bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wintertime Fjord‐Shelf Interaction and Ice Sheet Melting in Southeast Greenland
Authors: Fraser Neil J. , Inall Mark E. , Magaldi Marcello G. , Haine Thomas W. N. , Jones Sam C. 
Published: December 2018

AbstractA realistic numerical model was constructed to simulate the oceanic conditions and circulation in a large southeast Greenland fjord (Kangerdlugssuaq) and the adjacent shelf sea region during winter 2007–2008. The major outlet glaciers in this region recently destabilized, contributing to sea level rise and ocean freshening, with increased oceanic heating a probable trigger. It is not apparent a priori whether the fjord dynamics will be influenced by rotational effects, as the fjord width is comparable to the internal Rossby radius. The modeled currents, however, describe a highly three‐dimensional system, where rotational effects are of order‐one importance. Along‐shelf wind events drive a rapid baroclinic exchange, mediated by coastally trapped waves, which propagate from the shelf to the glacier terminus along the right‐hand boundary of the fjord. The terminus was regularly exposed to around 0.5 TW of heating over the winter season. Wave energy dissipation provoked vertical mixing, generating a buoyancy flux which strengthened overturning. The coastally trapped waves also acted to strengthen the cyclonic mean flow via Stokes' drift. Although the outgoing wave was less energetic and located at the opposite sidewall, the fjord did exhibit a resonant response, suggesting that fjords of this scale can also exhibit two‐dimensional dynamics. Long periods of moderate wind stress greatly enhanced the cross‐shelf delivery of heat toward the fjord, in comparison to stronger events over short intervals. This suggests that the timescale over which the shelf wind field varies is a key parameter in dictating wintertime heat delivery from the ocean to the ice sheet.
The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells
Authors: Shen Cheng-Ying , Chang Ya-Chu , Chen Li-Han , Lin Wen-Chun , Lee Yung-Hua , Yeh Shu-Tsen , Chen Hsin-Kuang , Fang Wentao , Hsu Chung-Ping , Lee Jang-Ming , Lu Tzu-Pin , Hsiao Pei-Wen , Lai Liang-Chuan , Tsai Mong-Hsun , Chuang Eric Y. 
Published: December 2018

AbstractSemaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells.
Taxonomic and functional heterogeneity of the gill microbiome in a symbiotic coastal mangrove lucinid species
Authors: Lim Shen Jean , Davis Brenton G , Gill Danielle E , Walton Jillian , Nachman Erika , Engel Annette Summers , Anderson Laurie C , Campbell Barbara J 
Published: December 2018

Abstract
Lucinidae clams harbor gammaproteobacterial thioautotrophic gill endosymbionts that are environmentally acquired. Thioautotrophic lucinid symbionts are related to metabolically similar symbionts associated with diverse marine host taxa and fall into three distinct phylogenetic clades. Most studies on the lucinid–bacteria chemosymbiosis have been done with seagrass-dwelling hosts, whose symbionts belong to the largest phylogenetic clade. In this study, we examined the taxonomy and functional repertoire of bacterial endosymbionts at an unprecedented resolution from Phacoides pectinatus retrieved from mangrove-lined coastal sediments, which are underrepresented in chemosymbiosis studies. The P. pectinatus thioautotrophic endosymbiont expressed metabolic gene variants for thioautotrophy, respiration, and nitrogen assimilation distinct from previously characterized lucinid thioautotrophic symbionts and other marine symbionts. At least two other bacterial species with different metabolisms were also consistently identified in the P. pectinatus gill microbiome, including a Kistimonas-like species and a Spirochaeta-like species. Bacterial transcripts involved in adhesion, growth, and virulence and mixotrophy were highly expressed, as were host-related hemoglobin and lysozyme transcripts indicative of sulfide/oxygen/CO2 transport and bactericidal activity. This study suggests the potential roles of P. pectinatus and its gill microbiome species in mangrove sediment biogeochemistry and offers insights into host and microbe metabolisms in the habitat.
Loss of the candidate tumor suppressor ZEB1 (TCF8, ZFHX1A) in Sézary syndrome
Authors: Caprini Elisabetta , Bresin Antonella , Cristofoletti Cristina , Helmer Citterich Mauro , Tocco Valeria , Scala Enrico , Monopoli Alessandro , Benucci Roberto , Narducci Maria Grazia , Russo Giandomenico 
Published: December 2018

AbstractCutaneous T-cell lymphoma is a group of incurable extranodal non-Hodgkin lymphomas that develop from the skin-homing CD4+ T cell. Mycosis fungoides and Sézary syndrome are the most common histological subtypes. Although next-generation sequencing data provided significant advances in the comprehension of the genetic basis of this lymphoma, there is not uniform consensus on the identity and prevalence of putative driver genes for this heterogeneous group of tumors. Additional studies may increase the knowledge about the complex genetic etiology characterizing this lymphoma. We used SNP6 arrays and GISTIC algorithm to prioritize a list of focal somatic copy-number alterations in a dataset of multiple sequential samples from 21 Sézary syndrome patients. Our results confirmed a prevalence of significant focal deletions over amplifications: single well-known tumor suppressors, such as TP53, PTEN, and RB1, are targeted by these aberrations. In our cohort, ZEB1 (TCF8, ZFHX1A) spans a deletion having the highest level of significance. In a larger group of 43 patients, we found that ZEB1 is affected by deletions and somatic inactivating mutations in 46.5% of cases; also, we found potentially relevant ZEB1 germline variants. The survival analysis shows a worse clinical course for patients with ZEB1 biallelic inactivation. Multiple abnormal expression signatures were found associated with ZEB1 depletion in Sézary patients we verified that ZEB1 exerts a role in oxidative response of Sézary cells. Our data confirm the importance of deletions in the pathogenesis of cutaneous T-cell lymphoma. The characterization of ZEB1 abnormalities in Sézary syndrome fulfils the criteria of a canonical tumor suppressor gene. Although additional confirmations are needed, our findings suggest, for the first time, that ZEB1 germline variants might contribute to the risk of developing this disease. Also, we provide evidence that ZEB1 activity in Sézary cells, influencing the reactive oxygen species production, affects cell viability and apoptosis.
Inactivation of Lon protease reveals a link between mitochondrial unfolded protein stress and mitochondrial translation inhibition
Authors: Pareek Gautam , Pallanck Leo J. 
Published: December 2018

AbstractThe mitochondrial Unfolded Protein Response (UPRmt) pathway confers protection from misfolded and aggregated proteins by activating factors that promote protein folding and degradation. Our recent work on Lon protease, a member of the mitochondrial ATPase Associated with diverse cellular Activities (AAA+) family of mitochondrial resident proteases, suggests that mitochondrial translational inhibition may also be a feature of the UPRmt pathway.
Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination
Authors: Codo Ana Campos , Saraiva Amanda Correia , dos Santos Leonardo Lima , Visconde Marina Francisco , Gales Ana Cristina , Zamboni Dario Simões , Medeiros Alexandra Ivo 
Published: December 2018

AbstractKlebsiella pneumoniae is a Gram-negative bacterium responsible for severe cases of nosocomial pneumonia. During the infectious process, both neutrophils and monocytes migrate to the site of infection, where they carry out their effector functions and can be affected by different patterns of cell death. Our data show that clinical strains of K. pneumoniae have dissimilar mechanisms for surviving within macrophages; these mechanisms include modulation of microbicidal mediators and cell death. The A28006 strain induced high IL-1β production and pyroptotic cell death in macrophages; by contrast, the A54970 strain induced high IL-10 production and low IL-1β production by macrophages. Pyroptotic cell death induced by the A28006 strain leads to a significant increase in bacterial sensitivity to hydrogen peroxide, and efferocytosis of the pyroptotic cells results in efficient bacterial clearance both in vitro and in vivo. In addition, the A54970 strain was able to inhibit inflammasome activation and pyroptotic cell death by inducing IL-10 production. Here, for the first time, we present a K. pneumoniae strain able to inhibit inflammasome activation, leading to bacterial survival and dissemination in the host. The understanding of possible escape mechanisms is essential in the search for alternative treatments against multidrug-resistant bacteria.
Variant of SNP rs1317082 at CCSlnc362 (RP11-362K14.5) creates a binding site for miR-4658 and diminishes the susceptibility to CRC
Authors: Shen Chaoqin , Yan Tingting , Wang Zhenhua , Su Heng-chuan , Zhu Xiaoqiang , Tian Xianglong , Fang Jing-Yuan , Chen Haoyan , Hong Jie 
Published: December 2018

AbstractGenome-wide association studies (GWAS) have identified several loci harboring variants that affected the risk of colorectal cancer; however, the specific mechanisms by which germline variation influenced the tumorigenesis of colorectal cancer (CRC) remains unrevealed. We found the T>C variant of rs1317082, locating at the exon 1 of lncRNA RP11-362K14.5 (CCSlnc362), was predicted to be a protective locus for cancer. However, the specific role of CCSlnc362 and the interaction between CCSlnc362 and rs1317082 variation in colorectal cancer and its mechanisms remain unclear. Here we explored the expression and function of CCSlnc362 in CRC cells and tissues. We found lncRNA CCSlnc362 expression was significantly increased in CRC samples. Follow-up functional experiments elucidated that downregulation of CCSlnc362 inhibited cell proliferation, arrested cell cycle, and promoted apoptosis in CRC cells. The T>C variant of rs1317082 at CCSlnc362 exon 1 created a binding site for miR-4658 to reduce the expression of CCSlnc362 and thus decreased the susceptibility to CRC. Our findings have provided supporting evidence for the protective role of rs1317082 variation and the potential oncogenic role of lncRNA CCSlnc362 in CRC. The data shed new light on the relationship between germline variation, miRNAs, and lncRNAs and opened a new avenue for targeted therapy in CRC.
Mast cells are essential intermediaries in regulating IL-33/ST2 signaling for an immune network favorable to mucosal healing in experimentally inflamed colons
Authors: He Zhigang , Song Jian , Hua Jie , Yang Muqing , Ma Yuanyuan , Yu Tianyu , Feng Junlan , Liu Bin , Wang Xiaodong , Li Yue , Li Jiyu 
Published: December 2018

AbstractMast cells (MCs) are potent tissue-resident immune cells that are distributed in the intraepithelial space of the intestine and have been implicated in regulating immune homeostasis and coordinating epithelial responses in inflamed mucosa of inflammatory bowel disease (IBD). IL-33 functions as an endogenous danger signal or alarmin in inflamed intestine segments. MCs highly express the IL-33 receptor ST2. However, the mechanisms underlying the immune regulation of MC-dependent IL-33/ST2 signaling at the barrier surface of the intestine remain largely unknown. We confirmed that MCs are required for the effective resolution of tissue damage using an experimental colitis model that allows for conditional ablation of MCs. After elucidating the IL-33 signaling involved in MC activity in the context of intestinal inflammation, we found that the function of restricted IL-33/ST2 signaling by MCs was consistent with an MC deficiency in response to the breakdown of the epithelial barrier. We observed that a tissue environment with a spectrum of protective cytokines was orchestrated by MC-dependent IL-33/ST2 signaling. Given the significant downregulation of IL-22 and IL-13 due to the loss of MC-dependent IL-33/ST2 signaling and their protective functions in inflammation settings, induction of IL-22 and IL-13 may be responsible for an immune network favorable to mucosal repair. Collectively, our data showed an important feedback loop in which cytokine cues from damaged epithelia activate MCs to regulate tissue environments essential for MC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.
Targeting of chondrocyte plasticity via connexin43 modulation attenuates cellular senescence and fosters a pro-regenerative environment in osteoarthritis
Authors: Varela-Eirín Marta , Varela-Vázquez Adrián , Guitián-Caamaño Amanda , Paíno Carlos Luis , Mato Virginia , Largo Raquel , Aasen Trond , Tabernero Arantxa , Fonseca Eduardo , Kandouz Mustapha , Caeiro José Ramón , Blanco Alfonso , Mayán María D. 
Published: December 2018

AbstractOsteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. In OA, chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favouring disease progression. Similar to other wound-healing disorders, chondrocytes from OA patients show a chronic increase in the gap junction channel protein connexin43 (Cx43), which regulates signal transduction through the exchange of elements or recruitment/release of signalling factors. Although immature or stem-like cells are present in cartilage from OA patients, their origin and role in disease progression are unknown. In this study, we found that Cx43 acts as a positive regulator of chondrocyte-mesenchymal transition. Overactive Cx43 largely maintains the immature phenotype by increasing nuclear translocation of Twist-1 and tissue remodelling and proinflammatory agents, such as MMPs and IL-1β, which in turn cause cellular senescence through upregulation of p53, p16INK4a and NF-κB, contributing to the senescence-associated secretory phenotype (SASP). Downregulation of either Cx43 by CRISPR/Cas9 or Cx43-mediated gap junctional intercellular communication (GJIC) by carbenoxolone treatment triggered rediferentiation of osteoarthritic chondrocytes into a more differentiated state, associated with decreased synthesis of MMPs and proinflammatory factors, and reduced senescence. We have identified causal Cx43-sensitive circuit in chondrocytes that regulates dedifferentiation, redifferentiation and senescence. We propose that chondrocytes undergo chondrocyte-mesenchymal transition where increased Cx43-mediated GJIC during OA facilitates Twist-1 nuclear translocation as a novel mechanism involved in OA progression. These findings support the use of Cx43 as an appropriate therapeutic target to halt OA progression and to promote cartilage regeneration.
Long non-coding RNA C5orf66-AS1 promotes cell proliferation in cervical cancer by targeting miR-637/RING1 axis
Authors: Rui Xiaohui , Xu Yun , Jiang Xiping , Ye Wenfeng , Huang Yaqing , Jiang Jingting 
Published: December 2018

AbstractLong non-coding RNA (lncRNA) plays an important role in the development of human malignant tumours. Recently, an increasing number of lncRNAs have been identified and investigated in a variety of tumours. However, the expression pattern and biological function of lncRNAs in cervical cancer still remain largely unexplored. Differentially expressed lncRNAs in cervical cancer and para-carcinoma tissues were identified by screening using The Cancer Genome Atlas (TCGA), and candidate lncRNAs were verified by quantitative real-time PCR. We found that lncRNAC5orf66-AS1 was significantly upregulated in cervical cancer tissues and cells. Over-expression of C5orf66-AS1 promoted the proliferation of cervical cancer cells, while downregulation of C5orf66-AS1 promoted the apoptosis of cervical cancer cells. C5orf66-AS1 was identified as the sponge of miR-637 by RNA immunoprecipitation (RIP) and luciferase reporter assays. Exogenous miR-637 and RING1 interventions could reverse the proliferation ability mediated by C5orf66-AS1 in cervical cancer cells. In vivo experiments also confirmed that downregulation of C5orf66-AS1 inhibited the tumour growth. LncRNA C5orf66-AS1, as a competitive endogenous RNA (ceRNA), regulated the effect of RING1 on the proliferation, apoptosis and cell cycle of cervical cancer cells through adsorbing miR-637. Taken together, our findings provided a new theoretical and experimental basis for investigating the pathogenesis and exploring effective therapeutic targets for cervical cancer.
Nutritional stress reprograms dedifferention in glioblastoma multiforme driven by PTEN/Wnt/Hedgehog axis: a stochastic model of cancer stem cells
Authors: Mondal Susmita , Bhattacharya Kaushik , Mandal Chitra 
Published: December 2018

AbstractThe emergence and maintenance of cancer stem-like cells (CSCs) are usually governed by tumor niche. Tumor niche always provides metabolic challenges to cancer cells and CSCs mostly because of tissue hypoxia. However, the role of micro-environmental nutritional stress (NS) in dedifferentiation of cancer cells is poorly defined. Here, we developed a stochastic model of CSCs by gradual nutritional deprivation in glioblastoma multiforme (GBM) cells used as a model system. Nutritional deprivation induced enhanced expression of glioblastoma stem-like cells (GSCs)-specific biomarkers with higher invasive and angiogenic properties. This NS-induced cells showed higher xenobiotic efflux ability, and hence exhibit resistance to multiple anticancer drugs. In the molecular level, such NS activated Wnt and Hedgehog (Hh) signaling pathways by stabilizing β-catenin and Gli1, respectively, through modulation of GSK3β/AKT axis. GBM-specific PTEN (phosphatase and tensin homolog) mutation contributed to better phenoconversion toward GSCs. Knocking down of PTEN coupled with NS induction enhanced neurosphere formation, GSC-specific biomarker expressions, and activation of Wnt/Hh signaling. Thus, such an in-depth understanding of dedifferentiation of GBM cells to GSCs under NS suggested that targeting Wnt/Hh signaling possibly be a better therapeutic approach.
Challenges hindering memristive neuromorphic hardware from going mainstream
Authors: Adam Gina C. , Khiat Ali , Prodromakis Themis 
Published: December 2018

AbstractMemristive devices have elicited intense research in the past decade thanks to their inherent low voltage operation, multi-bit storage and cost-effective manufacturability. Nonetheless, several outstanding performance and manufacturability challenges have prevented the widespread industry adoption of redox-based memristive matrices. Here, we discuss these challenges in terms of key metrics and propose a roadmap towards realizing competitive memristive-based neuromorphic processing systems.
Magic number colloidal clusters as minimum free energy structures
Authors: Wang Junwei , Mbah Chrameh Fru , Przybilla Thomas , Apeleo Zubiri Benjamin , Spiecker Erdmann , Engel Michael , Vogel Nicolas 
Published: December 2018

AbstractClusters in systems as diverse as metal atoms, virus proteins, noble gases, and nucleons have properties that depend sensitively on the number of constituent particles. Certain numbers are termed ‘magic’ because they grant the system with closed shells and exceptional stability. To this point, magic number clusters have been exclusively found with attractive interactions as present between atoms. Here we show that magic number clusters exist in a confined soft matter system with negligible interactions. Colloidal particles in an emulsion droplet spontaneously organize into a series of clusters with precisely defined shell structures. Crucially, free energy calculations demonstrate that colloidal clusters with magic numbers possess higher thermodynamic stability than those off magic numbers. A complex kinetic pathway is responsible for the efficiency of this system in finding its minimum free energy configuration. Targeting similar magic number states is a strategy towards unique configurations in finite self-organizing systems across the scales.
CSF1R regulates the dendritic cell pool size in adult mice via embryo-derived tissue-resident macrophages
Authors: Percin Gulce Itir , Eitler Jiri , Kranz Andrea , Fu Jun , Pollard Jeffrey W. , Naumann Ronald , Waskow Claudia 
Published: December 2018

AbstractRegulatory mechanisms controlling the pool size of spleen dendritic cells (DC) remain incompletely understood. DCs are continuously replenished from hematopoietic stem cells, and FLT3-mediated signals cell-intrinsically regulate homeostatic expansion of spleen DCs. Here we show that combining FLT3 and CSF1R-deficiencies results in specific and complete abrogation of spleen DCs in vivo. Spatiotemporally controlled CSF1R depletion reveals a cell-extrinsic and non-hematopoietic mechanism for DC pool size regulation. Lack of CSF1R-mediated signals impedes the differentiation of spleen macrophages of embryonic origin, and the resulted macrophage depletion during development or in adult mice results in loss of DCs. Moreover, embryo-derived macrophages are important for the physiologic regeneration of DC after activation-induced depletion in situ. In summary, we show that the differentiation of DC and their regeneration relies on ontogenetically distinct spleen macrophages, thereby providing a novel regulatory principle that may also be important for the differentiation of other hematopoietic cell types.
Migration alters oscillatory dynamics and promotes survival in connected bacterial populations
Authors: Gokhale Shreyas , Conwill Arolyn , Ranjan Tanvi , Gore Jeff 
Published: December 2018

AbstractMigration influences population dynamics on networks, thereby playing a vital role in scenarios ranging from species extinction to epidemic propagation. While low migration rates prevent local populations from becoming extinct, high migration rates enhance the risk of global extinction by synchronizing the dynamics of connected populations. Here, we investigate this trade-off using two mutualistic strains ofE. colithat exhibit population oscillations when co-cultured. In experiments, as well as in simulations using a mechanistic model, we observe that high migration rates lead to synchronization whereas intermediate migration rates perturb the oscillations and change their period. Further, our simulations predict, and experiments show, that connected populations subjected to more challenging antibiotic concentrations have the highest probability of survival at intermediate migration rates. Finally, we identify altered population dynamics, rather than recolonization, as the primary cause of extended survival.