Telomere induced senescence: end game signaling

The telomere-based model of cell aging has proven to among been among the most enduring hypotheses in cell biology. This model, suggesting that the gradual loss of telomere sequences during the proliferation of cultured human somatic cells imposes a barrier on cellular replicative potential, has been strongly supported by recent genetic and biochemical studies. In addition, evidence implicating telomere dynamics in organismal ageing and cancer progression in vivo suggest that such a process is likely to have considerable physiological relevance in homeostasis and disease. What is the sensing mechanism for shortened telomeres and what is the molecular basis for the ensuing checkpoint response? Moreover, what is the outcome when such failsafe mechanisms are lost? Here we will review the signaling pathways that are induced by alterations in telomere length and integrity and illustrate how these processes provoke downstream effects on cell proliferation and survival. In addition, we discuss how the telomere-induced pathways intersect with the DNA damage response and document how the failure in either process results in unrestrained chromosomal instability.     

Synthesis of demethylxanthohumol, a new potent apoptosis-inducing agent from hops

Starting from commercially available phloracetophenone (= 1-(2,4,6-trihydroxyphenyl)ethanone), we synthesized demethylxanthohumol (4), a derivative of xanthohumol, devoid of 6'-O-methyl group. Both are prenylchalcones derived from hops (Humulus lupulus). The synthesis was accomplished by an aldol condensation between MOM-protected acetophenone 2 and MOM-protected benzaldehyde 3. The resulting demethylxanthohumol (4) displayed antiproliferative properties. Demethylxanthohumol (4) induced also apoptosis via the mitochondrial pathway in BJAB cells (Burkitt lymphoma cell line) and in primary lymphoblasts of childhood acute lymphoblastic leukemia (ALL).     

Sex-linked differentiation between incipient species of Anopheles gambiae

Emerging species within the primary malaria vector Anopheles gambiae show different ecological preferences and significant prezygotic reproductive isolation. They are defined by fixed sequence differences in X-linked rDNA, but most previous studies have failed to detect large and significant differentiation between these taxa elsewhere in the genome, except at two other loci on the X chromosome near the rDNA locus. Hypothesizing that this pericentromeric region of the X chromosome may be accumulating differences faster than other regions of the genome, we explored the pattern and extent of differentiation between A. gambiae incipient species and a sibling species, A. arabiensis, from Burkina Faso, West Africa, at 17 microsatellite loci spanning the X chromosome. Interspecific differentiation was large and significant across the entire X chromosome. Among A. gambiae incipient species, we found some of the highest levels of differentiation recorded in a large region including eight independent loci near the centromere of the X chromosome. Outside of this region, no significant differentiation was detected. This pattern suggests that selection is playing a role in the emergence of A. gambiae incipient species. This process, associated with efficient exploitation of anthropogenic modifications to the environment, has public health implications as it fosters the spread of malaria transmission both spatially and temporally.     

Loss of in vitro metal ion binding specificity in mutant copper-zinc superoxide dismutases associated with familial amyotrophic lateral sclerosis

The presence of the copper ion at the active site of human wild type copper-zinc superoxide dismutase (CuZnSOD) is essential to its ability to catalyze the disproportionation of superoxide into dioxygen and hydrogen peroxide. Wild type CuZnSOD and several of the mutants associated with familial amyotrophic lateral sclerosis (FALS) (Ala(4) --> Val, Gly(93) --> Ala, and Leu(38) --> Val) were expressed in Saccharomyces cerevisiae. Purified metal-free (apoproteins) and various remetallated derivatives were analyzed by metal titrations monitored by UV-visible spectroscopy, histidine modification studies using diethylpyrocarbonate, and enzymatic activity measurements using pulse radiolysis. From these studies it was concluded that the FALS mutant CuZnSOD apoproteins, in direct contrast to the human wild type apoprotein, have lost their ability to partition and bind copper and zinc ions in their proper locations in vitro. Similar studies of the wild type and FALS mutant CuZnSOD holoenzymes in the "as isolated" metallation state showed abnormally low copper-to-zinc ratios, although all of the copper acquired was located at the native copper binding sites. Thus, the copper ions are properly directed to their native binding sites in vivo, presumably as a result of the action of the yeast copper chaperone Lys7p (yeast CCS). The loss of metal ion binding specificity of FALS mutant CuZnSODs in vitro may be related to their role in ALS.     

Individual colour patches as multicomponent signals

Colour patches are complex traits, the components of which may evolve independently through a variety of mechanisms. Although usually treated as simple, two-dimensional characters and classified as either structural or pigmentary, in reality colour patches are complicated, three-dimensional structures that often contain multiple pigment types and structural features. The basic dermal chromatophore unit of fishes, reptiles and amphibians consists of three contiguous cell layers. Xanthophores and erythrophores in the outermost layer contain carotenoid and pteridine pigments that absorb short-wave light; iridophores in the middle layer contain crystalline platelets that reflect light back through the xanthophores; and melanophores in the basal layer contain melanins that absorb light across the spectrum. Changes in any one component of a chromatophore unit can drastically alter the reflectance spectrum produced, and for any given adaptive outcome (e.g. an increase in visibility), there may be multiple biochemical or cellular routes that evolution could take, allowing for divergent responses by different populations or species to similar selection regimes. All of the mechanisms of signal evolution that previously have been applied to single ornaments (including whole colour patches) could potentially be applied to the individual components of colour patches. To reach a complete understanding of colour patch evolution, however, it may be necessary to take an explicitly multi-trait approach. Here, we review multiple trait evolution theory and the basic mechanisms of colour production in fishes, reptiles and amphibians, and use a combination of computer simulations and empirical examples to show how multiple trait evolution theory can be applied to the components of single colour patches. This integrative perspective on animal colouration opens up a host of new questions and hypotheses. We offer specific, testable functional hypotheses for the most common pigmentary (carotenoid, pteridine and melanin) and structural components of vertebrate colour patches.     

Diet is the primary determinant of bacterial community structure in the guts of higher termites

The gut microbiota of termites plays critical roles in the symbiotic digestion of lignocellulose. While phylogenetically ‘lower termites’ are characterized by a unique association with cellulolytic flagellates, higher termites (family Termitidae) harbour exclusively prokaryotic communities in their dilated hindguts. Unlike the more primitive termite families, which primarily feed on wood, they have adapted to a variety of lignocellulosic food sources in different stages of humification, ranging from sound wood to soil organic matter. In this study, we comparatively analysed representatives of different taxonomic lineages and feeding groups of higher termites to identify the major drivers of bacterial community structure in the termite gut, using amplicon libraries of 16S rRNA genes from 18 species of higher termites. In all analyses, the wood‐feeding species were clearly separated from humus and soil feeders, irrespective of their taxonomic affiliation, offering compelling evidence that diet is the primary determinant of bacterial community structure. Within each diet group, however, gut communities of termites from the same subfamily were more similar than those of distantly related species. A highly resolved classification using a curated reference database revealed only few genus‐level taxa whose distribution patterns indicated specificity for certain host lineages, limiting any possible cospeciation between the gut microbiota and host to short evolutionary timescales. Rather, the observed patterns in the host‐specific distribution of the bacterial lineages in termite guts are best explained by diet‐related differences in the availability of microhabitats and functional niches.     

Experimental Analysis of E2BB (LTIIb) Signal Peptide in Secretory Production of Reteplase in Escherichia coli

International Journal of Peptide Research and Therapeutics - Recombinant reteplase is the truncated form of tissue plasminogen activator. Signal peptides play a pivotal role in the secretion of...