Exact Hypersurface-Homogeneous Solutions in Cosmology and Astrophysics

A framework is introduced which explains the existence and similarities of most exact solutions of the Einstein equations with a wide range of sources for the class of hypersurface-homogeneous spacetimes which admit a Hamiltonian formulation. This class includes the spatially homogeneous cosmological models and the astrophysically interesting static spherically symmetric models as well as the stationary cylindrically symmetric models. The framework involves methods for finding and exploiting hidden symmetries and invariant submanifolds of the Hamiltonian formulation of the field equations. It unifies, simplifies and extends most known work on hypersurface-homogeneous exact solutions. It is shown that the same framework is also relevant to gravitational theories with a similar structure, like Brans-Dicke or higher-dimensional theories.Comment: 41 pages, REVTEX/LaTeX 2.09 file (don't use LaTeX2e !!!) Accepted for publication in Phys. Rev.

Distribution of small proteoglycans and glycosaminoglycans in humerus-related articular cartilage of chickens

The expression of components present in the cartilaginous extracellular matrix is related to development, gender, and genotype, as well as to the biomechanical properties of each type of cartilage. In the present study, we analyzed small proteoglycans and glycosaminoglycans present in different cartilages of the chicken wing after extraction with guanidine hydrochloride or papain. Quantitative analysis of glycosaminoglycans showed a larger amount in humeral cartilage (around 200 mg/g tissue) than in articular cartilage of the radius and ulna, with 138 and 80 mg/g tissue, respectively. Non-collagenous proteins isolated were predominantly from cartilage in the proximal regions of the humerus and radius. D4 fractions obtained by ultracentrifugation were separated by DEAE-Sephacel and Octyl-Sepharose chromatography and analyzed by SDS-PAGE. Two bands of 57 and 70-90 kDa were observed for all samples treated with ß-mercaptoethanol. Immunoblotting of these proteins was positive for the small proteoglycans fibromodulin and decorin, respectively. Apparently, the 57-kDa protein is present in macromolecular complexes of 160 and 200 kDa. Chondroitin sulfate was detected in all regions. HPLC analysis of the products formed by chondroitinase AC and ABC digestion mainly revealed ß-D-glucuronic acid and N-acetyl ß-D-galactosamine residues. The 4-sulfation/6-sulfation ratio was close to 3, except for the proximal cartilage of the radius (2.5). These results suggest functional differences between the scapula-humerus, humerus-ulna, and humerus-radius joints of the chicken wing. This study contributes to the understanding of the physiology of cartilage and joints of birds under different types of mechanical stress.38139

