Differential Gene Expression in High- and Low-Active Inbred Mice

Numerous candidate genes have been suggested in the recent literature with proposed roles in regulation of voluntary physical activity, with little evidence of these genes' functional roles. This study compared the haplotype structure and expression profile in skeletal muscle and brain of inherently high- (C57L/J) and low- (C3H/HeJ) active mice. Expression of nine candidate genes [Actn2, Actn3, Casq1, Drd2, Lepr, Mc4r, Mstn, Papss2, and Glut4 (a.k.a. Slc2a4)] was evaluated via RT-qPCR. SNPs were observed in regions of Actn2, Casq1, Drd2, Lepr, and Papss2; however, no SNPs were located in coding sequences or associated with any known regulatory sequences. In mice exposed to a running wheel, Casq1 (P = 0.0003) and Mstn (P = 0.002) transcript levels in the soleus were higher in the low-active mice. However, when these genes were evaluated in naïve animals, differential expression was not observed, demonstrating a training effect. Among naïve mice, no genes in either tissue exhibited differential expression between strains. Considering that no obvious SNP mechanisms were determined or differential expression was observed, our results indicate that genomic structural variation or gene expression data alone is not adequate to establish any of these genes' candidacy or causality in relation to regulation of physical activity

Cobalt catalysts for the oxidation of diesel soot particulate

Ceria-supported materials prepared by three routes, coprecipitation from aqueous solution containing both Co2+ and Ce3+ ions, and impregnation of preformed ceria gel with either cobalt(II) nitrate or cobalt(II) acetate, have been investigated for catalytic activity towards oxidation of diesel soot. All three materials catalyze the conversion of diesel soot particulate to carbon dioxide under a flow of either 6 vol.% O2 or 0.5 vol.% NO + 6 vol.% O2 in helium in the temperature range 573?613 K. The temperature of maximum conversion rate shows a small dependence on the particular catalyst and the composition of the oxidant. Raman spectroscopy of the ceria-supported cobalt catalysts indicate that the cobalt is present as Co3O4, but its average particle size in Co/CeO2 impregnated with Co acetate is smaller than the other two Co/CeO2 preparations. Features in the temperature-programmed reduction (TPR) profiles in the range 500?600 K, coincident with the temperature of catalytic activity, appear to be associated with reduction of the cobalt, suggesting a redox-type mechanism assisted by oxygen spillover on the CeO2 support. In contrast, cobalt supported on alumina, silica, and tin(IV) oxide obtained by coprecipitation show much lower activity due to the presence of dispersed Co2+ ions in these materials although small amounts of Co3O4 may be present on alumina and tin(IV) oxide.Fil: Harrison, Philip G.. The University of Nottingham; Reino UnidoFil: Ball, Ian K.. The University of Nottingham; Reino Unido. University Of Nottingham; Reino UnidoFil: Daniell, Wayne. Ludwig Maximilians Universitat; AlemaniaFil: Lukinskas, Povilas. Ludwig Maximilians Universitat; AlemaniaFil: Céspedes, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigaciones en Catálisis y Petroquímica ; ArgentinaFil: Miro, Eduardo Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigaciones en Catálisis y Petroquímica ; ArgentinaFil: Ulla, Maria Alicia del H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigaciones en Catálisis y Petroquímica ; Argentin

NuSTAR Hard X-ray Survey of the Galactic Center Region I: Hard X-ray Morphology and Spectroscopy of the Diffuse Emission

We present the first sub-arcminute images of the Galactic Center above 10 keV, obtained with NuSTAR. NuSTAR resolves the hard X-ray source IGR J17456-2901 into non-thermal X-ray filaments, molecular clouds, point sources and a previously unknown central component of hard X-ray emission (CHXE). NuSTAR detects four non-thermal X-ray filaments, extending the detection of their power-law spectra with $\Gamma\sim1.3$-$2.3$ up to ~50 keV. A morphological and spectral study of the filaments suggests that their origin may be heterogeneous, where previous studies suggested a common origin in young pulsar wind nebulae (PWNe). NuSTAR detects non-thermal X-ray continuum emission spatially correlated with the 6.4 keV Fe K$\alpha$ fluorescence line emission associated with two Sgr A molecular clouds: MC1 and the Bridge. Broad-band X-ray spectral analysis with a Monte-Carlo based X-ray reflection model self-consistently determined their intrinsic column density ($\sim10^{23}$ cm$^{-2}$), primary X-ray spectra (power-laws with $\Gamma\sim2$) and set a lower limit of the X-ray luminosity of Sgr A* flare illuminating the Sgr A clouds to $L_X \stackrel{>}{\sim} 10^{38}$ erg s$^{-1}$. Above ~20 keV, hard X-ray emission in the central 10 pc region around Sgr A* consists of the candidate PWN G359.95-0.04 and the CHXE, possibly resulting from an unresolved population of massive CVs with white dwarf masses $M_{\rm WD} \sim 0.9 M_{\odot}$. Spectral energy distribution analysis suggests that G359.95-0.04 is likely the hard X-ray counterpart of the ultra-high gamma-ray source HESS J1745-290, strongly favoring a leptonic origin of the GC TeV emission.Comment: 27 pages. Accepted for publication in the Astrophysical Journa

Differential Gene Expression in High- and Low-Active Inbred Mice

Numerous candidate genes have been suggested in the recent literature with proposed roles in regulation of voluntary physical activity, with little evidence of these genes’ functional roles. This study compared the haplotype structure and expression profile in skeletal muscle and brain of inherently high- (C57L/J) and low- (C3H/HeJ) active mice. Expression of nine candidate genes [Actn2, Actn3, Casq1, Drd2, Lepr, Mc4r, Mstn, Papss2, and Glut4 (a.k.a. Slc2a4)] was evaluated via RT-qPCR. SNPs were observed in regions of Actn2, Casq1, Drd2, Lepr, and Papss2; however, no SNPs were located in coding sequences or associated with any known regulatory sequences. In mice exposed to a running wheel, Casq1 (P=0.0003) and Mstn (P=0.002) transcript levels in the soleus were higher in the low-active mice. However, when these genes were evaluated in naïve animals, differential expression was not observed, demonstrating a training effect. Among naïve mice, no genes in either tissue exhibited differential expression between strains. Considering that no obvious SNP mechanisms were determined or differential expression was observed, our results indicate that genomic structural variation or gene expression data alone is not adequate to establish any of these genes’ candidacy or causality in relation to regulation of physical activity

Inhalational Anthrax Outbreak among Postal Workers, Washington, D.C., 2001

In October 2001, four cases of inhalational anthrax occurred in workers in a Washington, D.C., mail facility that processed envelopes containing Bacillus anthracis spores. We reviewed the envelopes’ paths and obtained exposure histories and nasal swab cultures from postal workers. Environmental sampling was performed. A sample of employees was assessed for antibody concentrations to B. anthracis protective antigen. Case-patients worked on nonoverlapping shifts throughout the facility. Environmental sampling showed diffuse contamination of the facility, suggesting multiple aerosolization events. Potential workplace exposures were similar for the case-patients and the sample of workers. All nasal swab cultures and serum antibody tests were negative. Available tools could not identify subgroups of employees at higher risk for exposure or disease. Prophylaxis was necessary for all employees. To protect postal workers against bioterrorism, measures to reduce the risk of occupational exposure are necessary

Age and Diet Affect Gene Expression Profiles in Canine Liver Tissue

BACKGROUND: The liver plays a central role in nutrient and xenobiotic metabolism, but its functionality declines with age. Senior dogs suffer from many of the chronic hepatic diseases as elderly humans, with age-related alterations in liver function influenced by diet. However, a large-scale molecular analysis of the liver tissue as affected by age and diet has not been reported in dogs. METHODOLOGY/PRINCIPAL FINDINGS: Liver tissue samples were collected from six senior (12-year old) and six young adult (1-year old) female beagles fed an animal protein-based diet (APB) or a plant protein-based diet (PPB) for 12 months. Total RNA in the liver tissue was extracted and hybridized to Affymetrix GeneChip® Canine Genome Arrays. Using a 2.0-fold cutoff and false discovery rate <0.10, our results indicated that expression of 234 genes was altered by age, while 137 genes were differentially expressed by diet. Based on functional classification, genes affected by age and/or diet were involved in cellular development, nutrient metabolism, and signal transduction. In general, gene expression suggested that senior dogs had an increased risk of the progression of liver disease and dysfunction, as observed in aged humans and rodents. In particular for aged liver, genes related to inflammation, oxidative stress, and glycolysis were up-regulated, whereas genes related to regeneration, xenobiotic metabolism, and cholesterol trafficking were down-regulated. Diet-associated changes in gene expression were more common in young adult dogs (33 genes) as compared to senior dogs (3 genes). CONCLUSION: Our results provide molecular insight pertaining to the aged canine liver and its predisposition to disease and abnormalities. Therefore, our data may aid in future research pertaining to age-associated alterations in hepatic function or identification of potential targets for nutritional management as a means to decrease incidence of age-dependent liver dysfunction

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function