Hyperlipidemia offers protection against Leishmania donovani infection: role of membrane cholesterol

Leishmania donovani (LD), the causative agent of visceral leishmaniasis (VL), extracts membrane cholesterol from macrophages and disrupts lipid rafts, leading to their inability to stimulate T cells. Restoration of membrane cholesterol by liposomal delivery corrects the above defects and offers protection in infected hamsters. To reinforce further the protective role of cholesterol in VL, mice were either provided a high-cholesterol (atherogenic) diet or underwent statin treatment. Subsequent LD infection showed that an atherogenic diet is associated with protection, whereas hypocholesterolemia due to statin treatment confers susceptibility to the infection. This observation was validated in apolipoprotein E knockout mice (AE) mice that displayed intrinsic hypercholesterolemia with hepatic granuloma, production of host-protective cytokines, and expansion of antileishmanial CD8⁺IFN- γ ⁺ and CD8⁺IFN- γ ⁺TNF- α ⁺ T cells in contrast to the wild-type C57BL/6 (BL/6) mice when infected with LD. Normal macrophages from AE mice (N-AE-M ϕ) showed 3-fold higher membrane cholesterol coupled with increased fluorescence anisotropy (FA) compared with wild-type macrophage (N-BL/6-M ϕ). Characterization of in vitro LD-infected AE macrophage (LD-AE-M ϕ) revealed intact raft architecture and ability to stimulate T cells, which were compromised in LD-BL/6-Mϕ. This study clearly indicates that hypercholesterolemia, induced intrinsically or extrinsically, can control the pathogenesis of VL by modulating immune repertoire in favor of the host.     

Synthesis, characterization, electrochemical and magnetic studies on manganese(III) complexes involving bridging carboxylates

A series of carboxylate-bridged manganese(III) complexes derived from Schiff bases obtained by the condensation of salicylaldehyde or 5-bromo-salicylaldehyde and different types of diamine have been synthesized and characterized and, in the case of [Mn₂(L1)₂(μ-ClCH₂COO)](ClO₄) (1), the structure has been obtained by X-ray crystallography. The structure of 1 consists of two manganese atoms separated by 5.487(3) Å and bridged by a carboxylate anion. This dinuclear structural unit is linked by bridging phenoxy oxygens to adjacent dinuclear units to produce a one-dimensional chain. Cyclic voltammograms of all the compounds exhibit grossly similar features consisting of a reversible or quasi-reversible Mn^III/Mn^II reduction and a Mn^III/Mn^IV oxidation. It has been observed that bromo-substitution stabilizes the lower oxidation state in the Mn^III/Mn^II couple and destabilizes the higher oxidation state in the Mn^III/Mn^IV couple. Variable temperature magnetic susceptibility measurements of 1 show a weak antiferromagnetic interaction. The magnetic behavior is satisfactorily modeled by inclusion of zero-field splitting and an intermolecular interaction component.     

Harmful algal blooms: combining excitability and competition

Harmful algal blooms (HABs) characterized by a large concentration of toxic species appear rather rarely, but have a severe impact on the whole ecosystem. To study on possible trigger mechanisms for the emergence of HABs, we consider a nutrient-phytoplankton-zooplankton model to find the conditions under which a toxic phytoplankton species is able to form a bloom by winning the competition against its nontoxic competitor. The basic mechanism is related to the excitability of the system, i.e., the ability to develop a large response on certain perturbations. In a large class of models, a HAB results from a combined effect of nutrient enrichment and selective predation on different phytoplankton populations by zooplankton. We show that the severity of HAB is controlled by nutrient enrichment and zooplankton abundance, while the frequency of its occurrence depends on the strength of selectivity of predation. Thereby the intricate interplay between excitability, competition, and selective grazing pressure builds the backbone of the mechanism of the emergence of HABs.     

Systematic revision and palaeobiogeography of Perisphinctes Waagen (Ammonoidea) from the Oxfordian of Kutch,India: Stratigraphic and evolutionary implications

Perisphinctes Waagen, 1869 is an important genus of the Oxfordian. In many areas the taxon has been excessively and subjectively split. Based on the material collected in Kutch (India), including the type specimens, we have grouped eight species previously described as distinct into one biological species, Perisphinctes indogermanus Waagen, 1875. It is characterized by strong sexual dimorphism. Macroconch shows high intraspecific variability. Microconch is previously described from Kutch in different generic names. Thirteen species of Dichotomosphinctes Buckman, 1926, Perisphinctes Waagen, 1869 and Lithacoceras Hyatt, 1900 are considered here as microconch which is lappeted. The precise age of P. indogermanus is disputed. A detailed stratigraphic analysis of several sections in this study suggests that the species ranges from early to middle Oxfordian. Perisphinctes indogermanus is distinct from other contemporary species of the world and abundant in the Indo-Madagascan Province. Kutch population of P. indogermanus has developed virgatotome style of ribbing in juvenile stage. During the middle Oxfordian marine transgression, the species along with many other ammonites of deeper habitat of the mainland basin reached the shallow shelf of eastern fringe of the Kutch Sea. Being peripherally isolated, it soon underwent an adaptive radiation that resulted in the origination of a new family Ataxioceratidae Buckman, 1921 whose members have neotenously retained the virgatotome ribbing in adult stage. The ataxioceratids later migrated to Europe and flourished during the Kimmeridgian.     

Synthesis, X-ray crystal structures and spectroscopic properties of two Ni(II) complexes of pyridoxal Schiff’s bases with diamines: Importance of steric factor in stabilization of water helices in the lattices of metal complex

Two Ni(II) complexes of the ligands N,N′-dipyridoxylethylenediimine (L₁H₂) and N,N′-dipyridoxyl-1,3-propanediimine (L₂H₂) were synthesized and their structures were determined by X-ray crystallography. The complexes are of formula Ni(L₁). 3H₂O (1·3H₂O) and Ni(L₂) (2). Both the complexes were found to be luminescent, but the quantum yields are significantly low compared to those of free ligands or their Zn(II) complexes. In 1·3H₂O the metallo-organic fragment forms a staircase like network and three water molecules occupy the void space created by the staircase like network. The water molecules are strongly H-bonded between themselves forming a helical chain along ‘b’ axis. Complex 2, in spite of having same number of hydrogen bonding sites as that of 1, can not accommodate water clusters in their lattice. It is argued, that small steric factors, which may affect conformations of the hydrogen donor/acceptor sites, plays an important role in stabilization of water helices in lattices of metal complex.     

Synthesis and spectroscopic properties of Ni(II) complexes of some aroyl hydrazone ligands with 2,6-diacetyl pyridine monooxime: X-ray crystal structure of the salicyloylhydrazone Ni(II) complex

Five Ni(II) complexes of aroyl hydrazone ligands with 2,6-diacetyl pyridine monooxime are reported. X-ray crystal structure of the Ni(II) salicyloylhydrazone complex is also reported. In these complexes Ni(II) is in a distorted octahedral N₄O₂ coordination environment, with each of the two ligands coordinating through the pyridine nitrogen, imino-hydrazone nitrogen and the deprotonated oxygen of the hydrazone moiety. The iminooxime group remain uncoordinated in both the ligands and the planes containing the CH₃-CN-OH groups are orthogonal to the adjacent pyridine rings. On excitation at 375 nm, the ligands as well as the Ni(II) complexes, show luminescence. However, the Ni(II) complexes have much lower quantum yield of emission than the free ligands.     

Virulence attenuation of a UDP-galactose/<Emphasis Type="Italic">N</Emphasis>-acetylglucosamine β1,4 galactosyltransferase expressing <Emphasis Type="Italic">Leishmania donovani</Emphasis> promastigote

Protozoan parasites of the genus Leishmania are the causative agent of leishmaniasis, a disease whose manifestations in humans range from mild cutaneous lesions to fatal visceral infections. Human visceral leishmaniasis is caused by Leishmania donovani. Long-term culture in vitro leads to the attenuation of the parasite. This loss of parasite virulence is associated with the expression of a developmentally regulated UDP-Galactose/N-acetylglucosamine beta 1-4 galactosyltransferase and galactose terminal glycoconjugates as determined by their agglutination with the pea nut agglutinin (PNA). Thus, all promastigotes passaged for more than 11 times were 100% agglutinated with PNA, and represent a homogeneous population of avirulent parasites. Identical concentrations of PNA failed to agglutinate promastigotes passaged for < or =5 times. These PNA(-) promastigotes were virulent. Promastigotes passaged from 5 to 10 times showed a mixed population. The identity of populations defined by virulence and PNA agglutination was confirmed by isolating PNA(+) avirulent and PNA(-) virulent clones from the 7th passage promastigotes. Only the PNA(+) clones triggered macrophage microbicidal activity. The PNA(+) clones lacked lipophosphoglycan. Intravenous administration of [(14)C] galactose-labeled parasite in BALB/c mice resulted in rapid clearance of the parasite from blood with a concomitant accumulation in the liver. By enzymatic assay and RT-PCR we have shown the association of a UDP-Galactose/N-acetylglucosamine beta1,4 galactosyltransferase with only the attenuated clones. By immunofluorescence we demonstrated that the enzyme is located in the Golgi apparatus. By western blot analysis and SDS-PAGE of the affinity-purified protein, we have been able to identify a 29 KDa galactose terminal protein from the avirulent clones.     

Self-regulation of rat liver GAP junction by phosphorylation

We have studied the functioning of rat liver Connexin 32 (C x 32) at the single channel level in presence of ATP. It was observed that ATP regulates the functioning of the channel by running down the junctional conductance. A non-specific exogenous protein phosphatase (alkaline phosphatase) reversed the rundown of junctional activity to its normal functioning state. Autoradiograhic studies demonstrate autophosphorylation of rat liver C x 32. These findings indicate a self-regulatory mechanism of the channel.