Synthesis of H2 in dirty ice mantles by fast ion energy loss: New experimental results increase the relevance of this mechanism

Recent experimental results support the importance of H2 production in molecular clouds by cosmic ray bombardment of the mantles of grains. The formation of molecules different from those originally present in the irradiated layer can be explained by the production of molecular fragments induced by the release of energy if the impinging fast particle. One way of considering the process is in terms of a transiently hot cylinder, initially about 50 A in diameter, that exists around the track of an individual fast ion. Since ice has a relatively low thermal conductivity, energy lost by the ion in the ice layers remains confined around the track for time long enough to be thermalized. The hot cylinder increases in diameter and decreases in temperature on a time scale of 10(exp -11) to 10(exp -10) sec. Molecular fragments that are formed in this high temperature region acquire enough mobility to recombine with different partners, forming new molecules. A Monte Carlo simulation of the interaction between cosmic rays and grain mantles, at various depths in the core of a spherical molecular cloud, was performed. The simulation was continued until 40,000 ions had hit each grain of the type and size chosen. During the performed experiments thin icy films made of H2O and CD4 mixed in the gas phase and deposited on a cold finger at 9 K were irradiated with 1.5 MeV helium beams. Among synthesized molecules were found H2, HD, and D2

On a mixed boundary value problem involving the p-Laplacian

In this paper we prove the existence of infinitely many solutions for a mixed boundary value problem involving the one dimensional p-Laplacian. A result on the existence of three solutions is also established. The approach is based on multiple critical points theorems.<br /

DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network analysis

SREBP1 and 2, are cholesterol sensors able to modulate cholesterol-related gene expression responses. SREBPs binding sites are characterized by the presence of multiple target sequences as SRE, NFY and SP1, that can be arranged differently in different genes, so that it is not easy to identify the binding site on the basis of direct DNA sequence analysis. This paper presents a complete workflow based on a one-dimensional Convolutional Neural Network (CNN) model able to detect putative SREBPs binding sites irrespective of target elements arrangements. The strategy is based on the recognition of SRE linked (less than 250 bp) to NFY sequences according to chromosomal localization derived from TF Immunoprecipitation (TF ChIP) experiments. The CNN is trained with several 100 bp sequences containing both SRE and NF-Y. Once trained, the model is used to predict the presence of SRE-NFY in the first 500 bp of all the known gene promoters. Finally, genes are grouped according to biological process and the processes enriched in genes containing SRE-NFY in their promoters are analyzed in details. This workflow allowed to identify biological processes enriched in SRE containing genes not directly linked to cholesterol metabolism and possible novel DNA patterns able to fill in for missing classical SRE sequences

Formation of Hydrogen, Oxygen, and Hydrogen Peroxide in Electron Irradiated Crystalline Water Ice

Water ice is abundant both astrophysically, for example in molecular clouds, and in planetary systems. The Kuiper belt objects, many satellites of the outer solar system, the nuclei of comets and some planetary rings are all known to be water-rich. Processing of water ice by energetic particles and ultraviolet photons plays an important role in astrochemistry. To explore the detailed nature of this processing, we have conducted a systematic laboratory study of the irradiation of crystalline water ice in an ultrahigh vacuum setup by energetic electrons holding a linear energy transfer of 4.3 +/- 0.1 keV mm-1. The irradiated samples were monitored during the experiment both on line and in situ via mass spectrometry (gas phase) and Fourier transform infrared spectroscopy (solid state). We observed the production of hydrogen and oxygen, both molecular and atomic, and of hydrogen peroxide. The likely reaction mechanisms responsible for these species are discussed. Additional formation routes were derived from the sublimation profiles of molecular hydrogen (90-140 K), molecular oxygen (147 -151 K) and hydrogen peroxide (170 K). We also present evidence on the involvement of hydroxyl radicals and possibly oxygen atoms as building blocks to yield hydrogen peroxide at low temperatures (12 K) and via a diffusion-controlled mechanism in the warming up phase of the irradiated sample.Comment: ApJ, March 2006, v639 issue, 43 pages, 7 figure

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network)

Fatty liver in familial hypobetalipoproteinemia: Triglyceride assembly into VLDL particles is affected by the extent of hepatic steatosis

