bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plin2-deficiency reduces lipophagy and results in increased lipid accumulation in the heart
Authors: Mardani Ismena , Tomas Dalen Knut , Drevinge Christina , Miljanovic Azra , Ståhlman Marcus , Klevstig Martina , Scharin Täng Margareta , Fogelstrand Per , Levin Max , Ekstrand Matias , Nair Syam , Redfors Björn , Omerovic Elmir , Andersson Linda , Kimmel Alan R. , Borén Jan , Levin Malin C. 
Published: May 2019

AbstractMyocardial dysfunction is commonly associated with accumulation of cardiac lipid droplets (LDs). Perilipin 2 (Plin2) is a LD protein that is involved in LD formation, stability and trafficking events within the cell. Even though Plin2 is highly expressed in the heart, little is known about its role in myocardial lipid storage. A recent report shows that cardiac overexpression of Plin2 result in massive myocardial steatosis suggesting that Plin2 stabilizes LDs. In this study, we hypothesized that deficiency in Plin2 would result in reduced myocardial lipid storage. In contrast to our hypothesis, we found increased accumulation of triglycerides in hearts, and specifically in cardiomyocytes, from Plin2−/− mice. Although Plin2−/− mice had markedly enhanced lipid levels in the heart, they had normal heart function under baseline conditions and under mild stress. However, after an induced myocardial infarction, stroke volume and cardiac output were reduced in Plin2−/− mice compared with Plin2+/+ mice. We further demonstrated that the increased triglyceride accumulation in Plin2-deficient hearts was caused by altered lipophagy. Together, our data show that Plin2 is important for proper hydrolysis of LDs.
Climate drivers of hospitalizations for mycoses in Brazil
Authors: Silva Fabrício Brito , Santos Jessflan Rafael Nascimento , da Silva Letícia Chagas , Gomes Wolia Costa , Villis Paulo Cesar Mendes , Gomes Eliane dos Santos , Pinheiro Edilene de Araújo Diniz , Azevedo Conceição de Maria Pedrozo e Silva , Dias Rosane da Silva , Monteiro Cristina de Andrade , Santos Julliana Ribeiro Alves 
Published: May 2019

AbstractClimate can modulate human health at large spatial scales, but the influence of global, regional, and local environments remains poorly understood, especially for neglected diseases, such as mycoses. In this work, we present the correlation between climatic variables and hospitalizations for mycoses in Brazilian state capitals, evaluating the period of 2008 to 2016 at different time scales. The results indicate that climate modulates the hospitalizations for mycoses differently at annual and monthly time scales, with minimum temperature as a key climatic variable during periods of high prevalence in the 10 Brazilian capitals with the highest hospitalizations for mycoses rates. The greatest number of hospitalizations coincided with La Niña events, while a reduction was observed during El Niño events, thereby demonstrating the influence of the Pacific Interdecadal Climate Oscillation on the prevalence of mycoses in Brazil. At a regional scale, the mycoses burden in Brazil appears to respond differently to local and global climatic drivers.
MicroRNA-130b functions as an oncomiRNA in non-small cell lung cancer by targeting tissue inhibitor of metalloproteinase-2
Authors: Hirono Takayuki , Jingushi Kentaro , Nagata Toshiyuki , Sato Masami , Minami Kentaro , Aoki Masaya , Takeda Aya Harada , Umehara Tadashi , Egawa Hiroshi , Nakatsuji Yoshino , Kitae Kaori , Ueda Yuko , Hase Hiroaki , Yamamoto Masatatsu , Shinsato Yoshinari , Kawahara Kohichi , Furukawa Tatsuhiko , Tsujikawa Kazutake 
Published: May 2019

AbstractNon-small cell lung cancer (NSCLC) is the most frequent cause of cancer-related death worldwide. Although many molecular-targeted drugs for NSCLC have been developed in recent years, the 5-year survival rate of patients with NSCLC remains low. Therefore, an improved understanding of the molecular mechanisms underlying the biology of NSCLC is essential for developing novel therapeutic strategies for the treatment of NSCLC. In this study, we examined the role of miR-130b in NSCLC. Our results showed that high expression of miR-130b in clinical specimens was significantly associated with poor overall survival in patients with NSCLC. Moreover, miR-130b expression was significantly increased in NSCLC clinical specimens from patients with vascular and lymphatic invasion. Consistent with this, overexpression of miR-130b promoted invasion and matrix metalloproteinase-2 (MMP-2) activity in A549 cells. Argonaute2 immunoprecipitation and gene array analysis identified tissue inhibitor of metalloproteinase-2 (TIMP-2) as a target of miR-130b. Invasion activity promoted by miR-130b was attenuated by TIMP-2 overexpression in A549 cells. Furthermore, TIMP-2 concentrations in serum were inversely correlated with relative miR-130b expression in tumor tissues from the same patients with NSCLC. Overall, miR-130b was found to act as an oncomiR, promoting metastasis by downregulating TIMP-2 and invasion activities in NSCLC cells.
Deep learning-based survival prediction of oral cancer patients
Authors: Kim Dong Wook , Lee Sanghoon , Kwon Sunmo , Nam Woong , Cha In-Ho , Kim Hyung Jun 
Published: May 2019

