bluuebunny/crossref_metadata_2025_split huggingface dataset:
The substrate specificity switch FlhB assembles onto the export gate to regulate type three secretion
Authors: Kuhlen Lucas , Johnson Steven , Zeitler Andreas , Bäurle Sandra , Deme Justin C. , Caesar Joseph J.  E. , Debo Rebecca , Fisher Joseph , Wagner Samuel , Lea Susan M. 
Published: March 2020

AbstractProtein secretion through type-three secretion systems (T3SS) is critical for motility and virulence of many bacteria. Proteins are transported through an export gate containing three proteins (FliPQR in flagella, SctRST in virulence systems). A fourth essential T3SS protein (FlhB/SctU) functions to “switch” secretion substrate specificity once the growing hook/needle reach their determined length. Here, we present the cryo-electron microscopy structure of an export gate containing the switch protein from a Vibrio flagellar system at 3.2 Å resolution. The structure reveals that FlhB/SctU extends the helical export gate with its four predicted transmembrane helices wrapped around FliPQR/SctRST. The unusual topology of the FlhB/SctU helices creates a loop wrapped around the bottom of the closed export gate. Structure-informed mutagenesis suggests that this loop is critical in gating secretion and we propose that a series of conformational changes in the T3SS trigger opening of the gate through interactions between FlhB/SctU and FliPQR/SctRST.
Structure of E3 ligase E6AP with a proteasome-binding site provided by substrate receptor hRpn10
Authors: Buel Gwen R. , Chen Xiang , Chari Raj , O’Neill Maura J. , Ebelle Danielle L. , Jenkins Conor , Sridharan Vinidhra , Tarasov Sergey G. , Tarasova Nadya I. , Andresson Thorkell , Walters Kylie J. 
Published: March 2020

AbstractRegulated proteolysis by proteasomes involves ~800 enzymes for substrate modification with ubiquitin, including ~600 E3 ligases. We report here that E6AP/UBE3A is distinguished from other E3 ligases by having a 12 nM binding site at the proteasome contributed by substrate receptor hRpn10/PSMD4/S5a. Intrinsically disordered by itself, and previously uncharacterized, the E6AP-binding domain in hRpn10 locks into a well-defined helical structure to form an intermolecular 4-helix bundle with the E6AP AZUL, which is unique to this E3. We thus name the hRpn10 AZUL-binding domain RAZUL. We further find in human cells that loss of RAZUL by CRISPR-based gene editing leads to loss of E6AP at proteasomes. Moreover, proteasome-associated ubiquitin is reduced following E6AP knockdown or displacement from proteasomes, suggesting that E6AP ubiquitinates substrates at or for the proteasome. Altogether, our findings indicate E6AP to be a privileged E3 for the proteasome, with a dedicated, high affinity binding site contributed by hRpn10.
Observation of dissipative chlorophyll-to-carotenoid energy transfer in light-harvesting complex II in membrane nanodiscs
Authors: Son Minjung , Pinnola Alberta , Gordon Samuel C. , Bassi Roberto , Schlau-Cohen Gabriela S. 
Published: March 2020

AbstractPlants prevent photodamage under high light by dissipating excess energy as heat. Conformational changes of the photosynthetic antenna complexes activate dissipation by leveraging the sensitivity of the photophysics to the protein structure. The mechanisms of dissipation remain debated, largely due to two challenges. First, because of the ultrafast timescales and large energy gaps involved, measurements lacked the temporal or spectral requirements. Second, experiments have been performed in detergent, which can induce non-native conformations, or in vivo, where contributions from homologous antenna complexes cannot be disentangled. Here, we overcome both challenges by applying ultrabroadband two-dimensional electronic spectroscopy to the principal antenna complex, LHCII, in a near-native membrane. Our data provide evidence that the membrane enhances two dissipative pathways, one of which is a previously uncharacterized chlorophyll-to-carotenoid energy transfer. Our results highlight the sensitivity of the photophysics to local environment, which may control the balance between light harvesting and dissipation in vivo.
Cancer associated fibroblast FAK regulates malignant cell metabolism
Authors: Demircioglu Fevzi , Wang Jun , Candido Juliana , Costa Ana S. H. , Casado Pedro , de Luxan Delgado Beatriz , Reynolds Louise E. , Gomez-Escudero Jesus , Newport Emma , Rajeeve Vinothini , Baker Ann-Marie , Roy-Luzarraga Marina , Graham Trevor A. , Foster Julie , Wang Yu , Campbell James J. , Singh Rajinder , Zhang Penglie , Schall Thomas J. , Balkwill Frances R. , Sosabowski Jane , Cutillas Pedro R. , Frezza Christian , Sancho Patricia , Hodivala-Dilke Kairbaan 
Published: March 2020

