Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition

Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration.     

Ethanol Administration in the Rat Decreases Prostacyclin Production by Isolated Brain Microvessels

The effects of short- and long-term ethanol administration to rats on basal levels and formation of prostacyclin (PGI2) measured as 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), and on lipid class content and fatty acid composition of isolated brain microvessels (BMV) were studied. After acute treatment (2 h, at the peak of plasma ethanol concentration) basal 6-keto-PGF1 alpha levels in BMV and release on incubation were reduced to 50% of control values. After chronic administration (15 days), PGI2 release was reduced to about 40% of control values, without changes in basal levels. Total lipid, phospholipid, and cholesterol levels in BMV, measured after prolonged administration of alcohol, were not modified. Also, only minor changes in the fatty acid composition of individual phospholipid classes were detected. The observed reduction of PGI2 synthesis in BMV thus could not be related to changes of the fatty acid precursor pool in the preparation. Precursor release and/or the biosynthetic pathways may be affected by ethanol administration.     

Plasmid-coded degradation of ethylbenzene and 1-phenylethanol in Pseudomonas fluorescens

Abstract Pseudomonas fluorescens EB carries genes for the catabolism of ethylbenzene and 1-phenylethanol on a plasmid. The size of the plasmid as measured by analysis of agarose electrophoresis gels after restriction endonuclease hydrolysis, was 253–267 kb. By treatment with Mitomycin C, mutants of EB strain were obtained bearing a plasmid which had undergone an extensive deletion of about 80 kb. These mutants have lost the ability to grow on ethylbenzene and 1-phenylethanol as well as to synthesize meta-cleavage enzymes.     

Applying macrophyte community indicators to assess anthropogenic pressures on shallow soft bottoms

Vegetated soft bottoms are under pressure due to a number of anthropogenic stressors, such as coastal exploitation and eutrophication. The ecological value of these biotopes has gained recognition through international conventions and the EU directives, which request methods for assessment of the environmental status of coastal areas. However, currently there is no appropriate method for assessing the status of shallow vegetated soft bottoms in the northern Baltic Sea. Therefore, we developed a macrophyte community index and tested its response in relation to important pressures (eutrophication and boating activity) and natural gradients (topographic openness, depth and salinity) on shallow bays in the northern Baltic Sea. The macrophyte index, and hence the proportion of sensitive to tolerant species, decreased with increasing phosphorus concentration, turbidity and level of boating activity, while the cumulative cover of macrophytes only showed a negative trend in response to increasing turbidity. Juvenile fish abundance was positively related to the index, indicating importance of sensitive macrophyte species for ecosystem functioning. As the index was tested in a wide geographic area, and showed a uniform response across natural gradients, it is a promising tool for assessment of environmental status that may be applied also in other vegetated soft-bottom areas.     

An electrophoretic approach to Basidiomycetes taxonomy: Intraspecific variability,varieties, ecological influences

Abstract

Basidiospores of several Basidiomycetes species were treated with electrophoretic techniques, comparing the different protein fractions of the soluble component of the spores wall. The electrophoretic data were elaborated to obtain dendrograms indicating the similarity degree. The method was set up and tested for its validity. The technique showed that the degree of variability within the observed species escaped any generalization, covering a broad range; it was possible to identify the varieties in dendrograms of species grown in the same/different geographical zones; the growing environment and the symbiotic host often influenced the electrophoretic pattern of the spore wall proteins and resulted in dendrograms reflecting the ecological conditions.

Abbreviations: ACP, acid phosphatases; EST, esterases; UPGMA, unweighed pair‐group method using arithmetical average     

Winter herbivory by voles during a population peak: the importance of plant quality

Bilberry shoots are one of the main food sources for grey-sided voles Clethrionomys rufocanus during winter. This study examined the relation between plant quality variables of bilberry Vaccinium myrtillus shoots, overall vegetation height, and the winter consumption of bilberry by grey-sided voles. Results show that only the phenolic concentration correlated significantly with the amount of bilberry biomass consumed, and bilberry consumption decreased with an increasing phenolic concentration. The best predictor of herbivory on bilberry was not plant quality but rather the overall vegetation height. This may be because the quality of bilberry shoots is high in all habitats and that predation is a greater mortality risk than nutritional deficiencies during winter.     

A Functionally Relevant Tool for the Body following Spinal Cord Injury

A tool such as a prosthetic device that extends or restores movement may become part of the identity of the person to whom it belongs. For example, some individuals with spinal cord injury (SCI) adapt their body and action representation to incorporate their wheelchairs. However, it remains unclear whether the bodily assimilation of a relevant external tool develops as a consequence of altered sensory and motor inputs from the body or of prolonged confinement sitting or lying in the wheelchair. To explore such relationships, we used a principal component analysis (PCA) on collected structured reports detailing introspective experiences of wheelchair use in 55 wheelchair-bound individuals with SCI. Among all patients, the regular use of a wheelchair induced the perception that the body’s edges are not fixed, but are instead plastic and flexible to include the wheelchair. The PCA revealed the presence of three major components. In particular, the functional aspect of the sense of embodiment concerning the wheelchair appeared to be modulated by disconnected body segments. Neither an effect of time since injury nor an effect of exposure to/experience of was detected. Patients with lesions in the lower spinal cord and with loss of movement and sensation in the legs but who retained upper body movement showed a higher degree of functional embodiment than those with lesions in the upper spinal cord and impairment in the entire body. In essence, the tool did not become an extension of the immobile limbs; rather, it became an actual tangible substitution of the functionality of the affected body part. These findings suggest that the brain can incorporate relevant artificial tools into the body schema via the natural process of continuously updating bodily signals. The ability to embody new essential objects extends the potentiality of physically impaired persons and can be used for their rehabilitation.