Similarities and differences in the effect of cocaine on α-adrenergic and muscarinic response

Similarities and differences in the effect of cocaine on [alpha]-adrenergic and muscarinic receptors were shown in three experimental models. The postsynaptic stimulating effect of cocaine, mediated by [alpha]-adrenergic receptors was revealed in uninnervated chick amnion and innervated rat vas deferens. In vas deferens cocaine caused an increase of the amount of active [alpha]-adrenergic receptors, the appearance of an additional receptor pool, and change in the dimerization level. Cocaine acted as an antagonist on muscarinic receptors of the chick amnion. The inhibition by cocaine of muscarinic receptors in the rat brain cortex membranes led to a decrease in the number of receptors and their partial monomerization. Thus, cocaine influences both the [alpha]-adrenergic and the muscarinic response at the receptor level. Experiments on various objects have shown that cocaine activates the [alpha]-adrenergic response and inhibits the muscarinic one.     

Context matters: On the road to responsible biosafety technologies in synthetic biology

Biosafety is a major challenge for developing for synthetic organisms. An early focus on application and their context could assist with the design of appropriate genetic safeguards. Subject Categories: Synthetic Biology & Biotechnology, S&S: Economics & Business

One of the goals of synthetic biology is the development of robust chassis cells for their application in medicine, agriculture, and the food, chemical and environmental industries. These cells can be streamlined by removing undesirable features and can be augmented with desirable functionalities to design an optimized organism. In a direct analogy with a car chassis, they provide the frame for different modules or “plug‐in” regulatory networks, metabolic pathways, or safety elements. In an effort to ensure a safe microbial chassis upfront, safety measures are implemented as genetic safeguards to limit risks such as unwanted cellular proliferation or horizontal gene transfer. Examples of this technology include complex genetic circuits, sophisticated metabolic dependencies (auxotrophies), and altered genomes (Schmidt & de Lorenzo, 2016; Asin‐Garcia et al, 2020). Much like seat belts or airbags in cars, these built‐in measures increase the safety of the chassis and of any organisms derived from it. Indeed, when it comes to safety, synthetic biology can still learn from a century‐old technology such as cars about the significance of context for the development of biosafety technologies.Every car today has seat belts installed by default. Yet, seat belts were not always a standard component; in fact, they were not even designed for cars to begin with. The original 2‐point belts were first used in aviation and only slowly introduced for motorized vehicles. Only after some redesign, the now‐common 3‐point car seat belts would become the life‐saving equipment that they are today. A proper understanding of the context of their application was therefore one of the crucial factors for their success and wide adoption. Context matters: It provides meaning for and defines what a technological application is best suited for. What was true for seat belts may be also true for biosafety technologies such as genetic safeguards.

… when it comes to safety, synthetic biology can still learn from a century‐old technology such as cars about the significance of context for the development of biosafety technologies.

Society has a much higher awareness of technology’s risks compared to the early days of cars. Society today requires that technological risks are anticipated and assessed before an innovation or its applications are widely deployed. In addition, society increasingly demands that research and innovation take into account societal needs and values. This has led to, among others, the Responsible Research and Innovation (RRI; von Schomberg, 2013) concept that has become prominent in European science policy. In a nutshell, RRI requires that innovative products and processes align with societal needs, expectations, and values in consultation with stakeholders. RRI and similar frameworks suggest that synthetic biology must anticipate and respond not only to risks, but also to societal views that frame its evaluation and risk assessment.     

Circular dichroism of cAMP-dependent protein kinase from pig brain

The circular dichroism spectra of phosphorylated and non-phosphorylated forms of cAMP-dependent protein kinase from pig brain and those of the catalytical and regulatory subunits of the enzyme were studied. The percentage of the secondary structure components of the subunits was calculated. cAMP was shown to cause conformational changes of the enzyme. The conformation of the cyclic nucleotide within the cAMP--regulatory subunit complex was established. It was assumed that the conformation of the cAMP molecule during enzyme activation is subjected to inversion.     

Compensation for behavioral disorders caused by 6-hydroxydopamine administration via the transplantation of embryonic tissue from the locus coeruleus in rats

Neonatal injection of 6-OHDA produces defects of sensory attention and emotional reactions in the rats. Possibility of compensation of these behavioural defects by the grafts of embryonal locus coeruleus (LC) tissue into the neocortex was investigated in male rats of the Wistar strain. Histological analysis revealed spindle-shaped and oval cells typical of LC in the neocortex of all animals with LC grafts. Characteristic green fluorescence of these noradrenergic cells was demonstrated by Falck's method. Normalization of the orienting reaction to sensory (tactile and visual) stimuli, as well as of frustration effects was observed in the animals with LC grafts, but not in the control groups with saline injections or hippocampal grafts. The data show the possibility of stable compensation of the behavioural defects resulting from neonatal injection of 6-OHDA by the grafts of embryonal tissue containing noradrenergic neurones.     

Influence of a specific histone kinase on the physico-chemical properties of chromatin In situ

The influence of a specific histone kinase, phosphorylating lysine-rich histone F₁, F_2a2, F_2b, on the physico-chemical properties of the chromatin in the whole undestroyed fixed cell, has been investigated.It was found that the exogenous histone kinase penetrates into the nuclei of the undestroyed fixed cells and into the isolated unfixed nuclei and changes the physico-chemical properties of the chromatin there, bringing about an increase in binding of a basic dye acridine orange and a decrease in its stability to heat.     

Sulfhydryl groups of cyclic AMP-dependent histone kinase from pig brain]

A preparative method of isolation of the histone kinase regulatory subunit has been developed. The total number of cysteine residues in the enzyme (13 residues) and in each of its subunits (3 residues in the catalytic subunit and 10 residues in the regulatory one), has been determined. Two disulfide bridges have been found in the regulatory subunits. The relative availability of the sulfhydryl groups with respect to different modifying agents has been studied. It has been demonstrated that SH-groups blocking does not change essentially the enzyme activity.