bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain insulin resistance impairs hippocampal synaptic plasticity and memory by increasing GluA1 palmitoylation through FoxO3a
Authors: Spinelli Matteo , Fusco Salvatore , Mainardi Marco , Scala Federico , Natale Francesca , Lapenta Rosita , Mattera Andrea , Rinaudo Marco , Li Puma Domenica Donatella , Ripoli Cristian , Grassi Alfonso , D’Ascenzo Marcello , Grassi Claudio 
Published: December 2017

AbstractHigh-fat diet (HFD) and metabolic diseases cause detrimental effects on hippocampal synaptic plasticity, learning, and memory through molecular mechanisms still poorly understood. Here, we demonstrate that HFD increases palmitic acid deposition in the hippocampus and induces hippocampal insulin resistance leading to FoxO3a-mediated overexpression of the palmitoyltransferase zDHHC3. The excess of palmitic acid along with higher zDHHC3 levels causes hyper-palmitoylation of AMPA glutamate receptor subunit GluA1, hindering its activity-dependent trafficking to the plasma membrane. Accordingly, AMPAR current amplitudes and, more importantly, their potentiation underlying synaptic plasticity were inhibited, as well as hippocampal-dependent memory. Hippocampus-specific silencing of Zdhhc3 and, interestingly enough, intranasal injection of the palmitoyltransferase inhibitor, 2-bromopalmitate, counteract GluA1 hyper-palmitoylation and restore synaptic plasticity and memory in HFD mice. Our data reveal a key role of FoxO3a/Zdhhc3/GluA1 axis in the HFD-dependent impairment of cognitive function and identify a novel mechanism underlying the cross talk between metabolic and cognitive disorders.
Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae
Authors: Pennini Meghan E. , De Marco Anna , Pelletier Mark , Bonnell Jessica , Cvitkovic Romana , Beltramello Martina , Cameroni Elisabetta , Bianchi Siro , Zatta Fabrizia , Zhao Wei , Xiao Xiaodong , Camara Maria M. , DiGiandomenico Antonio , Semenova Elena , Lanzavecchia Antonio , Warrener Paul , Suzich JoAnn , Wang Qun , Corti Davide , Stover C. Kendall 
Published: December 2017

AbstractEmerging multidrug-resistant bacteria are a challenge for modern medicine, but how these pathogens are so successful is not fully understood. Robust antibacterial vaccines have prevented and reduced resistance suggesting a pivotal role for immunity in deterring antibiotic resistance. Here, we show the increased prevalence ofKlebsiella pneumoniaelipopolysaccharide O2 serotype strains in all major drug resistance groups correlating with a paucity of anti-O2 antibodies in human B cell repertoires. We identify human monoclonal antibodies to O-antigens that are highly protective in mouse models of infection, even against heavily encapsulated strains. These antibodies, including a rare anti-O2 specific antibody, synergistically protect against drug-resistant strains in adjunctive therapy with meropenem, a standard-of-care antibiotic, confirming the importance of immune assistance in antibiotic therapy. These findings support an antibody-based immunotherapeutic strategy even for highly resistantK. pneumoniaeinfections, and underscore the effect humoral immunity has on evolving drug resistance.
HEB is required for the specification of fetal IL-17-producing γδ T cells
Authors: In Tracy S. H. , Trotman-Grant Ashton , Fahl Shawn , Chen Edward L. Y. , Zarin Payam , Moore Amanda J. , Wiest David L. , Zúñiga-Pflücker Juan Carlos , Anderson Michele K. 
Published: December 2017

AbstractIL-17-producing γδ T (γδT17) cells are critical components of the innate immune system. However, the gene networks that control their development are unclear. Here we show that HEB (HeLa E-box binding protein, encoded byTcf12) is required for the generation of a newly defined subset of fetal-derived CD73−γδT17 cells. HEB is required in immature CD24+CD73−γδ T cells for the expression ofSox4,Sox13, andRorc, and these genes are repressed by acute expression of the HEB antagonist Id3. HEB-deficiency also affects mature CD73+γδ T cells, which are defective in RORγt expression and IL-17 production. Additionally, the fetal TCRγ chain repertoire is altered, and peripheral Vγ4 γδ T cells are mostly restricted to the IFNγ-producing phenotype in HEB-deficient mice. Therefore, our work identifies HEB-dependent pathways for the development of CD73+and CD73−γδT17 cells, and provides mechanistic evidence for control of the γδT17 gene network by HEB.
Different carotenoid conformations have distinct functions in light-harvesting regulation in plants
Authors: Liguori Nicoletta , Xu Pengqi , van Stokkum Ivo H.M. , van Oort Bart , Lu Yinghong , Karcher Daniel , Bock Ralph , Croce Roberta 
Published: December 2017

