bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA ANCR inhibits the differentiation of mesenchymal stem cells toward definitive endoderm by facilitating the association of PTBP1 with ID2
Authors: Li Jing , Yang Yanlei , Fan Junfen , Xu Haoying , Fan Linyuan , Li Hongling , Zhao Robert Chunhua 
Published: June 2019

AbstractThe generation of definitive endoderm (DE) cells in sufficient numbers is a prerequisite for cell-replacement therapy for liver and pancreatic diseases. Previously, we reported that human adipose-derived mesenchymal stem cells (hAMSCs) can be induced to DE lineages and subsequent functional cells. Clarifying the regulatory mechanisms underlying the fate conversion from hAMSCs to DE is helpful for developing new strategies to improve the differentiation efficiency from hAMSCs to DE organs. Long noncoding RNAs (lncRNAs) have been shown to play pivotal roles in developmental processes, including cell fate determination and differentiation. In this study, we profiled the expression changes of lncRNAs and found that antidifferentiation noncoding RNA (ANCR) was downregulated during the differentiation of both hAMSCs and embryonic stem cells (ESCs) to DE cells. ANCR knockdown resulted in the elevated expression of DE markers in hAMSCs, but not in ESCs. ANCR overexpression reduced the efficiency of hAMSCs to differentiate into DE cells. Inhibitor of DNA binding 2 (ID2) was notably downregulated after ANCR knockdown. ID2 knockdown enhanced DE differentiation, whereas overexpression of ID2 impaired this process in hAMSCs. ANCR interacts with RNA-binding polypyrimidine tract-binding protein 1 (PTBP1) to facilitate its association with ID2 mRNA, leading to increased ID2 mRNA stability. Thus, the ANCR/PTBP1/ID2 network restricts the differentiation of hAMSCs toward DE. Our work highlights the inherent discrepancies between hAMSCs and ESCs. Defining hAMSC-specific signaling pathways might be important for designing optimal differentiation protocols for directing hAMSCs toward DE.
Phosphatidic acid homeostasis regulated by a type-2 phosphatidic acid phosphatase represents a novel druggable target in malaria intervention
Authors: Kumar Sah Raj , Garg Swati , Dangi Poonam , Ponnusamy Kalaiarasan , Singh Shailja 
Published: June 2019

AbstractType-2 phosphatidic acid phosphatase (PAP2) a member of PAP2 superfamily mediates the conversion of phosphatidic acid (PA) to diacylglycerol (DAG) and thus plays a pivotal role in numerous cellular signaling processes in diverse organisms. An elevated level of intracellular PA is detrimental for the cell and induces cell death. In this study we identified and characterized a PAP2 homologue in Plasmodium falciparum, PfPAP2 and further elucidated its significance in regulation of PA homeostasis in parasite life cycle. PfPAP2 is expressed in the blood stage and harbors the canonical acid phosphatase domain (APD) with signature motifs. PfPAP2 catalyzes the dephosphorylation of PA to produce DAG and inorganic phosphate (Pi). Propranolol, a generic inhibitor of PAP2, inhibited the phosphatase activity of PfPAP2 by binding to the active site of APD domain as evident by in silico docking and confirmed by surface plasmon resonance (SPR) analysis. Inhibition of native PfPAP2 by propranolol led to rise in intracellular PA mediating disruption of intracellular PA homeostasis in parasites. The propranolol mediated inhibition of PfPAP2 directed early secretion of a micronemal Perforin like Protein, PfPLP1 leading to untimely permeabilization and host cell egress. The merozoites following premature egress were non-invasive and were attenuated to invade erythrocytes and cannot continue next cycle growth. This study demonstrates that disruption of PA homeostasis can cause growth retardation in malaria parasites, and thus its master regulator, PfPAP2, can serve as a very good molecular target for antimalarial chemotherapeutic interventions.
Trends in erectile dysfunction research from 2008 to 2018: a bibliometric analysis
Authors: Hui Jialiang , He Shuhua , Liu Ruiyu , Zeng Qinyu , Zhang Haibo , Wei Anyang 
Published: June 2019

