Determinants of serum levels of surfactant proteins A and B and Clara cell protein CC16.

Increased leakage of surfactant proteins A and B (SP-A and SP-B) and Clara cell secretory protein (CC16) from the air spaces into the circulation occurs in a range of respiratory conditions. However, circulating levels depend not only on the rate of entry into the circulation, but also on the rate of clearance. In order to clarify the role of the kidney in the clearance of these proteins, serum levels were related to markers of glomerular filtration in 54 non-smoking patients with varying degrees of renal dysfunction, none of whom had respiratory disease or were receiving dialysis at the time of sampling. Serum SP-A was related to SP-B (r = 0.53, p < 0.001) and to CC16 (r = 0.33, p < 0.02). Similarly, SP-B was related to CC16 (r = 0.39, p < 0.004). Stepwise multiple linear regression analysis suggested that serum SP-A and SP-B are influenced by age (approximately 20 and approximately 25% of variance, respectively), whereas CC16 is determined by renal function and, to a lesser extent, by body weight (approximately 63% of variance in total). We conclude that CC16 is cleared from blood by the renal route, whereas SP-A and SP-B are not. Serum SP-A and SP-B are influenced by age, which we speculate reflects increased damage to the alveolocapillary barrier.     

Validation of ecological status concepts in UK rivers using historic diatom samples

We assessed the feasibility of using herbarium specimens to validate reference conditions in the UK by comparing diatom community composition of river sites with both recent and historic diatom samples. The question of substrate specificity was addressed by comparing epilithon (stone-derived) and epiphyton (plant-derived) samples from a number of rivers. No significant differences were found between the Trophic Diatom Index (TDI), species richness, species diversity, and percentage of motile valves between paired diatom samples (epilithic and epiphytic) from contemporary samples. Significant differences were recorded between a number of indices derived from analysis of the historic diatom samples on plant material sampled pre-1930 compared with diatoms from stones collected post-1990 from the same river location. The TDI, mean species richness, and species diversity and percentage of motile valves and nutrient tolerant valves were all significantly greater in the contemporary samples (p ≤ 0.05). The percentage of nutrient sensitive valves was significantly lower in the contemporary samples (p ≤ 0.05).The relative abundance of Achnanthidium minutissimum and Cocconeis placentula var. lineata was significantly greater on the herbarium material compared to matched contemporary samples. Calculated values for the TDI (43 ± 3) expected at reference conditions were similar to the observed TDI values derived from herbarium material (44 ± 12) showing no significant deviation in ecological status.     

Scavenging superoxide selectively in mouse forebrain is associated with improved cardiac function and survival following myocardial infarction

Dysregulation in central nervous system (CNS) signaling that results in chronic sympathetic hyperactivity is now recognized to play a critical role in the pathogenesis of heart failure (HF) following myocardial infarction (MI). We recently demonstrated that adenovirus-mediated gene transfer of cytoplasmic superoxide dismutase (Ad-Cu/ZnSOD) to forebrain circumventricular organs, unique sensory structures that lack a blood-brain barrier and link peripheral blood-borne signals to central nervous system cardiovascular circuits, inhibits both the MI-induced activation of these central signaling pathways and the accompanying sympathoexcitation. Here, we tested the hypothesis that this forebrain-targeted reduction in oxidative stress translates into amelioration of the post-MI decline in myocardial function and increase in mortality. Adult C57BL/6 mice underwent left coronary artery ligation or sham surgery along with forebrain-targeted gene transfer of Ad-Cu/ZnSOD or a control vector. The results demonstrate marked MI-induced increases in superoxide radical formation in one of these forebrain regions, the subfornical organ (SFO). Ad-Cu/ZnSOD targeted to this region abolished the increased superoxide levels and led to significantly improved myocardial function compared with control vector-treated mice. This was accompanied by diminished levels of cardiomyocyte apoptosis in the Ad-Cu/ZnSOD but not the control vector-treated group. These effects of superoxide scavenging with Ad-Cu/ZnSOD in the forebrain paralleled increased post-MI survival rates compared with controls. This suggests that oxidative stress in the SFO plays a critical role in the deterioration of cardiac function following MI and underscores the promise of CNS-targeted antioxidant therapy for the treatment of MI-induced HF.     

