Latitudinal clines in body size,but not in thermal tolerance or heat‐shock cognate 70 (HSC70), in the highly‐dispersing intertidal gastropod Littorina keenae (Gastropoda: Littorinidae)

Natural populations of widely‐distributed animals often exhibit clinal variation in phenotypic traits or in allele frequencies of a particular gene over their geographical range. A planktotrophic intertidal snail, Littorina keenae is broadly distributed along the north‐eastern Pacific coast through a large latitudinal range (24°50′N–43°18′N). We tested for latitudinal clines in two complex phenotypic traits – thermal tolerance and body size – and one single locus trait – heat shock cognate 70 (HSC70) – in L. keenae along almost its entire geographical range. We found only weak evidence for a latitudinal cline in the thermal tolerance and no evidence for a cline in allele frequencies at HSC70. However, as predicted by Bergmann's rule, we detected a strong latitudinal cline that accounted for 60% of the variance in body size (R² = 0.598; P < 0.001). In contrast, body size did not significantly affect thermal tolerance. HSC70 showed no genetic differentiation among the populations, supporting our previous mitochondrial gene‐based estimate of high gene flow during this snail's free‐swimming larval stage. Given that L. keenae experiences panmixia along its species range, the observed size cline may be partially or entirely caused by a phenotypically plastic response to local thermal environments rather than by genetic divergence in body size among populations in response to locally optimizing natural selection. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 100 , 494–505.     

Pyrrolo(iso)quinoline derivatives as 5-HT(2C) receptor agonists

A series of 1-(1-pyrrolo(iso)quinolinyl)-2-propylamines was synthesised and evaluated as 5-HT(2C) receptor agonists for the treatment of obesity. The general methods of synthesis of the precursor indoles are described. The functional efficacy and radioligand binding data for the compounds at 5-HT(2) receptor subtypes are reported. The analogue which showed the highest 5-HT(2C) binding affinity (27, 1.6nM) was found to be successful in reducing food intake in rats.     

Mammalian l-to-d-amino-acid-residue isomerase from platypus venom

The presence of d-amino-acid-containing polypeptides, defensin-like peptide (DLP)-2 and Ornithorhyncus venom C-type natriuretic peptide (OvCNP)b, in platypus venom suggested the existence of a mammalian d-amino-acid-residue isomerase(s) responsible for the modification of the all-l-amino acid precursors. We show here that this enzyme(s) is present in the venom gland extract and is responsible for the creation of DLP-2 from DLP-4 and OvCNPb from OvCNPa. The isomerisation reaction is freely reversible and under well defined laboratory conditions catalyses the interconversion of the DLPs to full equilibration. The isomerase is approximately 50-60 kDa and is inhibited by methanol and the peptidase inhibitor amastatin. This is the first known l-to-d-amino-acid-residue isomerase in a mammal.     

Effects of winter temperatures on the sex ratios ofAphytis melinus [Hym.: Aphelinidae] in the San Joaquin Valley of California

Laboratory bioassays of overwintering field populations of the California red scale parasitoidAphytis melinus DeBach showed a shift in sex ratio of F₁ progeny after prolonged exposure to winter temperatures in Tulare County, California. In 7 of 8 tests, short-term winter field exposure (<75 days) did not result in a significant male bias in sex ratios of F₁ progeny when compared to sex ratios observed in laboratory cultures maintained at 27°C. Long term exposure (109–139 days), however, resulted in significantly (P<0.05) higher male bias in F₁ sex ratios in 5 of 6 tests. These results from field populations ofA. melinus agree with conclusions of low temperature laboratory tests onAphytis species (lingnanensis, melinus) by other workers. Mention of a proprietary or commercial product in this paper does not constitute an endorsement of this product by the University of California.     

Modulation of the redox state of tubulin by the glutathione/glutaredoxin reductase system

Alterations in the redox status of proteins have been implicated in the pathology of several neurodegenerative diseases. We report that peroxynitrite-induced disulfides in porcine brain tubulin are repaired by the glutaredoxin reductase system composed of glutathione reductase, human or Escherichia coli glutaredoxin, reduced glutathione, and NADPH. Reduction of disulfide bonds between the alpha- and beta-tubulin subunits by the glutathione reductase system was assessed by Western blot. Tubulin cysteine oxidation and reduction was quantitated by monitoring the incorporation of 5-iodoacetamido-fluorescein, a thiol-specific labeling reagent. Tubulin disulfide bond reduction by the glutaredoxin reductase system restored tubulin polymerization activity that was lost following peroxynitrite addition. In support of redox modulations of tubulin by glutathione, thiol-disulfide exchange between tubulin and oxidized glutathione was detected and quantitated by HPLC. In addition, glutathionylation of tubulin was detected by dot blot using an anti-GSH antibody.     

