bluuebunny/crossref_metadata_2025_split huggingface dataset:
Munc18-1 is crucial to overcome the inhibition of synaptic vesicle fusion by αSNAP
Authors: Stepien Karolina P. , Prinslow Eric A. , Rizo Josep 
Published: September 2019

AbstractMunc18-1 and Munc13-1 orchestrate assembly of the SNARE complex formed by syntaxin-1, SNAP-25 and synaptobrevin, allowing exquisite regulation of neurotransmitter release. Non-regulated neurotransmitter release might be prevented by αSNAP, which inhibits exocytosis and SNARE-dependent liposome fusion. However, distinct mechanisms of inhibition by αSNAP were suggested, and it is unknown how such inhibition is overcome. Using liposome fusion assays, FRET and NMR spectroscopy, here we provide a comprehensive view of the mechanisms underlying the inhibitory functions of αSNAP, showing that αSNAP potently inhibits liposome fusion by: binding to syntaxin-1, hindering Munc18-1 binding; binding to syntaxin-1-SNAP-25 heterodimers, precluding SNARE complex formation; and binding to trans-SNARE complexes, preventing fusion. Importantly, inhibition by αSNAP is avoided only when Munc18-1 binds first to syntaxin-1, leading to Munc18-1-Munc13-1-dependent liposome fusion. We propose that at least some of the inhibitory activities of αSNAP ensure that neurotransmitter release occurs through the highly-regulated Munc18-1-Munc13-1 pathway at the active zone.
Nonlinear response of Northern Hemisphere stratospheric polar vortex to the Indo–Pacific warm pool (IPWP) Niño
Authors: Zhou Xin , Chen Quanliang , Xie Fei , Li Jianping , Li Minggang , Ding Ruiqiang , Li Yanjie , Xia Xin , Cheng Zhigang 
Published: September 2019

AbstractVariations in tropical sea surface temperatures (SST) have pronounced impacts on the stratospheric polar vortex, with the role of El Niño being the focus of much research interest. However, the Indo–Pacific warm pool (IPWP), which is the warmest body of seawater in the world, has received less attention. The IPWP has been warming in recent years. This paper presents for the first time the remarkable nonlinearity in Northern Hemisphere (NH) stratospheric circulation and temperature response to IPWP warming (the so-called IPWP Niño) in boreal winter. The magnitude of NH stratospheric vortex weakening is strong and significant in case of moderate IPWP Niño, but is weak and insignificant in strong IPWP Niño case. This phenomenon is robust in both the historical simulations and observations. An idealized model experiments forced with linear varying SST forcing in the IPWP region isolate the nonlinearities arising from IPWP Niño strength. Westward extension of precipitation into the Maritime Continent drives attenuation and westward shift of extratropical waves during strong IPWP Niño events. Linear wave interference analysis reveals this leads to weak interference between the climatological and anomalous stationary waves and thereby a weak response of the stratospheric vortex. These findings imply a distinct stratospheric vortex response to the IPWP Niño, and provide extended implications for the surface climate in the NH.
Disentangling the environmental impact of different human disturbances: a case study on islands
Authors: Steibl Sebastian , Laforsch Christian 
Published: September 2019

AbstractCoastal ecosystems suffer substantially from the worldwide population growth and its increasing land demands. A common approach to investigate anthropogenic disturbance in coastal ecosystems is to compare urbanized areas with unaffected control sites. However, the question remains whether different types of anthropogenic disturbance that are elements of an urbanized area have the same impact on beach ecosystems. By investigating small islands that are utilized for tourism, inhabited by the local population, or remained completely uninhabited, we disentangled different anthropogenic disturbances and analysed their impacts on hermit crabs as indicator species. We observed a negative impact on abundance on tourist islands and a negative impact on body size on local islands. In comparison to the uninhabited reference, both disturbances had an overall negative impact. As both forms of disturbance also impacted the underlying food resource and habitat availability differently, we propose that the findings from our study approach are valid for most obligate beach species in the same system. This demonstrates that in urbanized areas, the coastal ecosystem is not always impacted identically, which emphasizes the importance of considering the particular type of anthropogenic disturbance when planning conservation action in urbanized areas.
Plasma Protein Comparison between Dairy Cows with Inactive Ovaries and Estrus
Authors: Zhao Chang , Shu Shi , Bai Yunlong , Wang Dong , Xia Cheng , Xu Chuang 
Published: September 2019

