bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector
Authors: Giel-Moloney M. , Esteban M. , Oakes B. H. , Vaine M. , Asbach B. , Wagner R. , Mize G. J. , Spies A. G. , McElrath J. , Perreau M. , Roger T. , Ives A. , Calandra T. , Weiss D. , Perdiguero B. , Kibler K. V. , Jacobs B. , Ding S. , Tomaras G. D. , Montefiori D. C. , Ferrari G. , Yates N. L. , Roederer M. , Kao S. F. , Foulds K. E. , Mayer B. T. , Bennett C. , Gottardo R. , Parrington M. , Tartaglia J. , Phogat S. , Pantaleo G. , Kleanthous H. , Pugachev K. V. 
Published: December 2019

AbstractMultiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.
Respiratory syncytial virus A genotype classification based on systematic intergenotypic and intragenotypic sequence analysis
Authors: Muñoz-Escalante Juan Carlos , Comas-García Andreu , Bernal-Silva Sofía , Robles-Espinoza Carla Daniela , Gómez-Leal Guillermo , Noyola Daniel E. 
Published: December 2019

AbstractRespiratory syncytial virus (RSV), a leading cause of lower respiratory tract infections, is classified in two major groups (A and B) with multiple genotypes within them. Continuous changes in spatiotemporal distribution of RSV genotypes have been recorded since the identification of this virus. However, there are no established criteria for genotype definition, which affects the understanding of viral evolution, immunity, and development of vaccines. We conducted a phylogenetic analysis of 4,353 RSV-A G gene ectodomain sequences, and used 1,103 complete genome sequences to analyze the totallity of RSV-A genes. Intra- and intergenotype p-distance analysis and identification of molecular markers associated to specific genotypes were performed. Our results indicate that previously reported genotypes can be classified into nine distinct genotypes: GA1-GA7, SAA1, and NA1. We propose the analysis of the G gene ectodomain with a wide set of reference sequences of all genotypes for an accurate genotype identification.
Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens
Authors: Ferrer-González Edgar , Fujita Junso , Yoshizawa Takuya , Nelson Julia M. , Pilch Alyssa J. , Hillman Elani , Ozawa Mayuki , Kuroda Natsuko , Al-Tameemi Hassan M. , Boyd Jeffrey M. , LaVoie Edmond J. , Matsumura Hiroyoshi , Pilch Daniel S. 
Published: December 2019

AbstractAddressing the growing problem of antibiotic resistance requires the development of new drugs with novel antibacterial targets. FtsZ has been identified as an appealing new target for antibacterial agents. Here, we describe the structure-guided design of a new fluorescent probe (BOFP) in which a BODIPY fluorophore has been conjugated to an oxazole-benzamide FtsZ inhibitor. Crystallographic studies have enabled us to identify the optimal position for tethering the fluorophore that facilitates the high-affinity FtsZ binding of BOFP. Fluorescence anisotropy studies demonstrate that BOFP binds the FtsZ proteins from the Gram-positive pathogens Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae with Kd values of 0.6–4.6 µM. Significantly, BOFP binds the FtsZ proteins from the Gram-negative pathogens Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii with an even higher affinity (Kd = 0.2–0.8 µM). Fluorescence microscopy studies reveal that BOFP can effectively label FtsZ in all the above Gram-positive and Gram-negative pathogens. In addition, BOFP is effective at monitoring the impact of non-fluorescent inhibitors on FtsZ localization in these target pathogens. Viewed as a whole, our results highlight the utility of BOFP as a powerful tool for identifying new broad-spectrum FtsZ inhibitors and understanding their mechanisms of action.
Carrier Induced Hopping to Band Conduction in Pentacene
Authors: Rani Varsha , Kumar Pramod , Sharma Akanksha , Yadav Sarita , Singh Budhi , Ray Nirat , Ghosh Subhasis 
Published: December 2019

