Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical characterization and solution structure of nitrous oxide reductase from Alcaligenes xylosoxidans (NCIMB 11015).

Nitrous oxide reductase (N2OR) is the terminal enzyme involved in denitrification by microbes. No three-dimensional structural information has been published for this enzyme. We have isolated and characterised N2OR from Alcaligenes xylosoxidans (AxN2OR) as a homodimer of M(r) 134,000 containing seven to eight copper atoms per dimer. Comparison of sequence and compositional data with other N2ORs suggests that AxN2OR is typical and can be expected to have similar domain folding and subunit structure to other members of this family of enzymes. We present synchrotron X-ray-scattering data, analysed using a model-independent method for shape restoration, which gave a approximately 20 A resolution structure of the enzyme in solution, providing a glimpse of the structure of any N2OR and shedding light on the molecular architecture of the molecule. The specific activity of AxN2OR was approximately 6 mumol of N2O reduced.min-1. (mg of protein)-1; N2OR activity showed both base and temperature activation. The visible spectrum exhibited an absorption maximum at 550 nm with a shoulder at 635 nm. On oxidation with K3Fe(CN)6, the absorption maximum shifted to 540 nm and a new shoulder at 480 nm appeared. Reduction under anaerobic conditions resulted in the formation of an inactive blue form of the enzyme with a broad absorption maximum at 650 nm. As isolated, the enzyme shows an almost featureless EPR spectrum, which changes on oxidation to give an almost completely resolved seven-line hyperfine signal in the gII region, g = 2.18, with AII = 40 G, consistent with the enzyme being partially reduced as isolated. Both the optical and EPR spectra of the oxidized enzyme are characteristic of the presence of a CuA centre.
Belowground Bud Bank Distribution and Aboveground Community Characteristics along Different Moisture Gradients of Alpine Meadow in the Zoige Plateau, China

The belowground bud bank plays an important role in plant communities succession and maintenance. In order to understand the response of the bud bank to the sod layer moisture, we investigated the bud bank distribution, size, and composition of six different water gradient alpine meadows through excavating in the Zoige Plateau. The results showed: (1) The alpine meadow plant belowground buds were mainly distributed in the 0–10 cm sod layer, accounting for 74.2%–100% of the total. The total bud density of the swamp wetland and degraded meadow was the highest (16567.9 bud/m3) and the lowest (4839.5 bud/m3). (2) A decrease of the moisture plant diversity showed a trend of increasing first and then decreasing. Among six alpine meadows the swamp meadow plant diversity was the highest, and species richness, Simpson, Shannon–Wiener, and Pielou were 10.333, 0.871, 0.944, and 0.931, respectively. (3) The moisture was significantly positively correlated with the total belowground buds and short rhizome bud density. There were significant positive correlations with sod layer moisture and tiller bulb bud density. This study indicates that the moisture affected bud bank distribution and composition in the plant community, and the results provide important information for predicting plant community succession in the alpine meadow with future changes in precipitation patterns.
The influence of environment, as represented by diet and air pollution, upon incidence and prevalence of wheezing illnesses in young children

Purpose of reviewThe purpose of this review is to consider the collective influence of factors affecting recurrent wheezing in young children. Recent findingsSpecific allergen sensitization, upper respiratory infections, genetic polymorphisms and environmental factors have collectively been reported in the prevalence of and induction of recurrent wheezing in young children. Two examples of environmental factors are diet and exposure to air pollution, both of which are potentially modifiable. Recent investigations provide evidence that a ‘Mediterranean diet’ and a diet that emphasizes polyunsaturated fatty acids during pregnancy and early infancy, as well as breastfeeding, may be protective for wheezing, and that exposure to traffic-related pollution may be an independent factor in the incidence of wheezing in young children. SummaryRecent studies of early childhood wheezing demonstrate a potentially protective effect of diet and exposure to air pollution as a significant risk factor. An evaluation of collective factors influencing the presence of disease may help to broaden the clinical assessment and give parents and physicians the opportunity to potentially modify circumstances that promote the incidence of recurrent wheezing in infants and preschool aged children.
Experiences of French Speaking Immigrants and Non-immigrants Accessing Health Care Services in a Large Canadian City

French speakers residing in predominantly English-speaking communities have been linked to difficulties accessing health care. This study examined health care access experiences of immigrants and non-immigrants who self-identify as Francophone or French speakers in a mainly English speaking province of Canada. We used semi-structured interviews to gather opinions of recent users of physician and hospital services (N = 26). Language barriers and difficulties finding family doctors were experienced by both French speaking immigrants and non-immigrants alike. This was exacerbated by a general preference for health services in French and less interest in using language interpreters during a medical consultation. Some participants experienced emotional distress, were discontent with care received, often delayed seeking care due to language barriers. Recent immigrants identified lack of insurance coverage for drugs, transportation difficulties and limited knowledge of the healthcare system as major detractors to achieving health. This study provided the groundwork for future research on health issues of official language minorities in Canada.
Host-Seeking Mosquito Distribution in Habitat Mosaics of Southern Great Plains Cross-Timbers

ABSTRACT Landscape fragmentation often increases contact between humans, wildlife, and potential disease vectors. We examined how adult host-seeking mosquitoes respond to small-scale habitat differences within southern Great Plains cross-timber habitat mosaics in northern Oklahoma consisting of eastern red cedar (Juniperus virginianus L.) woodlands, mixed-deciduous woodlands, and adjacent grasslands. Mosquitoes responded most markedly to an overall grassland-woodland habitat gradient, with species separating by habitat based largely on tree density. Differences in abundance of host-seeking females occurred at fine spatial scales, sometimes varying dramatically over distances as little as 200 m when tree density changed abruptly. Tree type was not as important as tree density, although the West Nile virus vector Culex tarsalis Coquillett showed a greater affinity for areas containing eastern red cedar than for deciduous woodlands. The invasive Aedes albopictus Skuse showed equal affinity for both tree types. Conversion of grassland habitats in the Great Plains to more vegetated environments associated with humans (towns and homesteads) and the invasion of grasslands by eastern red cedar may change the species composition of mosquito, bird, and mammal assemblages and potentially alter arbovirus exposure for humans.
Dynamic behaviors of SF6 discharge process in short parallel-plate gaps

The two-dimensional hydrodynamic discharge model is presented based on the hydrodynamic mechanics theory and gas discharge characteristics, with a uniform applied field, during the discharge process of SF6 at atmospheric pressure, and it is established by adopting Poisson equation in conjunction with the continuity equations for electrons, negative and positive ions, besides, the photo - ionization is also considered in the proposed model. The Finite Difference-Flux Corrected Transport technique is used in numerical simulation of discharge process, in order to improve the accuracy and efficiency. Then the gap-space electric field distribution, space ions distribution are revealed from the microscopic mechanism, and the evolutions of the charged particles are obtained in detail, furthermore, the tempo-spatial critical point of the avalanche-to-streamer in this model is discovered, the influence of applied voltage and initial plasma charge density on the streamer characteristic are also investigated. The results show that the initial plasma charge density is closely related to the gradient slope of the gap-space electric field distribution and electron density distribution, meanwhile, the electric field strength, the propagation velocity and charge density of the streamer head increase with increasing applied voltage. Above results analysis can be in favor of further study of the discharge mechanism and provide the theoretical support for electrical equipment designed.
Non-redundant Signal Transduction of Interleukin-6-type Cytokines

The common use of the cytokine receptor gp130 has served as an explanation for the extremely redundant biological activities exerted by interleukin (IL)-6-type cytokines. Indeed, hardly any differences in signal transduction initiated by these cytokines are known. In the present study, we demonstrate that oncostatin M (OSM), but not IL-6 or leukemia inhibitory factor, induces tyrosine phosphorylation of the Shc isoforms p52 and p66 and their association with Grb2. Concomitantly, OSM turns out to be a stronger activator of ERK1/2 MAPKs. Shc is recruited to the OSM receptor (OSMR), but not to gp130. Binding involves Tyr861 of the OSMR, located within a consensus binding sequence for the Shc PTB domain. Moreover, Tyr861 is essential for activation of ERK1/2 and for full activation of the α2-macroglobulin promoter, but not for an exclusively STAT-responsive promoter. This study therefore provides evidence for qualitative differential signaling mechanisms exerted by IL-6-type cytokines.
Anti-SEMA3A Antibody: A Novel Therapeutic Agent to Suppress Glioblastoma Tumor Growth

