The problem of characters susceptible to parallel evolution in phylogenetic analysis: a reply to Marquès and Gnaspini (2001) with emphasis on cave life phenotypic evolution

Marquès and Gnaspini [Cladistics 17 (2001) 371–381] analyzed the problem of the phylogenetic treatment of characters submitted to parallel evolution. Their proposal aimed at preserving the potential phylogenetic significance of supposedly homoplastic characters and considering them for phylogeny reconstruction. As an example, they used the troglobiomorphic features of animals restricted to caves; according to their preliminary hypothesis of homoplasy, troglobitic animals would exhibit a particular phenotype, referred to as troglobiomorphic, which they would acquire under similar selective pressures from the subterranean environment. We examined Marquès and Gnaspini's approach not from the point of view of its technical flaws, but from the point of view of the authors’ basic assertions on the treatment of troglobiomorphic characters and more generally the inclusion/exclusion/transformation of characters prior to phylogenetic analysis. In the present paper, we argue that this approach is invalidated by the repeated use of ad hoc hypotheses, which are supported neither by an existing phylogenetic pattern nor by available data. We consequently contest the adequateness of this approach with a cladistic analysis of historical questions.     

Endocrine regulation of energy metabolism by the skeleton

The regulation of bone remodeling by an adipocyte-derived hormone implies that bone may exert a feedback control of energy homeostasis. To test this hypothesis we looked for genes expressed in osteoblasts, encoding signaling molecules and affecting energy metabolism. We show here that mice lacking the protein tyrosine phosphatase OST-PTP are hypoglycemic and are protected from obesity and glucose intolerance because of an increase in beta-cell proliferation, insulin secretion, and insulin sensitivity. In contrast, mice lacking the osteoblast-secreted molecule osteocalcin display decreased beta-cell proliferation, glucose intolerance, and insulin resistance. Removing one Osteocalcin allele from OST-PTP-deficient mice corrects their metabolic phenotype. Ex vivo, osteocalcin can stimulate CyclinD1 and Insulin expression in beta-cells and Adiponectin, an insulin-sensitizing adipokine, in adipocytes; in vivo osteocalcin can improve glucose tolerance. By revealing that the skeleton exerts an endocrine regulation of sugar homeostasis this study expands the biological importance of this organ and our understanding of energy metabolism.     

Thorezia vezerensisgen. et sp. nov., a new seed plant with multiovulate cupules from the Late Devonian of Belgium

The multiovulate cupule of a new spermatophyte, Thorezia vezerensisgen. et sp. nov., is described from the Late Devonian aged sediments from Trooz Quarry in Belgium. In gross morphology, it conforms to the Moresnetia morphotype and has a cupule that is composed of four independent quarters that each dichotomises three times. Each cupule quarter contains one single ovoid preovule with a long pedicel and an integument that has small apical teeth surrounding a rudimentary micropyle. Morphological variability in the materials examined is interpreted as being related to preovule maturity, and from this a good understanding of the ontogenetic development from preceding dispersal has been developed. Up to now, 17 spermatophyte species have been described, 11 of which come from eastern Laurussia. This diversity in eastern Laurussia contrasts strongly with the low diversity characterizing contemporaneous floras from other phytogeographical areas. We suggest here that the arid climatic conditions prevailing in eastern Laurussia favoured the development of diverse spermatophyte communities and contributed to reduced diversity and abundance of contemporaneous free-sporing plant diversity.     

Infections associated with monoclonal antibody and fusion protein therapy in humans

Monoclonal antibodies (mAbs), especially those that interact with immune or hematologic leukocyte membrane targets, have changed the outcome of numerous diseases. However, mAbs can block or reduce immune cells and cytokines, and can lead to increased risk of infection. Some of these risks are predictable and can be explained by their mechanisms of action. Others have been observed only after the mAbs were licensed and used extensively in patients. In this review, we focus on infectious complications that occur upon treatment with mAbs or Fc-containing fusion proteins targeting leukocyte membrane proteins, including CD52, CD20, tumor necrosis factor, VLA4, CD11a and CTLA4. We report their known infectious risks and the recommendations for their use. Although most of these drugs are clinically safe when the indications are respected, we emphasize the need for regular updating of pharmacovigilance data.Key words: monoclonal antibodies, infections, complication, human     

Selective inhibition of GluN2D-containing N-methyl-D-aspartate receptors prevents tissue plasminogen activator-promoted neurotoxicity both in vitro and in vivo

Background

Tau protein is the principal component of the neurofibrillary tangles found in Alzheimer's disease, where it is hyperphosphorylated on serine and threonine residues, and recently phosphotyrosine has been demonstrated. The Src-family kinase Fyn has been linked circumstantially to the pathology of Alzheimer's disease, and shown to phosphorylate Tyr18. Recently another Src-family kinase, Lck, has been identified as a genetic risk factor for this disease.

Results

In this study we show that Lck is a tau kinase. In vitro, comparison of Lck and Fyn showed that while both kinases phosphorylated Tyr18 preferentially, Lck phosphorylated other tyrosines somewhat better than Fyn. In co-transfected COS-7 cells, mutating any one of the five tyrosines in tau to phenylalanine reduced the apparent level of tau tyrosine phosphorylation to 25-40% of that given by wild-type tau. Consistent with this, tau mutants with only one remaining tyrosine gave poor phosphorylation; however, Tyr18 was phosphorylated better than the others.

Conclusions

Fyn and Lck have subtle differences in their properties as tau kinases, and the phosphorylation of tau is one mechanism by which the genetic risk associated with Lck might be expressed pathogenically.     

Anchorage of synthetic peptides onto liposomes via hydrazone and alpha-oxo hydrazone bonds. preliminary functional investigations

Synthetic peptidoliposomes have been designed and prepared according to a chemoselective ligation. Two aldehyde-functionalized lipidic anchors were synthesized and incorporated into the lipidic bilayers of unilamellar liposomes during their preparation. Complementary hydrazino acetyl peptides were synthesized on the solid phase using N,N',N'-tri(tert-butyloxycarbonyl)-hydrazino acetic acid and further coupled to the aldehyde groups displayed at the surface of the vesicles. Coupling yields were measured by amino acid hydrolysis following total acid hydrolysis. The ligation methodology proved superior to the simple insertion of lipopeptides, which was performed for comparison in terms of yields, implementation, and reproducibility. To check whether the grafted-peptides were accessible and functional, cytoplasmic sequences of LAMP protein (lysosomal associated membrane protein), which is involved in intracellular membrane trafficking, have been selected. Using this model, we demonstrated in vitro the specific interaction of the synthetic LAMP-peptidoliposomes with the cytoplasmic adaptor protein AP-3, a result that contributes to the understanding of protein sorting in cells. Thus, these results clearly indicate the usefulness of such peptidoliposomes, easily prepared by hydrazone chemoselective ligation, as a tool for biological investigation.     

Novel cell-penetrating alpha-keto-amide calpain inhibitors as potential treatment for muscular dystrophy

Dipeptide-derived alpha-keto-amide compounds with potent calpain inhibitory activity have been identified. These reversible covalent inhibitors have IC(50) values down to 25nM and exhibit greatly improved activity in muscle cells compared to the reference compound MDL28170. Several novel calpain inhibitors have shown positive effects on histological parameters in an animal model of Duchenne muscular dystrophy demonstrating their potential as a treatment option for this fatal disease.