A Pleistocene legacy structures variation in modern seagrass ecosystems.

Distribution of Earth's biomes is structured by the match between climate and plant traits, which in turn shape associated communities and ecosystem processes and services. However, that climate-trait match can be disrupted by historical events, with lasting ecosystem impacts. As Earth's environment changes faster than at any time in human history, critical questions are whether and how organismal traits and ecosystems can adjust to altered conditions. We quantified the relative importance of current environmental forcing versus evolutionary history in shaping the growth form (stature and biomass) and associated community of eelgrass (Zostera marina), a widespread foundation plant of marine ecosystems along Northern Hemisphere coastlines, which experienced major shifts in distribution and genetic composition during the Pleistocene. We found that eelgrass stature and biomass retain a legacy of the Pleistocene colonization of the Atlantic from the ancestral Pacific range and of more recent within-basin bottlenecks and genetic differentiation. This evolutionary legacy in turn influences the biomass of associated algae and invertebrates that fuel coastal food webs, with effects comparable to or stronger than effects of current environmental forcing. Such historical lags in phenotypic acclimatization may constrain ecosystem adjustments to rapid anthropogenic climate change, thus altering predictions about the future functioning of ecosystems.

Mitochondrial Dysfunction in Dopaminergic Neurons Derived from Patients with LRRK2- and SNCA-Associated Genetic Forms of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Some cases of PD may be caused by genetic factors, among which mutations in the LRRK2 and SNCA genes play an important role. To develop effective neuroprotective strategies for PD, it is important to diagnose the disease at the earliest stages of the neurodegenerative process. Therefore, the detection of diagnostic and prognostic markers of Parkinson's disease (PD) is an urgent medical need. Advances in induced pluripotent stem cell (iPSC) culture technology provide new opportunities for the search for new biomarkers of PD and its modeling in vitro. In our work, we used a new technology for multiplex profiling of gene expression using barcoding on the Nanostring platform to assess the activity of mitochondrial genes on iPSC-derived cultures of dopaminergic neurons obtained from patients with LRRK2- and SNCA-associated genetic forms PD and a healthy donor. Electron microscopy revealed ultrastructural changes in mitochondria in both LRRK2 and SNCA mutant cells, whereas mitochondria in cells from a healthy donor were normal. In a culture with the SNCA gene mutation, the ratio of the area occupied by mitochondria to the total area of the cytoplasm was significantly lower than in the control and in the line with the LRRK2 gene mutation. Transcriptome analysis of 105 mitochondria proteome genes using the Nanostring platform revealed differences between the diseased and normal cells in the activity of genes involved in respiratory complex function, the tricarboxylic acid cycle, ATP production, mitochondria-endoplasmic reticulum interaction, mitophagy, regulation of calcium concentration, and mitochondrial DNA replication.

The biogeography of community assembly: latitude and predation drive variation in community trait distribution in a guild of epifaunal crustaceans.

While considerable evidence exists of biogeographic patterns in the intensity of species interactions, the influence of these patterns on variation in community structure is less clear. Studying how the distributions of traits in communities vary along global gradients can inform how variation in interactions and other factors contribute to the process of community assembly. Using a model selection approach on measures of trait dispersion in crustaceans associated with eelgrass (Zostera marina) spanning 30° of latitude in two oceans, we found that dispersion strongly increased with increasing predation and decreasing latitude. Ocean and epiphyte load appeared as secondary predictors; Pacific communities were more overdispersed while Atlantic communities were more clustered, and increasing epiphytes were associated with increased clustering. By examining how species interactions and environmental filters influence community structure across biogeographic regions, we demonstrate how both latitudinal variation in species interactions and historical contingency shape these responses. Community trait distributions have implications for ecosystem stability and functioning, and integrating large-scale observations of environmental filters, species interactions and traits can help us predict how communities may respond to environmental change.

Biological Age Predictors: The Status Quo and Future Trends.

