bluuebunny/crossref_metadata_2025_split huggingface dataset:
PAS domain-containing phosphoglycerate kinase deficiency in Leishmania major results in increased autophagosome formation and cell death
Authors: Adhikari Ayan , Biswas Saroj , Mukherjee Aditi , Das Sumit , Adak Subrata 
Published: April 2019

Abstract
Per-Arnt-Sim (PAS) domains are structurally conserved and present in numerous proteins throughout all branches of the phylogenetic tree. Although PAS domain-containing proteins are major players for the adaptation to environmental stimuli in both prokaryotic and eukaryotic organisms, these types of proteins are still uncharacterized in the trypanosomatid parasites, Trypanosome and Leishmania. In addition, PAS-containing phosphoglycerate kinase (PGK) protein is uncharacterized in the literature. Here, we report a PAS domain-containing PGK (LmPAS-PGK) in the unicellular pathogen Leishmania. The modeled structure of N-terminal of this protein exhibits four antiparallel β sheets centrally flanked by α helices, which is similar to the characteristic signature of PAS domain. Activity measurements suggest that acidic pH can directly stimulate PGK activity. Localization studies demonstrate that the protein is highly enriched in the glycosome and its presence can also be seen in the lysosome. Gene knockout, overexpression and complement studies suggest that LmPAS-PGK plays a fundamental role in cell survival through autophagy. Furthermore, the knockout cells display a marked decrease in virulence when host macrophage and BALB/c mice were infected with them. Our work begins to clarify how acidic pH-dependent ATP generation by PGK is likely to function in cellular adaptability of Leishmania.
LncRNA-MALAT1 promotes neovascularization in diabetic retinopathy through regulating miR-125b/VE-cadherin axis
Authors: Liu Ping , Jia Song-Bai , Shi Jing-Ming , Li Wen-Jie , Tang Luo-Sheng , Zhu Xia-Hua , Tong Ping 
Published: April 2019

Abstract
Background: Diabetic retinopathy (DR) is currently the leading cause of blindness and visual disability in adults with diabetes mellitus (DM). Neovascularization has been identified as an important clinical property in DR, however, the exact mechanisms in DR neovascularization are still unclear and need further elucidation.
Methods: Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of long non-coding RNA (lncRNA)-metastasis associated lung adenocarcinoma transcript 1 (MALAT1), miR-125b and vascular endothelial-cadherin (VE-cadherin) in human retina microvascular endothelial cells (hRMECs) treated with high glucose (HG). Luciferase assay was used to detect interaction of MALAT1 with miR-125b and miR-125b with VE-cadherin. MTT assay, transwell assay, tube formation assay and vascular permeability assay were conducted to detect the cell viability, migration tube formation ability and permeability of hRMECs, respectively. ELISA was used to examine the release of VE-cadherin and vascular endothelial growth factor (VEGF). Western blotting was used to access the protein expression of VE-cadherin, VEGF, β-catenin, matrix metalloproteinase (MMP) 2 (MMP2) and MMP9.
Results: MALAT1 and VE-cadherin were up-regulated while miR-125b was down-regulated in hRMECs treated with HG. MALAT1 could competitively bind to miR-125b against VE-cadherin at the site of 3′-untranslated region (3′-UTR), leading to the up-regulation of VE-cadherin. Knockdown of MALAT1 inhibited the proliferation, migration, tube formation and vascular permeability of hRMECs induced by HG through up-regulating miR-125b. Furthermore, we found the deletion of MALAT1 suppressed the VE-cadherin/β-catenin complex and neovascularization related proteins expression, which was up-regulated by HG.
Conclusion: Knockdown of MALAT1 inhibited cell proliferation, migration and angiogenesis of hRMECs via suppressing the VE-cadherin/β-catenin complex through targeting miR-125b. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for DR.
Associations between cytotoxic T-lymphocyte-associated antigen 4 gene polymorphisms and diabetes mellitus: a meta-analysis of 76 case–control studies
Authors: Chen Min , Li ShuMin 
Published: April 2019

Abstract
Background: Several genetic association studies already investigated potential roles of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms in diabetes mellitus (DM), with inconsistent results. Therefore, we performed this meta-analysis to better assess the relationship between CTLA-4 gene polymorphisms and DM in a larger pooled population.
Methods: PubMed, Embase, Web of Science, and CNKI were systematically searched for eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of associations between CTLA-4 gene polymorphisms and DM in all possible genetic models.
Results: A total of 76 studies were finally included in our analyses. Significant associations with susceptibility to type 1 diabetes mellitus (T1DM) were detected for rs231775 (dominant model: P=0.008, OR = 0.83, 95%CI 0.73–0.95; recessive model: P=0.003, OR = 1.27, 95%CI 1.09–1.50; allele model: P=0.004, OR = 0.85, 95%CI 0.77–0.95) and rs5742909 (recessive model: P=0.02, OR = 1.50, 95%CI 1.05–2.13) polymorphisms in overall population. Further subgroup analyses revealed that rs231775 polymorphism was significantly associated with susceptibility to T1DM in Caucasians and South Asians, and rs5742909 polymorphism was significantly associated with susceptibility to T1DM in South Asians. Moreover, rs231775 polymorphism was also found to be significantly associated with susceptibility to type 2 diabetes mellitus (T2DM) in East Asians and South Asians.
Conclusions: Our findings indicated that rs231775 and rs5742909 polymorphisms may serve as genetic biomarkers of T1DM, and rs231775 polymorphism may also serve as a genetic biomarker of T2DM.
A gene signature predicts response to neoadjuvant chemotherapy in triple-negative breast cancer patients
Authors: Zheng Tianzhi , Pang Zhiyuan , Zhao Zhao 
Published: April 2019

Abstract
Triple-negative breast cancer (TNBC) accounts for approximately 15% of all breast cancer cases. TNBC is highly aggressive and associated with poor prognosis. The present study aimed to compare gene expression between TNBC patients with pathological complete response (pCR) and those with not complete response (nCR) to neoadjuvant chemotherapy. Microarray data of 16 TNBC patients received neoadjuvant chemotherapy were identified from the Gene Expression Omnibus database and 10 patients of them had pCR. We found that 250 coding genes and 155 long noncoding RNAs (lncRNAs) were statistically differentially expressed between patients with pCR and nCR. Receiver operator characteristic curve and area under the curve (AUC) were calculated to assess predictive value of differentially expressed genes. A gene signature of three coding genes and two lncRNA was developed: 2.318*TCF3 + 7.349*CREB1 + 0.891*CEP44 + 0.091*NR_023392.1 + 1.424*NR_048561.1 − 106.682. The gene signature was further validated and had an AUC = 0.829. In summary, we profiled gene expression in pCR patients and developed a gene signature, which was effective to predict pCR among TNBC patients received neoadjuvant chemotherapy.
Endothelial cell-derived small extracellular vesicles suppress cutaneous wound healing through regulating fibroblasts autophagy
Authors: Zeng Tingting , Wang Xiaoyi , Wang Wei , Feng Qiling , Lao Guojuan , Liang Ying , Wang Chuan , Zhou Jing , Chen Yuying , Liu Jing , Gao Haiqi , Lan Biyun , Wu Yuxi , Han Yuting , Liu Yanyan , Chen Hongxing , Liu Liyi , Yang Chuan , Yan Li , Ren Meng , Sun Kan 
Published: April 2019

Abstract
Diabetic foot ulcer is a life-threatening clinical problem in diabetic patients. Endothelial cell-derived small extracellular vesicles (sEVs) are important mediators of intercellular communication in the pathogenesis of several diseases. However, the exact mechanisms of wound healing mediated by endothelial cell-derived sEVs remain unclear. sEVs were isolated from human umbilical vein endothelial cells (HUVECs) pretreated with or without advanced glycation end products (AGEs). The roles of HUVEC-derived sEVs on the biological characteristics of skin fibroblasts were investigated both in vitro and in vivo. We demonstrate that sEVs derived from AGEs-pretreated HUVECs (AGEs-sEVs) could inhibit collagen synthesis by activating autophagy of human skin fibroblasts. Additionally, treatment with AGEs-sEVs could delay the wound healing process in Sprague–Dawley (SD) rats. Further analysis indicated that miR-106b-5p was up-regulated in AGEs-sEVs and importantly, in exudate-derived sEVs from patients with diabetic foot ulcer. Consequently, sEV-mediated uptake of miR-106b-5p in recipient fibroblasts reduces expression of extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in fibroblasts autophagy activation and subsequent collagen degradation. Collectively, our data demonstrate that miR-106b-5p could be enriched in AGEs-sEVs, then decreases collagen synthesis and delays cutaneous wound healing by triggering fibroblasts autophagy through reducing ERK1/2 expression.
The built memory: presenting the colonization villages in Spain by the newsreel of State NO-DO.
Authors: González Cubero Josefina , Zarza Arribas Alba 
Published: April 2019

