bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pro-inflammatory cytokines activate hypoxia-inducible factor 3α via epigenetic changes in mesenchymal stromal/stem cells
Authors: Cuomo Francesca , Coppola Antonietta , Botti Chiara , Maione Ciro , Forte Amalia , Scisciola Lucia , Liguori Giuseppina , Caiafa Ilaria , Ursini Matilde Valeria , Galderisi Umberto , Cipollaro Marilena , Altucci Lucia , Cobellis Gilda 
Published: April 2018

AbstractHuman mesenchymal stromal/stem cells (hMSCs) emerged as a promising therapeutic tool for ischemic disorders, due to their ability to regenerate damaged tissues, promote angiogenesis and reduce inflammation, leading to encouraging, but still limited results. The outcomes in clinical trials exploring hMSC therapy are influenced by low cell retention and survival in affected tissues, partially influenced by lesion’s microenvironment, where low oxygen conditions (i.e. hypoxia) and inflammation coexist. Hypoxia and inflammation are pathophysiological stresses, sharing common activators, such as hypoxia-inducible factors (HIFs) and NF-κB. HIF1α and HIF2α respond essentially to hypoxia, activating pathways involved in tissue repair. Little is known about the regulation of HIF3α. Here we investigated the role of HIF3α in vitro and in vivo. Human MSCs expressed HIF3α, differentially regulated by pro-inflammatory cytokines in an oxygen-independent manner, a novel and still uncharacterized mechanism, where NF-κB is critical for its expression. We investigated if epigenetic modifications are involved in HIF3α expression by methylation-specific PCR and histone modifications. Robust hypermethylation of histone H3 was observed across HIF3A locus driven by pro-inflammatory cytokines. Experiments in a murine model of arteriotomy highlighted the activation of Hif3α expression in infiltrated inflammatory cells, suggesting a new role for Hif3α in inflammation in vivo.
Switching between individual and collective motility in B lymphocytes is controlled by cell-matrix adhesion and inter-cellular interactions
Authors: Rey-Barroso Javier , Calovi Daniel S. , Combe Maud , German Yolla , Moreau Mathieu , Canivet Astrid , Wang Xiaobo , Sire Clément , Theraulaz Guy , Dupré Loïc 
Published: April 2018

AbstractLymphocytes alternate between phases of individual migration across tissues and phases of clustering during activation and function. The range of lymphocyte motility behaviors and the identity of the factors that govern them remain elusive. To explore this point, we here collected unprecedented statistics pertaining to cell displacements, cell:matrix and cell:cell interactions using a model B cell line as well as primary human B lymphocytes. At low cell density, individual B lymphocytes displayed a high heterogeneity in their speed and diffusivity. Beyond this intrinsic variability, B lymphocytes adapted their motility to the composition of extra-cellular matrix, adopting slow persistent walks over collagen IV and quick Brownian walks over fibronectin. At high cell density, collagen IV favored the self-assembly of B lymphocytes into clusters endowed with collective coordination, while fibronectin stimulated individual motility. We show that this behavioral plasticity is controlled by acto-myosin dependent adhesive and Arp2/3-dependent protrusive actin pools, respectively. Our study reveals the adaptive nature of B lymphocyte motility and group dynamics, which are shaped by an interplay between and cell:matrix and cell:cell interactions.
Mucin gel assembly is controlled by a collective action of non-mucin proteins, disulfide bridges, Ca2+-mediated links, and hydrogen bonding
Authors: Meldrum Oliver W. , Yakubov Gleb E. , Bonilla Mauricio R. , Deshmukh Omkar , McGuckin Michael A. , Gidley Michael J. 
Published: April 2018

AbstractMucus is characterized by multiple levels of assembly at different length scales which result in a unique set of rheological (flow) and mechanical properties. These physical properties determine its biological function as a highly selective barrier for transport of water and nutrients, while blocking penetration of pathogens and foreign particles. Altered integrity of the mucus layer in the small intestine has been associated with a number of gastrointestinal tract pathologies such as Crohn’s disease and cystic fibrosis. In this work, we uncover an intricate hierarchy of intestinal mucin (Muc2) assembly and show how complex rheological properties emerge from synergistic interactions between mucin glycoproteins, non-mucin proteins, and Ca2+. Using a novel method of mucus purification, we demonstrate the mechanism of assembly of Muc2 oligomers into viscoelastic microscale domains formed via hydrogen bonding and Ca2+-mediated links, which require the joint presence of Ca2+ ions and non-mucin proteins. These microscale domains aggregate to form a heterogeneous yield stress gel-like fluid, the macroscopic rheological properties of which are virtually identical to that of native intestinal mucus. Through proteomic analysis, we short-list potential protein candidates implicated in mucin assembly, thus paving the way for identifying the molecules responsible for the physiologically critical biophysical properties of mucus.
Unraveling the compromised biomechanical performance of type 2 diabetes- and Roux-en-Y gastric bypass bone by linking mechanical-structural and physico-chemical properties
Authors: Marin Carlos , Papantonakis Georgios , Sels Kathleen , van Lenthe G. Harry , Falgayrac Guillaume , Vangoitsenhoven Roman , Van der Schueren Bart , Penel Guillaume , Luyten Frank , Vandamme Katleen , Kerckhofs Greet 
Published: April 2018

AbstractType 2 diabetes mellitus (T2DM) is a metabolic disorder associated with obesity and hyperglycemia. Roux-en-Y gastric bypass (RYGB) surgery is a common treatment for severely obese patients and T2DM. Both RYGB and T2DM are linked to increased skeletal fragility, though the exact mechanisms are poorly understood. Our aim was to characterize the structural, mechanical and compositional properties of bones from diet-induced obese and RYGB-treated obese (bypass) mice to elucidate which the exact factors are contributing to the increased skeletal fragility. To achieve this, a combinatory approach including microfocus X-ray computed tomography, 3-point bending, finite element modeling and Raman spectroscopy, was used. Compared to aged-matched lean controls, the obese mice displayed decreased cortical thickness, trabecular bone loss, decreased stiffness and increased Young’s modulus. For the bypass mice, these alterations were even more pronounced, and additionally they showed low mineral-to-matrix ratio in the cortical endosteal area. Accumulation of the advanced glycation end-product (AGE) pentosidine was found in the cortex of obese and bypass groups and this accumulation was correlated with an increased Young’s modulus. In conclusion, we found that the increased fracture risk in T2DM- and post-RYGB bones is mainly driven by accumulation of AGEs and macro-structural alterations, generating biomechanical dysfunctionality.
A standardized flow cytometry network study for the assessment of circulating endothelial cell physiological ranges
Authors: Lanuti Paola , Simeone Pasquale , Rotta Gianluca , Almici Camillo , Avvisati Giuseppe , Azzaro Rosa , Bologna Giuseppina , Budillon Alfredo , Di Cerbo Melania , Di Gennaro Elena , Di Martino Maria Luisa , Diodato Annamaria , Doretto Paolo , Ercolino Eva , Falda Alessandra , Gregorj Chiara , Leone Alessandra , Losa Francesca , Malara Natalia , Marini Mirella , Mastroroberto Pasquale , Mollace Vincenzo , Morelli Michele , Muggianu Emma , Musolino Giuseppe , Neva Arabella , Pierdomenico Laura , Pinna Silvia , Piovani Giovanna , Roca Maria Serena , Russo Domenico , Scotti Lorenza , Tirindelli Maria Cristina , Trunzo Valentina , Venturella Roberta , Vitagliano Carlo , Zullo Fulvio , Marchisio Marco , Miscia Sebastiano 
Published: April 2018

AbstractCirculating endothelial cells (CEC) represent a restricted peripheral blood (PB) cell subpopulation with high potential diagnostic value in many endothelium-involving diseases. However, whereas the interest in CEC studies has grown, the standardization level of their detection has not. Here, we undertook the task to align CEC phenotypes and counts, by standardizing a novel flow cytometry approach, within a network of six laboratories. CEC were identified as alive/nucleated/CD45negative/CD34bright/CD146positive events and enumerated in 269 healthy PB samples. Standardization was demonstrated by the achievement of low inter-laboratory Coefficients of Variation (CVL), calculated on the basis of Median Fluorescence Intensity values of the most stable antigens that allowed CEC identification and count (CVL of CD34bright on CEC ~ 30%; CVL of CD45 on Lymphocytes ~ 20%). By aggregating data acquired from all sites, CEC numbers in the healthy population were captured (medianfemale = 9.31 CEC/mL; medianmale = 11.55 CEC/mL). CEC count biological variability and method specificity were finally assessed. Results, obtained on a large population of donors, demonstrate that the established procedure might be adopted as standardized method for CEC analysis in clinical and in research settings, providing a CEC physiological baseline range, useful as starting point for their clinical monitoring in endothelial dysfunctions.
1.5 °C carbon budget dependent on carbon cycle uncertainty and future non-CO2 forcing
Authors: Mengis Nadine , Partanen Antti-Ilari , Jalbert Jonathan , Matthews H. Damon 
Published: April 2018

