Connective Tissue Growth Factor Overexpression in Cardiomyocytes Promotes Cardiac Hypertrophy and Protection against Pressure Overload

Connective tissue growth factor (CTGF) is a secreted protein that is strongly induced in human and experimental heart failure. CTGF is said to be profibrotic; however, the precise function of CTGF is unclear. We generated transgenic mice and rats with cardiomyocyte-specific CTGF overexpression (CTGF-TG). To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat hearts under basal conditions and after stimulation with angiotensin II (Ang II) or isoproterenol, respectively. Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. In contrast to controls, Ang II treated CTGF-TG mice displayed preserved cardiac function. However, CTGF-TG mice developed age-dependent cardiac dysfunction at the age of 7 months. CTGF related heart failure was associated with Akt and JNK activation, but not with the induction of natriuretic peptides. Furthermore, cardiomyocytes from CTGF-TG mice showed unaffected cellular contractility and an increased Ca²⁺ reuptake from sarcoplasmatic reticulum. In an ischemia/reperfusion model CTGF-TG hearts did not differ from controls.Our data suggest that CTGF itself does not induce cardiac fibrosis. Moreover, it is involved in hypertrophy induction and cellular remodeling depending on the cardiac stress stimulus. Our new transgenic animals are valuable models for reconsideration of CTGF''s profibrotic function in the heart.     

The role of bioclimatic origin,residence time and habitat context in shaping non-native plant distributions along an altitudinal gradient

An important factor influencing whether or not a non-native plant species becomes invasive is the climate in the area of introduction. To become naturalised in the new range, a species must either be climatically pre-adapted (climate matching), have a high phenotypic plasticity, or be able to adapt genetically, which in the latter case may take many generations. Furthermore, patterns of successful establishment across species might vary with habitat context. To address the interaction of these factors on non-native species richness, we recorded the presence of non-native annual plant species along an altitudinal gradient on Tenerife (Canary Islands, Spain). We compared the distributions of species differing in bioclimatic origin (Mediterranean and temperate) and time since introduction (old and recent introductions), and compared richness patterns of these groups in anthropogenic and natural habitats. Non-native species richness increased strongly from lowlands to mid-altitudes, but dropped sharply at the transition from anthropogenic to natural habitats, and thereafter declined with altitude in the natural habitat. This pattern indicates that the altitude effects reflected changes in both climate and habitat context. Mediterranean and temperate species were distributed similarly along the altitudinal gradient, and we found no effect of bioclimatic origin on species distributions. As almost all species present at the highest sites also occurred in the lowlands, we conclude that most species were introduced to lowland sites and were therefore pre-adapted to those climatic conditions (lowland introduction filter). The altitudinal ranges of species tended to increase with time since introduction, and the species reaching the highest altitudes were mostly old introductions. This effect of time was more pronounced among Mediterranean than temperate species. Thus, while climatic pre-adaptation is important for establishment along this altitudinal gradient, species tend to extend their altitudinal range with time.     

Functional effects of mutations in cytochrome c oxidase related to prostate cancer

A number of missense mutations in subunit I of cytochrome c oxidase (CytcO) have previously been linked to prostate cancer (Petros et al., 2005). To investigate the effects of these mutations at the molecular level, in the present study we prepared four different structural variants of the bacterial Rhodobacter sphaeroides CytcO (cytochrome aa(3)), each carrying one amino-acid residue replacement corresponding to the following substitutions identified in the above-mentioned study: Asn11Ser, Ala122Thr, Ala341Ser and Val380Ile (residues Asn25, Ser168, Ala384 and Val423 in the R. sphaeroides oxidase). This bacterial CytcO displays essentially the same structural and functional characteristics as those of the mitochondrial counterpart. We investigated the overall activity, proton pumping and internal electron- and proton-transfer reactions in the structural variants. The results show that the turnover activities of the mutant CytcOs were reduced by at most a factor of two. All variants pumped protons, but in Ser168Thr, Ala384Ser and Val423Ile we observed slight internal proton leaks. In all structural variants the internal electron equilibrium was slightly shifted away from the catalytic site at high pH (10), resulting in a slower observed ferryl to oxidized transition. Even though the effects of the mutations were relatively modest, the results suggest that they destabilize the proton-gating machinery. Such effects could be manifested in the presence of a transmembrane electrochemical gradient resulting in less efficient energy conservation. This article is part of a Special Issue entitled: Allosteric cooperativity in respiratory proteins.     

Investigation of mercury concentrations in fur of phocid seals using stable isotopes as tracers of trophic levels and geographical regions

Recent studies have shown that the complementary analysis of mercury (Hg) concentrations and stable isotopic ratios of nitrogen (δ¹⁵N) and carbon (δ¹³C) can be useful for investigating the trophic influence on the Hg exposure and accumulation in marine top predators. In this study, we propose to evaluate the interspecies variability of Hg concentrations in phocids from polar areas and to compare Hg bioaccumulation between both hemispheres. Mercury concentrations, δ¹⁵N and δ¹³C were measured in fur from 85 individuals representing 7 phocidae species, a Ross seal (Ommatophoca rossii), Weddell seals (Leptonychotes weddellii), crabeater seals (Lobodon carcinophagus), harbour seals (Phoca vitulina), grey seals (Halichoerus grypus), ringed seals (Pusa hispida) and a bearded seal (Erignathus barbatus), from Greenland, Denmark and Antarctica. Our results showed a positive correlation between Hg concentrations and δ¹⁵N values among all individuals. Seals from the Northern ecosystems displayed greater Hg concentrations, δ¹⁵N and δ¹³C values than those from the Southern waters. Those geographical differences in Hg and stable isotopes values were likely due to higher environmental Hg concentrations and somewhat greater number of steps in Arctic food webs. Moreover, dissimilarities in feeding habits among species were shown through δ¹⁵N and δ¹³C analysis, resulting in an important interspecific variation in fur Hg concentrations. A trophic segregation was observed between crabeater seals and the other species, resulting from the very specific diet of krill of this species and leading to the lowest observed Hg concentrations.     

A Conversion Formula for Comparing Pulse Oximeter Desaturation Rates Obtained with Different Averaging Times

Objective

The number of desaturations determined in recordings of pulse oximeter saturation (SpO₂) primarily depends on the time over which values are averaged. As the averaging time in pulse oximeters is not standardized, it varies considerably between centers. To make SpO₂ data comparable, it is thus desirable to have a formula that allows conversion between desaturation rates obtained using different averaging times for various desaturation levels and minimal durations.

Methods

Oxygen saturation was measured for 170 hours in 12 preterm infants with a mean number of 65 desaturations <90% per hour of arbitrary duration by using a pulse oximeter in a 2–4 s averaging mode. Using 7 different averaging times between 3 and 16 seconds, the raw red-to-infrared data were reprocessed to determine the number of desaturations (D). The whole procedure was carried out for 7 different minimal desaturation durations (≥1, ≥5, ≥10, ≥15, ≥20, ≥25, ≥30 s) below SpO₂ threshold values of 80%, 85% or 90% to finally reach a conversion formula. The formula was validated by splitting the infants into two groups of six children each and using one group each as a training set and the other one as a test set.

Results

Based on the linear relationship found between the logarithm of the desaturation rate and the logarithm of the averaging time, the conversion formula is: D₂ = D₁ (T₂/T₁)^c, where D₂ is the desaturation rate for the desired averaging time T₂, and D₁ is the desaturation rate for the original averaging time T₁, with the exponent c depending on the desaturation threshold and the minimal desaturation duration. The median error when applying this formula was 2.6%.

Conclusion

This formula enables the conversion of desaturation rates between different averaging times for various desaturation thresholds and minimal desaturation durations.