Cecal Ligation and Puncture Results in Long-Term Central Nervous System Myeloid Inflammation

Survivors of sepsis often experience long-term cognitive and functional decline. Previous studies utilizing lipopolysaccharide injection and cecal ligation and puncture in rodent models of sepsis have demonstrated changes in depressive-like behavior and learning and memory after sepsis, as well as evidence of myeloid inflammation and cytokine expression in the brain, but the long-term course of neuroinflammation after sepsis remains unclear. Here, we utilize cecal ligation and puncture with greater than 80% survival as a model of sepsis. We found that sepsis survivor mice demonstrate deficits in extinction of conditioned fear, but no acquisition of fear conditioning, nearly two months after sepsis. These cognitive changes occur in the absence of neuronal loss or changes in synaptic density in the hippocampus. Sepsis also resulted in infiltration of monocytes and neutrophils into the CNS at least two weeks after sepsis in a CCR2 independent manner. Cellular inflammation is accompanied by long-term expression of pro-inflammatory cytokine and chemokine genes, including TNFα and CCR2 ligands, in whole brain homogenates. Gene expression analysis of microglia revealed that while microglia do express anti-microbial genes and damage-associated molecular pattern molecules of the S100A family of genes at least 2 weeks after sepsis, they do not express the cytokines observed in whole brain homogenates. Our results indicate that in a naturalistic model of infection, sepsis results in long-term neuroinflammation, and that this sustained inflammation is likely due to interactions among multiple cell types, including resident microglia and peripherally derived myeloid cells.     

MOLS sampling and its applications in structural biophysics

This review describes the MOLS method and its applications. This computational method has been developed in our laboratory primarily to explore the conformational space of small peptides and identify features of interest, particularly the minima, i.e., the low energy conformations. A systematic “brute-force” search through the vast conformational space for such features faces the insurmountable problem of combinatorial explosion, whilst other techniques, e.g., Monte Carlo searches, are somewhat limited in their region of exploration and may be considered inexhaustive. The MOLS method, on the other hand, uses a sampling technique commonly employed in experimental design theory to identify a small sample of the conformational space that nevertheless retains information about the entire space. The information is extracted using a technique that is a variant of the self-consistent mean field technique, which has been used to identify, for example, the optimal set of side-chain conformations in a protein. Applications of the MOLS method to understand peptide structure, predict the structures of loops in proteins, predict three-dimensional structures of small proteins, and arrive at the best conformation, orientation, and positions of a small molecule ligand in a protein receptor site have all yielded satisfactory results.     

A database for medicinal plants used in treatment of asthma

The knowledge of most plants used in the treatment of asthma, the plant part which is effective in treatment is confined to very few persons who are engaged in folklore medicine. However, this form of medicine is not very popular. Therefore, it is of considerable interest to ethno-botanical community to understand the plants and the parts used for treatment. Here, we describe AsthmaPlantBase, a database containing information of medicinal plants for treatment of asthma.

Availability     

Cytotoxic cobalt (III) Schiff base complexes: in vitro anti-proliferative,oxidative stress and gene expression studies in human breast and lung cancer cells

BioMetals - Increasing cancer drug chemo-resistance, especially in the treatment of breast and lung cancers, alarms the immediate need of newer and effective anticancer drugs. Until now,...     

Conformational space exploration of Met- and Leu-enkephalin using the MOLS method, molecular dynamics, and Monte Carlo simulation--a comparative study

We report here a comparative study of the molecular conformational energy landscape generated using the mutually orthogonal Latin squares (MOLS) method, molecular dynamics (MD), and Monte Carlo (MC) simulation. The MOLS method, as described earlier from our laboratory, uses an experimental design technique to rapidly and exhaustively sample the low energy conformations of a molecule. MD and MC simulations have been used to perform similar tasks. In the comparison reported here, the three methods were applied to a pair of neuropeptides, namely Met- and Leu-enkephalin. A set of 1500 conformations of these enkephalins were generated using these methods with CHARMM22 force field, and the resulting samples were analyzed to determine the extent and nature of coverage of the conformational space. The results indicate that the MOLS method samples a larger number of possible conformations and identifies conformations closer to the experimental structures than the MD and MC simulations.     

Draft Genome Sequence of Staphylococcus aureus ST672, an Emerging Disease Clone from India

We report the draft genome sequence of methicillin-resistant Staphylococcus aureus (MRSA) strain ST672, an emerging disease clone in India, from a septicemia patient. The genome size is about 2.82 Mb with 2,485 open reading frames (ORFs). The staphylococcal cassette chromosome mec (SCCmec) element (type V) and immune evasion cluster appear to be different from those of strain ST772 on preliminary examination.     

Intracellular mediators of transforming growth factor β superfamily signaling localize to endosomes in chicken embryo and mouse lenses in vivo

Background  

Endocytosis is a key regulator of growth factor signaling pathways. Recent studies showed that the localization to endosomes of intracellular mediators of growth factor signaling may be required for their function. Although there is substantial evidence linking endocytosis and growth factor signaling in cultured cells, there has been little study of the endosomal localization of signaling components in intact tissues or organs.