AbstractTo screen differentially expressed proteins in the blood dairy cows with inactive ovaries caused by a negative energy balance and to determine the roles of the identified proteins in the development of inactive ovaries.Holstein cows at 14 to 21 days postpartum in an intensive dairy farm were examined for their energy balance (EB) status by blood β-hydroxybutyrate (BHBA) and assigned to the inactive ovary (IO) group (n = 50) and the normal oestrus control (CON) group (n = 50) at 60 to 90 days postpartum by means of the oestrus manifestation, rectal examination and B-ultrasound examination. Fourteen differentially expressed proteins from 61 proteins in the plasma of dairy cows with IOs were identified by iTRAQ/LC-MS/MS and GO, KEGG, and PATHWAY analysis. Eleven expressed proteins were upregulated, and 3 expressed proteins were downregulated. Among the 10 differentially expressed proteins verified by Western blot or ELISA, the relative expression levels of ALDOB, IGFBP2, ITIH3 and LDHB in mixed samples and single samples were consistent with the proteomic protein results. PKM2, GPX3, ALDOB, RBP4 and AHSG were significantly different between the two groups (P < 0.05); APOA4 and SPAM1 were not significantly different (P > 0.05) but were still downregulated in the ovarian resting group. This study confirmed that 14 plasma differential proteins in the inactive ovaries of postpartum dairy cows were associated with follicular development, and these findings provide a foundation for further research on the mechanism and prevention of inactive ovaries in dairy cows.
Subsurface ocean flywheel of coupled climate variability in the Barents Sea hotspot of global warming
Authors: Schlichtholz Pawel 
Published: September 2019

AbstractAccelerated shrinkage of the Arctic sea ice cover is the main reason for the recent Arctic amplification of global warming. There is growing evidence that the ocean is involved in this phenomenon, but to what extent remains unknown. Here, a unique dataset of hydrographic profiles is used to infer the regional pattern of recent subsurface ocean warming and construct a skillful predictor for surface climate variability in the Barents Sea region - a hotspot of the recent climate change. It is shown that, in the era of satellite observations (1981–2018), summertime temperature anomalies of Atlantic water heading for the Arctic Ocean explain more than 80% of the variance of the leading mode of variability in the following winter sea ice concentration over the entire Northern Hemisphere, with main centers of action just in the Barents Sea region. Results from empirical forecast experiments demonstrate that predictability of the wintertime sea ice cover in the Barents Sea from subsurface ocean heat anomalies might have increased since the Arctic climate shift of the mid-2000s. In contrast, the corresponding predictability of the sea ice cover in the nearby Greenland Sea has been lost.
Biochemical and biophysical characterization of purified native CD20 alone and in complex with rituximab and obinutuzumab
Authors: Agez Morgane , Mandon Elodie Desuzinges , Iwema Thomas , Gianotti Reto , Limani Florian , Herter Sylvia , Mössner Ekkehard , Kusznir Eric A. , Huber Sylwia , Lauer Matthias , Ringler Philippe , Ferrara Claudia , Klein Christian , Jawhari Anass 
Published: September 2019

AbstractCD20 is a B-lymphocyte specific integral membrane protein, an activated-glycosylated phosphoprotein expressed on the surface of B-cells and a clinically validated target of monoclonal antibodies such as rituximab, ocrelizumab, ofatumumab and obinutuzumab in the treatment of all B cell lymphomas and leukemias as well as autoimmune diseases. Here, we report the extraction and purification of native CD20 from SUDHL4 and RAMOS cell lines. To improve the protein yield, we applied a calixarene-based detergent approach to solubilize, stabilize and purify native CD20 from HEK293 cells. Size Exclusion Chromatography (SEC) and Analytical Ultracentrifugation show that purified CD20 was non-aggregated and that CD20 oligomerization is concentration dependent. Negative stain electron microscopy and atomic force microscopy revealed homogenous populations of CD20. However, no defined structure could be observed. Interestingly, micellar solubilized and purified CD20 particles adopt uniformly confined nanodroplets which do not fuse and aggregate. Finally, purified CD20 could bind to rituximab and obinutuzumab as demonstrated by SEC, and Surface Plasmon Resonance (SPR). Specificity of binding was confirmed using CD20 antibody mutants to human B-cell lymphoma cells. The strategy described in this work will help investigate CD20 binding with newly developed antibodies and eventually help to optimize them. This approach may also be applicable to other challenging membrane proteins.
Exposure to excessive heat and impacts on labour productivity linked to cumulative CO2 emissions
Authors: Chavaillaz Yann , Roy Philippe , Partanen Antti-Ilari , Da Silva Laurent , Bresson Émilie , Mengis Nadine , Chaumont Diane , Matthews H. Damon 
Published: September 2019