AbstractTo avoid photodamage plants regulate the amount of excitation energy in the membrane at the level of the light-harvesting complexes (LHCs). It has been proposed that the energy absorbed in excess is dissipated via protein conformational changes of individual LHCs. However, the exact quenching mechanism remains unclear. Here we study the mechanism of quenching in LHCs that bind a single carotenoid species and are constitutively in a dissipative conformation. Via femtosecond spectroscopy we resolve a number of carotenoid dark states, demonstrating that the carotenoid is bound to the complex in different conformations. Some of those states act as excitation energy donors for the chlorophylls, whereas others act as quenchers. Via in silico analysis we show that structural changes of carotenoids are expected in the LHC protein domains exposed to the chloroplast lumen, where acidification triggers photoprotection in vivo. We propose that structural changes of LHCs control the conformation of the carotenoids, thus permitting access to different dark states responsible for either light harvesting or photoprotection.
Redox-switchable breathing behavior in tetrathiafulvalene-based metal–organic frameworks
Authors: Su Jian , Yuan Shuai , Wang Hai-Ying , Huang Lan , Ge Jing-Yuan , Joseph Elizabeth , Qin Junsheng , Cagin Tahir , Zuo Jing-Lin , Zhou Hong-Cai 
Published: December 2017

AbstractMetal–organic frameworks (MOFs) that respond to external stimuli such as guest molecules, temperature, or redox conditions are highly desirable. Herein, we coupled redox-switchable properties with breathing behavior induced by guest molecules in a single framework. Guided by topology, two flexible isomeric MOFs, compounds 1 and 2, with a formula of In(Me2NH2)(TTFTB), were constructed via a combination of [In(COO)4]− metal nodes and tetratopic tetrathiafulvalene-based linkers (TTFTB). The two compounds show different breathing behaviors upon the introduction of N2. Single-crystal X-ray diffraction, accompanied by molecular simulations, reveals that the breathing mechanism of 1 involves the bending of metal–ligand bonds and the sliding of interpenetrated frameworks, while 2 undergoes simple distortion of linkers. Reversible oxidation and reduction of TTF moieties changes the linker flexibility, which in turn switches the breathing behavior of 2. The redox-switchable breathing behavior can potentially be applied to the design of stimuli-responsive MOFs.
Viscosity jump in the lower mantle inferred from melting curves of ferropericlase
Authors: Deng Jie , Lee Kanani K. M. 
Published: December 2017

AbstractConvection provides the mechanism behind plate tectonics, which allows oceanic lithosphere to be subducted into the mantle as “slabs” and new rock to be generated by volcanism. Stagnation of subducting slabs and deflection of rising plumes in Earth’s shallow lower mantle have been suggested to result from a viscosity increase at those depths. However, the mechanism for this increase remains elusive. Here, we examine the melting behavior in the MgO–FeO binary system at high pressures using the laser-heated diamond-anvil cell and show that the liquidus and solidus of (Mg
x
Fe1−x
)O ferropericlase (x = ~0.52–0.98), exhibit a local maximum at ~40 GPa, likely caused by the spin transition of iron. We calculate the relative viscosity profiles of ferropericlase using homologous temperature scaling and find that viscosity increases 10–100 times from ~750 km to ~1000–1250 km, with a smaller decrease at deeper depths, pointing to a single mechanism for slab stagnation and plume deflection.
Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution
Authors: Baker Ann-Marie , Huang Weini , Wang Xiao-Ming Mindy , Jansen Marnix , Ma Xiao-Jun , Kim Jeffrey , Anderson Courtney M. , Wu Xingyong , Pan Liuliu , Su Nan , Luo Yuling , Domingo Enric , Heide Timon , Sottoriva Andrea , Lewis Annabelle , Beggs Andrew D. , Wright Nicholas A. , Rodriguez-Justo Manuel , Park Emily , Tomlinson Ian , Graham Trevor A. 
Published: December 2017

