Binding site identification of G protein-coupled receptors through a 3D Zernike polynomials-based method: application to C. elegans olfactory receptors.

Studying the binding processes of G protein-coupled receptors (GPCRs) proteins is of particular interest both to better understand the molecular mechanisms that regulate the signaling between the extracellular and intracellular environment and for drug design purposes. In this study, we propose a new computational approach for the identification of the binding site for a specific ligand on a GPCR. The method is based on the Zernike polynomials and performs the ligand-GPCR association through a shape complementarity analysis of the local molecular surfaces. The method is parameter-free and it can distinguish, working on hundreds of experimentally GPCR-ligand complexes, binding pockets from randomly sampled regions on the receptor surface, obtaining an Area Under ROC curve of 0.77. Given its importance both as a model organism and in terms of applications, we thus investigated the olfactory receptors of the C. elegans, building a list of associations between 21 GPCRs belonging to its olfactory neurons and a set of possible ligands. Thus, we can not only carry out rapid and efficient screenings of drugs proposed for GPCRs, key targets in many pathologies, but also we laid the groundwork for computational mutagenesis processes, aimed at increasing or decreasing the binding affinity between ligands and receptors.

High-Frequency and Ultra-High Frequency Ultrasound: Musculoskeletal Imaging up to 70 MHz.

Musculoskeletal (MSK) ultrasound has well-established advantages, able to investigate very small structures with high resolution and a quick and real-time dynamic evaluation with the possibility of contralateral comparison. Thus ultrasound has kept its own almost exclusive fields of application in daily clinical practice, and it is considered the first-level imaging technique to assess tendons, bursae, and capsuloligamentous structures of small peripheral joints as well as peripheral nerves. Up to now, however, clinical MSK ultrasound imaging could not go beyond the first 1 to 2 cm under the skin, using high-frequency probes up to 18 to 20 MHz with spatial resolution just below millimeters. We present the impressive technical advancements leading to image resolution as low as 30 µm using ultra-high frequency ultrasound (UHFUS) probes up to 70 MHz. High-frequency ultrasound and UHFUS, with frequencies ranging from 22 to 70 MHz, are promising tools to evaluate very superficial structures. In the MSK system, only two articles have assessed its value in limited case series. Future developments may be aimed to better assess ultrastructural changes of very superficial peripheral nerves and other thin structures such as pulleys, retinacula, and tendons.

Investigation of the binding between olfactory receptors and odorant molecules in C. elegans organism.

The molecular mechanisms regulating the complex sensory system that underlies olfaction are still not completely understood. The compounds formed from the interaction of Olfactory Receptors (ORs) with volatile molecules play a crucial role in producing the sense of olfaction. Therefore, it is necessary to investigate the binding mechanisms between these receptors and small ligands. In this work, we focus our attention on C.elegans, this is a particularly suitable model organism because it is characterized by a nervous system composed of only 302 neurons. To study olfaction in C.elegans, we select 21 ORs from its olfactory neurons, and present a pipeline, consisting of several computational methods, with the aim of proposing a set of possible candidates for binding the selected C.elegans ORs. This pipeline introduces an approach based on the selection of templates, and threading, that takes advantage of the structural redundancy among membrane receptors. This procedure is widely replicable because it is based on algorithms that are publicly available and are freely hosted on institutional servers.

Advanced Power Doppler Technique Increases Synovial Vascularity Detection in Patients with Rheumatoid Arthritis.

We compared the diagnostic performance of an advanced power Doppler technique (superb microvascular imaging [SMI]) with that of power Doppler Imaging (PDI) and B-mode ultrasound (US) in patients with early rheumatoid arthritis (RA) and RA under treatment with rituximab. Thirty patients (21 women aged 45 ± 11 y) affected by RA with remission to moderate disease activity were examined. Both hand joints were evaluated using US, PDI and SMI. Two radiologists reviewed all video clips and evaluated synovial vascularity intensity using a semi-quantitative scoring system. SMI revealed the presence of synovial vascularity in a significantly larger number of patients than PDI (p = 0.02). Inter-observer agreement for US, PDI and SMI was moderate (κ = 0.59), very good (κ = 0.87) and very good (κ = 0.82), respectively. We conclude that SMI detects more vessels than PDI in RA patients. This may allow increased sensitivity for early diagnosis of synovial inflammation, monitoring of its dynamic changes under therapy and evaluation of true imaging remission.

Arthroscopic repair of rotator cuff tear with a modified Mason-Allen stitch: mid-term clinical and ultrasound outcomes.

One of the most discussed point about arthroscopic full-thickness rotator cuff (RTC) repair is the strength of tendon-stitch interface. In the period between November 2003 and September 2004, in a series of 29 patients with primary isolated supraspinatus tear measuring > 2 cm a reconstruction using one titanium anchor and a modified Mason-Allen (MMA) stitch was done. These patients were prospectively collected in this study and then retrospectively evaluated. There were 21 men and 8 women with a mean age of 59.3 years. Patients were examined pre-operatively by a single sport medicine doctor, very experienced on shoulder pathology problem. Constant score, University of California at Los Angeles (UCLA) scale and Simple Shoulder Test (SST) were administered. After a minimum follow-up of 24 months patients were revaluated clinically by the same independent examiner. At the same time patients underwent an ultrasound shoulder examination to evaluate rotator cuff integrity. Clinically there was a significant improvement of Constant score, SST score and UCLA scale at followup. Twenty-five patients (86.2%) were satisfied, whether the other four patients (13.8%) stated that they would decline procedure. Recurrent rotator cuff tear was found in 11 patients (38%), who were all older than 60. All the patients but one with a pre-operative MRI grade III tendon tissue fatty infiltration, had a cuff re-tear. Arthroscopic supraspinatus tendon repair with one single anchor and MMA stitch is a reliable technique leading to a re-tear of 38% that is comparable with results reported in literature.