Ipr1 gene mediates innate immunity to tuberculosis

An estimated eight million people are infected each year with the pathogen Mycobacterium tuberculosis, and more than two million die annually. Yet only about 10% of those infected develop tuberculosis. Genetic variation within host populations is known to be significant in humans and animals, but the nature of genetic control of host resistance to tuberculosis remains poorly understood. Previously we mapped a new genetic locus on mouse chromosome 1, designated sst1 (for supersusceptibility to tuberculosis 1). Here we show that this locus mediates innate immunity in sst1 congenic mouse strains and identify a candidate gene, Intracellular pathogen resistance 1 (Ipr1), within the sst1 locus. The Ipr1 gene is upregulated in the sst1 resistant macrophages after activation and infection, but it is not expressed in the sst1 susceptible macrophages. Expression of the Ipr1 transgene in the sst1 susceptible macrophages limits the multiplication not only of M. tuberculosis but also of Listeria monocytogenes and switches a cell death pathway of the infected macrophages from necrosis to apoptosis. Our data indicate that the Ipr1 gene product might have a previously undocumented function in integrating signals generated by intracellular pathogens with mechanisms controlling innate immunity, cell death and pathogenesis.     

Sodium channel mutation leading to saxitoxin resistance in clams increases risk of PSP

Bivalve molluscs, the primary vectors of paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their capacity to accumulate PSP toxins (PSTs) which has a neural basis. PSTs cause human fatalities by blocking sodium conductance in nerve fibres. Here we identify a molecular basis for inter-population variation in PSP resistance within a species, consistent with genetic adaptation to PSTs. Softshell clams (Mya arenaria) from areas exposed to 'red tides' are more resistant to PSTs, as demonstrated by whole-nerve assays, and accumulate toxins at greater rates than sensitive clams from unexposed areas. PSTs lead to selective mortality of sensitive clams. Resistance is caused by natural mutation of a single amino acid residue, which causes a 1,000-fold decrease in affinity at the saxitoxin-binding site in the sodium channel pore of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans. Furthermore, global expansion of PSP to previously unaffected coastal areas might result in long-term changes to communities and ecosystems.     

Phyllosilicates on Mars and implications for early martian climate

The recent identification of large deposits of sulphates by remote sensing and in situ observations has been considered evidence of the past presence of liquid water on Mars. Here we report the unambiguous detection of diverse phyllosilicates, a family of aqueous alteration products, on the basis of observations by the OMEGA imaging spectrometer on board the Mars Express spacecraft. These minerals are mainly associated with Noachian outcrops, which is consistent with an early active hydrological system, sustaining the long-term contact of igneous minerals with liquid water. We infer that the two main families of hydrated alteration products detected-phyllosilicates and sulphates--result from different formation processes. These occurred during two distinct climatic episodes: an early Noachian Mars, resulting in the formation of hydrated silicates, followed by a more acidic environment, in which sulphates formed.     

In situ measurements of the physical characteristics of Titan's environment

On the basis of previous ground-based and fly-by information, we knew that Titan's atmosphere was mainly nitrogen, with some methane, but its temperature and pressure profiles were poorly constrained because of uncertainties in the detailed composition. The extent of atmospheric electricity ('lightning') was also hitherto unknown. Here we report the temperature and density profiles, as determined by the Huygens Atmospheric Structure Instrument (HASI), from an altitude of 1,400 km down to the surface. In the upper part of the atmosphere, the temperature and density were both higher than expected. There is a lower ionospheric layer between 140 km and 40 km, with electrical conductivity peaking near 60 km. We may also have seen the signature of lightning. At the surface, the temperature was 93.65 +/- 0.25 K, and the pressure was 1,467 +/- 1 hPa.     

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.     

Europe-wide reduction in primary productivity caused by the heat and drought in 2003

Future climate warming is expected to enhance plant growth in temperate ecosystems and to increase carbon sequestration. But although severe regional heatwaves may become more frequent in a changing climate, their impact on terrestrial carbon cycling is unclear. Here we report measurements of ecosystem carbon dioxide fluxes, remotely sensed radiation absorbed by plants, and country-level crop yields taken during the European heatwave in 2003. We use a terrestrial biosphere simulation model to assess continental-scale changes in primary productivity during 2003, and their consequences for the net carbon balance. We estimate a 30 per cent reduction in gross primary productivity over Europe, which resulted in a strong anomalous net source of carbon dioxide (0.5 Pg C yr(-1)) to the atmosphere and reversed the effect of four years of net ecosystem carbon sequestration. Our results suggest that productivity reduction in eastern and western Europe can be explained by rainfall deficit and extreme summer heat, respectively. We also find that ecosystem respiration decreased together with gross primary productivity, rather than accelerating with the temperature rise. Model results, corroborated by historical records of crop yields, suggest that such a reduction in Europe's primary productivity is unprecedented during the last century. An increase in future drought events could turn temperate ecosystems into carbon sources, contributing to positive carbon-climate feedbacks already anticipated in the tropics and at high latitudes.     

Physiological [Ca2+]i level and pump-leak turnover in intact red cells measured using an incorporated Ca chelator

The physiological actions of Ca2+ as a trigger and second messenger depend on the maintenance of large inward resting Ca2+ gradients across the cell plasma membrane. An ATP-fuelled Ca-pump, originally discovered and still best characterized in human red cells, is now believed to mediate resting Ca2+ extrusion in most animal cells. However, even in red cells, the truly physiological pump-leak turnover rate and cytoplasmic free Ca2+ level are unknown. Previous estimates were only very imprecise upper limits because normal intact red cells have a minute total pool of exchangeable Ca of less than 1 mumol 1 cells; Ca fluxes could not be measured without artificially increasing that pool with ionophores or disrupting the membrane to incorporate Ca buffers. Both procedures leave the membrane considerably leakier than in intact cells. Here, we have increased the exchangeable Ca pool by non-disruptively loading a Ca-chelator into intact cells, using intracellular hydrolysis of a membrane-permeant ester. The trapped chelator made the free cytoplasmic calcium concentration, [Ca2+]i, an easily defined function of directly measurable total cell Ca. We were then able to establish the physiological steady-state [Ca2+]i and pump-leak turnover rate of fresh cells suspended in their own plasma. If [Ca2+]i was lowered below the normal resting level, the Ca pump rate decreased according to the square of [Ca2+]i, and the inward Ca leak increased. The increase in leak did not develop if the cells were depleted of ATP and ADP.     

Effect of daily parenteral injection of betamethasone on histamine concentration of gastric tissue in albino rats

Summary Gastric tissue histamine concentration was determined in albino rats following daily parenteral injection of betamethasone over a period of 12 days. The result shows a highly significant fall in gastric tissue histamine concentration in comparison with that in saline-treated albino rats over a similar period.This investigation was carried out as a part of a project supported by a research grant from Medical Research Centre, Bombay Hospital Trust, Bombay, India.