AbstractIntra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not detect rare subclones. Here, we address these shortfalls by developing and validating BaseScope—a novel mutation-specific RNA in situ hybridization assay. We target common point mutations in the BRAF, KRAS and PIK3CA oncogenes in archival colorectal cancer samples to precisely map the spatial and morphological context of mutant subclones. Computational modeling suggests that subclones must arise sufficiently early, or carry a considerable fitness advantage, to form large or spatially disparate subclones. Examples of putative treatment-resistant cells isolated in small topographical areas are observed. The BaseScope assay represents a significant technical advance for in situ mutation detection that provides new insight into tumor evolution, and could have ramifications for selecting patients for treatment.
Weekly self-measurement of FEV1 and PEF and its impact on ACQ (asthma control questionnaire)-scores: 12-week observational study with 76 patients
Authors: Werner Christoph Ulrich , Linde Klaus , Schäffner Julia , Storr Constanze , Schneider Antonius 
Published: December 2017

AbstractThe “Asthma Control Questionnaire” (ACQ) is a very common questionnaire for assessing asthma control. This study compares different ACQ versions in a self-monitoring program over a 12-week period combining them with patients' self-measurements of peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1). The objective was to test the feasibility of FEV1-self-measurements and to compare ACQ versions regarding possible additional information given by lung function. In this prospective multicenter observational study 100 adult asthma patients, recruited at six family practices and two pulmologists' private practices in Germany, completed the ACQ weekly, performing self-measurements of PEF and FEV1. Seventy-six patients were included into final analysis with only 3% missing values. Scores for all ACQ versions improved significantly (all P-values < 0.05) with reductions of 32% for ACQ5, 31% for ACQ6, 22% for ACQ7-FEV1, and 21% for ACQ7-PEF with high Pearson’s correlation coefficients of all scores (r between 0.96 and 0.99). ACQ7-FEV1 scores were significantly higher than others. Separated courses of lung function parameters showed nearly no change, but ACQ5 and ACQ6 as scores for symptoms and reliever medication improved constantly. ACQ5 and ACQ6 revealed higher percentages of patients classified as “controlled” than ACQ7-scores. In conclusion, with only a few missing data points, our results suggest feasibility of FEV1-self-measurements. Courses of symptom-related and lung function-related ACQ items differ clearly. Our results support the GINA recommendations to consider symptoms and lung function separately. FEV1-self-measurements for research purposes may be included with the ACQ, but in clinical practice seem to measure a different domain to symptomatic asthma control.
A nontrivial crossover in topological Hall effect regimes
Authors: Denisov K. S. , Rozhansky I. V. , Averkiev N. S. , Lähderanta E. 
Published: December 2017

AbstractWe propose a new theory of the topological Hall effect (THE) in systems with non-collinear magnetization textures such as magnetic skyrmions. We solve the problem of electron scattering on a magnetic skyrmion exactly, for an arbitrary strength of exchange interaction and the skyrmion size. We report the existence of different regimes of THE and resolve the apparent contradiction between the adiabatic Berry phase theoretical approach and the perturbation theory for THE. We traced how the topological charge Hall effect transforms into the spin Hall effect upon varying the exchange interaction strength or the skyrmion size. This transformation has a nontrivial character: it is accompanied by an oscillating behavior of both charge and spin Hall currents. This hallmark of THE allows one to identify the chirality driven contribution to Hall response in the experiments.
Insulin in motion: The A6-A11 disulfide bond allosterically modulates structural transitions required for insulin activity
Authors: van Lierop Bianca , Ong Shee Chee , Belgi Alessia , Delaine Carlie , Andrikopoulos Sofianos , Haworth Naomi L. , Menting John G. , Lawrence Michael C. , Robinson Andrea J. , Forbes Briony E. 
Published: December 2017

