Effects of nutrient (N,P, C) enrichment upon the littoral diatom community of an oligotrophic high-mountain lake

The effects of nutrient additions upon the epilithic diatom communities and the algal standing crop were investigated in the oligotrophic, softwater Lake Piccolo Naret, situated in the Swiss alps. Nutrient-diffusing flower pot substrates were filled with either N (0.15 mol NaNO₃), P (0.015 mol Na₂HPO₄) or C (0.15 mol NaHCO₃) or combinations of them. Twenty-five pots representing eight treatments were placed into the lake in July 1991 and sampled after 42 days of exposure.On the surfaces of all pots containing P we measured higher algal biomasses as on the control pots. The chlorophyll-a maximum of 12.9 µg cm^{– 2} was obtained on NPC pots (0.47 µg cm^{– 2} on control pots). On pots with P, NP or NPC supply high amounts of green algae were detected, also reflected in an increased chl-b/chl-c ratio related to the controls which showed algal communities dominated by diatoms.The diatom communities on the control pots as well as on the pots with N, P and NP had a structure similar to the epilithic community in Lake Piccolo Naret (dominance identity > 58 %). However, the community structures of the diatoms from pots with C addition (C, NC, PC and NPC) differed considerably. This is discussed in view of the cell densities of dominant diatom species. For further comparisons the results of two additional high-mountain lakes are used. By means of a cluster analysis it could be shown that epilithic diatom communities were considerably influenced by C addition, while N and P supply were of minor importance.     

Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal

Advanced glycation end products (AGEs) from the Maillard reaction contribute to protein aging and the pathogenesis of age- and diabetes-associated complications. The alpha-dicarbonyl compound methylglyoxal (MG) is an important intermediate in AGE synthesis. Recent studies suggest that pyridoxamine inhibits formation of advanced glycation and lipoxidation products. We wanted to determine if pyridoxamine could inhibit MG-mediated Maillard reactions and thereby prevent AGE formation. When lens proteins were incubated with MG at 37 degrees C, pH 7.4, we found that pyridoxamine inhibits formation of methylglyoxal-derived AGEs concentration dependently. Pyridoxamine reduces MG levels in red blood cells and plasma and blocks formation of methylglyoxal-lysine dimer in plasma proteins from diabetic rats and it prevents pentosidine (an AGE derived from sugars) from forming in plasma proteins. Pyridoxamine also decreases formation of protein carbonyls and thiobarbituric-acid-reactive substances in plasma proteins from diabetic rats. Pyridoxamine treatment did not restore erythrocyte glutathione (which was reduced by almost half) in diabetic animals, but it enhanced erythrocyte glyoxalase I activity. We isolated a major product of the reaction between MG and pyridoxamine and identified it as methylglyoxal-pyridoxamine dimer. Our studies show that pyridoxamine reduces oxidative stress and AGE formation. We suspect that a direct interaction of pyridoxamine with MG partly accounts for AGE inhibition.     

Novel CCR1 antagonists with oral activity in the mouse collagen induced arthritis

Cinnamides as novel CCR1 antagonist chemotypes are described with high affinity to human and rodent receptors. A1B1 and A4B7 showed oral activity in the mouse collagen induced arthritis.     

Oxaloacetate decarboxylase of <Emphasis Type="Italic">Archaeoglobus fulgidus</Emphasis>: cloning of genes and expression in <Emphasis Type="Italic">Escherichia coli</Emphasis>

Archaeoglobus fulgidus harbors three consecutive and one distantly located gene with similarity to the oxaloacetate decarboxylase Na⁺ pump of Klebsiella pneumoniae (KpOadGAB). The water-soluble carboxyltransferase (AfOadA) and the biotin protein (AfOadC) were readily synthesized in Escherichia coli, but the membrane-bound subunits AfOadB and AfOadG were not. AfOadA was affinity purified from inclusion bodies after refolding and AfOadC was affinity purified from the cytosol. Isolated AfOadA catalyzed the carboxyltransfer from [4-¹⁴C]-oxaloacetate to the prosthetic biotin group of AfOadC or the corresponding biotin domain of KpOadA. Conversely, the carboxyltransferase domain of KpOadA exhibited catalytic activity not only with its pertinent biotin domain but also with AfOadC.     

