Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?

<p><b>Background:</b> Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.</p> <p><b>Methods and Findings:</b> In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).</p> <p><b>Conclusions:</b> In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.</p&gt

Atmospheric trace gases support primary production in Antarctic desert surface soil

LetterCultivation-independent surveys have shown that the desert soils of Antarctica harbour surprisingly rich microbial communities¹⁻³. Given that phototroph abundance varies across these Antarctic soils²·⁴, an enduring question is what supports life in those communities with low photosynthetic capacity³·⁵. Here we provide evidence that atmospheric trace gases are the primary energy sources of two Antarctic surface soil communities. We reconstructed 23 draft genomes from metagenomic reads, including genomes from the candidate bacterial phyla WPS-2 and AD3. The dominant community members encoded and expressed high-affinity hydrogenases, carbon monoxide dehydrogenases, and a RuBisCO lineage known to support chemosynthetic carbon fixation⁶·⁷. Soil microcosms aerobically scavenged atmospheric H₂ and CO at rates sufficient to sustain their theoretical maintenance energy and mediated substantial levels of chemosynthetic but not photosynthetic CO₂ fixation. We propose that atmospheric H₂, CO₂ and CO provide dependable sources of energy and carbon to support these communities, which suggests that atmospheric energy sources can provide an alternative basis for ecosystem function to solar or geological energy sources⁸·⁹. Although more extensive sampling is required to verify whether this process is widespread in terrestrial Antarctica and other oligotrophic habitats, our results provide new understanding of the minimal nutritional requirements for life and open the possibility that atmospheric gases support life on other planets.Mukan Ji, Chris Greening, Inka Vanwonterghem, Carlo R. Carere, Sean K. Bay, Jason A. Steen, Kate Montgomery, Thomas Lines, John Beardall, Josie van Dorst, Ian Snape, Matthew B. Stott, Philip Hugenholtz & Belinda C. Ferrar

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Microbial Influence on Arsenic Speciation: In Search of the Origins of Arsenic Resistance

Early life on Earth had to cope with heat, acidity and high dissolved metal(loid) concentrations. Arsenic (As) is one metalloid enriched in geothermal waters. In order to survive toxic arsenic levels, microorganisms developed arsenic resistance mechanisms for arsenic species present at that time. Modern hot springs provide an analog to early Earth conditions in terms of temperature and dissolved arsenic concentrations. The nucleic acid data suggest a hyperthermophilic root of life, which supports the hypothesis of hot springs providing ideal conditions to investigate the evolution of microbial arsenic resistance. Geothermal pools in Wai-O-Tapu, New Zealand, with different temperature, pH and redox condition were studied for their arsenic speciation and microbial diversity. On an Eh-pH diagram, all pools plotted within the arsenite (H 3AsO 3) stability field. Alongside arsenite, however, HPLC-ICPMS analyses also detected arsenate, organic arsenic and unknown arsenic species, suggesting active microbial transformation of As[III] via one or more arsenic resistance mechanisms

Microbial Influence on Arsenic Speciation: In Search of the Origins of Arsenic Resistance

Early life on Earth had to cope with heat, acidity and high dissolved metal(loid) concentrations. Arsenic (As) is one metalloid enriched in geothermal waters. In order to survive toxic arsenic levels, microorganisms developed arsenic resistance mechanisms for arsenic species present at that time. Modern hot springs provide an analog to early Earth conditions in terms of temperature and dissolved arsenic concentrations. The nucleic acid data suggest a hyperthermophilic root of life, which supports the hypothesis of hot springs providing ideal conditions to investigate the evolution of microbial arsenic resistance. Geothermal pools in Wai-O-Tapu, New Zealand, with different temperature, pH and redox condition were studied for their arsenic speciation and microbial diversity. On an Eh-pH diagram, all pools plotted within the arsenite (H 3AsO 3) stability field. Alongside arsenite, however, HPLC-ICPMS analyses also detected arsenate, organic arsenic and unknown arsenic species, suggesting active microbial transformation of As[III] via one or more arsenic resistance mechanisms

Alterations in blood lymphocyte subpopulations and hematologic values in neonatal calves after administration of a combination of multiple-antigen vaccines

OBJECTIVE: To evaluate alterations in lymphocyte subpopulations, CBC results, and clinical signs in neonatal calves inoculated with 3 commercially available proprietary multiple-antigen vaccines containing known quantities of endotoxin. DESIGN: Prospective, randomized controlled field trial. ANIMALS: 36 healthy Holstein heifer calves between 3 and 31 days old. PROCEDURE: Vaccines were administered to 18 calves according to label instructions, except for the recommended age of administration. The 18 other calves served as unvaccinated controls. Two weeks after entry into the study, calves were given secondary doses of the same vaccines. Calves in both groups were examined and blood samples were collected for determination of lymphocyte subpopulations and hematological parameters once daily for 5 days beginning on the day that both the primary and the secondary vaccinations were given. Lymphocyte subpopulations, including BoCD2+, BoCD4+, BoCD8+, B cells, and gamma/delta T cells, were determined by use of flow cytometry, using monoclonal antibodies as markers. RESULTS: Vaccinated calves did not develop clinical signs of illness. There were no significant differences in absolute numbers of lymphocyte subpopulations between vaccinated and unvaccinated calves. Vaccinated calves had significantly higher rectal temperatures, total WBC counts, and absolute neutrophil counts than did control calves. These differences persisted for 3 to 4 days after vaccination. CLINICAL IMPLICATIONS: Findings confirm empirical observations that vaccination with multiple products at the same time may induce evidence of an inflammatory response in most calves. Additional research is indicated to further evaluate the safety of using multiple vaccines simultaneously

Environmental, genomic and taxonomic perspectives on methanotrophic Verrucomicrobia

Contains fulltext : 75111.pdf (publisher's version ) (Closed access)13 p

<i>Pyrinomonas methylaliphatogenes</i> gen. nov., sp. nov., a novel group 4 thermophilic member of the phylum <i>Acidobacteria</i> from geothermal soils

An aerobic, thermophilic, moderately acidophilic non-spore-forming bacterium, strain K22T, wasisolated from geothermally heated soil at Mount Ngauruhoe, New Zealand. On the basis of 16SrRNA gene sequence similarity, K22T was shown to belong to subdivision 4 of the phylumAcidobacteria and to be most closely related to ‘Candidatus Chloracidobacterium thermophilum’(86 %) and Blastocatella fastidiosa (86 %). Cells stained Gram-negative and were catalase andoxidase-positive. The major fatty acids detected were iso-C15 : 0, iso-C17 : 0, iso-C19 : 0 and iso-C21 : 0 when standard lipid extraction protocols were employed. Analysis of the total cell lipid acidhydrolysate also detected membrane-spanning and ether lipids, which made up approximately40% of the total membrane composition. These lipids included dicarboxylic (iso-diabolic) acidand the glyceryl ether of alkyl analogues of iso-C15 : 0 and iso-diabolic acid. The G+C content ofthe genomic DNA was 59.6 mol% and the primary respiratory quinone was MK-8. Strain K22Tgrew at 50–69 6C with an optimum temperature of 65 6C and at pH 4.1–7.8 with an optimumgrowth pH of 6.5. NaCl tolerance was up to 1% (w/v). Cells displayed a chemoheterotrophic andobligately aerobic metabolism. Cells grew on nutrient broth, alginate, arabinose, Casamino acids,glucose, lactate, formate, mannose, sodium alginate, peptone, sucrose, tryptone, xanthan, xylan,xylose and yeast extract. Nitrogen sources included nitrate, ammonium, urea, yeast extract andCasamino acids, but not dinitrogen gas. The distinct phylogenetic position and the phenotypiccharacteristics separate strain K22T from all other members of the class Acidobacteria andindicate that it represents a novel species and genus, for which the name Pyrinomonasmethylaliphatogenes gen. nov., sp. nov. is proposed. The type strain of the type species is K22T(5DSM 25857T5ICMP 18710T)

Genetic variation in the interleukin-1 beta-converting enzyme associates with cognitive function. The PROSPER study

Inflammation is thought to play an important role in the development of cognitive decline and dementia in old age. The interleukin-1 signalling pathway may play a prominent role in this process. The gene encoding for interleukin-1 beta-converting enzyme (ICE) is likely to influence IL-1 beta levels. Inhibition of ICE decreases the age-related increase in IL-1 beta levels and may therefore improve memory function. We assessed whether genetic variation in the ICE gene associates with cognitive function in an elderly population. All 5804 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) were genotyped for the 10643GC, 9323GA, 8996AG and 5352GA polymorphisms in the ICE gene. Cross-sectional associations between the polymorphisms and cognitive function were assessed with linear regression. Longitudinal associations between polymorphisms, haplotypes and cognitive function were assessed with linear mixed models. All associations were adjusted for sex, age, education, country, treatment with pravastatin and version of test where appropriate. Subjects carrying the variants 10643C and 5352A allele had significantly lower IL-1 beta production levels (P &lt;0.01). Furthermore, we demonstrated that homozygous carriers of the 10643C and the 5352A allele performed better on all executive function tests at baseline and during follow-up compared to homozygous carriers of the wild-type allele (all P &lt;0.02). The haplotype with two variants present (10643C and 5352A) was associated with better executive function (all P &lt;0.02) compared to the reference haplotype without variants. For memory function the same trend was observed, although not significant. Genetic variation in the ICE gene is associated with better performance on cognitive function and lower IL-1 beta production levels. This suggests that low levels of IL-1 beta are protective for memory and learning deficits. Inhibition of ICE may therefore be an important therapeutic target for maintaining cognitive function in old ag