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Sample records for hypercalciuric stone-forming ghs

  1. Modeling Hypercalciuria in the Genetic Hypercalciuric Stone-Forming Rat

    PubMed Central

    Frick, Kevin K.; Krieger, Nancy S.; Bushinsky, David A.

    2015-01-01

    Purpose of Review In this review we discuss how the Genetic Hypercalciuric Stone-Forming (GHS) rats, which closely model idiopathic hypercalciuria and stone formation in humans, provide insights into the pathophysiology and consequences of clinical hypercalciuria. Recent Findings Hypercalciuria in the GHS rats is due to a systemic dysregulation of calcium transport, as manifest by increased intestinal calcium absorption, increased bone resorption and decreased renal tubule calcium reabsorption. Increased levels of vitamin D receptor in intestine, bone and kidney appear to mediate these changes. The excess receptors are biologically active and increase tissue sensitivity to exogenous vitamin D. Bones of GHS rats have decreased bone mineral density (BMD) as compared with Sprague Dawley rats, and exogenous 1,25(OH)2D3 exacerbates the loss of BMD. Thiazide diuretics improve the BMD in GHS rats. Summary Studying GHS rats allows direct investigation of the effects of alterations in diet and utilization of pharmacologic therapy on hypercalciuria, urine supersaturation, stone formation and bone quality in ways that are not possible in humans. PMID:26050120

  2. Pathophysiology of the Hypercalciuria in the Genetic Hypercalciuric Stone-Forming Rats

    NASA Astrophysics Data System (ADS)

    Bushinsky, David A.

    2007-04-01

    Given evidence for a genetic cause of hypercalciuria, we screened adult male and female Sprague-Dawley (SD) rats for hypercalciuria and used those with the highest urinary calcium excretion to breed the next generation, followed by subsequent selection and inbreeding of their most hypercalciuric progeny. By the 30th generation, and continuing to the present, the GHS rats (for Genetic Hypercalciuric Stone-forming rats) excrete 8-10 times as much calcium as simultaneously studied control rats The GHS rats were found to have defects in calcium transport in the intestine, kidneys and bone, similar to abnormalities found in many patients with idiopathic hypercalciuria. The GHS rats also form kidney stones. By the conclusion of an 18 wk study, all of the GHS rats formed stones, while there was no stone formation in similarly treated SD controls. The GHS rats, when fed a standard 1.2% calcium diet, form only poorly crystalline apatite stones. However, when 5% hydroxyproline is added to the diet of the GHS rats, they form only calcium oxalate stones.

  3. Integrative microRNA-gene expression network analysis in genetic hypercalciuric stone-forming rat kidney

    PubMed Central

    Lu, Yuchao; Qin, Baolong; Hu, Henglong; Zhang, Jiaqiao; Wang, Yufeng; Wang, Qing

    2016-01-01

    Background. MicroRNAs (miRNAs) influence a variety of biological functions by regulating gene expression post-transcriptionally. Aberrant miRNA expression has been associated with many human diseases. Urolithiasis is a common disease, and idiopathic hypercalciuria (IH) is an important risk factor for calcium urolithiasis. However, miRNA expression patterns and their biological functions in urolithiasis remain unknown. Methods and Results. A multi-step approach combining microarray miRNA and mRNA expression profile and bioinformatics analysis was adopted to analyze dysregulated miRNAs and genes in genetic hypercalciuric stone-forming (GHS) rat kidneys, using normal Sprague-Dawley (SD) rats as controls. We identified 2418 mRNAs and 19 miRNAs as significantly differentially expressed, over 700 gene ontology (GO) terms and 83 KEGG pathways that were significantly enriched in GHS rats. In addition, we constructed an miRNA-gene network that suggested that rno-miR-674-5p, rno-miR-672-5p, rno-miR-138-5p and rno-miR-21-3p may play important roles in the regulatory network. Furthermore, signal-net analysis suggested that NF-kappa B likely plays a crucial role in hypercalciuria urolithiasis. Conclusions. This study presents a global view of mRNA and miRNA expression in GHS rat kidneys, and suggests that miRNAs may be important in the regulation of hypercalciuria. The data provide valuable insights for future research, which should aim at validating the role of the genes featured here in the pathophysiology of hypercalciuria. PMID:27069814

  4. Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet.

    PubMed

    Frick, Kevin K; Asplin, John R; Culbertson, Christopher D; Granja, Ignacio; Krieger, Nancy S; Bushinsky, David A

    2014-05-01

    Genetic hypercalciuric stone-forming (GHS) rats demonstrate increased intestinal Ca absorption, increased bone resorption, and reduced renal tubular Ca reabsorption leading to hypercalciuria and all form kidney stones. GHS have increased vitamin D receptors (VDR) at these sites of Ca transport. Injection of 1,25(OH)2D3 (1,25D) leads to a greater increase in urine (u)Ca in GHS than in control Sprague-Dawley (SD), possibly due to the additional VDR. In GHS the increased uCa persists on a low-Ca diet (LCD) suggesting enhanced bone resorption. We tested the hypothesis that LCD, coupled to inhibition of bone resorption by alendronate (alen), would eliminate the enhanced 1,25D-induced hypercalciuria in GHS. SD and GHS were fed LCD and half were injected daily with 1,25D. After 8 days all were also given alen until euthanasia at day 16. At 8 days, 1,25D increased uCa in SD and to a greater extent in GHS. At 16 days, alen eliminated the 1,25D-induced increase in uCa in SD. However, in GHS alen decreased, but did not eliminate, the 1,25D-induced hypercalciuria, suggesting maximal alen cannot completely prevent the 1,25D-induced bone resorption in GHS, perhaps due to increased VDR. There was no consistent effect on mRNA expression of renal transcellular or paracellular Ca transporters. Urine CaP and CaOx supersaturation (SS) increased with 1,25D alone in both SD and GHS. Alen eliminated the increase in CaP SS in SD but not in GHS. If these results are confirmed in humans with IH, the use of bisphosphonates, such as alen, may not prevent the decreased bone density observed in these patients. PMID:24573387

  5. Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet

    PubMed Central

    Asplin, John R.; Culbertson, Christopher D.; Granja, Ignacio; Krieger, Nancy S.; Bushinsky, David A.

    2014-01-01

    Genetic hypercalciuric stone-forming (GHS) rats demonstrate increased intestinal Ca absorption, increased bone resorption, and reduced renal tubular Ca reabsorption leading to hypercalciuria and all form kidney stones. GHS have increased vitamin D receptors (VDR) at these sites of Ca transport. Injection of 1,25(OH)2D3 (1,25D) leads to a greater increase in urine (u)Ca in GHS than in control Sprague-Dawley (SD), possibly due to the additional VDR. In GHS the increased uCa persists on a low-Ca diet (LCD) suggesting enhanced bone resorption. We tested the hypothesis that LCD, coupled to inhibition of bone resorption by alendronate (alen), would eliminate the enhanced 1,25D-induced hypercalciuria in GHS. SD and GHS were fed LCD and half were injected daily with 1,25D. After 8 days all were also given alen until euthanasia at day 16. At 8 days, 1,25D increased uCa in SD and to a greater extent in GHS. At 16 days, alen eliminated the 1,25D-induced increase in uCa in SD. However, in GHS alen decreased, but did not eliminate, the 1,25D-induced hypercalciuria, suggesting maximal alen cannot completely prevent the 1,25D-induced bone resorption in GHS, perhaps due to increased VDR. There was no consistent effect on mRNA expression of renal transcellular or paracellular Ca transporters. Urine CaP and CaOx supersaturation (SS) increased with 1,25D alone in both SD and GHS. Alen eliminated the increase in CaP SS in SD but not in GHS. If these results are confirmed in humans with IH, the use of bisphosphonates, such as alen, may not prevent the decreased bone density observed in these patients. PMID:24573387

  6. 1,25(OH)2D3-enhanced hypercalciuria in genetic hypercalciuric stone-forming rats fed a low-calcium diet

    PubMed Central

    Asplin, John R.; Krieger, Nancy S.; Culbertson, Christopher D.; Asplin, Daniel M.; Bushinsky, David A.

    2013-01-01

    The inbred genetic hypercalciuric stone-forming (GHS) rats exhibit many features of human idiopathic hypercalciuria and have elevated levels of vitamin D receptors (VDR) in calcium (Ca)-transporting organs. On a normal-Ca diet, 1,25(OH)2D3 (1,25D) increases urine (U) Ca to a greater extent in GHS than in controls [Sprague-Dawley (SD)]. The additional UCa may result from an increase in intestinal Ca absorption and/or bone resorption. To determine the source, we asked whether 1,25D would increase UCa in GHS fed a low-Ca (0.02%) diet (LCD). With 1,25D, UCa in SD increased from 1.2 ± 0.1 to 9.3 ± 0.9 mg/day and increased more in GHS from 4.7 ± 0.3 to 21.5 ± 0.9 mg/day (P < 0.001). In GHS rats on LCD with or without 1,25D, UCa far exceeded daily Ca intake (2.6 mg/day). While the greater excess in UCa in GHS rats must be derived from bone mineral, there may also be a 1,25D-mediated decrease in renal tubular Ca reabsorption. RNA expression of the components of renal Ca transport indicated that 1,25D administration results in a suppression of klotho, an activator of the renal Ca reabsorption channel TRPV5, in both SD and GHS rats. This fall in klotho would decrease tubular reabsorption of the 1,25D-induced bone Ca release. Thus, the greater increase in UCa with 1,25D in GHS fed LCD strongly suggests that the additional UCa results from an increase in bone resorption, likely due to the increased number of VDR in the GHS rat bone cells, with a possible component of decreased renal tubular calcium reabsorption. PMID:23926184

  7. Sensitivity to calcium intake in calcium stone forming patients.

    PubMed

    Heilberg, I P; Martini, L A; Draibe, S A; Ajzen, H; Ramos, O L; Schor, N

    1996-01-01

    The absorptive or renal origin of hypercalciuria can be discriminated using an acute oral calcium load test (ACLT). Of 86 patients with calcium oxalate kidney stones, 28 (23%) were found to be hypercalciuric (HCa) and 58 (67%) normocalciuric (NCa) on their customary free diet, containing 542 +/- 29 mg/day (mean +/- SE) of calcium. Since the apparently normal 24-hour calcium excretion of many calcium stone formers (CSF) may be due to a combination of high calcium absorption with moderately low calcium intake, all patients were investigated by ACLT. Of 28 HCa patients, 13 (46%) were classified as absorptive (AH) and 15 (54%) as renal hypercalciuria (RH). Of the 58 NCa patients, 38 (65%) presented features of intestinal hyperabsorption and were therefore designated as AH-like, and 20 (35%) as RH-like. To further elucidate the role of dietary calcium in these CSF, a chronic calcium load test (CCLT), consisting of 1 g/day of oral Ca for 7 days, was designed. A positive response to the CCLT was considered to occur when urinary calcium (uCa) was > or = 4 mg/ kg/24 h on the 7th day. Among NCa patients, 29% of AH-like subjects responded to the CCLT and 71% did not; 50% of RH-like subjects also responded and 50% did not. In HCa patients, 85% of AH and 67% of RH subjects maintained uCa > or = 4 mg/kg/24 h after the CCLT and 15% of AH and 23% of RH subjects did not. However, a significant additional increase in mean uCa was not observed among HCa patients. All patients were submitted to a second evaluation of fasting calciuria (Ca/Cr). A modification of this parameter was noticed in 89% of RH-like and 78% of RH patients. In conclusion, these data suggest the presence of subpopulations of patients sensitive or not to calcium intake, regardless of whether the acute response to a calcium overload test suggested AH or RH. The CCLT disclosed dietary hypercalciuria in 21/58 (36%) of previously NCa patients. In these NCa patients, the ACLT may be replaced by the CCLT. The distinction

  8. The ghrelin receptors (GHS-R1a and GHS-R1b).

    PubMed

    Albarrán-Zeckler, Rosie G; Smith, Roy G

    2013-01-01

    The growth hormone (GH) secretagogue receptor (GHS-R1a) is a G protein-coupled receptor (GPCR) expressed in the brain as well as other areas of the body. In the early 1990s, this receptor was expression cloned in MERCK laboratories by using a group of synthesized small molecules known to increase GH release in humans and other animals. Since its discovery, hundreds of studies have shown the importance of this receptor and its endogenous ligand, ghrelin, in metabolism, neurotransmission, and behavior. Even more relevant are the prospective benefits that will result from pharmacologic manipulation of GHS-R1a. Multiple GHS-R1a agonists and antagonists are available for experimentation, and some have been used in patients with promising results. Studies in rodents have revealed intriguing potential roles for GHS-R1a modulation. Our goal in this chapter is to connect these studies with the inherent advantages of targeting this receptor pharmacologically. PMID:23652387

  9. Prophylactic effects of quercetin and hyperoside in a calcium oxalate stone forming rat model.

    PubMed

    Zhu, Wei; Xu, Yun-fei; Feng, Yuan; Peng, Bo; Che, Jian-ping; Liu, Min; Zheng, Jun-hua

    2014-12-01

    Quercetin and hyperoside (QH) are the two main constituents of the total flavone glycosides of Flos Abelmoschus manihot, which has been prescribed for treating chronic kidney disease for decades. This study aimed to investigate the effect of QH on calcium oxalate (CaOx) formation in ethylene glycol (EG)-fed rats. Rats were divided into three groups: an untreated stone-forming group, a QH-treated stone-forming group (20 mg/kg/day) and a potassium citrate-treated stone-forming group (potassium citrate was a worldwide-recognized calculi-prophylactic medicine). Ethylene glycol (0.5 %) was administered to the rats during the last week, and vitamin D3 was force-fed to induce hyperoxaluria and kidney calcium oxalate crystal deposition. 24 h urine samples were collected before and after inducing crystal deposits. Rats were killed and both kidneys were harvested after 3 weeks. Bisected kidneys were examined under a polarized light microscope for semi-quantification of the crystal-formation. The renal tissue superoxide dismutase and catalase levels were measured by Western blot. QH and potassium citrate have the ability to alkalinize urine. The number of crystal deposits decreased significantly in the QH-treated stone-forming group as compared to the other groups. Superoxide dismutase and catalase levels also increased significantly in the QH-treated stone-forming group, as compared with the untreated stone-forming group. QH administration has an inhibitory effect on the deposition of CaOx crystal in EG-fed rats and may be effective for preventing stone-forming disease. PMID:25085199

  10. Integrating GHS into the Ghrelin System

    PubMed Central

    Veldhuis, Johannes D.; Bowers, Cyril Y.

    2010-01-01

    Oligopeptide derivatives of metenkephalin were found to stimulate growth-hormone (GH) release directly by pituitary somatotrope cells in vitro in 1977. Members of this class of peptides and nonpeptidyl mimetics are referred to as GH secretagogues (GHSs). A specific guanosine triphosphatate-binding protein-associated heptahelical transmembrane receptor for GHS was cloned in 1996. An endogenous ligand for the GHS receptor, acylghrelin, was identified in 1999. Expression of ghrelin and homonymous receptor occurs in the brain, pituitary gland, stomach, endothelium/vascular smooth muscle, pancreas, placenta, intestine, heart, bone, and other tissues. Principal actions of this peptidergic system include stimulation of GH release via combined hypothalamopituitary mechanisms, orexigenesis (appetitive enhancement), insulinostasis (inhibition of insulin secretion), cardiovascular effects (decreased mean arterial pressure and vasodilation), stimulation of gastric motility and acid secretion, adipogenesis with repression of fat oxidation, and antiapoptosis (antagonism of endothelial, neuronal, and cardiomyocyte death). The array of known and proposed interactions of ghrelin with key metabolic signals makes ghrelin and its receptor prime targets for drug development. PMID:20798846

  11. Assessing applicants to the NASA flight program for their renal stone-forming potential

    NASA Technical Reports Server (NTRS)

    Pak, Charles Y. C.; Hill, Kathy; Cintron, Nitza M.; Huntoon, Carolyn

    1989-01-01

    Because spaceflight can provoke the formation of kidney stones, 24-hour urine samples for 104 male applicants were analyzed for stone-forming risk factors prior to their selection into the NASA astronaut-mission specialist corps. A high level of supersaturation (with either calcium oxalate, brushite, or monosodium urate) was noted in these applicants which predisposes them to the crystallization of stone-forming calcium salts. It is suggested that most of the abnormal stone risk factors found were environmental, rather than metabolic, in origin.

  12. Prevention of hypercalciuria and stone-forming propensity during prolonged bedrest by alendronate

    NASA Technical Reports Server (NTRS)

    Ruml, L. A.; Dubois, S. K.; Roberts, M. L.; Pak, C. Y.

    1995-01-01

    The bone loss and hypercalciuria induced by immobilization or the decreased gravitational forces of space are well described. Using a model of bedrest immobilization, the ability of a potent aminobisphosphonate, alendronate, to avert hypercalciuria and stone-forming propensity was tested. Sixteen male subjects participated in a randomized, placebo-controlled trial in which they received either 20 mg of alendronate or placebo 2 weeks prior to and during 3 weeks of strict bedrest. Parameters of bone and calcium metabolism and urinary crystallization of stone-forming salts were measured before and at the end of bedrest. In the placebo group, bedrest increased urinary calcium (209 +/- 47 to 267 +/- 60 mg/day, p < 0.01) and the saturation of calcium phosphate. Before bedrest, the alendronate group had a significantly lower serum calcium (8.8 +/- 0.4 vs. 9.6 +/- 0.5 mg/dl, p < 0.01) and higher serum PTH (62.4 +/- 33.1 vs. 23.1 +/- 7.5 pg/ml, p < 0.01) compared with the placebo group. Moreover, the alendronate group had a lower urinary calcium (75 +/- 41 mg/day) and saturation of calcium oxalate and calcium phosphate. These effects of alendronate were sustained during bedrest. Following bedrest in the alendronate group, urinary calcium rose to 121 +/- 50 mg/day, a value less than that in the placebo group before or during bedrest. Similarly, urinary saturation of calcium oxalate and calcium phosphate rose with bedrest in the alendronate-treated patients but remained lower than values obtained in placebo-treated patients before or during bedrest. Alendronate inhibits bone mineral loss and averts the hypercalciuria and increased propensity for the crystallization of stone-forming calcium salts which occurs during 3 weeks of strict bedrest.

  13. GHS Clock, a New Device for Precise Timing

    NASA Astrophysics Data System (ADS)

    Hayamizu, Tsutomu; Geshiro, Hiroyuki; Sôma, Mitsuru

    2000-12-01

    The Japanese shortwave time signals JJY will be shut down on 2001 March 31st. Astronomers who have been using JJY are seeking alternative methods for precise timing. The authors designed equipment, called the GHS Clock, that can be used with inexpensive GPS receivers to produce both an LED flash and a pip sound at the beginning of each second. Tests show that this device is accurate to about a microsecond.

  14. Similarity of urinary risk factors among stone-forming patients in five regions of the United States

    NASA Technical Reports Server (NTRS)

    Harvey, J. A.; Hill, K. D.; Pak, C. Y.

    1990-01-01

    Study Objective: To compare urinary biochemical risk factors among stone-forming patients in the Southeast (SE) or "stone belt" versus four other regions of the United States. Design: Prospective biochemical survey for regional comparisons. Setting: Referral-based nephrolithiasis clinics, urologists, nephrologists, and family practitioners. Patients: Consecutive sample of 3473 stone-forming patients who submitted 24-hour urine collections for biochemical analyses of stone-forming risk factors. Interventions: None. Subjects taking medication known to interfere with stone-forming risk factors were deleted from the final data compilation. Measurements and Main Results: Overall, the mean values for each urinary parameter spanned a narrow range without significant difference between the five regions. Among "metabolic" factors, 40% in the SE had hypercalciuria (> 6.25 mmol/d), compared to 35%-43% in other regions, and hyperuricosuria (> 4.2 mmol/d) was found in 16% in the SE versus 17%-19% elsewhere. Among "environmental" factors, low urine volume ( < 2 L/d) was found in 77% patients in the SE compared to 69%-78% elsewhere, and high sodium was encountered in 27% in the SE versus 24%-29% elsewhere. No differences were noted in occurrence of other abnormal risk factors: hyperoxaluria, hypocitraturia, low pH, high sulfate, high phosphorus, or low magnesium. Conclusions: Despite expected regional differences in nutritional and environmental influences, the results of this study showed a striking similarity in urinary biochemical risk factor profiles of stone-formers in all five regions of the United States.

  15. A Significant Role of the Truncated Ghrelin Receptor GHS-R1b in Ghrelin-induced Signaling in Neurons.

    PubMed

    Navarro, Gemma; Aguinaga, David; Angelats, Edgar; Medrano, Mireia; Moreno, Estefanía; Mallol, Josefa; Cortés, Antonio; Canela, Enric I; Casadó, Vicent; McCormick, Peter J; Lluís, Carme; Ferré, Sergi

    2016-06-17

    The truncated non-signaling ghrelin receptor growth hormone secretagogue R1b (GHS-R1b) has been suggested to simply exert a dominant negative role in the trafficking and signaling of the full and functional ghrelin receptor GHS-R1a. Here we reveal a more complex modulatory role of GHS-R1b. Differential co-expression of GHS-R1a and GHS-R1b, both in HEK-293T cells and in striatal and hippocampal neurons in culture, demonstrates that GHS-R1b acts as a dual modulator of GHS-R1a function: low relative GHS-R1b expression potentiates and high relative GHS-R1b expression inhibits GHS-R1a function by facilitating GHS-R1a trafficking to the plasma membrane and by exerting a negative allosteric effect on GHS-R1a signaling, respectively. We found a preferential Gi/o coupling of the GHS-R1a-GHS-R1b complex in HEK-293T cells and, unexpectedly, a preferential Gs/olf coupling in both striatal and hippocampal neurons in culture. A dopamine D1 receptor (D1R) antagonist blocked ghrelin-induced cAMP accumulation in striatal but not hippocampal neurons, indicating the involvement of D1R in the striatal GHS-R1a-Gs/olf coupling. Experiments in HEK-293T cells demonstrated that D1R co-expression promotes a switch in GHS-R1a-G protein coupling from Gi/o to Gs/olf, but only upon co-expression of GHS-R1b. Furthermore, resonance energy transfer experiments showed that D1R interacts with GHS-R1a, but only in the presence of GHS-R1b. Therefore, GHS-R1b not only determines the efficacy of ghrelin-induced GHS-R1a-mediated signaling but also determines the ability of GHS-R1a to form oligomeric complexes with other receptors, promoting profound qualitative changes in ghrelin-induced signaling. PMID:27129257

  16. [Globally harmonized system of classification and labelling of chemicals (GHS) and its implementation in Japan].

    PubMed

    Miyagawa, Muneyuki

    2010-01-01

    The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is a set of recommendations by the United Nations, first issued in 2003 as a communication tool for the sound management of chemicals, comprising harmonized classification criteria for physical, health and environmental hazards, a unified format for material safety data sheets (MSDS), and labeling elements including pictograms and hazard statements preassigned to each classification category. The GHS has been introduced into Japan and implemented in the regulatory framework for chemical safety. The Japanese Industrial Standards (JIS) adopted the GHS, and the GHS-based JIS rules have become the Japanese standards for labels and MSDS. The use of the JIS format for labels and MSDS is recommended by several competent authorities in Japan although mostly on a voluntary basis. In the workplace, however, GHS-based JIS labels and MSDS have become legal requirements by the Industrial Safety and Health Law since 2006; namely, issuing MSDS in such a format is mandatory for the 640 specified chemicals and also labeling for the 99 targeted chemicals*. Although the GHS provides definitions and classification criteria for 10 classes of health hazards (acute toxicity, skin and eye corrosion/irritation, sensitization, germ cell mutagenicity, carcinogenicity, reproductive toxicity, specific target organ toxicity single/repeated exposures, and aspiration hazard), it does not provide actual classification of chemicals, so that competent authorities and industries need to classify a number of chemicals and/or mixtures. Weight-of-evidence judgment and/or expert judgment would be necessary in many cases. In this paper, the outline of the GHS classification is described and problems of the GHS and its implementation are discussed. PMID:20134103

  17. The road to GHS: worker right-to-know in the 21st century.

    PubMed

    Karstadt, Myra L

    2012-01-01

    Of the three communications standards discussed, HI is definitely the outlier, as it emphasizes worker control of the process of identifying hazard and deemphasizes employer control of identification of hazards and dissemination of hazard information. GHS may not be as protective of American workers as HazCom is, but for workers in less-developed countries, where regulation of workplace health and safety is less strong than in the United States, Canada, many countries in Europe, and Japan, GHS--if adequately enforced-will likely represent an improvement in information on chemical hazards in the workplace. American workers may well see a decline in workplace protection against chemical hazards while protection may improve for workers in less-developed countries. This trade-off is part of the ongoing debate about globalization, of which worker protection from chemical hazards should be an important aspect. The next paper in this series will compare the proposed and final versions of GHS, and will discuss possible improvements to GHS to better serve American workers. As OSHA moves forward with the GHS rule, people and organizations concerned with worker right-to-know should consider possible improvements to GHS to better serve workers in the United States and worldwide. PMID:22550692

  18. Nutrient intake and urine composition in calcium oxalate stone-forming dogs: comparison with healthy dogs and impact of dietary modification.

    PubMed

    Stevenson, Abigail E; Blackburn, Judith M; Markwell, Peter J; Robertson, William G

    2004-01-01

    Nutrient intake and urine composition were analyzed in calcium oxalate (CaOx)stone-forming and healthy control dogs to identify factors that contribute to CaOx urolithiasis. Stone-forming dogs had significantly lower intake of sodium, calcium, potassium, and phosphorus and significantly higher urinary calcium and oxalate concentrations, calcium excretion, and CaOx relative supersaturation (RSS). Feeding a diet used in the treatment of canine lower urinary tract disease for 1 month was associated with increased intake of moisture, sodium, and fat; reduced intake of potassium and calcium; and decreased urinary calcium and oxalate concentrations, calcium excretion, and CaOx RSS. No clinical signs of disease recurrence were observed in the stone-forming dogs when the diet was fed for an additional 11 months. The results suggest that hypercalciuria and hyperoxaluria contribute to the formation of CaOx uroliths in dogs and show that dietary modifications can alter this process. PMID:15578454

  19. The development of the globally harmonized system (GHS) of classification and labelling of hazardous chemicals.

    PubMed

    Winder, Chris; Azzi, Rola; Wagner, Drew

    2005-10-17

    The hazards of chemicals can be classified using classification criteria that are based on physical, chemical and ecotoxicological endpoints. These criteria may be developed be iteratively, based on scientific or regulatory processes. A number of national and international schemes have been developed over the past 50 years, and some, such as the UN Dangerous Goods system or the EC system for hazardous substances, are in widespread use. However, the unnecessarily complicated multiplicity of existing hazard classifications created much unnecessary confusion at the user level, and a recommendation was made at the 1992 Rio Earth summit to develop a globally harmonized chemical hazard classification and compatible labelling system, including material safety data sheets and easily understandable symbols, that could be used for manufacture, transport, use and disposal of chemical substances. This became the globally harmonized system for the Classification and Labelling of Chemicals (GHS). The developmental phase of the GHS is largely complete. Consistent criteria for categorising chemicals according to their toxic, physical, chemical and ecological hazards are now available. Consistent hazard communication tools such as labelling and material safety data sheets are also close to finalisation. The next phase is implementation of the GHS. The Intergovernmental Forum for Chemical Safety recommends that all countries implement the GHS as soon as possible with a view to have the system fully operational by 2008. When the GHS is in place, the world will finally have one system for classification of chemical hazards. PMID:16039045

  20. The visceral fat compartment is independently associated with changes in urine constituent excretion in a stone forming population.

    PubMed

    Fram, Ethan B; Agalliu, Ilir; DiVito, Joseph; Hoenig, David M; Stern, Joshua M

    2015-06-01

    The objective of this study was to identify the independent effect of visceral fat on urine constituent excretion in a stone forming population. Using a database of 382 kidney stone patients with available visceral fat quantification, we created multiple linear regression models predicting changes in urinary solutes based on visceral fat area and body mass-index, divided by gender. Chi-square tests were used to compare stone composition by body mass-index and visceral fat area. Visceral fat predicts increases in urinary creatinine, sodium, and volume in men, but only urinary phosphate in women. In women, total body mass-index does not appear to modify this effect, but in men it is more pronounced in overweight patients for creatinine and volume only. Elevated visceral fat is associated with increased probability of uric acid stone composition. Different fat compartments likely effect urine composition in different ways. This effect appears to be different in men and women. Understanding and quantifying the effects of different fat compartments is probably important to understanding the metabolism of urolithiasis. PMID:25903669

  1. The usefulness of the validated SkinEthic™ RHE test method to identify skin corrosive UN GHS subcategories.

    PubMed

    Alépée, Nathalie; Robert, Clément; Tornier, Carine; Cotovio, José

    2014-06-01

    The SkinEthic™ Reconstructed Human Epidermis (RHE) test method has been adopted within the context of OECD TG 431 for distinguishing corrosive and non-corrosive chemicals. The EU CLP classification system requires subcategorising of corrosive chemicals into the three UN GHS subcategories 1A, 1B and 1C. Since the SkinEthic™ RHE method was originally validated to discriminate corrosives from non-corrosives, the present study was undertaken to investigate its usefulness to discriminate skin corrosive UN GHS subcategories. In total 84 substances were tested in three independent runs and two prediction models (PM) were assessed, representing a pre-defined validated prediction model (PM-A) and an alternative one defined post-hoc (PM-B). The results obtained with both PM were reproducible, as shown by the ⩾92.9% concordance of classification between runs for discriminating corrosives versus non-corrosives, and the ⩾85% concordance for discriminating the GHS subcategories versus non-corrosives. Moreover results confirmed a high sensitivity of the SkinEthic™ RHE method to predict corrosives (94.9%) and good specificity (⩾73.7%) independent of the PM applied. Regarding the identification of UN GHS corrosive subcategories, PM-A resulted in 86.1% correct classifications of the GHS subcategory 1A. When using the PM-B, the identification of GHS subcategory 1B-and-1C substances improved, with 63.4% correct sub-categorisation. If considering the 30 reference chemicals as recommended in the recently revised OECD TG 431 (2013), PM-A and PM-B achieved 78.9% and 83.3% accuracy respectively for the identification of GHS subcategories and non-corrosives. They correctly predicted 90% of GHS subcategory 1A and 80% of GHS non-corrosive substances independent of the PM used. In conclusion, the SkinEthic™ RHE test method is highly reproducible and sensitive for discriminating corrosive from non-corrosive substances. Furthermore it allows reliable identification of skin

  2. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. PMID:24929227

  3. Molecular identification of ghrelin receptor (GHS-R1a) and its functional role in the gastrointestinal tract of the guinea-pig.

    PubMed

    Kitazawa, Takio; Nakamura, Tatsuro; Saeki, Atsuki; Teraoka, Hiroki; Hiraga, Takeo; Kaiya, Hiroyuki

    2011-09-01

    Ghrelin stimulates gastric motility in vivo in the guinea-pig through activation of growth hormone secretagogue receptor (GHS-R). In this study, we identified GHS-R1a in the guinea-pig, and examined its distribution and cellular function and compared them with those in the rat. Effects of ghrelin in different regions of gastrointestinal tract were also examined. GHS-R1a was identified in guinea-pig brain cDNA. Amino acid identities of guinea-pig GHS-R1a were 93% to horses and 85% to dogs. Expression levels of GHS-R1a mRNA were high in the pituitary and hypothalamus, moderate in the thalamus, cerebral cortex, pons, medulla oblongata and olfactory bulb, and low in the cerebellum and peripheral tissues including gastrointestinal tract. Comparison of GHS-R1a expression patterns showed that those in the brain were similar but the expression level in the gastrointestinal tract was higher in rats than in guinea-pigs. Guinea-pig GHS-R1a expressed in HEK 293 cells responded to rat ghrelin and GHS-R agonists. Rat ghrelin was ineffective in inducing mechanical changes in the stomach and colon but caused a slight contraction in the small intestine. 1,1-Dimethyl-4-phenylpiperazinium and electrical field stimulation (EFS) caused cholinergic contraction in the intestine, and these contractions were not affected by ghrelin. Ghrelin did not change spontaneous and EFS-evoked [(3)H]-efflux from [(3)H]-choline-loaded ileal strips. In summary, guinea-pig GHS-R1a was identified and its functions in isolated gastrointestinal strips were characterized. The distribution of GHS-R1a in peripheral tissues was different from that in rats, suggesting that the functional role of ghrelin in the guinea-pig is different from that in other animal species. PMID:21843569

  4. Hypercalciuric Bone Disease

    NASA Astrophysics Data System (ADS)

    Favus, Murray J.

    2008-09-01

    Hypercalciuria plays an important causal role in many patients with calcium oxalate (CaOx) stones. The source of the hypercalciuria includes increased intestinal Ca absorption and decreased renal tubule Ca reabsorption. In CaOx stone formers with idiopathic hypercalciuria (IH), Ca metabolic balance studies have revealed negative Ca balance and persistent hypercalciuria in the fasting state and during low dietary Ca intake. Bone resorption may also contribute to the high urine Ca excretion and increase the risk of bone loss. Indeed, low bone mass by DEXA scanning has been discovered in many IH patients. Thiazide diuretic agents reduce urine Ca excretion and may increase bone mineral density (BMD), thereby reducing fracture risk. Dietary Ca restriction that has been used unsuccessfully in the treatment of CaOx nephrolithiasis in the past may enhance negative Ca balance and accelerate bone loss. DEXA scans may demonstrate low BMD at the spine, hip, or forearm, with no predictable pattern. The unique pattern of bone histologic changes in IH differs from other causes of low DEXA bone density including postmenopausal osteoporosis, male hypogonadal osteoporosis, and glucocorticoid-induced osteoporosis. Hypercalciuria appears to play an important pathologic role in the development of low bone mass, and therefore correction of urine Ca losses should be a primary target for treatment of the bone disease accompanying IH.

  5. The Expression of GHS-R in Primary Neurons Is Dependent upon Maturation Stage and Regional Localization

    PubMed Central

    Tonna, Noemi; Casnici, Claudia; Benfante, Roberta; Fornasari, Diego; Bianco, Fabio; Longhi, Renato; Marelli, Ornella

    2013-01-01

    Ghrelin is a hormone with a crucial role in the regulation of appetite, regulation of inflammation, glucose metabolism and cell proliferation. In the brain ghrelin neurons are located in the cortex (sensorimotor area, cingular gyrus), and the fibres of ghrelin neurons in hypothalamus project directly to the dorsal vagal complex (DVC). Ghrelin binds the growth hormone secretagogue receptor (GHS-R) a G-protein-coupled receptor with a widespread tissue distribution, indeed these receptors are localized both in nonnervous, organs/tissues (i.e. adipose tissue, myocardium, adrenals, gonads, lung, liver, arteries, stomach, pancreas, thyroid, and kidney) as well as in central nervous system (CNS) and higher levels of expression in the pituitary gland and the hypothalamus and lower levels of expression in other organs, including brain. A GHS-R specific monoclonal antibody has been developed and characterized and through it we demonstrate that GHS-R is expressed in primary neurons and that its expression is dependent upon their developmental stage and shows differences according to the brain region involved, with a more pronounced expression in hippocampal rather than cortical neurons. A characterization of GHS-R within the central nervous system is of extreme importance in order to gain insights on its role in the modulation of neurodegenerative events such as Alzheimer’s disease. PMID:23755116

  6. A comparison of mandatory and voluntary approaches to the implementation of Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in the management of hazardous chemicals.

    PubMed

    Ta, Goh Choo; Mokhtar, Mazlin Bin; Peterson, Peter John; Yahaya, Nadzri Bin

    2011-01-01

    The European Union (EU) and the World Health Organization (WHO) have applied different approaches to facilitate the implementation of the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS). The EU applied the mandatory approach by gazetting the EU Regulation 1272/2008 incorporating GHS elements on classification, labelling and packaging of substances and mixtures in 2008; whereas the WHO utilized a voluntary approach by incorporating GHS elements in the WHO guidelines entitled 'WHO Recommended Classification of Pesticides by Hazard' in 2009. We report on an analysis of both the mandatory and voluntary approaches practised by the EU and the WHO respectively, with close reference to the GHS 'purple book'. Our findings indicate that the mandatory approach practiced by the EU covers all the GHS elements referred to in the second revised edition of the GHS 'purple book'. Hence we can conclude that the EU has implemented the GHS particularly for industrial chemicals. On the other hand, the WHO guidelines published in 2009 should be revised to address concerns raised in this paper. In addition, both mandatory and voluntary approaches should be carefully examined because the classification results may be different. PMID:22020020

  7. Hazard banding in compliance with the new Globally Harmonised System (GHS) for use in control banding tools.

    PubMed

    Arnone, Mario; Koppisch, Dorothea; Smola, Thomas; Gabriel, Stefan; Verbist, Koen; Visser, Remco

    2015-10-01

    Many control banding tools use hazard banding in risk assessments for the occupational handling of hazardous substances. The outcome of these assessments can be combined with advice for the required risk management measures (RMMs). The Globally Harmonised System of Classification and Labelling of Chemicals (GHS) has resulted in a change in the hazard communication elements, i.e. Hazard (H) statements instead of Risk-phrases. Hazard banding schemes that depend on the old form of safety information have to be adapted to the new rules. The purpose of this publication is to outline the rationales for the assignment of hazard bands to H statements under the GHS. Based on this, this publication proposes a hazard banding scheme that uses the information from the safety data sheets as the basis for assignment. The assignment of hazard bands tiered according to the severity of the underlying hazards supports the important principle of substitution. Additionally, the set of assignment rules permits an exposure-route-specific assignment of hazard bands, which is necessary for the proposed route-specific RMMs. Ideally, all control banding tools should apply the same assignment rules. This GHS-compliant hazard banding scheme can hopefully help to establish a unified hazard banding strategy in the various control banding tools. PMID:26206396

  8. Guidance on classification for reproductive toxicity under the globally harmonized system of classification and labelling of chemicals (GHS).

    PubMed

    Moore, Nigel P; Boogaard, Peter J; Bremer, Susanne; Buesen, Roland; Edwards, James; Fraysse, Benoit; Hallmark, Nina; Hemming, Helena; Langrand-Lerche, Carole; McKee, Richard H; Meisters, Marie-Louise; Parsons, Paul; Politano, Valerie; Reader, Stuart; Ridgway, Peter; Hennes, Christa

    2013-11-01

    The Globally Harmonised System of Classification (GHS) is a framework within which the intrinsic hazards of substances may be determined and communicated. It is not a legislative instrument per se, but is enacted into national legislation with the appropriate legislative instruments. GHS covers many aspects of effects upon health and the environment, including adverse effects upon sexual function and fertility or on development. Classification for these effects is based upon observations in humans or from properly designed experiments in animals, although only the latter is covered herein. The decision to classify a substance based upon experimental data, and the category of classification ascribed, is determined by the level of evidence that is available for an adverse effect on sexual function and fertility or on development that does not arise as a secondary non-specific consequence of other toxic effect. This document offers guidance on the determination of level of concern as a measure of adversity, and the level of evidence to ascribe classification based on data from tests in laboratory animals. PMID:24274377

  9. Ghrelin receptor (GHS-R1A) antagonism alters preference for ethanol and sucrose in a concentration-dependent manner in prairie voles.

    PubMed

    Stevenson, J R; Francomacaro, L M; Bohidar, A E; Young, K A; Pesarchick, B F; Buirkle, J M; McMahon, E K; O'Bryan, C M

    2016-03-01

    Ghrelin receptor (GHS-R1A) activity has been implicated in reward for preferred foods and drugs; however, a recent study in our laboratory indicated that GHS-R1A antagonism reduces early (after only four exposures) preference for 20% ethanol, but not 10% sucrose in prairie voles, a genetically diverse high alcohol-consuming species. The purpose of the present study was to determine if these effects of GHS-R1A antagonism depend on the concentration of the rewarding solution being consumed. We first characterized preference for varying concentrations of ethanol and sucrose. Two bottle tests of each ethanol concentration versus water indicated that 10% and 20% ethanol are less preferred than 3% ethanol, and a follow-up direct comparison of 10% vs. 20% showed that 10% was preferred over 20%. Direct two-bottle comparisons of 2% vs. 5%, 2% vs. 10%, and 5% vs. 10% sucrose showed that 10% sucrose was most preferred, and 2% sucrose was least preferred. The effects of JMV 2959, a GHS-R1A antagonist, on preference for each concentration of ethanol and sucrose were then tested. In a between groups design prairie voles were given four two-hour drinking sessions in which animals had access to ethanol (3, 10, or 20%) versus water, or sucrose (2, 5, or 10%) versus water every other day. Saline habituation injections were given 30 min before the third drinking session. JMV 2959 (i.p.; 9 mg/kg), a GHS-R1A antagonist, or saline was administered 30 min before the fourth drinking session. JMV 2959 reduced preference for 20% ethanol and 2% sucrose, but had no significant effect on preference for the other ethanol and sucrose concentrations. These data identify constraints on the role of GHS-R1A in early preference for ethanol and sucrose, and the concentration-dependent effects suggest strong preference for a reward may limit the importance of GHS-R1A activity. PMID:26723269

  10. Estradiol and testosterone modulate the tissue-specific expression of ghrelin, ghs-r, goat and nucb2 in goldfish.

    PubMed

    Bertucci, Juan Ignacio; Blanco, Ayelén Melisa; Canosa, Luis Fabián; Unniappan, Suraj

    2016-03-01

    Ghrelin, and nesfatin-1 (encoded by nucleobindin2/nucb2) are two metabolic peptides with multiple biological effects in vertebrates. While sex steroids are known to regulate endogenous ghrelin and NUCB2 in mammals, such actions by steroids in fish remain unknown. This study aimed to determine whether estradiol (E2) and testosterone (T) affects the expression of preproghrelin, ghrelin/growth hormone secretagogue receptor (GHS-R), ghrelin O-acyl transferase (GOAT) and NUCB2 in goldfish (Carassius auratus). First, a dose-response assay was performed in which fish were intraperitoneally (ip) implanted with pellets containing 25, 50 or 100 μg/g body weight (BW) of E2 or T. It was found that sex steroids (100 μg/g BW) administered for 2.5 days achieved the highest E2 or T in circulation. In a second experiment, fish were ip implanted with pellets containing 100 μg/g BW of E2, T or without hormone (control). RT-qPCR analyses at 2.5 days post-administration show that gut preproghrelin and GOAT expression was upregulated by both E2 and T treatments, while the same effect was observed for GHS-R only in the pituitary. Both treatments also reduced hypothalamic preproghrelin mRNA expression. NUCB2 expression was increased in the forebrain of T treated group and reduced in the gut and pituitary under both treatments. These results show for the first time a modulation of preproghrelin and nucb2/nesfatin-1 by sex steroids in fish. The interaction between sex steroids and genes implicated in both metabolism and reproduction might help meeting the reproduction dependent energy demands in fish. PMID:26773340

  11. In Situ Localization and Rhythmic Expression of Ghrelin and ghs-r1 Ghrelin Receptor in the Brain and Gastrointestinal Tract of Goldfish (Carassius auratus)

    PubMed Central

    Unniappan, Suraj; Kah, Olivier; Gueguen, Marie-M.; Bertucci, Juan I.; Alonso-Gómez, Ángel L.; Valenciano, Ana I.; Isorna, Esther; Delgado, María J.

    2015-01-01

    Ghrelin is a gut-brain peptide hormone, which binds to the growth hormone secretagogue receptor (GHS-R) to regulate a wide variety of biological processes in fish. Despite these prominent physiological roles, no studies have reported the anatomical distribution of preproghrelin transcripts using in situ hybridization in a non-mammalian vertebrate, and its mapping within the different encephalic areas remains unknown. Similarly, no information is available on the possible 24-h variations in the expression of preproghrelin and its receptor in any vertebrate species. The first aim of this study was to investigate the anatomical distribution of ghrelin and GHS-R1a ghrelin receptor subtype in brain and gastrointestinal tract of goldfish (Carassius auratus) using immunohistochemistry and in situ hybridization. Our second aim was to characterize possible daily variations of preproghrelin and ghs-r1 mRNA expression in central and peripheral tissues using real-time reverse transcription-quantitative PCR. Results show ghrelin expression and immunoreactivity in the gastrointestinal tract, with the most abundant signal observed in the mucosal epithelium. These are in agreement with previous findings on mucosal cells as the primary synthesizing site of ghrelin in goldfish. Ghrelin receptor was observed mainly in the hypothalamus with low expression in telencephalon, pineal and cerebellum, and in the same gastrointestinal areas as ghrelin. Daily rhythms in mRNA expression were found for preproghrelin and ghs-r1 in hypothalamus and pituitary with the acrophase occurring at nighttime. Preproghrelin, but not ghs-r1a, displayed a similar daily expression rhythm in the gastrointestinal tract with an amplitude 3-fold higher than the rest of tissues. Together, these results described for the first time in fish the mapping of preproghrelin and ghrelin receptor ghs-r1a in brain and gastrointestinal tract of goldfish, and provide the first evidence for a daily regulation of both genes

  12. In Situ Localization and Rhythmic Expression of Ghrelin and ghs-r1 Ghrelin Receptor in the Brain and Gastrointestinal Tract of Goldfish (Carassius auratus).

    PubMed

    Sánchez-Bretaño, Aída; Blanco, Ayelén M; Unniappan, Suraj; Kah, Olivier; Gueguen, Marie-M; Bertucci, Juan I; Alonso-Gómez, Ángel L; Valenciano, Ana I; Isorna, Esther; Delgado, María J

    2015-01-01

    Ghrelin is a gut-brain peptide hormone, which binds to the growth hormone secretagogue receptor (GHS-R) to regulate a wide variety of biological processes in fish. Despite these prominent physiological roles, no studies have reported the anatomical distribution of preproghrelin transcripts using in situ hybridization in a non-mammalian vertebrate, and its mapping within the different encephalic areas remains unknown. Similarly, no information is available on the possible 24-h variations in the expression of preproghrelin and its receptor in any vertebrate species. The first aim of this study was to investigate the anatomical distribution of ghrelin and GHS-R1a ghrelin receptor subtype in brain and gastrointestinal tract of goldfish (Carassius auratus) using immunohistochemistry and in situ hybridization. Our second aim was to characterize possible daily variations of preproghrelin and ghs-r1 mRNA expression in central and peripheral tissues using real-time reverse transcription-quantitative PCR. Results show ghrelin expression and immunoreactivity in the gastrointestinal tract, with the most abundant signal observed in the mucosal epithelium. These are in agreement with previous findings on mucosal cells as the primary synthesizing site of ghrelin in goldfish. Ghrelin receptor was observed mainly in the hypothalamus with low expression in telencephalon, pineal and cerebellum, and in the same gastrointestinal areas as ghrelin. Daily rhythms in mRNA expression were found for preproghrelin and ghs-r1 in hypothalamus and pituitary with the acrophase occurring at nighttime. Preproghrelin, but not ghs-r1a, displayed a similar daily expression rhythm in the gastrointestinal tract with an amplitude 3-fold higher than the rest of tissues. Together, these results described for the first time in fish the mapping of preproghrelin and ghrelin receptor ghs-r1a in brain and gastrointestinal tract of goldfish, and provide the first evidence for a daily regulation of both genes

  13. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats.

    PubMed

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  14. Association of cord blood des-acyl ghrelin with birth weight, and placental GHS-R1 receptor expression in SGA, AGA, and LGA newborns.

    PubMed

    González-Domínguez, Martha I; Lazo-de-la-Vega-Monroy, Maria-Luisa; Zaina, Silvio; Sabanero, Myrna; Daza-Benítez, Leonel; Malacara, Juan Manuel; Barbosa-Sabanero, Gloria

    2016-07-01

    Although ghrelin in cord blood has been associated to birth weight, its role in fetal and postnatal growth has not been elucidated. The aim of this study was to analyze total ghrelin, acyl ghrelin (AG), and des-acyl ghrelin (DAG) in cord blood of newborns with idiopathic birth weight alterations, and to evaluate protein expression of placental GHS-R1, in order to investigate their correlation with birth weight and placental weight. We performed a cross-sectional comparative study in umbilical cord blood and placentas from healthy mothers of SGA, AGA, and LGA (small, adequate and large for gestational age) term newborns (n = 20 per group). Cord blood total ghrelin, AG, and DAG were measured by ELISA, and placental GHS-R1 expression was evaluated by Western blot. Cord blood DAG was higher in SGA compared to AGA newborns (902.1 ± 109.1 and 597.4 ± 58.2 pg/ml, respectively, p = 0.01) while LGA and AGA showed similar values (627.2 ± 76.4 pg/ml for LGA, p = 0.80). DAG negatively correlated with birthweight (r = -0.31, p = 0.02) and placental weight (r = -0.33, p = 0.02). No differences in AG or total ghrelin were found. GHS-R1 protein in placenta was not differentially expressed among SGA, AGA, and LGA. Our results suggest a role of DAG in intrauterine growth. Further studies are needed in order to elucidate the mechanisms by which DAG participates in fetal growth. PMID:26754660

  15. Ghrelin accelerates wound healing through GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways in combined radiation and burn injury in rats

    PubMed Central

    Liu, Cong; Huang, Jiawei; Li, Hong; Yang, Zhangyou; Zeng, Yiping; Liu, Jing; Hao, Yuhui; Li, Rong

    2016-01-01

    The therapeutic effect of ghrelin on wound healing was assessed using a rat model of combined radiation and burn injury (CRBI). Rat ghrelin, anti-rat tumor necrosis factor (TNF) α polyclonal antibody (PcAb), or selective antagonists of p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and growth hormone secretagogue receptor (GHS-R) 1a (SB203580, SP600125, and [D-Lys3]-GHRP-6, respectively), were administered for seven consecutive days. Levels of various signaling molecules were assessed in isolated rat peritoneal macrophages. The results showed that serum ghrelin levels and levels of macrophage glucocorticoid receptor (GR) decreased, while phosphorylation of p38MAPK, JNK, and p65 nuclear factor (NF) κB increased. Ghrelin inhibited the serum induction of proinflammatory mediators, especially TNF-α, and promoted wound healing in a dose-dependent manner. Ghrelin treatment decreased phosphorylation of p38MAPK, JNK, and p65NF-κB, and increased GR levels in the presence of GHS-R1a. SB203580 or co-administration of SB203580 and SP600125 decreased TNF-α level, which may have contributed to the inactivation of p65NF-κB and increase in GR expression, as confirmed by western blotting. In conclusion, ghrelin enhances wound recovery in CRBI rats, possibly by decreasing the induction of TNF-α or other proinflammatory mediators that are involved in the regulation of GHS-R1a-mediated MAPK-NF-κB/GR signaling pathways. PMID:27271793

  16. Short Time Exposure (STE) test in conjunction with Bovine Corneal Opacity and Permeability (BCOP) assay including histopathology to evaluate correspondence with the Globally Harmonized System (GHS) eye irritation classification of textile dyes.

    PubMed

    Oliveira, Gisele Augusto Rodrigues; Ducas, Rafael do Nascimento; Teixeira, Gabriel Campos; Batista, Aline Carvalho; Oliveira, Danielle Palma; Valadares, Marize Campos

    2015-09-01

    Eye irritation evaluation is mandatory for predicting health risks in consumers exposed to textile dyes. The two dyes, Reactive Orange 16 (RO16) and Reactive Green 19 (RG19) are classified as Category 2A (irritating to eyes) based on the UN Globally Harmonized System for classification (UN GHS), according to the Draize test. On the other hand, animal welfare considerations and the enforcement of a new regulation in the EU are drawing much attention in reducing or replacing animal experiments with alternative methods. This study evaluated the eye irritation of the two dyes RO16 and RG19 by combining the Short Time Exposure (STE) and the Bovine Corneal Opacity and Permeability (BCOP) assays and then comparing them with in vivo data from the GHS classification. The STE test (first level screening) categorized both dyes as GHS Category 1 (severe irritant). In the BCOP, dye RG19 was also classified as GHS Category 1 while dye RO16 was classified as GHS no prediction can be made. Both dyes caused damage to the corneal tissue as confirmed by histopathological analysis. Our findings demonstrated that the STE test did not contribute to arriving at a better conclusion about the eye irritation potential of the dyes when used in conjunction with the BCOP test. Adding the histopathology to the BCOP test could be an appropriate tool for a more meaningful prediction of the eye irritation potential of dyes. PMID:26026500

  17. Inotropic and lusitropic effects of ghrelin and their modulation by the endocardial endothelium, NO, prostaglandins, GHS-R1a and KCa channels.

    PubMed

    Soares, João-Bruno; Rocha-Sousa, Amândio; Castro-Chaves, Paulo; Henriques-Coelho, Tiago; Leite-Moreira, Adelino F

    2006-07-01

    Contractile effects of ghrelin (10(-9) to 10(-6) M) were tested in rat papillary muscles of normal (n = 50) and hypertrophic (n = 16) right ventricles (RV). RV hypertrophy was induced by pulmonary hypertension using monocrotaline. In normal muscles, ghrelin was added either alone (n = 9) or after pre-treatment with indomethacin (cycloxygenase inhibitor, 10(-5) M; n = 10), L-nitro-L-arginin (NO synthase inhibitor, 10(-4) M; n = 9), D-Lys(3)-GHRP-6 (GHS-R1a antagonist; 10(-4) M; n = 8) or apamin+charybdotoxin (KCa channels blockers; 10(-6) M, n =7 ), as well as after damaging the endocardial endothelium (n = 7). In hypertrophic muscles, ghrelin was added either alone (n = 9) or after pre-treatment with apamin+charybdotoxin (10(-6 M, n=7). Ghrelin concentration-dependently decreased active tension (AT) and maximal velocity of tension rise (negative inotropic effect), as well as, maximal velocity of tension decay (negative lusitropic effect) and time to AT (onset of relaxation). These effects were maximal at 10(-6) M, similar in normal and hypertrophic muscles and were significantly altered only by apamin+charybdotoxin, indomethacin and L-nitro-L-arginin. Apamin+charybdotoxin attenuated the negative inotropic effect, while indomethacin and L-nitro-L-arginin, respectively, blunted and exacerbated the premature onset of relaxation. In conclusion, ghrelin induces negative inotropic and lusitropic effects and an earlier onset of relaxation in normal and hypertrophic myocardium, which are independent of GHS-R1a, since they were not affected by D-Lys(3)-GHRP-6. The negative inotropic effect is partly mediated by KCa channels, while the earlier onset of relaxation is modulated by prostaglandins and NO. PMID:16417945

  18. Functional homology of gHs and gLs from EBV-related {gamma}-herpesviruses for EBV-induced membrane fusion

    SciTech Connect

    Omerovic, Jasmina; Longnecker, Richard . E-mail: r-longnecker@northwestern.edu

    2007-08-15

    Epstein-Barr virus (EBV) is a human {gamma}-herpesvirus that primarily infects B lymphocytes and epithelial cells. Entry of EBV into B cells requires the viral glycoproteins gp42, gH/gL and gB, while gp42 is not necessary for infection of epithelial cells. In EBV, gH and gL form two distinct complexes, a bipartite complex that contains only gH and gL, used for infection of epithelial cells, and a tripartite complex that additionally includes gp42, used for infection of B cells. The gH/gL complex is conserved within the herpesvirus family, but its exact role in entry and mechanism of fusion is not yet known. To understand more about the functionality of EBVgH/gL, we investigated the functional homology of gHs and gLs from human herpesvirus 8 (HHV8) and two primate (rhesus and marmoset) {gamma}-herpesviruses in EBV-mediated virus-free cell fusion assay. Overall, gHs and gLs from the more homologous primate herpesviruses were better at complementing EBV gH and gL in fusion than HHV8 gH and gL. Interestingly, marmoset gH was able to complement fusion with epithelial cells, but not B cells. Further investigation of this led to the discovery that EBVgH is the binding partner of gp42 in the tripartite complex and the absence of fusion with B cells in the presence of marmoset gH/gL is due to its inability to bind gp42.

  19. A ghrelin receptor (GHS-R1A) antagonist attenuates the rewarding properties of morphine and increases opioid peptide levels in reward areas in mice.

    PubMed

    Engel, Jörgen A; Nylander, Ingrid; Jerlhag, Elisabet

    2015-12-01

    Gut-brain hormones such as ghrelin have recently been suggested to have a role in reward regulation. Ghrelin was traditionally known to regulate food intake and body weight homoeostasis. In addition, recent work has pin-pointed that this peptide has a novel role in drug-induced reward, including morphine-induced increase in the extracellular levels of accumbal dopamine in rats. Herein the effect of the ghrelin receptor (GHS-R1A) antagonist, JMV2959, on morphine-induced activation of the mesolimbic dopamine system was investigated in mice. In addition, the effects of JMV2959 administration on opioid peptide levels in reward related areas were investigated. In the present series of experiment we showed that peripheral JMV2959 administration, at a dose with no effect per se, attenuates the ability of morphine to cause locomotor stimulation, increase the extracellular levels of accumbal dopamine and to condition a place preference in mice. JMV2959 administration significantly increased tissue levels of Met-enkephalin-Arg(6)Phe(7) in the ventral tegmental area, dynorphin B in hippocampus and Leu-enkephalin-Arg(6) in striatum. We therefore hypothesise that JMV2959 prevents morphine-induced reward via stimulation of delta receptor active peptides in striatum and ventral tegmental areas. In addition, hippocampal peptides that activate kappa receptor may be involved in JMV2959׳s ability to regulate memory formation of reward. Given that development of drug addiction depends, at least in part, of the effects of addictive drugs on the mesolimbic dopamine system the present data suggest that GHS-R1A antagonists deserve to be elucidated as novel treatment strategies of opioid addiction. PMID:26508707

  20. Determining the Depth of Injury in Bioengineered Tissue Models of Cornea and Conjunctiva for the Prediction of All Three Ocular GHS Categories

    PubMed Central

    Zorn-Kruppa, Michaela; Houdek, Pia; Wladykowski, Ewa; Engelke, Maria; Bartok, Melinda; Mewes, Karsten R.; Moll, Ingrid; Brandner, Johanna M.

    2014-01-01

    The depth of injury (DOI) is a mechanistic correlate to the ocular irritation response. Attempts to quantitatively determine the DOI in alternative tests have been limited to ex vivo animal eyes by fluorescent staining for biomarkers of cell death and viability in histological cross sections. It was the purpose of this study to assess whether DOI could also be measured by means of cell viability detected by the MTT assay using 3-dimensional (3D) reconstructed models of cornea and conjunctiva. The formazan-free area of metabolically inactive cells in the tissue after topical substance application is used as the visible correlate of the DOI. Areas of metabolically active or inactive cells are quantitatively analyzed on cryosection images with ImageJ software analysis tools. By incorporating the total tissue thickness, the relative MTT-DOI (rMTT-DOI) was calculated. Using the rMTT-DOI and human reconstructed cornea equivalents, we developed a prediction model based on suitable viability cut-off values. We tested 25 chemicals that cover the whole range of eye irritation potential based on the globally harmonized system of classification and labelling of chemicals (GHS). Principally, the MTT-DOI test method allows distinguishing between the cytotoxic effects of the different chemicals in accordance with all 3 GHS categories for eye irritation. Although the prediction model is slightly over-predictive with respect to non-irritants, it promises to be highly valuable to discriminate between severe irritants (Cat. 1), and mild to moderate irritants (Cat. 2). We also tested 3D conjunctiva models with the aim to specifically address conjunctiva-damaging substances. Using the MTT-DOI method in this model delivers comparable results as the cornea model, but does not add additional information. However, the MTT-DOI method using reconstructed cornea models already provided good predictability that was superior to the already existing established in vitro/ex vivo methods. PMID

  1. Sub-categorisation of skin corrosive chemicals by the EpiSkin™ reconstructed human epidermis skin corrosion test method according to UN GHS: revision of OECD Test Guideline 431.

    PubMed

    Alépée, N; Grandidier, M H; Cotovio, J

    2014-03-01

    The EpiSkin™ skin corrosion test method was formally validated and adopted within the context of OECD TG 431 for identifying corrosive and non-corrosive chemicals. The EU Classification, Labelling and Packaging Regulation (EU CLP) system requires the sub-categorisation of corrosive chemicals into the three UN GHS optional subcategories 1A, 1B and 1C. The present study was undertaken to investigate the usefulness of the validated EpiSkin™ test method to identify skin corrosive UN GHS Categories 1A, 1B and 1C using the original and validated prediction model and adapted controls for direct MTT reduction. In total, 85 chemicals selected by the OECD expert group on skin corrosion were tested in three independent runs. The results obtained were highly reproducible both within (>80%) and between (>78%) laboratories when compared with historical data. Moreover the results obtained showed that the EpiSkin™ test method is highly sensitive (99%) and specific (80%) in discriminating corrosive from non-corrosive chemicals and allows reliable and relevant identification of the different skin corrosive UN GHS subcategories, with high accuracies being obtained for both UN GHS Categories 1A (83%) and 1B/1C (76%) chemicals. The overall accuracy of the test method to subcategorise corrosive chemicals into three or two UN GHS subcategories ranged from 75% to 79%. Considering those results, the revised OECD Test Guideline 431 permit the use of EpiSkin™ for subcategorising corrosive chemicals into at least two classes (Category 1A and Category 1B/1C). PMID:24211528

  2. Reduced vertebral bone density in hypercalciuric nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Pietschmann, F.; Breslau, N. A.; Pak, C. Y.

    1992-01-01

    Dual-energy x-ray absorptiometry and single-photon absorptiometry were used to determine bone density at the lumbar spine and radial shaft in 62 patients with absorptive hypercalciuria, 27 patients with fasting hypercalciuria, and 31 nonhypercalciuric stone formers. Lumbar bone density was significantly lower in patients with absorptive (-10%) as well as in those with fasting hypercalciuria (-12%), with 74 and 92% of patients displaying values below the normal mean, whereas only 48% of the nonhypercalciuric stone formers had bone density values below the normal mean. In contrast, radial bone density was similar in all three groups of renal stone formers investigated. The comparison of urinary chemistry in patients with absorptive hypercalciuria and low normal bone density compared to those with high normal bone density showed a significantly increased 24 h urinary calcium excretion on random diet and a trend toward a higher 24 h urinary uric acid excretion and a higher body mass index in patients with low normal bone density. Moreover, among the patients with absorptive hypercalciuria we found a statistically significant correlation between the spinal bone density and the 24 h sodium and sulfate excretion and the urinary pH. These results gave evidence for an additional role of environmental factors (sodium and animal proteins) in the pathogenesis of bone loss in absorptive hypercalciuria. In conclusion, our data suggest an osteopenia of trabecular-rich bone tissues in patients with fasting and absorptive hypercalciurias.

  3. Retrospective analysis of the Draize test for serious eye damage/eye irritation: importance of understanding the in vivo endpoints under UN GHS/EU CLP for the development and evaluation of in vitro test methods.

    PubMed

    Adriaens, Els; Barroso, João; Eskes, Chantra; Hoffmann, Sebastian; McNamee, Pauline; Alépée, Nathalie; Bessou-Touya, Sandrine; De Smedt, Ann; De Wever, Bart; Pfannenbecker, Uwe; Tailhardat, Magalie; Zuang, Valérie

    2014-03-01

    For more than two decades, scientists have been trying to replace the regulatory in vivo Draize eye test by in vitro methods, but so far only partial replacement has been achieved. In order to better understand the reasons for this, historical in vivo rabbit data were analysed in detail and resampled with the purpose of (1) revealing which of the in vivo endpoints are most important in driving United Nations Globally Harmonized System/European Union Regulation on Classification, Labelling and Packaging (UN GHS/EU CLP) classification for serious eye damage/eye irritation and (2) evaluating the method's within-test variability for proposing acceptable and justifiable target values of sensitivity and specificity for alternative methods and their combinations in testing strategies. Among the Cat 1 chemicals evaluated, 36-65 % (depending on the database) were classified based only on persistence of effects, with the remaining being classified mostly based on severe corneal effects. Iritis was found to rarely drive the classification (<4 % of both Cat 1 and Cat 2 chemicals). The two most important endpoints driving Cat 2 classification are conjunctiva redness (75-81 %) and corneal opacity (54-75 %). The resampling analyses demonstrated an overall probability of at least 11 % that chemicals classified as Cat 1 by the Draize eye test could be equally identified as Cat 2 and of about 12 % for Cat 2 chemicals to be equally identified as No Cat. On the other hand, the over-classification error for No Cat and Cat 2 was negligible (<1 %), which strongly suggests a high over-predictive power of the Draize eye test. Moreover, our analyses of the classification drivers suggest a critical revision of the UN GHS/EU CLP decision criteria for the classification of chemicals based on Draize eye test data, in particular Cat 1 based only on persistence of conjunctiva effects or corneal opacity scores of 4. In order to successfully replace the regulatory in vivo Draize eye test, it will

  4. Potential etiologic role of brushite in the formation of calcium (renal) stones

    NASA Astrophysics Data System (ADS)

    Pak, Charles Y. C.

    1981-05-01

    Brushite may play an important regulatory role in the formation of calcium -containing renal stones. The urinary environment from patients with hypercalciuric nephrolithiasis is typically supersaturated and shows an increased propensity for the spontaneous nucleation of brushite. Brushite has been identified in "stone-forming" urine and in stones. This crystalline phase may undergo phase transformation to hydroxyapatite or cause heterogeneous nucleation or epitaxial growth of calcium oxalate. Thus, brushite may also participate in the formation of stones of hydroxypatite or calcium oxalate.

  5. The urine specific gravity dipstick: a useful tool to increase fluid intake in stone forming patients.

    PubMed

    McCormack, M; Dessureault, J; Guitard, M

    1991-12-01

    High fluid intake is the only preventive dietary measure that can be recommended to all patients with stones. However, the efficacy of dietary advice given to patients is unknown. We compared the impact of dietary advice to increase hydration (group 1, 57 patients) and of no dietary advice (group 2, 83 patients) on 24-hour urine volume. No significant difference was noted between groups 1 (1,624 ml.) and 2 (1,732 ml.). We then determined if urine specific gravity dipsticks could help patients increase the 24-hour urine volume. A correlation between 24-hour urine volume and mean urine specific gravity was performed on 263 randomly chosen patients. There was an inverse relationship between urine specific gravity and 24-hour urine volume with a correlation coefficient of 0.522 (y = 1.0207 - 0.00374x). Most patients (81.6%) with 24-hour urine volumes of less than 2.1 had a urine specific gravity of more than 1.010. The use of specific gravity dipsticks was evaluated as a tool to help 24 patients increase the 24-hour urine volume. The 24-hour urine volume increased significantly (p less than 0.05, paired Student's t test) in patients after feedback from specific gravity dipsticks when they were instructed to keep the urine specific gravity at or less than 1.010 (average 24-hour urine volume increased 192%). We conclude that dietary advice may be insufficient to modify fluid intake habits in stone patients. However, modifications of fluid intake habits may be improved by feedback from specific gravity dipsticks. PMID:1942321

  6. Evidence for normal vitamin D receptor messenger ribonucleic acid and genotype in absorptive hypercalciuria.

    PubMed

    Zerwekh, J E; Hughes, M R; Reed, B Y; Breslau, N A; Heller, H J; Lemke, M; Nasonkin, I; Pak, C Y

    1995-10-01

    Absorptive hypercalciuria (a stone-forming condition) is characterized by gut hyperabsorption of calcium, hypercalciuria, and reduced bone density. Inasmuch as these features implicate enhanced calcitriol action in gut and bone, we analyzed the vitamin D receptor (VDR) gene to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium. We have compared the frequency of a restriction fragment length polymorphism (Bsm I) associated with different alleles of the VDR gene in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects. There was no difference between the distribution of the VDR alleles in the patient population when compared with the normal population. The coding region of VDR messenger RNA was also normal, as determined by both DNA sequence analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients. On the basis of these results, we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the VDR and are not linked to a common VDR genotype. PMID:7559881

  7. Predicting GHS toxicity using RTCA and discrete-time Fourier transform.

    PubMed

    Chen, Jiao; Pan, Tianhong; Pu, Tianqing; Huang, Biao; Huang, Dorothy Yu; Zhang, Weiping; Gabos, Stephan; Jin, Can

    2016-02-01

    In order to promote the acceptance of cell-based toxicity testings, the accuracy of cytotoxicity test must be determined when compared to in vivo results. Traditional methods of cytotoxicity analysis, such as LC[Formula: see text] (concentration where 50% of the cells are killed) can be problematic since they have been found to vary with time. Technological advances in cytotoxicity testing make it easy to record the dynamic data on changes in cell proliferation, morphology, and damage. To effectively and reasonably analyze the dynamic data, we present a new in vitro toxicity assessed method using the discrete-time Fourier transform (DTFT) which maps the measured cell index from the time domain to the frequency domain. The direct current (DC) component of the DTFT is extracted as a feature which reflects the intensity of cytotoxicity. The smaller the value, the higher the cytotoxicity. Then, a novel toxicity index, as expressed in terms of DC[Formula: see text], is calculated. Results generated with selected test chemicals are compared favorably with data obtained from The Interagency Coordinating Committee on the Validation of Alternative Method (ICCVAM) report concerning the prediction of acute systemic toxicity in rodents. The method can be applied with the standard and high throughput to estimate acute rodent oral toxicity which reduces the number of animals required in subsequent pharmacological/toxicological studies. PMID:26708053

  8. Effect of Potassium Citrate on Calcium Phosphate Stones in a Model of Hypercalciuria.

    PubMed

    Krieger, Nancy S; Asplin, John R; Frick, Kevin K; Granja, Ignacio; Culbertson, Christopher D; Ng, Adeline; Grynpas, Marc D; Bushinsky, David A

    2015-12-01

    Potassium citrate is prescribed to decrease stone recurrence in patients with calcium nephrolithiasis. Citrate binds intestinal and urine calcium and increases urine pH. Citrate, metabolized to bicarbonate, should decrease calcium excretion by reducing bone resorption and increasing renal calcium reabsorption. However, citrate binding to intestinal calcium may increase absorption and renal excretion of both phosphate and oxalate. Thus, the effect of potassium citrate on urine calcium oxalate and calcium phosphate supersaturation and stone formation is complex and difficult to predict. To study the effects of potassium citrate on urine supersaturation and stone formation, we utilized 95th-generation inbred genetic hypercalciuric stone-forming rats. Rats were fed a fixed amount of a normal calcium (1.2%) diet supplemented with potassium citrate or potassium chloride (each 4 mmol/d) for 18 weeks. Urine was collected at 6, 12, and 18 weeks. At 18 weeks, stone formation was visualized by radiography. Urine citrate, phosphate, oxalate, and pH levels were higher and urine calcium level was lower in rats fed potassium citrate. Furthermore, calcium oxalate and calcium phosphate supersaturation were higher with potassium citrate; however, uric acid supersaturation was lower. Both groups had similar numbers of exclusively calcium phosphate stones. Thus, potassium citrate effectively raises urine citrate levels and lowers urine calcium levels; however, the increases in urine pH, oxalate, and phosphate levels lead to increased calcium oxalate and calcium phosphate supersaturation. Potassium citrate induces complex changes in urine chemistries and resultant supersaturation, which may not be beneficial in preventing calcium phosphate stone formation. PMID:25855777

  9. Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for Prader-Willi Syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prader-Willi syndrome (PWS) is a genetic disease characterized by persistent hunger and hyperphagia. The lack of the Snord116 small nucleolar RNA cluster has been identified as the major contributor to PWS symptoms. The Snord116 deletion (Snord116del) mouse model manifested a subset of PWS symptoms ...

  10. Identification, tissue distribution and functional characterization of the ghrelin receptor in West African lungfish, Protopterus annectens.

    PubMed

    Kaiya, Hiroyuki; Konno, Norifumi; Kangawa, Kenji; Uchiyama, Minoru; Miyazato, Mikiya

    2014-12-01

    We identified two ghrelin receptor isoforms, the ghrelin receptor type-1a (GHS-R1a) and its alternative splice form (GHS-R1b) for West African lungfish, Protopterus annectens. Lungfish GHS-R1a and 1b comprised 361 and 281 amino acids, respectively. Lungfish GHS-R1a showed the highest identity to coelacanth GHS-R1a (80.4%). The highest expression of GHS-R1a mRNAs was seen in the brain, liver, ovary, heart, intestine, and gills. GHS-R1b mRNAs were also detected in the same tissues with GHS-R1a, but their expression level was 1/20 that of GHS-R1a. In human embryonic kidney 293 cells transiently expressing lungfish GHS-R1a, rat and bullfrog ghrelin, and two GHS-R1a agonists, GHRP-6 and hexarelin, increased intracellular Ca(2+) concentrations. The intensity of the Ca(2+) increases induced by GHS-R1a agonists was twice when compared to that induced by ghrelin, although the median effective doses (ED50) were similar, suggesting a long-lasting effect of GHS-R1a agonists with similar affinity. We also examined changes in the GHS-R gene expression during an eight-week estivation. Body weight was slightly lowered, but plasma sodium and glucose concentrations decreased; plasma urea concentration increased significantly 4weeks after the start of estivation. Overall, expression of GHS-R1a mRNA decreased, but changes in GHS-R1b mRNA expression were inconsistent with those of GHS-R1a during estivation, suggesting an involvement of GHS-R in energy homeostasis, as seen in mammals. Our results suggest that the ghrelin-GHS-R1a system is present in this lungfish although ghrelin has not yet been found. The structure of GHS-R1a is closer to that of tetrapods than Actinopterygian fish, indicating a process of evolution that follows the Crossopterygii such as coelacanth. PMID:25093625

  11. Calcium-sensing receptor and aquaporin 2 interplay in hypercalciuria-associated renal concentrating defect in humans. An in vivo and in vitro study.

    PubMed

    Procino, Giuseppe; Mastrofrancesco, Lisa; Tamma, Grazia; Lasorsa, Domenica Rita; Ranieri, Marianna; Stringini, Gilda; Emma, Francesco; Svelto, Maria; Valenti, Giovanna

    2012-01-01

    One mechanism proposed for reducing the risk of calcium renal stones is activation of the calcium-sensing receptor (CaR) on the apical membranes of collecting duct principal cells by high luminal calcium. This would reduce the abundance of aquaporin-2 (AQP2) and in turn the rate of water reabsorption. While evidence in cells and in hypercalciuric animal models supports this hypothesis, the relevance of the interplay between the CaR and AQP2 in humans is not clear. This paper reports for the first time a detailed correlation between urinary AQP2 excretion under acute vasopressin action (DDAVP treatment) in hypercalciuric subjects and in parallel analyzes AQP2-CaR crosstalk in a mouse collecting duct cell line (MCD4) expressing endogenous and functional CaR. In normocalciurics, DDAVP administration resulted in a significant increase in AQP2 excretion paralleled by an increase in urinary osmolality indicating a physiological response to DDAVP. In contrast, in hypercalciurics, baseline AQP2 excretion was high and did not significantly increase after DDAVP. Moreover DDAVP treatment was accompanied by a less pronounced increase in urinary osmolality. These data indicate reduced urinary concentrating ability in response to vasopressin in hypercalciurics. Consistent with these results, biotinylation experiments in MCD4 cells revealed that membrane AQP2 expression in unstimulated cells exposed to CaR agonists was higher than in control cells and did not increase significantly in response to short term exposure to forskolin (FK). Interestingly, we found that CaR activation by specific agonists reduced the increase in cAMP and prevented any reduction in Rho activity in response to FK, two crucial pathways for AQP2 translocation. These data support the hypothesis that CaR-AQP2 interplay represents an internal renal defense to mitigate the effects of hypercalciuria on the risk of calcium precipitation during antidiuresis. This mechanism and possibly reduced medulla tonicity may

  12. Development of a Geriatric Scale of Hopelessness: Implications for Counseling and Intervention with the Depressed Elderly.

    ERIC Educational Resources Information Center

    Fry, P. S.

    1984-01-01

    Evaluated hopelessness, depression, and self-esteem among depressed elderly people (N=78) and developed a Geriatric Hopelessness Scale (GHS). As predicted, elderly subjects who scored high on the GHS showed significantly higher depression and lower self-esteem scores. (JAC)

  13. Characteristics of Participants in Australia's Get Healthy Telephone-Based Lifestyle Information and Coaching Service: Reaching Disadvantaged Communities and Those Most at Need

    ERIC Educational Resources Information Center

    O'Hara, Blythe J.; Phongsavan, Philayrath; Venugopal, Kamalesh; Bauman, Adrian E.

    2011-01-01

    To address increasing rates of overweight and obesity, a population-based telephone intervention was introduced in New South Wales, Australia. The Get Healthy Information and Coaching Service[R] (GHS) offered participants a 6-month coaching program or detailed self-help information. Determining the population reach of GHS is of public health…

  14. Thermogenic characterization of ghrelin receptor null mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ghrelin is the only known circulating orexigenic hormone that increases food intake and promotes adiposity, and these physiological functions of ghrelin are mediated through its receptor growth hormone secretagogue receptor (GHS-R). Ghrelin/GHS-R signaling plays a crucial role in energy homeostasis....

  15. End-of-life care at group homes for patients with dementia in Japan. Findings from an analysis of policy-related differences.

    PubMed

    Hirakawa, Yoshihisa; Masuda, Yuichiro; Uemura, Kazumasa; Kuzuya, Masafumi; Kimata, Takaya; Iguchi, Akihisa

    2006-01-01

    In Japan, the number of group homes for patients with dementia (GHs) has been increasing in recent years. A growing number of elderly people now prefer to spend their final years in group homes or other long-term care facilities, a choice that their families support. The aim of this nationwide study is to clarify the current end-of-life care policies and practices of GHs. The subjects were 3701 managing directors of GHs. Data were collected through mailed, anonymous, self-reported questionnaires in 2003. The content of the questionnaires included: (1) general characteristics of the GH, (2) end-of-life care policies and experiences, (3) available end-of-life care services at the GH, (4) staff education concerning end-of-life care, and (5) types of information provided to users and families. The response rate was 45.6%. Many GHs had implemented progressive policies for end-of-life care. GHs with progressive policies for end-of-life care were found to have different backgrounds than those with regressive policies. Only a few GHs provided end-of-life care education for their staff. GHs with progressive policies for end-of-life care tended to have the following characteristics: availability of medical intervention within and outside of the GH, self-contained physical plant and staff education about end-of-life care. Further research is needed to determine the most effective end-of-life care systems for GHs. PMID:16188331

  16. The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling: An in vitro study with cells expressing cloned human growth hormone secretagogue receptor.

