Drift effects and the cosmic ray density gradient in a solar rotation period: First observation with the Global Muon Detector Network (GMDN)

We present for the first time hourly variations of the spatial density gradient of 50 GeV cosmic rays within a sample solar rotation period in 2006. By inversely solving the transport equation, including diffusion, we deduce the gradient from the anisotropy that is derived from the observation made by the Global Muon Detector Network (GMDN). The anisotropy obtained by applying a new analysis method to the GMDN data is precise and free from atmospheric temperature effects on the muon count rate recorded by ground based detectors. We find the derived north-south gradient perpendicular to the ecliptic plane is oriented toward the Helioshperic Current Sheet (HCS) (i.e. southward in the toward sector of the Interplanetary Magnetic Field (IMF) and northward in the away sector). The orientation of the gradient component parallel to the ecliptic plane remains similar in both sectors with an enhancement of its magnitude seen after the Earth crosses the HCS. These temporal features are interpreted in terms of a local maximum of the cosmic ray density at the HCS. This is consistent with the prediction of the drift model for the $A<0$ epoch. By comparing the observed gradient with the numerical prediction of a simple drift model, we conclude that particle drifts in the large-scale magnetic field play an important role in organizing the density gradient, at least in the present $A<0$ epoch. We also found that corotating interaction regions did not have such a notable effect. Observations with the GMDN provide us with a new tool for investigating cosmic ray transport in the IMF.Comment: 35 pages, 10 figures, submitted to the Astrophysical Journa

Mesenchymal stromal cells inhibit NLRP3 inflammasome activation in a model of Coxsackievirus B3-induced inflammatory cardiomyopathy

Inflammation in myocarditis induces cardiac injury and triggers disease progression to heart failure. NLRP3 inflammasome activation is a newly identified amplifying step in the pathogenesis of myocarditis. We previously have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18 mRNA expression in CVB3-infected mice. ASC protein expression, essential for NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated in MSC-treated mice. Concomitantly, CVB3 infection in vitro induced NOD2 expression, NLRP3 inflammasome activation and IL-1β secretion in HL-1 cells, which was abolished after MSC supplementation. The inhibitory effect of MSC on NLRP3 inflammasome activity in HL-1 cells was partly mediated via secretion of the anti-oxidative protein stanniocalcin-1. Furthermore, MSC application in CVB3-infected mice reduced the percentage of NOD2-, ASC-, p10- and/or IL-1β- positive splenic macrophages, natural killer cells, and dendritic cells. The suppressive effect of MSC on inflammasome activation was associated with normalized expression of prominent regulators of myocardial contractility and fibrosis to levels comparable to control mice. In conclusion, MSC treatment in myocarditis could be a promising strategy limiting the adverse consequences of cardiac and systemic NLRP3 inflammasome activation

Arterial pressure changes monitoring with a new precordial noninvasive sensor

<p>Abstract</p> <p>Background</p> <p>Recently, a cutaneous force-frequency relation recording system based on first heart sound amplitude vibrations has been validated. A further application is the assessment of Second Heart Sound (S2) amplitude variations at increasing heart rates. The aim of this study was to assess the relationship between second heart sound amplitude variations at increasing heart rates and hemodynamic changes.</p> <p>Methods</p> <p>The transcutaneous force sensor was positioned in the precordial region in 146 consecutive patients referred for exercise (n = 99), dipyridamole (n = 41), or pacing stress (n = 6). The curve of S2 peak amplitude variation as a function of heart rate was computed as the increment with respect to the resting value.</p> <p>Results</p> <p>A consistent S2 signal was obtained in all patients. Baseline S2 was 7.2 ± 3.3 m<it>g</it>, increasing to 12.7 ± 7.7 m<it>g </it>at peak stress. S2 percentage increase was + 133 ± 104% in the 99 exercise, + 2 ± 22% in the 41 dipyridamole, and + 31 ± 27% in the 6 pacing patients (p < 0.05). Significant determinants of S2 amplitude were blood pressure, heart rate, and cardiac index with best correlation (R = .57) for mean pressure.</p> <p>Conclusion</p> <p>S2 recording quantitatively documents systemic pressure changes.</p

Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless ‘Frank–Starling Gain’ index

This paper briefly recapitulates the Frank–Starling law of the heart, reviews approaches to establishing diastolic and systolic force–length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called ‘Frank–Starling Gain’, calculated as the ratio of slopes of end-systolic and end-diastolic force–length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank–Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties

Sociodemographic correlates of food habits among school adolescents (12–15 year) in north Gaza Strip

Background: There is little information about meal patterns and food consumption of adolescents in Palestine. The objective of this study was to describe the association between sociodemographic factors and food intake, and meal patterns among Palestinian school adolescents (12–15 year) in North Gaza Strip. Methods: A cross-sectional study was conducted in 2002 comprising 944 subjects in 10 schools in Gaza city, Jabalia village and Jabalia refugee camp. Self-administered questionnaires were filled in by students and parents to obtain data on frequency of meals, food intake and sociodemographic characteristics. Results: High household socioeconomic status (SES) was associated with the increased number of meals and the increased intakes of many nutritious foods such as; animal food items, fruits and vegetables and dairy foods. The percentage of adolescents having breakfast daily of high and low SES was 74.5% vs 55% in boys and 65.6% vs 45% in girls. The percentage of girls with refugee status who had lunch was higher (90.2%) compared to the local citizen girls (83.9%), (p = 0.03). Girls were less likely to skip daily lunch (OR = 0.55, 95% CI = 0.36–0.87, p = 0.01) compared to boys. Risk of skipping lunch was three times higher among adolescents living in the village compared to Gaza well-off area (OR = 3.3, 95% CI = 1.72–6.31, p < 0.001). Adolescents who were having lunch daily were less likely to skip breakfast or dinner. Only 11.6% of boys and 16.2% of girls consumed fruits daily. In multivariate analysis, SES was positively associated with food frequency intake scores in both genders. Boys from the refugee camp and the village had a significant higher consumption of fruits and vegetables than boys from high and low income area in Gaza City, while it was the opposite in girls. Conclusion: Meal skipping is common, particularly among those of low SES and the intakes of many nutritious foods such as animal food items, fruits and vegetables and dairy foods seem to be low among adolescents of low SES. The results of this study could be used as an important baseline for future monitoring of the nutritional situation of adolescents.Abdallah H Abudayya, Hein Stigum, Zumin Shi, Yehia Abed and Gerd Holmboe-Ottese

Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway.

BACKGROUND: Type-2 diabetics have an increased risk of cardiomyopathy, and heart failure is a major cause of death among these patients. Growing evidence indicates that proinflammatory cytokines may induce the development of insulin resistance, and that anti-inflammatory medications may reverse this process. We investigated the effects of the oral administration of zinc and acetylsalicylic acid, in the form of bis(aspirinato)zinc(II)-complex Zn(ASA)2, on different aspects of cardiac damage in Zucker diabetic fatty (ZDF) rats, an experimental model of type-2 diabetic cardiomyopathy. METHODS: Nondiabetic control (ZL) and ZDF rats were treated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 29-30 weeks, the electrical activities, left-ventricular functional parameters and left-ventricular wall thicknesses were assessed. Nitrotyrosine immunohistochemistry, TUNEL-assay, and hematoxylin-eosin staining were performed. The protein expression of the insulin-receptor and PI3K/AKT pathway were quantified by Western blot. RESULTS: Zn(ASA)2-treatment significantly decreased plasma glucose concentration in ZDF rats (39.0 +/- 3.6 vs 49.4 +/- 2.8 mM, P < 0.05) while serum insulin-levels were similar among the groups. Data from cardiac catheterization showed that Zn(ASA)2 normalized the increased left-ventricular diastolic stiffness (end-diastolic pressure-volume relationship: 0.064 +/- 0.008 vs 0.084 +/- 0.014 mmHg/microl; end-diastolic pressure: 6.5 +/- 0.6 vs 7.9 +/- 0.7 mmHg, P < 0.05). Furthermore, ECG-recordings revealed a restoration of prolonged QT-intervals (63 +/- 3 vs 83 +/- 4 ms, P < 0.05) with Zn(ASA)2. Left-ventricular wall thickness, assessed by echocardiography, did not differ among the groups. However histological examination revealed an increase in the cardiomyocytes' transverse cross-section area in ZDF compared to the ZL rats, which was significantly decreased after Zn(ASA)2-treatment. Additionally, a significant fibrotic remodeling was observed in the diabetic rats compared to ZL rats, and Zn(ASA)2-administered ZDF rats showed a similar collagen content as ZL animals. In diabetic hearts Zn(ASA)2 significantly decreased DNA-fragmentation, and nitro-oxidative stress, and up-regulated myocardial phosphorylated-AKT/AKT protein expression. Zn(ASA)2 reduced cardiomyocyte death in a cellular model of oxidative stress. Zn(ASA)2 had no effects on altered myocardial CD36, GLUT-4, and PI3K protein expression. CONCLUSIONS: We demonstrated that treatment of type-2 diabetic rats with Zn(ASA)2 reduced plasma glucose-levels and prevented diabetic cardiomyopathy. The increased myocardial AKT activation could, in part, help to explain the cardioprotective effects of Zn(ASA)2. The oral administration of Zn(ASA)2 may have therapeutic potential, aiming to prevent/treat cardiac complications in type-2 diabetic patients