AbstractEmerging evidence suggests that cancer cell metabolism can be regulated by cancer-associated fibroblasts (CAFs), but the mechanisms are poorly defined. Here we show that CAFs regulate malignant cell metabolism through pathways under the control of FAK. In breast and pancreatic cancer patients we find that low FAK expression, specifically in the stromal compartment, predicts reduced overall survival. In mice, depletion of FAK in a subpopulation of CAFs regulates paracrine signals that increase malignant cell glycolysis and tumour growth. Proteomic and phosphoproteomic analysis in our mouse model identifies metabolic alterations which are reflected at the transcriptomic level in patients with low stromal FAK. Mechanistically we demonstrate that FAK-depletion in CAFs increases chemokine production, which via CCR1/CCR2 on cancer cells, activate protein kinase A, leading to enhanced malignant cell glycolysis. Our data uncover mechanisms whereby stromal fibroblasts regulate cancer cell metabolism independent of genetic mutations in cancer cells.
The temporal structure of the inner retina at a single glance
Authors: Zhao Zhijian , Klindt David A. , Maia Chagas André , Szatko Klaudia P. , Rogerson Luke , Protti Dario A. , Behrens Christian , Dalkara Deniz , Schubert Timm , Bethge Matthias , Franke Katrin , Berens Philipp , Ecker Alexander S. , Euler Thomas 
Published: March 2020

AbstractThe retina decomposes visual stimuli into parallel channels that encode different features of the visual environment. Central to this computation is the synaptic processing in a dense layer of neuropil, the so-called inner plexiform layer (IPL). Here, different types of bipolar cells stratifying at distinct depths relay the excitatory feedforward drive from photoreceptors to amacrine and ganglion cells. Current experimental techniques for studying processing in the IPL do not allow imaging the entire IPL simultaneously in the intact tissue. Here, we extend a two-photon microscope with an electrically tunable lens allowing us to obtain optical vertical slices of the IPL, which provide a complete picture of the response diversity of bipolar cells at a “single glance”. The nature of these axial recordings additionally allowed us to isolate and investigate batch effects, i.e. inter-experimental variations resulting in systematic differences in response speed. As a proof of principle, we developed a simple model that disentangles biological from experimental causes of variability and allowed us to recover the characteristic gradient of response speeds across the IPL with higher precision than before. Our new framework will make it possible to study the computations performed in the central synaptic layer of the retina more efficiently.
Using the circulating proteome to assess type I interferon activity in systemic lupus erythematosus
Authors: Smith Michael A. , Chiang Chia-Chien , Zerrouki Kamelia , Rahman Saifur , White Wendy I. , Streicher Katie , Rees William A. , Schiffenbauer Adam , Rider Lisa G. , Miller Frederick W. , Manna Zerai , Hasni Sarfaraz , Kaplan Mariana J. , Siegel Richard , Sinibaldi Dominic , Sanjuan Miguel A. , Casey Kerry A. 
Published: March 2020

AbstractType I interferon (IFN) drives pathology in systemic lupus erythematosus (SLE) and can be tracked via IFN-inducible transcripts in blood. Here, we examined whether measurement of circulating proteins, which enter the bloodstream from inflamed tissues, also offers insight into global IFN activity. Using a novel protocol we generated 1,132 aptamer-based protein measurements from anti-dsDNApos SLE blood samples and derived an IFN protein signature (IFNPS) that approximates the IFN 21-gene signature (IFNGS). Of 82 patients with SLE, IFNPS was elevated for 89% of IFNGS-high patients (49/55) and 26% of IFNGS-low patients (7/27). IFNGS-high/IFNPS-high patients exhibited activated NK, CD4, and CD8 T cells, while IFNPS-high only patients did not. IFNPS correlated with global disease activity in lymphopenic and non-lymphopenic patients and decreased following type I IFN neutralisation with anifrolumab in the SLE phase IIb study, MUSE. In summary, we developed a protein signature that reflects IFNGS and identifies a new subset of patients with SLE who have IFN activity.
Chemokine releasing particle implants for trapping circulating prostate cancer cells
Authors: Huang YiHui , Hakamivala Amirhossein , Li Shuxin , Nair Ashwin , Saxena Ramesh , Hsieh Jer-Tsong , Tang Liping 
Published: March 2020

