Os-186 and Os-187 Enrichments and High-He-3/He-4 sources in the Earth's Mantle: Evidence from Icelandic Picrites

Picrites from the neovolcanic zones in Iceland display a range in Os-187/Os-188O from 0.1297 to 0.1381 ((gamma)Os = 0.0 to 6.5) and uniform Os-186/Os-188 of 0.1198375+/-32 (2 (sigma)). The value for Os-186/Os-188 is within uncertainty of the present-day value for the primitive upper mantle of 0.1198398+/-16. These Os isotope systematics are best explained by ancient recycled crust or melt enrichment in the mantle source region. If so, then the coupled enrichments displayed in Os-186/Os-188 and Os-187/Os-188 from lavas of other plume systems must result from an independent process, the most viable candidate at present remains core-mantle interaction. While some plumes with high He-3/He-4, such as Hawaii, appear to have been subjected to detectable addition of Os (and possibly He) from the outer core, others such as Iceland do not. A positive correlation between Os-187/Os-188 and He-3/He-4 from 9.6 to 19 RA in Iceland picrites is best modeled as mixtures of 500 Ma or older ancient recycled crust mixed with primitive mantle, creating a hybrid source region that subsequently mixes with the convecting MORB mantle during ascent and melting. This multistage mechanism to explain these isotope systematics is consistent with ancient recycled crust juxtaposed with more primitive, relatively He-rich mantle, in convective isolation from the upper mantle, most likely in the lowermost mantle. This is inconsistent with models that propose random mixing between heterogeneities in the convecting upper mantle as a mechanism to explain the observed isotopic variation in oceanic lavas or models that produce a high He-3/He-4 signature in melt depleted and strongly outgassed, He-poor mantle. Instead these systematics require a deep mantle source to explain the 3He/4He signature in Iceland lavas. The He-3/He-4 of lavas derived from the Iceland plume changed over time, from a maximum of 50 RA at 60 Ma, to approximately 25-27 RA at present. The changes are coupled with distinct compositional gaps between the different aged lavas when H-3/He-4 is plotted versus various geochemical parameters such as Nd-143/Nd-144 and La/Sm. These relationships can be interpreted as an increase in the proportion of ancient recycled crust in the upwelling plume over this time period

Perventricular device closure of muscular ventricular septal defects on the beating heart: technique and results

AbstractObjectiveBoth surgical management and percutaneous device closure of muscular ventricular septal defects have drawbacks and limitations. This report describes our initial experience with intraoperative device closure of muscular ventricular septal defects without cardiopulmonary bypass in 6 consecutive patients.MethodsA median sternotomy or a subxiphoid minimally invasive incision was performed. Under continuous transesophageal echocardiographic guidance, the right ventricle free wall was punctured, and a wire was introduced across the largest defect. The Amplatzer (AGA Medical Corporation, Golden Valley, Minn) muscular ventricular septal defect occluding device (a self-expandable double-disk device) was used. An introducer sheath was fed over the wire, with the sheath tip positioned in the left ventricle cavity. The device was then advanced inside the sheath and deployed by retracting the sheath. Associated cardiac lesions, if any, can then be repaired during cardiopulmonary bypass. A similar technique can also be applied for periatrial closure of complex atrial septal defects.ResultsThe initial 6 patients are presented. Cardiopulmonary bypass was not needed in any patient for placement of the device and needed in 4 patients for repair of concomitant malformations only (double-outlet right ventricle, aortic arch hypoplasia, pulmonary artery band removal). No complications from using this technique occurred. Discharge echocardiograms showed no significant shunting across the ventricular septum.ConclusionsPerventricular closure of multiple muscular ventricular septal defects is safe and effective. We believe that this could become the treatment of choice for any infant with muscular ventricular septal defects or any child with muscular ventricular septal defect and associated cardiac defects

The structure of human 5-lipoxygenase

The synthesis of both proinflammatory leukotrienes and anti-inflammatory lipoxins requires the enzyme 5-lipoxygenase (5-LOX). 5-LOX activity is short-lived, apparently in part because of an intrinsic instability of the enzyme. We identified a 5-LOX-specific destabilizing sequence that is involved in orienting the carboxyl terminus, which binds the catalytic iron. Here, we report the crystal structure at 2.4 angstrom resolution of human 5-LOX stabilized by replacement of this sequence

Drawing out digital media: degrees of three dimensionality.