Alterations In The Achilles Tendon After Inflammation In Surrounding Tissue

Objective: To analyze the characteristics of the Achilles tendon of rats after induction of localized inflammation in the rat paw. Methods: In our study three groups were used: inflamed group with carrageenan in rat paw (G1); saline group (G2) and control group (G3). After 4 hours the animals were euthanized and the Achilles tendon removed. Results: No significant differences were observed in the analysis of non-collagenous proteins, glycosaminoglycans and hydroxyproline in the groups but a tendency of reduction was verified in G1. As regards the organization of collagen molecules, no differences were observed between groups. With respect to MMPs activity, a stronger presence of the active isoform of MMP-2 in G1 was observed, suggesting that the remodeling was occurring. Conclusion: Thus, we conclude that the inflammatory process in rat paw may affect the remodeling of tendons located near the inflamed site.205266269Maffulli, N., Kader, D., Tendinopathy of tendo Achillis (2002) J Bone Joint Surg Br, 84 (1), pp. 1-8Maffulli, N., Rupture of the Achilles tendon (1999) J Bone Joint Surg Am, 81 (7), pp. 1019-1036Järvinen, T.A., Kannus, P., Maffulli, N., Khan, K.M., Achilles tendon disorders: etiology and epidemiology (2005) Foot Ankle Clin, 10 (2), pp. 255-266Oliveira, F.S., Pinfildi, C.E., Parizoto, N.A., Liebano, R.E., Bossini, P.S., Garcia, E.B., Effect of low level laser therapy (830 nm) with different therapyregimes on the process of tissue repair in partial lesion calcaneous tendon (2009) Lasers Surg Med, 41 (4), pp. 271-276Karousou, E., Ronga, M., Vigetti, D., Passi, A., Maffulli, N., Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human Achilles tendon rupture (2008) Clin Orthop Relat Res, 466 (7), pp. 1577-1582Riley, G., Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology (2002) Matrix Biol, 21 (2), pp. 185-195Dario, B.E., Barquilha, G., Marques, R.M., Lesões esportivas: um estudo com atletas de basquetebol Bauruense (2010) Rev Bras Cienc Esporte, 31 (3), pp. 205-215Vieira, C.P., Aro, A.A., Almeida, M.S., de Mello, G.C., Antunes, E., Pimentel, E.R., Effects of acute inflammation induced in the rat paw on the deep digital flexor tendon (2012) Connect Tissue Res, 53 (2), pp. 160-168Tillander, B., Franzén, L.E., Nilsson, E., Norlin, R., Carrageenan-induced subacromial bursitis caused changes in the rat's rotator cuff (2001) J Orthop Res, 19 (3), pp. 441-447Winter, C.A., Risley, E.A., Nuss, G.W., Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs (1962) Proc Soc Exp Biol Med, 111, pp. 544-547Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Farndale, R.W., Buttle, D.J., Barrett, A.J., Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue (1986) Biochim Biophys Acta, 883 (2), pp. 173-177Marqueti, R.C., Parizotto, N.A., Chriguer, R.S., Perez, S.E., Selistre-de-Araujo, H.S.A., ndrogenic-anabolic steroids associated with mechanical loading inhibit matrix metallopeptidase activity and affect the remodeling of the achilles tendon in rats (2006) Am J Sports Med, 34 (8), pp. 1274-1280Vidal, B.C., Mello, M.L., Supramolecular order following binding of the dichroic birefringent sulfonic dye Ponceau SS to collagen fibers (2005) Biopolymers, 78 (3), pp. 121-128Riley, G., Tendinopathy:from basic science to treatment (2008) Nat Clin Pract Rheumatol, 4 (2), pp. 82-89Szabo, K.A., Ablin, R.J., Singhingh, G., Matrix metalloproteinases and the immune response (2004) Clin Appl Immun Rev, 4, pp. 295-319Chakraborti, S., Mandal, M., Das, S., Mandal, A., Chakraborti, T., Regulation of matrix metalloproteinases: an overview (2003) Mol Cell Biochem, 253 (1-2), pp. 269-285Magra, M., Maffulli, N., Matrix metalloproteases: a role in overuse tendinopathies (2005) Br J Sports Med, 39 (11), pp. 789-791Clutterbuck, A.L., Harris, P., Allaway, D., Mobasheri, A., Matrix metalloproteinases in inflammatory pathologies of the horse (2010) Vet J, 183 (1), pp. 27-38Marsolais, D., Duchesne, E., Côté, C.H., Frenette, J., Inflammatory cells do not decrease the ultimate tensile strength of intact tendons in vivo and in vitro: protective role of mechanical loading (2007) J Appl Physiol, 102 (1), pp. 11-1