    PubMed

    Tagami, Keita; Kashiwase, Yohei; Yokoyama, Akinobu; Nishimura, Hitomi; Miyano, Kanako; Suzuki, Masami; Shiraishi, Seiji; Matoba, Motohiro; Ohe, Yuichiro; Uezono, Yasuhito

    2016-08-01

    The growth hormone secretagogue receptor (GHS-R) belongs to Gαq-coupled G protein-coupled receptor (GPCR) that mediates growth hormone release, food intake, appetite, glucose metabolism and body composition. Ghrelin has been identified as an endogenous ligand for GHS-R, and it is the only orexigenic peptide found in the peripheral organs. Olanzapine, an atypical antipsychotic agent that binds to and inhibits the activation of GPCR for several neurotransmitters, has metabolic side effects such as excessive appetite and weight gain. Recently, studies have revealed that the orexigenic mechanism of olanzapine is mediated via GHS-R signaling, although the precise mechanisms have not been clarified. In this study, we investigated the effect of olanzapine on ghrelin-mediated GHS-R signaling by using an electrical impedance-based receptor biosensor assay system (CellKey™). Olanzapine at concentrations of 10(-7) and 10(-6)mol/L enhanced ghrelin-induced (10(-10)-10(-8)mol/L) GHS-R activation. A Ca(2+) imaging assay revealed that olanzapine (10(-7) and 10(-6)mol/L) enhanced ghrelin (10(-7) M)-induced GHS-R activity. In contrast, haloperidol (an antipsychotic agent) failed to enhance this ghrelin-mediated GHS-R activation, as demonstrated by both the CellKey™ and Ca(2+) imaging assays. Together, these results suggest that olanzapine, but not haloperidol, promotes appetite by enhancing ghrelin-mediated GHS-R signaling. PMID:26775231

  17. Diversification and coevolution of the ghrelin/growth hormone secretagogue receptor system in vertebrates.

    PubMed

    Tine, Mbaye; Kuhl, Heiner; Teske, Peter R; Tschöp, Matthias H; Jastroch, Martin

    2016-04-01

    The gut hormone ghrelin is involved in numerous metabolic functions, such as the stimulation of growth hormone secretion, gastric motility, and food intake. Ghrelin is modified by ghrelin O-acyltransferase (GOAT) or membrane-bound O-acyltransferase domain-containing 4 (MBOAT4) enabling action through the growth hormone secretagogue receptors (GHS-R). During the course of evolution, initially strong ligand/receptor specificities can be disrupted by genomic changes, potentially modifying physiological roles of the ligand/receptor system. Here, we investigated the coevolution of ghrelin, GOAT, and GHS-R in vertebrates. We combined similarity search, conserved synteny analyses, phylogenetic reconstructions, and protein structure comparisons to reconstruct the evolutionary history of the ghrelin system. Ghrelin remained a single-gene locus in all vertebrate species, and accordingly, a single GHS-R isoform was identified in all tetrapods. Similar patterns of the nonsynonymous (dN) and synonymous (dS) ratio (dN/dS) in the vertebrate lineage strongly suggest coevolution of the ghrelin and GHS-R genes, supporting specific functional interactions and common physiological pathways. The selection profiles do not allow confirmation as to whether ghrelin binds specifically to GOAT, but the ghrelin dN/dS patterns are more similar to those of GOAT compared to MBOAT1 and MBOAT2 isoforms. Four GHS-R isoforms were identified in teleost genomes. This diversification of GHS-R resulted from successive rounds of duplications, some of which remained specific to the teleost lineage. Coevolution signals are lost in teleosts, presumably due to the diversification of GHS-R but not the ghrelin gene. The identification of the GHS-R diversity in teleosts provides a molecular basis for comparative studies on ghrelin's physiological roles and regulation, while the comparative sequence and structure analyses will assist translational medicine to determine structure-function relationships of the

  18. Enhanced sympathetic nerve activity induced by neonatal colon inflammation induces gastric hypersensitivity and anxiety-like behavior in adult rats.

    PubMed

    Winston, John H; Sarna, Sushil K

    2016-07-01

    Gastric hypersensitivity (GHS) and anxiety are prevalent in functional dyspepsia patients; their underlying mechanisms remain unknown largely because of lack of availability of live visceral tissues from human subjects. Recently, we demonstrated in a preclinical model that rats subjected to neonatal colon inflammation show increased basal plasma norepinephrine (NE), which contributes to GHS through the upregulation of nerve growth factor (NGF) expression in the gastric fundus. We tested the hypothesis that neonatal colon inflammation increases anxiety-like behavior and sympathetic nervous system activity, which upregulates the expression of NGF to induce GHS in adult life. Chemical sympathectomy, but not adrenalectomy, suppressed the elevated NGF expression in the fundus muscularis externa and GHS. The measurement of heart rate variability showed a significant increase in the low frequency-to-high frequency ratio in GHS vs. the control rats. Stimulus-evoked release of NE from the fundus muscularis externa strips was significantly greater in GHS than in the control rats. Tyrosine hydroxylase expression was increased in the celiac ganglia of the GHS vs. the control rats. We found an increase in trait but not stress-induced anxiety-like behavior in GHS rats in an elevated plus maze. We concluded that neonatal programming triggered by colon inflammation upregulates tyrosine hydroxylase in the celiac ganglia, which upregulates the release of NE in the gastric fundus muscularis externa. The increase of NE release from the sympathetic nerve terminals concentration dependently upregulates NGF, which proportionately increases the visceromotor response to gastric distention. Neonatal programming concurrently increases anxiety-like behavior in GHS rats. PMID:27151940

  19. Charged scalar perturbations around Garfinkle-Horowitz-Strominger black holes

    NASA Astrophysics Data System (ADS)

    Zhang, Cheng-Yong; Zhang, Shao-Jun; Wang, Bin

    2015-10-01

    We examine the stability of the Garfinkle-Horowitz-Strominger (GHS) black hole under charged scalar perturbations. Employing the appropriate numerical methods, we show that the GHS black hole is always stable against charged scalar perturbations. This is different from the results obtained in the de Sitter and anti-de Sitter black holes. Furthermore, we argue that in the GHS black hole background there is no amplification of the incident charged scalar wave to cause the superradiance, so that the superradiant instability cannot exist in this spacetime.

  20. Molecular analysis of rat pituitary and hypothalamic growth hormone secretagogue receptors.

    PubMed

    McKee, K K; Palyha, O C; Feighner, S D; Hreniuk, D L; Tan, C P; Phillips, M S; Smith, R G; Van der Ploeg, L H; Howard, A D

    1997-04-01

    GH release is thought to occur under the reciprocal regulation of two hypothalamic peptides, GH releasing hormone (GHRH) and somatostatin, via their engagement with specific cell surface receptors on the anterior pituitary somatotroph. In addition, GH-releasing peptides, such as GHRP-6 and the nonpeptide mimetics, L-692,429 and MK-0677, stimulate GH release through their activation of a distinct receptor, the GH secretagogue receptor (GHS-R). The recent cloning of the GHS-R from human and swine pituitary gland identifies yet a third G protein-coupled receptor (GPC-R) involved in the control of GH release and further supports the existence of an undiscovered hormone that may activate this receptor. Using the human GHS-R as a probe, we report the isolation of a rat pituitary GHS-R cDNA derived from an unspliced, precursor mRNA. The rat cDNA encodes a protein of 364 amino acids containing seven transmembrane domains (7-TM) with >90% sequence identity to both the human and swine GHS-Rs. A single intron of approximately 2 kb divides the open reading frame into two exons encoding TM 1-5 and TM 6-7, thus placing the GHS-R into the intron-containing class of GPC-Rs. The intron maps to the site of sequence divergence between the human and swine type 1a and 1b GHS-R mRNAs. In addition, determination of the nucleotide sequence for the human GHS-R gene confirmed the position of an intron in the human GHS-R gene at this position. A full-length contiguous cDNA from rat hypothalamus was isolated and shown to be identical in its nucleotide and deduced amino acid sequence to the rat pituitary GHS-R. The cloned rat GHS-R binds [35S]MK-0677 with high affinity [dissociation constant (K(D)) = 0.7 nM] and is functionally active when expressed in HEK-293 cells. Expression of the rat GHS-R was observed specifically in the pituitary and hypothalamus when compared with control tissues. PMID:9092793

  1. Kidney Stones (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Kidney Stones KidsHealth > For Parents > Kidney Stones Print A ... remove the stones from their urinary tracts. How Kidney Stones Form It's the kidneys' job to remove ...

  2. Detection of gas hydrate sediments using prestack seismic AVA inversion

    NASA Astrophysics Data System (ADS)

    Zhang, Ru-Wei; Li, Hong-Qi; Zhang, Bao-Jin; Huang, Han-Dong; Wen, Peng-Fei

    2015-09-01

    Bottom-simulating reflectors (BSRs) in seismic profile always indicate the bottom of gas hydrate stability zone, but is difficult to determine the distribution and features of gas hydrate sediments (GHS). In this study, based on AVA forward modeling and angle-domain common-image gathers we use prestack AVA parameters consistency inversion in predicting gas hydrate sediments in the Shenhu area at northern slope of South China Sea, and obtain the vertical and lateral features and saturation of GHS.

  3. Periprandial changes and effects of short- and long-term fasting on ghrelin, GOAT, and ghrelin receptors in goldfish (Carassius auratus).

    PubMed

    Blanco, A M; Gómez-Boronat, M; Redondo, I; Valenciano, A I; Delgado, M J

    2016-08-01

    The periprandial profile and effects of short- (7 days) and long-term (30 days) fasting on the ghrelinergic system were studied in goldfish (Carassius auratus). Plasma levels of acyl-ghrelin, desacyl-ghrelin, and ghrelin O-acyl transferase (GOAT) were analyzed by enzymoimmunoassays, and expression of preproghrelin, goat and growth hormone secretagogue receptors (ghs-r) was quantified by real-time PCR. Circulating levels of acyl-ghrelin and GOAT rise preprandially, supporting the role of acyl-ghrelin as a meal initiator in this teleost. Consistently, preproghrelin and ghs-r1a1 expression increases 1 h before feeding time in intestinal bulb, suggesting that this receptor subtype might be involved in the preprandial action of ghrelin in this tissue. Significant postfeeding variations are detected for preproghrelin in telencephalon, goat in telencephalon and hypothalamus, ghs-r1a1 in vagal lobe, ghs-r1a2 and ghs-r2a1 in hypothalamus and ghs-r2a2 in telencephalon and vagal lobe, especially in unfed fish. Short- and long-term fasting significantly increase preproghrelin expression in telencephalon and gut. Goat expression is upregulated by short-term fasting in telencephalon and hypothalamus, and by both short- and long-term fasting in gut. Expression of ghs-r increases by fasting in telencephalon, while an upregulation of type 2, but not type 1, receptors is observed in vagal lobe. In intestinal bulb, ghs-r1a2 transcripts increase after both short- and long-term fasting. These results show a high dependence of the ghrelinergic system on feeding and nutritional status in fish, and demonstrate for the first time a differential implication of the various components of this system suggesting different roles for the four ghrelinergic receptor subtypes. PMID:27062032

  4. Second-phase validation study of short time exposure test for assessment of eye irritation potency of chemicals.

    PubMed

    Kojima, Hajime; Hayashi, Kazuhiko; Sakaguchi, Hitoshi; Omori, Takashi; Otoizumi, Takuya; Sozu, Takashi; Kuwahara, Hirofumi; Hayashi, Takumi; Sakaguchi, Mayumi; Toyoda, Akemi; Goto, Haruka; Watanabe, Shinichi; Ahiko, Kyoko; Nakamura, Tsuneaki; Morimoto, Takashi

    2013-09-01

    A Short Time Exposure (STE) test is a cytotoxicity test that uses SIRC cells (rabbit corneal cell line) to assess eye irritation potency following a 5-min chemical exposure. This second-phase validation study assessed the predictive capacity of the STE test using 40 coded test substances at three laboratories. A Validation Management Team (VMT) then evaluated the predictivity of the STE test for United Nation (UN) Globally Harmonized System (GHS) categories using 63 test substances including the results of the first-phase validation study. The STE test can assess not only the severe or corrosive ocular irritants (corresponding to the UN GHS Category 1) but also non-irritant (corresponding to UN GHS Non Category) from other toxicity classes, especially for limited types of test substances. The predictivity by STE test, however, was insufficient for identification of UN GHS categories (Category 1, Category 2, or Non Category). These results suggest that the STE test can be recommended as an initial step in a top-down approach to identification of severe irritants and test substances that require classification for eye irritation (UN GHS Category 1) as well as an initial step in a bottom-up approach to identification of test substances that do not require classification for eye irritation (UN GHS Non Category) from other toxicity classes, especially for limited types of test substances. On the other hand, the STE test is not considered adequate for the identification of mild or moderate irritants (i.e., UN GHS Categories 2A and 2B) and severe irritants (UN GHS Category 1). PMID:23747838

  5. The suppression of ghrelin signaling mitigates age-associated thermogenic impairment

    PubMed Central

    Bongmba, Odelia Y. N.; Ma, Xiaojun; Zhu, Xiongwei; Sheikh-Hamad, David; Sun, Yuxiang

    2014-01-01

    Aging is associated with severe thermogenic impairment, which contributes to obesity and diabetes in aging. We previously reported that ablation of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), attenuates age-associated obesity and insulin resistance. Ghrelin and obestatin are derived from the same preproghrelin gene. Here we showed that in brown adipocytes, ghrelin decreases the expression of thermogenic regulator but obestatin increases it, thus showing the opposite effects. We also found that during aging, plasma ghrelin and GHS-R expression in brown adipose tissue (BAT) are increased, but plasma obestatin is unchanged. Increased plasma ghrelin and unchanged obestatin during aging may lead to an imbalance of thermogenic regulation, which may in turn exacerbate thermogenic impairment in aging. Moreover, we found that GHS-R ablation activates thermogenic signaling, enhances insulin activation, increases mitochondrial biogenesis, and improves mitochondrial dynamics of BAT. In addition, we detected increased norepinephrine in the circulation, and observed that GHS-R knockdown in brown adipocytes directly stimulates thermogenic activity, suggesting that GHS-R regulates thermogenesis via both central and peripheral mechanisms. Collectively, our studies demonstrate that ghrelin signaling is an important thermogenic regulator in aging. Antagonists of GHS-R may serve as unique anti-obesity agents, combating obesity by activating thermogenesis. PMID:25543537

  6. Characteristics of participants in Australia's Get Healthy telephone-based lifestyle information and coaching service: reaching disadvantaged communities and those most at need.

    PubMed

    O'Hara, Blythe J; Phongsavan, Philayrath; Venugopal, Kamalesh; Bauman, Adrian E

    2011-12-01

    To address increasing rates of overweight and obesity, a population-based telephone intervention was introduced in New South Wales, Australia. The Get Healthy Information and Coaching Service® (GHS) offered participants a 6-month coaching program or detailed self-help information. Determining the population reach of GHS is of public health importance to ensure that the program reaches disadvantaged groups. This paper describes the socio-demographic and risk profile of participants (n = 4828) in the first 18 months of operations, determines how representative they are of the population, assesses changes in participants' socio-demographic profile and compares 'information-only' and 'coaching' participants. The results show that GHS users are representative of the adult population in relation to education, employment status, Aboriginal status, fruit and vegetable consumption and alcohol use. However, more female, middle-aged, English-speaking, rural and socially disadvantaged adults participated in GHS. Coaching Participants were more likely to be overweight and to be ex-smokers than the general population. There was substantial variability in GHS recruitment, when mass-reach television advertising was used, participants enrolled from a major city and from more disadvantaged communities. The GHS has broader population reach than many local interventions, but further efforts are needed to increase reach by Aboriginal communities, other minorities and men. PMID:21987479

  7. Longer term impact of the mass media campaign to promote the Get Healthy Information and Coaching Service®: increasing the saliency of a new public health program.

    PubMed

    O'Hara, Blythe J; Phongsavan, Philayrath; Gebel, Klaus; Banovic, Debbie; Buffett, Kym M; Bauman, Adrian E

    2014-11-01

    The Get Healthy Information and Coaching Service® (GHS) was introduced in New South Wales in February 2009. It used mass reach media advertising and direct mail and/or proactive marketing to recruit participants. This article reports on the long-term impact of the campaign on GHS participation from July 2011 to June 2012. A stand-alone population survey collected awareness, knowledge, and behavioral variables before the first advertising phase, (n = 1,544, August-September 2010), during the advertising period (n = 1,500, February-March 2011; n = 1,500, June-July 2011; n = 1,500, February 2012), and after the advertising period (n = 1,500, June-July 2012). GHS usage data (n = 6,095) were collated during July 2011-June 2012. Unprompted and prompted awareness of GHS mass media significantly increased (0% to 8.0%, p < .001; and 14.1% to 43.9%, p < .001, respectively) as well as knowledge and perceived effectiveness of the GHS. Those from the lowest three quintiles of socioeconomic disadvantage and respondents who were overweight or obese were significantly more likely to report prompted campaign awareness. The majority (84.4%) of new GHS calls occurred when television advertising was present. Participants who cited mass media as their referral source were significantly more likely to enroll in the intensive coaching program. Mass media campaigns remain an effective method of promoting a telephone-based statewide lifestyle program. PMID:24662895

  8. Tissue-specific expression of ghrelinergic and NUCB2/nesfatin-1 systems in goldfish (Carassius auratus) is modulated by macronutrient composition of diets.

    PubMed

    Blanco, Ayelén M; Bertucci, Juan I; Delgado, María J; Valenciano, Ana I; Unniappan, Suraj

    2016-05-01

    The macronutrient composition of diets is a very important factor in the regulation of body weight and metabolism. Several lines of research in mammals have shown that macronutrients differentially regulate metabolic hormones, including ghrelin and nesfatin-1 that have opposing effects on energy balance. This study aimed to determine whether macronutrients modulate the expression of ghrelin and the nucleobindin-2 (NUCB2) encoded nesfatin-1 in goldfish (Carassius auratus). Fish were fed once daily on control, high-carbohydrate, high-protein, high-fat and very high-fat diets for 7 (short-term) or 28 (long-term) days. The expression of preproghrelin, ghrelin O-acyl transferase (goat), growth hormone secretagogue receptor 1 (ghs-r1) and nucb2/nesfatin-1 mRNAs was quantified in the hypothalamus, pituitary, gut and liver. Short-term feeding with fat-enriched diets significantly increased nucb2 mRNA levels in hypothalamus and liver, preproghrelin, goat and ghs-r1 expression in pituitary, and ghs-r1 expression in gut. Fish fed on a high-protein diet exhibited a significant reduction in preproghrelin and ghs-r1 mRNAs in the liver. After long-term feeding, fish fed on high-carbohydrate and very high-fat diets had significantly increased preproghrelin, goat and ghs-r1 expression in pituitary. Feeding on a high-carbohydrate diet also upregulated goat and ghs-r1 transcripts in gut, while feeding on a high-fat diet elicited the same effect only for ghs-r1 in liver. Nucb2 expression increased in pituitary, while it decreased in gut after long-term feeding of a high-protein diet. Collectively, these results show for the first time in fish that macronutrients differentially regulate the expression of ghrelinergic and NUCB2/nesfatin-1 systems in central and peripheral tissues of goldfish. PMID:26805937

  9. Evidence for a far-traveled thrust sheet in the Greater Himalayan thrust system, and an alternative model to building the Himalaya

    NASA Astrophysics Data System (ADS)

    Khanal, S.; Robinson, D. M.; Kohn, M. J.; Mandal, S.

    2015-01-01

    The Galchhi shear zone underlies the Kathmandu klippe in central Nepal and has emerged as a key structure for discriminating competing models for the formation of the Himalayan orogenic wedge. New chronologic data from the Galchhi area suggest a new structural and orogenic interpretation. Zircons from quartzites and an orthogneiss restrict protolith deposition to between 467 + 7/ - 10 Ma and ~570 Ma, with metamorphic zircon growth at 23-29 Ma. Comparable data from the Greater Himalayan Sequence (GHS) at the intra-GHS Langtang thrust, north of Galchhi, similarly restrict GHS deposition to between 475 + 7/ - 3 and ~660 Ma. Undeformed pegmatites near Galchhi constrain movement of the Galchhi shear zone to ≥22.5 ± 2.3 Ma, long before slip of the Main Central Thrust in the region (≤17 Ma). Shear sense indicators in the Galchhi area indicate both top-to-the-south and top-to-the-north shears. The old age of movement, Neoproterozoic youngest detrital zircons, occurrence of top-to-the-south shear sense indicators, and intrusive Paleozoic granites, all suggest that the Galchhi shear zone is an intra-GHS top-to-the-south thrust, rather than either a thrust involving Lesser Himalayan rocks, or a top-to-the-north shear zone that juxtaposed Tethyan and GHS rocks during coeval movement of the Main Central Thrust. The GHS in Nepal was not emplaced as a single body of rock but consists of at least two ductile "thrust sheets," present in both the hinterland at Langtang and toward the foreland at Galchhi. GHS thrust sheets sequentially underplated during southward propagation of the thrust belt.

  10. Correlation of ghrelin concentration and ghrelin, ghrelin-O-acetyltransferase (GOAT) and growth hormone secretagogue receptor 1a mRNAs expression in the proventriculus and brain of the growing chicken.

    PubMed

    Kitazawa, Takio; Hiraga, Takeo; Teraoka, Hiroki; Yaosaka, Noriko; Kaiya, Hiroyuki

    2015-01-01

    To determine mechanisms for age-related decrease of GHS-R1a expression in the chicken proventriculus, changes in mRNA expression of ghrelin and ghrelin-O-acetyltransferase (GOAT) as well as ghrelin concentrations in the proventriculus and plasma were examined in growing chickens. Changes in expression levels of ghrelin, GOAT and GHS-R1a mRNAs were also examined in different brain regions (pituitary, hypothalamus, thalamus, cerebellum, cerebral cortex, olfactory bulb, midbrain and medulla oblongata). Ghrelin concentrations in the proventriculus and plasma increased with aging and reached plateaus at 30-50 days after hatching. High level of ghrelin mRNA decreased at 3 days after hatching, and it became stable at half of the initial level. Expression levels of GHS-R1a and GOAT decreased 3 or 5 days after hatching and became stable at low levels. Significant negative correlations were found between plasma ghrelin and mRNA levels of GOAT and GHS-R1a. Expression levels of ghrelin mRNA were different in the brain regions, but a significant change was not seen with aging. GHS-R1a expression was detected in all brain regions, and age-dependent changes were observed in the pituitary and cerebellum. Different from the proventriculus, the expression of GOAT in the brain increased or did not change with aging. These results suggest that decreased GHS-R1a and GOAT mRNA expression in the proventriculus is due to endogenous ghrelin-induced down-regulation. Expression levels of ghrelin, GOAT and GHS-R1a in the brain were independently regulated from that in the proventriculus, and age-related and region-dependent regulation pattern suggests a local effect of ghrelin system in chicken brain. PMID:25435492

  11. Combined vitamin D and calcium supplementation in vitamin D inadequate patients with urolithiasis: Impact on hypercalciuria and de novo stone formation

    PubMed Central

    Hesswani, Charles; Noureldin, Yasser A.; Elkoushy, Mohamed A.; Andonian, Sero

    2015-01-01

    Introduction: We examined the effect of combined vitamin D and calcium supplementation (VDCS) on urinary calcium excretion and de novo stone formation in vitamin D inadequate (VDI) urolithiasis patients. Methods: We retrospectively reviewed the data of VDI patients (serum 25-hydroxyvitamin D <75 nmol/L) followed at a tertiary stone centre between September 2009 and December 2014. VDI patients with history of urolithiasis, who were placed on VDCS for abnormal bone mineral density or hyperoxaluria, were included. Hypercalciuric patients and patients on thiazide diuretics were excluded. Metabolic stone workup and two 24-hour urine collections were performed before and after VDCS. Results: In total, we included 34 patients, with a mean age of 54.8 years and a mean body mass index of 25.7 kg/m2. After VDCS, there was a significant increase in the mean serum 25-hydroxyvitamin D (52.0 vs. 66.4 nmol/L, p < 0.001) and the mean urinary calcium excretion (3.80 vs. 5.64 mmol/d, p < 0.001). Eight (23.5%) patients developed de novo hypercalciuria. After a median follow-up of 39 (range: 7–60) months, 50% of hypercalciuric patients developed stones compared with 11.5% of non-hypercalciuric patients (p = 0.038). Conclusion: This study showed a significant effect of combined VDCS on mean urinary calcium excretion, de novo hypercalciuria, and stone development in VDI patients with history of urolithiasis. Therefore, VDI urolithiasis patients receiving VDCS are advised to have monitoring with 24-hour urine collections and imaging studies. Although small, our sample size was good enough to validate the statistical outcomes. Prospective studies are needed to confirm these results. PMID:26788229

  12. Inferred gas hydrate and permafrost stability history models linked to climate change in the Beaufort-Mackenzie Basin, Arctic Canada

    NASA Astrophysics Data System (ADS)

    Majorowicz, J.; Safanda, J.; Osadetz, K.

    2012-03-01

    Atmospheric methane from episodic gas hydrate (GH) destabilization, the "clathrate gun" hypothesis, is proposed to affect past climates, possibly since the Phanerozoic began or earlier. In the terrestrial Beaufort-Mackenzie Basin (BMB), GHs occur commonly below thick ice-bearing permafrost (IBP), but they are rare within it. Two end-member GH models, where gas is either trapped conventionally (Case 1) or where it is trapped dynamically by GH formation (Case 2), were simulated using profile (1-D) models and a 14 Myr ground surface temperature (GST) history based on marine isotopic data, adjusted to the study setting, constrained by deep heat flow, sedimentary succession conductivity, and observed IBP and Type I GH contacts in Mallik wells. Models consider latent heat effects throughout the IBP and GH intervals. Case 1 GHs formed at ~0.9 km depth only ~1 Myr ago by in situ transformation of conventionally trapped natural gas. Case 2 GHs begin to form at ~290-300 m ~6 Myr ago in the absence of lithological migration barriers. During glacial intervals Case 2 GH layers expand both downward and upward as the permafrost grows downward through and intercalated with GHs. The distinctive model results suggest that most BMB GHs resemble Case 1 models, based on the observed distinct and separate occurrences of GHs and IBP and the lack of observed GH intercalations in IBP. Case 2 GHs formed >255 m, below a persistent ice-filled permafrost layer that is as effective a seal to upward methane migration as are Case 1 lithological seals. All models respond to GST variations, but in a delayed and muted manner such that GH layers continue to grow even as the GST begins to increase. The models show that the GH stability zone history is buffered strongly by IBP during the interglacials. Thick IBP and GHs could have persisted since ~1.0 Myr ago and ~4.0 Myr ago for Cases 1 and 2, respectively. Offshore BMB IBP and GHs formed terrestrially during Pleistocene sea level low stands. Where

  13. Tectonic and metamorphic discontinuities in the Greater Himalayan Sequence in Central Himalaya: in-sequence shearing by accretion from the Indian plate

    NASA Astrophysics Data System (ADS)

    Carosi, Rodolfo

    2016-04-01

    The Greater Himalayan Sequence (GHS) is the main metamorphic unit of the Himalayas, stretching for over 2400 km, bounded to the South by the Main Central Thrust (MCT) and to the North by the South Tibetan Detachment (STD) whose contemporanous activity controlled its exhumation between 23 and 17 Ma (Godin et al., 2006). Several shear zones and/or faults have been recognized within the GHS, usually regarded as out of sequence thrusts. Recent investigations, using a multitechnique approach, allowed to recognize a tectonic and metamorphic discontinuity, localized in the mid GHS, with a top-to-the SW sense of shear (Higher Himalayan Discontinuity: HHD) (Carosi et al., 2010; Montomoli et al., 2013). U-(Th)-Pb in situ monazite ages provide temporal constraint of the acitivity of the HHD from ~ 27-25 Ma to 18-17 Ma. Data on the P and T evolution testify that this shear zone affected the tectono-metamorphic evolution of the belt and different P and T conditions have been recorded in the hanging-wall and footwall of the HHD. The HHD is a regional tectonic feature running for more than 700 km, dividing the GHS in two different portions (Iaccarino et al., 2015; Montomoli et al., 2015). The occurrence of even more structurally higher contractional shear zone in the GHS (above the HHD): the Kalopani shear zone (Kali Gandaki valley, Central Nepal), active from ~ 41 to 30 Ma (U-Th-Pb on monazite) points out to a more complex deformation pattern in the GHS characterized by in sequence shearing. The actual proposed models of exhumation of the GHS, based exclusively on the MCT and STD activities, are not able to explain the occurrence of the HHD and other in-sequence shear zones. Any model of the tectonic and metamorphic evolution of the GHS should account for the occurrence of the tectonic and metamorphic discontinuities within the GHS and its consequences on the metamorphic paths and on the assembly of Himalayan belt. References Godin L., Grujic D., Law, R. D. & Searle, M. P. 2006

  14. Taking two to tango: a role for ghrelin receptor heterodimerization in stress and reward

    PubMed Central

    Schellekens, Harriët; Dinan, Timothy G.; Cryan, John F.

    2013-01-01

    The gut hormone, ghrelin, is the only known peripherally derived orexigenic signal. It activates its centrally expressed receptor, the growth hormone secretagogue receptor (GHS-R1a), to stimulate food intake. The ghrelin signaling system has recently been suggested to play a key role at the interface of homeostatic control of appetite and the hedonic aspects of food intake, as a critical role for ghrelin in dopaminergic mesolimbic circuits involved in reward signaling has emerged. Moreover, enhanced plasma ghrelin levels are associated with conditions of physiological stress, which may underline the drive to eat calorie-dense “comfort-foods” and signifies a role for ghrelin in stress-induced food reward behaviors. These complex and diverse functionalities of the ghrelinergic system are not yet fully elucidated and likely involve crosstalk with additional signaling systems. Interestingly, accumulating data over the last few years has shown the GHS-R1a receptor to dimerize with several additional G-protein coupled receptors (GPCRs) involved in appetite signaling and reward, including the GHS-R1b receptor, the melanocortin 3 receptor (MC3), dopamine receptors (D1 and D2), and more recently, the serotonin 2C receptor (5-HT2C). GHS-R1a dimerization was shown to affect downstream signaling and receptor trafficking suggesting a potential novel mechanism for fine-tuning GHS-R1a receptor mediated activity. This review summarizes ghrelin's role in food reward and stress and outlines the GHS-R1a dimer pairs identified to date. In addition, the downstream signaling and potential functional consequences of dimerization of the GHS-R1a receptor in appetite and stress-induced food reward behavior are discussed. The existence of multiple GHS-R1a heterodimers has important consequences for future pharmacotherapies as it significantly increases the pharmacological diversity of the GHS-R1a receptor and has the potential to enhance specificity of novel ghrelin-targeted drugs. PMID

  15. Ghrelin receptor in Japanese fire belly newt, Cynops pyrrhogaster.

    PubMed

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2015-11-01

    We identified cDNA encoding a functional ghrelin receptor (growth hormone secretagogue-receptor 1a (GHS-R1a)) in a urodele amphibian, the Japanese fire belly newt (Cynops pyrrhogaster). Two functional receptor proteins, composed of 378- and 362-amino acids, were deduced from the identified cDNA because two candidate initiation methionine sites were found. The long-chain receptor protein shared 80%, 69%, and 59% identities with the bullfrog GHS-R1a, human GHS-R1a and tilapia GHS-R1a-like receptor, respectively. Phylogenetic analysis suggested that the newt receptor is grouped to the clade of the tetrapod homologs, and very closed to anuran amphibians. In functional analyses, homologous newt ghrelin, heterologous bullfrog and rat ghrelin, and a GHS-R1a agonist, GHRP-6 increased intracellular Ca(2+) concentration in human embryonic kidney (HEK) 293 cells stably expressed newt GHS-R1a. The responsiveness was much greater in the short-chain receptor than in the long-chain receptor. Both receptors preferred to bind Ser(3)-ghrelin including newt and rat ghrelin than Thr(3)-ghrelin with bullfrog ghrelin. GHRP-6 has a similar affinity to bullfrog ghrelin. GHS-R1a mRNA was expressed in the brain, pituitary, intestine, pancreas, testis and fat body with high level, and eyes, heart, stomach, liver, gall bladder, kidney and dorsal skin with low level. In a fasting experiment, gene expression of GHS-R1a in the brain and pituitary increased 4days after fasting, and the increased level decreased to the initial level 2weeks after fasting. These changes are consistent with the change in ghrelin mRNA. In contrast, expression of ghrelin and GHS-R1a mRNA in the stomach decreased on day 4 after fasting, and increased 2weeks after fasting. These results indicate that ghrelin and its receptor system are present and altered by energy states in this newt. PMID:26172570

  16. Exhumation of the Greater Himalayan Sequence Along the Zanskar Shear Zone, NW India

    NASA Astrophysics Data System (ADS)

    Basta, S.; Beck, E.; Burlick, T.

    2013-12-01

    The Zanskar Shear Zone (ZSZ), the western extent of the South Tibetan Detachment System, exposes high-grade metamorphic rocks of the Greater Himalayan Sequence (GHS) in its footwall. Granites and metapelites collected along the the ZSZ in the Suru River valley provide how and when the GHS rocks exhumed and were deformed. There are two suits of Paleozoic granites deformed within the ZSZ: Pan-African Cambrian-Ordovician granites at the cores of gneiss domes and Mississippian-Permian granites related to Panjal Traps magmatism. Age of Himalayan granites indicates 28-16 Ma which is concurrent with anatectic leucogranite crystallization. The metamorphic mineral assemblage indicates increasing metamorhic grade from NE to SW and comprises Qtz × Kfs + Pl + Bt × Ms × Sil × Ky × Grt × St × Chl × Tur × Rt. In addition to macroscopic evidence, strongly deformed quartz grains, deformation twins, pressure shadows, and kink bands have been observed to demonstrate micro-tectonics evidence. There are two different method to explain exhumation and deformation of the GHS metapelites: Electron backscatter diffraction (EBSD) crystallographic mapping and pseudosection modeling. While EBSD indicates the potential temperature of deformation, pseudosection modeling with Perple_X specifically presents the exhumation path of the GHS rocks. Pseudosection modeling with Perple_X , based on whole-rock geochemical analysis, is set pressure and temperature to 0.4-1.2 GPa and 300-900°C, and uses specific solution models, Bio(TCC), Chl(HP), St(HP), feldspar, Mica(CHA), Gt(HP), and hCrd, namely. These two methods are used by combining with geo/thermochronology data from U-Pb, 40Ar/39Ar, and (U-Th)/He, constraining the age of metamorphism, the cooling and exhumation time of the GHS rocks, and the end of shearing of deformation, respectively. 40Ar/39Ar dating on muscovite and biotite constrains cooling and exhumation ages of the GHS as ~20-19 Ma and 15 Ma, respectively. A metamorphic pressure

  17. Ghrelin receptor regulates adipose tissue inflammation in aging

    PubMed Central

    Buras, Eric D.; Yu, Kaijiang; Wang, Ruitao; Smith, C. Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr−/− mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsr−/− mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsr−/− mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance. PMID:26837433

  18. Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling

    PubMed Central

    Arabyan, Narine; Park, Dayoung; Foutouhi, Soraya; Weis, Allison M.; Huang, Bihua C.; Williams, Cynthia C.; Desai, Prerak; Shah, Jigna; Jeannotte, Richard; Kong, Nguyet; Lebrilla, Carlito B.; Weimer, Bart C.

    2016-01-01

    Complex glycans cover the gut epithelial surface to protect the cell from the environment. Invasive pathogens must breach the glycan layer before initiating infection. While glycan degradation is crucial for infection, this process is inadequately understood. Salmonella contains 47 glycosyl hydrolases (GHs) that may degrade the glycan. We hypothesized that keystone genes from the entire GH complement of Salmonella are required to degrade glycans to change infection. This study determined that GHs recognize the terminal monosaccharides (N-acetylneuraminic acid (Neu5Ac), galactose, mannose, and fucose) and significantly (p < 0.05) alter infection. During infection, Salmonella used its two GHs sialidase nanH and amylase malS for internalization by targeting different glycan structures. The host glycans were altered during Salmonella association via the induction of N-glycan biosynthesis pathways leading to modification of host glycans by increasing fucosylation and mannose content, while decreasing sialylation. Gene expression analysis indicated that the host cell responded by regulating more than 50 genes resulting in remodeled glycans in response to Salmonella treatment. This study established the glycan structures on colonic epithelial cells, determined that Salmonella required two keystone GHs for internalization, and left remodeled host glycans as a result of infection. These data indicate that microbial GHs are undiscovered virulence factors. PMID:27389966

  19. Telescoping of isotherms beneath the South Tibetan Detachment System, Mount Everest Massif

    NASA Astrophysics Data System (ADS)

    Law, R. D.; Jessup, M. J.; Searle, M. P.; Francsis, M. K.; Waters, D. J.; Cottle, J. M.

    2011-11-01

    Petrologic and microstructural/crystal fabric data indicate that isotherms recorded in Greater Himalayan Series (GHS) schists and gneisses in the footwall to the South Tibetan Detachment System (STDS) have undergone extreme telescoping during penetrative flow associated with southward extrusion of the GHS. In the Rongbuk Valley, to the north of Mount Everest, we have made three vertical sampling traverses from the STDS down into the GHS and estimated temperatures associated with penetrative deformation using the opening angles of quartz c-axis fabrics measured on dynamically recrystallized grains. From north to south, the deformation temperature data indicate apparent thermal field gradients of 369, 385 and 420 °C per km for our three traverses, traced over a maximum vertical sampling distance of 0.5 km. Adopting a differential flow path model, simple geometric analysis using sections drawn parallel to the local transport direction indicates that detachment-parallel transport magnitudes of 25-170 km are needed to explain the extreme telescoping of isotherms in the immediate footwall to the STDS, depending on assumed original geothermal gradient, dip of detachment, etc. These particle transport estimates are similar to those previously calculated from barometry data of GHS rocks in the Everest region and are compatible with channel flow models for extrusion and exhumation of the GHS.

  20. Genetic control of the humoral immune response to avian egg white lysozymes in the chicken

    SciTech Connect

    Flanagan, M.P.

    1987-01-01

    Chickens from two closely related sublines, GHs-B6 and GHs-B13, differing serologically at the major histocompatibility complex, were significantly different in their humoral response to three avian egg white lysozymes. Specific antisera levels were measured by radioimmunoassay using /sup 125/I-labeled lysozymes. Antibodies elicited in response to these lysozymes are assumed to be directed against sites on these lysozymes where their amino acid sequence differs from that of the recipient G. domesticus egg white lysozyme (HEL). GHs-B6 birds produced a high level of antibody in response to immunization of turkey (TEL), pheasant (PhL) and guinea hen (GHL) lysozymes. GHs-B13 birds produced no detectable antibody to TEL, were intermediate in their response to PhL and equaled the antibody production of GHs-B6 birds in response to GHL. Antisera to each lysozyme were examined for crossreactivity with all other lysozymes by use of a competitive binding assay.

  1. Salmonella Degrades the Host Glycocalyx Leading to Altered Infection and Glycan Remodeling.

    PubMed

    Arabyan, Narine; Park, Dayoung; Foutouhi, Soraya; Weis, Allison M; Huang, Bihua C; Williams, Cynthia C; Desai, Prerak; Shah, Jigna; Jeannotte, Richard; Kong, Nguyet; Lebrilla, Carlito B; Weimer, Bart C

    2016-01-01

    Complex glycans cover the gut epithelial surface to protect the cell from the environment. Invasive pathogens must breach the glycan layer before initiating infection. While glycan degradation is crucial for infection, this process is inadequately understood. Salmonella contains 47 glycosyl hydrolases (GHs) that may degrade the glycan. We hypothesized that keystone genes from the entire GH complement of Salmonella are required to degrade glycans to change infection. This study determined that GHs recognize the terminal monosaccharides (N-acetylneuraminic acid (Neu5Ac), galactose, mannose, and fucose) and significantly (p < 0.05) alter infection. During infection, Salmonella used its two GHs sialidase nanH and amylase malS for internalization by targeting different glycan structures. The host glycans were altered during Salmonella association via the induction of N-glycan biosynthesis pathways leading to modification of host glycans by increasing fucosylation and mannose content, while decreasing sialylation. Gene expression analysis indicated that the host cell responded by regulating more than 50 genes resulting in remodeled glycans in response to Salmonella treatment. This study established the glycan structures on colonic epithelial cells, determined that Salmonella required two keystone GHs for internalization, and left remodeled host glycans as a result of infection. These data indicate that microbial GHs are undiscovered virulence factors. PMID:27389966

  2. Analysis of the comprehensibility of chemical hazard communication tools at the industrial workplace.

    PubMed

    Ta, Goh Choo; Mokhtar, Mazlin Bin; Mohd Mokhtar, Hj Anuar Bin; Ismail, Azmir Bin; Abu Yazid, Mohd Fadhil Bin Hj

    2010-01-01

    Chemical classification and labelling systems may be roughly similar from one country to another but there are significant differences too. In order to harmonize various chemical classification systems and ultimately provide consistent chemical hazard communication tools worldwide, the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) was endorsed by the United Nations Economic and Social Council (ECOSOC). Several countries, including Japan, Taiwan, Korea and Malaysia, are now in the process of implementing GHS. It is essential to ascertain the comprehensibility of chemical hazard communication tools that are described in the GHS documents, namely the chemical labels and Safety Data Sheets (SDS). Comprehensibility Testing (CT) was carried out with a mixed group of industrial workers in Malaysia (n=150) and factors that influence the comprehensibility were analysed using one-way ANOVA. The ability of the respondents to retrieve information from the SDS was also tested in this study. The findings show that almost all the GHS pictograms meet the ISO comprehension criteria and it is concluded that the underlying core elements that enhance comprehension of GHS pictograms and which are also essential in developing competent persons in the use of SDS are training and education. PMID:20616463

  3. Ataxia and Hypogonadotropic Hypogonadism with Intrafamilial Variability Caused by RNF216 Mutation

    PubMed Central

    Alqwaifly, Mohammed; Bohlega, Saeed

    2016-01-01

    Gordon Holmes syndrome (GHS) is a distinct phenotype of autosomal recessive cerebellar ataxia, characterized by ataxia, dementia, reproductive defects and hypogonadism; it has been recently found to be associated with RNF216 mutation. We performed whole-exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome. We identified a novel splicing variant in RNF216 that is likely to abolish the canonical splice site at the junction of exon/intron 13 (NM_207111.3:c.2061G>A). We herein report two patients with GHS caused by a novel RNF216 mutation as the first follow up report on RNF216-related GHS, and show interfamilial variability of phenotype supporting the previously reported RNF216-related cases. PMID:27441066

  4. Ataxia and Hypogonadotropic Hypogonadism with Intrafamilial Variability Caused by RNF216 Mutation.

    PubMed

    Alqwaifly, Mohammed; Bohlega, Saeed

    2016-06-15

    Gordon Holmes syndrome (GHS) is a distinct phenotype of autosomal recessive cerebellar ataxia, characterized by ataxia, dementia, reproductive defects and hypogonadism; it has been recently found to be associated with RNF216 mutation. We performed whole-exome sequencing and filtered the resulting novel variants by the coordinates of the shared autozygome. We identified a novel splicing variant in RNF216 that is likely to abolish the canonical splice site at the junction of exon/intron 13 (NM_207111.3:c.2061G>A). We herein report two patients with GHS caused by a novel RNF216 mutation as the first follow up report on RNF216-related GHS, and show interfamilial variability of phenotype supporting the previously reported RNF216-related cases. PMID:27441066

  5. Towards a molecular-level theory of carbohydrate processivity in glycoside hydrolases.

    PubMed

    Beckham, Gregg T; Ståhlberg, Jerry; Knott, Brandon C; Himmel, Michael E; Crowley, Michael F; Sandgren, Mats; Sørlie, Morten; Payne, Christina M

    2014-06-01

    Polysaccharide depolymerization in nature is primarily accomplished by processive glycoside hydrolases (GHs), which abstract single carbohydrate chains from polymer crystals and cleave glycosidic linkages without dissociating after each catalytic event. Understanding the molecular-level features and structural aspects of processivity is of importance due to the prevalence of processive GHs in biomass-degrading enzyme cocktails. Here, we describe recent advances towards the development of a molecular-level theory of processivity for cellulolytic and chitinolytic enzymes, including the development of novel methods for measuring rates of key steps in processive action and insights gained from structural and computational studies. Overall, we present a framework for developing structure-function relationships in processive GHs and outline additional progress towards developing a fundamental understanding of these industrially important enzymes. PMID:24863902

  6. Global harmonisation of classification and labelling of hazardous chemicals.

    PubMed

    Pratt, Iona S

    2002-03-10

    The Globally Harmonised System (GHS) for classification and labelling will provide an internationally agreed system for hazard classification of chemical products and for communication of those hazards. Under the system, chemicals will be classified according to their physical (e.g. flammability), health/toxicological and environmental hazards. The toxicological endpoints used in the system are acute toxicity, irritation or corrosivity, sensitisation, carcinogenicity, mutagenicity, reproductive toxicity and chronic or repeat dose toxicity. The intended target audiences are those concerned with transport of dangerous goods, consumers, workers and emergency responders. Labels and safety data sheets (SDS) are the core tools of the GHS hazard communication system, and the harmonised labelling elements are symbols (within a pictogram), signal words and hazard statements. The GHS will use a building block approach in which application may vary according to the circumstances, type of product, and stage of life cycle, allowing selection of the elements appropriate to the needs of the various end users. PMID:11869813

  7. Dissecting conformational contributions to glycosidase catalysis and inhibition

    PubMed Central

    Speciale, Gaetano; Thompson, Andrew J; Davies, Gideon J; Williams, Spencer J

    2014-01-01

    Glycoside hydrolases (GHs) are classified into >100 sequence-based families. These enzymes process a wide variety of complex carbohydrates with varying stereochemistry at the anomeric and other ring positions. The shapes that these sugars adopt upon binding to their cognate GHs, and the conformational changes that occur along the catalysis reaction coordinate is termed the conformational itinerary. Efforts to define the conformational itineraries of GHs have focussed upon the critical points of the reaction: substrate-bound (Michaelis), transition state, intermediate (if relevant) and product-bound. Recent approaches to defining conformational itineraries that marry X-ray crystallography of enzymes bound to ligands that mimic the critical points, along with advanced computational methods and kinetic isotope effects are discussed. PMID:25016573

  8. Constraints on brittle field exhumation of the Everest-Makalu section of the Greater Himalayan Sequence: Implications for models of crustal flow

    NASA Astrophysics Data System (ADS)

    Streule, Michael J.; Carter, Andrew; Searle, Michael P.; Cottle, John M.

    2012-06-01

    New apatite and zircon fission track (FT) data from the summit slopes of Everest and along the Barun, Arun, Dudh Kosi, and Kangshung valleys that drain the Everest and Makalu massifs cover a vertical sample transect of almost 8000 m of the Eastern Nepal Greater Himalayan Sequence (GHS). Apatite FT ages range from 0.9 ± 0.3 Ma to 3.1 ± 0.3 Ma in the GHS with ages increasing systematically with elevation. Apatite FT ages in the Everest Series and summit Ordovician limestones are much older, up to 30.5 ± 5.1 Ma. Zircon FT ages from the GHS range from 3.8 ± 0.4 Ma to 16.3 ± 0.8 Ma. The brittle exhumation rates calculated from these data show the GHS was exhumed, since ˜9 Ma, at an average rate of 1.0 ± 0.2 mm/a. Pliocene exhumation rates are higher at 1.7 ± 0.3 mm/a. These values are not significantly different from the estimate of ductile exhumation rates of 1.8 mm/a recorded by metamorphic minerals undergoing decompression between 18.7 and 15.6 Ma but are well below the values (up to 10 mm/a) used by thermomechanical models for ductile channel flow in the GHS. If representative of the GHS these models will therefore require further `tuning'. Higher exhumation rates in the Pliocene have also been observed in other parts of the Himalaya and points to a regional cause, likely increased erosion due to the onset of late Pliocene-Pleistocene glaciation of the high Himalaya.

  9. Identification and localization of gastrointestinal hormones in the skin of the bullfrog Rana catesbeiana during periods of activity and hibernation.

    PubMed

    Wang, Huan; Zhou, Naizhen; Zhang, Rui; Wu, Yuanyuan; Zhang, Ruidong; Zhang, Shengzhou

    2014-10-01

    Amphibian skin and its secretions contain a wide variety of biogenic amines and biologically active peptides, some of which are either identical or highly homologous to gastrointestinal hormones (GHs) of higher vertebrates. This study investigated the distribution density and immunoreactive (IR) intensity of 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SS), pancreatic polypeptide (PP), neuropeptide Y (NPY) and glucagon (GLU) IR cells in the skin of the bullfrog Rana catesbeiana during periods of activity and hibernation. The results indicated that the six types of GHs were all present in the bullfrog skin and were most predominant in the epidermis and mucous glands. In dorsal skin, the density of the GHs-IR cells in mucous glands was higher than that in epidermis except for GAS-IR cells. In ventral skin, the density of 5-HT, PP and NPY-IR cells in mucous glands was also higher than that in the epidermis. During hibernation, the density of the six types of GHs-IR cells and the IR intensity of GAS, SS, NPY and GLU-IR cells in the epidermis of dorsal skin increased significantly. The IR intensity of SS, PP and NPY-IR cells in granular glands of ventral skin also increased significantly during hibernation. These results suggested that multiple types of GHs-IR cells present in the skin of R. catesbeiana, may play important roles in the regulation of the physiological functions of skin. Also, adaptive changes in the density and IR intensity of GHs-IR cells occurred during hibernation. PMID:25440532

  10. Impact of food restriction and cocaine on locomotion in ghrelin- and ghrelin-receptor knockout mice.

    PubMed

    Clifford, Shane; Zeckler, Rosie Albarran; Buckman, Sam; Thompson, Jeff; Hart, Nigel; Wellman, Paul J; Smith, Roy G

    2011-07-01

    Food restriction (FR) augments the behavioral and reinforcing effects of psychomotor stimulants such as cocaine or amphetamine; effects that may be related to the capacity of FR to increase plasma levels of ghrelin (GHR), a 28-amino acid orexigenenic peptide linked to activation of brain dopamine systems. The present study used wild-type (WT) mice or mutant mice sustaining knockout of either GHR [GHR((-/-)) ] or of the growth hormone secretagogue receptor [GHS-R((-/-)) ] and subjected to FR or not to evaluate the role of GHR and GHS-R in cocaine-stimulated locomotion. WT, GHR((-/-)) , and GHS-R((-/-)) mice were either restricted to 60% of baseline caloric intake or allowed to free-feed (FF). Mice were treated with 0, 1.25, 2.5 and 5.0 mg/kg cocaine on separate test days (in random dose order) and forward locomotion was recorded on each drug day for 45 minutes after drug dosing. Food (and water) was available immediately after (but not during) each activity test. For FF mice, there was no interaction between cocaine and GHR status on locomotion. FR-WT mice treated with saline exhibited significant increases in anticipatory locomotion (relative to FF-WT mice), whereas FR-GHS-R((-/-)) mice did not. Cocaine significantly increased locomotion in FR-GHR((-/-)) and FR-GHS-R((-/-)) mice to the levels noted in FR-WT mice. These results suggest that GHS-R activity, but not GHR activity, is required for FR to augment food-associated anticipatory locomotion, but do not support the contention that GHR pathways are required for the capacity of FR to augment the acute effect of cocaine on locomotion. PMID:21054685

  11. Ghrelin's Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction.

    PubMed

    Schellekens, Harriët; De Francesco, Pablo N; Kandil, Dalia; Theeuwes, Wessel F; McCarthy, Triona; van Oeffelen, Wesley E P A; Perelló, Mario; Giblin, Linda; Dinan, Timothy G; Cryan, John F

    2015-07-15

    Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghrelin's orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghrelin's orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management. PMID:25727097

  12. Comparison of the domain of validity of several approximate surface scatter theories

    NASA Astrophysics Data System (ADS)

    Choi, Narak; Harvey, James E.

    2012-10-01

    A new generalized Harvey-Shack (GHS) surface scatter theory is numerically compared to the classical small perturbation method (SPM), the Kirchhoff approximation method (KM) and the rigorous method of moment (MoM) for one-dimensional ideally conducting surfaces whose surface power spectral density function is Gaussian or abc-function. In spite of its simple analytic form, our numerical comparison shows that the new GHS theory is valid (with reasonable accuracy) over a broader range of surface parameter space than either of the two classical surface scatter theories.

  13. Microstructural analysis of the Greater Himalayan Sequence, Annapurna-Dhaulagiri Himalaya, central Nepal: Channel Flow and Orogen-parallel deformation.

    NASA Astrophysics Data System (ADS)

    Parsons, A. J.; Phillips, R. J.; Lloyd, G. E.; Searle, M. P.; Law, R. D.

    2014-12-01

    Knowledge of deformation processes that occur in the lithosphere during orogenesis can be gained from microstructural analysis of exhumed terranes and shear zones. Here, we use Crystallographic Preferred Orientation (CPO) and Anisotropy of Magnetic Susceptibility (AMS) data to reveal the kinematic evolution of the metamorphic core of the Himalayan orogen, the Greater Himalayan Sequence (GHS). The Himalayan orogen is commonly explained with models of channel flow, which describe the GHS as a partially molten, rheologically weak mid crustal channel. Extrusion of the channel was facilitated by coeval reverse- and normal-sense shear zones, at the lower and upper channel margins respectively. Whilst many thermobarometric studies support the occurrence of channel flow, the spatial and temporal distribution of strain within the GHS is one aspect of the model that is yet to be fully resolved. We present a quantified strain proxy profile for the GHS in the Annapurna-Dhaulagiri region of central Nepal and compare our results with the kinematic predictions of the channel flow model. Samples were collected along a NS transect through the Kali Gandaki valley of central Nepal for CPO and AMS analysis. Variations in CPO strength are used as a proxy for relative strain magnitude, whilst AMS data provide a proxy for strain ellipsoid shape. Combining this information with field and microstructural observations and thermobarometric constraints reveals the kinematic evolution of the GHS in this region. Low volumes of leucogranite and sillimanite bearing rocks and evidence of reverse-sense overprinting normal-sense shearing at the top of the GHS suggest that channel flow was not as intense as model predictions. Additionally, observed EW mineral lineations and oblate strain ellipsoid proxies in the Upper GHS, indicative of three dimensional flattening and orogen parallel stretching, cannot be explained by current channel flow models. Whilst the results do not refute the occurrence of

  14. Hybrid channel flow-type mechanisms in the Greater Himalayan Sequence (West Nepal): new constraints from vorticity of flow and quartz petrofabric analyses.

    NASA Astrophysics Data System (ADS)

    Frassi, Chiara

    2016-04-01

    Three main tectono-metamorphic units are classically recognized along the Himalayan belt: the Lesser Himalayan (LH), the Greater Himalayan sequence (GHS) and the Tibetan Sedimentary sequence (TSS). The GHS may be interpreted as a low-viscosity tabular body of mid-crustal rocks extruded southward in Miocene times beneath the Tibetan plateau between two parallel and opposite-sense crustal-scale shear zones: the Main Central thrust at the base, and the South Tibetan Detachment system at the top. The pre-/syn-shearing mineral assemblage documented within these crustal-scale shear zones indicates that the metamorphic grade increases toward the core of the GHS producing an inverted and a normal thermal gradient respectively on the top and on the bottom of the slab. In addition, thermal profiles estimated using both petrology- and microstructures/fabrics-based thermometers indicate that the metamorphic isograds are condensed. Although horizontal extension and vorticity estimates collected across the GHS could be strongly biased by the criteria used to define the map position of the MCT, published vorticity data document general shear flow (1>Wk>0) within the slab with a pure-shear component of flow slightly predominant within the core of the GHS whereas the simple-shear component seems to dominate at the top of the slab. The lower boundary of the GHS records a general shear flow with a comparable contribution of simple and pure shearing. The associated crustal extrusion is compatible with Couette - Poiseuille velocity flow profile as assumed in crustal-scale channel flow-type models In this study, the quartz c-axis petrofabrics, vorticity and deformation-temperature studies are integrated with microstructures and metamorphic studies to individuate the location of the MCT and to document the spatial distribution of ductile deformation patterns across the lower portion of the GHS exposed in the Chaudabise river valley in western Nepal. My results indicate that the Main

  15. Cystinuria in dogs: comparison of the cystinuric component of the Fanconi syndrome in basenji dogs to isolated cystinuria.

    PubMed

    McNamara, P D; Rea, C T; Bovee, K C; Reynolds, R A; Segal, S

    1989-01-01

    Two animal models for cystinuria have been examined: the Basenji dog with Fanconi syndrome and cystine stone-forming dogs of various breeds. Brush-border membranes were isolated from these animals and uptake of D-glucose and L-cystine was characterized. Experiments with isolated brush-border vesicles from Basenji dogs with cystinuria as a component of the Fanconi syndrome showed diminished sodium-dependent D-glucose uptake but no decrease in L-cystine uptake even though the cystine defect in vivo was as high as 94% (ie, 6% reabsorption). In contrast, brush-border vesicles isolated from the kidney of a cystine stone-forming dog (Welsh Corgi) with a cystine defect of only 16% (ie, 84% reabsorption) had decreased uptake of cystine compared to values found for Beagle and Basenji vesicles. Thus, cystinuria found in Basenji dogs with the Fanconi syndrome differs from that in classic stone-forming cystinuric dogs. The alteration responsible for the cystinuria of Basenji dogs with Fanconi syndrome does not appear to have a membrane locus and may reflect altered energetics for transport, which are not detected in isolated vesicles. The cystine defect in cystinuric stone-forming dogs does appear to be reflected in the isolated membrane. PMID:2909832

  16. 75 FR 12718 - Hazard Communication; Meetings Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-17

    ... Communication Standard in Washington, DC; Pittsburgh, PA; and Los Angeles, CA (74 FR 68756). OSHA will hold the... Classification and Labelling of Chemicals (GHS) (74 FR 50280). OSHA published a correction notice for the Notice of Proposed Rulemaking (NPRM) on November 5, 2009 (74 FR 57278). The deadline for submitting...

  17. Ghrelin receptor regulates appetite and satiety during aging in mice by regulating meal frequency and portion size but not total food intake

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aging is often associated with overweight and obesity. There exists a long-standing debate about whether meal pattern also contributes to the development of obesity. The orexigenic hormone ghrelin regulates appetite and satiety by activating its receptor, growth hormone secretagogue receptor (GHS-R)...

  18. Neuronal Deletion of Ghrelin Receptor Almost Completely Prevents Diet-Induced Obesity.

    PubMed

    Lee, Jong Han; Lin, Ligen; Xu, Pingwen; Saito, Kenji; Wei, Qiong; Meadows, Adelina G; Bongmba, Odelia Y N; Pradhan, Geetali; Zheng, Hui; Xu, Yong; Sun, Yuxiang

    2016-08-01

    Ghrelin signaling has major effects on energy and glucose homeostasis, but it is unknown whether ghrelin's functions are centrally and/or peripherally mediated. The ghrelin receptor, growth hormone secretagogue receptor (GHS-R), is highly expressed in the brain and detectable in some peripheral tissues. To understand the roles of neuronal GHS-R, we generated a mouse line where Ghsr gene is deleted in all neurons using synapsin 1 (Syn1)-Cre driver. Our data showed that neuronal Ghsr deletion abolishes ghrelin-induced spontaneous food intake but has no effect on total energy intake. Remarkably, neuronal Ghsr deletion almost completely prevented diet-induced obesity (DIO) and significantly improved insulin sensitivity. The neuronal Ghsr-deleted mice also showed improved metabolic flexibility, indicative of better adaption to different fuels. In addition, gene expression analysis suggested that hypothalamus and/or midbrain might be the sites that mediate the effects of GHS-R in thermogenesis and physical activity, respectively. Collectively, our results indicate that neuronal GHS-R is a crucial regulator of energy metabolism and a key mediator of DIO. Neuronal Ghsr deletion protects against DIO by regulating energy expenditure, not by energy intake. These novel findings suggest that suppressing central ghrelin signaling may serve as a unique antiobesity strategy. PMID:27207529

  19. 77 FR 68152 - Preparations for the 24th Session of the UN Sub-committee of Experts on the Globally Harmonized...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-15

    ... March 26th of this year, 77 FR 17574, and intends to update the standard from time to time through....S.C. 653, 655, 657), and Secretary's Order 1-2012 (77 FR 3912), (Jan. 25, 2012). Signed at... Experts on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)...

  20. 75 FR 69472 - Preparations for December UN Meetings on the Globally Harmonized System of Classification and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-12

    ....S.C. 653, 655, 657), 29 CFR part 1911, and Secretary's Order 4-2010 (75 FR 55355), (Sept. 10, 2010... System of Classification and Labelling of Chemicals (GHS) AGENCY: Occupational Safety and Health... the United Nations Subcommittee of Experts on the Globally Harmonized System of Classification...

  1. Dominant simple-shear deformation during peak metamorphism for the lower portion of the Greater Himalayan Sequence in West Nepal: New implications for hybrid channel flow-type mechanisms in the Dolpo region

    NASA Astrophysics Data System (ADS)

    Frassi, Chiara

    2015-12-01

    I conducted new vorticity and deformation temperatures studies to test competing models of the exhumation of the mid-crustal rocks exposed in the Dolpo region (West Nepal). My results indicate that the Main Central Thrust is located ∼5 km structurally below the previous mapped locations. Deformation temperature increasing up structural section from ∼450 °C to ∼650 °C and overlap with peak metamorphic temperature indicating that penetrative shearing was responsible for the exhumation of the GHS occurred at "close" to peak metamorphic conditions. I interpreted the telescoping and the inversion of the paleo-isotherms at the base of the GHS as produced mainly by a sub-simple shearing (Wm = 0.88-1) pervasively distributed through the lower portion of the GHS. My results are consistent with hybrid channel flow-type models where the boundary between lower and upper portions of the GHS, broadly corresponding to the tectonometamorphic discontinuity recently documented in west Nepal, represents the limit between buried material, affected by dominant simple shearing, and exhumed material affected by a general flow dominates by pure shearing. This interpretation is consistent with the recent models suggesting the simultaneous operation of channel flow- and critical wedge-type processes at different structural depth.

  2. Twisting of glycosidic bonds by hydrolases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Patterns of scissile bond twisting have been found in crystal structures of glycoside hydrolases (GHs) that are complexed with substrates and inhibitors. To estimate the increased potential energy in the substrates that results from this twisting, we have plotted torsion angles for the scissile bond...

  3. Physiological roles revealed by ghrelin and ghrelin receptor deficient mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ghrelin is a hormone made in the stomach and known primarily for its growth hormone releasing and orexigenic properties. Nevertheless, ghrelin through its receptor, the GHS-R1a, has been shown to exert many roles including regulation of glucose homeostasis, memory & learning, food addiction and neur...

  4. 49 CFR 172.401 - Prohibited labeling.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Recommendations (IBR, see § 171.7 of this subchapter); (2) The IMDG Code (IBR, see § 171.7 of this subchapter); (3... Chemicals (GHS) (IBR, see § 171.7 of this subchapter). (d) The provisions of paragraph (a) of this section... packaging is not visible during transportation; and (3) Loaded by the shipper and unloaded by the shipper...

  5. Ablations of ghrelin and ghrelin receptor exhibit differential metabolic phenotypes and thermogenic capacity during aging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is a hallmark of aging in many Western societies, and is a precursor to numerous serious age-related diseases. Ghrelin ("Ghrl"), via its receptor (growth hormone secretagogue receptor, GHS-R), is shown to stimulate GH secretion and appetite. Surprisingly, our previous studies showed that "Gh...

  6. Generic Hockey-Stick Model for Estimating Benchmark Dose and Potency: Performance Relative to BMDS and Application to Anthraquinone.

    PubMed

    Bogen, Kenneth T

    2011-01-01

    Benchmark Dose Model software (BMDS), developed by the U.S. Environmental Protection Agency, involves a growing suite of models and decision rules now widely applied to assess noncancer and cancer risk, yet its statistical performance has never been examined systematically. As typically applied, BMDS also ignores the possibility of reduced risk at low doses ("hormesis"). A simpler, proposed Generic Hockey-Stick (GHS) model also estimates benchmark dose and potency, and additionally characterizes and tests objectively for hormetic trend. Using 100 simulated dichotomous-data sets (5 dose groups, 50 animals/group), sampled from each of seven risk functions, GHS estimators performed about as well or better than BMDS estimators, and a surprising observation was that BMDS mis-specified all of six non-hormetic sampled risk functions most or all of the time. When applied to data on rodent tumors induced by the genotoxic chemical carcinogen anthraquinone (AQ), the GHS model yielded significantly negative estimates of net potency exhibited by the combined rodent data, suggesting that-consistent with the anti-leukemogenic properties of AQ and structurally similar quinones-environmental AQ exposures do not likely increase net cancer risk. In addition to its simplicity and flexibility, the GHS approach offers a unified, consistent approach to quantifying environmental chemical risk. PMID:21731536

  7. Into the twenty-first century with British households.

    PubMed

    Spicer, K; Diamond, I; Ni Bhrolchain, M

    1992-11-01

    "This paper takes [U.K.] General Household Survey (GHS) data at the micro level and ages these households by simulation to the year 2001. Differing scenarios are considered in order to accommodate high and low variants of each household type in the British household distribution." PMID:12157870

  8. Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ghrelin and the ghrelin receptor (GH secretagogue receptor, GHS-R) are believed to have important roles in energy homeostasis. We describe results from the first studies to be conducted in congenic (N10) adult ghrelin(-/-) and Ghsr(-/-) mice under conditions of both positive (high-fat diet) and nega...

  9. An integrated testing strategy for in vitro skin corrosion and irritation assessment using SkinEthic™ Reconstructed Human Epidermis.

    PubMed

    Alépée, Nathalie; Grandidier, Marie-Hélène; Tornier, Carine; Cotovio, José

    2015-10-01

    The SkinEthic™ Reconstructed Human Epidermis (RHE) method has been formally adopted for the regulatory assessment of skin irritation (OECD TG 439) and corrosion (OECD TG 431). Recently, the OECD adopted an Integrated Approach on Testing and Assessment (IATA) for skin corrosion and skin irritation (OECD GD 203), which provides guidance on the integration of existing and new information in a modular approach for classification and labelling. The present study aimed to evaluate the use of the SkinEthic™ RHE model within the proposed OECD IATA. Data on 86 substances were integrated in a bottom-up and top-down testing strategy to assess their capacity for EU CLP and UN GHS classifications. For EU CLP, strategies showed an accuracy of 84.8% to discriminate non-classified from classified substances, 94.4% to discriminate corrosive from non-corrosive substances, and 68.5% to discriminate the four (sub)-categories. For UN GHS, strategies showed an accuracy of 89.5% to discriminate non-classified from classified substances, 93.4% to discriminate corrosive from non-corrosive substances, and 74.2% to discriminate four GHS (sub)-categories (excluding Category 3). In conclusion, the integration of SkinEthic™ RHE irritation and corrosion data in a bottom-up and top-down testing strategy allows the classification of substances according to EU CLP and UN GHS. PMID:26187475

  10. Neuronal deletion of ghrelin receptor almost completely prevents diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ghrelin signaling has major effects on energy- and glucose-homeostasis, but it is unknown whether ghrelin's functions are centrally and/or peripherally mediated. The ghrelin receptor, Growth Hormone Secretagogue Receptor (GHS-R), is highly expressed in brain and detectable in some peripheral tissues...

  11. Methane Hydrate Dissociation and Gas Seepage on Global Upper Continental Slopes Driven by Intermediate Ocean Warming

    NASA Astrophysics Data System (ADS)

    Ruppel, C. D.; Weber, T.; Kessler, J. D.; Pohlman, J.; Skarke, A. D.

    2014-12-01

    Evidence suggests that the short-term temporal pattern of seafloor gas emissions may be largely driven by tidal/barometric pressure fluctuations. However, thermal perturbations in the overlying intermediate waters are a key factor leading to gas hydrate dissociation that liberates methane to feed cold seeps near the updip limit of gas hydrate stability (GHS) on upper continental slopes. Over the past 5 years, studies have documented temperature-driven methane release at intraseasonal to century-long timescales on the West Spitsbergen margin. Our data on the US Arctic margin show that bottom water temperature (BWT) perturbations over ~2.5 months cause the theoretical updip GHS limit to migrate ~1.5 km upslope, a level of dynamism that may manifest as the observed elevated methane concentrations over the upper slope. Given the documented decades-long increase in oceanic heat content due to global warming, it is not surprising that evidence is emerging that upper slope hydrate dissociation is a global, not merely arctic, phenomenon. On the northern US Atlantic margin, most of the ~600 newly-discovered methane seeps mapped between Cape Hatteras and Georges Bank occur on the upper continental slope near the updip limit of GHS (505-575 m). A BWT database based on ~35,000 CTD casts reveals subtle along-margin variations in the theoretical updip GHS limit and first-order agreement with the observed onset of seepage. Other historical datasets provide evidence for short-term BWT variations of >1ºC on the upper slope. Hudson Canyon, the largest US Atlantic margin shelf-break canyon, has reversing current patterns that amplify short-term BWT variations, making this location an apt laboratory for study of possible gas hydrate degradation processes. Hudson Canyon surveys conducted in 2014 identified dozens more seeps than the ~50 described in Skarke et al. (Fall Meeting 2013), particularly at the updip limit of GHS At this depth, CTDs show that BWTs were initially within GHS

  12. Th-Pb Monazite-in-Garnet Ages From the Greater Himalayan Sequence of Central Nepal

    NASA Astrophysics Data System (ADS)

    Gehrels, G.; Decelles, P.; Martin, A.

    2007-12-01

    431 new Th-Pb ages have been determined from rocks of the Greater Himalayan Sequence (GHS) of central Nepal. Some of these ages are reported by Martin et al. (2007, Chem. Geol.), most have not been reported previously. 42 samples were collected from transects along Kali Gandaki, Modi Khola, Seti Nadi, Madi Nadi, Nayu Ridge, and Marsyangdi Nadi in the Annapurna region, with three transects extending across the GHS and three transects concentrated near the base of the sequence. Garnet crystals were extracted from the samples, and monazite inclusions were identified by BSE imaging and then analyzed by LA-MC-ICPMS with a 10 micron laser beam. Where possible, inclusions were sampled from both cores and rims of the garnet crystals. The resulting ages belong to four groups: (1) 3 ages (all cores) between 801 Ma and 1407 Ma that are inherited from GHS protoliths, (2) 42 ages (all cores) from 550 Ma to 400 Ma (peak age of 487 Ma) that record early Paleozoic prograde metamorphism, (3) 102 ages (nearly all cores) scattered between 400 Ma and ~50 Ma that are interpreted as early Paleozoic grains which have experienced either Pb loss or overgrowth of Tertiary monazite, and (4) 284 ages (2/3 cores, 1/3 rims) between ca. 50 Ma and ca. 10 Ma, with cores only slightly (avg of 1.5 m.y.) older than rims. The Tertiary ages consistently young northward/upsection from ca. 35 to ca. 18 Ma, and in Marsyangdi Nadi define two separate panels that are interpreted to be imbricated along a north-dipping thrust fault. This fault is near the base of sillimanite-bearing rocks, similar to the Langtang thrust (Kohn et al. 2005, JMG), and may be partly responsible for the inverted metamorphic gradient discussed by many previous workers. Our preferred structural scenario is that the Tertiary monazite ages record progressive burial of the GHS by shortening in the Tethyan thrust belt between ca. 35 and ca. 18 Ma, termination of this metamorphism due to onset of motion along the MCT, and ca. 10 Ma

  13. Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin.

    PubMed

    Tannenbaum, G S; Bowers, C Y

    2001-02-01

    The class of novel synthetic compounds termed growth hormone secretagogues (GHSs) act in the hypothalamus through, as yet, unknown pathways. We performed physiologic and histochemical studies to further understand how the GHS system interacts with the well-established somatostatin (SRIF)/growth hormone-releasing hormone (GHRH) neuroendocrine system for regulating pulsatile GH secretion. Comparison of the GH-releasing activities of the hexapeptide growth hormone-releasing peptide-6 (GHRP-6) and GHRH administered intravenously to conscious adult male rats showed that the pattern of GH responsiveness to GHRP-6 was markedly time-dependent, similar to that observed with GHRH. Immunoneutralization of endogenous SRIF reversed the blunted GH response to GHRP-6 at trough times, suggesting that GHRP-6 neither disrupts nor inhibits the cyclical release of endogenous hypothalamic SRIF. By striking contrast, passive immunization with anti-GHRH serum virtually obliterated the GH responses to GHRP-6, irrespective of the time of administration. These findings suggest that the GHSs do not act by altering SRIF release but, rather, stimulate GH release via GHRH-dependent pathways. Our dual chromogenic and autoradiographic in situ hybridization experiments revealed that a subpopulation of GHRH mRNA-containing neurons in the arcuate (Arc) nucleus and ventromedial nucleus (VMN) of the hypothalamus expressed the GHS receptor (GHS-R) gene. These results provide strong anatomic evidence that GHSs may directly stimulate GHRH release into hypophyseal portal blood, and thereby influence GH secretion, through interaction with the GHS-R on GHRH- containing neurons. Altogether, these findings support the notion that an additional neuroendocrine pathway may exist to regulate pulsatile GH secretion, possibly through the influence of the newly discovered GHS natural peptide, ghrelin. PMID:11322498

  14. Hazard Classification of Household Chemical Products in Korea according to the Globally Harmonized System of Classification and labeling of Chemicals

    PubMed Central

    2013-01-01

    Objectives This study was conducted to review the validity of the need for the application of the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) to household chemical products in Korea. The study also aimed to assess the severity of health and environmental hazards of household chemical products using the GHS. Methods 135 products were classified as ‘cleaning agents and polishing agents’ and 98 products were classified as ‘bleaches, disinfectants, and germicides.’ The current status of carcinogenic classification of GHS and carcinogenicity was examined for 272 chemical substances contained in household chemical products by selecting the top 11 products for each of the product categories. In addition, the degree of toxicity was assessed through analysis of whether the standard of the Republic of Korea’s regulations on household chemical products had been exceeded or not. Results According to GHS health and environmental hazards, “acute toxicity (oral)” was found to be the highest for two product groups, ‘cleaning agents and polishing agents’, and ‘bleaches, disinfectants, and germicides’ (result of classification of 233 household chemical products) at 37.8% and 52.0% respectively. In an analysis of carcinogenicity assuming a threshold of IARC 2B for the substances in household chemical products, we found ‘cleaning agents and polishing agents’ to contain 12 chemical substances and ‘bleaches, disinfectants, and germicides’ 11 chemical substances. Conclusion Some of the household chemical products were found to have a high hazard level including acute toxicity and germ cell mutagenicity, carcinogenicity, and reproductive toxicity. Establishing a hazard information delivery system including the application of GHS to household chemical products in Korea is urgent as well. PMID:24472347

  15. GH-related and extra-endocrine actions of GH secretagogues in aging.

    PubMed

    Muller, Eugenio E; Rigamonti, Antonello E; Colonna, Vito De Gennaro; Locatelli, Vittorio; Berti, Ferruccio; Cella, Silvano G

    2002-01-01

    Growth hormone (GH) secretion declines with aging in mammals, including humans. Defective pituitary function does not play a major role in this event. Rather, age-related changes involving the function of specific hypothalamic peptides for GH regulation, GH-releasing hormone (GHRH) and somatostatin (SS), appear to be the fundamental factors. Experimental evidence indicates that GHRH synthesis is impaired with aging in the rat hypothalamus, and that a relative hyperfunction of the SS-ergic system is present. In the elderly, systemic, short-term administration of GHRH enhances GH secretion and increases the formation of the GH-dependent peptide IGF-1. In old dogs, a combination of GHRH and clonidine (CLO), an alpha(2)-adrenoceptor agonist, reportedly acting via GHRH stimulation and SS inhibition, is the most effective stimulus to rejuvenate the apulsatile GH secretion. Discovery of GH secretagogues (GHSs), a series of peptydil and non-peptydil synthetic molecules endowed with a strong GH-releasing activity, the cloning of a GHS receptor (GHS-R), present in the hypothalamus and the pituitary, the isolation of the endogenous ligand of GHS-R, ghrelin, a 28-amino acid peptide whose main source is the stomach, pose the issue for the physiologic role of the GHS/ghrelin system and forces revision of our current understanding of GH regulation in different GH deficiency (GHD) states, including aging. GHSs are very effective for enhancing GH secretion in old subjects, but long-term studies are needed to assess their safety and the real biological impact of GHS replacement therapy in aging. Therapeutic use of GHSs can also be envisaged to restore, via GH-independent mechanisms, functional, and structural age-related alterations, such as anorexia, sexual dysfunction, cardiovascular damage, bone loss. PMID:12392795

  16. Parafilimonas terrae gen. nov., sp. nov., isolated from greenhouse soil.

    PubMed

    Kim, Soo-Jin; Park, Joo-Hyeon; Lim, Jun-Muk; Ahn, Jae-Hyung; Anandham, Rangasamy; Weon, Hang-Yeon; Kwon, Soon-Wo

    2014-09-01

    A Gram-stain-negative, short rod-shaped, non-flagellated, yellow bacterium, designated strain 5GHs7-2(T), was isolated from a greenhouse soil sample in South Korea. 16S rRNA gene sequence analysis of strain 5GHs7-2(T) indicated that the isolate belonged to the family Chitinophagaceae, and exhibited the highest sequence similarities with members of the genera Terrimonas (89.2-92.6 %), Sediminibacterium (90.8-91.4 %) and Chitinophaga (89.2-91.7 %), Filimonas lacunae YT21(T) (91.7 %), members of the genus Segetibacter (90.2-91.6 %), Parasegetibacter luojiensis RHYL-37(T) (90.9 %) and Flavihumibacter petaseus T41(T) (91.2 %). Flexirubin-type pigments were present. The major cellular fatty acids of the novel strain were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The polar lipid profile consisted of a large amount of phosphatidylethanolamine, and moderate and small amounts of several unknown aminolipids and lipids. The only respiratory quinone of strain 5GHs7-2(T) was MK-7, and the DNA G+C content was 47.6 mol%. On the basis of the evidence presented, it is concluded that strain 5GHs7-2(T) represents a novel species of a new genus in the family Chitinophagaceae, for which the name Parafilimonas terrae gen. nov., sp. nov. is proposed. The type strain of the type species is 5GHs7-2(T) ( = KACC 17343(T) = DSM 28286(T)). PMID:24925599

  17. Claudins and the Kidney Volume 75: Annual Review of Physiology

    PubMed Central

    Hou, Jianghui; Rajagopal, Madhumitha; Yu, Alan S. L.

    2013-01-01

    Claudins are tight junction membrane proteins that regulate paracellular permeability of renal epithelia to small ions, solutes and water. Claudins interact within the cell membrane and between neighboring cells to form tight junction strands and constitute both the paracellular barrier and pore. The first extracellular domain of claudins is thought to be the pore-lining domain and contains the determinants of charge selectivity. Multiple claudins are expressed in different nephron segments and this likely determines the permeability properties of each segment. Recent evidence has identified claudin-2 as constituting the cation-reabsorptive pathway in the proximal tubule, claudin-14, -16 and -19 as forming a complex that regulates calcium transport in the thick ascending limb of the loop of Henle, and claudin-4, -7 and -8 as determinants of collecting duct choride permeability. Mutations in claudin-16 and -19 cause familial hypercalciuric hypomagnesemia. The roles of other claudins in kidney diseases remain to be fully elucidated. PMID:23140368

  18. Nephrolithiasis in pregnancy.

    PubMed

    Maikranz, P; Coe, F L; Parks, J; Lindheimer, M D

    1987-04-01

    Despite anatomic and physiologic changes that predispose to stone formation, nephrolithiasis in pregnancy remains an uncommon occurrence. Stones occur more frequently in multiparas, during the later stages of gestation, and without a difference in laterality. Correct diagnosis can be confusing. Ultrasound has become a primary diagnostic tool and limited excretory urograms are only recommended for complicated cases. Conservative management can result in spontaneous passage of most stones. When necessary, cystoscopy or surgery can be done safely. Preexisting stone disease is associated with an increased incidence of urinary tract infections in pregnancy. Renal colic often precipitates premature labor. Most drugs used to treat stone disease are contraindicated in gestation. Increased quantities of known inhibitors of stone formation are present in gestation and may explain why the incidence of stones is not increased in this hypercalciuric state. PMID:3555009

  19. The role of vitamin D receptor gene polymorphisms in Turkish infants with urolithiasis.

    PubMed

    Goknar, Nilufer; Öktem, Faruk; Torun, Emel; Gok, Ozlem; Demir, Aysegul Dogan; Kucukkoc, Mehmet; Kilic, Ulkan

    2016-01-01

    Polymorphisms in the vitamin D receptor (VDR) gene have recently been reported to be associated with urinary calculi in pediatric and adult cases, but no studies have looked at the youngest period of life. The purpose of this study was to investigate the role of VDR gene polymorphisms in infantile urolithiasis in a Turkish population. We compared a study group of 104 infants (55 girls and 49 boys, mean age 6.94 ± 3.81 months) with a control group of 96 infants (51 girls and 45 boys, mean age 7.51 ± 3.23) to evaluate their demographics and metabolic risk factors. PCR-based restriction analysis of the polymorphisms on the VDR gene (BsmI and TaqI) showed statistically significant differences between study and control groups (p = 0.001 and 0.043, respectively). In addition, the prevalence of the BsmI genotype was significantly different between the hypercalciuric and normocalciuric stone formers (p = 0.007). Allelic frequencies were similar between the urolithiasis and control groups (p > 0.05). The B allele of BsmI and the A allele of ApaI were more prevalent in the hypercalciuric stone formers than in the normocalciuric stone formers (p = 0.018 vs.0.036, respectively). These results suggest that the BsmI and TaqI VDR genotypes could be candidate genes leading to infantile urolithiasis. PMID:26908058

  20. P-T-t-d History of the Lahul Valley, NW Indian Himalaya

    NASA Astrophysics Data System (ADS)

    Nieblas, A.; Leech, M. L.

