HIV preferentially infects HIV-specific CD4+ T cells

HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.     

Failure to confirm NOTCH4 association with schizophrenia in a large population-based sample from Scotland

The NOTCH4 gene was recently reported to be associated with schizophrenia based on TDT analysis of 80 British trios. The strongest evidence for association derived from two microsatellites. We genotyped both loci in a large sample of unrelated Scottish schizophrenics and controls, but failed to replicate the reported association, finding instead that each putative schizophrenia-associated allele had a somewhat lower frequency in schizophrenics than in controls.     

Nitrogen fixation. Endocrine disrupters and flavonoid signalling

Nitrogen fixation is a symbiotic process initiated by chemical signals from legumes that are recognized by soil bacteria. Here we show that some endocrine-disrupting chemicals (EDCs), so called because of their effect on hormone-signalling pathways in animal cells, also interfere with the symbiotic signalling that leads to nitrogen fixation. Our results raise the possibility that these phytochemically activated pathways may have features in common with hormonal signalling in vertebrates, thereby extending the biological and ecological impact of EDCs.     

Direct observation of a submarine volcanic eruption from a sea-floor instrument caught in a lava flow

Our understanding of submarine volcanic eruptions has improved substantially in the past decade owing to the recent ability to remotely detect such events and to then respond rapidly with synoptic surveys and sampling at the eruption site. But these data are necessarily limited to observations after the event. In contrast, the 1998 eruption of Axial volcano on the Juan de Fuca ridge was monitored by in situ sea-floor instruments. One of these instruments, which measured bottom pressure as a proxy for vertical deformation of the sea floor, was overrun and entrapped by the 1998 lava flow. The instrument survived-being insulated from the molten lava by the solidified crust-and was later recovered. The data serendipitously recorded by this instrument reveal the duration, character and effusion rate of a sheet flow eruption on a mid-ocean ridge, and document over three metres of lava-flow inflation and subsequent drain-back. After the brief two-hour eruption, the instrument also measured gradual subsidence of 1.4 metres over the next several days, reflecting deflation of the entire volcano summit as magma moved into the adjacent rift zone. These findings are consistent with our understanding of submarine lava effusion, as previously inferred from seafloor observations, terrestrial analogues, and laboratory simulations.     

Early optical emission from the gamma-ray burst of 4 October 2002

Observations of the long-lived emission--or 'afterglow'--of long-duration gamma-ray bursts place them at cosmological distances, but the origin of these energetic explosions remains a mystery. Observations of optical emission contemporaneous with the burst of gamma-rays should provide insight into the details of the explosion, as well as into the structure of the surrounding environment. One bright optical flash was detected during a burst, but other efforts have produced negative results. Here we report the discovery of the optical counterpart of GRB021004 only 193 seconds after the event. The initial decline is unexpectedly slow and requires varying energy content in the gamma-ray burst blastwave over the course of the first hour. Further analysis of the X-ray and optical afterglow suggests additional energy variations over the first few days.     

An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus

Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.     

The speed of information in a 'fast-light' optical medium

One consequence of the special theory of relativity is that no signal can cause an effect outside the source light cone, the space-time surface on which light rays emanate from the source. Violation of this principle of relativistic causality leads to paradoxes, such as that of an effect preceding its cause. Recent experiments on optical pulse propagation in so-called 'fast-light' media--which are characterized by a wave group velocity upsilon(g) exceeding the vacuum speed of light c or taking on negative values--have led to renewed debate about the definition of the information velocity upsilon(i). One view is that upsilon(i) = upsilon(g) (ref. 4), which would violate causality, while another is that upsilon(i) = c in all situations, which would preserve causality. Here we find that the time to detect information propagating through a fast-light medium is slightly longer than the time required to detect the same information travelling through a vacuum, even though upsilon(g) in the medium vastly exceeds c. Our observations are therefore consistent with relativistic causality and help to resolve the controversies surrounding superluminal pulse propagation.     

A common origin for cosmic explosions inferred from calorimetry of GRB030329

Past studies have suggested that long-duration gamma-ray bursts have a 'standard' energy of E(gamma) approximately 10(51) erg in the ultra-relativistic ejecta, after correcting for asymmetries in the explosion ('jets'). But a group of sub-energetic bursts, including the peculiar GRB980425 associated with the supernova SN1998bw (E(gamma) approximately 10(48) erg), has recently been identified. Here we report radio observations of GRB030329 that allow us to undertake calorimetry of the explosion. Our data require a two-component explosion: a narrow (5 degrees opening angle) ultra-relativistic component responsible for the gamma-rays and early afterglow, and a wide, mildly relativistic component that produces the radio and optical afterglow more than 1.5 days after the explosion. The total energy release, which is dominated by the wide component, is similar to that of other gamma-ray bursts, but the contribution of the gamma-rays is energetically minor. Given the firm link of GRB030329 with SN2003dh, our result indicates a common origin for cosmic explosions in which, for reasons not yet understood, the energy in the highest-velocity ejecta is extremely variable.     

Microfluidic systems: high radial acceleration in microvortices

Microfluidic systems can conveniently be used for rapid analysis of biological samples. Here we describe a single re-circulating flow, or microvortex, that can generate a maximum fluid rotational velocity of up to 12 m s(-1) and a corresponding radial acceleration in excess of 10(6)g. Such microvortices may be exploited in centrifugal microdevices to investigate the effects of high radial acceleration on biological and chemical processes.