AbstractProstate cancer (PCa) is the most prevalent cancer in U.S. men and many other countries. Although primary PCa can be controlled with surgery or radiation, treatment options of preventing metastatic PCa are still limited. To develop a new treatment of eradicating metastatic PCa, we have created an injectable cancer trap that can actively recruit cancer cells in bloodstream. The cancer trap is composed of hyaluronic acid microparticles that have good cell and tissue compatibility and can extend the release of chemokines to 4 days in vitro. We find that erythropoietin (EPO) and stromal derived factor-1α can attract PCa in vitro. Animal results show that EPO-releasing cancer trap attracted large number of circulating PCa and significantly reduced cancer spreading to other organs compared with controls. These results support that cancer trap may serve as a unique device to sequester circulating PCa cells and subsequently reduce distant metastasis.
Purity determination of synthetic glucagon using a mass balance approach
Authors: Wang Xinxue , Zhang Fangyan , Li Hongmei , Xiao Peng , Su Fuhai , Xu Bei , Sun Wei , Song Dewei 
Published: March 2020

AbstractDue to the widespread use of synthetic peptide drugs, their quantification and the analysis of impurities have become increasingly important in clinical and medical settings. Moreover, quantifying proteins using synthetic peptides as internal or external standards is a general approach, and the key to this approach is the knowing purities of the peptides. In this paper, synthetic glucagon was quantified using a mass balance method. The impurities in glucagon were analyzed and then accurately quantified separately. Karl Fischer (KF) titration and ion chromatography (IC) were used to determine the water and trifluoroacetic acid (TFA) contents in the samples, respectively. Furthermore, the inorganic ion content in the samples was determined by inductively coupled plasma mass spectrometry (ICP-MS). The sequence of peptide impurities was identified by a Thermo Fisher Orbitrap mass. Samples were determined to be 896.36 ± 0.68 mg/g after subtracting all impurity masses from the sample mass. The result can be traced to SI units.
Taste, smell and food-related nausea and vomiting responses in hyperemesis gravidarum: A case-controlled study
Authors: Tan Peng Chiong , Kartik Balaraman , Thanendran Panjaratnam , Zakaria Rozita , Win Sandar Tin , Omar Siti Zawiah 
Published: March 2020

AbstractA case-controlled study was performed to evaluate taste and smell impairment, nausea or vomiting (NV) response to taste and smell and toleration to food texture, item and cooking method in hyperemesis gravidarum patients (HG) compared to gestation-matched controls from a university hospital and primary care clinic in Malaysia. Taste strips (4 base tastes), sniff sticks (16 selected smells) and a food-related questionnaire were used. 124 participants were recruited. Taste impairment was found in 13%(8/62) vs. 0%(0/62) P = 0.003 and the median for correct smell identification was 5[4–6] vs. 9[7–9] P < 0.001 in HG vs. controls. In HG, bitter was most likely (32%) and sweet taste least likely (5%) to provoke NV. In both arms, fish smell was most likely to provoke NV, 77% vs. 32% P < 0.001 and peppermint smell least likely 10% vs. 0% P = 0.012; NV response was significantly more likely for HG arm in 10/16 smells. In HG, worst and best NV responses to food-texture were pasty 69% and crunchy 26%; food-item, plain rice 71% and apple 16% and cooking-style, deep-frying 71% and steaming 55%. HG demonstrated taste and smell impairment and increased NV responses to many tastes and smells. Crunchy sweet uncooked food (apple or watermelon) maybe best tolerated in HG.
Machine learning for characterizing risk of type 2 diabetes mellitus in a rural Chinese population: the Henan Rural Cohort Study
Authors: Zhang Liying , Wang Yikang , Niu Miaomiao , Wang Chongjian , Wang Zhenfei 
Published: March 2020

AbstractWith the development of data mining, machine learning offers opportunities to improve discrimination by analyzing complex interactions among massive variables. To test the ability of machine learning algorithms for predicting risk of type 2 diabetes mellitus (T2DM) in a rural Chinese population, we focus on a total of 36,652 eligible participants from the Henan Rural Cohort Study. Risk assessment models for T2DM were developed using six machine learning algorithms, including logistic regression (LR), classification and regression tree (CART), artificial neural networks (ANN), support vector machine (SVM), random forest (RF) and gradient boosting machine (GBM). The model performance was measured in an area under the receiver operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value and area under precision recall curve. The importance of variables was identified based on each classifier and the shapley additive explanations approach. Using all available variables, all models for predicting risk of T2DM demonstrated strong predictive performance, with AUCs ranging between 0.811 and 0.872 using laboratory data and from 0.767 to 0.817 without laboratory data. Among them, the GBM model performed best (AUC: 0.872 with laboratory data and 0.817 without laboratory data). Performance of models plateaued when introduced 30 variables to each model except CART model. Among the top-10 variables across all methods were sweet flavor, urine glucose, age, heart rate, creatinine, waist circumference, uric acid, pulse pressure, insulin, and hypertension. New important risk factors (urinary indicators, sweet flavor) were not found in previous risk prediction methods, but determined by machine learning in our study. Through the results, machine learning methods showed competence in predicting risk of T2DM, leading to greater insights on disease risk factors with no priori assumption of causality.
Radiative MHD Casson Nanofluid Flow with Activation energy and chemical reaction over past nonlinearly stretching surface through Entropy generation
Authors: Shah Zahir , Kumam Poom , Deebani Wejdan 
Published: March 2020

AbstractIn the present research analysis we have addressed comparative investigation of radiative electrically conducting Casson nanofluid. Nanofluid Flow is assumed over a nonlinearly stretching sheet. Heat transport analysis is carried via joule dissipation, thermal behavior and convective boundary condition. To employ the radiative effect radiation was involved to show the diverse states of nanoparticles. Furthermore entropy optimization with activation energy and chemical reaction are considered. Thermodynamics 2nd law is applied to explore entropy generation rate. Nonlinear expression is simplified through similarity variables. The reduced ordinary system is tackled through optimal approach. Flow pattern was reported for wide range of scrutinized parameters. Computational consequences of velocity drag force, heat flux and concentration gradient are analyzed numerically in tables. Results verify that conduction mode augments with enhance of magnetic parameter.Increasing radiation boosts the temperature and entropy. Activation energy corresponds to augmented concentration. Heat transmission rate augments with the consideration of radiation source term.
The Global Flood Protection Benefits of Mangroves
Authors: Menéndez Pelayo , Losada Iñigo J. , Torres-Ortega Saul , Narayan Siddharth , Beck Michael W. 
Published: March 2020

AbstractCoastal flood risks are rising rapidly. We provide high resolution estimates of the economic value of mangroves forests for flood risk reduction every 20 km worldwide. We develop a probabilistic, process-based valuation of the effects of mangroves on averting damages to people and property. We couple spatially-explicit 2-D hydrodynamic analyses with economic models, and find that mangroves provide flood protection benefits exceeding $US 65 billion per year. If mangroves were lost, 15 million more people would be flooded annually across the world. Some of the nations that receive the greatest economic benefits include the USA, China, India and Mexico. Vietnam, India and Bangladesh receive the greatest benefits in terms of people protected. Many (>45) 20-km coastal stretches particularly those near cities receive more than $US 250 million annually in flood protection benefits from mangroves. These results demonstrate the value of mangroves as natural coastal defenses at global, national and local scales, which can inform incentives for mangrove conservation and restoration in development, climate adaptation, disaster risk reduction and insurance.
Rapid detection of CITES-listed shark fin species by loop-mediated isothermal amplification assay with potential for field use
Authors: But Grace Wing-Chiu , Wu Hoi-Yan , Shao Kwang-Tsao , Shaw Pang-Chui 
Published: March 2020

