bluuebunny/crossref_metadata_2025_split huggingface dataset:
The onset of sleep disturbances and their associations with anxiety after acute high-altitude exposure at 3700 m
Authors: Bian Shi-Zhu , Zhang Laiping , Jin Jun , Zhang Ji-Hang , Li Qian-Ning , Yu Jie , Chen Jian-Fei , Yu Shi-Yong , Zhao Xiao-Hui , Qin Jun , Huang Lan 
Published: July 2019

AbstractSleep disturbances and psychiatric repercussions pose great challenges at high altitude; however, few studies have investigated sleep disturbance and anxiety profiles and their associations after acute exposure in consecutive patients. Thus, we aimed to study the profiles of sleep disturbances in consecutive patients after high-altitude exposure and the association of such disturbances with anxiety. A total of 668 participants were recruited at sea level and 3700 m. The trials were performed at sea level (1 week prior to a 2-h flight to a high-altitude destination) and at 3700 m (24, 72, and 168 h). Sleep disturbances were assessed by self-reported sleep patterns and scores on the Athens Insomnia Scale (AIS). State anxiety was assessed using the Self-Rating Anxiety Scale (SAS). In our study, the incidence of sleep disturbances increased significantly after acute high-altitude exposure (65.3%, 434/668) and then gradually decreased after 72 h (50%, 141/282) and 168 h (44%, 124/282). The sleep assessments AIS [2.0 (4.0) vs. 4.0 (5.0)] and ESS [4.0 (4.0) vs. 5.0 (5.0)] increased significantly (p < 0.05). Also, the SAS increased significantly from 26.25 (3.75) to 28.75 (7.5). The SAS was significantly high in sleep disturbance group [31.25 (7.5) vs. 27.5 (5), p < 0.001] than in the non-sleep- disturbance group. The baseline SAS and AIS scores were significantly higher in participants with sleep disturbances than in those without (p < 0.01). Age, baseline insomnia, sleepiness, fatigue, and higher SAS were predictors of sleep disturbances in univariate regression (all p values < 0.05). However, only an older age (p = 0.045) and a higher baseline SAS (p = 0.018) remained independent predictors of sleep disturbances. Our findings indicated that acute high-altitude exposure triggers the onset of sleep disturbances, which are closely associated with anxiety. Furthermore, baseline state anxiety and age are independent predictors of sleep disturbances at high altitude.
mTOR hyperactivation in Down Syndrome underlies deficits in autophagy induction, autophagosome formation, and mitophagy
Authors: Bordi Matteo , Darji Sandipkumar , Sato Yutaka , Mellén Marian , Berg Martin J. , Kumar Asok , Jiang Ying , Nixon Ralph A. 
Published: July 2019

AbstractDown syndrome (DS), a complex genetic disorder caused by chromosome 21 trisomy, is associated with mitochondrial dysfunction leading to the accumulation of damaged mitochondria. Here we report that mitophagy, a form of selective autophagy activated to clear damaged mitochondria is deficient in primary human fibroblasts derived from individuals with DS leading to accumulation of damaged mitochondria with consequent increases in oxidative stress. We identified two molecular bases for this mitophagy deficiency: PINK1/PARKIN impairment and abnormal suppression of macroautophagy. First, strongly downregulated PARKIN and the mitophagic adaptor protein SQSTM1/p62 delays PINK1 activation to impair mitophagy induction after mitochondrial depolarization by CCCP or antimycin A plus oligomycin. Secondly, mTOR is strongly hyper-activated, which globally suppresses macroautophagy induction and the transcriptional expression of proteins critical for autophagosome formation such as ATG7, ATG3 and FOXO1. Notably, inhibition of mTOR complex 1 (mTORC1) and complex 2 (mTORC2) using AZD8055 (AZD) restores autophagy flux, PARKIN/PINK initiation of mitophagy, and the clearance of damaged mitochondria by mitophagy. These results recommend mTORC1-mTORC2 inhibition as a promising candidate therapeutic strategy for Down Syndrome.
A new bioavailable fenretinide formulation with antiproliferative, antimetabolic, and cytotoxic effects on solid tumors
Authors: Orienti Isabella , Francescangeli Federica , De Angelis Maria Laura , Fecchi Katia , Bongiorno-Borbone Lucilla , Signore Michele , Peschiaroli Angelo , Boe Alessandra , Bruselles Alessandro , Costantino Angelita , Eramo Adriana , Salvati Valentina , Sette Giovanni , Contavalli Paola , Zolla Lello , Oki Toshihiko , Kitamura Toshio , Spada Massimo , Giuliani Alessandro , Baiocchi Marta , La Torre Filippo , Melino Gerry , Tartaglia Marco , De Maria Ruggero , Zeuner Ann 
Published: July 2019

