Mitochondrial DNA Content in Human Omental Adipose Tissue

Background: Impairment of mitochondrial function plays an important role in obesity and the development of insulin resistance. The aim of this project was to investigate the mitochondrial DNA copy number in human omental adipose tissue with respect to obesity. Methods: The mitochondrial DNA (mtDNA) content per single adipocyte derived from abdominal omental adipose tissue was determined by quantitative RT-PCR in a group of 75 patients, consisting of obese and morbidly obese subjects, as well as non-obese controls. Additionally, basal metabolic rate and fat oxidation rate were recorded and expressed as total values or per kilogram fat mass. Results: MtDNA content is associated with obesity. Higher body mass index (BMI) resulted in a significantly elevated mtDNA count (ratio = 1.56; p = 0.0331) comparing non-obese (BMI < 30) to obese volunteers (BMI ≥ 30). The mtDNA count per cell was not correlated with age or gender. Diabetic patients showed a trend toward reduced mtDNA content. A seasonal change in mtDNA copy number could not be identified. In addition, a substudy investigating the basal metabolic rate and the fasting fat oxidation did not reveal any associations to the mtDNA count. Conclusions: The mtDNA content per cell of omental adipose tissue did not correlate with various clinical parameters but tended to be reduced in patients with diabetes, which may partly explain the impairment of mitochondrial function observed in insulin resistance. Furthermore, the mtDNA content was significantly increased in patients suffering from obesity (BMI above 30). This might reflect a compensatory response to the development of obesity, which is associated with impairment of mitochondrial functio

MSH Radiopeptides for Targeting Melanoma Metastases

Radiolabeled peptides have become important tools for preclinical cancer research and in nuclear oncology they serve as diagnostic and more recently also as therapeutic agents. Whereas the development of receptor-mediated targeting for therapy has been confined to some radiolabeled antibodies and somatostatin/SRIF analogs, recent research into radiolabeled -Melanocyte-stimulating hormone ( -MSH) and its receptor MC1R (over-)expressed by melanoma tumor cells has demonstrated that small metastatic melanoma lesions in experimental animals are specifically targeted by MSH radiopeptides. Thus MSH radiopharmaceuticals will eventually open a new avenue for the treatment of melanoma metastases in man, provided that the targeting efficiency can be further enhanced and nonspecific incorporation into nontarget organs, e.g., the kidneys, minimized. Some novel MSH lead compounds containing a glyco moiety, added negatively charged groups or a cyclic structure show very promising in vivo targeting characteristics

Attention to elders' voice in non-human primates

The observed respect and attention to elders' speech in traditional cultures appears to have a ‘universal’ component which questions its possible biological bases. Animals present differential attention to the vocalizations of other individuals according to their characteristics but little is known about the potential propensity to pay more attention to vocalizations of elders. On the basis of several hundreds of vocal exchanges recorded, here we show that aged female Campbell's monkeys (Cercopithecus campbelli), despite being significantly less ‘loquacious’ than their younger adult counterparts, elicit many more responses when calling. These findings show that attention to elders' vocal production appears in non-human primates, leading to new lines of questioning on human culture and language evolution

Biallelic variants in HECT E3 paralogs, HECTD4 and UBE3C, encoding ubiquitin ligases cause neurodevelopmental disorders that overlap with Angelman syndrome

Pathogenic variants in genes encoding ubiquitin E3 ligases are known to cause neurodevelopmental syndromes. Additional neurodevelopmental disorders associated with the other genes encoding E3 ligases are yet to be identified

Mitochondrial DNA content in human omental adipose tissue

BACKGROUND: Impairment of mitochondrial function plays an important role in obesity and the development of insulin resistance. The aim of this project was to investigate the mitochondrial DNA copy number in human omental adipose tissue with respect to obesity. METHODS: The mitochondrial DNA (mtDNA) content per single adipocyte derived from abdominal omental adipose tissue was determined by quantitative RT-PCR in a group of 75 patients, consisting of obese and morbidly obese subjects, as well as non-obese controls. Additionally, basal metabolic rate and fat oxidation rate were recorded and expressed as total values or per kilogram fat mass. RESULTS: MtDNA content is associated with obesity. Higher body mass index (BMI) resulted in a significantly elevated mtDNA count (ratio = 1.56; p = 0.0331) comparing non-obese (BMI > 30) to obese volunteers (BMI <or= 30). The mtDNA count per cell was not correlated with age or gender. Diabetic patients showed a trend toward reduced mtDNA content. A seasonal change in mtDNA copy number could not be identified. In addition, a substudy investigating the basal metabolic rate and the fasting fat oxidation did not reveal any associations to the mtDNA count. CONCLUSIONS: The mtDNA content per cell of omental adipose tissue did not correlate with various clinical parameters but tended to be reduced in patients with diabetes, which may partly explain the impairment of mitochondrial function observed in insulin resistance. Furthermore, the mtDNA content was significantly increased in patients suffering from obesity (BMI above 30). This might reflect a compensatory response to the development of obesity, which is associated with impairment of mitochondrial function

SRSF1 haploinsufficiency is responsible for a syndromic developmental disorder associated with intellectual disability

: SRSF1 (also known as ASF/SF2) is a non-small nuclear ribonucleoprotein (non-snRNP) that belongs to the arginine/serine (R/S) domain family. It recognizes and binds to mRNA, regulating both constitutive and alternative splicing. The complete loss of this proto-oncogene in mice is embryonically lethal. Through international data sharing, we identified 17 individuals (10 females and 7 males) with a neurodevelopmental disorder (NDD) with heterozygous germline SRSF1 variants, mostly de novo, including three frameshift variants, three nonsense variants, seven missense variants, and two microdeletions within region 17q22 encompassing SRSF1. Only in one family, the de novo origin could not be established. All individuals featured a recurrent phenotype including developmental delay and intellectual disability (DD/ID), hypotonia, neurobehavioral problems, with variable skeletal (66.7%) and cardiac (46%) anomalies. To investigate the functional consequences of SRSF1 variants, we performed in silico structural modeling, developed an in vivo splicing assay in Drosophila, and carried out episignature analysis in blood-derived DNA from affected individuals. We found that all loss-of-function and 5 out of 7 missense variants were pathogenic, leading to a loss of SRSF1 splicing activity in Drosophila, correlating with a detectable and specific DNA methylation episignature. In addition, our orthogonal in silico, in vivo, and epigenetics analyses enabled the separation of clearly pathogenic missense variants from those with uncertain significance. Overall, these results indicated that haploinsufficiency of SRSF1 is responsible for a syndromic NDD with ID due to a partial loss of SRSF1-mediated splicing activity