The newsreel of State used to show to Spanish society a determined image of architecture, conditioned by the political needs of Franco’s Regime. In this case, the subject of the cinematographic image of villages of colonization of the Tagus valley as presented by the NO-DO newsreel (Noticiarios y Documentales Cinematográficos) is studied. NO-DO was originally created as a propaganda tool and an instrument for the diffusion of “specially relevant” news from that time period.
The analysis of the architecture built by the National Institute of Colonization (INC) and showed in different editions of the newsreel allowed us to understand the ideological approach made by the Regime to the Spanish countryside, through the model of colonization of the territory, and how building was used as propaganda. The urban model proposed was defined by civic centres –usually square-shaped-, and church towers as urban milestones set in the landscape. For this reason, politic demonstrations in the representative public spaces of villages, through the delivering of houses and rural property to settlers, incorporated the context and living conditions in which new villages were built. At the same time, the visits to irrigation farms, new irrigation canals, and hydraulic and hydroelectric infrastructures exemplify the agrarian and irrigation policies during the autarchy, whereas in the next decades, and because of the economic and social development of the countryside, news about reservoirs were just referred to sports and leisure activities. Therefore, these cinematographic images of buildings, irrigation policies and the modernization of rural landscape presented in cinemas through the NO-DO newsreel are relevant, since they build a collective memoryof the architecture and engineering of that time. They also document the social, politic and economic role that the creation of Spanish villages of colonization at river basins had, specifically in one of the biggest rivers, the Tagus.
Glucose Responsiveness of β-Cells Depends on Fatty Acids
Authors: Gerst Felicia , Singer Christine , Noack Katja , Graf Dunia , Kaiser Gabriele , Panse Madhura , Kovarova Marketa , Schleicher Erwin , Häring Hans-Ulrich , Drews Gisela , Ullrich Susanne 
Published: April 2019

AbstractGlucose-stimulated insulin secretion (GSIS) is the gold standard for β-cell function. Both experimental and clinical diabetology, i. e., preceding transplantation of isolated human islets, depend on functional testing. However, multiple factors influence GSIS rendering the comparison of different in vitro tests of glucose responsiveness difficult. This study examined the influence of bovine serum albumin (BSA)-coupled fatty acids on GSIS. Isolated islet preparations of human donors and of 12-months old mice displayed impaired GSIS in the presence of 0.5% FFA-free BSA compared to 0.5% BSA (fraction V, not deprived from fatty acids). In aged INS-1E cells, i. e. at a high passage number, GSIS became highly sensitive to FFA-free BSA. Readdition of 30 µM palmitate or 30 µM oleate to FFA-free BSA did not rescue GSIS, while the addition of 100 µM palmitate and the raise of extracellular Ca2+from 1.3 to 2.6 mM improved glucose responsiveness. A high concentration of palmitate (600 µM), which fully activates FFA1, largely restored insulin secretion. The FFA1-agonist TUG-469 also increased insulin secretion but to a lesser extent than palmitate. Glucose- and TUG-induced Ca2+oscillations were impaired in glucose-unresponsive, i. e., aged INS-1E cells. These results suggest that fatty acid deprivation (FFA-free BSA) impairs GSIS mainly through an effect on Ca2+sensitivity.
Access to Biphenyls by Palladium-Catalyzed Oxidative Coupling of Phenyl Carbamates and Phenols
Authors: Bach Thorsten , Truchan Nadina , Jandl Christian , Pöthig Alexander , Breitenlechner Stefan 
Published: April 2019

