Home About us Contact
|
Home About us Contact | ||
|
|
||
Concomitant Loss (concomitant + loss)
Selected AbstractsLoss of signal transducer and activator of transcription 5 leads to hepatosteatosis and impaired liver regeneration,HEPATOLOGY, Issue 2 2007Yongzhi Cui Growth hormone controls many facets of a cell's biology through the transcription factors Stat5a and Stat5b (Stat5). However, whole body deletion of these genes from the mouse does not provide portentous information on cell-specific cytokine signaling. To explore liver-specific functions of Stat5, the entire Stat5 locus was deleted in hepatocytes using Cre-mediated recombination. Notably, Stat5-mutant mice developed fatty livers and displayed impaired proliferation of hepatocytes upon partial hepatectomy (PHx). Loss of Stat5 led to molecular consequences beyond the reduced expression of Stat5 target genes, such as those encoding suppressor of cytokine signaling 2 (SOCS2), Cish, and insulin-like growth factor 1 (IGF-1). In particular, circulating growth hormone levels were increased and correlated with insulin resistance and increased insulin levels. Aberrant growth hormone (GH)-induced activation of the transcription factors Stat1 and Stat3 was observed in mutant livers. To test whether some of the defects observed in liver-specific Stat5 deficient mice were due to aberrant Stat1 expression and activation, we generated Stat1,/, mice with a hepatocyte-specific deletion of Stat5. Concomitant loss of both Stat5 and Stat1 restored cell proliferation upon PHx but did not reverse fatty liver development. Thus the molecular underpinnings of some defects observed in the absence of Stat5 are the consequence of a deregulated activation of other signal transducers and activators of transcription (STAT) family members. Conclusion: Aberrant cytokine-Stat5 signaling in hepatocytes alters their physiology through increased activity of Stat1 and Stat3. Such cross-talk between different pathways could add to the complexity of syndromes observed in disease. (HEPATOLOGY 2007.) [source] Reactive species and early manifestation of insulin resistance in type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 2 2006L. E. Fridlyand The early stages of type 2 diabetes mellitus are characterized by the development of insulin resistance (IRe) in muscle cells and adipocytes with the concomitant loss of ,-cell compensation. We have extensively reviewed the literature related to metabolic and signalling pathways of reactive oxygen species (ROS) in regard to the coordinated development of oxidative stress and IRe. We considered the hypothesis that oxidative stress leads to IRe in muscle cells and adipocytes, but found that the data are more consistent with the hypothesis that the cellular mechanisms that protect against oxidative stress per se are capable of creating an ROS-dependent insulin-resistant state. Furthermore, ROS-induced mitochondrial dysfunction can lead to disruptions of lipid metabolism, increasing the intracellular lipid content, and, in addition, contribute to lipid-dependent IRe in myocytes. Together, these two ROS-activated pathways to IRe can contribute to a global state of profound resistance to insulin action. Therapeutic strategies should, therefore, be directed towards reducing insulin resistance without an increase in ROS production or concentration. Pharmacological or other approaches to IRe that result in the activation of mitochondrial biogenesis in particular could be highly beneficial in the prevention or treatment of both insulin resistance and type 2 diabetes. [source] Increasing Expression of the Retinoic X Receptor-B During Malignant Melanoma ProgressionJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005S.J. McAlhany Retinoic X receptor-b (RXR-b) is a heterodimerization partner for vitamin D receptor (VDR). 1,25-dihydroxyvitamin D3 activation of VDR leads to growth inhibition in numerous cell lines, including some melanoma lines. Evaluation of VDR and RXR-b expression in vivo in melanocytic neoplasms will increase our understanding of this pathways potential role in growth control. Previous studies in our laboratory showed decreased VDR expression in superficially invasive melanoma, and progressive loss of expression in deeply invasive melanomas and metastatic melanomas (MET). We next sought to evaluate RXR-b expression. Twenty-eight melanocytic neoplasms including 8 melanomas in situ (MIS), 9 primary invasive melanomas (PIM), and 11 MET were evaluated for RXR-b expression by immunohistochemistry. Nuclear labeling was assessed as 0 (0%), 1+(<5%), 2+(>5% but <50%), or 3+(>=50%). A significant increase in RXR-b expression from low (0,1+) to high (>1+) was found when comparing MIS to PIM and MET (chi2 p < 0.05). These data suggest: 1) potential loss of 1,25-dihydroxyvitamin D3 induced growth inhibition during melanoma progression may be due to decreased VDR expression without concomitant loss of RXR-b; and 2) increased RXR-b expression during melanoma progression may offer selective advantage through alternative signaling pathways. [source] ATPASE ACTIVITY, SURFACE HYDROPHOBICITY, SULFHYDRYL CONTENT AND PROTEIN DEGRADATION IN REFRIGERATED SEABASS MUSCLE IN MODIFIED ATMOSPHERE PACKAGINGJOURNAL OF FOOD BIOCHEMISTRY, Issue 1 2004PAYAP MASNIYOM The effect of modified atmosphere packaging (80% CO2, 10% O2, 10% N2) on ATPase activity, surface hydrophobicity, sulfhydryl content and degradation of proteins in seabass muscle during storage at 4C was investigated. No changes in Ca2+ -, Mg2+ -, Mg2+ -Ca2+ -ATPase activities of natural actomyosin (NAM) in seabass slices kept under MAP were observed throughout the storage for up to 21 days (P > 0.05). However, a slightly increased Mg2+ -EGTA-ATPase was found. For seabass slices stored under air atmosphere, Ca2+ -ATPase activity decreased, whereas Mg2+ -EGTA-ATPase activity increased (P < 0.05) with a concomitant loss in Ca2+ -sensitivity. Lower decreases in total sulfhydryl content but higher increases in surface hydrophobicity were observed in samples stored under MAP, compared to those kept under air atmosphere. No marked autolytic degradation in samples kept under MAP was observed throughout the storage as monitored by no changes in myosin heavy chain, free ,-amino acid and trichloroacetic acid soluble peptide. Conversely, a considerable degradation was found in samples kept under air atmosphere, especially after 9 days of storage. Therefore, MAP is a promising means to retard the changes in muscle proteins, especially degradation. [source] Rho kinase activates ezrin-radixin-moesin (ERM) proteins and mediates their function in cortical neuron growth, morphology and motility in vitroJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2007Matilda A. Haas Abstract The ezrin-radixin-moesin (ERM) family of proteins contribute to cytoskeletal processes underlying many vital cellular functions. Their previously elucidated roles in non-neuronal cells are an indication of their potential importance in CNS neurons. The specific mechanisms of their activation are unknown, but are likely to depend on factors such as the cell type and biological context. For ERM proteins to become active they must be phosphorylated at a specific C-terminal threonine residue. In non-neuronal cells, several kinases, including the Rho GTPase family member Rho kinase, have been identified as capable of phosphorylating the C-terminal threonine. In these experiments we have investigated specifically the potential role of Rho kinase mediated ERM activation in cortical neurons, utilizing a new pharmacologic inhibitor of Rho kinase and quantitative analysis of aspects of neuronal functions potentially mediated by ERM proteins. Rho kinase inhibition significantly suppressed aspects of neuronal development including neurite initiation and outgrowth, as well as growth cone morphology, with a concomitant loss of phosphorylated ERM immunolabeling in areas associated with neuronal growth. The ability of the Rho kinase inhibitor to decrease the amount of pERM protein was shown by immunoblotting. Post-injury responses were negatively affected by Rho kinase inhibition, namely by a significant decrease in the number of regenerative neurites. We investigated a novel role for ERM proteins in neuron migration using a post-injury motility assay, where Rho kinase inhibition resulted in significant and drastic reduction in neuron motility and phosphorylated ERM immunolabeling. Thus, Rho kinase is an important activator of ERMs in mediating specific neuronal functions. © 2006 Wiley-Liss, Inc. [source] Sintering Behavior and Conductivity Study of Yttrium-Doped BaCeO3,BaZrO3 Solid Solutions Using ZnO AdditivesJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 11 2009He Wang The effect of ZnO on the crystal structure, sintering behavior, and electrical conductivity of yttrium-doped BaCeO3,BaZrO3 was investigated by unfixing or fixing the yttrium content noted as BaCe0.5Zr0.3Y0.2,xZnxO2.9,0.5x and BaCe0.5Zr0.3Y0.2O2.9+yZnO, respectively. Studies on the two series revealed that BaO·ZnO eutectic, rather than ZnO, was responsible for the sintering densification. For BaCe0.5Zr0.3Y0.2,xZnxO2.9,0.5x, the evaporation of ZnO·BaO eutectic was observed after sintering at 1300°C for 10 h, and few impurities were detected by XRD with x<0.20. For BaCe0.5Zr0.3Y0.2O2.9+yZnO, the concomitant loss of BaO with ZnO caused A-site deficiency and led to impurities of Y2O3 for y=0.08 and 0.14, and Y2BaZnO5 for y=0.20 during the sintering. For both series, ZnO enhanced the relative density, which was above 97% with x or y varying from 0.02 to 0.08. Energy-dispersive X-ray spectroscopy analysis revealed that ZnO hardly entered the perovskite phase. The conductivity study also suggested that ZnO did not serve as a dopant and that yttrium content was essential for sustaining a high ionic conduction. Excessive ZnO was especially detrimental to the grain boundary conduction and thus lowered the total electrical conduction. The optimized composition of BaCe0.5Zr0.3Y0.2O2.9+0.04ZnO has been obtained, with both a high relative density (,98.5%) and a high electrical conductivity (1.35 × 10,2 S/cm at 600°C). [source] Land-use and cover changes (1988,2002) around budongo forest reserve, NW Uganda: implications for forest and woodland sustainabilityLAND DEGRADATION AND DEVELOPMENT, Issue 6 2008E. N. Mwavu Abstract Land-use and cover changes around Budongo Forest Reserve (BFR) were analysed from multi-temporal LandSat images (1988 and 2002) and associated field-based studies in 2003,2004. Three major land-use and cover classes: forest/woodland, sugarcane plantations and