The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes

Although human immunodeficiency virus-1 (HIV-1) infects quiescent and proliferating CD4+ lymphocytes, the virus replicates poorly in resting T cells. Factors that block viral replication in these cells might help to prolong the asymptomatic phase of HIV infection; however, the molecular mechanisms that control this process are not fully understood. Here we show that Murr1, a gene product known previously for its involvement in copper regulation, inhibits HIV-1 growth in unstimulated CD4+ T cells. This inhibition was mediated in part through its ability to inhibit basal and cytokine-stimulated nuclear factor (NF)-kappaB activity. Knockdown of Murr1 increased NF-kappaB activity and decreased IkappaB-alpha concentrations by facilitating phospho-IkappaB-alpha degradation by the proteasome. Murr1 was detected in CD4+ T cells, and RNA-mediated interference of Murr1 in primary resting CD4+ lymphocytes increased HIV-1 replication. Through its effects on the proteasome, Murr1 acts as a genetic restriction factor that inhibits HIV-1 replication in lymphocytes, which could contribute to the regulation of asymptomatic HIV infection and the progression of AIDS.     

Mitochondrial remnant organelles of Giardia function in iron-sulphur protein maturation

Giardia intestinalis (syn. lamblia) is one of the most widespread intestinal protozoan pathogens worldwide, causing hundreds of thousands of cases of diarrhoea each year. Giardia is a member of the diplomonads, often described as an ancient protist group whose primitive nature is suggested by the lack of typical eukaryotic organelles (for example, mitochondria, peroxisomes), the presence of a poorly developed endomembrane system and by their early branching in a number of gene phylogenies. The discovery of nuclear genes of putative mitochondrial ancestry in Giardia and the recent identification of mitochondrial remnant organelles in amitochondrial protists such as Entamoeba histolytica and Trachipleistophora hominis suggest that the eukaryotic amitochondrial state is not a primitive condition but is rather the result of reductive evolution. Using an in vitro protein reconstitution assay and specific antibodies against IscS and IscU--two mitochondrial marker proteins involved in iron-sulphur cluster biosynthesis--here we demonstrate that Giardia contains mitochondrial remnant organelles (mitosomes) bounded by double membranes that function in iron-sulphur protein maturation. Our results indicate that Giardia is not primitively amitochondrial and that it has retained a functional organelle derived from the original mitochondrial endosymbiont.     

DNA details

Handy helpers in this week's issue include a dual-purpose device for vertical electrophoresis and electroblotting, a triple-tray gel box and news of a new patent sequence data bank.     

Peripheral organs control central neurogenesis in the leech

Interactions between developing nerve centres and peripheral targets are known to affect neuronal survival and thus regulate the adult number of neurons in many systems. Here we provide evidence that peripheral tissues can also influence cell numbers by stimulating the production of neurons. In the leech Hirudo medicinalis, there is a population of several hundred neurons that is found only in the two segmental ganglia that innervate the genitalia and which seem to be added gradually during post-embryonic maturation. By monitoring 5-bromo-2'-deoxyuridine incorporation immunohistochemically, we have now determined that these neurons are actually born late in embryogenesis, well after all other central neurons are born and after efferent and afferent projections are established between these ganglia and the periphery. Ablation of the male genitalia early in embryogenesis, or evulsion of the nerves that connect them to the ganglia, prevent the birth of these neurons. However, they fail to appear ectopically when male genitalia are transplanted to other segments, despite innervation by local ganglia. We conclude that the generation of the late-appearing neurons depends on a highly localized signal produced by the male genitalia, to which only the ganglia that normally innervate these organs have the capacity to respond.     

微纳米加工

纳米技术的发展对人类社会产生了巨大的影响。纳米技术在纳米尺度上运作，同时有实际用途。纳米加工作为伴随纳米技术产生的一个新型行业，包括利用原子和分子制成单品进而制作亚微米尺度构件和系统的所有方法。微纳米加工领域的科学家面临的最大挑战之一即利用扭转、铸造及钻孔等技术来生产微小构件。