Fitness Benefits Research Articles

Context-dependent fitness benefits of antibiotic resistance mutations.

Context-dependent fitness benefits of antibiotic resistance mutations.

Impacts of invasion on a freshwater cleaning symbiosis

Organismal invasions have repeatedly been cited as a driving force behind the loss of biodiversity. Unlike many other impacts of invasion, the effect of invasion on native symbiont communities has received less attention. The introduction of invasive hosts presents a potential opportunity to native symbionts; invasive hosts could benefit native symbionts through providing a novel host environment that improves symbiont fitness relative to their fitness on native hosts. Alternatively, invasive hosts could noncompetent hosts for native symbionts, resulting in negative impacts on native symbiont abundance and diversity. Crayfish in the northern hemisphere host diverse assemblages of obligate annelid symbionts (P: Anellida, O: Branchiobdellida). Two invasive crayfish hosts in the genus Faxonius have been introduced and are interacting with the native crayfish hosts and their symbionts in three watersheds in western Virginia, USA. Previous studies suggest that the invasive host F. cristavarius is a less competent host for symbionts compared to native hosts in the genus Cambarus. We carried out an extensive survey in these watersheds to determine impacts of varying degrees of invasion on branchiobdellidan abundance and diversity. We also conducted a complementary host replacement experiment to investigate how increases in the relative abundance of invasive hosts contributes to observed patterns of symbiont abundance and diversity in the field. In our survey, as the proportion of invasive hosts at a site increased, branchiobdellidan abundance and diversity declined significantly. In the experiment, the worms dispersed onto both native and invasive hosts. As the percentage of noncompetent F. cristavarius hosts increased, the survival of branchiobdellidans declined. Both symbiont survival and opportunities for successful dispersal are reduced as this noncompetent invasive host progressively displaces native hosts, which imperils the integrity of native host-symbiont systems. Given that many native hosts accrue significant fitness benefits from their relationships with native symbionts, including hosts in our study system, losses of beneficial symbionts may produce a positive feedback loop that decreases invasion resistance of native species, exacerbates the effects of invasions, and presents a major conservation issue in invaded systems.

Relationship between Gross Motor Coordination and Health-Related Fitness in Serbian Preschool Children.

The relationship between motor coordination and physical fitness in preschool children is of significant interest due to its implications for overall health and development. This study aims to investigate the correlation between gross motor coordination, as assessed by the Körperkoordinationstest für Kinder (KTK), and health-related physical fitness components. A cross-sectional study, involving 139 preschool-aged children, was conducted. Physical fitness was assessed using the PREFIT fitness test battery, which includes measures of flexibility, muscular strength, speed/agility, and cardiorespiratory fitness. Motor coordination was evaluated using the KTK test, comprising four subtests. Pearson correlation analysis revealed weak to strong positive and negative correlations between motor coordination and various physical fitness measures, including flexibility (r = 0.402; p = 0.01), muscular strength (r = 0.178; r = 0.487; r = 0.601; p < 0.05), speed/agility (r = -0.742; p = 0.01), and endurance (r = 0.539; p = 0.01). Additionally, hierarchical regression analysis demonstrated significant influence of motor coordination on physical fitness, explaining a notable percentage of the variance across different fitness components (3.2-55%). The findings underscore the importance of motor coordination in shaping physical fitness levels in preschool children. Promoting motor coordination skills early in childhood may have long-term benefits for overall health and fitness.

Is biased mutation sufficient to save runaway sexual selection?

In the 1980s, groundbreaking theoretical studies showed that ornaments displayed during courtship can coevolve with preferences for such ornaments, leading to extreme exaggeration of both traits. Later models cast doubt on such "runaway" sexual selection, showing that even a small cost of preferences can prevent exaggerated ornaments from persisting long-term. It was subsequently shown that if mutations acting on the ornament are biased-tending to produce smaller rather than larger ornaments-then exaggeration can persist even in the presence of preference costs, seemingly vindicating the original models. Here, we unpack an implicit assumption of these "biased mutation" models: Mutations are assumed to lead, on average, to both smaller and less costly ornaments. Biased mutation consequently generates both a fitness cost (due to reduced mating success) and a fitness benefit (due to increased survival). We lift this assumption by separating an individual's investment in an ornament from their efficiency in converting such investment into ornament size. We assume that biased mutation acts only on efficiency but not on investment, and discuss the plausibility of this alternative assumption. Our model predicts that exaggerated ornaments and preferences can persist stably once they arise, but that strong initial preferences are needed to kick-start the runaway process. Consequently, biased mutation alone may not always be sufficient to save runaway sexual selection.

