Neuroprotective effect of Vinpocetine against 3- NP Induced reduction of body weight and oxidative stress in Rats

Huntington’s disease is a progressive, degenerative disease characterized by abnormal body movements symptoms like chorea and a reduction of body weight . Recently, it has been reported that oxidative stress, which is one of the pathological hallmarks of various neurodegenerative disorders, also plays an important role in the pathogenesis of Huntington’s disease.  3- Nitropropionic acid , a neurotoxin  treatment significantly reduction in body weight.  Intraperitoneal administration of 3-nitropropionic acid (10 mg/kg  for 14 days) caused significant loss of body weight and poor rentention of memory. Biochemical analysis revealed that 3-NP administration significantly increase in lipid peroxidation in the brains of rats.  The present study demonstrated that inhibition of type 1 phosphodiesterase (PDE1) by vinpocetine    (5, 10 & 20mg\kg) significantly reversed behavioral and biochemical dysfunction in 3-NP treated group. The result of the present study suggests facilitatory role of PDE1 enzyme in loss in body weight and oxidative stress following 3-NP injection

Neuroprotective effect of Vinpocetine against 3- NP Induced reduction of body weight and oxidative stress in Rats

Huntington’s disease is a progressive, degenerative disease characterized by abnormal body movements symptoms like chorea and a reduction of body weight . Recently, it has been reported that oxidative stress, which is one of the pathological hallmarks of various neurodegenerative disorders, also plays an important role in the pathogenesis of Huntington’s disease.  3- Nitropropionic acid , a neurotoxin  treatment significantly reduction in body weight.  Intraperitoneal administration of 3-nitropropionic acid (10 mg/kg  for 14 days) caused significant loss of body weight and poor rentention of memory. Biochemical analysis revealed that 3-NP administration significantly increase in lipid peroxidation in the brains of rats.  The present study demonstrated that inhibition of type 1 phosphodiesterase (PDE1) by vinpocetine    (5, 10 & 20mg\kg) significantly reversed behavioral and biochemical dysfunction in 3-NP treated group. The result of the present study suggests facilitatory role of PDE1 enzyme in loss in body weight and oxidative stress following 3-NP injection

Diffusion-negative MRI in acute ischemic stroke: a case report

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Risk of bias and the reporting of surgeons' experience in randomized controlled trials of total hip and total knee arthroplasty: A systematic review

Rationale, aims, and objectives: The potential bias introduced by surgeons' lack of comparable, relevant experience when performing the procedures in different arms of randomized controlled trials (RCTs) is arguably not well-managed or reported. The aim of this work was to review the frequency and nature with which surgeons' relevant experience is reported in RCTs of total hip (THA) and total knee arthroplasty (TKA), and to relate this to other risk of bias domains for this study design. Methods: A systematic review of RCTs comparing different minimally invasive procedures for TKA and comparisons of THA and hemiarthroplasty (HA). We searched MEDLINE, EMBASE, Science Citation Index, The Cochrane Library, Conference Proceedings Citation Index-Science (CPCI-S), Current Controlled Trials, and Clinical Trials.gov. Results: Seventy-five relevant RCTs were identified, 65 RCTs comparing minimally invasive with standard or other minimally invasive approaches to TKA, and 10 for THA compared with HA. Risk of bias based on the reported details of surgeons' relevant experience was categorized as low, high, or unclear. There was a clear distinction before and after 2009, with a substantial decrease in trials at high or unclear risk of bias after this date. There were no strong associations between this domain and other, standard risk of bias domains for RCTs. Conclusion: The surgeons' relevant experience in an evaluated procedure is often poorly reported but has improved since 2009. The variable is not adequately captured by any other risk of bias domain. Future work should concentrate on conducting research on a much larger sample of studies and in procedures other than knee and hip arthroplasty

Comparison of Quantitative Techniques including Xpert MTB/RIF to Evaluate Mycobacterial Burden

