Forebrain-specific deletion of Cdk5 in pyramidal neurons results in mania-like behavior and cognitive impairment

Cyclin-dependent kinase 5 (Cdk5) is associated with synaptic plasticity and cognitive function. Previous reports have demonstrated that Cdk5 is necessary for memory formation, although others have reported Cdk5 conditional knockout mouse models exhibiting enhanced learning and memory. Furthermore, how Cdk5 acts in specific cell populations to affect behavior and cognitive outcomes remains unclear. Here we conduct a behavioral characterization of a forebrain-specific Cdk5 conditional knockout mouse model under the αCaMKII promoter, in which Cdk5 is ablated in excitatory pyramidal neurons of the forebrain. The Cdk5 conditional knockouts exhibit hyperactivity in the open field, reduced anxiety, and reduced behavioral despair. Moreover, the Cdk5 conditional knockouts also display impaired spatial learning in the Morris water maze and are severely impaired in contextual fear memory, which correspond to deficits in synaptic transmission. Remarkably, the hyperactivity of the Cdk5 conditional knockouts can be ameliorated by the administration of lithium chloride, an inhibitor of GSK3β signaling. Collectively, our data reveal that Cdk5 ablation from forebrain excitatory neurons results in deleterious effects on emotional and cognitive behavior and highlight a key role for Cdk5 in regulating the GSK3β signaling pathway.National Institutes of Health (U.S.) (Grant T32 MH074249)National Institutes of Health (U.S.) (Grant R01 NS051874

High-Altitude Configuration of Non-Terrestrial Telecommunication Network using Optical Wireless Technologies

Non-terrestrial communication technologies will become a key component for the development of future 6th generation (6G) networks. Potentials, implementation prospects, problems and solutions for non-terrestrial telecommunications remain open areas for future research. The article discusses the use of millimeter and optical wavelengths in various configurations of multilevel space communications using LEO satellites, stratospheric platforms and unmanned repeaters. The comparison of the capacity of the Shannon channel for various multi-level scenarios of the satellite communication line is carried out. The directions of research are analyzed to ensure the continuity of communication, adaptation to weather conditions, and achieving a throughput of up to 100 Gbit/s

Anti-crisis management in Higher Education institutions of Ukraine during the Covid-19 pandemic

The article provides an overview of the anti-crisis managerial strategies of the Ministry of Education of Ukraine and educational authorities of Ukrainian higher education institutions in the context of the COVID-19 pandemic. The study comprises results of the on-line survey conducted between the 1st of March 2021 and 11th of April 2021 and covering 380 respondents (faculty members of 12 major higher education institutions in various regions of the country). The statistical and descriptive analysis of the challenges faced by Ukrainian teachers was carried out. The review makes clear that anti-crisis management activities (organizational, socio-psychological, technical, etc.) during corona-based closures have not yet been the object of sufficient surveys and therefore remain an unexplored phenomenon. The review presented proves the urgency of the problem of development of anti-crisis management activities and is intended to facilitate educational anti-crisis management. In addition, the study provides a relevant information basis for decisions and action in politics, administration and academic practice

Loss of Cyclin-Dependent Kinase 5 from Parvalbumin Interneurons Leads to Hyperinhibition, Decreased Anxiety, and Memory Impairment

Perturbations in fast-spiking parvalbumin (PV) interneurons are hypothesized to be a major component of various neuropsychiatric disorders; however, the mechanisms regulating PV interneurons remain mostly unknown. Recently, cyclin-dependent kinase 5 (Cdk5) has been shown to function as a major regulator of synaptic plasticity. Here, we demonstrate that genetic ablation of Cdk5 in PV interneurons in mouse brain leads to an increase in GABAergic neurotransmission and impaired synaptic plasticity. PVCre;fCdk5 mice display a range of behavioral abnormalities, including decreased anxiety and memory impairment. Our results reveal a central role of Cdk5 expressed in PV interneurons in gating inhibitory neurotransmission and underscore the importance of such regulation during behavioral tasks. Our findings suggest that Cdk5 can be considered a promising therapeutic target in a variety of conditions attributed to inhibitory interneuronal dysfunction, such as epilepsy, anxiety disorders, and schizophrenia.National Alliance for Research on Schizophrenia and Depression (U.S.) (Young Investigator Award)National Institutes of Health (U.S.) (Grant RO1-NS051874-16)Simons Foundation (Autism Research Initiative Grant

Thr83ala Gene Polymorphism Association with Arterial Calcification, Acute Coronary Syndrome and Ischemic Strokes in Older Adults

BACKGROUND: Calcification of the arteries of the lower extremities is a very common pathological process, which has an independent significance in the development of cardiovascular diseases. There is evidence that development of calcification of the arteries correlates with a mutation of the MGP protein gene representing by the Thr83Ala polymorphism.AIM: The purpose of the study was to analyse the connection of Thr83Ala polymorphism of the MGP gene with the development of calcification of the arteries of the lower extremities.METHODS: The study involved 80 patients. Half of them had signs of calcification of the arteries of the lower extremities. The allelic Thr83Ala polymorphism of the MGP protein gene was determined by polymerase chain reaction, establishing the presence of calcification of the arteries by radiological and dopplerographic methods.RESULTS: The study aimed to analyse the association of the Thr83Ala polymorphism of the matrix Gla protein gene with the development of calcification of the arteries of the lower extremities. The data obtained suggest that the replacement of threonine by alanine in the 83rd position of the MGP molecule can affect the functional properties of the protein and in particular its anticarcinogenic properties. Although there was no difference in the distribution of different variants of the genotype by Thr83Ala to the MGP gene polymorphism in patients with CA and healthy patients, but in the distribution of genotypes in the comparison groups separated by sex, it was found that in women, carriage of the Ala allele in a homozygous state is a factor, which protects the development of arterial calcination in the elderly and senile.CONCLUSION: Differences in the distribution of different variants of the genotype according to Thr83Ala to the polymorphism of the MGP gene between patients with CAD and healthy patients do not exceed the limits of statistical significance. In the distribution of genotypes in the comparison groups divided by sex, it was found that in women the carrier of the Ala-allele in the homozygous state is a factor that prevents the development of Menkeberg arteriosclerosis in the elderly and old age

Basolateral amygdala bidirectionally modulates stress-induced hippocampal learning and memory deficits through a p25/Cdk5-dependent pathway

Repeated stress has been suggested to underlie learning and memory deficits via the basolateral amygdala (BLA) and the hippocampus; however, the functional contribution of BLA inputs to the hippocampus and their molecular repercussions are not well understood. Here we show that repeated stress is accompanied by generation of the Cdk5 (cyclin-dependent kinase 5)-activator p25, up-regulation and phosphorylation of glucocorticoid receptors, increased HDAC2 expression, and reduced expression of memory-related genes in the hippocampus. A combination of optogenetic and pharmacosynthetic approaches shows that BLA activation is both necessary and sufficient for stress-associated molecular changes and memory impairments. Furthermore, we show that this effect relies on direct glutamatergic projections from the BLA to the dorsal hippocampus. Finally, we show that p25 generation is necessary for the stress-induced memory dysfunction. Taken together, our data provide a neural circuit model for stress-induced hippocampal memory deficits through BLA activity-dependent p25 generation.National Institutes of Health (U.S.) (Grant AG047661)National Institutes of Health (U.S.) (Grant NS051874)JPB FoundationSwiss National Science Foundation (Grant for Prospective Researchers)Human Frontier Science Program (Strasbourg, France) (Long-Term Postdoctoral Fellowship

Практичне використання методу генетичних алгоритмів для розв'язання задачі комівояжера в геоінформаційних системах

У статті проведено дослідження та адаптацію генетичного алгоритму як евристичного методу для розв’язання задачі комівояжера. Алгоритм застосовано у вигляді web-сервісу геоінформаційної системи з використанням картографічного інтерфейсу Яндекс.Карт.В статье проведено исследование и адаптацію генетического алгоритма как эврестического метода для решения задачи коммивояжера. Алгоритм применено в виде web-сервиса геоинформационной системы реализованного на базе интерфейса Яндекс.Карт.The paper investigated and improved the genetic algorithm like an heuristic method for solving the traveling salesman problem. Algorithm implemented as a web-service in framework of geographic information system based on Yandex.Maps interface

