bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myogenin promotes myocyte fusion to balance fibre number and size
Authors: Ganassi Massimo , Badodi Sara , Ortuste Quiroga Huascar Pedro , Zammit Peter S. , Hinits Yaniv , Hughes Simon M. 
Published: October 2018

AbstractEach skeletal muscle acquires its unique size before birth, when terminally differentiating myocytes fuse to form a defined number of multinucleated myofibres. Although mice in which the transcription factor Myogenin is mutated lack most myogenesis and die perinatally, a specific cell biological role for Myogenin has remained elusive. Here we report that loss of function of zebrafish myog prevents formation of almost all multinucleated muscle fibres. A second, Myogenin-independent, fusion pathway in the deep myotome requires Hedgehog signalling. Lack of Myogenin does not prevent terminal differentiation; the smaller myotome has a normal number of myocytes forming more mononuclear, thin, albeit functional, fast muscle fibres. Mechanistically, Myogenin binds to the myomaker promoter and is required for expression of myomaker and other genes essential for myocyte fusion. Adult myog mutants display reduced muscle mass, decreased fibre size and nucleation. Adult-derived myog mutant myocytes show persistent defective fusion ex vivo. Myogenin is therefore essential for muscle homeostasis, regulating myocyte fusion to determine both muscle fibre number and size.
Large-scale whole-exome sequencing association studies identify rare functional variants influencing serum urate levels
Authors: Tin Adrienne , Li Yong , Brody Jennifer A. , Nutile Teresa , Chu Audrey Y. , Huffman Jennifer E. , Yang Qiong , Chen Ming-Huei , Robinson-Cohen Cassianne , Macé Aurélien , Liu Jun , Demirkan Ayşe , Sorice Rossella , Sedaghat Sanaz , Swen Melody , Yu Bing , Ghasemi Sahar , Teumer Alexanda , Vollenweider Peter , Ciullo Marina , Li Meng , Uitterlinden André G. , Kraaij Robert , Amin Najaf , van Rooij Jeroen , Kutalik Zoltán , Dehghan Abbas , McKnight Barbara , van Duijn Cornelia M. , Morrison Alanna , Psaty Bruce M. , Boerwinkle Eric , Fox Caroline S. , Woodward Owen M. , Köttgen Anna 
Published: October 2018

AbstractElevated serum urate levels can cause gout, an excruciating disease with suboptimal treatment. Previous GWAS identified common variants with modest effects on serum urate. Here we report large-scale whole-exome sequencing association studies of serum urate and kidney function among ≤19,517 European ancestry and African-American individuals. We identify aggregate associations of low-frequency damaging variants in the urate transportersSLC22A12(URAT1;p = 1.3 × 10−56) andSLC2A9(p = 4.5 × 10−7). Gout risk in rareSLC22A12variant carriers is halved (OR = 0.5,p = 4.9 × 10−3). Selected rare variants inSLC22A12are validated in transport studies, confirming three as loss-of-function (R325W, R405C, and T467M) and illustrating the therapeutic potential of the new URAT1-blocker lesinurad. InSLC2A9, mapping of rare variants of large effects onto the predicted protein structure reveals new residues that may affect urate binding. These findings provide new insights into the genetic architecture of serum urate, and highlight molecular targets inSLC22A12andSLC2A9for lowering serum urate and preventing gout.
Local generation of hydrogen for enhanced photothermal therapy
Authors: Zhao Penghe , Jin Zhaokui , Chen Qian , Yang Tian , Chen Danyang , Meng Jin , Lu Xifeng , Gu Zhen , He Qianjun 
Published: October 2018

AbstractBy delivering the concept of clean hydrogen energy and green catalysis to the biomedical field, engineering of hydrogen-generating nanomaterials for treatment of major diseases holds great promise. Leveraging virtue of versatile abilities of Pd hydride nanomaterials in high/stable hydrogen storage, self-catalytic hydrogenation, near-infrared (NIR) light absorption and photothermal conversion, here we utilize the cubic PdH0.2 nanocrystals for tumour-targeted and photoacoustic imaging (PAI)-guided hydrogenothermal therapy of cancer. The synthesized PdH0.2 nanocrystals have exhibited high intratumoural accumulation capability, clear NIR-controlled hydrogen release behaviours, NIR-enhanced self-catalysis bio-reductivity, high NIR-photothermal effect and PAI performance. With these unique properties of PdH0.2 nanocrystals, synergetic hydrogenothermal therapy with limited systematic toxicity has been achieved by tumour-targeted delivery and PAI-guided NIR-controlled release of bio-reductive hydrogen as well as generation of heat. This hydrogenothermal approach has presented a cancer-selective strategy for synergistic cancer treatment.
Probing aggrephagy using chemically-induced protein aggregates
Authors: Janssen Anne F. J. , Katrukha Eugene A. , van Straaten Wendy , Verlhac Pauline , Reggiori Fulvio , Kapitein Lukas C. 
Published: October 2018

AbstractSelective types of autophagy mediate the clearance of specific cellular components and are essential to maintain cellular homeostasis. However, tools to directly induce and monitor such pathways are limited. Here we introduce the PIM (particles induced by multimerization) assay as a tool for the study of aggrephagy, the autophagic clearance of aggregates. The assay uses an inducible multimerization module to assemble protein clusters, which upon induction recruit ubiquitin, p62, and LC3 before being delivered to lysosomes. Moreover, use of a dual fluorescent tag allows for the direct observation of cluster delivery to the lysosome. Using flow cytometry and fluorescence microscopy, we show that delivery to the lysosome is partially dependent on p62 and ATG7. This assay will help in elucidating the spatiotemporal dynamics and control mechanisms underlying aggregate clearance by the autophagy–lysosomal system.
Molecular determinants of post-mastectomy breast cancer recurrence
Authors: Keene Kimberly S. , King Tari , Hwang E. Shelley , Peng Bo , McGuire Kandace P. , Tapia Coya , Zhang Hong , Bae Sejong , Nakhlis Faina , Klauber-Demore Nancy , Meszoely Ingrid , Sabel Michael S. , Willey Shawna C. , Eterovic Agda Karina , Hudis Cliff , Wolff Antonio C. , De Los Santos Jennifer , Thompson Alastair , Mills Gordon B. , Meric-Bernstam Funda 
Published: October 2018

AbstractBreast cancer (BC) adjuvant therapy after mastectomy in the setting of 1–3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, therapy naïve, T 1–3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy. This included 32 LRR, 34 DM, and 49 controls. RNAseq was performed on primary tumors in 110 patients; with no difference in RNA profiles between patients with LRR, DM, or controls. DNA analysis on 57 primary tumors (17 LRR, 15 DM, and 25 controls) identified significantly more NF1 mutations and mitogen-activated protein kinase (MAPK) pathway gene mutations in patients with LRR (24%, 47%) and DM (27%, 40%) compared to controls (0%, 0%; p < 0.0001 and p = 0.0070, respectively). Three patients had matched primary vs. LRR samples, one patient had a gain of a NF1 mutation in the LRR. There was no significant difference between the groups for PTEN loss or cleaved caspase 3 expression. The mean percentage Ki 67 labeling index was higher in patients with LRR (29.2%) and DM (26%) vs. controls (14%, p = 0.0045). In summary, mutations in the MAPK pathway, specifically NF1, were associated with both LRR and DM, suggesting that alterations in MAPK signaling are associated with a more aggressive tumor phenotype. Validation of these associations in tissues from randomized trials may support targeted therapy to reduce breast cancer recurrence.
Benefits of Early Treatment for Patients with Hepatic Myelopathy Secondary to TIPS: A Retrospective Study in Northern China
Authors: Zhao Hongwei , Yue Zhendong , Wang Lei , Fan Zhenhua , He Fuliang , Dong Xiaoqun , Liu Fuquan 
Published: October 2018

AbstractTransjugular intrahepatic portosystemic shunt (TIPS) is an effective therapy for reducing portal pressure. Hepatic myelopathy (HM), a rare complication of chronic liver diseases, remains obscure in terms of treatment and prognosis. We aimed to determine an optimal treat strategy for patients with HM after TIPS. Twenty-nine patients who developed HM after TIPS were stratified by time-lapse from onset to treatment: group A (n = 16), <6 months; group B (n = 13), ≥6 months. Therapeutic measures included shunt-limiting and medical treatments. Overall survival, lower-limb muscle strength, Fugl-Meyer score, Barthel index, and serum ammonia were recorded. Median survival time in group A or B was 30 months or 16.5 months, respectively (log rank p = 0.0172). All patients in group A obtained improvement in grading of muscle strength (p < 0.0001), Fugl-Meyer score (p = 0.0021), and Barthel index (p = 0.0003), particularly male patients and those subjected to shunt-limiting. Serum ammonia levels were decreased significantly in both group A (p = 0.0007) and group B (p = 0.0007). Collectively, once HM is confirmed after TIPS, active intervention is imperative and urgent, especially within the first 6 months from onset of symptom. TIPS shunt-limiting is particularly beneficial for rehabilitation in patients with early-onset HM.
Effects of dietary protein restriction followed by realimentation on growth performance and liver transcriptome alterations of lamb
Authors: Cui K. , Wang B. , Ma T. , Si B. W. , Zhang N. F. , Tu Y. , Diao Q. Y. 
Published: October 2018

AbstractThe present study aimed to investigate the compensatory effect of early protein restriction followed by a realimentation on growth performance of lamb and to explore the transcriptomic changes in liver. Thirty-two lambs with an initial birth weight of 2.3 ± 0.20 kg that were weaned on day 15 were randomly divided into two groups. The lambs were fed a basal diet with normal protein level (NPL, protein level in the milk replacer and starter, 25 and 21%, respectively) or low protein level (LPL, protein level in the milk replacer and starter, 19 and 15%, respectively) from 15 to 60 d, after which all lambs consumed the same diet with a normal protein level from 61 to 90 d. Protein restriction led to a significant decrease in average daily gain (ADG), body weight and liver weight (P < 0.05). Transcriptome analysis showed that 302 or 12 differentially expressed genes (DEGs) were identified during the restriction or recovery periods, respectively (P < 0.05). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that DEGs enriched in nutrient metabolism and antioxidant capacity were down-regulated, while vessel development and immunity response-related genes up-regulated. The genes involved in metabolism of tyrosine were still down-regulated in the realimentation phase. Studies in this area indicated the accelerated growth effect of early protein restriction followed by a realimentation on growth performance of lambs and explored the transcriptomics change of liver which can help to develop feeding strategies to optimize the use of feedstuffs and in providing a new perspective for the study of early nutrition and epigenetics in later life.
Reduced graphene oxide triggered epithelial-mesenchymal transition in A549 cells
Authors: Liao Yanyan , Wang Weiyi , Huang Xiaomei , Sun Yongyan , Tian Shen , Cai Peng 
Published: October 2018

AbstractGraphene and its derivatives have exhibited wide potential applications in electronics, structural engineering and medicine. However, over utilization and untreated discharge may cause its distribution into environmental as well as biological chain, which raised the concerns of potential health risk as a potential hazard. Accumulating evidence has demonstrated that graphene derivatives induce lung fibrosis in vivo, so overall goal of this study was to explore the molecular mechanisms underlying the pulmonary fibrotic responses of reduced graphene oxide (rGO), using in vitro assays. Epithelial-mesenchymal transition (EMT) has profound effect on development of pulmonary fibrosis. Herein, we evaluated the EMT effect of rGO samples on A549 cells. Firstly, rGO penetrated through the A549 cells membrane into the cytosol by endocytosis and located in late endosome and/or lysosomes observed via transmission electron microscopy (TEM), and were well tolerant by cells. Secondly, rGO promoted the cell migration and invasion capacities at lower doses (below 10 μg/ml), but significantly inhibited the capacities at 20 μg/ml. Moreover, rGO-induced EMT were evidenced by decreased expression of epithelial marker like E-cadherin, β-catenin, Smad4 and increased expression of mesenchymal markers like Vimentin, VEGF-B, TWIST1. Based on our findings, it is supposed that rGO can effectively induce EMT through altering epithelial–mesenchymal transition markers in A549 cells.
NLRP3 Inflammasome Modulates Post-Burn Lipolysis and Hepatic Fat Infiltration via Fatty Acid Synthase
Authors: Vinaik Roohi , Stanojcic Mile , Jeschke Marc G. 
Published: October 2018