Extra-pair paternity in two passerine birds breeding in a gradient of urbanisation.

Urbanisation has been increasing worldwide in recent decades, driving environmental change and exerting novel selective pressures on wildlife. Phenotypic differences between urban and rural individuals have been widely documented in several taxa. However, the extent to which urbanisation impacts mating strategies is less known. Here, we investigated extra-pair paternity variation in great tits (Parus major) and blue tits (Cyanistes caeruleus) breeding in nestboxes set in a gradient of urbanisation in Warsaw, Poland, over three breeding seasons. Urbanisation was quantified as the amount of light pollution, noise pollution, impervious surface area (ISA) and tree cover within a 100-m radius around each nestbox. We obtained genotypes for 1213 great tits at 7344 SNP markers and for 1299 blue tits at 9366 SNP markers with a genotyping-by-sequencing method, and inferred extra-pair paternity by computing a genomewide relatedness matrix. We report higher extra-pair paternity in blue tits breeding in more urbanised areas, for example, with higher light pollution and ISA, and lower tree cover. However, no such trend was found in great tits. Late-stage survival of individual nestlings in both species was not associated with paternity or urbanisation proxies, thus we were not able to detect fitness benefits or drawbacks of being an extra-pair offspring in relation to urbanisation. Our results contribute to the growing body of knowledge reporting on the effects of urbanisation on avian ecology and behaviour, and confirm species-specific and population-specific patterns of extra-pair paternity variation.

Coordination of care reduces conflict and predation risk in a cooperatively breeding bird

Abstract When two or more individuals cooperate to provision a shared brood, each carer may be able to maximize their payoffs by coordinating provisioning in relation to what others are doing. This investment “game” is not simply a matter of how much to invest but also of the relative timing of investment. Recent studies propose that temporal coordination of care in the forms of alternation (i.e., turn-taking) and synchrony (i.e., provisioning together) function to mitigate conflict between carers and reduce brood predation risk, respectively. Such coordination is widespread in biparental and cooperatively breeding birds, yet the fitness consequences have rarely been empirically tested. Here, we use a long-term study of long-tailed tits Aegithalos caudatus, a facultative cooperatively breeding bird with active coordination of care, to assess the support for these hypothesized functions for coordination of provisioning visits. First, we found evidence that turn-taking mitigates conflict between carers because, in cooperative groups, provisioning rates and offspring recruitment increased with the level of active alternation exhibited by carers and with the associated increase in provisioning rate parity between carers. In contrast, offspring recruitment did not increase with alternation in biparental nests, although it was positively correlated with parity of provisioning between carers, which is predicted to result from conflict mitigation. Second, synchronous nest visits were associated with a reduced probability of nest predation and thus increased brood survival, especially when provisioning rates were high. We attribute this effect to synchrony reducing carer activity near the nest. We conclude that temporal coordination of provisioning visits in the forms of alternation and synchrony both confer fitness benefits on carers and despite being intrinsically linked, these different kinds of coordination appear to serve different functions.

The retrotransposon-derived capsid genes PNMA1 and PNMA4 maintain reproductive capacity.

The human genome contains 24 gag-like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the ability to form capsids and even transfer cargo, their fitness benefit has remained elusive. Here we show that the gag-like genes PNMA1 and PNMA4 support reproductive capacity during aging. Analysis of donated human ovaries shows that expression of both genes declines normally with age, while several PNMA1 and PNMA4 variants identified in genome-wide association studies are causally associated with low testosterone, altered puberty onset, or obesity. Six-week-old mice lacking either Pnma1 or Pnma4 are indistinguishable from wild-type littermates, but by six months the mutant mice become prematurely subfertile, with precipitous drops in sex hormone levels, gonadal atrophy, and abdominal obesity; overall they produce markedly fewer offspring than controls. These findings expand our understanding of factors that maintain human reproductive health and lend insight into the domestication of retrotransposon-derived genes.

