Far-infrared spectroscopic images of M83

We have mapped the nearby face on barred spiral galaxy, M83 in the bright [CII] 158 μm, [OI] 63 and 146 μm, [NII] 122 μm, and [OIII] 88 μm fine-structure lines with the Long Wavelength Spectrometer (LWS) on ISO. The maps are nearly fully sampled, and cover the inner 6.75' x 6' region - essentially the entire optical disk. We also obtained a full LWS grating scan of the nucleus. The lines are detectable over the entire disk, and enhanced at the nucleus, where the [OI] 63 μm and [NII] lines are particularly strong. At the nucleus, the line ratios indicate a strong starburst headed by O9 stars. Surprisingly, the [OI] and [CII] line emission (from photodissociation regions) is not enhanced relative to [NII] (from low density HII regions) on the spiral arms. The line ratios are the same for the spiral arms and interarm regions. We find very strong emission in the [OIII] 88 μm, [OI] 146 μm, and [CII] lines at the intersection of the bar and spiral arm to the SW indicating particularly strong star formation activity there. The [OI] 63 μm/146 μm line ratio is quite small there likely the result of self absorption in the 63 μm line by enveloping clouds. The total luminosity of this emission peak is 1.2 x 109 Lodo

Genetics of height and risk of atrial fibrillation: A Mendelian randomization study.

BACKGROUND: Observational studies have identified height as a strong risk factor for atrial fibrillation, but this finding may be limited by residual confounding. We aimed to examine genetic variation in height within the Mendelian randomization (MR) framework to determine whether height has a causal effect on risk of atrial fibrillation. METHODS AND FINDINGS: In summary-level analyses, MR was performed using summary statistics from genome-wide association studies of height (GIANT/UK Biobank; 693,529 individuals) and atrial fibrillation (AFGen; 65,446 cases and 522,744 controls), finding that each 1-SD increase in genetically predicted height increased the odds of atrial fibrillation (odds ratio [OR] 1.34; 95% CI 1.29 to 1.40; p = 5 × 10-42). This result remained consistent in sensitivity analyses with MR methods that make different assumptions about the presence of pleiotropy, and when accounting for the effects of traditional cardiovascular risk factors on atrial fibrillation. Individual-level phenome-wide association studies of height and a height genetic risk score were performed among 6,567 European-ancestry participants of the Penn Medicine Biobank (median age at enrollment 63 years, interquartile range 55-72; 38% female; recruitment 2008-2015), confirming prior observational associations between height and atrial fibrillation. Individual-level MR confirmed that each 1-SD increase in height increased the odds of atrial fibrillation, including adjustment for clinical and echocardiographic confounders (OR 1.89; 95% CI 1.50 to 2.40; p = 0.007). The main limitations of this study include potential bias from pleiotropic effects of genetic variants, and lack of generalizability of individual-level findings to non-European populations. CONCLUSIONS: In this study, we observed evidence that height is likely a positive causal risk factor for atrial fibrillation. Further study is needed to determine whether risk prediction tools including height or anthropometric risk factors can be used to improve screening and primary prevention of atrial fibrillation, and whether biological pathways involved in height may offer new targets for treatment of atrial fibrillation

Does Preexisting Antiplatelet Treatment Influence Postthrombolysis Intracranial Hemorrhage in Community‐treated Ischemic Stroke Patients? An Observational Study

