Polymorphic tandem repeat region in interleukin-1α intron 6

Analysis of polymerase chain reaction amplified products from the sixth intron of the human interleukin-1 gene reveals a high polymorphism (polymorphism information content = 0.51) in a Caucasian population. Altogether, seven alleles have been defined ranging from 620 to 1220bp. This polymorphism is probably attributable to a variable number of 46-bp tandem repeats, each containing potential regulatory sequences.     

Sex determination and optimal development in the Moorish gecko,Tarentola mauritanica

Under temperature sex determination (TSD), sex is determined by temperature during embryonic development. Depending on ecological and physiological traits and plasticity, TSD species may face demographic collapse due to climate change. In this context, asymmetry in bilateral organisms can be used as a proxy for developmental instability and, therefore, deviations from optimal incubation conditions. Using Tarentola mauritanica gecko as a model, this study aimed first to confirm TSD, its pattern and pivotal temperature, and second to assess the local adaptation of TSD and variation of asymmetry patterns across four populations under different thermal regimes. Eggs were incubated at different temperatures, and hatchlings were sexed and measured. The number of lamellae was counted in adults and hatchlings. Results were compatible with a TSD pattern with males generated at low and females at high incubation temperatures. Estimated pivotal temperature coincided with the temperature producing lower embryonic mortality, evidencing selection towards balanced sex ratios. The temperature of oviposition was conservatively selected by gravid females. Asymmetry patterns found were likely related to nest temperature fluctuations. Overall, the rigidity of TSD may compromise reproductive success, and demographic stability in this species in case thermal nest choice becomes constrained by climate change.     

Vagal nerve and the gastric mucosal defense

An essential role for an intact vagal nerve has been proven in the development of gastric mucosal cyto- and general protection. On the other hand, chemically-induced (ethanol, HCl, indomethacin) gastric mucosal damage is enhanced after acute surgical vagotomy. The aims of this paper were to study the possible mechanisms of the vagal nerve in the development of gastric mucosal defense. The following questions were addressed: 1) effect of surgical vagotomy on the development of ethanol- (ETOH), HCl-, and indomethacin (IND)-induced gastric mucosal damage; 2) changes in the gastric mucosal defense by scavengers, prostacyclin and other compounds (small doses of atropine and cimetidine: 3) changes in the gastric mucosal vascular permeability due to chemicals; 4) effect of indomethacin in the ETOH and HCl models with and without surgical vagotomy; 5) changes in the gastric mucosal content of prostacyclin and PGE₂ in the ETOH and HCl models after surgical vagotomy; and 6) changes in the role of SH-groups in gastric mucosal defense after surgical vagotomy. It was found that: 1) the gastric mucosal damage produced by chemicals (ETOH, HCl, and indomethacin) was enhanced after surgical vagotomy; 2) the cyto- and general gastric protective effects of β-carotene, prostacyclin, and small doses of atropine and cimetidine disappeared after surgical vagotomy; 3) the vascular permeability due to chemicals (ETOH, HCl, indomethacin) significantly increased after surgical vagotomy in association with an increase in both number and severity of gastric mucosal lesions; 4) IND alone (in animals with an intact vagus) did not produce gastric mucosal lesions (in 1-h experiments), but it aggravated ETOH-induced gastric mucosal damage (both its number and severity); 5) the gastric mucosal levels of prostacyclin and PGE₂ decreased after surgical vagotomy; 6) IND application (after surgical vagotomy) decreased further the tissue levels of prostacyclin and PGE₂ in association with an increase of gastric mucosal damage; and 7) the gastric mucosal protective effects of SH-groups were abolished by surgical vagotomy.     

Secondary structure of β-hydroxydecanoyl thiol ester dehydrase, a 39-kDa protein, derived from Hα, Cα, Cβ and CO signal assignments and the Chemical Shift Index: Comparison with the crystal structure

Summary Nearly complete backbone ¹H, ¹⁵N and ¹³C signal assignments are reported for -hydroxydecanoyl thiol ester dehydrase, a 39-kDa homodimer containing 342 amino acids. Although ¹⁵N relaxation data show that the protein has a rotational correlation time of 18 ns, assignments were derived from triple-resonance experiments recorded at 500 MHz and pH 6.8, without deuteration. The Chemical Shift Index, CSI, identified two long helices and numerous -strands in dehydrase. The CSI predictions are in close agreement with the secondary structure identified in the recently derived crystal structure, particularly when one takes account of the numerous bulges in the -strands. The assignment of dehydrase and a large deuterated protein [Yamazaki et al. (1994) J. Am. Chem. Soc., 116, 11655–11666] suggest that assignment of 40–60 kDa proteins is feasible. Hence, further progress in understanding the chemical shift/structure relationship could open the way to determine the structures of such large proteins. Supplementary Material is available on request, comprising Table S1 listing the spectral parameters; Table S2 listing the assignments; Fig. S1 showing the 2D ¹H–¹⁵N HSQC spectrum; Fig. S2 showing sequential NOEs, secondary shifts, H-exchange and ³J_HN data; and Fig. S3 showing plots of the H, C, CO and C Chemical Shift Indexes.To whom correspondence should be addressed.     

The pollen-specific LIM protein PLIM-1 from sunflower binds nucleic acids in vitro

The protein PLIM-1 (formerly SF3) from sunflower is expressed exclusively in mature, free pollen. It contains two LIM domains associated with an acidic C-terminus comprising six copies of the pentapeptide motif (A,T,S) (E,D) TQN. We have expressed the pollen protein as well as some of its mutant forms inEscherichia coli and have used the bacterially produced proteins to study interactions with nucleic acids. Our studies show that the protein binds DNA and RNA in vitro to form large complexes, while mutant polypeptides containing either a single LIM domain or a destabilized first or second LIM domain do not. Although these data suggest that the biological function of PLIM-1 involves interactions with nucleic acids, its role in pollen development remains unclear.     

Exemestane experience in breast cancer treatment

Exemestane is a very potent, orally active, selective and long-lasting steroidal irreversible inhibitor of aromatase. It is 150 times more potent than aminoglutethimide (AG) in inhibiting human placental aromatase (K_i of 4.3 and 671 nM, respectively). The compound is presently under phase III evaluation in Europe and the U.S.A. for the treatment of postmenopausal advanced breast cancer (ABC). Clinical pharmacology studies have been carried out with single doses ranging from 0.5 to 800 mg and repeated doses of up to 600 mg a day, in 132 postmenopausal healthy volunteers and in 185 post-menopausal women with ABC. Results obtained using a very specific and sensitive analytical method (high performance liquid chromatography—radioimmunoassay; HPLC—RIA) indicated that exemestane is extremely effective in inhibiting plasma estrogens levels. Estrogen inhibition is clearly evident at 5 mg a day and maximal suppression for E₂, E₁ and E₁S (>85%, >90% and>90%, respectively) is obtained at 10–25 mg a day. Data from non-controlled phase II studies involving more than 400 patients indicated a clear anti-tumour activity in postmenopausal ABC patients failing multiple hormonal treatments. In 62 patients progressing on AG (≥500 mg a day) exemestane treatment resulted in an objective response rate of approximately 24%; disease stabilization ≥24 weeks was observed in an additional 24% of cases. With regard to safety, although daily doses up to 600 mg were administered, the maximal tolerated dose was not achieved; reported symptoms were mainly related to the pharmacological action of the compound and were usually mild to moderate in severity, resulting in the discontinuation of therapy in less than 3% of cases. In conclusion, the available results suggest that exemestane treatment is associated with minimal toxicity, and may be of significant benefit for ABC women who have exhausted conventional therapy.     

Seasonal cycle of nitrogen and phytoplankton biomass in a well-mixed coastal system (Eastern English Channel)

The hydrological structure of the French coastal part of the eastern English Channel is strongly linked with tidal regimes and riverine input. Two distinct water masses are separated by a frontal area and drift along the coast in SW–NE direction. These two water masses are well-mixed during the entire year. We studied the seasonal dynamic of nitrogenous nutrients, chlorophyll a and organic particulate carbon and nitrogen at two stations, characteristic of these water masses, during the year 1994. Results show (i) a winter stock of nitrate and ammonium, (ii) a pre-bloom period corresponding to the use of ammonium, (iii) a high bloom period of short duration using nitrate, (iv) a post-bloom period with little phytoplanktonic activity probably limited by nutrients other than nitrogen and (v) an autumnal period of reconstitution of stock. The essential difference between the two stations is the importance of winter stock of nutrients and of bloom chlorophyll a concentration, with the coastal station richer than the offshore one. An assumption about the nitrogen available for new production in this area gives a value of 57% of the winter stock of inorganic nitrogen.     

Inhibition enzyme-linked immunosorbent assay for detection of Pseudomonas fluorescens on meat surfaces.

An inhibition enzyme-linked immunosorbent assay was developed for Pseudomonas fluorescens enumeration of meat surfaces. The assay detected contamination levels as low as 3 x 10(5) bacteria per ml and could be completed within 4 h. It could be used as a framework for a test system for quantifying P. fluorescens spoilage in meat products.     

Energy cost and energy sources in karate

Energy costs and energy sources in karate (wado style) were studied in eight male practitioners (age 23.8 years, mass. 72.3 kg, maximal oxygen consumption (VO_2max) 36.8 ml · min^–1 · kg^–1) performing six katas (formal, organized movement sequences) of increasing duration (from approximately. 10 s to approximately 80 s). Oxygen consumption (VO₂) was determined during pre-exercise rest, the exercise period and the first 270 s of recovery in five consecutive expired gas collections. A blood sample for lactate (la^–) analysis was taken 5 min after the end of exercise. The overall amount of O₂ consumed during the exercise and in the following recovery increased linearly with the duration of exercise (t) from approximately 1.51 (for t equal to 10.5 s (SD 1.6)) to approximately 5.81, for t equal to 81.5 s (SD 1.0). The energy release from la^– production (VO_21a ^–) calculated assuming that an increase of 1 mmol · l^–1 la^– corresponded to a VO₂ of 3 mlO₂ · kg^–1 was negligible for t equal to or less than 20 s and increased to 17.3 ml · kg^–1 (la^– = 5.8 mmol · l^–1 above resting values) for t equal approximately to 80 s. The overall energy requirement (VO_2eq) as given by the sum of VO₂ and VO_2la ^– was described by VO_2eq = 0.87 + 0.071 · t (n = 64; r ² = 0.91), where VO_2eq is in litres and t in seconds. This equation shows that the metabolic power (VO_2eq · t ^–1) for this karate style is very high: from approximately 9.51 · min^–1 for t equal to 10 s to approximately 4.91 · min^–1 for t equal to 80 s, i.e. from 3.5 to 1.8 times the subjects' VO_2max. The fraction of VO_2eq derived from the amount of O₂ consumed during the exercise increased from 11% for t equal to 10 s to 41 % for t equal to 80 s whereas VO_21a ^– was negligible far t equal to or less than 20 s and increased to 13 % o for t equal to 80 s. The remaining fraction (from 90% for t equal to 10 s to 46% for t equal to 80 s), corresponding to the amount of O₂ consumed in the recovery after exercise, is derived from anaerobic alactic sources, i.e. from net splitting of high energy phosphates during the exercise.