    2015-12-01

    The Lahul Valley of NW India is located between the Zanskar Shear zone to the northwest and the Sangla detachment to the southeast. This region contains three east-trending, laterally-continuous tectonostratigraphic units separated by two major fault zones. To the south, low-grade metasediments of the Lesser Himalayan Sequence (LHS) are separated from high-grade crystalline rocks of the Greater Himalayan Sequence (GHS) by the north dipping Main Central Thrust (MCT). The northern extent of the GHS is separated from overlying low-grade sedimentary rocks of the Tethyan Himalayan Sequence (THS) along the north dipping South Tibetan Detachment System (STDS). There is controversy over the location and type of shear motion for the STDS in the ~50 km strip running through Lahul Valley where the STD is interpreted as a discrete fault, a dextral shear zone, and is unidentified in some areas along the trend of the STDS. This study focuses on understanding the pressure-temperature-time-deformation (P-T-t-d) evolution of THS and GHS rocks in Lahul Valley to better understand regional Cenozoic deformation and the location and role of the STDS in the extrusion of the GHS. Deformed granitics, migmatites, and leucogranites from the GHS contain a dominant mineralogy of Qz + Kfs + Pl + Bt + Ms ± Grt ± Ky ± St. Schists and phyllites from the THS contain a dominant mineralogy of Qz + Kfs + Pl + Bt + Ms ± Grt. Isochemical phase equilibria diagrams (pseudosections) are calculated in Perple_X using whole-rock chemistry data with solution models based on these mineral assemblages. Ti-in-quartz thermometry and the Fe-Mg exchange thermometry from garnet-biotite pairs used with mineral growth relationships constrain conditions during deformation and to establish P-T paths. U-Pb SHRIMP dating of zircon constrains peak metamorphic conditions and 40Ar/39Ar thermochronology of micas provide the cooling history along the valley and across the STDS. This multi-component approach to understand

  1. Titanite petrochronology supports protracted transport along a high-level thrust within the Greater Himalayan Sequence, Central Nepal.

    NASA Astrophysics Data System (ADS)

    Walters, J.; Kohn, M. J.

    2015-12-01

    Zr-in-titanite thermometry and U-Pb geochronology offer potential to recover prograde and retrograde temperature-time (T-t) histories from moderate- to high-grade metamorphic rocks, which in turn can elucidate tectonic processes. In this study, titanite-based T-t paths were determined along a transect across the proposed trace of the ductile South Tibetan Detachment System (STDS) in central Nepal. Titanite-bearing calcsilicates were sampled from the upper Greater Himalayan Sequence (GHS) through the putative lower Tethyan Himalayan Sequence (THS) along the Marsyandi River in the Annapurna Himal. T's decrease from 800 ºC to 650 ºC with increasing structural level, consistent with previous work that shows decreasing T structurally upwards towards the STDS. T-t trends separate into three groups, from structurally lowest to highest: I. increasing T from ~27 to ~15 Ma, II. constant T from ~50 to ~10 Ma, and III. Decreasing T from ~ 25 Ma to ~ 10 Ma. These data are consistent with synmetamorphic thrusting from ~25 Ma to ~15 Ma: Group I (structurally low) heated during burial, Group II (structurally intermediate) resided in the shear zone at quasi-static T, and Group III (structurally high) cooled during emplacement. After ~ 15 Ma, Groups I-III exhumed coherently, supported by decreasing T-t trends at all structural levels. These data are consistent with (a) titanite T-t paths from elsewhere in the Annapurna Himal, (b) the timing of heating of structurally lower GHS rocks from other Central Nepal locations, and (c) the occurrence of intra-GHS thrusts within the orogen. High-grade GHS transport more likely occurred through a series of in sequence thrusts, rather than ductile flow. Our data do not support a ductile STDS at this location, and instead indicate a GHS origin for rocks previously assigned to the Tethyan. Significant extensional throw appears absent at this structural level, whereas shortening within the GHS and Himalaya is greater than commonly assumed.

  2. Who Benefits from Government Healthcare Subsidies? An Assessment of the Equity of Healthcare Benefits Distribution in China

    PubMed Central

    Chen, Mingsheng; Fang, Guixia; Wang, Lidan; Wang, Zhonghua; Zhao, Yuxin; Si, Lei

    2015-01-01

    Background Improving the equitable distribution of government healthcare subsidies (GHS), particularly among low-income citizens, is a major goal of China’s healthcare sector reform in China. Objectives This study investigates the distribution of GHS in China between socioeconomic populations at two different points in time, examines the comparative distribution of healthcare benefits before and after healthcare reforms in Northwest China, compares the parity of distribution between urban and rural areas, and explores factors that influence equitable GHS distribution. Methods Benefit incidence analysis of GHS progressivity was performed, and concentration and Kakwani indices for outpatient, inpatient, and total healthcare were calculated. Two rounds of household surveys that used multistage stratified samples were conducted in 2003 (13,564 respondents) and 2008 (12,973 respondents). Data on socioeconomics, healthcare payments, and healthcare utilization were collected using household interviews. Results High-income individuals generally reap larger benefits from GHS, as reflected by positive concentration indices, which indicates a regressive system. Concentration indices for inpatient care were 0.2199 (95% confidence interval [CI], 0.0829 to 0.3568) and 0.4445 (95% CI, 0.3000 to 0.5890) in 2002 (urban vs. rural, respectively), and 0.3925 (95% CI, 0.2528 to 0.5322) and 0.4084 (95% CI, 0.2977 to 0.5190) in 2007. Outpatient healthcare subsidies showed different distribution patterns in urban and rural areas following the redesign of rural healthcare insurance programs (urban vs. rural: 0.1433 [95% CI, 0.0263 to 0.2603] and 0.3662 [95% CI, 0.2703 to 0.4622] in 2002, respectively; 0.3063 [95% CI, 0.1657 to 0.4469] and −0.0273 [95% CI, −0.1702 to 0.1156] in 2007). Conclusions Our study demonstrates an inequitable distribution of GHS in China from 2002 to 2007; however, the inequity was reduced, especially in rural outpatient services. Future healthcare reforms in

  3. Renal function in space: the link between osteoporosis, hypercalciuria, and aquaporins.

    PubMed

    Gaspare De Santo, Natale; Cirillo, Massimo; Valenti, Giovanna; Perna, Alessandra; Anastasio, Pietro; Drummer, Christian

    2005-01-01

    This article reviews bone adaptation to microgravity, during manned space missions, in humans undergoing Head Down Tilt (HDT) and in Hind-Limb-Suspended Rats. Under microgravity conditions, bone loss occurs in association with hypercalciuria, which in turn modulates Aquaporin 2 (AQP2) excretion in urine, thus avoiding stone forming in space. This report discloses the need to prevent bone loss in order to prepare for long stays at lunar bases or voyages to Mars. PMID:15648031

  4. Evaluation of Musa (Paradisiaca Linn. cultivar)--"Puttubale" stem juice for antilithiatic activity in albino rats.

    PubMed

    Prasad, K V; Bharathi, K; Srinivasan, K K

    1993-10-01

    The fresh juice of Musa stem (Puttubale) was tested for its antilithiatic activity. Zinc discs were implanted in the urinary bladder of albino rats to induce urolithiasis. The stones formed were mainly of magnesium ammonium phosphate with traces of calcium oxalate. Musa stem juice (3 mL/rat/day orally) was found to be effective in reducing the formation and also in dissolving the pre-formed stones. PMID:8112813

  5. Patient factors predict functional outcomes after cruciate retaining TKA: a 2-year follow-up analysis.

    PubMed

    Roth, Justin S; Buehler, Knute C; Shen, Jianhua; Naughton, Marybeth

    2013-09-01

    We analyzed preoperative patient characteristics and postoperative functional outcomes to identify the most predictive preoperative characteristics of postoperative functional outcome for Cruciate Retaining (CR) TKA. In a prospective, multicenter study, 307 knees with minimum 2-year follow-up were first divided into groups based on 2-year functional performance. Logistic regression then determined SF-36 General Health Score (GHS) to be the most predictive preoperative patient characteristic. Subsequently, a second analysis was performed using preoperative SF-36 GHS to stratify patients into groups. Statistical significance was achieved in both analyses by gender, BMI and hypertension. Statistical significance was achieved in a single analysis by age, preoperative narcotic use, preoperative metabolic medication usage, preoperative pulmonary disease and preoperative use of medication for anxiety or depression. PMID:23523205

  6. ¹H, ¹³C and ¹⁵N backbone and side-chain resonance assignments of a family 36 carbohydrate binding module of xylanase from Paenibacillus campinasensis.

    PubMed

    Wang, Yu-Sheng; Ko, Chun-Han; Chang, Hao-Ting; Yang, Kai-Jay; Chen, Yu-Jen; Huang, Shing-Jong; Fang, Pei-Ju; Chang, Chi-Fon; Tzou, Der-Lii M

    2014-10-01

    Paenibacillus campinasensis BL11 isolated from black liquor secretes multiple glycoside hydrolases (GHs) against all kinds of polysaccharides. GH consists of a catalytic module and non-catalytic carbohydrate-binding modules (CBMs), in which CBMs append to the catalytic module, mediating specific interactions with insoluble carbohydrates to promote the hydrolysis efficiency of the cognate enzyme. Endo-β-1,4-xylanase (XylX) is one of the GHs reveals high enzymatic activity in a wide range of pH and thermal endurance, suitable for bioconversion and bio-refinement applications. In this work, we report the resonance assignments of a family 36 CBM (characterized as CBM36) derived from XylX. Our investigations will facilitate molecular structure determination and molecular dynamics analysis of CBMs. PMID:23835623

  7. Alternative methods for the replacement of eye irritation testing.

    PubMed

    Lotz, Christian; Schmid, Freia F; Rossi, Angela; Kurdyn, Szymon; Kampik, Daniel; De Wever, Bart; Walles, Heike; Groeber, Florian K

    2016-01-01

    In the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test has been criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation.This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and the current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed in regard of possible limitations and their status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be applicable to predict all GHS categories. PMID:26626125

  8. Preparation and Characterization of Stimuli-Responsive Magnetic Nanoparticles

    NASA Astrophysics Data System (ADS)

    Wang, Shixing; Zhou, Yang; Guan, Wen; Ding, Bingjun

    2008-08-01

    In this work, the main attention was focused on the synthesis of stimuli-responsive magnetic nanoparticles (SR-MNPs) and the influence of glutathione concentration on its cleavage efficiency. Magnetic nanoparticles (MNPs) were first modified with activated pyridyldithio. Then, MNPs modified with activated pyridyldithio (MNPs-PDT) were conjugated with 2, 4-diamino-6-mercaptopyrimidine (DMP) to form SR-MNPs via stimuli-responsive disulfide linkage. Fourier transform infrared spectra (FTIR), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) were used to characterize MNPs-PDT. The disulfide linkage can be cleaved by reduced glutathione (GHS). The concentration of glutathione plays an important role in controlling the cleaved efficiency. The optimum concentration of GHS to release DMP is in the millimolar range. These results had provided an important insight into the design of new MNPs for biomedicine applications, such as drug delivery and bio-separation.

  9. The influence of the Goos-Hänchen effect on seismic data processing and AVO in attenuating media

    NASA Astrophysics Data System (ADS)

    Wang, Zhiyong

    2015-11-01

    The Goos-Hänchen (GH) effect induced by the total reflection of an incident beam of P-wave from a low-impedance medium to a high-impedance medium at near- and post-critical angles was theoretically simulated and discussed. For both PP- and PSV-waves, there may be large GH shifts (GHS) and penetration depths (PD) for both lossless and attenuating media. As the Q-factor increases, or the frequency of the seismic wave decreases, the GH effect is increased. However, in attenuating media, there may be non-zero GHS and PD at all non-zero incident angles, not just post-critical angles. GHS may be either positive or negative, while PD is positive only. Compared to the Q-factor in the incident medium, the Q-factor in the transmission medium may play a more dominant role in the determination of reflection coefficients, GHS, and PD. The GH-induced normal moveout (NMO) discrepancy of the PSV-wave may be larger than that of the PP-wave. Due to the GH effect, there may be an angle discrepancy (at fixed offset) between the GH-modified incident angle and the traditional incident angle. In addition, the GH effect at a given offset may produce two or three reflected waves, from different incident angles. These results suggest that, within their assumptions, the GH effect may lead to errors in NMO estimates and the vertical location of the reflector. Furthermore, there may be errors in offsets, incident angles, and reflection amplitudes, in the analyses of the amplitude variation with offset (AVO). These GH effects might be more important for seismic data at fixed offsets and shallow layers, and for sonic log data, which might fall into the post-critical angle regime. Therefore, there may be a necessity to take into account the GH effect in the interpretation of wide-angle reflection data in NMO and AVO analyses.

  10. Crustal channel flows: 2. Numerical models with implications for metamorphism in the Himalayan-Tibetan orogen

    NASA Astrophysics Data System (ADS)

    Jamieson, Rebecca A.; Beaumont, Christopher; Medvedev, Sergei; Nguyen, Mai H.

    2004-06-01

    Results from a thermal-mechanical model (HT1) that includes midcrustal channel flow are compatible with many features of the Himalayan-Tibetan system. Radioactive self-heating and rheological weakening of thickened model orogenic crust lead to the formation of a hot, low-viscosity midcrustal channel and a broad plateau. Channel material, corresponding to the Greater Himalayan Sequence (GHS), flows outward from beneath the plateau in response to topographically induced differential pressure. At the plateau flank it is exhumed by focused surface denudation and juxtaposed with cooler, newly accreted material corresponding to the Lesser Himalayan Sequence (LHS). The model channel is bounded by coeval thrust and normal sense ductile shear zones, interpreted to represent the Main Central Thrust (MCT) zone and South Tibetan Detachment system, respectively. Inverted metamorphism associated with the model MCT zone results from distributed ductile shear along the MCT and extrusion of the hot channel. A variety of model P-T-t path styles, resembling those observed in the GHS and LHS, are produced for points traveling through contrasting tectonic regimes that coexist in different parts of the model. Predicted times of peak metamorphism, cooling, and erosion of metamorphic facies are generally compatible with observations, although model GHS cooling ages are too young. The times of M1 and M2 metamorphic "events" observed in the GHS correspond to model times of maximum burial and maximum heating, respectively. The results highlight the need to integrate tectonics and metamorphism in continental collision models and demonstrate the importance of lateral transport of both heat and material in large hot orogens.

  11. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    PubMed

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland. PMID:27052215

  12. Devil's Claw to Suppress Appetite—Ghrelin Receptor Modulation Potential of a Harpagophytum procumbens Root Extract

    PubMed Central

    Torres-Fuentes, Cristina; Theeuwes, Wessel F.; McMullen, Michael K.; McMullen, Anna K.; Dinan, Timothy G.; Cryan, John F.; Schellekens, Harriët

    2014-01-01

    Ghrelin is a stomach-derived peptide that has been identified as the only circulating hunger hormone that exerts a potent orexigenic effect via activation of its receptor, the growth hormone secretagogue receptor (GHS-R1a). Hence, the ghrelinergic system represents a promising target to treat obesity and obesity-related diseases. In this study we analysed the GHS-R1a receptor activating potential of Harpagophytum procumbens, popularly known as Devil's Claw, and its effect on food intake in vivo. H. procumbens is an important traditional medicinal plant from Southern Africa with potent anti-inflammatory and analgesic effects. This plant has been also used as an appetite modulator but most evidences are anecdotal and to our knowledge, no clear scientific studies relating to appetite modulation have been done to this date. The ghrelin receptor activation potential of an extract derived from the dried tuberous roots of H. procumbens was analysed by calcium mobilization and receptor internalization assays in human embryonic kidney cells (Hek) stably expressing the GHS-R1a receptor. Food intake was investigated in male C57BL/6 mice following intraperitoneal administration of H. procumbens root extract in ad libitum and food restricted conditions. Exposure to H. procumbens extract demonstrated a significant increased cellular calcium influx but did not induce subsequent GHS-R1a receptor internalization, which is a characteristic for full receptor activation. A significant anorexigenic effect was observed in male C57BL/6 mice following peripheral administration of H. procumbens extract. We conclude that H. procumbens root extract is a potential novel source for potent anti-obesity bioactives. These results reinforce the promising potential of natural bioactives to be developed into functional foods with weight-loss and weight maintenance benefits. PMID:25068823

  13. Multidomain, Surface Layer-associated Glycoside Hydrolases Contribute to Plant Polysaccharide Degradation by Caldicellulosiruptor Species.

    PubMed

    Conway, Jonathan M; Pierce, William S; Le, Jaycee H; Harper, George W; Wright, John H; Tucker, Allyson L; Zurawski, Jeffrey V; Lee, Laura L; Blumer-Schuette, Sara E; Kelly, Robert M

    2016-03-25

    The genome of the extremely thermophilic bacterium Caldicellulosiruptor kronotskyensisencodes 19 surface layer (S-layer) homology (SLH) domain-containing proteins, the most in any Caldicellulosiruptorspecies genome sequenced to date. These SLH proteins include five glycoside hydrolases (GHs) and one polysaccharide lyase, the genes for which were transcribed at high levels during growth on plant biomass. The largest GH identified so far in this genus, Calkro_0111 (2,435 amino acids), is completely unique toC. kronotskyensisand contains SLH domains. Calkro_0111 was produced recombinantly inEscherichia colias two pieces, containing the GH16 and GH55 domains, respectively, as well as putative binding and spacer domains. These displayed endo- and exoglucanase activity on the β-1,3-1,6-glucan laminarin. A series of additional truncation mutants of Calkro_0111 revealed the essential architectural features required for catalytic function. Calkro_0402, another of the SLH domain GHs inC. kronotskyensis, when produced inE. coli, was active on a variety of xylans and β-glucans. Unlike Calkro_0111, Calkro_0402 is highly conserved in the genus Caldicellulosiruptorand among other biomass-degrading Firmicutes but missing from Caldicellulosiruptor bescii As such, the gene encoding Calkro_0402 was inserted into the C. besciigenome, creating a mutant strain with its S-layer extensively decorated with Calkro_0402. This strain consequently degraded xylans more extensively than wild-typeC. bescii The results here provide new insights into the architecture and role of SLH domain GHs and demonstrate that hemicellulose degradation can be enhanced through non-native SLH domain GHs engineered into the genomes of Caldicellulosiruptorspecies. PMID:26814128

  14. Thermo-kinematic evolution of the Annapurna-Dhaulagiri Himalaya, central Nepal: The Composite Orogenic System

    NASA Astrophysics Data System (ADS)

    Parsons, A. J.; Law, R. D.; Lloyd, G. E.; Phillips, R. J.; Searle, M. P.

    2016-04-01

    The Himalayan orogen represents a "Composite Orogenic System" in which channel flow, wedge extrusion, and thrust stacking operate in separate "Orogenic Domains" with distinct rheologies and crustal positions. We analyze 104 samples from the metamorphic core (Greater Himalayan Sequence, GHS) and bounding units of the Annapurna-Dhaulagiri Himalaya, central Nepal. Optical microscopy and electron backscatter diffraction (EBSD) analyses provide a record of deformation microstructures and an indication of active crystal slip systems, strain geometries, and deformation temperatures. These data, combined with existing thermobarometry and geochronology data are used to construct detailed deformation temperature profiles for the GHS. The profiles define a three-stage thermokinematic evolution from midcrustal channel flow (Stage 1, >700°C to 550-650°C), to rigid wedge extrusion (Stage 2, 400-600°C) and duplexing (Stage 3, <280-400°C). These tectonic processes are not mutually exclusive, but are confined to separate rheologically distinct Orogenic Domains that form the modular components of a Composite Orogenic System. These Orogenic Domains may be active at the same time at different depths/positions within the orogen. The thermokinematic evolution of the Annapurna-Dhaulagiri Himalaya describes the migration of the GHS through these Orogenic Domains and reflects the spatial and temporal variability in rheological boundary conditions that govern orogenic systems.

  15. Caldicellulosiruptor Core and Pangenomes Reveal Determinants for

    SciTech Connect

    Blumer-Schuette, Sara E.; Giannone, Richard J; Zurawski, Jeffrey V; Ozdemir, Inci; Ma, Qin; Yin, Yanbin; Xu, Ying; Kataeva, Irena; Poole, Farris; Adams, Michael W. W.; Hamilton-Brehm, Scott; Elkins, James G; Larimer, Frank W; Land, Miriam L; Hauser, Loren John; Cottingham, Robert W; Hettich, Robert {Bob} L; Kelly, Robert M

    2012-01-01

    Extremely thermophilic bacteria of the genus Caldicellulosiruptor utilize carbohydrate components of plant cell walls, including cellulose and hemicellulose, facilitated by a diverse set of glycoside hydrolases (GHs). From a biofuel perspective, this capability is crucial for deconstruction of plant biomass into fermentable sugars. While all species from the genus grow on xylan and acidpretreated switchgrass, growth on crystalline cellulose is variable. The basis for this variability was examined using microbiological, genomic, and proteomic analyses of eight globally diverse Caldicellulosiruptor species. The open Caldicellulosiruptor pangenome (4,009 open reading frames [ORFs]) encodes 106 GHs, representing 43 GH families, but only 26 GHs from 17 families are included in the core (noncellulosic) genome (1,543 ORFs). Differentiating the strongly cellulolytic Caldicellulosiruptor species from the others is a specific genomic locus that encodes multidomain cellulases from GH families 9 and 48, which are associated with cellulose-binding modules. This locus also encodes a novel adhesin associated with type IV pili, which was identified in the exoproteome bound to crystalline cellulose. Taking into account the core genomes, pangenomes, and individual genomes, the ancestral Caldicellulosiruptor was likely cellulolytic and evolved, in some cases, into species that lost the ability to degrade crystalline cellulose while maintaining the capacity to hydrolyze amorphous cellulose and hemicellulose.

  16. Effects of ghrelin and des-acyl ghrelin on neurogenesis of the rat fetal spinal cord

    SciTech Connect

    Sato, Miho; Nakahara, Keiko; Goto, Shintaro; Kaiya, Hiroyuki; Miyazato, Mikiya . E-mail: a0d201u@cc.miyazaki-u.ac.jp; Date, Yukari; Nakazato, Masamitsu; Kangawa, Kenji; Murakami, Noboru

    2006-11-24

    Expressions of the growth hormone secretagogue receptor (GHS-R) mRNA and its protein were confirmed in rat fetal spinal cord tissues by RT-PCR and immunohistochemistry. In vitro, over 3 nM ghrelin and des-acyl ghrelin induced significant proliferation of primary cultured cells from the fetal spinal cord. The proliferating cells were then double-stained using antibodies against the neuronal precursor marker, nestin, and the cell proliferation marker, 5-bromo-2'-deoxyuridine (BrdU), and the nestin-positive cells were also found to be co-stained with antibody against GHS-R. Furthermore, binding studies using [{sup 125}I]des-acyl ghrelin indicated the presence of a specific binding site for des-acyl ghrelin, and confirmed that the binding was displaced with unlabeled des-acyl ghrelin or ghrelin. These results indicate that ghrelin and des-acyl ghrelin induce proliferation of neuronal precursor cells that is both dependent and independent of GHS-R, suggesting that both ghrelin and des-acyl ghrelin are involved in neurogenesis of the fetal spinal cord.

  17. Effect of chronic hyperghrelinemia on ingestive action of ghrelin.

    PubMed

    Wei, Wei; Qi, Xiang; Reed, Jason; Ceci, Jeff; Wang, Hui-Qun; Wang, Guiyun; Englander, Ella W; Greeley, George H

    2006-03-01

    The stomach hormone ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). Systemic administration of ghrelin will cause elevations in growth hormone (GH) secretion, food intake, adiposity, and body growth. Ghrelin also affects insulin secretion, gastric acid secretion, and gastric motility. Several reports indicate that repeated or continuous activation of GHS-R by exogenous GHSs or ghrelin results in a diminished GH secretory response. The purpose of this study was to examine the extent to which the acute stimulation of food intake by exogenous ghrelin is altered by chronic hyperghrelinemia in transgenic mice that overexpress the human ghrelin gene. The present findings show that the orexigenic action of exogenous ghrelin is not diminished by a chronic hyperghrelinemia and indicate that the food ingestive pathway of the GHS-R is not susceptible to desensitization. In contrast, the epididymal fat pad growth response, like the GH response, to exogenous ghrelin is blunted in ghrelin transgenic mice with chronic hyperghrelinemia. PMID:16210421

  18. A novel GH secretagogue, A233, exhibits enhanced growth activity and innate immune system stimulation in teleosts fish.

    PubMed

    Martinez, Rebeca; Ubieta, Kenia; Herrera, Fidel; Forellat, Alina; Morales, Reynold; de la Nuez, Ania; Rodriguez, Rolando; Reyes, Osvaldo; Oliva, Ayme; Estrada, Mario P

    2012-09-01

    In teleosts fish, secretion of GH is regulated by several hypothalamic factors that are influenced by the physiological state of the animal. There is an interaction between immune and endocrine systems through hormones and cytokines. GH in fish is involved in many physiological processes that are not overtly growth related, such as saltwater osmoregulation, antifreeze synthesis, and the regulation of sexual maturation and immune functions. This study was conducted to characterize a decapeptide compound A233 (GKFDLSPEHQ) designed by molecular modeling to evaluate its function as a GH secretagogue (GHS). In pituitary cell culture, the peptide A233 induces GH secretion and it is also able to increase superoxide production in tilapia head-kidney leukocyte cultures. This effect is blocked by preincubation with the GHS receptor antagonist [d-Lys(3)]-GHRP6. Immunoneutralization of GH by addition of anti-tilapia GH monoclonal antibody blocked the stimulatory effect of A233 on superoxide production. These experiments propose a GH-mediated mechanism for the action of A233. The in vivo biological action of the decapeptide was also demonstrated for growth stimulation in goldfish and tilapia larvae (P<0.001). Superoxide dismutase levels, antiprotease activity, and lectin titer were enhanced in tilapia larvae treated with this novel molecule. The decapeptide A233 designed by molecular modeling is able to function as a GHS in teleosts and enhance parameters of the innate immune system in the fish larvae. PMID:22707376

  19. Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP.

    PubMed

    Shi, Chang-He; Schisler, Jonathan C; Rubel, Carrie E; Tan, Song; Song, Bo; McDonough, Holly; Xu, Lei; Portbury, Andrea L; Mao, Cheng-Yuan; True, Cadence; Wang, Rui-Hao; Wang, Qing-Zhi; Sun, Shi-Lei; Seminara, Stephanie B; Patterson, Cam; Xu, Yu-Ming

    2014-02-15

    Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder characterized by ataxia and hypogonadism. Recently, it was suggested that disordered ubiquitination underlies GHS though the discovery of exome mutations in the E3 ligase RNF216 and deubiquitinase OTUD4. We performed exome sequencing in a family with two of three siblings afflicted with ataxia and hypogonadism and identified a homozygous mutation in STUB1 (NM_005861) c.737C→T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein). CHIP plays a central role in regulating protein quality control, in part through its ability to function as an E3 ligase. Loss of CHIP function has long been associated with protein misfolding and aggregation in several genetic mouse models of neurodegenerative disorders; however, a role for CHIP in human neurological disease has yet to be identified. Introduction of the Thr246Met mutation into CHIP results in a loss of ubiquitin ligase activity measured directly using recombinant proteins as well as in cell culture models. Loss of CHIP function in mice resulted in behavioral and reproductive impairments that mimic human ataxia and hypogonadism. We conclude that GHS can be caused by a loss-of-function mutation in CHIP. Our findings further highlight the role of disordered ubiquitination and protein quality control in the pathogenesis of neurodegenerative disease and demonstrate the utility of combining whole-exome sequencing with molecular analyses and animal models to define causal disease polymorphisms. PMID:24113144

  20. The alcohol-induced locomotor stimulation and accumbal dopamine release is suppressed in ghrelin knockout mice.

    PubMed

    Jerlhag, Elisabet; Landgren, Sara; Egecioglu, Emil; Dickson, Suzanne L; Engel, Jörgen A

    2011-06-01

    Ghrelin, the first endogenous ligand for the type 1A growth hormone secretagogue receptor (GHS-R1A), plays a role in energy balance, feeding behavior, and reward. Previously, we showed that pharmacologic and genetic suppression of the GHS-R1A attenuates the alcohol-induced stimulation, accumbal dopamine release, and conditioned place preference as well as alcohol consumption in mice, implying that the GHS-R1A is required for alcohol reward. The present study further elucidates the role of ghrelin for alcohol-induced dopamine release in nucleus accumbens and locomotor stimulation by means of ghrelin knockout mice. We found that the ability of alcohol to increase accumbal dopamine release in wild-type mice is not observed in ghrelin knockout mice. Furthermore, alcohol induced a locomotor stimulation in the wild-type mice and ghrelin knockout mice; however, the locomotor stimulation in homozygote mice was significantly lower than in the wild-type mice. The present series of experiments suggest that endogenous ghrelin may be required for the ability of alcohol to activate the mesolimbic dopamine system. PMID:21145690

  1. Fungal glycoside hydrolases for saccharification of lignocellulose: outlook for new discoveries fueled by genomics and functional studies

    SciTech Connect

    Jovanovic, Iva; Magnuson, Jon K.; Collart, Frank R.; Robbertse, Barbara; Adney, William S.; Himmel, Michael E.; Baker, Scott E.

    2009-08-01

    Genome sequencing of a variety of fungi is a major initiative currently supported by the Department of Energy’s Joint Genome Institute. Encoded within the genomes of many fungi are upwards of 200+ enzymes called glycoside hydrolases (GHs). GHs are known for their ability to hydrolyze the polysaccharide components of lignocellulosic biomass. Production of ethanol and “next generation” biofuels from lignocellulosic biomass represents a sustainable route to biofuels production. However this process has to become more economical before large scale operations are put into place. Identifying and characterizing GHs with improved properties for biomass degradation is a key factor for the development of cost effective processes to convert biomass to fuels and chemicals. With the recent explosion in the number of GH encoding genes discovered by fungal genome sequencing projects, it has become apparent that improvements in GH gene annotation processes have to be developed. This will enable more informed and efficient decision making with regard to selection and utilization of these important enzymes in bioprocess that produce fuels and chemicals from lignocellulosic feedstocks.

  2. Growing degree hours - a simple, accurate, and precise protocol to approximate growing heat summation for grapevines.

    PubMed

    Gu, S

    2016-08-01

    Despite its low accuracy and consistency, growing degree days (GDD) has been widely used to approximate growing heat summation (GHS) for regional classification and phenological prediction. GDD is usually calculated from the mean of daily minimum and maximum temperatures (GDDmm) above a growing base temperature (T gb). To determine approximation errors and accuracy, daily and cumulative GDDmm was compared to GDD based on daily average temperature (GDDavg), growing degree hours (GDH) based on hourly temperatures, and growing degree minutes (GDM) based on minute-by-minute temperatures. Finite error, due to the difference between measured and true temperatures above T gb is large in GDDmm but is negligible in GDDavg, GDH, and GDM, depending only upon the number of measured temperatures used for daily approximation. Hidden negative error, due to the temperatures below T gb when being averaged for approximation intervals larger than measuring interval, is large in GDDmm and GDDavg but is negligible in GDH and GDM. Both GDH and GDM improve GHS approximation accuracy over GDDmm or GDDavg by summation of multiple integration rectangles to reduce both finite and hidden negative errors. GDH is proposed as the standardized GHS approximation protocol, providing adequate accuracy and high precision independent upon T gb while requiring simple data recording and processing. PMID:26589826

  3. Caldicellulosiruptor Core and Pangenomes Reveal Determinants for Noncellulosomal Thermophilic Deconstruction of Plant Biomass

    PubMed Central

    Blumer-Schuette, Sara E.; Giannone, Richard J.; Zurawski, Jeffrey V.; Ozdemir, Inci; Ma, Qin; Yin, Yanbin; Xu, Ying; Kataeva, Irina; Poole, Farris L.; Adams, Michael W. W.; Hamilton-Brehm, Scott D.; Elkins, James G.; Larimer, Frank W.; Land, Miriam L.; Hauser, Loren J.; Cottingham, Robert W.; Hettich, Robert L.

    2012-01-01

    Extremely thermophilic bacteria of the genus Caldicellulosiruptor utilize carbohydrate components of plant cell walls, including cellulose and hemicellulose, facilitated by a diverse set of glycoside hydrolases (GHs). From a biofuel perspective, this capability is crucial for deconstruction of plant biomass into fermentable sugars. While all species from the genus grow on xylan and acid-pretreated switchgrass, growth on crystalline cellulose is variable. The basis for this variability was examined using microbiological, genomic, and proteomic analyses of eight globally diverse Caldicellulosiruptor species. The open Caldicellulosiruptor pangenome (4,009 open reading frames [ORFs]) encodes 106 GHs, representing 43 GH families, but only 26 GHs from 17 families are included in the core (noncellulosic) genome (1,543 ORFs). Differentiating the strongly cellulolytic Caldicellulosiruptor species from the others is a specific genomic locus that encodes multidomain cellulases from GH families 9 and 48, which are associated with cellulose-binding modules. This locus also encodes a novel adhesin associated with type IV pili, which was identified in the exoproteome bound to crystalline cellulose. Taking into account the core genomes, pangenomes, and individual genomes, the ancestral Caldicellulosiruptor was likely cellulolytic and evolved, in some cases, into species that lost the ability to degrade crystalline cellulose while maintaining the capacity to hydrolyze amorphous cellulose and hemicellulose. PMID:22636774

  4. Diversity of glycosyl hydrolases from cellulose-depleting communities enriched from casts of two earthworm species.

    PubMed

    Beloqui, Ana; Nechitaylo, Taras Y; López-Cortés, Nieves; Ghazi, Azam; Guazzaroni, María-Eugenia; Polaina, Julio; Strittmatter, Axel W; Reva, Oleg; Waliczek, Agnes; Yakimov, Michail M; Golyshina, Olga V; Ferrer, Manuel; Golyshin, Peter N

    2010-09-01

    The guts and casts of earthworms contain microbial assemblages that process large amounts of organic polymeric substrates from plant litter and soil; however, the enzymatic potential of these microbial communities remains largely unexplored. In the present work, we retrieved carbohydrate-modifying enzymes through the activity screening of metagenomic fosmid libraries from cellulose-depleting microbial communities established with the fresh casts of two earthworm species, Aporrectodea caliginosa and Lumbricus terrestris, as inocula. Eight glycosyl hydrolases (GHs) from the A. caliginosa-derived community were multidomain endo-beta-glucanases, beta-glucosidases, beta-cellobiohydrolases, beta-galactosidase, and beta-xylosidases of known GH families. In contrast, two GHs derived from the L. terrestris microbiome had no similarity to any known GHs and represented two novel families of beta-galactosidases/alpha-arabinopyranosidases. Members of these families were annotated in public databases as conserved hypothetical proteins, with one being structurally related to isomerases/dehydratases. This study provides insight into their biochemistry, domain structures, and active-site architecture. The two communities were similar in bacterial composition but significantly different with regard to their eukaryotic inhabitants. Further sequence analysis of fosmids and plasmids bearing the GH-encoding genes, along with oligonucleotide usage pattern analysis, suggested that those apparently originated from Gammaproteobacteria (pseudomonads and Cellvibrio-like organisms), Betaproteobacteria (Comamonadaceae), and Alphaproteobacteria (Rhizobiales). PMID:20622123

  5. Growing degree hours - a simple, accurate, and precise protocol to approximate growing heat summation for grapevines

    NASA Astrophysics Data System (ADS)

    Gu, S.

    2016-08-01

    Despite its low accuracy and consistency, growing degree days (GDD) has been widely used to approximate growing heat summation (GHS) for regional classification and phenological prediction. GDD is usually calculated from the mean of daily minimum and maximum temperatures (GDDmm) above a growing base temperature ( T gb). To determine approximation errors and accuracy, daily and cumulative GDDmm was compared to GDD based on daily average temperature (GDDavg), growing degree hours (GDH) based on hourly temperatures, and growing degree minutes (GDM) based on minute-by-minute temperatures. Finite error, due to the difference between measured and true temperatures above T gb is large in GDDmm but is negligible in GDDavg, GDH, and GDM, depending only upon the number of measured temperatures used for daily approximation. Hidden negative error, due to the temperatures below T gb when being averaged for approximation intervals larger than measuring interval, is large in GDDmm and GDDavg but is negligible in GDH and GDM. Both GDH and GDM improve GHS approximation accuracy over GDDmm or GDDavg by summation of multiple integration rectangles to reduce both finite and hidden negative errors. GDH is proposed as the standardized GHS approximation protocol, providing adequate accuracy and high precision independent upon T gb while requiring simple data recording and processing.

  6. Circulating ghrelin and leptin concentrations and growth hormone secretagogue receptor abundance in liver, muscle, and adipose tissue of beef cattle exhibiting differences in composition of gain.

    PubMed

    Jennings, J S; Wertz-Lutz, A E; Pritchard, R H; Weaver, A D; Keisler, D H; Bruns, K

    2011-12-01

    Data from species other than cattle indicate that ghrelin and GH secretagogue receptor (GHS-R) could play a key role in fat deposition, energy homeostasis, or glucose metabolism by directly affecting liver and adipose tissue metabolism. Beef steers (n = 72) were used to test the hypothesis that plasma ghrelin and leptin concentrations and abundance of the GHS-R in liver, muscle, and adipose tissues differ in steers exhibiting differences in composition of gain. At trial initiation (d 0), 8 steers were slaughtered for initial carcass composition. The remaining 64 steers were stratified by BW, allotted to pen, and treatment was assigned randomly to pen. Steers were not implanted with anabolic steroids. Treatments were 1) a low-energy (LE) diet fed during the growing period (0 to 111 d) followed by a high-energy (HE) diet during the finishing period (112 to 209 d; LE-HE) or 2) the HE diet for the duration of the trial (1 to 209 d; HE-HE). Eight steers per treatment were slaughtered on d 88, 111, 160, and 209. Carcass ninth, tenth, and eleventh rib sections were dissected for chemical composition and regression equations were developed to predict compositional gain. Liver, muscle, and subcutaneous adipose tissues were frozen in liquid nitrogen for subsequent Western blotting for GHS-R. Replicate blood samples collected before each slaughter were assayed for ghrelin and leptin concentrations. When compared at a common compositional fat end-point, the rate of carcass fat accretion (g·kg of shrunk BW(-1)) was greater (P < 0.001) in HE-HE steers whereas the rate of carcass protein accretion (g·kg of shrunk BW(-1)) was less (P < 0.001) compared with LE-HE steers. When compared at a common compositional fat end-point, plasma leptin, ghrelin, and insulin concentrations were greater (P < 0.05) for HE-HE compared with LE-HE steers. Abundance of the GHS-R, to which ghrelin binds, increased over time in liver and adipose tissue but did not differ as a result of treatment

  7. Accuracy of reported flash point values on material safety data sheets and the impact on product classification.

    PubMed

    Radnoff, Diane

    2013-01-01

    Material Safety Data Sheets (MSDSs) are the foundation of worker right-to-know legislation for chemical hazards. Suppliers can use product test data to determine a product's classification. Alternatively, they may use evaluation and professional judgment based on test results for the product or a product, material, or substance with similar properties. While the criteria for classifying products under the new Globally Harmonized System of Classification and Labeling of Chemicals (GHS) are different, a similar process is followed. Neither the current Workplace Hazardous Materials Information System (WHMIS) nor GHS require suppliers to test their products to classify them. In this project 83 samples of products classified as flammable or combustible, representing a variety of industry sectors and product types, were collected. Flash points were measured and compared to the reported values on the MSDSs. The classifications of the products were then compared using the WHMIS and GHS criteria. The results of the study indicated that there were significant variations between the disclosed and measured flash point values. Overall, more than one-third of the products had flash points lower than that disclosed on the MSDS. In some cases, the measured values were more than 20°C lower than the disclosed values. This could potentially result in an underestimation regarding the flammability of the product so it is important for employers to understand the limitations in the information provided on MSDSs when developing safe work procedures and training programs in the workplace. Nearly one-fifth of the products were misclassified under the WHMIS system as combustible when the measured flash point indicated that they should be classified as flammable when laboratory measurement error was taken into account. While a similar number of products were misclassified using GHS criteria, the tendency appeared to be to "over-classify" (provide a hazard class that was more conservative

  8. Chemical evolution of Himalayan leucogranites based on an O, U-Pb and Hf study of zircon

    NASA Astrophysics Data System (ADS)

    Hopkinson, Thomas N.; Warren, Clare J.; Harris, Nigel B. W.; Hammond, Samantha J.; Parrish, Randall R.

    2015-04-01

    Crustal melting is a characteristic process at convergent plate margins, where crustal rocks are heated and deformed. Miocene leucogranite sheets and plutons are found intruded into the high-grade metasedimentary core (the Greater Himalayan Sequence, GHS) across the Himalayan orogen. Previously-published Himalayan whole-rock data suggest that these leucogranites formed from a purely meta-sedimentary source, isotopically similar to those into which they now intrude. Bulk rock analyses carry inherent uncertainties, however: they may hide contributions from different contributing sources, and post-crystallization processes such as fluid interaction may significantly alter the original chemistry. In contrast, zircon is more able to retain precise information of the contributing sources of the melt from which it crystallises whilst its resistant nature is impervious to post-magmatic processes. This multi-isotope study of Oligocene-Miocene leucogranite zircons from the Bhutan Himalaya, seeks to differentiate between various geochemical processes that contribute to granite formation. Hf and O isotopes are used to detect discrete changes in melt source while U-Pb isotopes provide the timing of zircon crystallisation. Our data show that zircon rims of Himalayan age yield Hf-O signatures that lie within the previously reported whole-rock GHS field, confirming the absence of a discernible mantle contribution to the leucogranite source. Importantly, we document a decrease in the minimum ɛHf values during Himalayan orogenesis through time, correlating to a change in Hf model age from 1.4 Ga to 2.4 Ga. Nd model ages for the older Lesser Himalayan metasediments (LHS) that underthrust the GHS are significantly older than those for the GHS (2.4-2.9 Ga compared with 1.4-2.2 Ga), and as such even minor contributions of LHS material incorporated into a melt would significantly increase the resulting Hf model age. Hence our leucogranite data suggest either a change of source within

  9. Role of 1,25-Dihydroxy Vitamin D3 and Parathyroid Hormone in Urinary Calcium Excretion in Calcium Stone Formers

    PubMed Central

    Kim, Won Tae; Kim, Yong-June; Yun, Seok Joong; Shin, Kyung-Sub; Choi, Young Deuk; Kim, Wun-Jae

    2014-01-01

    Purpose To find out the possible role of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] and parathyroid hormone (PTH) as intrinsic factors in urinary calcium stone formers (SFs), we investigated their relationship with serum and urinary biochemical parameters. Materials and Methods A total of 326 calcium SFs (male: 204, female: 122) were enrolled and underwent outpatient metabolic evaluations including 1,25(OH)2D3 and PTH as well as serum and 24-hour urinary biochemical parameters. As control, 163 age- and sex-matched (2:1) individuals (non-SFs) who have never urinary stone episode were included. Results 1,25(OH)2D3 level was positively correlated with urinary calcium excretion (r=0.347, p<0.001). The hypercalciuric group and recurrent SFs had higher serum 1,25(OH)2D3 levels than the normocalciuric group (p<0.001) and first SFs (p=0.050). In the adjusted multiple linear regression analysis, serum 1,25(OH)2D3 level (β=0.259, p<0.001) and serum PTH level (β=-0.160, p<0.001) were significantly correlated with urinary calcium excretion. The patients in highest tertile of 1,25(OH)2D3 had a more than 3.1 fold risk of hypercalciuria than those in the lowest tertile (odds ratio=3.14, 95% confidence interval: 1.431-6.888, p=0.004). No correlation was observed between PTH and 1,25(OH)2D3 (R=0.005, p=0.929) in calcium SFs, while a negative correlation was found in controls (R=-0.269, p=0.001). Conclusion 1,25(OH)2D3 was closely correlated with urinary calcium excretion, and high 1,25(OH)2D3 levels were detected in the hypercalciuric group and in recurrent SFs. However, 1,25(OH)2D3 was not correlated with PTH in calcium SFs. These findings suggest that 1,25(OH)2D3 might be important intrinsic factor for altered calcium regulation in SFs. PMID:25048492

  10. Impaired bone formation in male idiopathic osteoporosis: further reduction in the presence of concomitant hypercalciuria

    NASA Technical Reports Server (NTRS)

    Zerwekh, J. E.; Sakhaee, K.; Breslau, N. A.; Gottschalk, F.; Pak, C. Y.

    1992-01-01

    We present iliac bone histomorphometric data and related biochemical data from 16 nonalcoholic men (50 +/- 11 (SD) years) referred for evaluation of spontaneous skeletal and/or appendicular fractures and reduced spinal bone density. All men were eugonadal and had no known underlying disorder associated with osteopenia. For the group, mean serum chemistry values were within normal limits including immunoreactive parathyroid hormone, osteocalcin and serum 1,25-dihydroxyvitamin D [1,25(OH)2D]. Nine men demonstrated hypercalciuria (greater than or equal to 0.1 mmol/kg per day) while on a constant metabolic diet of 20 mmol/day Ca. Their 24-hour urinary calcium was significantly greater than that for the remaining 7 men (7.4 +/- 1.6 vs. 5.0 +/- 0.8 mmol/day, p = 0.003), as was their calciuric response to a 1 g oral calcium load (0.23 +/- 0.06 vs. 0.15 +/- 0.05 Ca/creatinine, p = 0.042). Serum parameters (including parathyroid hormone and 1,25(OH)2D) of hypercalciuric and normocalciuric men were not significantly different. Histomorphometric indices for cancellous bone demonstrated significant differences between the entire group of osteoporotic men and age-adjusted normal values for bone volume (11.4 +/- 4.0% vs. 23.2 +/- 4.4%), osteoid surface (5.6 +/- 3.9% vs. 12.1 +/- 4.6%), osteoblastic surface (2.0 +/- 2.3% vs. 3.9 +/- 1.9%), and mineralizing surface (1.9 +/- 2.4% vs. 5.1 +/- 2.7%); there were also significant differences in bone formation rate (total surface referent) (0.004 +/- 0.001 vs. 0.011 +/- 0.006 mm3/mm2 per year). Compared with the normocalciuric group the 9 hypercalciuric men had significantly lower osteoblastic surfaces (1.6 +/- 1.9% vs. 2.5 +/- 2.6%) and mineralizing surfaces (1.4 +/- 1.5% vs. 2.7 +/- 3.2%).(ABSTRACT TRUNCATED AT 250 WORDS).

  11. Renal-Stone Risk Assessment During Space Shuttle Flights

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy A.; Pietrzyk, Robert A.; Pak, Charles Y. C.

    1996-01-01

    The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. 24-hr urine samples were collected prior to, during space flight, and following landing. Urinary factors associated with renal stone formation were analyzed and the relative urinary supersaturation ratios of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. Food and fluid consumption was recorded for a 48-hr period ending with the urine collection. Urinary composition changed during flight to favor the crystallization of stone-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. The importance of the hypercalciuria was noted since renal excretion was high relative to the intake.

  12. [MICROBIAL COMMUNITIES ON KIDNEY STONES].

    PubMed

    Romanova, Yu M; Mulabaev, N S; Tolordava, E R; Seregin, A V; Seregin, I V; Alexeeva, N V; Stepanova, T V; Levina, G A; Barhatova, O I; Gamova, N A; Goncharova, S A; Didenko, L V; Rakovskaya, I V

    2015-01-01

    The clinical material obtained surgically in patients with kidney stone disease (KSD) was tested for content of the stone microflora using PCR and standard microbiological methods. It was demonstrated that about 50% of stones in patients with KSD were infected with various infection agents as observed using standard microbiological and molecular genetic methods. The percentage of detection of the Mycoplasma hominis using cultural method is lower than the percentage detected using PCR, which is due to difficult isolation and cultivation, as well as DNA fragments of mycoplasma observed after antibiotic therapy. Studies based on modern microscopy methods showed that microorganisms on the surface of the kidney stone formed multispecies biofilms. PMID:26182663

  13. [Medical applications of the magnet from antiquity to the nineteenth century].

    PubMed

    Boutaric, J J

    1994-01-01

    Although the magnet was a marginal therapeutic mean, it was employed from antiquity to the XIXth century, either to treat various ailments by application on the skin or by absorption, or to take out alien metallic bodies. It was used in its natural magnet or magnetic stone form till the XVIIth century, and under the form termed synthetic magnet or tempered steel made magnet starting with the XVIIth century. These applications are listed in chronological order here, pointing out how remarkably continuous has been the use of the magnet by medicine for many centuries. PMID:11640336

  14. Carcass composition of market weight pigs subjected to heat stress in utero and during finishing.

    PubMed

    Cruzen, S M; Boddicker, R L; Graves, K L; Johnson, T P; Arkfeld, E K; Baumgard, L H; Ross, J W; Safranski, T J; Lucy, M C; Lonergan, S M

    2015-05-01

    Objectives were to investigate the effects of prolonged gestational and/or postnatal heat stress on performance and carcass composition of market weight pigs. Pregnant gilts were exposed to gestational heat stress (GHS, 28°C to 34°C, diurnal) or thermal neutral (18°C to 22°C, diurnal) conditions during the entire gestation or during the first or second half of gestation. At 14 wk of age (58 ± 5 kg), barrows were housed in heat stress (32°C, HS) or thermal neutral (21°C, TN) conditions. Feed intake and BW were recorded weekly, and body temperature parameters were monitored twice weekly until slaughter (109 ± 5 kg). Organs were removed and weighed, and loin eye area (LEA) and back fat thickness (BF) were measured after carcass chilling. Carcass sides were separated into lean, separable fat, bone, and skin components and were weighed. Moisture, lipid, and protein content were determined in the LM at the 10th rib. Data were analyzed using a split plot with random effect of dam nested within gestational treatment. Carcass measurements included HCW as a covariate to control for weight. Planned orthogonal contrast statements were used to evaluate the overall effect of GHS in the first half, second half, or any part of gestation. Gestational heat stress did not alter postnatal performance or most body temperature parameters (P > 0.10). However, ADFI in the finishing period was increased (P < 0.05) in response to GHS, particularly in pigs receiving GHS in the first half of gestation. Gestational heat stress during the first half of gestation decreased head weight as a percent of BW (P = 0.02), whereas GHS in the second half of gestation decreased bone weight as a percent of BW (P = 0.02). Heat stress reduced ADG, BW, and HCW (P < 0.0001). Lean tissue was increased in HS pigs on both a weight and percentage basis (P < 0.0001), but LEA was similar to TN carcasses (P = 0.38). Carcasses from HS barrows also had less carcass separable fat (P < 0.01) and tended to have

  15. Non-medical use of prescription pain relievers among high school students in China: a multilevel analysis

    PubMed Central

    Guo, Lan; Xu, Yan; Deng, Jianxiong; He, Yuan; Gao, Xue; Li, Pengsheng; Wu, Hong; Zhou, Jinhua; Lu, Ciyong

    2015-01-01

    Objectives Given the differences between general high school (GHS) and vocational high school (VHS) students, this study aimed to investigate the lifetime prevalence of non-medical use of prescription pain relievers (NMUPPR) among high school students as well as the associations between NMUPPR and individual-level factors and school category. Methods A cross-sectional study was conducted in GHS and VHS students in 2012 in Chongqing, and 11 906 students’ questionnaires were completed and qualified for the survey. Self-reported NMUPPR and information regarding individual-level determinants and school category were collected. A multilevel multivariate logistic regression model was fitted to explore independent predictors of NMUPPR. Results The total lifetime prevalence of NMUPPR was 11.3%, and NMUPPR was more prevalent among VHS students (15.8%) compared with GHS students (9.8%). Overall, the results indicated that VHS students were more likely to be involved in NMUPPR (adjusted OR (AOR)=1.64, 95% CI 1.42 to 1.89). Regarding the individual-level predictors of NMUPPR, below-average family economic status was negatively correlated with NMUPPR (AOR=0.77, 95% CI 0.60 to 0.98), and students with more pocket money were more likely to be engaged in NMUPPR. Students who had difficult family relationships, had poor relationships with teachers, had parents or friends who engaged in non-medical prescription drug use, and considered or attempted suicide were more likely to be engaged in NMUPPR. Conclusions NMUPPR among high school students is a multidetermined phenomenon. The current findings indicate that VHS students are an important subgroup of adolescents and highlight the need for additional research as well as targeted prevention and intervention programmes for NMUPPR. PMID:26169805

  16. Analysis of Draize eye irritation testing and its prediction by mining publicly available 2008-2014 REACH data.

    PubMed

    Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

    2016-01-01

    Public data from ECHA online dossiers on 9,801 substances encompassing 326,749 experimental key studies and additional information on classification and labeling were made computable. Eye irritation hazard, for which the rabbit Draize eye test still represents the reference method, was analyzed. Dossiers contained 9,782 Draize eye studies on 3,420 unique substances, indicating frequent retesting of substances. This allowed assessment of the test's reproducibility test based on all substances tested more than once. There was a 10% chance of a non-irritant evaluation given after a prior severe-irritant result as given by UN GHS classification criteria. The most reproducible outcomes were the results negative (94% reproducible) and severe eye irritant (73% reproducible). To evaluate whether other GHS categorizations predict eye irritation we built a dataset of 5,629 substances (1,931 'irritant' and 3,698 'non-irritant'). The two best decision trees with up to three other GHS classifications resulted in balanced accuracies of 68% and 73%, i.e., in the rank order of the Draize rabbit eye test itself, but both use inhalation toxicity data ("May cause respiratory irritation"), which is not typically available. Next, a dataset of 929 substances with at least one Draize study was mapped to PubChem to compute chemical similarity using 2D conformational fingerprints and Tanimoto similarity. Using a minimum similarity of 0.7 and simple classification by the closest chemical neighbor resulted in balanced accuracy from 73% over 737 substances to 100% at a threshold of 0.975 over 41 substances. This represents a strong support of read-across and (Q)SAR approaches in this area. PMID:26863293

  17. Piloting proactive marketing to recruit disadvantaged adults to a community-wide obesity prevention program.

    PubMed

    O'Hara, Blythe J; Eggins, Dianne; Phongsavan, Philayrath; Milat, Andrew J; Bauman, Adrian E; Wiggers, John

    2015-01-01

    Population-wide obesity prevention and treatment programs are fundamental to addressing the increasing overweight and obesity rates in socioeconomically disadvantaged populations. Innovative recruitment strategies, including proactive marketing strategies, are needed to ensure such programs have universal reach and target vulnerable populations. This study aimed to determine the success of proactive recruitment to Australia's Get Healthy Information and Coaching Service® (GHS) and to assess whether the recruitment strategy influenced participants' outcomes. Sociodemographic information was collected from all GHS participants who joined the service between February 2009 and August 2013, and anthropometric information regarding behavioural risk factors was collected from all GHS coaching participants at baseline and six months. Data were analysed according to the participants' referral source (self-referral and secondary referral versus proactive recruitment). Participants recruited through proactive marketing were more likely to be male, aged 50 years or older, have high school education, not be in paid employment and be from the lowest three quintiles of socioeconomic advantage. The risk factor profile of coaching participants recruited through proactive marketing did not vary significantly from those recruited via other mechanisms, although they were less likely to be obese and less likely to have a higher 'at risk' waist circumference measurement. Proactively recruited coaching participants reported significant improvements from baseline to six months (consistent with improvements made by participants recruited through other strategies), although they were significantly more likely to withdraw from coaching before they completed the six-month program.Proactive marketing facilitated use of an obesity prevention service; similar services may have greater reach if proactive marketing recruitment strategies are used. These strategies could be encouraged to assist

  18. Microarchitecture, but Not Bone Mechanical Properties, Is Rescued with Growth Hormone Treatment in a Mouse Model of Growth Hormone Deficiency

    PubMed Central

    Kristensen, Erika; Hallgrímsson, Benedikt; Morck, Douglas W.; Boyd, Steven K.

    2012-01-01

    Growth hormone (GH) deficiency is related to an increased fracture risk although it is not clear if this is due to compromised bone quality or a small bone size. We investigated the relationship between bone macrostructure, microarchitecture and mechanical properties in a GH-deficient (GHD) mouse model undergoing GH treatment commencing at an early (prepubertal) or late (postpubertal) time point. Microcomputed tomography images of the femur and L4 vertebra were obtained to quantify macrostructure and vertebral trabecular microarchitecture, and mechanical properties were determined using finite element analyses. In the GHD animals, bone macrostructure was 25 to 43% smaller as compared to the GH-sufficient (GHS) controls (P < 0.001). GHD animals had 20% and 19% reductions in bone volume ratio (BV/TV) and trabecular thickness (Tb.Th), respectively. Whole bone mechanical properties of the GHD mice were lower at the femur and vertebra (67% and 45% resp.) than the GHS controls (P < 0.001). Both early and late GH treatment partially recovered the bone macrostructure (15 to 32 % smaller than GHS controls) and the whole bone mechanical properties (24 to 43% larger than GHD animals) although there remained a sustained 27–52% net deficit compared to normal mice (P < 0.05). Importantly, early treatment with GH led to a recovery of BV/TV and Tb.Th with a concomitant improvement of trabecular mechanical properties. Therefore, the results suggest that GH treatment should start early, and that measurements of microarchitecture should be considered in the management of GHD. PMID:22505889

  19. Strengthening global health security capacity--Vietnam demonstration project, 2013.

    PubMed

    Tran, Phu Dac; Vu, Long Ngoc; Nguyen, Hien Tran; Phan, Lan Trong; Lowe, Wayne; McConnell, Michelle S; Iademarco, Michael F; Partridge, Jeffrey M; Kile, James C; Do, Trang; Nadol, Patrick J; Bui, Hien; Vu, Diep; Bond, Kyle; Nelson, David B; Anderson, Lauren; Hunt, Kenneth V; Smith, Nicole; Giannone, Paul; Klena, John; Beauvais, Denise; Becknell, Kristi; Tappero, Jordan W; Dowell, Scott F; Rzeszotarski, Peter; Chu, May; Kinkade, Carl

    2014-01-31

    Over the past decade, Vietnam has successfully responded to global health security (GHS) challenges, including domestic elimination of severe acute respiratory syndrome (SARS) and rapid public health responses to human infections with influenza A(H5N1) virus. However, new threats such as Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A(H7N9) present continued challenges, reinforcing the need to improve the global capacity to prevent, detect, and respond to public health threats. In June 2012, Vietnam, along with many other nations, obtained a 2-year extension for meeting core surveillance and response requirements of the 2005 International Health Regulations (IHR). During March-September 2013, CDC and the Vietnamese Ministry of Health (MoH) collaborated on a GHS demonstration project to improve public health emergency detection and response capacity. The project aimed to demonstrate, in a short period, that enhancements to Vietnam's health system in surveillance and early detection of and response to diseases and outbreaks could contribute to meeting the IHR core capacities, consistent with the Asia Pacific Strategy for Emerging Diseases. Work focused on enhancements to three interrelated priority areas and included achievements in 1) establishing an emergency operations center (EOC) at the General Department of Preventive Medicine with training of personnel for public health emergency management; 2) improving the nationwide laboratory system, including enhanced testing capability for several priority pathogens (i.e., those in Vietnam most likely to contribute to public health emergencies of international concern); and 3) creating an emergency response information systems platform, including a demonstration of real-time reporting capability. Lessons learned included awareness that integrated functions within the health system for GHS require careful planning, stakeholder buy-in, and intradepartmental and interdepartmental coordination and

  20. Margins of safety provided by COSHH Essentials and the ILO Chemical Control Toolkit.

    PubMed

    Jones, Rachael M; Nicas, Mark

    2006-03-01

    COSHH Essentials, developed by the UK Health and Safety Executive, and the Chemical Control Toolkit (Toolkit) proposed by the International Labor Organization, are 'control banding' approaches to workplace risk management intended for use by proprietors of small and medium-sized businesses. Both systems group chemical substances into hazard bands based on toxicological endpoint and potency. COSSH Essentials uses the European Union's Risk-phrases (R-phrases), whereas the Toolkit uses R-phrases and the Globally Harmonized System (GHS) of Classification and Labeling of Chemicals. Each hazard band is associated with a range of airborne concentrations, termed exposure bands, which are to be attained by the implementation of recommended control technologies. Here we analyze the margin of safety afforded by the systems and, for each hazard band, define the minimal margin as the ratio of the minimum airborne concentration that produced the toxicological endpoint of interest in experimental animals to the maximum concentration in workplace air permitted by the exposure band. We found that the minimal margins were always <100, with some ranging to <1, and inversely related to molecular weight. The Toolkit-GHS system generally produced margins equal to or larger than COSHH Essentials, suggesting that the Toolkit-GHS system is more protective of worker health. Although, these systems predict exposures comparable with current occupational exposure limits, we argue that the minimal margins are better indicators of health protection. Further, given the small margins observed, we feel it is important that revisions of these systems provide the exposure bands to users, so as to permit evaluation of control technology capture efficiency. PMID:16172140

  1. The role of ghrelin in the regulation of glucose homeostasis.

    PubMed

    Alamri, Bader N; Shin, Kyungsoo; Chappe, Valerie; Anini, Younes

    2016-04-01

    Ghrelin is a 28-amino acid (aa) stomach-derived peptide discovered in 1999 as the endogenous ligand for growth hormone secretagogue-receptor (GHS-R). Ghrelin-producing cells constitute a distinct group of endocrine cells dispersed throughout the gastric mucosa and to a lesser extent in the small intestine and the endocrine pancreas. Ghrelin plasma levels rise during fasting and chronic caloric restriction to stimulate food intake and fat storage and to prevent life-threatening falls in blood glucose. Plasma ghrelin levels decrease after a meal is consumed and in conditions of energy surplus (such as obesity). Ghrelin has emerged as a key player in the regulation of appetite and energy homeostasis. Ghrelin achieves these functions through binding the ghrelin receptor GHS-R in appetite-regulating neurons and in peripheral metabolic organs including the endocrine pancreas. Ghrelin levels are negatively correlated with body mass index (BMI) and insulin resistance. In addition, ghrelin secretion is impaired in obesity and insulin resistance. Several studies highlight an important role for ghrelin in glucose homeostasis. Genetic, immunological, and pharmacological blockade of ghrelin signaling resulted in improved glucose tolerance and insulin sensitivity. Furthermore, exogenous ghrelin administration was shown to decrease glucose-induced insulin release and increase glucose level in both humans and rodents. GHS-R was shown to be expressed in pancreatic β-cells and ghrelin suppressed insulin release via a Ca2+-mediated pathway. In this review, we provide a detailed summary of recent advances in the field that focuses on the role of insulin and insulin resistance in the regulation of ghrelin secretion and on the role of ghrelin in glucose-stimulated insulin secretion (GSIS). PMID:27235674

  2. Expression of prepro-ghrelin and related receptor genes in the rat adrenal gland and evidences that ghrelin exerts a potent stimulating effect on corticosterone secretion by cultured rat adrenocortical cells.

    PubMed

    Rucinski, Marcin; Ziolkowska, Agnieszka; Tyczewska, Marianna; Malendowicz, Ludwik K

    2009-08-01

    The orexigenic peptide ghrelin (GHREL) and obestatin (OBS) originate from the same peptide precursor, preproghrelin (ppGHREL). Apart from orexigenic effect, GHREL also regulates neuroendocrine function. We investigated GHREL and OBS effects on corticosterone secretion by freshly isolated and cultured rat adrenocortical cells. Classic RT-PCR revealed the presence of ppGHREL, GHS-R1a, GPR39v1 and GPR39v2 and GOAT4 (ghrelin O-acyl transferase) mRNAs in rat adrenals and cultured for 4 days rat adrenocortical cells. Expression of ppGHREL, GHS-R1a, and GOAT genes was notably higher in the cortex than in medulla. High expression level of GOAT gene was found in the zona glomerulosa, while expression level of both GPR39v1 and GPR39v2 genes was similar in adrenal cortical zones and in medulla. In freshly isolated cells neither GHREL nor OBS had an effect on corticosteroid output. Prolonged exposure of cultured cells to GHREL resulted in a potent, comparable to ACTH, stimulating effect of GHREL on corticosterone secretion. Prolonged exposure to OBS was ineffective. Neither GHREL nor OBS had any effect on proliferation of studied cells, while ACTH notably lowered it. GHREL down regulated GHS-R1a gene expression while both ACTH and GHREL stimulated expression level of GPR39v1 gene. Expression of CYP11A1 gene was notably stimulated and that of StAR gene remained unaffected by ACTH or GHREL. Thus, our study is the first to demonstrate direct stimulating effect of GHREL on corticosterone output by cultured rat adrenocortical cells. This stimulating action differs from that evoked by ACTH and is not dependent on the presence of functional ACTH receptor. PMID:19416745

  3. The Ophthalmic Branch of the Gutenberg Health Study: Study Design, Cohort Profile and Self-Reported Diseases

    PubMed Central

    Höhn, René; Kottler, Ulrike; Peto, Tunde; Blettner, Maria; Münzel, Thomas; Blankenberg, Stefan; Lackner, Karl J.; Beutel, Manfred

    2015-01-01

    Purpose This paper describes the study design, methodology, cohort profile and self-reported diseases in the ophthalmological branch of the Gutenberg Health Study (GHS). Methods The GHS is an ongoing, prospective, interdisciplinary, single-center, population-based cohort study in Germany. The main goals of the ophthalmological section are to assess the prevalence and incidence of ocular diseases and to explore risk factors, genetic determinants and associations with systemic diseases and conditions. The eye examination at baseline included a medical history, self-reported eye diseases, visual acuity, refractive errors, intraocular pressure, visual field, pachymetry, keratometry, fundus photography and tear sampling. The 5-year follow-up visit additionally encompassed optical coherence tomography, anterior segment imaging and optical biometry. The general examination included anthropometry; blood pressure measurement; carotid artery ultrasound; electrocardiogram; echocardiography; spirometry; cognitive tests; questionnaires; assessment of mental conditions; and DNA, RNA, blood and urine sampling. Results Of 15,010 participants (aged 35-74 years at the time of inclusion), ocular data are available for 14,700 subjects (97.9%). The mean visual acuity (standard deviation), mean spherical equivalent, median decimal visual acuity, and mean intraocular pressure were 0.08 (0.17) logMar, -0.42 (2.43) diopters, 0.9 and 14.24 (2.79) mm Hg, respectively. The frequencies of self-reported strabismus, glaucoma, surgery for retinal detachment and retinal vascular occlusions were 2.7%, 2.3%, 0.2% and 0.4%, respectively. Conclusions The GHS is the most extensive dataset of ophthalmic diseases and conditions and their risk factors in Germany and one of the largest cohorts worldwide. This dataset will provide new insight in the epidemiology of ophthalmic diseases and related medical specialties. PMID:25775251

  4. Starch-degrading polysaccharide monooxygenases.

    PubMed

    Vu, Van V; Marletta, Michael A

    2016-07-01

    Polysaccharide degradation by hydrolytic enzymes glycoside hydrolases (GHs) is well known. More recently, polysaccharide monooxygenases (PMOs, also known as lytic PMOs or LPMOs) were found to oxidatively degrade various polysaccharides via a copper-dependent hydroxylation. PMOs were previously thought to be either GHs or carbohydrate binding modules (CBMs), and have been re-classified in carbohydrate active enzymes (CAZY) database as auxiliary activity (AA) families. These enzymes include cellulose-active fungal PMOs (AA9, formerly GH61), chitin- and cellulose-active bacterial PMOs (AA10, formerly CBM33), and chitin-active fungal PMOs (AA11). These PMOs significantly boost the activity of GHs under industrially relevant conditions, and thus have great potential in the biomass-based biofuel industry. PMOs that act on starch are the latest PMOs discovered (AA13), which has expanded our perspectives in PMOs studies and starch degradation. Starch-active PMOs have many common structural features and biochemical properties of the PMO superfamily, yet differ from other PMO families in several important aspects. These differences likely correlate, at least in part, to the differences in primary and higher order structures of starch and cellulose, and chitin. In this review we will discuss the discovery, structural features, biochemical and biophysical properties, and possible biological functions of starch-active PMOs, as well as their potential application in the biofuel, food, and other starch-based industries. Important questions regarding various aspects of starch-active PMOs and possible economical driving force for their future studies will also be highlighted. PMID:27170366

  5. Ghrelin gene products and the regulation of food intake and gut motility.

    PubMed

    Chen, Chih-Yen; Asakawa, Akihiro; Fujimiya, Mineko; Lee, Shou-Dong; Inui, Akio

    2009-12-01

    A breakthrough using "reverse pharmacology" identified and characterized acyl ghrelin from the stomach as the endogenous cognate ligand for the growth hormone (GH) secretagogue receptor (GHS-R) 1a. The unique post-translational modification of O-n-octanoylation at serine 3 is the first in peptide discovery history and is essential for GH-releasing ability. Des-acyl ghrelin, lacking O-n-octanoylation at serine 3, is also produced in the stomach and remains the major molecular form secreted into the circulation. The third ghrelin gene product, obestatin, a novel 23-amino acid peptide identified from rat stomach, was found by comparative genomic analysis. Three ghrelin gene products actively participate in modulating appetite, adipogenesis, gut motility, glucose metabolism, cell proliferation, immune, sleep, memory, anxiety, cognition, and stress. Knockdown or knockout of acyl ghrelin and/or GHS-R1a, and overexpression of des-acyl ghrelin show benefits in the therapy of obesity and metabolic syndrome. By contrast, agonism of acyl ghrelin and/or GHS-R1a could combat human anorexia-cachexia, including anorexia nervosa, chronic heart failure, chronic obstructive pulmonary disease, liver cirrhosis, chronic kidney disease, burn, and postsurgery recovery, as well as restore gut dysmotility, such as diabetic or neurogenic gastroparesis, and postoperative ileus. The ghrelin acyl-modifying enzyme, ghrelin O-Acyltransferase (GOAT), which attaches octanoate to serine-3 of ghrelin, has been identified and characterized also from the stomach. To date, ghrelin is the only protein to be octanylated, and inhibition of GOAT may have effects only on the stomach and is unlikely to affect the synthesis of other proteins. GOAT may provide a critical molecular target in developing novel therapeutics for obesity and type 2 diabetes. PMID:20038570

  6. The role of ghrelin signalling for sexual behaviour in male mice.

    PubMed

    Egecioglu, Emil; Prieto-Garcia, Luna; Studer, Erik; Westberg, Lars; Jerlhag, Elisabet

    2016-03-01

    Ghrelin, a gut-brain signal, is well known to regulate energy homeostasis, food intake and appetite foremost via hypothalamic ghrelin receptors (GHS-R1A). In addition, ghrelin activates the reward systems in the brain, namely the mesolimbic dopamine system, and regulates thereby the rewarding properties of addictive drugs as well as of palatable foods. Given that the mesolimbic dopamine system mandates the reinforcing properties of addictive drugs and natural rewards, such as sexual behaviour, we hypothesize that ghrelin plays an important role for male sexual behaviour, a subject for the present studies. Herein we show that ghrelin treatment increases, whereas pharmacological suppression (using the GHSR-1A antagonist JMV2959) or genetic deletion of the GHS-R1A in male mice decreases the sexual motivation for as well as sexual behaviour with female mice in oestrus. Pre-treatment with L-dopa (a dopamine precursor) prior to treatment with JMV2959 significantly increased the preference for female mouse compared with vehicle treatment. On the contrary, treatment with 5-hydroxythyptohan (a precursor for serotonin) prior to treatment with JMV2959 decreased the sexual motivation compared to vehicle. In separate experiments, we show that ghrelin and GHS-R1A antagonism do not affect the time spent over female bedding as measured in the androgen-dependent bedding test. Collectively, these data show that the hunger hormone ghrelin and its receptor are required for normal sexual behaviour in male mice and that the effects of the ghrelin signalling system on sexual behaviour involve dopamine neurotransmission. PMID:25475101

  7. Noninflammatory upregulation of nerve growth factor underlies gastric hypersensitivity induced by neonatal colon inflammation.

    PubMed

    Li, Qingjie; Winston, John H; Sarna, Sushil K

    2016-02-01

    Gastric hypersensitivity is one of the key contributors to the postprandial symptoms of epigastric pain/discomfort, satiety, and fullness in functional dyspepsia patients. Epidemiological studies found that adverse early-life experiences are risk factors for the development of gastric hypersensitivity. Preclinical studies found that neonatal colon inflammation elevates plasma norepinephrine (NE), which upregulates expression of nerve growth factor (NGF) in the muscularis externa of the gastric fundus. Our goal was to investigate the cellular mechanisms by which NE upregulates the expression of NGF in gastric hypersensitive (GHS) rats, which were subjected previously to neonatal colon inflammation. Neonatal colon inflammation upregulated NGF protein, but not mRNA, in the gastric fundus of GHS rats. Western blotting showed upregulation of p110γ of phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K), phosphoinositide-dependent kinase-1 (PDK1), pAKT(Ser473), and phosphorylated 4E-binding protein (p4E-BP1)(Thr70), suggesting AKT activation and enhanced NGF protein translation. AKT inhibitor MK-2206 blocked the upregulation of NGF in the fundus of GHS rats. Matrix metalloproteinase 9 (MMP-9), the major NGF-degrading protease, was suppressed, indicating that NGF degradation was impeded. Incubation of fundus muscularis externa with NE upregulated NGF by modulating the protein translation and degradation pathways. Yohimbine, an α2-adrenergic receptor antagonist, upregulated plasma NE and NGF expression by activating the protein translation and degradation pathways in naive rats. In contrast, a cocktail of adrenergic receptor antagonists suppressed the upregulation of NGF by blocking the activation of the protein translation and degradation pathways. Our findings provide evidence that the elevation of plasma NE induces NGF expression in the gastric fundus. PMID:26608656

  8. Expression and localization of ghrelin and its receptor in ovarian follicles during different stages of development and the modulatory effect of ghrelin on granulosa cells function in buffalo.

    PubMed

    Gupta, M; Dangi, S S; Singh, G; Sarkar, M

    2015-01-01

    Ghrelin, a hormone predominantly found in the stomach, was recently described as a factor that controls female reproductive function. The aim of our study was to investigate the expression and localization of ghrelin and its active receptor, growth hormone secretagogue receptor type 1a (GHS-R1a) in buffalo ovarian follicles of different follicular size and to investigate role of ghrelin on estradiol (E2) secretion, aromatase (CYP19A1), proliferating cell nuclear antigen (PCNA) and apoptosis regulator Bax gene expression on granulosa cell culture. Using real time PCR and western blot, we measured gene and protein expression of examined factors. Localization was done with immunofluorescence method. Expression of ghrelin increased with follicle size with significantly highest in dominant or pre-ovulatory follicle (P<0.05). Expression of GHS-R1a was comparable in medium and large follicle but was higher than small follicles (P<0.05). Both the factors were localized in granulosa and theca cells. Pattern of intensity of immunofluorescence was similar with mRNA and protein expression. In the in vitro study granulosa cells (GCs) were cultured and treated with ghrelin each at 1, 10 and 100ng/ml concentrations for two days after obtaining 75-80 per cent confluence. Ghrelin treatment significantly (P<0.05) inhibited E2 secretion, CYP19A1 expression, apoptosis and promoted cell proliferation. In conclusion, this study provides novel evidence for the presence of ghrelin and receptor GHS-R1a in ovarian follilcles and modulatory role of ghrelin on granulosa cell function in buffalo. PMID:25275756

  9. Do university hospitals perform better than general hospitals? A comparative analysis among Italian regions

    PubMed Central

    Grillo Ruggieri, Tommaso; Podetti, Silvia

    2016-01-01

    Objective The aim of this research was to investigate how university hospitals (UHs) perform compared with general hospitals (GHs) in the Italian healthcare system. Design and setting 27 indicators of overall performance were selected and analysed for UHs and GHs in 10 Italian regions. The data refer to 2012 and 2013 and were selected from two performance evaluation systems based on hospital discharge administrative data: the Inter-Regional Performance Evaluation System developed by the Management and Health Laboratory of the Scuola Superiore Sant'Anna of Pisa and the Italian National Outcome Evaluation Programme developed by the National Agency for Healthcare Services. The study was conducted in 2 stages and by combining 2 statistical techniques. In stage 1, a non-parametric Mann-Whitney U test was carried out to compare the performance of UHs and GHs on the selected set of indicators. In stage 2, a robust equal variance test between the 2 groups of hospitals was carried out to investigate differences in the amount of variability between them. Results The overall analysis gave heterogeneous results. In general, performance was not affected by being in the UH rather than the GH group. It is thus not possible to directly associate Italian UHs with better results in terms of appropriateness, efficiency, patient satisfaction and outcomes. Conclusions Policymakers and managers should further encourage hospital performance evaluations in order to stimulate wider competition aimed at assigning teaching status to those hospitals that are able to meet performance requirements. In addition, UH facilities could be integrated with other providers that are responsible for community, primary and outpatient services, thereby creating a joint accountability for more patient-centred and integrated care. PMID:27507233

  10. The Seveso II experience in the application of generic substance criteria to identify major hazard sites.

    PubMed

    Wood, Maureen Heraty

    2009-11-15

    Europe is currently in the process of finalising legislation to align its criteria for classifying and labelling dangerous substances with the new Globally Harmonised System of Classification and Labelling of Chemicals (GHS), replacing the criteria that have been in place within the European Union since the establishment in 1967 of Directive 67/548/EC on the Classification and Labelling of Dangerous Substances. The Seveso II Directive is potentially the piece of EU legislation most affected by this re-classification because coverage of sites under the Directive is determined to a large extent on the basis of the presence of certain generic categories of substances on site as defined by 67/548/EC. The European Commission in concert with the Member States has launched an initiative to review the current Seveso generic classifications with the view to adjusting these provisions as appropriate in light of the pending GHS-EU harmonisation. In doing so, it must foresee and take into account the inevitable inequalities that may result when the general conditions of a generalised approach are altered. This paper gives an overview of the Seveso qualifying criteria and corrective measures that have been used in the past to address its limitations in relation to specific substances and categories of substances. Adaptation of the criteria to the GHS classification is not likely to alter these limitations, but could generate new cases where they are again in evidence. Therefore, this analysis offers insight on what types of potential unforeseen and unintended consequences that changes to the current generic criteria (i.e., certain sites are inappropriately covered or not covered, as the case may be) may entail, while also highlighting how well different structural and administrative elements may function to address these situations. PMID:19632041

  11. Purification of rat and human ghrelins.

    PubMed

    Kojima, Masayasu; Hosoda, Hiroshi; Kangawa, Kenji

    2012-01-01

    Small synthetic molecules called growth hormone secretagogues (GHSs) stimulate the release of growth hormone (GH) from the pituitary. They act through the GHS-R, a G-protein-coupled receptor highly expressed in the hypothalamus and pituitary. Using an orphan receptor strategy with a stable cell line expressing GHS-R, we purified endogenous ligands for GHS-R from rat and human stomach and named it "ghrelin," after a word root (ghre) in Proto-Indo-European languages meaning "grow." Ghrelin is a peptide hormone in which the third amino acid, usually a serine but in some species a threonine, is modified by a fatty acid; this modification is essential for ghrelin's activity. The main active form of rat ghrelin is 28-amino acid peptides with n-octanoyl modification. In rat stomach, a second type of ghrelin peptide was purified, identified as des-Gln14-ghrelin. With the exception of the deletion of Gln14, des-Gln14-ghrelin is identical to ghrelin, retaining the n-octanoic acid modification. Des-Gln14-ghrelin is encoded by an mRNA created by alternative splicing of the ghrelin gene. As in the rat, the major active form of human ghrelin is a 28-amino acid peptide with an n-octanoylated Ser3. However, in human stomach, several minor forms of human ghrelin peptides have been isolated. These can be classified into four groups by the type of acylation observed at Ser3 and into two groups by the amino acids in length. The discovery of ghrelin indicates that the release of GH from the pituitary and appetite stimulation might be regulated by ghrelin derived from the stomach. PMID:22975045

  12. The thermostable β-1,3-1,4-glucanase from Clostridium thermocellum improves the nutritive value of highly viscous barley-based diets for broilers.

    PubMed

    Ribeiro, T; Lordelo, M M S; Prates, J A M; Falcão, L; Freire, J P B; Ferreira, L M A; Fontes, C M G A

    2012-01-01

    1. Microbial β-1,3-1,4-glucanases improve the nutritive value of barley-based diets for poultry by effectively decreasing the degree of polymerisation of the anti-nutritive soluble β-glucans. Glycoside hydrolases (GHs) acting on recalcitrant polysaccharides display a modular architecture comprising a catalytic domain linked to one or more non-catalytic Carbohydrate-Binding Modules (CBMs). 2. GHs and CBMs have been classified in different families based on primary structure similarity (see CAZy webpage at http://www.cazy.org ). The role of CBMs is to anchor the appended GHs into their target substrates, therefore eliciting the efficient hydrolysis of structural carbohydrates. 3. Here we describe the biochemical properties of the family 16 GH from Clostridium thermocellum, termed CtGlc16A. CtGlc16A is a thermostable enzyme that specifically acts on β-1,3-1,4-glucans with a remarkable catalytic activity (38000 U/mg protein). 4. CtGlc16A, individually or fused to the family 11 β-glucan-binding domain of cellulase CtLic26A-Cel5E of C. thermocellum, was used to supplement a highly viscous barley-based diet for broilers. 5. The data showed that birds fed on diets supplemented with the recombinant enzymes displayed an improved performance when compared with birds given diets not supplemented with exogenous enzymes. However, inclusion of the non-catalytic CBMs had no influence on the capacity of CtGlc16A to reduce the anti-nutritive effects of soluble β-1,3-1,4-glucans. 6. The data suggest that at elevated dosage rates, CBMs might be unable to potentiate the catalytic activity of appended catalytic domains; this effect may only be revealed when feed enzymes are incorporated at low levels. PMID:22646788

  13. Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis

    PubMed Central

    Qiu, Wen-Cai; Wang, Zhi-Gang; Wang, Wei-Gang; Yan, Jun; Zheng, Qi

    2008-01-01

    AIM: To investigate the potential therapeutic significance of ghrelin and growth hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility disorders. METHODS: A diabetic mouse model was established by intraperitoneal (ip) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6 (20-200 μg/kg), and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of ghrelin or GHRP-6 (100 μg/kg) was also investigated. The effects of ghrelin or GHRP-6 (0.01-10 μmol/L) on spontaneous or carbachol-induced contractile amplitude were also investigated in vitro, in gastric fundic circular strips taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a transcripts in the fundic strips of diabetic mice was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: We established a diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6 accelerated gastric emptying in diabetic mice with gastroparesis. In the presence of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100 μg/kg) failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations. CONCLUSION: Ghrelin and GHRP-6 increase gastric emptying in diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic pathways in the enteric nervous system. PMID:18322959

  14. Strontium oral load test in children with idiopathic hypercalciuria.

    PubMed

    Fernández, Porfirio; Santos, Fernando; Sotorrío, Pilar; Mayordomo, Juan; Ferrero, Luis

    2007-09-01

    Increased intestinal calcium absorption may play an important role in the pathogenesis of idiopathic hypercalciuria in children. Calcium absorption was assessed by an oral strontium load test in 22 prepubertal children (13 male) with idiopathic hypercalciuria, urinary calcium excretion 6.48 +/- 0.60 mg/kg per day (range 4.12-13.40 mg/kg per day), and ten healthy, young, normocalciuric controls (six male). After administration of 2.65 mg/kg of strontium chloride (SrCl(2)), the serum concentrations of strontium at 30 min, 60 min, 120 min, 240 min, and the fraction of the absorbed dose (FAD%) at 30 min, 60 min and 240 min, were similar in both groups. FAD% at 120 min was lower (P < 0.05) in hypercalciuric children than in controls (11.84 +/- 0.96% vs 15.87 +/- 1.77%). Values of the area under the curve were not different between both groups. In children with idiopathic hypercalciuria, serum basal intact parathyroid hormone (PTH) (r = -0.59, P = 0.004) and the 1,25-dihydroxyvitamin D/PTH ratio (r = 0.65; P = 0.001) were correlated with the serum concentration of strontium at 60 min. The study reported here provides, for the first time, the results of a strontium oral load test in children with idiopathic hypercalciuria. With this method no major alterations of intestinal calcium absorption were found in this disorder. PMID:17541793

  15. Claudins and the kidney.

    PubMed

    Hou, Jianghui; Rajagopal, Madhumitha; Yu, Alan S L

    2013-01-01

    Claudins are tight junction membrane proteins that regulate paracellular permeability of renal epithelia to small ions, solutes, and water. Claudins interact within the cell membrane and between neighboring cells to form tight junction strands and constitute both the paracellular barrier and the pore. The first extracellular domain of claudins is thought to be the pore-lining domain and contains the determinants of charge selectivity. Multiple claudins are expressed in different nephron segments; such differential expression likely determines the permeability properties of each segment. Recent evidence has identified claudin-2 as constituting the cation-reabsorptive pathway in the proximal tubule; claudin-14, -16, and -19 as forming a complex that regulates calcium transport in the thick ascending limb of the loop of Henle; and claudin-4, -7, and -8 as determinants of collecting duct chloride permeability. Mutations in claudin-16 and -19 cause familial hypercalciuric hypomagnesemia with nephrocalcinosis. The roles of other claudins in kidney diseases remain to be fully elucidated. PMID:23140368

  16. Localization and function of the renal calcium-sensing receptor.

    PubMed

    Riccardi, Daniela; Valenti, Giovanna

    2016-07-01

    The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca(2+)) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone. Aberrant Ca(2+) sensing by the parathyroid glands, as a result of altered CaSR expression or function, is associated with impaired divalent cation homeostasis. CaSR activators that mimic the effects of Ca(2+) (calcimimetics) have been designed to treat hyperparathyroidism, and CaSR antagonists (calcilytics) are in development for the treatment of hypercalciuric disorders. The kidney expresses a CaSR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner. This Review discusses the roles of the renal CaSR and the potential impact of pharmacological modulation of the CaSR on renal function. PMID:27157444

  17. Nephrolithiasis in pregnancy.

    PubMed

    Maikranz, P; Lindheimer, M; Coe, F

    1994-06-01

    Although the anatomical and physiological changes of normal pregnancy may predispose to kidney stone formation, it remains an uncommon occurrence. Correct diagnosis is often difficult. Ultrasonography has become the primary radiological diagnostic tool, with a limited excretory urogram only necessary in complicated cases. Nephrolithiasis during pregnancy occurs more frequently during the later stages of gestation, in multiparas, and without a difference in laterality. Conservative management with bed rest, hydration and analgesia can result in spontaneous passage of most stones in gravidas. Past experience of several groups suggests that cystoscopy and/or surgery can usually be done safely when absolutely necessary. Pre-existing stone disease can increase the incidence of maternal urinary tract infections by 10-20%. The most common obstetric complications of stones during gestation is premature labour induced by renal colic. Most drugs normally used to treat stone disease are contraindicated in gestation. Known inhibitors of stone formation are present in gestation and may partially explain why the incidence of stones is not increased in this hypercalciuric state. PMID:7924013

  18. Ghrelin Receptors in Non-Mammalian Vertebrates

    PubMed Central

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2012-01-01

    The growth hormone secretagogue-receptor (GHS-R) was discovered in humans and pigs in 1996. The endogenous ligand, ghrelin, was discovered 3 years later, in 1999, and our understanding of the physiological significance of the ghrelin system in vertebrates has grown steadily since then. Although the ghrelin system in non-mammalian vertebrates is a subject of great interest, protein sequence data for the receptor in non-mammalian vertebrates has been limited until recently, and related biological information has not been well organized. In this review, we summarize current information related to the ghrelin receptor in non-mammalian vertebrates. PMID:23882259

  19. Novel expression and functional role of ghrelin in chicken ovary.

    PubMed

    Sirotkin, A V; Grossmann, R; María-Peon, M T; Roa, J; Tena-Sempere, M; Klein, S

    2006-09-26

    Ghrelin has recently emerged as pleiotropic regulator of a wide array of endocrine and non-endocrine functions. The former likely includes the control of gonadal function, as expression of ghrelin and its putative receptor, the GH secretagogue receptor type 1a (GHS-R1a), has been described in mammalian gonads, and direct effects of ghrelin in the control of testicular secretion and cell proliferation have been reported. Yet, the expression and/or functional role of ghrelin in gonads from non-mammalian species remain to be analyzed. The present study aimed to evaluate the expression of ghrelin and GHS-R genes in the chicken ovary, and to assess the potential involvement of ghrelin in the direct control of chick ovarian function. To this end, RT-PCR assays for ghrelin and GHS-R1a mRNAs were performed in ovarian tissue, and cultures of chicken ovarian cells were conducted in the presence of increasing doses (1, 10 or 100 ng/ml) of the ghrelin analog, ghrelin 1-18. Our results demonstrate that both ghrelin and GHS-R1a mRNAs are expressed in chick ovarian tissue. Moreover, challenge of ovarian granulosa cells with ghrelin 1-18 was able to induce markers of proliferation (i.e. expression of both PCNA and cyclin), and to modulate markers of apoptosis (i.e. decreased expression of caspase-3, bax, bcl-2 and TUNEL-positive cells). Moreover, ghrelin 1-18 increased the expression of PCNA, cyclin, bax and p53 in cultures of ovarian follicular fragments, where it also stimulated the release of progesterone, estradiol, arginine-vasotocin (AVT) and IGF-I, but not of testosterone. In conclusion, our study provides novel evidence for the gonadal expression of the genes encoding ghrelin and its cognate receptor in a non-mammalian species, i.e. the chicken ovary, and unravels the potential involvement of this newly discovered molecule in the control of key gonadal functions in the chick, such as proliferation, apoptosis, and hormone release. PMID:16891055

  20. Is increasing MB ratio a positive indicator of declining leprosy?

    PubMed

    Kumar, Anil; Girdhar, B K

    2006-03-01

    In recent years, an increasing MB ratio-trend has been seen in most state reported leprosy data in India and elsewhere. The programme of leprosy all over the world has been integrated with general health system (GHS). This has given rise to gross under reporting of leprosy cases and increasing MB ratio. This paper examines this critical issue and attempt to find out the causes of this trend. The findings suggest clearly that increasing MB ratio is the result of early cases of leprosy being missed out. This can be to the extent of 73% when MB ratio is reached to 47.5%. PMID:17370687

  1. Identification and functional characterization of two alternatively spliced growth hormone secretagogue receptor transcripts from the pituitary of black seabream Acanthopagrus schlegeli.

    PubMed

    Chan, Chi-Bun; Cheng, Christopher H K

    2004-02-12

    Two cDNA transcripts, namely sbGHSR-1a and sbGHSR-1b, for growth hormone secretagogue receptor (GHSR), were identified from the seabream pituitary. When translated, the sbGHSR-1a encodes for a protein of 385 amino acids (aa) with seven putative transmembrane domains and the sbGHSR-1b contains 295 aa with five putative transmembrane domains. Tissue distribution studies indicated that the two receptors are mainly expressed in the central nervous system of the fish. The sbGHSR-1a transcript has the highest expression level in the pituitary. The sbGHSR-1b transcript, on the other hand, has the highest expression level in the telencephalon. Genomic Southern analysis indicated that there is a single gene for GHSR in the seabream genome. Comparison of the cDNA sequences of sbGHSR1a and sbGHSR1b with the seabream genomic sequence indicated that the presence of the two receptor transcripts is a result of alternative splicing of the single GHSR gene. The two receptor cDNAs were expressed in cultured eukaryotic cells for functional analyses. A variety of structurally diverse growth hormone secretogogues (GHS), including the peptide GHS (GHRP-6 and ghrelin), the benzolactam GHS (L692,585) and the spiropiperidine GHS (L163,255), were able to trigger an elevation of intracellular Ca(2+) ion concentration in HEK293 cells expressing sbGHSR-1a, but not in cells expressing sbGHSR-1b. Microphysiometry revealed that an increase in extracellular acidification rate (EAR) could be detected in CHO cells expressing the sbGHSR-1a receptor when stimulated with GHRP-6. On the contrary, CHO cells expressing the sbGHSR-1b receptor registered no detectable EAR changes. However, when sbGHSR-1b was co-expressed with sbGHSR-1a in HEK293 cells, the signal transduction capacity of sbGHSR-1a was attenuated. This is the first report on the identification of a GHSR-1b transcript from species other than mammals and the demonstration that receptor interaction might provide a possible explanation for the

  2. Development of a new device for precise timing

    NASA Astrophysics Data System (ADS)

    Hayamizu, Tsutomu; Soma, Mitsuru; Geshiro, Hiroyuki; Hashiguchi, Takashi

    2001-09-01

    The Japanese shortwave time signals JJY were shut down on 2001 March 31st. Astronomers who have been using JJY are seeking alternative methods for precise timing. We designed equipment, called the GHS Clock, that can be used with inexpensive GPS receivers to produce both an LED flash and a pip sound at the beginning of each second. According to the GPS receiver manual, this device has an accuracy better than 500 nano-seconds, and our tests show that it usually has an accuracy better than 200 nano-seconds.

  3. Measurement of Clathrate Hydrate Thermodynamic Stability in the Presence of Ammonia

    NASA Technical Reports Server (NTRS)

    Dunham, Marc

    2012-01-01

    There is a lack of data available for the stability of clathrate hydrates in the presence of ammonia for low-to-moderate pressures in the 0-10 MPa range. Providing such data will allow for a better understanding of natural mass transfer processes on celestial bodies like Titan and Enceladus, on which destabilization of clathrates may be responsible for replenishment of gases in the atmosphere. The experimental process utilizes a custom-built gas handling system (GHS) and a cryogenic calorimeter to allow for the efficient testing of samples under varying pressures and gas species.

  4. Strain distribution across the Greater Himalayan Sequence, Annapurna-Dhaulagiri, Nepal

    NASA Astrophysics Data System (ADS)

    Parsons, A. J.; Phillips, R. J.; Lloyd, G. E.; Searle, M. P.; Law, R. D.; Ferre, E. C.

    2012-12-01

    The Himalaya provides a unique natural laboratory to observe orogenic processes at a variety of temporal and spatial scales. The potential for these observations to serve as kinematic and geodynamic analogues for past orogens relies on a robust understanding of the evolution of the Himalayan mountain belt. Field structural data, supported by thermobaromety, geochronology and thermodynamic modelling, generally support a channel flow model in which a partially molten middle crust layer, the Greater Himalaya Sequence (GHS), was extruded to the south during Miocene time bounded by high-strain ductile shears above and below. This model suggests that the GHS, the metamorphic core of the orogen, represents an exhumed, rheologically weak, mid-crustal channel. Lateral flow of the channel was driven southwards by the lithostatic pressure gradient between the 5 km high Tibetan plateau and the < 1 km elevation and average crustal thickness of the Indian plate. The vertical distribution of strain across the GHS is one element of the channel flow hypothesis that is yet to be fully investigated. This project considers this issue by examining specifically, the vertical distribution and evolution of strain across the GHS and bounding units. A variety of techniques, that include SEM electron back scattered diffraction (EBSD) and anisotropy of magnetic susceptibility (AMS) will be used to analyse samples collected during recent field work in the Annapurna-Dhaulagiri Himal, central Nepal. These samples were collected from two transects along the Modi Khola valley and the Kali Gandaki valley. EBSD will be used to measure the lattice preferred orientation of individual mineral phases of these samples, providing a proxy for strain and valuable information on deformation mechanisms. Given specific magnetic carriers, AMS will be used to provide a proxy for finite strain in samples that are too heterogeneous for EBSD. Combined EBSD and AMS data will be augmented by additional strain and

  5. Identifying the ionically bound cell wall and intracellular glycoside hydrolases in late growth stage Arabidopsis stems: implications for the genetic engineering of bioenergy crops

    PubMed Central

    Wei, Hui; Brunecky, Roman; Donohoe, Bryon S.; Ding, Shi-You; Ciesielski, Peter N.; Yang, Shihui; Tucker, Melvin P.; Himmel, Michael E.

    2015-01-01

    Identifying the cell wall-ionically bound glycoside hydrolases (GHs) in Arabidopsis stems is important for understanding the regulation of cell wall integrity. For cell wall proteomics studies, the preparation of clean cell wall fractions is a challenge since cell walls constitute an open compartment, which is more likely to contain a mixture of intracellular and extracellular proteins due to cell leakage at the late growth stage. Here, we utilize a CaCl2-extraction procedure to isolate non-structural proteins from Arabidopsis whole stems, followed by the in-solution and in-gel digestion methods coupled with Nano-LC-MS/MS, bioinformatics and literature analyses. This has led to the identification of 75 proteins identified using the in-solution method and 236 proteins identified by the in-gel method, among which about 10% of proteins predicted to be secreted. Together, eight cell wall proteins, namely AT1G75040, AT5G26000, AT3G57260, AT4G21650, AT3G52960, AT3G49120, AT5G49360, and AT3G14067, were identified by the in-solution method; among them, three were the GHs (AT5G26000, myrosinase 1, GH1; AT3G57260, β-1,3-glucanase 2, GH17; AT5G49360, bifunctional XYL 1/α-L-arabinofuranosidase, GH3). Moreover, four more GHs: AT4G30270 (xyloglucan endotransferase, GH16), AT1G68560 (bifunctional α-l-arabinofuranosidase/XYL, GH31), AT1G12240 (invertase, GH32) and AT2G28470 (β-galactosidase 8, GH35), were identified by the in-gel solution method only. Notably, more than half of above identified GHs are xylan- or hemicellulose-modifying enzymes, and will likely have an impact on cellulose accessibility, which is a critical factor for downstream enzymatic hydrolysis of plant tissues for biofuels production. The implications of these cell wall proteins identified at the late growth stage for the genetic engineering of bioenergy crops are discussed. PMID:26029221

  6. Identifying the ionically bound cell wall and intracellular glycoside hydrolases in late growth stage Arabidopsis stems: Implications for the genetic engineering of bioenergy crops

    SciTech Connect

    Wei, Hui; Brunecky, Roman; Donohoe, Bryon S.; Ding, Shi -You; Ciesielski, Peter N.; Yang, Shihui; Tucker, Melvin P.; Himmel, Michael E.

    2015-05-13

    Identifying the cell wall-ionically bound glycoside hydrolases (GHs) in Arabidopsis stems is important for understanding the regulation of cell wall integrity. For cell wall proteomics studies, the preparation of clean cell wall fractions is a challenge since cell walls constitute an open compartment, which is more likely to contain a mixture of intracellular and extracellular proteins due to cell leakage at the late growth stage. Here, for this study, we utilize a CaCl2-extraction procedure to isolate non-structural proteins from Arabidopsis whole stems, followed by the in-solution and in-gel digestion methods coupled with Nano-LC-MS/MS, bioinformatics and literature analyses. This has led to the identification of 75 proteins identified using the in-solution method and 236 proteins identified by the in-gel method, among which about 10% of proteins predicted to be secreted. Together, eight cell wall proteins, namely AT1G75040, AT5G26000, AT3G57260, AT4G21650, AT3G52960, AT3G49120, AT5G49360, and AT3G14067, were identified by the in-solution method; among them, three were the GHs (AT5G26000, myrosinase 1, GH1; AT3G57260, β-1,3-glucanase 2, GH17; AT5G49360, bifunctional XYL 1/α-L-arabinofuranosidase, GH3). Moreover, four more GHs: AT4G30270 (xyloglucan endotransferase, GH16), AT1G68560 (bifunctional α-l-arabinofuranosidase/XYL, GH31), AT1G12240 (invertase, GH32) and AT2G28470 (β-galactosidase 8, GH35), were identified by the in-gel solution method only. Notably, more than half of above identified GHs are xylan- or hemicellulose-modifying enzymes, and will likely have an impact on cellulose accessibility, which is a critical factor for downstream enzymatic hydrolysis of plant tissues for biofuels production. Finally, the implications of these cell wall proteins identified at the late growth stage for the genetic engineering of bioenergy crops are discussed.

  7. Identifying the ionically bound cell wall and intracellular glycoside hydrolases in late growth stage Arabidopsis stems: Implications for the genetic engineering of bioenergy crops

    DOE PAGESBeta

    Wei, Hui; Brunecky, Roman; Donohoe, Bryon S.; Ding, Shi -You; Ciesielski, Peter N.; Yang, Shihui; Tucker, Melvin P.; Himmel, Michael E.

    2015-05-13

    Identifying the cell wall-ionically bound glycoside hydrolases (GHs) in Arabidopsis stems is important for understanding the regulation of cell wall integrity. For cell wall proteomics studies, the preparation of clean cell wall fractions is a challenge since cell walls constitute an open compartment, which is more likely to contain a mixture of intracellular and extracellular proteins due to cell leakage at the late growth stage. Here, for this study, we utilize a CaCl2-extraction procedure to isolate non-structural proteins from Arabidopsis whole stems, followed by the in-solution and in-gel digestion methods coupled with Nano-LC-MS/MS, bioinformatics and literature analyses. This has ledmore » to the identification of 75 proteins identified using the in-solution method and 236 proteins identified by the in-gel method, among which about 10% of proteins predicted to be secreted. Together, eight cell wall proteins, namely AT1G75040, AT5G26000, AT3G57260, AT4G21650, AT3G52960, AT3G49120, AT5G49360, and AT3G14067, were identified by the in-solution method; among them, three were the GHs (AT5G26000, myrosinase 1, GH1; AT3G57260, β-1,3-glucanase 2, GH17; AT5G49360, bifunctional XYL 1/α-L-arabinofuranosidase, GH3). Moreover, four more GHs: AT4G30270 (xyloglucan endotransferase, GH16), AT1G68560 (bifunctional α-l-arabinofuranosidase/XYL, GH31), AT1G12240 (invertase, GH32) and AT2G28470 (β-galactosidase 8, GH35), were identified by the in-gel solution method only. Notably, more than half of above identified GHs are xylan- or hemicellulose-modifying enzymes, and will likely have an impact on cellulose accessibility, which is a critical factor for downstream enzymatic hydrolysis of plant tissues for biofuels production. Finally, the implications of these cell wall proteins identified at the late growth stage for the genetic engineering of bioenergy crops are discussed.« less

  8. Ghrelin Decreases Firing Activity of Gonadotropin-Releasing Hormone (GnRH) Neurons in an Estrous Cycle and Endocannabinoid Signaling Dependent Manner

    PubMed Central

    Farkas, Imre; Vastagh, Csaba; Sárvári, Miklós; Liposits, Zsolt

    2013-01-01

    The orexigenic peptide, ghrelin is known to influence function of GnRH neurons, however, the direct effects of the hormone upon these neurons have not been explored, yet. The present study was undertaken to reveal expression of growth hormone secretagogue receptor (GHS-R) in GnRH neurons and elucidate the mechanisms of ghrelin actions upon them. Ca2+-imaging revealed a ghrelin-triggered increase of the Ca2+-content in GT1-7 neurons kept in a steroid-free medium, which was abolished by GHS-R-antagonist JMV2959 (10µM) suggesting direct action of ghrelin. Estradiol (1nM) eliminated the ghrelin-evoked rise of Ca2+-content, indicating the estradiol dependency of the process. Expression of GHS-R mRNA was then confirmed in GnRH-GFP neurons of transgenic mice by single cell RT-PCR. Firing rate and burst frequency of GnRH-GFP neurons were lower in metestrous than proestrous mice. Ghrelin (40nM-4μM) administration resulted in a decreased firing rate and burst frequency of GnRH neurons in metestrous, but not in proestrous mice. Ghrelin also decreased the firing rate of GnRH neurons in males. The ghrelin-evoked alterations of the firing parameters were prevented by JMV2959, supporting the receptor-specific actions of ghrelin on GnRH neurons. In metestrous mice, ghrelin decreased the frequency of GABAergic mPSCs in GnRH neurons. Effects of ghrelin were abolished by the cannabinoid receptor type-1 (CB1) antagonist AM251 (1µM) and the intracellularly applied DAG-lipase inhibitor THL (10µM), indicating the involvement of retrograde endocannabinoid signaling. These findings demonstrate that ghrelin exerts direct regulatory effects on GnRH neurons via GHS-R, and modulates the firing of GnRH neurons in an ovarian-cycle and endocannabinoid dependent manner. PMID:24124622

  9. The Formation of Urinary Calculi

    PubMed Central

    Joly, J. Swift

    1928-01-01

    Normal urine is always grossly super-saturated in regard to the stone-forming salts, which are kept in solution by the action of the colloids. This action is best explained by the theory of adsorption. The amount of the stone-forming salts which can be held in solution depends on the surface area of the colloid, and therefore on its state of subdivision. Precipitation of these salts is due to failure of the colloid to hold them in solution. It may be due to an insufficient quantity, but is more probably due to coagulation of the colloid. When precipitation occurs in the urinary passages, the crystals are usually retained in the lower calyx of the kidney. A crystalline deposit tends to grow into crystalline concretions under the action of surface energy, thus forming true primary calculi. Stones of this type soon irritate the wall of the cavity in which they are contained and cause a reactionary exudate. The laminated stone is formed by continued deposition of crystals, coupled with rhythmic precipitation of a foreign colloid derived from the exudate. Stones originating in infected media are formed in a similar manner. PMID:19986433

  10. Effect of renal insufficiency on stone recurrence in patients with urolithiasis.

    PubMed

    Kang, Ho Won; Seo, Sung Phil; Kim, Won Tae; Kim, Yong-June; Yun, Seok-Joong; Lee, Sang-Cheol; Kim, Wun-Jae

    2014-08-01

    The study was designed to assess the relationship between glomerular filtration rate (GFR) and urinary stone-forming constituents, and to assess the effect of renal insufficiency on stone recurrence risk in first stone formers (SF). Baseline serum creatinine levels were obtained, and renal insufficiency was defined as creatinine clearance ≤60 mL/min (Cockroft-Gault). This retrospective case-control study consists of 342 first SF; 171 SF with normal renal function were selected with 1:1 propensity scores matched to 171 SF with renal insufficiency. Urinary metabolic evaluation was compared to renal function. GFR was positively correlated with urinary calcium, uric acid, and citrate excretion. Subjects with renal insufficiency had significantly lower urinary calcium, uric acid, and citrate excretion than those with normal renal function, but not urine volume. With regard to urinary metabolic abnormalities, similar results were obtained. SF with renal insufficiency had lower calcium oxalate supersaturation indexes and stone recurrence rates than SF with normal renal function. Kaplan-Meier curves showed similar results. In conclusion, GFR correlates positively with urinary excretion of stone-forming constituents in SF. This finding implies that renal insufficiency is not a risk factor for stone recurrence. PMID:25120325

  11. Renal stone risk assessment during Space Shuttle flights

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Pietrzyk, R. A.; Pak, C. Y.

    1997-01-01

    PURPOSE: The metabolic and environmental factors influencing renal stone formation before, during, and after Space Shuttle flights were assessed. We established the contributing roles of dietary factors in relationship to the urinary risk factors associated with renal stone formation. MATERIALS AND METHODS: 24-hr. urine samples were collected prior to, during space flight, and following landing. Urinary and dietary factors associated with renal stone formation were analyzed and the relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were calculated. RESULTS: Urinary composition changed during flight to favor the crystallization of calcium-forming salts. Factors that contributed to increased potential for stone formation during space flight were significant reductions in urinary pH and increases in urinary calcium. Urinary output and citrate, a potent inhibitor of calcium-containing stones, were slightly reduced during space flight. Dietary intakes were significantly reduced for a number of variables, including fluid, energy, protein, potassium, phosphorus and magnesium. CONCLUSIONS: This is the first in-flight characterization of the renal stone forming potential in astronauts. With the examination of urinary components and nutritional factors, it was possible to determine the factors that contributed to increased risk or protected from risk. In spite of the protective components, the negative contributions to renal stone risk predominated and resulted in a urinary environment that favored the supersaturation of stone-forming salts. Dietary and pharmacologic therapies need to be assessed to minimize the potential for renal stone formation in astronauts during/after space flight.

  12. New applications of fiber-optic IR spectroscopy in urologic practice

    NASA Astrophysics Data System (ADS)

    Cytron, Shmuel E.; Kravchick, Sergey; Sela, Ben-Ami; Shulzinger, Evgeny; Vasserman, Irena; Raichlin, Yosef; Katzir, Abraham

    2002-03-01

    The objective of this work was to use infrared (IR) fiberoptic spectroscopy for the analysis of urinary salts. Urine samples were obtained (with no sample preparation) from two groups of patients: 24 stone forming patients, after shock wave lithotripsy, and 24 normal subjects of similar ages. IR absorption measurements were performed in real time, using Fiberoptic Evanescent Wave Spectroscopy system, based on IR transmitting silver halide fibers. The absorption data were compared with the IR spectra of aqueous solutions with known concentrations of known urinary salts. The results were then used for the study of the chemical composition of salts in urine samples and for a quantitative analysis of the concentration of these salts. We established the composition of the stones in 20 of the 24 stone forming patients, based on the characteristic absorption peaks for oxalates, carbonates, urates and phosphates observed in their urinary samples. We also determined the concentrations of these salts in the urine samples with average error of 20 percent.

  13. Urine risk factors in children with calcium kidney stones and their siblings.

    PubMed

    Bergsland, Kristin J; Coe, Fredric L; White, Mark D; Erhard, Michael J; DeFoor, William R; Mahan, John D; Schwaderer, Andrew L; Asplin, John R

    2012-06-01

    Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence, treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone-forming children, we compared chemical measurements and the crystallization properties of 24-h urine collections from 129 stone formers matched to 105 non-stone-forming siblings and 183 normal, healthy children with no family history of stones, all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones. PMID:22358148

  14. Urine risk factors in children with calcium kidney stones and their siblings

    PubMed Central

    Bergsland, Kristin J.; Coe, Fredric L.; White, Mark D.; Erhard, Michael J.; DeFoor, William R.; Mahan, John D.; Schwaderer, Andrew L.; Asplin, John R.

    2012-01-01

    Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone forming children, we compared chemical measurements and the crystallization properties of 24-hour urine collections from 129 stone formers matched to 105 non-stone forming siblings and 183 normal, healthy children with no family history of stones; all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones. PMID:22358148

  15. Mathematical model to estimate risk of calcium-containing renal stones

    NASA Technical Reports Server (NTRS)

    Pietrzyk, R. A.; Feiveson, A. H.; Whitson, P. A.

    1999-01-01

    BACKGROUND/AIMS: Astronauts exposed to microgravity during the course of spaceflight undergo physiologic changes that alter the urinary environment so as to increase the risk of renal stone formation. This study was undertaken to identify a simple method with which to evaluate the potential risk of renal stone development during spaceflight. METHOD: We used a large database of urinary risk factors obtained from 323 astronauts before and after spaceflight to generate a mathematical model with which to predict the urinary supersaturation of calcium stone forming salts. RESULT: This model, which involves the fewest possible analytical variables (urinary calcium, citrate, oxalate, phosphorus, and total volume), reliably and accurately predicted the urinary supersaturation of the calcium stone forming salts when compared to results obtained from a group of 6 astronauts who collected urine during flight. CONCLUSIONS: The use of this model will simplify both routine medical monitoring during spaceflight as well as the evaluation of countermeasures designed to minimize renal stone development. This model also can be used for Earth-based applications in which access to analytical resources is limited.

  16. Clinical, demographic, and laboratory characteristics of children with nephrolithiasis.

    PubMed

    Sas, David J; Becton, Lauren J; Tutman, Jeffrey; Lindsay, Laura A; Wahlquist, Amy H

    2016-06-01

    While the incidence of pediatric kidney stones appears to be increasing, little is known about the demographic, clinical, laboratory, imaging, and management variables in this patient population. We sought to describe various characteristics of our stone-forming pediatric population. To that end, we retrospectively reviewed the charts of pediatric patients with nephrolithiasis confirmed by imaging. Data were collected on multiple variables from each patient and analyzed for trends. For body mass index (BMI) controls, data from the general pediatrics population similar to our nephrolithiasis population were used. Data on 155 pediatric nephrolithiasis patients were analyzed. Of the 54 calculi available for analysis, 98 % were calcium based. Low urine volume, elevated supersaturation of calcium phosphate, elevated supersaturation of calcium oxalate, and hypercalciuria were the most commonly identified abnormalities on analysis of 24-h urine collections. Our stone-forming population did not have a higher BMI than our general pediatrics population, making it unlikely that obesity is a risk factor for nephrolithiasis in children. More girls presented with their first stone during adolescence, suggesting a role for reproductive hormones contributing to stone risk, while boys tended to present more commonly at a younger age, though this did not reach statistical significance. These intriguing findings warrant further investigation. PMID:26467033

  17. Gene-targeted metagenomic analysis of glucan-branching enzyme gene profiles among human and animal fecal microbiota

    PubMed Central

    Lee, Sunghee; Cantarel, Brandi; Henrissat, Bernard; Gevers, Dirk; Birren, Bruce W; Huttenhower, Curtis; Ko, GwangPyo

    2014-01-01

    Glycoside hydrolases (GHs), the enzymes that breakdown complex carbohydrates, are a highly diversified class of key enzymes associated with the gut microbiota and its metabolic functions. To learn more about the diversity of GHs and their potential role in a variety of gut microbiomes, we used a combination of 16S, metagenomic and targeted amplicon sequencing data to study one of these enzyme families in detail. Specifically, we employed a functional gene-targeted metagenomic approach to the 1-4-α-glucan-branching enzyme (gBE) gene in the gut microbiomes of four host species (human, chicken, cow and pig). The characteristics of operational taxonomic units (OTUs) and operational glucan-branching units (OGBUs) were distinctive in each of hosts. Human and pig were most similar in OTUs profiles while maintaining distinct OGBU profiles. Interestingly, the phylogenetic profiles identified from 16S and gBE gene sequences differed, suggesting the presence of different gBE genes in the same OTU across different vertebrate hosts. Our data suggest that gene-targeted metagenomic analysis is useful for an in-depth understanding of the diversity of a particular gene of interest. Specific carbohydrate metabolic genes appear to be carried by distinct OTUs in different individual hosts and among different vertebrate species' microbiomes, the characteristics of which differ according to host genetic background and/or diet. PMID:24108330

  18. Recombinant protein production facility for fungal biomass-degrading enzymes using the yeast Pichia pastoris

    PubMed Central

    Haon, Mireille; Grisel, Sacha; Navarro, David; Gruet, Antoine; Berrin, Jean-Guy; Bignon, Christophe

    2015-01-01

    Filamentous fungi are the predominant source of lignocellulolytic enzymes used in industry for the transformation of plant biomass into high-value molecules and biofuels. The rapidity with which new fungal genomic and post-genomic data are being produced is vastly outpacing functional studies. This underscores the critical need for developing platforms dedicated to the recombinant expression of enzymes lacking confident functional annotation, a prerequisite to their functional and structural study. In the last decade, the yeast Pichia pastoris has become increasingly popular as a host for the production of fungal biomass-degrading enzymes, and particularly carbohydrate-active enzymes (CAZymes). This study aimed at setting-up a platform to easily and quickly screen the extracellular expression of biomass-degrading enzymes in P. pastoris. We first used three fungal glycoside hydrolases (GHs) that we previously expressed using the protocol devised by Invitrogen to try different modifications of the original protocol. Considering the gain in time and convenience provided by the new protocol, we used it as basis to set-up the facility and produce a suite of fungal CAZymes (GHs, carbohydrate esterases and auxiliary activity enzyme families) out of which more than 70% were successfully expressed. The platform tasks range from gene cloning to automated protein purifications and activity tests, and is open to the CAZyme users’ community. PMID:26441929

  19. Acute Toxicity Comparison of Single-Walled Carbon Nanotubes in Various Freshwater Organisms

    PubMed Central

    Chung, Young Shin; Kim, Tae Gyu; Kim, Jin Kwon; Lee, Ji Hyun; Lee, Yong Hwa; Kang, Sung Wook

    2015-01-01

    While the commercialization of single-walled carbon nanotubes (SWCNTs) is rapidly expanding, the environmental impact of this nanomaterial is not well understood. Therefore, the present study evaluates the acute aquatic toxicity of SWCNTs towards two freshwater microalgae (Raphidocelis subcapitata and Chlorella vulgaris), a microcrustacean (Daphnia magna), and a fish (Oryzias latipes) based on OECD test guidelines (201, 202, and 203). According to the results, the SWCNTs inhibited the growth of the algae R. subcapitata and C. vulgaris with a median effective concentration (EC50) of 29.99 and 30.96 mg/L, respectively, representing “acute category 3” in the Globally Harmonized System (GHS) of classification and labeling of chemicals. Meanwhile, the acute toxicity test using O. latipes and D. magna did not show any mortality/immobilizing effects up to a concentration of 100.00 mg/L SWCNTs, indicating no hazard category in the GHS classification. In conclusion, SWCNTs were found to induce acute ecotoxicity in freshwater microalgae, yet not in D. magna and medaka fish. PMID:25654094

  20. Ghrelin, food intake, and botanical extracts: A Review

    PubMed Central

    Rezaie, Peyman; Mazidi, Mohsen; Nematy, Mohsen

    2015-01-01

    A kind of growth hormone secretagogue (GHS), ghrelin, was first isolated from the rat stomach and plays a major role in the activation of the growth hormone secretagogue receptor 1a (GHS-R1a) resulting the release of growth hormone (GH). The preproghrelin gene is placed on chromosome 3, at locus 3p25 –2 in humans and constitutes five exons and three introns. Ghrelin is most plentifully expressed in particular cells in the oxyntic glands of the gastric epithelium, initially named X/A-like cells. Almost 60-70% of circulating ghrelin is secreted by the stomach. Plasma ghrelin concentration alters throughout the day. Ghrelin has been suggested to act as a meal initiator because of its appetite-stimulating influences in free feeding rats in short period. In addition to ghrelin’s function as a meal motivator, it seems to contribute in long-term energy balance and nutritional status. In addition, many studies have been carried out in order to investigate the effects of natural and medicinal plants and botanical extracts on appetite, food intake, energy hemostasis, and the level of related hormones including ghrelin. Due to the importance of ghrelin in nutritional and medical sciences, this review was performed to understand new aspects of this hormone’s function. PMID:26445708

  1. Molten sodium-induced graphitization towards highly crystalline and hierarchical porous graphene frameworks

    NASA Astrophysics Data System (ADS)

    Wang, Huanwen; Zhang, Yu; Wu, Xing-Long; Fan, Haosen; Luo, Zhong-Zhen; Madhavi, Srinivasan; Yan, Qingyu

    2015-09-01

    Mass production of high quality graphene platelets has attracted considerable interest for potential applications in various fields. Nevertheless, in literature, the graphite oxide (GO)-derived graphene is always lacking high crystallinity and hierarchical porosity. Herein, we report a new molten sodium-induced graphitization for mass-fabricating highly crystalline and porous graphene sheets. The 3D graphene hydrogels (GHs) obtained from GO by the hydrothermal self-assembly are directly annealed in molten sodium at 800 °C. As a result, the D band intensity in Raman spectroscopy is reduced significantly, while 2D band intensity is increased prominently, which is a typical characteristic of highly crystalline graphene. More importantly, the resulting Na-GFs-800 sample exhibits increased surface area and narrow mesopore size distribution (∼3.6 nm). The excellent supercapacitive performance of Na-GFs-800 has been demonstrated in an organic symmetric system. Meanwhile, the possible interaction mechanism between molten sodium and GHs has been proposed in the text.

  2. A Trapped Covalent Intermediate of a Glycoside Hydrolase on the Pathway to Transglycosylation. Insights from Experiments and Quantum Mechanics/Molecular Mechanics Simulations.

    PubMed

    Raich, Lluís; Borodkin, Vladimir; Fang, Wenxia; Castro-López, Jorge; van Aalten, Daan M F; Hurtado-Guerrero, Ramón; Rovira, Carme

    2016-03-16

    The conversion of glycoside hydrolases (GHs) into transglycosylases (TGs), i.e., from enzymes that hydrolyze carbohydrates to enzymes that synthesize them, represents a promising solution for the large-scale synthesis of complex carbohydrates for biotechnological purposes. However, the lack of knowledge about the molecular details of transglycosylation hampers the rational design of TGs. Here we present the first crystallographic structure of a natural glycosyl-enzyme intermediate (GEI) of Saccharomyces cerevisiae Gas2 in complex with an acceptor substrate and demonstrate, by means of quantum mechanics/molecular mechanics metadynamics simulations, that it is tuned for transglycosylation (ΔG(⧧) = 12 kcal/mol). The 2-OH···nucleophile interaction is found to be essential for catalysis: its removal raises the free energy barrier significantly (11 and 16 kcal/mol for glycosylation and transglycosylation, respectively) and alters the conformational itinerary of the substrate (from (4)C1 → [(4)E](⧧) → (1,4)B/(4)E to (4)C1 → [(4)H3](⧧) → (4)C1). Our results suggest that changes in the interactions involving the 2-position could have an impact on the transglycosylation activity of several GHs. PMID:26859322

  3. 'Translational formative evaluation': critical in up-scaling public health programmes.

    PubMed

    O'Hara, Blythe J; Phongsavan, Philayrath; King, Lesley; Develin, Elizabeth; Milat, Andrew J; Eggins, Dianne; King, Elizabeth; Smith, Joanne; Bauman, Adrian E

    2014-03-01

    The process of generating evidence-based public health interventions is understood to include steps that define the issue, generate and test solutions in controlled settings, replicate and then disseminate more widely. However, to date models have not considered the types and scale of formative evaluation tasks that are needed to up-scale interventions, from efficacy to population-wide dissemination in the real world. In this paper, we propose that an additional stage of 'translational formative evaluation' is necessary for the translation of effectiveness evidence into wide-scale public health practice. We illustrate the utility of translational formative evaluation, through a case study of the Get Healthy Information and Coaching Service(®) (GHS), a population-based telephone service designed to assist adults change lifestyle-related behaviours. The additional translational formative evaluation steps comprised synthesis of efficacy studies, qualitative research with the wider target audience, environmental analysis and stakeholder consultation. They produced precise recommendations to refine GHS design and implementation. Translational formative evaluation is a necessary intermediate step, following efficacy studies and a precursor to population-wide implementation of public health programmes. PMID:23630131

  4. Recombinant protein production facility for fungal biomass-degrading enzymes using the yeast Pichia pastoris.

    PubMed

    Haon, Mireille; Grisel, Sacha; Navarro, David; Gruet, Antoine; Berrin, Jean-Guy; Bignon, Christophe

    2015-01-01

    Filamentous fungi are the predominant source of lignocellulolytic enzymes used in industry for the transformation of plant biomass into high-value molecules and biofuels. The rapidity with which new fungal genomic and post-genomic data are being produced is vastly outpacing functional studies. This underscores the critical need for developing platforms dedicated to the recombinant expression of enzymes lacking confident functional annotation, a prerequisite to their functional and structural study. In the last decade, the yeast Pichia pastoris has become increasingly popular as a host for the production of fungal biomass-degrading enzymes, and particularly carbohydrate-active enzymes (CAZymes). This study aimed at setting-up a platform to easily and quickly screen the extracellular expression of biomass-degrading enzymes in P. pastoris. We first used three fungal glycoside hydrolases (GHs) that we previously expressed using the protocol devised by Invitrogen to try different modifications of the original protocol. Considering the gain in time and convenience provided by the new protocol, we used it as basis to set-up the facility and produce a suite of fungal CAZymes (GHs, carbohydrate esterases and auxiliary activity enzyme families) out of which more than 70% were successfully expressed. The platform tasks range from gene cloning to automated protein purifications and activity tests, and is open to the CAZyme users' community. PMID:26441929

  5. Molecular evolution of GPCRs: Ghrelin/ghrelin receptors.

    PubMed

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2014-06-01

    After the discovery in 1996 of the GH secretagogue-receptor type-1a (GHS-R1a) as an orphan G-protein coupled receptor, many research groups attempted to identify the endogenous ligand. Finally, Kojima and colleagues successfully isolated the peptide ligand from rat stomach extracts, determined its structure, and named it ghrelin. The GHS-R1a is now accepted to be the ghrelin receptor. The existence of the ghrelin system has been demonstrated in many animal classes through biochemical and molecular biological strategies as well as through genome projects. Our work, focused on identifying the ghrelin receptor and its ligand ghrelin in laboratory animals, particularly nonmammalian vertebrates, has provided new insights into the molecular evolution of the ghrelin receptor. In mammals, it is assumed that the ghrelin receptor evolution is in line with the plate tectonics theory. In contrast, the evolution of the ghrelin receptor in nonmammalian vertebrates differs from that of mammals: multiplicity of the ghrelin receptor isoforms is observed in nonmammalian vertebrates only. This multiplicity is due to genome duplication and polyploidization events that particularly occurred in Teleostei. Furthermore, it is likely that the evolution of the ghrelin receptor is distinct from that of its ligand, ghrelin, because only one ghrelin isoform has been detected in all species examined so far. In this review, we summarize current knowledge related to the molecular evolution of the ghrelin receptor in mammalian and nonmammalian vertebrates. PMID:24353285

  6. Determination of growth hormone secretagogue pralmorelin (GHRP-2) and its metabolite in human urine by liquid chromatography/electrospray ionization tandem mass spectrometry.

    PubMed

    Okano, Masato; Sato, Mitsuhiko; Ikekita, Ayako; Kageyama, Shinji

    2010-07-30

    GHRP-2 (pralmorelin, D-Ala-D-(beta-naphthyl)-Ala-Ala-Trp-D-Phe-Lys-NH(2)), which belongs to a class of growth hormone secretagogue (GHS), is intravenously used to diagnose growth hormone (GH) deficiency. Because it may be misused in expectation of a growth-promoting effect by athletes, the illicit use of GHS by athletes has been prohibited by the World Anti-Doping Agency (WADA). Therefore, the mass spectrometric identification of urinary GHRP-2 and its metabolite D-Ala-D-(beta-naphthyl)-Ala-Ala-OH (AA-3) was studied using liquid chromatography/electrospray ionization tandem mass spectrometry for doping control purposes. The method consists of solid-phase extraction using stable-isotope-labeled GHRP-2 as an internal standard and subsequent ultra-performance liquid chromatography/tandem mass spectrometry, and the two target peptides were determined at urinary concentrations of 0.5-10 ng/mL. The recoveries ranged from 84 to 101%, and the assay precisions were calculated as 1.6-3.8% (intra-day) and 1.9-4.3% (inter-day). Intravenous administration of GHRP-2 in ten male volunteers was studied to demonstrate the applicability of the method. In all ten cases, unchanged GHRP-2 and its specific metabolite AA-3 were detected in urine. PMID:20552695

  7. StratBAM: A Discrete-Event Simulation Model to Support Strategic Hospital Bed Capacity Decisions.

    PubMed

    Devapriya, Priyantha; Strömblad, Christopher T B; Bailey, Matthew D; Frazier, Seth; Bulger, John; Kemberling, Sharon T; Wood, Kenneth E

    2015-10-01

    The ability to accurately measure and assess current and potential health care system capacities is an issue of local and national significance. Recent joint statements by the Institute of Medicine and the Agency for Healthcare Research and Quality have emphasized the need to apply industrial and systems engineering principles to improving health care quality and patient safety outcomes. To address this need, a decision support tool was developed for planning and budgeting of current and future bed capacity, and evaluating potential process improvement efforts. The Strategic Bed Analysis Model (StratBAM) is a discrete-event simulation model created after a thorough analysis of patient flow and data from Geisinger Health System's (GHS) electronic health records. Key inputs include: timing, quantity and category of patient arrivals and discharges; unit-level length of care; patient paths; and projected patient volume and length of stay. Key outputs include: admission wait time by arrival source and receiving unit, and occupancy rates. Electronic health records were used to estimate parameters for probability distributions and to build empirical distributions for unit-level length of care and for patient paths. Validation of the simulation model against GHS operational data confirmed its ability to model real-world data consistently and accurately. StratBAM was successfully used to evaluate the system impact of forecasted patient volumes and length of stay in terms of patient wait times, occupancy rates, and cost. The model is generalizable and can be appropriately scaled for larger and smaller health care settings. PMID:26310949

  8. Chemical hazards in the organisation.

    PubMed

    Winder, Chris

    2012-01-01

    The use of hazardous chemicals in organisations represents a substantial risk to occupational health, safety and the environment (OHSE). Organisational directors and managers have a responsibility to provide and maintain organisational management systems that manage these risks. The risk management approach of establishing organisational considerations, identifying chemical hazards (health and environmental), assessing and controlling risks and evaluating management activities has become the de facto means of managing organisational hazards in general and may be satisfactorily applied to the management of chemicals in the organisation. The Globally Harmonized System for the Classification and Labelling of Chemicals (GHS) is now at the forefront of major regulatory issues facing the chemicals manufacturing industry and downstream users of chemicals. The GHS offers one system for the classification of all dangerous, toxic and environmental (ecotoxic) effects of chemicals. Organisations should develop occupational health, safety and environment (OHSE) management systems which contain programs and procedures that contain systems for inventory control, hazard communication, competency training, risk assessment and control, transport and storage, monitoring and health surveillance, chemical emergencies (including accident investigation), waste minimisation and disposal, record keeping and management system review. PMID:22945564

  9. Ancient origin of placental expression in the growth hormone genes of anthropoid primates.

    PubMed

    Papper, Zack; Jameson, Natalie M; Romero, Roberto; Weckle, Amy L; Mittal, Pooja; Benirschke, Kurt; Santolaya-Forgas, Joaquin; Uddin, Monica; Haig, David; Goodman, Morris; Wildman, Derek E

    2009-10-01

    In anthropoid primates, growth hormone (GH) genes have undergone at least 2 independent locus expansions, one in platyrrhines (New World monkeys) and another in catarrhines (Old World monkeys and apes). In catarrhines, the GH cluster has a pituitary-expressed gene called GH1; the remaining GH genes include placental GHs and placental lactogens. Here, we provide cDNA sequence evidence that the platyrrhine GH cluster also includes at least 3 placenta expressed genes and phylogenetic evidence that placenta expressed anthropoid GH genes have undergone strong adaptive evolution, whereas pituitary-expressed GH genes have faced strict functional constraint. Our phylogenetic evidence also points to lineage-specific gene gain and loss in early placental mammalian evolution, with at least three copies of the GH gene present at the time of the last common ancestor (LCA) of primates, rodents, and laurasiatherians. Anthropoid primates and laurasiatherians share gene descendants of one of these three copies, whereas rodents and strepsirrhine primates each maintain a separate copy. Eight of the amino-acid replacements that occurred on the lineage leading to the LCA of extant anthropoids have been implicated in GH signaling at the maternal-fetal interface. Thus, placental expression of GH may have preceded the separate series of GH gene duplications that occurred in catarrhines and platyrrhines (i.e., the roles played by placenta-expressed GHs in human pregnancy may have a longer evolutionary history than previously appreciated). PMID:19805162

  10. Protective effects of ginseng leaf extract using enzymatic extraction against oxidative damage of UVA-irradiated human keratinocytes.

    PubMed

    Kim, Mi-Ryung; Lee, Hyun-Sun; Choi, Hyeon-Son; Kim, Sun Young; Park, Yooheon; Suh, Hyung Joo

    2014-06-01

    UVA is responsible for numerous biological effects on the skin, including premature aging characterized by wrinkles, leathery texture, and mottled pigmentation. The objective of this study was evaluating the protective effect of ginseng leaf extract prepared by Ultraflo L on skin from photodamage. Anti-wrinkle effect of ginseng leaf extract with or without Ultraflo L treatment were tested on human keratinocyte cells (HaCaT) irradiated with ultraviolet (UV) A. Ginseng leaves inhibited ROS generation, GHS depletion, and expression of MMP-2 and MMP-9 induced by UVA irradiation. The glutathione (GSH) content of the cells was significantly increased by over 25 μg mL(-1) of Ultraflo-treated extract (UTGL) as well as by over 100 μg mL(-1) of nonenzyme-treated extract (NEGL) compared to control. UTGL and NEGL treatments significantly decreased expression of metalloproteinase (MMP)-2 and 9 compared with control, but inhibitory effects of two groups on expression of MMPs were not significantly different. Overall, ULtraflo L-treated ginseng leaves inhibited ROS generation, GHS depletion, and expression of MMP-2 and MMP-9 in UVA photodamaged HaCat cells. From these results, enzyme-treated ginseng leaf extract has advantages over untreated ginseng leaves and have potential as a skin protective ingredient against UVA-induced photodamage. PMID:24736942

  11. Transitional change in rat fetal cell proliferation in response to ghrelin and des-acyl ghrelin during the last stage of pregnancy

    SciTech Connect

    Inoue, Yoshiyuki; Nakahara, Keiko; Kangawa, Kenji; Murakami, Noboru

    2010-03-12

    Expression of mRNA for the ghrelin receptor, GHS-R1a, was detected in various peripheral and central tissues of fetal rats, including skin, bone, heart, liver, gut, brain and spinal cord, on embryonic day (ED)15 and ED17. However, its expression in skin, bone, heart and liver, but not in gut, brain and spinal cord, became relatively weak on ED19 and disappeared after birth (ND2). Ghrelin and des-acyl ghrelin facilitated the proliferation of cultured fetal (ED17, 19), but not neonatal (ND2), skin cells. On the other hand, with regard to cells from the spinal cord and hypothalamus, the proliferative effect of ghrelin continued after birth, whereas the effect of des-acyl ghrelin on neurogenesis in these tissues was lost at the ED19 fetal and ND2 neonatal stages. Immunohistochemistry revealed that the cells in the hypothalamus induced to proliferate by ghrelin at the ND2 stage were positive for nestin and glial fibrillary acidic protein. These results suggest that in the period immediately prior to, and after birth, rat fetal cells showing proliferation in response to ghrelin and des-acyl ghrelin are at a transitional stage characterized by alteration of the expression of GHS-R1a and an undefined des-acyl ghrelin receptor, their responsiveness varying among different tissues.

  12. SWeRF—A Method for Estimating the Relevant Fine Particle Fraction in Bulk Materials for Classification and Labelling Purposes

    PubMed Central

    2014-01-01

    In accordance with the European regulation for classification, labelling and packaging of substances and mixtures (CLP) as well as the criteria as set out in the Globally Harmonized System (GHS), fine fraction of crystalline silica (CS) has been classified as a specific target organ toxicity, the specific organ in this case being the lung. Generic cut-off values for products containing a fine fraction of CS trigger the need for a method for the quantification of the fine fraction of CS in bulk materials. This article describes the so-called SWeRF method, the size-weighted relevant fine fraction. The SWeRF method combines the particle size distribution of a powder with probability factors from the EN 481 standard and allows the relevant fine fraction of a material to be calculated. The SWeRF method has been validated with a number of industrial minerals. This will enable manufacturers and blenders to apply the CLP and GHS criteria for the classification of mineral products containing RCS a fine fraction of CS. PMID:24389081

  13. Catestatin and GABAAR related feeding habits rely on dopamine, ghrelin plus leptin neuroreceptor expression variations.

    PubMed

    Mele, Maria; Iachetta, Giuseppina; Alò, Raffaella; Avolio, Ennio; Fazzari, Gilda; Carelli, Antonio; Laforgia, Vincenza; Canonaco, Marcello

    2016-04-01

    Catestatin (CST), an endogenously small sympathoinhibitory peptide is capable of interfering with the major cerebral neuroreceptor-blocking site, i.e. γ-aminobutyric acidA receptor (GABAAR) system especially in limbic brain areas that are involved with feeding behaviors. The GABAARergic-related effects seem to derive from its interaction with other molecular neuroreceptors such as dopaminergic, ghrelin and leptinergic. In this context, the present study aimed to investigate probable feeding responses (eating and drinking) induced by treatment with CST and the GABAAR antagonist bicucullin (BIC) alone or simultaneously (CST+BIC) in the Syrian hibernating hamster (Mesocricetus auratus) model. Hamsters that received these compounds via intracerebroventricular infusions displayed notable variations of feeding and drinking bouts. In particular, an anorexigenic response was evident following treatment with CST while BIC evoked a significant increase of eating and drinking behaviors. Surprisingly when both agents were given simultaneously, a predominating anorexigenic response was detected as shown by evident CST-dependent reduction of feeding bouts. Contextually such behaviors, especially those following the combined treatment were tightly correlated with the significantly increased cerebral dopamine receptor 1 (D1) plus reduced ghrelin receptor (GhsR) and leptin receptor (LepR) transcript levels. Overall, the anorexigenic effect of CST deriving from its tight interaction with GABAARs activity plus D1 and GhsR transcripts tends to propose these neuronal elements as pivotal factors responsible for feeding disorders. PMID:26875516

  14. The utility of scores in the decision to salvage or amputation in severely injured limbs

    PubMed Central

    Shanmuganathan, Rajasekaran

    2008-01-01

    The decision to amputate or salvage a severely injured limb can be very challenging to the trauma surgeon. A misjudgment will result in either an unnecessary amputation of a valuable limb or a secondary amputation after failed salvage. Numerous scores have been proposed to provide guidelines to the treating surgeon, the notable of which are Mangled extremity severity score (MESS); the predictive salvage index (PSI); the Limb Salvage Index (LSI); the Nerve Injury, Ischemia, Soft tissue injury, Skeletal injury, Shock and Age of patient (NISSSA) score; and the Hannover fracture scale-97 (HFS-97). These scores have all been designed to evaluate limbs with combined orthopaedic and vascular injuries and have a poor sensitivity and specificity in evaluating IIIB injuries. Recently the Ganga Hospital Score (GHS) has been proposed which is specifically designed to evaluate a IIIB injury. Another notable feature of GHS is that it offers guidelines in the choice of the appropriate reconstruction protocol. The basis of the commonly used scores with their utility have been discussed in this paper. PMID:19753223

  15. Acute toxicity comparison of single-walled carbon nanotubes in various freshwater organisms.

    PubMed

    Sohn, Eun Kyung; Chung, Young Shin; Johari, Seyed Ali; Kim, Tae Gyu; Kim, Jin Kwon; Lee, Ji Hyun; Lee, Yong Hwa; Kang, Sung Wook; Yu, Il Je

    2015-01-01

    While the commercialization of single-walled carbon nanotubes (SWCNTs) is rapidly expanding, the environmental impact of this nanomaterial is not well understood. Therefore, the present study evaluates the acute aquatic toxicity of SWCNTs towards two freshwater microalgae (Raphidocelis subcapitata and Chlorella vulgaris), a microcrustacean (Daphnia magna), and a fish (Oryzias latipes) based on OECD test guidelines (201, 202, and 203). According to the results, the SWCNTs inhibited the growth of the algae R. subcapitata and C. vulgaris with a median effective concentration (EC50) of 29.99 and 30.96 mg/L, respectively, representing "acute category 3" in the Globally Harmonized System (GHS) of classification and labeling of chemicals. Meanwhile, the acute toxicity test using O. latipes and D. magna did not show any mortality/immobilizing effects up to a concentration of 100.00 mg/L SWCNTs, indicating no hazard category in the GHS classification. In conclusion, SWCNTs were found to induce acute ecotoxicity in freshwater microalgae, yet not in D. magna and medaka fish. PMID:25654094

  16. A Novel Member of GH16 Family Derived from Sugarcane Soil Metagenome.

    PubMed

    Alvarez, Thabata Maria; Liberato, Marcelo Vizoná; Cairo, João Paulo L Franco; Paixão, Douglas A A; Campos, Bruna M; Ferreira, Marcel R; Almeida, Rodrigo F; Pereira, Isabela O; Bernardes, Amanda; Ematsu, Gabriela C G; Chinaglia, Mariana; Polikarpov, Igor; de Oliveira Neto, Mario; Squina, Fabio Marcio

    2015-09-01

    Glycoside hydrolases (GHs) are enzymes found in all living kingdoms that are involved in multiple physiological functions. Due to their multiple enzymatic activities, GHs are broadly applied in bioethanol, food, and paper industry. In order to increase the productivity of these industrial processes, a constant search for novel and efficient enzymes has been proved to be necessary. In this context, metagenomics is a powerful approach to achieve this demand. In the current study, we describe the discovery and characterization of a novel member of GH16 family derived from the sugarcane soil metagenome. The enzyme, named SCLam, has 286 amino acid residues and displays sequence homology and activity properties that resemble known laminarases. SCLam is active against barley beta-glucan, laminarin, and lichenan (72, 33, and 10 U mg(-1), respectively). The optimal reaction conditions were identified as 40 °C and pH 6.5. The low-resolution structure was determined using the small-angle X-ray scattering technique, revealing that SCLam is a monomer in solution with a radius of gyration equal to 19.6 Å. To the best of our knowledge, SCLam is the first nonspecific (1,3/1,3:1,4)-β-D-glucan endohydrolase (EC 3.2.1.6) recovered by metagenomic approach to be characterized. PMID:26242386

  17. Lignocellulose degradation mechanisms across the Tree of Life.

    PubMed

    Cragg, Simon M; Beckham, Gregg T; Bruce, Neil C; Bugg, Timothy D H; Distel, Daniel L; Dupree, Paul; Etxabe, Amaia Green; Goodell, Barry S; Jellison, Jody; McGeehan, John E; McQueen-Mason, Simon J; Schnorr, Kirk; Walton, Paul H; Watts, Joy E M; Zimmer, Martin

    2015-12-01

    Organisms use diverse mechanisms involving multiple complementary enzymes, particularly glycoside hydrolases (GHs), to deconstruct lignocellulose. Lytic polysaccharide monooxygenases (LPMOs) produced by bacteria and fungi facilitate deconstruction as does the Fenton chemistry of brown-rot fungi. Lignin depolymerisation is achieved by white-rot fungi and certain bacteria, using peroxidases and laccases. Meta-omics is now revealing the complexity of prokaryotic degradative activity in lignocellulose-rich environments. Protists from termite guts and some oomycetes produce multiple lignocellulolytic enzymes. Lignocellulose-consuming animals secrete some GHs, but most harbour a diverse enzyme-secreting gut microflora in a mutualism that is particularly complex in termites. Shipworms however, house GH-secreting and LPMO-secreting bacteria separate from the site of digestion and the isopod Limnoria relies on endogenous enzymes alone. The omics revolution is identifying many novel enzymes and paradigms for biomass deconstruction, but more emphasis on function is required, particularly for enzyme cocktails, in which LPMOs may play an important role. PMID:26583519

  18. U-Pb SHRIMP geochronology of leucogranites from the Greater Himalayan Sequence in Zanskar and from the Karakoram fault zone, NW India

    NASA Astrophysics Data System (ADS)

    Horton, F.; Sommerfeld, J.; Hassett, W. C.; Leech, M. L.

    2010-12-01

    New U-Pb SHRIMP ages have been obtained from the westernmost limb of the South Tibetan Detachment in northwest India, locally known as the Zanskar Shear Zone (ZSZ), and from the dextral strike-slip Karakoram fault zone. This research investigates the extent of mid-crustal anatexis and ductile exhumation of the Greater Himalaya Sequence (GHS) in the western Himalaya, and explores a possible relationship between Zanskar and Karakoram fault zone leucogranites. Zircon Hf isotope signatures, measured with laser ablation ICP-MS, identify potential sources of the anatectic leucogranites. Along the ZSZ, samples were collected from the Nun-Kun and Suru valleys in the west and from Haptal valley ~100 km to the southeast. Leucogranite from the lowest structurally-exposed GHS in Suru valley yields a monazite age of 19.2±0.4 Ma, which is significantly younger than the 25.1±0.6 Ma monazite age of a psammitic schist near the ZSZ. Monazites give an age of 20.7±0.4 Ma for a Haptal valley migmatite and an adjacent late-stage pegmatite dike in a small leucogranite pluton has monazite ages ranging from 25.9±1.3 to 19.0±0.9 Ma. While these ages suggest coeval leucogranite emplacement along the entire ZSZ, only leucogranites in the east yielded inherited monazite ages of ~470 Ma and ~450 Ma that are indicative of a Cambro-Ordovician pan-African source. The western segment of the ZSZ exhibits less extensional offset and leucocratic melts appear to have migrated further from migmatite source regions than in the east. These along-strike variations suggest that the structural transition from a compact shear zone in the east to dispersed extensional shear zones near Pensi La may represent the westernmost extent of ductile melt-facilitated GHS exhumation. Miocene leucogranite emplacement also occurred along the Karakoram fault, which raises the question of whether the fault served as a conduit for mid-crustal GHS melts. In Nubra Valley, a leucogranite from the Karakoram fault zone

  19. Geochronogy of leucogranites in Yadong region: constraints on the age of the South Tibetan Detachment System in central-eastern Himalaya

    NASA Astrophysics Data System (ADS)

    Liu, Zhi-Chao; Wu, Fu-Yuan; Ji, Wei-Qiang; Wang, Jian-Gang; Liu, Xiao-Chi

    2016-04-01

    The South Tibetan Detachment System (STDS) is a series of low-angle normal faults with an extension of more than 2000 km along strike of the Himalaya orogen (Burchfiel et al., 1992). It separates the high-grade rocks of the Greater Himalaya Sequence (GHS) from the generally low-grade metasedimentary rocks of Tethyan Himalaya Sequence (THS) above. Knowing the timing of deformations related to the STDS is critical to understanding the exhumation history of the Himalaya. In central-eastern Himalaya, the STDS is disrupted by a major northeast-trending fault zone that was referred as Yadong Cross Structure (YCS). Exposures of the STDS either side of the YCS have been well determined, and the cessation timing of shearing have been estimated prior to 22~16 Ma for the western section and younger than 12 Ma for the eastern section (see the review in Leloup et al., 2010). It suggests that the YCS is key region that corresponds to a major timing discontinuity. However, the exposure of STDS in Yadong region and its activity timing has not been well constrained. Field mapping of the Yadong region reveals that a klippen of Cambrian biotite schist, chlorite schist, calcischists and quartzite, and Ordovician limestones of the THS units was resting on garnet-sillimanite-plagioclase gneisses, augen granitic gneisses and migmatites of the GHS basement (China University of Geosciences, 2005, unpublished). Structural relationships indicate that the contact is a low-angle normal fault, which was termed as Yadong shear zone (Xu et al., 2013). We correlate the Yadong shear zone to the STDS following the broader convention that STDS is defined as the contact between the THS and GHS. There are two leucogranite plutons within the shear zone, the Dingga pluton to the north and the Gaowu pluton to the south. They intruded into both GHS and THS, with the main bodies are undeformed and isotropic. Furthermore, there are numbers of undeformed dykes crosscut the foliations of the country rocks

  20. Ultrastrucural Investigation of Crystal deposits in Npt2a knockout mice: Are they similar to Human Randall's plaques?

    PubMed Central

    Khan, Saeed R.; Canales, Benjamin K.

    2013-01-01

    Purpose Idiopathic calcium oxalate (CaOx) stones are suggested to develop attached to renal interstitial calcium phosphate (CaP) deposits, the Randall's plaques (RP), Sodium phosphate co-transporter (Npt2a) null mice are hypercalciuric, hyperphosphaturic, and produce tubular and interstitial CaP deposits. To determine if this mouse is suitable for RP investigations, we chronologically studied their location, structure, and composition. Materials and Methods Kidneys of Npt2a null mice of two days to a year old were examined by light, scanning (SEM) and transmission electron microscopy (TEM). Electron diffraction and energy dispersive x-ray microanalyses were performed to determine the mineral composition. Results Poorly crystalline biological apatite deposits were seen in lumens of collecting ducts. Deposits consisted of aggregates of approx 5μm diameter microspheres of concentrically organized needle or plate-like matrix rich crystals. Epithelium/ crystal interfaces were filled with membrane bound vesicles. Some tubules were completely occluded by crystals, occasionally lost their epithelium and crystals moved into the interstitium. Conclusions CaP crystals formed in tubular lumen and organized as microspheres. The aggregation of CaP crystals produced nuclei, which grew by the addition of crystals on periphery, eventually becoming large enough to occlude tubular lumen and obliterate tubular epithelium, leading to the relocation of microliths into interstitium. The pathogenesis of interstitial deposits of the Npt2a null mice appears different from that proposed for RP's. Since Npt2a null mice purge their renal crystal deposits, these mice may serve as a model to investigate elimination of crystal deposits seen in children and adults with nephrocalcinosis PMID:21784483

  1. Epigenetic Regulation of MicroRNAs Controlling CLDN14 Expression as a Mechanism for Renal Calcium Handling

    PubMed Central

    Gong, Yongfeng; Himmerkus, Nina; Plain, Allein; Bleich, Markus

    2015-01-01

    The kidney has a major role in extracellular calcium homeostasis. Multiple genetic linkage and association studies identified three tight junction genes from the kidney—claudin-14, -16, and -19—as critical for calcium imbalance diseases. Despite the compelling biologic evidence that the claudin-14/16/19 proteins form a regulated paracellular pathway for calcium reabsorption, approaches to regulate this transport pathway are largely unavailable, hindering the development of therapies to correct calcium transport abnormalities. Here, we report that treatment with histone deacetylase (HDAC) inhibitors downregulates renal CLDN14 mRNA and dramatically reduces urinary calcium excretion in mice. Furthermore, treatment of mice with HDAC inhibitors stimulated the transcription of renal microRNA-9 (miR-9) and miR-374 genes, which have been shown to repress the expression of claudin-14, the negative regulator of the paracellular pathway. With renal clearance and tubule perfusion techniques, we showed that HDAC inhibitors transiently increase the paracellular cation conductance in the thick ascending limb. Genetic ablation of claudin-14 or the use of a loop diuretic in mice abrogated HDAC inhibitor-induced hypocalciuria. The genetic mutations in the calcium-sensing receptor from patients with autosomal dominant hypocalcemia (ADH) repressed the transcription of miR-9 and miR-374 genes, and treatment with an HDAC inhibitor rescued the phenotypes of cell and animal models of ADH. Furthermore, systemic treatment of mice with antagomiRs against these miRs relieved claudin-14 gene silencing and caused an ADH-like phenotype. Together, our findings provide proof of concept for a novel therapeutic principle on the basis of epigenetic regulation of renal miRs to treat hypercalciuric diseases. PMID:25071082

  2. A first record of eclogite from Nepal and consequences for the tectonic evolution of the Greater Himalayan Sequence

    NASA Astrophysics Data System (ADS)

    Parkinson, C. D.; Kohn, M. J.

    2002-05-01

    Eclogites are extremely rare in the Himalayan orogen, with only 3 documented occurrences in the Kaghan valley (Pakistan), Tso Morari (NW India), and the Kharta (S. Tibet). We have discovered severely retrograded eclogite within the Greater Himalayan Sequence (GHS) of the Arun valley in the Makalu-Everest region, eastern Nepal. It occurs as rare relict cores in 30-120 cm thick discontinuous amphibolitised layers and boudins within quartzo-feldspathic gneisses (Barun gneiss) of the GHS, between Hatiya and Chepuwa villages. The eclogites are stratigraphically contiguous with the surrounding felsic rocks, and are interpreted to represent metamorphosed basaltic sills or flows. Constituent minerals comprise: Grt, Cpx, Pl, Hbl, Qz and Bi, with minor Cal, Ms, Ttn, Ilm, Chl, Ap and Zrn. Matrix Cpx grains (up to 1.5 cm) are diopsidic (with < 5 mol% jd), but in many cases display symplectite textures of Ca-Na Pl + Di and/or variable retrogression to Hbl + Pl + Qz. Grts are generally homogeneous (in the range: alm55-58.sps1-3.prp10-15.grs21-28), but some large zoned grains (up to 1 cm diameter) preserve considerable prp contents (up to 37 mol%) in the cores and mantles. Rare inclusions of Cpx in Grt contain Jd contents generally in the range 15-25 mol%. Relatively prp-poor (10-18 mol%) rims contain inclusions of Qz + Pl + Bio + Hbl. Most Grts are surrounded by coronas of calcic Pl. Preliminary P-T determinations indicate P > 14 kbar (Jd content of Cpx) at 670-710oC (Grt-Cpx thermometry) for the peak eclogite assemblage. Symplectites grew during granulite facies retrogression at 6-8 kbar and 680-740oC. Final amphibolite reequilibration is indicated by growth of Hbl + Pl + Chl + Ilm likely at T < 600oC. Peak pressures for these rocks are considerably higher than those generally accepted for the Barun gneiss (5-8 kbar at 750-800oC), because an early high-P stage of recrystallization has been obliterated in the surrounding felsic Barun gneisses by the later granulite and

  3. P-T-t-d History of the Greater Himalaya Sequence metapelites in the Zanskar Shear Zone, NW India

    NASA Astrophysics Data System (ADS)

    Beck, E.; Leech, M. L.; Basta, S.

    2013-12-01

    Greater Himalaya Sequence (GHS) metapelites deformed in the Zanskar Shear Zone (ZSZ) record geochemical and structural evidence of a complex history. This study applies a multi-component approach to understanding the metamorphic and deformational evolution of the high-grade metapelites in western Himalaya. Samples collected from NE to SW from the ZSZ, along Malung Takpo, record increasing metamorphic grade and decreasing mylonitization with increased distance from the shear zone. Microscopic evidence for variable degrees of deformation includes: change in crystal size, foliation development, pressure shadows, and kink bands. The dominant mineralogy is Qz+Kfs+Pl+Bt+Ms+Grt+Ky×Sil×St+opaques. Advanced isochemical phase diagrams (pseudosections) are calculated in Perple_X using whole-rock geochemical (XRF) data for six samples. The pseudosection conditions range 3-15 kbar and 300-800°C and use the solution models Bio(TCC), Chl(HP), St(HP), hCrd, feldspar, Mica(CHA), and Gt(HP) with modifications made to increase the models' accuracy. The generated phase equilibria diagrams, in conjunction with observed mineral growth relationships, are used to determine the P-T paths and illustrate peak and retrograde metamorphic events. Three dating techniques [U-Pb, 40Ar/39Ar, and (U-Th)/He] are incorporated to constrain timing along the P-T paths. U-Pb SHRIMP dating of monazite constrains the timing of regional metamorphism to ~27 Ma. 40Ar/39Ar dating of muscovite and biotite yields ages of ~20-19 Ma and 15 Ma, respectively, for cooling and exhumation through the middle crust. Dates acquired from (U-Th)/He analyses of monazite and zircon will indicate the timing of the end of movement along the ZSZ. Electron backscatter diffraction (EBSD) maps crystallographic orientation of minerals and is used to determine their responses to deformation. Crystallographic responses in quartz and feldspar are used to constrain the conditions during deformation. This will be supplemented by

  4. The nutrition consult for recurrent stone formers.

    PubMed

    Penniston, Kristina L

    2015-07-01

    Diet is implicated in stone formation and growth. Whether alone or in concert with pharmacologics, dietary changes may be useful in reducing recurrence but only when they correct dietary stone-forming risks. Patients benefit from recommendations individualized to their food preferences as well as to lifestyle, age, food knowledge and access, preparation skills, and cultural and ethnic identities. Urologists can provide general dietary recommendations but often lack the time to provide the full complement of individualized nutrition care offered by a registered dietitian nutritionist (RDN). Urologists can partner with and refer patients to a RDN for any component of the nutrition care process: assessment of diet, diagnosis of dietary factors that contribute to stone risk factors, intervention formulation and implementation, and monitoring the effectiveness of the intervention and modifying it as needed to maintain suitably low dietary risk for stone recurrence. PMID:26025494

  5. A simple method for quantitating the propensity for calcium oxalate crystallization in urine

    NASA Technical Reports Server (NTRS)

    Wabner, C. L.; Pak, C. Y.

    1991-01-01

    To assess the propensity for spontaneous crystallization of calcium oxalate in urine, the permissible increment in oxalate is calculated. The previous method required visual observation of crystallization with the addition of oxalate, this warranted the need for a large volume of urine and a sacrifice in accuracy in defining differences between small incremental changes of added oxalate. Therefore, this method has been miniaturized and spontaneous crystallization is detected from the depletion of radioactive oxalate. The new "micro" method demonstrated a marked decrease (p < 0.001) in the permissible increment in oxalate in urine of stone formers versus normal subjects. Moreover, crystallization inhibitors added to urine, in vitro (heparin or diphosphonate) or in vivo (potassium citrate administration), substantially increased the permissible increment in oxalate. Thus, the "micro" method has proven reliable and accurate in discriminating stone forming from control urine and in distinguishing changes of inhibitory activity.

  6. Gender Distribution of Pediatric Stone Formers

    NASA Astrophysics Data System (ADS)

    Novak, Thomas E.; Trock, Bruce J.; Lakshmanan, Yegappan; Gearhart, John P.; Matlaga, Brian R.

    2008-09-01

    Recent epidemiologic evidence suggests that the gender prevalence among adult stone-formers is changing, with an increasing incidence of stone disease among women. No similar data have ever been reported for the pediatric stone-forming population. We performed a study to define the gender distribution among pediatric stone-formers using a large-scale national pediatric database. Our findings suggest that gender distribution among stone formers varies by age with male predominance in the first decade of life shifting to female predominance in the second decade. In contrast to adults, females in the pediatric population are more commonly affected by stones than are males. The incidence of pediatric stone disease appears to be increasing at a great rate in both sexes. Further studies should build on this hypothesis-generating work and define the effects of metabolic and environmental risk factors that may influence stone risk in the pediatric patient population

  7. Effects of microgravity on renal stone risk assessment

    NASA Technical Reports Server (NTRS)

    Pietrzyk, R. A.; Pak, C. Y. C.; Cintron, N. M.; Whitson, P. A.

    1992-01-01

    Physiologic changes induced during human exposure to the microgravity environment of space may contribute to an increased potential for renal stone formation. Renal stone risk factors obtained 10 days before flight and immediately after return to earth indicated that calcium oxalate and uric acid stone-forming potential was increased after space flights of 4-10 days. These data describe the need for examining renal stone risk during in-flight phases of space missions. Because of limited availability of space and refrigerated storage on spacecraft, effective methods must be developed for collecting urine samples in-flight and for preserving (or storing) them at temperatures and under conditions commensurate with mission constraints.

  8. Kidney stone risk following Roux-en-Y gastric bypass surgery

    PubMed Central

    Gonzalez, Ricardo D.

    2014-01-01

    Since the first report in 2005, Roux-en-Y gastric bypass (RYGB) surgery has been linked to a variety of metabolic changes that alter kidney stone risk. The studies with the highest level of evidence, performed in non-stone forming patients before and after RYGB, cite a number of kidney stone risk factors, including a 25% increase in urinary oxalate, a 30% decrease in urinary citrate, and reduction in urine volume by half a liter. In addition to these, recent clinical and experimental studies have contributed to our understanding of the pathophysiology of stone disease in this unique population. This review summarizes the current RYGB urinary chemistry profiles and epidemiological studies, outlines known and theoretical mechanisms of hyperoxaluria and hypocitrituria, and provides some standard recommendations for reducing stone risk in RYGB stone formers as well as some novel ones, including correction of metabolic acidosis and use of probiotics. PMID:25473624

  9. The potential role of salt abuse on the risk for kidney stone formation

    NASA Technical Reports Server (NTRS)

    Sakhaee, K.; Harvey, J. A.; Padalino, P. K.; Whitson, P.; Pak, C. Y.