AbstractEstimates of the 1.5 °C carbon budget vary widely among recent studies, emphasizing the need to better understand and quantify key sources of uncertainty. Here we quantify the impact of carbon cycle uncertainty and non-CO2 forcing on the 1.5 °C carbon budget in the context of a prescribed 1.5 °C temperature stabilization scenario. We use Bayes theorem to weight members of a perturbed parameter ensemble with varying land and ocean carbon uptake, to derive an estimate for the fossil fuel (FF) carbon budget of 469 PgC since 1850, with a 95% likelihood range of (411,528) PgC. CO2 emissions from land-use change (LUC) add about 230 PgC. Our best estimate of the total (FF + LUC) carbon budget for 1.5 °C is therefore 699 PgC, which corresponds to about 11 years of current emissions. Non-CO2 greenhouse gas and aerosol emissions represent equivalent cumulative CO2 emissions of about 510 PgC and −180 PgC for 1.5 °C, respectively. The increased LUC, high non-CO2 emissions and decreased aerosols in our scenario, cause the long-term FF carbon budget to decrease following temperature stabilization. In this scenario, negative emissions would be required to compensate not only for the increasing non-CO2 climate forcing, but also for the declining natural carbon sinks.
Accurate estimation of 5-methylcytosine in mammalian mitochondrial DNA
Authors: Matsuda Shigeru , Yasukawa Takehiro , Sakaguchi Yuriko , Ichiyanagi Kenji , Unoki Motoko , Gotoh Kazuhito , Fukuda Kei , Sasaki Hiroyuki , Suzuki Tsutomu , Kang Dongchon 
Published: April 2018

AbstractWhilst 5-methylcytosine (5mC) is a major epigenetic mark in the nuclear DNA in mammals, whether or not mitochondrial DNA (mtDNA) receives 5mC modification remains controversial. Herein, we exhaustively analysed mouse mtDNA using three methods that are based upon different principles for detecting 5mC. Next-generation bisulfite sequencing did not give any significant signatures of methylation in mtDNAs of liver, brain and embryonic stem cells (ESCs). Also, treatment with methylated cytosine-sensitive endonuclease McrBC resulted in no substantial decrease of mtDNA band intensities in Southern hybridisation. Furthermore, mass spectrometric nucleoside analyses of highly purified liver mtDNA preparations did not detect 5-methyldeoxycytidine at the levels found in the nuclear DNA but at a range of only 0.3–0.5% of deoxycytidine. Taken together, we propose that 5mC is not present at any specific region(s) of mtDNA and that levels of the methylated cytosine are fairly low, provided the modification occurs. It is thus unlikely that 5mC plays a universal role in mtDNA gene expression or mitochondrial metabolism.
Snf1/AMPK is involved in the mitotic spindle alignment in Saccharomyces cerevisiae
Authors: Tripodi Farida , Fraschini Roberta , Zocchi Monica , Reghellin Veronica , Coccetti Paola 
Published: April 2018

AbstractBefore anaphase onset, budding yeast cells must align the mitotic spindle parallel to the mother-bud axis to ensure proper chromosome segregation. The protein kinase Snf1/AMPK is a highly conserved energy sensor, essential for adaptation to glucose limitation and in response to cellular stresses. However, recent findings indicate that it plays important functions also in non-limiting glucose conditions. Here we report a novel role of Snf1/AMPK in the progression through mitosis in glucose-repressing condition. We show that active Snf1 is localized to the bud neck from bud emergence to cytokinesis in a septin-dependent manner. In addition, loss of Snf1 induces a delay of the metaphase to anaphase transition that is due to a defect in the correct alignment of the mitotic spindle. In particular, genetic data indicate that Snf1 promotes spindle orientation acting in parallel with Dyn1 and in concert with Kar9. Altogether this study describes a new role for Snf1 in mitosis and connects cellular metabolism to mitosis progression.
Proteomic profiling of human cancer pseudopodia for the identification of anti-metastatic drug candidates
Authors: Choi Sunkyu , Bhagwat Aditya M. , Al Mismar Rasha , Goswami Neha , Ben Hamidane Hisham , Sun Lu , Graumann Johannes 
Published: April 2018

