bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboxyl-terminal modulator protein regulates Akt signaling during skeletal muscle atrophy in vitro and a mouse model of amyotrophic lateral sclerosis
Authors: Wang Junmei , Fry Colin M. E. , Walker Chandler L. 
Published: March 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease involving motor neuron death, paralysis and, ultimately, respiratory failure. Motor neuron dysfunction leads to target skeletal muscle atrophy involving dysregulation of downstream cell survival, growth and metabolic signaling. Decreased Akt activity is linked to muscle atrophy in ALS and is associated with increased atrophy gene expression. Unfortunately, the regulating mechanism of Akt activity in atrophic muscle remains unclear. Recent research indicates a role of carboxyl-terminal modulator protein (CTMP) in Akt-signaling related neurologic dysfunction and skeletal muscle metabolism. CTMP is known to bind and reduce Akt phosphorylation and activation. We hypothesized that CTMP expression might progressively increase in ALS skeletal muscle as the disease progresses, downregulating Akt activity. We found that CTMP protein expression significantly increased in hindlimb skeletal muscle in the mSOD1G93A mouse model of ALS in late stages of the disease (P < 0.05), which negatively correlated with Akt phosphorylation over this period (R2 = −0.77). Co-immunoprecipitation of Akt revealed CTMP binding in pre-symptomatic and end-stage skeletal muscle, suggesting a possible direct role in reduced Akt signaling during disease progression. Inflammatory TNFα and downstream cellular degradation process markers for autophagy, lysosome production, and atrophy significantly increased in a pattern corresponding to increased CTMP expression and reduced Akt phosphorylation. In an in vitro model of skeletal muscle atrophy, differentiated C2C12 cells exhibited reduced Akt activity and decreased FOXO1 phosphorylation, a process known to promote transcription of atrophy genes in skeletal muscle. These results corresponded with increased Atrogin-1 expression compared to healthy control cells (P < 0.05). Transfection with CTMP siRNA significantly increased Akt phosphorylation in atrophic C2C12 cells, corresponding to significantly decreased CTMP expression. In conclusion, this is the first study to provide evidence for a link between elevated CTMP expression, downregulated Akt phosphorylation and muscle atrophy in ALS and clearly demonstrates a direct influence of CTMP on Akt phosphorylation in an in vitro muscle cell atrophy model.
Spatio-temporal patterns and characteristics of swine shipments in the U.S. based on Interstate Certificates of Veterinary Inspection
Authors: Gorsich Erin E. , Miller Ryan S. , Mask Holly M. , Hallman Clayton , Portacci Katie , Webb Colleen T. 
Published: March 2019

AbstractDomestic swine production in the United States is a critical economic and food security industry, yet there is currently no large-scale quantitative assessment of swine shipments available to support risk assessments. In this study, we provide a national-level characterization of the swine industry by quantifying the demographic (i.e. age, sex) patterns, spatio-temporal patterns, and the production diversity within swine shipments. We characterize annual networks of swine shipments using a 30% stratified sample of Interstate Certificates of Veterinary Inspection (ICVI), which are required for the interstate movement of agricultural animals. We used ICVIs in 2010 and 2011 from eight states that represent 36% of swine operations and 63% of the U.S. swine industry. Our analyses reflect an integrated and spatially structured industry with high levels of spatial heterogeneity. Most shipments carried young swine for feeding or breeding purposes and carried a median of 330 head (range: 1–6,500). Geographically, most shipments went to and were shipped from Iowa, Minnesota, and Nebraska. This work, therefore, suggests that although the swine industry is variable in terms of its size and type of swine, counties in states historically known for breeding and feeding operations are consistently more central to the shipment network.
Clinical and endoscopic characteristics of sessile serrated adenomas/polyps with dysplasia/adenocarcinoma in a Korean population: A Korean Association for the Study of Intestinal Diseases (KASID) multicenter study
Authors: Kim Ki-Hyun , Kim Kyeong-Ok , Jung Yunho , Lee Jun , Kim Sang-Wook , Kim Jae-Hyun , Kim Tae-Jun , Cho Young-Seok , Joo Young-Eun 
Published: March 2019