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

<p>Abstract</p> <p>Background</p> <p>Globally, gastric cancer is the second most common cause of cancer-related death, with the majority of the health burden borne by economically less-developed countries.</p> <p>Methods</p> <p>Here, we report a genetic characterization of 50 gastric adenocarcinoma samples, using affymetrix SNP arrays and Illumina mRNA expression arrays as well as Illumina sequencing of the coding regions of 384 genes belonging to various pathways known to be altered in other cancers.</p> <p>Results</p> <p>Genetic alterations were observed in the WNT, Hedgehog, cell cycle, DNA damage and epithelial-to-mesenchymal-transition pathways.</p> <p>Conclusions</p> <p>The data suggests targeted therapies approved or in clinical development for gastric carcinoma would be of benefit to ~22% of the patients studied. In addition, the novel mutations detected here, are likely to influence clinical response and suggest new targets for drug discovery.</p

TRIM27 Negatively Regulates NOD2 by Ubiquitination and Proteasomal Degradation

NOD2, the nucleotide-binding domain and leucine-rich repeat containing gene family (NLR) member 2 is involved in mediating antimicrobial responses. Dysfunctional NOD2 activity can lead to severe inflammatory disorders, but the regulation of NOD2 is still poorly understood. Recently, proteins of the tripartite motif (TRIM) protein family have emerged as regulators of innate immune responses by acting as E3 ubiquitin ligases. We identified TRIM27 as a new specific binding partner for NOD2. We show that NOD2 physically interacts with TRIM27 via the nucleotide-binding domain, and that NOD2 activation enhances this interaction. Dependent on functional TRIM27, ectopically expressed NOD2 is ubiquitinated with K48-linked ubiquitin chains followed by proteasomal degradation. Accordingly, TRIM27 affects NOD2-mediated pro-inflammatory responses. NOD2 mutations are linked to susceptibility to Crohns disease. We found that TRIM27 expression is increased in Crohns disease patients, underscoring a physiological role of TRIM27 in regulating NOD2 signaling. In HeLa cells, TRIM27 is partially localized in the nucleus. We revealed that ectopically expressed NOD2 can shuttle to the nucleus in a Walker A dependent manner, suggesting that NOD2 and TRIM27 might functionally cooperate in the nucleus. We conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases.Funding Agencies|German Research Foundation (DFG)|SFB670-NG01|Swedish Society of Medicine||Regional Research Council of South-East Sweden (FORSS)||Swedish Research Council division of Medicine||Gustav V 90th anniversary foundation||Italian Telethon Foundation||DFG|SE 1122/2-1|</p