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A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3
No full textAbstract: This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback loops. The Nrf2 pathway is believed to be a component of the anti-aging program responsible for the healthspan and longevity. Nrf2 enables stress adaptation by activating cell antioxidant defense and other metabolic processes via control of expression of over 200 target genes in response to various types of stress. The GSK3 system represents a “regulating valve” that controls fine oscillations in the Nrf2 level, unlike Keap1, which prevents significant changes in the Nrf2 content in the absence of oxidative stress and which is inactivated by the oxidative stress. Furthermore, GSK3 modifies core circadian clock proteins (Bmal1, Clock, Per, Cry, and Rev-erbα). Phosphorylation by GSK3 leads to the inactivation and degradation of circadian rhythm-activating proteins (Bmal1 and Clock) and vice versa to the activation and nuclear translocation of proteins suppressing circadian rhythms (Per and Rev-erbα) with the exception of Cry protein, which is likely to be implicated in the fine tuning of biological clock. Functionally, GSK3 appears to be one of the hubs in the cross-regulation of circadian rhythms and antioxidant defense. Here, we present the data on the crosstalk between the most powerful cell antioxidant mechanism, the Nrf2 system, and the biorhythm-regulating system in mammals, including the impact of GSK3 overexpression and knockout on the Nrf2 signaling. Understanding the interactions between the regulatory cascades linking homeostasis maintenance and cell response to oxidative stress will help in elucidating molecular mechanisms that underlie aging and longevity
Identifying the impacts of the COVID-19 pandemic on service access for people who use drugs (PWUD): A national qualitative study
No full textIntroduction: Closures and reductions in capacity of select health and social services in response to the COVID-19 pandemic may have placed people who use drugs (PWUD) at a disproportionately increased risk for experiencing harms, and resulted in critical treatment disruptions. We conducted the current national study among a cohort of PWUD to understand how COVID-19 has affected service access, including any significant impacts PWUD may have experienced. Results will contribute to the evidence base for informing future pandemic and public health policy planning for vulnerable populations. Methods: The project involved qualitative telephone-based interviews with 196 adult (aged 18+) PWUD from across Canada. Eligibility criteria included daily or weekly use of psychoactive substance(s), and/or current enrollment in opioid agonist treatment (OAT). Data collection took place between May and July 2020. Data underwent thematic analyses, and common themes informed the results. Results: Most participants experienced detrimental service access issues and treatment disruptions during COVID-19, including reduced access to harm reduction services, OAT, withdrawal management and treatment services, medical professionals (e.g., addictions and mental health counseling), shelters/housing, and food banks. Positive impacts included greater access to OAT take-home ‘carries’ and prescription deliveries. Decreases in service capacity resulted in increased health issues and risky substance use behaviors among PWUD, such as unaccompanied substance use, sharing/re-use of supplies, and overdose events. Conclusions: Reductions in the accessibility of critical services PWUD rely on during COVID-19 has increased existent substance use and health issues among PWUD, while decreasing their ability to mitigate risks related to substance use. Thus, the expansion of the depth and breadth of support options is crucial. Services must remain open and flexible to the unique needs of PWUD during COVID-19, while novel and effective adaptations and interventions should remain available and accessible post-COVID-19
City size effect on migration and poverty: Study of million-plus cities in india
No full textCity size plays an important role in the context of growing urbanization in developing countries, such as India. In the backdrop of this fact certain questions are pertinent: whether economic activities are concentrated in a few large cities; which economic factors determine the size of large cities; whether it is possible to trace different groups among the large cities, and whether the relationship pertaining to city size, migration, and poverty is discernible are some of the research issues which are analyzed in this paper by considering 47 million-plus cities in India. The estimated Pareto distribution suggests that within the group of large million-plus cities, production is not so diversified, though the extreme form of concentration such as primacy or rank size rule does not hold either. In fact, three broad groups are evident, as brought out by the results of the cluster analysis. Both OLS and Tobit regression results indicate that the wage rate, amount of municipal solid waste generation, and the number of salaried employed persons are positively associated with city population while the number of registered motor vehicles has a negative effect on it. However, the infrastructure index calculated through factor analysis does not show any significant effect on the city size. Based on the results of factor analysis, increased migration and reduced poverty are seen to be associated with city size. Finally, we bring out the important policy suggestions for sustainable urban development
