Differential targeting of Gbetagamma-subunit signaling with small molecules

G protein betagamma subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gbetagamma subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gbetagamma subunit functions. Several compounds bound to Gbetagamma subunits with affinities from 0.1 to 60 muM and selectively modulated functional Gbetagamma-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy.     

Development of a buried bag technique to study biochars incorporated in a compost or composting medium

Purpose

The purpose was to develop a netbag technique suitable for burying biochar in a compost or composting medium, followed by its collection in a clean state (i.e., free of compost debris) without loss or damage, for physicochemical analyses. Collection in a clean state is required to ensure that the analytical data of various biochars are representative and comparable. Five criteria were identified to evaluate the suitability of netbag.

Materials and methods

A small netbag (3.5?×?3.5 cm) was developed using nylon fabric (30-μm mesh) to contain ～1 g of biochar. A production system was developed to make 15 netbags per batch. Unlike commonly used litterbags, polypropylene was used to seal netbags. Two experiments were conducted in which three biochars, made from macadamia nutshell, hardwood shaving, and chicken litter, were co-composted with chicken manure and sawdust and also incubated with a chicken litter-based commercial compost. Biochars were added at the rates of 5 or 10 % in the co-composting and 10 or 20 % in the incubation experiments. The biochar-containing netbags were buried in the co-composting and incubation mediums for 133 days. Various physicochemical analyses were conducted with netbag-biochars and their compost mediums.

Results and discussion

The netbags collected after both experiments showed no visible sign of degradation. The weight of netbag-biochars from co-composting and incubation systems did not reduce significantly over the experimental period, thereby indicating no loss of biochar. No visible evidence of entry of solid particles from compost medium was found on the netbag-biochars. Pretests indicated that the netbag and biochars absorbed pore solution from the medium. Findings showed that elements translocated between the netbag-biochar and compost medium. A colony of coccus bacteria was found on the surface of composted chicken litter biochar, denoting probable entry of bacteria from compost medium. Unlike conventional litterbags, the netbags were suitable for burying and extracting biochar in compost/composting mediums due to smaller size, smaller mesh, and strong sealing with polypropylene.

Conclusions

The netbags addressed all the five criteria. Therefore, it was concluded that, in the co-compost or incubated-compost medium, the biochar retained in the netbag and the biochar mixed with the medium were exposed to a similar bio-oxidative environment, and netbag-biochar represents the biochar in the medium. This means that these netbags can be used as a convenient means to examine the effects of the composting process or incubation in compost on biochar.

     

Altered Serum Thyrotropin Concentrations in Dogs with Primary Hypoadrenocorticism before and during Treatment

Background

Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA.

Objective

Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism.

Animals

Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled.

Methods

cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA.

Results

cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01–0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0‐2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5‐3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3‐3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2–4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation.

Conclusions and Clinical Relevance

Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH.     

Characterization of Functional Properties of Gluten Proteins in Spelt Cultivars Using Rheological and Quality Factor Measurements

Wet glutens of 27 European spelt (Triticum aestivum ssp. spelta (L.) Thell.) cultivars were examined using fundamental rheological methods (oscillatory and creep tests) in conjunction with the determination of moisture contents of these glutens and the wet gluten contents of the flours. Furthermore, SDS sedimentation volumes were determined. A special baking test for spelt was developed that encompassed the characteristic elements used in the production of traditional German spelt speciality breads. Various significant correlations between gluten properties and baking results were found for three sets of spelt cultivars obtained from different demographic locations and years of harvest. Furthermore, the relationship between baking results (response) and gluten properties (predictors) could be modeled quite well with the help of multiple linear regression analysis. Radar charts used to profile the gluten properties of a particular cultivar showed a great amount of diversity within the spelt material, but there were also similarities between several cultivars. The differences between spelt cultivars should be taken into account when characterizing spelt in general terms or when comparing spelt and modern wheat.