Relationship of ovarian hormones to hypoxemia in women residents of 4,300 m

Prevalence of excessive erythrocytosis, the main sign of chronic mountain sickness (CMS), is greater in postmenopausal Andean women than in premenopausal women. It is uncertain whether this greater prevalence is related to the decline in female hormones and ventilatory function after the occurrence of the menopause. To study this, we compared the physiological variables involved in the physiopathology of CMS [end-tidal CO(2) (PET(CO(2)), Torr) and end-tidal O(2) (PET(O(2)), Torr), arterial oxygen saturation (Sa(O(2)), %), and Hb concentration (g/dl)] and progesterone and estradiol levels between postmenopausal and premenopausal women, both in the luteal and follicular phases. Women residing in Cerro de Pasco (n = 33; 4,300 m) aged 26--62 yr were studied. Postmenopausal women compared with premenopausal women in the luteal phase had lower PET(O(2)) (48 +/- 4 vs. 53 +/- 2 Torr, P = 0.005) and Sa(O(2)) levels (82 +/- 12 vs. 88 +/- 12%, P < 0.005) and higher PET(CO(2)) (34 +/- 2 vs. 29 +/- 3 Torr, P = 0.005) and Hb concentration (19 +/- 1 vs. 14 +/- 2 g/dl, P < 0.005). In addition, plasma progesterone was negatively correlated with PET(CO(2)) and positively correlated with PET(O(2)) and Sa(O(2)). No clear relationship was found among the cycle phases between estradiol and the variables studied. In conclusion, our results reveal that, before menopause, there is better oxygenation and lower Hb levels in women long residing at altitude, and this is associated with higher levels of progesterone in the luteal phase of the cycle.     

Recognition of Carbohydrate Epitopes Specific for Electron-Dense Granule Antigens from Entamoeba histolytica by Monoclonal Antibodies in the Cecal Content of Infected Hamsters

Saccharomyces cerevisiae CGR1 encodes a 120-amino acid protein with a predominant nucleolar localization. In this study we report the identification and cloning of the ortholog, cgrA, from Aspergillus nidulans. The cgrA gene is comprised of three exons on A. nidulans Chromosome 7. The cDNA contains a single open reading frame (ORF) that would encode a protein of 114 amino acids with 44% sequence identity to yeast Cgr1p. A plasmid expressing cgrA complemented the impaired growth phenotype of a yeast strain that can be inducibly depleted of CGR1, and a green fluorescent protein (GFP)-tagged CgrA protein had the same nucleolar localization as the corresponding yeast protein. These results identify cgrA as the A. nidulans ortholog of yeast CGR1 and suggest evolutionary conservation of nucleolar localization mechanisms used by these proteins. Received: 14 September 2000 / Accepted: 13 November 2000     

Litomosoides sigmodontis in mice: reappraisal of an old model for filarial research

Onchocerciasis and lymphatic filariasis (LF) are major causes of severe morbidity and considerable socio-economic problems throughout the tropics. Vector control and mass chemotherapy have helped to control these infections in some regions, but the temporary success of such measures argues strongly for the development of vaccines. Success in such a venture will require detailed knowledge of protective immune responses in conjunction with the identification of target antigens. By comparison with other important parasitic infections, such as schistosomiasis and leishmaniasis, work on the development of vaccines for onchocerciasis and LF has been constrained because of the difficulties of producing cyclical and patent filarial infection in laboratory mice. Wolfgang Hoffmann and colleagues here outline the opportunities presented by the rodent filaria Litomosoides sigmodontis for filarial research.     

Density and dispersal of the loaiasis vector Chrysops dimidiata in southern Cameroon

By mark-release-recapture experiments, we assessed the density of loaisis vectors, Chrysops dimidiata Wulp plus some Chrysops silacea Austen (Diptera: Tabanidae) and estimated their range of flight in the secondary forest of southern Cameroon. In 1993, the release point was at the centre of the study area and recapture points were at 1,100 m radius. In 1994, releases were on the periphery of the study area and recapture sites were 400-8,000 m from the release points. Results were concordant and showed Chrysops female densities of 785-3,682 flies/ km2. The theoretical flight range was < 6,000 m, with a maximum distance of 4,500 m observed. These results are considered promising for the use of vector control methods against loaiasis.     