Combined Exercise and Mindset Training During a Pediatric Cardiac Fitness and Rehabilitation Program Benefits Youth with a Range of Congenital Heart Disease.

Pediatric cardiac fitness and rehabilitation programs vary widely in structure and content. The Cardiac Fitness Program (CFP) is built on traditional training pillars of aerobic, strength, and flexibility, and adds a fourth, training a positive mindset. This study assesses whether the systematic and comprehensive framework of the CFP results in broad benefits for a range of patients with congenital heart disease (CHD). Data from participants between 01/2017 and 12/2022 were analyzed. Pre- and post-CFP cardiopulmonary exercise test parameters, strength and flexibility metrics, and mindset survey results were compared overall, and by sex, age, diagnosis, and hemodynamic level. Of 62 participants (median age 15.5years, range 8 to 23, 50% female), 3% had simple, 37% complex, 24% single ventricle CHD, and 35% arrhythmia, cardiomyopathy, or transplant. Significant improvements were noted in aerobic fitness (mean 9 ± 15% increase in % predicted peak oxygen consumption, p < 0.001). Strength metrics significantly improved (each p < 0.001), as did flexibility (p < 0.001). Patient-reported positive mindset scores did not improve significantly (mean increase 1.8 ± 5.1, p = 0.10, n = 25), whereas parents reported significant improvements (5.9 ± 10.4, p = 0.02, n = 20). Improvements were not significantly different by sex, age, diagnosis, or hemodynamic level. Comprehensive training across four pillars of fitness yields significant improvements in aerobic fitness, strength, flexibility, and parent-reported mindset scores for pediatric CHD patients, regardless of patient characteristics, diagnosis type, or severity of hemodynamic limitation. Further study is warranted into optimal standardization of training and whether a comprehensive approach amplifies individual pillars to create more than the sum of its parts.

Positive spatial and temporal density‐dependence drive early reproductive economy‐of‐scale effects of masting in a European old‐growth forest community

Abstract Masting, the spatial synchronization of interannual variation in seed production, can enhance reproductive efficiency through positive density‐dependent processes (DD) that result in economies of scale (EOS), such as decreased pollen limitation and predator satiation in years of high reproduction. While the general occurrence of such EOS effects has been documented for masting species, few studies simultaneously investigated how spatial and temporal variation in reproduction affects pollination and predation. Furthermore, it is unclear whether the same mechanisms apply to co‐occurring species with different levels of conspecific density, pollen limitation, and seed defences. Here, we use a long‐term dataset with high spatial resolution of seed production of European beech (Fagus sylvatica), Norway spruce (Picea abies), and silver fir (Abies alba) in a primeval montane forest to investigate the relationship between reproductive effort, pollination efficiency and predispersal predation by insects. We found that, along the temporal axis, the proportion of sound (fertilized and unpredated) seeds correlated positively with annual seed production over the 14‐year study period in all three species, most strongly in beech and only weakly in silver fir. Moreover, the results show that in beech, spatial seed density interacts with plot‐wide annual seed rain to enhance DD effects on seed predation, suggesting additive effects of synchronous reproduction on fitness benefits. Synthesis: For both pollination and predispersal predation in beech and spruce, the strongest DD effects occur at low levels of reproduction and quickly reach asymptotes at higher levels, suggesting the presence of thresholds in different EOS mechanisms. As variability and synchrony in mast‐seeding are expected to decline with climate change, EOS effects driven by DD may remain stable until the threshold is reached, at which sudden declines would result in devastating effects on the availability of viable seeds for germination and recruitment.

