Origin of AIDS: contaminated polio vaccine theory refuted

Despite strong evidence to the contrary, speculation continues that the AIDS virus, human immunodeficiency virus type 1 (HIV-1), may have crossed into humans as a result of contamination of the oral polio vaccine (OPV). This 'OPV/AIDS theory' claims that chimpanzees from the vicinity of Stanleyville--now Kisangani in the Democratic Republic of Congo--were the source of a simian immunodeficiency virus (SIVcpz) that was transmitted to humans when chimpanzee tissues were allegedly used in the preparation of OPV. Here we show that SIVcpz is indeed endemic in wild chimpanzees of this region but that the circulating virus is phylogenetically distinct from all strains of HIV-1, providing direct evidence that these chimpanzees were not the source of the human AIDS pandemic.     

Pilus chaperones represent a new type of protein-folding catalyst

Adhesive type 1 pili from uropathogenic Escherichia coli strains have a crucial role during infection by mediating the attachment to and potentially the invasion of host tissue. These filamentous, highly oligomeric protein complexes are assembled by the 'chaperone-usher' pathway, in which the individual pilus subunits fold in the bacterial periplasm and form stoichiometric complexes with a periplasmic chaperone molecule that is essential for pilus assembly. The chaperone subsequently delivers the subunits to an assembly platform (usher) in the outer membrane, which mediates subunit assembly and translocation to the cell surface. Here we show that the periplasmic type 1 pilus chaperone FimC binds non-native pilus subunits and accelerates folding of the subunit FimG by 100-fold. Moreover, we find that the FimC-FimG complex is formed quantitatively and very rapidly when folding of FimG is initiated in the presence of both FimC and the assembly-competent subunit FimF, even though the FimC-FimG complex is thermodynamically less stable than the FimF-FimG complex. FimC thus represents a previously unknown type of protein-folding catalyst, and simultaneously acts as a kinetic trap preventing spontaneous subunit assembly in the periplasm.     

Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks

Hindlimb loss has evolved repeatedly in many different animals by means of molecular mechanisms that are still unknown. To determine the number and type of genetic changes underlying pelvic reduction in natural populations, we carried out genetic crosses between threespine stickleback fish with complete or missing pelvic structures. Genome-wide linkage mapping shows that pelvic reduction is controlled by one major and four minor chromosome regions. Pitx1 maps to the major chromosome region controlling most of the variation in pelvic size. Pelvic-reduced fish show the same left-right asymmetry seen in Pitx1 knockout mice, but do not show changes in Pitx1 protein sequence. Instead, pelvic-reduced sticklebacks show site-specific regulatory changes in Pitx1 expression, with reduced or absent expression in pelvic and caudal fin precursors. Regulatory mutations in major developmental control genes may provide a mechanism for generating rapid skeletal changes in natural populations, while preserving the essential roles of these genes in other processes.     

Thymosin beta4 activates integrin-linked kinase and promotes cardiac cell migration, survival and cardiac repair

Heart disease is a leading cause of death in newborn children and in adults. Efforts to promote cardiac repair through the use of stem cells hold promise but typically involve isolation and introduction of progenitor cells. Here, we show that the G-actin sequestering peptide thymosin beta4 promotes myocardial and endothelial cell migration in the embryonic heart and retains this property in postnatal cardiomyocytes. Survival of embryonic and postnatal cardiomyocytes in culture was also enhanced by thymosin beta4. We found that thymosin beta4 formed a functional complex with PINCH and integrin-linked kinase (ILK), resulting in activation of the survival kinase Akt (also known as protein kinase B). After coronary artery ligation in mice, thymosin beta4 treatment resulted in upregulation of ILK and Akt activity in the heart, enhanced early myocyte survival and improved cardiac function. These findings suggest that thymosin beta4 promotes cardiomyocyte migration, survival and repair and the pathway it regulates may be a new therapeutic target in the setting of acute myocardial damage.     

Photosynthetic microbial mats in the 3,416-Myr-old ocean

Recent re-evaluations of the geological record of the earliest life on Earth have led to the suggestion that some of the oldest putative microfossils and carbonaceous matter were formed through abiotic hydrothermal processes. Similarly, many early Archaean (more than 3,400-Myr-old) cherts have been reinterpreted as hydrothermal deposits rather than products of normal marine sedimentary processes. Here we present the results of a field, petrographic and geochemical study testing these hypotheses for the 3,416-Myr-old Buck Reef Chert, South Africa. From sedimentary structures and distributions of sand and mud, we infer that deposition occurred in normal open shallow to deep marine environments. The siderite enrichment that we observe in deep-water sediments is consistent with a stratified early ocean. We show that most carbonaceous matter was formed by photosynthetic mats within the euphotic zone and distributed as detrital matter by waves and currents to surrounding environments. We find no evidence that hydrothermal processes had any direct role in the deposition of either the carbonaceous matter or the enclosing sediments. Instead, we conclude that photosynthetic organisms had evolved and were living in a stratified ocean supersaturated in dissolved silica 3,416 Myr ago.     

New light shed on the oldest insect

Insects are the most diverse lineage of all life in numbers of species, and ecologically they dominate terrestrial ecosystems. However, how and when this immense radiation of animals originated is unclear. Only a few fossils provide insight into the earliest stages of insect evolution, and among them are specimens in chert from Rhynie, Scotland's Old Red Sandstone (Pragian; about 396-407 million years ago), which is only slightly younger than formations harbouring the earliest terrestrial faunas. The most well-known animal from Rhynie is the springtail Rhyniella praecursor (Entognatha; Collembola), long considered to be the oldest hexapod. For true insects (Ectognatha), the oldest records are two apparent wingless insects from later in the Devonian period of North America. Here we show, however, that a fragmentary fossil from Rhynie, Rhyniognatha hirsti, is not only the earliest true insect but may be relatively derived within basal Ectognatha. In fact, Rhyniognatha has derived characters shared with winged insects, suggesting that the origin of wings may have been earlier than previously believed. Regardless, Rhyniognatha indicates that insects originated in the Silurian period and were members of some of the earliest terrestrial faunas.     

Evidence for dynamically organized modularity in the yeast protein-protein interaction network

In apparently scale-free protein-protein interaction networks, or 'interactome' networks, most proteins interact with few partners, whereas a small but significant proportion of proteins, the 'hubs', interact with many partners. Both biological and non-biological scale-free networks are particularly resistant to random node removal but are extremely sensitive to the targeted removal of hubs. A link between the potential scale-free topology of interactome networks and genetic robustness seems to exist, because knockouts of yeast genes encoding hubs are approximately threefold more likely to confer lethality than those of non-hubs. Here we investigate how hubs might contribute to robustness and other cellular properties for protein-protein interactions dynamically regulated both in time and in space. We uncovered two types of hub: 'party' hubs, which interact with most of their partners simultaneously, and 'date' hubs, which bind their different partners at different times or locations. Both in silico studies of network connectivity and genetic interactions described in vivo support a model of organized modularity in which date hubs organize the proteome, connecting biological processes--or modules--to each other, whereas party hubs function inside modules.     

Cell-cycle checkpoints and cancer

All life on earth must cope with constant exposure to DNA-damaging agents such as the Sun's radiation. Highly conserved DNA-repair and cell-cycle checkpoint pathways allow cells to deal with both endogenous and exogenous sources of DNA damage. How much an individual is exposed to these agents and how their cells respond to DNA damage are critical determinants of whether that individual will develop cancer. These cellular responses are also important for determining toxicities and responses to current cancer therapies, most of which target the DNA.