AbstractCumulative CO2 emissions are a robust predictor of mean temperature increase. However, many societal impacts are driven by exposure to extreme weather conditions. Here, we show that cumulative emissions can be robustly linked to regional changes of a heat exposure indicator, as well as the resulting socioeconomic impacts associated with labour productivity loss in vulnerable economic sectors. We estimate historical and future increases in heat exposure using simulations from eight Earth System Models. Both the global intensity and spatial pattern of heat exposure evolve linearly with cumulative emissions across scenarios (1% CO2, RCP4.5 and RCP8.5). The pattern of heat exposure at a given level of global temperature increase is strongly affected by non-CO2 forcing. Global non-CO2 greenhouse gas emissions amplify heat exposure, while high local emissions of aerosols could moderate exposure. Considering CO2 forcing only, we commit ourselves to an additional annual loss of labour productivity of about 2% of total GDP per unit of trillion tonne of carbon emitted. This loss doubles when adding non-CO2 forcing of the RCP8.5 scenario. This represents an additional economic loss of about 4,400 G$ every year (i.e. 0.59 $/tCO2), varying across countries with generally higher impact in lower-income countries.
Novel mitochondrial complex I-inhibiting peptides restrain NADH dehydrogenase activity
Authors: Xue Yao-Peng , Kao Mou-Chieh , Lan Chung-Yu 
Published: September 2019

AbstractThe emergence of drug-resistant fungal pathogens is becoming increasingly serious due to overuse of antifungals. Antimicrobial peptides have potent activity against a broad spectrum of pathogens, including fungi, and are considered a potential new class of antifungals. In this study, we examined the activities of the newly designed peptides P-113Du and P-113Tri, together with their parental peptide P-113, against the human fungal pathogen Candida albicans. The results showed that these peptides inhibit mitochondrial complex I, specifically NADH dehydrogenase, of the electron transport chain. Moreover, P-113Du and P-113Tri also block alternative NADH dehydrogenases. Currently, most inhibitors of the mitochondrial complex I are small molecules or artificially-designed antibodies. Here, we demonstrated novel functions of antimicrobial peptides in inhibiting the mitochondrial complex I of C. albicans, providing insight in the development of new antifungal agents.
Endoscopic Radiofrequency Ablation Prolongs Survival of Patients with Unresectable Hilar Cholangiocellular Carcinoma - A Case-Control Study
Authors: Bokemeyer Arne , Matern Philipp , Bettenworth Dominik , Cordes Friederike , Nowacki Tobias Max , Heinzow Hauke , Kabar Iyad , Schmidt Hartmut , Ullerich Hansjoerg , Lenze Frank 
Published: September 2019

AbstractThe life expectancy of unresectable hilar cholangiocellular carcinomas (CCCs) is very limited and endoscopic radiofrequency ablation (ERFA) of the biliary tract may prolong survival. Our single-center-study retrospectively analysed all CCC cases, in whom ERFAs of the biliary tract were performed between 2012 and 2017 and compared these to historical control cases who received the standard treatment of sole stent application. ERFA was performed in 32 patients with malignant biliary strictures that were mainly caused by Bismuth III and IV hilar CCCs (66%). 14 of these patients received repeated ERFAs, for an overall performance of 54 ERFAs. Stents were applied after examination of all patients (100%). Adverse events occurred in 18.5% of examinations. Case-control analysis revealed that the survival time of cases with unresectable Bismuth type III and IV hilar CCCs (n = 20) treated with combined ERFA and stent application significantly increased compared to controls (n = 22) treated with sole stent application (342 +/− 57 vs. 221 +/− 26 days; p = 0.046). In conclusion, ERFA therapy significantly prolonged survival in patients with unresectable Bismuth type III and IV hilar CCC. As an effective and safe method, ERFA should be considered as a palliative treatment for all these patients.
Microbiota fingerprints within the oral cavity of cetaceans as indicators for population biomonitoring
Authors: Soares-Castro Pedro , Araújo-Rodrigues Helena , Godoy-Vitorino Filipa , Ferreira Marisa , Covelo Pablo , López Alfredo , Vingada José , Eira Catarina , Santos Pedro Miguel 
Published: September 2019

AbstractThe composition of mammalian microbiota has been related with the host health status. In this study, we assessed the oral microbiome of 3 cetacean species most commonly found stranded in Iberian Atlantic waters (Delphinus delphis, Stenella coeruleoalba and Phocoena phocoena), using 16S rDNA-amplicon metabarcoding. All oral microbiomes were dominated by Proteobacteria, Firmicutes, Bacteroidetes and Fusobacteria bacteria, which were also predominant in the oral cavity of Tursiops truncatus. A Constrained Canonical Analysis (CCA) showed that the major factors shaping the composition of 38 oral microbiomes (p-value < 0.05) were: (i) animal species and (ii) age class, segregating adults and juveniles. The correlation analysis also grouped the microbiomes by animal stranding location and health status. Similar discriminatory patterns were detected using the data from a previous study on Tursiops truncatus, indicating that this correlation approach may facilitate data comparisons between different studies on several cetacean species. This study identified a total of 15 bacterial genera and 27 OTUs discriminating between the observed CCA groups, which can be further explored as microbiota fingerprints to develop (i) specific diagnostic assays for cetacean population conservation and (ii) bio-monitoring approaches to assess the health of marine ecosystems from the Iberian Atlantic basin, using cetaceans as bioindicators.
Novel approach to synthesize NiCo2S4 composite for high-performance supercapacitor application with different molar ratio of Ni and Co
Authors: Shinde S. K. , Ramesh Sivalingam , Bathula C. , Ghodake G. S. , Kim D.-Y. , Jagadale A. D. , Kadam A. A. , Waghmode D. P. , Sreekanth T. V. M. , Kim Heung Soo , Nagajyothi P. C. , Yadav H. M. 
Published: September 2019

AbstractHere, we developed a new approach to synthesize NiCo2S4 thin films for supercapacitor application using the successive ionic layer adsorption and reaction (SILAR) method on Ni mesh with different molar ratios of Ni and Co precursors. The five different NiCo2S4 electrodes affect the electrochemical performance of the supercapacitor. The NiCo2S4 thin films demonstrate superior supercapacitance performance with a significantly higher specific capacitance of 1427 F g−1 at a scan rate of 20 mV s−1. These results indicate that ternary NiCo2S4 thin films are more effective electrodes compared to binary metal oxides and metal sulfides.
Proinflammatory profile of neonatal monocytes induced by microbial ligands is downmodulated by histamine
Authors: Branco Anna Cláudia Calvielli Castelo , Pereira Nátalli Zanete , Yoshikawa Fábio Seiti Yamada , Oliveira Luanda Mara da Silva , Teixeira Franciane Mouradian Emidio , Oliveira Luana de Mendonça , Pietrobon Anna Julia , Torrealba Marina Passos , de Lima Josenilson Feitosa , Duarte Alberto José da Silva , Sato Maria Notomi 
Published: September 2019

AbstractAlthough the neonatal period is characterized by relative immunological immaturity, an inflammatory response due to Toll-like receptor (TLR) activation is observed. Histamine may be one of the factors playing a role in restraining inflammation during the early stages of life. Therefore, we evaluated the responsiveness of human cord blood cells to TLR4 agonists and the immunomodulatory function of histamine in the inflammatory response. Compared with adults, mononuclear cells (MNCs) from newborns (NBs) exhibit impaired production of IFN-γ-inducible chemokines, such as CXCL10 and CXCL9, upon lipopolysaccharide (LPS) stimulation. Notably, LPS induced a 5-fold increase in CCL2 secretion in NBs. Evaluation of the effect of histamine on LPS-induced CCL2 secretion showed an inhibitory effect in the majority of adults, whereas this effect was detectable in all NBs. Histamine receptor (HR) blockage revealed partial involvement of H1R, H2R and H4R in LPS-induced CCL2 inhibition in MNCs from both NBs and adults. As monocytes are the main type of mononuclear cell that produces CCL2, we evaluated genes related to TLR signaling upon LPS stimulation. Monocytes from NBs showed up-regulation of genes associated with JAK/STAT/NF-κB and IFN signaling. Some differentially expressed genes encoding proinflammatory factors were preferentially detected in LPS-activated monocytes from NBs, and markedly down-regulated by histamine. The immunomodulatory role of histamine on CCL2 and CXCL8 was detected at the transcript and protein levels. Our findings show that NBs have enhanced CCL2 responsiveness to LPS, and that histamine acts in immune homeostasis during the neonatal period to counterbalance the robustness of TLR stimulation.
Trace biomarkers associated with spontaneous preterm birth from the maternal serum metabolome of asymptomatic nulliparous women – parallel case-control studies from the SCOPE cohort
Authors: Souza Renato T. , McKenzie Elizabeth J. , Jones Beatrix , de Seymour Jamie V. , Thomas Melinda M. , Zarate Erica , Han Ting Li , McCowan Lesley , Sulek Karolina , Villas-Boas Silas , Kenny Louise C. , Cecatti José G. , Baker Philip N. 
Published: September 2019

