Mafb and c-Maf Have Prenatal Compensatory and Postnatal Antagonistic Roles in Cortical Interneuron Fate and Function

1. Download high-res image (175KB)
2. Download full-size image

     

Heterologous expression of a mammalian protein tyrosine phosphatase gene in Leishmania: effect on differentiation

Leishmania is a protozoan pathogen which is transmitted to humans through the bite of an infected sandfly. This infection results in a spectrum of diseases throughout the developing world, collectively known as leishmaniasis. During its life cycle, Leishmania differentiates from the promastigote stage in the sandfly vector into the amastigote stage in the mammalian host where it multiplies exclusively in macrophage phagolysosomes. Although differentiation of Leishmania is essential for its survival and pathogenesis in the mammalian host, this process is poorly understood. In higher eukaryotic cells, protein tyrosine phosphorylation plays a central role in cell proliferation, differentiation and overall function. We have therefore investigated the role of protein tyrosine phosphorylation in Leishmania differentiation by undertaking complementary approaches to mediate protein tyrosine dephosphorylation in vivo. In the present study, L. donovani were engineered to express a mammalian protein tyrosine phosphatase, or were treated with inhibitors of protein tyrosine kinases, and the resulting phenotype was examined. Both approaches resulted in a partial differentiation from promastigotes to amastigotes including the expression of the amastigote specific A2 protein, morphological change and increased virulence. These data provide support for the involvement of tyrosine phosphorylation in the differentiation of Leishmania.     

Two new end-to-end single dicyanamide bridged Cu(II) complexes with Schiff base ligands: Structural, electrochemical and magnetic properties

The synthesis, crystal structures and magnetic properties of two different copper(II) complexes of formula [Cu(L¹)(dca)]_n · nClO₄ (1) and [Cu(L²)]₂(dca)(ClO₄) (2) [L¹ = N,N-dimethylethylene-N′-(pyridine-2-carbaldiiminato), HL² = N,N-dimethylethylene-N′-salicylaldiiminato, dca = dicyanamide anion] are described. Spectroscopic and electrochemical properties have also been discussed. A one-dimensional chain structure with single, symmetrical, μ_1,5-dca bridges is found in compound 1. The copper atom in 1 has a square pyramidal geometry. A tridentate Schiff base ligand, having NNN donor sites, and one nitrogen atom from dca occupy the basal plane. N(18) of a neighbouring unit occupies the apical site. The Schiff base used in compound 2 is a tridentate anion with NNO donor sites, which changes the structure in a dinuclear unit of copper atoms bridged by single end-to-end dicyanamide ion. The environment around copper in 2 is square planar. Magnetic susceptibility measurements for 1 and 2 reveal the occurrence of weak antiferromagnetic interaction through the dca ligand.     

TP53 codon 72 polymorphism and type 2 diabetes: a case–control study in South Indian population

Molecular Biology Reports - TP53 functions primarily as a tumor suppressor, controlling a myriad of signalling pathways that prevent a cell from undergoing malignant transformation. This tumor...     

Unveiling the role of Dps in the organization of mycobacterial nucleoid

In order to preserve genetic information in stress conditions, bacterial DNA is organized into higher order nucleoid structure. In this paper, with the help of Atomic Force Microscopy, we show the different structural changes in mycobacterial nucleoid at different points of growth in the presence of different concentrations of glucose in the medium. We also observe that in Mycobacterium smegmatis, two different Dps proteins (Dps1 and Dps2) promote two types of nucleoid organizations. At the late stationary phase, under low glucose availability, Dps1 binds to DNA to form a very stable toroid structure. On the other hand, under the same condition, Dps2-DNA complex forms an incompletely condensed toroid and finally forms a further stable coral reef structure in the presence of RNA. This coral reef structure is stable in high concentration of bivalent ion like Mg(2+).     

Bayesian data integration and variable selection for pan-cancer survival prediction using protein expression data

Accurate prognostic prediction using molecular information is a challenging area of research, which is essential to develop precision medicine. In this paper, we develop translational models to identify major actionable proteins that are associated with clinical outcomes, like the survival time of patients. There are considerable statistical and computational challenges due to the large dimension of the problems. Furthermore, data are available for different tumor types; hence data integration for various tumors is desirable. Having censored survival outcomes escalates one more level of complexity in the inferential procedure. We develop Bayesian hierarchical survival models, which accommodate all the challenges mentioned here. We use the hierarchical Bayesian accelerated failure time model for survival regression. Furthermore, we assume sparse horseshoe prior distribution for the regression coefficients to identify the major proteomic drivers. We borrow strength across tumor groups by introducing a correlation structure among the prior distributions. The proposed methods have been used to analyze data from the recently curated “The Cancer Proteome Atlas” (TCPA), which contains reverse-phase protein arrays–based high-quality protein expression data as well as detailed clinical annotation, including survival times. Our simulation and the TCPA data analysis illustrate the efficacy of the proposed integrative model, which links different tumors with the correlated prior structures.     

Structural and thermodynamic analyses of the interaction between melittin and lipopolysaccharide

Lipopolysaccharide (LPS), the major constituent of the outer membrane of Gram-negative bacteria, is the very first site of interactions with the antimicrobial peptides. In this work, we have determined a solution conformation of melittin, a well-known membrane active amphiphilic peptide from honey bee venom, by transferred nuclear Overhauser effect (Tr-NOE) spectroscopy in its bound state with lipopolysaccharide. The LPS bound conformation of melittin is characterized by a helical structure restricted only to the C-terminus region (residues A15-R24) of the molecule. Saturation transfer difference (STD) NMR studies reveal that several C-terminal residues of melittin including Trp19 are in close proximity with LPS. Isothermal titration calorimetry (ITC) data demonstrates that melittin binding to LPS or lipid A is an endothermic process. The interaction between melittin and lipid A is further characterized by an equilibrium association constant (Ka) of 2.85 x 10(6) M(-1) and a stoichiometry of 0.80, melittin/lipid A. The estimated free energy of binding (delta G0), -8.8 kcal mol(-1), obtained from ITC experiments correlates well with a partial helical structure of melittin in complex with LPS. Moreover, a synthetic peptide fragment, residues L13-Q26 or mel-C, derived from the C-terminus of melittin has been found to contain comparable outer membrane permeabilizing activity against Escherichia coli cells. Intrinsic tryptophan fluorescence experiments of melittin and mel-C demonstrate very similar emission maxima and quenching in presence of LPS micelles. The Red Edge Excitation Shift (REES) studies of tryptophan residue indicate that both peptides are located in very similar environment in complex with LPS. Collectively, these results suggest that a helical conformation of melittin, at its C-terminus, could be an important element in recognition of LPS in the outer membrane.