bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paid employment and common mental disorders in 50–64-year olds: analysis of three cross-sectional nationally representative survey samples in 1993, 2000 and 2007
Authors: Perera G. , Di Gessa G. , Corna L. M. , Glaser K. , Stewart R. 
Published: August 2017

Aims.Associations between employment status and mental health are well recognised, but evidence is sparse on the relationship between paid employment and mental health in the years running up to statutory retirement ages using robust mental health measures. In addition, there has been no investigation into the stability over time in this relationship: an important consideration if survey findings are used to inform future policy. The aim of this study is to investigate the association between employment status and common mental disorder (CMD) in 50–64-year old residents in England and its stability over time, taking advantage of three national mental health surveys carried out over a 14-year period.Methods.Data were analysed from the British National Surveys of Psychiatric Morbidity of 1993, 2000 and 2007. Paid employment status was the primary exposure of interest and CMD the primary outcome – both ascertained identically in all three surveys (CMD from the revised Clinical Interview Schedule). Multivariable logistic regression models were used.Results.The prevalence of CMD was higher in people not in paid employment across all survey years; however, this association was only present for non-employment related to poor health as an outcome and was not apparent in those citing other reasons for non-employment. Odds ratios for the association between non-employment due to ill health and CMD were 3.05 in 1993, 3.56 in 2000, and 2.80 in 2007, after adjustment for age, gender, marital status, education, social class, housing tenure, financial difficulties, smoking status, recent physical health consultation and activities of daily living impairment.Conclusions.The prevalence of CMD was higher in people not in paid employment for health reasons, but was not associated with non-employment for other reasons. Associations had been relatively stable in strength from 1993 to 2007 in those three cross-sectional nationally representative samples.
CHAC2, downregulated in gastric and colorectal cancers, acted as a tumor suppressor inducing apoptosis and autophagy through unfolded protein response
Authors: Liu Shuiping , Fei Weiqiang , Shi Qinglan , Li Qiang , Kuang Yeye , Wang Chan , He Chao , Hu Xiaotong 
Published: August 2017

AbstractTumor suppressor genes play a key role in cancer pathogenesis. Through massive expression profiling we identified CHAC2 as a frequently downregulated gene in gastric and colorectal cancers. Immunohistochemistry and western blot revealed that CHAC2 was downregulated in most tumor tissues, and 3-year survival rate of patients with high CHAC2 expression was significantly higher than that of patients with low CHAC2 expression (P<0.001 and P=0.001, respectively). The data of univariate analysis and multivariate analysis suggested that CHAC2 could serve as an independent prognostic marker. Our results showed for the first time that CHAC2 was degraded by the ubiquitin-proteasome pathway and CHAC2 expression inhibited tumor cell growth, proliferation, migration in vitro and in vivo. Mechanistic study showed that CHAC2 induced mitochondrial apoptosis and autophagy through unfolded protein response. So in gastric and colorectal cancer CHAC2 acted as a tumor suppressor and might have therapeutic implication for patients.
Long noncoding RNA XIST expedites metastasis and modulates epithelial–mesenchymal transition in colorectal cancer
Authors: Chen Dong-liang , Chen Le-zong , Lu Yun-xin , Zhang Dong-sheng , Zeng Zhao-lei , Pan Zhi-zhong , Huang Peng , Wang Feng-hua , Li Yu-hong , Ju Huai-qiang , Xu Rui-hua 
Published: August 2017

