Hyperandrogenism and Obesity: Ominous Co-Morbidities

This review has a two-fold objective. One, it addresses the association of hyperandrogenism and obesity and the complex metabolic derangements that are part of the problem. Clinical management of these co-morbidities is challenging and complex. Second, this article will aid health care providers with the key features to an early diagnosis and intervention to decrease the morbidities in the short as well as long term. Method: Systematic review of articles and information on the topic of interest that were published in the last 15 years. Conclusion: Obesity and hyperandrogenism are integral parts of Metabolic Syndrome/Polycystic Ovarian Syndrome (PCOS)/Hyperandrogenism, Insulin resistance, and Acanthosis Nigricans (HAIR-AN). With the childhood obesity epidemic, the metabolic syndrome and the associated abnormalities are routinely seen in clinical practice and these have a tremendous economic burden on the society and the quality of life

Obesity and Hyperandrogenism

This chapter has a two-fold objective. One, it addresses the association of hyperandrogenism and obesity and the complex metabolic derangements that are part of the problem. Clinical management of these co-morbidities is challenging and complex. Second, this article will aid health care providers with the key features to an early diagnosis and intervention to decrease the morbidities in the short as well as long term. Method: Systematic review of articles and information on the topic of interest that were published in the last 15 years. Conclusion: Obesity and hyperandrogenism are integral parts of Metabolic Syndrome/Polycystic Ovarian Syndrome (PCOS)/Hyperandrogenism, Insulin resistance, and Acanthosis Nigricans (HAIR-AN). With the childhood obesity epidemic, the metabolic syndrome and the associated abnormalities are routinely seen in clinical practice and these have a tremendous economic burden on the society and the quality of life

Hyperandrogenism and Obesity

This chapter has a two-fold objective. One, ti addresses the association of hyperandrogenism and obesity and the complex metabolic derangements that are part of the problem. Clinical management of these co-morbidities is challenging and complex. Second, this chapter will aid health care providers with the key features to an early diagnosis and intervention to decrease the morbidities in the short as well as long term. Method: Systematic review of articles and information on the topic of interest that were published in the last 15 years. Conclusion: Obesity and hyperandrogenism are integral parts of Metabolic Syndrome/Polycystic Ovarian Syndrome (PCOS)/Hyperandrogenism, Insulin resistance, and Acanthosis Nigricans (HAIR-AN). With the childhood obesity epidemic, the metabolic syndrome and the associated abnormalities are routinely seen in clinical practice and these have a tremendous economic burden on the society and the quality of life

Hyperandrogenism and Obesity

This chapter has a two-fold objective. One, ti addresses the association of hyperandrogenism and obesity and the complex metabolic derangements that are part of the problem. Clinical management of these co-morbidities is challenging and complex. Second, this chapter will aid health care providers with the key features to an early diagnosis and intervention to decrease the morbidities in the short as well as long term. Method: Systematic review of articles and information on the topic of interest that were published in the last 15 years. Conclusion: Obesity and hyperandrogenism are integral parts of Metabolic Syndrome/Polycystic Ovarian Syndrome (PCOS)/Hyperandrogenism, Insulin resistance, and Acanthosis Nigricans (HAIR-AN). With the childhood obesity epidemic, the metabolic syndrome and the associated abnormalities are routinely seen in clinical practice and these have a tremendous economic burden on the society and the quality of life

Obesity and Hyperandrogenism

This chapter has a two-fold objective. One, it addresses the association of hyperandrogenism and obesity and the complex metabolic derangements that are part of the problem. Clinical management of these co-morbidities is challenging and complex. Second, this article will aid health care providers with the key features to an early diagnosis and intervention to decrease the morbidities in the short as well as long term. Method: Systematic review of articles and information on the topic of interest that were published in the last 15 years. Conclusion: Obesity and hyperandrogenism are integral parts of Metabolic Syndrome/Polycystic Ovarian Syndrome (PCOS)/Hyperandrogenism, Insulin resistance, and Acanthosis Nigricans (HAIR-AN). With the childhood obesity epidemic, the metabolic syndrome and the associated abnormalities are routinely seen in clinical practice and these have a tremendous economic burden on the society and the quality of life

Detachment of Breast Tumor Cells Induces Rapid Secretion of Exosomes Which Subsequently Mediate Cellular Adhesion and Spreading

Exosomes are nano-vesicles secreted by a wide range of mammalian cell types. These vesicles are abundant in serum and other extracellular fluids and contain a large repertoire of proteins, mRNA and microRNA. Exosomes have been implicated in cell to cell communication, the transfer of infectious agents, and neurodegenerative diseases as well as tumor progression. However, the precise mechanisms by which they are internalized and/or secreted remain poorly understood. In order to follow their release and uptake in breast tumor cells in real time, cell-derived exosomes were tagged with green fluorescent protein (GFP)-CD63 while human serum exosomes were rhodamine isothiocynate-labeled. We show that detachment of adherent cells from various substrata induces a rapid and substantial secretion of exosomes, which then concentrate on the cell surfaces and mediate adhesion to various extracellular matrix proteins. We also demonstrate that disruption of lipid rafts with methyl-beta-cyclodextrin (MβCD) inhibits the internalization of exosomes and that annexins are essential for the exosomal uptake mechanisms. Taken together, these data suggest that cellular detachment is accompanied by significant release of exosomes while cellular adhesion and spreading are enhanced by rapid uptake and disposition of exosomes on the cell surface

Depalmitoylated Ras traffics to and from the Golgi complex via a nonvesicular pathway

Palmitoylation is postulated to regulate Ras signaling by modulating its intracellular trafficking and membrane microenvironment. The mechanisms by which palmitoylation contributes to these events are poorly understood. Here, we show that dynamic turnover of palmitate regulates the intracellular trafficking of HRas and NRas to and from the Golgi complex by shifting the protein between vesicular and nonvesicular modes of transport. A combination of time-lapse microscopy and photobleaching techniques reveal that in the absence of palmitoylation, GFP-tagged HRas and NRas undergo rapid exchange between the cytosol and ER/Golgi membranes, and that wild-type GFP-HRas and GFP-NRas are recycled to the Golgi complex by a nonvesicular mechanism. Our findings support a model where palmitoylation kinetically traps Ras on membranes, enabling the protein to undergo vesicular transport. We propose that a cycle of depalmitoylation and repalmitoylation regulates the time course and sites of Ras signaling by allowing the protein to be released from the cell surface and rapidly redistributed to intracellular membranes

2-Aminopurine Inhibits Lipid Accumulation Induced by Apolipoprotein E-Deficient Lipoprotein in Macrophages: Potential Role of Eukaryotic Initiation Factor-2␣ Phosphorylation in Foam Cell Formation

ABSTRACT We previously reported that apolipoprotein (Apo) E-deficient, ApoB48-containing (E Ϫ /B48) lipoproteins inhibited expression of lysosomal hydrolase and transformed mouse peritoneal macrophages (MPMs) into foam cells. The present study examined the effect of 2-aminopurine (2-AP), an inhibitor of eukaryotic initiation factor (eIF)-2␣ phosphorylation, on E Ϫ /B48 lipoprotein-induced changes in gene expression and foam cell formation. Our data demonstrated that E Ϫ /B48 lipoproteins enhanced phosphorylation of eIF-2␣ in macrophages. Incubation of MPMs with E Ϫ /B48 lipoproteins inhibited the translation efficiency of mRNAs encoding lysosomal acid lipase, cathepsin B, and cation-dependent mannose 6 phosphate receptor, with a parallel reduction in the level of these proteins. Addition of 2-AP to the culture media alleviated the suppressive effect of E Ϫ /B48 lipoproteins on lysosomal hydrolase mRNA translation, increased macrophage degradation of E Ϫ /B48 lipoproteins, and inhibited foam cell formation. Transfection of MPMs with a nonphosphorylatable eIF-2␣ mutant also attenuated the suppressive effect of E Ϫ /B48 lipoproteins on expression of lysosomal acid lipase, associated with a reduced accumulation of cellular cholesterol esters. This is the first demonstration that ApoE-deficient lipoproteins inhibit lysosomal hydrolase synthesis and transform macrophages into foam cells through induction of eIF-2␣ phosphorylation

Functional Changes in Muscle Afferent Neurones in an Osteoarthritis Model: Implications for Impaired Proprioceptive Performance

Impaired proprioceptive performance is a significant clinical issue for many who suffer osteoarthritis (OA) and is a risk factor for falls and other liabilities. This study was designed to evaluate weight-bearing distribution in a rat model of OA and to determine whether changes also occur in muscle afferent neurones.Intracellular recordings were made in functionally identified dorsal root ganglion neurones in acute electrophysiological experiments on the anaesthetized animal following measurements of hind limb weight bearing in the incapacitance test. OA rats but not naïve control rats stood with less weight on the ipsilateral hind leg (P = 0.02). In the acute electrophysiological experiments that followed weight bearing measurements, action potentials (AP) elicited by electrical stimulation of the dorsal roots differed in OA rats, including longer AP duration (P = 0.006), slower rise time (P = 0.001) and slower maximum rising rate (P = 0.03). Depolarizing intracellular current injection elicited more APs in models than in naïve muscle afferent neurones (P = 0.01) indicating greater excitability. Axonal conduction velocity in model animals was slower (P = 0.04).The present study demonstrates changes in hind limb stance accompanied by changes in the functional properties of muscle afferent neurones in this derangement model of OA. This may provide a possible avenue to explore mechanisms underlying the impaired proprioceptive performance and perhaps other sensory disorders in people with OA

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead