Human Ability to Recognize Kin Visually Within Primates

The assessment of relatedness is a key determinant in the evolution of social behavior in primates. Humans are able to detect kin visually in their own species using facial phenotypes, and facial resemblance in turn influences both prosocial behaviors and mating decisions. This suggests that cognitive abilities that allow facial kin detection in conspecifics have been favored in the species by kin selection. We investigated the extent to which humans are able to recognize kin visually by asking human judges to assess facial resemblance in 4 other primate species (common chimpanzees, western lowland gorillas, mandrills, and chacma baboons) on the basis of pictures of faces. Humans achieved facial interspecific kin recognition in all species except baboons. Facial resemblance is a reliable indicator of relatedness in at least chimpanzees, gorillas, and mandrills, and future work should explore if the primates themselves also share the ability to detect kin facially.     

Acetylcholinesterase inhibitory guided fractionation of Melissa officinalis L.

The plant Melissa officinalis L. has been used traditionally in the treatment of cognitive dysfunction. Based on its traditional medicinal use, it was assessed for its clinical efficacy in mild to moderate Alzheimer’s patients. The plant was effective in the management of the disease. Therefore, based on this result, a similar plant extract was prepared in order to be screened for bioactivities which are relevant in Alzheimer’s disease therapy. The extract was recently screened for antioxidant activity and it showed a wide range of antioxidant properties. Another important bioactivity is acetylcholinesterase inhibition, which the extract was screened for in the current investigation. The extract was capable of inhibiting the enzyme in a time and dose-dependent manner. Activity of the extract at 10 min was estimated as 1.72 ± 0.16 μg equivalents of physostigmine/mg of the extract. Acetylcholinesterase inhibitory guided fractionation of the extract was then carried out. Most of the fractions showed inhibitory activity and were more potent than the extract. The contents of the most potent fraction were identified as cis- and trans-rosmarinic acid isomers and a rosmarinic acid derivative using LC-DAD-ESI-MS and NMR methods.     

The role of gamma A/gamma ' fibrinogen in plasma factor XIII activation

Factor XIII zymogen activation is a complex series of events that involve fibrinogen acting in several different roles. This report focuses on the role of fibrinogen as a cofactor in factor XIII activation by thrombin. We demonstrate that fibrinogen has two distinct activities that lead to an increased rate of factor XIII activation. First, the thrombin proteolytic activity is increased by fibrin. The cleavage rates of both a small chromogenic substrate and the factor XIII activation peptide are increased in the presence of either the major fibrin isoform, gammaA/gammaA fibrin, or a minor variant form, gammaA/gamma' fibrin. This enhancement of thrombin activity by fibrin is independent of fibrin polymerization and requires only cleavage of the fibrinopeptides. Subsequently, gammaA/gamma' fibrinogen accelerates plasma factor XIII activation by a non-proteolytic mechanism. This increased rate of activation results in a slightly more rapid cross-linking of fibrin gammaA and gamma' chains and a significantly more rapid cross-linking of fibrin alpha chain multimers. Together, these results show that although both forms of fibrin increase the rate of activation peptide cleavage by thrombin, gammaA/gamma' fibrinogen also increases the rate of factor XIII activation in a non-proteolytic manner. A revised model of factor XIII activation is presented below.     

Searching algorithm for type IV secretion system effectors 1.0: a tool for predicting type IV effectors and exploring their genomic context

Type IV effectors (T4Es) are proteins produced by pathogenic bacteria to manipulate host cell gene expression and processes, divert the cell machinery for their own profit and circumvent the immune responses. T4Es have been characterized for some bacteria but many remain to be discovered. To help biologists identify putative T4Es from the complete genome of α- and γ-proteobacteria, we developed a Perl-based command line bioinformatics tool called S4TE (searching algorithm for type-IV secretion system effectors). The tool predicts and ranks T4E candidates by using a combination of 13 sequence characteristics, including homology to known effectors, homology to eukaryotic domains, presence of subcellular localization signals or secretion signals, etc. S4TE software is modular, and specific motif searches are run independently before ultimate combination of the outputs to generate a score and sort the strongest T4Es candidates. The user keeps the possibility to adjust various searching parameters such as the weight of each module, the selection threshold or the input databases. The algorithm also provides a GC% and local gene density analysis, which strengthen the selection of T4E candidates. S4TE is a unique predicting tool for T4Es, finding its utility upstream from experimental biology.     

2, 5-Di(Tert-Butyl)-1, 4-Benzohydroquinone —A Novel Mobilizer Of The Inositol 1,4,5-Trisphosphate-Sensitive Ca2+ Pool

Isolated hepatocytes and the isolated perfused rat liver have been used to study the alterations of cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) produced by 2,5-di(tert-butyl)-l.4-benzohydroquinone (tBuBHQ), a potent inhibitor of hepatic microsomal Ca²⁺ sequestration (Moore. G.A., McConkey. D.J., Kass, G.E.N., OBrien, P.J. and Orrenius, S. FEBS Lett.,224, 331-336). (1987). Addition of tBuBHQ to isolated hepatocytes caused a rapid increase in [Ca²⁺]_i which was similar in magnitude to the [Ca²⁺]_i elevation induced by the Ca²⁺ mobilizing hormone, vasopressin. In contrast with vasopressin which caused a Ca²⁺ transient, tBuBHQ elevated [Ca²⁺]_i to a new steady state that was maintained for up to 15-20min. When vasopressin was administered during the tBuBHQ-induced period of elevated [Ca²⁺]_i. [Ca²⁺]_i, rapidly returned to basal levels. Similarly, if vasopressin was administered just prior to tBuBHQ, the resultant tBuBHQ-dependent change in [Ca²⁺]_i was transient. and not sustained. The hydroquinone mobilized the same intracellular Ca²⁺ pool as inositol 1,4,5-trisphosphate. but tBuBHQ did not produce any detectable inositol polyphosphate accumulation. IBuBHQ stimulated glucose release from perifused hepatocytes. mimicking the effect of vasopressin. In the perfused liver, tBuBHQ infusion produced a single, slow and prolonged release of Ca²⁺ into the perfusate and inhibition of subsequent vasopressin-induced Ca²⁺ effluxes. Inhibition of the response to vasopressin was reversed over time, and closely correlated with the extent of inhibition of both Ca²⁺ sequestration and (Ca²⁺-Mg²⁺)-ATPase activity in microsomes isolated from the isolated perfused liver. The present results are consistent with tBuBHQ inhibiting ATP-dependent Ca²⁺ sequestration by a direct effect on the endoplasmic reticular Ca²⁺ pump, which results in net Ca²⁺ release and elevation of [Ca²⁺]_i. Furthermore. vasopressin appears to stimulate active removal of increased [Ca²⁺] from the hepatocyte cytosol by a mechanism which does not depend on reuptake of Ca²⁺ into the endoplasmic reticulum

2,5-Di(tert-butyl) -l,4-benmhydroquinone. calcium. hepatocytes. perfused liver, endoplasmic reticulum     

The Platelet Integrin αIIbβ3 Differentially Interacts with Fibrin Versus Fibrinogen

Fibrinogen binding to the integrin αIIbβ3 mediates platelet aggregation and spreading on fibrinogen-coated surfaces. However, in vivo αIIbβ3 activation and fibrinogen conversion to fibrin occur simultaneously, although the relative contributions of fibrinogen versus fibrin to αIIbβ3-mediated platelet functions are unknown. Here, we compared the interaction of αIIbβ3 with fibrin and fibrinogen to explore their differential effects. A microscopic bead coated with fibrinogen or monomeric fibrin produced by treating the immobilized fibrinogen with thrombin was captured by a laser beam and repeatedly brought into contact with surface-attached purified αIIbβ3. When αIIbβ3-ligand complexes were detected, the rupture forces were measured and displayed as force histograms. Monomeric fibrin displayed a higher probability of interacting with αIIbβ3 and a greater binding strength. αIIbβ3-fibrin interactions were also less sensitive to inhibition by abciximab and eptifibatide. Both fibrinogen- and fibrin-αIIbβ3 interactions were partially inhibited by RGD peptides, suggesting the existence of common RGD-containing binding motifs. This assumption was supported using the fibrin variants αD97E or αD574E with mutated RGD motifs. Fibrin made from a fibrinogen γ′/γ′ variant lacking the γC αIIbβ3-binding motif was more reactive with αIIbβ3 than the parent fibrinogen. These results demonstrate that fibrin is more reactive with αIIbβ3 than fibrinogen. Fibrin is also less sensitive to αIIbβ3 inhibitors, suggesting that fibrin and fibrinogen have distinct binding requirements. In particular, the maintenance of αIIbβ3 binding activity in the absence of the γC-dodecapeptide and the α-chain RGD sequences suggests that the αIIbβ3-binding sites in fibrin are not confined to its known γ-chain and RGD motifs.