AbstractFenretinide is a synthetic retinoid characterized by anticancer activity in preclinical models and favorable toxicological profile, but also by a low bioavailability that hindered its clinical efficacy in former clinical trials. We developed a new formulation of fenretinide complexed with 2-hydroxypropyl-beta-cyclodextrin (nanofenretinide) characterized by an increased bioavailability and therapeutic efficacy. Nanofenretinide was active in cell lines derived from multiple solid tumors, in primary spheroid cultures and in xenografts of lung and colorectal cancer, where it inhibited tumor growth independently from the mutational status of tumor cells. A global profiling of pathways activated by nanofenretinide was performed by reverse-phase proteomic arrays and lipid analysis, revealing widespread repression of the mTOR pathway, activation of apoptotic, autophagic and DNA damage signals and massive production of dihydroceramide, a bioactive lipid with pleiotropic effects on several biological processes. In cells that survived nanofenretinide treatment there was a decrease of factors involved in cell cycle progression and an increase in the levels of p16 and phosphorylated p38 MAPK with consequent block in G0 and early G1. The capacity of nanofenretinide to induce cancer cell death and quiescence, together with its elevated bioavailability and broad antitumor activity indicate its potential use in cancer treatment and chemoprevention.
Transforming growth factor-β is involved in maintaining oocyte meiotic arrest by promoting natriuretic peptide type C expression in mouse granulosa cells
Authors: Yang Jing , Zhang Yu , Xu Xiaoting , Li Jia , Yuan Feifei , Bo Shumin , Qiao Jie , Xia Guoliang , Su Youqiang , Zhang Meijia 
Published: July 2019

AbstractNatriuretic peptide type C (NPPC) secreted by mural granulosa cells (MGCs) maintains oocyte meiotic arrest via the activation of guanylyl cyclase-linked natriuretic peptide receptor 2 (NPR2). Here, we investigated the effect of transforming growth factor (TGF)-β on NPPC expression in MGCs and oocyte maturation. TGF-β ligands (TGFB1 and TGFB3, but not TGFB2) and receptors (TGFBR1 and TGFBR2) were predominantly expressed in MGCs. The activation of the follicle-stimulating hormone (FSH) receptor by FSH/equine chorionic gonadotropin (eCG) increased the levels of TGFB1, TGFBR2, and TGF-β downstream SMAD proteins in MGCs, which were decreased following the activation of the luteinizing hormone (LH) receptor by human chorionic gonadotropin (hCG). TGF-β significantly increased the gene and protein levels of NPPC in cultured MGCs through SMAD3 binding to Nppc promoter regions. In the presence of FSH, TGF-β further increased NPPC levels and inhibited oocyte meiotic resumption of cumulus-oocyte complexes (COCs). Moreover, Tgfbr2-specific depletion in granulosa cells using Fshr-Cre mice reduced NPPC mRNA and protein levels, resulting in the weak maintenance of oocyte meiotic arrest within large antral follicles. Tgfbr2 depletion also impaired follicle development, ovulation, and female fertility. Taken together, TGF-β-promoted NPPC in MGCs is involved in maintaining oocyte meiotic arrest. FSH and LH could regulate NPPC levels in MGCs via TGF-β and then control the process of oocyte meiosis.
Mitofusin 1 is required for female fertility and to maintain ovarian follicular reserve
Authors: Zhang Man , Bener Muhammed Burak , Jiang Zongliang , Wang Tianren , Esencan Ecem , Scott III Richard , Horvath Tamas , Seli Emre 
Published: July 2019