AbstractThe structural transitions required for insulin to activate its receptor and initiate regulation of glucose homeostasis are only partly understood. Here, using ring-closing metathesis, we substitute the A6-A11 disulfide bond of insulin with a rigid, non-reducible dicarba linkage, yielding two distinct stereo-isomers (cisandtrans). Remarkably, only thecisisomer displays full insulin potency, rapidly lowering blood glucose in mice (even under insulin-resistant conditions). It also posseses reduced mitogenic activityin vitro. Further biophysical, crystallographic and molecular-dynamics analyses reveal that the A6-A11 bond configuration directly affects the conformational flexibility of insulin A-chainN-terminal helix, dictating insulin’s ability to engage its receptor. We reveal that in native insulin, contraction of the Cα-Cαdistance of the flexible A6-A11 cystine allows the A-chainN-terminal helix to unwind to a conformation that allows receptor engagement. This motion is also permitted in thecisisomer, with its shorter Cα-Cαdistance, but prevented in the extendedtransanalogue. These findings thus illuminate for the first time the allosteric role of the A6-A11 bond in mediating the transition of the hormone to an active conformation, significantly advancing our understanding of insulin action and opening up new avenues for the design of improved therapeutic analogues.
Elevation of autophagy markers in Sjögren syndrome dry eye
Authors: Byun Yong-Soo , Lee Hyun Jung , Shin Soojung , Chung So-Hyang 
Published: December 2017

AbstractAutophagy is known to be implicated in the pathogenesis of Sjögren syndrome (SS), but evidences are limited. We aimed to examine the levels of autophagy markers in tear film and conjunctival epithelial cells from SS dry eye patients, and analyze their correlations with clinical features. Patients with SS dry eye exhibited lower Schirmer values, lower tear breakup time, and higher ocular staining scores. In tears, ATG5 and LC3B-II/I levels were significantly higher in SS dry eye. ATG5 and LC3B-II mRNA in the conjunctiva were also elevated in SS dry eye compared with non-SS dry eye. The immunostaining of conjunctival epithelium showed a punctate pattern of ATG5 and LC3B-II in SS dry eye. These staining patterns were also observed in the lacrimal gland of SS animal models. ATG5 levels in tears and the conjunctival epithelium strongly correlated with ocular staining scores, and one month of topical corticosteroid treatment reduced both ATG5 and LC3B-II/I levels in tear film and the conjunctival epithelium of patients with SS dry eye. Our results suggest that autophagy is enhanced or dysregulated in SS and autophagy markers may be serve as both diagnostic and therapeutic biomarkers in SS dry eye.
Improving Gene Regulatory Network Inference by Incorporating Rates of Transcriptional Changes
Authors: Desai Jigar S. , Sartor Ryan C. , Lawas Lovely Mae , Jagadish S. V. Krishna , Doherty Colleen J. 
Published: December 2017

AbstractOrganisms respond to changes in their environment through transcriptional regulatory networks (TRNs). The regulatory hierarchy of these networks can be inferred from expression data. Computational approaches to identify TRNs can be applied in any species where quality RNA can be acquired, However, ChIP-Seq and similar validation methods are challenging to employ in non-model species. Improving the accuracy of computational inference methods can significantly reduce the cost and time of subsequent validation experiments. We have developed ExRANGES, an approach that improves the ability to computationally infer TRN from time series expression data. ExRANGES utilizes both the rate of change in expression and the absolute expression level to identify TRN connections. We evaluated ExRANGES in five data sets from different model systems. ExRANGES improved the identification of experimentally validated transcription factor targets for all species tested, even in unevenly spaced and sparse data sets. This improved ability to predict known regulator-target relationships enhances the utility of network inference approaches in non-model species where experimental validation is challenging. We integrated ExRANGES with two different network construction approaches and it has been implemented as an R package available here: http://github.com/DohertyLab/ExRANGES. To install the package type: devtools::install_github(“DohertyLab/ExRANGES”).
Fisheries-independent surveys identify critical habitats for young scalloped hammerhead sharks (Sphyrna lewini) in the Rewa Delta, Fiji
Authors: Marie Amandine D. , Miller Cara , Cawich Celso , Piovano Susanna , Rico Ciro 
Published: December 2017

AbstractSharp declines in numerous shark populations around the world have generated considerable interest in better understanding and characterising their biology, ecology and critical habitats. The scalloped hammerhead shark (SHS,Sphyrna lewini) is subject to a multitude of natural and anthropogenic threats that are often exacerbated within the coastal embayments and estuaries used during SHS early life stages. In this study, we describe the temporal and spatial distribution, age class composition, and reproductive biology of SHS in the Rewa Delta (RD), Fiji. A total of 1054 SHS (including 796 tagged individuals; 101 of which were recaptured) were captured from September 2014 to March 2016 in the RD. A majority of the captures in this area were neonates and young-of-the-year (YOY) (99.8%). Significant seasonality in patterns of occurrence of both neonates and YOY individuals suggests a defined parturition period during the austral summer. Between the seven sampling sites in the RD we also found significant differences in SHS neonate catch per unit of effort, and average total length of individuals. According to the data, the RD is likely to represent an important nursery area for SHS up to one year of age.
Hypoxia-inducible factor 1α is Essential for Macrophage-mediated Erythroblast Proliferation in Acute Friend Retrovirus Infection
Authors: Schreiber Timm , Quinting Theresa , Dittmer Ulf , Fandrey Joachim , Sutter Kathrin 
Published: December 2017