AbstractBurns result in generalized catabolism, lipolysis, and hyperinflammation. NLRP3 inflammasome, a mediator of hyperinflammation, is upregulated in burn patients’ adipose tissue within 7 days post-burn. However, its role during the acute phase is unknown. Here, wild-type (WT) and NLRP3 knockout (NLRP3−/−) mice were exposed to 25% TBSA scald burn. Flow cytometric analysis demonstrated greater liver macrophage infiltration in NLRP3−/− yet decreased protein expression of NLRP3 components, ER stress, and apoptosis. NLRP3−/− had increased circulating free fatty acids (FFA), fatty deposition and liver weight 1 hour post-burn. Alterations in adipose fatty acid synthase (Fasn) expression affects FFA levels post-burn; WT have an early peak in Fasn gene and protein expression that is lost in NLRP3−/−, resulting in increased lipolysis and hepatic fatty deposition. In summary, our findings reveal that NLRP3 inflammasome activation is a double-edged sword. While prolonged inflammation and long-term effects of macrophage activation are associated with poor outcomes, acute inflammation may be beneficial. These results highlight the important metabolic role that NLRP3 inflammasome plays in the acute phase, ultimately affecting survival post-burn.
Cytometric analysis of adipose tissue reveals increments of adipocyte progenitor cells after weight loss induced by bariatric surgery
Authors: García-Rubio Jesús , León Josefa , Redruello-Romero Anaïs , Pavón Esther , Cozar Antonio , Tamayo Francisco , Caba-Molina Mercedes , Salmerón Javier , Carazo Ángel 
Published: October 2018

AbstractObesity-related comorbidities are, in large part, originated from the dysfunction of adipose tissue. Most of them revert after the normalization of body mass. Adipose tissue is essentially occupied by adipocytes. However, different populations of immunological cells and adipocyte precursor cells (AdPCs) are the main cellular components of tissue. During obesity, body fat depots acquire a low-level chronic inflammation and adipocytes increase in number and volume. Conversely, weight loss improves the inflammatory phenotype of adipose tissue immune cells and reduces the volume of adipocytes. Nevertheless, very little is known about the evolution of the human AdPCs reservoir. We have developed a flow cytometry-based methodology to simultaneously quantify the main cell populations of adipose tissue. Starting from this technical approach, we have studied human adipose tissue samples (visceral and subcutaneous) obtained at two different physiological situations: at morbid obesity and after bariatric surgery-induced weight loss. We report a considerable increase of the AdPCs reservoir after losing weight and several changes in the immune cells populations of adipose tissue (mast cells increase, neutrophils decrease and macrophages switch phenotype). No changes were observed for T-lymphocytes, which are discussed in the context of recent findings.
Improving face identity perception in age-related macular degeneration via caricaturing
Authors: Lane Jo , Rohan Emilie M. F. , Sabeti Faran , Essex Rohan W. , Maddess Ted , Barnes Nick , He Xuming , Robbins Rachel A. , Gradden Tamara , McKone Elinor 
Published: October 2018

AbstractPatients with age-related macular degeneration (AMD) have difficulty recognising people’s faces. We tested whether this could be improved using caricaturing: an image enhancement procedure derived from cortical coding in a perceptual ‘face-space’. Caricaturing exaggerates the distinctive ways in which an individual’s face shape differs from the average. We tested 19 AMD-affected eyes (from 12 patients; ages 66–93 years) monocularly, selected to cover the full range of vision loss. Patients rated how different in identity people’s faces appeared when compared in pairs (e.g., two young men, both Caucasian), at four caricature strengths (0, 20, 40, 60% exaggeration). This task gives data reliable enough to analyse statistically at the individual-eye level. All 9 eyes with mild vision loss (acuity ≥ 6/18) showed significant improvement in identity discrimination (higher dissimilarity ratings) with caricaturing. The size of improvement matched that in normal-vision young adults. The caricature benefit became less stable as visual acuity further decreased, but caricaturing was still effective in half the eyes with moderate and severe vision loss (significant improvement in 5 of 10 eyes; at acuities from 6/24 to poorer than <6/360). We conclude caricaturing has the potential to help many AMD patients recognise faces.
Microsphere-mediated optical contrast tuning for designing imaging systems with adjustable resolution gain
Authors: Migliozzi Daniel , Gijs Martin A. M. , Huszka Gergely 
Published: October 2018