AbstractMitochondria are dynamic organelles that continually adapt their structure through fusion and fission in response to changes in their bioenergetic environment. Targeted deletion of mitochondrial fusion protein mitofusin1 (MFN1) in oocytes resulted in female infertility associated with failure to achieve oocyte maturation. Oocyte-granulosa cell communication was impaired, and cadherins and connexins were downregulated, resulting in follicle developmental arrest at the secondary follicle stage. Deletion of MFN1 in oocytes resulted in mitochondrial dysfunction and altered mitochondrial dynamics, as well as accumulation of ceramide, which contributed to increased apoptosis and a reproductive phenotype that was partially rescued by treatment with ceramide synthesis inhibitor myriocin. Absence of MFN1 and resulting apoptotic cell loss also caused depletion of ovarian follicular reserve, and a phenotype consistent with accelerated female reproductive aging.
CD160 serves as a negative regulator of NKT cells in acute hepatic injury
Authors: Kim Tae-Jin , Park Gayoung , Kim Jeongmin , Lim Seon Ah , Kim Jiyoung , Im Kyungtaek , Shin Min Hwa , Fu Yang-Xin , Del Rio Maria-Luisa , Rodriguez-Barbosa Jose-Ignacio , Yee Cassian , Suh Kyung-Suk , Kim Seong-Jin , Ha Sang-Jun , Lee Kyung-Mi 
Published: July 2019

AbstractCD160 and BTLA both bind to herpes virus entry mediator. Although a negative regulatory function of BTLA in natural killer T (NKT) cell activation has been reported, whether CD160 is also involved is unclear. By analyzing CD160−/−mice and mixed bone marrow chimeras, we show that CD160 is not essential for NKT cell development. However, CD160−/−mice exhibit severe liver injury after in vivo challenge with α-galactosylceramide (α-GalCer). Moreover, CD160−/−mice are more susceptible to Concanavalin A challenge, and display elevated serum AST and ALT levels, hyperactivation of NKT cells, and enhanced IFN-γ, TNF, and IL-4 production. Lastly, inhibition of BTLA by anti-BTLA mAb aggravates α-GalCer-induced hepatic injury in CD160−/−mice, suggesting that both CD160 and BTLA serve as non-overlapping negative regulators of NKT cells. Our data thus implicate CD160 as a co-inhibitory receptor that delivers antigen-dependent signals in NKT cells to dampen cytokine production during early innate immune activation.
Regulatory pathways governing murine coronary vessel formation are dysregulated in the injured adult heart
Authors: Payne Sophie , Gunadasa-Rohling Mala , Neal Alice , Redpath Andia N. , Patel Jyoti , Chouliaras Kira M. , Ratnayaka Indrika , Smart Nicola , De Val Sarah 
Published: July 2019

AbstractThe survival of ischaemic cardiomyocytes after myocardial infarction (MI) depends on the formation of new blood vessels. However, endogenous neovascularization is inefficient and the regulatory pathways directing coronary vessel growth are not well understood. Here we describe three independent regulatory pathways active in coronary vessels during development through analysis of the expression patterns of differentially regulated endothelial enhancers in the heart. The angiogenic VEGFA-MEF2 regulatory pathway is predominantly active in endocardial-derived vessels, whilst SOXF/RBPJ and BMP-SMAD pathways are seen in sinus venosus-derived arterial and venous coronaries, respectively. Although all developmental pathways contribute to post-MI vessel growth in the neonate, none are active during neovascularization after MI in adult hearts. This was particularly notable for the angiogenic VEGFA-MEF2 pathway, otherwise active in adult hearts and during neoangiogenesis in other adult settings. Our results therefore demonstrate a fundamental divergence between the regulation of coronary vessel growth in healthy and ischemic adult hearts.
An inter-model assessment of the role of direct air capture in deep mitigation pathways
Authors: Realmonte Giulia , Drouet Laurent , Gambhir Ajay , Glynn James , Hawkes Adam , Köberle Alexandre C. , Tavoni Massimo 
Published: July 2019