There is no single universal biomarker yet to estimate overall health status and longevity prospects. Moreover, a consensual approach to the very concept of aging and the means of its assessment are yet to be developed. Markers of aging could facilitate effective health control, more accurate life expectancy estimates, and improved health and quality of life. Clinicians routinely use several indicators that could be biomarkers of aging. Duly validated in a large cohort, models based on a combination of these markers could provide a highly accurate assessment of biological age and the pace of aging. Biological aging is a complex characteristic of chronological age (usually), health-to-age concordance, and medically estimated life expectancy. This study is a review of the most promising techniques that could soon be used in routine clinical practice. Two main selection criteria were applied: a sufficient sample size and reliability based on validation. The selected biological age calculators were grouped according to the type of biomarker used: (1) standard clinical and laboratory markers; (2) molecular markers; and (3) epigenetic markers. The most accurate were the calculators, which factored in a variety of biomarkers. Despite their demonstrated effectiveness, most of them require further improvement and cannot yet be considered for use in standard clinical practice. To illustrate their clinical application, we reviewed their use during the COVID-19 pandemic.

On stabilization of scattering resonances in recombination reaction that forms ozone.

Calculations of energy transfer in the recombination reaction that forms ozone are carried out within the framework of the mixed quantum/classical theory and using the dimensionally reduced 2D-model of ozone molecule, with bending motion neglected. Recombination rate coefficients are obtained at room temperature for symmetric and asymmetric isotopomers of singly and doubly substituted isotopologues. The processes of resonance formation, spontaneous decay, collisional dissociation, and stabilization by bath gas (Ar) are all characterized and taken into account within the steady-state approximation for kinetics. The focus is on stabilization step, where the mysterious isotopic η-effect was thought to originate from. Our results indicate no difference in cross sections for stabilization of scatteringresonances in symmetric and asymmetric isotopomers. As practical results, the general and simple analytic models for stabilization and dissociation cross sections are presented, which can be applied to resonances in any ozone molecule, symmetric or asymmetric, singly or doubly substituted. Present calculations show some isotope effect that looks similar to the experimentally observed η-effect, and the origin of this phenomenon is in the rates of formation/decay of scatteringresonances, determined by their widths, that are somewhat larger in asymmetric isotopomers than in their symmetric analogues. However, the approximate two-dimensional model used here is insufficient for consistent and reliable description of all features of the isotopic effect in ozone. Calculations using an accurate 3D model are still needed.

On molecular origin of mass-independent fractionation of oxygen isotopes in the ozone forming recombination reaction.

Theoretical treatment of ozone forming reaction is developed within the framework of mixed quantum/classical dynamics. Formation and stabilization steps of the energy transfer mechanism are both studied, which allows simultaneous capture of the delta zero-point energy effect and η-effect and identification of the molecular level origin of mass-independent isotope fractionation. The central role belongs to scattering resonances; dependence of their lifetimes on rotational excitation, asymmetry; and connection of their vibrational wave functions to two different reaction channels. Calculations, performed within the dimensionally reduced model of ozone, are in semiquantitative agreement with experiment.

GWAS reveals genetic basis of a predisposition to severe COVID-19 through in silico modeling of the FYCO1 protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is heavily reliant on its natural ability to "hack" the host's genetic and biological pathways. The genetic susceptibility of the host is a key factor underlying the severity of the disease. Polygenic risk scores are essential for risk assessment, risk stratification, and the prevention of adverse outcomes. In this study, we aimed to assess and analyze the genetic predisposition to severe COVID-19 in a large representative sample of the Russian population as well as to build a reliable but simple polygenic risk score model with a lower margin of error. Another important goal was to learn more about the pathogenesis of severe COVID-19. We examined the tertiary structure of the FYCO1 protein, the only gene with mutations in its coding region and discovered changes in the coiled-coil domain. Our findings suggest that FYCO1 may accelerate viral intracellular replication and excessive exocytosis and may contribute to an increased risk of severe COVID-19. We found significant associations between COVID-19 and LZTFL1, FYCO1, XCR1, CCR9, TMLHE-AS1, and SCYL2 at 3p21.31. Our findings further demonstrate the polymorphic nature of the severe COVID-19 phenotype.

Mortality and survival in nonagenarians during the COVID-19 pandemic: Unstable equilibrium of aging.

