Elucidating the Population Histories and Transmission Dynamics of Papillomaviruses Using Phylogenetic Trees

Using gene genealogies constructed from gene sequence data, we show that both the mucosal and cutaneous papillomaviruses (PV)—supergroups A and B—appear to have been transmitted through susceptible populations faster than exponentially. The data and methods involved (1) examining the PV database for phylogenetic signal in an L1 open reading frame (ORF) fragment and an E1 ORF segment, (2) demonstrating that the same two fragments have evolved in a way consistent with a molecular clock, and (3) applying methods of phylogenetic tree analysis that test different scenarios for the dynamics of viral transmission within populations. The results indicate increases in PV populations of both supergroups A and B in the recent past. This form of the increases, which fit a null model of population growth with an exponent increasing in time, is compatible with the fact that human populations have grown at a faster than exponential rate, thus increasing the numbers of susceptible hosts for HPVs. There are, however, indications that the population of supergroup A has now stopped increasing in size. Received: 4 June 1996 / Accepted: 12 August 1996     

Microsatellite loci to assess genetic variation in Tor putitora

Seven polymorphic microsatellite DNA loci were identified in golden mahseer, Tor putitora, through cross‐species amplification. Thirty‐two primers developed for three cyprinid fishes were tested in the study. The genetic variation detected at each microsatellite locus in T. putitora specimens (n = 107), collected from three different rivers and one lake was assessed. The allele frequencies deviated significantly from that expected under Hardy–Weinberg equilibrium. The mean observed heterozygosity values ranged from 0.29 to 0.40. Significant genotype heterogeneity indicated that the samples were not drawn from the same gene pool. The results indicate that the identified microsatellite loci exhibit promise for use in fine scale population structure analyses of T. putitora.     

Decreased DNA repair in familial Alzheimer's disease

Alterations in the capacity of a cell to repair DNA lesions play an important role in a number of human diseases. We and others have demonstrated defective DNA repair of alkylation damage in cells from patients with Alzheimer's disease. It has been hypothesized that this defect is related to the cause of Alzheimer's disease and results in the accumulation of lesions in the central nervous system neurons. One prediction of this hypothesis is that in dominantly inherited Alzheimer's disease, the repair defect will be present in half of the offspring of affected patients long before they develop symptoms of the disease. In order to test the hypothesis that decreased DNA repair is responsible for familial Alzheimer's disease and their at-risk offspring we have studied DNA repair in these individuals after exposure of lymphoblasts to alkylating agents. Our results indicate that cell lines from affected patients repair significantly less damage in 3 h than cell lines from healthy controls. A small number of at-risk individuals were also studied and some of these had lower levels of repair, although more cell lines from individuals in this group must be studied. These findings provide further support for defective DNA repair playing a role in the pathogenesis of Alzheimer's disease.     

Randia retroflexa (Rubiaceae), a new species from southern Mexico

A new species of Rubiaceae,Randia retroflexa, is described and illustrated from Veracruz, Oaxaca, and Chiapas in southern Mexico. An armed canopy vine of lowland and lower montane tropical evergreen forest, it is distinguished by its paired reflexed spines and hirsute pubescence. Its distribution, habitat, and specimen citations are given and affinities are discussed.     

Two flavonoid glycosides from the bark of Prosopis juliflora

Two new glycosides, kaempferol 4′-methyl ether 3-O-β-d-galactopyranoside and retusin 7-O-neohesperidoside, have been characterized from the stem bark of Prosopis juliflora.     

The effects of insulin and tunicamycin on insulin receptors of cultured fibroblasts

The effect of down-regulation on the intracellular pool of insulin receptors and the role of glycosylation in recovery from down-regulation have been studied in fibroblastic cultures from the skin of non-diabetic mice. In control cultures, 55% of the total specific [¹²⁵I]insulin-binding activity was in the intracellular compartment. Insulin caused a time- and concentration-dependent decrease in the number of cell surface insulin receptors, with no significant change in total insulin receptors. This decrease in surface receptors was accompanied by an increase in the specific binding of [¹²⁵I]insulin in the intracellular compartment. Removal of insulin from down-regulated cells resulted in a time-dependent increase in the binding of [¹²⁵I]insulin to surface receptors, reaching 90% of that in controls by 12 h. The recovery of surface insulin receptors after removal of insulin was blocked by incubation of cultures with tunicamycin, but not by cycloheximide. These results indicate that down-regulation of surface insulin receptors by insulin is associated with translocation of receptors into the intracellular pool and suggest that protein glycosylation is important in insulin receptor recycling and externalization.     

Dynamics of Physical Interaction between HIV-1 Nef and ASK1: Identifying the Interacting Motif(S)

FasL mediated preferential apoptosis of bystander CTLs while protection of infected CD4⁺T cells remains one of the hallmarks of immune evasion during HIV infection. The property of infected host cells to evade cell-autonomous apoptosis emanates from ability of HIV-1Nef -protein to physically interact with ASK-1 and thereby inhibit its enzymatic activity. The specific domains of HIV-1Nef through which it may interact with ASK1 and thereby impair the ASK1 activity remain unidentified so far and represent a major challenge towards developing clear understanding about the dynamics of this interaction. Using mammalian two hybrid screen in association with site directed mutagenesis and competitive inhibitor peptides, we identified constituent minimal essential domain (152 DEVGEANN 159) through which HIV-1Nef interacts with ASK1 and inhibits its function. Furthermore our study also unravels a novel alternate mechanism underlying HIV-1 Nef mediated ASK1 functional modulation, wherein by potentiating the inhibitory ser⁹⁶⁷ phosphorylation of ASK1, HIV-1Nef negatively modulated ASK1function.     

Current advances and future prospects in production of recombinant insulin and other proteins to treat diabetes mellitus

Biotechnology Letters - Diabetes mellitus is the most prevalent deadly disease caused by the destruction and dysfunction of pancreatic β cells that consequentially increased blood glucose...