bluuebunny/crossref_metadata_2025_split huggingface dataset:
GnRH impairs diabetic wound healing through enhanced NETosis
Authors: Lee Yun Sang , Kang Sung Un , Lee Myung-Hoon , Kim Haeng-Jun , Han Chang-Hak , Won Ho-Ryun , Park Young Uk , Kim Chul-Ho 
Published: June 2019

Abstract
It has been reported that neutrophil extracellular traps (NETs) impair wound healing in diabetes and that inhibiting NET generation (NETosis) improves wound healing in diabetic mice. Gonadotropin-releasing hormone (GnRH) agonists are associated with a greater risk of diabetes. However, the role of GnRH in diabetic wound healing is unclear. We determined whether GnRH-promoted NETosis and induced more severe and delayed diabetic wound healing. A mouse model of diabetes was established using five injections with streptozotocin. Mice with blood glucose levels >250 mg/dL were then used in the experiments. GnRH agonist treatment induced delayed wound healing and increased NETosis at the skin wounds of diabetic mice. In contrast, GnRH antagonist treatment inhibited GnRH agonist-induced delayed wound healing. The expression of NETosis markers PAD4 and citrullinated histone H3 were increased in the GnRH-treated diabetic skin wounds in diabetic mice and patients. In vitro experiments also showed that neutrophils expressed a GnRH receptor and that GnRH agonist treatment increased NETosis markers and promoted phorbol myristate acetate (PMA)-induced NETosis in mouse and human neutrophils. Furthermore, GnRH antagonist treatment suppressed the expression of NETosis markers and PMA-induced NETosis, which were increased by GnRH treatment. These results indicated that GnRH-promoted NETosis and that increased NETosis induced delayed wound healing in diabetic skin wounds. Thus, inhibition of GnRH might be a novel treatment of diabetic foot ulcers.
Mass cytometry reveals systemic and local immune signatures that distinguish inflammatory bowel diseases
Authors: Rubin Samuel J. S. , Bai Lawrence , Haileselassie Yeneneh , Garay Gotzone , Yun Chohee , Becker Laren , Streett Sarah E. , Sinha Sidhartha R. , Habtezion Aida 
Published: June 2019

AbstractInflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis. Each disease is characterized by a diverse set of potential manifestations, which determine patients’ disease phenotype. Current understanding of phenotype determinants is limited, despite increasing prevalence and healthcare costs. Diagnosis and monitoring of disease requires invasive procedures, such as endoscopy and tissue biopsy. Here we report signatures of heterogeneity between disease diagnoses and phenotypes. Using mass cytometry, we analyze leukocyte subsets, characterize their function(s), and examine gut-homing molecule expression in blood and intestinal tissue from healthy and/or IBD subjects. Some signatures persist in IBD despite remission, and many signatures are highly represented by leukocytes that express gut trafficking molecules. Moreover, distinct systemic and local immune signatures suggest patterns of cell localization in disease. Our findings highlight the importance of gut tropic leukocytes in circulation and reveal that blood-based immune signatures differentiate clinically relevant subsets of IBD.
Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia
Authors: Minuesa Gerard , Albanese Steven K. , Xie Wei , Kazansky Yaniv , Worroll Daniel , Chow Arthur , Schurer Alexandra , Park Sun-Mi , Rotsides Christina Z. , Taggart James , Rizzi Andrea , Naden Levi N. , Chou Timothy , Gourkanti Saroj , Cappel Daniel , Passarelli Maria C. , Fairchild Lauren , Adura Carolina , Glickman J. Fraser , Schulman Jessica , Famulare Christopher , Patel Minal , Eibl Joseph K. , Ross Gregory M. , Bhattacharya Shibani , Tan Derek S. , Leslie Christina S. , Beuming Thijs , Patel Dinshaw J. , Goldgur Yehuda , Chodera John D. , Kharas Michael G. 
Published: June 2019

AbstractThe MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08–2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI’s oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.
Sub-stoichiometric 2D covalent organic frameworks from tri- and tetratopic linkers
Authors: Banerjee Tanmay , Haase Frederik , Trenker Stefan , Biswal Bishnu P. , Savasci Gökcen , Duppel Viola , Moudrakovski Igor , Ochsenfeld Christian , Lotsch Bettina V. 
Published: June 2019

