Morphologic changes in the vein after different numbers of radiofrequency ablation cycles.

Objective: It has not yet been clarified whether it is possible to decrease the percentage of recurrences after radiofrequency (RF) ablation by way of increasing the number of RF ablation cycles. The aim of this study was to assess the morphologic changes in excised vein fragments after different durations of RF ablation exposure.

Methods: In the first part of the study, we performed a morphologic analysis of eight cases of great saphenous vein (GSV) recanalization 6 months after RF ablation.

Radiofrequency ablation or stripping of large-diameter incompetent great saphenous varicose veins with C2 or C3 disease.

Objective: The objectives of this study were to compare the results of radiofrequency ablation (RFA) and stripping for large-diameter varicose target veins for the period of 1 year, based on a composite end point; to analyze the pain severity on a digital rating scale for 7 days after RFA and stripping; and to detect the factors affecting the level of postoperative pain using the cluster analysis.

Methods: This was a multicenter retrospective cohort study. Two groups, stripping ≥14 mm and RFA ≥14 mm, of 129 varicose vein disease patients underwent surgical treatment in three specialized clinics.

Historeceptomic Fingerprints for Drug-Like Compounds.

Most drugs exert their beneficial and adverse effects through their combined action on several different molecular targets (polypharmacology). The true molecular fingerprint of the direct action of a drug has two components: the ensemble of all the receptors upon which a drug acts and their level of expression in organs/tissues. Conversely, the fingerprint of the adverse effects of a drug may derive from its action in bystander tissues.

Specific increase in potency via structure-based design of a TCR.

Adoptive immunotherapy with Ag-specific T lymphocytes is a powerful strategy for cancer treatment. However, most tumor Ags are nonreactive "self" proteins, which presents an immunotherapy design challenge. Recent studies have shown that tumor-specific TCRs can be transduced into normal PBLs, which persist after transfer in ∼30% of patients and effectively destroy tumor cells in vivo.

Sequence-conserved and antibody-accessible sites in the V1V2 domain of HIV-1 gp120 envelope protein.

The immune-correlates analysis of the RV144 trial suggested that epitopes targeted by protective antibodies (Abs) reside in the V1V2 domain of gp120. We mapped V1V2 positional sequence variation onto the conserved V1V2 structural fold and showed that while most of the solvent-accessible V1V2 amino acids vary between strains, there are two accessible molecular surface regions that are conserved and also naturally antigenic. These sites may contain epitopes targeted by broadly cross-reactive anti-V1V2 antibodies.

Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations.

Many of the gene mutations found in genetic disorders, including cancer, result in premature termination codons (PTC) and the rapid degradation of their mRNAs by nonsense-mediated RNA decay (NMD). We used virtual library screening, targeting a pocket in the SMG7 protein, a key component of the NMD mechanism, to identify compounds that disrupt the SMG7-UPF1 complex and inhibit NMD. Several of these compounds upregulated NMD-targeted mRNAs at nanomolar concentrations, with minimal toxicity in cell-based assays.

Computational prediction of neutralization epitopes targeted by human anti-V3 HIV monoclonal antibodies.

The extreme diversity of HIV-1 strains presents a formidable challenge for HIV-1 vaccine design. Although antibodies (Abs) can neutralize HIV-1 and potentially protect against infection, antibodies that target the immunogenic viral surface protein gp120 have widely variable and poorly predictable cross-strain reactivity. Here, we developed a novel computational approach, the Method of Dynamic Epitopes, for identification of neutralization epitopes targeted by anti-HIV-1 monoclonal antibodies (mAbs).

Specific small molecule inhibitors of Skp2-mediated p27 degradation.

In the ubiquitin proteasome system, the E3 ligase SCF-Skp2 and its accessory protein, Cks1, promote proliferation largely by inducing the degradation of the CDK inhibitor p27. Overexpression of Skp2 in human cancers correlates with poor prognosis, and deregulation of SCF-Skp2-Cks1 promotes tumorigenesis in animal models. We identified small molecule inhibitors specific to SCF-Skp2 activity using in silico screens targeted to the binding interface for p27.

Can the energy gap in the protein-ligand binding energy landscape be used as a descriptor in virtual ligand screening?

The ranking of scores of individual chemicals within a large screening library is a crucial step in virtual screening (VS) for drug discovery. Previous studies showed that the quality of protein-ligand recognition can be improved using spectrum properties and the shape of the binding energy landscape. Here, we investigate whether the energy gap, defined as the difference between the lowest energy pose generated by a docking experiment and the average energy of all other generated poses and inferred to be a measure of the binding energy landscape sharpness, can improve the separation power between true binders and decoys with respect to the use of the best docking score.

Recovering protein-protein and domain-domain interactions from aggregation of IP-MS proteomics of coregulator complexes.

Coregulator proteins (CoRegs) are part of multi-protein complexes that transiently assemble with transcription factors and chromatin modifiers to regulate gene expression. In this study we analyzed data from 3,290 immuno-precipitations (IP) followed by mass spectrometry (MS) applied to human cell lines aimed at identifying CoRegs complexes. Using the semi-quantitative spectral counts, we scored binary protein-protein and domain-domain associations with several equations.

Stacking and hydrogen bonding: DNA cooperativity at melting.

By taking into account base-base stacking interactions we improve the Generalized Model of Polypeptide Chain (GMPC). Based on a one-dimensional Potts-like model with many-particle interactions, the GMPC describes the helix-coil transition in both polypeptides and polynucleotides. In the framework of the GMPC we show that correctly introduced nearest-neighbor stacking interactions against the background of hydrogen bonding lead to increased stability (melting temperature) and, unexpectedly, to decreased cooperativity (maximal correlation length).