New tetromycin derivatives with anti-trypanosomal and protease inhibitory activities

Four new tetromycin derivatives, tetromycins 1-4 and a previously known one, tetromycin B (5) were isolated from Streptomyces axinellae Pol001(T) cultivated from the Mediterranean sponge Axinella polypoides. Structures were assigned using extensive 1D and 2D NMR spectroscopy as well as HRESIMS analysis. The compounds were tested for antiparasitic activities against Leishmania major and Trypanosoma brucei, and for protease inhibition against several cysteine proteases such as falcipain, rhodesain, cathepsin L, cathepsin B, and viral proteases SARS-CoV M(pro), and PL(pro). The compounds showed antiparasitic activities against T. brucei and time-dependent inhibition of cathepsin L-like proteases with K(i) values in the low micromolar range.     

Pathogenesis of West Nile virus lineage 1 and 2 in experimentally infected large falcons

West Nile virus (WNV) is a zoonotic flavivirus that is transmitted by blood-suckling mosquitoes with birds serving as the primary vertebrate reservoir hosts (enzootic cycle). Some bird species like ravens, raptors and jays are highly susceptible and develop deadly encephalitis while others are infected subclinically only. Birds of prey are highly susceptible and show substantial mortality rates following infection. To investigate the WNV pathogenesis in falcons we inoculated twelve large falcons, 6 birds per group, subcutaneously with viruses belonging to two different lineages (lineage 1 strain NY 99 and lineage 2 strain Austria). Three different infection doses were utilized: low (approx. 500 TCID50), intermediate (approx. 4 log10 TCID50) and high (approx. 6 log10 TCID50). Clinical signs were monitored during the course of the experiments lasting 14 and 21 days. All falcons developed viremia for two weeks and shed virus for almost the same period of time. Using quantitative real-time RT-PCR WNV was detected in blood, in cloacal and oropharyngeal swabs and following euthanasia and necropsy of the animals in a variety of neuronal and extraneuronal organs. Antibodies to WNV were first time detected by ELISA and neutralization assay after 6 days post infection (dpi). Pathological findings consistently included splenomegaly, non-suppurative myocarditis, meningoencephalitis and vasculitis. By immunohistochemistry WNV-antigens were demonstrated intralesionally. These results impressively illustrate the devastating and possibly deadly effects of WNV infection in falcons, independent of the genetic lineage and dose of the challenge virus used. Due to the relatively high virus load and long duration of viremia falcons may also be considered competent WNV amplifying hosts, and thus may play a role in the transmission cycle of this zoonotic virus.     

A comparison of somatic cell count between organic and conventional dairy cow herds in West Germany stressing dry period related changes

Mastitis is one of the major threats to animal health and thus to productivity in all dairy farming systems. Previous studies of organic dairy herds have indicated better udder health in organic herds, as compared to conventional herds but opposite results have also been reported. In view of the great implications that the dry period (DP) has on udder health, we aimed to compare milk performance data between organic and conventional dairy herds by specifically addressing the relation of somatic cell counts in milk (SCC) before and after the DP. On 68 farms (35 organic, 33 conventional) in Western Germany individual cow and herd production data were recorded next to data on SCC (herd, individual) between June 2002 and June 2004. For data analysis, SCC values > 150,000 cells/mL were defined as indicative for disorders of udder health.     

Impact of land-use type and bark- and leaf-harvesting on population structure and fruit production of the baobab tree (Adansonia digitata L.) in a semi-arid savanna,West Africa

Non-timber forest products (NTFPs) strongly contribute to livelihood security in the semi-arid tropics. There is increasing concern about the population status of NTFP-providing trees and therefore a need for their sustainable use. Thus, this study examines the impact of land-use type on the multipurpose baobab tree (Adansonia digitata L.) in Burkina Faso, combined with rates and patterns of bark- and leaf-harvesting, and their impact on fruit production. We compared stands in a protected area (W National Park of Burkina Faso) with those of surrounding communal area (fallows, croplands and villages) to obtain an indication on the status of the baobab population, to assess its harvesting tolerance and to estimate to what extent their actual use is sustainable. Our results reveal that land-use type has an impact on the population structure of the baobab. The size class distribution curve of park stands was inverse J-shape which indicates good rejuvenation, while the curve of fallows, croplands and villages stands was bell-shaped, indicating a lack of recruitment. However, a high number of seedlings were recorded in villages. Nearly all baobabs were pruned and debarked in villages, croplands and fallows while half of the individuals were harvested in the park. Most of the trees were pruned and debarked moderately. Debarking and pruning were slightly size specific. Pruning in interaction with tree-size had a significant impact on fruit production. In contrast, debarking had no effect on fruit production. We conclude that despite the land-use impact and the intense harvesting, baobabs are still well preserved in the communal area due to their longevity, extremely low adult mortality rates and traditional management practices. However, land-use intensifications may lead to increasing pressure on baobab populations in the future. Therefore, adapted management strategies are needed to guarantee the persistence of this important species and to avoid a shortage of baobab products.     

Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115

Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to its interesting preclinical broad-spectrum antitumor potential, we report here new antioxidant and anti-protease activities for this compound. Using the ferric reducing antioxidant power (FRAP) assay, a strong antioxidant potential of diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant antioxidant and protective capacity from genomic damage induced by the reactive oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases rhodesain and cathepsin L at an IC₅₀ of 70–90 µM. It also showed antiparasitic activity against trypomastigote forms of Trypanosoma brucei with an IC₅₀ of 13.5 µM. These results showed unprecedented antioxidant and anti-protease activities of diazepinomicin, thus further highlighting its potential as a future drug candidate.     

Impact of the antibiotic sulfadiazine and pig manure on the microbial community structure in agricultural soils

Large amounts of veterinary antibiotics enter soil via manure of treated animals. The effects on soil microbial community structure are not well investigated. In particular, the impact of antibiotics in the presence of manure is poorly understood. In this study, two agricultural soils, a sandy Cambisol (KS) and a loamy Luvisol (ML), were spiked with manure and sulfadiazine (SDZ; 0, 10 and 100 μg g^?1) and incubated for 1, 4, 32 and 61 days. Untreated controls received only water. The microbial community structure was characterised by investigating phospholipid fatty acids (PLFA) and using PCR–denaturing gradient gel electrophoresis (DGGE) of 16S rDNA. The total concentration of PLFA increased with addition of manure and was reduced by both SDZ concentrations at incubation times >4 days. The SDZ addition decreased the bacteria:fungi ratio. The largest stress level, measured as ratio of PLFA (cyc17:0 + cyc19:0)/(16:1ω7c + 18:1ω7c), was found for the controls, followed by the manure treatments and the SDZ treatments. A discriminant analysis of the PLFA clearly separated treatments and incubation times. Both soils differed in total PLFA concentrations and Gram^?:Gram⁺ ratios, but showed similar changes in PLFA pattern upon soil treatment. Effects of manure and SDZ on the bacterial community structure were also revealed by DGGE analysis. Effects on pseudomonads and β-proteobacteria were less pronounced. While community structure remained altered even after two months, the extractable concentrations of SDZ decreased exponentially and the remaining solution concentrations after 32 days were ≤27% of the spiking concentration. Our results demonstrate that a single addition of SDZ has prolonged effects on the microbial community structure in soils.     

Potential renal acid load in the diet of children and adolescents: impact of food groups, age and time trends

OBJECTIVE: The impact of acid-base balance on health is widely accepted. Here, we describe the potential renal acid load (PRAL) in the diet of healthy German children and adolescents. DESIGN: The Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study is an ongoing longitudinal (open cohort) study (start 1985) collecting detailed data on diet, growth, development and metabolism in infants, children and adolescents. SETTING: Research Institute of Child Nutrition, Dortmund. SUBJECTS: Seven hundred and twenty children and adolescents (351 boys and 369 girls), aged 3-18 years, provided 4187 yearly collected 3-day dietary records between 1995 and 2005. RESULTS: Mean daily PRAL was positive in all age/sex groups (6-21 mEq day-1), and significantly higher in boys than in girls after the age of 8 years, even when calculated as mEq MJ-1. Fruits, vegetables and potatoes had a negative impact on PRAL; cheese, dairy products, cereals/bread and meat/fish/eggs had a positive impact. In a mixed linear model, PRAL, expressed as mEq day-1 and mEq MJ-1, remained stable during the study period, since time trends of PRAL-relevant food groups countervail each other. PRAL intake (mEq MJ-1) was significantly positively associated (P < 0.0001) with fat intake (% of energy intake, %E), but negatively with carbohydrate intake (%E; P < 0.0001). CONCLUSIONS: The analysis of dietary habits in our sample of German children and adolescents showed a moderate excess of acidity. Especially older boys should be encouraged to eat more potatoes and vegetables as good sources of dietary alkalinity. The PRAL concept is compatible with current concepts for a healthy diet.     

From genetic diversity and structure to conservation: Genetic signature of recent population declines in three mouse lemur species (Microcebus spp.)

The exceptional biodiversity of Madagascar is threatened by anthropogenic landscape changes that took place during the 2000 years of human colonization. This study focuses on the influence of geographic distance and forest fragmentation on genetic diversity and population differentiation of three rare, nocturnal, arboreal lemur species in northwestern Madagascar. Historic declines in population sizes as a consequence of forest fragmentation are quantified and dated. Eighteen sites were visited, and a total of 205 Microcebus ravelobensis, 45 M. bongolavensis and 78 M. danfossi were genotyped with eight microsatellite loci. Genetic differentiation among the sites, as measured by F_ST, ranged from 0.01 to 0.19. These values were significant in almost all cases and indicated genetic structure in the samples. Isolation-by-distance was detected in one species and a STRUCTURE analysis indicated that fragmentation further promoted genetic differentiation. Bayesian methods revealed that populations from all three species underwent a major demographic collapse of around two orders of magnitude. This decrease probably began after the arrival of humans, most likely within the last 500 years. This result suggests that anthropogenic changes may have been limited during the first 1500 years of human colonization in all three ranges. Two of the study species (M. danfossi, M. bongolavensis) lack effectively protected areas in their ranges. Consequently, quick conservation actions are now needed in order to secure the remaining genetic diversity of these species.