the-synergistic-effect-visible-light-gentamycin-on-pseudomona

The Synergistic Effect of Visible Light and Gentamycin on <em>Pseudomona aeruginosa</em> Microorganisms

Recently there were several publications on the  bactericidal effect of visible light, most of them claiming that blue part of  the spectrum (400 nm-500 ...

The cytoskeleton is a dynamic network that undergoes restructuring during a variety of cellular events including cell contact formation, cell invasion and the mitotic phase of the cell cycle. Here, we review the contribution of the cytoskeletal network to the inductive activity of glucocorticoids by focusing on the hormonal control of glutamine synthetase in the chick neural retina. Depolymerization of the cytoskeleton in cells of the intact retinal tissue inhibits the hormonal induction of glutamine synthetase, but does not alter the cellular amount of the glucocorticoid-receptor protein or the ability of the receptor molecules to translocate into the nucleus. Inhibition of glutamine synthetase induction occurs via a mechanism that involves elevation of c-Jun protein accumulation and repression of glucocorticoid-receptor transcriptional activity. Unlike growth factors and other c-Jun inducing stimuli that control the transcription of the c-Jun gene, depolymerization of the cytoskeleton elevates c-Jun accumulation by upregulating the translation of the c-Jun transcript. We postulate that the cytoskeletal-dependent increase in c-Jun accumulation is involved in cell contact control of both cell proliferation and transcriptional activity of the glucocorticoid-receptor protein.

Cytoskeletal and cell contact control of the glucocorticoid pathway.

The target of rapamycin (TOR), a central controller of cell growth, is found in two distinct, highly conserved multiprotein complexes. Three recent papers in Cell (Jacinto et al., 2006), Developmental Cell (shiota et al., 2006; this issue), and Current Biology (Frias et al., 2006) shed light on mTOR complex 2 (mTORC2) composition and in vivo function. An important new finding is that mTORC2 determines Akt/PKB substrate specificity rather than absolute activity.

mTORC2 Caught in a SINful Akt.

TOR (Target of Rapamycin) is a highly conserved protein kinase and a central controller of cell growth. TOR is found in two functionally and structurally distinct multiprotein complexes termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2). In the present study, we developed a two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS) based proteomic strategy to identify new mammalian TOR (mTOR) binding proteins. We report the identification of Proline-rich Akt substrate (PRAS40) and the hypothetical protein Q6MZQ0/FLJ14213/CAE45978 as new mTOR binding proteins. PRAS40 binds mTORC1 via Raptor, and is an mTOR phosphorylation substrate. PRAS40 inhibits mTORC1 autophosphorylation and mTORC1 kinase activity toward eIF-4E binding protein (4E-BP) and PRAS40 itself. HeLa cells in which PRAS40 was knocked down were protected against induction of apoptosis by TNFalpha and cycloheximide. Rapamycin failed to mimic the pro-apoptotic effect of PRAS40, suggesting that PRAS40 mediates apoptosis independently of its inhibitory effect on mTORC1. Q6MZQ0 is structurally similar to proline rich protein 5 (PRR5) and was therefore named PRR5-Like (PRR5L). PRR5L binds specifically to mTORC2, via Rictor and/or SIN1. Unlike other mTORC2 members, PRR5L is not required for mTORC2 integrity or kinase activity, but dissociates from mTORC2 upon knock down of tuberous sclerosis complex 1 (TSC1) and TSC2. Hyperactivation of mTOR by TSC1/2 knock down enhanced apoptosis whereas PRR5L knock down reduced apoptosis. PRR5L knock down reduced apoptosis also in mTORC2 deficient cells. The above suggests that mTORC2-dissociated PRR5L may promote apoptosis when mTOR is hyperactive. Thus, PRAS40 and PRR5L are novel mTOR-associated proteins that control the balance between cell growth and cell death.

PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis.

raptor is a specific and essential component of mammalian TOR complex 1 (mTORC1), a key regulator of cell growth and metabolism. To investigate a role of adipose mTORC1 in regulation of adipose and whole-body metabolism, we generated mice with an adipose-specific knockout of raptor (raptor(ad-/-)). Compared to control littermates, raptor(ad-/-) mice had substantially less adipose tissue, were protected against diet-induced obesity and hypercholesterolemia, and exhibited improved insulin sensitivity. Leanness was in spite of reduced physical activity and unaffected caloric intake, lipolysis, and absorption of lipids from the food. White adipose tissue of raptor(ad-/-) mice displayed enhanced expression of genes encoding mitochondrial uncoupling proteins characteristic of brown fat. Leanness of the raptor(ad-/-) mice was attributed to elevated energy expenditure due to mitochondrial uncoupling. These results suggest that adipose mTORC1 is a regulator of adipose metabolism and, thereby, controls whole-body energy homeostasis.

Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration.

Mammalian Target of Rapamycin (mTOR) is a highly conserved protein kinase that functions as part of two distinct multiprotein complexes to regulate growth and metabolism. This review describes the most important recent advances in the mTOR signaling field. In addition, we provide an overview on the functions of mTOR in different organs, with a special focus on the role of mTOR in whole body energy metabolism.

mTOR and the control of whole body metabolism.

Mammalian target of rapamycin (mTOR), a highly conserved protein kinase that controls cell growth and metabolism in response to nutrients and growth factors, is found in 2 structurally and functionally distinct multiprotein complexes termed mTOR complex 1 (mTORC1) and mTORC2. mTORC2, which consists of rictor, mSIN1, mLST8, and mTOR, is activated by insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB. Though the role of mTOR in single cells is relatively well characterized, the role of mTOR signaling in specific tissues and how this may contribute to overall body growth is poorly understood. To examine the role of mTORC2 in an individual tissue, we generated adipose-specific rictor knockout mice (rictor(ad-/-)). Rictor(ad-/-) mice are increased in body size due to an increase in size of nonadipose organs, including heart, kidney, spleen, and bone. Furthermore, rictor(ad-/-) mice have a disproportionately enlarged pancreas and are hyperinsulinemic, but glucose tolerant, and display elevated levels of insulin-like growth factor 1 (IGF1) and IGF1 binding protein 3 (IGFBP3). These effects are observed in mice on either a high-fat or a normal diet, but are generally more pronounced in mice on a high-fat diet. Our findings suggest that adipose tissue, in particular mTORC2 in adipose tissue, plays an unexpectedly central role in controlling whole-body growth.

mTOR complex 2 in adipose tissue negatively controls whole-body growth.

Mammalian target of rapamycin complex 2 (mTORC2) phosphorylates and activates AGC kinase family members, including Akt, SGK1, and PKC, in response to insulin/IGF1. The liver is a key organ in insulin-mediated regulation of metabolism. To assess the role of hepatic mTORC2, we generated liver-specific rictor knockout (LiRiKO) mice. Fed LiRiKO mice displayed loss of Akt Ser473 phosphorylation and reduced glucokinase and SREBP1c activity in the liver, leading to constitutive gluconeogenesis, and impaired glycolysis and lipogenesis, suggesting that the mTORC2-deficient liver is unable to sense satiety. These liver-specific defects resulted in systemic hyperglycemia, hyperinsulinemia, and hypolipidemia. Expression of constitutively active Akt2 in mTORC2-deficient hepatocytes restored both glucose flux and lipogenesis, whereas glucokinase overexpression rescued glucose flux but not lipogenesis. Thus, mTORC2 regulates hepatic glucose and lipid metabolism via insulin-induced Akt signaling to control whole-body metabolic homeostasis. These findings have implications for emerging drug therapies that target mTORC2.

Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c.

Detection of DNA mutations is critical for scientific research and diagnostic procedures. Here, we propose a novel interdisciplinary method for rapid and simple detection of DNA mutations. We show that heating a solution containing DNA and gold nanoparticles results in degradation of the DNA. Surprisingly, we found that the DNA can be protected against degradation, if an oligonucleotide that matches the DNA is added to the solution. Moreover, the level of degradation indicates the presence of mutations in the DNA. The method is sensitive enough to indicate even a single nucleotide difference, and has the potential to ultimately replace initial medical genetic tests. As proof of concept, we demonstrate a clear detection of two of the most common mutations leading to Cystic Fibrosis.

Gold nanoparticles-based biosensing of single nucleotide DNA mutations.

In this article, we investigate the thermal degradation of deoxyribonucleic acid (DNA). We find that under dry conditions, complete DNA degradation occurs at above 190Â°C. In addition, as the boiling temperature of water is pressure dependent, we have investigated the thermal degradation of the DNA in water for different applied partial pressures. This information is important for fundamental understanding of DNA structure and energetics, and can be useful for biomedical applications such as thermal targeting of DNA in cancer cells, as well as for basic research.

Article	Year
Cytoskeletal and cell contact control of the glucocorticoid pathway. Molecular and cellular endocrinology\| PubMed ID: 16687209	2006
mTORC2 Caught in a SINful Akt. Developmental cell\| PubMed ID: 17011481	2006
PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis. PloS one\| PubMed ID: 18030348	2007
Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell metabolism\| PubMed ID: 19046571	2008
mTOR and the control of whole body metabolism. Current opinion in cell biology\| PubMed ID: 19261457	2009
mTOR complex 2 in adipose tissue negatively controls whole-body growth. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 19497867	2009
Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c. Cell metabolism\| PubMed ID: 22521878	2012
Gold nanoparticles-based biosensing of single nucleotide DNA mutations. International journal of biological macromolecules\| PubMed ID: 23597712	2013
Thermal degradation of DNA. DNA and cell biology\| PubMed ID: 23621849	2013

Pazit Polak

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