AbstractShark fin is a delicacy in many Asian countries. Overexploitation of sharks for shark fin trading has led to a drastic reduction in shark population. To monitor international trade of shark fin products and protect the endangered species from further population decline, we present rapid, user-friendly and sensitive diagnostic loop-mediated isothermal amplification (LAMP) and effective polymerase chain reaction (PCR) assays for all twelve CITES-listed shark species. Species-specific LAMP and PCR primers were designed based on cytochrome oxidase I (COI) and NADH2 regions. Our LAMP and PCR assays have been tested on 291 samples from 93 shark and related species. Target shark species could be differentiated from non-target species within three hours from DNA extraction to LAMP assay. The LAMP assay reported here is a simple and robust solution for on-site detection of CITES-listed shark species with shark fin products.
Genetic and physical mapping of loci for resistance to blackleg disease in canola (Brassica napus L.)
Authors: Raman Rosy , Diffey Simon , Barbulescu Denise M. , Coombes Neil , Luckett David , Salisbury Phil , Cowley Raymond , Marcroft Steve , Raman Harsh 
Published: March 2020

AbstractSustainable canola production is essential to meet growing human demands for vegetable oil, biodiesel, and meal for stock feed markets. Blackleg, caused by the fungal pathogen, Leptosphaeria maculans is a devastating disease that can lead to significant yield loss in many canola production regions worldwide. Breakdown of race-specific resistance to L. maculans in commercial cultivars poses a constant threat to the canola industry. To identify new alleles, especially for quantitative resistance (QR), we analyzed 177 doubled haploid (DH) lines derived from an RP04/Ag-Outback cross. DH lines were evaluated for QR under field conditions in three experiments conducted at Wagga Wagga (2013, 2014) and Lake Green (2015), and under shade house conditions using the ‘ascospore shower’ test. DH lines were also characterized for qualitative R gene-mediated resistance via cotyledon tests with two differential single spore isolates, IBCN17 and IBCN76, under glasshouse conditions. Based on 18,851 DArTseq markers, a linkage map representing 2,019 unique marker bins was constructed and then utilized for QTL detection. Marker regression analysis identified 22 significant marker associations for resistance, allowing identification of two race-specific resistance R genes, Rlm3 and Rlm4, and 21 marker associations for QR loci. At least three SNP associations for QR were repeatedly detected on chromosomes A03, A07 and C04 across phenotyping environments. Physical mapping of markers linked with these consistent QR loci on the B. napus genome assembly revealed their localization in close proximity of the candidate genes of B. napus BnaA03g26760D (A03), BnaA07g20240D (A07) and BnaC04g02040D (C04). Annotation of these candidate genes revealed their association with protein kinase and jumonji proteins implicated in defense resistance. Both Rlm3 and Rlm4 genes identified in this DH population did not show any association with resistance loci detected under either field and/or shade house conditions (ascospore shower) suggesting that both genes are ineffective in conferring resistance to L. maculans in Australian field conditions. Taken together, our study identified sequence-based molecular markers for dissecting R and QR loci to L. maculans in a canola DH population from the RP04/Ag-Outback cross.
Edaphic and temporal patterns of Tuber melanosporum fruitbody traits and effect of localised peat-based amendment
Authors: Garcia-Barreda Sergi , Marco Pedro , Martín-Santafé María , Tejedor-Calvo Eva , Sánchez Sergio 
Published: March 2020

AbstractInTuber melanosporumcultivation, fruitbody traits are gaining relevance due to their increasing prominence on prices. We investigated the edaphic and temporal patterns of fruitbody traits and characterised the effect of truffle nests (localised peat-based amendment supplemented withT. melanosporumspores) on traits. We monitored fruitbody traits throughout two fruiting seasons in three blocks along a soil gradient. Each trait followed specific edaphic and temporal patterns. The number of fruitbodies per dig and spore maturity followed characteristic within-season trends, whereas fruitbody weight and infestation by truffle beetles were subject to complex interactions among edaphic and temporal variables, suggesting a relevant influence of annual environmental conditions. The application of truffle nests increased fruitbody depth, improved its shape and decreased infestation by truffle beetles. Nests increased the number of fruitbodies per dig, but only in two of the soils, suggesting a relevant role of the bulk soil/substrate interface in fruiting initiation. These results outline a complex scenario, with each trait being differently affected by environmental factors. In this scenario, nests proved to effectively modify several traits, although not always in the desired direction.