Phenoxazine nucleoside derivatives with a multiple activity against RNA and DNA viruses
No full textEmerging and re-emerging viruses periodically cause outbreaks and epidemics all over the world, eventually leading to global events such as the current pandemic of the novel SARS-CoV-2 coronavirus infection COVID-19. Therefore, an urgent need for novel antivirals is crystal clear. Here we present the synthesis and evaluation of an antiviral activity of phenoxazine-based nucleoside analogs divided into three groups: (1) 8-alkoxy-substituted, (2) acyclic, and (3) carbocyclic. The antiviral activity was assessed against a structurally and phylogenetically diverse panel of RNA and DNA viruses from 25 species. Four compounds (11a-c, 12c) inhibited 4 DNA/RNA viruses with EC ≤ 20 μM. Toxicity of the compounds for the cell lines used for virus cultivation was negligible in most cases. In addition, previously reported and newly synthesized phenoxazine derivatives were evaluated against SARS-CoV-2, and some of them showed promising inhibition of reproduction with EC values in low micromolar range, although accompanied by commensurate cytotoxicity. 50 5
Utilization of LSTM neural network for water production forecasting of a stepped solar still with a corrugated absorber plate
No full textThis study introduces a long short-term memory (LSTM) neural network model to forecast the freshwater yield of a stepped solar still and a conventional one. The stepped solar still was equiped by a copper corrugated absorber plate. The thermal performance of the stepped solar still is compared with that of conventional single slope solar still. The heat transfer coefficients of convection, evaporation, and radiation process have been evaluated. The exergy and energy efficiencies of both solar stills have been also evaluated. The yield of the stepped solar still is enhanced by about 128 % compared with that of conventional solar still. Then, the proposed LSTM neural network method is utilized to forecast the hourly yield of the investigated solar stills. Field experimental data was used to train and test the developed model. The freshwater yield was used in a time series form to train the proposed model. The forecasting accuracy of the proposed model was compared with those obtained by conventional autoregressive integrated moving average (ARIMA) and was evaluated using different statistical assessment measures. The coefficient of determination of the forecasted results has a high value of 0.97 and 0.99 for the conventional and the stepped solar still, respectively
European Resuscitation Council Guidelines 2021: Basic Life Support
No full textThe European Resuscitation Council has produced these basic life support guidelines, which are based on the 2020 International Consensus on Cardiopulmonary Resuscitation Science with Treatment Recommendations. The topics covered include cardiac arrest recognition, alerting emergency services, chest compressions, rescue breaths, automated external defibrillation (AED), CPR quality measurement, new technologies, safety, and foreign body airway obstruction
Monoclonal Antibody HlyIIC‑15 to C-End Domain HlyII B. cereus Interacts with the Trombin Recognition Site
No full textAbstract: Among the panel of monoclonal antibodies to the recombinant protein HlyIICTD Bacillus cereus an antibody was found capable of forming an immune complex with a thrombin recognition region, the amino acid sequence of which is located inside the recombinant HlyIICTD. Localization of the epitope was carried out using peptide phage display methods, as well as enzyme immunoassay and immunoblotting for interaction with recombinant proteins, either containing or not containing individual components HlyIICTD. The identified epitope is located in the region of the thrombin site and retains the ability to interact with the antibody after the proteolyotic attack of the protein by thrombin. © 2020, Pleiades Publishing, Ltd
Genomic history of the seventh pandemic of cholera in Africa
No full textThe seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa. © 2017, American Association for the Advancement of Science. All rights reserved
The microbial metabolite desaminotyrosine protects from influenza through type I interferon
No full textThe microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN. © 2017, American Association for the Advancement of Science. All rights reserved