AbstractCancer metastasis causes approximately 90% of all cancer-related death and independent of the advancement of cancer therapy, a majority of late stage patients suffers from metastatic cancer. Metastasis implies cancer cell migration and invasion throughout the body. Migration requires the formation of pseudopodia in the direction of movement, but a detailed understanding of this process and accordingly strategies of prevention remain elusive. Here, we use quantitative proteomic profiling of human cancer pseudopodia to examine this mechanisms essential to metastasis formation, and identify potential candidates for pharmacological interference with the process. We demonstrate that Prohibitins (PHBs) are significantly enriched in the pseudopodia fraction derived from cancer cells, and knockdown of PHBs, as well as their chemical inhibition through Rocaglamide (Roc-A), efficiently reduces cancer cell migration.
Phylogeny, biogeography and methodology: a meta-analytic perspective on heterogeneity in adult marine turtle survival rates
Authors: Pfaller Joseph B. , Chaloupka Milani , Bolten Alan B. , Bjorndal Karen A. 
Published: April 2018

AbstractComparative syntheses of key demographic parameters are critical not only for identifying data gaps, but also for evaluating sources of heterogeneity among estimates. Because demographic studies frequently exhibit heterogeneity, evaluating sources of heterogeneity among estimates can inform biological patterns and conservation actions more broadly. To better understand adult survival in marine turtles and avoid drawing inaccurate conclusions from current estimates, we conducted a comprehensive meta-analysis to test how heterogeneity among estimates was partitioned among phylogenetic, biogeographic and methodological factors. Fifty-nine studies from five marine turtle species met the minimum selection criteria for inclusion in our meta-analysis. Heterogeneity among survival estimates was first partitioned between differences in ocean basin (Indo-PacificversusAtlantic), then by differences among family/tribe within the Indo-Pacific (CheloniniversusCarettini and Dermochelidae). However, apparent differences attributed to biogeography (ocean basin effect) and phylogeny (family/tribe effect) were highly correlated with methodological differences in tag type, model type, habitat type and study duration, thereby confounding biological interpretations and complicating efforts to use many current survival estimates in population assessments. Our results highlight the importance of evaluating sources of heterogeneity when interpreting patterns among similar demographic studies and directly inform efforts to identify research priorities for marine turtles globally.
Recurrent Neural Networks for Multivariate Time Series with Missing Values
Authors: Che Zhengping , Purushotham Sanjay , Cho Kyunghyun , Sontag David , Liu Yan 
Published: April 2018

AbstractMultivariate time series data in practical applications, such as health care, geoscience, and biology, are characterized by a variety of missing values. In time series prediction and other related tasks, it has been noted that missing values and their missing patterns are often correlated with the target labels, a.k.a., informative missingness. There is very limited work on exploiting the missing patterns for effective imputation and improving prediction performance. In this paper, we develop novel deep learning models, namely GRU-D, as one of the early attempts. GRU-D is based on Gated Recurrent Unit (GRU), a state-of-the-art recurrent neural network. It takes two representations of missing patterns, i.e., masking and time interval, and effectively incorporates them into a deep model architecture so that it not only captures the long-term temporal dependencies in time series, but also utilizes the missing patterns to achieve better prediction results. Experiments of time series classification tasks on real-world clinical datasets (MIMIC-III, PhysioNet) and synthetic datasets demonstrate that our models achieve state-of-the-art performance and provide useful insights for better understanding and utilization of missing values in time series analysis.
Comparative biogeography of the gut microbiome between Jinhua and Landrace pigs
Authors: Xiao Yingping , Kong Fanli , Xiang Yun , Zhou Weidong , Wang Junjun , Yang Hua , Zhang Guolong , Zhao Jiangchao 
Published: April 2018