Objectives Intracranial hemorrhage ( ICH ) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between preexisting antiplatelet use and the safety of intravenous ( IV ) thrombolysis have been limited by low event rates. The objective of this study was to determine whether preexisting antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders. Methods Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004 and 24 other hospitals from 2007 to 2010 as part of a cluster‐randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a prespecified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow‐up imaging (primary outcome). Symptomatic ICH ( sICH ) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to postthrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta‐analytic techniques. Results There were 830 patients included, with 47% having documented preexisting antiplatelet treatment. The mean (± standard deviation [SD]) age was 69 (±15) years, and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use and 19.3% with antiplatelet use (absolute risk difference = 4.2%, 95% confidence interval [CI] = −1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference = 3.1%, 95% CI = −1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio [OR] = 1.1, 95% CI = 0.8 to 1.7) or sICH (OR = 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference = 11.9%, 95% CI = 0.1% to 23.6%). The meta‐analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference = 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference = 4%, 95% CI = 2.3% to 5.6%). The meta‐analytic adjusted OR of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4). Conclusions The authors did not find that preexisting antiplatelet use was associated with postthrombolysis ICH or sICH in this cohort of community treated patients. Preexisting tobacco use, younger age, and lower severity were associated with lower odds of sICH . The meta‐analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH , along with increased odds of sICH in patients with preexisting antiplatelet use. Resumen ¿Influye el Tratamiento Antiagregante Previo en la Hemorragia Intracraneal tras la Trombolisis en los Pacientes con Ictus Isquémicos Tratados en la Comunidad? Un Estudio Observacional Objetivos La hemorragia intracraneal ( HIC ) tras la trombolisis de un ictus agudo se asocia con malos resultados. Los estudios previos de la relación entre el uso de antiagregantes y la seguridad de la trombolisis intravenosa ( IV ) han estado limitados por los porcentajes bajos de sucesos. El objetivo de este estudio fue determinar si el tratamiento antiagregante previo está asociado con la evidencia radiológica de HIC tras el control por los factores de confusión relevantes. Metodología Se identificaron los casos consecutivos de pacientes tratados con trombolisis en el SU de múltiples formas. Se recogieron los datos de forma retrospectiva de cuatro hospitales de 1996 a 2004 y de 24 hospitales distintos de 2007 a 2010 como parte de un ensayo clínico aleatorizado en racimos. Se utilizó la misma tabla resumen de historia clínica durante ambos periodos de tiempo y los datos fueron sometidos a numerosos controles de calidad. Las hemorragias se clasificaron siguiendo una metodología preestablecida: la HIC se definió como la presencia de hemorragia en las interpretaciones radiológicas de las imágenes de seguimiento (resultado primario); y la HIC sintomática ( HIC s) se definió como la HIC radiológica asociada con un empeoramiento clínico. Se construyó un modelo multivariable de regresión logística para ajustar los factores clínicos previamente identificados como relacionados con un la HIC tras la trombolisis. Los análisis de sensibilidad se realizaron mediante técnicas de metanálisis y se combinaron los resultados ajustados y no ajustados de esta investigación con los estudios externos previamente publicados en este tema. Resultados Se incluyeron 830 pacientes, de los cuales el 47% tenía documentado tratamiento antiagregante previo. La media de edad fue de 69 años, y el 53% eran varones. La proporción no ajustada de pacientes con cualquier tipo de HIC fue del 15,1% sin toma de antiagregante y del 19,3% con la toma de antiagregante (diferencia del riesgo absoluto 4,2%, IC 95% = −1,2% a 9,6%); y para las HIC s fue del 6,1% sin toma de antiagregantes y del 9% con la toma de antiagregantes (diferencia absoluta del riesgo 3,1%, IC 95% = −1% a 6,7%). Tras ajustar por los factores de confusión, la toma de antiagregantes no se asoció de forma significativa con la HIC radiológica ( OR 1,1, IC 95% = 0,8 a 1,7]) o HIC s ( OR 1,3, IC 95% = 0,7 a 2,2). En los pacientes de 81 años o más, hubo mayor riesgo de HIC radiológica (diferencia de riesgo absoluta 11,9%, IC 95% = 0,1% a 23,6%). El metanálisis que combinó los hallazgos de esta investigación con los trabajos similares previos encontró un riesgo no ajustado incrementado para la HIC radiológica (diferencia absoluta del riesgo 4,9%, IC 95% = 0,7% a 9%) y de HIC s (diferencia absoluta del riesgo 4%, IC 95% = 2,3% a 5,6%). La odds ratio ajustada del metanálisis de HIC s para los pacientes con tratamiento de antigregantes fue de 1,6 ( IC 95% = 1,1 a 2,4). Conclusiones Los autores no encontraron que la toma previa de antigregantes se asocie con la HIC o la HIC s tras la trombolisis en esta cohorte de pacientes tratados en la comunidad. El consumo previo de tabaco, la edad más joven y la menor gravedad se asociaron con odds ratio menores de HIC s. El metanálisis demostró un incremento bajo, aunque estadísticamente significativo, de riesgo absoluto de HIC radiológica o de HIC s, con una odds ratio aumentada de HIC s en los pacientes con toma previa de antiagregantes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96759/1/acem12077.pd

Pp65 antigenemia, plasma real-time PCR and DBS test in symptomatic and asymptomatic cytomegalovirus congenitally infected newborns

<p>Abstract</p> <p>Background</p> <p>Many congenitally cytomegalovirus-infected (cCMV) neonates are at risk for severe consequences, even if they are asymptomatic at birth. The assessment of the viral load in neonatal blood could help in identifying the babies at risk of sequelae.</p> <p>Methods</p> <p>In the present study, we elaborated the results obtained on blood samples collected in the first two weeks of life from 22 symptomatic and 48 asymptomatic newborns with cCMV diagnosed through urine testing. We evaluated the performances of two quantitative methods (pp65 antigenemia test and plasma Real-time PCR) and the semi-quantitative results of dried blood sample (DBS) test in the aim of identifying a valid method for measuring viral load.</p> <p>Results</p> <p>Plasma qPCR and DBS tests were positive in 100% of cases, antigenemia in 81%. Only the latter test gave quantitatively different results in symptomatic versus asymptomatic children. qPCR values of 10³copies/ml were found in 52% of newborn. "Strong" DBS test positivity cases had higher median values of both pp65 positive PBL and DNA copies/ml than cases with a "weak" positivity.</p> <p>Conclusions</p> <p>As expected antigenemia test was less sensitive than molecular tests and DBS test performed better on samples with higher rates of pp65 positive PBL and higher numbers of DNA copies/ml. The prognostic significance of the results of these tests will be evaluated on completion of the ongoing collection of follow-up data of these children.</p

Hydroxyl radical-aided thermal pretreatment of algal biomass for enhanced biodegradability

BACKGROUND: Algal biomass, known as a potential feedstock for biofuel production, has cell wall structures that differ from terrestrial biomass. The existing methods for processing algae are limited to conventional pretreatments for terrestrial biomass. RESULTS: In this study, we investigated a novel hydroxyl radical-aided approach for pretreating different types of algal biomass. In this process, hydroxyl radicals formed by a Fenton system were employed in combination with heating to alter the crystalline structure and hydrogen bonds of cellulose in the algal biomass. FeSO(4) and H(2)O(2) at low concentrations were employed to initiate the formation of hydroxyl radicals. This method releases trapped polysaccharides in algal cell walls and converts them into fermentable sugars. The effects of temperature, time, and hydroxyl radical concentration were analyzed. The optimal pretreatment condition [100 °C, 30 min, and 5.3 mM H(2)O(2) (determined FeSO(4) concentration of 11.9 mM)] was identified using a central composite design. Complete (100 %) carbohydrate recovery was achieved with some algal biomass without formation of inhibitors such as hydroxymethylfurfural and furfural as by-products. Both microalgal and macroalgal biomasses showed higher enzymatic digestibility of cellulose conversion (>80 %) after the milder pretreatment condition. CONCLUSION: Hydroxyl radical-aided thermal pretreatment was used as a novel method to convert the carbohydrates in the algal cell wall into simple sugars. Overall, this method increased the amount of glucose released from the algal biomass. Overall, enhanced algal biomass digestibility was demonstrated with the proposed pretreatment process. The new pretreatment requires low concentration of chemical solvents and milder temperature conditions, which can prevent the toxic and corrosive effects that typically result from conventional pretreatments. Our data showed that the advantages of the new pretreatment include higher carbohydrate recovery, no inhibitor production, and lower energy consumption. The new pretreatment development mimicking natural system could be useful for biochemical conversion of algal biomass to fuels and chemicals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13068-015-0372-2) contains supplementary material, which is available to authorized users

Myofibrillogenesis regulator 1 induces hypertrophy by promoting sarcomere organization in neonatal rat cardiomyocytes

