Balance between asymmetric allocation and repair of somatic damage in unicellular life forms as an ancient form of r/K selection.

Over the course of multiple divisions, cells accumulate diverse nongenetic, somatic damage including misfolded and aggregated proteins and cell wall defects. If the rate of damage accumulation exceeds the rate of dilution through cell growth, a dedicated mitigation strategy is required to prevent eventual population collapse. Strategies for somatic damage control can be divided into two categories, asymmetric allocation and repair, which are not, in principle, mutually exclusive. We explore a mathematical model to identify the optimal strategy, maximizing the total cell number, over a wide range of environmental and physiological conditions. The optimal strategy is primarily determined by extrinsic, damage-independent mortality and the physiological model for damage accumulation that can be either independent (linear) or increasing (exponential) with respect to the prior accumulated damage. Under the linear regime, the optimal strategy is either exclusively repair or asymmetric allocation, whereas under the exponential regime, the optimal strategy is a combination of asymmetry and repair. Repair is preferred when extrinsic mortality is low, whereas at high extrinsic mortality, asymmetric damage allocation becomes the strategy of choice. We hypothesize that at an early stage of life evolution, optimization over repair and asymmetric allocation of somatic damage gave rise to r and K selection strategists.

In viral games, refs go to the replay.

After more than 2 years of intensive investigation, the direct ancestors of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unidentified. Molecular epidemiology strongly supports a timeline marked by multiple, independent zoonoses in late 2019 (Pekar et al, 2022) solidifying the consensus hypothesis that close relatives of SARS-CoV-2 with high zoonotic potential were naturally circulating prior to the start of the pandemic (Andersen et al, 2020). Understanding where and when these ancestors acquired the genomic features that resulted in a virus with epidemic potential could enable the identification and mitigation of future pandemic viruses, even before the first human infection.

Human pathogenic RNA viruses establish noncompeting lineages by occupying independent niches.

Many pathogenic viruses are endemic among human populations and can cause a broad variety of diseases, some potentially leading to devastating pandemics. How virus populations maintain diversity and what selective pressures drive population turnover is not thoroughly understood. We conducted a large-scale phylodynamic analysis of 27 human pathogenic RNA viruses spanning diverse life history traits, in search of unifying trends that shape virus evolution. For most virus species, we identify multiple, cocirculating lineages with low turnover rates. These lineages appear to be largely noncompeting and likely occupy semiindependent epidemiological niches that are not regionally or seasonally defined. Typically, intralineage mutational signatures are similar to interlineage signatures. The principal exception are members of the family Picornaviridae, for which mutations in capsid protein genes are primarily lineage defining. Interlineage turnover is slower than expected under a neutral model, whereas intralineage turnover is faster than the neutral expectation, further supporting the existence of independent niches. The persistence of virus lineages appears to stem from limited outbreaks within small communities, so that only a small fraction of the global susceptible population is infected at any time. As disparate communities become increasingly connected through globalization, interaction and competition between lineages might increase as well, which could result in changing selective pressures and increased diversification and/or pathogenicity. Thus, in addition to zoonotic events, ongoing surveillance of familiar, endemic viruses appears to merit global attention with respect to the prevention or mitigation of future pandemics.

Molecular adaptations during viral epidemics.

In 1977, the world witnessed both the eradication of smallpox and the beginning of the modern age of genomics. Over the following half-century, 7 epidemic viruses of international concern galvanized virologists across the globe and led to increasingly extensive virus genome sequencing. These sequencing efforts exerted over periods of rapid adaptation of viruses to new hosts, in particular, humans provide insight into the molecular mechanisms underpinning virus evolution. Investment in virus genome sequencing was dramatically increased by the unprecedented support for phylogenomic analyses during the COVID-19 pandemic. In this review, we attempt to piece together comprehensive molecular histories of the adaptation of variola virus, HIV-1 M, SARS, H1N1-SIV, MERS, Ebola, Zika, and SARS-CoV-2 to the human host. Disruption of genes involved in virus-host interaction in animal hosts, recombination including genome segment reassortment, and adaptive mutations leading to amino acid replacements in virus proteins involved in host receptor binding and membrane fusion are identified as the key factors in the evolution of epidemic viruses.

Ongoing global and regional adaptive evolution of SARS-CoV-2.

Understanding the trends in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution is paramount to control the COVID-19 pandemic. We analyzed more than 300,000 high-quality genome sequences of SARS-CoV-2 variants available as of January 2021. The results show that the ongoing evolution of SARS-CoV-2 during the pandemic is characterized primarily by purifying selection, but a small set of sites appear to evolve under positive selection. The receptor-binding domain of the spike protein and the region of the nucleocapsid protein associated with nuclear localization signals (NLS) are enriched with positively selected amino acid replacements. These replacements form a strongly connected network of apparent epistatic interactions and are signatures of major partitions in the SARS-CoV-2 phylogeny. Virus diversity within each geographic region has been steadily growing for the entirety of the pandemic, but analysis of the phylogenetic distances between pairs of regions reveals four distinct periods based on global partitioning of the tree and the emergence of key mutations. The initial period of rapid diversification into region-specific phylogenies that ended in February 2020 was followed by a major extinction event and global homogenization concomitant with the spread of D614G in the spike protein, ending in March 2020. The NLS-associated variants across multiple partitions rose to global prominence in March to July, during a period of stasis in terms of interregional diversity. Finally, beginning in July 2020, multiple mutations, some of which have since been demonstrated to enable antibody evasion, began to emerge associated with ongoing regional diversification, which might be indicative of speciation.

CTRL - a label-free artificial intelligence method for dynamic measurement of single-cell volume.

Measuring the physical size of a cell is valuable in understanding cell growth control. Current single-cell volume measurement methods for mammalian cells are labor intensive, inflexible and can cause cell damage. We introduce CTRL: Cell Topography Reconstruction Learner, a label-free technique incorporating the deep learning algorithm and the fluorescence exclusion method for reconstructing cell topography and estimating mammalian cell volume from differential interference contrast (DIC) microscopy images alone. The method achieves quantitative accuracy, requires minimal sample preparation, and applies to a wide range of biological and experimental conditions. The method can be used to track single-cell volume dynamics over arbitrarily long time periods. For HT1080 fibrosarcoma cells, we observe that the cell size at division is positively correlated with the cell size at birth (sizer), and there is a noticeable reduction in cell size fluctuations at 25% completion of the cell cycle in HT1080 fibrosarcoma cells.

Ergodicity, hidden bias and the growth rate gain.

Many single-cell observables are highly heterogeneous. A part of this heterogeneity stems from age-related phenomena: the fact that there is a nonuniform distribution of cells with different ages. This has led to a renewed interest in analytic methodologies including use of the 'von Foerster equation' for predicting population growth and cell age distributions. Here we discuss how some of the most popular implementations of this machinery assume a strong condition on the ergodicity of the cell cycle duration ensemble. We show that one common definition for the term ergodicity, 'a single individual observed over many generations recapitulates the behavior of the entire ensemble' is implied by the other, 'the probability of observing any state is conserved across time and over all individuals' in an ensemble with a fixed number of individuals but that this is not true when the ensemble is growing. We further explore the impact of generational correlations between cell cycle durations on the population growth rate. Finally, we explore the 'growth rate gain'-the phenomenon that variations in the cell cycle duration leads to an improved population-level growth rate-in this context. We highlight that, fundamentally, this effect is due to asymmetric division.

Trends in depression prevalence in the USA from 2005 to 2015: widening disparities in vulnerable groups.

BACKGROUND: Major depression is associated with significant disability, morbidity, and mortality. The current study estimated trends in the prevalence of major depression in the US population from 2005 to 2015 overall and by demographic subgroups. METHODS: Data were drawn from the National Survey on Drug Use and Health (NSDUH), an annual cross-sectional study of US persons ages 12 and over (total analytic sample N = 607 520). Past-year depression prevalence was examined annually among respondents from 2005 to 2015. Time trends in depression prevalence stratified by survey year were tested using logistic regression. Data were re-analyzed stratified by age, gender, race/ethnicity, income, and education. RESULTS: Depression prevalence increased significantly in the USA from 2005 to 2015, before and after controlling for demographics. Increases in depression were significant for the youngest and oldest age groups, men, and women, Non-Hispanic White persons, the lowest income group, and the highest education and income groups. A significant year × demographic interaction was found for age. The rate of increase in depression was significantly more rapid among youth relative to all older age groups. CONCLUSIONS: The prevalence of depression increased significantly in the USA from 2005 to 2015. The rate of increase in depression among youth was significantly more rapid relative to older groups. Further research into understanding the macro level, micro level, and individual factors that are contributing to the increase in depression, including factors specific to demographic subgroups, would help to direct public health prevention and intervention efforts.

The twisted tauopathies: surface interactions of helically patterned filaments seen in alzheimer's disease and elsewhere.

This paper broadly examines the dynamics of helically patterned filaments interacting with a surface and focuses on the surface interaction of amyloid fibrils formed by tau protein. Two structures are addressed in detail: cylindrical filaments with periodic thinning (CF-PT) and paired helical filaments (PHFs). PHFs are observed in neural tissue affected by Alzheimer's disease and may aggregate to form the pathological neurofibrillary tangles associated with the illness. Work using electron microscopy has demonstrated the conversion of CF-PT into PHFs in vitro, suggesting CF-PT to be a PHF precursor in vivo. Here we model CF-PT as a patterned elastic rod placed on a flat surface (characteristic of the environment during microscopy) and examine the conformational changes resulting in stable surface bonding. Analysis of this conformational space reveals structures resembling PHFs and thus provides a mechanistic explanation of the CF-PT to PHF transition. We develop a general phase diagram of the filament conformation as a function of filament twist and bend rigidity. Results of this work also suggest that we can obtain desired filament conformations by patterning interactions of elastic filaments with a substrate, and therefore can be used as a method in microfabrication.

EVALUATION OF BILATERAL ASYMMETRY BETWEEN UPPER LIMB MASSES IN RIGHT-HANDED YOUNG ADULTS OF BOTH SEXES.

The study introduced a novel precise method for measurement and calculation of upper arm mass and to assess the difference between masses of upper limbs on the dominant and non-dominant sides of the body of right-handed participants. Forty healthy untrained male (n = 20; M age = 20.8 yr., SD = 1.2) and female (n = 20; M age = 20.7 yr., SD = 1.3) participants without a history of upper-extremity pathology participated. Kinematic and kinetic data were collected during arm motion. The mass of each arm was calculated. Each participant performed 20 movements with each arm. Most often the dominant arm was more massive than the non-dominant in both sex groups; however, mass was more symmetric for female participants than for male participants. Regression equations related to total body mass were calculated for each arm independently.

Influence of spatial accuracy constraints on reaction time and maximum speed of performance of unilateral movements.

The goal was to study reaction time and maximal velocity of upper limbs of healthy young adults of both sexes during transition from a simple to a more involved task. Performance of dominant and non-dominant arms was recorded. Participants were 43 healthy, right-handed, untrained men (n=22) and women (n=21), 18-22 years old. The simple task required a single jerk-like movement. The involved task required both speed and accuracy where necessity for high speed of performance was emphasized. The effectiveness of transition between tasks was calculated for both reaction time and maximal velocity. No lateral differences were found. Men usually had a shorter reaction time on both tasks and a higher maximal velocity in the simple task. Women were more effective at modifying velocity.

Evidence that microgynes of Myrmica rubra ants are social parasites that attack old host colonies.

Ant microgynes are miniaturized queen forms found together with normal queens (macrogynes) in species occurring across the ant phylogeny. Their role is not yet fully understood: in some cases, they seem to be nonparasitic alternative reproductive morphs, in others incipient social parasites, and thus potential models for studying the evolution of social parasitism. Whether they are regarded as parasitic or not has traditionally been based on genetic differentiation from syntopic macrogynes and/or the queen/worker ratio of their offspring rather than measuring fitness traits. We confirmed previously reported genetic differentiation between microgynes and macrogynes of Myrmica rubra in a population studied for the first time. Further, we measured virulence and infectivity of M. rubra microgynes in a controlled laboratory experiment. Nests headed only by macrogynes (controls), only by microgynes, and naturally and artificially mixed nests were kept under identical conditions. We found reduction in worker numbers of both naturally and artificially mixed macrogyne/microgyne nests compared with controls, and strong reduction but also surprising variation in fitness of nests headed only by microgynes. Microgyne nests produced workers, males and microgynes. Microgynes did not themselves reproduce in artificially mixed nests, but reproduced most in naturally mixed nests that had lost their macrogyne queen. This, together with higher mortality of field-collected macrogyne queens from naturally infested colonies and greater estimated relative age of macrogyne queens in naturally infected nests, suggests that they preferentially exploit older host colonies. We conclude that M. rubra microgynes are intraspecific social parasites specialized on exploiting old host colonies.

Evaluation and application of a paper-based device for the determination of reactive phosphate in soil solution.