AbstractThe Cox proportional hazards model commonly used to evaluate prognostic variables in survival of cancer patients may be too simplistic to properly predict a cancer patient’s outcome since it assumes that the outcome is a linear combination of covariates. In this retrospective study including 255 patients suitable for analysis who underwent surgical treatment in our department from 2000 to 2017, we applied a deep learning-based survival prediction method in oral squamous cell carcinoma (SCC) patients and validated its performance. Survival prediction using DeepSurv, a deep learning based-survival prediction algorithm, was compared with random survival forest (RSF) and the Cox proportional hazard model (CPH). DeepSurv showed the best performance among the three models, the c-index of the training and testing sets reaching 0.810 and 0.781, respectively, followed by RSF (0.770/0.764), and CPH (0.756/0.694). The performance of DeepSurv steadily improved with added features. Thus, deep learning-based survival prediction may improve prediction accuracy and guide clinicians both in choosing treatment options for better survival and in avoiding unnecessary treatments.
26Al/10Be Burial Dating of the Middle Pleistocene Yiyuan Hominin Fossil Site, Shandong Province, Northern China
Authors: Guo Yun , Sun Chengkai , Luo Lan , Yang Linlin , Han Fei , Tu Hua , Lai Zhongping , Jiang Hongchen , Bae Christopher J. , Shen Guanjun , Granger Darryl 
Published: May 2019

AbstractThe Yiyuan hominin fossil site is one of the few localities in China where a partial skullcap and several loose teeth of Homo erectus have been discovered. Yiyuan was previously assigned broadly to the Middle Pleistocene by biostratigraphical correlation and ESR/U-series dating. Here, we report the first application of a radio-isotopic dating method to the site. 26Al/10Be burial dating results derived from two sand samples from the fossiliferous deposits show that the hominin fossils can be confidently dated to 0.64 ± 0.08 Ma (million years ago). The reliability of this age is supported by the zero age of modern fluvial sediment near the cave. Our result is consistent with the age estimation based on biostratigraphic correlation and supports the argument that the Yiyuan and Zhoukoudian Locality 1 H. erectus fossils are contemporaneous. The results presented here, along with other recent chronological studies on Chinese Middle Pleistocene hominin sites, indicate that the time span from 600–400 ka (thousand years ago) is a critical period for human evolution in East Asia. Importantly, this time bracket includes several major climatic changes that would have influenced hominins, both morphologically and behaviorally.
The role of membrane excitability in pancreatic β-cell glucotoxicity
Authors: Shyr Zeenat A. , Wang Zhiyu , York Nathaniel W. , Nichols Colin G. , Remedi Maria S. 
Published: May 2019

AbstractPersistent hyperglycemia is causally associated with pancreatic β-cell dysfunction and loss of pancreatic insulin. Glucose normally enhances β-cell excitability through inhibition of KATP channels, opening of voltage-dependent calcium channels, increased [Ca2+]i, which triggers insulin secretion. Glucose-dependent excitability is lost in islets from KATP-knockout (KATP-KO) mice, in which β-cells are permanently hyperexcited, [Ca2+]i, is chronically elevated and insulin is constantly secreted. Mouse models of human neonatal diabetes in which KATP gain-of-function mutations are expressed in β-cells (KATP-GOF) also lose the link between glucose metabolism and excitation-induced insulin secretion, but in this case KATP-GOF β-cells are chronically underexcited, with permanently low [Ca2+]i and lack of glucose-dependent insulin secretion. We used KATP-GOF and KATP-KO islets to examine the role of altered-excitability in glucotoxicity. Wild-type islets showed rapid loss of insulin content when chronically incubated in high-glucose, an effect that was reversed by subsequently switching to low glucose media. In contrast, hyperexcitable KATP-KO islets lost insulin content in both low- and high-glucose, while underexcitable KATP-GOF islets maintained insulin content in both conditions. Loss of insulin content in chronic excitability was replicated by pharmacological inhibition of KATP by glibenclamide, The effects of hyperexcitable and underexcitable islets on glucotoxicity observed in in vivo animal models are directly opposite to the effects observed in vitro: we clearly demonstrate here that in vitro, hyperexcitability is detrimental to islets whereas underexcitability is protective.
Heat shock factor 1 protects germ cell proliferation during early ovarian differentiation in medaka
Authors: Furukawa Fumiya , Hamasaki Shin , Hara Seiji , Uchimura Tomoya , Shiraishi Eri , Osafune Natsumi , Takagi Hisanori , Yazawa Takashi , Kamei Yasuhiro , Kitano Takeshi 
Published: May 2019

AbstractThe heat shock response is important for the viability of all living organisms. It involves the induction of heat shock proteins whose expression is mainly regulated by heat shock factor 1 (HSF1). Medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system. High water temperature (HT) inhibits the female-type proliferation of germ cells and induces the masculinisation of XX medaka in some cases during gonadal sex differentiation. Here, we investigated the roles of HSF1 on the proliferation of germ cells using HSF1 knockout medaka. Loss of HSF1 function under HT completely inhibited the female-type proliferation of germ cells, induced the expression of the anti-Mullerian hormone receptor type 2 (amhr2) and apoptosis-related genes, and suppressed that of the dead end (dnd) and heat shock protein-related genes. Moreover, the loss of HSF1 and AMHR2 function under HT recovered female-type proliferation in germ cells, while loss of HSF1 function under HT induced gonadal somatic cell apoptosis during early sex differentiation. These results strongly suggest that HSF1 under the HT protects the female-type proliferation of germ cells by inhibiting amhr2 expression in gonadal somatic cells. These findings provide new insights into the molecular mechanisms underlying environmental sex determination.
Effects of Pre-Anthesis Drought, Heat and Their Combination on the Growth, Yield and Physiology of diverse Wheat (Triticum aestivum L.) Genotypes Varying in Sensitivity to Heat and drought stress
Authors: Qaseem Mirza Faisal , Qureshi Rahmatullah , Shaheen Humaira 
Published: May 2019

AbstractIndependent and combined drought and heat stress negatively affect wheat yield and physiology. The present study was aimed to quantify effects of Drought [D], heat [H] and combined heat and drought [HD] during reproductive stage on wheat yield and to identify physio-biochemical traits which were strongly associated with improved yield and tolerance of wheat under stressful conditions. One hundred and eight elite diverse wheat genotypes were exposed to [H], [D] and [HD] treatments from heading till maturity. Grain yield was reduced by 56.47%, 53.05% and 44.66% under [HD], [H] and [D] treatment, respectively. The [HD] treatment affects the grain yield by reducing metabolism and mobilization of reserves to developing grains and leaves. Disintegration of membrane structure, chlorophyll and protein molecules was higher under [H] stress than [D] stress while water status of genotypes and sink strength was more affected by [D] than [H] stress. Multivariate analysis showed a strong correlation of chlorophyll content before and after anthesis, water-soluble carbohydrates (WSC), proline content (PC) and all other studies agronomic and physiological traits with grain yield while days to anthesis (DTA) and days to maturity (DTM) were negatively associated with grain yield under stress showing advantage of early maturity during stress. Traits having a major contribution in the first two principal components under different stress treatments may lead to improved varieties with heat and drought stress tolerance. To best of over knowledge, the present study is the first detailed study which used physiological and biochemical traits to explain the variation in grain yield and related traits in diverse wheat germplasm.
Acute-on-chronic liver disease enhances phenylephrine-induced endothelial nitric oxide release in rat mesenteric resistance arteries through enhanced PKA, PI3K/AKT and cGMP signalling pathways
Authors: Caracuel Laura , Sastre Esther , Llévenes Pablo , Prieto Isabel , Funes Tania , Aller Mª Ángeles , Arias Jaime , Balfagón Gloria , Blanco-Rivero Javier 
Published: May 2019