AbstractPrediction of spontaneous preterm birth (sPTB) in asymptomatic women remains a great challenge; accurate and reproducible screening tools are still not available in clinical practice. We aimed to investigate whether the maternal serum metabolome together with clinical factors could be used to identify asymptomatic women at risk of sPTB. We conducted two case-control studies using gas chromatography-mass spectrometry to analyse maternal serum samples collected at 15- and 20-weeks’ gestation from 164 nulliparous women from Cork, and 157 from Auckland. Smoking and vaginal bleeding before 15 weeks were the only significant clinical predictors of sPTB for Auckland and Cork subsets, respectively. Decane, undecane, and dodecane were significantly associated with sPTB (FDR < 0.05) in the Cork subset. An odds ratio of 1.9 was associated with a one standard deviation increase in log (undecane) in a multiple logistic regression which also included vaginal bleeding as a predictor. In summary, elevated serum levels of the alkanes decane, undecane, and dodecane were associated with sPTB in asymptomatic nulliparous women from Cork, but not in the Auckland cohort. The association is not strong enough to be a useful clinical predictor, but suggests that further investigation of the association between oxidative stress processes and sPTB risk is warranted.
Phosphorylation of adducin-1 by cyclin-dependent kinase 5 is important for epidermal growth factor-induced cell migration
Authors: Su Chia-Yi , Yan Ruei-Liang , Hsu Wen-Hsin , Chu Ching-Tung , Chang Hsuan-Chia , Lai Chien-Chen , Hsu Hui-Ping , Chen Hong-Chen 
Published: September 2019

AbstractCyclin-dependent kinase 5 (Cdk5) is predominantly expressed in neuron and plays an important role in neuronal physiology. Increasing evidence also indicates that Cdk5 may contribute to malignant progression of some types of cancers; however, the underlying mechanism remains elusive. In this study, we found that Cdk5 directly phosphorylated the actin-binding protein adducin-1 (ADD1) at T724 in vitro and in intact cells. The capability of the phosphomimetic T724D mutant to bind to actin filaments was lower than that of wild type ADD1 and the T724A mutant. Cdk5 co-localized with ADD1 at the lamellipodia upon epidermal growth factor (EGF) stimulation. The increased lamellipodia formation and cell migration of human breast cancer cells MDA-MB-231 by EGF were accompanied by Cdk5 activation and increased phosphorylation of ADD1 at T724. Depletion of Cdk5 in MDA-MB-231 cells abrogated the effects of EGF on ADD1 T724 phosphorylation, lamellipodia formation, and cell migration. Likewise, depletion of ADD1 suppressed the effects of EGF on lamellipodia formation, cell migration, and invasion, all of which were restored by FLAG-ADD1 WT and the T724D mutant, but not the T724A mutant. Together, our results suggest that phosphorylation of ADD1 at T724 by Cdk5 is important for EGF-induced cell migration and invasion.
Biochemical characterization of phosphoenolpyruvate carboxykinases from Arabidopsis thaliana
Authors: Rojas Bruno E. , Hartman Matías D. , Figueroa Carlos M. , Leaden Laura , Podestá Florencio E. , Iglesias Alberto A. 
Published: September 2019

Abstract
ATP-dependent phosphoenolpyruvate carboxykinases (PEPCKs, EC 4.1.1.49) from C4 and CAM plants have been widely studied due to their crucial role in photosynthetic CO2 fixation. However, our knowledge on the structural, kinetic and regulatory properties of the enzymes from C3 species is still limited. In this work, we report the recombinant production and biochemical characterization of two PEPCKs identified in Arabidopsis thaliana: AthPEPCK1 and AthPEPCK2. We found that both enzymes exhibited high affinity for oxaloacetate and ATP, reinforcing their role as decarboxylases. We employed a high-throughput screening for putative allosteric regulators using differential scanning fluorometry and confirmed their effect on enzyme activity by performing enzyme kinetics. AthPEPCK1 and AthPEPCK2 are allosterically modulated by key intermediates of plant metabolism, namely succinate, fumarate, citrate and α-ketoglutarate. Interestingly, malate activated and glucose 6-phosphate inhibited AthPEPCK1 but had no effect on AthPEPCK2. Overall, our results demonstrate that the enzymes involved in the critical metabolic node constituted by phosphoenolpyruvate are targets of fine allosteric regulation.