Anti-LEPR polyclonal antibody [Biotin]

Background: The clinical phenotype of patients with monogenic obesity due to mutations in the leptin receptor (LEPR) or melanocortin 4 receptor (MC4R) gene is characterized by impaired satiety and hyperphagia, leading to extreme, sometimes life-threatening weight gain. Subjects/methods: In a case series, we analysed the effect of an off-label methylphenidate (MPH) use for 1 year as an individual treatment approach on eating behaviour (Child Eating Behaviour Questionnaire [CEBQ]), appetite (visual analogue scales) and body mass index (BMI) trajectories in five patients with severe obesity due to mutations in the LEPR (n = 3) or MC4R (n = 2) gene. Results: After 1 year use of MPH (20 mg/day divided in two to three doses), BMI (Delta BMIT0-T1 (x) over bar: -0.7 +/- 0.9 kg/m(2)), BMI standard deviation score (SDS) (Delta BMI-SDST0-T1 (x) over bar: -0.32 +/- 0.20), and %BMIP95 (Delta%BMIP95(T0-T1) (x) over bar: -6.6 +/- 7.8%) decreased. BMI-SDS velocity decreased from +0.17 +/- 0.22 to -0.30 +/- 0.20. Appetite and CEBQ subscale scores for "food responsiveness" and "enjoyment of food" decreased. We observed adverse effects with increase in self-reported frequency of disordered sleep, nervousness, hyperactivity, and tics. Conclusions: The observed decrease in BMI trajectories with MPH use for one year is clinically meaningful in this group of patients, since the natural course would have been associated with a pronounced increase in BMI, leading to comorbidities and complications over time.

We carried out whole genome resequencing of 127 chicken including red jungle fowl and multiple populations of commercial broilers and layers to perform a systematic screening of adaptive changes in modern chicken (Gallus gallus domesticus). We uncovered >21 million high quality SNPs of which 34% are newly detected variants. This panel comprises >115,000 predicted amino-acid altering substitutions as well as 1,100 SNPs predicted to be stop-gain or -loss, several of which reach high frequencies. Signatures of selection were investigated both through analyses of fixation and differentiation to reveal selective sweeps that may have had prominent roles during domestication and breed development. Contrasting wild and domestic chicken we confirmed selection at the BCO2 and TSHR loci and identified 34 putative sweeps co-localized with ALX1, KITLG, EPGR, IGF1, DLK1, JPT2, CRAMP1, and GLI3, among others. Analysis of enrichment between groups of wild vs. commercials and broilers vs. layers revealed a further panel of candidate genes including CORIN, SKIV2L2 implicated in pigmentation and LEPR, MEGF10 and SPEF2, suggestive of production-oriented selection. SNPs with marked allele frequency differences between wild and domestic chicken showed a highly significant deficiency in the proportion of amino-acid altering mutations (P<2.5x10(-6)). The results contribute to the understanding of major genetic changes that took place during the evolution of modern chickens and in poultry breeding. Author summary Domestic chickens (Gallus gallus domesticus) provide a critical resource for animal proteins for human nutrition worldwide. Chickens were primarily domesticated from the red jungle fowl (Gallus gallus gallus), a bird that still runs wild in most of Southeast Asia. Human driven selection during domestication and subsequent specialization into meat type (broilers) and egg layer (layers) birds has left detectable signatures of selection within the genome of modern chicken. In this study, we performed whole genome sequencing of 127 chicken including the red jungle fowl and multiple populations of commercial broilers and layers to perform a systematic screening of adaptive changes in modern chicken. Analysis of selection provided a comprehensive list of several tens of independent loci that are likely to have contributed to domestication or improving production. SNP by SNP comparison of allele frequency between groups of wild and domestic chicken showed a highly significant deficiency of the proportion of amino acid altering mutations. This implies that commercial birds have undergone purifying selection reducing the frequency of deleterious variants.