AbstractTumor progression and metastasis is the main cause of death in colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) are critical regulators in various diseases including human cancer. In this study, we found that lncRNA XIST was overexpressed in CRC cell lines and tissues. High expression of lncRNA XIST was associated with adverse overall survival in CRC patients. Knockdown of lncRNA XIST remarkably inhibited CRC cell proliferation, invasion, epithelial–mesenchymal transition (EMT) and CRC stem cell formation in vitro as well as tumor growth and metastasis in vivo. Further study indicated that knockdown of lncRNA XIST markedly increased the expression of microRNA-200b-3p (miR-200b-3p) that has been found to be downregulated in CRC tissues and cell lines, and luciferase activity assay indicated that lncRNA XIST could bind directly with miR-200b-3p. Moreover, knockdown of lncRNA XIST significantly reduced the expression of ZEB1, which was the direct target of miR-200b-3p, and the tumor suppressive effects caused by knockdown of lncRNA XIST could be rescued by re-expression of ZEB1 in CRC cells. Overall, our study demonstrated how lncRNA XIST regulates CRC progression and metastasis by competing for miR-200b-3p to modulate the expression of ZEB1. lncRNA XIST may be used as a biomarker to predict prognosis in CRC patients.
Retinol saturase coordinates liver metabolism by regulating ChREBP activity
Authors: Heidenreich Steffi , Witte Nicole , Weber Pamela , Goehring Isabel , Tolkachov Alexander , von Loeffelholz Christian , Döcke Stephanie , Bauer Michael , Stockmann Martin , Pfeiffer Andreas F. H. , Birkenfeld Andreas L. , Pietzke Matthias , Kempa Stefan , Muenzner Matthias , Schupp Michael 
Published: August 2017

AbstractThe liver integrates multiple metabolic pathways to warrant systemic energy homeostasis. An excessive lipogenic flux due to chronic dietary stimulation contributes to the development of hepatic steatosis, dyslipidemia and hyperglycemia. Here we show that the oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. Liver-specific depletion of RetSat in dietary obese mice lowers hepatic and circulating TGs and normalizes hyperglycemia. Mechanistically, RetSat depletion reduces the activity of carbohydrate response element binding protein (ChREBP), a cellular hexose-phosphate sensor and inducer of lipogenesis. Defects upon RetSat depletion are rescued by ectopic expression of ChREBP but not by its putative enzymatic product 13,14-dihydroretinol, suggesting that RetSat affects hepatic glucose sensing independent of retinol conversion. Thus, RetSat is a critical regulator of liver metabolism functioning upstream of ChREBP. Pharmacological inhibition of liver RetSat may represent a therapeutic approach for steatosis.
Artificial web of disclination lines in nematic liquid crystals
Authors: Wang Mengfei , Li Yannian , Yokoyama Hiroshi 
Published: August 2017

AbstractDisclinations are topological singularities of molecular arrangement in liquid crystals, which typically occur when the average orientation of molecules makes aπrotation along a fictitious closed loop taken inside the liquid crystal. Depending on the sense of molecular rotation, the disclination lines are either of 1/2 or −1/2 strength. When two disclination lines with the opposite strength meet, they are annihilated without trace. It is hence generally considered difficult in the nematic phase to stabilize a condensed array of free-standing disclination lines without the aid of topological objects like colloidal inclusions. Here we show that a free-standing web of 1/2-strength twist disclination lines can be stably formed in thin liquid crystal cells by means of a judicious combination of orientationally patterned confining surfaces fabricated by the micropatterned photoalignment technique. Theoretical model indicates that disclination lines are held apart at the intersection by a repulsive force generated by the Frank elasticity.
DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial
Authors: Wolf Denise M. , Yau Christina , Sanil Ashish , Glas Annuska , Petricoin Emanuel , Wulfkuhle Julia , Severson Tesa M. , Linn Sabine , Brown-Swigart Lamorna , Hirst Gillian , Buxton Meredith , DeMichele Angela , Hylton Nola , Symmans Fraser , Yee Doug , Paoloni Melissa , Esserman Laura , Berry Don , Rugo Hope , Olopade Olufunmilayo , van ‘t Veer Laura 
Published: August 2017

AbstractVeliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2− patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2− patients (VC: 72 and concurrent controls: 44). We also evaluated the 70-gene ultra-high risk signature (MP1/2), one of the biomarkers used to define subtype in the trial. We used logistic modeling to assess biomarker performance. Successful biomarkers were combined using a simple voting scheme to refine the ‘predicted sensitive’ group and Bayesian modeling used to estimate the pathologic complete response rates. BRCA1/2 germline mutation status associated with VC response, but its low prevalence precluded further evaluation. PARPi-7, BRCA1ness, and MP1/2 specifically associated with response in the VC arm but not the control arm. Neither CIN70 nor PARP1 protein specifically predicted VC response. When we combined the PARPi-7 and MP1/2 classifications, the 42% of triple negative patients who were PARPi7-high and MP2 had an estimated pCR rate of 75% in the VC arm. Only 11% of HR+/HER2− patients were PARPi7-high and MP2; but these patients were also more responsive to VC with estimated pathologic complete response rates of 41%. PARPi-7, BRCA1ness and MP1/2 signatures may help refine predictions of VC response, thereby improving patient care.
Mining novel starch-converting Glycoside Hydrolase 70 enzymes from the Nestlé Culture Collection genome database: The Lactobacillus reuteri NCC 2613 GtfB
Authors: Gangoiti Joana , van Leeuwen Sander S. , Meng Xiangfeng , Duboux Stéphane , Vafiadi Christina , Pijning Tjaard , Dijkhuizen Lubbert 
Published: August 2017