Introduction: Aging puts the human body under an immense stress and makes it extremely susceptible to many diseases, often leading to poor outcomes and even death. Long-living individuals represent a unique group of people who withstood the stress of time and offer an abundance of information on the body's ability to endure the pressure of aging. In this study, we sought to identify predictors of overall one-year mortality in 1641 long-living individuals. Additionally, we analyzed risk factors for COVID-19-related morality, since statistics demonstrated an extreme vulnerability of older adults. Methods: We conducted a two-stage evaluation, including a comprehensive geriatric assessment for major aging-associated: frailty, cognitive impairment, frontal lobe dysfunction, chronic pain, anxiety, risk of falls, sensory deficit, depression, sarcopenia, risk of malnutrition, fecal and urinary incontinence, dependence in Activities of Daily Living, dependence in Instrumental Activities of Daily Living, polypragmasia, and orthostatic hypotension; extensive blood testing, a survey, and a one-year follow-up interview. Results: The most reliable predictors of overall mortality were cognitive impairment, malnutrition, frailty, aging-associated diseases and blood markers indicating malnutrition-induced metabolic dysfunctions (decreased levels of protein fractions, iron, 25-hydroxyvitamin D, and HDL), and aging biomarkers, such as IGF-1 and N-terminal pro b-type natriuretic peptide. In post-COVID 19 participants, the most significant mortality predictors among geriatric syndromes were depression, frontal lobe dysfunction and frailty, and similar to overall mortality blood biomarkers - 25-hydroxyvitamin D, IGF-1, HDL as well as high white blood cell, neutrophils counts and proinflammatory markers. Based on the results, we built a predictive model of overall mortality in the long-living individuals with f-score=0.76. Conclusion: The most sensitive and reliable predictors of mortality were modifiable. This is another evidence of the critical importance of proper geriatric care and support for individuals in their "golden years". These results could facilitate geriatric institutions in their pursuit for providing improved care and could aid physicians in detecting early signs of potentially deadly outcomes. Additionally, our findings could be used in developing day-to-day care guidelines, which would greatly improve prevention statistics.

Genetics of psycho-emotional well-being: genome-wide association study and polygenic risk score analysis.

Background: Psycho-emotional well-being is essential for living a life of satisfaction and fulfillment. However, depression and anxiety have become the leading mental health issues worldwide, according to the World Health Organization. Both disorders have been linked to stress and other psychological factors. Their genetic basis remains understudied. Methods: In 2020-2021, the psycho-emotional well-being of 30,063 Russians with no known psychiatric history was assessed using the Hospital Anxiety and Depression Scale (HADS) for general mental health and the HADS subscale A (anxiety) for anxiety. Following the original instructions, an anxiety score of ≥11 points was used as the anxiety threshold. A genome-wide association study was performed to find associations between anxiety and HADS/HADS-A scores using linear and logistic regressions based on HADS/HADS-A scores as binary and continuous variables, respectively. In addition, the links between anxiety, sociodemographic factors (such as age, sex, and employment), lifestyle (such as physical activity, sleep duration, and smoking), and markers of caffeine and alcohol metabolism were analyzed. To assess the risk of anxiety, polygenic risk score modeling was carried out using open-access software and principal component analysis (PCA) to simplify the calculations (ROC AUC = 89.4 ± 2.2% on the test set). Results: There was a strong positive association between HADS/HADS-A scores and sociodemographic factors and lifestyle. New single-nucleotide polymorphisms (SNPs) with genome-wide significance were discovered, which had not been associated with anxiety or other stress-related conditions but were located in genes previously associated with bipolar disorder, schizophrenia, or emotional instability. The CACNA1C variant rs1205787230 was associated with clinical anxiety (a HADS-A score of ≥11 points). There was an association between anxiety levels (HADS-A scores) and genes involved in the activity of excitatory neurotransmitters: PTPRN2 (rs3857647), DLGAP4 (rs8114927), and STK24 (rs9517326). Conclusion: Our results suggest that calcium channels and monoamine neurotransmitters, as well as SNPs in genes directly or indirectly affecting neurogenesis and synaptic functions, may be involved in the development of increased anxiety. The role of some non-genetic factors and the clinical significance of physiological markers such as lifestyle were also demonstrated.

Efficient quantum-classical method for computing thermal rate constant of recombination: application to ozone formation.

Efficient method is proposed for computing thermal rate constant of recombination reaction that proceeds according to the energy transfer mechanism, when an energized molecule is formed from reactants first, and is stabilized later by collision with quencher. The mixed quantum-classical theory for the collisional energy transfer and the ro-vibrational energy flow [M. Ivanov and D. Babikov, J. Chem. Phys. 134, 144107 (2011)] is employed to treat the dynamics of molecule + quencher collision. Efficiency is achieved by sampling simultaneously (i) the thermal collision energy, (ii) the impact parameter, and (iii) the incident direction of quencher, as well as (iv) the rotational state of energized molecule. This approach is applied to calculate third-order rate constant of the recombination reaction that forms the (16)O(18)O(16)O isotopomer of ozone. Comparison of the predicted rate vs. experimental result is presented.

