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- Astuto, L. M., et al.
(författare)
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CDH23 mutation and phenotype heterogeneity : a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness
- 2002
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 71:2, s. 262-275
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type I is characterized by congenital hearing loss, retinitis pigmentosa (RP), and variable vestibular areflexia. Usher syndrome type ID, one of seven Usher syndrome type I genetic localizations, have been mapped to a chromosomal interval that overlaps with a nonsyndromic-deafness localization, DFNB12. Mutations in CDH23, a gene that encodes a putative cell-adhesion protein with multiple cadherin-like domains, are responsible for both Usher syndrome and DFNB12 nonsyndromic deafness. Specific CDH23 mutational defects have been identified that differentiate these two phenotypes. Only missense mutations of CDH23 have been observed in families with nonsyndromic deafness, whereas nonsense, frameshift, splice-site, and missense mutations have been identified in families with Usher syndrome. In the present study, a panel of 69 probands with Usher syndrome and 38 probands with recessive nonsyndromic deafness were screened for the presence of mutations in the entire coding region of CDH23, by heteroduplex, single-strand conformation polymorphism, and direct sequence analyses. A total of 36 different CDH23 mutations were detected in 45 families; 33 of these mutations were novel, including 18 missense, 3 nonsense, 5 splicing defects, 5 microdeletions, and 2 insertions. A total of seven mutations were common to more than one family. Numerous exonic and intronic polymorphisms also were detected. Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina. Furthermore, patients with mutations in CDH23 display a wide range of hearing loss and RP phenotypes, differing in severity, age at onset, type, and the presence or absence of vestibular areflexia.
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| 3. |
- Ahmed, K. Matin, et al.
(författare)
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Arsenic enrichment in groundwater of the alluvial aquifers in Bangladesh : an overview
- 2004
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Ingår i: Applied Geochemistry. - : Elsevier BV. - 0883-2927 .- 1872-9134. ; 19:2, s. 181-200
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Tidskriftsartikel (refereegranskat)abstract
- Arsenic in the groundwater of Bangladesh is a serious natural calamity and a public health hazard. Most groundwater from the shallow alluvial aquifers (<150 m), particularly in the Holocene plain lands, are vulnerable to As-enrichment. Delta plains and flood plains of the Ganges-Brahmaputra river system are moderately to severely enriched and more than 60% of the tube wells are affected. Shallow aquifers in the Meghna river basin and coastal plains are extremely enriched with more than 80% of the tube wells affected. Aquifers in the Pleistocene uplands and Tertiary hills are low in As. The vertical lithofacies sequence of the sediments from highly enriched areas of the country show two distinct lithofacies associations-a dominantly sandy channel-fill association and a fine-grained over bank association. The sediments can be grouped into 4 distinct lithofacies, viz. clay, silty clay, silty sand and sand. Thin section petrography of the As-enriched aquifer sands shows that the sands are of quartzolithic type and derived from the collision suture and fold thrust belt of the recycled orogen provenance. Groundwater is characterized by circum-neutral pH with a moderate to strong reducing nature. The waters are generally of Ca-Mg-HCO3 or Ca-Na-HCO3 type, with HCO3- as the principal anion. Low SO42- and NO3-, and high dissolved organic C (DOC) and NH4+ concentrations are typical chemical characteristics of groundwater. The presence of dissolved sulfides in these groundwaters indicates reduction Of SO4. Total As concentration in the analyzed wells vary between 2.5 and 846 mug l(-1) with a dominance of As(III) species (67-99%). Arsenic(III) concentrations were fairly consistent with the DOC and NH4+ contents. The HNO3 extractable concentrations of As (As-NO3) in the sediments (0.5-17.7 mg kg(-1)), indicate a significant positive correlation with Fe-NO3, Mn-NO3, Al-NO3 and P-NO3. The concentrations Of S-NO3 (816-1306 mg kg(-1)) peaked in the clay sediments with high organic matter (up to 4.5 wt.%). Amounts of oxalate extractable As (As..) and Fe (Fe x) ranged between 0.1-8.6 mg kg(-1) and 0.4-5.9 g kg(-1), respectively. Arsenic(ox) was positively correlated with Fe-ox, Mn-ox, and Al-ox in these sediments. Insignificant amounts of opaque minerals (including pyrite/arsenopyrite) and the presence of high As contents in finer sediments suggests that some As is incorporated in the authigenically precipitated sulfides in the reducing sediments. Moreover, the chemical extractions suggest the presence of siderite and vivianite as solid phases, which may control the aqueous chemistry of Fe and PO43-. Reductive dissolution of Fe oxyhydroxide present as coatings on sand grains as well as altered mica (biotite) is envisaged as the main mechanism for the release of As into groundwater in the sandy aquifer sediments.
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| 4. |
- Bokhari, S H, et al.
(författare)
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A networking laboratory for the developing world
- 2004
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Ingår i: IEEE Communications Magazine. - 0163-6804 .- 1558-1896. ; 42:2, s. 106-113
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Tidskriftsartikel (refereegranskat)abstract
- Internet-based communication is assuming an increasingly important role in the developing world. It is thus crucial that students be exposed to contemporary networking equipment in a realistic setting, in order to connect theoretical material taught in lecture courses with the realities of physical hardware. To this end, a large computer networking laboratory has been set up to provide a realistic environment for teaching internetworking concepts. This laboratory provides university-level students with a testbed to experiment with fundamental issues of internetworking in a way that cannot be provided by simulators and to a degree of rigor not possible with the commonly available laboratory setups designed for technicians. We describe the motivations for setting up the laboratory, its network structure and equipment, and the type of experiments students conduct. The laboratory structure is influenced heavily by the limited funds-at our disposal - a common problem in the developing world. Many of the problems we faced in setting up our equipment (such as the crucial impact of proper electrical grounding on system performance) are not ordinarily encountered in developed nations. Our experiences are thus likely to be of value to others in the developing world who are contemplating setting up experimental facilities for teaching networking.
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| 6. |
- Davani, B, et al.
(författare)
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Aged transgenic mice with increased glucocorticoid sensitivity in pancreatic beta-cells develop diabetes
- 2004
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 5353 Suppl 1, s. S51-S59
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are diabetogenic hormones because they decrease glucose uptake, increase hepatic glucose production, and inhibit insulin release. To study the long-term effects of increased glucocorticoid sensitivity in β-cells, we studied transgenic mice overexpressing the rat glucocorticoid receptor targeted to the β-cells using the rat insulin I promoter. Here we report that these mice developed hyperglycemia both in the fed and the overnight-fasted states at 12–15 months of age. Progression from impaired glucose tolerance, previously observed in the same colony at the age of 3 months, to manifest diabetes was not associated with morphological changes or increased apoptosis in the β-cells. Instead, our current results suggest that the development of diabetes is due to augmented inhibition of insulin secretion through α2-adrenergic receptors (α2-ARs). Thus, we found a significantly higher density of α2-ARs in the islets of transgenic mice compared with controls, based on binding studies with the α2-AR agonist UK 14304. Furthermore, incubation of islets with benextramine, a selective antagonist of the α2-AR, restored insulin secretion in response to glucose in isolated islets from transgenic mice, whereas it had no effect on control islets. These results indicate that the chronic enhancement of glucocorticoid signaling in pancreatic β-cells results in hyperglycemia and impaired glucose tolerance. This effect may involve signaling pathways that participate in the regulation of insulin secretion via the α2-AR.
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| 10. |
- Khan, A, et al.
(författare)
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Long-term leptin treatment of ob/ob mice improves glucose-induced insulin secretion
- 2001
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 25:6, s. 816-821
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Previous studies have demonstrated that leptin inhibits glucose-stimulated insulin secretion from isolated islets, although a lack of leptin effect on insulin secretion has also been reported. The effect of long term in vivo leptin treatment of insulin secretion has, however, not been established. Therefore, in the present study, we have evaluated the effect of long term in vivo treatment of leptin on glucose-induced insulin secretion in ob/ob mice. METHODS: After 7 days' treatment of leptin (100 microg daily s.c.), insulin release was measured in isolated islets by batch incubation followed by radioimmunoassay. Glucose utilization and oxidation were measured by measuring the formation of (3)H(2)O and (14)CO(2) from [5-(3)H] and [U-(14)C] glucose, respectively. Glucose-6-phosphatase activity was measured by measuring the conversion of (14)C-glucose-6-P to (14)C-glucose. In addition, immunohistochemistry of pancreatic specimens was undertaken for study of expression of insulin, GLUT-2 and hormone-sensitive lipase (HSL). RESULTS: Leptin treatment significantly improved insulin secretion both at 5.5 mM (by 15%; P<0.05) and 16.7 mM (by 85%; P<0.001) glucose, compared to vehicle-treated controls. Furthermore, whereas leptin treatment did not affect islet insulin or DNA contents, a significant decrease in islet triglyceride content and glucose-6-phosphatase activity was observed. Moreover, the immunocytochemical data revealed an increased immunostaining for insulin, GLUT-2 and hormone-sensitive lipase (HSL) in islets from leptin-treated ob/ob mice. CONCLUSION: The results suggest that long-term leptin treatment of ob/ob mice improves glucose-stimulated insulin secretion in parallel with reduced glucose-6-phosphatase activity, increased HSL and decreased triglyceride levels in islets. These perturbations may explain the improvement of glucose-stimulated insulin secretion induced by leptin.
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