    1993-01-01

    The kidney stone-forming risk of a high sodium diet was evaluated by assessing the effect of such a diet on the crystallization of stone-forming salts in urine. Fourteen normal subjects participated in 2 phases of study of 10 days duration each, comprising a low sodium phase (basal metabolic diet containing 50 mmol. sodium per day) and a high sodium phase (basal diet plus 250 mmol. sodium chloride per day). The high sodium intake significantly increased urinary sodium (34 +/- 12 to 267 +/- 56 mmol. per day), calcium (2.73 +/- 1.03 to 3.93 +/- 1.51 mmol. per day) and pH (5.79 +/- 0.44 to 6.15 +/- 0.25), and significantly decreased urinary citrate (3.14 +/- 1.19 to 2.52 +/- 0.83 mmol. per day). Arterialized venous blood bicarbonate and total serum carbon dioxide concentrations decreased significantly during the high sodium diet, whereas serum chloride concentration increased. However, no change in arterialized venous pH was detected. Thus, a high sodium intake not only increased calcium excretion, but also increased urinary pH and decreased citrate excretion. The latter effects are probably due to sodium-induced bicarbonaturia and a significant decrease in serum bicarbonate concentration, respectively. Commensurate with these changes, the urinary saturation of calcium phosphate (brushite) and monosodium urate increased, and the inhibitor activity against calcium oxalate crystallization (formation product) decreased. The net effect of a high sodium diet was an increased propensity for the crystallization of calcium salts in urine.

  10. Alkali absorption and citrate excretion in calcium nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Sakhaee, K.; Williams, R. H.; Oh, M. S.; Padalino, P.; Adams-Huet, B.; Whitson, P.; Pak, C. Y.

    1993-01-01

    The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p < 0.001). In 11 patients with distal renal tubular acidosis (RTA), urinary citrate excretion was subnormal relative to net GI alkali absorption, with data from most patients residing outside the 95% confidence ellipse described for normal subjects. However, the normal relationship between urinary citrate and net absorbed alkali was maintained in 11 patients with chronic diarrheal syndrome (CDS) and in 124 stone-forming patients devoid of RTA or CDS, half of whom had "idiopathic" hypocitraturia. The 18 stone-forming patients without RTA or CDS received potassium citrate (30-60 mEq/day). Both urinary citrate and net GI alkali absorption increased, yielding a significantly positive correlation (r = 0.62, p < 0.0001), with the slope indistinguishable from that of normal subjects. Thus, urinary citrate was normally dependent on the net GI absorption of alkali. This dependence was less marked in RTA, confirming the renal origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

  11. New pathophysiological concepts underlying pathogenesis of pigment gallstones

    PubMed Central

    Vítek, Libor; Carey, Martin C.

    2011-01-01

    SUMMARY Pigment gallstones, which are much less frequent than cholesterol stones, are classified descriptively as ‘black’ or ‘brown’. They are composed mostly of calcium hydrogen bilirubinate, Ca(HUCB)2, which is polymerized and oxidized in ‘black‘ stones but remains unpolymerized in ‘brown’ stones. Black stones form in sterile gallbladder bile but brown stones form secondary to stasis and anaerobic bacterial infection in any part of the biliary tree, including the gallbladder. Other calcium salts coprecipitate in both stone types; crystalline calcium phosphate and/or carbonate in the case of ‘black’ stones and amorphous calcium salts of long chain saturated fatty acids (‘soaps’) in the case of ‘brown’ stones. Cholesterol is present in variable proportions in ‘brown’ more than ‘black’ stones and, in the latter, the bile sterol may be totally absent. The ‘scaffolding’ of both stone types is a mixed mucin glycoprotein matrix secreted by epithelial cells lining the biliary tree. The critical pathophysiological prerequisite for ‘black’ stone formation is ‘hyperbilirubinbilia’ (biliary hypersecretion of bilirubin conjugates). It is due principally to hemolysis, ineffective erythropoiesis, or pathologic enterohepatic cycling of unconjugated bilirubin. Endogenous biliary β-glucuronidase hydrolysis of bilirubin conjugates in gallbladder bile provides HUCB− molecules that precipitate as insoluble salts with ionized Ca. Putatively, reactive oxygen species secreted by an inflamed gallbladder mucosa are responsible for transforming the initial soft yellow precipitates into hard black [Ca(HUCB)2]n polymers. Despite ‘brown’ gallstones being soft and amenable to mechanical removal, chronic anaerobic infection of the biliary tree is often markedly resistant to eradication. PMID:21978438

  12. Strengthening of Graphene Aerogels with Tunable Density and High Adsorption Capacity towards Pb2+

    PubMed Central

    Han, Zhuo; Tang, Zhihong; Shen, Shuling; Zhao, Bin; Zheng, Guangping; Yang, Junhe

    2014-01-01

    Graphene aerogels (GAs) with high mechanical strength, tunable density and volume have been prepared only via soaking graphene hydrogels (GHs) in ammonia solution. The density and volume of the obtained GAs are controlled by adjusting the concentration of ammonia solution. Although volume of the GAs decreases with increasing the concentration of ammonia solution, its specific surface area maintains at about 350 m2 g−1, and the inner structure changes to radial after ammonia solution treatment. Thus, GAs are particularly suitable for the adsorption and energy storage applications owing to their high specific surface area and unique porous structure. The adsorption capacity of GAs for Pb2+ from aqueous solution maintains at about 80 mg g−1, which could reach as high as 5000 g m−3 per unit volume and they can be separated easily from water after adsorption. PMID:24848100

  13. Giant hydronephrosis due to ureteropelvic junction obstruction: A rare case report, and a review of the literature

    PubMed Central

    WANG, QI-FEI; ZENG, GUANG; ZHONG, LIN; LI, QUAN-LIN; CHE, XIANG-YU; JIANG, TAO; ZHANG, ZHI-WEI; ZHENG, WEI; TANG, QI-ZHEN; CHEN, FENG; WANG, KE-NAN

    2016-01-01

    The hydronephrotic kidney, resulting from a ureteropelvic junction obstruction (UPJO), presents commonly as a clinical condition, with the presence of usually no more than 1–2 liters in the collecting system, but a very small number of cases of giant hydronephroses (GHs) has been reported in adults. A GH is defined as the adult renal pelvis containing >1 liter of urine, or at least 1.5% of the body weight. In the majority of cases, the range of the hydronephrotic kidney remains restricted to the renal area. However, the patient described in the present case report had a range for the hydronephrotic kidney which occupied almost the entire abdominal cavity (~24 l), and cases such as these are rarely presented; therefore the aim of the present case study was to document a clear case of GH resulting from UPJO, also accompanied by a review of the current literature. PMID:27330757

  14. Measurement-induced-nonlocality for Dirac particles in Garfinkle-Horowitz-Strominger dilation space-time

    NASA Astrophysics Data System (ADS)

    He, Juan; Xu, Shuai; Ye, Liu

    2016-05-01

    We investigate the quantum correlation via measurement-induced-nonlocality (MIN) for Dirac particles in Garfinkle-Horowitz-Strominger (GHS) dilation space-time. It is shown that the physical accessible quantum correlation decreases as the dilation parameter increases monotonically. Unlike the case of scalar fields, the physical accessible correlation is not zero when the Hawking temperature is infinite owing to the Pauli exclusion principle and the differences between Fermi-Dirac and Bose-Einstein statistics. Meanwhile, the boundary of MIN related to Bell-violation is derived, which indicates that MIN is more general than quantum nonlocality captured by the violation of Bell-inequality. As a by-product, a tenable quantitative relation about MIN redistribution is obtained whatever the dilation parameter is. In addition, it is worth emphasizing that the underlying reason why the physical accessible correlation and mutual information decrease is that they are redistributed to the physical inaccessible regions.

  15. “Newton’s cradle” proton relay with amide–imidic acid tautomerization in inverting cellulase visualized by neutron crystallography

    PubMed Central

    Nakamura, Akihiko; Ishida, Takuya; Kusaka, Katsuhiro; Yamada, Taro; Fushinobu, Shinya; Tanaka, Ichiro; Kaneko, Satoshi; Ohta, Kazunori; Tanaka, Hiroaki; Inaka, Koji; Higuchi, Yoshiki; Niimura, Nobuo; Samejima, Masahiro; Igarashi, Kiyohiko

    2015-01-01

    Hydrolysis of carbohydrates is a major bioreaction in nature, catalyzed by glycoside hydrolases (GHs). We used neutron diffraction and high-resolution x-ray diffraction analyses to investigate the hydrogen bond network in inverting cellulase PcCel45A, which is an endoglucanase belonging to subfamily C of GH family 45, isolated from the basidiomycete Phanerochaete chrysosporium. Examination of the enzyme and enzyme-ligand structures indicates a key role of multiple tautomerizations of asparagine residues and peptide bonds, which are finally connected to the other catalytic residue via typical side-chain hydrogen bonds, in forming the “Newton’s cradle”–like proton relay pathway of the catalytic cycle. Amide–imidic acid tautomerization of asparagine has not been taken into account in recent molecular dynamics simulations of not only cellulases but also general enzyme catalysis, and it may be necessary to reconsider our interpretation of many enzymatic reactions. PMID:26601228

  16. Structure-activity analysis of the growth hormone secretagogue GHRP-6 by alpha- and beta-amino gamma-lactam positional scanning.

    PubMed

    Boutard, Nicolas; Jamieson, Andrew G; Ong, Huy; Lubell, William D

    2010-01-01

    Incorporation of amino lactams into biologically active peptides restricts conformational mobility and may enhance selectivity and increase potency. alpha- and beta-amino gamma-lactams (Agl and Bgl), in both S and R configurations, were introduced into the growth hormone secretagogue GHRP-6 using a Fmoc-compatible solid-phase protocol relying on N-alkylation with five- and six-membered cyclic sulfamidates, followed by lactam annulation under microwave heating. Using this protocol in conjunction with IRORI Kan techniques furnished eleven new GHRP-6 analogs, and their binding affinity IC50 values on both the growth hormone secretagogue receptor 1a (GHS-R1a) and CD36 receptors are herein reported. The results indicate that selectivity towards one receptor or the other can be modulated by lactam substitution, typically at the Ala3 and the D-Phe5 positions. PMID:19954433

  17. Who Cares? Pre and Post Abortion Experiences among Young Females in Cape Coast Metropolis, Ghana.

    PubMed

    Esia-Donkoh, Kobina; Darteh, Eugene K M; Blemano, Harriet; Asare, Hagar

    2015-06-01

    Issues of abortion are critical in Ghana largely due to its consequences on sexual and reproductive health. The negative perception society attaches to it makes it difficult for young females to access services and share their experiences. This paper examines the pre and post abortion experiences of young females; a subject scarcely researched in the country. Twenty-one clients of Planned Parenthood Association of Ghana (PPAG) clinic at Cape Coast were interviewed. Guided by the biopsychosocial model, the study revealed that fear of societal stigma, shame, and rejection by partners, as well as self-imposed stigma constituted some of the pre and post abortion experiences the respondents. Other experiences reported were bleeding, severe abdominal pain and psychological pain. The Ghana Health Services (GHS) and other service providers should partner the PPAG clinic to integrate psychosocial treatment in its abortion services while intensifying behaviour change communication and community-based stigma-reduction education in the Metropolis. PMID:26506657

  18. Detection of the greenhouse gas signal from space - A progress report

    NASA Technical Reports Server (NTRS)

    Barnett, T. P.; Haskins, R.; Chahine, M.

    1991-01-01

    The spatial distribution of the expected changes in the atmospheric water vapor content and cloud cover, as predicted by the transient greenhouse gas (GHG) simulation of Hansen et al. (1988), are examined to determine whether the signals would be large enough and unique enough to be useful in a GHG detection study. The nature of the predicted GHG signal was first examined using the transient CO2 run from the GISS ocean/atmosphere general circulation model. Next, the remotely sensed irradiance characteristics data (as the measure of water vapor content) supplied by the HIRS/MSU sensors for the area of the equatorial cold tongue region (the region in which there are no measurement stations). It is shown that HIRS/MSU signals can provide data necessary for detecting GHS signals in atmospheric moisture for regions where ground observations are not possible.

  19. Testing the channel flow model in the eastern Himalaya, eastern Bhutan: insights from preliminary thermobarometric data

    NASA Astrophysics Data System (ADS)

    Agustsson, K. S.; Gordon, S. M.; Long, S. P.; Seward, G. G.; Zeiger, K. J.; Penfold, M. L.

    2013-12-01

    The study of modern continent-continent collision provides insight into the links between the upper and lower crust, including the processes involved in the deep burial and exhumation of crustal rocks. Rocks of the Greater Himalayan Sequence (GHS), which were buried to mid- to lower-crustal levels, are exposed throughout the Himalayan orogenic belt, between the top-to-the-south Main Central Thrust and the top-to-the-north South Tibetan Detachment. The GHS consists of orthogneiss, metasedimentary rocks, and large-scale (>100 km2) leucogranite bodies. Within the Bhutan Himalaya, the top-to-the south Kakhtang Thrust (KT) separates the GHS into upper (GHSu) and lower (GHSl) structural levels. Previous studies have mapped the location of the KT by the crossing of the second sillimanite isograd and by a significant increase in the volume of crystallized melt. Previous work in Bhutan has mainly focused on the GHSl, whereas the extrusion of the higher-temperature GHSu has not been well studied, and there is little quantitative data describing the P-T history of these rocks. In order to test between different end-member models for the exhumation of the GHSu, including channel flow and critical taper, new thermobarometry data was collected from a transect of samples across the KT. The channel-flow model predicts that the GHSu would have achieved peak upper-amphibolite facies P-T conditions followed by retrograde, near-isothermal decompression. In contrast, the critical-taper model predicts near-isobaric cooling of the GHSu. The electron microprobe at UC-Santa Barbara was used to measure the composition of and test for zoning within garnet, plagioclase, and biotite. Garnets in all four samples are typically subhedral to euhedral and show relatively weak zonation and flat Mg, Fe, and Ca profiles. A few garnets do exhibit bell-shaped Mn and Ca profiles. In addition, a ca. 100 μm rim high in Mg, Ca and Mn but low in Fe is present on all garnets and is indicative of diffusional

  20. Classification & Labelling Inventory: role of ECHA and notification requirements.

    PubMed

    Schöning, Gabriele

    2011-01-01

    The CLP Regulation introduces the criteria of the UN Globally Harmonised System of Classification and Labelling (UN GHS) in the EU. The European Chemicals Agency (ECHA) manages the CLP related tasks - such as harmonised classification and labelling, handling requests for alternative names and maintaining the Classification & Labelling Inventory (C&L) - to ensure consistent implementation in the EU. The obligations for industry depend on their role in the supply chain. Manufacturers and importers have to notify to ECHA the identity and classification and labelling of substances within one month of placing them on the market either on their own or in a mixture, and regardless of the quantitity. As of 3 January 2011 ECHA has received some 3.1 million notifications of over 107 000 substances. This information is stored in the C&L Inventory and accessible to Member State Competent Authorities. The non-confidential information will be made publicly available on ECHA's website in 2011. PMID:21709382

  1. Multiple rewards from a treasure trove of novel glycoside hydrolase and polysaccharide lyase structures: new folds, mechanistic details, and evolutionary relationships.

    PubMed

    Fushinobu, Shinya; Alves, Victor D; Coutinho, Pedro M

    2013-10-01

    Recent progress in three-dimensional structure analyses of glycoside hydrolases (GHs) and polysaccharide lyases (PLs), the historically relevant enzyme classes involved in the cleavage of glycosidic bonds of carbohydrates and glycoconjugates, is reviewed. To date, about 80% and 95% of the GH and PL families, respectively, have a representative crystal structure. New structures have been determined for enzymes acting on plant cell wall polysaccharides, sphingolipids, blood group antigens, milk oligosaccharides, N-glycans, oral biofilms and dietary seaweeds. Some GH enzymes have very unique catalytic residues such as the Asp-His dyad. New methods such as high-speed atomic force microscopy and computational simulation have opened up a path to investigate both the dynamics and the detailed molecular interactions displayed by these enzymes. PMID:23816329

  2. Cubit Adaptive Meshing Algorithm Library

    Energy Science and Technology Software Center (ESTSC)

    2004-09-01

    CAMAL (Cubit adaptive meshing algorithm library) is a software component library for mesh generation. CAMAL 2.0 includes components for triangle, quad and tetrahedral meshing. A simple Application Programmers Interface (API) takes a discrete boundary definition and CAMAL computes a quality interior unstructured grid. The triangle and quad algorithms may also import a geometric definition of a surface on which to define the grid. CAMAL’s triangle meshing uses a 3D space advancing front method, the quadmore » meshing algorithm is based upon Sandia’s patented paving algorithm and the tetrahedral meshing algorithm employs the GHS3D-Tetmesh component developed by INRIA, France.« less

  3. LAHS: A novel harmony search algorithm based on learning automata

    NASA Astrophysics Data System (ADS)

    Enayatifar, Rasul; Yousefi, Moslem; Abdullah, Abdul Hanan; Darus, Amer Nordin

    2013-12-01

    This study presents a learning automata-based harmony search (LAHS) for unconstrained optimization of continuous problems. The harmony search (HS) algorithm performance strongly depends on the fine tuning of its parameters, including the harmony consideration rate (HMCR), pitch adjustment rate (PAR) and bandwidth (bw). Inspired by the spur-in-time responses in the musical improvisation process, learning capabilities are employed in the HS to select these parameters based on spontaneous reactions. An extensive numerical investigation is conducted on several well-known test functions, and the results are compared with the HS algorithm and its prominent variants, including the improved harmony search (IHS), global-best harmony search (GHS) and self-adaptive global-best harmony search (SGHS). The numerical results indicate that the LAHS is more efficient in finding optimum solutions and outperforms the existing HS algorithm variants.

  4. De Novo Analysis of Wolfiporia cocos Transcriptome to Reveal the Differentially Expressed Carbohydrate-Active Enzymes (CAZymes) Genes During the Early Stage of Sclerotial Growth

    PubMed Central

    Zhang, Shaopeng; Hu, Bingxiong; Wei, Wei; Xiong, Ying; Zhu, Wenjun; Peng, Fang; Yu, Yang; Zheng, Yonglian; Chen, Ping

    2016-01-01

    The sclerotium of Wolfiporia cocos has been used as an edible mushroom and/or a traditional herbal medicine for centuries. W. cocos sclerotial formation is dependent on parasitism of the wood of Pinus species. Currently, the sclerotial development mechanisms of W. cocos remain largely unknown and the lack of pine resources limit the commercial production. The CAZymes (carbohydrate-active enzymes) play important roles in degradation of the plant cell wall to provide carbohydrates for fungal growth, development, and reproduction. In this study, the transcript profiles from W. cocos mycelium and 2-months-old sclerotium, the early stage of sclerotial growth, were specially analyzed using de novo sequencing technology. A total of 142,428,180 high-quality reads of mycelium and 70,594,319 high-quality reads of 2-months-old sclerotium were obtained. Additionally, differentially expressed genes from the W. cocos mycelium and 2-months-old sclerotium stages were analyzed, resulting in identification of 69 CAZymes genes which were significantly up-regulated during the early stage of sclerotial growth compared to that of in mycelium stage, and more than half of them belonged to glycosyl hydrolases (GHs) family, indicating the importance of W. cocos GHs family for degrading the pine woods. And qRT-PCR was further used to confirm the expression pattern of these up-regulated CAZymes genes. Our results will provide comprehensive CAZymes genes expression information during W. cocos sclerotial growth at the transcriptional level and will lay a foundation for functional genes studies in this fungus. In addition, our study will also facilitate the efficient use of limited pine resources, which is significant for promoting steady development of Chinese W. cocos industry. PMID:26870032

  5. Insulinotropic action of bombesin-like peptides mediated by gastrin-releasing peptide receptors in steers.

    PubMed

    Zhao, H Q; Yao, G; Yannaing, S; ThanThan, S; Kuwayama, H

    2016-01-01

    The present study characterizes the receptor that mediates the insulinotropic action of bombesin-like peptides (BLP) in ruminants. Eight Holstein steers were randomly and intravenously injected with synthetic bovine gastrin-releasing peptide (GRP; 0.9 nmol/kg BW), neuromedin B (NMB; 0.9 nmol/kg BW), or neuromedin C (NMC; 0.9 nmol/kg BW), each alone or combined with the antagonist of GRP receptors N-acetyl-GRP-OCHCH (N-GRP-EE; 22.5 nmol/kg BW) or the antagonist of GH secretagogue receptor type 1a (GHS-R1a) [D-Lys]-GHRP-6 (21.5 nmol/kg BW). Blood samples were collected at -10, 0 (just before injection), 5, 10, 15, 20, 30, 45, 60, 75, and 90 min relative to injection time. Levels of injected peptides, insulin, and glucose in plasma were analyzed. Results showed that the peak of insulin levels was seen at 5 min after injection of NMC or GRP. Plasma glucose was observed in 2 phases; a significant rise followed a remarkable fall after NMC or GRP administration compared with injection of the vehicle ( < 0.05). On a same molar basis, effects of GRP on insulin and glucose were more potent than those of NMC ( < 0.05). The NMC-induced changes of insulin and glucose were completely blocked by N-GRP-EE, but [D-Lys]-GHRP-6 did not block any of these changes. Administration of NMB or N-GRP-EE alone did not change the circulating levels of insulin or glucose during any of the sampling time points ( > 0.05). These results indicated that the insulinotropic action of BLP is mediated by GRP receptors but not through a ghrelin/GHS-R1a pathway and that BLP may be involved in the regulation of glucose homeostasis in ruminants. PMID:26812312

  6. Development Characteristics of PMMA in alternative alcohol:water mixtures

    NASA Astrophysics Data System (ADS)

    Ocola, Leonidas E.

    2015-03-01

    The most widely used resist in electron beam lithography is polymethylmethacrylate (PMMA). The standard developers used are solution mixtures of isopropanol (IPA) and methyl isobutyl ketone (MIBK) in a ratio of 3:1 and mixtures of IPA and water (H2O) in a ratio of 7:3. The Globally Harmonized System (GHS) classification entry for IPA includes: Specific target organ toxicity - single exposure (Category 3). MIBK is much more hazardous than IPA. The only GHS classification entry for Ethanol is: Flammable liquids (Category 2), i.e. more environmentally safe. Using Ethanol/H2O as a developer will therefore enable lower hazardous waste disposal costs to cleanrooms. We find Ethanol/H2O at 85% volume (2:1 molar) exhibits excellent lithography results as good as with IPA/H2O, and better contrast and sensitivity than IPA/H2O and MIBK/IPA developers. Lithographic data shows trends similar to published cosolvency data, but differ too much to be explained by it. In addition, unusual development at 50% volume concentrations for both IPA and Ethanol in H2O show dramatic pothole formation instead of uniform thickness loss found in standard contrast curve exposures. We believe local pockets of concentrated alcohol water molar mixtures are responsible for such behavior. This work was supported by the Department of Energy under Contract No. DE-AC02-06CH11357. Use of the Center for Nanoscale Materials was supported by the U. S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.

  7. Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model.

    PubMed

    Kaluzhny, Yulia; Kandárová, Helena; d'Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

    2015-01-01

    To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492. PMID:26325674

  8. Increased linear bone growth by GH in the absence of SOCS2 is independent of IGF‐1

    PubMed Central

    Dobie, Ross; Ahmed, Syed F.; Staines, Katherine A.; Pass, Chloe; Jasim, Seema; MacRae, Vicky E.

    2015-01-01

    Growth hormone (GH) signaling is essential for postnatal linear bone growth, but the relative importance of GHs actions on the liver and/or growth plate cartilage remains unclear. The importance of liver derived insulin like‐growth factor‐1 (IGF‐1) for endochondral growth has recently been challenged. Here, we investigate linear growth in Suppressor of Cytokine Signaling‐2 (SOCS2) knockout mice, which have enhanced growth despite normal systemic GH/IGF‐1 levels. Wild‐type embryonic ex vivo metatarsals failed to exhibit increased linear growth in response to GH, but displayed increased Socs2 transcript levels (P < 0.01). In the absence of SOCS2, GH treatment enhanced metatarsal linear growth over a 12 day period. Despite this increase, IGF‐1 transcript and protein levels were not increased in response to GH. In accordance with these data, IGF‐1 levels were unchanged in GH‐challenged postnatal Socs2‐/‐ conditioned medium despite metatarsals showing enhanced linear growth. Growth‐plate Igf1 mRNA levels were not elevated in juvenile Socs2‐/‐ mice. GH did however elevate IGF‐binding protein 3 levels in conditioned medium from GH challenged metatarsals and this was more apparent in Socs2‐/‐ metatarsals. GH did not enhance the growth of Socs2‐/‐ metatarsals when the IGF receptor was inhibited, suggesting that IGF receptor mediated mechanisms are required. IGF‐2 may be responsible as IGF‐2 promoted metatarsal growth and Igf2 expression was elevated in Socs2‐/‐ (but not WT) metatarsals in response to GH. These studies emphasise the critical importance of SOCS2 in regulating GHs ability to promote bone growth. Also, GH appears to act directly on the metatarsals of Socs2‐/‐ mice, promoting growth via a mechanism that is independent of IGF‐1. J. Cell. Physiol. 9999: 2796–2806, 2015. © 2015 Wiley Periodicals, Inc. PMID:25833299

  9. Integrating optical fabrication and metrology into the optical design process

    NASA Astrophysics Data System (ADS)

    Harvey, James E.

    2014-12-01

    Image degradation due to scattered radiation from residual optical fabrication errors is a serious problem in many short wavelength (X-ray/EUV) imaging systems. Most commercially-available image analysis codes (ZEMAX, Code V, ASAP, FRED, etc.) currently require the scatter behavior (BSDF data) to be provided as input in order to calculate the image quality of such systems. This BSDF data is difficult to measure and rarely available for the operational wavelengths of interest. Since the smooth-surface approximation is often not satisfied at these short wavelengths, the classical Rayleigh-Rice expression that indicates the BRDF is directly proportional to the surface PSD cannot be used to calculate BRDFs from surface metrology data for even slightly rough surfaces. However, an FFTLog numerical Hankel transform algorithm enables the practical use of the computationally intensive Generalized Harvey-Shack (GHS) surface scatter theory [1] to calculate BRDFs from surface PSDs for increasingly short wavelengths that violate the smooth surface approximation implicit in the Rayleigh-Rice surface scatter theory [2-3]. The recent numerical validation [4] of the GHS theory (a generalized linear systems formulation of surface scatter theory), and an analysis of image degradation due to surface scatter in the presence of aberrations [5] has provided credence to the development of a systems engineering analysis of image quality as degraded not only by diffraction effects and geometrical aberrations, but to scattering effects due to residual optical fabrication errors as well. These advances, combined with the continuing increase in computer speed, leave us poised to fully integrate optical metrology and fabrication into the optical design process.

  10. Disability prevalence and disability-related employment gaps in the UK 1998-2012: Different trends in different surveys?

    PubMed

    Baumberg, Ben; Jones, Melanie; Wass, Victoria

    2015-09-01

    The persistently low employment rate among disabled individuals has been an enduring concern of governments across developed countries and has been the subject of a succession of policy initiatives, including labour market activation programmes, equality laws and welfare reform. A key indicator of progress is the trend in the disability-related employment gap, the percentage point difference between the employment rate for disabled and non-disabled individuals. Confusingly for the UK, studies undertaken between 1998 and 2012 have simultaneously reported both a widening and a narrowing of the gap. The source of the discrepancy can be found in the choice of survey, the General Household Survey (GHS) or the Labour Force Survey (LFS), although both use a common conception of disability and collect self-reported information from a random sample of households. The literature has analysed these surveys separately from each other and ignored inter-survey differences in findings. The Health Survey for England (HSE), a third national household survey, replicates the GHS questions on disability but has had limited use in this context. This empirical study compares the trends in disability prevalence and the disability-related employment gap across the three surveys using a three-stage harmonisation process. The negative relationship between the prevalence of disability and the employment gap found in cross-section inter-survey comparisons prompts an initial focus on differences in the definition of disability as an explanation of the discrepancy. This is broadened to include differences in survey methods and sample composition. Differences in the trend in disability prevalence and the employment gap remain following harmonisation for definition, survey method and sample composition. It is the LFS, the main policy-influencing and policy-assessment survey, which generates outlying results. As such, we cannot be confident that the disability-related employment gap has narrowed

  11. The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells

    PubMed Central

    Prudente, Sabrina; Morini, Eleonora; Larmon, Jay; Andreozzi, Francesco; Pietro, Natalia Di; Nigro, Angela; Gervino, Ernest V; Mannino, Gaia Chiara; Bacci, Simonetta; Hauser, Thomas H; Bellacchio, Emanuele; Formoso, Gloria; Pellegrini, Fabio; Proto, Vittoria; Menzaghi, Claudia; Frittitta, Lucia; Pandolfi, Assunta; Sesti, Giorgio; Doria, Alessandro; Trischitta, Vincenzo

    2013-01-01

    Objective Obesity and cardiovascular disease recognize a common metabolic soil and may therefore share part of their genetic background. Genome-wide association studies have identified variability at the SH2B1 locus as a predictor of obesity. We investigated whether SNP rs4788102, which captures the entire SH2B1 variability, is associated with coronary artery disease (CAD) and/or myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM). Design and Setting SNP rs4788102 was typed in 2,015 White subjects with T2DM from three CAD case-control studies [n=740 from the Gargano Hearth Study (GHS, Italy); n=818 from the Joslin Hearth Study (JHS, Boston); n=457 from the University of Catanzaro (CZ, Italy)]. Results SNP rs4788102 (G/A) was not associated with CAD (overall allelic OR=1.06, 95% CI=0.93-1.21; p=0.37). On the contrary, it was associated with MI in GHS (1.42, 1.12-1.81; p=0.004) and in the three samples analyzed together (1.21, 1.04-1.41; p=0.016). Insulin stimulated nitric oxide synthase (NOS) activity in human vein endothelial cells from G/G (n=4, p=0.03) but not the G/A (n=5, p=0.83) genotype. Of the SNPs in perfect LD with rs4788102, one (rs7498665) affects amino acid polarity (Ala484Thr) and falls into a highly conserved protein segment of SH2B1 containing a class II SH3 domain binding site. Conclusions Variability at the SH2B1 obesity locus is associated with MI in diabetic patients and with reduced insulin-stimulated NOS activity in human endothelial cells. Further studies are needed to replicate this association and dissect the biology underlying this finding. PMID:21907990

  12. Ghrelin signaling in heart remodeling of adult obese mice.

    PubMed

    Lacerda-Miranda, Glauciane; Soares, Vivian M; Vieira, Anatalia K G; Lessa, Juliana G; Rodrigues-Cunha, Alessandra C S; Cortez, Erika; Garcia-Souza, Erica P; Moura, Anibal S

    2012-05-01

    Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), has been suggested to be associated to obesity, insulin secretion, cardiovascular growth and homeostasis. GHS-R has been found in most of the tissues, and among the hormone action it is included the regulation of heart energy metabolism. Therefore, hypernutrition during early life leads to obesity, induces cardiac hypertrophy, compromises myocardial function, inducing heart failure in adulthood. We examined ghrelin signaling process in cardiac remodeling in these obese adult mice. The cardiomyocytes (cmy) of left ventricle were analyzed by light microscopy and stereology, content and phosphorilation of cardiac proteins: ghrelin receptor (growth hormone secretagogue receptor 1a, GHSR-1a), protein kinase B (AKT and pAKT), phosphatidil inositol 3 kinase (PI3K), AMP-activated protein kinase (AMPK and pAMPK) and actin were achieved by Western blotting. GHSR-1a gene expression was analyzed by Real Time-PCR. We observed hyperglycemia and higher liver and visceral fat weight in obese when compared to control group. Obese mice presented a marked increase in heart weight/tibia length, indicating an enlarged heart size or a remodeling process. Obese mice had increased GHSR-1a content and expression in the heart associated to PI3K content and increased AKT content and phosphorylation. In contrast, AMPK content and phosphorylation in heart was not different between experimental groups. Ghrelin plasma levels in obese group were decreased when compared to control group. Our data suggest that remodeled myocardial in adult obese mice overnourished in early life are associated with higher phosphorylation of GHSR-1a, PI3K and AKT but not with AMPK. PMID:22407166

  13. Hepatic receptors for homologous growth hormone in the eel

    SciTech Connect

    Hirano, T. )

    1991-03-01

    The specific binding of 125I-labeled eel growth hormone (eGH) to liver membranes of the eel was examined. The specific binding to the 10,000g pellet was greater than that to the 600g pellet. The specific binding was linear up to about 100 mg fresh tissue, and was saturable with increasing amounts of membrane. The specific binding was pH-, temperature-, and time-dependent, with the optimum pH at 7.4, and greater specific binding was obtained at 15 and 25 degrees than at 35 degrees. Scatchard analysis of liver binding gave an association constant of 1.1 x 10(9) M-1 and a capacity of 105 fmol/mg protein. The receptor preparation was highly specific for GHs. Natural and recombinant eel GHs as well as recombinant salmon GH competed equally with 125I-eGH for the receptor sites of the 10,000g liver membrane. Ovine GH was more potent in displacing the labeled eGH than the homologous eel hormone. Tilapia GH and ovine prolactin (PRL) were needed in greater amounts (40 times) than eGH to displace the labeled eGH. Salmon and tilapia PRLs were still less potent (500 times) than eGH. There was no displacement with eel PRL. No significant change in the specific binding was seen 1 week after hypophysectomy, whereas injection of eGH into the hypophysectomized eel caused a significant reduction after 24 hr. The binding to the membrane fractions from gills, kidney, muscle, intestine, and brain was low and exclusively nonspecific, indicating the presence of specific GH receptors predominantly in the liver.

  14. The N-Glycan Cluster from Xanthomonas campestris pv. campestris

    PubMed Central

    Dupoiron, Stéphanie; Zischek, Claudine; Ligat, Laetitia; Carbonne, Julien; Boulanger, Alice; Dugé de Bernonville, Thomas; Lautier, Martine; Rival, Pauline; Arlat, Matthieu; Jamet, Elisabeth; Lauber, Emmanuelle; Albenne, Cécile

    2015-01-01

    N-Glycans are widely distributed in living organisms but represent only a small fraction of the carbohydrates found in plants. This probably explains why they have not previously been considered as substrates exploited by phytopathogenic bacteria during plant infection. Xanthomonas campestris pv. campestris, the causal agent of black rot disease of Brassica plants, possesses a specific system for GlcNAc utilization expressed during host plant infection. This system encompasses a cluster of eight genes (nixE to nixL) encoding glycoside hydrolases (GHs). In this paper, we have characterized the enzymatic activities of these GHs and demonstrated their involvement in sequential degradation of a plant N-glycan using a N-glycopeptide containing two GlcNAcs, three mannoses, one fucose, and one xylose (N2M3FX) as a substrate. The removal of the α-1,3-mannose by the α-mannosidase NixK (GH92) is a prerequisite for the subsequent action of the β-xylosidase NixI (GH3), which is involved in the cleavage of the β-1,2-xylose, followed by the α-mannosidase NixJ (GH125), which removes the α-1,6-mannose. These data, combined to the subcellular localization of the enzymes, allowed us to propose a model of N-glycopeptide processing by X. campestris pv. campestris. This study constitutes the first evidence suggesting N-glycan degradation by a plant pathogen, a feature shared with human pathogenic bacteria. Plant N-glycans should therefore be included in the repertoire of molecules putatively metabolized by phytopathogenic bacteria during their life cycle. PMID:25586188

  15. Factors Associated with Problematic Vocalizations in Nursing Home Residents With Dementia

    PubMed Central

    Beck, Cornelia; Richards, Kathy; Doan, Rebecca; Landes, Reid D.; Whall, Ann; Algase, Donna; Kolanowski, Ann; Feldman, Zachary

    2011-01-01

    Purpose of the Study: Problematic vocalizations (PVs) are the most frequent and persistent disruptive behaviors exhibited by nursing home residents with dementia. Understanding factors associated with these behaviors are important to prevent or reduce them. We used the Need-Driven Dementia-Compromised Behavior model to identify the characteristics of persons with dementia who are likely to display nonaggressive and aggressive PVs and the conditions under which these behaviors are likely to occur and persist. Design and Methods: This multisite descriptive study included 138 residents of 17 nursing homes, and approximately half had a history of PVs. Background data were gathered through interviews, chart reviews, and administration of physical and neuropsychological assessments. Proximal data were obtained from observations and videotapes. Results: When the 2 subscales of the Verbal Behavior Scale were used as the dependent variables, agreeableness and conscientiousness, positive affect, and discomfort were associated with nonaggressive vocalizations, and general health state (GHS), age, and negative and positive affect were associated with aggressive vocalizations. When the verbally agitated (nonaggressive) section of the Cohen-Mansfield Agitation Inventory was the dependent variable, the background factors of gender, agreeableness, GHS, and age remained predictors, as did the proximal factors of affect and discomfort. Implications: We identified 5 background factors and 3 proximal factors as risk factors for PVs in persons with dementia, with variation between nonaggressive or aggressive PVs. These data provide direction for caregiving for persons with dementia and design of interventions to prevent or reduce PVs. PMID:21292752

  16. Nanoparticulate TiO2 protection of midgut damage in the silkworm (Bombyx mori) following phoxim exposure.

    PubMed

    Wang, Ling; Su, Mingyu; Zhao, Xiaoyang; Hong, Jie; Yu, Xiaohong; Xu, Bingqing; Sheng, Lei; Liu, Dong; Shen, Weide; Li, Bing; Hong, Fashui

    2015-04-01

    Bombyx mori (B. mori) is often subjected to phoxim poisoning in China due to phoxim exposure, which leads to a decrease in silk production. Nanoparticulate (NP) titanium dioxide (nano-TiO2) has been shown to attenuate damages in B. mori caused by phoxim exposure. However, little is known about the molecular mechanisms of midgut injury due to organophosphorus insecticide exposure and its repair by nano-TiO2 pretreatment. In this study, phoxim exposure for 36 h led to significant decreases in body weight and survival and increased oxidative stress and midgut injury. Pretreatment with nano-TiO2 attenuated the phoxim-induced midgut injury, increased body weight and survival, and decreased oxidative stress in the midgut of B. mori. Digital gene-expression data showed that exposure to phoxim results in significant changes in the expression of 254 genes in the phoxim-exposed midgut and 303 genes in phoxim + nano-TiO2-exposed midgut. Specifically, phoxim exposure led to upregulation of Tpx, α-amylase, trypsin, and glycoside hydrolase genes involved in digestion and absorption. Phoxim exposure also led to the downregulation of Cyp450 and Cyp4C1 genes involved in an antioxidant capacity. In contrast, a combination of both phoxim and nano-TiO2 treatment significantly decreased the change in α-amylase, trypsin, and glycoside hydrolases (GHs), which are involved in digestion and absorption. These results indicated that Tpx, α-amylase, trypsin, GHs, Cyp450, and Cyp4C1 may be potential biomarkers of midgut toxicity caused by phoxim exposure and the attenuation of these toxic impacts by nano-TiO2. PMID:25552327

  17. Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    PubMed Central

    2013-01-01

    Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also

  18. Pressure-temperature-time-deformation path of kyanite-bearing migmatitic paragneiss in the Kali Gandaki valley (Central Nepal): Investigation of Late Eocene-Early Oligocene melting processes

    NASA Astrophysics Data System (ADS)

    Iaccarino, Salvatore; Montomoli, Chiara; Carosi, Rodolfo; Massonne, Hans-Joachim; Langone, Antonio; Visonà, Dario

    2015-08-01

    Kyanite-bearing migmatitic paragneiss of the lower Greater Himalayan Sequence (GHS) in the Kali Gandaki transect (Central Himalaya) was investigated. In spite of the intense shearing, it was still possible to obtain many fundamental information for understanding the processes active during orogenesis. Using a multidisciplinary approach, including careful meso- and microstructural observations, pseudosection modelling (with PERPLE_X), trace element thermobarometry and in situ monazite U-Th-Pb geochronology, we constrained the pressure-temperature-time-deformation path of the studied rock, located in a structural key position. The migmatitic gneiss has experienced protracted prograde metamorphism after the India-Asia collision (50-55 Ma) from ~ 43 Ma to 28 Ma. During the late phase (36-28 Ma) of this metamorphism, the gneiss underwent high-pressure melting at "near peak" conditions (710-720 °C/1.0-1.1 GPa) leading to kyanite-bearing leucosome formation. In the time span of 25-18 Ma, the rock experienced decompression and cooling associated with pervasive shearing reaching P-T conditions of 650-670 °C and 0.7-0.8 GPa, near the sillimanite-kyanite transition. This time span is somewhat older than previously reported for this event in the study area. During this stage, additional, but very little melt was produced. Taking the migmatitic gneiss as representative of the GHS, these data demonstrate that this unit underwent crustal melting at about 1 GPa in the Eocene-Early Oligocene, well before the widely accepted Miocene decompressional melting related to its extrusion. In general, kyanite-bearing migmatite, as reported here, could be linked to the production of the high-Ca granitic melts found along the Himalayan belt.

  19. Eye Irritation Test (EIT) for Hazard Identification of Eye Irritating Chemicals using Reconstructed Human Cornea-like Epithelial (RhCE) Tissue Model

    PubMed Central

    Kaluzhny, Yulia; Kandárová, Helena; d’Argembeau-Thornton, Laurence; Kearney, Paul; Klausner, Mitchell

    2015-01-01

    To comply with the Seventh Amendment to the EU Cosmetics Directive and EU REACH legislation, validated non-animal alternative methods for reliable and accurate assessment of ocular toxicity in man are needed. To address this need, we have developed an eye irritation test (EIT) which utilizes a three dimensional reconstructed human cornea-like epithelial (RhCE) tissue model that is based on normal human cells. The EIT is able to separate ocular irritants and corrosives (GHS Categories 1 and 2 combined) and those that do not require labeling (GHS No Category). The test utilizes two separate protocols, one designed for liquid chemicals and a second, similar protocol for solid test articles. The EIT prediction model uses a single exposure period (30 min for liquids, 6 hr for solids) and a single tissue viability cut-off (60.0% as determined by the MTT assay). Based on the results for 83 chemicals (44 liquids and 39 solids) EIT achieved 95.5/68.2/ and 81.8% sensitivity/specificity and accuracy (SS&A) for liquids, 100.0/68.4/ and 84.6% SS&A for solids, and 97.6/68.3/ and 83.1% for overall SS&A. The EIT will contribute significantly to classifying the ocular irritation potential of a wide range of liquid and solid chemicals without the use of animals to meet regulatory testing requirements. The EpiOcular EIT method was implemented in 2015 into the OECD Test Guidelines as TG 492. PMID:26325674

  20. Reliability and Validity of Amharic Version of EORTC QLQ-C 30 Questionnaire among Gynecological Cancer Patients in Ethiopia

    PubMed Central

    Ayana, Birhanu Abera; Negash, Shiferaw; Yusuf, Lukman; Tigeneh, Wendemagegnhu

    2016-01-01

    Background Cancer is a growing public health problem worldwide. The focus of cancer treatment, in addition to curation, is improving the quality of life (QOL). This study aimed to assess the reliability and validity of Amharic version of European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) among gynecological cancer patients in Ethiopia. Methods A facility-based cross-sectional study was conducted using the Amharic version of EORTC QLQ-C30 on 153 gynecological cancer patients in Tikur Anbassa Specialized Hospital (TASH), Addis Ababa, Ethiopia. Descriptive statistics, correlation analysis and multivariable linear regression were employed in statistical analysis. Results The Amharic version of EORTC QLQ-C30 had a Cronbach’s α value of 0.81. The internal consistency for each domain of EORTC QLQ-C30 was also acceptable (Cronbach’s α >0.7) except for cognitive function domain (Cronbach’s α = 0.29). Stepwise multivariable linear regression analysis showed that emotional functioning (p<0.001), fatigue (p<0.001) and social functioning (p = 0.004) were the determinative scales of EORTC QLQ-C30 on global health status (GHS). The clinical validity test (Known group validity) showed that there were significant differences in score for twelve out of 15 domains, between surgery and radiation scheduled patients. All items of emotional function, role function, fatigue, and GHS meet the discriminate validity criterion. Conclusion The Amharic version of EORTC QLQ-C30 found to be reliable and had an acceptable validity to assess the QOL for gynecological cancer patients. We recommend further work on the validity and responsiveness of the EORTC QLQ-C30 with stronger design. PMID:27304066

  1. Fertility, birth timing and marital breakdown: a reinterpretation of the evidence.

    PubMed

    Murphy, M J

    1984-10-01

    The conventional view that childlessness was associated with higher than average risk of marital breakdown was questioned on the basis of analysis of divorce records. The General Household Survey (GHS) is a large scale multipurpose continuous household survey in Great Britain. Since 1979, it has contained an expanded family information section addressed to women under 50 which, for ever-married women, collects information about numbers and dates of marriages, births (both inside and outside marriage) and, in the case of marriages which have ended, the reason for ending (death, divorce or separation), the date when cohabitation ceased and the date of absolute decree if available. In 1980, there were 5017 ever-married women aged 16-49 for whom marriage and fertility histories were obtained. Some results are shown for the interval between separation and divorce based on life table methods for women aged 50 and under. The marriage duration data suggest that, apart from very short and very long durations, the proportion of separation not followed by divorce by 10 years is reasonably constant, about 13%. The median interval is around 2.5 years, with short and long duration marriages having above-average intervals, partly due to restictions on divorce in the early years of marriage. The proportion of marriages breaking down at various marriage durations by the fertility status at the start of the year in question is shown. The proportion is calculated as the number of marriages which were intact at various specified marriage durations, but which had broken down in 1, 5 or 10 years and which could have experienced the full period in the absence of breakdown. At short durations, early childbearing (including premarital births) is associated with higher than average probabilities of breakdown. The impression given by these results is different from other studies. Retrospective multipurpose surveys such as the GHS appear to have many advantages over administrative records

  2. Bone disease in primary hypercalciuria

    PubMed Central

    Sella, Stefania; Cattelan, Catia; Realdi, Giuseppe; Giannini, Sandro

    2008-01-01

    Primary Hypercalciuria (PH) is very often accompanied with some degrees of bone demineralization. The most frequent clinical condition in which this association has been observed is calcium nephrolithiasis. In patients affected by this disorder bone density is very frequently low and increased susceptibility to fragility fractures is reported. The very poor definition of this bone disease from a histomorphometric point of view is a crucial aspect. At present, the most common finding seems to be a low bone turnover condition. Many factors are involved in the complex relationships between bone loss and PH. Since bone loss was mainly reported in patients with fasting hypercalciuria, a primary alteration in bone metabolism was proposed as a cause of both hypercalciuria and bone demineralization. This hypothesis was strengthened by the observation that some bone resorbing-cytokines, such as IL-1, IL-6, and TNF-α are high in hypercalciuric patients. The effect of an excessive response to the acid load induced by dietary protein intake seems an additional factor explaining a primitive alteration of bone. The intestine plays a major role in the clinical course of bone disease in PH. Patients with absorptive hypercalciuria less frequently show bone disease and a reduction in dietary calcium greatly increases the probability of bone loss in PH subjects. It has recently been reported that greater bone loss is associated with a larger increase in intestinal calcium absorption in PH patients. Considering the absence of PTH alterations, it was proposed that this is not a compensatory phenomenon, but probably the marker of disturbed cell calcium transport, involving both intestinal and bone tissues. While renal hypercalciuria is rather uncommon, the kidney still seems to play a role in the pathogenesis of bone loss of PH patients, possibly via the effect of mild to moderate urinary phosphate loss with secondary hypophosphatemia. In conclusion, bone loss is very common in PH

  3. Diet and renal stone formation.

    PubMed

    Trinchieri, A

    2013-02-01

    The relationship between diet and the formation of renal stones is demonstrated, but restrictive diets do not take into account the complexity of metabolism and the complex mechanisms that regulate the saturation and crystallization processes in the urine. The restriction of dietary calcium can reduce the urinary excretion of calcium but severe dietary restriction of calcium causes hyperoxaluria and a progressive loss of bone mineral component. Furthermore urinary calcium excretion is influenced by other nutrients than calcium as sodium, potassium, protein and refined carbohydrates. Up to 40% of the daily excretion of oxalate in the urine is from dietary source, but oxalate absorption in the intestine depends linearly on the concomitant dietary intake of calcium and is influenced by the bacterial degradation by several bacterial species of intestinal flora. A more rational approach should be based on the cumulative effects of foods and different dietary patterns on urinary saturation rather than on the effect of single nutrients. A diet based on a adequate intake of calcium (1000-1200 mg per day) and containment of animal protein and salt can decrease significantly urinary supersaturation for calcium oxalate and reduce the relative risk of stone recurrence in hypercalciuric renal stone formers. The DASH-style diet that is high in fruits and vegetables, moderate in low-fat dairy products and low in animal proteins and salt is associated with a lower relative supersaturation for calcium oxalate and a marked decrease in risk of incident stone formation. All the diets above mentioned have as a common characteristic the reduction of the potential acid load of the diet that can be correlated with a higher risk of recurrent nephrolithiasis, because the acid load of diet is inversely related to urinary citrate excretion. The restriction of protein and salt with an adequate calcium intake seem to be advisable but should be implemented with the advice to increase the intake

  4. Renal Stone Risk During Space Flight

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy A.; Pietrzyk, Robert A.; Sams, Clarence F.; Pak, Charles Y. C.; Jones, Jeffrey A.

    1999-01-01

    Space flight produces a number of metabolic and physiological changes in the crewmembers exposed to microgravity. Following launch, body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary chemical composition may lead to the potentially serious consequences of renal stone formation. Previous data collected immediately after space flight indicate changes in the urine chemistry favoring an increased risk of calcium oxalate and uric acid stone formation (n = 323). During short term Shuttle space flights, the changes observed include increased urinary calcium and decreased urine volume, pH and citrate resulting in a greater risk for calcium oxalate and brushite stone formation (n = 6). Results from long duration Shuttle/Mir missions (n = 9) followed a similar trend and demonstrated decreased fluid intake and urine volume and increased urinary calcium resulting in a urinary environment saturated with the calcium stone-forming salts. The increased risk occurs rapidly upon exposure to microgravity, continues throughout the space flight and following landing. Dietary factors, especially fluid intake, or pharmacologic intervention can significantly influence the urinary chemical composition. Increasing fluid intake to produce a daily urine output of 2 liters/day may allow the excess salts in the urine to remain in solution, crystals formation will not occur and a renal stone will not develop. Results from long duration crewmembers (n = 2) who had urine volumes greater than 2.5 L/day minimized their risk of renal stone formation. Also, comparisons of stone-forming risk in short duration crewmembers clearly identified greater risk in those who produced less than 2 liters of urine/day. However, hydration and increased urine output does not correct the underlying calcium excretion due to bone loss and only treats the symptoms and not the cause of the increased urinary salts

  5. Effects of ghrelin and its analogues on chicken ovarian granulosa cells.

    PubMed

    Sirotkin, A V; Grossmann, R

    2008-02-01

    The aim of these in vitro experiments was (1) to examine the effects of ghrelin on the basic functions of ovarian cells (proliferation, apoptosis, secretory activity); (2) to determine the possible involvement of the GHS-R1a receptor and PKA- and MAPK-dependent post-receptor intracellular signalling cascades; (3) to identify the active part of the 28-amino acid molecule responsible for the effects of ghrelin on ovarian cells. We compared the effect of full-length ghrelin 1-28, a synthetic activator of GHS-R1a, GHRP6, and ghrelin molecular fragments 1-18 and 1-5 on cultured chicken ovarian cells. Indices of cell apoptosis (expression of the apoptotic peptide bax and the anti-apoptotic peptide bcl-2), proliferation (expression of proliferation-associated peptide PCNA), and expression of protein kinases (PKA and MAPK) within ovarian granulosa cells were analysed by immunocytochemistry. The secretion of progesterone (P(4)), testosterone (T), estradiol (E(2)) and arginine-vasotocin (AVT) by isolated ovarian follicular fragments was evaluated by RIA/EIA. It was observed that accumulation of bax was increased by ghrelin 1-28, GHRP6 and ghrelin 1-18, but not by ghrelin 1-5. Expression of bcl-2 was suppressed by addition of ghrelin 1-28, GHRP6 and ghrelin 1-5, but promoted by ghrelin 1-18. The occurrence of PCNA was reduced by ghrelin 1-28, GHRP6, ghrelin 1-18 and ghrelin 1-5. An increase in the expression of MAPK/ERK1, 2 was observed after addition of ghrelin 1-28, GHRP6 and ghrelin 1-18, but not ghrelin 1-5. The accumulation of PKA decreased after treatment with ghrelin 1-28 and increased after treatment with GHRP6 and ghrelin 1-18 but not ghrelin 1-5. Secretion of P(4) by ovarian follicular fragments was decreased after addition of ghrelin 1-28 or ghrelin 1-5 but stimulated by GHRP6 and ghrelin 1-18. Testosterone secretion was inhibited by ghrelins 1-28 and 1-18, but not by GHRP6 or ghrelin 1-5. Estradiol secretion was reduced after treatment with ghrelin 1-28 but

  6. Isotopic analysis of northern Himalayan gneiss domes

    NASA Astrophysics Data System (ADS)

    Hassett, W. C.

    2010-12-01

    The Leo Pargil, Renbu, and Yalashangbo gneiss domes are among the western and eastern most in the chain of north Himalayan gneiss domes. The processes of gneiss dome formation are still debated, but there is a growing consensus that they result from the diapiric rise of pooled melt from a mid-crustal, ductile channel (Whitney et al., 2004). Under the channel flow model, the ductile channel is exhumed towards the southern Himalayan range front and is exposed as the Greater Himalayan Sequence (GHS) (Beaumont et al., 2004). Gneiss domes should have a petrogenetic relationship to the GHS if the channel flow theory is correct. Geochemical investigation of these gneiss domes can therefore help to determine their provenance and mode of origin. Leo Pargil is composed of high-grade metamorphic rocks consisting of schists, phyllites, metasiltstone, metagraywacke, and subordinate quartzites, with numerous cm-m scale two-mica granite, tourmaline granite, and leucogranite dikes that constitute between 10% and 50% of the host rock (Thiede, 2006). The Renbu gneiss dome consists of an undeformed two-mica leucogranite pluton intruded into Triassic shales, and lies on the west side of a northerly trending graben belonging to the Yadong-Gulu rift system (Miller, unpublished). The Yalashangbo gneiss dome consists of muscovite-biotite granite pluton, with common pegmatite dikes and gneisses (Zhang et al., 2007). Leo Pargil has relict U/Pb zircon core ages ranging from Late Archean to Middle Paleozoic (2.8 Ga to 400 Ma) and Middle Eocene to Middle Miocene ages (49 Ma to 15 Ma) for zircon rims. The Renbu dome has relict U/Pb zircon core ages ranging from Late Archean to Late Triassic (2.5 Ga to 200 Ma) and Late Eocene to Late Miocene ages (39 Ma to 7 Ma) for zircon rims. Yalashangbo has relict U/Pb zircon core ages ranging from Late Paleoproterozoic to Middle Cretaceous (1.8 Ga to 115 Ma), but has no zircon rim ages and therefore does not record the timing of most recent magmatism

  7. South African farm workers' interpretation of risk assessment data expressed as pictograms on pesticide labels

    SciTech Connect

    Rother, Hanna-Andrea

    2008-11-15

    chemical labels under the new Globally Harmonized System for the Classification and Labelling of Chemicals (GHS). Particularly as the GHS pictograms were not piloted prior to adoption of the system and represent complex risk assessment data such as chronic hazards. Public health and pesticide policy, backed by relevant research, need to address developing applicable and effective pesticide risk communication tools, particularly for developing country populations. Merely providing risk assessment derived information in a pictogram does not ensure that an end-user will interpret the message as intended and be able to make risk decisions which mitigate risks from exposures to pesticides or chemicals in general.

  8. Progression from South-Directed to Orogen-Parallel Mid-Crustal Flow on the Southern Margin of the Tibetan Plateau, Ama Drime Massif, Tibet

    NASA Astrophysics Data System (ADS)

    Jessup, M. J.; Cottle, J. M.; Newell, D. L.; Berger, A. L.; Spotila, J. A.

    2008-12-01

    In the South Tibetan Himalaya, two major detachment systems are exposed in the Ama Drime and Mount Everest Massifs. These structures represent a fundamental shift in the dynamics of the Himalayan orogen, recording a progression from south-directed to orogen-parallel mid-crustal flow and exhumation. The South Tibetan detachment system (STDS) accommodated exhumation of the Greater Himalayan series (GHS) until the Middle Miocene. A relatively narrow mylonite zone that progressed into a brittle detachment accommodated exhumation of the GHS. Northward, in the down-dip direction (Dzakaa Chu and Doya La), a 1-km-wide distributed zone of deformation that lacks a foliation-parallel brittle detachment characterizes the STDS. Leucogranites in the footwall of the STDS range between 17-18 Ma. Previously published 40Ar/39Ar ages suggest that movement on the STDS ended by ~ 16 Ma in Rongbuk Valley and ~ 13 Ma near Dinggye. This once continuous section of the STDS is displaced by the trans- Himalayan Ama Drime Massif and Xainza-Dinggye graben. Two oppositely dipping normal faults and shear zones that bound the Ama Drime Massif record orogen-parallel extension. During exhumation, deformation was partitioned into relatively narrow (100-300-m-thick) mylonite zones that progressed into brittle faults/detachments, which offset Quaternary deposits. U(-Th-)Pb geochronology of mafic lenses suggests that the core of the ADM reached granulite facies at ~ 15 Ma. Leucogranites in the footwall of the detachment faults range between 12-11 Ma: significantly younger than those related to movement on the STDS. Previously published 40Ar/39Ar ages from the eastern limb of the Ama Drime Massif suggest that exhumation progressed into the footwall of the Nyüonno detachment between ~ 13-10 Ma. (U-Th)/He apatite ages record a minimum exhumation rate of ~ 1mm/yr between 1.5-3.0 Ma that was enhanced by focused denudation in the trans-Himalayan Arun River gorge. Together these bracket the timing (~ 12 Ma

  9. 21 Ma Eclogite From the Main Central Thrust Sheet, Eastern Nepal Himalaya

    NASA Astrophysics Data System (ADS)

    Corrie, S. L.; Kohn, M. J.; Vervoort, J. D.; Parkinson, C. D.

    2007-12-01

    Though uncommon throughout the Himalaya, eclogites have been documented in the Kaghan Valley of Pakistan, the Tso Morari dome in India, the Kharta region of Tibet, and the Makalu-Everest region of the Arun River valley in eastern Nepal. The Kaghan and Tso Morari UHP eclogites have been dated at ~50 Ma, and are commonly viewed as reflecting aborted subduction of the leading edge of the Indian plate during the initial stages of Indo- Asian collision. Here we show that the Arun eclogites are significantly younger, only ~21 Ma, so reflect either different origins, or substantial time lags in tectonics along strike. The Arun eclogites are stratigraphically continuous with the surrounding Greater Himalayan Sequence (GHS) felsic gneisses, and have been interpreted as metamorphosed basaltic sills. P-T conditions have been estimated at >14 kbar at 670-710 °C. The GHS in this region overlies Lesser Himalayan rocks along the Main Central Thrust (MCT), which can be traced for over 2000 km along strike. Lu-Hf dates from garnet separates in one relict eclogite indicate an age of 20.7±0.4 Ma (MSWD = 2.2). Five garnet amphibolites from nearby were also dated via Lu-Hf, and their ages range from 14-20 Ma (13.9±2.5, 14.1±0.3, 14.5±2.8, 15.1±0.6, and 19.8±1.1 Ma). The ~21 Ma age obtained from the eclogite postdates eclogite ages from the western Himalaya (Kaghan and Tso Morari) by ~30 Myr, and has important implications for tectonic models of Himalayan orogenesis. One possible model is that (aborted) subduction, slab breakoff, and ascent of India's leading edge occurred diachronously: ~50 Ma in the western Himalaya, ~20 Ma in eastern Nepal, and presumably even younger in the eastern Himalaya. Alternatively, because the Arun eclogites did not reach ultra-high pressure conditions seen by western eclogites (only ≥45, not ≥90 km depth), they may simply reflect deepening or longer transport of the MCT in the Arun area. Regardless, a ~21 Ma age for these eclogites combined with

  10. GUESS-ing Polygenic Associations with Multiple Phenotypes Using a GPU-Based Evolutionary Stochastic Search Algorithm

    PubMed Central

    Hastie, David I.; Zeller, Tanja; Liquet, Benoit; Newcombe, Paul; Yengo, Loic; Wild, Philipp S.; Schillert, Arne; Ziegler, Andreas; Nielsen, Sune F.; Butterworth, Adam S.; Ho, Weang Kee; Castagné, Raphaële; Munzel, Thomas; Tregouet, David; Falchi, Mario; Cambien, François; Nordestgaard, Børge G.; Fumeron, Fredéric; Tybjærg-Hansen, Anne; Froguel, Philippe; Danesh, John; Petretto, Enrico; Blankenberg, Stefan; Tiret, Laurence; Richardson, Sylvia

    2013-01-01

    Genome-wide association studies (GWAS) yielded significant advances in defining the genetic architecture of complex traits and disease. Still, a major hurdle of GWAS is narrowing down multiple genetic associations to a few causal variants for functional studies. This becomes critical in multi-phenotype GWAS where detection and interpretability of complex SNP(s)-trait(s) associations are complicated by complex Linkage Disequilibrium patterns between SNPs and correlation between traits. Here we propose a computationally efficient algorithm (GUESS) to explore complex genetic-association models and maximize genetic variant detection. We integrated our algorithm with a new Bayesian strategy for multi-phenotype analysis to identify the specific contribution of each SNP to different trait combinations and study genetic regulation of lipid metabolism in the Gutenberg Health Study (GHS). Despite the relatively small size of GHS (n = 3,175), when compared with the largest published meta-GWAS (n>100,000), GUESS recovered most of the major associations and was better at refining multi-trait associations than alternative methods. Amongst the new findings provided by GUESS, we revealed a strong association of SORT1 with TG-APOB and LIPC with TG-HDL phenotypic groups, which were overlooked in the larger meta-GWAS and not revealed by competing approaches, associations that we replicated in two independent cohorts. Moreover, we demonstrated the increased power of GUESS over alternative multi-phenotype approaches, both Bayesian and non-Bayesian, in a simulation study that mimics real-case scenarios. We showed that our parallel implementation based on Graphics Processing Units outperforms alternative multi-phenotype methods. Beyond multivariate modelling of multi-phenotypes, our Bayesian model employs a flexible hierarchical prior structure for genetic effects that adapts to any correlation structure of the predictors and increases the power to identify associated variants. This

  11. The Gutenberg Health Study: measuring psychosocial factors at work and predicting health and work-related outcomes with the ERI and the COPSOQ questionnaire

    PubMed Central

    2013-01-01

    Background Several instruments have been developed to assess psychosocial workload. We compared two of these instruments, the Effort-Reward Imbalance (ERI) model and the Copenhagen Psychosocial Questionnaire (COPSOQ) with regard to congruent validity and internal validity. Methods This analysis is based on a population-based sample of the baseline examination of 2,783 employees from the Gutenberg Health Study (GHS). About half of the participants completed the ERI questionnaire (n = 1,342), the other half completed the COPSOQ (n = 1,441). First, the two samples were compared and descriptive analyses were carried out calculating mean values for both instruments in general, then separately for age, gender and main occupational groups. Second, we analyzed the relationship between ERI and COPSOQ scales on the workplace situation and on the workplace outcomes: job satisfaction, general health, burnout, satisfaction with life, by applying stepwise logistic regression analysis. Results and discussion For the majority of occupations, high effort as reflected by the ERI corresponded with high demands as reflected by the COPSOQ. Comparably, high reward (according to ERI) yielded a good agreement with high “influence and development” (according to COPSOQ). However, we could also find differences between ERI and COPSOQ concerning the intensity of psychosocial workload in some occupations (e.g., physicians/pharmacists or warehouse managers/warehousemen/transport workers). These differences point to differing theoretical concepts of ERI and COPSOQ. When the ability of ERI and COPSOQ was examined to determine the associations with health and work outcomes, burnout could be better predicted by the COPSOQ; this might be due to the fact that COPSOQ comprises the constructs “work-privacy conflict” and “emotional demand”, which are closely related to burnout. However, methodological differences between these instruments limit their direct comparability. Conclusions

  12. Sharing Physician Notes Through an Electronic Portal is Associated With Improved Medication Adherence: Quasi-Experimental Study

    PubMed Central

    Darer, Jonathan; Tang, Xiaoqin; Thompson, Jason; Tusing, Lorraine; Fossa, Alan; Delbanco, Tom

    2015-01-01

    Background In surveys, interviews, and focus groups, patients taking medications and offered Web portal access to their primary care physicians’ (PCPs) notes report improved adherence to their regimens. However, objective confirmation has yet to be reported. Objective To evaluate the association between patient Internet portal access to primary care physician visit notes and medication adherence. Methods This study is a retrospective comparative analysis at one site of the OpenNotes quasi-experimental trial. The setting includes primary care practices at the Geisinger Health System (GHS) in Danville, Pennsylvania. Participants include patients 18 years of age or older with electronic portal access, GHS primary care physicians, and Geisinger health plan insurance, and taking at least one antihypertensive or antihyperlipidemic agent from March 2009 to June 2011. Starting in March 2010, intervention patients were invited and reminded to read their PCPs' notes. Control patients also had Web portal access throughout, but their PCPs' notes were not available. From prescription claims, adherence was assessed by using the proportion of days covered (PDC). Patients with a PDC ≥.80 were considered adherent and were compared across groups using generalized linear models. Results A total of 2147 patients (756 intervention participants, 35.21%; 1391 controls, 64.79%) were included in the analysis. Compared to those without access, patients invited to review notes were more adherent to antihypertensive medications—adherence rate 79.7% for intervention versus 75.3% for control group; adjusted risk ratio, 1.06 (95% CI 1.00-1.12). Adherence was similar among patient groups taking antihyperlipidemic agents—adherence rate 77.6% for intervention versus 77.3% for control group; adjusted risk ratio, 1.01 (95% CI 0.95-1.07). Conclusions Availability of notes following PCP visits was associated with improved adherence by patients prescribed antihypertensive, but not

  13. Correction: Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    PubMed Central

    2014-01-01

    Abstract The version of this article published in BMC Genomics 2013, 14: 274, contains 9 unpublished genomes (Botryobasidium botryosum, Gymnopus luxurians, Hypholoma sublateritium, Jaapia argillacea, Hebeloma cylindrosporum, Conidiobolus coronatus, Laccaria amethystina, Paxillus involutus, and P. rubicundulus) downloaded from JGI website. In this correction, we removed these genomes after discussion with editors and data producers whom we should have contacted before downloading these genomes. Removing these data did not alter the principle results and conclusions of our original work. The relevant Figures 1, 2, 3, 4 and 6; and Table 1 have been revised. Additional files 1, 3, 4, and 5 were also revised. We would like to apologize for any confusion or inconvenience this may have caused. Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 94 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed

  14. Identification of a ghrelin-like peptide in two species of shark, Sphyrna lewini and Carcharhinus melanopterus.

    PubMed

    Kawakoshi, Akatsuki; Kaiya, Hiroyuki; Riley, Larry G; Hirano, Tetsuya; Grau, E Gordon; Miyazato, Mikiya; Hosoda, Hiroshi; Kangawa, Kenji

    2007-05-01

    In this study, we identified a ghrelin-like peptide (ghrelin-LP) in two elasmobranchs. The peptide, isoforms and cDNA encoding its precursor were isolated from the stomach of two sharks, the hammerhead (HH) shark (Sphyrna lewini) and the black-tip reef (BTR) shark (Carcharhinus melanopterus). The ghrelin-LP isolated from each shark was found to be 25 amino acids in length and exhibit high sequence homology with each other; only three amino acids were different. As has been shown in tetrapod and teleost fish ghrelins, shark ghrelin-LPs possess two forms that are distinguished by having the third serine residue (Ser) acylated by either octanoic or decanoic acid. The N-terminal four residues (GVSF), known as the active core of ghrelin, are not identical to those of other species (GSSF). Nevertheless, shark ghrelin-LP elevated Ca(2+) levels in CHO cell line expressing the growth hormone secretagogue receptor (GHS-R). Unlike teleosts ghrelin's, shark ghrelin-LPs are not amidated at the C-terminus. Messenger RNA of ghrelin-LP in the HH shark was predominantly expressed in the stomach as seen in other species, followed by the brain, intestine, gill, heart and liver. The nucleotide sequence of the ghrelin-LP gene in the HH shark was characterized to compare organization of the ghrelin gene with those in other species. The size of the HH ghrelin-LP gene was 8541 bp, two to ten times larger than that of other species studied to date. The HH ghrelin-LP gene is composed of five exons and four introns, which is the same as ghrelin genes in mammals, chicken and rainbow trout. In conclusion, the shark ghrelin-LPs identified in this study exhibit many characteristics for ghrelin in terms of peptide modifications, GHS-R activation, tissue distribution, and gene organization; however, it is necessary to further clarify their biological properties such as growth hormone-releasing or orexigenic activity before designating these peptides as ghrelin. PMID:17362948

  15. Self-reported utilization of mental health services in the adult German population--evidence for unmet needs? Results of the DEGS1-Mental Health Module (DEGS1-MH).

    PubMed

    Mack, Simon; Jacobi, Frank; Gerschler, Anja; Strehle, Jens; Höfler, Michael; Busch, Markus A; Maske, Ulrike E; Hapke, Ulfert; Seiffert, Ingeburg; Gaebel, Wolfgang; Zielasek, Jürgen; Maier, Wolfgang; Wittchen, Hans-Ulrich

    2014-09-01

    This paper provides up-to-date data on service use for mental health problems and disorders among adults aged 18-79 years in Germany derived from the Mental Health Module of the German Health Interview and Examination Survey for Adults (DEGS1-MH; N=4483). Data are based exclusively on self-report. Respondents were examined by clinically trained interviewers with a modified version of the Composite International Diagnostic Interview DIA-X/M-CIDI to assess diagnoses according to the criteria of DSM-IV-TR. Service use, i.e. contact to mental health care services, due to mental health problems was assessed for the past 12 months and lifetime, by type of sector and type of institution. Among respondents with a 12-month diagnosis of a mental disorder, 23.5% of the women and 11.6% of the men reported any service use in the past 12 months. Service use depends on type of diagnosis, comorbidity and socio-demographic characteristics. Lowest 12-month utilization rates were found for substance use disorders (15.6%; lifetime use 37.3%), highest for psychotic disorders (40.5%; lifetime 72.1%). Further, a considerable time lap was found between disorder onset and subsequent service use among the majority of cases with anxiety and mood disorders. This paper provides self-reported epidemiological data on mental health service use in Germany, complementing administrative statistics and the predecessor mental health module of the German Health Interview and Examination Survey (GHS-MHS) from 1998. Despite considerable changes in the mental health field in Germany and the existence of a comprehensive mental health care system without major financial barriers, we find no indications of substantially higher utilization rates for mental disorders as compared to other comparable European countries. Further, no indications of major overall changes in utilization rates are apparent. To pinpoint areas with unmet needs, more detailed analyses of the data are needed taking into account type

  16. Citrate and renal calculi: an update

    NASA Technical Reports Server (NTRS)

    Pak, C. Y.

    1994-01-01

    Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease.

  17. Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate kidney stones.

    PubMed

    Massey, L K; Roman-Smith, H; Sutton, R A

    1993-08-01

    Dietary restriction of oxalate intake has been used as therapy to reduce the risk of recurrence of calcium oxalate kidney stones. Although urinary oxalate is derived predominantly from endogenous synthesis, it may also be affected by dietary intake of oxalate and calcium. The risk of increasing urinary oxalate excretion by excessive consumption of dietary oxalate is greatest in individuals with a high rate of oxalate absorption, both with and without overt intestinal disease. Although oxalate-rich foods enhanced excretion of urinary oxalate in normal volunteers, the increase was not proportional to the oxalate content of the food. Only eight foods--spinach, rhubarb, beets, nuts, chocolate, tea, wheat bran, and strawberries--caused a significant increase in urinary oxalate excretion. Restriction of dietary calcium enhances oxalate absorption and excretion, whereas an increase in calcium intake may reduce urinary oxalate excretion by binding more oxalate in the gut. This review of the literature indicates that initial dietary therapy for stone-forming individuals can be limited to the restriction of foods definitely shown to increase urinary oxalate. The effects of oxalate-restricted diets on urinary oxalate should be evaluated by means of laboratory analyses of urine composition. Subsequent long-term therapy can be recommended if beneficial results are obtained from oxalate restriction at an appropriate calcium intake. PMID:8335871

  18. Prevention and treatment of nephrolithiasis: a review on the role of spa therapy.

    PubMed

    Mennuni, G; Serio, A; Fontana, M; Nocchi, S; Costantino, C; Tanzi, G; Stornelli, G; Fraioli, A

    2015-01-01

    The prevalence and incidence of nephrolithiasis is reported to be increasing across the world. It is a disease of increased urinary concentration of stone-forming salts. The physicochemical mechanism of stone formation includes precipitation, homogenous/heterogeneous nucleation, growth, aggregation and concretion of various modulators in urine. Necessary condition to develop stones is urinary supersaturation, due to reduced urinary volume or to an excesses solutes. Fluid intake is the main determinant of urine volume. Urine dilution can significantly decrease both the crystallization rate of the urinary salts and the aggregation of the crystals. A correct fluid intake can act on different effects: urinary tract washing, urinary volume increasing and dilution of solutes. In addition mineral waters have other particular features: greater diuretic effect, more important urinary dilution with solutes and microbial concentration reduction, urinary pH changes, superior washout effect due to mechanical effects and ureteral contractions. Adequate water intake is the most important conservative strategy in urolithiasis prevention; particularly hydropinotherapy with oligomineral water should be considered as an important instrument to prevent stones in subjects predisposed to the disease (family members of people suffering from kidney stones), to reduce relapses, and can help to eliminate residual fragments also after extracorporeal shock wave lithotripsy. It is recommended a management with increased mineral water intake to promote urine volume of at least 2.5L each day to prevent stone formation. Obviously water intake shall be varied in relation to the presence of contraindications or any diseases. PMID:26550821

  19. The influence of bacteria on struvite crystal habit and its importance in urinary stone formation

    NASA Astrophysics Data System (ADS)

    Clapham, L.; McLean, R. J. C.; Nickel, J. C.; Downey, J.; Costerton, J. W.

    1990-07-01

    Infection-induced urinary stones form as a result of a urinary tract infection by urease-producing bacteria. These stones are not totally crystalline in nature but rather consist of an agglomeration of bacteria, organic matrix, and crystal of struvite (MgNH 4PO 4· 6H 2O). Crystal formation is related to the ability of the bacteria to effect an increase in the urine pH. Another equally important bacterial role lies in their formation of a 'biofilm' which later becomes the organic matrix constituent of the stone. Results of the present in vitro study indicate that crystals are formed more readily if produced within the bacterial biofilm than in the surrounding urine. It is proposed that supersaturation, due in part to a bacterial-induced pH increase and in part to the metal binding tendency of the biofilm, leads to crystal formation via a gel growth mechanism within the biofilm itself. In time further bacterial cell division, microcolony.

  20. Application of SERS spectroscopy for detection of trace components in urinary deposits

    NASA Astrophysics Data System (ADS)

    Pucetaite, Milda; Velicka, Martynas; Tamosaityte, Sandra; Sablinskas, Valdas

    2014-03-01

    Surface-enhanced Raman scattering (SERS) spectroscopy can be a useful tool in regard to disease diagnosis and prevention. Advantage of SERS over conventional Raman spectroscopy is its significantly increased signal (up to factor of 106-108) which allows detection of trace amounts of substances in the sample. So far, this technique is successfully used for analysis of food, pieces of art and various biochemical/biomedical samples. In this work, we survey the possibility of applying SERS spectroscopy for detection of trace components in urinary deposits. Early discovery together with the identification of the exact chemical composition of urinary sediments could be crucial for taking appropriate preventive measures that inhibit kidney stone formation or growth processes. In this initial study, SERS spectra (excitation wavelength - 1064 nm) of main components of urinary deposits (calcium oxalate, uric acid, cystine, etc.) were recorded by using silver (Ag) colloid. Spectra of 10-3-10-5 M solutions were obtained. While no/small Raman signal was detected without the Ag colloid, characteristic peaks of the substances could be clearly separated in the SERS spectra. This suggests that even small amounts of the components could be detected and taken into account while determining the type of kidney stone forming in the urinary system. We found for the first time that trace amounts of components constituting urinary deposits could be detected by SERS spectroscopy. In the future study, the analysis of centrifuged urine samples will be carried out.

  1. Micovascular integration into porous polyHEMA scaffold

    NASA Astrophysics Data System (ADS)

    Cho, Eugenia H.; Boico, Alina; Wisniewski, Natalie A.; Gant, Rebecca; Helton, Kristen L.; Brown, Nga L.; Register, Janna K.; Vo-Dinh, Tuan; Schroeder, Thies; Klitzman, Bruce

    2014-03-01

    Surface-enhanced Raman scattering (SERS) spectroscopy can be a useful tool in regard to disease diagnosis and prevention. Advantage of SERS over conventional Raman spectroscopy is its significantly increased signal (up to factor of 106-108) which allows detection of trace amounts of substances in the sample. So far, this technique is successfully used for analysis of food, pieces of art and various biochemical/biomedical samples. In this work, we survey the possibility of applying SERS spectroscopy for detection of trace components in urinary deposits. Early discovery together with the identification of the exact chemical composition of urinary sediments could be crucial for taking appropriate preventive measures that inhibit kidney stone formation or growth processes. In this initial study, SERS spectra (excitation wavelength - 1064 nm) of main components of urinary deposits (calcium oxalate, uric acid, cystine, etc.) were recorded by using silver (Ag) colloid. Spectra of 10-3-10-5 M solutions were obtained. While no/small Raman signal was detected without the Ag colloid, characteristic peaks of the substances could be clearly separated in the SERS spectra. This suggests that even small amounts of the components could be detected and taken into account while determining the type of kidney stone forming in the urinary system. We found for the first time that trace amounts of components constituting urinary deposits could be detected by SERS spectroscopy. In the future study, the analysis of centrifuged urine samples will be carried out.

  2. [Can examination of spontaneous urine samples adequately replace 24-hour-urine samples for determining excretory rate of various lithogenic and inhibitory substances in metabolic evaluation of kidney calculi patients?].

