Plasma concentrations of natriuretic peptides in normal cats and normotensive and hypertensive cats with chronic kidney disease

ObjectivesTo determine if natriuretic peptide concentrations are increased in cats with systemic hypertension and/or chronic kidney disease (CKD).Animals22 normal cats, 13 normotensive cats with mild-moderate CKD (NT-CKD), 15 hypertensive cats with mild-moderate CKD (HT-CKD) and 8 normotensive cats with severe CKD (NT-CKD-severe).MethodsN-terminal pro-B-type (NT-proBNP) and pro-A-type (NT-proANP) natriuretic peptides were measured in plasma samples from all cats using commercially available assays and concentrations in the normal and diseased groups compared using non-parametric statistical tests. Spearman's rank correlation was used to test for an association between natriuretic peptide and creatinine concentrations.ResultsNT-proANP was significantly higher in the NT-CKD-severe than the normal group of cats (P = 0.006) but there were no other differences between groups. NT-proBNP concentrations were significantly higher in the HT-CKD group than both the normal (P < 0.001) and the NT-CKD (P < 0.001) groups. NT-proBNP concentrations were also higher in the NT-CKD-severe (P < 0.001) and the NT-CKD (P = 0.005) groups than the normal group. NT-proANP but not NT-proBNP was significantly and positively associated with plasma creatinine concentration.ConclusionsMeasurement of NT-proBNP shows promise as a diagnostic marker for systemic hypertension in the cat. Its concentration is not significantly increased in cats with mild-moderate normotensive CKD.     

Canopy vs. understory: Does tree diversity affect bee and wasp communities and their natural enemies across forest strata?

Bees and wasps provide important ecosystem services such as pollination and biocontrol in crop-dominated landscapes, but surprisingly little information is available on hymenopteran communities in temperate forest ecosystems. Species richness and abundance of bees and wasps can be hypothesised to increase with plant diversity, structural complexity, and availability of food and nesting resources. By experimentally exposing standardised nesting sites, we examined abundance and species richness of cavity-nesting bees (pollinators), wasps (predators) and their associated parasitoids across a tree diversity gradient in a temperate deciduous forest habitat. In addition, spatial distribution of individuals and species across forest strata (canopy vs. understory) was tested. Abundance and species richness was high for predatory wasps, but generally low for pollinators. Species-rich forest stands supported increased abundance, but not species richness, of pollinators and predatory wasps, and also increased abundance and species richness of natural enemies. In addition, the forests showed a distinct spatial stratification in that abundance of bees, wasps and parasitoids as well as parasitism rates were higher in the canopy than understory. We conclude that particularly the canopy in temperate forest stands can serve as an important habitat for predatory wasp species and natural enemies, but not bee pollinators. Enhanced tree diversity was related to increased hymenopteran abundance, which is likely to be linked to an increase in nesting and food resources in mixed forest stands.     

Microbial regulation in gorgonian corals

Gorgonian corals possess many novel natural products that could potentially mediate coral-bacterial interactions. Since many bacteria use quorum sensing (QS) signals to facilitate colonization of host organisms, regulation of prokaryotic cell-to-cell communication may represent an important bacterial control mechanism. In the present study, we examined extracts of twelve species of Caribbean gorgonian corals, for mechanisms that regulate microbial colonization, such as antibacterial activity and QS regulatory activity. Ethanol extracts of gorgonians collected from Puerto Rico and the Florida Keys showed a range of both antibacterial and QS activities using a specific Pseudomonas aeruginosa QS reporter, sensitive to long chain AHLs and a short chain N-acylhomoserine lactones (AHL) biosensor, Chromobacterium violaceium. Overall, the gorgonian corals had higher antimicrobial activity against non-marine strains when compared to marine strains. Pseudopterogorgia americana, Pseusopterogorgia acerosa, and Pseudoplexuara flexuosa had the highest QS inhibitory effect. Interestingly, Pseudoplexuara porosa extracts stimulated QS activity with a striking 17-fold increase in signal. The stimulation of QS by P. porosa or other elements of the holobiont may encourage colonization or recruitment of specific microbial species. Overall, these results suggest the presence of novel stimulatory QS, inhibitory QS and bactericidal compounds in gorgonian corals. A better understanding of these compounds may reveal insight into coral-microbial ecology and whether a therapeutic potential exists.     