Nine months in space: effects on human autonomic cardiovascular regulation.

We studied three Russian cosmonauts to better understand how long-term exposure to microgravity affects autonomic cardiovascular control. We recorded the electrocardiogram, finger photoplethysmographic pressure, and respiratory flow before, during, and after two 9-mo missions to the Russian space station Mir. Measurements were made during four modes of breathing: 1) uncontrolled spontaneous breathing; 2) stepwise breathing at six different frequencies; 3) fixed-frequency breathing; and 4) random-frequency breathing. R wave-to-R wave (R-R) interval standard deviations decreased in all and respiratory frequency R-R interval spectral power decreased in two cosmonauts in space. Two weeks after the cosmonauts returned to Earth, R-R interval spectral power was decreased, and systolic pressure spectral power was increased in all. The transfer function between systolic pressures and R-R intervals was reduced in-flight, was reduced further the day after landing, and had not returned to preflight levels by 14 days after landing. Our results suggest that long-duration spaceflight reduces vagal-cardiac nerve traffic and decreases vagal baroreflex gain and that these changes may persist as long as 2 wk after return to Earth.     

Francisella tularensis Vaccines Elicit Concurrent Protective T- and B-Cell Immune Responses in BALB/cByJ Mice

In the last decade several new vaccines against Francisella tularensis, which causes tularemia, have been characterized in animal models. Whereas many of these vaccine candidates showed promise, it remains critical to bridge the preclinical studies to human subjects, ideally by taking advantage of correlates of protection. By combining in vitro intramacrophage LVS replication with gene expression data through multivariate analysis, we previously identified and quantified correlative T cell immune responses that discriminate vaccines of different efficacy. Further, using C57BL/6J mice, we demonstrated that the relative levels of gene expression vary according to vaccination route and between cell types from different organs. Here, we extended our studies to the analysis of T cell functions of BALB/cByJ mice to evaluate whether our approach to identify correlates of protection also applies to a Th2 dominant mouse strain. BALB/cByJ mice had higher survival rates than C57BL/6J mice when they were immunized with suboptimal vaccines and challenged. However, splenocytes derived from differentially vaccinated BALB/cByJ mice controlled LVS intramacrophage replication in vitro in a pattern that reflected the hierarchy of protection observed in C57BL/6J mice. In addition, gene expression of selected potential correlates revealed similar patterns in splenocytes of BALB/cByJ and C57BL/6J mice. The different survival patterns were related to B cell functions, not necessarily to specific antibody production, which played an important protective role in BALB/cByJ mice when vaccinated with suboptimal vaccines. Our studies therefore demonstrate the range of mechanisms that operate in the most common mouse strains used for characterization of vaccines against F. tularensis, and illustrate the complexity necessary to define a comprehensive set of correlates.     

Rise of oceanographic barriers in continuous populations of a cetacean: the genetic structure of harbour porpoises in Old World waters

Background

Understanding the role of seascape in shaping genetic and demographic population structure is highly challenging for marine pelagic species such as cetaceans for which there is generally little evidence of what could effectively restrict their dispersal. In the present work, we applied a combination of recent individual-based landscape genetic approaches to investigate the population genetic structure of a highly mobile extensive range cetacean, the harbour porpoise in the eastern North Atlantic, with regards to oceanographic characteristics that could constrain its dispersal.

Results

Analyses of 10 microsatellite loci for 752 individuals revealed that most of the sampled range in the eastern North Atlantic behaves as a 'continuous' population that widely extends over thousands of kilometres with significant isolation by distance (IBD). However, strong barriers to gene flow were detected in the south-eastern part of the range. These barriers coincided with profound changes in environmental characteristics and isolated, on a relatively small scale, porpoises from Iberian waters and on a larger scale porpoises from the Black Sea.

Conclusion

The presence of these barriers to gene flow that coincide with profound changes in oceanographic features, together with the spatial variation in IBD strength, provide for the first time strong evidence that physical processes have a major impact on the demographic and genetic structure of a cetacean. This genetic pattern further suggests habitat-related fragmentation of the porpoise range that is likely to intensify with predicted surface ocean warming.