The evaluation and validation of a new low-cost microfluidic paper-based analytical device (µPAD) for the determination of reactive phosphate in soil solution is described. This device allows up to 15 replicate measurements of reactive phosphate on one credit card-sized device and requires only a desktop or hand scanner for signal detection and quantification. The proposed method showed a linear response between 0.1 and 1.0 mg L and between 1.0 and 10.0 mg L P with a limit of detection of 0.05 mg L P. When applied to the analysis of soil solution, there was excellent agreement between results obtained using the µPAD and those obtained by a reference spectrophotometric method, as indicated by the following regression equation: [P] = (0.997 ± 0.005)[P] - (0.020 ± 0.008) ( = 0.997; = 110). It was found that the ambient temperature storage stability of the µPAD could be extended to 15 d by incorporating a removable polymeric interleaving sheet between the adjacent paper layers of the device. The observed sensitivity of the µPADs to sunlight, which was manifested by photoreduction of the chromogenic molybdate reagent used in the assay, was overcome by preparing the µPADs with an ultraviolet-filtering laminating material. The proposed method is rapid, with a reaction time of only 10 min, is easy to perform, and is suitable for application in the field.

[Relationship between inertial features of the upper extremity and simple reaction time in boys and girls aged 17-18].

The latent period of visual sensor-motor reaction depends, in part, on the sensory and integrative processes in the brain, but is also influenced by the rate of the muscle contraction. There is no clear evidence in the literature whether the rotational inertia of segments of limbs has any direct effect on the reaction time. The aim of our study was to identify this relationship. The study involved 566 right handed students aged 16-17 of both genders beginning their post puberty period. Reaction time was measured during experimental adduction of the forearm and hand, using a special rotating handle and lever connected to a computer that recorded the reaction time (+/- 1 ms). Calculations of the rotational inertia were carried out using regression models by Zatsiorsky and other authors. Each gender group was divided into three subgroups: with high, medium and low values of rotational inertia. It was found that individuals with high values of rotational inertia of forearm and wrist demonstrated significantly longer reaction times. This pattern was apparent in both gender groups. Although males illustrated greater values of rotational inertia than females they demonstrated relatively shorter reaction times. This contradiction can be explained by greater muscle power of young men. We recommend taking into account the amount of rotational inertia of the responsive segment in all kinds of research which require measurement of reaction time.

Risk of kidney stones with surgical intervention in living kidney donors.

A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio 0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000 person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are reassuring for the safety of living kidney donation.

Unicellular life balances asymmetric allocation and repair of somatic damage representing the origin of r/K selection.

Over the course of multiple divisions, cells accumulate diverse non-genetic, somatic damage including misfolded and aggregated proteins and cell wall defects. If the rate of damage accumulation exceeds the rate of dilution through cell growth, a dedicated mitigation strategy is required to prevent eventual population collapse. Strategies for somatic damage control can be divided into two categories, asymmetric allocation and repair, which are not, in principle, mutually exclusive. Through mathematical modelling, we identify the optimal strategy, maximizing the total cell number, over a wide range of environmental and physiological conditions. The optimal strategy is primarily determined by extrinsic (damage-independent) mortality and the physiological model for damage accumulation that can be either independent (linear) or increasing (exponential) with respect to the prior accumulated damage. Under the linear regime, the optimal strategy is either exclusively repair or asymmetric allocation whereas under the exponential regime, the optimal strategy is mixed. Repair is preferred when extrinsic mortality is low, whereas at high extrinsic mortality, asymmetric damage allocation becomes the strategy of choice. We hypothesize that optimization over somatic damage repair and asymmetric allocation in early cellular life forms gave rise to the r and K selection strategies.

Dispersal and gene flow in the rare, parasitic Large Blue butterfly Maculinea arion.

Dispersal is crucial for gene flow and often determines the long-term stability of meta-populations, particularly in rare species with specialized life cycles. Such species are often foci of conservation efforts because they suffer disproportionally from degradation and fragmentation of their habitat. However, detailed knowledge of effective gene flow through dispersal is often missing, so that conservation strategies have to be based on mark-recapture observations that are suspected to be poor predictors of long-distance dispersal. These constraints have been especially severe in the study of butterfly populations, where microsatellite markers have been difficult to develop. We used eight microsatellite markers to analyse genetic population structure of the Large Blue butterfly Maculinea arion in Sweden. During recent decades, this species has become an icon of insect conservation after massive decline throughout Europe and extinction in Britain followed by reintroduction of a seed population from the Swedish island of Öland. We find that populations are highly structured genetically, but that gene flow occurs over distances 15 times longer than the maximum distance recorded from mark-recapture studies, which can only be explained by maximum dispersal distances at least twice as large as previously accepted. However, we also find evidence that gaps between sites with suitable habitat exceeding ∼20km induce genetic erosion that can be detected from bottleneck analyses. Although further work is needed, our results suggest that M. arion can maintain fully functional metapopulations when they consist of optimal habitat patches that are no further apart than ∼10km.