AbstractThe feasibility of large-scale biological CO2removal to achieve stringent climate targets remains unclear. Direct Air Carbon Capture and Storage (DACCS) offers an alternative negative emissions technology (NET) option. Here we conduct the first inter-model comparison on the role of DACCS in 1.5 and 2 °C scenarios, under a variety of techno-economic assumptions. Deploying DACCS significantly reduces mitigation costs, and it complements rather than substitutes other NETs. The key factor limiting DACCS deployment is the rate at which it can be scaled up. Our scenarios’ average DACCS scale-up rates of 1.5 GtCO2/yr would require considerable sorbent production and up to 300 EJ/yr of energy input by 2100. The risk of assuming that DACCS can be deployed at scale, and finding it to be subsequently unavailable, leads to a global temperature overshoot of up to 0.8 °C. DACCS should therefore be developed and deployed alongside, rather than instead of, other mitigation options.
Extraction of higher-order nonlinear electronic response in solids using high harmonic generation
Authors: Han Seunghwoi , Ortmann Lisa , Kim Hyunwoong , Kim Yong Woo , Oka Takashi , Chacon Alexis , Doran Brent , Ciappina Marcelo , Lewenstein Maciej , Kim Seung-Woo , Kim Seungchul , Landsman Alexandra S. 
Published: July 2019

AbstractNonlinear susceptibilities are key to ultrafast lightwave driven optoelectronics, allowing petahertz scaling manipulation of the signal. Recent experiments retrieved a 3rd order nonlinear susceptibility by comparing the nonlinear response induced by a strong laser field to a linear response induced by the otherwise identical weak field. The highly nonlinear nature of high harmonic generation (HHG) has the potential to extract even higher order nonlinear susceptibility terms. However, up till now, such characterization has been elusive due to a lack of direct correspondence between high harmonics and nonlinear susceptibilities. Here, we demonstrate a regime where such correspondence can be clearly made, extracting nonlinear susceptibilities (7th, 9th, and 11th) from sapphire of the same order as the measured high harmonics. The extracted high order susceptibilities show angular-resolved periodicities arising from variation in the band structure with crystal orientation. Our results open a door to multi-channel signal processing, controlled by laser polarization.
Towards a standardized bioinformatics infrastructure for N- and O-glycomics
Authors: Rojas-Macias Miguel A. , Mariethoz Julien , Andersson Peter , Jin Chunsheng , Venkatakrishnan Vignesh , Aoki Nobuyuki P. , Shinmachi Daisuke , Ashwood Christopher , Madunic Katarina , Zhang Tao , Miller Rebecca L. , Horlacher Oliver , Struwe Weston B. , Watanabe Yu , Okuda Shujiro , Levander Fredrik , Kolarich Daniel , Rudd Pauline M. , Wuhrer Manfred , Kettner Carsten , Packer Nicolle H. , Aoki-Kinoshita Kiyoko F. , Lisacek Frédérique , Karlsson Niclas G. 
Published: July 2019