Mixed fermentation for natural product drug discovery

Natural products continue to play a major role in drug discovery and development. However, chemical redundancy is an ongoing problem. Genomic studies indicate that certain groups of bacteria and fungi have dozens of secondary metabolite pathways that are not expressed under standard laboratory growth conditions. One approach to more fully access the metabolic potential of cultivatable microbes is mixed fermentation, where the presence of neighboring microbes may induce secondary metabolite synthesis. Research to date indicates that mixed fermentation can result in increased antibiotic activity in crude extracts, increased yields of previously described metabolites, increased yields of previously undetected metabolites, analogues of known metabolites resulting from combined pathways and, importantly, induction of previously unexpressed pathways for bioactive constituents.     

Cellulose microfibrils from banana rachis: Effect of alkaline treatments on structural and morphological features

Four different alkaline treatments for isolation of cellulose microfibrils from vascular bundles of banana rachis were comparatively studied. Isolated cellulose microfibrils were characterized using high performance anion exchange chromatography for neutral sugar composition, as well as attenuated total reflection Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray and electron diffraction and solid-state ¹³C NMR. The cellulose microfibrils treated with peroxide alkaline, peroxide alkaline–hydrochloric acid or 5 wt% potassium hydroxide had average diameters of 3–5 nm, estimated lengths of several micrometers. Although the interpretation of their structure is difficult because of the low cristallinity, X-ray diffraction, ¹³C NMR and ATR-FTIR results suggested that cellulose microfibrils from banana rachis could be either interpreted as cellulose IV₁ or cellulose Iβ. The specimens treated with a more concentrated KOH solution (18 wt%) were still microfibrillated but their structure was converted to cellulose II.     

Predicting future distributions of mountain plants under climate change: does dispersal capacity matter?

Many studies have investigated the potential impacts of climate change on the distribution of plant species, but few have attempted to constrain projections through plant dispersal limitations. Instead, most studies published so far have simplified dispersal as either unlimited or null. However, depending on the dispersal capacity of a species, landscape fragmentation, and the rate of climatic change, these assumptions can lead to serious over- or underestimation of the future distribution of plant species.
To quantify the discrepancies between simulations accounting for dispersal or not, we carried out projections of future distribution over the 21st century for 287 mountain plant species in a study area of the western Swiss Alps. For each species, simulations were run for four dispersal scenarios (unlimited dispersal, no dispersal, realistic dispersal, and realistic dispersal with long-distance dispersal events) and under four climate change scenarios.
Although simulations accounting for realistic dispersal limitations did significantly differ from those considering dispersal as unlimited or null in terms of projected future distribution, the unlimited dispersal simplification did nevertheless provide good approximations for species extinctions under more moderate climate change scenarios. Overall, simulations accounting for dispersal limitations produced, for our mountainous study area, results that were significantly closer to unlimited dispersal than to no dispersal. Finally, analysis of the temporal pattern of species extinctions over the entire 21st century revealed that important species extinctions for our study area might not occur before the 2080–2100 period, due to the possibility of a large number of species shifting their distribution to higher elevation.     

Synthesis and biological evaluation of new heterocyclic quinolinones as anti-parasite and anti-HIV drug candidates

We have synthesized quinolinones with potential antiparasitic and anti-HIV activities by an original two-step method involving microwave irradiation and have evaluated their activities against Plasmodium falciparum, Leishmania donovani, Trichomonas vaginalis, and HIV. None of the tested compounds had been previously described using this method of synthesis. One of the compounds had interesting antiparasitic and anti-HIV activity, which could be improved by substitution with different radicals.     

Gene expression profiling of single bovine embryos uncovers significant effects of in vitro maturation, fertilization and culture

In vitro production (IVP) has been shown to affect embryonic gene expression and often result in large offspring syndrome (LOS) in cattle and sheep. To dissect the effects of in vitro maturation, fertilization and culture on bovine embryos, we compared the expression profiles of single blastocysts generated by: (1) in vitro maturation, fertilization and culture (IVF); (2) in vivo maturation, fertilization and in vitro culture (IVD); and (3) in vivo maturation, fertilization and development (AI). To conduct expression profiling, total RNA was isolated from individual embryos, linearly amplified and hybridized to a custom bovine cDNA microarray containing approximately 6,300 unique genes. There were 306, 367, and 200 genes differentially expressed between the AI and IVD, IVF and IVD, and AI and IVF comparisons, respectively. Interestingly, 44 differentially expressed genes were identified between the AI embryos and both the IVF and IVD embryos, making these potential candidates for LOS. There were 60 genes differentially expressed between the IVF embryos and the AI and IVD embryos. The Gene Ontology category "RNA processing" was over-represented among the genes that were down-regulated in the IVF embryos, indicating an effect of in vitro oocyte maturation/fertilization on the ability to transcribe maternal RNA stores. A culture effect on the expression of genes involved in translation was also observed by the comparison of AI with IVD embryos.