AbstractCharge transport in organic thin films which are generally polycrystalline is typically limited by the localization of the carriers at lattice defects resulting in low carrier mobilities and carriers move from one state to another state by hopping. However, charge transport in organic semiconductors in their single crystalline phase is coherent due to band conduction and mobilities are not limited by disorder resulting in higher carrier mobility. So it is a challenge to enhance the carrier mobility in a thin film which is the preferred choice for all organic devices. Here, we show that it is possible to increase the carrier mobility in polycrystalline thin films by injecting sufficient carriers such that Fermi level can be moved into the region of high density in Gaussian density of states of molecular solids. When the hopping transport happens through the molecular energy levels whose density is low, mobility is decided by incoherent transport however, when the the hopping transport happens through the energy levels with high density, mobility is decided by coherent transport, as in band conduction. We present results highlighting the observation of both band-like and hopping conduction in polycrystalline organic thin films by varying the concentration of injected charge. More importantly the transition from hopping to band transport is reversible. The observed carrier mobilities in both the regimes match well with theoretical estimates of hopping mobility and band mobility determined from first principles density functional theory.
Critical role of CRAG, a splicing variant of centaurin-γ3/AGAP3, in ELK1-dependent SRF activation at PML bodies
Authors: Nagashima Shun , Takeda Keisuke , Shiiba Isshin , Higashi Mizuho , Fukuda Toshifumi , Tokuyama Takeshi , Matsushita Nobuko , Nagano Seiichi , Araki Toshiyuki , Kaneko Mari , Shioi Go , Inatome Ryoko , Yanagi Shigeru 
Published: December 2019

AbstractCRMP-5-associated GTPase (CRAG), a short splicing variant of centaurin-γ3/AGAP3, is predominantly expressed in the developing brain. We previously demonstrated that CRAG, but not centaurin-γ3, translocates to the nucleus and activates the serum response factor (SRF)-c-Fos pathway in cultured neuronal cells. However, the physiological relevance of CRAG in vivo is unknown. Here, we found that CRAG/centaurin-γ3–knockout mice showed intensively suppressed kainic acid-induced c-fos expression in the hippocampus. Analyses of molecular mechanisms underlying CRAG-mediated SRF activation revealed that CRAG has an essential role in GTPase activity, interacts with ELK1 (a co-activator of SRF), and activates SRF in an ELK1-dependent manner. Furthermore, CRAG and ELK1 interact with promyelocytic leukaemia bodies through SUMO-interacting motifs, which is required for SRF activation. These results suggest that CRAG plays a critical role in ELK1-dependent SRF-c-fos activation at promyelocytic leukaemia bodies in the developing brain.
Simultaneous influence of sympathetic autonomic stress on Schlemm’s canal, intraocular pressure and ocular circulation
Authors: Chen Wei , Chen Zhiqi , Xiang Yan , Deng Chaohua , Zhang Hong , Wang Junming 
Published: December 2019

AbstractThis study aimed to investigate changes in Schlemm’s canal, intraocular pressure and ocular blood circulation following the activation of the sympathetic nervous system. Twenty healthy volunteers were enrolled in this study. The cold pressor test (CPT) was adopted. Cross-sectional area of Schlemm’s canal (SCAR), superficial and deep retinal vessel densities (s-RVD;d-RVD), pupil diameter (PD), intraocular pressure (IOP), mean ocular perfusion pressure (MOPP) and heart rate variability (HRV) were measured at three time-points: baseline (T0) and 5 min (T1) and 10 min (T2) after the CPT. After cold stimulation, LF/HF index (the ratio of low frenquency and high frenquency) increased significantly. IOP decreased from 16.9 ± 1.9 mmHg at baseline to 16.4 ± 2.7 mmHg at T1 and to 15.2 ± 2.7 mmHg at T2. The nasal cross-sectional area of SCAR (SCAR-n) increased from 6283.9 ± 2696.2 µm2 at baseline to 8392.9 ± 3258.7 µm2 at T1 and to 10422.0 ± 3643.8 µm2 at T2. The temporal cross-sectional area of SCAR (SCAR-t) increased from 6414.5 ± 2218.7 µm2 at baseline to 8610.8 ± 2317.1 µm2 at T1 and to 11544.0 ± 4129.2 µm2 at T2. The expansion of Schlemm’s canal was observed after the CPT might be caused by sympathetic nerve stimulation, subsequently leading to decreased IOP.
A novel index equivalent to the myocardial performance index for right ventricular functional assessment in children and adolescent patients
Authors: Hayabuchi Yasunobu , Homma Yukako , Kagami Shoji 
Published: December 2019

