Structure/function relationships of phospholipases C Beta.

Phospholipases C beta (PLC-βs) are essential components of the signal transduction of metazoans. They catalyze the production of the second messengers inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) from the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2). These enzymes are activated by G-protein-coupled receptors (GPCRs) through the interaction with the alpha subunit of heterotrimeric G-proteins belonging to the Gq family (Gαq), the Gβγ subunits released by the inhibitory G-protein (Gi) and Ca2+ ions.

Assessment of myocardial adrenergic innervation with a solid-state dedicated cardiac cadmium-zinc-telluride camera: first clinical experience.

Aims: To investigate the relationships between regional adrenergic innervation heterogeneity, myocardial perfusion, and contractile function obtained by means of a low-dose imaging protocol with a cadmium-zinc-telluride (CZT) dedicated camera.

Methods: Twenty-eight patients with or without ischaemic heart disease underwent (123)I-metaiodobenzylguanidine (MIBG) planar scintigraphic and CZT early and delayed evaluations followed by (99m)Tc-tetrofosmin rest gated CZT with a single-day protocol. The heart-to-mediastinum ratio and the washout rate were computed from planar (123)I-MIBG images.

Association between left ventricular regional sympathetic denervation and mechanical dyssynchrony in phase analysis: a cardiac CZT study.

Purpose: To evaluate the relationships among myocardial sympathetic innervation, perfusion and mechanical synchronicity assessed with cardiac cadmium-zinc-telluride (CZT) scintigraphy.

Methods: A group of 29 patients underwent an evaluation of myocardial perfusion with (99m)Tc-tetrofosmin CZT scintigraphy and adrenergic innervation with (123)I-metaiodobenzylguanidine (MIBG) CZT scintigraphy. The summed rest score (SRS), motion score (SMS) and thickening score (STS), as well as the summed (123)I-MIBG defect score (SS-MIBG), were determined.

Characterization of C-S Lyase from C. diphtheriae: a possible target for new antimicrobial drugs.

The emergence of antibiotic resistance in microbial pathogens requires the identification of new antibacterial drugs. The biosynthesis of methionine is an attractive target because of its central importance in cellular metabolism. Moreover, most of the steps in methionine biosynthesis pathway are absent in mammals, lowering the probability of unwanted side effects.

One stage, full-mouth, ultrasonic debridement in the treatment of severe chronic periodontitis in smokers: a preliminary, blind and randomized clinical trial.

Objective: The aim of this clinical trial was to assess the performance of a full-mouth ultrasonic debridement protocol in the treatment of severe chronic periodontitis in comparison with scaling and root planing in a quadrant-wise procedure in smokers.

Materials And Methods: The trial consisted of 30 participants presenting with periodontitis divided into 3 groups: Group FMUD - full-mouth ultrasonic debridement, i.e.

GOMoDo: A GPCRs online modeling and docking webserver.

G-protein coupled receptors (GPCRs) are a superfamily of cell signaling membrane proteins that include >750 members in the human genome alone. They are the largest family of drug targets. The vast diversity and relevance of GPCRs contrasts with the paucity of structures available: only 21 unique GPCR structures have been experimentally determined as of the beginning of 2013.

Feasibility of [(123)I]-meta-iodobenzylguanidine dynamic 3-D kinetic analysis in vivo using a CZT ultrafast camera: preliminary results.

Purpose: No data are yet available in the literature concerning 3-D [(123)I]-meta-iodobenzylguanidine ([(123)I]-MIBG) kinetics in vivo. In this study we investigated the feasibility of dynamic 3-D [(123)I]-MIBG kinetic analysis using a CZT ultrafast camera.

Methods: The study group comprised 16 patients consecutively scheduled for [(123)I]-MIBG cardiac scintigraphy for clinical purpose who were studied using a CZT camera (NM530c, GE).

Gated SPECT evaluation of left ventricular function using a CZT camera and a fast low-dose clinical protocol: comparison to cardiac magnetic resonance imaging.

Purpose: CZT technology allows ultrafast low-dose myocardial scintigraphy but its accuracy in assessing left ventricular function is still to be defined.