Purpose Glioblastoma (GBM) is classified as one of the most aggressive and lethal brain tumor. Great strides have been made in understanding the genomic and molecular underpinnings of GBM, which translated into development of new therapeutic approaches to combat such deadly disease. However, there are only few therapeutic agents that can effectively inhibit GBM invasion in a clinical framework. In an effort to address such challenges, we have generated anti-SEMA3A monoclonal antibody as a potential therapeutic antibody against GBM progression. Materials and Methods We employed public glioma datasets, Repository of Molecular Brain Neoplasia Data and The Cancer Genome Atlas, to analyze SEMA3A mRNA expression in human GBM specimens. We also evaluated for protein expression level of SEMA3A via tissue microarray (TMA) analysis. Cell migration and proliferation kinetics were assessed in various GBM patient-derived cells (PDCs) and U87-MG cell-line for SEMA3A antibody efficacy. GBM patient-derived xenograft (PDX) models were generated to evaluate tumor inhibitory effect of anti-SEMA3A antibody in vivo. Results By combining bioinformatics and TMA analysis, we discovered that SEMA3A is highly expressed in human GBM specimens compared to non-neoplastic tissues. We developed three different anti-SEMA3A antibodies, in fully human IgG form, through screening phage-displayed synthetic antibody library using a classical panning method. Neutralization of SEMA3A significantly reduced migration and proliferation capabilities of PDCs and U87-MG cell line in vitro. In PDX models, treatment with anti-SEMA3A antibody exhibited notable tumor inhibitory effect through down-regulation of cellular proliferative kinetics and tumor-associated macrophages recruitment. Conclusion In present study, we demonstrated tumor inhibitory effect of SEMA3A antibody in GBM progression and present its potential relevance as a therapeutic agent in a clinical framework.
A Combination RNAi-Chemotherapy Layer-by-Layer Nanoparticle for Systemic Targeting of KRAS/P53 with Cisplatin to Treat Non–Small Cell Lung Cancer

Purpose: Mutation of the Kirsten ras sarcoma viral oncogene homolog (KRAS) and loss of p53 function are commonly seen in patients with non–small cell lung cancer (NSCLC). Combining therapeutics targeting these tumor-defensive pathways with cisplatin in a single-nanoparticle platform are rarely developed in clinic. Experimental Design: Cisplatin was encapsulated in liposomes, which multiple polyelectrolyte layers, including siKRAS and miR-34a were built on to generate multifunctional layer-by-layer nanoparticle. Structure, size, and surface charge were characterized, in addition to in vitro toxicity studies. In vivo tumor targeting and therapy was investigated in an orthotopic lung cancer model by microCT, fluorescence imaging, and immunohistochemistry. Results: The singular nanoscale formulation, incorporating oncogene siKRAS, tumor-suppressor stimulating miR-34a, and cisplatin, has shown enhanced toxicity against lung cancer cell line, KP cell. In vivo, systemic delivery of the nanoparticles indicated a preferential uptake in lung of the tumor-bearing mice. Efficacy studies indicated prolonged survival of mice from the combination treatment. Conclusions: The combination RNA-chemotherapy in an LbL formulation provides an enhanced treatment efficacy against NSCLC, indicating promising potential in clinic. Clin Cancer Res; 23(23); 7312–23. ©2017 AACR.
Salvage chemotherapy using gemcitabine for taxane/platinum-resistant recurrent ovarian cancer: a single institutional experience.

BACKGROUND The purpose of this study was to report on the safety and efficacy of gemcitabine used as salvage chemotherapy for ovarian cancer. PATIENTS AND METHODS From January 2002 to October 2011, 27 patients were treated with gemcitabine for platinum-resistant recurrent ovarian cancer. Gemcitabine (800 mg/m(2)) was given on days 1, 8, and 15 of every 28 days. The patients' medical records were retrospectively reviewed. RESULTS All 27 patients had previously received paclitaxel/carboplatin doublet and their disease had become platinum-resistant. The median number of previous chemotherapy regimens was 2 (range 1-7). A total of 114 cycles of single-agent gemcitabine were administered, with a median of 3 (range 1-10). No complete responses were observed. Partial response (PR) was observed in five patients (18.5%). Eight patients demonstrated stable disease (SD). The median duration of response for 5 responders was 4 months (range 2-6 months). The median survival time was 15 months. Patients with PR or SD (n=13) had significantly better survival compared with the group with progressive disease (n=14) (p=0.03, by univariate analysis). In addition, multivariate Cox proportional hazards analysis revealed that responses to gemcitabine were a significant factor for survival (hazard ratio=0.08, 95% confidence interval=0.0138 to 0.5614, p=0.01). Cases with hematological toxicity included 10 patients (37.0%) with grade 3/4 neutropenia, 3 patients (11.1%) with grade 3 thrombocytopenia, and 3 patients (11.1%) with grade 3 anemia. Non-hematological toxicity was well-tolerated. CONCLUSION Gemcitabine (800 mg/m(2)) used for recurrent ovarian cancer possesses a modest activity and a well-tolerated toxicity.
Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction

Introduction: The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. Materials and Methods: IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. Results: IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. Conclusions: IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR.
Long-Term Follow-Up in 128 Patients With Primary Antiphospholipid Syndrome: Do They Develop Lupus?