AbstractInsufficient penile erection to facilitate vaginal penetration is a medical condition referred to as erectile dysfunction (ED). By the year 2025, the number of ED cases across the world is expected to reach 322 million. There are numerous publications and studies in the field of ED over the past decades. Our aim is to comprehensively analyze the global scientific outputs of ED research and show the trends and hotspots in ED research. Data of publications were downloaded from the Web of Science Core Collection. We used CiteSpace IV and Excel 2016 to analyze literature information, including journals, countries/regions, institutes, authors, citation reports, and research frontiers. Until October 26, 2018, a total of 8880 papers in ED research were identified as published between 2008 and 2018. Journal of Sexual Medicine published the most articles. The United States contributed the most publications and occupied leading positions in H-index value and the number of ESI top papers. Maggi M owned the highest co-citations. The keyword “Oxidative stress” ranked first in the research front-line. The amount of articles published in ED research has been stable from 2008 to 2018. The United States showed enormous progress in ED research, and is still the dominant country. Oxidative stress, vardenafil, and late-onset hypogonadism were the latest research frontiers and should be paid more attention.
Pathologic gene network rewiring implicates PPP1R3A as a central regulator in pressure overload heart failure
Authors: Cordero Pablo , Parikh Victoria N. , Chin Elizabeth T. , Erbilgin Ayca , Gloudemans Michael J. , Shang Ching , Huang Yong , Chang Alex C. , Smith Kevin S. , Dewey Frederick , Zaleta Kathia , Morley Michael , Brandimarto Jeff , Glazer Nicole , Waggott Daryl , Pavlovic Aleksandra , Zhao Mingming , Moravec Christine S. , Tang W. H. Wilson , Skreen Jamie , Malloy Christine , Hannenhalli Sridhar , Li Hongzhe , Ritter Scott , Li Mingyao , Bernstein Daniel , Connolly Andrew , Hakonarson Hakon , Lusis Aldons J. , Margulies Kenneth B. , Depaoli-Roach Anna A. , Montgomery Stephen B. , Wheeler Matthew T. , Cappola Thomas , Ashley Euan A. 
Published: June 2019

AbstractHeart failure is a leading cause of mortality, yet our understanding of the genetic interactions underlying this disease remains incomplete. Here, we harvest 1352 healthy and failing human hearts directly from transplant center operating rooms, and obtain genome-wide genotyping and gene expression measurements for a subset of 313. We build failing and non-failing cardiac regulatory gene networks, revealing important regulators and cardiac expression quantitative trait loci (eQTLs). PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions, and highlights metabolic pathway regulation associated with increased cardiomyocyte size and perturbed respiratory metabolism. Mice lacking PPP1R3A are protected against pressure-overload heart failure. We present a global gene interaction map of the human heart failure transition, identify previously unreported cardiac eQTLs, and demonstrate the discovery potential of disease-specific networks through the description of PPP1R3A as a central regulator in heart failure.
Urinary tract colonization is enhanced by a plasmid that regulates uropathogenic Acinetobacter baumannii chromosomal genes
Authors: Di Venanzio Gisela , Flores-Mireles Ana L. , Calix Juan J. , Haurat M. Florencia , Scott Nichollas E. , Palmer Lauren D. , Potter Robert F. , Hibbing Michael E. , Friedman Laura , Wang Bin , Dantas Gautam , Skaar Eric P. , Hultgren Scott J. , Feldman Mario F. 
Published: June 2019

AbstractMultidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries the plasmid pAB5, a member of the family of large conjugative plasmids that represses the type VI secretion system (T6SS) in multiple Acinetobacter strains. pAB5 confers niche specificity, as its carriage improves UPAB1 survival in a CAUTI model and decreases virulence in a pneumonia model. Comparative proteomic and transcriptomic analyses show that pAB5 regulates the expression of multiple chromosomally-encoded virulence factors besides T6SS. Our results demonstrate that plasmids can impact bacterial infections by controlling the expression of chromosomal genes.
Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance
Authors: Agudelo Leandro Z. , Ferreira Duarte M. S. , Dadvar Shamim , Cervenka Igor , Ketscher Lars , Izadi Manizheh , Zhengye Liu , Furrer Regula , Handschin Christoph , Venckunas Tomas , Brazaitis Marius , Kamandulis Sigitas , Lanner Johanna T. , Ruas Jorge L. 
Published: June 2019