Spatial patterns of microbial denitrification genes change in response to poultry litter placement and cover crop species in an agricultural soil

Subsurface-banding manure and winter cover cropping are farming techniques designed to reduce N loss. Little is known, however, about the effects of these management tools on denitrifying microbial communities and the greenhouse gases they produce. Abundances of bacterial (16S), fungal (ITS), and denitrification genes (nirK, nirS, nosZ-I, and nosZ-II) were measured in soil samples collected from a field experiment testing the combination of cereal rye and hairy vetch cover cropping with either surface-broadcasted or subsurface-banded poultry litter. The spatial distribution of genes was mapped to identify potential denitrifier hotspots. Spatial distribution maps showed increased 16S rRNA genes around the manure band, but no denitrifier hotspots. Soil depth and nitrate concentration were the strongest drivers of gene abundance, but bacterial gene abundance also differed by gene, soil characteristics, and management methods. Gene copy number of nirK was higher under cereal rye than hairy vetch and positively associated with soil moisture, while nirS gene copies did not differ between cover crop species. The nirS gene copies increased when manure was surface broadcasted compared to subsurface banded and was positively associated with pH. Soil moisture and pH were positively correlated to nosZ-II but not to nosZ-I gene copy numbers. We observed stronger correlations between nosZ-I and nirS, and nosZ-II and nirK gene copies compared to the reverse pairings. Agricultural management practices differentially affect spatial distributions of genes coding for denitrification enzymes, leading to changes in the composition of the denitrifying community.     

Incidence of and risks associated with Giardia infections in herds on dairy farms in the New York City Watershed

Background

The primary aims of this study were to determine the incidence of Giardia infections in dairy herds on farms in the New York City Watershed region and to evaluate risk factors associated with infections. Because co-infections of Giardia and Cryptosporidium spp. are common in this population, we also evaluated the effect of herd infection status on Giardia infections.

Methods

Farms were grouped into three cohorts based on their prior infection status with Giardia and/or Cryptosporidium spp. The sampling plan included collecting fecal samples from all calves below 30 days of age and proportional sampling of calves, young stock, and adults. A total of 10,672 fecal samples were collected and analyzed for the presence of Giardia cysts using zinc sulfate flotation. Herds enrolled in the study were sampled seasonally for a study period of two years. The probability of shedding cysts past a certain age and the factors that influenced the likelihood of shedding were evaluated using survival analysis. Linear regression was used to evaluate factors that were associated with the intensity of shedding.

Results

The majority of Giardia infections occurred in calves within their first 180 days of age, with the most number of calves shedding Giardia cysts between 11 and 20 days of age. The incidence of shedding of Giardia cysts ranged from 0.0004 per animal day for cattle in the low risk cohort to 0.0011 per animal day for cattle in the high risk cohort. The likelihood of shedding was influenced by the prior infection status of the herd and the season of collection. Infected animals shed on average 9,658 cysts/gram and the intensity of shedding Giardia cysts varied significantly with the age (p < 0.0001) and the season of collection (p = 0.0151 for Spring).

Conclusion

Giardia infections are common in dairy herds in the New York City watershed, particularly in calves less than 6 months of age. Seasonality may be an important factor in the perpetuation of infections based on changes in management practices corresponding to weather patterns of a particular season. A dairy herd''s prior infection status with Cryptosporidium influences the likelihood of infection with Giardia.     

Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.     

Comparison of chemistry analytes between 2 portable, commercially available analyzers and a conventional laboratory analyzer in reptiles

Background: Advantages of handheld and small bench‐top biochemical analyzers include requirements for smaller sample volume and practicality for use in the field or in practices, but little has been published on the performance of these instruments compared with standard reference methods in analysis of reptilian blood. Objective: The aim of this study was to compare reptilian blood biochemical values obtained using the Abaxis VetScan Classic bench‐top analyzer and a Heska i‐STAT handheld analyzer with values obtained using a Roche Hitachi 911 chemical analyzer. Methods: Reptiles, including 14 bearded dragons (Pogona vitticeps), 4 blue‐tongued skinks (Tiliqua gigas), 8 Burmese star tortoises (Geochelone platynota), 10 Indian star tortoises (Geochelone elegans), 5 red‐tailed boas (Boa constrictor), and 5 Northern pine snakes (Pituophis melanoleucus melanoleucus), were manually restrained, and a single blood sample was obtained and divided for analysis. Results for concentrations of albumin, bile acids, calcium, glucose, phosphates, potassium, sodium, total protein, and uric acid and activities of aspartate aminotransferase and creatine kinase obtained from the VetScan Classic and Hitachi 911 were compared. Results for concentrations of chloride, glucose, potassium, and sodium obtained from the i‐STAT and Hitachi 911 were compared. Results: Compared with results from the Hitachi 911, those from the VetScan Classic and i‐STAT had variable correlations, and constant or proportional bias was found for many analytes. Bile acid data could not be evaluated because results for 44 of 45 samples fell below the lower linearity limit of the VetScan Classic. Conclusions: Although the 2 portable instruments might provide measurements with clinical utility, there were significant differences compared with the reference analyzer, and development of analyzer‐specific reference intervals is recommended.     

Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins

Synthetic genetic devices that interface with native cellular pathways can be used to change natural networks to implement new forms of control and behavior. The engineering of gene networks has been limited by an inability to interface with native components. We describe a class of RNA control devices that overcome these limitations by coupling increased abundance of particular proteins to targeted gene expression events through the regulation of alternative RNA splicing. We engineered RNA devices that detect signaling through the nuclear factor κB and Wnt signaling pathways in human cells and rewire these pathways to produce new behaviors, thereby linking disease markers to noninvasive sensing and reprogrammed cellular fates. Our work provides a genetic platform that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior.