Mars' volatile and climate history.

There is substantial evidence that the martian volatile inventory and climate have changed markedly throughout the planet's history. Clues come from areas as disparate as the history and properties of the deep interior, the composition of the crust and regolith, the morphology of the surface, composition of the present-day atmosphere, and the nature of the interactions between the upper atmosphere and the solar wind. We piece together the relevant observations into a coherent view of the evolution of the martian climate, focusing in particular on the observations that provide the strongest constraints.     

A massive cloud of cold atomic hydrogen in the outer Galaxy.

A large fraction of the mass of the interstellar medium in our Galaxy is in the form of warm (103-104 K) and cool (50-100 K) atomic hydrogen (H i) gas. Cold (10-30 K) regions are thought to be dominated by dense clouds of molecular hydrogen. Cold H i is difficult to observe, and therefore our knowledge of its abundance and distribution in the interstellar medium is poor. The few known clouds of cold H i are much smaller in size and mass than typical molecular clouds. Here we report the discovery that the H i supershell GSH139-03-69 is very cold (10 K). It is about 2 kiloparsecs in size and as massive as the largest molecular complexes. The existence of such an immense structure composed of cold atomic hydrogen in the interstellar medium runs counter to the prevailing view that cold gas resides almost exclusively in clouds dominated by molecular hydrogen.     

Mutational analysis of a protein-folding pathway

The effects of amino-acid replacements on the disulphide-coupled folding pathway of bovine pancreatic trypsin inhibitor have been examined. Replacements at three sites destabilize the native protein relative to the unfolded state, but have different effects on the relative stabilities of the disulphide-bonded folding intermediates, thus allowing the roles of the altered residues during folding to be distinguished.     

Protective effect of Shigyaku-to,a traditional Chinese herbal medicine,on the infection of herpes simplex virus type 1 (HSV-1) in mice

The antiviral activity of Shigyaku-to (TJS-109), a traditional Chinese herbal medicine, was investigated in mice infected with herpes simplex virus type 1 (HSV-1). TJS-109 is a combination of the medicinal plant extracts fromZingiberis siccatum rhizoma,Aconiti tuber andGlycyrrhizae radix in a specific proportion. Mice infected with a 10 LD₅₀ dose of HSV-1 were treated with TJS-109 orally at doses of 1.25 to 20 mg/kg 2 days before, and 1 and 4 days after the infection. The treated groups had 80% (1.25 mg/kg), 40% (5 mg/kg) and 23% (20 mg/kg) mortality rates 25 days after the infection as compared with a 100% mortality rate in control mice treated with saline. When HSV-1 infected mice (recipients) received CD8⁺T cell fractions derived from spleens of mice treated with TJS-109 (donors), 70% of recipients survived, as compared with 0% survivors in the groups of mice treated with saline, B cell fractions, CD4⁺ T cell fractions or macrophage-enriched fractions prepared from the same donors. TJS-109 did not show any virucidal activities against HSV-1 or any virostatic activities on the growth of HSV-1 in Vero cells. These results suggest that TJS-109 protected mice exposed to lethal amounts of HSV-1 through the activation of CD8⁺ T cells.     

Inositol 1,4,5-trisphosphate activates a channel from smooth muscle sarcoplasmic reticulum

Inositol 1,4,5-trisphosphate (InsP3) can initiate calcium release into the cytoplasm in a variety of cells. From experiments using permeabilized cells, membrane vesicles, and patch-clamp techniques, it has been suggested that InsP3 acts by directly opening calcium channels. Here, we show that InsP3 induced openings of channels in planar lipid bilayers into which vesicles made from aortic muscle sarcoplasmic reticulum (SR) were incorporated. Activation of channels by InsP3 was not observed when vesicles made from SR of cardiac or skeletal muscle were incorporated into planar lipid bilayers. The present study demonstrates for the first time unique properties of an InsP3-gated calcium channel in sarcoplasmic reticulum vesicles from vascular smooth muscle. This InsP3-activated channel from aortic SR differs strikingly from the calcium-gated calcium channel of striated muscle SR in single-channel conductance and pharmacology.     