Plasmonic effects in tin disulfide nanostructured thin films obtained by the close-spaced vacuum sublimation

This work reports the investigation of plasmonic effects in tin disulfide (SnS2) nanostructured films obtained by the close-spaced vacuum sublimation method (CSS). Structural properties and phase composition of SnS2 films were studied with the help of field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), Xray diffraction (XRD) and Raman spectroscopy. Surface morphology and optical polarization properties of SnS2 films deposited at different substrate temperature were investigated by modulation-polarization spectroscopy (MPS). Surface plasmon resonances (SPR) with localized and polariton types were observed by measuring of angular and spectral characteristics of polarization difference. Radiative and nonradiative modes of surface plasmons have been analyzed at different light incident angles. The influence of surface morphology on resonant parameters of different types of SPR was studied. Correlation between the experimental results and theoretical calculations was established. The refractive and absorption indexes were found for the SnS2 films at different substrate temperature

Speckle tracking dobutamine stress echocardiography diagnostic accuracy in primary coronary arteries disease diagnosi

The aim of the work was to evaluate STE feasibility as DSE visualization method and its accuracy compared to coronary angiography (CAG) in the patients with moderate-tohigh coronary arteries disease (CAD) risk. Materials and methods: We prospectively examined 140 pts (84 (60.0%) men) with suspected CAD in order to verify diagnosis and evaluate myocardial viability and coronary reserve. Results: Mean LV EF was 54.4±15.8%. All pts had normal BP and HR during the test. There were no significant hemodynamics alterations during the test. There were no significant complications during DSE – 15 (12.9%) cases of different relatively low-grade supraventricular and ventricular arrhythmia, mainly transitory without interventions. There were 116 (82.9%) positive DSE results, of which 2 (1.72%) were false-positive. In 2 (8.3%) pts with negative DSE results CAG revealed 1-vessel insignificant (50 – 70%) lesions with developed collaterals (false-negative results). According to DSE and CAG results, 96 (82.3%) pts underwent revascularization interventions – 86 (89.6%) PCI’s and (10.4%) CABG surgeries. Sensitivity and specificity of DSE with STE for primary CAD diagnosis according to “golden standard” CAG results were 98.3% and 91.7%, respectively, with identical positive and negative predictive value and very high method overall accuracy (AUC = 0.98) and OR = 627.0 (p<0.0001). Sensitivity and specificity of DSE with STE for defining indications for intervention and revascularization were 97.9% and 91.7%, respectively, with high overall accuracy (AUC = 0.95; OR = 564.0, p<0.0001). Combined quantification of ΔGLS and ΔWMSI for primary CAD diagnosis showed significantly lower sensitivity 86.2% (р=0.0002) and specificity 80.4% (р=0.0064) with significantly lower integral method accuracy (AUC 0.83, р<0.0001). Conclusions: DSE with STE as a visualization method is a safe and optimal method for ischemia diagnosis and myocardial viability and coronary reserve evaluation in the pts with CAD suspicion. Given the lower ΔGLS and ΔWMSI accuracy compared to integral DSE with STE result evaluation, as well as frequent GLS growth in significant amount of patients with definite positive test result, authors recommend evaluating integral test result rather than strain value

A microRNA negative feedback loop downregulates vesicle transport and inhibits fear memory

The SNARE-mediated vesicular transport pathway plays major roles in synaptic remodeling associated with formation of long-term memories, but the mechanisms that regulate this pathway during memory acquisition are not fully understood. Here we identify miRNAs that are up-regulated in the rodent hippocampus upon contextual fear-conditioning and identify the vesicular transport and synaptogenesis pathways as the major targets of the fear-induced miRNAs. We demonstrate that miR-153, a member of this group, inhibits the expression of key components of the vesicular transport machinery, and down-regulates Glutamate receptor A1 trafficking and neurotransmitter release. MiR-153 expression is specifically induced during LTP induction in hippocampal slices and its knockdown in the hippocampus of adult mice results in enhanced fear memory. Our results suggest that miR-153, and possibly other fear-induced miRNAs, act as components of a negative feedback loop that blocks neuronal hyperactivity at least partly through the inhibition of the vesicular transport pathway.Brain & Behavior Research Foundation (Young Investigator Award)JPB Foundatio