Effects of green fluorescent protein or beta-glucuronidase tagging on the accumulation and pathogenicity of a resistance-breaking Lettuce mosaic virus isolate in susceptible and resistant lettuce cultivars

The RNA genome of a resistance-breaking isolate of Lettuce mosaic virus (LMV-E) was engineered to express the jellyfish green fluorescent protein (GFP) or beta-glucuronidase (GUS) fused to the helper-component proteinase (HC-Pro) to study LMV invasion and spread in susceptible and resistant lettuce cultivars. Virus accumulation and movement were monitored by either histochemical GUS assays or detection of GFP fluorescence under UV light. The GFP- and GUS-tagged viruses spread systemically in the susceptible lettuce cultivars Trocadero and Vanguard, where they induced attenuated symptoms, compared with the wild-type virus. Accumulation of the GFP-tagged virus was reduced but less affected than in the case of the GUS-tagged virus. Systemic movement of both recombinant viruses was very severely affected in Vanguard 75, a lettuce cultivar nearly isogenic to Vanguard but carrying the resistance gene mo1(2). Accumulation of the recombinant viruses in systemically infected leaves was either undetectable (GUS-tag) or erratic, strongly delayed, and inhibited by as much as 90% (GFP-tag). As a consequence, and contrary to the parental virus, the recombinant viruses were not able to overcome the protection afforded by the mo1(2) gene. Taken together, these results indicate that GUS or GFP tagging of the HC-Pro of LMV has significant negative effects on the biology of the virus, abolishing its resistance-breaking properties and reducing its pathogenicity in susceptible cultivars.     

Four residues of the extracellular N-terminal domain of the NR2A subunit control high-affinity Zn2+ binding to NMDA receptors

NMDA receptors are allosterically inhibited by Zn2+ ions in a voltage-independent manner. The apparent affinity for Zn2+ of the heteromeric NMDA receptors is determined by the subtype of NR2 subunit expressed, with NR2A-containing receptors being the most sensitive (IC50, approximately 20 nM) and NR2C-containing receptors being the least sensitive (IC50, approximately 30 microM). Using chimeras constructed from these two NR2 subtypes, we show that the N-terminal LIVBP-like domain of the NR2A subunit controls the high-affinity Zn2+ inhibition. Mutations at four residues in this domain markedly reduce Zn2+ affinity (by up to >500-fold) without affecting either receptor activation by glutamate and glycine or inhibition by extracellular protons and Ni2+ ions, indicating that these residues most likely participate in high-affinity Zn2+ binding.     

Lipogenic enzyme activities in subcutaneous adipose tissue and skeletal muscle from neonatal pigs consuming maternal or formula milk

The influence of maternal and formula milk on lipid metabolism was studied in 7-day-old pigs. Lipid content, fatty acid composition, lipogenic enzyme activities and expression of GLUT4 mRNA were determined in subcutaneous adipose tissue and skeletal muscle from pigs that were bottle-fed formula milk (F) or sow milk (SM), or were sow-reared (SR). Bottle-fed pigs were isoenergetically fed and achieved similar daily body weight gain. SR pigs have a higher (P < 0.05) body weight gain than bottle-fed pigs. Lipid content of adipose tissue was lower (P < 0.05) in F than in SM and SR pigs. In muscle, lipid content did not differ significantly between groups. In adipose tissue, acetyl-CoA-carboxylase (CBX), fatty acid synthase (FAS), malic enzyme (ME), glucose-6-phosphate-dehydrogenase (G6PDH) and lipoprotein lipase (LPL) activities and GLUT4 mRNA levels were higher (P < 0.05) in SR than in bottle-fed pigs. In muscle, ME and G6PDH activities and GLUT4 mRNA were higher (P < 0.05) in F than in SM and SR pigs; LPL was not detected. The present study indicates that lipogenic enzyme activities and GLUT4 mRNA expression are regulated differently in subcutaneous adipose tissue and skeletal muscle in the neonatal pig.     

Characterization of a Snorhizobium meliloti ATP-binding cassette histidine transporter also involved in betaine and proline uptake

The symbiotic soil bacterium Sinorhizobium meliloti uses the compatible solutes glycine betaine and proline betaine for both protection against osmotic stress and, at low osmolarities, as an energy source. A PCR strategy based on conserved domains in components of the glycine betaine uptake systems from Escherichia coli (ProU) and Bacillus subtilis (OpuA and OpuC) allowed us to identify a highly homologous ATP-binding cassette (ABC) binding protein-dependent transporter in S. meliloti. This system was encoded by three genes (hutXWV) of an operon which also contained a fourth gene (hutH2) encoding a putative histidase, which is an enzyme involved in the first step of histidine catabolism. Site-directed mutagenesis of the gene encoding the periplasmic binding protein (hutX) and of the gene encoding the cytoplasmic ATPase (hutV) was done to study the substrate specificity of this transporter and its contribution in betaine uptake. These mutants showed a 50% reduction in high-affinity uptake of histidine, proline, and proline betaine and about a 30% reduction in low-affinity glycine betaine transport. When histidine was used as a nitrogen source, a 30% inhibition of growth was observed in hut mutants (hutX and hutH2). Expression analysis of the hut operon determined using a hutX-lacZ fusion revealed induction by histidine, but not by salt stress, suggesting this uptake system has a catabolic role rather than being involved in osmoprotection. To our knowledge, Hut is the first characterized histidine ABC transporter also involved in proline and betaine uptake.