    PubMed

    Brändle, E; Melzer, H; Gomez-Anson, B; Flohr, P; Kleinschmidt, K; Sieberth, H G; Hautmann, R E

    1996-03-01

    The gold standard for metabolic evaluation of stone-forming patients is the 24-h urine specimen. Recently, some authors have suggested that for routine metabolic evaluation spot urine samples are as valuable as the 24-h urine specimen. The purpose of our study, was to determine the value of the spot urine sample in comparison with the 24-h urine specimens. Eighty-eight healthy volunteers on different diets were investigated (32 vegetarians, 12 body-builders without protein concentrates, 28 body-builders on protein concentrates, and 16 subjects on a regular European diet). Using 24-h specimens, excretion rates of oxalate, calcium, sodium and potassium were determined. The concentration ratio of these electrolytes to creatinine was calculated for spot urine samples. A highly significant correlation between the excretion rates and the results of the spot urine samples was found for all parameters. However, the correlations showed considerable variations. On the other hand, we were able to show that creatinine excretion is highly dependent on daily protein intake, body weight and glomerular filtration rate. This leads to a considerable inter- and intraindividual variation in creatinine excretion. This variation of the creatinine excretion is the major cause for the variation in the results of spot urine samples. It is concluded that spot urine samples are an inadequate substitute for the 24-h urine specimen and that the 24-h urine specimen is still the basis for metabolic evaluation in stone patients. PMID:8650847

  3. Expression of bone matrix proteins in urolithiasis model rats.

    PubMed

    Yasui, T; Fujita, K; Sasaki, S; Sato, M; Sugimoto, M; Hirota, S; Kitamura, Y; Nomura, S; Kohri, K

    1999-08-01

    Urinary calcium stones are a pathological substance, and they show similarities to physiological mineralization and other pathological mineralizations. The expression of messenger (m) RNAs of osteopontin (OPN), matrix Gla protein (MGP), osteonectin (ON) and osteocalcin (OC) in bones and teeth has been described. We previously identified OPN as an important stone matrix protein. In addition, the spontaneous calcification of arteries and cartilage in mice lacking MGP was recently reported, a finding which indicates that MGP has a function as an inhibitor of mineralization. Here, we examined the mRNA expressions of OPN, MGP, ON, and OC in the kidneys of stone-forming model rats administered an oxalate precursor, ethylene glycol (EG) for up to 28 days. The Northern blotting showed that the mRNA expressions of OPN and MGP were markedly increased with the administration of EG, but their expression patterns differed. The OPN mRNA expression reached the maximal level at day 7 after the initiation of the EG treatment and showed no significant difference after 14 and 28 days, whereas the MGP mRNA expression rose gradually to day 28. The in situ hybridization demonstrated that the cell type expressing OPN mRNA was different from that expressing MGP. We suggest that OPN acts on calcification and MGP acts on suppression. PMID:10460895

  4. Antiurolithiatic and antioxidant activity of Hordeum vulgare seeds on ethylene glycol-induced urolithiasis in rats

    PubMed Central

    Shah, Jignesh G.; Patel, Bharat G.; Patel, Sandip B.; Patel, Ravindra K.

    2012-01-01

    Objective: The objective was to investigate the antiurolithiatic and antioxidant activity of ethanolic extract of Hordeum vulgare seeds (EHV) on ethylene glycol-induced urolithiasis in Wistar albino rats. Materials and Methods: Urolithiasis was produced in Wistar albino rats by adding 0.75% v/v ethylene glycol (EG) to drinking water for 28 days. The ethanolic extract of Hordeum vulgare seeds (EHV) was assessed for its curative and preventive action in urolithiasis. In preventive treatment, the EHV given from 1st day to 28th day, while in the curative regimen, the EHV was given from 15th day to 28th day. Various renal functional and injury markers such as urine volume, calcium, phosphate, uric acid, magnesium, urea, and oxalate were evaluated using urine, serum, and kidney homogenate. Antioxidant parameters such as lipid peroxidation, superoxide dismutase, and catalase were also determined. Results: The EHV treatment (both preventive and curative) increased the urine output significantly compared to the control. The EHV treatment significantly reduced the urinary excretion of the calcium, phosphate, uric acid, magnesium, urea, and oxalate and increased the excretion of citrate compared to EG control. The increased deposition of stone forming constituents in the kidneys of calculogenic rats were significantly lowered by curative and preventive treatment with EHV. It was also observed that the treatment with EHV produced significant decrease in lipid peroxidation, and increased levels of superoxide dismutase and catalase. Conclusion: These results suggest the usefulness of ethanolic extract of Hordeum vulgare seeds as an antiurolithiatic and antioxidant agent. PMID:23248392

  5. Nutrition and renal stone disease in space

    NASA Technical Reports Server (NTRS)

    Zerwekh, Joseph E.

    2002-01-01

    There is a growing body of evidence from the National Aeronautics and Space Administration and the Russian space program showing that humans exposed to the microgravity environment of space have a greater risk for developing renal stones. Increased bone resorption and the attendant hypercalciuria and hyperphosphaturia contribute significantly to raising the urinary state of saturation with respect to the calcium salts, namely calcium oxalate and calcium phosphate. In addition, other environmental and dietary factors may adversely affect urine composition and increase stone formation risk during space flight. For example, reductions in urinary volume, pH, and citrate contribute to raising stone formation risk. In addition to raising the risk for calcium stone formation, this metabolic profile is conducive to the formation of uric acid stones. Although observations to date have suggested that there may actually be a reduced food intake during the early phase of flight, crew members on longer-duration flights may increase food intake and be at increased risk for stone formation. Taken together, these findings support the use of nutritional recommendations for crew members that would serve to reduce the stone-forming propensity of the urinary environment. Pharmacologic intervention should be directed at raising urinary volumes, diminishing bone losses, and preventing reductions in urinary pH and citrate. Success in reducing the risk for stone formation in astronauts would also be of potential major benefit to the estimated 20 million Americans with nephrolithiasis.

  6. Nutrition and renal stone disease in space.

    PubMed

    Zerwekh, Joseph E

    2002-10-01

    There is a growing body of evidence from the National Aeronautics and Space Administration and the Russian space program showing that humans exposed to the microgravity environment of space have a greater risk for developing renal stones. Increased bone resorption and the attendant hypercalciuria and hyperphosphaturia contribute significantly to raising the urinary state of saturation with respect to the calcium salts, namely calcium oxalate and calcium phosphate. In addition, other environmental and dietary factors may adversely affect urine composition and increase stone formation risk during space flight. For example, reductions in urinary volume, pH, and citrate contribute to raising stone formation risk. In addition to raising the risk for calcium stone formation, this metabolic profile is conducive to the formation of uric acid stones. Although observations to date have suggested that there may actually be a reduced food intake during the early phase of flight, crew members on longer-duration flights may increase food intake and be at increased risk for stone formation. Taken together, these findings support the use of nutritional recommendations for crew members that would serve to reduce the stone-forming propensity of the urinary environment. Pharmacologic intervention should be directed at raising urinary volumes, diminishing bone losses, and preventing reductions in urinary pH and citrate. Success in reducing the risk for stone formation in astronauts would also be of potential major benefit to the estimated 20 million Americans with nephrolithiasis. PMID:12361779

  7. Antiurolithiatic effect of lithocare against ethylene glycol-induced urolithiasis in Wistar rats

    PubMed Central

    Lulat, Sumaiya I.; Yadav, Yogesh Chand; Balaraman, R.; Maheshwari, Rajesh

    2016-01-01

    Aim: This study is aimed to investigate the protective effect of Lithocare (LC) (a polyherbal formulation) against ethylene glycol (EG) induced urolithiasis in Wistar rats. Materials and Methods: The protective effect of LC (400 and 800 mg/kg) was evaluated using EG-induced urolithiasis in rats. Results: Administration of EG in drinking water resulted in hyperoxaluria, hypocalcemia as well as an increased renal excretion of phosphate. Supplementation with LC significantly reduced the urinary calcium, oxalate, and phosphate excretion dose-dependently. There was a significant reduction in the levels of calcium, oxalate as well as a number of calcium oxalate crystals deposits in the kidney tissue of rats administered with LC in EG-treated rats. There was a significant reduction in creatinine, urea, uric acid, and blood urea nitrogen when LC was administered in EG-treated rats. Conclusions: From this study, it was concluded that the supplementation of LC protected EG-induced urolithiasis as it reduced the growth of urinary stones. The mechanism underlying this effect might be due to its antioxidant, diuretic, and reduction in stone-forming constituents. PMID:26997728

  8. Studying inhibition of calcium oxalate stone formation: an in vitro approach for screening hydrogen sulfide and its metabolites

    PubMed Central

    Vaitheeswari, S.; Sriram, R.; Brindha, P.; Kurian, Gino A.

    2015-01-01

    ABSTRACT Purpose: Calcium oxalate urolithiasis is one of the most common urinary tract diseases and is of high prevalence. The present study proposes to evaluate the antilithiatic property of hydrogen sulfide and its metabolites like thiosulfate & sulfate in an in vitro model. Materials and Methods: The antilithiatic activity of sodium hydrogen sulfide (NaSH), sodium thiosulfate (Na2S2O3) and sodium sulfate (Na2SO4) on the kinetics of calcium oxalate crystal formation was investigated both in physiological buffer and in urine from normal and recurrent stone forming volunteers. The stones were characterized by optical and spectroscopic techniques. Results: The stones were characterized to be monoclinic, prismatic and bipyramidal habit which is of calcium monohydrate and dihydrate nature. The FTIR displayed fingerprint corresponding to calcium oxalate in the control while in NaSH treated, S=O vibrations were visible in the spectrum. The order of percentage inhibition was NaSH>Na2S2O3>Na2SO4. Conclusion: Our study indicates that sodium hydrogen sulfide and its metabolite thiosulfate are inhibitors of calcium oxalate stone agglomeration which makes them unstable both in physiological buffer and in urine. This effect is attributed to pH changes and complexing of calcium by S2O3 2-and SO4 2- moiety produced by the test compounds. PMID:26200543

  9. Artificial tektites: an experimental technique for capturing the shapes of spinning drops.

    PubMed

    Baldwin, Kyle A; Butler, Samuel L; Hill, Richard J A

    2015-01-01

    Determining the shapes of a rotating liquid droplet bound by surface tension is an archetypal problem in the study of the equilibrium shapes of a spinning and charged droplet, a problem that unites models of the stability of the atomic nucleus with the shapes of astronomical-scale, gravitationally-bound masses. The shapes of highly deformed droplets and their stability must be calculated numerically. Although the accuracy of such models has increased with the use of progressively more sophisticated computational techniques and increases in computing power, direct experimental verification is still lacking. Here we present an experimental technique for making wax models of these shapes using diamagnetic levitation. The wax models resemble splash-form tektites, glassy stones formed from molten rock ejected from asteroid impacts. Many tektites have elongated or 'dumb-bell' shapes due to their rotation mid-flight before solidification, just as we observe here. Measurements of the dimensions of our wax 'artificial tektites' show good agreement with equilibrium shapes calculated by our numerical model, and with previous models. These wax models provide the first direct experimental validation for numerical models of the equilibrium shapes of spinning droplets, of importance to fundamental physics and also to studies of tektite formation. PMID:25564381

  10. Artificial tektites: an experimental technique for capturing the shapes of spinning drops

    NASA Astrophysics Data System (ADS)

    Baldwin, Kyle A.; Butler, Samuel L.; Hill, Richard J. A.

    2015-01-01

    Determining the shapes of a rotating liquid droplet bound by surface tension is an archetypal problem in the study of the equilibrium shapes of a spinning and charged droplet, a problem that unites models of the stability of the atomic nucleus with the shapes of astronomical-scale, gravitationally-bound masses. The shapes of highly deformed droplets and their stability must be calculated numerically. Although the accuracy of such models has increased with the use of progressively more sophisticated computational techniques and increases in computing power, direct experimental verification is still lacking. Here we present an experimental technique for making wax models of these shapes using diamagnetic levitation. The wax models resemble splash-form tektites, glassy stones formed from molten rock ejected from asteroid impacts. Many tektites have elongated or `dumb-bell' shapes due to their rotation mid-flight before solidification, just as we observe here. Measurements of the dimensions of our wax `artificial tektites' show good agreement with equilibrium shapes calculated by our numerical model, and with previous models. These wax models provide the first direct experimental validation for numerical models of the equilibrium shapes of spinning droplets, of importance to fundamental physics and also to studies of tektite formation.

  11. Artificial tektites: an experimental technique for capturing the shapes of spinning drops

    PubMed Central

    Baldwin, Kyle A.; Butler, Samuel L.; Hill, Richard J. A.

    2015-01-01

    Determining the shapes of a rotating liquid droplet bound by surface tension is an archetypal problem in the study of the equilibrium shapes of a spinning and charged droplet, a problem that unites models of the stability of the atomic nucleus with the shapes of astronomical-scale, gravitationally-bound masses. The shapes of highly deformed droplets and their stability must be calculated numerically. Although the accuracy of such models has increased with the use of progressively more sophisticated computational techniques and increases in computing power, direct experimental verification is still lacking. Here we present an experimental technique for making wax models of these shapes using diamagnetic levitation. The wax models resemble splash-form tektites, glassy stones formed from molten rock ejected from asteroid impacts. Many tektites have elongated or ‘dumb-bell' shapes due to their rotation mid-flight before solidification, just as we observe here. Measurements of the dimensions of our wax ‘artificial tektites' show good agreement with equilibrium shapes calculated by our numerical model, and with previous models. These wax models provide the first direct experimental validation for numerical models of the equilibrium shapes of spinning droplets, of importance to fundamental physics and also to studies of tektite formation. PMID:25564381

  12. Modification by food of the calcium absorbability and physicochemical effects of calcium citrate

    NASA Technical Reports Server (NTRS)

    Wabner, C. L.; Pak, C. Y.

    1992-01-01

    The food-calcium (Ca) interaction was examined in 12 healthy women (mean age 38 years) maintained on a constant metabolic diet. They underwent three phases of study, comprised of control (no Ca), Ca citrate (1 g Ca/day) during meals, and Ca citrate separately from meals. Each phase was 7 days in length and two 24-hour urine samples were collected on days 6 and 7. The rise from the control phase in urinary Ca was slightly more prominent when Ca citrate was given with meals than without (68 and 62%, respectively). The fall in urinary phosphorus was equivalent at about 25% between Ca citrate phases. The rise in urinary citrate and pH and the decline in urinary ammonium were more prominent when Ca citrate was given with meals; however, the changes were small or nonsignificant. The urinary saturation of Ca oxalate, brushite or monosodium urate did not differ between the two Ca citrate phases. There was a nonsignificant rise in serum iron during Ca citrate phases. The results suggest that: 1) dissolution and absorption of Ca citrate might be slightly greater when given with food than without; 2) that the ability of Ca citrate to attenuate crystallization of stone-forming Ca salts in urine is not modified by food; and 3) that Ca citrate may not impair iron absorption from food.

  13. [Infection-induced urinary stones].

    PubMed

    Bichler, K-H; Eipper, E; Naber, K

    2003-01-01

    Infection stones make up approximately 15% of urinary stone diseases and are thus an important group. These stones are composed of struvite and/or carbonate apatite. The basic precondition for the formation of infection stones is a urease-positive urinary tract infection. Urease is necessary to split urea into ammonia and CO(2). As a result, ammonia ions can form and at the same time alkaline urine develops, both being preconditions for the formation of struvite and carbonate apatite crystals. When these crystals are deposited infection stones form. Pathogenetically, various risk factors play a role: urinary obstruction, neurogenic bladder, dRTA, and MSK. If these infections are not treated and the stones are not removed, the kidney will be damaged. Modern methods are available for stone removal, e.g., ESWL and/or instrumental urinary stone removal. Here, especially less invasive methods are preferable. Any treatment must be adjusted to the patient individually. Patients should be examined frequently for recurrent urinary tract infections and stone recurrences, and new infections must be resolutely treated. Good therapy and prophylaxis are possible with present-day treatment modalities. PMID:12574884

  14. Kidney Stones

    PubMed Central

    Kleeman, Charles R.; Coburn, Jack W.; Brickman, Arnold S.; Lee, David B. N.; Narins, Robert G.; Ehrlich, Richard M.

    1980-01-01

    The prevalence of kidney stones has steadily risen during this century; passage of a calculus and a positive family history increase the probability of recurrence. Findings from recent studies on the cause of renal calculi have stressed crystallization and crystal aggregation of stone minerals from supersaturated urine, rather than excessive organic matrix. Absence of normal urine inhibitors of calcium salts is also stressed. Formation of calcium oxalate stones is the major problem. Therapy with decreased calcium and oxalate intake, thiazides, phosphate salts and allopurinol in various combinations has substantially decreased the prevalence of recurrent stones. The rationale for the use of allopurinol is that uric acid salts enhance the tendency for calcium oxalate to crystallize from supersaturated urine. The hypercalciuria seen in 30 percent to 40 percent of patients with oxalate stones is usually caused by intestinal hyperabsorption of calcium. Although patients with uric acid calculi constitute only a small fraction of those in whom stones form, they represent a group in whom good medical therapy, based on sound physiologic principles, has proved extremely successful. Renal tubular syndromes lead to nephrocalcinosis and lithiasis through hypercalciuria, alkaline urine and hypocitraturia, the latter an inhibitor of calcium salt precipitation. Recent advances in surgical techniques are discussed, including the rationale for removing staghorn calculi. The ileal ureter and coagulum pyelolithotomy deserve special emphasis. ImagesFigure 2.Figure 4.Figure 5.Figure 7. PMID:7385835

  15. Elemental Content of Calcium Oxalate Stones from a Canine Model of Urinary Stone Disease

    PubMed Central

    Killilea, David W.; Westropp, Jodi L.; Shiraki, Ryoji; Mellema, Matthew; Larsen, Jennifer; Kahn, Arnold J.; Kapahi, Pankaj; Chi, Thomas; Stoller, Marshall L.

    2015-01-01

    One of the most common types of urinary stones formed in humans and some other mammals is composed of calcium oxalate in ordered hydrated crystals. Many studies have reported a range of metals other than calcium in human stones, but few have looked at stones from animal models such as the dog. Therefore, we determined the elemental profile of canine calcium oxalate urinary stones and compared it to reported values from human stones. The content of 19 elements spanning 7-orders of magnitude was quantified in calcium oxalate stones from 53 dogs. The elemental profile of the canine stones was highly overlapping with human stones, indicating similar inorganic composition. Correlation and cluster analysis was then performed on the elemental profile from canine stones to evaluate associations between the elements and test for potential subgrouping based on elemental content. No correlations were observed with the most abundant metal calcium. However, magnesium and sulfur content correlated with the mineral hydration form, while phosphorous and zinc content correlated with the neuter status of the dog. Inter-elemental correlation analysis indicated strong associations between barium, phosphorous, and zinc content. Additionally, cluster analysis revealed subgroups within the stones that were also based primarily on barium, phosphorous, and zinc. These data support the use of the dog as a model to study the effects of trace metal homeostasis in urinary stone disease. PMID:26066810

  16. Sedimentary rocks in our mouth: dental pulp stones made by nanobacteria

    NASA Astrophysics Data System (ADS)

    Ciftcioglu, Neva; Ciftcioglu, Vefa; Vali, Hojatollah; Turcott, Eduardo; Kajander, E. Olavi

    1998-07-01

    The mechanisms of dental pulp stone formation are still largely unknown. Pulp stones are mainly composed of carbonate apatite. Only few experimental reports have elucidated the potential of some selected bacteria to produce apatite under in vitro conditions using special calcification media. The tested stone forming bacteria were, in fact, often better known for their cariogenic potential. Our preliminary work with 18 dental pulp stones from Turkey, selected only by severity of the stone formation, indicated the presence of nanobacterial antigens in the demineralized stones. Furthermore, high incidence of kidney stones and gall stones in the patient group and in their parents was found. This raises the implication that nanobacteria may enter the body also via oral route, in addition to the parenteral and transplacental routes. The role of nanobacteria in dental pulp stone formation was further studied by following nanobacterial colonization and mineral formation on human tooth in vitro. Two molar teeth, one having pulp stone and one without, were vertically cut into two pieces, sterilized by autoclaving and incubated with or without nanobacteria in DMEM. Electron microscopic observations indicate that nanobacteria can cause apatite stone formation on tooth surface. The sever from of dental pulp stone formation might be associated with nanobacteria. This form of dental disease results in loss of teeth due to osteolytic processes. This addresses the necessity for a study on unconventional mineral-forming bacteria as a cause for human diseases.

  17. Chemistry and Materials Science Directorate 2002 Postdoctoral Symposium

    SciTech Connect

    Wirth, B D

    2002-08-14

    The understanding of the physical mechanisms by which important biological inhibitors control the nucleation, growth, aggregation, and phase transformation of calcium oxalate crystals at fundamental level is of importance not only to the advances in biomineralization but also to the development of stone disease therapy. Of the three phases of calcium oxalate crystalline, calcium oxalate monohydrate (COM) and dehydrate (COD) are found in the majority of stones formed in the urinary system. Only COM, a major inorganic component of kidney stones, produces adverse physiological effects to human, however. Although a great deal of research has been carried out on the modulation of nucleation, growth, aggregation, and phase transformation of calcium oxalates by biological molecules, the basic mechanism has not yet been determined due to inherent limitations of those techniques that have been utilized The invention of atomic force microscopy (AFM) has opened a new avenue for the study of the crystal growth in general. One can now probe the growth kinetics and dynamics, and morphology of crystal surfaces down to molecular levels as a typical AFM has a lateral resolution of nanometers. In this study, in situ AFM was used to monitor the COM surface under controlled growth conditions. The growth on both (-101) and (010) faces was investigated. The effect of the macromolecules such as citrate and uropontin to the growth of surfaces was also explored. In this presentation, the structural basis for the observed results will be discussed and the implications of the findings to the field of medicine will also be addressed.

  18. Prediction of renal crystalline size distributions in space using a PBE analytic model. 2. Effect of dietary countermeasures.

    PubMed

    Kassemi, Mohammad; Thompson, David

    2016-09-01

    An analytic Population Balance Equation model is used to assess the efficacy of citrate, pyrophosphate, and augmented fluid intake as dietary countermeasures aimed at reducing the risk of renal stone formation for astronauts. The model uses the measured biochemical profile of the astronauts as input and predicts the steady-state size distribution of the nucleating, growing, and agglomerating renal calculi subject to biochemical changes brought about by administration of these dietary countermeasures. Numerical predictions indicate that an increase in citrate levels beyond its average normal ground-based urinary values is beneficial but only to a limited extent. Unfortunately, results also indicate that any decline in the citrate levels during space travel below its normal urinary values on Earth can easily move the astronaut into the stone-forming risk category. Pyrophosphate is found to be an effective inhibitor since numerical predictions indicate that even at quite small urinary concentrations, it has the potential of shifting the maximum crystal aggregate size to a much smaller and plausibly safer range. Finally, our numerical results predict a decline in urinary volume below 1.5 liters/day can act as a dangerous promoter of renal stone development in microgravity while urinary volume levels of 2.5-3 liters/day can serve as effective space countermeasures. PMID:27279491

  19. The risk of renal stone formation during and after long duration space flight

    NASA Technical Reports Server (NTRS)

    Whitson, P. A.; Pietrzyk, R. A.; Morukov, B. V.; Sams, C. F.

    2001-01-01

    BACKGROUND: The formation of a renal stone during space flight may have serious negative effects on the health of the crewmember and the success of the mission. Urinary biochemical factors and the influence of dietary factors associated with renal stone development were assessed during long duration Mir Space Station missions. METHODS: Twenty-four-hour urine samples were collected prior to, during and following long duration space flight. The relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were determined. RESULTS: Changes in the urinary biochemistry of crewmembers during long duration spaceflight demonstrated increases in the supersaturation of the stone-forming salts. In-flight hypercalciuria was evident in a number of individual crewmembers and 24-hour dietary fluid intake and urine volume were significantly lower. During flight, there was a significant increase in brushite supersaturation. CONCLUSIONS: These data suggest acute effects of space flight and postflight changes in the urinary biochemistry favoring increased crystallization in the urine. The effects of dietary intake, especially fluid intake, may have a significant impact on the potential for renal stone formation. Efforts are now underway to assess the efficacy of a countermeasure to mitigate the increased risk. Copyright 2001 S. Karger AG, Basel.

  20. Crystal aggregation in kidney stones; a polymer aggregation problem?

    NASA Astrophysics Data System (ADS)

    Wesson, J.; Beshensky, A.; Viswanathan, P.; Zachowicz, W.; Kleinman, J.

    2008-03-01

    Kidney stones most frequently form as aggregates of calcium oxalate monohydrate (COM) crystals with organic layers between them, and the organic layers contain principally proteins. The pathway leading to the formation of these crystal aggregates in affected people has not been identified, but stone forming patients are thought to have a defect in the structure or distribution of urinary proteins, which normally protect against stone formation. We have developed two polyelectrolyte models that will induce COM crystal aggregation in vitro, and both are consistent with possible urinary protein compositions. The first model was based on mixing polyanionic and polycationic proteins, in portions such that the combined protein charge is near zero. The second model was based on reducing the charge density on partially charged polyanionic proteins, specifically Tamm-Horsfall protein, the second most abundant protein in urine. Both models demonstrated polymer phase separation at solution conditions where COM crystal aggregation was observed. Correlation with data from other bulk crystallization measurements suggest that the anionic side chains form critical binding interactions with COM surfaces that are necessary along with the phase separation process to induce COM crystal aggregation.

  1. Computational fluid dynamics analysis of salivary flow and its effect on sialolithogenesis

    PubMed Central

    Zhu, P; Lin, Y; Lin, H; Xu, Y; Zheng, QY; Han, Y

    2014-01-01

    OBJECTIVE Sialolithiasis is a common disease caused by intraductal stones, formed by reduction in salivary flow, salivary stagnation, and metabolic events. We used computational fluid dynamics to investigate changes in salivary flow field around parotid stones of different shapes. MATERIALS AND METHODS Three-dimensional configurations of the Stensen’s duct were reconstructed from computed tomography sialographic images. Fluid dynamics modeling was used to analyze the salivary flow field around stones under unstimulated and stimulated conditions. RESULTS The majority of sialoliths were oval-shaped (59/98), followed by irregular (24/98) and round (15/98). Salivary velocity was significantly higher around streamlined stones, compared with round (P = 0.013) and oval (P = 0.025) types. Changes in salivary flow field around sialoliths were found to affect the pattern of mineral deposition in saliva. The area of low velocity around the round stone was double the size observed around the streamlined stone during the unstimulated state, whereas in the stimulated state, local vortexes were formed on the downstream side of round and oval stones. CONCLUSIONS Salivary flow field around sialoliths plays an important role in the progression of multicentric stones, and analysis of the salivary dynamics during sialolithiasis may provide deeper understandings of the condition and aid in developing successful treatment strategies. PMID:24164693

  2. Effect of drinking parsley leaf tea on urinary composition and urinary stones' risk factors.

    PubMed

    Alyami, Fahad A; Rabah, Danny M

    2011-05-01

    To investigate the effect of parsley leaf tea on urine composition and the inhibitors of urinary tract stones formation, we studied 20 healthy volunteers who were divided into two groups: the first group of 10 subjects drank daily 1,200 mL of parsley leaf tea for 2 weeks, while the second group drank at least 1,200 mL daily of bottled water for the same period. This was followed by a 2-week "washout" period before the two groups were crossed over for another 2 weeks. During the experimental phase, 24-h urine samples were collected at baseline, on day 14, and at the end of the 6-week period and different urinary parameters were measured and analyzed statistically. We found no significant difference in the urine volume, pH, sodium, potassium, chloride, urea, creatinine, phosphorus, magnesium, uric acid, cystine, or citric acid. Further research is needed to evaluate the effects of parsley leaf tea on urinary parameters in healthy and stone-forming patients. PMID:21566309

  3. Uric acid stones following hepatic transplantation.

    PubMed

    Hwang, Mei-Tsuey; Goldfarb, David S

    2004-12-01

    We report the case of a 52 year old man with a history of insulin-requiring diabetes and hepatitis B with cirrhosis who received an orthotopic liver transplant. One year later he developed renal colic and was found to have a 3 mm stone at the left ureterovesical junction. Numerous other stones formed and infrared spectroscopy analysis demonstrated all to be composed of 100% uric acid. Urine collections demonstrated a low urine pH of 5.1 without hyperuricosuria. His stones were effectively prevented with potassium citrate therapy. Few incidence data are available for uric acid stone occurrence in solid organ recipients. Calcineurin inhibitors are thought to often cause hyperuricemia on the basis of decreased urate excretion. However, this effect would not be expected to cause hyperuricosuria nor uric acid stones. This class of drugs may also be associated with low urine pH, perhaps on the basis of hypoaldosteronism, but the contribution of such a syndrome to uric acid stone formation is not established. PMID:15565437

  4. Renal calculi: emergency department diagnosis and treatment.

    PubMed

    Carter, Michelle R; Green, Brad R

    2011-07-01

    The acute treatment of kidney stones (urolithiasis) addresses pain management and focuses on the effects of the morbidity associated with an obstructed renal system. Minimal fluid intake, resulting in decreased urine production and a high concentration of stone-forming salts, is a leading factor in renal calculi development. Radio-opaque calcareous stones account for 70% to 75% of renal calculi. Microscopic hematuria in the presence of acute flank pain is suggestive of renal colic, but the absence of red blood cells does not exclude urolithiasis. Furthermore, many inflammatory and infectious conditions cause hematuria, demonstrating the low specificity of urinalysis testing. The diagnostic modality of choice is a noncontrast computed tomography (CT); ultrasonography s preferred in pregnant patients and children. Combining opioids with non-steroidal anti-inflammatory drugs (NSAIDs) is the optimal evidence-based regimen to treat severe symptoms. Rapid intravenous (IV) hydration has not shown a benefit. Potentially life-threatening diagnoses including abdominal aortic aneurysm, ovarian torsion, and appendicitis may mimic renal colic and must be ruled out. PMID:22164398

  5. Histopathology Predicts the Mechanism of Stone Formation

    NASA Astrophysics Data System (ADS)

    Evan, Andrew P.

    2007-04-01

    About 5% of American women and 12% of men will develop a kidney stone at some time in their life and these numbers appear to be on the rise. Despite years of scientific research into the mechanisms of stone formation and growth, limited advances have been made until recently. Randall's original observations and thoughts on the mechanisms for kidney stone formation have been validated for idiopathic calcium oxalate stone formers (ICSF) but not for most other stone forming groups. Our current studies on selected groups of human stone formers using intraoperative papillary biopsies has shown overwhelming evidence for the presence of Randall's plaque in ICSF and that stone formation and growth are exclusively linked to its availability to urinary ions and proteins. Intense investigation of the plaque-stone junction is needed if we are to understand the factors leading to the overgrowth process on exposed regions of plaque. Such information should allow the development of treatment strategies to block stone formation in ICSF patients. Patients who form brushite stones, or who form apatite stones because of distal renal tubular acidosis (dRTA), or patients with calcium oxalate stones due to obesity bypass procedures, or patients with cystinuria, get plugged inner medullary collecting ducts (IMCD) which leads to total destruction of the lining cells and focal sites of interstitial fibrosis. These stone formers have plaque but at levels equal to or below non-stone formers, which would suggest that they form stones by a different mechanism than do ICSF patients.

  6. Do Kidney Stone Formers Have A Kidney Disease?

    PubMed Central

    Zisman, Anna L.; Evan, Andrew P.; Coe, Fredric L.; Worcester, Elaine M.

    2015-01-01

    Nephrolithiasis is a highly prevalent disorder affecting approximately one in eleven people and is associated with multiple complications including hypertension, cardiovascular disease, and chronic kidney disease. Significant epidemiologic associations with chronic kidney disease and ESRD have been noted and are reviewed herein, but debate persists in the literature as to whether kidney stone formation is a pathogenic process contributing to kidney disease. Corroborating evidence supporting the presence of kidney disease in stone formers includes the variability of renal function by stone type, the positive association of stone size with renal dysfunction, the presence of markers of renal injury in the urine of even asymptomatic stone formers, and direct evidence of renal tissue injury on histopathology. Proposed pathogenic mechanisms include recurrent obstruction and comorbid conditions such as recurrent urinary tract infections and structural abnormalities. Recent work evaluating the renal histopathology of different groups of stone formers adds further granularity, suggesting variability in mechanisms of renal injury by stone type and confirming the pathogenic effects of crystal formation. Genetic abnormalities leading to stone formation including cystinuria and primary hyperoxaluria, among others, contribute to the burden of disease in the stone-forming population. PMID:26376133

  7. Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent

    PubMed Central

    Crost, Emmanuelle H.; Tailford, Louise E.; Le Gall, Gwenaelle; Fons, Michel; Henrissat, Bernard; Juge, Nathalie

    2013-01-01

    Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease. PMID:24204617

  8. Suitability of the isolated chicken eye test for classification of extreme pH detergents and cleaning products.

    PubMed

    Cazelle, Elodie; Eskes, Chantra; Hermann, Martina; Jones, Penny; McNamee, Pauline; Prinsen, Menk; Taylor, Hannah; Wijnands, Marcel V W

    2015-04-01

    A.I.S.E. investigated the suitability of the regulatory adopted ICE in vitro test method (OECD TG 438) with or without histopathology to identify detergent and cleaning formulations having extreme pH that require classification as EU CLP/UN GHS Category 1. To this aim, 18 extreme pH detergent and cleaning formulations were tested covering both alkaline and acidic extreme pHs. The ICE standard test method following OECD Test Guideline 438 showed good concordance with in vivo classification (83%) and good and balanced specificity and sensitivity values (83%) which are in line with the performances of currently adopted in vitro test guidelines, confirming its suitability to identify Category 1 extreme pH detergent and cleaning products. In contrast to previous findings obtained with non-extreme pH formulations, the use of histopathology did not improve the sensitivity of the assay whilst it strongly decreased its specificity for the extreme pH formulations. Furthermore, use of non-testing prediction rules for classification showed poor concordance values (33% for the extreme pH rule and 61% for the EU CLP additivity approach) with high rates of over-prediction (100% for the extreme pH rule and 50% for the additivity approach), indicating that these non-testing prediction rules are not suitable to predict Category 1 hazards of extreme pH detergent and cleaning formulations. PMID:25614451

  9. Enzymatic Cleavage of Glycosidic Bonds: Strategies on How to Set Up and Control a QM/MM Metadynamics Simulation.

    PubMed

    Raich, L; Nin-Hill, A; Ardèvol, A; Rovira, C

    2016-01-01

    Carbohydrates play crucial roles in many biological processes, from cell-cell adhesion to chemical signaling. Their complexity and diversity, related to α/β anomeric configuration, ring substituents, and conformational variations, require a diverse set of enzymes for their processing. Among them, glycoside hydrolases (GHs) are responsible for the hydrolysis of one of the strongest bonds in nature: the glycosidic bond. These highly specialized biological catalysts select particular conformations their carbohydrate substrates to enhance catalysis. The evolution of this conformation during the reaction of glycosidic bond cleavage, known as the conformational catalytic itinerary, is of fundamental interest in glycobiology, with impact on inhibitor and drug design. Here we review some of the aspects and the main strategies one needs to take into account when simulating a reaction in a GH enzyme using QM/MM metadynamics. Several specific aspects are highlighted, from the importance of the distortion of the substrate at the Michaelis complex to the variable control during the metadynamics simulation or the analysis of the reaction mechanism and conformational itinerary. The increasing speed of computer power and methodological advances have added a vital tool to the study of GH mechanisms, as shown here and recent reviews. It is hoped that this chapter will serve as a first guide for those attempting to perform a metadynamics simulation of these relevant and fascinating enzymes. PMID:27498638

  10. Effects of Ghrelin on the Proteolytic Pathways of Alzheimer's Disease Neuronal Cells.

    PubMed

    Cecarini, Valentina; Bonfili, Laura; Cuccioloni, Massimiliano; Keller, Jeffrey N; Bruce-Keller, Annadora J; Eleuteri, Anna Maria

    2016-07-01

    Ghrelin is an orexigenic hormone with a role in the onset and progression of neurodegenerative disorders. It has been recently associated to Alzheimer's disease (AD) for its neuroprotective and anti-apoptotic activity. In the present study, we dissected the effect of ghrelin treatment on the two major intracellular proteolytic pathways, the ubiquitin-proteasome system (UPS) and autophagy, in cellular models of AD (namely SH-SY5Y neuroblastoma cells stably transfected with either the wild-type AβPP gene or the 717 valine-to-glycine AβPP-mutated gene). Ghrelin showed a growth-promoting effect on neuronal cells inducing also time-dependent modifications of the growth hormone secretagogue receptor type 1 (GHS-R1) expression. Interestingly, we demonstrated for the first time that ghrelin was able to activate the proteasome in neural cells playing also a role in the interplay between the UPS and autophagy. Our data provide a novel mechanism by which circulating hormones control neural homeostasis through the regulation of proteolytic pathways implicated in AD. PMID:26033219

  11. Nutritional State-Dependent Ghrelin Activation of Vasopressin Neurons via Retrograde Trans-Neuronal–Glial Stimulation of Excitatory GABA Circuits

    PubMed Central

    Haam, Juhee; Halmos, Katalin C.; Di, Shi

    2014-01-01

    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal–glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal–glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal–glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis. PMID:24790191

  12. Sequence and Bioinformatic Analysis of Family 1 Glycoside Hydrolase (GH) 1 Gene from the Oomycete Pythium myriotylum Drechsler.

    PubMed

    Nair, R Aswati; Geethu, C; Sangwan, Amit; Pillai, P Padmesh

    2015-06-01

    The oomycetous phytopathogen Pythium myriotylum secretes cellulases for growth/nutrition of the necrotroph. Cellulases are multi-enzyme system classified into different glycoside hydrolase (GH) families. The present study deals with identification and characterization of GH gene sequence from P. myriotylum by a PCR strategy using consensus primers. Cloning of the full-length gene sequence using genome walker strategy resulted in identification of 1230-bp P. myriotylum GH gene sequence, designated as PmGH1. Analysis revealed that PmGH1 encodes a predicted cytoplasmic 421 amino acid protein with an apparent molecular weight of 46.77 kDa and a theoretical pI of 8.11. Tertiary structure of the deduced amino acid sequence showed typical (α/β)8 barrel folding of family 1 GHs. Sequence characterization of PmGH1 identified the conserved active site residues, viz., Glu 181 and Glu 399, that function as acid-base catalyst and catalytically active nucleophile, respectively. Binding sites for N-acetyl-D-glucosamine (NAG) were revealed in the PmGH1 3D structure with Glu181 and Glu399 positioned on either side to form a catalytic pair. Phylogenetic analysis indicated a closer affiliation of PmGH1 with sequences of GH1 family. Results presented are first attempts providing novel insights into the evolutionary and functional perspectives of the identified P. myriotylum GH. PMID:25877398

  13. Glycoside Hydrolase MoGls2 Controls Asexual/Sexual Development, Cell Wall Integrity and Infectious Growth in the Rice Blast Fungus.

    PubMed

    Li, Mengying; Liu, Xinyu; Liu, Zhixi; Sun, Yi; Liu, Muxing; Wang, Xiaoli; Zhang, Haifeng; Zheng, Xiaobo; Zhang, Zhengguang

    2016-01-01

    N-linked glycosylation is a way of glycosylation for newly synthesized protein, which plays a key role in the maturation and transport of proteins. Glycoside hydrolases (GHs) are essential in this process, and are involved in processing of N-linked glycoproteins or degradation of carbohydrate structures. Here, we identified and characterized MoGls2 in Magnaporthe oryzae, which is a yeast glucosidase II homolog Gls2 and is required for trimming the final glucose in N-linked glycans and normal cell wall synthesis. Target deletion of MoGLS2 in M. oryzae resulted in a reduced mycelial growth, an increased conidial production, delayed conidial germination and loss the ability of sexual reproduction. Pathogenicity assays revealed that the ΔMogls2 mutant showed significantly decreased in virulence and infectious growth. Further studies showed that the mutant was less sensitive to salt and osmotic stress, and increased sensitivity to cell wall stresses. Additionally, the ΔMogls2 mutant showed a defect in cell wall integrity. Our results indicate that MoGls2 is a key protein for the growth and development of M. oryzae, involving in the regulation of asexual/sexual development, stress response, cell wall integrity and infectious growth. PMID:27607237

  14. Ghrelin stimulates myogenic differentiation in a mouse muscle satellite cell line and in primary cultures of bovine myoblasts.

    PubMed

    Montoya-Flores, D; Mora, O; Tamariz, E; González-Dávalos, L; González-Gallardo, A; Antaramian, A; Shimada, A; Varela-Echavarría, A; Romano-Muñoz, J L

    2012-08-01

    Ghrelin is an acylated hormone that influences food intake, energy metabolism and reproduction, among others. Ghrelin may also stimulate proliferating myoblast cell differentiation and multinucleated myotube fusion. The aim of this work was to assess the effect of human ghrelin (hGHRL) and human ghrelin fragment 1-18 (hGHRL1-18) on myoblast differentiation by means of mRNA expression and protein level. Two types of cells were tested, the cell line i28 obtained from mouse skeletal muscle and primary cultures of bovine myoblasts. Both ghrelin and its N-terminal fragment hGHRL1-18 were used at concentrations of 0, 0.01, 0.1, 1, 10 and 100 nm. Treatments were applied to pre-confluent cultures and were maintained for 4 days. We determined that between 0.1 and 100 nm, hGHRL and hGRHL1-18 had similar effects on myogenic differentiation of i28 cells (p < 0.01). On the other hand, only the higher concentrations (10 and 100 nm) of hGHRL stimulated bovine myoblast differentiation. These results could be attributed to the presence, in both i28 cells and in bovine myoblasts, of the mRNA for GHS-R1a and CD36 receptors. The use of ghrelin in livestock production is still questionable because of the limited effects shown in this study, and additional research is needed in this field. PMID:21777295

  15. Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism

    PubMed Central

    Yeh, Andrew P.; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Bakolitsa, Constantina; Cai, Xiaohui; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Chiu, Michelle; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Lam, Winnie W.; Marciano, David; McMullan, Daniel; Miller, Mitchell D.; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Puckett, Christina; Reyes, Ron; Tien, Henry J.; Trame, Christine B.; van den Bedem, Henry; Weekes, Dana; Wooten, Tiffany; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    BT2081 from Bacteroides thetaiotaomicron (GenBank accession code NP_810994.1) is a member of a novel protein family consisting of over 160 members, most of which are found in the different classes of Bacteroidetes. Genome-context analysis lends support to the involvement of this family in carbohydrate metabolism, which plays a key role in B. thetaiotaomicron as a predominant bacterial symbiont in the human distal gut microbiome. The crystal structure of BT2081 at 2.05 Å resolution represents the first structure from this new protein family. BT2081 consists of an N-terminal domain, which adopts a β-sandwich immunoglobulin-like fold, and a larger C-terminal domain with a β-sandwich jelly-roll fold. Structural analyses reveal that both domains are similar to those found in various carbohydrate-active enzymes. The C-terminal β-jelly-roll domain contains a potential carbohydrate-binding site that is highly conserved among BT2081 homologs and is situated in the same location as the carbohydrate-binding sites that are found in structurally similar glycoside hydrolases (GHs). However, in BT2081 this site is partially occluded by surrounding loops, which results in a deep solvent-accessible pocket rather than a shallower solvent-exposed cleft. PMID:20944224

  16. Missense mutations in the growth hormone receptor dimerization region in Laron syndrome

    SciTech Connect

    Berg, M.A.; Francke, U. |; Geffner, M.E.; Bersch, N.

    1994-09-01

    Laron syndrome (LS) is an autosomal recessively inherited condition characterized by insensitivity to endogenous and exogenous GH. Affected individuals have severe episodes and other characteristic features. GH receptor gene mutations are present in all affected individuals in whom molecular studies have been reported. The GH receptor is a plasma membrane-spanning protein in which the extracellular domain binds circulating GH and the intracellular domain interacts with the JAK-2 kinase and possibly other intracellular signaling molecules. GH receptor dimerization occurs on GH binding and is thought to be required for normal signal transduction. We have studied the GH receptor genes of four unrelated individuals affected with LS from the United States, Italy, Saudi Arabia, and India. We have identified four different missense mutations that alter consecutive amino acids 152 to 155 in or near the dimerization domain of the GH receptor. One of these mutations, D152H, has been reported previously in Asian LS patients and, in in vitro studies, the mutant receptor was unable to dimerize. This report increases to over 20 the number of different GH receptor gene mutations that have been reported in LS patients and defines the first apparent mutational {open_quotes}hotspot{close_quotes} region in this gene. This cluster of mutations in patients with classic LS phenotype provides additional in vivo evidence that receptor dimerization plays an important role in signaling GH`s growth promoting and metabolic effects. Further in vitro studies of the mutations in this region are in progress.

  17. Comparative Community Proteomics Demonstrates the Unexpected Importance of Actinobacterial Glycoside Hydrolase Family 12 Protein for Crystalline Cellulose Hydrolysis

    PubMed Central

    Hiras, Jennifer; Wu, Yu-Wei; Deng, Kai; Nicora, Carrie D.; Aldrich, Joshua T.; Frey, Dario; Kolinko, Sebastian; Robinson, Errol W.; Jacobs, Jon M.; Adams, Paul D.; Northen, Trent R.; Simmons, Blake A.

    2016-01-01

    ABSTRACT Glycoside hydrolases (GHs) are key enzymes in the depolymerization of plant-derived cellulose, a process central to the global carbon cycle and the conversion of plant biomass to fuels and chemicals. A limited number of GH families hydrolyze crystalline cellulose, often by a processive mechanism along the cellulose chain. During cultivation of thermophilic cellulolytic microbial communities, substantial differences were observed in the crystalline cellulose saccharification activities of supernatants recovered from divergent lineages. Comparative community proteomics identified a set of cellulases from a population closely related to actinobacterium Thermobispora bispora that were highly abundant in the most active consortium. Among the cellulases from T. bispora, the abundance of a GH family 12 (GH12) protein correlated most closely with the changes in crystalline cellulose hydrolysis activity. This result was surprising since GH12 proteins have been predominantly characterized as enzymes active on soluble polysaccharide substrates. Heterologous expression and biochemical characterization of the suite of T. bispora hydrolytic cellulases confirmed that the GH12 protein possessed the highest activity on multiple crystalline cellulose substrates and demonstrated that it hydrolyzes cellulose chains by a predominantly random mechanism. This work suggests that the role of GH12 proteins in crystalline cellulose hydrolysis by cellulolytic microbes should be reconsidered. PMID:27555310

  18. Effect of zink oxyde nanoparticles on the test function of water organisms of different trophic levels

    NASA Astrophysics Data System (ADS)

    Morgalev, Yu; Morgaleva, T.; Gosteva, I.; Morgalev, S.; Kulizhskiy, S.; Astafurova, T.

    2015-11-01

    The toxicity of zinc oxide nanoparticles (nZnO) with particle size Δ50 = 20 nm was evaluated according to the degree of toxicity of the aqueous disperse system (DS) with biological testing methods using a set of test organisms representing the major trophic levels.We observed the influence of the concentration degree of nZnO on toxic effects level on the fluorescence of the bacterial biosensor "Ekolyum-13", the chemotactic response of ciliates Paramecium caudatum, the rate of growth of unicellular algae Chlorella vulgaris Bayer, mortality of entomostracans Daphnia magna Straus and fish Danio rerio. The detected values of L(E)C50 are: for biosensor "Ekolyum-13" - 0.30 mg/L, for ciliates Paramecium caudatum - 0.14 mg/L, for Chlorella vulgaris Bayer - 0.17 mg/L and for Daphnia magna Straus - 0.52 mg/L. No toxicity of nZnO was detected in relation to fish Danio rerio, L(E)C50 > 100 mg/L. In assessing the maximum effect of nZnO according to GHS and EU Directive 93/67/ EEC, it is assigned to dangerous substances with a high degree of toxicity "Acute toxicity 1".

  19. Ghrelin Protects against Dexamethasone-Induced INS-1 Cell Apoptosis via ERK and p38MAPK Signaling

    PubMed Central

    2016-01-01

    Glucocorticoid excess induces apoptosis of islet cells, which may result in diabetes. In this study, we investigated the protective effect of ghrelin on dexamethasone-induced INS-1 cell apoptosis. Our data showed that ghrelin (0.1 μM) inhibited dexamethasone-induced (0.1 μM) apoptosis of INS-1 cells and facilitated cell proliferation. Moreover, ghrelin upregulated Bcl-2 expression, downregulated Bax expression, and decreased caspase-3 activity. The protective effect of ghrelin against dexamethasone-induced INS-1 cell apoptosis was mediated via growth hormone secretagogue receptor 1a. Further studies revealed that ghrelin increased ERK activation and decreased p38MAPK expression after dexamethasone treatment. Ghrelin-mediated protection of dexamethasone-induced apoptosis of INS-1 cells was attenuated using the ERK inhibitor U0126 (10 μM), and cell viability increased using the p38MAPK inhibitor SB203580 (10 μM). In conclusion, ghrelin could protect against dexamethasone-induced INS-1 cell apoptosis, at least partially via GHS-R1a and the signaling pathway of ERK and p38MAPK. PMID:27190513

  20. Molecular characterization of a family 5 glycoside hydrolase suggests an induced-fit enzymatic mechanism

    PubMed Central

    Liberato, Marcelo V.; Silveira, Rodrigo L.; Prates, Érica T.; de Araujo, Evandro A.; Pellegrini, Vanessa O. A.; Camilo, Cesar M.; Kadowaki, Marco A.; Neto, Mario de O.; Popov, Alexander; Skaf, Munir S.; Polikarpov, Igor

    2016-01-01

    Glycoside hydrolases (GHs) play fundamental roles in the decomposition of lignocellulosic biomaterials. Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity. Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms. The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite. This is the first example of a multidomain GH relying on large amplitude motions of the CBM46 for assembly of the catalytically competent form of the enzyme. PMID:27032335

  1. Progress in Small Molecule and Biologic Therapeutics Targeting Ghrelin Signaling.

    PubMed

    McGovern, Kayleigh R; Darling, Joseph E; Hougland, James L

    2016-01-01

    Ghrelin is a circulating peptide hormone involved in regulation of a wide array of physiological processes. As an endogenous ligand for growth hormone secretagogue receptor (GHSR1a), ghrelin is responsible for signaling involved in energy homeostasis, including appetite stimulation, glucose metabolism, insulin signaling, and adiposity. Ghrelin has also been implicated in modulation of several neurological processes. Dysregulation of ghrelin signaling is implicated in diseases related to these pathways, including obesity, type II diabetes, and regulation of appetite and body weight in patients with Prader-Willi syndrome. Multiple steps in the ghrelin signaling pathway are available for targeting in the development of therapeutics for these diseases. Agonists and antagonists of GHS-R1a have been widely studied and have shown varying levels of effectiveness within ghrelin-related physiological pathways. Agents targeting ghrelin directly, either through depletion of ghrelin levels in circulation or inhibitors of ghrelin O-acyltransferase whose action is required for ghrelin to become biologically active, are receiving increasing attention as potential therapeutic options. We discuss the approaches utilized to target ghrelin signaling and highlight the current challenges toward developing small-molecule agents as potential therapeutics for ghrelin-related diseases. PMID:26202202

  2. Subchronic Inhalation Toxicity Study of n-pentane in Rats

    PubMed Central

    Cho, Hae-Won; Han, Jeong-Hee; Lee, Sung-Bae; Chung, Yong-Hyun; Rim, Kyung-Taek; Yang, Jeong-Sun

    2012-01-01

    Objectives This study was conducted in order to obtain information concerning the health hazards that may result from a 13 week inhalation exposure of n-pentane in Sprague-Dawley rats. Methods This study was conducted in accordance with the Organization for Economic Co-operation and Development (OECD) guidelines for the testing of chemicals No. 413 'Subchronic inhalation toxicity: 90-day study (as revised in 2009)'. The rats were divided into 4 groups (10 male and 10 female rats in each group), and were exposed to 0, 340, 1,530, and 6,885 ppm n-pentane in each exposure chamber for 6 hour/day, 5 days/week, for 13 weeks. All of the rats were sacrificed at the end of the treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, locomotion activity, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were assessed. Results During the period of testing, there were no treatment related effects on the clinical findings, body weight, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, relative organ weight, and histopathological findings. Conclusion The no-observable-adverse-effect level (NOAEL) of n-pentane is evaluated as being more than 6,885 ppm (20.3 mg/L) in both male and female rats. n-pentane was not a classified specific target organ toxicity in the globally harmonized classification system (GHS). PMID:23019535

  3. Relamorelin: A Novel Gastrocolokinetic Synthetic Ghrelin Agonist

    PubMed Central

    Camilleri, Michael; Acosta, Andres

    2015-01-01

    Synthetic ghrelin agonists, predominantly small molecules, are being developed as prokinetic agents that may prove useful in the treatment of gastrointestinal motility disorders. Relamorelin (RM-131) is a pentapeptide synthetic ghrelin analog that activates the growth hormone secretagogue (GHS)-1a (also called the ghrelin) receptor with approximately 6-fold greater potency than natural ghrelin. The ability of relamorelin to stimulate growth hormone (GH) release is comparable to that of native ghrelin. Relamorelin has enhanced efficacy and plasma stability compared to native ghrelin. In this review, we discuss the pharmacokinetics, pharmacodynamics and potential indications for relamorelin. Relamorelin is administered subcutaneously, dosed daily or twice daily. Relamorelin is being studied for the treatment of patients with gastrointestinal motility disorders. Phase IIA pharmacodynamic studies have demonstrated acceleration of gastric emptying in patients with type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) and upper gastrointestinal symptoms. In a phase IIA study in patients with diabetic gastroparesis, relamorelin accelerated gastric emptying and significantly improved vomiting frequency compared to placebo and improved other symptoms of gastroparesis in a pre-specified subgroup of patients with vomiting at baseline. In patients with chronic idiopathic constipation with defined transit profile at baseline, relamorelin relieved constipation and accelerated colonic transit compared to placebo. These characteristics suggest that this new ghrelin analog shows great promise to relieve patients with upper or lower gastrointestinal motility disorders. PMID:25545036

  4. The use of human adipose-derived stem cells based cytotoxicity assay for acute toxicity test.

    PubMed

    Abud, Ana Paula Ressetti; Zych, Jaiesa; Reus, Thamile Luciane; Kuligovski, Crisciele; de Moraes, Elizabeth; Dallagiovanna, Bruno; de Aguiar, Alessandra Melo

    2015-12-01

    Human adipose-derived stem cells (ADSC) were evaluated as cell culture model for cytotoxicity assay and toxicity prediction by using the neutral red uptake assay (NRU). In this study, we compared ADSC and the murine cell line BALB/c 3T3 clone A31 to predict the toxicity of 12 reference substances as recommended by the Interagency Coordinating Committee on the Validation of Alternative Methods. We predicted the LD50 for RC-rat-only weight and RC-rat-only millimole regressions for both cell culture models. For RC rat-only weight regression, both cells had the same accordance (50%), while for RC rat-only millimole regression, the accordance was 50% for ADSC and 42% for 3T3s. Thus, ADSC have similar capability for GHS class prediction as the 3T3 cell line for the evaluated reference substances. Therefore, ADSCs showed the potential to be considered a novel model for use in evaluating cytotoxicity in drug development and industry as well as for regulatory purposes to reduce or replace the use of laboratory animals with acceptable sensitivity for toxicity prediction in humans. These cells can be used to complete the results from other models, mainly because of its human origin. Moreover, it is less expensive in comparison with other existing models. PMID:26382612

  5. Analysis of the Local Lymph Node Assay (LLNA) variability for assessing the prediction of skin sensitisation potential and potency of chemicals with non-animal approaches.

    PubMed

    Dumont, Coralie; Barroso, João; Matys, Izabela; Worth, Andrew; Casati, Silvia

    2016-08-01

    The knowledge of the biological mechanisms leading to the induction of skin sensitisation has favoured in recent years the development of alternative non-animal methods. During the formal validation process, results from the Local Lymph Node Assay (LLNA) are generally used as reference data to assess the predictive capacity of the non-animal tests. This study reports an analysis of the variability of the LLNA for a set of chemicals for which multiple studies are available and considers three hazard classification schemes: POS/NEG, GHS/CLP and ECETOC. As the type of vehicle used in a LLNA study is known to influence to some extent the results, two analyses were performed: considering the solvent used to test the chemicals and without considering the solvent. The results show that the number of discordant classifications increases when a chemical is tested in more than one solvent. Moreover, it can be concluded that study results leading to classification in the strongest classes (1A and EXT) seem to be more reliable than those in the weakest classes. This study highlights the importance of considering the variability of the reference data when evaluating non-animal tests. PMID:27085510

  6. A Noncellulosomal Mannanase26E Contains a CBM59 in Clostridium cellulovorans

    PubMed Central

    Yamamoto, Kosuke; Tamaru, Yutaka

    2014-01-01

    A multicomponent enzyme-complex prevents efficient degradation of the plant cell wall for biorefinery. In this study, the method of identifying glycoside hydrolases (GHs) to degrade hemicelluloses was demonstrated. The competence of C. cellulovorans, which changes to be suitable for degradation of each carbon source, was used for the method. C. cellulovorans was cultivated into locust bean gum (LBG) that is composed of galactomannan. The proteins produced by C. cellulovorans were separated into either fractions binding to crystalline cellulose or not. Proteins obtained from each fraction were further separated by SDS-PAGE and were stained with Coomassie Brilliant Blue and were detected for mannanase activity. The proteins having the enzymatic activity for LBG were cut out and were identified by mass spectrometry. As a result, four protein bands were classified into glycosyl hydrolase family 26 (GH26) mannanases. One of the identified mannanases, Man26E, contains a carbohydrate-binding module (CBM) family 59, which binds to xylan, mannan, and Avicel. Although mannose and galactose are the same as a hexose, the expression patterns of the proteins from C. cellulovorans were quite different. More interestingly, zymogram for mannanase activity showed that Man26E was detected in only LBG medium. PMID:24795881

  7. Subsite-specific contributions of different aromatic residues in the active site architecture of glycoside hydrolase family 12

    PubMed Central

    Zhang, Xiaomei; Wang, Shuai; Wu, Xiuyun; Liu, Shijia; Li, Dandan; Xu, Hao; Gao, Peiji; Chen, Guanjun; Wang, Lushan

    2015-01-01

    The active site architecture of glycoside hydrolase (GH) is a contiguous subregion of the enzyme constituted by residues clustered in the three-dimensional space, recognizing the monomeric unit of ligand through hydrogen bonds and hydrophobic interactions. Mutations of the key residues in the active site architecture of the GH12 family exerted different impacts on catalytic efficiency. Binding affinities between the aromatic amino acids and carbohydrate rings were quantitatively determined by isothermal titration calorimetry (ITC) and the quantum mechanical (QM) method, showing that the binding capacity order of Tyr>Trp>His (and Phe) was determined by their side-chain properties. The results also revealed that the binding constant of a certain residue remained unchanged when altering its location, while the catalytic efficiency changed dramatically. Increased binding affinity at a relatively distant subsite, such as the mutant of W7Y at the −4 subsite, resulted in a marked increase in the intermediate product of cellotetraose and enhanced the reactivity of endoglucanase by 144%; while tighter binding near the catalytic center, i.e. W22Y at the −2 subsite, enabled the enzyme to bind and hydrolyze smaller oligosaccharides. Clarification of the specific roles of the aromatics at different subsites may pave the way for a more rational design of GHs. PMID:26670009

  8. In vitro assessment of eye irritancy using the Reconstructed Human Corneal Epithelial SkinEthic HCE model: application to 435 substances from consumer products industry.

    PubMed

    Cotovio, José; Grandidier, Marie-Hélène; Lelièvre, Damien; Bremond, Christelle; Amsellem, Carolle; Maloug, Saber; Ovigne, Jean-Marc; Loisel-Joubert, Sophie; Lee, Aline Van Der; Minondo, Anne-Marie; Capallere, Christophe; Bertino, Béatrice; Alépée, Nathalie; Tinois-Tessonneaud, Estelle; de Fraissinette, Anne De Brugerolle; Meunier, Jean-Roch; Leclaire, Jacques

    2010-03-01

    The 7th amendment of the EU Cosmetics Directive led to the ban of eye irritation testing for cosmetic ingredients in animals, effective from March 11th 2009. Over the last 20years, many efforts have been made to find reliable and relevant alternative methods. The SkinEthic HCE model was used to evaluate the in vitro eye irritancy potential of substances from a cosmetic industry portfolio. An optimized protocol based on a specific 1-h treatment and a 16-h post-treatment incubation period was first assessed on a set of 102 substances. The prediction model (PM) based on a 50% viability cut-off, allowed to draw up two classes (Irritants and Non-Irritants), with good associated sensitivity (86.2%) and specificity (83.5%). To check the robustness of the method, the evaluated set was expanded up to 435 substances. Final performances maintained a high level and were characterized by an overall accuracy value > 82% when using EU or GHS classification rules. Results showed that the SkinEthic HCE test method is a promising in vitro tool for the prediction of eye irritancy. Optimization datasets were shared with the COLIPA Eye Irritation Project Team and ECVAM experts, and reviewed as part of an ongoing progression to enter an ECVAM prospective validation study for eye irritation. PMID:19913609

  9. Advances in the application of high T_c superconductors to microwave devices for analog signal processing

    NASA Astrophysics Data System (ADS)

    Mage, J. C.; Marcilhac, B.; Mercandalli, M.; Lemaître, Y.; Barrau, S.; Dessertenne, B.; Mansart, D.; Castera, J. P.; Hartemann, P.

    1994-07-01

    During the last five years, the surface resistance R_s (10 GHs, 77 K) of YBCO thin films has decreased from a value of about 10 to 20 milliohms — i.e. the same as cooled pure copper or as bulk YBCO — down to values lower than 200 micro-ohms, close to the theoretical value of 100 micro-ohms obtained by a straightforward calculation from BCS theory. This improvement of R_s is due to a better quality of the material from random grain ceramics to quasi epitaxial films. These highly textured films can be obtained by many deposition methods : sputtering, laser ablation, co-evaporation, molecular beam epitaxy, MOCVD, using heating sample holders in order to obtain in situ crystal oriented layers. The value of the surface resistance is about one hundred times lower than that of usual metallizations, which can be used either to improve the specifications of some components by two order of magnitude such as high Q 3D resonators (Q > 10^6 for low phase noise oscillators) and high Q inductances (Q > 10^4 for circuit matching of antennae in the MHz range) or to reduce the size of voluminous devices such as filter banks for multiplexing or spectral analysis.

  10. Clinical application of ghrelin in the field of surgery.

    PubMed

    Takiguchi, Shuji; Murakami, Kohei; Yanagimoto, Yoshitomo; Takata, Akihiro; Miyazaki, Yasuhiro; Mori, Masaki; Doki, Yuichiro

    2015-07-01

    Ghrelin was discovered as an intrinsic ligand for the growth hormone (GH)-secretagogue receptor (GHS-R) in 1999. The endogenous production of ghrelin occurs mainly in the stomach. Ghrelin has multiple functions; it has orexigenic action, stimulates GH secretion, has anti-inflammatory activities, stimulates gastrointestinal activity, stabilizes heart function and has other metabolic roles. Moreover, ghrelin is the only gastrointestinal hormone known to stimulate appetite. In the past decade, clinical applications of ghrelin have been attempted for various pathologies, based on its anabolic function, including applications for patients with anorexia nervosa and cachexia due to chronic heart, renal or pulmonary diseases. In the field of surgery, we have conducted several clinical trials using exogenous ghrelin in patients undergoing total gastrectomy, esophagectomy and neoadjuvant chemotherapy, including cisplatin treatment, and consistently obtained unique and striking benefits in these patients. Ghrelin comprehensively improves the patients' general conditions and quality of life via its pleiotropic physiological functions. This characteristic is unique and different from the existing drugs; therefore, ghrelin may be an indispensable supplement to prevent surgical stress and postoperative sequelae. This review summarizes the recent advances toward the clinical application of ghrelin. PMID:25366350

  11. Beyond the metabolic role of ghrelin: a new player in the regulation of reproductive function.

    PubMed

    Muccioli, Giampiero; Lorenzi, Teresa; Lorenzi, Maria; Ghè, Corrado; Arnoletti, Elisa; Raso, Giuseppina Mattace; Castellucci, Mario; Gualillo, Oreste; Meli, Rosaria

    2011-12-01

    Ghrelin is a gastric peptide, discovered by Kojima et al. (1999) [55] as a result of the search for an endogenous ligand interacting with the "orphan receptor" GHS-R1a (growth hormone secretagogue receptor type 1a). Ghrelin is composed of 28 aminoacids and is produced mostly by specific cells of the stomach, by the hypothalamus and hypophysis, even if its presence, as well as that of its receptors, has been demonstrated in many other tissues, not least in gonads. Ghrelin potently stimulates GH release and participates in the regulation of energy homeostasis, increasing food intake, decreasing energy output and exerting a lipogenetic effect. Furthermore, ghrelin influences the secretion and motility of the gastrointestinal tract, especially of the stomach, and, above all, profoundly affects pancreatic functions. Despite of these previously envisaged activities, it has recently been hypothesized that ghrelin regulates several aspects of reproductive physiology and pathology. In conclusion, ghrelin not only cooperates with other neuroendocrine factors, such as leptin, in the modulation of energy homeostasis, but also has a crucial role in the regulation of the hypothalamic-pituitary gonadal axis. In the current review we summarize the main targets of this gastric peptide, especially focusing on the reproductive system. PMID:22074955

  12. In vivo-in vitro comparison of acute respiratory tract toxicity using human 3D airway epithelial models and human A549 and murine 3T3 monolayer cell systems.

    PubMed

    Sauer, Ursula G; Vogel, Sandra; Hess, Annemarie; Kolle, Susanne N; Ma-Hock, Lan; van Ravenzwaay, Bennard; Landsiedel, Robert

    2013-02-01

    The usefulness of in vitro systems to predict acute inhalation toxicity was investigated. Nineteen substances were tested in three-dimensional human airway epithelial models, EpiAirway™ and MucilAir™, and in A549 and 3T3 monolayer cell cultures. IC(50) values were compared to rat four-hour LC(50) values classified according to EPA and GHS hazard categories. Best results were achieved with a prediction model distinguishing toxic from non-toxic substances, with satisfactory specificities and sensitivities. Using a self-made four-level prediction model to classify substances into four in vitro hazard categories, in vivo-in vitro concordance was mediocre, but could be improved by excluding substances causing pulmonary edema and emphysema in vivo. None of the test systems was outstanding, and there was no evidence that tissue or monolayer systems using respiratory tract cells provide an added value. However, the test systems only reflected bronchiole epithelia and alveolar cells and investigated cytotoxicity. Effects occurring in other cells by other mechanisms could not be recognised. Further work should optimise test protocols and expand the set of substances tested to define applicability domains. In vivo respiratory toxicity data for in vitro comparisons should distinguish different modes of action, and their relevance for human health effects should be ensured. PMID:23085368

  13. Mechanistic insights into a Ca2+-dependent family of α-mannosidases in a human gut symbiont

    PubMed Central

    Zhu, Yanping; Suits, Michael D. L.; Thompson, Andrew J.; Chavan, Sambhaji; Dinev, Zoran; Dumon, Claire; Smith, Nicola; Moremen, Kelley W.; Xiang, Yong; Siriwardena, Aloysius; Williams, Spencer J.; Gilbert, Harry J.; Davies, Gideon J.

    2014-01-01

    Colonic bacteria, exemplified by Bacteroides thetaiotaomicron, play a key role in maintaining human health by harnessing large families of glycoside hydrolases (GHs) to exploit dietary polysaccharides and host glycans as nutrients. Such GH family expansion is exemplified by the 23 family GH92 glycosidases encoded by the B. thetaiotaomicron genome. Here we show that these are α-mannosidases that act via a single displacement mechanism to utilize host N-glycans. The three-dimensional structure of two GH92 mannosidases defines a family of two-domain proteins in which the catalytic center is located at the domain interface, providing acid (glutamate) and base (aspartate) assistance to hydrolysis in a Ca2+-dependent manner. The three-dimensional structures of the GH92s in complex with inhibitors provide insight into the specificity, mechanism and conformational itinerary of catalysis. Ca2+ plays a key catalytic role in helping distort the mannoside away from its ground-state 4C1 chair conformation toward the transition state. PMID:20081828

  14. The Geisinger MyCode Community Health Initiative: an electronic health record-linked biobank for Precision Medicine research

    PubMed Central

    Carey, David J.; Fetterolf, Samantha N.; Davis, F. Daniel; Faucett, William A.; Kirchner, H. Lester; Mirshahi, Uyenlinh; Murray, Michael F.; Smelser, Diane T.; Gerhard, Glenn S.; Ledbetter, David H.

    2015-01-01

    Purpose Geisinger Health System (GHS) provides an ideal platform for Precision Medicine. Key elements are the integrated health system, stable patient population, and electronic health record (EHR) infrastructure. In 2007 Geisinger launched MyCode®, a system-wide biobanking program to link samples and EHR data for broad research use. Methods Patient-centered input into MyCode® was obtained using participant focus groups. Participation in MyCode® is based on opt-in informed consent and allows recontact, which facilitates collection of data not in the EHR, and, since 2013, the return of clinically actionable results to participants. MyCode® leverages Geisinger’s technology and clinical infrastructure for participant tracking and sample collection. Results MyCode® has a consent rate of >85% with more than 90,000 participants currently, with ongoing enrollment of ~4,000 per month. MyCode® samples have been used to generate molecular data, including high-density genotype and exome sequence data. Genotype and EHR-derived phenotype data replicate previously reported genetic associations. Conclusion The MyCode® project has created resources that enable a new model for translational research that is faster, more flexible, and more cost effective than traditional clinical research approaches. The new model is scalable, and will increase in value as these resources grow and are adopted across multiple research platforms. PMID:26866580

  15. Effects of ghrelin and motilin on smooth muscle contractility of the isolated gastrointestinal tract from the bullfrog and Japanese fire belly newt.

    PubMed

    Kitazawa, Takio; Shimazaki, Misato; Kikuta, Ayumi; Yaosaka, Noriko; Teraoka, Hiroki; Kaiya, Hiroyuki

    2016-06-01

    Ghrelin has been identified in some amphibians and is known to stimulate growth hormone release and food intake as seen in mammals. Ghrelin regulates gastrointestinal motility in mammals and birds. The aim of this study was to determine whether ghrelin affects gastrointestinal smooth muscle contractility in bullfrogs (anuran) and Japanese fire belly newts (urodelian) in vitro. Neither bullfrog ghrelin nor rat ghrelin affected longitudinal smooth muscle contractility of gastrointestinal strips from the bullfrog. Expression of growth hormone secretagogue receptor 1a (GHS-R1a) mRNA was confirmed in the bullfrog gastrointestinal tract, and the expression level in the gastric mucosa was lower than that in the intestinal mucosa. In contrast, some gastrointestinal peptides, including substance P, neurotensin and motilin, and the muscarinic receptor agonist carbachol showed marked contraction, indicating normality of the smooth muscle preparations. Similar results were obtained in another amphibian, the Japanese fire belly newt. Newt ghrelin and rat ghrelin did not cause any contraction in gastrointestinal longitudinal muscle, whereas substance P and carbachol were effective causing contraction. In conclusion, ghrelin does not affect contractility of the gastrointestinal smooth muscle in anuran and urodelian amphibians, similar to results for rainbow trout and goldfish (fish) but different from results for rats and chickens. The results suggest diversity of ghrelin actions on the gastrointestinal tract across animals. This study also showed for the first time that motilin induces gastrointestinal contraction in amphibians. PMID:26704852

  16. Toxicity of various silver nanoparticles compared to silver ions in Daphnia magna

    PubMed Central

    2012-01-01

    Background To better understand the potential ecotoxicological impacts of silver nanoparticles released into freshwater environments, the Daphnia magna 48-hour immobilization test was used. Methods The toxicities of silver nitrate, two types of colloidal silver nanoparticles, and a suspension of silver nanoparticles were assessed and compared using standard OECD guidelines. Also, the swimming behavior and visible uptake of the nanoparticles by Daphnia were investigated and compared. The particle suspension and colloids used in the toxicity tests were well-characterized. Results The results obtained from the exposure studies showed that the toxicity of all the silver species tested was dose and composition dependent. Plus, the silver nanoparticle powders subsequently suspended in the exposure water were much less toxic than the previously prepared silver nanoparticle colloids, whereas the colloidal silver nanoparticles and AgNO3 were almost similar in terms of mortality. The silver nanoparticles were ingested by the Daphnia and accumulated under the carapace, on the external body surface, and connected to the appendages. All the silver species in this study caused abnormal swimming by the D. magna. Conclusion According to the present results, silver nanoparticles should be classified according to GHS (Globally Harmonized System of classification and labeling of chemicals) as "category acute 1" to Daphnia neonates, suggesting that the release of nanosilver into the environment should be carefully considered. PMID:22472056

  17. Far-field microwave dosimetry in a rhesus monkey model

    SciTech Connect

    Olsen, R.G.; Griner, T.A.; Prettyman, G.D.

    1980-01-01

    Dosimetric measurements were made in a muscle-equivalent model of an adult rhesus monkey subjected to far-field irradiation at 1.29 GHz. Profiles of microwave-induced heating in the model were obtained at eight locations, and a gradient-layer whole-body calorimeter was used to measure total absorbed energy. Average specific absorption rate (SAR) was calculated both from the calorimeter experiments and from the local temperature measurements. Thermographic imaging techniques were used to qualitatively show the microwave-induced surface heating patterns. For this model the calculated average SAR was 0.15 9W/dg)/(mW/cm2) which, at 1.29 GHs, makes the absorption cross section 84% of the geometric shadow cross section. The SAR is about three times that predicted for a prolate spheroidal model of similar mass. A disproportionally high absorption occurred in the legs of the model positioned parallel to the E-polarization because of what is believed to be partial-body resonance.

  18. The Role of Semantics in Open-World, Integrative, Collaborative Science Data Platforms

    NASA Astrophysics Data System (ADS)

    Fox, Peter; Chen, Yanning; Wang, Han; West, Patrick; Erickson, John; Ma, Marshall

    2014-05-01

    As collaborative science spreads into more and more Earth and space science fields, both participants and funders are expressing stronger needs for highly functional data and information capabilities. Characteristics include a) easy to use, b) highly integrated, c) leverage investments, d) accommodate rapid technical change, and e) do not incur undue expense or time to build or maintain - these are not a small set of requirements. Based on our accumulated experience over the last ~ decade and several key technical approaches, we adapt, extend, and integrate several open source applications and frameworks to handle major portions of functionality for these platforms. This includes: an object-type repository, collaboration tools, identity management, all within a portal managing diverse content and applications. In this contribution, we present our methods and results of information models, adaptation, integration and evolution of a networked data science architecture based on several open source technologies (Drupal, VIVO, the Comprehensive Knowledge Archive Network; CKAN, and the Global Handle System; GHS). In particular we present the Deep Carbon Observatory - a platform for international science collaboration. We present and discuss key functional and non-functional attributes, and discuss the general applicability of the platform.

  19. Multi-laboratory evaluation of SkinEthic HCE test method for testing serious eye damage/eye irritation using solid chemicals and overall performance of the test method with regard to solid and liquid chemicals testing.

    PubMed

    Alépée, N; Adriaens, E; Grandidier, M H; Meloni, M; Nardelli, L; Vinall, C J; Toner, F; Roper, C S; Van Rompay, A R; Leblanc, V; Cotovio, J

    2016-08-01

    A prospective multicentre study of the reconstructed human corneal epithelial tissue-based in vitro test method (SkinEthic™ HCE) was conducted to evaluate its usefulness to identify chemicals as either not classified for serious eye damage/eye irritation (No Cat.) or as classified (Cat. 1/Cat. 2) within UN GHS. The aim of this study was to demonstrate the transferability and reproducibility of the SkinEthic™ HCE EITS protocol for solids and define its predictive capacity. Briefly, 60 chemicals were three times tested (double blinded) in 3 laboratories and 35 additional chemicals were tested three times in one laboratory. Good within laboratory reproducibility was achieved of at least 95% (57/60) and 96.8% (92/95) for the extended data set. Furthermore, the overall concordance between the laboratories was 96.7% (58/60). The accuracy of the SkinEthic™ HCE EITS for the extended dataset, based on bootstrap resampling, was 81.0% (95% CI: 78.9% to 83.2%) with a sensitivity of 90.5% (95% CI: 88.1% to 92.9%) and specificity of 73.6% (95% CI: 71.7% to 75.5%). Overall, 200 chemicals were tested (105 liquids (EITL protocol) and 95 solids (EITS protocol)) resulting in a sensitivity of 95.2%, specificity of 72.1% and accuracy of 83.7%, thereby meeting all acceptance criteria for predictive capacity. PMID:26989001

  20. ILO activities in the area of chemical safety.

    PubMed

    Obadia, Isaac

    2003-08-21

    The ILO has been active in the area of safety in the use of chemicals at work since the year of its creation in 1919, including the development of international treaties and other technical instruments, the provision of technical assistance to its member States, and the development of chemical safety information systems. The two key ILO standards in this area are the Conventions on safety in the use of chemicals at work (No. 170, 1990), and the Prevention of Major Industrial Accidents (No. 174, 1993). The ILO Programme on occupational safety, health and environment (Safe Work) is currently responsible for ILO chemical safety activities. In the past two decades, most of ILO work in this area has been carried out within the context of inter-agency collaboration frameworks linking the ILO, WHO, UNEP, FAO, UNIDO, UNITAR, and the OECD, including the International Programme on Chemical Safety (IPCS), the Inter-Organisation Programme for the Sound Management of Chemicals (IOMC), and the Intergovernmental Forum on Chemical Safety (IFCS). Apart from the regular development, updating and dissemination of chemical safety information data bases such as the IPCS International Chemical Cards, the elaboration of a Globally harmonized system for the classification and labelling of Chemicals (GHS) has been the most outstanding achievement of this international collaboration on chemical safety. PMID:12909402

  1. Comparison between bioconcentration factor (BCF) data provided by industry to the European Chemicals Agency (ECHA) and data derived from QSAR models.

    PubMed

    Petoumenou, Maria I; Pizzo, Fabiola; Cester, Josep; Fernández, Alberto; Benfenati, Emilio

    2015-10-01

    The bioconcentration factor (BCF) is the ratio of the concentration of a chemical in an organism to the concentration in the surrounding environment at steady state. It is a valuable indicator of the bioaccumulation potential of a substance. BCF is an essential environmental property required for regulatory purposes within the Registration, Evaluation, Authorization and restriction of Chemicals (REACH) and Globally Harmonized System (GHS) regulations. In silico models for predicting BCF can facilitate the risk assessment for aquatic toxicology and reduce the cost and number of animals used. The aim of the present study was to examine the correlation of BCF data derived from the dossiers of registered chemicals submitted to the European Chemical Agency (ECHA) with the results of a battery of Quantitative Structure-Activity Relationship (QSAR). After data pruning, statistical analysis was performed using the predictions of the selected models. Results in terms of R(2) had low rating around 0.5 for the pruned dataset. The use of the model applicability domain index (ADI) led to an improvement of the performance for compounds falling within it. The variability of the experimental data and the use of different parameters to define the applicability domain can influence the performance of each model. All available information should be adapted to the requirements of the regulation to obtain a safe decision. PMID:26282223

  2. Vegetarian diet and mental disorders: results from a representative community survey

    PubMed Central

    2012-01-01

    Background The present study investigated associations between vegetarian diet and mental disorders. Methods Participants were drawn from the representative sample of the German Health Interview and Examination Survey and its Mental Health Supplement (GHS-MHS). Completely vegetarian (N = 54) and predominantly vegetarian (N = 190) participants were compared with non-vegetarian participants (N = 3872) and with a non-vegetarian socio-demographically matched subsample (N = 242). Results Vegetarians displayed elevated prevalence rates for depressive disorders, anxiety disorders and somatoform disorders. Due to the matching procedure, the findings cannot be explained by socio-demographic characteristics of vegetarians (e.g. higher rates of females, predominant residency in urban areas, high proportion of singles). The analysis of the respective ages at adoption of a vegetarian diet and onset of a mental disorder showed that the adoption of the vegetarian diet tends to follow the onset of mental disorders. Conclusions In Western cultures vegetarian diet is associated with an elevated risk of mental disorders. However, there was no evidence for a causal role of vegetarian diet in the etiology of mental disorders. PMID:22676203

  3. Operationalizing the Learning Health Care System in an Integrated Delivery System

    PubMed Central

    Psek, Wayne A.; Stametz, Rebecca A.; Bailey-Davis, Lisa D.; Davis, Daniel; Darer, Jonathan; Faucett, William A.; Henninger, Debra L.; Sellers, Dorothy C.; Gerrity, Gloria

    2015-01-01

    Introduction: The Learning Health Care System (LHCS) model seeks to utilize sophisticated technologies and competencies to integrate clinical operations, research and patient participation in order to continuously generate knowledge, improve care, and deliver value. Transitioning from concept to practical application of an LHCS presents many challenges but can yield opportunities for continuous improvement. There is limited literature and practical experience available in operationalizing the LHCS in the context of an integrated health system. At Geisinger Health System (GHS) a multi-stakeholder group is undertaking to enhance organizational learning and develop a plan for operationalizing the LHCS system-wide. We present a framework for operationalizing continuous learning across an integrated delivery system and lessons learned through the ongoing planning process. Framework: The framework focuses attention on nine key LHCS operational components: Data and Analytics; People and Partnerships; Patient and Family Engagement; Ethics and Oversight; Evaluation and Methodology; Funding; Organization; Prioritization; and Deliverables. Definitions, key elements and examples for each are presented. The framework is purposefully broad for application across different organizational contexts. Conclusion: A realistic assessment of the culture, resources and capabilities of the organization related to learning is critical to defining the scope of operationalization. Engaging patients in clinical care and discovery, including quality improvement and comparative effectiveness research, requires a defensible ethical framework that undergirds a system of strong but flexible oversight. Leadership support is imperative for advancement of the LHCS model. Findings from our ongoing work within the proposed framework may inform other organizations considering a transition to an LHCS. PMID:25992388

  4. Cosmetics Europe multi-laboratory pre-validation of the EpiOcular™ reconstituted human tissue test method for the prediction of eye irritation.

