CLOCK is suggested to associate with comorbid alcohol use and depressive disorders

<p>Abstract</p> <p>Background</p> <p>Depression and alcohol abuse or dependence (AUD) co-occur in the general population more frequently than expected by chance. Alcohol use influences the circadian rhythms generated by the central pacemaker in the suprachiasmatic nucleus, and circadian rhythm alterations in turn are common in depressive disorders as well as among persons addicted to alcohol.</p> <p>Methods</p> <p>32 SNPs in 19 circadian clockwork related genes were analyzed using DNA from 76 individuals with comorbid depression and AUD, 446 individuals with AUD and 517 healthy controls with no psychiatric diagnosis. The individuals participated in a nationwide health examination study, representative of the general population aged 30 and over in Finland.</p> <p>Results</p> <p>The <it>CLOCK </it>haplotype TTGC formed by SNPs rs3805151, rs2412648, rs11240 and rs2412646, was associated with increased risk for comorbidity (OR = 1.65, 95% CI = 1.14-2.28, P = 0.0077). The SNPs of importance for this suggestive association were rs2412646 and rs11240 indicating location of the functional variation in the block downstream rs2412648. There was no indication for association between <it>CLOCK </it>and AUD.</p> <p>Conclusion</p> <p>Our findings suggest an association between the <it>CLOCK </it>gene and the comorbid condition of alcohol use and depressive disorders. Together with previous reports it indicates that the <it>CLOCK </it>variations we found here may be a vulnerability factor to depression given the exposure to alcohol in individuals having AUD.</p

Utilization of photon orbital angular momentum in the low-frequency radio domain

We show numerically that vector antenna arrays can generate radio beams which exhibit spin and orbital angular momentum characteristics similar to those of helical Laguerre-Gauss laser beams in paraxial optics. For low frequencies (< 1 GHz), digital techniques can be used to coherently measure the instantaneous, local field vectors and to manipulate them in software. This opens up for new types of experiments that go beyond those currently possible to perform in optics, for information-rich radio physics applications such as radio astronomy, and for novel wireless communication concepts.Comment: 4 pages, 5 figures. Changed title, identical to the paper published in PR

The Australian Aboriginal Birth Cohort study: socio-economic status at birth and cardiovascular risk factors to 25 years of age

Objectives: To determine whether socio‐economic status at birth is associated with differences in risk factors for cardiovascular disease — body mass index (BMI), blood pressure, blood lipid levels — during the first 25 years of life.Design: Analysis of prospectively collected data.Setting, participants: 570 of 686 children born to Aboriginal mothers at the Royal Darwin Hospital during 1987–1990 and recruited for the Aboriginal Birth Cohort Study in the Northern Territory. Participants resided in 46 urban and remote communities across the NT. The analysed data were collected at three follow‐ups: Wave 2 in 1998–2001 (570 participants; mean age, 11 years), Wave 3 in 2006–2008 (442 participants; mean age, 18 years), and Wave 4 in 2014–2016 (423 participants; mean age, 25 years).Main outcome measures: Cardiovascular disease risk factors by study wave and three socio‐economic measures at the time of birth: area‐level Indigenous Relative Socioeconomic Outcomes (IRSEO) index score and location (urban, remote) of residence, and parity of mother.Results: Area‐level IRSEO of residence at birth influenced BMI (P Conclusions: Our longitudinal life course analyses indicate that area‐level socio‐economic factors at birth influence the prevalence of major cardiovascular disease risk factors among Indigenous Australians during childhood and early adulthood.</p

CRY2 Is Associated with Depression

Abnormalities in the circadian clockwork often characterize patients with major depressive and bipolar disorders. Circadian clock genes are targets of interest in these patients. CRY2 is a circadian gene that participates in regulation of the evening oscillator. This is of interest in mood disorders where a lack of switch from evening to morning oscillators has been postulated.We observed a marked diurnal variation in human CRY2 mRNA levels from peripheral blood mononuclear cells and a significant up-regulation (P = 0.020) following one-night total sleep deprivation, a known antidepressant. In depressed bipolar patients, levels of CRY2 mRNA were decreased (P = 0.029) and a complete lack of increase was observed following sleep deprivation. To investigate a possible genetic contribution, we undertook SNP genotyping of the CRY2 gene in two independent population-based samples from Sweden (118 cases and 1011 controls) and Finland (86 cases and 1096 controls). The CRY2 gene was significantly associated with winter depression in both samples (haplotype analysis in Swedish and Finnish samples: OR = 1.8, P = 0.0059 and OR = 1.8, P = 0.00044, respectively).We propose that a CRY2 locus is associated with vulnerability for depression, and that mechanisms of action involve dysregulation of CRY2 expression

Establishment of a Transgenic Mouse Model Specifically Expressing Human Serum Amyloid A in Adipose Tissue

Obesity and obesity co-morbidities are associated with a low grade inflammation and elevated serum levels of acute phase proteins, including serum amyloid A (SAA). In the non-acute phase in humans, adipocytes are major producers of SAA but the function of adipocyte-derived SAA is unknown. To clarify the role of adipocyte-derived SAA, a transgenic mouse model expressing human SAA1 (hSAA) in adipocytes was established. hSAA expression was analysed using real-time PCR analysis. Male animals were challenged with a high fat (HF) diet. Plasma samples were subjected to fast protein liquid chromatography (FPLC) separation. hSAA, cholesterol and triglyceride content were measured in plasma and in FPLC fractions. Real-time PCR analysis confirmed an adipose tissue-specific hSAA gene expression. Moreover, the hSAA gene expression was not influenced by HF diet. However, hSAA plasma levels in HF fed animals (37.7±4.0 µg/mL, n = 7) were increased compared to those in normal chow fed animals (4.8±0.5 µg/mL, n = 10; p<0.001), and plasma levels in the two groups were in the same ranges as in obese and lean human subjects, respectively. In FPLC separated plasma samples, the concentration of hSAA peaked in high-density lipoprotein (HDL) containing fractions. In addition, cholesterol distribution over the different lipoprotein subfractions as assessed by FPLC analysis was similar within the two experimental groups. The established transgenic mouse model demonstrates that adipose tissue produced hSAA enters the circulation, resulting in elevated plasma levels of hSAA. This new model will enable further studies of metabolic effects of adipose tissue-derived SAA

Proteomic analysis at the sites of clinical infection with invasive Streptococcus pyogenes

Invasive Streptococcus pyogenes infections are rare, with often-unexplained severity. Prompt diagnosis is desirable, as deaths can occur rapidly following onset and there is an increased, but preventable, risk to contacts. Here, proteomic analyses of clinical samples from invasive human S. pyogenes infections were undertaken to determine if novel diagnostic targets could be detected, and to augment our understanding of disease pathogenesis. Fluid samples from 17 patients with confirmed invasive S. pyogenes infection (empyema, septic arthritis, necrotising fasciitis) were analysed by proteomics for streptococcal and human proteins; 16/17 samples had detectable S. pyogenes DNA. Nineteen unique S. pyogenes proteins were identified in just 6/17 samples, and 15 of these were found in a single pleural fluid sample including streptococcal inhibitor of complement, trigger factor, and phosphoglycerate kinase. In contrast, 469 human proteins were detected in patient fluids, 177 (38%) of which could be identified as neutrophil proteins, including alpha enolase and lactotransferrin which, together, were found in all 17 samples. Our data suggest that streptococcal proteins are difficult to detect in infected fluid samples. A vast array of human proteins associated with leukocyte activity are, however, present in samples that deserve further evaluation as potential biomarkers of infection