AbstractThe aims of the present study were to develop and check the utility and feasibility of a novel right ventricular (RV) functional index (RV angular velocity; RVω, s−1) derived from the angular velocity in harmonic oscillator kinematics obtained from the RV pressure waveform. We hypothesized that RVω reflects the myocardial performance index (MPI), which represents global RV function. A total of 132 consecutive patients, ranging in age from 3 months to 34 years with various cardiac diseases were included in this prospective study. RVω was defined as the difference between the peak derivative of pressure (dP/dt_max − dP/dt_min) divided by the difference between the maximum and minimum pressure (Pmax – Pmin). RVω showed significant negative correlations with the pulsed-wave Doppler-derived myocardial performance index (PWD-MPI) and the tissue Doppler imaging-derived MPI (TDI-MPI) (r = −0.52 and −0.51, respectively; both p < 0.0001). RVω also showed significant positive correlations with RV fractional area change (RVFAC) and RV ejection fraction (RVEF) (r = 0.41 and 0.39, respectively; both p < 0.0001), as well as a significant negative correlation with tricuspid E/e′ (r = −0.19, p = 0.0283). The clinical feasibility and utility of RVω for assessing global RV performance, incorporating both systolic and diastolic function, were demonstrated.
Ferromagnetism from non-magnetic ions: Ag-doped ZnO
Authors: Ali Nasir , A. R. Vijaya , Khan Zaheer Ahmed , Tarafder Kartick , Kumar Anuvesh , Wadhwa Manoj K. , Singh Budhi , Ghosh Subhasis 
Published: December 2019

AbstractTo develop suitable ferromagnetic oxides with Curie temperature (TC) at or above room temperature for spintronic applications, a great deal of research in doping ZnO with magnetic ions is being carried out over last decade. As the experimental results on magnetic ions doped ZnO are highly confused and controversial, we have investigated ferromagnetism in non-magnetic ion, Ag, doped ZnO. When Ag replaces Zn in ZnO, it adopts 4d9 configuration for Ag2+ which has single unpaired spin and suitable exchange interaction among these spins gives rise to ferromagnetism in ZnO with above room temperature TC. Experimentally, we have observed room temperature ferromagnetism (RTFM) in Ag-doped ZnO with Ag concentration varied from 0.03% to 10.0%. It is shown that zinc vacancy (VZn) enhances the ferromagnetic ordering (FMO) while oxygen vacancy (VO) retards the ferromagnetism in Ag-doped ZnO. Furthermore, the theoretical investigation revealed that VZn along with Ag2+ ions play a pivotal role for RTFM in Ag-doped ZnO. The Ag2+-Ag2+ interaction is ferromagnetic in the same Zn plane whereas anti-ferromagnetic in different Zn planes. The presence of VZn changes the anti-ferromagnetic to ferromagnetic state with a magnetic coupling energy of 37 meV. Finally, it has been established that the overlapping of bound magnetic polarons is responsible for RTFM in low doping concentration. However, anti-ferromagnetic coupling sets in at higher doping concentrations and hence weakens the FMO to a large extent.
Association between Serum Gamma-glutamyl transferase and Intracranial Arterial Calcification in Acute Ischemic Stroke Subjects
Authors: Yao Tao , Li Jing , Long Qi , Li Gang , Ding Yanbin , Cui Qin , Liu Zhichao 
Published: December 2019

AbstractIntracranial artery calcification (IAC) is an important risk factor for cerebral infarction and a key biomarker for intracranial artery stenosis. Gamma-glutamyl transferase (GGT) has been independently associated with increased cardiovascular events and coronary calcification. Our study assessed whether GGT is an independent factor for IAC in acute ischemic stroke (AIS) patients. This cross-sectional study involved a total of 754 patients with AIS (mean age: 65 ± 13.2 years). All the patients had received brain computed tomography angiography (CTA) examination to evaluate IAC. Further, serum GGT levels and other biochemical parameters were analyzed. The average GGT level in patients who died was also significantly increased (37.0 ± 26.8 vs 29.0 ± 21.5 U/L, p = 0.012). Partial correlation analysis showed that serum GGT levels were associated with NIHSS score at admission after adjustment for age and gender was considered (r = 0.150, p = 0.001). Logistic regression analysis showed that serum GGT levels independently predicted all-cause mortality (OR = 1.036, 95% CI: 1.014–1.060, p = 0.002), NIHSS scores (β = 0.051, 95% CI: 0.020–0.082, p = 0.001) and IAC scores (β = 0.006, 95% CI: 0.003–0.014, p = 0.005) in male patients. Each SD (standard deviation) increase of serum GGT levels was also associated with risk of all-cause mortality (OR = 2.272, 95% CI: 1.364–3.787, P = 0.002). GGT levels in patients with severe IAC were significantly elevated (37.6 ± 33.6 vs 28.6 ± 19.2, p < 0.001). However, serum GGT levels could not independently predict the severity of IAC in AIS patients. Our study identified that serum GGT levels were significantly elevated in patients who died, and the GGT levels had a certain association with the risk of death and IAC in male patients.
Dimorphic metabolic and endocrine disorders in mice lacking the constitutive androstane receptor
Authors: Lukowicz Céline , Ellero-Simatos Sandrine , Régnier Marion , Oliviero Fabiana , Lasserre Frédéric , Polizzi Arnaud , Montagner Alexandra , Smati Sarra , Boudou Frédéric , Lenfant Françoise , Guzylack-Pirou Laurence , Menard Sandrine , Barretto Sharon , Fougerat Anne , Lippi Yannick , Naylies Claire , Bertrand-Michel Justine , Belgnaoui Afifa Ait , Theodorou Vassilia , Marchi Nicola , Gourdy Pierre , Gamet-Payrastre Laurence , Loiseau Nicolas , Guillou Hervé , Mselli-Lakhal Laïla 
Published: December 2019

AbstractMetabolic diseases such as obesity, type II diabetes and hepatic steatosis are a public health concern in developed countries. The metabolic risk is gender‐dependent. The constitutive androstane receptor (CAR), which is at the crossroads between energy metabolism and endocrinology, has recently emerged as a promising therapeutic agent for the treatment of obesity and type 2 diabetes. In this study we sought to determine its role in the dimorphic regulation of energy homeostasis. We tracked male and female WT and CAR deficient (CAR−/−) mice for over a year. During aging, CAR−/− male mice developed hypercortisism, obesity, glucose intolerance, insulin insensitivity, dyslipidemia and hepatic steatosis. Remarkably, the latter modifications were absent, or minor, in female CAR−/− mice. When ovariectomized, CAR−/− female mice developed identical patterns of metabolic disorders as observed in male mice. These results highlight the importance of steroid hormones in the regulation of energy metabolism by CAR. They unveil a sexually dimorphic role of CAR in the maintenance of endocrine and metabolic homeostasis underscoring the importance of considering sex in treatment of metabolic diseases.
Combined use of a microbial restoration substrate and avirulent Ralstonia solanacearum for the control of tomato bacterial wilt
Authors: Zheng Xuefang , Zhu Yujing , Wang Jieping , Wang Ziran , Liu Bo 
Published: December 2019

AbstractTomato bacterial wilt (BW) caused by Ralstonia solanacearum seriously restricts tomato production and no effective control measures are available. A microbial restoration substrate (MRS) had been proved to be effective control of tomato BW in a greenhouse cultivation. In this study, MRS was combined with an avirulent Ralstonia solanacearum (aRS) strain to control the disease under an open field condition. In the two consecutive year (2017 and 2018) trials, the combined use of aRS and MRS resulted in better disease control compared with either aRS or MRS alone. Moreover, the combined treatment was more effective than expected and suggesting a synergistic control effect. Compared with control (CK, non-aRS or MRS), the application of aRS and MRS treatments alone or in combination could all promote plant growth, increase root activity and yield (e.g. the yield for the treatment of aRS + MRS increased by 463.64% in 2017). Soil nutrients, including soil organic carbon, total nitrogen, total phosphorus and total potassium contents were also significantly increased by the application of aRS and MRS treatments alone or in combination (P < 0.05). The application of MRS or in combination with aRS changed the soil from acidic to neutral, which is one of the key factors for controlling BW. The soil enzymatic activities were notably influenced by the combined use of aRS and MRS, which increased urease (87.37% in 2017 and 60.89% in 2018), catalase (93.67% in 2017 and 279.37% in 2018) and alkaline phosphatase activities (193.77% in 2017 and 455.73% in 2018). These results suggest that the combination of MRS and aRS could effectively control tomato BW and thus represents a promising new tool to control this disease.
Comorbid Medical Conditions as Predictors of Overall Survival in Glioblastoma Patients
Authors: Carr Matthew T. , Hochheimer Camille J. , Rock Andrew K. , Dincer Alper , Ravindra Lakshmi , Zhang Fan Lily , Opalak Charles F. , Poulos Nora , Sima Adam P. , Broaddus William C. 
Published: December 2019