Familial hypobetalipoproteinemia (FHBL) subjects may develop fatty liver. Liver fat was assessed in 21 FHBL with six different apolipoprotein B (apoB) truncations (apoB-4 to apoB-89) and 14 controls by magnetic resonance spectroscopy (MRS). Liver fat percentages were 16.7 ± 11.5 and 3.3 ± 2.9 (mean ± SD) (P = 0.001). Liver fat percentage was positively correlated with body mass index, waist circumference, and areas under the insulin curves of 2 h glucose tolerance tests, suggesting that obesity may affect the severity of liver fat accumulation in both groups. Despite 5-fold differences in liver fat percentage, mean values for obesity and insulin indexes were similar. Thus, for similar degrees of obesity, FHBL subjects have more hepatic fat. VLDL-triglyceride (TG)-fatty acids arise from plasma and nonplasma sources (liver and splanchnic tissues). To assess the relative contributions of each, [2H2] palmitate was infused over 12 h in 13 FHBL subjects and 11 controls. Isotopic enrichment of plasma free palmitate and VLDL-TG-palmitate was determined by mass spectrometry. Nonplasma sources contributed 51 ± 15% in FHBL and 37 ± 13% in controls (P = 0.02). Correlations of liver fat percentage and percent VLDL-TG-palmitate from liver were r = 0.89 (P = 0.0001) for FHBL subjects and r = 0.69 (P = 0.01) for controls. Thus, apoB truncation-producing mutations result in fatty liver and in altered assembly of VLDL-TG

Lipid Peroxidation, Nitric Oxide Metabolites, and Their Ratio in a Group of Subjects with Metabolic Syndrome

Our aim was to evaluate lipid peroxidation, expressed as thiobarbituric acid-reactive substances (TBARS), nitric oxide metabolites (nitrite + nitrate) expressed as NOx, and TBARS/NOx ratio in a group of subjects with metabolic syndrome (MS). In this regard we enrolled 106 subjects with MS defined according to the IDF criteria, subsequently subdivided into diabetic (DMS) and nondiabetic (NDMS) and also into subjects with a low triglycerides/HDL-cholesterol (TG/HDL-C) index or with a high TG/HDL-C index. In the entire group and in the four subgroups of MS subjects we found an increase in TBARS and NOx levels and a decrease in TBARS/NOx ratio in comparison with normal controls. Regarding all these parameters no statistical difference between DMS and NDMS was evident, but a significant increase in NOx was present in subjects with a high TG/HDL-C index in comparison with those with a low index. In MS subjects we also found a negative correlation between TBARS/NO x ratio and TG/HDL-C index. Considering the hyperactivity of the inducible NO synthase in MS, these data confirm the altered redox and inflammatory status that characterizes the MS and suggest a link between lipid peroxidation, inflammation, and insulin resistance, evaluated as TG/HDL-C index

Replication of linkage of familial hypobetalipoproteinemia to chromosome 3p in six kindreds

Familial hypobetalipoproteinemia (FHBL) is a genetically heterogeneous condition characterized by very low apolipoprotein B (apoB) concentrations in plasma and/or low levels of LDL-cholesterol (LDL-C) with a propensity to developing fatty liver. In a minority of cases, truncation-specifying mutations of the apoB gene (APOB) are etiologic, but the genetic basis of most cases is unknown. We previously reported linkage of FHBL to a 10 cM region on 3p21.1-22 in one kindred. The objectives of the current study were to identify other FHBL families with linkage to 3p and to narrow the FHBL susceptibility region on 3p. Six additional FHBL kindreds unlinked to the APOB region on chromosome 2 were genotyped with polymorphic markers spanning a region of approximately 13 cM on chromosome 3. Quantitative linkage analyses indicated that the FHBL in these families was linked to 3p21.1-22. Haplotype analysis identified several meiotic crossover events, allowing us to narrow the critical region from 10 cM to 2.0 cM, between markers D3S2407 and D3S1767

RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

In this study, by using different techniques (i.e. Northern blot hybridization, RT-PCR and Southern blot hybridization) on various normal rat tissues, we were able to identify liver, kidney, heart, small intestine, brain, spleen, stomach and prostate as tissues in which the ApoH gene is transcribed. Moreover, for some of these tissues, by in situ hybridization, we found a specific localization of apoH transcripts. For instance epithelial cells of the bile ducts in liver and of the proximal tubules in kidney are the major sites of apoH synthesis. Our data suggest that some of the different physiological roles proposed for apoH could correlate with its direct expression, while others could correlate with its absorption from bloodstream or adjacent cells

Lipoprotein abnormalities in chronic kidney disease and renal transplantation

Chronic kidney disease (CKD) is one of the most important risk factors for cardiovascular disease (CVD). Despite the kidney having no direct implications for lipoproteins metabolism, advanced CKD dyslipidemia is usually present in patients with CKD, and the frequent lipid and lipoprotein alterations occurring in these patients play a role of primary importance in the development of CVD. Although hypertriglyceridemia is the main disorder, a number of lipoprotein abnormalities occur in these patients. Different enzymes pathways and proteins involved in lipoprotein metabolism are impaired in CKD. In addition, treatment of uremia may modify the expression of lipoprotein pattern as well as determine acute changes. In renal transplantation recipients, the main lipid alteration is hypercholesterolemia, while hypertriglyceridemia is less pronounced. In this review we have analyzed lipid and lipoprotein disturbances in CKD and also their relationship with progression of renal disease. Hypolipidemic treatments may also change the natural history of CVD in CKD patients and may represent important strategies in the management of CKD patients