AbstractCovalent organic frameworks (COFs) are typically designed by breaking down the desired network into feasible building blocks - either simple and highly symmetric, or more convoluted and thus less symmetric. The linkers are chosen complementary to each other such that an extended, fully condensed network structure can form. We show not only an exception, but a design principle that allows breaking free of such design rules. We show that tri- and tetratopic linkers can be combined to form imine-linked [4 + 3] sub-stoichiometric 2D COFs featuring an unexpected bex net topology, and with periodic uncondensed amine functionalities which enhance CO2 adsorption, can be derivatized in a subsequent reaction, and can also act as organocatalysts. We further extend this class of nets by including a ditopic linker to form [4 + 3 + 2] COFs. The results open up possibilities towards a new class of sub-valent COFs with unique structural, topological and compositional complexities for diverse applications.
Adenoviral vaccine targeting multiple neoantigens as strategy to eradicate large tumors combined with checkpoint blockade
Authors: D’Alise Anna Morena , Leoni Guido , Cotugno Gabriella , Troise Fulvia , Langone Francesca , Fichera Imma , De Lucia Maria , Avalle Lidia , Vitale Rosa , Leuzzi Adriano , Bignone Veronica , Di Matteo Elena , Tucci Fabio Giovanni , Poli Valeria , Lahm Armin , Catanese Maria Teresa , Folgori Antonella , Colloca Stefano , Nicosia Alfredo , Scarselli Elisa 
Published: June 2019

AbstractNeoantigens (nAgs) are promising tumor antigens for cancer vaccination with the potential of inducing robust and selective T cell responses. Genetic vaccines based on Adenoviruses derived from non-human Great Apes (GAd) elicit strong and effective T cell-mediated immunity in humans. Here, we investigate for the first time the potency and efficacy of a novel GAd encoding multiple neoantigens. Prophylactic or early therapeutic vaccination with GAd efficiently control tumor growth in mice. In contrast, combination of the vaccine with checkpoint inhibitors is required to eradicate large tumors. Gene expression profile of tumors in regression shows abundance of activated tumor infiltrating T cells with a more diversified TCR repertoire in animals treated with GAd and anti-PD1 compared to anti-PD1. Data suggest that effectiveness of vaccination in the presence of high tumor burden correlates with the breadth of nAgs-specific T cells and requires concomitant reversal of tumor suppression by checkpoint blockade.
PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport
Authors: Siddiqui Nida , Zwetsloot Alexander James , Bachmann Alice , Roth Daniel , Hussain Hamdi , Brandt Jonathan , Kaverina Irina , Straube Anne 
Published: June 2019

AbstractThe kinesin-3 KIF1C is a fast organelle transporter implicated in the transport of dense core vesicles in neurons and the delivery of integrins to cell adhesions. Here we report the mechanisms of autoinhibition and release that control the activity of KIF1C. We show that the microtubule binding surface of KIF1C motor domain interacts with its stalk and that these autoinhibitory interactions are released upon binding of protein tyrosine phosphatase PTPN21. The FERM domain of PTPN21 stimulates dense core vesicle transport in primary hippocampal neurons and rescues integrin trafficking in KIF1C-depleted cells. In vitro, human full-length KIF1C is a processive, plus-end directed motor. Its landing rate onto microtubules increases in the presence of either PTPN21 FERM domain or the cargo adapter Hook3 that binds the same region of KIF1C tail. This autoinhibition release mechanism allows cargo-activated transport and might enable motors to participate in bidirectional cargo transport without undertaking a tug-of-war.
Intertwined topological phases induced by emergent symmetry protection
Authors: González-Cuadra Daniel , Bermudez Alejandro , Grzybowski Przemysław R. , Lewenstein Maciej , Dauphin Alexandre 
Published: June 2019