AbstractGlioblastoma (GBM) is an aggressive central nervous system tumor with a poor prognosis. This study was conducted to determine any comorbid medical conditions that are associated with survival in GBM. Data were collected from medical records of all patients who presented to VCU Medical Center with GBM between January 2005 and February 2015. Patients who underwent surgery/biopsy were considered for inclusion. Cox proportional hazards regression modeling was performed to assess the relationship between survival and sex, race, and comorbid medical conditions. 163 patients met inclusion criteria. Comorbidities associated with survival on individual-characteristic analysis included: history of asthma (Hazard Ratio [HR]: 2.63; 95% Confidence Interval [CI]: 1.24–5.58; p = 0.01), hypercholesterolemia (HR: 1.95; 95% CI: 1.09–3.50; p = 0.02), and incontinence (HR: 2.29; 95% CI: 0.95–5.57; p = 0.07). History of asthma (HR: 2.22; 95% CI: 1.02–4.83; p = 0.04) and hypercholesterolemia (HR: 1.99; 95% CI: 1.11–3.56; p = 0.02) were associated with shorter survival on multivariable analysis. Surgical patients with GBM who had a prior history of asthma or hypercholesterolemia had significantly higher relative risk for mortality on individual-characteristic and multivariable analyses.
Proline improves switchgrass growth and development by reduced lignin biosynthesis
Authors: Guan Cong , Cen Hui-Fang , Cui Xin , Tian Dan-Yang , Tadesse Dimiru , Zhang Yun-Wei 
Published: December 2019

AbstractTransgenic switchgrass overexpressing Lolium perenne L. delta1-pyrroline 5-carboxylate synthase (LpP5CS) in group I (TG4 and TG6 line) and group II (TG1 and TG2 line) had significant P5CS and ProDH enzyme activities, with group I plants (TG4 and TG6) having higher P5CS and lower ProDH enzyme activity, while group II plants had higher ProDH and lower P5CS enzyme activity. We found group II transgenic plants showed stunted growth, and the changed proline content in overexpressing transgenic plants may influence the growth and development in switchgrass. RNA-seq analysis showed that KEGG enrichment included phenylpropanoid biosynthesis pathway among group I, group II and WT plants, and the expression levels of genes related to lignin biosynthesis were significantly up-regulated in group II. We also found that lignin content in group II transgenic plants was higher than that in group I and WT plants, suggesting that increased lignin content may suppress switchgrass growth and development. This study uncover that proline can appropriately reduce lignin biosynthesis to improve switchgrass growth and development. Therefore, appropriate reduction in lignin content and increase in biomass are important for bioenergy crop to lower processing costs for biomass fermentation-derived fuels.
Distinct pathways for zinc metabolism in the terrestrial slug Arion vulgaris
Authors: Dvorak Martin , Schnegg Raimund , Salvenmoser Willy , Palacios Òscar , Lindner Herbert , Zerbe Oliver , Hansel Armin , Leiminger Markus , Steiner Gerhard , Dallinger Reinhard , Lackner Reinhard 
Published: December 2019

AbstractIn most organisms, the concentration of free Zn2+ is controlled by metallothioneins (MTs). In contrast, no significant proportions of Zn2+ are bound to MTs in the slug, Arion vulgaris. Instead, this species possesses cytoplasmic low-molecular-weight Zn2+ (LMW Zn) binding compound that divert these metal ions into pathways uncoupled from MT metabolism. Zn2+ is accumulated in the midgut gland calcium cells of Arion vulgaris, where they associate with a low-molecular-weight ligand with an apparent molecular mass of ~ 2,000 Da. Mass spectrometry of the semi-purified LMW Zn binding compound combining an electrospray ion source with a differential mobility analyser coupled to a time-of-flight mass spectrometer revealed the presence of four Zn2+-containing ion signals, which arise from disintegration of one higher MW complex resulting in an ion-mobility diameter of 1.62 nm and a molecular mass of 837 Da. We expect that the novel Zn2+ ion storage pathway may be shared by many other gastropods, and particularly species that possess Cd-selective MT isoforms or variants with only very low affinity to Zn2+.