Analyzing Successful Aging and Longevity: Risk Factors and Health Promoters in 2020 Older Adults.

Geriatric syndromes (GSs) and aging-associated diseases (AADs) are common side effects of aging. They are affecting the lives of millions of older adults and placing immense pressure on healthcare systems and economies worldwide. It is imperative to study the factors causing these conditions and develop a holistic framework for their management. The so-called long-lived individuals-people over the age of 90 who managed to retain much of their health and functionality-could be holding the key to understanding these factors and their health implications. We analyzed the health status and lifestyle of the long-lived individuals and identified risk factors for GSs. Family history greatly contributes to the health and prevention of cognitive decline in older adults. Lifestyle and certain socioeconomic factors such as education, the age of starting to work and retiring, job type and income level, physical activity, and hobby were also associated with certain GSs. Moreover, the levels of total protein, albumin, alpha-1 globulins, high-density lipoprotein, free triiodothyronine, and 25-hydroxyvitamin D were direct indicators of the current health status. The proposed mathematical model allows the prediction of successful aging based on family history, social and economic factors, and life-long physical activity (f1 score = 0.72, AUC = 0.68, precision = 0.83 and recall = 0.64).

Collisional stabilization of van der Waals states of ozone.

The mixed quantum-classical theory developed earlier [M. Ivanov and D. Babikov, J. Chem. Phys. 134, 144107 (2011)] is employed to treat the collisional energy transfer and the ro-vibrational energy flow in a recombination reaction that forms ozone. Assumption is that the van der Waals states of ozone are formed in the O + O(2) collisions, and then stabilized into the states of covalent well by collisions with bath gas. Cross sections for collision induced dissociation of van der Waals states of ozone, for their stabilization into the covalent well, and for their survival in the van der Waals well are computed. The role these states may play in the kinetics of ozone formation is discussed.

Mixed quantum-classical theory for the collisional energy transfer and the rovibrational energy flow: application to ozone stabilization.

A mixed quantum-classical approach to the description of collisional energy transfer is proposed in which the vibrational motion of an energized molecule is treated quantum mechanically using wave packets, while the collisional motion of the molecule and quencher and the rotational motion of the molecule are treated using classical trajectories. This accounts rigorously for quantization of vibrational states, zero-point energy, scattering resonances, and permutation symmetry of identical atoms, while advantage is taken of the classical scattering regime. Energy is exchanged between vibrational, rotational, and translational degrees of freedom while the total energy is conserved. Application of this method to stabilization of the van der Waals states in ozone is presented. Examples of mixed quantum-classical trajectories are discussed, including an interesting example of supercollision. When combined with an efficient grid mapping procedure and the reduced dimensionality approximation, the method becomes very affordable computationally.

Diagnosis and Management of Autism Spectrum Disorders in Russia: Clinical-Biological Approaches.

The study describes the latest recommended and adopted clinical and management practice for children and adults with autistic spectrum disorder (ASD) in Russia and discusses the most recent research work by Russian clinicians and neuroscientists in the field. The study also presents data from the first epidemiological studies on ASD prevalence and explores the latest recommendations for clinical-biological assessments for ASD diagnosis and management in Russia. The authors call for collaboration of experts in ASD field to exchange clinical and research ideas between professionals from Russia and Western European countries and expand our mutual knowledge about ASD. This should include clinical and neurobiological studies aiming to develop differential rational approaches for ASD individual management throughout lifespan of these affected individuals.

Role of nitric oxide and related molecules in schizophrenia pathogenesis: biochemical, genetic and clinical aspects.

Currently, schizophrenia is considered a multifactorial disease. Over the past 50 years, many investigators have considered the role of toxic free radicals in the etiology of schizophrenia. This is an area of active research which is still evolving. Here, we review the recent data and current concepts on the roles of nitric oxide (NO) and related molecules in the pathogenesis of schizophrenia. NO is involved in storage, uptake and release of mediators and neurotransmitters, including glutamate, acetylcholine, noradrenaline, GABA, taurine and glycine. In addition, NO diffuses across cell membranes and activates its own extrasynaptic receptors. Further, NO is involved in peroxidation and reactive oxidative stress. Investigations reveal significant disturbances in NO levels in the brain structures (cerebellum, hypothalamus, hippocampus, striatum) and fluids of subjects with schizophrenia. Given the roles of NO in central nervous system development, these changes may result in neurodevelopmental changes associated with schizophrenia. We describe here the recent literature on NOS gene polymorphisms on schizophrenia, which all point to consistent results. We also discuss how NO may be a new target for the therapy of mental disorders. Currently there have been 2 randomized double-blind placebo-controlled trials of L-lysine as an NOS inhibitor in the CNS.