The oxidative cross-coupling of phenols (3 equiv) to various substituted phenyl N,N-diethylcarbamates was explored with a variety of substrates. Pd(OAc)2 was employed as the catalyst (20 mol%) and K2S2O8 as the stoichiometric oxidant in trifluoroacetic acid as the solvent (50 °C, 2 h). Carbamates without or with a substituent on the phenyl ring (Me, Ph, Cl, OMe) underwent the reaction unless the phenyl substituent was too strongly electron withdrawing (CN). Cross-coupling occurred exclusively in the ortho position relative to the carbamate group. The regioselectivity at the phenol (ortho or para to hydroxy) was mainly determined by steric factors. Yields up to 60–70% were achieved for specific carbamate/phenol combinations.
Interpretation and integration of “creating shared value” in Asia: implications for strategy research and practice
Authors: Kim Rebecca Chunghee , Saito Akira , Avvari V. Mohan 
Published: April 2019

Abstract“Creating shared value” (CSV) appears on contemporary business agendas. But despite empirical evidence concerning its popularity, serious questions about the logic of CSV are raised by scholars. This paper focuses on CSV in the Asian context. Using in-depth interviews with key informants from Japan, Korea, and India, we employ a strategy-as-practice approach and develop propositions related to CSV in Asia. We identify three characteristics of Asian business practices that shape CSV in Asia: a survival sense, a strong ethical stance, and business-in-society dynamics. Finally, we introduce a preliminary framework for Asian CSV along with suggestions for future research and practice.
Position-controlled laser-induced creation of rutile TiO2 nanostructures
Authors: Kalb Julian , Weller Fabian , Irmler Lukas , Knittel Vanessa , Graus Philipp , Boneberg Johannes , Schmidt-Mende Lukas 
Published: April 2019

Abstract
For potential applications of nanostructures, control over their position is important. In this report, we introduce two continuous wave laser-based lithography techniques which allow texturing thin TiO2 films to create a fine rutile TiO2 structure on silicon via spatially confined oxidation or a solid–liquid–solid phase transition, for initial layers, we use titanium and anatase TiO2, respectively. A frequency-doubled Nd:YAG laser at a wavelength of 532 nm is employed for the lithography process and the samples are characterized with scanning electron microscopy. The local orientation of the created rutile crystals is determined by the spatial orientation of hydrothermally grown rutile TiO2 nanorods. Depending on the technique, we obtain either randomly aligned or highly ordered nanorod ensembles. An additional chemically inert SiO2 cover layer suppresses the chemical and electronic surface properties of TiO2 and is removed locally with the laser treatment. Hence, the resulting texture provides a specific topography and crystal structure as well as a high contrast of surface properties on a nanoscale, including the position-controlled growth of TiO2 nanorods.
Predicting support for flood mitigation based on flood insurance purchase behavior
Authors: Shao Wanyun , Feng Kairui , Lin Ning 
Published: April 2019

Abstract
What is the decision-making mechanism people rely upon to mitigate flood risk? Applying Bayesian Network modeling to a comprehensive survey dataset for the US Gulf Coast, we find that the overall support for flood mitigation can be inferred from flood insurance purchase behavior (i.e. without insurance versus with insurance purchased mandatorily, voluntarily, or both). Therefore, we propose a theoretical decision-making mechanism composed of two dimensions including informed flood risk and sense of insecurity. The informed flood risk is the primary determinant on one’s overall support for flood mitigation. Risk mitigation decisions are largely contingent on the level of risk that is effectively conveyed to individuals. Additionally, sense of insecurity plays a moderate role in determining individuals’ overall support for flood mitigation. The sense of insecurity can move people toward overall support for mitigation, but the effect is not as large as the informed risk. Results of this study have fundamental policy implications. The flood risk informed by Federal Emergency Management Agency’s flood maps not only provides the compulsory basis for flood insurance purchase but also determines individuals’ overall support for flood mitigation. Flood map inaccuracy can immensely mislead individuals’ overall risk mitigation decision. Meanwhile, this flood risk mitigation decision-making mechanism inferred from a survey data in the US Gulf Coast needs to be tested and validated elsewhere.
The drivers of nonlinear local temperature change under global warming
Authors: King Andrew D 
Published: April 2019