Insect Stage-Specific Receptor Adenylate Cyclases Are Localized to Distinct Subdomains of the Trypanosoma brucei Flagellar Membrane

Increasing evidence indicates that the Trypanosoma brucei flagellum (synonymous with cilium) plays important roles in host-parasite interactions. Several studies have identified virulence factors and signaling proteins in the flagellar membrane of bloodstream-stage T. brucei, but less is known about flagellar membrane proteins in procyclic, insect-stage parasites. Here we report on the identification of several receptor-type flagellar adenylate cyclases (ACs) that are specifically upregulated in procyclic T. brucei parasites. Identification of insect stage-specific ACs is novel, as previously studied ACs were constitutively expressed or confined to bloodstream-stage parasites. We show that procyclic stage-specific ACs are glycosylated, surface-exposed proteins that dimerize and possess catalytic activity. We used gene-specific tags to examine the distribution of individual AC isoforms. All ACs examined localized to the flagellum. Notably, however, while some ACs were distributed along the length of the flagellum, others specifically localized to the flagellum tip. These are the first transmembrane domain proteins to be localized specifically at the flagellum tip in T. brucei, emphasizing that the flagellum membrane is organized into specific subdomains. Deletion analysis reveals that C-terminal sequences are critical for targeting ACs to the flagellum, and sequence comparisons suggest that differential subflagellar localization might be specified by isoform-specific C termini. Our combined results suggest insect stage-specific roles for a subset of flagellar adenylate cyclases and support a microdomain model for flagellar cyclic AMP (cAMP) signaling in T. brucei. In this model, cAMP production is compartmentalized through differential localization of individual ACs, thereby allowing diverse cellular responses to be controlled by a common signaling molecule.     

The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA α5 inverse agonists for the treatment of cognitive dysfunction

Lead optimisation of the imidazo[1,5-a][1,2,4]-triazolo[1,5-d][1,4]benzodiazepine class led to the identification of two clinical leads [RO4882224 (11) and RO4938581 (44)] functioning as novel potent and selective GABA_A α5 inverse agonists. The unique pharmacological profiles and optimal pharmacokinetic profiles resulted in in vivo activity in selected cognition models.     

Cost-Effectiveness of Clinical Decision Support System in Improving Maternal Health Care in Ghana

ObjectiveThis paper investigated the cost-effectiveness of a computer-assisted Clinical Decision Support System (CDSS) in the identification of maternal complications in Ghana.MethodsA cost-effectiveness analysis was performed in a before- and after-intervention study. Analysis was conducted from the provider’s perspective. The intervention area was the Kassena- Nankana district where computer-assisted CDSS was used by midwives in maternal care in six selected health centres. Six selected health centers in the Builsa district served as the non-intervention group, where the normal Ghana Health Service activities were being carried out.ResultsComputer-assisted CDSS increased the detection of pregnancy complications during antenatal care (ANC) in the intervention health centres (before-intervention= 9 /1,000 ANC attendance; after-intervention= 12/1,000 ANC attendance; P-value=0.010). In the intervention health centres, there was a decrease in the number of complications during labour by 1.1%, though the difference was not statistically significant (before-intervention =107/1,000 labour clients; after-intervention= 96/1,000 labour clients; P-value=0.305). Also, at the intervention health centres, the average cost per pregnancy complication detected during ANC (cost –effectiveness ratio) decreased from US$17,017.58 (before-intervention) to US$15,207.5 (after-intervention). Incremental cost –effectiveness ratio (ICER) was estimated at US$1,142. Considering only additional costs (cost of computer-assisted CDSS), cost per pregnancy complication detected was US$285.ConclusionsComputer –assisted CDSS has the potential to identify complications during pregnancy and marginal reduction in labour complications. Implementing computer-assisted CDSS is more costly but more effective in the detection of pregnancy complications compared to routine maternal care, hence making the decision to implement CDSS very complex. Policy makers should however be guided by whether the additional benefit is worth the additional cost.     

Homing chemokines in rheumatoid arthritis

In about 20% of patients with rheumatoid arthritis, B and T lymphocytes recruited into the inflamed synovium are organized into complex microstructures, which resemble secondary lymphoid organs. The development of such lymphoid aggregates with germinal centers appears to contribute to the pathogenesis of the disease. Growing evidence indicates that chemokines and their receptors control the recruitment and positioning of leukocytes as well as their organization into node-like lymphoid structures. Here, we comment on recent studies highlighting the importance of chemokines in rheumatoid arthritis, in particular of B-cell-activating chemokine-1 in lymphoid neogenesis in the inflamed synovium.