AbstractAcute-on-chronic liver disease is a clinical syndrome characterized by decompensated liver fibrosis, portal hypertension and splanchnic hyperdynamic circulation. We aimed to determine whether the alpha-1 agonist phenylephrine (Phe) facilitates endothelial nitric oxide (NO) release by mesenteric resistance arteries (MRA) in rats subjected to an experimental microsurgical obstructive liver cholestasis model (LC). Sham-operated (SO) and LC rats were maintained for eight postoperative weeks. Phe-induced vasoconstriction (in the presence/absence of the NO synthase –NOS- inhibitor L-NAME) and vasodilator response to NO donor DEA-NO were analysed. Phe-induced NO release was determined in the presence/absence of either H89 (protein kinase –PK- A inhibitor) or LY 294002 (PI3K inhibitor). PKA and PKG activities, alpha-1 adrenoceptor, endothelial NOS (eNOS), PI3K, AKT and soluble guanylate cyclase (sGC) subunit expressions, as well as eNOS and AKT phosphorylation, were determined. The results show that LC blunted Phe-induced vasoconstriction, and enhanced DEA-NO-induced vasodilation. L-NAME increased the Phe-induced contraction largely in LC animals. The Phe-induced NO release was greater in MRA from LC animals. Both H89 and LY 294002 reduced NO release in LC. Alpha-1 adrenoceptor, eNOS, PI3K and AKT expressions were unchanged, but sGC subunit expression, eNOS and AKT phosphorylation and the activities of PKA and PKG were higher in MRA from LC animals. In summary, these mechanisms may help maintaining splanchnic vasodilation and hypotension observed in decompensated LC.
Formation of Surface Silver Nano-network Structures through Hot Electron Regulated Diffusion-limited Aggregation
Authors: Yao Yu-Feng , Yang Shaobo , Teng Chin-Chou , Chou Keng-Ping , Liu Chi-Wu , Kuo Yang , Kiang Yean-Woei , Yang Chih-Chung 
Published: May 2019

AbstractA surface Ag nano-network pattern is formed by first depositing Ag nanoparticles (NPs) on a conductive template, which has a certain defect structure, and then illuminating the Ag NPs with ultraviolet (UV) light in a moist environment. Such an Ag nano-network pattern consists of multiple connected Brownian trees (BTs), which are produced through the diffusion-limited aggregation (DLA) process. In the DLA process, diffuse Ag+ ions, which are generated by UV light illumination and dissolved by a thin adsorbed water layer on the surfaces of the Ag NPs and used GaN template, settle to form a BT through the combination with excited hot electrons migrating into the template from the Ag NPs. The lateral transport of hot electrons in the template is regulated by the distributions of threading dislocation and point defect cluster in the template, which eventually become the centers of BTs. The structure of a surface Ag nano-network can potentially serve as a transparent conductor.
The effectiveness of hyposaline treatments against host-attached salmon lice
Authors: Sievers Michael , Oppedal Frode , Ditria Ellen , Wright Daniel W. 
Published: May 2019

AbstractUnderstanding how salinity affects marine parasites is vital to understanding their ecology and treatment, particularly for host-parasite systems that traverse marine and freshwater realms such as the globally important Atlantic salmon (Salmo salar), salmon louse (Lepeophtheirus salmonis) system. Growing concerns for wild fish populations, and decreased efficiencies and burgeoning costs of lice treatments for farmed fish has necessitated more environmentally and socially acceptable delousing procedures, such as hyposaline treatments. The effect of brackish water on L. salmonis following primary attachment is largely unknown, with experimental evidence derived mostly from unattached or newly attached copepodids, or adult stages. We aimed to understand how attached lice respond to hyposaline environments to assess effectiveness as a parasite management strategy and to help better define delousing areas used by wild fish. Louse development at 4, 12, 19 and 26 ppt, and survival at 4 ppt, decreased as exposure times increased, but survival was otherwise unaffected. Subjecting salmon to fluctuating, repeat exposures did not influence efficacy. We confirm that free-swimming stages are susceptible, and show that attached copepodids were more tolerant than previously predicted based on experiments on alternate development stages. These results improve our understanding of the utility of hyposaline treatments in aquaculture and self-treating in wild fish, and could apply to other fish-lice parasite systems. Further, these data are important for models predicting host-parasite interactions and can contribute to predictive models on the transmission dynamics of sea lice from farm to wild fish.
In vivo metal selectivity of metal-dependent biosynthesis of cobalt-type nitrile hydratase in Rhodococcus bacteria: a new look at the nitrile hydratase maturation mechanism?
Authors: Lavrov Konstantin V , Shemyakina Anna O , Grechishnikova Elena G , Novikov Andrey D , Kalinina Tatyana I , Yanenko Alexander S 
Published: May 2019