AbstractMacrophages are the frontline of defence against foreign microorganisms, including bacteria, parasites, and viruses. During acute viral infection, macrophages must invade the inflamed tissue toward low oxygen concentrations, where genetic cellular responses depend on hypoxia-inducible factors (HIF). In the study reported here we investigated the role of HIF-1α in macrophage function during acute retroviral infection. Wild-type and myeloid cell–specificHIF-1αknockout mice were infected with Friend retrovirus (FV), and immune response was analysed 7 and 10 days after infection. FV infection led to increased spleen weight in wild-type and knockout mice, whereas a profound proliferation of erythroblasts was seen only in wild-type mice. The number of spleen-infiltrating macrophages was also significantly lower in knockout animals. Macrophage invasion after FV infection in wild-type mice led to elevated amounts of activated macrophage-stimulating 1 protein that resulted in massive proliferation of erythrocyte precursor cells. This proliferation was absent from knockout mice because of impaired invasion capabilities of HIF-1α–deficient macrophages. Our study elucidated a novel mechanism of FV-induced erythrocyte precursor cell proliferation.
Advanced Sulfur-Silicon Full Cell Architecture for Lithium Ion Batteries
Authors: Ye Rachel , Bell Jeffrey , Patino Daisy , Ahmed Kazi , Ozkan Mihri , Ozkan Cengiz S. 
Published: December 2017

AbstractLithium-ion batteries are crucial to the future of energy storage. However, the energy density of current lithium-ion batteries is insufficient for future applications. Sulfur cathodes and silicon anodes have garnered a lot of attention in the field due their high capacity potential. Although recent developments in sulfur and silicon electrodes show exciting results in half cell formats, neither electrode can act as a lithium source when put together into a full cell format. Current methods toward incorporating lithium in sulfur-silicon full cells involves prelithiating silicon or using lithium sulfide. These methods however, complicate material processing and creates safety hazards. Herein, we present a novel full cell battery architecture that bypasses the issues associated with current methods. This battery architecture gradually integrates controlled amounts of pure lithium into the system by allowing lithium the access to external circuit. A high specific energy density of 350 Wh/kg after 250 cycles at C/10 was achieved using this method. This work should pave the way for future researches into sulfur-silicon full cells.
Interaction of RNA-binding protein HuR and miR-466i regulates GM-CSF expression
Authors: Chen Jing , Adamiak William , Huang Ganlei , Atasoy Ulus , Rostami Abdolmohamad , Yu Shiguang 
Published: December 2017

AbstractGranulocyte-macrophage colony-stimulating factor (GM-CSF) produced by T helper 17 (Th17) cells plays an essential role in autoimmune diseases. Transcriptional regulation of Th17 cell differentiation has been extensively studied, but post-transcriptional regulation of Th17 cell differentiation has remained less well characterized. The RNA-binding protein HuR functions to promote the stability of target mRNAs via binding the AU-rich elements of the 3′ untranslated region (3′UTR) of numerous pro-inflammatory cytokines including IL-4, IL-13, IL-17 and TNF-α. However, whether HuR regulates GM-CSF expression in Th17 cells has not been fully investigated. Here we showed that HuR conditional knockout (KO) Th17 cells have decreased GM-CSF mRNA in comparison with wild-type (WT) Th17 cells, and that HuR binds directly to GM-CSF mRNA 3′UTR. Interestingly, HuR deficiency increased the levels of certain microRNA expression in Th17 cells; for example, miR-466i functioned to mediate GM-CSF and IL-17 mRNA decay, which was confirmed by in vitro luciferase assay. Furthermore, we found that HuR promoted Mxi1 expression to inhibit certain miRNA expression. Taken together, these findings indicate that interaction of HuR and miR-466i orchestrates GM-CSF expression in Th17 cells.