Evaluation of nitric acid donor, transdermal glycerol trinitrate patches for facilitating cervical ripening: a randomised controlled trial.

Purpose: To evaluate the efficacy and safety of transdermal glycerol trinitrate skin patches as an additive and effective agent for facilitating cervical ripening for labour induction.

Methods: This was a double-blinded prospective randomised clinical trial carried out in a major obstetric unit in India. Women who planned for labour induction were randomly allocated for induction either by combined application of glycerol trinitrate skin patches [GTN patch] and intracervical dinoprostone gel or by the gel only.

VISTA is an acidic pH-selective ligand for PSGL-1.

Co-inhibitory immune receptors can contribute to T cell dysfunction in patients with cancer. Blocking antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) partially reverse this effect and are becoming standard of care in an increasing number of malignancies. However, many of the other axes by which tumours become inhospitable to T cells are not fully understood.

Generating High-Accuracy Peptide-Binding Data in High Throughput with Yeast Surface Display and SORTCERY.

Library methods are widely used to study protein-protein interactions, and high-throughput screening or selection followed by sequencing can identify a large number of peptide ligands for a protein target. In this chapter, we describe a procedure called "SORTCERY" that can rank the affinities of library members for a target with high accuracy. SORTCERY follows a three-step protocol.

A Prospective, double-blinded randomized controlled study comparing two different Trendelenburg tilts in laparoscopically assisted vaginal hysterectomy positioning.

Background: Bispectral index (BIS) used for intra-operative depth assessment under general anesthesia (GA) can be altered by different factors. This study was designed to detect the alteration in BIS reading with two different Trendelenburg (TBG) tilt in laparoscopically assisted vaginal hysterectomy (LAVH) procedure.

Materials And Methods: A prospective, double-blinded, randomized controlled study was designed involving 40 American Society of Anesthesiologists Grade I and II female patients, aged 35-60 years, scheduled to undergo LAVH under GA.

Potent and specific peptide inhibitors of human pro-survival protein Bcl-xL.

The Bcl-2 family of proteins plays a critical role regulating apoptosis, and pro-survival Bcl-2 family members are important therapeutic targets due to their overexpression in different cancers. Pro-apoptotic Bcl-2 homology 3 (BH3)-only proteins antagonize pro-survival Bcl-2 protein functions by binding directly to them, and a sub-class of BH3-only proteins termed sensitizers can initiate apoptosis via this mechanism in response to diverse signals. The five pro-survival proteins Bcl-xL, Mcl-1, Bcl-2, Bcl-w and Bfl-1 differ in their binding preferences, with Bcl-xL, Bcl-2 and Bcl-w sharing similar interaction profiles for many natural sensitizers and small molecules.

SORTCERY-A High-Throughput Method to Affinity Rank Peptide Ligands.

Uncovering the relationships between peptide and protein sequences and binding properties is critical for successfully predicting, re-designing and inhibiting protein-protein interactions. Systematically collected data that link protein sequence to binding are valuable for elucidating determinants of protein interaction but are rare in the literature because such data are experimentally difficult to generate. Here we describe SORTCERY, a high-throughput method that we have used to rank hundreds of yeast-displayed peptides according to their affinities for a target interaction partner.

Peptide ligands for pro-survival protein Bfl-1 from computationally guided library screening.

Pro-survival members of the Bcl-2 protein family inhibit cell death by binding short helical BH3 motifs in pro-apoptotic proteins. Mammalian pro-survival proteins Bcl-x(L), Bcl-2, Bcl-w, Mcl-1, and Bfl-1 bind with varying affinities and specificities to native BH3 motifs, engineered peptides, and small molecules. Biophysical studies have determined interaction patterns for these proteins, particularly for the most-studied family members Bcl-x(L) and Mcl-1.

Predictive Bcl-2 family binding models rooted in experiment or structure.

Proteins of the Bcl-2 family either enhance or suppress programmed cell death and are centrally involved in cancer development and resistance to chemotherapy. BH3 (Bcl-2 homology 3)-only Bcl-2 proteins promote cell death by docking an α-helix into a hydrophobic groove on the surface of one or more of five pro-survival Bcl-2 receptor proteins. There is high structural homology within the pro-death and pro-survival families, yet a high degree of interaction specificity is nevertheless encoded, posing an interesting and important molecular recognition problem.

Management of abnormal uterine bleeding in women with mechanical heart valve prosthesis and anticoagulant therapy.

In a prospective observational case series, we assessed the effects and management and outcome of oral anticoagulant associated abnormal uterine bleeding in women with mechanical heart valve prosthesis. Six women with mechanical heart valve prosthesis, who were admitted with persistent severe vaginal bleeding between 2003 and 2010, were evaluated. For each woman, detailed history, treatment received, if there was any complication and their final outcome and satisfaction were recorded.

Determinants of BH3 binding specificity for Mcl-1 versus Bcl-xL.

Interactions among Bcl-2 family proteins are important for regulating apoptosis. Prosurvival members of the family interact with proapoptotic BH3 (Bcl-2-homology-3)-only members, inhibiting execution of cell death through the mitochondrial pathway. Structurally, this interaction is mediated by binding of the alpha-helical BH3 region of the proapoptotic proteins to a conserved hydrophobic groove on the prosurvival proteins.

High-throughput analysis of the protein sequence-stability landscape using a quantitative yeast surface two-hybrid system and fragment reconstitution.

Stability evaluation of many mutants can lead to a better understanding of the sequence determinants of a structural motif and of factors governing protein stability and protein evolution. The traditional biophysical analysis of protein stability is low throughput, limiting our ability to widely explore sequence space in a quantitative manner. In this study, we have developed a high-throughput library screening method for quantifying stability changes, which is based on protein fragment reconstitution and yeast surface display.

High-affinity fragment complementation of a fibronectin type III domain and its application to stability enhancement.

The tenth fibronectin type III (FN3) domain of human fibronectin (FNfn10), a prototype of the ubiquitous FN3 domain, is a small, monomeric beta-sandwich protein. In this study, we have bisected FNfn10 in each loop to generate a total of six fragment pairs. We found that fragment pairs bisected at multiple loops of FNfn10 show complementation in vivo as tested with a yeast two-hybrid system.