Abstract
How the pattern of the Earth’s surface warming will change under global warming represents a fundamental question for our understanding of the climate system with implications for regional projections. Despite the importance of this problem there have been few analyses of nonlinear local temperature change as a function of global warming. Individual climate models project nonlinearities, but drivers of nonlinear local change are poorly understood. Here, I present a framework for the identification and quantification of local nonlinearities using a time-slice analysis of a multi-model ensemble. Accelerated local warming is more likely over land than ocean per unit global warming. By examining changes across the model ensemble, I show that models that exhibit summertime drying over mid-latitude land regions, such as in central Europe, tend to also project locally accelerated warming relative to global warming, and vice versa. A case study illustrating some uses of this framework for nonlinearity identification and analysis is presented for north-eastern Australia. In this region, model nonlinear warming in summertime is strongly connected to changes in precipitation, incoming shortwave radiation, and evaporative fraction. In north-eastern Australia, model nonlinearity is also connected to projections for El Niño. Uncertainty in nonlinear local warming patterns contributes to the spread in regional climate projections, so attempts to constrain projections are explored. This study provides a framework for the identification of local temperature nonlinearities as a function of global warming and analysis of associated drivers under prescribed global warming levels.
CFTR mutation compromises spermatogenesis by enhancing miR-15b maturation and suppressing its regulatory target CDC25A†
Authors: Chen Yan , Li Xiaoliang , Liao Huijuan , Leung Xiaotong , He Jiabei , Wang Xiang , Li Fuping , Yue Huanxun , Xu Wenming 
Published: April 2019

Abstract
MicroRNAs (miRNAs) have recently been shown to be important for spermatogenesis; both DROSHA and Dicer1 KO mice exhibit infertility due to abnormal miRNA expression. However, the roles of individual miRNAs in spermatogenesis remain elusive. Here we demonstrated that miR-15b, a member of the miR-15/16 family, is primarily expressed in testis. A miR-15b transgenic mouse model was constructed to investigate the role of miR-15b in spermatogenesis. Impaired spermatogenesis was observed in miR-15b transgenic mice, suggesting that appropriate expression of miR-15b is vital for spermatogenesis. Furthermore, we demonstrated that overexpression of miR-15b reduced CDC25A gene post-transcriptional activity by targeting the 3′-UTR region of CDC25A, thus regulating spermatogenesis. In vitro results further demonstrated that a mutation in CFTR could affect the interaction between Ago2 with Dicer1 and that Dicer1 activity regulates miR-15b expression. We extended our study to azoospermia patients and found that infertile patients have a significantly higher level of miR-15b in semen and plasma samples. Taken together, we propose that CFTR regulation of miR-15b could be involved in the post-transcriptional regulation of CDC25A in mammalian testis and that miR-15b is important for spermatogenesis.
Impaired decidualization caused by downregulation of circadian clock gene BMAL1 contributes to human recurrent miscarriage†
Authors: Lv Shijian , Wang Na , Ma Jin , Li Wei-Ping , Chen Zi-Jiang , Zhang Cong 
Published: April 2019

Abstract
Recurrent miscarriage (RM) is characterized by two or more consecutive losses of a clinically established intrauterine pregnancy at early gestation. To date, the etiology of RM remains poorly understood. Impaired decidualization is thought to predispose women to subsequent pregnancy failure. The transcriptional factor brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL1) controls circadian rhythms and regulates a very large diversity of physiological processes. BMAL1 is essential for fertility. Here, we investigated the expression and function of BMAL1 in human decidualization and its relation with RM. A total of 39 decidua samples were collected. We also examined human endometrial stromal cells (HESCs) and primary endometrial stromal cells (ESCs), and primary decidual stromal cells (DSCs) isolated from decidua of first-trimester pregnancies. Compared to normal pregnant women, the expression of BMAL1 was reduced in the decidual tissues from individuals with RM. After in vitro induction of decidualization, the transcription of BMAL1 in both HESCs and primary ESCs was increased. This is in line with the relatively higher expression of BMAL1 in DSCs than in ESCs. Silencing of BMAL1 resulted in impaired decidualization. Moreover, levels of tissue inhibitors of metalloproteinases (TIMPs) increased significantly upon decidualization. Further experiments demonstrated that BMAL1 silencing curtails the ability of DSCs to restrict excessive trophoblast invasion via downregulation of TIMP3. Our study demonstrates a functional role for BMAL1 during decidualization: the downregulation of BMAL1 in RM leads to impaired decidualization and aberrant trophoblast invasion by regulating TIMP3 and consequently predisposing individuals for RM.