Abstract
This study highlights the effect of heavy metal ions on the expression of cobalt-containing nitrile hydratase (NHase) in Rhodococcus strains, which over-produce this enzyme. Both metal-dependent derepression of transcription and maturation of NHase were considered. We demonstrated that nickel ions can derepress the NHase promoter in several Rhodococcus strains. The cblA gene of a cobalt-dependent transcriptional repressor was shown to be indispensable for nickel-mediated derepression. As for maturation, we showed that nickel ions could not replace cobalt ions during the synthesis of active NHase. We also revealed that the amount of β-subunit decreased during NHase expression without added cobalt. We showed this using three variants of NHase in vivo synthesis: by using nickel- or urea-induced synthesis in cblA+ strains, and by using metal-independent constitutive synthesis in cblA− strains. In all cases, we found that the amount of β-subunit was significantly lower than the amount of α-subunit. In contrast, equimolar amounts of both subunits were synthesized after growth in the presence of added cobalt. Nickel did not affect NHase synthesis in mixtures with cobalt. This suggests that the metal selectivity in cblA-dependent regulation of NHase transcription was too low to discriminate between cobalt and nickel, but the selectivity of the NHase maturation mechanism was high enough to do so. Moreover, we can assume that the β-subunit is more subject to proteolytic degradation without the addition of cobalt, than the α-subunit. This indicates that cobalt ions presumably play an unknown role in the stability of the β-subunit in vivo.
Colonic electrical stimulation promotes colonic motility through regeneration of myenteric plexus neurons in slow transit constipation beagles
Authors: Wang Yongbin , Wang Qian , Kuerban Kudelaidi , Dong Mengxue , Qi Feilong , Li Gang , Ling Jie , Qiu Wei , Zhang Wenzhong , Ye Li 
Published: May 2019

AbstractSlow transit constipation (STC) is a common disease characterized by markedly delayed colonic transit time as a result of colonic motility dysfunction. It is well established that STC is mostly caused by disorders of relevant nerves, especially the enteric nervous system (ENS). Colonic electrical stimulation (CES) has been regarded as a valuable alternative for the treatment of STC. However, little report focuses on the underlying nervous mechanism to normalize the delayed colonic emptying and relieve symptoms. In the present study, the therapeutic effect and the influence on ENS triggered by CES were investigated in STC beagles. The STC beagle model was established by oral administration of diphenoxylate/atropine and alosetron. Histopathology, electron microscopy, immunohistochemistry, Western blot analysis and immunofluorescence were used to evaluate the influence of pulse train CES on myenteric plexus neurons. After 5 weeks of treatment, CES could enhance the colonic electromyogram (EMG) signal to promote colonic motility, thereby improving the colonic content emptying of STC beagles. HE staining and transmission electron microscopy confirmed that CES could regenerate ganglia and synaptic vesicles in the myenteric plexus. Immunohistochemical staining showed that synaptophysin (SYP), protein gene product 9.5 (PGP9.5), cathepsin D (CAD) and S-100B in the colonic intramuscular layer were up-regulated by CES. Western blot analysis and immunofluorescence further proved that CES induced the protein expression of SYP and PGP9.5. Taken together, pulse train CES could induce the regeneration of myenteric plexus neurons, thereby promoting the colonic motility in STC beagles.
Oxidative and endoplasmic reticulum stresses are involved in palmitic acid-induced H9c2 cell apoptosis
Authors: Yang Lei , Guan Gaopeng , Lei Lanjie , Liu Jianyun , Cao Lingling , Wang Xiangguo 
Published: May 2019

Abstract
Palmitic acid (PA) is the most common saturated long-chain fatty acid that causes damage to heart muscle cells. However, the molecular mechanism of PA toxicity in myocardial cells is not fully understood. In the present study, we explored the effects of PA on proliferation and apoptosis of H9c2 cardiomyocytes, and uncovered the signaling pathways involved in PA toxicity. Our study revealed induction of both oxidative and endoplasmic reticulum (ER) stresses and exacerbation of apoptosis in PA-treated H9c2 cells. Inhibition of oxidative stress by N-acetylcysteine (NAC) reduced apoptosis and decreased ER stress in PA-treated H9c2 cells. Moreover, inhibition of ER stress by 4-phenyl butyric acid decreased apoptosis and attenuated oxidative stress. In summary, the present study demonstrated that oxidative stress coordinates with ER stress to play important roles in PA-induced H9c2 cell apoptosis.