Introduction: Accurate quantification of mycobacterial load is important for the evaluation of patient infectiousness, disease severity and monitoring treatment response in human and in-vitro laboratory models of disease. We hypothesized that newer techniques would perform as well as solid media culture to quantify mycobacterial burden in laboratory specimens. Methods: We compared the turn-around-time, detection-threshold, dynamic range, reproducibility, relative discriminative ability, of 4 mycobacterial load determination techniques: automated liquid culture (BACTEC-MGIT-960), [3H]-uracil incorporation assays, luciferase-reporter construct bioluminescence, and quantitative PCR(Xpert -MTB/RIF) using serial dilutions of Mycobacterium bovis and Mycobacterium tuberculosis H37RV. Mycobacterial colony-forming-units(CFU) using 7H10-Middlebrook solid media served as the reference standard. Results: All 4 assays correlated well with the reference standard, however, bioluminescence and uracil assays had a detection threshold ≥1×103 organisms. By contrast, BACTEC-MGIT-960 liquid culture, although only providing results in days, was user-friendly, had the lowest detection threshold (<10 organisms), the greatest discriminative ability (1 vs. 10 organisms; p = 0.02), and the best reproducibility (coefficient of variance of 2% vs. 38% compared to uracil incorporation; p = 0.02). Xpert-MTB/RIF correlated well with mycobacterial load, had a rapid turn-around-time (<2 hours), was user friendly, but had a detection limit of ~100 organisms. Conclusions: Choosing a technique to quantify mycobacterial burden for laboratory or clinical research depends on availability of resources and the question being addressed. Automated liquid culture has good discriminative ability and low detection threshold but results are only obtained in days. Xpert MTB/RIF provides rapid quantification of mycobacterial burden, but has a poorer discrimination and detection threshold

BLM and RMI1 alleviate RPA inhibition of topoIIIα decatenase activity

RPA is a single-stranded DNA binding protein that physically associates with the BLM complex. RPA stimulates BLM helicase activity as well as the double Holliday junction dissolution activity of the BLM-topoisomerase IIIα complex. We investigated the effect of RPA on the ssDNA decatenase activity of topoisomerase IIIα. We found that RPA and other ssDNA binding proteins inhibit decatenation by topoisomerase IIIα. Complex formation between BLM, TopoIIIα, and RMI1 ablates inhibition of decatenation by ssDNA binding proteins. Together, these data indicate that inhibition by RPA does not involve species-specific interactions between RPA and BLM-TopoIIIα-RMI1, which contrasts with RPA modulation of double Holliday junction dissolution. We propose that topoisomerase IIIα and RPA compete to bind to single-stranded regions of catenanes. Interactions with BLM and RMI1 enhance toposiomerase IIIα activity, promoting decatenation in the presence of RPA

Probing anomalous tbW couplings in single-top production using top polarization at the Large Hadron Collider

We study the sensitivity of the Large Hadron Collider (LHC) to anomalous tbW couplings in single-top production in association with a W^- boson followed by semileptonic decay of the top. We calculate top polarization and the effects of these anomalous couplings to it at two centre-of-mass (cm) energies of 7 TeV and 14 TeV. As a measure of top polarization, we look at various laboratory frame distributions of its decay products, viz., lepton angular and energy distributions and b-quark angular distributions, without requiring reconstruction of the rest frame of the top, and study the effect of anomalous couplings on these distributions. We construct certain asymmetries to study the sensitivity of these distributions to anomalous tbW couplings. We find that 1\sigma limits on real and imaginary parts of the dominant anomalous coupling Ref_{2R} which may be obtained by utilizing these asymmetries at the LHC with cm energy of 14 TeV and an integrated luminosity of 10 fb^{-1} will be significantly better than the expectations from direct measurements of cross sections and some other variables at the LHC and over an order of magnitude better than the indirect limits.Comment: 25 pages, 34 figure

Next-generation sequencing using microfluidic PCR enrichment for molecular autopsy.

BACKGROUND: We aimed to determine the mutation yield and clinical applicability of "molecular autopsy" following sudden arrhythmic death syndrome (SADS) by validating and utilizing low-cost high-throughput technologies: Fluidigm Access Array PCR-enrichment with Illumina HiSeq 2000 next generation sequencing (NGS). METHODS: We validated and optimized the NGS platform with a subset of 46 patients by comparison with Sanger sequencing of coding exons of major arrhythmia risk-genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, RYR2). A combined large multi-ethnic international SADS cohort was sequenced utilizing the NGS platform to determine overall molecular yield; rare variants identified by NGS were subsequently reconfirmed by Sanger sequencing. RESULTS: The NGS platform demonstrated 100% sensitivity for pathogenic variants as well as 87.20% sensitivity and 99.99% specificity for all substitutions (optimization subset, n = 46). The positive predictive value (PPV) for NGS for rare substitutions was 16.0% (27 confirmed rare variants of 169 positive NGS calls in 151 additional cases). The overall molecular yield in 197 multi-ethnic SADS cases (mean age 22.6 ± 14.4 years, 68% male) was 5.1% (95% confidence interval 2.0-8.1%), representing 10 cases carrying pathogenic or likely pathogenic risk-mutations. CONCLUSIONS: Molecular autopsy with Fluidigm Access Array and Illumina HiSeq NGS utilizing a selected panel of LQTS/BrS and CPVT risk-genes offers moderate diagnostic yield, albeit requiring confirmatory Sanger-sequencing of mutational variants

Arctic marine secondary organic aerosol contributes significantly to summertime particle size distributions in the Canadian Arctic Archipelago

Summertime Arctic aerosol size distributions are strongly controlled by natural regional emissions. Within this context, we use a chemical transport model with sizeresolved aerosol microphysics (GEOS-Chem-TOMAS) to interpret measurements of aerosol size distributions from the Canadian Arctic Archipelago during the summer of 2016, as part of the "NETwork on Climate and Aerosols: Addressing key uncertainties in Remote Canadian Environments" (NETCARE) project. Our simulations suggest that condensation of secondary organic aerosol (SOA) from precursor vapors emitted in the Arctic and near Arctic marine (ice-free seawater) regions plays a key role in particle growth events that shape the aerosol size distributions observed at Alert (82.5° N, 62.3° W), Eureka (80.1° N, 86.4° W), and along a NETCARE ship track within the Archipelago. We refer to this SOA as Arctic marine SOA (AMSOA) to reflect the Arctic marine-based and likely biogenic sources for the precursors of the condensing organic vapors. AMSOA from a simulated flux (500 μgm-2 day-1, north of 50° N) of precursor vapors (with an assumed yield of unity) reduces the summertime particle size distribution model-observation mean fractional error 2- to 4-fold, relative to a simulation without this AMSOA. Particle growth due to the condensable organic vapor flux contributes strongly (30 %-50 %) to the simulated summertime-mean number of particles with diameters larger than 20 nm in the study region. This growth couples with ternary particle nucleation (sulfuric acid, ammonia, and water vapor) and biogenic sulfate condensation to account for more than 90% of this simulated particle number, which represents a strong biogenic influence. The simulated fit to summertime size-distribution observations is further improved at Eureka and for the ship track by scaling up the nucleation rate by a factor of 100 to account for other particle precursors such as gas-phase iodine and/or amines and/or fragmenting primary particles that could be missing from our simulations. Additionally, the fits to the observed size distributions and total aerosol number concentrations for particles larger than 4 nm improve with the assumption that the AMSOA contains semivolatile species: the model-observation mean fractional error is reduced 2- to 3-fold for the Alert and ship track size distributions. AMSOA accounts for about half of the simulated particle surface area and volume distributions in the summertime Canadian Arctic Archipelago, with climaterelevant simulated summertime pan-Arctic-mean top-of-theatmosphere aerosol direct (-0:04Wm-2) and cloud-albedo indirect (-0:4Wm-2) radiative effects, which due to uncertainties are viewed as an order of magnitude estimate. Future work should focus on further understanding summertime Arctic sources of AMSOA

Mechanism of Werner DNA Helicase: POT1 and RPA Stimulates WRN to Unwind beyond Gaps in the Translocating Strand

WRN belongs to the RecQ family of DNA helicases and it plays a role in recombination, replication, telomere maintenance and long-patch base excision repair. Here, we demonstrate that WRN efficiently unwinds DNA substrates containing a 1-nucleotide gap in the translocating DNA strand, but when the gap size is increased to 3-nucleotides unwinding activity significantly declines. In contrast, E. coli UvrD (3′→5′ helicase), which recognizes nicks in DNA to initiate unwinding, does not unwind past a 1-nucleotide gap. This unique ability of WRN to bypass gaps supports its involvement in DNA replication and LP-BER where such gaps can be produced by glycosylases and the apurinic/apyrimidinic endonuclease 1 (APE1). Furthermore, we tested telomere repeat binding factor 2 (TRF2), both variants 1 and 2 of protector of telomeres 1 (POT1v1 and POT1v2) and RPA on telomeric DNA substrates containing much bigger gaps than 3-nucleotides in order to determine whether unwinding could be facilitated through WRN-protein interaction. Interestingly, POT1v1 and RPA are capable of stimulating WRN helicase on gapped DNA and 5′-overhang substrates, respectively