Independent fitness consequences of group size variation in Verreaux’s sifakas

The costs and benefits of group living are also reflected in intraspecific variation in group size. Yet, little is known about general patterns of fitness consequences of this variation. We use demographic records collected over 25 years to determine how survival and reproductive success vary with group size in a Malagasy primate. We show that female reproductive rates of Verreaux’s sifakas (Propithecus verreauxi) are not affected by total group size, but that they are supressed by the number of co-resident females, whereas mortality rates are significantly higher in larger groups. Neither annual rainfall nor the adult sex ratio have significant effects on birth and death rates. Hence, these sifakas enjoy the greatest net fitness benefits at small, and not the predicted intermediate group sizes. Thus, independent fitness proxies can vary independently as a function of group size as well as other factors, leading to deviations from optimal intermediate group sizes.

We like to move it - patients with schizophrenia spectrum disorders are impaired in estimating their physical fitness levels and benefit from individualized exercise.

People with schizophrenia spectrum disorders (SSD) engage less in physical activity than healthy individuals. The impact of subjectively assessed physical fitness levels on motivation for sports engagement and its relation to objective fitness parameters in SSD is unclear. 25 patients with SSD (P-SSD) and 24 healthy controls (H-CON) participated in a randomized controlled study. Individual anaerobic thresholds (AT) were determined by an incremental exercise test and on separate days, aerobic exercise (cycling at 80% of workload at AT) and non-exercise control (sitting on an ergometer without cycling) sessions were performed. Demographic, clinical and objective physical fitness data (i.e., weekly physical activity, workload at AT, heart rate) were collected. Subjective physical fitness parameters were assessed before and after exercise and control sessions. Weekly physical activity in P-SSD was lower than in H-CON (p < 0.05) attributed to reduced engagement in sport activities (p < 0.001). Workload and percentage of predicted maximal heart rate at AT were also reduced in P-SSD compared to H-CON (both p < 0.05). Although objective and subjective physical fitness parameters were related in H-CON (p < 0.01), this relationship was absent in P-SSD. However, during exercise sessions subjective physical fitness ratings increased to a stronger extent in P-SSD than H-CON (p < 0.05). The missing relationship between subjective and objective physical fitness parameters in people with SSD may represent a barrier for stronger engagement in physical activity. Accordingly, supervised exercise interventions with individually adjusted workload intensity may support realistic subjective fitness estimations and enhance motivation for sports activity in individuals with SSD.

Wolbachia impacts microbiome diversity and fitness-associated traits for Drosophila melanogaster in a seasonally fluctuating environment.

The microbiome contributes to many different host traits, but its role in host adaptation remains enigmatic. The fitness benefits of the microbiome often depend on ecological conditions, but theory suggests that fluctuations in both the microbiome and environment modulate these fitness benefits. Moreover, vertically transmitted bacteria might constrain the ability of both the microbiome and host to respond to changing environments. Drosophila melanogaster provides an excellent system to investigate the impacts of interactions between the microbiome and the environment. To address this question, we created field mesocosms of D. melanogaster undergoing seasonal environmental change with and without the vertically transmitted bacteria, Wolbachia pipientis. Sampling temporal patterns in the microbiome revealed that Wolbachia constrained microbial diversity. Furthermore, Wolbachia and a dominant member of the microbiome, Commensalibacter, were associated with differences in two higher-order fitness traits, starvation resistance and lifespan. Our work here suggests that the interplay between the abiotic context and microbe-microbe interactions may shape key host phenotypes that underlie adaptation to changing environments. We conclude by exploring the consequences of complex interactions between Wolbachia and the microbiome for our understanding of eco-evolutionary processes that shape host-microbiome interactions.

Therapeutic Quality Affects Physical Fitness Benefits of Home Exercise Interventions in Older Adults: A Systematic Review, Meta-Analysis, and Meta-Regression.