AbstractThe coactivator PGC-1α1 is activated by exercise training in skeletal muscle and promotes fatigue-resistance. In exercised muscle, PGC-1α1 enhances the expression of kynurenine aminotransferases (Kats), which convert kynurenine into kynurenic acid. This reduces kynurenine-associated neurotoxicity and generates glutamate as a byproduct. Here, we show that PGC-1α1 elevates aspartate and glutamate levels and increases the expression of glycolysis and malate-aspartate shuttle (MAS) genes. These interconnected processes improve energy utilization and transfer fuel-derived electrons to mitochondrial respiration. This PGC-1α1-dependent mechanism allows trained muscle to use kynurenine metabolism to increase the bioenergetic efficiency of glucose oxidation. Kat inhibition with carbidopa impairs aspartate biosynthesis, mitochondrial respiration, and reduces exercise performance and muscle force in mice. Our findings show that PGC-1α1 activates the MAS in skeletal muscle, supported by kynurenine catabolism, as part of the adaptations to endurance exercise. This crosstalk between kynurenine metabolism and the MAS may have important physiological and clinical implications.
Rearrangement of the transmembrane domain interfaces associated with the activation of a GPCR hetero-oligomer
Authors: Xue Li , Sun Qian , Zhao Han , Rovira Xavier , Gai Siyu , He Qianwen , Pin Jean-Philippe , Liu Jianfeng , Rondard Philippe 
Published: June 2019

AbstractG protein-coupled receptors (GPCRs) can integrate extracellular signals via allosteric interactions within dimers and higher-order oligomers. However, the structural bases of these interactions remain unclear. Here, we use the GABAB receptor heterodimer as a model as it forms large complexes in the brain. It is subjected to genetic mutations mainly affecting transmembrane 6 (TM6) and involved in human diseases. By cross-linking, we identify the transmembrane interfaces involved in GABAB1-GABAB2, as well as GABAB1-GABAB1 interactions. Our data are consistent with an oligomer made of a row of GABAB1. We bring evidence that agonist activation induces a concerted rearrangement of the various interfaces. While the GB1-GB2 interface is proposed to involve TM5 in the inactive state, cross-linking of TM6s lead to constitutive activity. These data bring insight for our understanding of the allosteric interaction between GPCRs within oligomers.
Vertical saccades and antisaccades: complementary markers for motor and cognitive impairment in Parkinson’s disease
Authors: Waldthaler Josefine , Tsitsi Panagiota , Svenningsson Per 
Published: June 2019

AbstractPrevious studies provide partly contradictory results about the characteristics of saccades in PD and the possible effects of levodopa, which may be attributed to different study design regarding disease stages, medication state or cognitive functioning. We studied horizontal and vertical visually guided saccades (VGS) and antisaccades (AS) in 40 patients with PD with and without postural instability in On and Off medication state as well as in 20 healthy controls (HC). Motor and cognitive performance were assessed using UPDRS, Montreal Cognitive Assessment (MoCA) and Frontal Assessment Battery (FAB). The PD group showed decreased VGS amplitudes and increased vertical VGS and AS latencies. Only relatively few studies had assessed vertical saccades in PD so far. However, our results indicate that vertical saccadic amplitude may be a supportive marker in diagnosing PD since upwards gain demonstrated an AUC of 0.85 for the discrimination of PD and HC. Only more advanced patients in Hoehn & Yahr stage 3 executed higher numbers of AS errors than HC. Since the AS error rate correlated with FAB and MoCA scores, AS performance seems to reflect cognitive ability in PD. Furthermore, the correlation of AS latency with the UPDRS axial subscore promotes the recently highlighted connection between postural control and executive function in PD. Levodopa did not alter saccade amplitudes and had opposing effects on the initiation of VGS and AS: Levodopa intake prolonged VGS latency, but decreased AS latency. Possible mechanisms by which levodopa may be capable of partially reversing the impaired balance between voluntary and reflexive cortical saccade initiation of PD are discussed.
Optimization of Bone Scaffold Porosity Distributions
Authors: Poh Patrina S. P. , Valainis Dvina , Bhattacharya Kaushik , van Griensven Martijn , Dondl Patrick 
Published: June 2019

