Association between a rare SNP in the second intron of human Agouti related protein gene and increased BMI

<p>Abstract</p> <p>Background</p> <p>The agouti related protein (AGRP) is an endogenous antagonist of the melanocortin 4 receptor and is one of the most potent orexigenic factors. The aim of the present study was to assess the genetic variability of <it>AGRP </it>gene and investigate whether the previously reported SNP rs5030980 and the rs11575892, a SNP that so far has not been studied with respect to obesity is associated with increased body mass index (BMI).</p> <p>Methods</p> <p>We determined the complete sequence of the <it>AGRP </it>gene and upstream promoter region in 95 patients with severe obesity (BMI > 35 kg/m²). Three polymorphisms were identified: silent mutation c.123G>A (rs34123523) in the second exon, non-synonymous mutation c.199G>A (rs5030980) and c.131-42C>T (rs11575892) located in the second intron. We further screened rs11575892 in a selected group of 1135 and rs5030980 in group of 789 participants from the Genome Database of Latvian Population and Latvian State Research Program Database.</p> <p>Results</p> <p>The CT heterozygotes of rs11575892 had significantly higher mean BMI value (p = 0.027). After adjustment for age, gender and other significant non-genetic factors (presence of diseases), the BMI levels remained significantly higher in carriers of the rs11575892 T allele (p = 0.001). The adjusted mean BMI value of CC genotype was 27.92 ± 1.01 kg/m²(mean, SE) as compared to 30.97 ± 1.03 kg/m²for the CT genotype. No association was found between rs5030980 and BMI.</p> <p>Conclusion</p> <p>This study presents an association of rare allele of <it>AGRP </it>polymorphism in heterozygous state with increased BMI. The possible functional effects of this polymorphism are unclear but may relate to splicing defects.</p

Breeding productivity, nest-site selection and conservation needs of the endemic Turkestan Ground-jay Podoces panderi

The Turkestan Ground-jay Podoces panderi, a corvid endemic to the deserts of Central Asia, is both understudied and under-protected. Using standardised nest-monitoring protocols and nest cameras, we estimated its breeding productivity for the first time as 0.586 fledglings per nesting attempt (inter-quartile range, IQR 0.413‒0.734), strongly constrained by a diverse set of predator species (accounting for 88% of failures), supporting the broad pattern that a wide spectrum of nest predators operate in arid environments. The probability of nest success for the 35 days from the start of incubation to fledging was low, 0.186 ± 0.06 se (N = 37), with no influence of season date, nest height or nest shrub species. However, pervasive shrub harvest severely limited availability of taller shrubs for nest-site selection, and thus our ability to detect any effect of height on nest survival. Mean clutch size was 4.8 ± 0.8 sd while hatching probability of an egg from a clutch surviving incubation was 0.800 ± 0.050 se and fledging probability was 0.824 ± 0.093 se for individual chicks in successful nests (i.e. that fledged one or more chicks). Two shrub genera, saxaul Haloxylon spp. and Calligonum spp., were used for nesting more frequently than expected (χ152 = 784.02, P < 0.001), highlighting their importance to breeding habitat suitability. This near-sole reliance on these taller shrub genera, both targeted for illegal cutting, indicates that habitat degradation may lead to increased predation and declines in productivity. Habitat conservation is, therefore, likely to be the most important management strategy for the species and other components of desert systems, as management of so diverse a set of nest predators would be both impractical and inappropriate

Preventing foot ulceration in diabetes:systematic review and meta-analyses of RCT data

Aims/hypothesis: Foot ulceration is a serious complication for people with diabetes that results in high levels of morbidity for individuals and significant costs for health and social care systems. Nineteen systematic reviews of preventative interventions have been published, but none provides a reliable numerical summary of treatment effects. The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to make the best possible use of the currently available data. Methods: We conducted a systematic review and meta-analysis of RCTs of preventative interventions for foot ulceration. OVID MEDLINE and EMBASE were searched to February 2019 and the Cochrane Central Register of Controlled Trials to October 2018. RCTs of interventions to prevent foot ulcers in people with diabetes who were free from foot ulceration at trial entry were included. Two independent reviewers read the full-text articles and extracted data. The quality of trial reporting was assessed using the Cochrane Risk of Bias tool. The primary outcome of foot ulceration was summarised using pooled relative risks in meta-analyses. Results: Twenty-two RCTs of eight interventions were eligible for analysis. One trial of digital silicone devices (RR 0.07 [95% CI 0.01, 0.55]) and meta-analyses of dermal infrared thermometry (RR 0.41 [95% CI 0.19, 0.86]), complex interventions (RR 0.59 [95% CI 0.38, 0.90], and custom-made footwear and offloading insoles (RR 0.53 [95% CI 0.33, 0.85]) showed beneficial effects for these interventions. Conclusions/interpretation: Four interventions were identified as being effective in preventing foot ulcers in people with diabetes, but uncertainty remains about what works and who is most likely to benefit

Adenosine A1 receptor: Functional receptor-receptor interactions in the brain

Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A1 receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A2A, A3, neuropeptide Y, and purinergic P2Y1 receptors will be described in the first part. The second part deals with interactions between A1Rs and ionotropic receptors, especially GABAA, NMDA, and P2X receptors as well as ATP-sensitive K+ channels. Finally, the review will discuss new approaches towards treating neurological disorders

Is exposure to formaldehyde in air causally associated with leukemia?—A hypothesis-based weight-of-evidence analysis

Recent scientific debate has focused on the potential for inhaled formaldehyde to cause lymphohematopoietic cancers, particularly leukemias, in humans. The concern stems from certain epidemiology studies reporting an association, although particulars of endpoints and dosimetry are inconsistent across studies and several other studies show no such effects. Animal studies generally report neither hematotoxicity nor leukemia associated with formaldehyde inhalation, and hematotoxicity studies in humans are inconsistent. Formaldehyde's reactivity has been thought to preclude systemic exposure following inhalation, and its apparent inability to reach and affect the target tissues attacked by known leukemogens has, heretofore, led to skepticism regarding its potential to cause human lymphohematopoietic cancers. Recently, however, potential modes of action for formaldehyde leukemogenesis have been hypothesized, and it has been suggested that formaldehyde be identified as a known human leukemogen. In this article, we apply our hypothesis-based weight-of-evidence (HBWoE) approach to evaluate the large body of evidence regarding formaldehyde and leukemogenesis, attending to how human, animal, and mode-of-action results inform one another. We trace the logic of inference within and across all studies, and articulate how one could account for the suite of available observations under the various proposed hypotheses. Upon comparison of alternative proposals regarding what causal processes may have led to the array of observations as we see them, we conclude that the case fora causal association is weak and strains biological plausibility. Instead, apparent association between formaldehyde inhalation and leukemia in some human studies is better interpreted as due to chance or confounding

The environmental impacts of palm oil in context

Delivering the Sustainable Development Goals (SDGs) requires balancing demands on land between agriculture (SDG 2) and biodiversity (SDG 15). The production of vegetable oils, and in particular palm oil, illustrates these competing demands and trade-offs. Palm oil accounts for 40% of the current global annual demand for vegetable oil as food, animal feed, and fuel (210 million tons (Mt)), but planted oil palm covers less than 5-5.5% of total global oil crop area (ca. 425 Mha), due to oil palm’s relatively high yields5. Recent oil palm expansion in forested regions of Borneo, Sumatra, and the Malay Peninsula, where >90% of global palm oil is produced, has led to substantial concern around oil palm’s role in deforestation. Oil palm expansion’s direct contribution to regional tropical deforestation varies widely, ranging from 3% in West Africa to 47% in Malaysia. Oil palm is also implicated in peatland draining and burning in Southeast Asia. Documented negative environmental impacts from such expansion include biodiversity declines, greenhouse gas emissions, and air pollution. However, oil palm generally produces more oil per area than other oil crops, is often economically viable in sites unsuitable for most other crops, and generates considerable wealth for at least some actors. Global demand for vegetable oils is projected to increase by 46% by 20509. Meeting this demand through additional expansion of oil palm versus other vegetable oil crops will lead to substantial differential effects on biodiversity, food security, climate change, land degradation, and livelihoods. Our review highlights that, although substantial gaps remain in our understanding of the relationship between the environmental, socio-cultural and economic impacts of oil palm, and the scope, stringency and effectiveness of initiatives to address these, there has been little research into the impacts and trade-offs of other vegetable oil crops. 65 Greater research attention needs to be given to investigating the impacts of palm oil production 66 compared to alternatives for the trade-offs to be assessed at a global scale