The international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) tool is a new instrument developed to evaluate the therapeutic quality of exercise interventions. Home-based exercise has been shown to improve physical fitness in older adults, but its effects may be influenced by therapeutic quality. The purpose of this systematic review was to describe the therapeutic quality of home-based exercise interventions for community-dwelling older adults and examine the relationship between therapeutic quality and changes in physical fitness. Six electronic databases and 2 clinical trial registries were searched for randomized controlled trials investigating the effects of home-based exercise on physical fitness in community-dwelling older adults (≥60 years). Therapeutic quality was evaluated using the i-CONTENT tool for items of patient selection, type of exercise, safety, type/timing of outcomes, exercise dose, and adherence. International Consensus on Therapeutic Exercise aNd Training items were used to explain heterogeneity in meta-regression analyses. Risk of bias, certainty of evidence and credibility of analyses were assessed. Thirty-six trials (n = 6157 participants) were identified. Most studies (≥66.7%) had high or probably high therapeutic quality for i-CONTENT items, except exercise dose (47.2%) and adherence (16.7%). Interventions improved upper- (N = 20 trials; standardized mean difference [SMD] = 0.39; 95% CI, 0.13-0.64; low certainty of evidence) and lower-body strength (N = 28; SMD = 0.42; 95% CI, 0.08-0.77; very low certainty), and aerobic fitness (N = 8; SMD = 0.42; 95% CI, 0.08-0.77; very low certainty). For exercise dose, low- or probably low-quality studies negatively influenced effects on upper- (estimated β = -.48; P = .049; moderate credibility) and lower-body strength (estimated β = -.77; P = .048; moderate credibility). For adherence, low- or probably low-quality studies negatively influenced effects on aerobic fitness (estimated β = -.97; P = .02; low credibility). Home-based exercise may improve upper- and lower-body strength, as well as aerobic fitness in older adults. However, the effectiveness of interventions is affected by inadequate dosing of exercise programs and adherence issues. Physical therapists should have the best available evidence to support their clinical decision making, especially when designing and monitoring home programs.

Clonal competition assays identify fitness signatures in cancer progression and resistance in multiple myeloma.

Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses is one of the biggest clinical challenges. TP53 alterations are established high-risk markers and are included in the current disease staging criteria. KRAS is the most frequently mutated gene affecting around 20% of MM patients. Applying Clonal Competition Assays (CCA)byco-culturing color-labeled genetically modified cell models, we recently showed that mono- and biallelic alterations in TP53 transmit a fitness advantage to the cells. Here, we report a similar dynamic for two mutations in KRAS (G12A and A146T), providing a biological rationale for the high frequency of KRAS and TP53 alterations at MM relapse. Resistance mutations, on the other hand, did not endow MM cells with a general fitness advantage but rather presented a disadvantage compared to the wild-type. CUL4B KO and IKZF1 A152T transmit resistance against immunomodulatory agents, PSMB5 A20T to proteasome inhibition. However, MM cells harboring such lesions only outcompete the culture in the presence of the respective drug. To better prevent the selection of clones with the potential of inducing relapse, these results argue in favor of treatment-free breaks or a switch of the drug class given as maintenance therapy. In summary, the fitness benefit of TP53 and KRAS mutations was not treatment-related, unlike patient-derived drug resistance alterations that may only induce an advantage under treatment. CCAs are suitable models for the study of clonal evolution and competitive (dis)advantages conveyed by a specific genetic lesion of interest, and their dependence on external factors such as the treatment.

A 12-week Taijiquan practice improves balance control and functional fitness in fall-prone postmenopausal women.

Falls are the leading cause of accidental death among older persons, with postmenopausal women facing a greater hazard of falling due to osteoporosis. This study aimed to examine the effects of Taijiquan practice on balance control and functional fitness in at-risk females. Chinese women who self-reported a tendency to fall and had a baseline one-leg stand test time (4.1 s in the Taijiquan group) below the national average for their age group (60-64 years: 10.9 s, 65-69 years: 9.9 s) were assigned to either a control group (n = 26, mean age = 63.9 years) or a Taijiquan group (n = 24, mean age = 63.9 years). The Taijiquan group participated in a 12-week supervised intervention, while the control group maintained their daily activities. The average duration of each exercise session was 52 min. Static balance and functional fitness were assessed at the beginning and end of the intervention. After 12 weeks, the Taijiquan group significantly outperformed the control group in terms of balance, flexibility, and muscular fitness (all p < 0.05). Participants in the Taijiquan group improved their one-leg stand by 61.0% (+2.5 s, Hedge's g = 0.85), arm curl by 8.3% (+1.7 repetitions, g = 0.53), handgrip strength by 8.3% (+1.9 kg, g = 0.65), and sit-and-reach by 163.2% (+6.2 cm, g = 1.17). The improvement in balance, coupled with other functional fitness benefits, suggests that Taijiquan could serve as a useful exercise for older women with an elevated risk of falling.

EFFECTS OF CARDIAC REHABILITATION IN PATIENTS WITH VENTRICULAR ASSIST DEVICES: A SCOPING REVIEW

Introduction Ventricular assist devices represent a treatment option for patients with advanced heart failure, offering control over various haemodynamic variables. Similarly, the prescription of exercise within a cardiac rehabilitation programme for heart failure patients is recommended to reduce symptoms, hospitalisations, improve cardiorespiratory fitness, and increase exercise tolerance. Therefore, exercise prescription can impact those with ventricular assist devices. Given the limited evidence on exercise-based cardiac rehabilitation programmes for this population, this review aims to describe the most commonly used strategies and their health benefits when physical exercise is included in a cardiac rehabilitation programme for patients with ventricular assist devices. Materials and Methods An exploratory review was conducted through searches in the databases: PubMed, SCOPUS, PeDro, and ScienceDirect. The search was limited to studies published between 2013 and 2023. Filters were applied independently by title, abstract, and full text. The included articles were analysed based on the description of the types of cardiac rehabilitation strategies used in patients with ventricular assist devices. Results Seven articles were included. Each programme employed a cardiopulmonary exercise test before prescribing physical exercise. The most commonly used strategy was aerobic exercise, predominantly high-intensity interval training (HIIT) with intensities close to 90% of peak VO2, followed by continuous moderate-intensity exercise. Limb strength exercises were included in three programmes. Conclusions The analysed literature suggests that cardiac rehabilitation in patients with ventricular assist devices is safe and can provide benefits in cardiorespiratory fitness and exercise tolerance. High-intensity interval training is identified as an appropriate strategy for achieving results, offering short-term improvements.

Evidence for female dominance in the Milne-Edwards' sportive lemur (Lepilemur edwardsi).

Female dominance over males is more frequent in Malagasy lemurs than in other primate clades, but patterns of female-male dominance vary among species, and few data are available for one particularly species-rich genus, Lepilemur. We investigated the types, temporal distribution, and outcome of female-male agonistic conflicts in the Milne-Edwards' sportive lemur (Lepilemur edwardsi). Ten L. edwardsi belonging to five social units were equipped with radio collars and observed during 79 focal follows between May and November 1998. We quantified agonistic conflicts, monthly conflict rates, and documented the winner and context for all conflicts. Female-male agonistic conflicts (N = 162) occurred at a mean rate of 0.21 conflicts/hour within groups. Agonistic conflicts peaked during the birth season and occurred mostly in unknown or infant proximity contexts. Females won 96% of all decided agonistic conflicts (N = 154). Other outcomes occurred only when females were with infants during the birth season. In that context, one female sometimes withdrew from her pair partner, and another female withdrew or fled from an extra-group male whose attacks eventually led to infanticide. Our results suggest female dominance in pair-living L. edwardsi. We hypothesize that elevated female aggression may convey fitness benefits to female Lepilemur because it generally allows females to intervene quickly and efficiently on behalf of their infants against nonfather males who may approach the newborn infants when they are parked in vegetation.

Combining quantitative proteomics and interactomics for a deeper insight into molecular differences between human cell lines.