AbstractThe dual role played by symmetry in many-body physics manifests itself through two fundamental mechanisms: spontaneous symmetry breaking and topological symmetry protection. These two concepts, ubiquitous in both condensed matter and high energy physics, have been applied successfully in the last decades to unravel a plethora of complex phenomena. Their interplay, however, remains largely unexplored. Here we report how, in the presence of strong correlations, symmetry protection emerges from a set of configurations enforced by another broken symmetry. This mechanism spawns different intertwined topological phases, where topological properties coexist with long-range order. Such a singular interplay gives rise to interesting static and dynamical effects, including interaction-induced topological phase transitions constrained by symmetry breaking, as well as a self-adjusted fractional pumping. This work paves the way for further exploration of exotic topological features in strongly-correlated quantum systems.
Progressive expression of PPARGC1α is associated with hair miniaturization in androgenetic alopecia
Authors: Ho Bryan Siu-Yin , Vaz Candida , Ramasamy Srinivas , Chew Elaine Guo Yan , Mohamed Jameelah Sheik , Jaffar Huma , Hillmer Axel , Tanavde Vivek , Bigliardi-Qi Mei , Bigliardi Paul Lorenz 
Published: June 2019

AbstractCurrent opinion views androgens as the pathogenic driver in the miniaturization of hair follicles of androgenetic alopecia by interfering with the dermal papilla. This cannot be the sole cause and therefore it is important for therapeutic and diagnostic purposes to identify additional pathways. Comparative full transcriptome profile analysis of the hair bulb region of normal and miniaturized hair follicles from vertex and occipital region in males with and without androgenetic alopecia revealed that next to the androgen receptor as well the retinoid receptor and particularly the PPAR pathway is involved in progressive hair miniaturization. We demonstrate the concurrent up-regulation of PPARGC1a in the epithelial compartment and androgen receptor in the dermal papilla of miniaturized hair. Dynamic Ppargc1a expression in the mouse hair cycle suggests a possible role in regulating hair growth and differentiation. This is supported by reduced proliferation of human dermal papilla and predominantly epithelial keratinocytes after incubation with AICAR, the agonist for AMPK signaling which activates PPARGC1a and serves as co-activator of PPARγ. In addition, miRNA profiling shows enrichment of miRNA-targeted genes in retinoid receptors and PPARGC1α/PPARγ signaling, and antigen presentation pathways.
Structure-Activity Relationships of Baicalein and its Analogs as Novel TSLP Inhibitors
Authors: Park Bernie Byunghoon , Choi Jae Wan , Park Dawon , Choi Doyoung , Paek Jiwon , Kim Hyun Jung , Son Se-Young , Mushtaq Ameeq Ul , Shin Hyeji , Kim Sang Hoon , Zhou Yuanyuan , Lim Taehyeong , Park Ji Young , Baek Ji-Young , Kim Kyul , Kwon Hongmok , Son Sang-Hyun , Chung Ka Young , Jeong Hyun-Ja , Kim Hyung-Min , Jung Yong Woo , Lee Kiho , Lee Ki Yong , Byun Youngjoo , Jeon Young Ho 
Published: June 2019

AbstractThymic stromal lymphopoietin (TSLP) plays an important role in the differentiation and proliferation of Th2 cells, resulting in eosinophilic inflammation and numerous allergic diseases. Baicalein (1), a major component of Scutellaria baicalensis, was found to be the first small molecule to block TSLP signaling pathways. It inhibited effectively eosinophil infiltration in house dust mite-induced and ovalbumin-challenged mouse models. Structure-activity relationship studies identified compound 11a, a biphenyl flavanone analog, as a novel human TSLP inhibitor for the discovery and development of new anti-allergic drugs.
Crustal CO2 contribution to subduction zone degassing recorded through calc-silicate xenoliths in arc lavas
Authors: Whitley Sean , Gertisser Ralf , Halama Ralf , Preece Katie , Troll Valentin R. , Deegan Frances M. 
Published: June 2019

AbstractInteraction between magma and crustal carbonate at active arc volcanoes has recently been proposed as a source of atmospheric CO2, in addition to CO2 released from the mantle and subducted oceanic crust. However, quantitative constraints on efficiency and timing of these processes are poorly established. Here, we present the first in situ carbon and oxygen isotope data of texturally distinct calcite in calc-silicate xenoliths from arc volcanics in a case study from Merapi volcano (Indonesia). Textures and C-O isotopic data provide unique evidence for decarbonation, magma-fluid interaction, and the generation of carbonate melts. We report extremely light δ13CPDB values down to −29.3‰ which are among the lowest reported in magmatic systems so far. Combined with the general paucity of relict calcite, these extremely low values demonstrate highly efficient remobilisation of crustal CO2 over geologically short timescales of thousands of years or less. This rapid release of large volumes of crustal CO2 may impact global carbon cycling.
Differences in Colistin Administration and Bacterial and Treatment Outcomes in Critically Ill Patients
Authors: Jung Sunmi , Chung Eun Kyoung , Jun Min Sun , Son Eun Sun , Rhie Sandy Jeong 
Published: June 2019