Hypothalamic S1p/s1pr1 axis controls energy homeostasis

Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats5485

Hypothalamic S1p/s1pr1 Axis Controls Energy Homeostasis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats.5Capes-12900-13-3; CAPES; Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Schwartz, M.W., Woods, S.C., Porte, D., Jr., Seeley, R.J., Baskin, D.G., Central nervous system control of food intake (2000) Nature, 404, pp. 661-671Munzberg, H., Huo, L., Nillni, E.A., Hollenberg, A.N., Bjorbaek, C., Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin (2003) Endocrinology, 144, pp. 2121-2131Myers, M.G., Cowley, M.A., Munzberg, H., Mechanisms of leptin action and leptin resistance (2008) Annu. Rev. Physiol., 70, pp. 537-556Janoschek, R., Gp130 signaling in proopiomelanocortin neurons mediates the acute anorectic response to centrally applied ciliary neurotrophic factor (2006) Proc. Natl Acad. Sci. USA, 103, pp. 10707-10712Johnen, H., Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1 (2007) Nat. Med., 13, pp. 1333-1340Ropelle, E.R., IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKbeta and ER stress inhibition (2010) PLoS Biol., 8El-Haschimi, K., Pierroz, D.D., Hileman, S.M., Bjorbaek, C., Flier, J.S., Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity (2000) J. Clin. Invest., 105, pp. 1827-1832Ernst, M.B., Enhanced Stat3 activation in POMC neurons provokes negative feedback inhibition of leptin and insulin signaling in obesity (2009) J. Neurosci., 29, pp. 11582-11593Gao, Q., Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals (2007) Nat. Med., 13, pp. 89-94Ghilardi, N., Defective STAT signaling by the leptin receptor in diabetic mice (1996) Proc. Natl Acad. Sci. USA, 93, pp. 6231-6235Frias, M.A., James, R.W., Gerber-Wicht, C., Lang, U., Native and reconstituted HDL activate Stat3 in ventricular cardiomyocytes via ERK1/2: Role of sphingosine-1-phosphate (2009) Cardiovasc. Res., 82, pp. 313-323Gurgui, M., Broere, R., Kalff, J.C., Van Echten-Deckert, G., Dual action of sphingosine 1-phosphate in eliciting proinflammatory responses in primary cultured rat intestinal smooth muscle cells (2010) Cell Signal., 22, pp. 1727-1733Lee, H., STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors (2010) Nat. Med., 16, pp. 1421-1428Liang, J., Sphingosine-1-phosphate links persistent STAT3 activation, chronic intestinal inflammation, and development of colitis-associated cancer (2013) Cancer Cell, 23, pp. 107-120Spiegel, S., Milstien, S., The outs and the ins of sphingosine-1-phosphate in immunity (2011) Nat. Rev. Immunol., 11, pp. 403-415Spiegel, S., Milstien, S., Functions of the multifaceted family of sphingosine kinases and some close relatives (2007) J. Biol. Chem., 282, pp. 2125-2129Loh, K.C., Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway (2012) PLoS One, 7Lopez, M., Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin (2008) Cell. Metab., 7, pp. 389-399Oo, M.L., Engagement of S1P(1)-degradative mechanisms leads to vascular leak in mice (2011) J. Clin. Invest., 121, pp. 2290-2300Means, C.K., Brown, J.H., Sphingosine-1-phosphate receptor signalling in the heart (2009) Cardiovasc. Res., 82, pp. 193-200Schwartz, M.W., Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus (1997) Diabetes, 46, pp. 2119-2123Cowley, M.A., Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus (2001) Nature, 411, pp. 480-484Bates, S.H., STAT3 signalling is required for leptin regulation of energy balance but not reproduction (2003) Nature, 421, pp. 856-859Mynard, V., Guignat, L., Devin-Leclerc, J., Bertagna, X., Catelli, M.G., Different mechanisms for leukemia inhibitory factor-dependent activation of two proopiomelanocortin promoter regions (2002) Endocrinology, 143, pp. 3916-3924Bousquet, C., Zatelli, M.C., Melmed, S., Direct regulation of pituitary proopiomelanocortin by STAT3 provides a novel mechanism for immunoneuroendocrine