 is a key intermediate in regulation of mitochondrial p53 translocation through a HS-induced ROS-p53 transcription-independent apoptosis pathway. In this context, we revealed p53 had a crucial role in a HS-induced mitochondrial apoptotic pathway, where p53 protein rapidly translocated into mitochondria in endothelial cells both in vitro and in vivo. In particular, HS caused an increase in p53 phosphorylation at Ser46 that facilitated interactions with phosphorylation-dependent prolyl-isomerase Pin1, which has a key role in promoting HS-induced localization of p53 to mitochondria. Furthermore, we also found ROS production was a critical mediator in HS-induced Pin1/p53 signaling and was involved in regulating mitochondrial apoptosis pathway activation. Therefore, we have contributed to our profound understanding of the mechanism underlying HS-induced endothelial dysfunction in an effort to reduce the mortality and morbidity of heat stroke.
Unfolded protein response is an early, non-critical event during hepatic stellate cell activation
Authors: Mannaerts Inge , Thoen Lien F. R. , Eysackers Nathalie , Cubero Francisco Javier , Batista Leite Sofia , Coldham Iain , Colle Isabelle , Trautwein Christian , van Grunsven Leo A. 
Published: February 2019

AbstractHepatic stellate cells activate upon liver injury and help at restoring damaged tissue by producing extracellular matrix proteins. A drastic increase in matrix proteins results in liver fibrosis and we hypothesize that this sudden increase leads to accumulation of proteins in the endoplasmic reticulum and its compensatory mechanism, the unfolded protein response. We indeed observe a very early, but transient induction of unfolded protein response genes during activation of primary mouse hepatic stellate cells in vitro and in vivo, prior to induction of classical stellate cell activation genes. This unfolded protein response does not seem sufficient to drive stellate cell activation on its own, as chemical induction of endoplasmic reticulum stress with tunicamycin in 3D cultured, quiescent stellate cells is not able to induce stellate cell activation. Inhibition of Jnk is important for the transduction of the unfolded protein response. Stellate cells isolated from Jnk knockout mice do not activate as much as their wild-type counterparts and do not have an induced expression of unfolded protein response genes. A timely termination of the unfolded protein response is essential to prevent endoplasmic reticulum stress-related apoptosis. A pathway known to be involved in this termination is the non-sense-mediated decay pathway. Non-sense-mediated decay inhibitors influence the unfolded protein response at early time points during stellate cell activation. Our data suggest that UPR in HSCs is differentially regulated between acute and chronic stages of the activation process. In conclusion, our data demonstrates that the unfolded protein response is a JNK1-dependent early event during hepatic stellate cell activation, which is counteracted by non-sense-mediated decay and is not sufficient to drive the stellate cell activation process. Therapeutic strategies based on UPR or NMD modulation might interfere with fibrosis, but will remain challenging because of the feedback mechanisms between the stress pathways.