AbstractThe mass spectrometry (MS)-based analysis of free polysaccharides and glycans released from proteins, lipids and proteoglycans increasingly relies on databases and software. Here, we review progress in the bioinformatics analysis of protein-released N- and O-linked glycans (N- and O-glycomics) and propose an e-infrastructure to overcome current deficits in data and experimental transparency. This workflow enables the standardized submission of MS-based glycomics information into the public repository UniCarb-DR. It implements the MIRAGE (Minimum Requirement for A Glycomics Experiment) reporting guidelines, storage of unprocessed MS data in the GlycoPOST repository and glycan structure registration using the GlyTouCan registry, thereby supporting the development and extension of a glycan structure knowledgebase.
Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response
Authors: Antunes Krist Helen , Fachi José Luís , de Paula Rosemeire , da Silva Emanuelle Fraga , Pral Laís Passariello , dos Santos Adara Áurea , Dias Greicy Brisa Malaquias , Vargas José Eduardo , Puga Renato , Mayer Fabiana Quoos , Maito Fábio , Zárate-Bladés Carlos R. , Ajami Nadim J. , Sant’Ana Marcella Ramos , Candreva Thamiris , Rodrigues Hosana Gomes , Schmiele Marcio , Silva Clerici Maria Teresa Pedrosa , Proença-Modena José Luiz , Vieira Angélica Thomas , Mackay Charles R. , Mansur Daniel , Caballero Mauricio T. , Marzec Jacqui , Li Jianying , Wang Xuting , Bell Douglas , Polack Fernando P. , Kleeberger Steven R. , Stein Renato T. , Vinolo Marco Aurélio Ramirez , de Souza Ana Paula Duarte 
Published: July 2019

AbstractSevere respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants <2 years-old. Here we describe that high-fiber diet protects mice from RSV infection. This effect was dependent on intestinal microbiota and production of acetate. Oral administration of acetate mediated interferon-β (IFN-β) response by increasing expression of interferon-stimulated genes in the lung. These effects were associated with reduction of viral load and pulmonary inflammation in RSV-infected mice. Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice. Activation of Gpr43 in pulmonary epithelial cells reduced virus-induced cytotoxicity and promoted antiviral effects through IFN-β response. The effect of acetate on RSV infection was abolished in Gpr43−/− mice. Our findings reveal antiviral effects of acetate involving IFN-β in lung epithelial cells and engagement of GPR43 and IFNAR.
Integrated analyses of murine breast cancer models reveal critical parallels with human disease
Authors: Rennhack Jonathan P. , To Briana , Swiatnicki Matthew , Dulak Caleb , Ogrodzinski Martin P. , Zhang Yueqi , Li Caralynn , Bylett Evan , Ross Christina , Szczepanek Karol , Hanrahan William , Jayatissa Muthu , Lunt Sophia Y. , Hunter Kent , Andrechek Eran R. 
Published: July 2019

AbstractMouse models have an essential role in cancer research, yet little is known about how various models resemble human cancer at a genomic level. Here, we complete whole genome sequencing and transcriptome profiling of two widely used mouse models of breast cancer, MMTV-Neu and MMTV-PyMT. Through integrative in vitro and in vivo studies, we identify copy number alterations in key extracellular matrix proteins including collagen 1 type 1 alpha 1 (COL1A1) and chondroadherin (CHAD) that drive metastasis in these mouse models. In addition to copy number alterations, we observe a propensity of the tumors to modulate tyrosine kinase-mediated signaling through mutation of phosphatases such as PTPRH in the MMTV-PyMT mouse model. Mutation in PTPRH leads to increased phospho-EGFR levels and decreased latency. These findings underscore the importance of understanding the complete genomic landscape of a mouse model and illustrate the utility this has in understanding human cancers.
Effect of the software binning and averaging data during microcomputed tomography image acquisition
Authors: Friedrichsdorf Simone Peixe , Arana-Chavez Victor Elias , Cattaneo Paolo Maria , Spin-Neto Rubens , Dominguez Gladys Cristina 
Published: July 2019