    PubMed

    Pfannenbecker, U; Bessou-Touya, S; Faller, C; Harbell, J; Jacob, T; Raabe, H; Tailhardat, M; Alépée, N; De Smedt, A; De Wever, B; Jones, P; Kaluzhny, Y; Le Varlet, B; McNamee, P; Marrec-Fairley, M; Van Goethem, F

    2013-03-01

    Cosmetics Europe, The Personal Care Association (known as Colipa before 2012), conducted a program of technology transfer and within/between laboratory reproducibility of MatTek Corporation's EpiOcular™ Eye Irritation Test (EIT) as one of the two human reconstructed tissue test methods. This EIT EpiOcular™ used a single exposure period for each chemical and a prediction model based on a cut-off in relative survival [ ≤60%=irritant (I) (GHS categories 2 and 1); >60%=no classification (NC)]. Test substance single exposure time was 30 min with a 2-h post-exposure incubation for liquids and 90 min with an 18-h post-exposure incubation for solids. Tissue viability was determined by tetrazolium dye (MTT) reduction. Combinations of 20 coded chemicals were tested in 7 laboratories. Standardized laboratory documentation was used by all laboratories. Twenty liquids (11 NC/9 I) plus 5 solids (3 NC/2 I) were selected so that both exposure regimens could be assessed. Concurrent positive (methyl acetate) and negative (water) controls were tested in each trial. In all, 298 independent trials were performed and demonstrated 99.7% agreement in prediction (NC/I) across the laboratories. Coefficients of variation for the% survival for tissues from each treatment group across laboratories were generally low. This protocol has entered in 2010 the experimental phase of a formal ECVAM validation program. PMID:23159500

  5. A noncellulosomal mannanase26E contains a CBM59 in Clostridium cellulovorans.

    PubMed

    Yamamoto, Kosuke; Tamaru, Yutaka

    2014-01-01

    A multicomponent enzyme-complex prevents efficient degradation of the plant cell wall for biorefinery. In this study, the method of identifying glycoside hydrolases (GHs) to degrade hemicelluloses was demonstrated. The competence of C. cellulovorans, which changes to be suitable for degradation of each carbon source, was used for the method. C. cellulovorans was cultivated into locust bean gum (LBG) that is composed of galactomannan. The proteins produced by C. cellulovorans were separated into either fractions binding to crystalline cellulose or not. Proteins obtained from each fraction were further separated by SDS-PAGE and were stained with Coomassie Brilliant Blue and were detected for mannanase activity. The proteins having the enzymatic activity for LBG were cut out and were identified by mass spectrometry. As a result, four protein bands were classified into glycosyl hydrolase family 26 (GH26) mannanases. One of the identified mannanases, Man26E, contains a carbohydrate-binding module (CBM) family 59, which binds to xylan, mannan, and Avicel. Although mannose and galactose are the same as a hexose, the expression patterns of the proteins from C. cellulovorans were quite different. More interestingly, zymogram for mannanase activity showed that Man26E was detected in only LBG medium. PMID:24795881

  6. Carbohydrate-active enzymes from pigmented Bacilli: a genomic approach to assess carbohydrate utilization and degradation

    PubMed Central

    2011-01-01

    Background Spore-forming Bacilli are Gram-positive bacteria commonly found in a variety of natural habitats, including soil, water and the gastro-intestinal (GI)-tract of animals. Isolates of various Bacillus species produce pigments, mostly carotenoids, with a putative protective role against UV irradiation and oxygen-reactive forms. Results We report the annotation of carbohydrate active enzymes (CAZymes) of two pigmented Bacilli isolated from the human GI-tract and belonging to the Bacillus indicus and B. firmus species. A high number of glycoside hydrolases (GHs) and carbohydrate binding modules (CBMs) were found in both isolates. A detailed analysis of CAZyme families, was performed and supported by growth data. Carbohydrates able to support growth as the sole carbon source negatively effected carotenoid formation in rich medium, suggesting that a catabolite repression-like mechanism controls carotenoid biosynthesis in both Bacilli. Experimental results on biofilm formation confirmed genomic data on the potentials of B. indicus HU36 to produce a levan-based biofilm, while mucin-binding and -degradation experiments supported genomic data suggesting the ability of both Bacilli to degrade mammalian glycans. Conclusions CAZy analyses of the genomes of the two pigmented Bacilli, compared to other Bacillus species and validated by experimental data on carbohydrate utilization, biofilm formation and mucin degradation, suggests that the two pigmented Bacilli are adapted to the intestinal environment and are suited to grow in and colonize the human gut. PMID:21892951

  7. Aquatic Toxicity Comparison of Silver Nanoparticles and Silver Nanowires

    PubMed Central

    Kim, Tae Gyu; Kim, Jin Kwon; Kim, Ellen; Lee, Ji Hyun; Chung, Young Shin

    2015-01-01

    To better understand the potential ecotoxicological impact of silver nanoparticles (AgNPs) and silver nanowires (AgNWs) released into freshwater environments, the toxicities of these nanomaterials were assessed and compared using Organization for Economic Cooperation and Development (OECD) test guidelines, including a “Daphnia sp., acute immobilization test,” “Fish, acute toxicity test,” and “freshwater alga and cyanobacteria, growth inhibition test.” Based on the estimated median lethal/effective concentrations of AgNPs and AgNWs, the susceptibility to the nanomaterials was different among test organisms (daphnia > algae > fish), suggesting that the AgNPs are classified as “category acute 1” for Daphnia magna, “category acute 2” for Oryzias latipes, and “category acute 1” for Raphidocelis subcapitata, while the AgNWs are classified as “category acute 1” for Daphnia magna, “category acute 2” for Oryzias latipes, and “category acute 2” for Raphidocelis subcapitata, according to the GHS (Globally Harmonized System of Classification and Labelling of Chemicals). In conclusion, the present results suggest that more attention should be paid to prevent the accidental or intentional release of silver nanomaterials into freshwater aquatic environments. PMID:26125025

  8. Extracellular Glycoside Hydrolase Activities in the Human Oral Cavity.

    PubMed

    Inui, Taichi; Walker, Lauren C; Dodds, Michael W J; Hanley, A Bryan

    2015-08-15

    Carbohydrate availability shifts when bacteria attach to a surface and form biofilm. When salivary planktonic bacteria form an oral biofilm, a variety of polysaccharides and glycoproteins are the primary carbon sources; however, simple sugar availabilities are limited due to low diffusion from saliva to biofilm. We hypothesized that bacterial glycoside hydrolase (GH) activities would be higher in a biofilm than in saliva in order to maintain metabolism in a low-sugar, high-glycoprotein environment. Salivary bacteria from 13 healthy individuals were used to grow in vitro biofilm using two separate media, one with sucrose and the other limiting carbon sources to a complex carbohydrate. All six GHs measured were higher in vitro when grown in the medium with complex carbohydrate as the sole carbon source. We then collected saliva and overnight dental plaque samples from the same individuals and measured ex vivo activities for the same six enzymes to determine how oral microbial utilization of glycoconjugates shifts between the planktonic phase in saliva and the biofilm phase in overnight dental plaque. Overall higher GH activities were observed in plaque samples, in agreement with in vitro observation. A similar pattern was observed in GH activity profiles between in vitro and ex vivo data. 16S rRNA gene analysis showed that plaque samples had a higher abundance of microorganisms with larger number of GH gene sequences. These results suggest differences in sugar catabolism between the oral bacteria located in the biofilm and those in saliva. PMID:26048943

  9. New insights in ghrelin orexigenic effect.

    PubMed

    Diéguez, Carlos; da Boit, Kátia; Novelle, Marta G; Martínez de Morentin, Pablo B; Nogueiras, Rubén; López, Miguel

    2010-01-01

    Ghrelin, a peptide hormone first discovered as the endogenous ligand of the growth hormone secretagogue receptor (GHS-R), is predominantly produced and released into the circulation by ghrelin cells (X/A-like) of the stomach fundus cells. Ghrelin has multiple actions in multiple tissues. In particular, it is the most potent known endogenous orexigenic peptide, and plays a significant role in glucose homeostasis: deletion of the genes encoding ghrelin and/or its receptor prevents high-fat diet from inducing obesity, increases insulin levels, enhances glucose-stimulated insulin secretion and improves peripheral insulin sensitivity. In addition to its already mentioned roles, ghrelin has other activities including stimulation of pituitary hormones secretion, regulation of gastric and pancreatic activity, modulation of fatty acid metabolism via specific control of AMP-activated protein kinase (AMPK), and cardiovascular and hemodynamic activities. In addition, modulation of cartilage and bone homeostasis, sleep and behavioral influences, and modulation of the immune system, as well as effects on cell proliferation, are other relevant actions of ghrelin. In this review, we summarize several aspects of ghrelin effects at hypothalamic level and their implications in the control of food intake and energy balance. PMID:20616512

  10. Classification of dermal sensitizers in pharmaceutical manufacturing.

    PubMed

    Winkler, Gian C; Perino, Christopher; Araya, Selene H; Bechter, Rudolf; Kuster, Martin; Lovsin Barle, Ester

    2015-08-01

    Workers in development and manufacturing of pharmaceuticals are at risk for occupational contact dermatitis (OCD) of irritative (ICD) or allergic (ACD) origin, due to contacts with reactive intermediates (IM) and drug substances (DS). We examined, if alternative methods could replace presently used animal tests for identification of ACD in pharmaceutical development and manufacturing, without apparent loss of worker health, in line with regulations. The status of alternative methods for regulatory toxicology for consumer products has recently been reviewed by the Organisation for Economic Co-operation and Development (OECD) and the European Commission's Joint Research Center (JRC) for the European Chemicals Agency (ECHA). They concluded that prediction of skin sensitization potential, extent and quality by in vitro methods, for regulatory assessments, will depend on the regulatory purpose and level of confidence required. Some alternative methods are currently in validation. Current Globally Harmonized System (GHS) regulations on classification, labeling and packaging of substances and mixtures depend on human and animal data, whereas alternative methods may provide supportive evidence. Since the levels of workplace skin exposure to DS and IM in manufacturing of pharmaceuticals are usually not known, it is not possible to conduct quantitative risk assessments based on threshold calculations for contact sensitizers. PMID:26028366

  11. Multi-laboratory validation of SkinEthic HCE test method for testing serious eye damage/eye irritation using liquid chemicals.

    PubMed

    Alépée, N; Leblanc, V; Adriaens, E; Grandidier, M H; Lelièvre, D; Meloni, M; Nardelli, L; Roper, C S; Santirocco, E; Toner, F; Van Rompay, A; Vinall, J; Cotovio, J

    2016-03-01

    A prospective multicentric study of the reconstructed human corneal epithelial tissue-based in vitro test method (SkinEthic™ HCE) was conducted to evaluate its usefulness to identify chemicals as either not classified for serious eye damage/eye irritation (No Cat.) or as classified (Cat. 1/Cat. 2) within UN GHS. The aim of this study was to demonstrate the transferability and reproducibility of the SkinEthic™ HCE EITL protocol for liquids and define its predictive capacity. Briefly, 60 chemicals were three times tested (double blinded) in 3 laboratories and 45 additional chemicals were tested three times in one laboratory. Good within laboratory reproducibility was achieved of at least 88.3% (53/60) and 92.4% (97/105) for the extended data set. Furthermore, the overall concordance between the laboratories was 93.3% (56/60). The accuracy of the SkinEthic™ HCE EITL for the extended dataset, based on bootstrap resampling, was 84.4% (95% CI: 81.9% to 87.6%) with a sensitivity of 99.0% (95% CI: 96.4% to 100%) and specificity of 68.5% (95% CI: 64.0% to 74.0%), thereby meeting all acceptance criteria for predictive capacity. This efficient transferable and reproducible assay is a promising tool to be integrated within a battery of assays to perform an eye irritation risk assessment. PMID:26612353

  12. Hazard and risk assessment of teratogenic chemicals under REACH.

    PubMed

    Prutner, Wiebke

    2013-01-01

    In 2007, a new European chemicals legislation was implemented: Regulation (EC) No. 1907/2006, also known as "REACH." It obliges companies to take the main responsibility for the valid information on the safe use of the chemicals they manufacture and/or place on the European market. So they must, for example, register their chemicals at the European Chemicals Agency (ECHA) and submit extensive substance-related registration dossiers containing information on the substances' intrinsic hazardous properties and documentation of their risk assessment. REACH regulates the registration and evaluation process as well as the authorization and restriction procedure. In addition, classification, labeling, and packaging of chemicals apply in accordance with Regulation (EC) No. 1272/2008 ("CLP Regulation"). It implements almost completely the provisions of the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (UN GHS) into European legislation and will fully replace the Dangerous Substances Directive (67/548/EEC) and the Dangerous Preparations Directive (1999/45/EC) by 2015. According to both the old and the new classification system, teratogenic chemicals are classified as developmental toxicants, with developmental toxicity falling within the hazard class of reproductive toxicity. REACH as well as the CLP Regulation provide several procedures in which reproductive toxicants take a special position because their harmful effects are considered particularly serious. Teratogenic substances are not explicitly named by these legal texts but, as they constitute as developmental toxicants a hazard differentiation of reproductive toxicity, they are implicitly always included by the provisions. PMID:23138924

  13. Molecular characterization of a family 5 glycoside hydrolase suggests an induced-fit enzymatic mechanism

    NASA Astrophysics Data System (ADS)

    Liberato, Marcelo V.; Silveira, Rodrigo L.; Prates, Érica T.; de Araujo, Evandro A.; Pellegrini, Vanessa O. A.; Camilo, Cesar M.; Kadowaki, Marco A.; Neto, Mario De O.; Popov, Alexander; Skaf, Munir S.; Polikarpov, Igor

    2016-04-01

    Glycoside hydrolases (GHs) play fundamental roles in the decomposition of lignocellulosic biomaterials. Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity. Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms. The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite. This is the first example of a multidomain GH relying on large amplitude motions of the CBM46 for assembly of the catalytically competent form of the enzyme.

  14. Protecting Space Travelers from Kidney Stones: Renal Stone Risk During Space Flight

    NASA Technical Reports Server (NTRS)

    Whitson, Peggy; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

    2002-01-01

    Renal stones, popularly known as kidney or bladder stones, are small rock-like objects formed in the kidneys or urinary tract by deposits of calcium and other minerals. The problem arises when the stones block the drainage of the kidney, resulting in urinary obstruction and pain. Passing these stones can be one of the most painful experiences a person will endure so doctors often prescribe pain relievers to ease the experience. Drinking plenty of fluids, which help flush waste out of the body, and eating a well-balanced diet are the first steps to preventing stones. For individuals at risk, this may not be enough, and a doctor may recommend a special diet and medications. Unfortunately, approximately 60 percent of people who have had a renal stone will experience a recurrence. This is particularly true of men, who are four to five times more likely to develop stones than women. Renal stones do not discriminate based on age; even children are at risk. Astronauts are particularly at risk of developing renal stones because they lose bone and muscle mass; calcium, other minerals, and protein normally used for bone and muscle end up in the bloodstream and then in the kidneys. Without plenty of fluid to wash them away, crystals can form and then grow into stones. This factor compounds the risk for astronauts, since they also perceive that they are less thirsty in space and will drink less than normal during the mission. To minimize all of these factors, doctors must instead treat the stone-forming compounds with medication. This study will use potassium citrate to reduce the risk of stone formation. Renal stones are never convenient, but they are a particular concern for astronauts who have limited access to treatment during flight. Researchers are examining how earthbound preventions for renal stone formation work in flight, ensuring missions are not ended prematurely due to this medical condition. During STS-107, earthbound preventions and treatments become astronauts

  15. Renal intratubular crystals and hyaluronan staining occur in stone formers with bypass surgery but not with idiopathic calcium oxalate stones.

    PubMed

    Evan, Andrew P; Coe, Fredric L; Gillen, Daniel; Lingeman, James E; Bledsoe, Sharon; Worcester, Elaine M

    2008-03-01

    Whether idiopathic calcium oxalate (CaOx) stone formers form inner medullary collecting duct (IMCD) crystal deposits bears on pathogenetic mechanisms of stone formation. In prior work, using light and transmission electron microscopy, we have found no IMCD crystal deposits. Here, we searched serial sections of papillary biopsies from a prior study of 15 idiopathic calcium oxalate stone formers, 4 intestinal bypass patients with CaOx stones, and 4 non-stone-forming subjects, and biopsies from an additional hitherto unreported 15 idiopathic calcium oxalate stone formers and 1 bypass patient using polarized light oil immersion optics, for deposits overlooked in our original study. We found no IMCD deposits in any of 1,500 serial sections from the 30 idiopathic calcium oxalate stone formers, nor in 87 additional sections from a frozen idiopathic calcium oxalate stone former biopsy sample processed without exposure to aqueous solutions. Among 4 of the 5 bypass patients but in none of the 30 idiopathic calcium oxalate stone formers or 4 normal stone formers, we found tiny birefringent thin crystalline overlays on scattered IMCD cell membranes. We also found IMCD lumen deposits in two bypass patients that contained mixed birefringent and nonbirefringent crystals, presumably CaOx and apatite. In the bypass patients, we observed focal apical IMCD cell hyaluronan staining, which was absent in idiopathic calcium oxalate stone formers. The absence of any IMCD deposits in 1,500 serial sections of biopsies from 30 idiopathic calcium oxalate stone formers allows us to place the upper limit on the probability of their occurrence at approximately 0.002 and place the lower limit of their size at the resolution of the optics (<0.2 mu). The tiny deposits in bypass patients may be the initial crystal lesion. PMID:18286613

  16. Stone Composition as a Function of Age and Sex

    PubMed Central

    Rule, Andrew D.; Krambeck, Amy E.; Williams, James C.; Bergstralh, Eric J.; Mehta, Ramila A.; Moyer, Thomas P.

    2014-01-01

    Background and objectives Kidney stones are heterogeneous but often grouped together. The potential effects of patient demographics and calendar month (season) on stone composition are not widely appreciated. Design, setting, participants, & measurements The first stone submitted by patients for analysis to the Mayo Clinic Metals Laboratory during 2010 was studied (n=43,545). Stones were classified in the following order: any struvite, any cystine, any uric acid, any brushite, majority (≥50%) calcium oxalate, or majority (≥50%) hydroxyapatite. Results Calcium oxalate (67%) was the most common followed by hydroxyapatite (16%), uric acid (8%), struvite (3%), brushite (0.9%), and cystine (0.35%). Men accounted for more stone submissions (58%) than women. However, women submitted more stones than men between the ages of 10–19 (63%) and 20–29 (62%) years. Women submitted the majority of hydroxyapatite (65%) and struvite (65%) stones, whereas men submitted the majority of calcium oxalate (64%) and uric acid (72%) stones (P<0.001). Although calcium oxalate stones were the most common type of stone overall, hydroxyapatite stones were the second most common before age 55 years, whereas uric acid stones were the second most common after age 55 years. More calcium oxalate and uric acid stones were submitted in the summer months (July and August; P<0.001), whereas the season did not influence other stone types. Conclusions It is well known that calcium oxalate stones are the most common stone type. However, age and sex have a marked influence on the type of stone formed. The higher number of stones submitted by women compared with men between the ages of 10 and 29 years old and the change in composition among the elderly favoring uric acid have not been widely appreciated. These data also suggest increases in stone risk during the summer, although this is restricted to calcium oxalate and uric acid stones. PMID:25278549

  17. Recent advances in managing and understanding nephrolithiasis/nephrocalcinosis

    PubMed Central

    Gambaro, Giovanni; Trinchieri, Alberto

    2016-01-01

    Urinary stone disease is a very common disease whose prevalence is still increasing. Stone formation is frequently associated with other diseases of affluence such as hypertension, osteoporosis, cardiovascular disease, metabolic syndrome, and insulin resistance. The increasing concentration of lithogenic solutes along the different segments of the nephron involves supersaturation conditions leading to the formation, growth, and aggregation of crystals. Crystalline aggregates can grow free in the tubular lumen or coated on the wall of the renal tubule. Plugs of crystalline material have been highlighted in the tubular lumen in some patients, but crystalline growth starting from plaques of calcium phosphate within the renal papillae has been demonstrated in others. Urinary supersaturation is the result of a complex interaction between predisposing genetic features and environmental factors. Dietary intake is certainly the most important environmental risk factor. In particular, an insufficient intake of dietary calcium (<600 mg/day) can increase the intestinal absorption of oxalate and the risk of calcium oxalate stone formation. Other possible risk factors that have been identified include excessive intake of salt and proteins. The potential role of dietary acid load seems to play an important role in causing a state of subclinical chronic acidosis; therefore, the intake of vegetables is encouraged in stone-forming patients. Consumption of sugar-sweetened soda and punch is associated with a higher risk of stone formation, whereas consumption of coffee, tea, beer, wine, and orange juice is associated with a lower risk. A high fluid intake is widely recognized as the cornerstone of prevention of all forms of stones. The effectiveness of protein and salt restriction has been evaluated in some studies that still do not allow definitive conclusions to be made. Calcium stone formation can be prevented by the use of different drugs with different mechanisms of action

  18. Alcea rosea root extract as a preventive and curative agent in ethylene glycol-induced urolithiasis in rats

    PubMed Central

    Ahmadi, Marzieh; Rad, Abolfazl Khajavi; Rajaei, Ziba; Hadjzadeh, Mousa-Al-Reza; Mohammadian, Nema; Tabasi, Nafiseh Sadat

    2012-01-01

    Introduction: Alcea rosea L. is used in Asian folk medicine as a remedy for a wide range of ailments. The aim of the present study was to investigate the effect of hydroalcoholic extract of Alcea rosea roots on ethylene glycol-induced kidney calculi in rats. Materials and Methods: Male Wistar rats were randomly divided into control, ethylene glycol (EG), curative and preventive groups. Control group received tap drinking water for 28 days. Ethylene glycol (EG), curative and preventive groups received 1% ethylene glycol for induction of calcium oxalate (CaOx) calculus formation; preventive and curative subjects also received the hydroalcoholic extract of Alcea rosea roots in drinking water at dose of 170 mg/kg, since day 0 or day 14, respectively. Urinary oxalate concentration was measured by spectrophotometer on days 0, 14 and 28. On day 28, the kidneys were removed and examined histopathologically under light microscopy for counting the calcium oxalate deposits in 50 microscopic fields. Results: In both preventive and curative protocols, treatment of rats with hydroalcoholic extract of Alcea rosea roots significantly reduced the number of kidney calcium oxalate deposits compared to ethylene glycol group. Administration of Alcea rosea extract also reduced the elevated urinary oxalate due to ethylene glycol. Conclusion: Alcea rosea showed a beneficial effect in preventing and eliminating calcium oxalate deposition in the rat kidney. This effect is possibly due to diuretic and anti-inflammatory effects or presence of mucilaginous polysaccharides in the plant. It may also be related to lowering of urinary concentration of stone-forming constituents. PMID:22701236

  19. Physicochemical action of potassium-magnesium citrate in nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Pak, C. Y.; Koenig, K.; Khan, R.; Haynes, S.; Padalino, P.

    1992-01-01

    Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS).

  20. Phenotype-Genotype Correlations and Estimated Carrier Frequencies of Primary Hyperoxaluria.

    PubMed

    Hopp, Katharina; Cogal, Andrea G; Bergstralh, Eric J; Seide, Barbara M; Olson, Julie B; Meek, Alicia M; Lieske, John C; Milliner, Dawn S; Harris, Peter C

    2015-10-01

    Primary hyperoxaluria (PH) is a rare autosomal recessive disease characterized by oxalate accumulation in the kidneys and other organs. Three loci have been identified: AGXT (PH1), GRHPR (PH2), and HOGA1 (PH3). Here, we compared genotype to phenotype in 355 patients in the Rare Kidney Stone Consortium PH registry and calculated prevalence using publicly available whole-exome data. PH1 (68.4% of families) was the most severe PH type, whereas PH3 (11.0% of families) showed the slowest decline in renal function but the earliest symptoms. A group of patients with disease progression similar to that of PH3, but for whom no mutation was detected (11.3% of families), suggested further genetic heterogeneity. We confirmed that the AGXT p.G170R mistargeting allele resulted in a milder PH1 phenotype; however, other potential AGXT mistargeting alleles caused more severe (fully penetrant) disease. We identified the first PH3 patient with ESRD; a homozygote for two linked, novel missense mutations. Population analysis suggested that PH is an order of magnitude more common than determined from clinical cohorts (prevalence, approximately 1:58,000; carrier frequency, approximately 1:70). We estimated PH to be approximately three times less prevalent among African Americans than among European Americans because of a limited number of common European origin alleles. PH3 was predicted to be as prevalent as PH1 and twice as common as PH2, indicating that PH3 (and PH2) cases are underdiagnosed and/or incompletely penetrant. These results highlight a role for molecular analyses in PH diagnostics and prognostics and suggest that wider analysis of the idiopathic stone-forming population may be beneficial. PMID:25644115

  1. Difference in 24-Hour Urine Composition between Diabetic and Non-Diabetic Adults without Nephrolithiasis

    PubMed Central

    Qin, Jing; Duan, Xiaolu; Liu, Yang; Zhao, Zhijian; Yuan, Jian; Wan, Shaw P.; Zeng, Guohua

    2016-01-01

    Background Diabetic patients are more likely to develop kidney stones than the general population. The underlying mechanisms for this disparity remain to be elucidated. Little is known about the relationship between urine composition and diabetes mellitus in non-stone-forming individuals. We sought to examine the differences in the 24-hour (24-h) urine composition between diabetic and non-diabetic adults who were not stone formers. Methods A convenience sample of 538 individuals without a history of nephrolithiasis, gout, hyperparathyroidism, or gastroenteric diseases participated in this study. The 24-h urine profiles of 115 diabetic adults were compared with those of 423 non-diabetic adults. Diabetes was defined by self-reported physician diagnosis or medication use. All participants were non-stone formers confirmed by urinary tract ultrasonography. Participants provided a fasting blood sample and a single 24-h urine collection for stone risk analysis. Student’s t-test was used to compare mean urinary values. Linear regression models were adjusted for age, gender, body mass index, hypertension, fasting serum glucose, serum total cholesterol, estimated creatinine clearance rate and urinary factors. Results Univariable analysis showed that the diabetic participants had significantly higher 24-h urine volumes and lower urine calcium and magnesium excretions than non-diabetic participants (all P < 0.05). After multivariate adjustment, no significant differences in 24-h urine composition were observed between diabetic and non-diabetic participants except for a slightly increased 24-h urine volume in diabetic participants (all P > 0.05). The main limitation of this study is that the convenience samples and self-reported data may have been sources of bias. Conclusion Our data showed that there were no differences in 24-h urine composition between diabetic and non-diabetic adults who are not stone formers. The reason for it might be the improved glycemic control in

  2. Quality Assessment of Urinary Stone Analysis: Results of a Multicenter Study of Laboratories in Europe.

    PubMed

    Siener, Roswitha; Buchholz, Noor; Daudon, Michel; Hess, Bernhard; Knoll, Thomas; Osther, Palle J; Reis-Santos, José; Sarica, Kemal; Traxer, Olivier; Trinchieri, Alberto

    2016-01-01

    After stone removal, accurate analysis of urinary stone composition is the most crucial laboratory diagnostic procedure for the treatment and recurrence prevention in the stone-forming patient. The most common techniques for routine analysis of stones are infrared spectroscopy, X-ray diffraction and chemical analysis. The aim of the present study was to assess the quality of urinary stone analysis of laboratories in Europe. Nine laboratories from eight European countries participated in six quality control surveys for urinary calculi analyses of the Reference Institute for Bioanalytics, Bonn, Germany, between 2010 and 2014. Each participant received the same blinded test samples for stone analysis. A total of 24 samples, comprising pure substances and mixtures of two or three components, were analysed. The evaluation of the quality of the laboratory in the present study was based on the attainment of 75% of the maximum total points, i.e. 99 points. The methods of stone analysis used were infrared spectroscopy (n = 7), chemical analysis (n = 1) and X-ray diffraction (n = 1). In the present study only 56% of the laboratories, four using infrared spectroscopy and one using X-ray diffraction, fulfilled the quality requirements. According to the current standard, chemical analysis is considered to be insufficient for stone analysis, whereas infrared spectroscopy or X-ray diffraction is mandatory. However, the poor results of infrared spectroscopy highlight the importance of equipment, reference spectra and qualification of the staff for an accurate analysis of stone composition. Regular quality control is essential in carrying out routine stone analysis. PMID:27248840

  3. Recent advances in managing and understanding nephrolithiasis/nephrocalcinosis.

    PubMed

    Gambaro, Giovanni; Trinchieri, Alberto

    2016-01-01

    Urinary stone disease is a very common disease whose prevalence is still increasing. Stone formation is frequently associated with other diseases of affluence such as hypertension, osteoporosis, cardiovascular disease, metabolic syndrome, and insulin resistance. The increasing concentration of lithogenic solutes along the different segments of the nephron involves supersaturation conditions leading to the formation, growth, and aggregation of crystals. Crystalline aggregates can grow free in the tubular lumen or coated on the wall of the renal tubule. Plugs of crystalline material have been highlighted in the tubular lumen in some patients, but crystalline growth starting from plaques of calcium phosphate within the renal papillae has been demonstrated in others. Urinary supersaturation is the result of a complex interaction between predisposing genetic features and environmental factors. Dietary intake is certainly the most important environmental risk factor. In particular, an insufficient intake of dietary calcium (<600 mg/day) can increase the intestinal absorption of oxalate and the risk of calcium oxalate stone formation. Other possible risk factors that have been identified include excessive intake of salt and proteins. The potential role of dietary acid load seems to play an important role in causing a state of subclinical chronic acidosis; therefore, the intake of vegetables is encouraged in stone-forming patients. Consumption of sugar-sweetened soda and punch is associated with a higher risk of stone formation, whereas consumption of coffee, tea, beer, wine, and orange juice is associated with a lower risk. A high fluid intake is widely recognized as the cornerstone of prevention of all forms of stones. The effectiveness of protein and salt restriction has been evaluated in some studies that still do not allow definitive conclusions to be made. Calcium stone formation can be prevented by the use of different drugs with different mechanisms of action

  4. The osteopontin-controlled switching of calcium oxalate monohydrate morphologies in artificial urine provides insights into the formation of papillary kidney stones.

    PubMed

    Langdon, Aaron; Grohe, Bernd

    2016-10-01

    The protein osteopontin (OPN) plays an important role in preventing the formation of calcium oxalate monohydrate (COM) kidney stones. To gain insight into these mechanisms, crystallization was induced by addition of human kidney OPN to artificial urine (ionic strength comparable to urine; without citrate), and the OPN-COM interaction studied using a combination of scanning electron (SEM) and confocal microscopy. By SEM, we found that increasing OPN concentrations formed large monoclinic penetration twins (no protein added) and, at higher concentrations (1-, 2μg/ml OPN), super and hyper twins with crystal habits not found in previous studies. For instance, the hyper twins indicate well-facetted gearwheel-like habits with "teeth" developed in all crystallographic directions. At OPN concentrations ≥2μg/ml, a switching to small dumbbell-shaped COM habits with fine-textured surfaces occurred. Confocal microscopy of these dumbbells indicates protein incorporation in almost the entire crystal structure (in contrast to facetted COM), proposing a threshold concentration of ∼2μg/ml OPN for the facetted to the non-facetted habit transformation. Both the gearwheel-like and the dumbbell-shaped habit are again found side-by-side (presumably triggered by OPN concentration gradients within the sample) in in-vitro formed conglomerates, which resemble cross-sections of papillary kidney stones. The abrupt transformation from facetted to non-facetted habits and the unique compliance of the two in-vitro formed habits with the two main morphologies found in papillary kidney stones propose that OPN is a main effector in direct stone-forming processes. Moreover, stone structures which exhibit these two morphologies side-by-side might serve as a novel indicator for OPN concentrations surrounding those structures. PMID:27362921

  5. KIDNEY STONE INCIDENCE AND METABOLIC URINARY CHANGES AFTER MODERN BARIATRIC SURGERY: REVIEW OF CLINICAL STUDIES, EXPERIMENTAL MODELS, AND PREVENTION STRATEGIES

    PubMed Central

    Canales, Benjamin K.; Hatch, Marguerite

    2014-01-01

    Bariatric surgery has been associated with increased metabolic kidney stone risk and post-operative stone formation. A MEDLINE search, performed for articles published between January 2005 and November 2013, identified 24 pertinent studies containing 683 bariatric patients with 24-hour urine profiles, 6,777 bariatric patients with kidney stone incidence, and 7,089 non-stone forming controls. Of all procedures reviewed, only Roux-en-Y gastric bypass (RYGB) was linked to post-operative kidney stone development, increasing stone incidence two-fold in non-stone formers (8.5%) and four-fold in patients with previous stone history (16.7%). High quality evidence from 7 studies (n=277 patients) before and after RYGB identified the following post-RYGB urinary lithogenic risk factors: 30% reduction in urine volume (the main driver of urinary crystal saturation), 40% reduction in urinary citrate (a potent stone inhibitor), and 50% increase in urinary oxalate (a stone promotor). Based on this, a summary of strategies to reduce calcium oxalate stone risk following RYGB is provided. Furthermore, recent experimental RYGB studies are assessed for insights into the pathophysiology of oxalate handling, and the literature in gut anion (oxalate) transport is reviewed. Finally, as a potential probiotic therapy for hyperoxaluria, primary data from our laboratory is presented, demonstrating a 70% reduction in urinary oxalate levels in four experimental RYGB animals after colonization with Oxalobacter formigines, a non-pathogenic gut commensal that uses oxalate as an energy source. Overall, urine profiles and kidney stone risk following bariatric surgery appear modifiable by dietary adjustments, appropriate supplementation, and lifestyle changes. For hyperoxaluria resistant to dietary oxalate restriction and calcium binding, well-designed human investigations are needed to identify additional means of lowering urinary oxalate, such as Oxalobacter colonization or empiric pyridoxine therapy

  6. Molecular modifiers reveal a mechanism of pathological crystal growth inhibition.

    PubMed

    Chung, Jihae; Granja, Ignacio; Taylor, Michael G; Mpourmpakis, Giannis; Asplin, John R; Rimer, Jeffrey D

    2016-08-25

    Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization--citrate and hydroxycitrate--exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of

  7. Quality Assessment of Urinary Stone Analysis: Results of a Multicenter Study of Laboratories in Europe

    PubMed Central

    Siener, Roswitha; Buchholz, Noor; Daudon, Michel; Hess, Bernhard; Knoll, Thomas; Osther, Palle J.; Reis-Santos, José; Sarica, Kemal; Traxer, Olivier; Trinchieri, Alberto

    2016-01-01

    After stone removal, accurate analysis of urinary stone composition is the most crucial laboratory diagnostic procedure for the treatment and recurrence prevention in the stone-forming patient. The most common techniques for routine analysis of stones are infrared spectroscopy, X-ray diffraction and chemical analysis. The aim of the present study was to assess the quality of urinary stone analysis of laboratories in Europe. Nine laboratories from eight European countries participated in six quality control surveys for urinary calculi analyses of the Reference Institute for Bioanalytics, Bonn, Germany, between 2010 and 2014. Each participant received the same blinded test samples for stone analysis. A total of 24 samples, comprising pure substances and mixtures of two or three components, were analysed. The evaluation of the quality of the laboratory in the present study was based on the attainment of 75% of the maximum total points, i.e. 99 points. The methods of stone analysis used were infrared spectroscopy (n = 7), chemical analysis (n = 1) and X-ray diffraction (n = 1). In the present study only 56% of the laboratories, four using infrared spectroscopy and one using X-ray diffraction, fulfilled the quality requirements. According to the current standard, chemical analysis is considered to be insufficient for stone analysis, whereas infrared spectroscopy or X-ray diffraction is mandatory. However, the poor results of infrared spectroscopy highlight the importance of equipment, reference spectra and qualification of the staff for an accurate analysis of stone composition. Regular quality control is essential in carrying out routine stone analysis. PMID:27248840

  8. Inviting Patients to Read Their Doctors’ Notes: A Quasi-experimental Study and a Look Ahead

    PubMed Central

    Delbanco, Tom; Walker, Jan; Bell, Sigall K.; Darer, Jonathan D.; Elmore, Joann G.; Farag, Nadine; Feldman, Henry J.; Mejilla, Roanne; Ngo, Long; Ralston, James D.; Ross, Stephen E.; Trivedi, Neha; Vodicka, Elisabeth; Leveille, Suzanne G.

    2013-01-01

    Background Little information exists about what primary care physicians (PCPs) and patients experience if patients are invited to read their doctors’ office notes. Objective To evaluate the effect on doctors and patients of facilitating patient access to visit notes over secure Internet portals. Design Quasi-experimental trial of PCPs and patient volunteers in a year-long program that provided patients with electronic links to their doctors’ notes. Setting Primary care practices at Beth Israel Deaconess Medical Center (BIDMC) in Massachusetts, Geisinger Health System (GHS) in Pennsylvania, and Harborview Medical Center (HMC) in Washington. Participants 105 PCPs and 13 564 of their patients who had at least 1 completed note available during the intervention period. Measurements Portal use and electronic messaging by patients and surveys focusing on participants’ perceptions of behaviors, benefits, and negative consequences. Results 11 797 of 13 564 patients with visit notes available opened at least 1 note (84% at BIDMC, 92% at GHS, and 47% at HMC). Of 5391 patients who opened at least 1 note and completed a postintervention survey, 77% to 87% across the 3 sites reported that open notes helped them feel more in control of their care; 60% to 78% of those taking medications reported increased medication adherence; 26% to 36% had privacy concerns; 1% to 8% reported that the notes caused confusion, worry, or offense; and 20% to 42% reported sharing notes with others. The volume of electronic messages from patients did not change. After the intervention, few doctors reported longer visits (0% to 5%) or more time addressing patients’ questions outside of visits (0% to 8%), with practice size having little effect; 3% to 36% of doctors reported changing documentation content; and 0% to 21% reported taking more time writing notes. Looking ahead, 59% to 62% of patients believed that they should be able to add comments to a doctor’s note. One out of 3 patients

  9. Orogen-scale along-strike continuity in quartz recrystallization microstructures adjacent to the Main Central Thrust: implications for deformation temperatures, strain rates and flow stresses

    NASA Astrophysics Data System (ADS)

    Law, Richard

    2015-04-01

    Traced for ~ 1500 km along the foreland edge of the Himalaya from NW India to Bhutan published reports indicate a remarkable along-strike continuity of quartz recrystallization microstructures in the footwall and hanging wall to the Main Central Thrust (MCT). Recrystallization in Lesser Himalayan Series (LHS) rocks in the footwall to the MCT is dominated by grain boundary bulging (BLG) microstructures, while recrystallization in Greater Himalayan Series (GHS) rocks in the hanging wall is dominated by grain boundary migration microstructures that traced structurally upwards transition in to the anatectic core of the GHS. In foreland-positioned high-strain rocks adjacent to the MCT recrystallization is dominated by subgrain rotation (SGR) with transitional BLG-SGR and SGR-GBM microstructures being recorded at structural distances of up to a few hundred meters below and above the MCT, respectively. Correlation with available information on temperatures of metamorphism indicated by mineral phase equilibria and RSCM data suggests that recrystallization in the structural zones dominated by BLG, SGR and GBM occurred at temperatures of ~ 350-450, 450-550 and 550- > 650 °C, respectively. It should be kept in mind, however, that these temperatures are likely to be 'close-to-peak' temperatures of metamorphism, whereas penetrative shearing and recrystallization may have continued during cooling. The dominance of SGR along the more foreland-positioned exposures of the MCT intuitively suggests that shearing occurred under a relatively restricted range of deformation temperatures and strain rates. Plotting the 'close-to-peak' 450-500 °C temperatures of metamorphism indicated for SGR-dominated rocks located at up to a few hundred meters below/above the MCT on the quartz recrystallization map developed by Stipp et al. (2002) indicates 'ball-park' strain rates of ~ 10-13 to 10-10 sec-1. However, only strain rates slower than 10-12 sec-1 on the MCT are likely to be compatible with

  10. Metatranscriptomic Analyses of Plant Cell Wall Polysaccharide Degradation by Microorganisms in the Cow Rumen

    PubMed Central

    Dai, Xin; Tian, Yan; Li, Jinting; Su, Xiaoyun; Wang, Xuewei; Zhao, Shengguo; Liu, Li; Luo, Yingfeng; Liu, Di; Zheng, Huajun; Wang, Jiaqi; Dong, Zhiyang

    2014-01-01

    The bovine rumen represents a highly specialized bioreactor where plant cell wall polysaccharides (PCWPs) are efficiently deconstructed via numerous enzymes produced by resident microorganisms. Although a large number of fibrolytic genes from rumen microorganisms have been identified, it remains unclear how they are expressed in a coordinated manner to efficiently degrade PCWPs. In this study, we performed a metatranscriptomic analysis of the rumen microbiomes of adult Holstein cows fed a fiber diet and obtained a total of 1,107,083 high-quality non-rRNA reads with an average length of 483 nucleotides. Transcripts encoding glycoside hydrolases (GHs) and carbohydrate binding modules (CBMs) accounted for ∼1% and ∼0.1% of the total non-rRNAs, respectively. The majority (∼98%) of the putative cellulases belonged to four GH families (i.e., GH5, GH9, GH45, and GH48) and were primarily synthesized by Ruminococcus and Fibrobacter. Notably, transcripts for GH48 cellobiohydrolases were relatively abundant compared to the abundance of transcripts for other cellulases. Two-thirds of the putative hemicellulases were of the GH10, GH11, and GH26 types and were produced by members of the genera Ruminococcus, Prevotella, and Fibrobacter. Most (∼82%) predicted oligosaccharide-degrading enzymes were GH1, GH2, GH3, and GH43 proteins and were from a diverse group of microorganisms. Transcripts for CBM10 and dockerin, key components of the cellulosome, were also relatively abundant. Our results provide metatranscriptomic evidence in support of the notion that members of the genera Ruminococcus, Fibrobacter, and Prevotella are predominant PCWP degraders and point to the significant contribution of GH48 cellobiohydrolases and cellulosome-like structures to efficient PCWP degradation in the cow rumen. PMID:25501482

  11. Substrate-specific transcription of the enigmatic GH61 family of the pathogenic white-rot fungus Heterobasidion irregulare during growth on lignocellulose.

    PubMed

    Yakovlev, Igor; Vaaje-Kolstad, Gustav; Hietala, Ari M; Stefańczyk, Emil; Solheim, Halvor; Fossdal, Carl Gunnar

    2012-08-01

    The GH61 represents the most enigmatic Glycoside Hydrolase family (GH) regarding enzymatic activity and importance in cellulose degradation. Heterobasidion irregulare is a necrotizing pathogen and white-rot fungus that causes enormous damages in conifer forests. The genome of H. irregulare allowed identification of ten HiGH61 genes. qRT-PCR analysis separate the HiGH61 members into two groups; one that show up regulation on lignocellulosic substrates (HiGH61A, HiGH61B, HiGH61D, HiGH61G, HiGH61H, and HiGH61I) and a second showing either down-regulation or constitutive expression (HiGH61C, HiGH61E, HiGH61F, and HiGH61J). HiGH61H showed up to 17,000-fold increase on spruce heartwood suggesting a pivotal role in cellulose decomposition during saprotrophic growth. Sequence analysis of these genes reveals that all GH61s except HiGH61G possess the conserved metal-binding motif essential for activity. The sequences also divide into groups having either an insert near the N terminus or an insert near the second catalytic histidine, which may represent extensions of the substrate-binding surface. Three of the HiGH61s encode cellulose-binding modules (CBM1). Interestingly, HiGH61H and HiGH61I having CBM1s are up-regulated on pure cellulose. There was a common substrate-specific induction patterns of the HiGH61s with several reference cellulolytic and hemicellulolytic GHs, this taken together with their low transcript levels on media lacking lignocellulose, reflect the concerted nature of cell wall polymer degradation. PMID:22718248

  12. Genomewide analysis of polysaccharides degrading enzymes in 11 white- and brown-rot Polyporales provides insight into mechanisms of wood decay.

    PubMed

    Hori, Chiaki; Gaskell, Jill; Igarashi, Kiyohiko; Samejima, Masahiro; Hibbett, David; Henrissat, Bernard; Cullen, Dan

    2013-01-01

    To degrade the polysaccharides, wood-decay fungi secrete a variety of glycoside hydrolases (GHs) and carbohydrate esterases (CEs) classified into various sequence-based families of carbohydrate-active enzymes (CAZys) and their appended carbohydrate-binding modules (CBM). Oxidative enzymes, such as cellobiose dehydrogenase (CDH) and lytic polysaccharide monooxygenase (LPMO, formerly GH61), also have been implicated in cellulose degradation. To examine polysaccharide-degrading potential between white- and brown-rot fungi, we performed genomewide analysis of CAZys and these oxidative enzymes in 11 Polyporales, including recently sequenced monokaryotic strains of Bjerkandera adusta, Ganoderma sp. and Phlebia brevispora. Furthermore, we conducted comparative secretome analysis of seven Polyporales grown on wood culture. As a result, it was found that genes encoding cellulases belonging to families GH6, GH7, GH9 and carbohydrate-binding module family CBM1 are lacking in genomes of brown-rot polyporales. In addition, the presence of CDH and the expansion of LPMO were observed only in white-rot genomes. Indeed, GH6, GH7, CDH and LPMO peptides were identified only in white-rot polypores. Genes encoding aldose 1-epimerase (ALE), previously detected with CDH and cellulases in the culture filtrates, also were identified in white-rot genomes, suggesting a physiological connection between ALE, CDH, cellulase and possibly LPMO. For hemicellulose degradation, genes and peptides corresponding to GH74 xyloglucanase, GH10 endo-xylanase, GH79 β-glucuronidase, CE1 acetyl xylan esterase and CE15 glucuronoyl methylesterase were significantly increased in white-rot genomes compared to brown-rot genomes. Overall, relative to brown-rot Polyporales, white-rot Polyporales maintain greater enzymatic diversity supporting lignocellulose attack. PMID:23935027

  13. De novo transcriptome sequencing and analysis of the cereal cyst nematode, Heterodera avenae.

    PubMed

    Kumar, Mukesh; Gantasala, Nagavara Prasad; Roychowdhury, Tanmoy; Thakur, Prasoon Kumar; Banakar, Prakash; Shukla, Rohit N; Jones, Michael G K; Rao, Uma

    2014-01-01

    The cereal cyst nematode (CCN, Heterodera avenae) is a major pest of wheat (Triticum spp) that reduces crop yields in many countries. Cyst nematodes are obligate sedentary endoparasites that reproduce by amphimixis. Here, we report the first transcriptome analysis of two stages of H. avenae. After sequencing extracted RNA from pre parasitic infective juvenile and adult stages of the life cycle, 131 million Illumina high quality paired end reads were obtained which generated 27,765 contigs with N50 of 1,028 base pairs, of which 10,452 were annotated. Comparative analyses were undertaken to evaluate H. avenae sequences with those of other plant, animal and free living nematodes to identify differences in expressed genes. There were 4,431 transcripts common to H. avenae and the free living nematode Caenorhabditis elegans, and 9,462 in common with more closely related potato cyst nematode, Globodera pallida. Annotation of H. avenae carbohydrate active enzymes (CAZy) revealed fewer glycoside hydrolases (GHs) but more glycosyl transferases (GTs) and carbohydrate esterases (CEs) when compared to M. incognita. 1,280 transcripts were found to have secretory signature, presence of signal peptide and absence of transmembrane. In a comparison of genes expressed in the pre-parasitic juvenile and feeding female stages, expression levels of 30 genes with high RPKM (reads per base per kilo million) value, were analysed by qRT-PCR which confirmed the observed differences in their levels of expression levels. In addition, we have also developed a user-friendly resource, Heterodera transcriptome database (HATdb) for public access of the data generated in this study. The new data provided on the transcriptome of H. avenae adds to the genetic resources available to study plant parasitic nematodes and provides an opportunity to seek new effectors that are specifically involved in the H. avenae-cereal host interaction. PMID:24802510

  14. Characterization of the toxicological hazards of hydrocarbon solvents.

    PubMed

    Mckee, Richard H; Adenuga, M David; Carrillo, Juan-Carlos

    2015-04-01

    Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum processing streams, containing only carbon and hydrogen atoms, with carbon numbers ranging from approximately C5-C20 and boiling between approximately 35-370°C. Many of the hydrocarbon solvents have complex and variable compositions with constituents of 4 types, alkanes (normal paraffins, isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one- and two-ring species). Because of the compositional complexity, hydrocarbon solvents are now identified by a nomenclature ("the naming convention") that describes them in terms of physical/chemical properties and compositional elements. Despite the compositional complexity, most hydrocarbon solvent constituents have similar toxicological properties, and the overall toxicological hazards can be characterized in generic terms. To facilitate hazard characterization, the solvents were divided into 9 groups (categories) of substances with similar physical and chemical properties. Hydrocarbon solvents can cause chemical pneumonitis if aspirated into the lung, and those that are volatile can cause acute CNS effects and/or ocular and respiratory irritation at exposure levels exceeding occupational recommendations. Otherwise, there are few toxicologically important effects. The exceptions, n-hexane and naphthalene, have unique toxicological properties, and those solvents containing constituents for which classification is required under the Globally Harmonized System (GHS) are differentiated by the substance names. Toxicological information from studies of representative substances was used to fulfill REACH registration requirements and to satisfy the needs of the OECD High Production Volume (HPV) initiative. As shown in the examples provided, the hazard characterization data can be used for hazard classification and for occupational exposure limit recommendations. PMID:25868376

  15. The Amygdala as a Neurobiological Target for Ghrelin in Rats: Neuroanatomical, Electrophysiological and Behavioral Evidence

    PubMed Central

    Alvarez-Crespo, Mayte; Skibicka, Karolina P.; Farkas, Imre; Molnár, Csilla S.; Egecioglu, Emil; Hrabovszky, Erik; Liposits, Zsolt; Dickson, Suzanne L.

    2012-01-01

    Here, we sought to demonstrate that the orexigenic circulating hormone, ghrelin, is able to exert neurobiological effects (including those linked to feeding control) at the level of the amygdala, involving neuroanatomical, electrophysiological and behavioural studies. We found that ghrelin receptors (GHS-R) are densely expressed in several subnuclei of the amygdala, notably in ventrolateral (LaVL) and ventromedial (LaVM) parts of the lateral amygdaloid nucleus. Using whole-cell patch clamp electrophysiology to record from cells in the lateral amygdaloid nucleus, we found that ghrelin reduced the frequency of mEPSCs recorded from large pyramidal-like neurons, an effect that could be blocked by co-application of a ghrelin receptor antagonist. In ad libitum fed rats, intra-amygdala administration of ghrelin produced a large orexigenic response that lasted throughout the 4 hr of testing. Conversely, in hungry, fasted rats ghrelin receptor blockade in the amygdala significantly reduced food intake. Finally, we investigated a possible interaction between ghrelin's effects on feeding control and emotional reactivity exerted at the level of the amygdala. In rats allowed to feed during a 1-hour period between ghrelin injection and anxiety testing (elevated plus maze and open field), intra-amygdala ghrelin had no effect on anxiety-like behavior. By contrast, if the rats were not given access to food during this 1-hour period, a decrease in anxiety-like behavior was observed in both tests. Collectively, these data indicate that the amygdala is a valid target brain area for ghrelin where its neurobiological effects are important for food intake and for the suppression of emotional (anxiety-like) behaviors if food is not available. PMID:23071554

  16. Children's misunderstandings of hazard warning signs in the new globally harmonized system for classification and labeling.

    PubMed

    Latham, Garry; Long, Tony; Devitt, Patric

    2013-12-01

    Accidental chemical poisoning causes more than 35 000 child deaths every year across the world, and it leads to disease, disability, and suffering for many more children. Children's ignorance of dangers and their failure to interpret hazard warning signs as intended contribute significantly to this problem. A new Globally Harmonized System for Classification and Labeling is being implemented internationally with a view to unifying the current multiple and disparate national systems. This study was designed to establish a productive, effective means of teaching the new GHS warning signs to primary school children (aged 7-11 years). A pre-test, post-test, follow-up test design was employed, with a teaching intervention informed by a Delphi survey of expert opinion. Children from one school formed the experimental group (n = 49) and a second school provided a control group (n = 23). Both groups showed a gain in knowledge from pre-test to post-test, the experimental group with a larger gain but which was not statistically significant. However, longer-term retention of knowledge, as shown by the follow-up test, was statistically significantly greater in the experimental group (p = 0.001). The employment of teaching to match children's preferred learning styles, and the use of active learning were found to be related to improved retention of knowledge. Part of the study involved eliciting children's interpretation of standard hazard warning symbols, and this provoked considerable concern over the potential for dangerous misinterpretation with disastrous consequences. This article focuses on the reasons for such misconception and the action required to address this successfully in testing the intervention. PMID:23964825

  17. High Level Expression of a Novel Family 3 Neutral β-Xylosidase from Humicola insolens Y1 with High Tolerance to D-Xylose

    PubMed Central

    Xia, Wei; Shi, Pengjun; Xu, Xinxin; Qian, Lichun; Cui, Ying; Xia, Mengjuan; Yao, Bin

    2015-01-01

    A novel β-xylosidase gene of glycosyl hydrolase (GH) family 3, xyl3A, was identified from the thermophilic fungus Humicola insolens Y1, which is an innocuous and non-toxic fungus that produces a wide variety of GHs. The cDNA of xyl3A, 2334 bp in length, encodes a 777-residue polypeptide containing a putative signal peptide of 19 residues. The gene fragment without the signal peptide-coding sequence was cloned and overexpressed in Pichia pastoris GS115 at a high level of 100 mg/L in 1-L Erlenmeyer flasks without fermentation optimization. Recombinant Xyl3A showed both β-xylosidase and α-arabinfuranosidase activities, but had no hydrolysis capacity towards polysaccharides. It was optimally active at pH 6.0 and 60°C with a specific activity of 11.6 U/mg. It exhibited good stability over pH 4.0–9.0 (incubated at 37°C for 1 h) and at temperatures of 60°C and below, retaining over 80% maximum activity. The enzyme had stronger tolerance to xylose than most fungal GH3 β-xylosidases with a high Ki value of 29 mM, which makes Xyl3A more efficient to produce xylose in fermentation process. Sequential combination of Xyl3A following endoxylanase Xyn11A of the same microbial source showed significant synergistic effects on the degradation of various xylans and deconstructed xylo-oligosaccharides to xylose with high efficiency. Moreover, using pNPX as both the donor and acceptor, Xyl3A exhibited a transxylosylation activity to synthesize pNPX2. All these favorable properties suggest that Xyl3A has good potential applications in the bioconversion of hemicelluloses to biofuels. PMID:25658646

  18. Analysis of AtGUS1 and AtGUS2 in Arabidopsis root apex by a highly sensitive TSA-MISH method.

    PubMed

    Bruno, Leonardo; Ronchini, Matteo; Gagliardi, Olimpia; Corinti, Tamara; Chiappetta, Adriana; Gerola, Paolo; Bitonti, Maria B

    2015-01-01

    A new highly sensitive whole-mount in situ hybridization method, based on tyramide signal amplification (TSA-MISH) was developed and a combined GFP detection and TSA-MISH procedure was applied for the first time in plants, to precisely define the spatial pattern of AtGUS1 and AtGUS2 expression in the root apex. β-glucuronidases (GUSs) belonging to the glycosyl hydrolases (GHs) 79 family, are widely distributed in plants, but their functional role has not yet been fully investigated. In the model system Arabidopsis Thaliana, three different AtGUS genes have been identified which encode proteins with putative different fates. Endogenous GUS expression has been detected in different organs and tissues, but the cyto-histological domains of gene expression remain unclear. The results here reported show co-expression of AtGUS1 and AtGUS2 in different functional zones of the root apex (the cap central zone, the root cap meristem, the staminal cell niche and the cortical cell layers of the proximal meristem), while AtGUS2 is exclusively expressed in the cap peripheral layer and in the epidermis in the elongation zone. Interestingly, both genes are not expressed in the stelar portion of the proximal meristem. A spatial (cortex vs. stele) and temporal (proximal meristem vs. transition zone) regulation of AtGUS1 and AtGUS2 expression is therefore active in the root apex. This expression pattern, although globally consistent with the involvement of GUS activity in both cell proliferation and elongation, clearly indicates that AtGUS1 and AtGUS2 could control distinct downstream process depending on the developmental context and the interaction with other players of root growth control. In the future, the newly developed approaches may well be very useful to dissect such interactions. PMID:26505256

  19. Brain Mapping of Ghrelin O-Acyltransferase in Goldfish (Carassius Auratus): Novel Roles for the Ghrelinergic System in Fish?

    PubMed

    Blanco, Ayelén M; Sánchez-Bretaño, Aída; Delgado, María J; Valenciano, Ana I

    2016-06-01

    Ghrelin O-acyltransferase (GOAT) is the enzyme responsible for acylation of ghrelin, a gut-brain hormone with important roles in many physiological functions in vertebrates. Many aspects of GOAT remain to be elucidated, especially in fish, and particularly its anatomical distribution within the different brain areas has never been reported to date. The present study aimed to characterize the brain mapping of GOAT using RT-qPCR and immunohistochemistry in a teleost, the goldfish (Carassius auratus). Results show that goat transcripts are expressed in different brain areas of the goldfish, with the highest levels in the vagal lobe. Using immunohistochemistry, we also report the presence of GOAT immunoreactive cells in different encephalic areas, including the telencephalon, some hypothalamic nuclei, pineal gland, optic tectum and cerebellum, although they are especially abundant in the hindbrain. Particularly, an important signal is observed in the vagal lobe and some fiber tracts of the brainstem, such as the medial longitudinal fasciculus, Mauthneri fasciculus, secondary gustatory tract and spinothalamic tract. Most of the forebrain areas where GOAT is detected, particularly the hypothalamic nuclei, also express the ghs-r1a ghrelin receptor and other appetite-regulating hormones (e.g., orexin and NPY), supporting the role of ghrelin as a modulator of food intake and energy balance in fish. Present results are the first report on the presence of GOAT in the brain using imaging techniques. The high presence of GOAT in the hindbrain is a novelty, and point to possible new functions for the ghrelinergic system in fish. Anat Rec, 299:748-758, 2016. © 2016 Wiley Periodicals, Inc. PMID:27064922

  20. Toward production from gas hydrates: Current status, assessment of resources, and simulation-based evaluation of technology and potential

    USGS Publications Warehouse

    Moridis, G.J.; Collett, T.S.; Boswell, R.; Kurihara, M.; Reagan, M.T.; Koh, C.; Sloan, E.D.

    2009-01-01

    Gas hydrates (GHs) are a vast energy resource with global distribution in the permafrost and in the oceans. Even if conservative estimates are considered and only a small fraction is recoverable, the sheer size of the resource is so large that it demands evaluation as a potential energy source. In this review paper, we discuss the distribution of natural GH accumulations, the status of the primary international research and development (R&D) programs, and the remaining science and technological challenges facing the commercialization of production. After a brief examination of GH accumulations that are well characterized and appear to be models for future development and gas production, we analyze the role of numerical simulation in the assessment of the hydrate-production potential, identify the data needs for reliable predictions, evaluate the status of knowledge with regard to these needs, discuss knowledge gaps and their impact, and reach the conclusion that the numerical-simulation capabilities are quite advanced and that the related gaps either are not significant or are being addressed. We review the current body of literature relevant to potential productivity from different types of GH deposits and determine that there are consistent indications of a large production potential at high rates across long periods from a wide variety of hydrate deposits. Finally, we identify (a) features, conditions, geology and techniques that are desirable in potential production targets; (b) methods to maximize production; and (c) some of the conditions and characteristics that render certain GH deposits undesirable for production. Copyright ?? 2009 Society of Petroleum Engineers.

  1. Functional characterization of cellulases identified from the cow rumen fungus Neocallimastix patriciarum W5 by transcriptomic and secretomic analyses

    PubMed Central

    2011-01-01

    Background Neocallimastix patriciarum is one of the common anaerobic fungi in the digestive tracts of ruminants that can actively digest cellulosic materials, and its cellulases have great potential for hydrolyzing cellulosic feedstocks. Due to the difficulty in culture and lack of a genome database, it is not easy to gain a global understanding of the glycosyl hydrolases (GHs) produced by this anaerobic fungus. Results We have developed an efficient platform that uses a combination of transcriptomic and proteomic approaches to N. patriciarum to accelerate gene identification, enzyme classification and application in rice straw degradation. By conducting complementary studies of transcriptome (Roche 454 GS and Illumina GA IIx) and secretome (ESI-Trap LC-MS/MS), we identified 219 putative GH contigs and classified them into 25 GH families. The secretome analysis identified four major enzymes involved in rice straw degradation: β-glucosidase, endo-1,4-β-xylanase, xylanase B and Cel48A exoglucanase. From the sequences of assembled contigs, we cloned 19 putative cellulase genes, including the GH1, GH3, GH5, GH6, GH9, GH18, GH43 and GH48 gene families, which were highly expressed in N. patriciarum cultures grown on different feedstocks. Conclusions These GH genes were expressed in Pichia pastoris and/or Saccharomyces cerevisiae for functional characterization. At least five novel cellulases displayed cellulytic activity for glucose production. One β-glucosidase (W5-16143) and one exocellulase (W5-CAT26) showed strong activities and could potentially be developed into commercial enzymes. PMID:21849025

  2. De Novo Transcriptome Sequencing and Analysis of the Cereal Cyst Nematode, Heterodera avenae

    PubMed Central

    Kumar, Mukesh; Gantasala, Nagavara Prasad; Roychowdhury, Tanmoy; Thakur, Prasoon Kumar; Banakar, Prakash; Shukla, Rohit N.; Jones, Michael G. K.; Rao, Uma

    2014-01-01

    The cereal cyst nematode (CCN, Heterodera avenae) is a major pest of wheat (Triticum spp) that reduces crop yields in many countries. Cyst nematodes are obligate sedentary endoparasites that reproduce by amphimixis. Here, we report the first transcriptome analysis of two stages of H. avenae. After sequencing extracted RNA from pre parasitic infective juvenile and adult stages of the life cycle, 131 million Illumina high quality paired end reads were obtained which generated 27,765 contigs with N50 of 1,028 base pairs, of which 10,452 were annotated. Comparative analyses were undertaken to evaluate H. avenae sequences with those of other plant, animal and free living nematodes to identify differences in expressed genes. There were 4,431 transcripts common to H. avenae and the free living nematode Caenorhabditis elegans, and 9,462 in common with more closely related potato cyst nematode, Globodera pallida. Annotation of H. avenae carbohydrate active enzymes (CAZy) revealed fewer glycoside hydrolases (GHs) but more glycosyl transferases (GTs) and carbohydrate esterases (CEs) when compared to M. incognita. 1,280 transcripts were found to have secretory signature, presence of signal peptide and absence of transmembrane. In a comparison of genes expressed in the pre-parasitic juvenile and feeding female stages, expression levels of 30 genes with high RPKM (reads per base per kilo million) value, were analysed by qRT-PCR which confirmed the observed differences in their levels of expression levels. In addition, we have also developed a user-friendly resource, Heterodera transcriptome database (HATdb) for public access of the data generated in this study. The new data provided on the transcriptome of H. avenae adds to the genetic resources available to study plant parasitic nematodes and provides an opportunity to seek new effectors that are specifically involved in the H. avenae-cereal host interaction. PMID:24802510

  3. Isolation and Complete Genome Sequence of Algibacter alginolytica sp. nov., a Novel Seaweed-Degrading Bacteroidetes Bacterium with Diverse Putative Polysaccharide Utilization Loci.

    PubMed

    Sun, Cong; Fu, Ge-Yi; Zhang, Chong-Ya; Hu, Jing; Xu, Lin; Wang, Rui-Jun; Su, Yue; Han, Shuai-Bo; Yu, Xiao-Yun; Cheng, Hong; Zhang, Xin-Qi; Huo, Ying-Yi; Xu, Xue-Wei; Wu, Min

    2016-05-15

    The members of the phylum Bacteroidetes are recognized as some of the most important specialists for the degradation of polysaccharides. However, in contrast to research on Bacteroidetes in the human gut, research on polysaccharide degradation by marine Bacteroidetes is still rare. The genus Algibacter belongs to the Flavobacteriaceae family of the Bacteroidetes, and most species in this genus are isolated from or near the habitat of algae, indicating a preference for the complex polysaccharides of algae. In this work, a novel brown-seaweed-degrading strain designated HZ22 was isolated from the surface of a brown seaweed (Laminaria japonica). On the basis of its physiological, chemotaxonomic, and genotypic characteristics, it is proposed that strain HZ22 represents a novel species in the genus Algibacter with the proposed name Algibacter alginolytica sp. nov. The genome of strain HZ22, the type strain of this species, harbors 3,371 coding sequences (CDSs) and 255 carbohydrate-active enzymes (CAZymes), including 104 glycoside hydrolases (GHs) and 18 polysaccharide lyases (PLs); this appears to be the highest proportion of CAZymes (∼7.5%) among the reported strains in the class Flavobacteria Seventeen polysaccharide utilization loci (PUL) are predicted to be specific for marine polysaccharides, especially algal polysaccharides from red, green, and brown seaweeds. In particular, PUL N is predicted to be specific for alginate. Taking these findings together with the results of assays of crude alginate lyases, we prove that strain HZ22(T) can completely degrade alginate. This work reveals that strain HZ22(T) has good potential for the degradation of algal polysaccharides and that the structure and related mechanism of PUL in strain HZ22(T) are worth further research. PMID:26969704

  4. Transcriptomic Analysis of the Rice White Tip Nematode, Aphelenchoides besseyi (Nematoda: Aphelenchoididae)

    PubMed Central

    Li, Danlei; Wang, Zhiying; Dong, Airong; Chen, Qiaoli; Liu, Xiaohan

    2014-01-01

    Background The rice white tip nematode Aphelenchoides besseyi, a devastating nematode whose genome has not been sequenced, is distributed widely throughout almost all the rice-growing regions of the world. The aims of the present study were to define the transcriptome of A. besseyi and to identify parasite-related, mortality-related or host resistance-overcoming genes in this nematode. Methodology and Principal Findings Using Solexa/Illumina sequencing, we profiled the transcriptome of mixed-stage populations of A. besseyi. A total of 51,270 transcripts without gaps were produced based on high-quality clean reads. Of all the A. besseyi transcripts, 9,132 KEGG Orthology assignments were annotated. Carbohydrate-active enzymes of glycoside hydrolases (GHs), glycosyltransferases (GTs), carbohydrate esterases (CEs) and carbohydrate-binding modules (CBMs) were identified. The presence of the A. besseyi GH45 cellulase gene was verified by in situ hybridization. Given that 13 unique A. besseyi potential effector genes were identified from 41 candidate effector homologs, further studies of these homologs are merited. Finally, comparative analyses were conducted between A. besseyi contigs and Caenorhabditis elegans genes to look for orthologs of RNAi phenotypes, neuropeptides and peptidases. Conclusions and Significance The present results provide comprehensive insight into the genetic makeup of A. besseyi. Many of this species' genes are parasite related, nematode mortality-related or necessary to overcome host resistance. The generated transcriptome dataset of A. besseyi reported here lays the foundation for further studies of the molecular mechanisms related to parasitism and facilitates the development of new control strategies for this species. PMID:24637831

  5. Computational investigation of the pH dependence of loop flexibility and catalytic function in glycoside hydrolases.

    PubMed

    Bu, Lintao; Crowley, Michael F; Himmel, Michael E; Beckham, Gregg T

    2013-04-26

    Cellulase enzymes cleave glycosidic bonds in cellulose to produce cellobiose via either retaining or inverting hydrolysis mechanisms, which are significantly pH-dependent. Many fungal cellulases function optimally at pH ~5, and their activities decrease dramatically at higher or lower pH. To understand the molecular-level implications of pH in cellulase structure, we use a hybrid, solvent-based, constant pH molecular dynamics method combined with pH-based replica exchange to determine the pK(a) values of titratable residues of a glycoside hydrolase (GH) family 6 cellobiohydrolase (Cel6A) and a GH family 7 cellobiohydrolase (Cel7A) from the fungus Hypocrea jecorina. For both enzymes, we demonstrate that a bound substrate significantly affects the pKa values of the acid residues at the catalytic center. The calculated pK(a) values of catalytic residues confirm their proposed roles from structural studies and are consistent with the experimentally measured apparent pKa values. Additionally, GHs are known to impart a strained pucker conformation in carbohydrate substrates in active sites for catalysis, and results from free energy calculations combined with constant pH molecular dynamics suggest that the correct ring pucker is stable near the optimal pH for both Cel6A and Cel7A. Much longer molecular dynamics simulations of Cel6A and Cel7A with fixed protonation states based on the calculated pK(a) values suggest that pH affects the flexibility of tunnel loops, which likely affects processivity and substrate complexation. Taken together, this work demonstrates several molecular-level effects of pH on GH enzymes important for cellulose turnover in the biosphere and relevant to biomass conversion processes. PMID:23504310

  6. Arabinoxylan Oligosaccharide Hydrolysis by Family 43 and 51 Glycosidases from Lactobacillus brevis DSM 20054

    PubMed Central

    Hell, Johannes; Lorenz, Cindy; Böhmdorfer, Stefan; Rosenau, Thomas; Kneifel, Wolfgang

    2013-01-01

    Due to their potential prebiotic properties, arabinoxylan-derived oligosaccharides [(A)XOS] are of great interest as functional food and feed ingredients. While the (A)XOS metabolism of Bifidobacteriaceae has been extensively studied, information regarding lactic acid bacteria (LAB) is still limited in this context. The aim of the present study was to fill this important gap by characterizing candidate (A)XOS hydrolyzing glycoside hydrolases (GHs) identified in the genome of Lactobacillus brevis DSM 20054. Two putative GH family 43 xylosidases (XynB1 and XynB2) and a GH family 43 arabinofuranosidase (Abf3) were heterologously expressed and characterized. While the function of XynB1 remains unclear, XynB2 could efficiently hydrolyze xylooligosaccharides. Abf3 displayed high specific activity for arabinobiose but could not release arabinose from an (A)XOS preparation. However, two previously reported GH 51 arabinofuranosidases from Lb. brevis were able to specifically remove α-1,3-linked arabinofuranosyl residues from arabino-xylooligosaccharides (AXHm3 specificity). These results imply that Lb. brevis is at least genetically equipped with functional enzymes in order to hydrolyze the depolymerization products of (arabino)xylans and arabinans. The distribution of related genes in Lactobacillales genomes indicates that GH 43 and, especially, GH 51 glycosidase genes are rare among LAB and mainly occur in obligately heterofermentative Lactobacillus spp., Pediococcus spp., members of the Leuconostoc/Weissella branch, and Enterococcus spp. Apart from the prebiotic viewpoint, this information also adds new perspectives on the carbohydrate (i.e., pentose-oligomer) metabolism of LAB species involved in the fermentation of hemicellulose-containing substrates. PMID:23995921

  7. Cellulase Linkers Are Optimized Based on Domain Type and Function: Insights from Sequence Analysis, Biophysical Measurements, and Molecular Simulation

    PubMed Central

    Sammond, Deanne W.; Payne, Christina M.; Brunecky, Roman; Himmel, Michael E.; Crowley, Michael F.; Beckham, Gregg T.

    2012-01-01

    Cellulase enzymes deconstruct cellulose to glucose, and are often comprised of glycosylated linkers connecting glycoside hydrolases (GHs) to carbohydrate-binding modules (CBMs). Although linker modifications can alter cellulase activity, the functional role of linkers beyond domain connectivity remains unknown. Here we investigate cellulase linkers connecting GH Family 6 or 7 catalytic domains to Family 1 or 2 CBMs, from both bacterial and eukaryotic cellulases to identify conserved characteristics potentially related to function. Sequence analysis suggests that the linker lengths between structured domains are optimized based on the GH domain and CBM type, such that linker length may be important for activity. Longer linkers are observed in eukaryotic GH Family 6 cellulases compared to GH Family 7 cellulases. Bacterial GH Family 6 cellulases are found with structured domains in either N to C terminal order, and similar linker lengths suggest there is no effect of domain order on length. O-glycosylation is uniformly distributed across linkers, suggesting that glycans are required along entire linker lengths for proteolysis protection and, as suggested by simulation, for extension. Sequence comparisons show that proline content for bacterial linkers is more than double that observed in eukaryotic linkers, but with fewer putative O-glycan sites, suggesting alternative methods for extension. Conversely, near linker termini where linkers connect to structured domains, O-glycosylation sites are observed less frequently, whereas glycines are more prevalent, suggesting the need for flexibility to achieve proper domain orientations. Putative N-glycosylation sites are quite rare in cellulase linkers, while an N-P motif, which strongly disfavors the attachment of N-glycans, is commonly observed. These results suggest that linkers exhibit features that are likely tailored for optimal function, despite possessing low sequence identity. This study suggests that cellulase

  8. Functional Analyses of Multiple Lichenin-Degrading Enzymes from the Rumen Bacterium Ruminococcus albus 8▿†

    PubMed Central

    Iakiviak, Michael; Mackie, Roderick I.; Cann, Isaac K. O.

    2011-01-01

    Ruminococcus albus 8 is a fibrolytic ruminal bacterium capable of utilization of various plant cell wall polysaccharides. A bioinformatic analysis of a partial genome sequence of R. albus revealed several putative enzymes likely to hydrolyze glucans, including lichenin, a mixed-linkage polysaccharide of glucose linked together in β-1,3 and β-1,4 glycosidic bonds. In the present study, we demonstrate the capacity of four glycoside hydrolases (GHs), derived from R. albus, to hydrolyze lichenin. Two of the genes encoded GH family 5 enzymes (Ra0453 and Ra2830), one gene encoded a GH family 16 enzyme (Ra0505), and the last gene encoded a GH family 3 enzyme (Ra1595). Each gene was expressed in Escherichia coli, and the recombinant protein was purified to near homogeneity. Upon screening on a wide range of substrates, Ra0453, Ra2830, and Ra0505 displayed different hydrolytic properties, as they released unique product profiles. The Ra1595 protein, predicted to function as a β-glucosidase, preferred cleavage of a nonreducing end glucose when linked by a β-1,3 glycosidic bond to the next glucose residue. The major product of Ra0505 hydrolysis of lichenin was predicted to be a glucotriose that was degraded only by Ra0453 to glucose and cellobiose. Most importantly, the four enzymes functioned synergistically to hydrolyze lichenin to glucose, cellobiose, and cellotriose. This lichenin-degrading enzyme mix should be of utility as an additive to feeds administered to monogastric animals, especially those high in fiber. PMID:21890664

  9. Reduced toxicity polyester resins and microvascular pre-preg tapes for advanced composites manufacturing

    NASA Astrophysics Data System (ADS)

    Poillucci, Richard

    Advanced composites manufacturing broadly encapsulates topics ranging from matrix chemistries to automated machines that lay-up fiber-reinforced materials. Environmental regulations are stimulating research to reduce matrix resin formulation toxicity. At present, composites fabricated with polyester resins expose workers to the risk of contact with and inhalation of styrene monomer, which is a potential carcinogen, neurotoxin, and respiratory irritant. The first primary goal of this thesis is to reduce the toxicity associated with polyester resins by: (1) identification of potential monomers to replace styrene, (2) determination of monomer solubility within the polyester, and (3) investigation of approaches to rapidly screen a large resin composition parameter space. Monomers are identified based on their ability to react with polyester and their toxicity as determined by the Globally Harmonized System (GHS) and a green screen method. Solubilities were determined by the Hoftyzer -- Van Krevelen method, Hansen solubility parameter database, and experimental mixing of monomers. A combinatorial microfluidic mixing device is designed and tested to obtain distinct resin compositions from two input chemistries. The push for safer materials is complemented by a thrust for multifunctional composites. The second primary goal of this thesis is to design and implement the manufacture of sacrificial fiber materials suitable for use in automated fiber placement of microvascaular multifunctional composites. Two key advancements are required to achieve this goal: (1) development of a roll-to-roll method to place sacrificial fibers onto carbon fiber pre-preg tape; and (2) demonstration of feasible manufacture of microvascular carbon fiber plates with automated fiber placement. An automated method for placing sacrificial fibers onto carbon fiber tapes is designed and a prototype implemented. Carbon fiber tows with manual placement of sacrificial fibers is implemented within an

  10. Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE™.

    PubMed

    Choi, Seunghye; Lee, Miri; Lee, Su-Hyon; Jung, Haeng-Sun; Kim, Seol-Yeong; Chung, Tae-Young; Choe, Tae-boo; Chun, Young-Jin; Lim, Kyung-Min

    2015-09-01

    Evaluation of the eye irritation is essential in the development of new cosmetic products. Draize rabbit eye irritation test has been widely used in which chemicals are directly applied to rabbit eye, and the symptoms and signs of eyes are scored. However, due to the invasive procedure, it causes substantial pain and discomfort to animals. Recently, we reported in vitro eye irritation test method using a 3D human corneal epithelial model (MCTT HCE™) which is reconstructed from remaining human tissues after a corneal transplantation. This model exhibited an excellent predictive capacity for 25 reference chemicals (sensitivity 100%, specificity 77% and accuracy 88% vs. GHS). To improve the test performance, we explored new biomarkers for the eye irritation through transcriptomic approach. Three surfactants were selected as model eye irritants that include sodium lauryl sulfate, benzalkonium chloride and triton X-100. After test chemicals were treated, we investigated differentially expressed genes through a whole-gene microarray (Affymetrix GeneChip(®) Human Gene 2.0 ST Array, 48,000 probes). As a result, we identified that mRNAs of cornifelin (CNFN), a constituent of the insoluble cornified cell envelope of stratified squamous epithelia, and early growth response-1 (EGR1), a nuclear transcriptional regulator, were significantly up-regulated by all three irritants. Up-regulation of CNFN and EGR1 was further confirmed by Q-RT-PCR, and immunohistochemistry revealed increased level of CNFN in irritant-treated tissues, supporting the relevance of CNFN and EGR1 as new biomarkers for eye irritation. PMID:25377654

  11. Changes in the ghrelin hormone pathway maybe part of an unusual gastric system in monotremes.

    PubMed

    He, Chuan; Tsend-Ayush, Enkhjargal; Myers, Mark A; Forbes, Briony E; Grützner, Frank

    2013-09-15

    Ghrelin is a growth hormone (GH)-releasing and appetite-regulating peptide predominately released from the stomach. Ghrelin is evolutionarily highly conserved and known to have a wide range of functions including the regulation of metabolism by maintaining an insulin-glucose balance. The peptide is produced as a single proprotein, which is later proteolytically cleaved. Ghrelin exerts its biological function after O-n-octanoylation at residue serine 3, which is catalyzed by ghrelin O-acyl transferase (GOAT) and allows binding to the growth hormone secretagogue receptor (GHS-R 1a). Genes involved in the ghrelin pathway have been identified in a broad range of vertebrate species, however, little is known about this pathway in the basal mammalian lineage of monotremes (platypus and echidna). Monotremes are particularly interesting in this context, as they have undergone massive changes in stomach anatomy and physiology, accompanied by a striking loss of genes involved in gastric function. In this study, we investigated genes in the ghrelin pathway in monotremes. Using degenerate PCR, database searches and synteny analysis we found that genes encoding ghrelin and GOAT are missing in the platypus genome, whilst, as has been reported in other species, the GHSR is present and expressed in brain, pancreas, kidney, intestine, heart and stomach. This is the first report suggesting the loss of ghrelin in a mammal. The loss of this gene may be related to changes to the platypus digestive system and raises questions about the control of blood glucose levels and insulin response in monotreme mammals. In addition, the conservation of the ghrelin receptor gene in platypus indicates that another ligand(s) maybe acting via this receptor in monotremes. PMID:23770219

  12. A catch-up validation study of an in vitro skin irritation test method using reconstructed human epidermis LabCyte EPI-MODEL24.

    PubMed

    Kojima, Hajime; Katoh, Masakazu; Shinoda, Shinsuke; Hagiwara, Saori; Suzuki, Tamie; Izumi, Runa; Yamaguchi, Yoshihiro; Nakamura, Maki; Kasahawa, Toshihiko; Shibai, Aya

    2014-07-01

    Three validation studies were conducted by the Japanese Society for Alternatives to Animal Experiments in order to assess the performance of a skin irritation assay using reconstructed human epidermis (RhE) LabCyte EPI-MODEL24 (LabCyte EPI-MODEL24 SIT) developed by the Japan Tissue Engineering Co., Ltd. (J-TEC), and the results of these studies were submitted to the Organisation for Economic Co-operation and Development (OECD) for the creation of a Test Guideline (TG). In the summary review report from the OECD, the peer review panel indicated the need to resolve an issue regarding the misclassification of 1-bromohexane. To this end, a rinsing operation intended to remove exposed chemicals was reviewed and the standard operating procedure (SOP) revised by J-TEC. Thereafter, in order to confirm general versatility of the revised SOP, a new validation management team was organized by the Japanese Center for the Validation of Alternative Methods (JaCVAM) to undertake a catch-up validation study that would compare the revised assay with similar in vitro skin irritation assays, per OECD TG No. 439 (2010). The catch-up validation and supplementary studies for LabCyte EPI-MODEL24 SIT using the revised SOPs were conducted at three laboratories. These results showed that the revised SOP of LabCyte EPI-MODEL24 SIT conformed more accurately to the classifications for skin irritation under the United Nations Globally Harmonised System of Classification and Labelling of Chemicals (UN GHS), thereby highlighting the importance of an optimized rinsing operation for the removal of exposed chemicals in obtaining consistent results from in vitro skin irritation assays. PMID:24122860

  13. Antiphospholipid antibodies in a large population-based cohort: genome-wide associations and effects on monocyte gene expression.

    PubMed

    Müller-Calleja, Nadine; Rossmann, Heidi; Müller, Christian; Wild, Philipp; Blankenberg, Stefan; Pfeiffer, Norbert; Binder, Harald; Beutel, Manfred E; Manukyan, Davit; Zeller, Tanja; Lackner, Karl J

    2016-07-01

    The antiphospholipid syndrome (APS) is characterised by venous and/or arterial thrombosis and pregnancy morbidity in women combined with the persistent presence of antiphospholipid antibodies (aPL). We aimed to identify genetic factors associated with the presence of aPL in a population based cohort. Furthermore, we wanted to clarify if the presence of aPL affects gene expression in circulating monocytes. Titres of IgG and IgM against cardiolipin, β2glycoprotein 1 (anti-β2GPI), and IgG against domain 1 of β2GPI (anti-domain 1) were determined in approx. 5,000 individuals from the Gutenberg Health Study (GHS) a population based cohort of German descent. Genotyping was conducted on Affymetrix Genome-Wide Human SNP 6.0 arrays. Monocyte gene expression was determined in a subgroup of 1,279 individuals by using the Illumina HT-12 v3 BeadChip. Gene expression data were confirmed in vitro and ex vivo by qRT-PCR. Genome wide analysis revealed significant associations of anti-β2GPI IgG and APOH on chromosome 17, which had been previously identified by candidate gene approaches, and of anti-domain1 and MACROD2 on chromosome 20 which has been listed in a previous GWAS as a suggestive locus associated with the occurrence of anti-β2GPI antibodies. Expression analysis confirmed increased expression of TNFα in monocytes and identified and confirmed neuron navigator 3 (NAV3) as a novel gene induced by aPL. In conclusion, MACROD2 represents a novel genetic locus associated with aPL. Furthermore, we show that aPL induce the expression of NAV3 in monocytes and endothelial cells. This will stimulate further research into the role of these genes in the APS. PMID:27098658

  14. Bayesian integrated testing strategy (ITS) for skin sensitization potency assessment: a decision support system for quantitative weight of evidence and adaptive testing strategy.

    PubMed

    Jaworska, Joanna S; Natsch, Andreas; Ryan, Cindy; Strickland, Judy; Ashikaga, Takao; Miyazawa, Masaaki

    2015-12-01

    The presented Bayesian network Integrated Testing Strategy (ITS-3) for skin sensitization potency assessment is a decision support system for a risk assessor that provides quantitative weight of evidence, leading to a mechanistically interpretable potency hypothesis, and formulates adaptive testing strategy for a chemical. The system was constructed with an aim to improve precision and accuracy for predicting LLNA potency beyond ITS-2 (Jaworska et al., J Appl Toxicol 33(11):1353-1364, 2013) by improving representation of chemistry and biology. Among novel elements are corrections for bioavailability both in vivo and in vitro as well as consideration of the individual assays' applicability domains in the prediction process. In ITS-3 structure, three validated alternative assays, DPRA, KeratinoSens and h-CLAT, represent first three key events of the adverse outcome pathway for skin sensitization. The skin sensitization potency prediction is provided as a probability distribution over four potency classes. The probability distribution is converted to Bayes factors to: 1) remove prediction bias introduced by the training set potency distribution and 2) express uncertainty in a quantitative manner, allowing transparent and consistent criteria to accept a prediction. The novel ITS-3 database includes 207 chemicals with a full set of in vivo and in vitro data. The accuracy for predicting LLNA outcomes on the external test set (n = 60) was as follows: hazard (two classes)-100 %, GHS potency classification (three classes)-96 %, potency (four classes)-89 %. This work demonstrates that skin sensitization potency prediction based on data from three key events, and often less, is possible, reliable over broad chemical classes and ready for practical applications. PMID:26612363

  15. How sugars pucker: electronic structure calculations map the kinetic landscape of five biologically paramount monosaccharides and their implications for enzymatic catalysis.

    PubMed

    Mayes, Heather B; Broadbelt, Linda J; Beckham, Gregg T

    2014-01-22

    Glycoside hydrolases (GHs) distort carbohydrate ring geometry along particular "catalytic itineraries" during the cleavage of glycosidic bonds, illustrating the relationship between substrate conformation and reactivity. Previous theoretical studies of thermodynamics of isolated monosaccharides offer insights into the catalytic itineraries of particular sugars. However, kinetic accessibility of carbohydrate puckering conformations and the role of exocyclic groups have not yet been thoroughly addressed. Here we present the first complete library of low-energy local minima and puckering interconversion transition states for five biologically relevant pyranose sugars: β-xylose, β-mannose, α-glucose, β-glucose, and β-N-acetylglucosamine. These were obtained by a thorough theoretical investigation each of the 38 IUPAC designated puckering geometries and all possible conformations of the exocyclic groups. These calculations demonstrate that exocyclic groups must be explicitly considered when examining these interconversion pathways. Furthermore, these data enable evaluation of previous hypotheses of why enzymes perturb ring geometries from the low-energy equatorial chair ((4)C1) conformation. They show that the relative thermodynamics alone do not universally correlate with GH catalytic itineraries. For some sugars, particular puckers offer both catalytically favorable electronic structure properties, such as anomeric carbon partial charge, and low kinetic barriers to achieve a given puckering conformation. However, different factors correlate with catalytic itineraries for other sugars; for β-N-acetylglucosamine, the key N-acetyl arm confounds the puckering landscape and appears to be the crucial factor. Overall, this study reveals a more comprehensive understanding of why particular puckering geometries are favored in carbohydrate catalysis concomitant with the complexity of glycobiology. PMID:24368073

  16. Analysis of the level of comprehension of chemical hazard labels: a case for Zambia.

    PubMed

    Banda, Samuel F; Sichilongo, Kwenga

    2006-06-15

    We have surveyed the impact of chemical hazard label elements on four target sectors, i.e. the agricultural, industrial, transport and the consumer (the general public) sectors, in order to assess the type of reactions the respondents perceive to a given chemical label element such as symbol, hazard phrase, color, and hazard signal word. The survey revealed that the level of education, gender and/or age did not influence the respondents' perception of the extent of hazard but rather familiarity or frequency of use of the chemicals and acquaintance with chemical label elements was significant in the assessment of the extent of perceived hazard posed by a given chemical. Symbols such as the St Andrews Cross--though common--is virtually not understood by more than 80% of the respondents in all the sectors. We noted that respondents appreciate symbols they can relate to, which are flame-like, ghost-like and exert immediate impacts to respondents. Color codes have found use in the agriculture sector because of their ease to be recalled especially by the majority of illiterate farm workers. The survey revealed that red in agricultural circles is well associated with high toxicity while other colors such as yellow and blue can not clearly be associated with hazard. The word "toxic" is not used in the industry and transport sectors where the most hazard signal word is "danger". The Globally Harmonized System (GHS) classification adopted "danger" and "warning" for use as signal words. The survey revealed that effective chemical hazard symbols must not be too abstract to the client but should contain features that are known or easily comprehended. PMID:16426665

  17. Mechanisms of gender-specific regulation of mouse sulfotransferases (Sults).

    PubMed

    Alnouti, Yazen; Klaassen, Curtis D

    2011-03-01

    1. Marked gender differences in the expression of sulfotransferases (Sults) are known to exist in several species including rats, mice and hamsters. However, the mechanism for this gender difference is not known. Therefore, in the present study, it was determined whether sex and/or growth hormone (GH) are responsible for the gender difference in the expression of Sults using gonadectomized (GNX), hypophysectomized (HX) and GH-releasing hormone receptor-deficient little (lit/lit) mouse models. 2. Sult1a1 and Papss2 in liver and kidney, and Sult1d1 in liver are female-predominant in mice because of suppressive effects of both androgens and male-pattern GH secretion. Sult2a1/a2 is the most markedly female-predominant Sult in mouse liver due to suppressive effects of androgens and male-pattern GH secretion, as well as stimulatory effects by estrogens and female-pattern GH secretion. Sult3a1 is female-predominant in mouse liver due to suppressive effects of androgens as well as stimulatory effects of estrogens and female-pattern GH secretion. Sult1c1 expression is male-predominant in mouse liver and kidney because of stimulatory effects of androgens in males. Sult4a1 expression is female-predominant in mouse brain due to stimulatory effects of estrogens. 3. In conclusion, gender-divergent Sults are mostly female-predominant and Sult1c1 is the only male-dominant Sult. The gender differences in expression of various mouse Sults are influenced by various mechanisms involving sex and/or GHs. PMID:21091322

  18. Noise Annoyance Is Associated with Depression and Anxiety in the General Population- The Contribution of Aircraft Noise

    PubMed Central

    Beutel, Manfred E.; Jünger, Claus; Klein, Eva M.; Wild, Philipp; Lackner, Karl; Blettner, Maria; Binder, Harald; Michal, Matthias; Wiltink, Jörg; Brähler, Elmar; Münzel, Thomas

    2016-01-01

    Background While noise annoyance has become recognized as an important environmental stressor, its association to mental health has hardly been studied. We therefore determined the association of noise annoyance to anxiety and depression and explored the contribution of diverse environmental sources to overall noise annoyance. Patients and Methods We investigated cross-sectional data of n = 15.010 participants of the Gutenberg Health Study (GHS), a population-based, prospective, single-center cohort study in Mid-Germany (age 35 to 74 years). Noise annoyance was assessed separately for road traffic, aircraft, railways, industrial, neighborhood indoor and outdoor noise (“during the day”; “in your sleep”) on 5-point scales (“not at all” to “extremely”); depression and anxiety were assessed by the PHQ-9, resp. GAD-2. Results Depression and anxiety increased with the degree of overall noise annoyance. Compared to no annoyance, prevalence ratios for depression, respectively anxiety increased from moderate (PR depression 1.20; 95%CI 1.00 to 1.45; PR anxiety 1.42; 95% CI 1.15 to 1.74) to extreme annoyance (PR depression 1.97; 95%CI 1.62 to 2.39; PR anxiety 2.14; 95% CI 1.71 to 2.67). Compared to other sources, aircraft noise annoyance was prominent affecting almost 60% of the population. Interpretation Strong noise annoyance was associated with a two-fold higher prevalence of depression and anxiety in the general population. While we could not relate annoyance due to aircraft noise directly to depression and anxiety, we established that it was the major source of annoyance in the sample, exceeding the other sources in those strongly annoyed. Prospective follow-up data will address the issue of causal relationships between annoyance and mental health. PMID:27195894

  19. Socioeconomic differentials and availability of domestic water in South Africa

    NASA Astrophysics Data System (ADS)

    Dungumaro, Esther W.

    The past few decades has seen massive efforts to increasing provision of domestic water. However, water is still unavailable to many people most of them located in sub-Saharan Africa, South Asia and East Asia. Furthermore, availability of water varies greatly both spatially and temporary. While other people pay so dearly for domestic water others have an easy access to adequate clean water and sanitation. Accessibility and affordability of domestic water and sanitation is determined by a great variety of factors including socioeconomic status of households. The main objective of the paper is to inform on factors which need to be taken into account when coming up with projects to provide domestic water. It is more critical when the issue of water pricing comes into the equation. Water pricing has many facets, including equity, willingness to pay and affordability. In this premise, it is deemed important to understand the socioeconomic characteristics of the people before deciding on the amount of money they will have to pay for water consumption. It is argued that understanding people’s socioeconomic situation will greatly help to ensure that principles of sustainability and equity in water allocation and pricing are achieved. To do so, the paper utilized 2002 South Africa General Household Survey (GHS), to analyze socioeconomic variables and availability of domestic water. Analysis was mainly descriptive. However, logistic regression analysis was also utilized to determine the likelihood of living in a household that obtain water from a safe source. The study found that there is a strong relationship between availability of domestic water and socioeconomic conditions. Economic status, household size and to a lesser extent gender of head of household were found to be strong predictors of living in a household which obtained water from a safe source. The paper recommends that needs and priorities for interventions in water provision should take into account

  20. Insight into Dominant Cellulolytic Bacteria from Two Biogas Digesters and Their Glycoside Hydrolase Genes

    PubMed Central

    Zhang, Jun; Zhang, Lei; Geng, Alei; Liu, Fanghua; Zhao, Guoping; Wang, Shengyue; Zhou, Zhihua; Yan, Xing

    2015-01-01

    Diverse cellulolytic bacteria are essential for maintaining high lignocellulose degradation ability in biogas digesters. However, little was known about functional genes and gene clusters of dominant cellulolytic bacteria in biogas digesters. This is the foundation to understand lignocellulose degradation mechanisms of biogas digesters and apply these gene resource for optimizing biofuel production. A combination of metagenomic and 16S rRNA gene clone library methods was used to investigate the dominant cellulolytic bacteria and their glycoside hydrolase (GH) genes in two biogas digesters. The 16S rRNA gene analysis revealed that the dominant cellulolytic bacteria were strains closely related to Clostridium straminisolvens and an uncultured cellulolytic bacterium designated BG-1. To recover GH genes from cellulolytic bacteria in general, and BG-1 in particular, a refined assembly approach developed in this study was used to assemble GH genes from metagenomic reads; 163 GH-containing contigs ≥ 1 kb in length were obtained. Six recovered GH5 genes that were expressed in E. coli demonstrated multiple lignocellulase activities and one had high mannanase activity (1255 U/mg). Eleven fosmid clones harboring the recovered GH-containing contigs were sequenced and assembled into 10 fosmid contigs. The composition of GH genes in the 163 assembled metagenomic contigs and 10 fosmid contigs indicated that diverse GHs and lignocellulose degradation mechanisms were present in the biogas digesters. In particular, a small portion of BG-1 genome information was recovered by PhyloPythiaS analysis. The lignocellulase gene clusters in BG-1 suggested that it might use a possible novel lignocellulose degradation mechanism to efficiently degrade lignocellulose. Dominant cellulolytic bacteria of biogas digester possess diverse GH genes, not only in sequences but also in their functions, which may be applied for production of biofuel in the future. PMID:26070087

  1. Construction of a rice glycoside hydrolase phylogenomic database and identification of targets for biofuel research

    PubMed Central

    Sharma, Rita; Cao, Peijian; Jung, Ki-Hong; Sharma, Manoj K.; Ronald, Pamela C.

    2013-01-01

    Glycoside hydrolases (GH) catalyze the hydrolysis of glycosidic bonds in cell wall polymers and can have major effects on cell wall architecture. Taking advantage of the massive datasets available in public databases, we have constructed a rice phylogenomic database of GHs (http://ricephylogenomics.ucdavis.edu/cellwalls/gh/). This database integrates multiple data types including the structural features, orthologous relationships, mutant availability, and gene expression patterns for each GH family in a phylogenomic context. The rice genome encodes 437 GH genes classified into 34 families. Based on pairwise comparison with eight dicot and four monocot genomes, we identified 138 GH genes that are highly diverged between monocots and dicots, 57 of which have diverged further in rice as compared with four monocot genomes scanned in this study. Chromosomal localization and expression analysis suggest a role for both whole-genome and localized gene duplications in expansion and diversification of GH families in rice. We examined the meta-profiles of expression patterns of GH genes in twenty different anatomical tissues of rice. Transcripts of 51 genes exhibit tissue or developmental stage-preferential expression, whereas, seventeen other genes preferentially accumulate in actively growing tissues. When queried in RiceNet, a probabilistic functional gene network that facilitates functional gene predictions, nine out of seventeen genes form a regulatory network with the well-characterized genes involved in biosynthesis of cell wall polymers including cellulose synthase and cellulose synthase-like genes of rice. Two-thirds of the GH genes in rice are up regulated in response to biotic and abiotic stress treatments indicating a role in stress adaptation. Our analyses identify potential GH targets for cell wall modification. PMID:23986771

  2. Validation study of the in vitro skin irritation test with the LabCyte EPI-MODEL24.

    PubMed

    Kojima, Hajime; Ando, Yoko; Idehara, Kenji; Katoh, Masakazu; Kosaka, Tadashi; Miyaoka, Etsuyoshi; Shinoda, Shinsuke; Suzuki, Tamie; Yamaguchi, Yoshihiro; Yoshimura, Isao; Yuasa, Atsuko; Watanabe, Yukihiko; Omori, Takashi

    2012-03-01

    A validation study on an in vitro skin irritation assay was performed with the reconstructed human epidermis (RhE) LabCyte EPI-MODEL24, developed by Japan Tissue Engineering Co. Ltd (Gamagori, Japan). The protocol that was followed in the current study was an optimised version of the EpiSkin protocol (LabCyte assay). According to the United Nations Globally Harmonised System (UN GHS) of classification for assessing the skin irritation potential of a chemical, 12 irritants and 13 non-irritants were validated by a minimum of six laboratories from the Japanese Society for Alternatives to Animal Experiments (JSAAE) skin irritation assay validation study management team (VMT). The 25 chemicals were listed in the European Centre for the Validation of Alternative Methods (ECVAM) performance standards. The reconstructed tissues were exposed to the chemicals for 15 minutes and incubated for 42 hours in fresh culture medium. Subsequently, the level of interleukin-1 alpha (IL-1 α) present in the conditioned medium was measured, and tissue viability was assessed by using the MTT assay. The results of the MTT assay obtained with the LabCyte EPI-MODEL24 (LabCyte MTT assay) demonstrated high within-laboratory and between-laboratory reproducibility, as well as high accuracy for use as a stand-alone assay to distinguish skin irritants from non-irritants. In addition, the IL-1α release measurements in the LabCyte assay were clearly unnecessary for the success of this model in the classification of chemicals for skin irritation potential. PMID:22558976

  3. Association of gas hydrate formation in fluid discharges with anomalous hydrochemical profiles

    NASA Astrophysics Data System (ADS)

    Matveeva, T.

    2009-04-01

    Numerous investigations worldwide have shown that active underwater fluid discharge produces specific structures on the seafloor such as submarine seepages, vents, pockmarks, and collapse depressions. Intensive fluxes of fluids, especially of those containing hydrocarbon gases, result in specific geochemical and physical conditions favorable for gas hydrate (GH) formation. GH accumulations associated with fluid discharge are usually controlled by fluid conduits such as mud volcanoes, diapirs or faults. During last decade, subaqueous GHs become the subject of the fuel in the nearest future. However, the expediency of their commercial development can be proved solely by revealing conditions and mechanisms of GH formation. Kinetic of GH growth (although it is incompletely understood) is one of the important parameters controlling their formation among with gas solubility, pressure, temperature, gas quantity and others. Original large dataset on hydrate-related interstitial fluids obtained from different fluid discharge areas at the Sea of Okhotsk, Black Sea, Gulf of Cadiz, Lake Baikal (Eastern Siberia) allow to suggest close relation of the subaqueous GH formation process to anomalous hydrochemical profiles. We have studied the chemical and isotopic composition of interstitial fluids from GH-bearing and GH-free sediments obtained at different GH accumulations. Most attention was paid to possible influence of the interstitial fluid chemistry on the kinetic of GH formation in a porous media. The influence of salts on methane solubility within hydrate stability zones was considered by Handa (1990), Zatsepina & Buffet (1998), and later by Davie et al. (2004) from a theoretical point of view. Our idea is based on the experimentally proved fact that fugacity coefficient of methane dissolved in saline gas-saturated water which is in equilibrium with hydrates, is higher than that in more fresh water though the solubility is lower. Therefore, if a gradient of water salinity

  4. Concentrated flow erosion processes under planned fire

    NASA Astrophysics Data System (ADS)

    Langhans, Christoph; Noske, Phil; Van Der Sant, Rene; Lane, Patrick; Sheridan, Gary

    2016-04-01

    , the erosion of coarser material was more threshold dependent as mobilized stones form granular lobes that can readily stop or re-mobilize depending on stream power. Low severity sites had much more trapping objects remaining on the soils surface than higher severity sites, which means that high fire severity increases the probability of sediment transport to the channels, especially for coarse material.

  5. Short term tolvaptan increases water intake and effectively decreases urinary calcium oxalate, calcium phosphate, and uric acid supersaturations

    PubMed Central

    Cheungpasitporn, Wisit; Erickson, Stephen B.; Rule, Andrew D.; Enders, Felicity; Lieske, John C.

    2016-01-01

    Purpose Many patients cannot effectively increase water intake and urine volume to prevent urinary stones. Tolvaptan, a V2 receptor antagonist, blocks water reabsorption in the collecting duct and should reduce urinary supersaturation (SS) of stone forming solutes, but this has never been proven. Materials and Methods We conducted a double blind, randomized, placebo-controlled, crossover study in 21 adult calcium urinary stone formers stratified as majority calcium oxalate(CaOx, n=10) or calcium phosphate(CaP, n=11). Patients received tolvaptan 45 mg/day or placebo for 1 week, followed by a washout week and crossover to tolvaptan or placebo for week 3. A 24h urines was collected at the end of weeks 1 and 3. Results Tolvaptan vs. placebo decreased urinary osmolality (204±96 vs 529±213 mOsm/kg, P<0.001) and increased urinary volume (4.8±2.9 vs 1.8±0.9 L, P<0.001). The majority of urinary solute excretion rates including sodium and calcium did not significantly change, although oxalate secretion slightly increased (23±8 to 15±8 mg/24h, P = 0.009). Urinary CaOx SS (−0.01±1.14 vs 0.95±0.87 DG, P<0.001), CaP SS (−1.66±1.17 vs −0.13±1.02 DG, P<0.001) and Uric Acid SS (−2.05±4.05 vs −5.24±3.12 DG, P=0.04) all dramatically decreased. Effects did not differ between CaOx and CaP groups (P>0.05 for all interactions). Conclusions Tolvaptan increases urine volume and decreases urinary SS in calcium stone formers. Further study is needed to determine if long term use of V2 receptor antagonists results in fewer stone events. PMID:26598423

  6. Artificial tektites: an experimental technique for capturing the shapes of spinning drops

    NASA Astrophysics Data System (ADS)

    Baldwin, K. A.

    2014-12-01

    Tektites are small stones formed from rapidly cooling drops of molten rock ejected from high velocity asteroid impacts with the Earth, that freeze into a myriad of shapes during flight. Many splash-form tektites have an elongated or dumb-bell shape owing to their rotation prior to solidification[1]. Here we present a novel method for creating 'artificial tektites' from spinning drops of molten wax, using diamagnetic levitation to suspend the drops[2]. We find that the solid wax models produced this way are the stable equilibrium shapes of a spinning liquid droplet held together by surface tension. In addition to the geophysical interest in tektite formation, the stable equilibrium shapes of liquid drops have implications for many physical phenomena, covering a wide range of length scales, from nuclear physics (e.g. in studies of rapidly rotating atomic nuclei), to astrophysics (e.g. in studies of the shapes of astronomical bodies such as asteroids, rapidly rotating stars and event horizons of rotating black holes). For liquid drops bound by surface tension, analytical and numerical methods predict a series of stable equilibrium shapes with increasing angular momentum. Slowly spinning drops have an oblate-like shape. With increasing angular momentum these shapes become secularly unstable to a series of triaxial pseudo-ellipsoids that then evolve into a family of two-lobed 'dumb-bell' shapes as the angular momentum is increased still further. Our experimental method allows accurate measurements of the drops to be taken, which are useful to validate numerical models. This method has provided a means for observing tektite formation, and has additionally confirmed experimentally the stable equilibrium shapes of liquid drops, distinct from the equivalent shapes of rotating astronomical bodies. Potentially, this technique could be applied to observe the non-equilibrium dynamic processes that are also important in real tektite formation, involving, e.g. viscoelastic

  7. The Climate and its Impacts on deterioration and weathering rate of EI-Nadura Temple in El- Kharga Oasis, Western Desert of Egypt.

    NASA Astrophysics Data System (ADS)

    Ismael, Hossam

    2015-04-01

    Undoubtedly, El-Kharga Oasis monumental sites are considered an important part of our world's cultural heritage in the South Western Desert of Egypt. These sites are scattered on the floor of the oasis representing ancient civilizations. The Roman stone monuments in Kharga represent cultural heritage of an outstanding universal value. Such those monuments have suffered weathering deterioration. There are various elements which affect the weathering process of stone monuments: climate conditions, shapes of cultural heritages, exposed time periods, terrains, and vegetation around them, etc. Among these, climate conditions are the most significant factor affecting the deterioration of Archeological sites in Egypt. El- Kharga Oasis belongs administratively to the New Valley Governorate. It is located in the southern part of the western desert of Egypt, lies between latitudes 22°30'14" and 26°00'00" N, and between 30°27'00" and 30°47'00" E. The area of El Kharga Oasis covers about 7500 square kilometers. Pilot studies were carried out on the EI-Nadura Temple, composed of sandstones originating from the great sand sea. The major objective of this study is to monitor and measure the weathering features and the weathering rate affecting the building stones forming El-Nadora Roman building rocks in cubic cm. To achieve these aims, the present study used analysis of climatic data such as annual and seasonal solar radiation, Monthly average number of hours of sunshine, maximum and minimum air temperatures, wind speed, which have obtained from actual field measurements and data Meteorological Authority of El-Kharga station for the period 1977 to 2010 (33 years), and from the period 1941-2050 (110 years) as a long term of temperature data. Several samples were collected and examined by polarizing microscopy (PLM), X-ray diffraction analysis (XRD) and scanning electron microscopy equipped with an energy dispersive X-ray analysis system (SEM-EDX). The results were in

  8. Unified theory on the pathogenesis of Randall's plaques and plugs.

    PubMed

    Khan, Saeed R; Canales, Benjamin K

    2015-01-01

    Kidney stones develop attached to sub-epithelial plaques of calcium phosphate (CaP) crystals (termed Randall's plaque) and/or form as a result of occlusion of the openings of the Ducts of Bellini by stone-forming crystals (Randall's plugs). These plaques and plugs eventually extrude into the urinary space, acting as a nidus for crystal overgrowth and stone formation. To better understand these regulatory mechanisms and the pathophysiology of idiopathic calcium stone disease, this review provides in-depth descriptions of the morphology and potential origins of these plaques and plugs, summarizes existing animal models of renal papillary interstitial deposits, and describes factors that are believed to regulate plaque formation and calcium overgrowth. Based on evidence provided within this review and from the vascular calcification literature, we propose a "unified" theory of plaque formation-one similar to pathological biomineralization observed elsewhere in the body. Abnormal urinary conditions (hypercalciuria, hyperoxaluria, and hypocitraturia), renal stress or trauma, and perhaps even the normal aging process lead to transformation of renal epithelial cells into an osteoblastic phenotype. With this de-differentiation comes an increased production of bone-specific proteins (i.e., osteopontin), a reduction in crystallization inhibitors (such as fetuin and matrix Gla protein), and creation of matrix vesicles, which support nucleation of CaP crystals. These small deposits promote aggregation and calcification of surrounding collagen. Mineralization continues by calcification of membranous cellular degradation products and other fibers until the plaque reaches the papillary epithelium. Through the activity of matrix metalloproteinases or perhaps by brute physical force produced by the large sub-epithelial crystalline mass, the surface is breached and further stone growth occurs by organic matrix-associated nucleation of CaOx or by the transformation of the outer layer

  9. Seasonal variations in urinary risk factors among patients with nephrolithiasis

    NASA Technical Reports Server (NTRS)

    Hill, K.; Poindexter, J.; Pak, C. Y.

    1991-01-01

    Twenty-four hour urine specimens from 5,677 stone-forming patients throughout the United States were analyzed for seasonal variations in urinary risk factors for nephrolithiasis. Determinations were performed for urine volume, pH, calcium, oxalate, phosphorus, sodium, magnesium, citrate, sulfate, uric acid, and the relative supersaturation (RS) of calcium oxalate, brushite, monosodium urate, and uric acid. Criteria for significant seasonal variation included a significant difference in monthly means of risk factors, seasonal grouping of the data by the Student-Newman-Keuls multiple range test, consistent year-to-year trends and a physiologically significant range. Minimum urine volume of 1.54 +/- 0.70 SD L/day occurred in October while a maximum urine volume of 1.76 +/- 0.78 SD L/day was observed during February. Minimum urine pH of 5.94 +/- 0.64 SD was observed during July and August while a maximum pH of 6.18 +/- 0.61 SD was observed during February. Daily urinary excretion of sodium was lowest during August, 158 +/- 74 SD mEq/day and highest during February 177 +/- 70 SD mEq/day. The RS of brushite and uric acid were found to display significant pH-dependent seasonal variation with a maximum RS of uric acid 2.26 +/- 1.98 SD in June and a low of 1.48 +/- 1.30 SD in February. Maximum RS of brushite 2.75 +/- 2.58 was observed during February. Minimum RS of brushite 1.93 +/- 1.70 SD was observed in June. Phosphorus excretion displayed seasonal variation about a spring-fall axis with a maximum value 1042 +/- 373 SD mg/day in April and a minimum value of 895 +/- 289 SD mg/day. Urine volume, sodium, and pH were significantly lower during the summer (June, July, August) than in the winter (December, January, February). The RS of uric acid was higher, but that of brushite and monosodium urate was lower in the summer than in the winter. The seasonal changes observed in urine volume, pH, sodium, and the RS of brushite and uric acid are consistent with summertime sweating

  10. Use of drugs for nephrolithiasis.

    PubMed

    Marangella, Martino; Vitale, Corrado; Bagnis, Cristiana; Petrarulo, Michele; Tricerri, Alberto

    2008-05-01

    Renal stone disease often begins by renal colic. In order to manage this event adequately, several goals should be pursued: first, attenuate pain; second, favour progression and spontaneous expulsion of stones; third, prevent from obstructive and infectious complications. All of the aforementioned points pertain to medical management of this disease. Concerning prevention, it is widely agreed that pathogenesis of kidney stones is a consequence of abnormalities in urine environment, leading to a disequilibrium between promoters and inhibitors of crystallization. Therefore, the rationale for therapy is to make urine less conductive to stone formation, by both decreasing state of saturation and increasing inhibitory potential. In only some types of stone-forming salts it is possible to obtain undersaturation with the solid phase. Indeed, uric acid stones can be chemically dissolved by using alkali and allopurinol. To a lesser extent, this also applies to cystine stones, with the use of thiols and alkali. In these subsets, the aforementioned tools are also effective to prevent new stone formation. Much more challenging appears the treatment of calcium containing stones. About 10% of such stones is caused by systemic disorders and, in these cases, the prevention of new stones is successfully accomplished by curing the underlying disease. For instance, parathyroidectomy cures calcium nephrolithiasis in case of hyperparathyroidism. However, the majority of patients with calcium stones are idiopathic stone-formers, in whom metabolic abnormalities often occur, namely, hypercalciuria, hyperoxaluria, hypocitraturia. The correction of these abnormalities by using thiazide diuretics, alkaline citrates, potassium phosphate and bisphosphonates is based on the prevailing metabolic defect. Among the most recent available tools, Oxalobacter Formigenes and probiotics have been proposed to treat primary or secondary hyperoxalurias. In general, the treatment of stone disease reduces

  11. 'I Used to Fight with Them but Now I Have Stopped!': Conflict and Doctor-Nurse-Anaesthetists' Motivation in Maternal and Neonatal Care Provision in a Specialist Referral Hospital

    PubMed Central

    Aberese-Ako, Matilda; Agyepong, Irene Akua; Gerrits, Trudie; Van Dijk, Han

    2015-01-01

    Background and Objectives This paper analyses why and how conflicts occur and their influence on doctors and nurse-anaesthetists' motivation in the provision of maternal and neonatal health care in a specialist hospital. Methodology The study used ethnographic methods including participant observation, conversation and in-depth interviews over eleven months in a specialist referral hospital in Ghana. Qualitative analysis software Nvivo 8 was used for coding and analysis of data. Main themes identified in the analysis form the basis for interpreting and reporting study findings. Ethics Statement Ethical clearance was obtained from the Ghana Health Service Ethics Review board (approval number GHS-ERC:06/01/12) and from the University of Wageningen. Written consent was obtained from interview participants, while verbal consent was obtained for conversations. To protect the identity of the hospital and research participants pseudonyms are used in the article and the part of Ghana in which the study was conducted is not mentioned. Results Individual characteristics, interpersonal and organisational factors contributed to conflicts. Unequal power relations and distrust relations among doctors and nurse-anaesthetists affected how they responded to conflicts. Responses to conflicts including forcing, avoiding, accommodating and compromising contributed to persistent conflicts, which frustrated and demotivated doctors and nurse-anaesthetists. Demotivated workers exhibited poor attitudes in collaborating with co-workers in the provision of maternal and neonatal care, which sometimes led to poor health worker response to client care, consequently compromising the hospital's goal of providing quality health care to clients. Conclusion To improve health care delivery in health facilities in Ghana, health managers and supervisors need to identify conflicts as an important phenomenon that should be addressed whenever they occur. Effective mechanisms including training managers

  12. Role of BGT-1 and BGT-2, two predicted GPI-anchored glycoside hydrolases/glycosyltransferases, in cell wall remodeling in Neurospora crassa.

    PubMed

    Martínez-Núñez, Leonora; Riquelme, Meritxell

    2015-12-01

    Neurospora crassa BGT-1 (NCU06381) and BGT-2 (NCU09175) are two putative glycoside hydrolases (GHs) with additional predicted glycosyltransferase activity and binding sites for a glycosyl phosphatidyl inositol (GPI) anchor that would facilitate their attachment to the plasma membrane (PM). To discern their role in key morphogenetic events during vegetative development of N. crassa, BGT-1 and BGT-2 were labeled with the green fluorescent protein (GFP). The gfp was inserted immediately after the signal peptide sequence, within the bgt-1 encoding sequence, or directly before the GPI-binding site in the case of bgt-2. Both BGT-1-GFP and BGT-2-GFP were observed at the PM of the hyphal apical dome, excluding the foremost apical region and the Spitzenkörper (Spk), where chitin and β-1,3-glucan synthases have been previously found. These and previous studies suggest a division of labor of the cell wall synthesizing machinery at the hyphal dome: at the very tip, glucans are synthesized by enzymes that accumulate at the Spk, before getting incorporated into the PM, whereas at the subtending zone below the apex, glucans are presumably hydrolyzed, producing amenable ends for further branching and crosslinking with other cell wall polymers. Additionally, BGT-1-GFP and BGT-2-GFP were observed at the leading edge of new developing septa, at unreleased interconidial junctions, at conidial poles, at germling and hyphal fusion sites, and at sites of branch emergence, all of them processes that seemingly involve cell wall remodeling. Even though single and double mutant strains for the corresponding genes did not show a drastic reduction of growth rate, bgt-2Δ and bgt-1Δ::bgt-2Δ strains exhibited an increased resistance to the cell wall stressors calcofluor white (CW) and congo red (CR) than the reference strain, which suggests they present significant architectural changes in their cell wall. Furthermore, the conidiation defects observed in the mutants indicate a significant

  13. Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.

    PubMed

    López-López, Ana Laura; Jaime, Herlinda Bonilla; Escobar Villanueva, María Del Carmen; Padilla, Malinalli Brianza; Palacios, Gonzalo Vázquez; Aguilar, Francisco Javier Alarcón

    2016-07-01

    Stress is considered to be a causal agent of chronic degenerative diseases, such as cardiovascular disease, diabetes mellitus, arthritis and Alzheimer's. Chronic glucocorticoid and catecholamine release into the circulation during the stress response has been suggested to activate damage mechanisms, which in the long term produce metabolic alterations associated with oxidative stress and inflammation. However, the consequences of stress in animal models for periods longer than 40days have not been explored. The goal of this work was to determine whether chronic unpredictable mild stress (CUMS) produced alterations in the redox state and the inflammatory profile of rats after 20, 40, and 60days. CUMS consisted of random exposure of the animals to different stressors. The following activities were measured in the liver and pancreas: reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and protein oxidation. Similarly, serum cytokine levels (IL-6, TNF-α, IL-1β, and IL-10) were determined. CUMS activated the stress response from day 20 until day 60. In the liver and pancreas, GHS levels were decreased from day 40, whereas protein lipid peroxidation and protein oxidation were increased. This is the first work to report that the pancreas redox state is subject to chronic stress conditions. The TAC was constant in the liver and reduced in the pancreas. An increase in the TNF-α, IL-1β, and IL-6 inflammatory markers and a decrease in the IL-10 level due to CUMS was shown, thereby resulting in the generation of a systemic inflammation state after 60days of treatment. Together, the CUMS consequences on day 60 suggest that both processes can contribute to the development of chronic degenerative diseases, such as cardiovascular disease and diabetes mellitus. CUMS is an animal model that in addition to avoiding habituation activates damage mechanisms such as oxidative stress and low-grade chronic

  14. Aspects regarding vertical distribution of greenhouse gases resulted from in situ airborne measurements

    NASA Astrophysics Data System (ADS)

    Boscornea, Andreea; Sorin Vajaiac, Nicolae; Ardelean, Magdalena; Benciu, Silviu Stefan

    2016-04-01

    In the last decades the air quality, as well as other components of the environment, has been severely affected by uncontrolled emissions of gases - most known as greenhouse gases (GHG). The main role of GHG is given by the direct influence on the Earth's radiative budget, through Sun light scattering and indirectly by participating in cloud formation. Aldo, many efforts were made for reducing the high levels of these pollutants, e.g., International Panel on Climate Change (IPCC) initiatives, Montreal Protocol, etc., this issue is still open. In this context, this study aims to present several aspects regarding the vertical distribution in the lower atmosphere of some greenhouse gases: water vapours, CO, CO2 and methane. Bucharest and its metropolitan area is one of the most polluted regions of Romania due to high traffic. For assessing the air quality of this area, in situ measurements of water vapours, CO, CO2 and CH4 were performed using a Britten Norman Islander BN2 aircraft equipped with a Picarro gas analyser, model G2401-mc, able to provide precised, continuous and accurate data in real time. This configuration consisting in aircraft and airborne instruments was tested for the first time in Romania. For accomplishing the objectives of the measurement campaign, there were proposed several flight strategies which included vertical and horizontal soundings from 105 m to 3300 m and vice-versa around Clinceni area (20 km West of Bucharest). During 5 days (25.08.2015 - 31.08.2015) were performed 7 flights comprising 10h 18min research flight hours. The measured concentrations of GHS ranged between 0.18 - 2.2 ppm for water vapours with an average maximum value of 1.7 ppm, 0.04 - 0.53 ppm for CO with an average maximum value of 0.21 ppm, 377 - 437.5 ppm for CO2 with an average maximum value of 397 ppm and 1.7 - 6.1 ppm for CH4 with an average maximum value of 2.195 ppm. It was noticed that measured concentrations of GHG are decreasing for high values of sounding

  15. When the clinic becomes a home. Successful VCT and ART services in a stressful environment.

    PubMed

    Dapaah, Jonathan Mensah; Spronk, Rachel

    2016-12-01

    With the upscaling of antiretroviral therapy (ART) in resource-poor countries, many HIV-positive persons in Ghana have been accessing treatment in hospitals. Prevalence is relatively low compared to other African countries, 1.30%. HIV/AIDS remains heavily stigmatised in Ghana, which influences the provision and use of ART. This article investigates how HIV-positive persons accessing care and treatment go about their everyday lives in the ART clinic and how they have eventually come to see the clinic as a safe place that they call 'home'. The study took place in two Ghanaian hospitals in the Ashanti Region which in 2013 had the country's highest HIV prevalence rate of 1.30% [Ghana Health Service [GHS]/National AIDS Control Programme [NACP] (2013). 2013 HIV Sentinel Survey Report, Accra, Ghana]. It was conducted through ethnographic research, with data gathered in the two facilities through participant observation, conversations and in-depth interviews. It took place over a period of 15 months, between 2007 and 2010. In all, 24 health workers and 22 clients were interviewed in depth, while informal conversations were held with many others. The findings show that clients have adopted the clinic as a second home and used it to carry out various activities in order to avoid identification and stigmatisation as People Living with AIDS (PLWA). The most dramatic outcome was that, contrary to Ghanaian norms and values, people turned to non-kin for assistance. Accordingly, fellow clients and health personnel, rather than relatives, have become their 'therapy management group' [Janzen, J. M. (1987). Therapy Management: Concept, Reality, Process. Medical Anthropology Quarterly, 1(1), 68-84]. The clients have thus created a fictive family within the clinic - made up of health workers (as 'parents'), the clients themselves (as 'children') and the peer educators (as 'aunts' and 'uncles'). In the face of persistent stigma associated with HIV infection in Ghana, the use of the

  16. Ghrelin and obestatin inhibit enucleation-induced adrenocortical proliferation in the rat.

    PubMed

    Rucinski, Marcin; Trejter, Marcin; Ziolkowska, Agnieszka; Tyczewska, Marianna; Malendowicz, Ludwik K

    2010-05-01

    Studies involving the role of ghrelin (GHREL) in regulating the proliferative activity of various cell types have obtained variable results depending primarily on the experimental model applied. It was recently reported that neither GHREL nor obestatin (OBS) affected the proliferative activity of cultured rat adrenocortical cells. In view of the conflicting results, we investigated the effects of GHREL and OBS on the proliferative activity of rat adrenocortical cells in a model of bilateral enucleation-induced adrenocortical regeneration in the rat. Rats were sacrificed 5 or 8 days after surgery. Twenty-four hours before being sacrificed, the appropriate groups were infused with 3 nmol GHREL or OBS/100 g. The mitotic index was assessed using the stachmokinetic method with vincristine. In comparison with intact rats, expression levels of ppGHREL, BAX, JUN-B and JUN-C genes were notably higher in regenerating adrenals, and neither GHREL nor OBS infusion affected these levels. Expression levels of the GHS-R, GPR39v2 and FOS genes were affected neither by adrenal enucleation nor GHREL or OBS infusion. Expression of only two studied genes, GPR39v1 and EGR1, was regulated by OBS. In the regenerating adrenal glands, GPR39v1 and EGR1 mRNA levels were higher than the levels in intact animals. GHREL infusion had no effect while OBS infusion notably stimulated GPR39v1 mRNA levels in the regenerating adrenal gland and evoked an opposite effect on EGR1 mRNA. OBS administration resulted in a potent decrease in the mitotic index of the studied cells, an effect found at both days 5 and 8 of the experiment. GHREL exerted a similar effect only at day 5 of adrenocortical regeneration. Neither GHREL nor OBS had an effect on blood aldosterone concentrations. GHREL infusion lowered plasma corticosterone concentration at day 5 but not 8 of the experiment, while OBS administration was ineffective. Thus, this study is the first to demonstrate that, in vivo, both GHREL and OBS inhibit the

  17. The modular architecture of Cellvibrio japonicus mannanases in glycoside hydrolase families 5 and 26 points to differences in their role in mannan degradation.

    PubMed

    Hogg, Deborah; Pell, Gavin; Dupree, Paul; Goubet, Florence; Martín-Orúe, Susana M; Armand, Sylvie; Gilbert, Harry J

    2003-05-01

    beta-1,4-Mannanases (mannanases), which hydrolyse mannans and glucomannans, are located in glycoside hydrolase families (GHs) 5 and 26. To investigate whether there are fundamental differences in the molecular architecture and biochemical properties of GH5 and GH26 mannanases, four genes encoding these enzymes were isolated from Cellvibrio japonicus and the encoded glycoside hydrolases were characterized. The four genes, man5A, man5B, man5C and man26B, encode the mannanases Man5A, Man5B, Man5C and Man26B, respectively. Man26B consists of an N-terminal signal peptide linked via an extended serine-rich region to a GH26 catalytic domain. Man5A, Man5B and Man5C contain GH5 catalytic domains and non-catalytic carbohydrate-binding modules (CBMs) belonging to families 2a, 5 and 10; Man5C in addition contains a module defined as X4 of unknown function. The family 10 and 2a CBMs bound to crystalline cellulose and ivory nut crystalline mannan, displaying very similar properties to the corresponding family 10 and 2a CBMs from Cellvibrio cellulases and xylanases. CBM5 bound weakly to these crystalline polysaccharides. The catalytic domains of Man5A, Man5B and Man26B hydrolysed galactomannan and glucomannan, but displayed no activity against crystalline mannan or cellulosic substrates. Although Man5C was less active against glucomannan and galactomannan than the other mannanases, it did attack crystalline ivory nut mannan. All the enzymes exhibited classic endo-activity producing a mixture of oligosaccharides during the initial phase of the reaction, although their mode of action against manno-oligosaccharides and glucomannan indicated differences in the topology of the respective substrate-binding sites. This report points to a different role for GH5 and GH26 mannanases from C. japonicus. We propose that as the GH5 enzymes contain CBMs that bind crystalline polysaccharides, these enzymes are likely to target mannans that are integral to the plant cell wall, while GH26

  18. The modular architecture of Cellvibrio japonicus mannanases in glycoside hydrolase families 5 and 26 points to differences in their role in mannan degradation.

    PubMed Central

    Hogg, Deborah; Pell, Gavin; Dupree, Paul; Goubet, Florence; Martín-Orúe, Susana M; Armand, Sylvie; Gilbert, Harry J

    2003-01-01

    beta-1,4-Mannanases (mannanases), which hydrolyse mannans and glucomannans, are located in glycoside hydrolase families (GHs) 5 and 26. To investigate whether there are fundamental differences in the molecular architecture and biochemical properties of GH5 and GH26 mannanases, four genes encoding these enzymes were isolated from Cellvibrio japonicus and the encoded glycoside hydrolases were characterized. The four genes, man5A, man5B, man5C and man26B, encode the mannanases Man5A, Man5B, Man5C and Man26B, respectively. Man26B consists of an N-terminal signal peptide linked via an extended serine-rich region to a GH26 catalytic domain. Man5A, Man5B and Man5C contain GH5 catalytic domains and non-catalytic carbohydrate-binding modules (CBMs) belonging to families 2a, 5 and 10; Man5C in addition contains a module defined as X4 of unknown function. The family 10 and 2a CBMs bound to crystalline cellulose and ivory nut crystalline mannan, displaying very similar properties to the corresponding family 10 and 2a CBMs from Cellvibrio cellulases and xylanases. CBM5 bound weakly to these crystalline polysaccharides. The catalytic domains of Man5A, Man5B and Man26B hydrolysed galactomannan and glucomannan, but displayed no activity against crystalline mannan or cellulosic substrates. Although Man5C was less active against glucomannan and galactomannan than the other mannanases, it did attack crystalline ivory nut mannan. All the enzymes exhibited classic endo-activity producing a mixture of oligosaccharides during the initial phase of the reaction, although their mode of action against manno-oligosaccharides and glucomannan indicated differences in the topology of the respective substrate-binding sites. This report points to a different role for GH5 and GH26 mannanases from C. japonicus. We propose that as the GH5 enzymes contain CBMs that bind crystalline polysaccharides, these enzymes are likely to target mannans that are integral to the plant cell wall, while GH26

  19. Evaluation of RPE-Select: A Web-Based Respiratory Protective Equipment Selector Tool

    PubMed Central

    Vaughan, Nick; Rajan-Sithamparanadarajah, Bob; Atkinson, Robert

    2016-01-01

    This article describes the evaluation of an open-access web-based respiratory protective equipment selector tool (RPE-Select, accessible at http://www.healthyworkinglives.com/rpe-selector). This tool is based on the principles of the COSHH-Essentials (C-E) control banding (CB) tool, which was developed for the exposure risk management of hazardous chemicals in the workplace by small and medium sized enterprises (SMEs) and general practice H&S professionals. RPE-Select can be used for identifying adequate and suitable RPE for dusts, fibres, mist (solvent, water, and oil based), sprays, volatile solids, fumes, gases, vapours, and actual or potential oxygen deficiency. It can be applied for substances and products with safety data sheets as well as for a large number of commonly encountered process-generated substances (PGS), such as poultry house dusts or welding fume. Potential international usability has been built-in by using the Hazard Statements developed for the Globally Harmonised System (GHS) and providing recommended RPE in picture form as well as with a written specification. Illustration helps to compensate for the variabilities in assigned protection factors across the world. RPE-Select uses easily understandable descriptions/explanations and an interactive stepwise flow for providing input/answers at each step. The output of the selection process is a report summarising the user input data and a selection of RPE, including types of filters where applicable, from which the user can select the appropriate one for each wearer. In addition, each report includes ‘Dos’ and ‘Don’ts’ for the recommended RPE. RPE-Select outcomes, based on up to 20 hypothetical use scenarios, were evaluated in comparison with other available RPE selection processes and tools, and by 32 independent users with a broad range of familiarities with industrial use scenarios in general and respiratory protection in particular. For scenarios involving substances having safety

  20. Progress in Open-World, Integrative, Collaborative Science Data Platforms (Invited)

    NASA Astrophysics Data System (ADS)

    Fox, P. A.

    2013-12-01

    As collaborative, or network science spreads into more Earth and space science fields, both the participants and their funders have expressed a very strong desire for highly functional data and information capabilities that are a) easy to use, b) integrated in a variety of ways, c) leverage prior investments and keep pace with rapid technical change, and d) are not expensive or time-consuming to build or maintain. In response, and based on our accumulated experience over the last decade and a maturing of several key technical approaches, we have adapted, extended, and integrated several open source applications and frameworks that handle major portions of functionality for these platforms. At minimum, these functions include: an object-type repository, collaboration tools, an ability to identify and manage all key entities in the platform, and an integrated portal to manage diverse content and applications, with varied access levels and privacy options. At a conceptual level, science networks (even small ones) deal with people, and many intellectual artifacts produced or consumed in research, organizational and/our outreach activities, as well as the relations among them. Increasingly these networks are modeled as knowledge networks, i.e. graphs with named and typed relations among the 'nodes'. Nodes can be people, organizations, datasets, events, presentations, publications, videos, meetings, reports, groups, and more. In this heterogeneous ecosystem, it is also important to use a set of common informatics approaches to co-design and co-evolve the needed science data platforms based on what real people want to use them for. In this contribution, we present our methods and results for information modeling, adapting, integrating and evolving a networked data science and information architecture based on several open source technologies (Drupal, VIVO, the Comprehensive Knowledge Archive Network; CKAN, and the Global Handle System; GHS). In particular we present both

  1. Microglial Inhibitory Mechanism of Coenzyme Q10 Against Aβ (1-42) Induced Cognitive Dysfunctions: Possible Behavioral, Biochemical, Cellular, and Histopathological Alterations

    PubMed Central

    Singh, Arti; Kumar, Anil

    2015-01-01

    Rationale: Alzheimer’s disease (AD) is a debilitating disease with complex pathophysiology. Amyloid beta (Aβ) (1-42) is a reliable model of AD that recapitulates many aspects of human AD. Objective: The intent of the present study was to investigate the neuroprotective potential of Coenzyme Q10 (CoQ10) and its modulation by minocycline (microglial inhibitor) against Aβ (1-42) induced cognitive dysfunction in rats. Method: Intrahippocampal (i.h.) Aβ (1-42) (1 μg/μl; 4μl/site) were administered followed by drug treatment with galantamine (2 mg/kg), CoQ10 (20 and 40 mg/kg), minocycline (50 and 100 mg/kg) and their combinations for a period of 21 days. Various neurobehavioral parameters followed by biochemical, acetylcholinesterase (AChE) level, proinflammatory markers (TNF-α), mitochondrial respiratory enzyme complexes (I-IV) and histopathological examinations were assessed. Results: Aβ (1-42) administration significantly impaired cognitive performance in Morris water maze (MWM) performance test, causes oxidative stress, raised AChE level, caused neuroinflammation, mitochondrial dysfunction and histopathological alterations as compared to sham treatment. Treatment with CoQ10 (20 and 40 mg/kg) and minocycline (50 and 100 mg/kg) alone for 21 days significantly improved cognitive performance as evidenced by reduced transfer latency and increased time spent in target quadrant (TSTQ), reduced AChE activity, oxidative damage (reduced LPO, nitrite level and restored SOD, catalase and GHS levels), TNF-α level, restored mitochondrial respiratory enzyme complex (I, II, III, IV) activities and histopathological alterations as compared to Aβ (1-42) treated animals. Further, combinations of minocycline (50 and 100 mg/kg) with CoQ10 (20 and 40 mg/kg) significantly modulates the protective effect of CoQ10 dose dependently as compared to their effect alone. Conclusion: The present study suggests that the neuroprotective effect of CoQ10 could be due to its microglia

  2. Genomic organisation of the chicken ghrelin gene and its single nucleotide polymorphisms detected by denaturing high-performance liquid chromatography.

    PubMed

    Nie, Q; Zeng, H; Lei, M; Ishag, N A; Fang, M; Sun, B; Yang, G; Zhang, X

    2004-10-01

    (1) Ghrelin is a novel endogenous ligand for the growth hormone secretagogue receptor (GHS-R) and is expressed primarily in the stomach and hypothalamus with the probable function of stimulating GH secretion and food intake both in mammals and poultry. The complete sequences of ghrelin gene have been reported in humans and mice; however, that of chickens remains unclear. (2) Here, we report the complete sequence of chicken ghrelin gene (submitted to Genbank; accession number AY303688), which consists of 5 exons and 4 introns. As in mice, the first exon of chicken ghrelin gene does not encode any amino acid. (3) Scanning point mutations with denaturing high-performance liquid chromatography (DHPLC) using WAVE DNA Fragment Analysis Systems and confirmed with direct sequencing for polymerase chain reaction (PCR) products, we analysed the single nucleotide polymorphisms (SNPs) in the entire gene of chicken ghrelin. (4) Results showed that there were 19 SNPs in chicken ghrelin gene, and most of these SNPs were scattered in the 4 introns. In these SNPs, one mutation in exon 5 (A2355G) led to the change of amino acid from glutamine to arginine (Gln 113 Arg): as a result a different ghrelin precursor instead of a mature peptide was produced. In addition, one SNP in 5'UTR (C223G) determined the presence or absence of a potential binding site of transcription factor serum response factor (SRF), which might affect the expression of chicken ghrelin gene. Some of the SNPs detected in the present study could be used in quantitative trait loci (QTL) mapping for growth characters in chickens. (5) Because one SNP is located in a polymorphic site of restriction enzyme PagI of intron 4, it was possible to design a PCR-RFLP procedure and analyse the diversity of 10 chicken populations. Results showed the allelic frequencies of C2100T differ among these breeds, however, no significant difference was observed between imported breeds and Chinese native ones, nor between egg layers and

  3. Antioxidative responses of the tissues of two wild populations of Pelophylax kl. esculentus frogs to heavy metal pollution.

    PubMed

    Prokić, Marko D; Borković-Mitić, Slavica S; Krizmanić, Imre I; Mutić, Jelena J; Vukojević, Vesna; Nasia, Mohammed; Gavrić, Jelena P; Despotović, Svetlana G; Gavrilović, Branka R; Radovanović, Tijana B; Pavlović, Slađan Z; Saičić, Zorica S

    2016-06-01

    Heavy metal pollution of the aquatic environment is of great concern worldwide. Heavy metals are capable of inducing oxidative stress by increasing the formation of reactive oxygen species (ROS), and directly affecting the antioxidant defense system (AOS) in living organisms. The frog Pelophylax kl. esculentus is a semiaquatic species with semipermeable skin and a complex lifecycle, and represents a potentially useful bioindicator organism. The aim of this study was to investigate the accumulation of several heavy metals (Cd, Co, Cr, Cu, Fe, Hg, Ni, Pb and Zn), and their effects on selected parameters of the AOS, including the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), phase II biotransformation enzyme glutathione-S-transferase (GST), the total glutathione (GSH) contents and sulfhydryl (SH) group concentrations, as well as cholinesterases (ChEs) activities in the liver, skin and muscle of P. kl. esculentus. Frog samples were collected at two sites (the Danube-Tisza-Danube canal (DTDC) and the river Ponjavica) in Serbia, which are characterized by different levels of metal pollution. Differences between the metal contents in different tissues showed that the skin of frogs from the DTDC accumulated statistically higher concentrations of Cd, Cu, Pb and Zn, while only the Fe concentration was lower. No significant differences between metal concentrations in muscle tissues of frogs from the DTDC and Ponjavica were observed. Examination of the parameters of the AOS revealed that frogs from the DTDC had higher concentrations of GSH in the liver and of SH groups in the skin and muscle, whereas the activities of the antioxidative enzymes SOD, GHS-Px and GR in the liver and of GR in the skin were lower than in frogs from the Ponjavica. The relationship between metal concentrations and AOS parameters showed the highest number of correlations with GSH, GR and CAT, and with Ni, Zn, Hg, Cr and Cd. Based

  4. Diversity and Strain Specificity of Plant Cell Wall Degrading Enzymes Revealed by the Draft Genome of Ruminococcus flavefaciens FD-1

    PubMed Central

    Berg Miller, Margret E.; Antonopoulos, Dionysios A.; Rincon, Marco T.; Band, Mark; Bari, Albert; Akraiko, Tatsiana; Hernandez, Alvaro; Thimmapuram, Jyothi; Henrissat, Bernard; Coutinho, Pedro M.; Borovok, Ilya; Jindou, Sadanari; Lamed, Raphael; Flint, Harry J.; Bayer, Edward A.; White, Bryan A.

    2009-01-01

    Background Ruminococcus flavefaciens is a predominant cellulolytic rumen bacterium, which forms a multi-enzyme cellulosome complex that could play an integral role in the ability of this bacterium to degrade plant cell wall polysaccharides. Identifying the major enzyme types involved in plant cell wall degradation is essential for gaining a better understanding of the cellulolytic capabilities of this organism as well as highlighting potential enzymes for application in improvement of livestock nutrition and for conversion of cellulosic biomass to liquid fuels. Methodology/Principal Findings The R. flavefaciens FD-1 genome was sequenced to 29x-coverage, based on pulsed-field gel electrophoresis estimates (4.4 Mb), and assembled into 119 contigs providing 4,576,399 bp of unique sequence. As much as 87.1% of the genome encodes ORFs, tRNA, rRNAs, or repeats. The GC content was calculated at 45%. A total of 4,339 ORFs was detected with an average gene length of 918 bp. The cellulosome model for R. flavefaciens was further refined by sequence analysis, with at least 225 dockerin-containing ORFs, including previously characterized cohesin-containing scaffoldin molecules. These dockerin-containing ORFs encode a variety of catalytic modules including glycoside hydrolases (GHs), polysaccharide lyases, and carbohydrate esterases. Additionally, 56 ORFs encode proteins that contain carbohydrate-binding modules (CBMs). Functional microarray analysis of the genome revealed that 56 of the cellulosome-associated ORFs were up-regulated, 14 were down-regulated, 135 were unaffected, when R. flavefaciens FD-1 was grown on cellulose versus cellobiose. Three multi-modular xylanases (ORF01222, ORF03896, and ORF01315) exhibited the highest levels of up-regulation. Conclusions/Significance The genomic evidence indicates that R. flavefaciens FD-1 has the largest known number of fiber-degrading enzymes likely to be arranged in a cellulosome architecture. Functional analysis of the genome has

  5. Energy-efficient distributed constructions of miniumum spanning tree for wireless ad-hoc networks

    SciTech Connect

    Kumar, V. S. A.; Pandurangan, G.; Khan, M.

    2004-01-01

    The Minimum Spanning Tree (MST) problem is one of the most important and commonly occurring primitive in the design and operation of data and communication networks. While there a redistributed algorithms for the MST problem these require relatively large number of messages and time, and are fairly involved, require synchronization and a lot of book keeping; this makes these algorithms impractical for emerging technologies such as ad hoc and sensor networks. In such networks, a sensor has very limited power, and any algorithm needs to be simple, local and energy efficient for being practical. Motivated by these considerations, we study the performance of a class of simple and local algorithms called Nearest Neighbor Tree (NNT) algorithms for energy-efficient construction of MSTs in a wireless ad hoc setting. These employ a very simple idea to eliminate the work involved in cycle detection in other MST algorithms: each node chooses a distinct rank, and connects to the closest node of higher rank. We consider two variants of the NNT algorithms, obtained by two ways of choosing the ranks: (i) Random NNT, in which each node chooses a rank randomly, and (ii) Directional NNT, in which each node uses directional information for choosing the rank. We show provable bounds on the performance of these algorithms in instances obtained by uniformly distributed points in the unit square. Finally, we perform extensive simulations of our algorithms. We tested our algorithms on both uniformly random distributions of points, and on realistic distributions of points in an urban setting. The cost of the tree found by the NNT algorithms is within a factor of 2 of the MST, but there is more than a ten-fold saving on the energy and about a five fold saving on the number of messages sent. Also, our algorithms are significantly simpler to implement compared to, for instance, the GHS algorithm, which is essentially optimal with regards to the message complexity. Thus, our results

  6. Evaluation of RPE-Select: A Web-Based Respiratory Protective Equipment Selector Tool.

    PubMed

    Vaughan, Nick; Rajan-Sithamparanadarajah, Bob; Atkinson, Robert

    2016-08-01

    This article describes the evaluation of an open-access web-based respiratory protective equipment selector tool (RPE-Select, accessible at http://www.healthyworkinglives.com/rpe-selector). This tool is based on the principles of the COSHH-Essentials (C-E) control banding (CB) tool, which was developed for the exposure risk management of hazardous chemicals in the workplace by small and medium sized enterprises (SMEs) and general practice H&S professionals. RPE-Select can be used for identifying adequate and suitable RPE for dusts, fibres, mist (solvent, water, and oil based), sprays, volatile solids, fumes, gases, vapours, and actual or potential oxygen deficiency. It can be applied for substances and products with safety data sheets as well as for a large number of commonly encountered process-generated substances (PGS), such as poultry house dusts or welding fume. Potential international usability has been built-in by using the Hazard Statements developed for the Globally Harmonised System (GHS) and providing recommended RPE in picture form as well as with a written specification. Illustration helps to compensate for the variabilities in assigned protection factors across the world. RPE-Select uses easily understandable descriptions/explanations and an interactive stepwise flow for providing input/answers at each step. The output of the selection process is a report summarising the user input data and a selection of RPE, including types of filters where applicable, from which the user can select the appropriate one for each wearer. In addition, each report includes 'Dos' and 'Don'ts' for the recommended RPE. RPE-Select outcomes, based on up to 20 hypothetical use scenarios, were evaluated in comparison with other available RPE selection processes and tools, and by 32 independent users with a broad range of familiarities with industrial use scenarios in general and respiratory protection in particular. For scenarios involving substances having safety data sheets

  7. Molecular evolution of GH in primates: characterisation of the GH genes from slow loris and marmoset defines an episode of rapid evolutionary change.

    PubMed

    Wallis, O C; Zhang, Y P; Wallis, M

    2001-06-01

    Pituitary growth hormone (GH), like several other protein hormones, shows an unusual episodic pattern of molecular evolution in which sustained bursts of rapid change are imposed on long periods of very slow evolution (near-stasis). A marked period of rapid change occurred in the evolution of GH in primates or a primate ancestor, and gave rise to the species specificity that is characteristic of human GH. We have defined more precisely the position of this burst by cloning and sequencing the GH genes for a prosimian, the slow loris (Nycticebus pygmaeus) and a New World monkey, marmoset (Callithrix jacchus). Slow loris GH is very similar in sequence to pig GH, demonstrating that the period of rapid change occurred during primate evolution, after the separation of lines leading to prosimians and higher primates. The putative marmoset GH is similar in sequence to human GH, demonstrating that the accelerated evolution occurred before divergence of New World monkeys and Old World monkeys/apes. The burst of change was confined largely to coding sequence for mature GH, and is not marked in other components of the gene sequence including signal peptide, 5' upstream region and introns. A number of factors support the idea that this episode of rapid change was due to positive adaptive selection. Thus (1) there is no apparent loss of function of GH in man compared with non-primates, (2) after the episode of rapid change the rate of evolution fell towards the slow basal level that is seen for most mammalian GHs, (3) the accelerated rate of substitution for the exons of the GH gene significantly exceeds that for introns, and (4) the amino acids contributing to the hydrophobic core of GH are strongly conserved when higher primate and other GH sequences are compared, and for coding sequences other than that coding for hydrophobic core residues the rate of substitution for non-synonymous sites (K(A)) is significantly greater than that for synonymous sites (K(S)). In slow loris, as

  8. An in vitro skin irritation test (SIT) using the EpiDerm reconstructed human epidermal (RHE) model.

    PubMed

    Kandárová, Helena; Hayden, Patrick; Klausner, Mitchell; Kubilus, Joseph; Sheasgreen, John

    2009-01-01

    The EpiDerm Skin Irritation test (EpiDerm SIT) was developed and validated for in vitro skin irritation testing of chemicals, including cosmetic and pharmaceutical ingredients. The EpiDerm SIT utilizes the 3D in vitro reconstructed human epidermal (RHE) model EpiDerm. The procedure described in this protocol allows for discrimination between irritants of GHS category 2 and non-irritants. The test is performed over the course of a 4 day time period, consisting of pre-incubation, 60 minute exposure, 42 hour post-incubation and MTT viability assay. After tissue receipt and overnight pre-incubation (Day 0), tissues are topically exposed to the test chemicals (Day 1), which can be liquid, semisolid, solid or waxy. Three tissues are used for each test chemical, as well as for the positive control (5% aq. SDS solution), and a negative control (DPBS). Chemical exposure lasts for 60 minutes, 35 min of which the tissues are kept in an incubator at 37 degrees C. The test substances are then removed from the tissue surface by an extensive washing procedure. The tissue inserts are blotted and transferred to fresh medium. After a 24 hr incubation period (Day 2), the medium is exchanged. The medium can be saved for further analysis of cytokines or other endpoints of interest. After the medium exchange, tissues are incubated for an additional 18 hours. At the end of the entire 42 h post-incubation (day 3), the tissues are transferred into yellow MTT solution and incubated for 3 hours. The resultant purple-blue formazan salt, formed mainly by mitochondrial metabolism, is extracted for 2 hours using isopropanol. The optical density of the extracted formazan is determined using a spectrophotometer. A chemical is classified as an irritant if the tissue viability relative to the negative control treated tissues is reduced below 50%. This procedure can be used as full replacement of the in vivo rabbit skin irritation test for hazard identification and labeling of chemicals in line with

  9. Probabilistic Modeling of the Renal Stone Formation Module

    NASA Technical Reports Server (NTRS)

    Best, Lauren M.; Myers, Jerry G.; Goodenow, Debra A.; McRae, Michael P.; Jackson, Travis C.

    2013-01-01

    randomly sampling the probability distributions of the electrolyte concentrations and system parameters that are inputs into the deterministic model. The total urine chemistry concentrations are used to determine the urine chemistry activity using the Joint Expert Speciation System (JESS), a biochemistry model. Information used from JESS is then fed into the deterministic growth model. Outputs from JESS and the deterministic model are passed back to the probabilistic model where a multivariate regression is used to assess the likelihood of a stone forming and the likelihood of a stone requiring clinical intervention. The parameters used to determine to quantify these risks include: relative supersaturation (RS) of calcium oxalate, citrate/calcium ratio, crystal number density, total urine volume, pH, magnesium excretion, maximum stone width, and ureteral location. Methods and Validation: The RSFM is designed to perform a Monte Carlo simulation to generate probability distributions of clinically significant renal stones, as well as provide an associated uncertainty in the estimate. Initially, early versions will be used to test integration of the components and assess component validation and verification (V&V), with later versions used to address questions regarding design reference mission scenarios. Once integrated with the deterministic component, the credibility assessment of the integrated model will follow NASA STD 7009 requirements.

  10. Ernst Florens Friedrich Chladni (1756-1827) and the origins of modern meteorite research

    NASA Astrophysics Data System (ADS)

    Marvin, Ursula B.

    1996-09-01

    inaugurated internationally—although opposition lingered on until 1803 April, when nearly 3,000 stones fell at L'Aigle in Normandy and transformed the last skeptics into believers. Chladni immediately received full credit for his hypothesis of falls, but decades passed before his linking of falling bodies with fireballs received general acceptance. His hypothesis of their origin met with strong resistance from those who argued that stones formed within the Earth's atmosphere or were ejected by lunar volcanoes. After 1860, when both of these hypotheses were abandoned, there followed a century of debate between proponents of an interstellar vs. a planetary origin. Not until the 1950s did conclusive evidence of their elliptical orbits establish meteorite parent bodies as members of the solar system. Thus, nearly 200 years passed before the questions of origin that Chladni raised finally were resolved.

  11. Biomimetic Randall’s Plaque as an In Vitro Model System for Studying the Role of Acidic Biopolymers in Idiopathic Stone Formation

    PubMed Central

    Chidambaram, Archana; Rodriguez, Douglas; Khan, Saeed; Gower, Laurie

    2014-01-01

    Randall’s plaque (RP) deposits seem to be consistent among the most common type of kidney stone formers, idiopathic calcium oxalate stone formers. This group forms calcium oxalate renal stones without any systemic symptoms, which contributes to the difficulty of understanding and treating this painful and recurring disease. Thus, the development of an in vitro model system to study idiopathic nephrolithiasis, beginning with RP pathogenesis, can help in identifying how plaques, and subsequently stones, form. One main theory of RP formation is that calcium phosphate deposits initially form in the basement membrane of the thin loops of Henle, which then fuse and spread into the interstitial tissue, and ultimately make their way across the urothelium, where upon exposure to the urine, the mineralized tissue serves as a nidus for overgrowth with calcium oxalate into a stone. Our group has found that many of the unusual morphologies found in RP and stones, such as concentrically-laminated spherulites and mineralized collagenous tissue, can be reproduced in vitro using a polymer-induced liquid-precursor (PILP) process, in which acidic polypeptides induce a liquid-phase amorphous precursor to the mineral, yielding non-equilibrium crystal morphologies. Given that there are many acidic proteins and polysaccharides present in the renal tissue and urine, we have put for the hypothesis that the PILP system may be involved in urolithiasis. Therefore, our goal is to develop an in vitro model system of these two stages of composite stone formation in order to study the role that various acidic macromolecules may play. In our initial experiments presented here, the development of “biomimetic” RP was investigated, which will then serve as a nidus for calcium oxalate overgrowth studies. In order to mimic the tissue environment, MatriStem® (ACell, Inc.), a decellularized porcine urinary bladder matrix was used, because it has both an intact epithelial basement membrane surface

  12. Tools for Material Design and Selection

    NASA Astrophysics Data System (ADS)

    Wehage, Kristopher

    -dimensional microstructures are generated by Random Sequential Adsorption (RSA) of voxelized ellipses representing the coarse grain phase. A simulated annealing algorithm is used to geometrically optimize the placement of the ellipses in the model to achieve varying user-defined configurations of spatial arrangement of the coarse grains. During the simulated annealing process, the ellipses are allowed to overlap up to a specified threshold, allowing triple junctions to form in the model. Once the simulated annealing process is complete, the remaining space is populated by smaller ellipses representing the ultra-fine grain phase. Uniform random orientations are assigned to the grains. The program generates text files that can be imported in to Crystal Plasticity Finite Element Analysis Software for stress analysis. Finally, numerical methods and programming are applied to current issues in green engineering and hazard assessment. To understand hazards associated with materials and select safer alternatives, engineers and designers need access to up-to-date hazard information. However, hazard information comes from many disparate sources and aggregating, interpreting and taking action on the wealth of data is not trivial. In light of these challenges, a Framework for Automated Hazard Assessment based on the GreenScreen list translator is presented. The framework consists of a computer program that automatically extracts data from the GHS-Japan hazard database, loads the data into a machine-readable JSON format, transforms the JSON document in to a GreenScreen JSON document using the GreenScreen List Translator v1.2 and performs GreenScreen Benchmark scoring on the material. The GreenScreen JSON documents are then uploaded to a document storage system to allow human operators to search for, modify or add additional hazard information via a web interface.

  13. Depositional Provenance of the Himalayan Metamorphic Core of Garhwal Region, India: Constrained by U-Pb and Hf isotopes in zircons

    NASA Astrophysics Data System (ADS)

    Spencer, C. J.; Harris, R. A.

    2011-12-01

    U-Pb and Hf isotopes in zircon from the highly metamorphosed core of the Himalaya in the Garhwal Region of India indicate that the ortho- and paragneiss units of the Greater Himalayan Sequence are geochemical distinct from the older Lesser Himalayan Crystalline Sequence. Zircon grains from the Paleoproterozoic metasediments of the Lesser Himalayan Crystalline Sequence yield U-Pb crystallization ages from 1614±14 Ma to, 2679±14 Ma with a single distinct peak in the age spectra at 1870 Ma. ɛHf values from zircon in the Lesser Himalayan Crystalline Sequence range from 1 to -8. In contrast, zircon grains from the Neoproterozoic paragneiss of the Greater Himalayan Sequence yield U-Pb crystallization ages from 481±10 Ma to, 2560±8 Ma with a single distinct peak at 860 Ma. ɛHf values from these zircons range from 13 to -21. The orthogneiss unit of Greater Himalayan Sequence yields zircon grians with U-Pb crystallization ages from 416±2 Ma to, 2740±2 Ma with a single distinct peak at 472 Ma. These grains often exhibited older inherited cores ranging from ~800 Ma to ~2740 Ma with Cambro-Ordovician rims (416 Ma to 510 Ma). The ɛHf values of zircon grains in orthogneiss have two distinct modes: the ~860 Ma inherited zircon cores have a similar range to the ~860 Ma zircons from the GHS paragneiss (13 to -21) while the ~480 Ma rims range from -7 to -11. The detrital zircon U-Pb age spectra from the Greater Himalayan Sequence paragneiss in the Garhwal region differs significantly from the U-Pb age spectra in other parts of the range (Nepal and Bhutan). These differences indicate wide lateral variations in provenance for the various source regions of the Greater Himalayan Sequence paragneiss. Comparisons of the U-Pb and Hf data from the Garhwal region with other regions with zircon grains of ~500 Ma show overlap with deposits of the Aravalli shield of India. In paragneiss of the Greater Himalayan Sequence the most juvenile ɛHf values overlap with those of the northern

  14. Protective role of glutathione reductase in paraquat induced neurotoxicity.

    PubMed

    Djukic, Mirjana M; Jovanovic, Marina D; Ninkovic, Milica; Stevanovic, Ivana; Ilic, Katarina; Curcic, Marijana; Vekic, Jelena

    2012-08-30

    observed only for O₂·⁻, at 7th days. We concluded that oxidative/nitrosative stress and excitotoxicity are the most important events since the early stage of PQ induced neurotoxicity. Based on the ratio GSSG/GSH, the oxidation of GSH to GSSG is probably dominant way of GHS depletion and main reason for reduced antioxidative defense against PQ harmful oxidative effect. The GR pre-treatment resulted in the absence of Parkinson's disease-like symptoms and mortality of the rats. Additionally, oxidative/nitrosative stress did not developed, as well as almost diminished metabolism of the VBRs at 24th hours (as has been documented in the PQ group) did not occurred in the GR+PQ, suggesting a neuroprotective role for the GR in PQ induced neurotoxicity. PMID:22721943

  15. Sequentially sampled gas hydrate water, coupled with pore water and bottom water isotopic and ionic signatures at the Kukuy mud volcano, Lake Baikal: ambiguous deep-rooted source of hydrate-forming water

    NASA Astrophysics Data System (ADS)

    Minami, Hirotsugu; Hachikubo, Akihiro; Sakagami, Hirotoshi; Yamashita, Satoshi; Soramoto, Yusuke; Kotake, Tsuyoshi; Takahashi, Nobuo; Shoji, Hitoshi; Pogodaeva, Tatyana; Khlystov, Oleg; Khabuev, Andrey; Naudts, Lieven; De Batist, Marc

    2014-06-01

    The isotopic and ionic composition of pure gas hydrate (GH) water was examined for GHs recovered in three gravity cores (165-193 cm length) from the Kukuy K-9 mud volcano (MV) in Lake Baikal. A massive GH sample from core St6GC4 (143-165 cm core depth interval) was dissociated progressively over 6 h in a closed glass chamber, and 11 sequentially collected fractions of dissociated GH water analyzed. Their hydrogen and oxygen isotopic compositions, and the concentrations of Cl- and HCO3 - remained essentially constant over time, except that the fraction collected during the first 50 minutes deviated partly from this pattern. Fraction #1 had a substantially higher Cl- concentration, similar to that of pore water sampled immediately above (135-142 cm core depth) the main GH-bearing interval in that core. Like the subsequent fractions, however, the HCO3 - concentration was markedly lower than that of pore water. For the GH water fractions #2 to #11, an essentially constant HCO3 -/Cl- ratio of 305 differed markedly from downcore pore water HCO3 -/Cl- ratios of 63-99. Evidently, contamination of the extracted GH water by ambient pore water probably adhered to the massive GH sample was satisfactorily restricted to the initial phase of GH dissociation. The hydrogen and oxygen isotopic composition of hydrate-forming water was estimated using the measured isotopic composition of extracted GH water combined with known isotopic fractionation factors between GH and GH-forming water. Estimated δD of -126 to -133‰ and δ18O of -15.7 to -16.7‰ differed partly from the corresponding signatures of ambient pore water (δD of -123‰, δ18O of -15.6‰) and of lake bottom water (δD of -121‰, δ18O of -15.8‰) at the St6GC4 coring site, suggesting that the GH was not formed from those waters. Observations of breccias in that core point to a possible deep-rooted water source, consistent with published thermal measurements for the neighboring Kukuy K-2 MV. By contrast, the pore