grassland/shifting-cultivation/settlements were clearly discriminated. The area under sugarcane cultivation increased over 17-fold, from 690,ha in 1988 to 12729,ha in 2002, with a concomitant loss of about 4680,ha (8·2 per cent) of forest/woodland, mainly on the southern boundary of BFR. Land-use and cover changes were a result of (a) agricultural expansion, (b) increasing human population, exacerbated by large influxes of refugees, (c) conflicts of interest and political interference in the management of BFR and (d) unclear land tenure. Agriculture is the main land-use practice and source of income to local people, with commercial sugarcane and tobacco as the primary cash crops. Individual smallholder sugarcane plantations covered distances ranging from 30 to 1440,m along the BFR edge, with no buffer zone, resulting in direct conflicts between farmers and forest wild animals. There is an ever-increasing need for more land for agricultural expansion, resulting in continued loss of forest/woodland on private/communal lands and encroachment into BFR. This unsustainable agricultural expansion and the local people's perception of BFR as an obstacle to agriculture, threatens the conservation of its threatened wild plants (e.g. Raphia farinifera) and the endangered chimpanzees. Therefore, their sustainable management for both development and conservation will require strong and incorruptible institutions that will seek a balance between resource exploitation and conservation. Copyright © 2008 John Wiley & Sons, Ltd. [source] Plasma phospholipids implicated in the matrix effect observed in liquid chromatography/tandem mass spectrometry bioanalysis: evaluation of the use of colloidal silica in combination with divalent or trivalent cations for the selective removal of phospholipids from plasmaRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 18 2008Steven T. Wu The feasibility of the use of colloidal silica in combination with a number of divalent or trivalent cations for the removal of plasma phospholipids was evaluated by sequentially adding the two reagents (i.e., colloidal silica and a cation) directly to blank plasma samples or plasma samples spiked with analytes. Three representative plasma phospholipids were monitored to determine the efficiency of the phospholipids removal under different reagent combinations. The recovery of each spiked analyte was also monitored under each condition in order to determine if any of the analyte was removed along with the phospholipids. By optimizing the amounts of the reagents used and the sequence of the addition of the reagents, quantitative and reproducible removal of the phospholipids was achieved. Using the finally selected lanthanum cation, the removal of phospholipids was achieved with minimal concomitant loss of the ten investigated analytes which were carefully selected to incorporate functional groups that could potentially interact with the added reagents and hence could be removed along with the phospholipids. Copyright © 2008 John Wiley & Sons, Ltd. [source] ORIGINAL RESEARCH: Prevalence and Evaluation of Sexual Health Problems,HSDD in EuropeTHE JOURNAL OF SEXUAL MEDICINE, Issue 2007Alessandra Graziottin MD ABSTRACT Introduction., The complex condition of the menopause is experienced by all women going through the physical and emotional changes associated with ovarian sexual hormones loss. It may impact directly on their physical and mental health. Aim., The complexity of this condition makes it necessary to accumulate large bodies of data to define the patterns and trends in its evaluable manifestations. To this end, large amounts of data were collected on women from France, Germany, Italy, and the United Kingdom, via the Women's International Survey on Health and Sexuality. Main Outcome Measures., The key measures within the survey were the Profile of Female of Sexual Function© (PFSF©) and the Personal Distress Scale© (PDS©). Results., The survey yielded 2,467 responders aged between 20 and 70, capturing women with surgical and natural menopausal status and those with premenopausal status. In the four EU countries studied, sexual activity decreases by age. An increase in female sexual dysfunction (FSD), particularly loss of sexual desire, is directly correlated with increasing age. However, the distress associated with loss of sexual desire is inversely correlated with age. Cultural and context-dependent factors modulate the percentage of any FSD in the different European countries. This is exemplified in the significant intercountry variation observed in the percentage of low desire in women aged 20,49, with normal ovarian function. However, when women undergo surgical menopause, with concomitant loss of their sexual hormones, the culture-related differences are blunted. Conclusions., The findings of this survey have implications for the understanding of hypoactive sexual desire disorder (HSDD), not only the way it should be assessed in clinical practice, but also the most appropriate means for its treatment. Testosterone deficiency is a significant cause of HSDD, and new therapies have been investigated which offer considerable potential to address this hormonal etiology. Graziottin A. Prevalence and evaluation of sexual health problems,HSDD in Europe. J Sex Med 2007;4(suppl 3):211,219. [source] | |||||||||||||