AbstractSessile serrated adenomas/polyps (SSA/Ps) are precancerous lesions that account for one-third of colorectal cancers. The endoscopic and pathologic differentiation between SSA/Ps without dysplasia (SSA/POs) and SSA/Ps with dysplasia or adenocarcinoma (SSA/PDAs) can be difficult. This study aimed to assess the clinical characteristics of SSA/PDs. This multicenter retrospective cohort study included 532 patients who underwent endoscopic resection and were pathologically diagnosed with SSA/POs and SSA/PDAs. Initially, medical, endoscopic, and histopathological records of patients who underwent endoscopic resection of SSA/POs and SSA/PDAs at eight university hospitals in Korea between January 2005 and December 2015 were reviewed. A total of 307 (57.7%) patients were detected in men and 319 (60.0%) were located in the proximal colon. Most SSA/Ps had a flat, slightly elevated, or sessile morphology. The most prevalent endoscopic findings of SSA/Ps were nodular surface (244, 45.9%), disrupted vascular pattern (232, 43.6%), altered fold contour (141, 26.5%), dome-shaped morphology (135, 25.4%), and pale color (115, 21.6%). SSA/POs were more commonly found in the proximal colon, compared to SSA/PDAs. SSA/PDAs displayed 0-Ip, Isp, IIb or IIa + IIc morphologies more frequently, while SSA/POs displayed 0-Is or IIa morphology more frequently. The frequency of a rim of debris/bubbles was significantly higher in SSA/POs, while nodular surface and disrupted vascular pattern were significantly higher in SSA/PDAs. In the univariate analysis of endoscopic features, SSA/PDAs were significantly associated with the distal colon location, 0-Isp and IIb morphologies, nodular surface, and disrupted vascular pattern. In the multivariate analysis, 0-IIb, nodular surface, and disrupted vascular pattern were significantly associated with SSA/PDAs. SSA/Ps with 0-IIb morphology, nodular surface and disrupted vascular pattern are associated with an increased risk of dysplasia or adenocarcinoma.
Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States
Authors: Chen Fangzhou , Knutson Todd P. , Rossow Stephanie , Saif Linda J. , Marthaler Douglas G. 
Published: March 2019

AbstractThe epidemiology and genetic diversity oftransmissible gastroenteritis virus(TGEV) in the United States (US) was investigated by testing clinical cases for TGEV by real time RT-PCR between January 2008 and November 2016. Prevalence of TGEV ranged between 3.8–6.8% and peaked during cold months until March 2013, in which prevalence decreased to < 0.1%. Nineteen complete TGEV genomes and a single strain ofporcine respiratory coronavirus(PRCV) from the US were generated and compared to historical strains to investigate the evolution of these endemic coronaviruses. Sixteen of our TGEV strains share 8 unique deletions and 119 distinct amino acid changes, which might greatly affect the biological characteristics of the variant TGEV, and resulted in a “variant” genotype of TGEV. The “variant” genotype shared similar unique deletions and amino acid changes with the recent PRCV strain identified in this study, suggesting a recombination event occurred between the ‘‘variant’’ TGEV and PRCV. Moreover, the results indicate the “variant” genotype is the dominant genotype circulating in the US. Therefore, this study provides insight into the occurrence, origin, genetic characteristics, and evolution of TGEV and PRCV circulating in the US.
Germline susceptibility variants impact clinical outcome and therapeutic strategies for stage III colorectal cancer
Authors: Lin Peng-Chan , Yeh Yu-Min , Wu Pei-Ying , Hsu Keng-Fu , Chang Jang-Yang , Shen Meng-Ru 
Published: March 2019

AbstractAlthough somatic mutations are the main cause of cancer, underlying germline alterations may affect cancer outcome. There is little information on comprehensive analysis of germline genome sequencing for cancer healthcare strategy. Here we studied the implication of germline cancer-associated variants on cancer counselling and therapeutic strategies by germline whole genome and tumor targeted sequencing. Fifty-five gynecological and 104 colorectal cancer (CRC) patients were enrolled. We identified 22 germline pathogenic variants in 16 cancer-associated genes. Most of them are involved in DNA repair signaling, including MLH1, BRCA1/2, MUTYH, ATM, PMS2, MSH6, BAP1, and FANCA. About 6% of cancer patients presented the secondary findings of germline variants with non-oncogenic impact, mainly on the cardiovascular system which should be carefully monitored during chemotherapy. CRC patients carrying germline susceptibility variants had better disease-free survival than those without variants. Importantly, in the CRC model, the underlying germline alterations mold the tumor somatic alteration landscape. NOTCH1 mutation was the most common somatic mutation in recurrent CRC, implying a potential therapeutic target in adjuvant setting. In conclusion, both tumor genome and germline sequence data have to be analyzed to have a more complete picture of the overall genetic foundation of cancer.
Photoelasticity-based evaluation of cellular contractile force for phenotypic discrimination of vascular smooth muscle cells
Authors: Sugita Shukei , Mizutani Eri , Hozaki Masatoshi , Nakamura Masanori , Matsumoto Takeo 
Published: March 2019