Methods: The study group comprised 55 patients (23 women, mean age 63 ± 9 years) referred for myocardial perfusion scintigraphy. The patients were studied at rest using a CZT camera (Discovery NM530c; GE Healthcare) and a low-dose (99m)Tc-tetrofosmin clinical protocol (mean dose 264 ± 38 MBq).

Novel ALPL genetic alteration associated with an odontohypophosphatasia phenotype.

Hypophosphatasia (HPP) is an inherited disorder of mineral metabolism caused by mutations in ALPL, encoding tissue non-specific alkaline phosphatase (TNAP). Here, we report the molecular findings from monozygotic twins, clinically diagnosed with tooth-specific odontohypophosphatasia (odonto-HPP). Sequencing of ALPL identified two genetic alterations in the probands, including a heterozygous missense mutation c.

Coarse-grained/molecular mechanics of the TAS2R38 bitter taste receptor: experimentally-validated detailed structural prediction of agonist binding.

Bitter molecules in humans are detected by ∼25 G protein-coupled receptors (GPCRs). The lack of atomic resolution structure for any of them is complicating an in depth understanding of the molecular mechanisms underlying bitter taste perception. Here, we investigate the molecular determinants of the interaction of the TAS2R38 bitter taste receptor with its agonists phenylthiocarbamide (PTC) and propylthiouracil (PROP).

Gender differences in the evaluation of coronary artery disease with a cadmium-zinc telluride camera.

Purpose: Coronary artery disease remains one of the most significant causes of morbidity and mortality among women. The published literature shows the importance of standard single photon emission computed tomography in the evaluation of women with known or suspected ischaemic heart disease, in terms of target intervention and clinical treatment. The purpose of the present study was to ascertain the diagnostic accuracy of cadmium-zinc-telluride (CZT) myocardial perfusion imaging according to gender, within a prospective database of patients with known or suspected coronary artery disease, using coronary angiography as the reference standard.

Identification of aldolase and ferredoxin reductase within the dbt operon of Burkholderia fungorum DBT1.

Burkholderia fungorum DBT1, first isolated from settling particulate matter of an oil refinery wastewater, is a bacterial strain which has been shown capable of utilizing several polycyclic aromatic hydrocarbons (PAHs) including dibenzothiophene (DBT). In particular, this microbe is able to efficiently degrade DBT through the Kodama pathway. Previous investigations have lead to the identification of six genes, on a total of eight, required for DBT degradation.

A Candidate Ion-Retaining State in the Inward-Facing Conformation of Sodium/Galactose Symporter: Clues from Atomistic Simulations.

The recent Vibrio parahaemolyticus sodium/galactose (vSGLT) symporter crystal structure captures the protein in an inward-facing substrate-bound conformation, with the sodium ion placed, by structural alignment, in a site equivalent to the Na2 site of the leucine transporter (LeuT). A recent study, based on molecular dynamics simulations, showed that the sodium ion spontaneously leaves its initial position diffusing outside vSGLT, toward the intracellular space. This suggested that the crystal structure corresponds to an ion-releasing state of the transporter.

On-field investigation and process modelling of end-of-life vehicles treatment in the context of Italian craft-type authorized treatment facilities.

The present article analyses the current situation of End-of-Life-of-Vehicles (ELVs) management in Europe, with particular attention on Italian condition. Similarly to other European countries, metal recycling is the main activity of the whole system, but such situation is evolving due to the 2000/53/EC Directive, which sets out targets for Reuse, Recycling and Recovery of ELVs. Due to the relevance of the ELVs problem, in 2008 Italian Ministry of Environment subscribed a framework agreement with competent stakeholders as carmakers, dismantlers, shredders.

Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming.

Recent studies indicate that human-induced pluripotent stem cells contain genomic structural variations and point mutations in coding regions. However, these studies have focused on fibroblast-derived human induced pluripotent stem cells, and it is currently unknown whether the use of alternative somatic cell sources with varying reprogramming efficiencies would result in different levels of genetic alterations. Here we characterize the genomic integrity of eight human induced pluripotent stem cell lines derived from five different non-fibroblast somatic cell types.

Hybrid molecular mechanics/coarse-grained simulations for structural prediction of G-protein coupled receptor/ligand complexes.

Understanding how ligands bind to G-protein coupled receptors (GPCRs) provides insights into a myriad of cell processes and is crucial for drug development. Here we extend a hybrid molecular mechanics/coarse-grained (MM/CG) approach applied previously to enzymes to GPCR/ligand complexes. The accuracy of this method for structural predictions is established by comparison with recent atomistic molecular dynamics simulations on the human β2 adrenergic receptor, a member of the GPCRs superfamily.

Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells.

Generation of human induced pluripotent stem cells (hiPSCs) by the expression of specific transcription factors depends on successful epigenetic reprogramming to a pluripotent state. Although hiPSCs and human embryonic stem cells (hESCs) display a similar epigenome, recent reports demonstrated the persistence of specific epigenetic marks from the somatic cell type of origin and aberrant methylation patterns in hiPSCs. However, it remains unknown whether the use of different somatic cell sources, encompassing variable levels of selection pressure during reprogramming, influences the level of epigenetic aberrations in hiPSCs.

Cigarette smoke inhalation influences bone healing of post-extraction tooth socket: a histometric study in rats.

The aim of this study was to evaluate, histometrically, the bone healing of the molar extraction socket just after cigarette smoke inhalation (CSI). Forty male Wistar rats were randomly assigned to a test group (animals exposed to CSI, starting 3 days before teeth extraction and maintained until sacrifice; n=20) and a control group (animals never exposed to CSI; n=20). Second mandibular molars were bilaterally extracted and the animals (n=5/group/period) were sacrificed at 3, 7, 10 and 14 days after surgery.

Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc.

The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcription factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133(+) cells lose their hematopoietic signature and are converted into CB-induced neuronal-like cells (CB-iNCs) by the ectopic expression of the transcription factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immunophenotyping, and electrophysiological analysis show that CB-iNCs acquire a distinct neuronal phenotype characterized by the expression of multiple neuronal markers.

Evaluation of ischaemia in obese patients: feasibility and accuracy of a low-dose protocol with a cadmium-zinc telluride camera.

Purpose: Obesity is a significant and independent risk factor for cardiovascular disease, and assessing ischaemia in obese patients is clinically important but sometimes difficult because of imaging artefacts. The aim of this study was to evaluate the feasibility and diagnostic accuracy of stress/rest imaging with a cadmium-zinc telluride (CZT) camera using a low-dose protocol in a series of consecutive obese patients referred for the evaluation of coronary artery disease.

Methods: We considered 148 consecutive obese patients (mean BMI 39 ± 7 kg/m(2)) with known or suspected coronary artery disease referred to our laboratory for stress/rest myocardial perfusion imaging.

Gene expression analysis in microdissected samples from decalcified tissues.

Objective: The aim of this study was to determine the impact of standard methods for processing decalcified highly mineralized tissues on RNA yield and quality from microdissected samples.

Design: Rat mandibles were fixed with either formalin-based or ethanol-based fixatives, decalcified in 20% ethylenediaminetetraacetic acid solution for 15 days, and embedded in paraffin. Transversal sections of the molars were mounted on membrane glass slides for laser capture microdissection.

Impact of supragingival therapy on subgingival microbial profile in smokers versus non-smokers with severe chronic periodontitis.

Background: The aim of this study was to assess subgingival microbiological changes in smokers versus non-smokers presenting severe chronic periodontitis after supragingival periodontal therapy (ST).

Methods: Non-smokers (n=10) and smokers (n=10) presenting at least nine teeth with probing pocket depth (PPD) (≥5 mm), bleeding on probing (BoP), and no history of periodontal treatment in the last 6 months were selected. Clinical parameters assessed were plaque index (PI), BoP, PPD, relative gingival margin position (rGMP) and relative clinical attachment level (rCAL).

Structural requirements for cooperativity in ileal bile acid-binding proteins.

Ileal bile acid-binding proteins (I-BABP), belonging to the family of intracellular lipid-binding proteins, control bile acid trafficking in enterocytes and participate in regulating the homeostasis of these cholesterol-derived metabolites. I-BABP orthologues share the same structural fold and are able to host up to two ligands in their large internal cavities. However variations in the primary sequences determine differences in binding properties such as the degree of binding cooperativity.