Novel Bradykinin Analogues Modified in the N-Terminal Part of the Molecule with a Variety of Acyl Substituents

In the current work we present some pharmacological characteristics of ten new analogues of bradykinin (Arg–Pro–Pro–Gly–Phe–Ser–Pro–Phe–Arg) modified in the N-terminal part of the molecule with a variety of acyl substituents. Of the many acylating agents used previously with B2 receptor antagonists, the following residues were chosen: 1-adamantaneacetic acid (Aaa), 1-adamantanecarboxylic acid (Aca), 4-tert-butylbenzoic acid (t-Bba), 4-aminobenzoic acid (Aba), 12-aminododecanoic acid (Adc), succinic acid (Sua), 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 3-(4-hydroxyphenyl)propionic acid and 6-hydroxy-2-naphthoic acid. Biological activity of the compounds was assessed in the in vivo rat blood pressure test and the in vitro rat uterus test. Surprisingly, N-terminal substitution of the bradykinin peptide chain itself with aforementioned groups resulted in antagonists of bradykinin in the pressor test and suppressed agonistic potency in the uterotonic test. These interesting findings need further studies as they can be helpful for designing more potent B2 receptor blockers

Thought experiment: Decoding cognitive processes from the fMRI data of one individual

Wegrzyn M, Aust J, Barnstorf L, et al. Thought experiment: Decoding cognitive processes from the fMRI data of one individual. PLOS ONE. 2018;13(9): e0204338.Cognitive processes, such as the generation of language, can be mapped onto the brain using fMRI. These maps can in turn be used for decoding the respective processes from the brain activation patterns. Given individual variations in brain anatomy and organization, analyzes on the level of the single person are important to improve our understanding of how cognitive processes correspond to patterns of brain activity. They also allow to advance clinical applications of fMRI, because in the clinical setting making diagnoses for single cases is imperative. In the present study, we used mental imagery tasks to investigate language production, motor functions, visuo-spatial memory, face processing, and resting-state activity in a single person. Analysis methods were based on similarity metrics, including correlations between training and test data, as well as correlations with maps from the NeuroSynth meta-analysis. The goal was to make accurate predictions regarding the cognitive domain (e.g. language) and the specific content (e.g. animal names) of single 30-second blocks. Four teams used the dataset, each blinded regarding the true labels of the test data. Results showed that the similarity metrics allowed to reach the highest degrees of accuracy when predicting the cognitive domain of a block. Overall, 23 of the 25 test blocks could be correctly predicted by three of the four teams. Excluding the unspecific rest condition, up to 10 out of 20 blocks could be successfully decoded regarding their specific content. The study shows how the information contained in a single fMRI session and in each of its single blocks can allow to draw inferences about the cognitive processes an individual engaged in. Simple methods like correlations between blocks of fMRI data can serve as highly reliable approaches for cognitive decoding. We discuss the implications of our results in the context of clinical fMRI applications, with a focus on how decoding can support functional localization

Biochemical mechanisms of neurotoxicity caused by cadmium

Kadm (Cd) zaliczany do metali ciężkich jest jednym z ważniejszych składników zanieczyszczających środowisko życia ludzi i zwierząt. Ekspozycja środowiskowa na kadm może prowadzić do wchłaniania jego związków do organizmu i toksycznego oddziaływania na układ nerwowy. W artykule przedstawiono różne poglądy dotyczące biochemicznych mechanizmów neurotoksycznego działania kadmu. Opisano zaburzenia w komórkowym systemie antyoksydacyjnym, wytwarzanie reaktywnych form tlenu i azotu, zaburzenia w produkcji energii w szlakach metabolicznych, zmiany w metabolizmie amin biogennych, aminokwasów neuroprzekaźnikowych i jonów wapnia oraz inhibicję białek enzymatycznych.Cadmium (Cd), which belongs to the heavy metals, is one of the major polluting component of human and animal environment. Exposure to cadmium can lead to absorption of the compounds to the organism and consequently, the toxic effects in the nervous system. The paper presents various views on the biochemical mechanisms of neurotoxicity caused by cadmium. This paper describes the disturbances in the cellular antioxidant system, generation of reactive oxygen and nitrogen species, changes in energy production in the metabolic pathways, changes in the metabolism of biogenic amines, neurotransmitter amino acids and calcium ions and inhibition of enzymatic proteins

Glutathione-dependent responses of plants to drought: a review

Water is a renewable resource. However, with the human population growth, economic development and improved living standards, the world’s supply of fresh water is steadily decreasing and consequently water resources for agricultural production are limited and diminishing. Water deficiency is a significant problem in agriculture and increasing efforts are currently being made to understand plant tolerance mechanisms and to develop new tools (especially molecular) that could underpin plant breeding and cultivation. However, the biochemical and molecular mechanisms of plant water deficit tolerance are not fully understood, and the data available is incomplete. Here, we review the significance of glutathione and its related enzymes in plant responses to drought. Firstly, the roles of reduced glutathione and reduced/ oxidized glutathione ratio, are discussed, followed by an extensive discussion of glutathione related enzymes, which play an important role in plant responses to drought. Special attention is given to the S-glutathionylation of proteins, which is involved in cell metabolism regulation and redox signaling in photosynthetic organisms subjected to abiotic stress. The review concludes with a brief overview of future perspectives for the involvement of glutathione and related enzymes in drought stress responses