CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression.

Pulmonary delivery of plasmid DNA (pDNA)/cationic liposome complexes is associated with an acute unmethylated CG dinucleotide (CpG)-mediated inflammatory response and brief duration of transgene expression. We demonstrate that retention of even a single CpG in pDNA is sufficient to elicit an inflammatory response, whereas CpG-free pDNA vectors do not. Using a CpG-free pDNA expression vector, we achieved sustained (≥56 d) in vivo transgene expression in the absence of lung inflammation

Genetic Association for Renal Traits among Participants of African Ancestry Reveals New Loci for Renal Function

Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m2), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10−7) and FNDC1 (p-value = 3.0×10−7) for UACR, and KCNQ1 with eGFR (p = 3.6×10−6). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish

The Uptake of Integrated Perinatal Prevention of Mother-to-Child HIV Transmission Programs in Low- and Middle-Income Countries: A Systematic Review

BACKGROUND: The objective of this review was to assess the uptake of WHO recommended integrated perinatal prevention of mother-to-child transmission (PMTCT) of HIV interventions in low- and middle-income countries. METHODS AND FINDINGS: We searched 21 databases for observational studies presenting uptake of integrated PMTCT programs in low- and middle-income countries. Forty-one studies on programs implemented between 1997 and 2006, met inclusion criteria. The proportion of women attending antenatal care who were counseled and who were tested was high; 96% (range 30-100%) and 81% (range 26-100%), respectively. However, the overall median proportion of HIV positive women provided with antiretroviral prophylaxis in antenatal care and attending labor ward was 55% (range 22-99%) and 60% (range 19-100%), respectively. The proportion of women with unknown HIV status, tested for HIV at labor ward was 70%. Overall, 79% (range 44-100%) of infants were tested for HIV and 11% (range 3-18%) of them were HIV positive. We designed two PMTCT cascades using studies with outcomes for all perinatal PMTCT interventions which showed that an estimated 22% of all HIV positive women attending antenatal care and 11% of all HIV positive women delivering at labor ward were not notified about their HIV status and did not participate in PMTCT program. Only 17% of HIV positive antenatal care attendees and their infants are known to have taken antiretroviral prophylaxis. CONCLUSION: The existing evidence provides information only about the initial PMTCT programs which were based on the old WHO PMTCT guidelines. The uptake of counseling and HIV testing among pregnant women attending antenatal care was high, but their retention in PMTCT programs was low. The majority of women in the included studies did not receive ARV prophylaxis in antenatal care; nor did they attend labor ward. More studies evaluating the uptake in current PMTCT programs are urgently needed

Search for effective Lorentz and CPT violation using ZEUS data

Lorentz and CPT symmetry in the quark sector of the Standard Model are studied in the context of an effective field theory using ZEUS e±p data. Symmetry-violating effects can lead to time-dependent oscillations of otherwise time-independent observables, including scattering cross sections. An analysis using five years of inclusive neutral-current deep inelastic scattering events corresponding to an integrated HERA luminosity of 372 pb-1 at s=318 GeV has been performed. No evidence for oscillations in sidereal time has been observed within statistical and systematic uncertainties. Constraints, most for the first time, are placed on 42 coefficients parametrizing dominant CPT-even dimension-four and CPT-odd dimension-five spin-independent modifications to the propagation and interaction of light quarks

Scaled momentum distributions for K-S(0) and Λ /̄ Λ in DIS at HERA

Scaled momentum distributions for the strange hadrons K0S and Λ/Λ¯ were measured in deep inelastic ep scattering with the ZEUS detector at HERA using an integrated luminosity of 330 pb−1. The evolution of these distributions with the photon virtuality, Q 2, was studied in the kinematic region 10 < Q 2  < 40000 GeV2 and 0.001 < x < 0.75, where x is the Bjorken scaling variable. Clear scaling violations are observed. Predictions based on different approaches to fragmentation were compared to the measurements. Leading-logarithm parton-shower Monte Carlo calculations interfaced to the Lund string fragmentation model describe the data reasonably well in the whole range measured. Next-to-leading-order QCD calculations based on fragmentation functions, FFs, extracted from e + e − data alone, fail to describe the measurements. The calculations based on FFs extracted from a global analysis including e + e −, ep and pp data give an improved description. The measurements presented in this paper have the potential to further constrain the FFs of quarks, anti-quarks and gluons yielding K0S and Λ/Λ¯ strange hadrons

Impact of jet-production data on the next-to-next-to-leading-order determination of HERAPDF2.0 parton distributions

The HERAPDF2.0 ensemble of parton distribution functions (PDFs) was introduced in 2015. The final stage is presented, a next-to-next-to-leading-order (NNLO) analysis of the HERA data on inclusive deep inelastic ep scattering together with jet data as published by the H1 and ZEUS collaborations. A perturbative QCD fit, simultaneously of αs(M2Z) and the PDFs, was performed with the result αs(M2Z)=0.1156±0.0011 (exp) +0.0001−0.0002 (model +parameterisation) ±0.0029 (scale). The PDF sets of HERAPDF2.0Jets NNLO were determined with separate fits using two fixed values of αs(M2Z), αs(M2Z)=0.1155 and 0.118, since the latter value was already chosen for the published HERAPDF2.0 NNLO analysis based on HERA inclusive DIS data only. The different sets of PDFs are presented, evaluated and compared. The consistency of the PDFs determined with and without the jet data demonstrates the consistency of HERA inclusive and jet-production cross-section data. The inclusion of the jet data reduced the uncertainty on the gluon PDF. Predictions based on the PDFs of HERAPDF2.0Jets NNLO give an excellent description of the jet-production data used as input