AbstractThe Glycoside hydrolase (GH) family 70 originally was established for glucansucrases of lactic acid bacteria (LAB) converting sucrose into α-glucan polymers. In recent years we have identified 3 subfamilies of GH70 enzymes (designated GtfB, GtfC and GtfD) as 4,6-α-glucanotransferases, cleaving (α1 → 4)-linkages in maltodextrins/starch and synthesizing new (α1 → 6)-linkages. In this work, 106 putative GtfBs were identified in the Nestlé Culture Collection genome database with ~2700 genomes, and the L. reuteri NCC 2613 one was selected for further characterization based on variations in its conserved motifs. Using amylose the L. reuteri NCC 2613 GtfB synthesizes a low-molecular-mass reuteran-like polymer consisting of linear (α1 → 4) sequences interspersed with (α1 → 6) linkages, and (α1 → 4,6) branching points. This product specificity is novel within the GtfB subfamily, mostly comprising 4,6-α-glucanotransferases synthesizing consecutive (α1 → 6)-linkages. Instead, its activity resembles that of the GtfD 4,6-α-glucanotransferases identified in non-LAB strains. This study demonstrates the potential of large-scale genome sequence data for the discovery of enzymes of interest for the food industry. The L. reuteri NCC 2613 GtfB is a valuable addition to the starch-converting GH70 enzyme toolbox. It represents a new evolutionary intermediate between families GH13 and GH70, and provides further insights into the structure-function relationships of the GtfB subfamily enzymes.
Mitogenome Sequencing in the Genus Camelus Reveals Evidence for Purifying Selection and Long-term Divergence between Wild and Domestic Bactrian Camels
Authors: Mohandesan Elmira , Fitak Robert R. , Corander Jukka , Yadamsuren Adiya , Chuluunbat Battsetseg , Abdelhadi Omer , Raziq Abdul , Nagy Peter , Stalder Gabrielle , Walzer Chris , Faye Bernard , Burger Pamela A. 
Published: August 2017

AbstractThe genusCamelusis an interesting model to study adaptive evolution in the mitochondrial genome, as the three extant Old World camel species inhabit hot and low-altitude as well as cold and high-altitude deserts. We sequenced 24 camel mitogenomes and combined them with three previously published sequences to study the role of natural selection under different environmental pressure, and to advance our understanding of the evolutionary history of the genusCamelus. We confirmed the heterogeneity of divergence across different components of the electron transport system. Lineage-specific analysis of mitochondrial protein evolution revealed a significant effect of purifying selection in the concatenated protein-coding genes in domestic Bactrian camels. The estimateddN/dS < 1 in the concatenated protein-coding genes suggested purifying selection as driving force for shaping mitogenome diversity in camels. Additional analyses of the functional divergence in amino acid changes between species-specific lineages indicated fixed substitutions in various genes, with radical effects on the physicochemical properties of the protein products. The evolutionary time estimates revealed a divergence between domestic and wild Bactrian camels around 1.1 [0.58–1.8] million years ago (mya). This has major implications for the conservation and management of the critically endangered wild species,Camelus ferus.
Measuring proteins with greater speed and resolution while reducing sample size
Authors: Hsieh Vincent H. , Wyatt Philip J. 
Published: August 2017

AbstractA multi-angle light scattering (MALS) system, combined with chromatographic separation, directly measures the absolute molar mass, size and concentration of the eluate species. The measurement of these crucial properties in solution is essential in basic macromolecular characterization and all research and production stages of bio-therapeutic products. We developed a new MALS methodology that has overcome the long-standing, stubborn barrier to microliter-scale peak volumes and achieved the highest resolution and signal-to-noise performance of any MALS measurement. The novel design simultaneously facilitates online dynamic light scattering (DLS) measurements. As National Institute of Standards and Technology (NIST) new protein standard reference material (SRM 8671) is becoming the benchmark molecule against which many biomolecular analytical techniques are assessed and evaluated, we present its measurement results as a demonstration of the unique capability of our system to swiftly resolve and measure sharp (20~25 µL full-width-half-maximum) chromatography peaks. Precise measurements of protein mass and size can be accomplished 10 times faster than before with improved resolution. In the meantime the sample amount required for such measurements is reduced commensurately. These abilities will have far-reaching impacts at every stage of the development and production of biologics and bio-therapeutic formulations.
The Influence of Different Maternal Microbial Communities on the Development of Infant Gut and Oral Microbiota
Authors: Drell Tiina , Štšepetova Jelena , Simm Jaak , Rull Kristiina , Aleksejeva Aira , Antson Anne , Tillmann Vallo , Metsis Madis , Sepp Epp , Salumets Andres , Mändar Reet 
Published: August 2017

AbstractVery few studies have analyzed how the composition of mother’s microbiota affects the development of infant’s gut and oral microbiota during the first months of life. Here, microbiota present in the mothers’ gut, vagina, breast milk, oral cavity, and mammary areola were compared with the gut and oral microbiota of their infants over the first six months following birth. Samples were collected from the aforementioned body sites from seven mothers and nine infants at three different time points over a 6-month period. Each sample was analyzed with 16S rRNA gene sequencing. The gut microbiota of the infants harbored distinct microbial communities that had low similarity with the various maternal microbiota communities. In contrast, the oral microbiota of the infants exhibited high similarity with the microbiota of the mothers’ breast milk, mammary areola and mouth. These results demonstrate that constant contact between microbial communities increases their similarity. A majority of the operational taxonomic units in infant gut and oral microbiota were also shared with the mothers’ gut and oral communities, respectively. The disparity between the similarity and the proportion of the OTUs shared between infants’ and mothers’ gut microbiota might be related to lower diversity and therefore competition in infants’ gut microbiota.
Diversification dynamics of rhynchostomatian ciliates: the impact of seven intrinsic traits on speciation and extinction in a microbial group
Authors: Vďačný Peter , Rajter Ľubomír , Shazib Shahed Uddin Ahmed , Jang Seok Won , Shin Mann Kyoon 
Published: August 2017

AbstractCiliates are a suitable microbial model to investigate trait-dependent diversification because of their comparatively complex morphology and high diversity. We examined the impact of seven intrinsic traits on speciation, extinction, and net-diversification of rhynchostomatians, a group of comparatively large, predatory ciliates with proboscis carrying a dorsal brush (sensoric structure) and toxicysts (organelles used to kill the prey). Bayesian estimates under the binary-state speciation and extinction model indicate that two types of extrusomes and two-rowed dorsal brush raise diversification through decreasing extinction. On the other hand, the higher number of contractile vacuoles and their dorsal location likely increase diversification via elevating speciation rate. Particular nuclear characteristics, however, do not significantly differ in their diversification rates and hence lineages with various macronuclear patterns and number of micronuclei have similar probabilities to generate new species. Likelihood-based quantitative state diversification analyses suggest that rhynchostomatians conform to Cope’s rule in that their diversity linearly grows with increasing body length and relative length of the proboscis. Comparison with other litostomatean ciliates indicates that rhynchostomatians are not among the cladogenically most successful lineages and their survival over several hundred million years could be associated with their comparatively large and complex bodies that reduce the risk of extinction.
Determination of the physiological and pathological roles of E2F3 in adult tissues
Authors: Gamper Ivonne , Burkhart Deborah L. , Bywater Megan J. , Garcia Daniel , Wilson Catherine H. , Kreuzaler Peter A. , Arends Mark J. , Zheng Yao-Wu , Perfetto Alessandra , Littlewood Trevor D. , Evan Gerard I. 
Published: August 2017

AbstractWhile genetically engineered mice have made an enormous contribution towards the elucidation of human disease, it has hitherto not been possible to tune up or down the level of expression of any endogenous gene. Here we describe compound genetically modified mice in which expression of the endogenous E2f3 gene may be either reversibly elevated or repressed in adult animals by oral administration of tetracycline. This technology is, in principle, applicable to any endogenous gene, allowing direct determination of both elevated and reduced gene expression in physiological and pathological processes. Applying this switchable technology to the key cell cycle transcription factor E2F3, we demonstrate that elevated levels of E2F3 drive ectopic proliferation in multiple tissues. By contrast, E2F3 repression has minimal impact on tissue proliferation or homeostasis in the majority of contexts due to redundancy of adult function with E2F1 and E2F2. In the absence of E2F1 and E2F2, however, repression of E2F3 elicits profound reduction of proliferation in the hematopoietic compartments that is rapidly lethal in adult animals.
Celecoxib normalizes the tumor microenvironment and enhances small nanotherapeutics delivery to A549 tumors in nude mice
Authors: Zhang Bo , Jin Kai , Jiang Ting , Wang Lanting , Shen Shun , Luo Zimiao , Tuo Yanyan , Liu Xianping , Hu Yu , Pang Zhiqing 
Published: August 2017

AbstractBarriers presented by the tumor microenvironment including the abnormal tumor vasculature and interstitial matrix invariably lead to heterogeneous distribution of nanotherapeutics. Inspired by the close association between cyclooxygenase-2 (COX-2) and tumor-associated angiogenesis, as well as tumor matrix formation, we proposed that tumor microenvironment normalization by COX-2 inhibitors might improve the distribution and efficacy of nanotherapeutics for solid tumors. The present study represents the first time that celecoxib, a special COX-2 inhibitor widely used in clinics, was explored to normalize the tumor microenvironment and to improve tumor nanotherapeutics delivery using a human-derived A549 tumor xenograft as the solid tumor model. Immunofluorescence staining of tumor slices demonstrated that oral celecoxib treatment at a dose of 200 mg/kg for two weeks successfully normalized the tumor microenvironment, including tumor-associated fibroblast reduction, fibronectin bundle disruption, tumor vessel normalization, and tumor perfusion improvement. Furthermore, it also significantly enhanced the in vivo accumulation and deep penetration of 22-nm micelles rather than 100-nm nanoparticles in tumor tissues by in vivo imaging and distribution experiments and improved the therapeutic efficacy of paclitaxel-loaded micelles in tumor xenograft-bearing mouse models in the pharmacodynamics experiment. As celecoxib is widely and safely used in clinics, our findings may have great potential in clinics to improve solid tumor treatment.
Associations of estimated glomerular filtration rate and blood urea nitrogen with incident coronary heart disease: the Dongfeng-Tongji Cohort Study
Authors: Jiang Haijing , Li Jun , Yu Kuai , Yang Handong , Min Xinwen , Chen Huanqian , Wu Tangchun 
Published: August 2017

AbstractEstimated glomerular filtration rate (eGFR) has been reported to be associated with risk of incident coronary heart disease (CHD), and blood urea nitrogen (BUN) has been shown to be a strong predictor of mortality in patients with heart failure (HF). However, such epidemiological evidence from Chinese population was still limited. We used Cox proportional-hazards regression models to investigate the associations of eGFR and BUN with risk of incident CHD in the prospective Dongfeng-Tongji (DFTJ) cohort. After fully adjusted for potential confounders, a 10-unit decline in eGFR was associated with higher risk for CHD (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.01–1.09); compared with individuals with normal eGFR levels (eGFR ≥ 90 ml/min per 1.73 m2), individuals with a mild-to-severe eGFR decline (15 to 60 ml/min per 1.73 m2) were at significantly greater risk for CHD (HR 1.25, 95% CI 1.05–1.48; P = 0.011). Compared with individuals in the lowest tertile of BUN, those in the highest tertile were at significantly greater risk for CHD (HR 1.17, 95% CI 1.03–1.33; P = 0.014). In conclusion, a mild-to-severe decline in eGFR or a raised level of BUN might be associated with increased risk of incident CHD in middle-aged and elderly Chinese populations.