Conserved residues in RF-NH2 receptor models identify predicted contact sites in ligand-receptor binding.

Peptides in the RF-NH2 family are grouped together based on an amidated dipeptide C terminus and signal through G-protein coupled receptors (GPCRs) to influence diverse physiological functions. By determining the mechanisms underlying RF-NH2 signaling targets can be identified to modulate physiological activity; yet, how RF-NH2 peptides interact with GPCRs is relatively unexplored. We predicted conserved residues played a role in Drosophila melanogaster RF-NH2 ligand-receptor interactions. In this study D. melanogaster rhodopsin-like family A peptide GPCRs alignments identified eight conserved residues unique to RF-NH2 receptors. Three of these residues were in extra-cellular loops of modeled RF-NH2 receptors and four in transmembrane helices oriented into a ligand binding pocket to allow contact with a peptide. The eighth residue was unavailable for interaction; yet its conservation suggested it played another role. A novel hydrophobic region representative of RF-NH2 receptors was also discovered. The presence of rhodopsin-like family A GPCR structural motifs including a toggle switch indicated RF-NH2s signal classically; however, some features of the DMS receptors were distinct from other RF-NH2 GPCRs. Additionally, differences in RF-NH2 receptor structures which bind the same peptide explained ligand specificity. Our novel results predicted conserved residues as RF-NH2 ligand-receptor contact sites and identified unique and classic structural features. These discoveries will aid antagonist design to modulate RF-NH2 signaling.

Neuropeptide F peptides act through unique signaling pathways to affect cardiac activity.

Elucidating how neuropeptides affect physiology may result in delineating peptidergic mechanisms and identifying antagonists for application in basic and translational science. Human neuropeptide Y (NPY) regulates cardiac activity; frequently invertebrates contain orthologs of vertebrate peptides. We report invertebrate NPY-like neuropeptide F (NPF) arrested the signal frequency of the slow phase of the cardiac cycle (EC50 = 1 pM); however, signal frequency of the fast phase was affected only minimally. Neuropeptide F decreased the duration of the slow phase by ~70% (EC50 = 0.6 pM), but increased the duration of the fast phase by ~57% (EC50 = 10nM). Short NPF-1 (sNPF-1) decreased the signal frequency of the slow phase by ~70% (EC50 = 9 nM); yet, signal frequency of the fast phase was unaffected. Short NPF-1 decreased the duration of the slow phase ~55% (EC50 ~50 nM), but increased the duration of the fast phase ~20% without dose dependency. Neuropeptide F and sNPF-1 increased isoelectric period duration. This novel report demonstrated NPY-like peptides are cardioactive but functionally unique. These data contribute to understanding how invertebrate orthologs affect cardiovascular activity. Dipteran fast and slow phases may be generated from separate pacemakers in the abdominal heart and in the anterior thoracocephalic aorta, respectively. Thus, our research suggests NPF and sNPF-1 act through different mechanisms to regulate cardiac activity. Invertebrate NPY-like peptides act in olfaction and feeding yet mechanisms which are associated with their cardioactive effects remain unknown; our work may provide evidence linking their roles in sensory response and cardiac activity.

[Relation between hypogonadism and malocclusion in beta-thalassemia major patients: analysis of 122 subjects]. / Relazione tra ipogonadismo e malocclusione dentaria in pazienti affetti da beta-talassemia major. Studio su 122 pazienti.

AIM: The type of malocclusion most often seen in beta thalassemic patients is represented by Angle's II class, which however cannot be considered significant in the patients studied in this research. The only causal factor indicated by medical literature for this pathology is medullary hyperplasia due to inefficient erythropoiesis which occurs in patients transfused at low hemoglobin levels. The aim of this research is to evaluate the influence of other factors as well, particularly sexual development, the level of seric ferritin, ALT, and age at first transfusion. METHODS: One-hundred and twenty-two b thalassemic patients and 39 homozygotes, aged between 16 and 27, undergoing treatment at the "Ospedale Regionale per le Microcitemie di Cagliari", have been analysed. RESULTS: The results of the statistic analysis have shown that hypogonadism can play an important role in determining malocclusions in male beta thalassemic patients (Odds ratio 4,5; CI 1,5-13). No other factor has shown any statistically relevant influence on dental occlusion. CONCLUSION: It would therefore be interesting to further investigate the hormonal mechanisms that can alter bone development in thalassemic youngsters: the prevention of such alterations will surely contribute to improving the quality of life in these patients, particularly now that their life expectancy has been significantly extended by the progress made in transfusional therapy and ferrochelation.

Thalassaemia types and their incidence in Sardinia.

The frequency of thalassaemia syndromes in Sardinia was examined by a population survey. The data indicate that about 12.6% of the Sardinian subjects are carriers of beta-thalassaemia, while 6.9% of the population carries an alpha-thalassaemia gene, with a slight difference between the various provinces. These are among the highest frequencies of thalassaemia genes found in a Caucasian population today. A survey of hospital inpatients and outpatients showed a newborn incidence of homozygous beta-thalassaemia of 1 in 300. The reasons for the difference between the expected and observed incidence figures are discussed. Moreover, 3 subjects with deltabeta0-thalassaemia trait, 6 carriers of heterocellular persistence of fetal haemoglobin (HPFH), 1 sickle cell trait, and 3 subjects with Hb J Sardegna were found. Genetic heterogeneity of beta-thalassaemia syndromes in this population may generally result from interaction of alpha- and beta-thalassaemia genes.

Quantitation of Hb a2 with DE-52 microchromatography in whole blood as screening test for beta-thalassemia heterozygotes.

HB A2 was assayed by means of DE-52 microchromatography in hemolysates from 285 normal subjects and 223 beta-thalassemia heterozygotes. No overlap was found between both groups. Comparable results were observed analyzing whole blood samples collected in capillary tubes from 550 normal subjects and 295 beta-thalassemia heterozygotes. Our results demonstrate that this technique is useful in a screening program for beta-thalassemia trait.