2013 Political Discussions in Foreign Affairs Committee of British Parliament on Iranian Nuclear Issue

The debate on Iran’s nuclear program in the Foreign Affairs Committee of the British Parliament, held in February 2013, in anticipation of the resumption of negotiations between Iran and the “six” of international mediators, is considered. Particular attention is paid to the position of experts invited to the meeting: representatives of academia, public organizations, military analysts. The high expert and analytical level of the meeting, which made it possible to develop effective political initiatives is noted. The most pressing issues raised during the parliamentary debates are considered. It was proved that both the deputies and the invited experts considered the further development of Tehran’s nuclear program dangerous. The authors dwell in detail on theways to resolve the Iranian nuclear problem, recommended by experts at a committee meeting: from increasing sanctions pressure to finding ways of a diplomatic settlement. The relevance of the study is due to the fact that the Iranian nuclear problem continues to be a toxic factor in the Middle East region. The novelty of the study lies in the fact that the attempt is made to reveal the position of the British Parliament members and leading experts on Iranian foreign policy. It is concluded that the political position expressed by the deputies and experts in the parliament testified to the readiness of the parties to negotiate and develop a consensus on the Iranian nuclear program.

The Use of the Adaptation Potential Reduction Model for Reproductive Toxicity Research In Vivo

The modeling of adaptation potential decrease in rats due to modification of the diet’s vitamin–mineral composition allows to increase animals’ sensitivity to toxic load in reprotoxicological experiments. The threshold values of vitamins B1, B2, B3, and B6 and mineral substances Fe3+ and Mg2+ in the diet, which lead to a considerable reduction of laboratory animals’ adaptation potential, have been determined as 19% (from the basic level in the diet) for males and 18% for females. The efficiency of this model has been confirmed in a reprotoxicological experiment with glyphosate as a toxic factor: the action of the toxic factor against the background of reduced availability of B vitamins and salts Fe3+ and Mg2+ led to significant changes in such indicators of reproductive function as mating efficiency, postimplantation loss, and the total number of alive pups, while the toxic effect of glyphosate was not so pronounced against the normal level of essential substances. The obtained results prove that this adaptation potential reduction model can be recommended for the research of the low-toxicity objects reproductive toxicity in rats and for the safety assessment of novel food, in particular.

Acidosis and toxic hemolysis – goals of pathogenetictreatment of polyorgan pathology in COVID-19

The article presents analyzis of the data of the clinical course of Covid-19 and probable pathogenetic mechanisms of lesions, which are presented in foreign and domestic literature. The hypothesis about the hematotoxic effect of the SARS-CoV-2 virus is considered, which may cause its multi-system action. An analogy is made of the pathogenesis of multiple organ lesions in case of viral infection and in acute poisoning with hemolytic poisons and iron preparations, in which the development of metabolic acidosis, toxic hemolysis, and an increase in free hemoglobin and iron ions in the blood plasma are the central link. The article proposes to use a set of diagnostic measures aimed at confirming the hematotoxic component during SARS-CoV-2 infection and methods for assessing the severity of the condition, adopted in clinical toxicology.Taking into account the experience of treating acute poisoning with hemolytic poisons, attention is focused on the importance of using alkalizing therapy in order to remove the products of hemoglobin breakdown and prevent acute nephritic failure. When confirming the presence of a toxic factor, methods aimed at eliminating toxic products of hemolysis can be used – antidote therapy and methods of surgical detoxification. This complex of therapeutic measures in clinical toxicology is effective, aimed at the prevention of acute renal failure and toxic coagulopathy. The authors believe that the hypothesis of a hematotoxic factor in the pathogenesis of Covid-19 requires a targeted therapeutic strategy and targeted study.

