Developmental expression of a 53 KD dentin sialoprotein in rat tooth organs.

Rat dentin contains a major sialic acid-rich glycoprotein, DSP, with an overall composition similar to that of bone sialoproteins but whose biological role in dentinogenesis is unknown. Using polyclonal affinity-purified antibodies to rat DSP and four immunohistochemical methods of detection, we studied the cell and tissue localization of DSP and the time course of its appearance during odontoblast differentiation. DSP first appeared within young odontoblasts concomitant with early secretion of pre-dentin matrix and before the onset of mineralization but was absent in pre-odontoblasts. DSP immunostaining also localized within secretory odontoblasts and was intense in odontoblastic processes. Early pre-dentin stained positive for DSP, in contrast to more mature pre-dentin, where immunoreactivity was less intense and more restricted to odontoblastic processes. In the zone of mineralized dentin matrix, a moderate and uniform staining pattern was evident. Intense immunostaining was also seen within the cells and matrix of dental pulp during dentinogenesis. Other cells and tissues within the tooth organ and those surrounding it were non-reactive. These findings suggest that DSP is developmentally expressed in cells of the odontoblastic lineage and may be a biochemical marker of odontoblastic activity.     

Low serum insulin-like growth factor-1 in patients with erectile dysfunction

Objective

Endothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED.

Materials and methods

All men were evaluated for ED and divided into two groups: 80 patients suffering from ED for >?1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated.

Results

The mean age of patients in ED group was 60.4?±?11.3 years and 55.4?±?9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5?±?38.3 and 132.5?±?53.3 ng/ mL, respectively, P?<?0.001). The IGF-1 levels were positively correlated with ED score (r?=?0.623, P?<?0.01).

Conclusion

In this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population.

     

How an Inhibitor Bound to Subunit Interface Alters Triosephosphate Isomerase Dynamics

The tunnel region at triosephosphate isomerase (TIM)’s dimer interface, distant from its catalytic site, is a target site for certain benzothiazole derivatives that inhibit TIM’s catalytic activity in Trypanosoma cruzi, the parasite that causes Chagas disease. We performed multiple 100-ns molecular-dynamics (MD) simulations and elastic network modeling (ENM) on both apo and complex structures to shed light on the still unclear inhibitory mechanism of one such inhibitor, named bt10. Within the time frame of our MD simulations, we observed stabilization of aromatic clusters at the dimer interface and enhancement of intersubunit hydrogen bonds in the presence of bt10, which point to an allosteric effect rather than destabilization of the dimeric structure. The collective dynamics dictated by the topology of TIM is known to facilitate the closure of its catalytic loop over the active site that is critical for substrate entrance and product release. We incorporated the ligand’s effect on vibrational dynamics by applying mixed coarse-grained ENM to each one of 54,000 MD snapshots. Using this computationally efficient technique, we observed altered collective modes and positive shifts in eigenvalues due to the constraining effect of bt10 binding. Accordingly, we observed allosteric changes in the catalytic loop’s dynamics, flexibility, and correlations, as well as the solvent exposure of catalytic residues. A newly (to our knowledge) introduced technique that performs residue-based ENM scanning of TIM revealed the tunnel region as a key binding site that can alter global dynamics of the enzyme.     

Comparative effect of clonidine and growth hormone (GH)-releasing hormone on GH secretion in adult patients on chronic glucocorticoid therapy.

Glucocorticoids are thought to inhibit growth hormone (GH) secretion through an enhancement of endogenous somatostatin tone. The aim of our study was to evaluate the effects of GH-releasing hormone (GHRH) and clonidine, an alpha-2-adrenergic agonist which increases GH secretion acting at the hypothalamic level with an unknown mechanism, on GH secretion in seven adult patients (3M, 4F) with non endocrine diseases and on daily immunosuppressive glucocorticoid therapy. Eleven normal subjects (7M, 4F) served as controls. Steroid-treated patients showed a blunted GH response to GHRH (GH peak 8.3 +/- 3 micrograms/L) with respect to normal subjects (GH peak 19.3 +/- 2.4 micrograms/L). The GH responses to clonidine were also blunted (p less than 0.05) in steroid-treated patients (GH peak 5.8 +/- 2.8 micrograms/L) with respect to normal subjects (GH peak 17.6 +/- 2.3 micrograms/L). No significant differences between the GH responses to GHRH and clonidine were observed either in steroid-treated or in normal subjects. Clonidine is not able to enhance GH secretion similar to GHRH in patients chronically treated with steroids. It can be hypothesized that clonidine does not elicit GH secretion decreasing hypothalamic somatostatin tone.     

An automated system for genome analysis to support microbial whole-genome shotgun sequencing

We developed a semi-automated genome analysis system called GAMBLER in order to support the current whole-genome sequencing project focusing on alkaliphilic Bacillus halodurans C-125. GAMBLER was designed to reduce the human intervention required and to reduce the complications in annotating thousands of ORFs in the microbial genome. GAMBLER automates three major routines: analyzing assembly results provided by genome assembler software, assigning ORFs, and homology searching. GAMBLER is equipped with an interface for convenience of annotation. All processes and options are manipulatable through a WWW browser that enables scientists to share their genome analysis results without choosing computer platforms.     

Comparative effect of galanin and pyridostigmine on the growth hormone response to growth hormone-releasing hormone in normal aged subjects.

The aim of our study was to investigate the effects of aging on the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) alone and in combination with either the neuropeptide galanin or the acetylcholinesterase inhibitor pyridostigmine (PD) in normal subjects. In protocol 1 (GHRH/galanin), 9 old healthy volunteers, ranging in age from 68 to 97 years, and 6 young subjects, ranging in age from 25 to 31 years, received: (a) human GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) porcine galanin, 500 micrograms in 100 ml saline, as an intravenous infusion from -10 to 30 min combined with GHRH, 100 micrograms i.v. at time 0. In protocol 2 (GHRH/PD), 14 old healthy volunteers, ranging in age from 65 to 91 years, and 11 young subjects, ranging in age from 19 to 34 years, received: (a) GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) PD, 120 mg administered per os 60 min before GHRH, 100 micrograms as an intravenous bolus. Blood samples for GH were drawn at -75, -60 (time of PD administration), -45, -30, -15, -10 (time of beginning of galanin infusion), 0 (time of GHRH injection), 15, 30, 45, 60, 90, and 120 min. The GH response to GHRH was significantly (< 0.05) enhanced either by galanin or PD pretreatment both in young and old subjects. However, the GH response to GHRH alone or combined with either galanin or PD was significantly greater in the young subjects as compared to the old subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genomic analysis to screen potential genes and mutations in children with non-syndromic early onset severe obesity: a multicentre study in Turkey

Molecular Biology Reports - Obesity is a complex genetic-based pediatric disorder which triggers life-threatening conditions. Therefore, the understanding the molecular mechanisms of obesity has...