Somatostatin as a mediator of the effect of neurotensin on pentagastrin-stimulated acid secretion in rats

Neurotensin and somatostatin have both been shown to inhibit gastric acid secretion, but no interaction between these peptides has been demonstrated. To determine whether somatostatin might be a mediator of neurotensin's effect on pentagastrin-stimulated gastric acid secretion, we performed the following three experiments. First, we collected 0.2-ml samples of portal venous blood as frequently as every 5 min, and we confirmed a significant release of somatostatin-like immunoreactivity into portal venous blood during neurotensin-induced inhibition of acid secretion. This release of somatostatin-like immunoreactivity and inhibition of acid secretion were only seen in pentobarbital-anesthetized rats, but no sustained release of somatostatin-like immunoreactivity or inhibition of acid secretion occurred in urethane-anesthetized animals. In the second experiment, we analyzed portal plasma by high pressure liquid chromatography, and found that portal somatostatin-like immunoreactivity in blood collected during neurotensin infusion was composed of a single peak corresponding to somatostatin-14. In the third experiment, we found that infusion of antibody to somatostatin prevented neurotensin from inhibiting pentagastrin-stimulated acid secretion. Taken together, these data show that somatostatin, possibly from the stomach itself, is a necessary mediator of neurotensin's inhibitory effect in pentobarbital-anesthetized rats.     

Chromosomal variation in social voles: a Robertsonian fusion in Günther’s vole

The study reports on chromosomes in several populations of social voles from south-eastern Europe and the Middle East. The standard karyotypes of individuals of Microtus hartingi and Microtus guentheri originating from both south-eastern Europe and Asia Minor comprised 54 mostly acrocentric chromosomes. However, variation between populations was found in the amount and distribution of C-heterochromatin in certain autosomes and the sex chromosomes. Furthermore, a specific pattern of argyrophilic nucleolar organizer region distribution was recorded in different geographic populations. In a population from Asia Minor, a heterozygous centric fusion of two autosomes was found. The G-banded karyotypes of M. guentheri and Microtus socialis were compared, and tandem fusions of autosomes were suggested as possible mechanism of the divergence. The karyotypes of the nine currently recognized species of social voles are reviewed, and implications of chromosomal data for systematics are evaluated.     

The extremo-α-carbonic anhydrase (CA) from Sulfurihydrogenibium azorense,the fastest CA known,is highly activated by amino acids and amines

The α-carbonic anhydrase (CA, EC 4.2.1.1) from the extremophilic bacterium Sulfurihydrogenibium azorense (SazCA) was recently shown to be the fastest CA known. Here we investigated this enzyme for its activation with a series of amino acids and amines. The best SazCA activators were d-Phe, l-DOPA, l- and d-Trp, dopamine and serotonin, which showed activation constants in the range of 3–23 nM. l- and d-His, l-Phe, l-Tyr, 2-pyridyl-methylamine and L-adrenaline were also effective activators (K_As in the range of 62–90 nM), whereas d-Dopa, d-Tyr and several heterocyclic amines showed activity in the micromolar range. The good thermal stability, robustness, very high catalytic activity and propensity to be activated by simple amino acids and amines, make SazCA a very interesting candidate for biomimetic CO₂ capture processes.     

Hair-bearing submental artery island flap for reconstruction of mustache and beard

Loss of mustache and beard in the adult male caused by severe burn, trauma, or tumor resection may cause cosmetic and psychological problems for these patients. Reconstruction of the elements of the face presents difficult and often daunting problems for plastic surgeons. The tissue that will be used for this purpose should have the same characteristics as the facial area, consisting of thin, pliable, hair-bearing tissue with a good color match. There is a very limited amount of donor area that has these characteristics. A hair-bearing submental island flap was used successfully for mustache and beard reconstruction in 11 male patients during the last 5 years. The scar was on the mentum in four cases, right cheek in two cases, right half of the upper lip in two cases, left cheek in one case, left half of the upper lip in one case, and both sides of the upper lip in one case. The submental island flap is supplied by the submental artery, a branch of the facial artery. The maximum flap size was 13 x 6 cm and the minimum size was 6 x 3 cm (average, 10 x 4 cm) in this series. Direct closure was achieved at all donor sites. Patients were followed up for 6 months to 5 years. No major complication was noted other than one case of temporary palsy of the marginal mandibular branch of the facial nerve. The mean postoperative stay was 7 days. Color and texture match were good. Hair growth on the flap was normal, and characteristics of the hair were the same as the intact side of the face in all patients. The submental island flap is safe, rapid, and simple to raise and leaves a well-hidden donor-site scar. The authors believe that the submental artery island flap surpasses the other flaps in reconstruction of the mustache and beard in male patients. Application of the technique and results are discussed in this article.     

Genetic diversity for grain nutrients in wild emmer wheat: potential for wheat improvement

Background and Aims

Micronutrient malnutrition, particularly zinc and iron deficiency, afflicts over three billion people worldwide due to low dietary intake. In the current study, wild emmer wheat (Triticum turgidum ssp. dicoccoides), the progenitor of domesticated wheat, was tested for (1) genetic diversity in grain nutrient concentrations, (2) associations among grain nutrients and their relationships with plant productivity, and (3) the association of grain nutrients with the eco-geographical origin of wild emmer accessions.

Methods

A total of 154 genotypes, including wild emmer accessions from across the Near Eastern Fertile Crescent and diverse wheat cultivars, were characterized in this 2-year field study for grain protein, micronutrient (zinc, iron, copper and manganese) and macronutrient (calcium, magnesium, potassium, phosphorus and sulphur) concentrations.

Key Results

Wide genetic diversity was found among the wild emmer accessions for all grain nutrients. The concentrations of grain zinc, iron and protein in wild accessions were about two-fold greater than in the domesticated genotypes. Concentrations of these compounds were positively correlated with one another, with no clear association with plant productivity, suggesting that all three nutrients can be improved concurrently with no yield penalty. A subset of 12 populations revealed significant genetic variation between and within populations for all minerals. Association between soil characteristics at the site of collection and grain nutrient concentrations showed negative associations between soil clay content and grain protein and between soil-extractable zinc and grain zinc, the latter suggesting that the greatest potential for grain nutrient minerals lies in populations from micronutrient-deficient soils.

Conclusions

Wild emmer wheat germplasm offers unique opportunities to exploit favourable alleles for grain nutrient properties that were excluded from the domesticated wheat gene pool.     

Phenylthiazolyl-hydrazide and its derivatives are potent inhibitors of tau aggregation and toxicity in vitro and in cells

One of the key pathological features of Alzheimer's disease is the aggregation of tau protein. We are therefore searching for compounds capable of inhibiting this reaction. On the basis of an initial screen of 200000 compounds [Pickhardt, M., Gazova, Z., von Bergen, M., Khlistunova, I., Wang, Y., Hascher, A., Mandelkow, E. M., Biernat, J., and Mandelkow, E. (2005) Anthraquinones inhibit tau aggregation and dissolve Alzheimer's paired helical filaments in vitro and in cells, J. Biol. Chem. 280, 3628-3635], we performed an in silico screen and predicted a new phenylthiazolyl-hydrazide (PTH) compound as a possible hit [Larbig, G., Pickhardt, M., Lloyd, D. G., Schmidt, B., and Mandelkow, E. (2007) Screening for inhibitors of tau protein aggregation into Alzheimer paired helical filaments: A ligand based approach results in successful scaffold hopping. Curr. Alzheimer Res. 4 (3), 315-323.]. Synthesis of this compound showed that it was indeed active in terms of inhibiting de novo tau aggregation and disassembling preformed aggregates (IC50 = 7.7 microM and DC50 = 10.8 microM). We have now synthesized 49 similar structures and identified the core of the PTHs to be crucial for activity, thus representing a lead structure. Analysis of the binding epitope by saturation transfer difference NMR shows strong interactions between the tau protein and the ligand in the aromatic regions of the inhibitor. By chemical variation of the core, we improved the inhibitory potency five-fold. The compounds showed a low toxicity as judged by an N2A cell model of tau aggregation and lend themselves for further development.