Targeting TRAIL

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as Apo2L, has been investigated in the past decade for its promising anticancer activity due to its ability to selectively induce apoptosis in tumoral cells by binding to TRAIL receptors (TRAIL-R). Macromolecules such as agonistic monoclonal antibodies and recombinant TRAIL have not proven efficacious in clinical studies, therefore several small molecules acting as TRAIL-R agonists are emerging in the scientific literature. In this work we focus on systemizing these drug molecules described in the past years, in order to better understand and predict the requirements for a novel anti-tumoral therapy based on the TRAIL-R-induced apoptotic mechanism.     

Concentration-dependent differential induction of necrosis or apoptosis by HIV-1 lytic peptide 1

The mechanism by which human immunodeficiency virus type 1 induces depletion of CD4+ T-lymphocytes remains controversial, but may involve cytotoxic viral proteins. Synthetic peptides (lentivirus lytic peptide type 1) corresponding to the carboxyl terminus of the human immunodeficiency virus type 1 transmembrane glycoprotein induce cytopathology at concentrations of 100 nM and above. At these concentrations lentivirus lytic peptide type 1 disrupts mitochondrial integrity of CD4+ T-lymphoblastoid cells and induces other changes characteristic of necrosis. In contrast, at concentrations of 20 nM, lentivirus lytic peptide type 1 potently induces apoptosis. Thus, the mechanism by which human immunodeficiency virus type 1 mediates cell death, necrosis or apoptosis, may depend, in part, on the tissue concentration of transmembrane glycoprotein.     

Evaluation of Holocene pollen records from the Romanian Plain

This study is a critical review of pollen analyses carried out on Holocene sequences from 15 sites in and near the Romanian Plain. Three sites come from natural sediments, 10 sites are from anthropogenic deposits and two are from both anthropogenic and natural settings. The general reconstruction is of a steppe-forest-steppe vegetation through the Holocene. The nature of the deposits, however, casts doubts on this reconstruction. Deposits of archaeological sites generally yield pollen spectra that are influenced by human activities and thus unsuitable for vegetation reconstructions. Loess deposits are also unfavorable for pollen preservation because of high pH and porosity. Consequently, pollen spectra from loess deposits are strongly biased by selective pollen destruction. Research and experiments carried out by several authors suggest that spectra dominated by Asteraceae, Poaceae, Chenopodiaceae or Pinus pollen in soils and loess are a result of selective pollen destruction, especially if low pollen concentrations, progressive pollen deterioration or high frequencies of deteriorated or unidentifiable pollen are evidenced. The fact that pollen records from the Romanian Plain come from loess, alkaline peat or archaeological sites reduces their reliability for reconstructions of vegetation. The vegetation history of similar regions in Hungary, Bulgaria and Turkey suggests that early Holocene steppe vegetation was gradually replaced by forest or forest-steppe vegetation in the late Holocene. Records from lake sediments are required to find out whether the Holocene vegetation history of the Romanian Plain was similar.     

Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson's disease

Tyrosinase is a key enzyme in the synthesis of melanin in skin and hair and has also been proposed to contribute to the formation of neuromelanin (NM). The presence of NM, which is biochemically similar to melanin in peripheral tissues, identifies groups of neurons susceptible in Parkinson's disease (PD). Whether tyrosinase is beneficial or detrimental to neurons is unclear; whilst the enzyme activity of tyrosinase generates dopamine-quinones and other oxidizing compounds, NM may form a sink for such radical species. In the present study, we demonstrated that tyrosinase is expressed at low levels in the human brain. We found that mRNA, protein and enzyme activity are all present but at barely detectable levels. In cell culture systems, expression of tyrosinase increases neuronal susceptibility to oxidizing conditions, including dopamine itself. We related these in vitro observations to the human disease by assessing whether there was any genetic association between the gene encoding tyrosinase and idiopathic PD. We found neither genotypic or haplotypic association with three polymorphic markers of the gene. This argues against a strong genetic association between tyrosinase and PD, although the observed contribution to cellular toxicity suggests that a biochemical association is likely.