Epidemiological parameters of HIV transmission

Epidemiological data on the main determinants of the transmission potential of HIV-1 in specific at risk groups in slowly accumulating, but many uncertainties remain.     

Possible demographic consequences of AIDS in developing countries

Simple mathematical models of the transmission dynamics of HIV that incorporate demographic and epidemiological processes to assess the potential impact of AIDS on human population growth and structure in developing countries suggest that AIDS is capable of changing population growth rates from positive to negative values over timescales of a few decades. The disease is predicted to have little if any impact on the dependency ratio of a population, defined as the number of children below age 15 years and elderly people over 64 years, divided by the number of adults between 15 to 64 years.     

CHFR: a key checkpoint component implicated in a wide range of cancers

CHFR (Checkpoint with Forkhead-associated and RING finger domains) has been implicated in a checkpoint regulating entry into mitosis. However, the details underlying its roles and regulation are unclear due to conflicting lines of evidence supporting different notions of its functions. We provide here an overview of how CHFR is thought to contribute towards regulating mitotic entry and present possible explanations for contradictory observations published on the functions and regulation of CHFR. Furthermore, we survey key data showing correlations between promoter hypermethylation or down-regulation of CHFR and cancers, with a view on the likely reasons why different extents of correlations have been reported. Lastly, we explore the possibilities of exploiting CHFR promoter hypermethylation status in diagnostics and therapeutics for cancer patients. With keen interest currently focused on the association between hypermethylation of CHFR and cancers, details of how CHFR functions require further study to reveal how its absence might possibly contribute to tumorigenesis.     

Potential of community-wide chemotherapy or immunotherapy to control the spread of HIV-1

Whether zidovudine (3'-azido-3'-deoxythymidine, AZT) should be offered to symptomless individuals infected with human immunodeficiency virus type-1 (HIV-1), in the hope of delaying or even preventing progression to AIDS, has been much debated. The discussion has focused on the efficacy of the drug in delaying progression to disease, the severity of its side-effects, and the likelihood of its prolonged and widespread use resulting in zidovudine-resistant strains of the virus. Little attention has been given to the degree to which treatment reduces the infectiousness of symptomless patients, and to the concomitant implications for the overall transmission rate of HIV-1 in the community. Here we use simple mathematical models to show that community treatment with antiviral drugs or immunotherapies that lengthen the incubation period of AIDS without significantly reducing the infectiousness of treated individuals, can increase the rate at which HIV-1 infection spreads (which is fairly obvious) and can even, under certain circumstances, increase the AIDS-related death rate in the community (which is less obvious).     

Role for the nitrogenase MoFe protein alpha-subunit in FeMo-cofactor binding and catalysis

Two components constitute Mo-dependent nitrogenase (EC 1.18.6.1)--the Fe protein (a homodimer encoded by nifH) and the MoFe protein (an alpha 2 beta 2 tetramer encoded by nifDK). The MoFe protein provides the substrate-binding site and probably contains six prosthetic groups of two types--four Fe-S centres and two Fe- and Mo-containing cofactors. To determine the distribution and catalytic function of these metalloclusters, we and others are attempting to change the catalytic and spectroscopic features of nitrogenase by substituting specific amino acids targeted as potential metallocluster ligands, particularly those to the FeMo-cofactor, which is responsible for the biologically unique electron paramagnetic resonance signal (S = 3/2) of nitrogenase, and is believed to be the N2-reducing site. Here we describe mutant strains of Azotobacter vinelandii that have single amino-acid substitutions within the MoFe protein alpha-subunit. These substitutions alter both substrate-reduction properties and the unique electron paramagnetic resonance signal, indicating that the FeMo-cofactor is associated with both the alpha-subunit and the substrate-reducing site.     

全能选手 Mercedes B-Class

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