Abstract: We retrospectively studied a large cohort of patients with primary antiphospholipid syndrome (APS) from 4 different referral centers to analyze the clinical and serologic features and, specifically, to determine the number of patients going on to develop systemic lupus erythematosus (SLE) or other autoimmune disease after long-term follow-up. The study included 128 unselected patients with primary APS who fulfilled the Sapporo International Criteria from 4 different tertiary hospitals in the United Kingdom, Mexico, and Spain. The patients had attended the referral centers between January 1987 and July 2001. We reviewed clinical and serologic characteristics according to a pre-established protocol. We used univariate analysis with the chi-squared or Fisher exact test and logistic regression to analyze possible factors related to the coexistence of SLE and APS. Ninety-seven female and 31 male patients fulfilled the criteria, with a median age of 42 ± 12 years (range, 16-79 yr), and with a mean follow-up of 9 ± 3 years (range, 2-15 yr). The main manifestations included deep vein thrombosis in 62 patients (48%), arterial thrombosis in 63 (49%) patients, pregnancy loss in 177/320 (55%) cases, and pulmonary embolism in 37 (30%) patients. Other clinical manifestations were migraine in 51 (40%) patients, thrombocytopenia in 48 (38%), livedo reticularis in 47 (37%), and valvular disease in 27 (21%). Serologic findings were anticardiolipin antibodies (aCL) IgG positive in 110 (86%) patients, aCL IgM in 36 (39%), lupus anticoagulant in 71 (65%), antinuclear antibodies in 47 (37%), and positive Coombs test in 5 (4%) patients. During the follow-up and after a median disease duration of 8.2 years (range, 1-14 yr), 11 (8%) patients developed SLE, 6 (5%) developed lupus-like disease, and 1 (1%) developed myasthenia gravis. The remaining 110 patients (86%) continued to have primary APS. After the univariate analysis, a family history of lupus, the presence of Raynaud phenomenon, migraine, psychiatric features, multiple sclerosis-like features, hemolytic anemia, low C3 and C4, and Coombs positivity conferred a statistically significant risk for the subsequent development of SLE (p < 0.05). Only the presence of Coombs positivity had statistical significance (odds ratio, 66.4; 95% confidence interval, 1.6-2714; p = 0.027) after the logistic regression evaluation. The current study confirms that progression from primary APS to SLE or lupus-like disease is unusual, even after a long follow-up. Only 3 patients developed anti-dsDNA antibodies. The presence of a positive Coombs test might be a marker for the development of SLE in patients with primary APS. Abbreviations: aCL = anticardiolipin antibodies, ANA = antinuclear antibodies, aPL = antiphospholipid antibodies, APS = antiphospholipid syndrome, ENA = extractable nuclear antigens, INR = International Normalized Ratio, LLD = lupus-like disease, MRI = magnetic resonance imaging, MS = multiple sclerosis, SLE = systemic lupus erythematosus, TIA = transient ischemic attack.
Attitudes of Canadian Nephrologists toward Dialysis Modality Selection

Objective To determine the opinions and attitudes of Canadian nephrologists about dialysis modality decisions and optimal dialysis system design. Participants Members of the Canadian Society of Nephrology. Intervention A mailed survey questionnaire. Results A 66% response rate was obtained. Decisions about modality are reported to be based most strongly on patient preference (4.4 on a scale from 1 to 5), followed by quality of life (4.06), morbidity (3.97), mortality (3.85), and rehabilitation (3.69), while neither facility (1.78) nor physician (1.62) reimbursement are important. When asked about the current relative utilization of each modality, nephrologists felt that hospital-based hemodialysis (HD) is slightly overutilized (2.53), continuous ambulatory peritoneal dialysis (CAPD) is about right (3.00), while cycler peritoneal dialysis (PD) (3.53), community-based full (3.83) and self-care HD (3.91), and home HD (4.02) are underutilized. A hypothetical question about optimal distribution to maximize survival revealed that a type of HD should constitute 62.8% of the mix, with more emphasis on cycler PD (14.9%), community-based full care HD (13.8%), self-care HD (14.5%), and home HD (9.0%) than is current practice. However, when the goal was to maximize cost effectiveness, HD fell slightly to 57.8%. Conclusions These survey results suggest that the current national average 66%/34% HD/PD ratio is reasonable. However, there appears to be a consensus that Canada could evolve to a more cost-effective, community-based dialysis system without compromising patient outcomes.
Association between ABCB1 polymorphism and response to sodium valproate treatment in Malaysian epilepsy patients

Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypes were assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.