Comparative chromosome painting discloses homologous Segments in distantly related mammals

Comparative chromosome painting, termed ZOO-FISH, using DNA libraries from flow sorted human chromosomes 1,16,17 and X, and mouse chromosome 11 discloses the presence of syntenic groups in distantly related mammalian Orders ranging from primates (Homo sapiens), rodents (Mus musculus), even-toed ungulates (Muntiacus muntjak vaginalis and Muntiacus reevesi) and whales (Balaenoptera physalus). These mammalian Orders have evolved separately for 55-80 million years (Myr). We conclude that ZOO-FISH can be used to generate comparative chromosome maps of a large number of mammalian species

Polymorphisms in the SAA1/2 Gene Are Associated with Carotid Intima Media Thickness in Healthy Han Chinese Subjects: The Cardiovascular Risk Survey

BACKGROUND: Serum amyloid A protein (SAA) is not only an inflammatory factor, but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein (HDL), which has been linked to atherosclerosis. However, the relationship between genetic polymorphisms of SAA and the intima-media thickness (IMT) of the common carotid artery in healthy subjects remains unclear. We investigated the role of SAA1 and SAA2 gene polymorphisms with IMT in a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study. METHODOLOGY/PRINCIPAL FINDINGS: Anthropometric and B-mode ultrasound of the carotid IMT were measured in 1914 subjects (849 men; 1065 women) recruited from seven cities in Xinjiang province, (western China). Four SNPs (rs12218, rs2229338, rs1059559, and rs2468844) were genotyped by use of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The SNP rs12218 was associated with carotid IMT by analyses of a dominate model (P<0.001) and additive model (P = 0.003), and the difference remained significant after multivariate adjustment (P = 0.008, P<0.001, respectively). This relationship was also observed in rs2468844 after multivariate adjustment by recessive model analysis (P = 0.011) but this was not observed in rs2229338 and rs1059559 before and after multivariate adjustment. These associations were not modified by serum HDL concentration. Furthermore, there were significant interactions between rs2468844 and rs12218 (interaction P<0.001) and rs2229338 (interaction P = 0.001) on carotid IMT. CONCLUSION/SIGNIFICANCE: Both rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects

Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis

The cystic fibrosis gene was recently cloned, and a three-base deletion removing phenylalanine 508 from the coding region was identified as the mutation on the majority of cystic fibrosis chromosomes. We used the polymerase chain reaction and hybridization with allele-specific oligonucleotides to analyze the presence or absence of this mutation on 439 cystic fibrosis chromosomes and 433 normal chromosomes from non-Ashkenazic white families. This mutation was present on 75.8 percent of the cystic fibrosis chromosomes. Using the DNA markers XV-2c and KM-19, we found that 96 percent of cystic fibrosis chromosomes with the mutation had a single DNA haplotype that occurs frequently with cystic fibrosis chromosomes. This haplotype was also found on 54 percent of the cystic fibrosis chromosomes without the three-base deletion. The three-base deletion was found on only 30.3 percent of cystic fibrosis chromosomes from Ashkenazic families, although the common cystic fibrosis haplotype was present on 97 percent of cystic fibrosis chromosomes from Ashkenazic families. The ability to detect the common mutation causing cystic fibrosis represents a major improvement in prenatal diagnosis and heterozygote detection, particularly in families in which no DNA sample is available from the affected child, and provides an improved method of testing for spouses of carriers of cystic fibrosis. Mutation analysis introduces the possibility of population-based screening programs for carriers, which on the basis of the sample in this study, would currently identify about 57 percent of the non-Ashkenazic white couples at risk.published_or_final_versio

Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models

The distances over which biological molecules and their complexes can function range from a few nanometres, in the case of folded structures, to millimetres, for example during chromosome organization. Describing phenomena that cover such diverse length, and also time scales, requires models that capture the underlying physics for the particular length scale of interest. Theoretical ideas, in particular, concepts from polymer physics, have guided the development of coarse-grained models to study folding of DNA, RNA, and proteins. More recently, such models and their variants have been applied to the functions of biological nanomachines. Simulations using coarse-grained models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure

Length of stay and associated costs of obesity related hospital admissions in Ireland

BACKGROUND: Obesity is the cause of other chronic diseases, psychological problems, obesity shortens the lifespan and puts strain on health systems. The risk associated with childhood obesity in particular, which will accelerate the development of adult morbidity and mortality, has been identified as an emerging public health problem. METHODS: To estimate the length of stay and associated hospital costs for obesity related illnesses a cost of illness study was set up. All discharges from all acute hospitals in the Republic of Ireland from 1997 to 2004 with a principal or secondary diagnostic code for obesity for all children from 6 to 18 years of age and for adults were collected.A discharge frequency was calculated by dividing obesity related discharges by the total number of diagnoses (principal and secondary) for each year. The hospital costs related to obesity was calculated based on the total number of days care. RESULTS: The discharge frequency of obesity related conditions increased from 1.14 in 1997 to 1.49 in 2004 for adults and from 0.81 to 1.37 for children. The relative length of stay (number of days in care for obesity related conditions per 1000 days of hospital care given) increased from 1.47 in 1997 to 4.16 in 2004 for children and from 3.68 in 1997 to 6.74 in 2004 for adults.Based on the 2001 figures for cost per inpatient bed day, the annual hospital cost was calculated to be 4.4 Euromillion in 1997, increasing to 13.3 Euromillion in 2004. At a 20% variable hospital cost the cost ranges from 0.9 Euromillion in 1997 to 2.7 Euromillion in 2004; a 200% increase. CONCLUSION: The annual increase in the proportion of hospital discharges related to obesity is alarming. This increase is related to a significant increase in economic costs. This paper emphasises the need for action at an early stage of life. Health promotion and primary prevention of obesity should be high on the political agenda

Central blood pressure and pulse wave velocity: relationship to target organ damage and cardiovascular morbidity-mortality in diabetic patients or metabolic syndrome. An observational prospective study. LOD-DIABETES study protocol

<p>Abstract</p> <p>Background</p> <p>Diabetic patients show an increased prevalence of non-dipping arterial pressure pattern, target organ damage and elevated arterial stiffness. These alterations are associated with increased cardiovascular risk.</p> <p>The objectives of this study are the following: to evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of target organ damage and the appearance of cardiovascular episodes (cardiovascular mortality, myocardial infarction, chest pain and stroke) in patients with type 2 diabetes mellitus or metabolic syndrome.</p> <p>Methods/Design</p> <p><b>Design</b>: This is an observational prospective study with 5 years duration, of which the first year corresponds to patient inclusion and initial evaluation, and the remaining four years to follow-up.</p> <p><b>Setting</b>: The study will be carried out in the urban primary care setting.</p> <p><b>Study population</b>: Consecutive sampling will be used to include patients diagnosed with type 2 diabetes between 20-80 years of age. A total of 110 patients meeting all the inclusion criteria and none of the exclusion criteria will be included.</p> <p><b>Measurements</b>: Patient age and sex, family and personal history of cardiovascular disease, and cardiovascular risk factors. Height, weight, heart rate and abdominal circumference. Laboratory tests: hemoglobin, lipid profile, creatinine, microalbuminuria, glomerular filtration rate, blood glucose, glycosylated hemoglobin, blood insulin, fibrinogen and high sensitivity C-reactive protein. Clinical and 24-hour ambulatory (home) blood pressure monitoring and self-measured blood pressure. Common carotid artery ultrasound for the determination of mean carotid intima-media thickness. Electrocardiogram for assessing left ventricular hypertrophy. Ankle-brachial index. Retinal vascular study based on funduscopy with non-mydriatic retinography and evaluation of pulse wave morphology and pulse wave velocity using the SphygmoCor system. The medication used for diabetes, arterial hypertension and hyperlipidemia will be registered, together with antiplatelet drugs.</p> <p>Discussion</p> <p>The results of this study will help to know and quantify the prognostic value of central arterial pressure and pulse wave velocity in relation to the evolution of the subclinical target organ damage markers and the possible incidence of cardiovascular events in patients with type 2 diabetes mellitus.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT01065155</p

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm