Sequence variations of ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1, CRHR1 and NTRK2: association with major depression and antidepressant response in Mexican-Americans

We studied seven genes that reflect events relevant to antidepressant action at four sequential levels: (1) entry into the brain, (2) binding to monoaminergic transporters, and (3) distal effects at the transcription level, resulting in (4) changes in neurotrophin and neuropeptide receptors. Those genes are ATP-binding cassette subfamily B member 1 (ABCB1), the noradrenaline, dopamine, and serotonin transporters (SLC6A2, SLC6A3 and SLC6A4), cyclic AMP-responsive element binding protein 1 (CREB1), corticotropin-releasing hormone receptor 1 (CRHR1) and neurotrophic tyrosine kinase type 2 receptor (NTRK2). Sequence variability for those genes was obtained in exonic and flanking regions. A total of 56 280 000 bp across were sequenced in 536 unrelated Mexican Americans from Los Angeles (264 controls and 272 major depressive disorder (MDD)). We detected in those individuals 419 single nucleotide polymorphisms (SNPs); the nucleotide diversity was 0.00054±0.0001. Of those, a total of 204 novel SNPs were identified, corresponding to 49% of all previously reported SNPs in those genes: 72 were in untranslated regions, 19 were in coding sequences of which 7 were non-synonymous, 86 were intronic and 27 were in upstream/downstream regions. Several SNPs or haplotypes in ABCB1, SLC6A2, SLC6A3, SLC6A4, CREB1 and NTRK2 were associated with MDD, and in ABCB1, SLC6A2 and NTRK2 with antidepressant response. After controlling for age, gender and baseline 21-item Hamilton Depression Rating Scale (HAM-D21) score, as well as correcting for multiple testing, the relative reduction of HAM-D21 score remained significantly associated with two NTRK2-coding SNPs (rs2289657 and rs56142442) and the haplotype CAG at rs2289658 (splice site), rs2289657 and rs2289656. Further studies in larger independent samples will be needed to confirm these associations. Our data indicate that extensive assessment of sequence variability may contribute to increase understanding of disease susceptibility and drug response. Moreover, these results highlight the importance of direct re-sequencing of key candidate genes in ethnic minority groups in order to discover novel genetic variants that cannot be simply inferred from existing databases

Access to housing subsidies, housing status, drug use and HIV risk among low-income U.S. urban residents

<p>Abstract</p> <p>Background</p> <p>Much research has shown an association between homelessness and unstable housing and HIV risk but most has relied on relatively narrow definitions of housing status that preclude a deeper understanding of this relationship. Fewer studies have examined access to housing subsidies and supportive housing programs among low-income populations with different personal characteristics. This paper explores personal characteristics associated with access to housing subsidies and supportive housing, the relationship between personal characteristics and housing status, and the relationship between housing status and sexual risk behaviors among low-income urban residents.</p> <p>Methods</p> <p>Surveys were conducted with 392 low-income residents from Hartford and East Harford, Connecticut through a targeted sampling plan. We measured personal characteristics (income, education, use of crack, heroin, or cocaine in the last 6 months, receipt of welfare benefits, mental illness diagnosis, arrest, criminal conviction, longest prison term served, and self-reported HIV diagnosis); access to housing subsidies or supportive housing programs; current housing status; and sexual risk behaviors. To answer the aims above, we performed univariate analyses using Chi-square or 2-sided ANOVA's. Those with significance levels above (0.10) were included in multivariate analyses. We performed 2 separate multiple regressions to determine the effects of personal characteristics on access to housing subsidies and access to supportive housing respectively. We used multinomial main effects logistic regression to determine the effects of housing status on sexual risk behavior.</p> <p>Results</p> <p>Being HIV positive or having a mental illness predicted access to housing subsidies and supportive housing, while having a criminal conviction was not related to access to either housing subsidies or supportive housing. Drug use was associated with poorer housing statuses such as living on the street or in a shelter, or temporarily doubling up with friends, acquaintances or sex partners. Living with friends, acquaintances or sex partners was associated with greater sexual risk than those living on the street or in other stable housing situations.</p> <p>Conclusions</p> <p>Results suggest that providing low-income and supportive housing may be an effective structural HIV prevention intervention, but that the availability and accessibility of these programs must be increased.</p

Cosmology with the Laser Interferometer Space Antenna

The Laser Interferometer Space Antenna (LISA) has two scientific objectives of cosmological focus: to probe the expansion rate of the universe, and to understand stochastic gravitational-wave backgrounds and their implications for early universe and particle physics, from the MeV to the Planck scale. However, the range of potential cosmological applications of gravitational wave observations extends well beyond these two objectives. This publication presents a summary of the state of the art in LISA cosmology, theory and methods, and identifies new opportunities to use gravitational wave observations by LISA to probe the universe

Vulnerability of marine megafauna to global at-sea anthropogenic threats

Marine megafauna species are affected by a wide range of anthropogenic threats. To evaluate the risk of such threats, species' vulnerability to each threat must first be determined. We build on the existing threats classification scheme and ranking system of the International Union for Conservation of Nature (IUCN) Red List of Threatened Species by assessing the vulnerability of 256 marine megafauna species to 23 at-sea threats. The threats we considered included individual fishing gear types, climate-change-related subthreats not previously assessed, and threats associated with coastal impacts and maritime disturbances. Our ratings resulted in 70 species having high vulnerability (v > 0.778 out of 1) to at least 1 threat, primarily drifting longlines, temperature extremes, or fixed gear. These 3 threats were also considered to have the most severe effects (i.e., steepest population declines). Overall, temperature extremes and plastics and other solid waste were rated as affecting the largest proportion of populations. Penguins, pinnipeds, and polar bears had the highest vulnerability to temperature extremes. Bony fishes had the highest vulnerability to drifting longlines and plastics and other solid waste; pelagic cetaceans to 4 maritime disturbance threats; elasmobranchs to 5 fishing threats; and flying birds to drifting longlines and 2 maritime disturbance threats. Sirenians and turtles had the highest vulnerability to at least one threat from all 4 categories. Despite not necessarily having severe effects for most taxonomic groups, temperature extremes were rated among the top threats for all taxa except bony fishes. The vulnerability scores we provide are an important first step in estimating the risk of threats to marine megafauna. Importantly, they help differentiate scope from severity, which is key to identifying threats that should be prioritized for mitigation

Protein Quality and the Protein to Carbohydrate Ratio within a High Fat Diet Influences Energy Balance and the Gut Microbiota In C57BL/6J Mice

peer-reviewedMacronutrient quality and composition are important determinants of energy balance and the gut microbiota. Here, we investigated how changes to protein quality (casein versus whey protein isolate; WPI) and the protein to carbohydrate (P/C) ratio within a high fat diet (HFD) impacts on these parameters. Mice were fed a low fat diet (10% kJ) or a high fat diet (HFD; 45% kJ) for 21 weeks with either casein (20% kJ, HFD) or WPI at 20%, 30% or 40% kJ. In comparison to casein, WPI at a similar energy content normalised energy intake, increased lean mass and caused a trend towards a reduction in fat mass (P = 0.08), but the protein challenge did not alter oxygen consumption or locomotor activity. WPI reduced HFD-induced plasma leptin and liver triacylglycerol, and partially attenuated the reduction in adipose FASN mRNA in HFD-fed mice. High throughput sequence-based analysis of faecal microbial populations revealed microbiota in the HFD-20% WPI group clustering closely with HFD controls, although WPI specifically increased Lactobacillaceae/Lactobacillus and decreased Clostridiaceae/Clostridium in HFD-fed mice. There was no effect of increasing the P/C ratio on energy intake, but the highest ratio reduced HFD-induced weight gain, fat mass and plasma triacylglycerol, non-esterified fatty acids, glucose and leptin levels, while it increased lean mass and oxygen consumption. Similar effects were observed on adipose mRNA expression, where the highest ratio reduced HFD-associated expression of UCP-2, TNFa and CD68 and increased the diet-associated expression of b3-AR, LPL, IR, IRS-1 and GLUT4. The P/C ratio also impacted on gut microbiota, with populations in the 30/ 40% WPI groups clustering together and away from the 20% WPI group. Taken together, our data show that increasing the P/C ratio has a dramatic effect on energy balance and the composition of gut microbiota, which is distinct from that caused by changes to protein quality.KN is supported by the Teagasc Vision Programme on Obesity, which also funded the work detailed in this manuscript. LM is supported by a Teagasc PhD Walsh Fellowship. HMR is supported by SFI PI (11/PI/1119)