AbstractVascular smooth muscle cells (VSMCs) have two distinct phenotypes: contractile and synthetic. The major difference between these phenotypes lies in the magnitude of the contractile force produced by the cell. Although traction force microscopy (TFM) is often used to evaluate cellular contractile force, this method requires complex preprocessing and a sufficiently compliant substrate. To evaluate the contractile force and the phenotype of living VSMCs with minimal effort and in a manner independent of the substrate stiffness, we propose a photoelasticity-based method using retardation, which is related to the difference between the first and second principal stresses and their orientation. The results demonstrate that actin filaments co-localize with areas of high retardation in cells, indicating that the retardation of VSMCs is promoted by actin filaments. The retardation of cells treated with calyculin A and Y-27632 tended to be larger and smaller, respectively, than that of control cells. Cell traction force significantly correlates with total cell retardation (r2 = 0.38). The retardation of contractile VSMCs (passage 2) was significantly higher than that of synthetic VSMCs (passage 12). These results indicate that cell retardation can be used to assess cell contractile force and, thus, determine the phenotype of VSMCs.
Prognostic Significance of Mean Platelet Volume on Local Advanced Non-Small Cell Lung Cancer Managed with Chemoradiotherapy
Authors: Sakin Abdullah , Secmeler Saban , Arici Serdar , Geredeli Caglayan , Yasar Nurgul , Demir Cumhur , Aksaray Ferdi , Cihan Sener 
Published: March 2019

AbstractMean platelet volume (MPV), the most commonly used measure of platelet size, and is altered in patients with malignancies. The aim of this study was to investigate the effect of MPV on overall survival (OS) of patients with locally advanced (Stage IIIA/B) inoperable non-small cell lung cancer (NSCLC). This retrospective study included patients who received concomitant chemoradiotherapy (CCRT) with cisplatin + etoposide regimen due to locally advanced stage IIIA/B NSCLC. The study included a total of 115 cases, consisting of 110 (95.7%) male and 5 (4.2%) female patients. The mean age of the patients was 61.3 ± 10.4 (22–82) years. ROC curve generated by MPV for OS yielded an AUC of 0.746 (95% CI 0.659–0.833), (p < 0.001). MPV was detected as >9 fL with a sensitivity of 74.4% and a specificity of 72.0%. In patients with stage IIIA, median OS was 45.0 months (95% CI 17.3–74.1) and 21 months (95% CI 10.6–31.3) in groups with MPV > 9.0 fL and ≤9.0 fL, respectively (p = 0.013). In patients with stage IIIB, median OS was 44.0 months (95% CI 13.8–60.6) and 16 months (95% CI 9.5–22.4) in groups with MPV > 9.0 fL and ≤9.0 fL, respectively (p = 0.036). ECOG performance score, total platelet count, and MPV were found as the most significant independent factors affecting survival (p < 0.001, p = 0.008, and, p = 0.034, respectively). In this study, we showed that decreased pre-treatment MPV was an independent risk factor for survival in NSCLC patients who were administered CCRT. As part of routine complete blood count panel, MPV may represent one of the easiest measuring tools as an independent prognostic marker for survival in locally advanced NSCLC.
Induction of tumor-specific CTL responses using the C-terminal fragment of Viral protein R as cell penetrating peptide
Authors: Gross D. A. , Leborgne C. , Chappert P. , Masurier C. , Leboeuf M. , Monteilhet V. , Boutin S. , Lemonnier F. A. , Davoust J. , Kichler A. 
Published: March 2019

AbstractThe discovery of tumor-associated antigens recognized by T lymphocytes opens the possibility of vaccinating cancer patients with defined antigens. However, one of the major limitation of peptide-based vaccines is the low immunogenicity of antigenic peptides. Interestingly, if these epitopes are directly delivered into the cytoplasm of antigen presenting cells, they can be efficiently presented via the direct MHC class I presentation pathway. To improve antigen entry, one promising approach is the use of cell penetrating peptides (CPPs). However, most studies use a covalent binding of the CPP with the antigen. In the present study, we focused on the C-terminal domain of Vpr which was previously demonstrated to efficiently deliver plasmid DNA into cells. We provide evidence that the peptides Vpr55-91 and Vpr55-82 possess the capacity of delivering proteins and epitopes into cell lines as well as into human primary dendritic cells, without the necessicity for a chemical linkage. Moreover, immunization of HLA-A2 transgenic mice with Vpr55-91 as the sole adjuvant is able to induce antigen-specific cytotoxic T lymphocytes against multiple tumor epitopes.
Determinants of high platelet reactivity in patients with acute coronary syndromes treated with ticagrelor
Authors: Adamski Piotr , Buszko Katarzyna , Sikora Joanna , Niezgoda Piotr , Fabiszak Tomasz , Ostrowska Małgorzata , Barańska Malwina , Karczmarska-Wódzka Aleksandra , Navarese Eliano Pio , Kubica Jacek 
Published: March 2019

AbstractHigh platelet reactivity (HPR) is a risk factor for stent thrombosis, a potentially lethal complication of percutaneous coronary intervention. HPR is also associated with increased risk of myocardial infarction and death in invasively-treated patients with acute coronary syndrome (ACS). HPR occurs even in ACS patients treated with ticagrelor, a state-of-the-art antiplatelet agent, especially during the first hours of treatment. Patient-level pharmacodynamic data obtained from 102 ACS subjects enrolled in two prospective, pharmacodynamic trials were analysed in order to identify clinical features related with increased odds of on-ticagrelor HPR during the first two hours after ticagrelor loading dose in ACS patients. Presence of ST-segment elevation myocardial infarction (versus non-ST-segment elevation ACS) and morphine co-administration were the strongest predictors of HPR at 1 and 2 hours after ticagrelor loading dose according to linear regression analyses, multiple backward stepwise logistic regression analyses and generalized estimating equation model. By pinpointing simple to recognize clinical features, the results of this study facilitate identification of ACS patients who have the highest odds of HPR during the initial phase of treatment with ticagrelor, and who could potentially benefit from alternative treatment strategies.
Similarities, variations, and evolution of cytochrome P450s in Streptomyces versus Mycobacterium
Authors: Senate Louisa Moshoeshoe , Tjatji Martin Phalane , Pillay Kayla , Chen Wanping , Zondo Ntokozo Minenhle , Syed Puleng Rosinah , Mnguni Fanele Cabangile , Chiliza Zinhle Edith , Bamal Hans Denis , Karpoormath Rajshekhar , Khoza Thandeka , Mashele Samson Sitheni , Blackburn Jonathan Michael , Yu Jae-Hyuk , Nelson David R. , Syed Khajamohiddin 
Published: March 2019

AbstractCytochrome P450 monooxygenases (P450s) found in all domains of life are known for their catalytic versatility and stereo- and regio-specific activity. While the impact of lifestyle on P450 evolution was reported in many eukaryotes, this remains to be addressed in bacteria. In this report, Streptomyces and Mycobacterium, belonging to the phylum Actinobacteria, were studied owing to their contrasting lifestyles and impacts on human. Analyses of all P450s and those predicted to be associated with secondary metabolism have revealed that different lifestyles have affected the evolution of P450s in these bacterial genera. We have found that while species in both genera have essentially the same number of P450s in the genome, Streptomyces P450s are much more diverse than those of Mycobacterium. Moreover, despite both belonging to Actinobacteria, only 21 P450 families were common, and 123 and 56 families were found to be unique to Streptomyces and Mycobacterium, respectively. The presence of a large and diverse number of P450s in Streptomyces secondary metabolism contributes to antibiotic diversity, helping to secure the niche. Conversely, based on the currently available functional data, types of secondary metabolic pathways and associated P450s, mycobacterial P450s seem to play a role in utilization or synthesis of lipids.
Intrinsic timescales of sensory integration for motion perception
Authors: Choi Woochul , Paik Se-Bum 
Published: March 2019