Recombination of ozone via the chaperon mechanism.

The recombination of ozone via the chaperon mechanism, i.e., ArO+O2 --> Ar+O3 and ArO2+O --> Ar+O3, is studied by means of classical trajectories and a pairwise additive Ar-O3 potential energy surface. The recombination rate coefficient has a strong temperature dependence, which approximately can be described by T(-n) with n approximately 3. It is negligible for temperatures above 700 K or so, but it becomes important for low temperatures. The calculations unambiguously affirm the conclusions of Hippler et al. [J. Chem. Phys. 93, 6560 (1990)] and Luther et al. [Phys. Chem. Chem. Phys. 7, 2764 (2005)] that the chaperon mechanism makes a sizable contribution to the recombination of O3 at room temperature and below. The dependence of the chaperon recombination rate coefficient on the isotopomer, studied for two different isotope combinations, is only in rough qualitative agreement with the experimental data. The oxygen atom isotope exchange reaction involving ArO and ArO2 van der Waals complexes is also investigated; the weak binding of O or O2 to Ar has only a small effect.

Temperature dependent energy transfer in Ar-O3 collisions.

The energy transfer between argon atoms and ozone complexes O3*, excited in the region of the dissociation threshold, is calculated for fixed temperatures (100 K< or =T < or =2500 K) using classical trajectories. The internal energy of ozone is resolved in terms of vibrational and rotational energies. For all temperatures, energy flows from O3* to Ar. The vibrational energy transfer, relative to k(B)T, is very small below 500 K, but gradually increases towards high temperatures. The relative rotational energy transfer, on the other hand, monotonously decreases with T; around 1100 K it falls below the relative vibrational energy transfer. Thermally averaged cross sections for vibrational and rotational energy transfers are also calculated. The implications for the stabilization of ozone complexes in the energy transfer model are discussed.

Intra- and intermolecular energy transfer in highly excited ozone complexes.

The energy transfer of highly excited ozone molecules is investigated by means of classical trajectories. Both intramolecular energy redistribution and the intermolecular energy transfer in collisions with argon atoms are considered. The sign and magnitude of the intramolecular energy flow between the vibrational and the rotational degrees of freedom crucially depend on the projection K(a) of the total angular momentum of ozone on the body-fixed a axis. The intermolecular energy transfer in single collisions between O(3) and Ar is dominated by transfer of the rotational energy. In accordance with previous theoretical predictions, the direct vibrational de-excitation is exceedingly small. Vibration-rotation relaxation in multiple Ar+O(3) collisions is also studied. It is found that the relaxation proceeds in two clearly distinguishable steps: (1) During the time between collisions, the vibrational degrees of freedom are "cooled" by transfer of energy to rotation; even at low pressure equilibration of the internal energy is slow compared to the time between collisions. (2) In collisions, mainly the rotational modes are "cool" by energy transfer to argon.

Microbiology of formation waters from the deep repository of liquid radioactive wastes Severnyi.

The presence, diversity, and geochemical activity of microorganisms in the Severnyi repository of liquid radioactive wastes were studied. Cultivable anaerobic denitrifiers, fermenters, sulfate-reducers, and methanogens were found in water samples from a depth of 162-405 m below sea level. Subsurface microorganisms produced methane from [2-(14)C]acetate and [(14)C]CO(2), formed hydrogen sulfide from Na(2) (35)SO(4), and reduced nitrate to dinitrogen in medium with acetate. The cell numbers of all studied groups of microorganisms and rates of anaerobic processes were higher in the zone of dispersion of radioactive wastes. Microbial communities present in the repository were able to utilise a wide range of organic and inorganic compounds and components of waste (acetate, nitrate, and sulfate) both aerobically and anaerobically. Bacterial production of gases may result in a local increase of the pressure in the repository and consequent discharge of wastes onto the surface. Microorganisms can indirectly decrease the mobility of radionuclides due to consumption of oxygen and production of sulfide, which favours deposition of metals. These results show the necessity of long-term microbiological and radiochemical monitoring of the repository.