Human myofibrillogenesis regulator 1, a novel 17-kDa protein, is closely involved in cardiac hypertrophy. We studied the molecular mechanism that links MR-1 to hypertrophic response. Hypertrophic hallmarks such as cell size and [3H]-leucine incorporation were significantly increased when MR-1 was transfected into cardiomyocytes for 48 h. However, sarcomere organization was promoted when MR-1 was transfected for 8 h. The finding that cardiac hypertrophy was induced long after increase of sarcomere organization indicates that the promoted sarcomere organization may be one of the crucial factors causing hypertrophy. Furthermore, when MR-1 was transfected into cardiomyocytes, the nuclear localization of myomesin-1 was shifted to the cytoplasm. Transfection with small ubiquitin-like modifier-1 (SUMO-1) mimicked the effect of MR-1 inducing translocation of myomesin-1. However, transfection with SUMO-1 in MR-1-silenced cardiomyocytes failed to induce translocation and sarcomere organization, even though SUMO-1 expression was at the same level. Overexpression of MR-1 may induce cardiomyocyte hypertrophy via myomesin-1-mediated sarcomere organization

Identification of excreted iron superoxide dismutase for the diagnosis of Phtytomonas

An excreted iron superoxide dismutase (FeSODe) of pI 3.6 with a molecular weight of 28-30 kDa was detected in the in vitro culture of Phytomonas isolated from Euphorbia characias (SODeCHA) and from Lycopersicon esculentum (SODeTOM), in Grace's medium without serum. These FeSODe excreted into the medium had immunogenic capacity: the positivity of the anti-SODeCHA serum persisted to a dilution of 1/30,000, and for the anti-SODeTOM to 1/10,000 by Western blot. In addition, cross reaction was detected between the anti-SODe serum of Phytomonas isolated from E. characias against SODeTOM, and the anti-SODe serum from L. esculentum with SODeCHA. This characteristic offers the possibility of its use to diagnose plant trypanosomatids. The validation of the test was confirmed by experimental inoculation of tomato fruits with Phytomonas isolated from L. esculentum. At 7, 10, 15, and 21 days post infection, it was possible to detect the presence of the parasites with the anti-SODe serum of Phytomonas isolated from L. esculentum at a dilution of 1/250. These serological results were confirmed by visualization of the parasites by optical microscopy. The data of this study confirm that the SOD is sufficient to identify a trypanosomatid isolated from plants as belonging to the genus Phytomonas.Finacial support: ATP 2002/03: Circulation of Trypanosomatidae Project (CIRAD, France), grant BIO-2000-1429 (University of Granada, Spain)

Fumarate Analogs Act as Allosteric Inhibitors of the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P)-ME enzyme activity

Palmitate-Induced β-Cell Dysfunction Is Associated with Excessive NO Production and Is Reversed by Thiazolidinedione-Mediated Inhibition of GPR40 Transduction Mechanisms

BACKGROUND: Type 2 diabetes often displays hyperlipidemia. We examined palmitate effects on pancreatic islet function in relation to FFA receptor GPR40, NO generation, insulin release, and the PPARgamma agonistic thiazolidinedione, rosiglitazone. PRINCIPAL FINDINGS: Rosiglitazone suppressed acute palmitate-stimulated GPR40-transduced PI hydrolysis in HEK293 cells and insulin release from MIN6c cells and mouse islets. Culturing islets 24 h with palmitate at 5 mmol/l glucose induced beta-cell iNOS expression as revealed by confocal microscopy and increased the activities of ncNOS and iNOS associated with suppression of glucose-stimulated insulin response. Rosiglitazone reversed these effects. The expression of iNOS after high-glucose culturing was unaffected by rosiglitazone. Downregulation of GPR40 by antisense treatment abrogated GPR40 expression and suppressed palmitate-induced iNOS activity and insulin release. CONCLUSION: We conclude that, in addition to mediating acute FFA-stimulated insulin release, GPR40 is an important regulator of iNOS expression and dysfunctional insulin release during long-term exposure to FFA. The adverse effects of palmitate were counteracted by rosiglitazone at GPR40, suggesting that thiazolidinediones are beneficial for beta-cell function in hyperlipidemic type 2 diabetes