An organism's ability to thrive in changing environmental conditions requires the capacity for making flexible behavioral responses. Here we show that, in the nematode Caenorhabditis elegans, foraging responses to changes in food availability require nlp-12, a homolog of the mammalian neuropeptide cholecystokinin (CCK). nlp-12 expression is limited to a single interneuron (DVA) that is postsynaptic to dopaminergic neurons involved in food-sensing, and presynaptic to locomotory control neurons. NLP-12 release from DVA is regulated through the D1-like dopamine receptor DOP-1, and both nlp-12 and dop-1 are required for normal local food searching responses. nlp-12/CCK overexpression recapitulates characteristics of local food searching, and DVA ablation or mutations disrupting muscle acetylcholine receptor function attenuate these effects. Conversely, nlp-12 deletion reverses behavioral and functional changes associated with genetically enhanced muscle acetylcholine receptor activity. Thus, our data suggest that dopamine-mediated sensory information about food availability shapes foraging in a context-dependent manner through peptide modulation of locomotory output.

Hyperglycemia with severe reduction of plasma insulin level is frequently associated with acute ischemic heart disease. Since insulin is reported to be an anti thrombotic humoral factor, the mechanism of the impaired insulin synthesis was investigated. The plasma from the patients with acute myocardial infarction (AMI) was analyzed by SDS-polyacrylamide gel electrophoresis. Dermcidin isoform 2 (dermcidin) was determined by enzyme linked immunosorbent assay. Insulin synthesis was determined by in vitro translation of glucose induced insulin mRNA synthesis in the pancreatic β cells. Nitric oxide (NO) was determined by methemoglobin method. SDS-polyacrylamide gel electrophoresis of AMI plasma demonstrated the presence of a novel protein band of Mr 11 kDa that was determined to be dermcidin. Addition of 0.1 μM dermcidin inhibited insulin synthesis by >65 fold compared to control through the inhibition of NO synthesis in the pancreatic cells. The oral administration of 150 mg acetyl salicylic acid (aspirin) to the AMI patients increased the plasma insulin level from 13 (median) to 143 μunits/dl (median) with concomitant decrease of plasma dermcidin level from 112 to 9 nM in these patients within 12 h. It was also found that while the injection of 3.0 ± 0.05 (n = 10) nmol dermcidin with 0.25 ± 0.03 μmol ADP/g body weight caused coronary thrombus in mice, ADP itself at this concentration failed to produce thrombus. These results indicated that dermcidin was a novel platelet aggregating agent, and potentiated the ADP induced thrombosis in the animal model as well as acutely inhibited glucose induced insulin synthesis.

Background:C-reactive protein (CRP) is useful as marker of severity in malaria. African studies have shown that serum CRP levels correlate with parasite burden and complications in malaria, especially falciparum. However, there are very few data on CRP levels in Indian malaria patients.Materials and Methods:We assessed CRP levels in malaria patients at presentation and studied for any relation of CRP levels with subsequent prognosis. Statistical tests included student's t-test, Mann Whitney U test, and chi square test, all with 2-tailed analyzes.Results:Of 71 patients in our study, 42 (59.1%) were infected with P. falciparum. 23 (32.4%) patients needed admission and 10 (14.1%) died. Average CRP levels were quite high in malaria patients (31.29 ± 20.4 mg/L). There was no significant difference in CRP between vivax and falciparum cases. Admitted patients had significantly higher CRP levels compared to those treated on outdoor basis (47.11 ± 19.13 vs. 23.71 ± 16.35 mg/L; P < 0.0001). 8 patients were admitted with multiple complications. They had significantly high CRP level compared to those with 1 complication (P = 0.015). Also, patients who died had higher CRP levels compared to survivors (P = 0.000346). CRP levels at presentation showed positive correlation with duration of hospital stay (r = 0.59; P < 0.05). CRP levels >35 mg/L was highly sensitive in predicting mortality.Conclusion:Our study in Indian population corroborates the findings in African studies regarding prognostic role of CRP in malaria. CRP is an effective biomarker in assessing malaria severity and also for follow-up.

Protein palmitoylation involves the post-translational attachment of palmitate in thioester linkage to cysteine residues of proteins. The labile nature of the thioester linkage makes possible the palmitoylation-depalmitoylation cycles that have emerged in recent times as additions to the repertoire of cellular control mechanisms. However, detailed understanding of these cycles has been limited by the lack of knowledge of the transferases and thioesterases likely to be involved. Here, we describe the purification of a protein-palmitoyl acyltransferase (PAT) from human erythrocytes. PAT behaved as a peripheral membrane protein and catalyzed the attachment of palmitate in thioester linkage to the ␤-subunit of spectrin. On SDS-polyacrylamide gel electrophoresis, PAT appeared as a 70-kDa polypeptide. Antibody against this polypeptide could immunodeplete PAT activity from the crude extract, confirming the assignment of the 70-kDa polypeptide as PAT. PAT-mediated spectrin palmitoylation could be inhibited by nonradioactive palmitoyl-, myristoyl-, or stearoyl-CoA. The apparent K m for palmitoyl-CoA was 16 M.A large number of proteins in cells are modified by the covalent attachment of long chain saturated fatty acid residues (1-3). The two most common modifications involve acylation with myristate and palmitate. Myristate is usually attached to an N-terminal glycine via an amide bond in a relatively stable linkage. Palmitate is usually attached via a thioester bond to cysteine residues of proteins. Palmitoylation occurs in membrane proteins with hydrophobic transmembrane segments as well as in hydrophilic proteins such as Ras (1-4). These lipid modifications have often been implicated in membrane association of the modified proteins (5). Palmitoylation occurs posttranslationally. Moreover, rapid turnover of the protein-bound fatty acid has been shown for several proteins (6 -8). The recent surge of interest in studying protein palmitoylation is largely due to the fact that a number of proteins involved in intracellular signaling are palmitoylated, and this appears to be regulated by the activation status of these proteins (9 -12). Palmitoylation occurs in, among others, the families of (i) G protein-linked receptors, (ii) the subunits of heterotrimeric G proteins, and (iii) the non-receptor tyrosine kinases. Palmitate plays a role in the membrane association of these polypeptides.Moreover, recent evidence suggests that this may regulate protein-protein interactions such as those between growth cone-associated protein 43 and G o␣ in neurons (13). Although evidence that the interactions of G proteins with effectors are regulated by palmitoylation is becoming compelling, very little is known about the enzymes involved in the catalysis of the palmitoylation and depalmitoylation of these or other proteins.A clear understanding of the palmitoylation-depalmitoylation cycle as a cellular control mechanism obviously entails characterization of the protein palmitoyltransferase(s) and thioesterase(s). A thioesterase has recently b...

Chandipura virus, a member of the vesiculovirus genera, has been recently recognized as an emerging human pathogen. Previously, we have shown that Chandipura virus Nucleocapsid protein N is capable of binding to both specific viral leader RNA as well as non-viral RNA sequences, albeit in distinct monomeric and oligomeric states, respectively. Here, we distinguish the regions of N involved in oligomerization and RNA binding using a panel of deletion mutants. We demonstrate that deletion in the N-terminal arm completely abrogates self-association of N protein. Monomer N specifically recognizes viral leader RNA using its C-terminal 102 residues, while oligomerization generates an additional RNA binding surface involving the N-terminal 320 amino acids of N overlapping with a protease resistant core that is capable of forming nucleocapsid like structure and also binding heterogeneous RNA sequences. Finally, we propose a model to explain the mechanism of genome encapsidation of this important human pathogen.