"Drawing Out Digital Media" is a research cluster based within Gray’s School of Art at Robert Gordon University. The cluster explores how new technologies might lead to new visual/physical/conceptual forms, and raise questions about existing definitions and established practices. The presentation discusses "Degrees of Three Dimensionality", a recent exhibition of work-in-progress by the cluster

Conversion of human 5-lipoxygenase to a 15-lipoxygenase by a point mutation to mimic phosphorylation at Serine-663

The enzyme 5-lipoxygenase (5-LOX) initiates biosynthesis of the proinflammatory leukotriene lipid mediators and, together with 15-LOX, is also required for synthesis of the anti-inflammatory lipoxins. The catalytic activity of 5-LOX is regulated through multiple mechanisms, including Ca 2+-targeted membrane binding and phosphorylation at specific serine residues. To investigate the consequences of phosphorylation at S663, we mutated the residue to the phosphorylation mimic Asp, providing a homogenous preparation suitable for catalytic and structural studies. The S663D enzyme exhibits robust 15-LOX activity, as determined by spectrophotometric and HPLC analyses, with only traces of 5-LOX activity remaining; synthesis of the anti-inflammatory lipoxin A4 from arachidonic acid is also detected. The crystal structure of the S663D mutant in the absence and presence of arachidonic acid (in the context of the previously reported Stable-5-LOX) reveals substantial remodeling of helices that define the active site so that the once fully encapsulated catalytic machinery is solvent accessible. Our results suggest that phosphorylation of 5-LOX at S663 could not only down-regulate leukotriene synthesis but also stimulate lipoxin production in inflammatory cells that do not express 15-LOX, thus redirecting lipid mediator biosynthesis to the production of proresolving mediators of inflammation. © FASEB

Pneumococcal carriage following PCV13 delivered as one primary and one booster dose (1 + 1) compared to two primary doses and a booster (2 + 1) in UK infants

In January 2020 the UK changed from a 2 + 1 schedule for 13-valent pneumococcal conjugate vaccine (PCV13) to a 1 + 1 schedule (doses at 3 and 12 months) based on a randomized immunogenicity trial comparing the two schedules. Carriage prevalence measured at the time of booster and 6 months later in 191 of the 213 study infants was 57 % (109/191) and 60 % (114/190) respectively. There were eight episodes of vaccine-type (VT) or vaccine-related 6C carriage in the 2 + 1 and six in the 1 + 1 group; ≥4-fold rises in serotype-specific IgG in 71 children with paired post-booster and follow up blood samples at 21–33 months of age were found in 20 % (7/35) of the 2 + 1 and 15 % (6/41) of the 1 + 1 group. VTs identified in carriage and inferred from serology were similar comprising 3, 19A and 19F. Dropping a priming dose from the 2 + 1 PCV 13 schedule did not increase VT carriage in the study cohort. Ongoing population level carriage studies will be important to confirm this

Monitoring the emergence of community transmission of influenza A/H1N1 2009 in England: a cross sectional opportunistic survey of self sampled telephone callers to NHS Direct

Objective To evaluate ascertainment of the onset of community transmission of influenza A/H1N1 2009 (swine flu) in England during the earliest phase of the epidemic through comparing data from two surveillance systems

Long-term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence.