AbstractA subject-specific process of perceptual decision making is of importance to how the brain translates its interpretation of sensory information into behavior. In particular, a number of studies reported substantial variation across the observers’ decision behavior, which may reflect different profiles of evidence accumulated by each individual. However, a detailed profile of perceptual integration has not yet been verified from human behavioral data. To address the issue, we precisely measured the time course of sensory integration, as the “sensory integration kernel” of subjects, using a coherence-varying motion discrimination task. We found that each subject has a distinct profile of sensory integration. We observed that kernel size (maximum sensory integration interval) is consistent within subjects, independent of external stimuli conditions. The observed kernel could accurately predict subject-specific perceptual behaviors and explain the inter-individual variation of observed behaviors. Surprisingly, the performance of most subjects did not improve in proportion to increased duration of the stimulus, but was maximized when the stimulus duration matched their kernel size. We also found that the observed kernel size was strongly correlated with the subject-specific perceptual characteristics for illusory motion. Our results suggest that perceptual decisions arise from intrinsic decision dynamics, and on individual timescales of sensory integration.
Association Between Vitamin D and Adrenal Parameters with Metabolic and Inflammatory Markers in Polycystic Ovary Syndrome
Authors: Maidana P. , Fritzler A. , Mocarbel Y. , Perez Lana M. B. , González D. , Rosales M. , González de Chazal F. , Sternberg K. , Lamas Majek E. , Mallea-Gil S. , Genovesi E. , Pelayo M. , Fabre B. , Mesch V. 
Published: March 2019

AbstractVitamin D deficiency has been related with metabolic alterations in polycystic ovary syndrome (PCOS). As well, hyperactivation of adrenal axis can be programmed early in life and could be related later with PCOS development. Our aim was to establish the relationship between vitamin D and adrenal parameters with metabolic alterations and inflammation markers in PCOS. In 73 patients and 33 controls, 25-hydroxyvitamin D (25-OH-D), total and bioavailable testosterone (TT and bioT), androstenedione (A4), SHBG, cortisol, insulin, and C-reactive protein (hs-CRP) were determined; HOMA and lipid accumulation product (LAP) index were calculated. All parameters were higher in patients than in controls, except for SHBG and 25-OH-D which were lower. Binary regression analysis showed that differences in TT, bioT, A4, insulin and HOMA were independent of body mass index and waist circumference but SHBG, hs-CRP, LAP and 25-OH-D were related to body weight and fat distribution. Binary logistic regression analysis showed that cortisol and 25-OH-D could be associated to PCOS development. Correlations found between LAP and insulin, HOMA and hs-CRP confirm it is a good indicator of metabolic complications. Vitamin D and cortisol association to PCOS development justifies future research to understand the role of vitamin D in PCOS and analyze patient’s perinatal history and its possible relationship with hyperactivation of adrenal axis in adult life.
First Evidence for Mechanism of Inverse Ripening from In-situ TEM and Phase-Field Study of δ′ Precipitation in an Al-Li Alloy
Authors: Park Jiwon , Kamachali Reza Darvishi , Kim Sung-Dae , Kim Su-Hyeon , Oh Chang-Seok , Schwarze Christian , Steinbach Ingo 
Published: March 2019

AbstractIn-situ TEM investigation of aging response in an Al–7.8 at.% Li was performed at 200 °C up to 13 hours. Semi-spherical δ′ precipitates growing up to an average radius of 7.5 nm were observed. The size and number of individual precipitates were recorded over time and compared to large-scale phase-field simulations without and with a chemo-mechanical coupling effect, that is, concentration dependence of the elastic constants of the matrix solid solution phase. This type of coupling was recently reported in theoretical studies leading to an inverse ripening process where smaller precipitates grew at the expense of larger ones. Considering this chemo-mechanical coupling effect, the temporal evolution of number density, average radius, and size distribution of the precipitates observed in the in-situ experiment were explained. The results indicate that the mechanism of inverse ripening can be active in this case. Formation of dislocations and precipitate-free zones are discussed as possible disturbances to the chemo-mechanical coupling effect and consequent inverse ripening process.