AbstractThe intestinal microbiome is critically important in shaping a variety of host physiological responses. However, it remains elusive on how gut microbiota impacts overall growth and more specifically, adipogenesis. Using the pig as an animal model, we compared the differences in bacterial community structure throughout the intestinal tract in two breeds (Landrace and Jinhua) of pigs with distinct phenotypes. The Landrace is a commercial purebred and the Jinhua is a Chinese indigenous, slow-growing breed with high propensity for fat deposition. Using 16S rRNA gene sequencing, we revealed that the bacterial communities are more diverse in the duodenum, jejunum, and cecum of Jinhua pigs than in those of Landrace pigs, whereas the ileal and colonic microbiota show a similar complexity between the two breeds. Furthermore, a number of bacterial taxa differentially exist in Jinhua and Landrace pigs throughout the entire intestinal tract, with the jejunal and ileal microbiome showing the greatest contrast. Functional prediction of the bacterial community suggested increased fatty acid biosynthesis in Jinghua pigs, which could partially explain their adiposity phenotype. Further studies are warranted to experimentally verify the relative contribution of each enriched bacterial species and their effect on adipogenesis and animal growth.
Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice
Authors: Hirose Misa , Schilf Paul , Gupta Yask , Zarse Kim , Künstner Axel , Fähnrich Anke , Busch Hauke , Yin Junping , Wright Marvin N. , Ziegler Andreas , Vallier Marie , Belheouane Meriem , Baines John F , Tautz Diethard , Johann Kornelia , Oelkrug Rebecca , Mittag Jens , Lehnert Hendrik , Othman Alaa , Jöhren Olaf , Schwaninger Markus , Prehn Cornelia , Adamski Jerzy , Shima Kensuke , Rupp Jan , Häsler Robert , Fuellen Georg , Köhling Rüdiger , Ristow Michael , Ibrahim Saleh M. 
Published: April 2018

AbstractMutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e., the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum of diseases but also physiological processes, including endurance exercise performance in athletes. However, the phenotypic consequences of limited levels of naturally arising heteroplasmy have not been experimentally studied to date. We hence generated a conplastic mouse strain carrying the mitochondrial genome of an AKR/J mouse strain (B6-mtAKR) in a C57BL/6 J nuclear genomic background, leading to >20% heteroplasmy in the origin of light-strand DNA replication (OriL). These conplastic mice demonstrate a shorter lifespan as well as dysregulation of multiple metabolic pathways, culminating in impaired glucose metabolism, compared to that of wild-type C57BL/6 J mice carrying lower levels of heteroplasmy. Our results indicate that physiologically relevant differences in mtDNA heteroplasmy levels at a single, functionally important site impair the metabolic health and lifespan in mice.
The value of radial endobronchial ultrasound-guided bronchial brushing in peripheral non-squamous non-small cell lung cancer
Authors: Yu Kai-Lun , Tsai Tzu-Hsiu , Ho Chao-Chi , Liao Wei-Yu , Lin Ching-Kai , Hsu Chia-Lin , Shih Jin-Yuan 
Published: April 2018

AbstractRadial endobronchial ultrasound (R-EBUS) is one important diagnostic approach in non-small cell lung cancers (NSCLC). However, the small samples obtained from R-EBUS-guided transbronchial biopsies are sometimes insufficient for pathological and molecular diagnosis. Herein, we investigated the suitability of R-EBUS-guided bronchial brushing specimens for NSCLC diagnosis and EGFR genotyping. We enrolled 941 consecutive patients with peripheral pulmonary lesions who underwent R-EBUS. Cytology-positive brushing specimens from non-squamous NSCLC patients were tested for EGFR mutations. Non-squamous NSCLC was diagnosed in 624 patients (66.3%). Positive cytology was documented in the brushing samples of 376 patients (60.3%). Higher diagnostic yields were obtained in patients exhibiting bronchus signs on chest tomography, and those with R-EBUS probe located within the lesion. EGFR genotyping was successfully performed in 363 samples (96.5% of cytology-positive brushing samples). EGFR genotyping concordance between brushing specimens and matched tissue samples was 88.7% (kappa = 0.745, P < 0.001). Furthermore, 144 non-squamous NSCLC patients (23.1%) with failed pathological diagnosis or EGER sequencing by R-EBUS-guided transbronchial biopsy required repeat biopsies. However, it was achieved successfully from the brushing specimens of 57 patients (39.6%). In conclusion, for patients with peripheral lung cancer, R-EBUS-guided bronchial brushing could provide an additional sampling method for diagnosis and EGFR genotyping.