Cellular functional pathways have evolved through selection based on fitness benefits conferred through protein intra- and inter-molecular interactions that comprise all protein conformational features and protein-protein interactions, collectively referred to as the interactome. While the interactome is regulated by proteome levels, it is also regulated independently by, post translational modification, co-factor, and ligand levels, as well as local protein environmental factors, such as osmolyte concentration, pH, ionic strength, temperature and others. In modern biomedical research, cultivatable cell lines have become an indispensable tool, with selection of optimal cell lines that exhibit specific functional profiles being critical for success in many cases. While it is clear that cell lines derived from different cell types have differential proteome levels, increased understanding of large-scale functional differences requires additional information beyond abundance level measurements, including how protein conformations and interactions are altered in certain cell types to shape functional landscapes. Here, we employed quantitative in vivo protein cross-linking coupled to mass spectrometry to probe large-scale protein conformational and interaction changes among three commonly employed human cell lines, HEK293, MCF-7, and HeLa cells. Isobaric quantitative Protein Interaction Reporter (iqPIR) technologies were used to obtain quantitative values of cross-linked peptides across three cell lines. These data illustrated highly reproducible (R2 values larger than 0.8 for all biological replicates) quantitative interactome levels across multiple biological replicates. We also measured protein abundance levels in these cells using data independent acquisition quantitative proteomics methods. Combining quantitative interactome and proteomics information allowed visualization of cell type-specific interactome changes mediated by proteome level adaptations as well as independently regulated interactome changes to gain deeper insight into possible drivers of these changes. Among the biggest detected alterations in protein interactions and conformations are changes in cytoskeletal proteins, RNA-binding proteins, chromatin remodeling complexes, mitochondrial proteins, and others. Overall, these data demonstrate the utility and reproducibility of quantitative cross-linking to study systems-level interactome variations. Moreover, these results illustrate how combined quantitative interactomics and proteomics can provide unique insight on cellular functional landscapes.

Distinguishing mutants that resist drugs via different mechanisms by examining fitness tradeoffs.

There is growing interest in designing multidrug therapies that leverage tradeoffs to combat resistance. Tradeoffs are common in evolution and occur when, for example, resistance to one drug results in sensitivity to another. Major questions remain about the extent to which tradeoffs are reliable, specifically, whether the mutants that provide resistance to a given drug all suffer similar tradeoffs. This question is difficult because the drug-resistant mutants observed in the clinic, and even those evolved in controlled laboratory settings, are often biased towards those that provide large fitness benefits. Thus, the mutations (and mechanisms) that provide drug resistance may be more diverse than current data suggests. Here, we perform evolution experiments utilizing lineage-tracking to capture a fuller spectrum of mutations that give yeast cells a fitness advantage in fluconazole, a common antifungal drug. We then quantify fitness tradeoffs for each of 774 evolved mutants across 12 environments, finding these mutants group into 6 classes with characteristically different tradeoffs. Their unique tradeoffs may imply that each group of mutants affects fitness through different underlying mechanisms. Some of the groupings we find are surprising. For example, we find some mutants that resist single drugs do not resist their combination, while others do. And some mutants to the same gene have different tradeoffs than others. These findings, on one hand, demonstrate the difficulty in relying on consistent or intuitive tradeoffs when designing multidrug treatments. On the other hand, by demonstrating that hundreds of adaptive mutations can be reduced to a few groups with characteristic tradeoffs, our findings may yet empower multidrug strategies that leverage tradeoffs to combat resistance. More generally speaking, by grouping mutants that likely affect fitness through similar underlying mechanisms, our work guides efforts to map the phenotypic effects of mutation.

Analysis of Common Exercise Modalities in Improving Athletic Performance in Older Adults: A Narrative Review.

Exercise leads to robust cardiovascular, musculoskeletal, and psychological benefits that improve quality of life and longevity for older adults, but accompanying improvements in athletic parameters are less well explored. The aim of this review is to summarize some of the most common exercise modalities, namely, Pilates, martial arts (tai chi, Japanese-style karate, hard martial arts), locomotion (brisk walking/jogging and running), Masters sports, resistance training, and high-intensity interval training, in improving athletic performance for older adults. Regular participation in these activities can have robust yet unique impacts on physical performance that prolong exercise participation. In particular, this review will explore benefits in cardiorespiratory fitness, power, strength, flexibility, and balance, thereby hopefully improving endurance, exercise adherence, and overall fall risk. A narrative literature review was performed to explore benefits, pitfalls, and recommendations for some of the most popular exercise modalities for older adults.