AbstractAdditive manufacturing (AM) is a rapidly emerging technology that has the potential to produce personalized scaffolds for tissue engineering applications with unprecedented control of structural and functional design. Particularly for bone defect regeneration, the complex coupling of biological mechanisms to the scaffolds’ properties has led to a predominantly trial-and-error approach. To mitigate this, shape or topology optimization can be a useful tool to design a scaffold architecture that matches the desired design targets, albeit at high computational cost. Here, we consider an efficient macroscopic optimization routine based on a simple one-dimensional time-dependent model for bone regeneration in the presence of a bioresorbable polymer scaffold. The result of the optimization procedure is a scaffold porosity distribution which maximizes the stiffness of the scaffold and regenerated bone system over the entire regeneration time, so that the propensity for mechanical failure is minimized.
Electric field tuning of spin splitting in topological insulator quantum dots doped with a single magnetic ion
Authors: Li Xiaojing , Yang Wen , Lin Liangzhong , Wu Zhenhua 
Published: June 2019

AbstractWe investigate theoretically the electron spin states in a disk-shaped topological insulator quantum dot (TIQD) containing a single magnetic Mn2+ ion. We demonstrate that the energy spectra and the density distributions of the symmetry-protected edge states in a HgTe TIQD can be modulated effectively by a single magnetic impurity Mn2+. Additionally, when an in-plane external electric field is applied., it not only tunes the spin splittings of edge states via the s(p)-d exchange interaction between the electron (hole) and the magnetic Mn2+ ion respectively, but also gives rise to the bright-to-dark transitions in the optical transition spectrum. Such spin properties of TIQDs with single Mn2+ ion as illustrated in this work could offer a new platform for topological electro-optical devices.
Ctt1 catalase activity potentiates antifungal azoles in the emerging opportunistic pathogen Saccharomyces cerevisiae
Authors: Martins Dorival , Nguyen Dao , English Ann M. 
Published: June 2019

AbstractFungi respond to antifungal drugs by increasing their antioxidant stress response. How this impacts antifungal efficacy remains controversial and not well understood. Here we examine the role of catalase activity in the resistance of Saccharomyces cerevisiae to the common antifungals, fluconazole and miconazole, for which we report minimum inhibitory concentrations (MICs) of 104 and 19 μM, respectively. At sub-MIC concentrations, fluconazole and miconazole stimulate catalase activity 2-3-fold but, unexpectedly, deletion of cytosolic catalase (ctt1) makes cells more resistant to these azoles and to clotrimazole, itraconazole and posaconazole. On the other hand, upregulating Ctt1 activity by preconditioning with 0.2 mM H2O2 potentiates miconazole 32-fold and fluconazole 4-fold. Since H2O2 preconditioning does not alter the resistance of ctt1Δ cells, which possess negligible catalase activity, we link azole potentiation with Ctt1 upregulation. In contrast, sod2Δ cells deleted for mitochondrial superoxide dismutase are 4–8-fold more azole sensitive than wild-type cells, revealing that Sod2 activity protects cells against azole toxicity. In fact, the ctt1Δ mutant has double the Sod2 activity of wild-type cells so ctt1 deletion increases azole resistance in part by Sod2 upregulation. Notably, deletion of peroxisomal/mitochondrial cta1 or cytosolic sod1 does not alter fluconazole or miconazole potency.
Iron-mediated aggregation and toxicity in a novel neuronal cell culture model with inducible alpha-synuclein expression
Authors: Bartels Martin , Weckbecker Daniel , Kuhn Peer-Hendrik , Ryazanov Sergey , Leonov Andrei , Griesinger Christian , Lichtenthaler Stefan F. , Bötzel Kai , Giese Armin 
Published: June 2019

AbstractParkinson’s disease (PD) represents an increasing problem in society. The oligomerization of alpha-synuclein (αSyn) is a suggested key event in its pathogenesis, yet the pathological modes of action remain to be fully elucidated. To identify potential disease-modifying therapeutics and to study αSyn-mediated toxic mechanisms, we established cell lines with inducible overexpression of different αSyn constructs: αSyn, αSyn coupled to the fluorescence protein Venus (αSyn-Venus), and αSyn coupled to the N-terminal or C-terminal part of Venus (V1S and SV2, respectively) for a bimolecular fluorescence complementation assay (BiFC). Inducibility was achieved by applying modified GAL4-UAS or Cre-loxP systems and addition of tebufenozide or 4-OH-tamoxifen, respectively. Expression constructs were stably integrated into the host genome of H4 neuroglioma cells by lentiviral transduction. We here demonstrate a detailed investigation of the expression characteristics of inducible H4 cells showing low background expression and high inducibility. We observed increased protein load and aggregation of αSyn upon incubation with DMSO and FeCl3along with an increase in cytotoxicity. In summary, we present a system for the creation of inducibly αSyn-overexpressing cell lines holding high potential for the screening for modulators of αSyn aggregation and αSyn-mediated toxicity.
Superintense Laser-driven Ion Beam Analysis
Authors: Passoni M. , Fedeli L. , Mirani F. 
Published: June 2019

AbstractIon beam analysis techniques are among the most powerful tools for advanced materials characterization. Despite their growing relevance in a widening number of fields, most ion beam analysis facilities still rely on the oldest accelerator technologies, with severe limitations in terms of portability and flexibility. In this work we thoroughly address the potential of superintense laser-driven proton sources for this application. We develop a complete analytical and numerical framework suitable to describe laser-driven ion beam analysis, exemplifying the approach for Proton Induced X-ray/Gamma-ray emission, a technique of widespread interest. This allows us to propose a realistic design for a compact, versatile ion beam analysis facility based on this novel concept. These results can pave the way for ground-breaking developments in the field of hadron-based advanced materials characterization.
Tear film lipid layer increase after diquafosol instillation in dry eye patients with meibomian gland dysfunction: a randomized clinical study
Authors: Fukuoka Shima , Arita Reiko 
Published: June 2019

AbstractDiquafosol promotes secretion of tear fluid and mucin at the ocular surface and is administered for treatment of dry eye (DE). Tear film lipid layer is secreted from meibomian glands and stabilizes the tear film. We recently showed that diquafosol administration increased lipid layer thickness (LLT) for up to 60 min in normal human eyes. We here evaluated tear film lipid layer in DE patients (n = 47) with meibomian gland dysfunction (MGD) before as well as 30, 60, and 90 min after diquafosol administration. One drop of artificial tears or one drop of diquafosol was applied randomly to the eyes of each patient. Diquafosol significantly increased LLT at 30 (P < 0.001) and 60 (P = 0.042) min and noninvasive tear film breakup time for at least 90 min (P < 0.001 at each assessment point). Artificial tears had no such effect. Diquafosol significantly improved the tear interferometric pattern compared with artificial tears (P < 0.001 at each assessment point). A single topical administration of diquafosol thus improved LLT and tear film stability in DE patients with MGD, suggesting that diquafosol is a potential treatment not only for aqueous-deficient DE but also for evaporative DE associated with MGD.
Plant detritus is selectively consumed by estuarine copepods and can augment their survival
Authors: Harfmann Jennifer , Kurobe Tomofumi , Bergamaschi Brian , Teh Swee , Hernes Peter 
Published: June 2019

AbstractParticulate material comprising the detrital remains of terrestrial plants and macrophytes is a substantial source of organic matter to estuaries and therefore has the potential to support the energy demands of the pelagic aquatic food web. Despite the prevalence of macrophytic or terrestrial particulate organic carbon (tPOC), phytoplankton are nutritionally superior and are thought to be the primary food resource for zooplankton. However, estuarine phytoplankton primary productivity abundances can wax and wane, and often production cannot meet heterotrophic energy needs. In this study, we examined how tPOC (detritus of macrophytes and grasses) may affect survival of a calanoid copepod (Eurytemora affinis) common in the San Francisco Estuary (SFE), an estuary with relatively low phytoplankton primary productivity. Using chemical biomarkers and a targeted DNA metagenomic methodology, we show that E. affinis consumed tPOC (dominated by Schoenoplectus sp., or tule) even when phytoplankton were abundant and tPOC was scarce. Furthermore, we found that a mixed diet of phytoplankton and terrestrial material (1:3 carbon ratio) enhanced the survival of E. affinis over a diet of phytoplankton alone. These data show that tPOC can be a vital supplementary food source for zooplankton, perhaps extending survival during low phytoplankton periods, and may help explain elevated zooplankton abundances in tidal wetlands and other detrital-dominated regions.