Covalent Modification of p53 by ()-1-(4-Methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one.

is commonly mutated in cancer, giving rise to loss of wild-type tumor suppressor function and increases in gain-of-function oncogenic roles. Thus, inhibition of mutant p53 and reactivation of wild-type function represents a potential means to target diverse tumor types. ()-1-(4-Methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one (NSC59984), first identified from a high-throughput screen, induces wild-type p53 signaling and antiproliferative effects while inhibiting mutant p53 gain-of-function activities.

Crystal structure and mechanistic studies of the PPM1D serine/threonine phosphatase catalytic domain.

Protein phosphatase 1D (PPM1D, Wip1) is induced by the tumor suppressor p53 during DNA damage response signaling and acts as an oncoprotein in several human cancers. Although PPM1D is a potential therapeutic target, insights into its atomic structure were challenging due to flexible regions unique to this family member. Here, we report the first crystal structure of the PPM1D catalytic domain to 1.

Alkyl-substituted N-methylaryl-N'-aryl-4-aminobenzamides: A new series of small molecule inhibitors for Wip1 phosphatase.

The wild-type p53 induced phosphatase 1 (Wip1), a member of the serine/threonine-specific PP2C family, is overexpressed in numerous human cancers. Wip1 dephosphorylates p53 as well as several kinases (such as p38 MAPK, ATM, Chk1, and Chk2) in the DNA damage response pathway that are responsible for maintaining genomic stability and preventing oncogenic transformation. As a result, Wip1 is an attractive target for synthetic inhibitors that could be further developed into therapeutics to treat some cancers.

Study of quality of life and depression in people living with HIV/AIDS in India.

The aim of this study was to assess the quality of life (QOL) and the severity of depression in people living with HIV/AIDS (PLWHA) and investigate its correlates. This was a cross-sectional study on 700 PLWHA in India. World Health Organization QOL HIV (WHOQOL HIV-BREF) and Patient Health Questionnaire-9 (PHQ-9) were used to assess QOL and depression in PLWHA, respectively.

Crystal structures and kinetics of N-acetylneuraminate lyase from Fusobacterium nucleatum.

N-Acetyl-D-neuraminic acid lyase (NanA) catalyzes the breakdown of sialic acid (Neu5Ac) to N-acetyl-D-mannosamine (ManNAc) and pyruvate. NanA plays a key role in Neu5Ac catabolism in many pathogenic and bacterial commensals where sialic acid is available as a carbon and nitrogen source. Several pathogens or commensals decorate their surfaces with sialic acids as a strategy to escape host innate immunity.

Conformational transitions of the sodium-dependent sugar transporter, vSGLT.

Sodium-dependent transporters couple the flow of Na ions down their electrochemical potential gradient to the uphill transport of various ligands. Many of these transporters share a common core structure composed of a five-helix inverted repeat and deliver their cargo utilizing an alternating-access mechanism. A detailed characterization of inward-facing conformations of the Na-dependent sugar transporter from (vSGLT) has previously been reported, but structural details on additional conformations and on how Na and ligand influence the equilibrium between other states remains unknown.

Automation aided optimization of cloning, expression and purification of enzymes of the bacterial sialic acid catabolic and sialylation pathways enzymes for structural studies.

The process of obtaining a well-expressing, soluble and correctly folded constructs can be made easier and quicker by automating the optimization of cloning, expression and purification. While there are many semiautomated pipelines available for cloning, expression and purification, there is hardly any pipeline that involves complete automation. Here, we achieve complete automation of all the steps involved in cloning and in vivo expression screening.

Calculating Gamma Camera Uniformity Parameters: Beyond the Vendor-specific Protocol.

Objectives: The aim of this study was to develop and verify a personal computer-based software tool for calculating uniformity indices of gamma camera.

Materials And Methods: The program was developed in MATLAB R2013b under Microsoft Windows operating system. Noise-less digital phantoms with known uniformity parameters were used to verify the accuracy of the program.

Combinatorial Pairwise Assembly Efficiently Generates High Affinity Binders and Enables a "Mix-and-Read" Detection Scheme.

We show that a combinatorial library constructed by random pairwise assembly of low affinity binders can efficiently generate binders with increased affinity. Such a library based on the Sso7d scaffold, from a pool of low affinity binders subjected to random mutagenesis, contained putative high affinity clones for a model target (lysozyme) at higher frequency than a library of monovalent mutants generated by random mutagenesis alone. Increased binding affinity was due to intramolecular avidity generated by linking binders targeting nonoverlapping epitopes; individual binders of K ∼ 1.

A technique for automatically extracting useful field of view and central field of view images.

Introduction: It is essential to ensure the uniform response of the single photon emission computed tomography gamma camera system before using it for the clinical studies by exposing it to uniform flood source. Vendor specific acquisition and processing protocol provide for studying flood source images along with the quantitative uniformity parameters such as integral and differential uniformity. However, a significant difficulty is that the time required to acquire a flood source image varies from 10 to 35 min depending both on the activity of Cobalt-57 flood source and the pre specified counts in the vendors protocol (usually 4000K-10,000K counts).

Development of a conversion program to make SIMIND-generated SPECT data interfile acceptable to Xeleris.

The Monte Carlo code SIMIND is used in nuclear medicine for research purposes, and also for testing the validity of various applications. Conversion of a SIMIND-generated interfile (header and image data file) is required to process the simulated image data on a Xeleris workstation. Currently there is no conversion program provided with SIMIND to convert its interfile, which is acceptable in any nuclear medicine workstation.