AbstractThe desired target steady-state average colistin concentration (Css,avg) to balance between therapeutic effectiveness and nephrotoxicity is largely unclear. The objective of this study was to evaluate the effect of the desired target colistin Css,avgon the effectiveness and safety of IV colistin therapy in critically ill patients. Overall, 153 critically ill patients (71% males) receiving IV colistin were retrospectively analyzed. The desired target colistin Css,avgwas estimated based on the daily colistin dose and creatinine clearance of each patient. No significant predictor for clinical cure was identified. However, microbiological outcome was significantly associated with pneumonia compared to bacteremia (odds ratio [OR] 0.092, 95% confidence interval [CI] [0.033–0.251],P < 0.001) and the use of IV colistin loading dose (OR 2.783, 95% CI [1.126–6.880],P = 0.027). Colistin-associated nephrotoxicity was significantly less likely to occur in patients who received inhaled colistin close to the time of IV colistin therapy (OR 0.331, CI [0.119–0.925],P = 0.035). The desired target Css,avgof colistin was not associated with treatment outcomes or the risk of nephrotoxicity. Loading dose and inhaled colistin use near the time of IV colistin therapy may be considered to maximize therapeutic effectiveness and minimize the risk of colistin-associated nephrotoxicity, respectively.
Framework to Estimate Total Particulate Mass and Nicotine Delivered to E-cig Users from Natural Environment Monitoring Data
Authors: Hensel Edward C. , Eddingsaas Nathan C. , DiFrancesco A. Gary , Jayasekera Shehan , O’Dea Sean , Robinson Risa J. 
Published: June 2019

AbstractA framework describing the joint effect of user topography behavior and product characteristics of one exemplar device on the total particulate mass (TPM) and aerosol constituent yield delivered to a user is presented and validated against seven user-specific ‘playback’ emissions observations. A pen-style e-cig was used to collect emissions across puff flow rates and durations spanning the range observed in the natural environment. Emissions were analyzed with GC-MS and used to construct empirical correlations for TPM concentration and nicotine mass ratio. TPM concentration was demonstrated to depend upon both puff flow rate and duration, while nicotine mass ratio was not observed to be flow-dependent under the conditions presented. The empirical model for TPM and nicotine yield demonstrated agreement with experimental observations, with Pearson correlation coefficients of r = 0.79 and r = 0.86 respectively. The mass of TPM and nicotine delivered to the mouth of an e-cig user are dependent upon the puffing behavior of the user. Product-specific empirical models of emissions may be used in conjunction with participant-specific topography observations to accurately quantify the mass of TPM and nicotine delivered to a user.
Genome of the tropical plant Marchantia inflexa: implications for sex chromosome evolution and dehydration tolerance
Authors: Marks Rose A. , Smith Jeramiah J. , Cronk Quentin , Grassa Christopher J. , McLetchie D. Nicholas 
Published: June 2019

AbstractWe present a draft genome assembly for the tropical liverwort, Marchantia inflexa, which adds to a growing body of genomic resources for bryophytes and provides an important perspective on the evolution and diversification of land plants. We specifically address questions related to sex chromosome evolution, sexual dimorphisms, and the genomic underpinnings of dehydration tolerance. This assembly leveraged the recently published genome of related liverwort, M. polymorpha, to improve scaffolding and annotation, aid in the identification of sex-linked sequences, and quantify patterns of sequence differentiation within Marchantia. We find that genes on sex chromosomes are under greater diversifying selection than autosomal and organellar genes. Interestingly, this is driven primarily by divergence of male-specific genes, while divergence of other sex-linked genes is similar to autosomal genes. Through analysis of sex-specific read coverage, we identify and validate genetic sex markers for M. inflexa, which will enable diagnosis of sex for non-reproductive individuals. To investigate dehydration tolerance, we capitalized on a difference between genetic lines, which allowed us to identify multiple dehydration associated genes two of which were sex-linked, suggesting that dehydration tolerance may be impacted by sex-specific genes.
Association between the pig genome and its gut microbiota composition
Authors: Crespo-Piazuelo Daniel , Migura-Garcia Lourdes , Estellé Jordi , Criado-Mesas Lourdes , Revilla Manuel , Castelló Anna , Muñoz María , García-Casco Juan M. , Fernández Ana I. , Ballester Maria , Folch Josep M. 
Published: June 2019

AbstractThe gut microbiota has been evolving with its host along the time creating a symbiotic relationship. In this study, we assess the role of the host genome in the modulation of the microbiota composition in pigs. Gut microbiota compositions were estimated through sequencing the V3-V4 region of the 16S rRNA gene from rectal contents of 285 pigs. A total of 1,261 operational taxonomic units were obtained and grouped in 18 phyla and 101 genera.Firmicutes(45.36%) andBacteroidetes(37.47%) were the two major phyla obtained, whereas at genus levelPrevotella(7.03%) andTreponema(6.29%) were the most abundant. Pigs were also genotyped with a high-throughput method for 45,508 single nucleotide polymorphisms that covered the entire pig genome. Subsequently, genome-wide association studies were made among the genotypes of these pigs and their gut microbiota composition. A total of 52 single-nucleotide polymorphisms distributed in 17 regions along the pig genome were associated with the relative abundance of six genera;Akkermansia,CF231,Phascolarctobacterium,Prevotella,SMB53, andStreptococcus. Our results suggest 39 candidate genes that may be modulating the microbiota composition and manifest the association between host genome and gut microbiota in pigs.
Computational identification of protein-protein interactions in model plant proteomes
Authors: Ding Ziyun , Kihara Daisuke 
Published: June 2019

AbstractProtein-protein interactions (PPIs) play essential roles in many biological processes. A PPI network provides crucial information on how biological pathways are structured and coordinated from individual protein functions. In the past two decades, large-scale PPI networks of a handful of organisms were determined by experimental techniques. However, these experimental methods are time-consuming, expensive, and are not easy to perform on new target organisms. Large-scale PPI data is particularly sparse in plant organisms. Here, we developed a computational approach for detecting PPIs trained and tested on known PPIs of Arabidopsis thaliana and applied to three plants, Arabidopsis thaliana, Glycine max (soybean), and Zea mays (maize) to discover new PPIs on a genome-scale. Our method considers a variety of features including protein sequences, gene co-expression, functional association, and phylogenetic profiles. This is the first work where a PPI prediction method was developed for is the first PPI prediction method applied on benchmark datasets of Arabidopsis. The method showed a high prediction accuracy of over 90% and very high precision of close to 1.0. We predicted 50,220 PPIs in Arabidopsis thaliana, 13,175,414 PPIs in corn, and 13,527,834 PPIs in soybean. Newly predicted PPIs were classified into three confidence levels according to the availability of existing supporting evidence and discussed. Predicted PPIs in the three plant genomes are made available for future reference.
Polymorphism Control of Layered MoTe2 through Two-Dimensional Solid-Phase Crystallization
Authors: Huang Jyun-Hong , Hsu Hao-Hua , Wang Ding , Lin Wei-Ting , Cheng Chun-Cheng , Lee Yao-Jen , Hou Tuo-Hung 
Published: June 2019

AbstractTwo-dimensional (2D) molybdenum ditelluride (MoTe2) exhibits an intriguing polymorphic nature, showing stable semiconducting 2H and metallic 1T′ phases at room temperature. Polymorphism in MoTe2 presents new opportunities in developing phase-change memory, high- performance transistors, and spintronic devices. However, it also poses challenges in synthesizing homogeneous MoTe2 with a precisely controlled phase. Recently, a new yet simple method using sputtering and 2D solid-phase crystallization (SPC) is proposed for synthesizing high-quality and large-area MoTe2. This study investigates the polymorphism control of MoTe2 synthesis using 2D SPC. The Te/Mo ratio and oxygen content in the as-sputtered films correlate strongly with the final phase and electrical properties of SPC MoTe2. Furthermore, the SPC thermal budget may be exploited for stabilizing a deterministic phase. The comprehensive experiments presented in this work demonstrate the versatile and precise controllability on the MoTe2 phase by using the simple 2D SPC technique.