AbstractUpon illumination, a dielectric microsphere (μS) can generate a photonic nanojet (PNJ), which plays a role in the super-resolution imaging of a sample placed in the μS’s immediate proximity. Recent microscopy implementations pioneered this concept but, despite the experimental characterization and theoretical modeling of the PNJ, the key physical factors that enable optimization of such imaging systems are still debated. Here, we systematically analyzed the parameters that govern the resolution increase in the case of large-diameter (>20 µm) μS-assisted incoherent microscopy by studying both the illumination and the detection light paths. We determined the enhanced-resolution zone created by the μS, in which the detection system has a net resolution gain that we calculated theoretically and subsequently confirmed experimentally. Our results quantitatively describe the resolution enhancement mediated by the optical contrast between the μS and its surrounding medium, and provide concrete means for designing μS-enhanced imaging systems for several application requirements.
Ag surface segregation in nanoporous Au catalysts during CO oxidation
Authors: Pia Giorgio , Sogne Elisa , Falqui Andrea , Delogu Francesco 
Published: October 2018

AbstractThe present study focuses on the modification of surface compositional profiles induced in nanoporous (NP) Au catalysts by the catalytic oxidation of carbon monoxide to carbon dioxide in the presence of oxygen. The phenomenon has deep implications concerning the catalytic behavior of NP Au foams in particular, and more in general for the design of more efficient catalysts. Aimed at gaining deeper insight into the mechanisms governing surface segregation, we exposed NP Au foams containing residual Ag to a mixture of gaseous carbon monoxide and oxygen at different temperature. Structural and surface composition analyses pointed out the concomitant occurrence of both NP Au coarsening and Ag surface segregation processes. Experimental findings suggest for Ag surface segregation a two-stage kinetics. During the initial, rapid coarsening of the NP Au structure, Ag surface segregation is mediated by surface rearrangements, which allow the Ag atoms to reach the surface at anomalously fast rate. As coarsening decelerates, the slower diffusion of buried Ag atoms towards the surface predominates, due to favorable chemical interactions with adsorbed oxygen. This novel mechanism’s understanding can benefit strategic areas of science and technology.
Antiretroviral resistance, genotypic characterization and origin of Human Immunodeficiency Virus among the infected wives of Intravenous drug users in Manipur
Authors: Sharma Adhikarimayum Lakhikumar , Singh Thiyam Ramsing , Singh Lisam Shanjukumar 
Published: October 2018

AbstractIncreasing incidence of drug resistance is ascertained to be the main obstacles in limiting the virus among the human immunodeficiency virus (HIV) infected individuals. This study investigates the drug resistance mutations (DRMs), genetic variants and origin of transmitted drug resistance of HIV-1 among the HIV-1 infected wives of intravenous drug users (IDUs) in Manipur. 44 HIV pol gene sequences were generated from 56 blood samples by viral gene amplification and sequencing. Sequences were then analysed for drug resistance, genetic variants and origin. The result revealed that among the treatment naive cases, 35.7% had Transmitted Drug Resistance Mutations (TDRMs) while among treatment experienced cases, 50% had Acquired Drug Resistant Mutations (ADRMs). These TDRMs and ADRMs conferred resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and/or protease inhibitors (PIs). Majority of the isolated HIV-1 sequences (77.3%) were subtype C while 9.1% was discordant subtype, 6.8% was subtype B, 4.5% was CRF_01AE and 2.3% was URF_BC. TDRM strains were found to be introduced from Myanmar, Vietnam and mainland India. This study also reveals the appearance of CRF_01AE for the first time in Manipur. The finding of this study indicates high prevalence of drug resistant mutations and complex molecular epidemiology in Manipur.
CH3NH3PbX3 (X = I, Br) encapsulated in silicon carbide/carbon nanotube as advanced diodes
Authors: Zhang Lishu , Dai Xinyue , Li Tao , Li Jie , Li Hui 
Published: October 2018

AbstractWe employ first-principles density functional theory (DFT) calculations to study CH3NH3PbX3 (X = I, Br) and its encapsulation into the silicon carbide nanotube and carbon nanotube (CNT). Our results indicate that these devices show diode behaviors which act on negative bias voltage but do not work under positive voltage. When they are encapsulated into SiC nanotube and CNT, their electronic properties would be changed, especially, electric currents mainly exist at positive bias region. Corresponding transmission spectra and density of states are provided to interpret the transport mechanism of the CH3NH3PbX3 (X = I, Br) as a diode. These findings open a new door to microelectronics and integrated circuit components, providing theoretical foundation for innovation of the new generation of electronic materials.