AbstractThis study describes the effect of the software binning and data averaging during micro CT volume acquisition, on the assessment of root resorption volumes. The mesial roots (n = 9), after orthodontic tooth movement during 14 days, were scanned, using a micro CT system (9 µm/pixel). All roots were reconstructed and the volumes of the resorption lacunae evaluated. The height and width of the pixels vary according to the parameters (A1, A2, A3, A4, A5, A6, A7, A8, A9) used during the scan. In the root #1 the mean volumes of resorption were similar in A4 and A7; in the root #2 there was no similarity in the mean volumes of resorption in any of the parameters; in root #3 only A4 presented mean volume different from zero (3.05 × 10°). In the root #5, the A1 and A7 presented similar mean volumes and in the A6 and A9 presented near mean volumes. In the root #9 the A1, A4, and A7 presented similar mean volumes and A6 and A9 also had similar mean volumes. Significant difference was detected in the volume of resorption among the roots #2, #5 and #9 (p = 0.04). When analyzing delicate structures such as the roots of rats’ molars, the variation of such parameters will significantly influence the results.
Insights about multi-targeting and synergistic neuromodulators in Ayurvedic herbs against epilepsy: integrated computational studies on drug-target and protein-protein interaction networks
Authors: Choudhary Neha , Singh Vikram 
Published: July 2019

AbstractEpilepsy, that comprises a wide spectrum of neuronal disorders and accounts for about one percent of global disease burden affecting people of all age groups, is recognised asapasmarain the traditional medicinal system of Indian antiquity commonly known as Ayurveda. Towards exploring the molecular level complex regulatory mechanisms of 63 anti-epileptic Ayurvedic herbs and thoroughly examining the multi-targeting and synergistic potential of 349 drug-like phytochemicals (DPCs) found therein, in this study, we develop an integrated computational framework comprising of network pharmacology and molecular docking studies. Neuromodulatory prospects of anti-epileptic herbs are probed and, as a special case study, DPCs that can regulate metabotropic glutamate receptors (mGluRs) are inspected. A novel methodology to screen and systematically analyse the DPCs having similar neuromodulatory potentialvis-à-visDrugBank compounds (NeuMoDs) is developed and 11 NeuMoDs are reported. A repertoire of 74 DPCs having poly-pharmacological similarity with anti-epileptic DrugBank compounds and those under clinical trials is also reported. Further, high-confidence PPI-network specific to epileptic protein-targets is developed and the potential of DPCs to regulate its functional modules is investigated. We believe that the presented schema can open-up exhaustive explorations of indigenous herbs towards meticulous identification of clinically relevant DPCs against various diseases and disorders.
Reduced Proprotein convertase subtilisin/kexin 9 (PCSK9) function increases lipoteichoic acid clearance and improves outcomes in Gram positive septic shock patients
Authors: Leung Alex K. K. , Genga Kelly Roveran , Topchiy Elena , Cirstea Mihai , Shimada Tadanaga , Fjell Chris , Russell James A. , Boyd John H. , Walley Keith R. 
Published: July 2019

AbstractPrevious studies have shown lipopolysaccharide from Gram-negative bacteria is cleared from the circulation via LDL receptors on hepatocytes, which are downregulated by PCSK9. Whether clearance of Gram positive bacterial lipoteichoic acid (LTA) shows similar dependence on PCSK9, and whether this is clinically relevant in Gram positive human sepsis, is unknown. We examined survival data from three cohorts of patients who had Gram positive septic shock (n = 170, n = 130, and n = 59) and found that patients who carried a PCSK9 loss-of-function (LOF) allele had significantly higher 28-day survival (73.8%) than those with no LOF alleles (52.8%) (p = 0.000038). Plasma clearance of LTA was also found to be increased in PCSK9 knockout mice compared to wildtype control mice (p = 0.002). In addition, hepatocytes pre-treated with recombinant wildtype PCSK9 showed a dose-dependent decrease in uptake of fluorescently-labeled LTA (p < 0.01). In comparison to wildtype PCSK9, hepatocytes pre-treated with 3 different LOF variants of recombinant PCSK9 showed an increase in LTA uptake. This study shows the clearance of LTA follows a similar route as lipopolysaccharide, which is dependent on hepatic LDL receptors. This has important implications in health as strategies aimed at inhibiting PCSK9 function may be an effective treatment option for both Gram-positive and negative sepsis.