An MD2-derived peptide promotes LPS aggregation,facilitates its internalization in THP-1 cells,and inhibits LPS-induced pro-inflammatory responses

MD2, a 160-residue accessory glycoprotein, is responsible for the recognition and binding of Gram-negative bacterial membrane component, lipopolysaccharide (LPS). Internalization of pathogen inside the mononuclear phagocytes has also been attributed to MD2 which leads to the clearance of pathogens from the host. However, not much is known about the segments in MD2 that are responsible for LPS interaction or internalization of pathogen inside the defense cells. A 16-residue stretch (MD54) from MD2 protein has been identified that possesses a short heptad repeat sequence and four cationic residues enabling it to participate in both hydrophobic and electrostatic interactions with LPS. An MD54 analog of the same size was also designed in which a leucine residue at a heptadic position was replaced with an alanine residue. MD54 but not its analog, MMD54 induced aggregation of LPS and aided in its internalization within THP-1 monocytes. Furthermore, MD54 inhibited LPS-induced nuclear translocation of NF-κB in PMA-treated THP-1 and TLR4/MD2/CD14-transfected HEK-293T cells and the production of pro-inflammatory cytokines. In addition, in in vivo experiments, MD54 showed marked protection and survival of mice against LPS-induced inflammation and death. Overall, we have identified a short peptide with heptad repeat sequence from MD2 that can cause aggregation of LPS and abet in its internalization within THP-1 cells, resulting in attenuation of LPS-induced pro-inflammatory responses in vitro and in vivo.     

Electron diffraction of the metallic elements in the pineal organ of a freshwater fish, Mystus vittatus (Bloch.)

By electron diffraction pattern the presence of metallic elements, particularly chromium-nickel, chromium phosphide, copper, aluminum-copper and zinc has been shown in the pineal organ of a freshwater teleost, M. vittatus. It is likely that their occurrence within the pineal is due to binding with the neurosecretory material fractions/ligands.     

Histochemical localization of acetylcholinesterase in the glycogen body (sinus rhomboidalis) of common brown dove,Streptopelia senegalensis and house sparrow,Passer domesticus

Summary Acetylcholinesterase (AChE) activity was studied in the glycogen bodies of the spinal cords of 2 birds namelyStreptopelia senegalensis andPasser domesticus. A possible functional significance of AChE in the light of relative enzymatic localization especially in Hoffmann-Kolliker nuclei (motor cell groups), substantia gelatinosa and other regions of gray matter of 2 avian glycogen bodies has been discussed.     

A possible role of guanine-deaminase inhibitor

Zusammenfassung Diskussion über die Frage der Ätiologic der Xanthinurie.     

Structural basis of HutP-mediated anti-termination and roles of the Mg2+ ion and L-histidine ligand

HutP regulates the expression of the hut structural genes of Bacillus subtilis by an anti-termination mechanism and requires two components, Mg2+ ions and L-histidine. HutP recognizes three UAG triplet units, separated by four non-conserved nucleotides on the terminator region. Here we report the 1.60-A resolution crystal structure of the quaternary complex (HutP-L-histidine-Mg2+-21-base single-stranded RNA). In the complex, the RNA adopts a novel triangular fold on the hexameric surface of HutP, without any base-pairing, and binds to the protein mostly by specific protein-base interactions. The structure explains how the HutP and RNA interactions are regulated critically by the l-histidine and Mg2+ ion through the structural rearrangement. To gain insights into these structural rearrangements, we solved two additional crystal structures (uncomplexed HutP and HutP-L-histidine-Mg2+) that revealed the intermediate structures of HutP (before forming an active structure) and the importance of the Mg2+ ion interactions in the complexes.     

Seasonal dynamics of recurrent epidemics

Seasonality is a driving force that has a major effect on the spatio-temporal dynamics of natural systems and their populations. This is especially true for the transmission of common infectious diseases (such as influenza, measles, chickenpox and pertussis), and is of great relevance for host-parasite relationships in general. Here we gain further insights into the nonlinear dynamics of recurrent diseases through the analysis of the classical seasonally forced SIR (susceptible, infectious or recovered) epidemic model. Our analysis differs from other modelling studies in that the focus is more on post-epidemic dynamics than the outbreak itself. Despite the mathematical intractability of the forced SIR model, we identify a new threshold effect and give clear analytical conditions for predicting the occurrence of either a future epidemic outbreak, or a 'skip'-a year in which an epidemic fails to initiate. The threshold is determined by the population's susceptibility measured after the last outbreak and the rate at which new susceptible individuals are recruited into the population. Moreover, the time of occurrence (that is, the phase) of an outbreak proves to be a useful parameter that carries important epidemiological information. In forced systems, seasonal changes can prevent late-peaking diseases (that is, those having high phase) from spreading widely, thereby increasing population susceptibility, and controlling the triggering and intensity of future epidemics. These principles yield forecasting tools that should have relevance for the study of newly emerging and re-emerging diseases controlled by seasonal vectors.