Both clinical and environmentalCaulobacterspecies act as opportunistic pathogens

ABSTRACTTheCaulobactergenus, including the widely-studied model organismCaulobacter crescentus, has been thought to be non-pathogenic and thus proposed as a bioengineering vector for various environmental remediation and medical purposes. However,Caulobacterspecies have been implicated as the causative agents of several hospital-acquired infections, raising the question of whether these clinical isolates represent an emerging pathogenic species or whetherCaulobacterson whole possess previously-unappreciated virulence capability. Given the proposed environmental and medical applications forC. crescentus, understanding the potential pathogenicity and human health implications of this bacterium is crucial. Consequently, we sequenced a clinicalCaulobacterisolate to determine if it has acquired novel virulence determinants. We found that the clinical isolate represents a new species,Caulobacter mirare. C. mirarephylogenetically resembles bothC. crescentusand the relatedC. segnis, which was also thought to be non-pathogenic. The similarity to otherCaulobactersand lack of obvious pathogenesis markers suggested thatC. mirareis not unique amongstCaulobactersand that consequently otherCaulobactersmay also have the potential to be virulent. We tested this hypothesis by characterizing the ability ofCaulobactersto infect the model animal hostGalleria mellonella. In this context, two different lab strains ofC. crescentusproved to be as pathogenic asC. mirare, while lab strains ofE. coliwere non-pathogenic. Further characterization showed thatCaulobacterpathogenesis is mediated by a dose-dependent, cell-associated toxic factor that does not require active bacterial cells or host cellular innate immunity to elicit its toxic effects. Finally, we show thatC. crescentusdoes not grow well in standard clinical culture conditions, suggesting thatCaulobacterinfections may be more common than generally appreciated but rarely cultured. Taken together, our findings redefineCaulobactersas opportunistic pathogens and highlight the importance of broadening our methods for identifying and characterizing pathogens.AUTHOR SUMMARYBacterial species have historically been classified as either capable of causing disease in an animal (pathogenic) or not.Caulobacterspecies represent a class of bacteria that were thought to be non-pathogenic.Caulobactershave been widely studied and proposed to be used for various industrial and medical applications due to their presumed safety. However, recent reports of humanCaulobacterinfections raised the question of whether disease-causingCaulobactershave acquired special factors that help them cause disease or whether the ability to infect is a more general feature of mostCaulobacters. By combining genomic sequencing and animal infection studies we show that a clinicalCaulobacterstrain is similar to labCaulobactersand that allCaulobactersstudied can infect a model host. We explore the mechanism of this infectivity and show that it is due to a toxic factor that associates withCaulobactercells. We also provide a possible explanation for whyCaulobactershave not traditionally been isolated from human patients, owing to their inability to tolerate the salt levels used in most medical culturing systems.

Normal aging induces A1-like astrocyte reactivity

The decline of cognitive function occurs with aging, but the mechanisms responsible are unknown. Astrocytes instruct the formation, maturation, and elimination of synapses, and impairment of these functions has been implicated in many diseases. These findings raise the question of whether astrocyte dysfunction could contribute to cognitive decline in aging. We used the Bac-Trap method to perform RNA sequencing of astrocytes from different brain regions across the lifespan of the mouse. We found that astrocytes have region-specific transcriptional identities that change with age in a region-dependent manner. We validated our findings using fluorescence in situ hybridization and quantitative PCR. Detailed analysis of the differentially expressed genes in aging revealed that aged astrocytes take on a reactive phenotype of neuroinflammatory A1-like reactive astrocytes. Hippocampal and striatal astrocytes up-regulated a greater number of reactive astrocyte genes compared with cortical astrocytes. Moreover, aged brains formed many more A1 reactive astrocytes in response to the neuroinflammation inducer lipopolysaccharide. We found that the aging-induced up-regulation of reactive astrocyte genes was significantly reduced in mice lacking the microglial-secreted cytokines (IL-1α, TNF, and C1q) known to induce A1 reactive astrocyte formation, indicating that microglia promote astrocyte activation in aging. Since A1 reactive astrocytes lose the ability to carry out their normal functions, produce complement components, and release a toxic factor which kills neurons and oligodendrocytes, the aging-induced up-regulation of reactive genes by astrocytes could contribute to the cognitive decline in vulnerable brain regions in normal aging and contribute to the greater vulnerability of the aged brain to injury.