interfacing (2000) J. Clin. Invest., 106, pp. 1417-1425Bousquet, C., Melmed, S., Critical role for STAT3 in murine pituitary adrenocorticotropin hormone leukemia inhibitory factor signaling (1999) J. Biol. Chem., 274, pp. 10723-10730Andreux, P.A., Systems genetics of metabolism: The use of the BXD murine reference panel for multiscalar integration of traits (2012) Cell, 150, pp. 1287-1299Guissouma, H., Froidevaux, M.S., Hassani, Z., Demeneix, B.A., In vivo siRNA delivery to the mouse hypothalamus confirms distinct roles of TR beta isoforms in regulating TRH transcription (2006) Neurosci. Lett., 406, pp. 240-243Froidevaux, M.S., The co-chaperone XAP2 is required for activation of hypothalamic thyrotropin-releasing hormone transcription in vivo (2006) EMBO Rep., 7, pp. 1035-1039Nagahashi, M., Sphingosine-1-phosphate produced by sphingosine kinase 1 promotes breast cancer progression by stimulating angiogenesis and lymphangiogenesis (2012) Cancer Res., 72, pp. 726-735Brinkmann, V., Fingolimod (FTY720): Discovery and development of an oral drug to treat multiple sclerosis (2010) Nat. Rev. Drug Discov., 9, pp. 883-897Graler, M.H., Goetzl, E.J., The immunosuppressant FTY720 down-regulates sphingosine 1-phosphate G-protein-coupled receptors (2004) FASEB J., 18, pp. 551-553Guo, H., An activated protein C analog stimulates neuronal production by human neural progenitor cells via a PAR1-PAR3-S1PR1-Akt pathway (2013) J. Neurosci., 33, pp. 6181-6190Ishii, I., Fukushima, N., Ye, X., Chun, J., Lysophospholipid receptors: Signaling and biology (2004) Annu. Rev. Biochem., 73, pp. 321-354Walter, D.H., Sphingosine-1-phosphate stimulates the functional capacity of progenitor cells by activation of the CXCR4-dependent signaling pathway via the S1P3 receptor (2007) Arterioscler. Thromb. Vasc. Biol., 27, pp. 275-282Grossberg, A.J., Arcuate nucleus proopiomelanocortin neurons mediate the acute anorectic actions of leukemia inhibitory factor via gp130 (2010) Endocrinology, 151, pp. 606-616Febbraio, M.A., Gp130 receptor ligands as potential therapeutic targets for obesity (2007) J. Clin. Invest., 117, pp. 841-849Samad, F., Hester, K.D., Yang, G., Hannun, Y.A., Bielawski, J., Altered adipose and plasma sphingolipid metabolism in obesity: A potential mechanism for cardiovascular and metabolic risk (2006) Diabetes, 55, pp. 2579-2587Bence, K.K., Neuronal PTP1B regulates body weight, adiposity and leptin action (2006) Nat. Med., 12, pp. 917-924Chiarreotto-Ropelle, E.C., Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats (2013) Am. J. Physiol. Endocrinol. Metab., 305, pp. E649-E659Picardi, P.K., Reduction of hypothalamic protein tyrosine phosphatase improves insulin and leptin resistance in diet-induced obese rats (2008) Endocrinology, 149, pp. 3870-3880Milanski, M., Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: Implications for the pathogenesis of obesity (2009) J. Neurosci., 29, pp. 359-370Purkayastha, S., Zhang, G., Cai, D., Uncoupling the mechanisms of obesity and hypertension by targeting hypothalamic IKK-beta and NF-kappaB (2011) Nat. Med., 17, pp. 883-887Zhang, X., Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity (2008) Cell, 135, pp. 61-73Laviano, A., Meguid, M.M., Rossi-Fanelli, F., Cancer anorexia: Clinical implications, pathogenesis, and therapeutic strategies (2003) Lancet Oncol., 4, pp. 686-694Tisdale, M.J., Biology of cachexia (1997) J. Natl Cancer Inst., 89, pp. 1763-1773Pchejetski, D., Circulating sphingosine-1-phosphate inversely correlates with chemotherapy-induced weight gain during early breast cancer (2010) Breast Cancer Res. Treat., 124, pp. 543-549Ponnusamy, S., Communication between host organism and cancer cells is transduced by systemic sphingosine kinase 1/sphingosine 1-phosphate signalling to regulate tumour metastasis (2012) EMBO Mol. Med., 4, pp. 761-775Mellon, P.L., Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis (1990) Neuron, 5, pp. 1-1