Effect of intralipid infusion on serum high- and low-density lipoprotein cholesterol,lecithin: Cholesterol acyltransferase,and lipoprotein lipase in tumor-bearing rats

We compared the effects of 0.45% normal saline (NS), 5% Intralipid^® (IL), and 16.7% glucose (Glu) infusions on total serum triglycerides and cholesterol, serum high-(HDL-c) and low-density lipoprotein cholesterol (LDL-c), and activity of serum lecithin: cholesterol acyltransferase (LCAT), and serum lipoprotein lipase (LPL) in rats implanted with a fibrosarcoma. In tumor-bearing rats given NS, a two-fold increase in total serum cholesterol, a four-fold increase in LDL-c, and a five-fold decrease in the HDL-c/LDL-c ratio were observed compared to tumor-free rats. In tumor-bearing rats administered IL, a two-fold increase in total serum triglyceride and cholesterol, a three-fold increase in HDL-c and HDL-c/LDL-c ratio, and a two-fold increase in LPL activity were observed compared to tumor-bearing rats administered NS. In tumor-bearing rats administered Glu, a two-fold decrease in total serum cholesterol, a two-fold decrease in HDL-c, and a three-fold decrease in LDL-c were observed compared to tumor-bearing rats administered NS. Tumor weights and LCAT activity did not differ significantly between treatment groups. Previous results have demonstrated that lipophilic compounds that interact with plasma lipoproteins have altered pharmacological effects when administered with IL. Therefore, this study suggests that IL infusions alter the HDL-c/LDL-c ratio and could affect the pharmacological behavior of anticancer compounds that predominantly distribute into the LDL fraction upon entrance into the bloodstream.     

Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12).

Retinitis pigmentosa (RP) comprises a clinically and genetically heterogeneous group of diseases that afflicts approximately 1.5 million people worldwide. Affected individuals suffer from a progressive degeneration of the photoreceptors, eventually resulting in severe visual impairment. To isolate candidate genes for chorioretinal diseases, we cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method. One of these cDNAs (RET3C11) mapped to chromosome 1q31-q32.1, a region harbouring a gene involved in a severe form of autosomal recessive RP characterized by a typical preservation of the para-arteriolar RPE (RP12; ref. 3). The full-length cDNA encodes an extracellular protein with 19 EGF-like domains, 3 laminin A G-like domains and a C-type lectin domain. This protein is homologous to the Drosophila melanogaster protein crumbs (CRB), and denoted CRB1 (crumbs homologue 1). In ten unrelated RP patients with preserved para-arteriolar RPE, we identified a homozygous AluY insertion disrupting the ORF, five homozygous missense mutations and four compound heterozygous mutations in CRB1. The similarity to CRB suggests a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. The distinct RPE abnormalities observed in RP12 patients suggest that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration.     

Susceptibility to testicular germ-cell tumours in a 129.MOLF-Chr 19 chromosome substitution strain.

The identification of genes that control susceptibility to testicular germ-cell tumours (TGCTs), the most common cancer affecting young men, has been difficult. In laboratory mice, TGCTs arise from primordial germ cells in only the 129 inbred strains, and susceptibility is under multigenic control. The spontaneously arising mutation Ter (ref. 5) on mouse chromosome 18 (Refs 6,7) increases TGCT frequency on a 129/Sv background. We originally used Ter in genetic crosses to identify loci that control tumorigenesis. A genome scan of tumour-bearing progeny from backcrosses between the 129/Sv-Ter/+ and MOLF/Ei strains provided modest evidence that MOLF-derived alleles on chromosome 19 enhance development of bilateral TGCTs (ref. 9). To obtain independent evidence for linkage to the MOLF chromosome, we made an autosomal chromosome substitution strain (CSS; or 'consomic strain') in which chromosome 19 of 129/Sv+/+ was replaced by its MOLF-derived homologue. The unusually high frequency of TGCTs in this CSS (even in the absence of the Ter mutation) provides evidence confirming the genome survey results, identifies linkage for a naturally occurring strain variant allele that confers susceptibility to TGCTs and illustrates the power of CSSs in complex trait analysis.