BACKGROUND: Chronic infection with hepatitis B virus (HBV) arising in childhood is associated with hepatocellular carcinoma in adult life. Between 1986 and 1990, approximately 120,000 Gambian newborns were enrolled in a randomised controlled trial to assess the effectiveness of infant HBV vaccination on the prevention of hepatocellular carcinoma in adulthood. These children are now in adolescence and approaching adulthood, when the onset of sexual activity may challenge their hepatitis B immunity. Thus a booster dose in adolescence could be important to maintain long-term protection. METHODS: Fifteen years after the start of the HBV infant vaccination study, 492 vaccinated and 424 unvaccinated children were identified to determine vaccine efficacy against infection and carriage in adolescence. At the same time, 297 of the 492 infant-vaccinated subjects were randomly offered a booster dose of HBV vaccine. Anti-HBs was measured before the booster, and two weeks and 1 year afterwards (ISRCTN71271385). RESULTS: Vaccine efficacy 15 years after vaccination was 67.0% against infection as manifest by anti-HBc positivity (95% CI 58.2-74.6%), and 96.6% against HBsAg carriage (95% CI 91.5-100%). 31.2% of participants had detectable anti-HBs with a GMC of 32 IU/l. For 168 boosted participants GMC anti-HBs responses were 38 IU/l prior to vaccination, 524 IU/l two weeks after boosting, and 101 IU/l after 1 year. CONCLUSIONS: HBV vaccination in infants confers very good protection against carriage up to 15 years of age, although a large proportion of vaccinated subjects did not have detectable anti-HBs at this age. The response to boosting persisted for at least a year. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN71271385

Risk Factors for and Clinical Outcome of Congenital Cytomegalovirus Infection in a Peri-Urban West-African Birth Cohort

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide. Epidemiology and clinical outcomes are known to vary with socio-economic background, but few data are available from developing countries, where the overall burden of infectious diseases is frequently high. METHODOLOGY/PRINCIPAL FINDINGS: As part of an ongoing birth cohort study in The Gambia among term infants, urine samples were collected at birth and tested by PCR for the presence of CMV DNA. Risk factors for transmission and clinical outcome were assessed, including placental malaria infection. Babies were followed up at home monthly for morbidity and anthropometry, and at one year of age a clinical evaluation was performed. The prevalence of congenital CMV infection was 5.4% (40/741). A higher prevalence of hepatomegaly was the only significant clinical difference at birth. Congenitally infected children were more often first born babies (adjusted odds ratio (OR) 5.3, 95% confidence interval (CI) 2.0-13.7), more frequently born in crowded compounds (adjusted OR 2.9, 95%CI 1.0-8.3) and active placental malaria was more prevalent (adjusted OR 2.9, 95%CI 1.0-8.4). These associations were corrected for maternal age, bed net use and season of birth. During the first year of follow up, mothers of congenitally infected children reported more health complaints for their child. CONCLUSIONS/SIGNIFICANCE: In this study, the prevalence of congenital CMV among healthy neonates was much higher than previously reported in industrialised countries, and was associated with active placental malaria infection. There were no obvious clinical implications during the first year of life. The effect of early life CMV on the developing infant in the Gambia could be mitigated by environmental factors, such as the high burden of other infections.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Maintenance of Large Subpopulations of Differentiated CD8 T-Cells Two Years after Cytomegalovirus Infection in Gambian Infants

BACKGROUND: In a previously published study, we found that large differentiated subpopulations of CD8 T-cells emerged rapidly after CMV infection in young infants and persisted throughout the following year. Here we describe a follow-up study conducted on the same infants to establish whether the differentiated subpopulations continued through the second year post-infection. METHODOLOGY / PRINCIPAL FINDINGS: CMV-specific cells identified using tetramers remained more activated and differentiated than the overall CD8 population. The large subpopulation of differentiated cytotoxic (CD28(-)CD62L(-)Bcl-2(low)CD95(+)perforin(+)) cells that emerged rapidly after infection remained stable after two years. No similar subpopulation was found in CMV-uninfected infants indicating that two years after infection, CMV remained a major factor in driving CD8 T-cell differentiation. Although markers of activation (CD45R0 and HLA-D) declined throughout the first year, HLA-D expression continued to decline during the second year and CD45R0 expression increased slightly. The age-related increase in IFNgamma response observed during the first year continued but was non-significant during the second year, indicating that the rate of functional improvement had slowed substantially. CONCLUSIONS / SIGNIFICANCE: The large differentiated subpopulations of CD8 T-cells that had emerged immediately after CMV infection persisted through the second year post-infection, while levels of activation and functional capacity remained fairly constant.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe