Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking

Synaptic transmission is mediated by a complex set of molecular events that must be coordinated in time and space. While many proteins that function at the synapse have been identified, the signaling pathways regulating these molecules are poorly understood. Pak5 (p21-activated kinase 5) is a brain-specific isoform of the group II Pak kinases whose substrates and roles within the central nervous system are largely unknown. To gain insight into the physiological roles of Pak5, we engineered a Pak5 mutant to selectively radiolabel its substrates in murine brain extract. Using this approach, we identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. These results implicate Pak5 in Pacsin1- and Synaptojanin1-mediated synaptic vesicle trafficking and may partially account for the cognitive and behavioral deficits observed in group II Pak-deficient mice.     

An Integrated Alcohol Abuse and Medical Treatment Model for Patients with Hepatitis C

Background  

Patients with chronic hepatitis C virus (HCV) infection have high rates of alcohol consumption, which is associated with progression of fibrosis and lower response rates to HCV treatment.     

Periodontal dressing may influence the clinical outcome of non-surgical periodontal treatment: a split-mouth study

To cite this article:
Int J Dent Hygiene 10 , 2012; 284–289
DOI: 10.1111/j.1601‐5037.2010.00493.x Genovesi AM, Ricci M, Marchisio O, Covani U.Periodontal dressing may influence the clinical outcome of non surgical periodontal treatment: a split‐mouth study. Abstract: Introduction: After scaling and root planning (SRP), healing induces the formation of a junctional long epithelium rather than a new connective attachment. We hypothesize that the placement of a periodontal dressing will be able to prevent detachment of coagulum inducing proper healing and improving periodontal parameters. Materials and methods: This split‐mouth study included 30 patients with periodontitis with ages ranging from 35 to 70 years. Probing pocket depth (PD), probing attachment level (PAL), bleeding on probing index (BoP) and plaque index (PI) were assessed before and after therapy. The group of patients received SRP in a span of 24 h. Then, a periodontal dressing was applied on the test side and it was removed after 1 week. Results: Control group: The difference between PD values at baseline and after therapy was 1.6 ± 0.6 mm. The difference in PAL (ΔPAL) measurement was 1.4 ± 0.4. Test group: there was a greater PD reduction, this being 2.4 ± 0.6 mm on average. The difference in PAL was 2.5 ± 0.4 mm. Conclusions: Our results clearly suggest that the use of a periodontal dressing improves the periodontal parameters after an SRP procedure. This is probably due to clot stabilization and prevention of bacterial colonization during wound healing.     

Dronedarone reduces arterial thrombus formation

Dronedarone has been associated with a reduced number of first hospitalisation due to acute coronary syndromes. Whether this is only due to the reduction in ventricular heart rate and blood pressure or whether other effects of dronedarone may be involved is currently elusive. This study was designed to investigate the role of dronedarone in arterial thrombus formation. C57Bl/6 mice were treated with dronedarone and arterial thrombosis was investigated using a mouse photochemical injury model. Dronedarone inhibited carotid artery thrombus formation in vivo (P?<?0.05). Thrombin- and collagen-induced platelet aggregation was impaired in dronedarone-treated mice (P?<?0.05), and expression of plasminogen activator inhibitor-1 (PAI1), an inhibitor of the fibrinolytic system, was reduced in the arterial wall (P?<?0.05). In contrast, the level of tissue factor (TF), the main trigger of the coagulation cascade, and that of its physiological inhibitor, TF pathway inhibitor, did not differ. Similarly, coagulation times as measured by prothrombin time and activated partial thromboplastin time were comparable between the two groups. Dronedarone inhibits thrombus formation in vivo through inhibition of platelet aggregation and PAI1 expression. This effect occurs within the range of dronedarone concentrations measured in patients, and may represent a beneficial pleiotropic effect of this drug.     

A new β chain hemoglobin variant with increased oxygen affinity: Hb Santa Giusta Sardegna [β93(F9)Cys→Trp; HBB c.282T>G

During a screening program for the identification of β-thalassemia (β-thal) carriers in Sardinia, Italy, we identified two subjects with increased hemoglobin (Hb) levels and an abnormal Hb variant. The same variant was detected in a family member. DNA sequencing revealed a TGT > TGG mutation at codon 93 of the β-globin gene. Structural analysis demonstrated that the cystine residue at position 93 of the β chain was substituted by tryptophan. Since this amino acid substitution had not yet been reported, we designated this variant Hb Santa Giusta Sardegna for the place of birth of the subjects. This amino acid substitution occurs at the tyrosine pocket of the β chain as well as at the α1β2/α2β1 contact of the quaternary structure of the molecule. The presence of this Hb in the hemolysate causes an increased oxygen affinity, a slightly reduced Bohr effect and a reduced heme-heme interaction (n(50), Hill's constant) in comparison with those of Hb A.     

First detection of Hb Taybe [α38(C3) or α39(C4) Thr→0 (α1)] in an Italian child

Hb Taybe [α38(C3) or α39(C4) Thr→0 (α1)] is an unstable hemoglobin (Hb) variant caused by a deletion of a threonine residue at codon 39 of the α1-globin chain. Usually asymptomatic or with minimal hematological abnormalities in the heterozygous state, Hb Taybe becomes clinically evident in compound heterozygosity with α-thalassemia (α-thal) or in homozygous patients. To date, Hb Taybe has been described in Israeli-Arab and Greek individuals. We report, for the first time, a patient with chronic hemolytic anemia due to the presence of Hb Taybe in trans to the α2 initiation codon mutation ATG>ACG in an Italian child. Hb Taybe was not evident at Hb analysis with cellulose acetate electrophoresis and high performance liquid chromatography (HPLC). Globin biosynthetic studies revealed an α/β-globin ratio in the range of β-thal trait. Consequently, an investigation of the α- and β-globin genes was requested in order to avoid missing any rare globin chain variant and to offer accurate genetic counseling.