scholarly journals Population Heterogeneity in Mutation Rate Increases the Frequency of Higher-Order Mutants and Reduces Long-Term Mutational Load

2016 ◽  
pp. msw244 ◽  
Author(s):  
Helen K. Alexander ◽  
Stephanie I. Mayer ◽  
Sebastian Bonhoeffer
Keyword(s):  
Mutation Rate ◽  
Higher Order ◽  
Population Heterogeneity ◽  
Mutational Load

scholarly journals Population heterogeneity in mutation rate increases mean fitness and the frequency of higher order mutants

2016 ◽  
Author(s):  
Helen K. Alexander ◽  
Stephanie I. Mayer ◽  
Sebastian Bonhoeffer
Keyword(s):  
Mutation Rate ◽  
Relative Effect ◽  
Relative Increase ◽  
Higher Order ◽  
Population Heterogeneity ◽  
Arbitrary Distribution ◽  
Rate Heterogeneity ◽  
Standing Variation ◽  
A Genome ◽  
Mean Fitness

AbstractMutation rate is a crucial evolutionary parameter that has typically been treated as a constant in population genetic analyses. However, mutation rate is likely to vary among co-existing individuals within a population, due to genetic polymorphisms, heterogeneous environmental influences, and random physiological fluctuations. We explore the consequences of such mutation rate heterogeneity in a model allowing an arbitrary distribution of mutation rate among individuals, either with or without inheritance. We find that variation of mutation rate about the mean results in a higher probability of producing zero or many simultaneous mutations on a genome. Moreover, it increases the frequency of higher order mutants even under ongoing mutation and selection. We gain a quantitative understanding of how this frequency depends on moments of the mutation rate distribution and selection coefficients. In particular, in a two-locus model, heterogeneity leads to a relative increase in double mutant frequency proportional to the squared coefficient of variation of the mutation rate. Relative effect sizes increase with the number of loci. Finally, this clustering of deleterious mutations into fewer individuals results in a higher population mean fitness. Our results imply that mutation rate heterogeneity allows a population to maintain a higher level of adaptedness to its current environment, while simultaneously harboring greater genetic diversity in the standing variation, which could be crucial for future adaptation to a new environment. Our results also have implications for interpreting mutation rate estimates and mutant frequencies in data.

scholarly journals “Is It Overtraining or Just Work Ethic?”: Coaches’ Perceptions of Overtraining in High-Performance Strength Sports

Sports ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 85
Author(s):  
Lee Bell ◽  
Alan Ruddock ◽  
Tom Maden-Wilkinson ◽  
Dave Hembrough ◽  
David Rogerson
Keyword(s):  
Physical Performance ◽  
Thematic Analysis ◽  
High Performance ◽  
Higher Order ◽  
Short Term ◽  
Semistructured Interviews ◽  
Diagnostic Symptoms ◽  
Careful Manipulation ◽  
Sport Coaches

Optimal physical performance is achieved through the careful manipulation of training and recovery. Short-term increases in training demand can induce functional overreaching (FOR) that can lead to improved physical capabilities, whereas nonfunctional overreaching (NFOR) or the overtraining syndrome (OTS) occur when high training-demand is applied for extensive periods with limited recovery. To date, little is known about the OTS in strength sports, particularly from the perspective of the strength sport coach. Fourteen high-performance strength sport coaches from a range of strength sports (weightlifting; n = 5, powerlifting; n = 4, sprinting; n = 2, throws; n = 2, jumps; n = 1) participated in semistructured interviews (mean duration 57; SD = 10 min) to discuss their experiences of the OTS. Reflexive thematic analysis resulted in the identification of four higher order themes: definitions, symptoms, recovery and experiences and observations. Additional subthemes were created to facilitate organisation and presentation of data, and to aid both cohesiveness of reporting and publicising of results. Participants provided varied and sometimes dichotomous perceptions of the OTS and proposed a multifactorial profile of diagnostic symptoms. Prevalence of OTS within strength sports was considered low, with the majority of participants not observing or experiencing long-term reductions in performance with their athletes.

Homework questions designed to require higher-order cognitive skills in an undergraduate animal physiology course did not produce desirable difficulties, testing effects, or improvements in information retention

2021 ◽  
Author(s):  
Caitlin N Cadaret ◽  
Dustin T Yates
Keyword(s):  
Undergraduate Students ◽  
Cognitive Skills ◽  
Higher Order ◽  
Information Retention ◽  
Desirable Difficulties ◽  
Animal Physiology ◽  
Initial Learning ◽  
Retention Of Knowledge ◽  
Practical Exam

Abstract Studies show that retrieval practices such as homework assignments that are completed during the encoding phase of learning benefit knowledge acquisition and retention. In addition, desirable difficulties, which are strategies that intentionally create a greater challenge during initial learning to enhance encoding and retrieval pathways, also benefit learning long term. Our objective was to determine whether weekly homework questions intended to create desirable difficulties by requiring higher-order cognitive skills (HOCS) benefited students’ long-term retention of physiology concepts compared to questions designed to require lower-order cognitive skills (LOCS). Undergraduate students in a junior-level animal physiology course were presented information during weekly laboratory periods, and then required to complete retrieval practices in the form of online homework assignments 5 d after each lab. Homework questions were formatted per Bloom’s Taxonomy to require HOCS (i.e. level 4 or 5) or LOCS (i.e. level 1 or 2). Information retention was assessed the next week via performance on an in-class quiz and again at semesters’ end via performance on a final practical exam. We observed no differences in performance on the in-class quiz or final practical exam between students randomly assigned to complete homework with HOCS questions compared to LOCS questions. However, students that received homework with HOCS questions had decreased (P < 0.05) performance scores on 9 out of the 11 homework assignments compared to those receiving homework with LOCS questions. These findings indicate that desirable difficulties were not created by our HOCS homework questions because students receiving these more difficult retrieval practices did not achieve equal success on them. As a result, this attempt to create variations in cognitive demand did not enhance retention of knowledge in this study.

The role of service fairness in the service quality – relationship quality – customer loyalty chain

2015 ◽  
Vol 25 (6) ◽  
pp. 744-776 ◽  
Author(s):  
Apostolos Giovanis ◽  
Pinelopi Athanasopoulou ◽  
Evangelos Tsoukatos
Keyword(s):  
Service Quality ◽  
Relationship Quality ◽  
Customer Loyalty ◽  
Higher Order ◽  
Equation Modeling ◽  
Content Type ◽  
Order Construct ◽  
Service Fairness

Purpose – The purpose of this paper is to extend the well-established nomological network of service quality-relationship quality-customer loyalty by introducing service fairness – a distinct service evaluation concept. Specifically, the study aims to investigate the impact of service fairness on relationship quality as a complementary to service quality driver, and the direct and indirect effect of service fairness on customer loyalty in the presence of service quality and relationship quality in a no failure/recovery effort service context. Design/methodology/approach – A telephone survey of a random sample of 408 customers of auto repair and maintenance services was implemented using a structured questionnaire with established scales. Data were analyzed with partial least squares path methodology, a structural equation modeling methodology. Findings – Interactional fairness is the most important formative determinant of customers’ overall fairness perception, followed by procedural and distributive fairness. Relationship quality measured as a higher order construct, made of satisfaction; trust; affective and calculative commitment, is the main determinant of customer loyalty. Also, it partially mediates, along with service quality, the relationship between service fairness and customer loyalty and fully mediates the effect of service quality on customer loyalty. Finally, service fairness has the highest overall effect on customer loyalty. Research limitations/implications – The sample is industry-specific and this may affect generalizability of findings. Also, the cross-sectional design adopted does not reflect temporal changes. Practical implications – Interactional fairness is of utmost importance to customers of the investigated industry. So, customers should be fairly treated at every point of contact. Also, service quality is heavily affected by service fairness. Thus, fair service leads to high-perceived service quality. Third, service quality affects customer loyalty only through relationship quality. Only when service quality is coupled by long-term quality relationships, signs of customer loyalty appear. Finally, service fairness influences customer loyalty mainly through service and relationship quality and has the highest overall effect on customer loyalty. So, fairly treating customers is crucial for developing long-term relationships that lead to customer loyalty. Originality/value – The role of service fairness in the service quality-relationship quality-customer loyalty chain is investigated and using a higher order construct for relationship quality.

scholarly journals Long-term observations of pulsars in the globular clusters 47 Tucanae and M15

2017 ◽  
Vol 13 (S337) ◽  
pp. 251-254
Author(s):  
A. Ridolfi ◽  
P. C. C. Freire ◽  
M. Kramer ◽  
C. G. Bassa ◽  
F. Camilo ◽  
...  
Keyword(s):  
Gravitational Potential ◽  
Globular Clusters ◽  
Higher Order ◽  
The Other ◽  
Line Of Sight ◽  
Physical Parameters ◽  
Spin Period ◽  
Emission Beam ◽  
System Geometry

AbstractMulti-decade observing campaigns of the globular clusters 47 Tucanae and M15 have led to an outstanding number of discoveries. Here, we report on the latest results of the long-term observations of the pulsars in these two clusters. For most of the pulsars in 47 Tucanae we have measured, among other things, their higher-order spin period derivatives, which have in turn provided stringent constraints on the physical parameters of the cluster, such as its distance and gravitational potential. For M15, we have studied the relativistic spin precession effect in PSR B2127+11C. We have used full-Stokes observations to model the precession effect, and to constrain the system geometry. We find that the visible beam of the pulsar is swiftly moving away from our line of sight and may very soon become undetectable. On the other hand, we expect to see the opposite emission beam sometime between 2041 and 2053.

scholarly journals Structural and Functional Basis for an EBNA1 Hexameric Ring in Epstein-Barr Virus Episome Maintenance

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Julianna S. Deakyne ◽  
Kimberly A. Malecka ◽  
Troy E. Messick ◽  
Paul M. Lieberman
Keyword(s):  
Crystal Structure ◽  
Dna Binding ◽  
Complex Formation ◽  
Epstein Barr Virus ◽  
Higher Order ◽  
Order Complex ◽  
Barr Virus ◽  
Naturally Occurring ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) establishes a stable latent infection that can persist for the life of the host. EBNA1 is required for the replication, maintenance, and segregation of the latent episome, but the structural features of EBNA1 that confer each of these functions are not completely understood. Here, we have solved the X-ray crystal structure of an EBNA1 DNA-binding domain (DBD) and discovered a novel hexameric ring oligomeric form. The oligomeric interface pivoted around residue T585 as a joint that links and stabilizes higher-order EBNA1 complexes. Substitution mutations around the interface destabilized higher-order complex formation and altered the cooperative DNA-binding properties of EBNA1. Mutations had both positive and negative effects on EBNA1-dependent DNA replication and episome maintenance with OriP. We found that one naturally occurring polymorphism in the oligomer interface (T585P) had greater cooperative DNA binding in vitro, minor defects in DNA replication, and pronounced defects in episome maintenance. The T585P mutant was compromised for binding to OriP in vivo as well as for assembling the origin recognition complex subunit 2 (ORC2) and trimethylated histone 3 lysine 4 (H3K4me3) at OriP. The T585P mutant was also compromised for forming stable subnuclear foci in living cells. These findings reveal a novel oligomeric structure of EBNA1 with an interface subject to naturally occurring polymorphisms that modulate EBNA1 functional properties. We propose that EBNA1 dimers can assemble into higher-order oligomeric structures important for diverse functions of EBNA1. IMPORTANCE Epstein-Barr virus is a human gammaherpesvirus that is causally associated with various cancers. Carcinogenic properties are linked to the ability of the virus to persist in the latent form for the lifetime of the host. EBNA1 is a sequence-specific DNA-binding protein that is consistently expressed in EBV tumors and is the only viral protein required to maintain the viral episome during latency. The structural and biochemical mechanisms by which EBNA1 allows the long-term persistence of the EBV genome are currently unclear. Here, we have solved the crystal structure of an EBNA1 hexameric ring and characterized key residues in the interface required for higher-order complex formation and long-term plasmid maintenance.

scholarly journals The Management and Outcome of Higher Order Multifetal Pregnancies: Obstetric, Neonatal and Follow-up Data

Twin Research ◽  
2001 ◽  
Vol 4 (1) ◽  
pp. 4-11
Author(s):  
Mark H. Yudin ◽  
Elizabeth V. Asztalos ◽  
Ann Jefferies ◽  
Jon F.R. Barrett
Keyword(s):  
Statistical Analysis ◽  
Motor Skills ◽  
Gestational Age ◽  
Neurodevelopmental Outcome ◽  
Higher Order ◽  
Neurodevelopmental Outcomes ◽  
Significant Difference ◽  
Before And After

AbstractThe objective of this study was to describe current obstetric, neonatal, and long-term neurodevelopmental outcomes of higher order multifetal gestations (≥ 3 fetuses) in the 1990s. We also intended to identify a target gestational age at which neonatal and neurodevelopmental morbidities are low. Records from all multifetal pregnancies (≥ 3 viable fetuses ≥ 20 weeks gestation) delivered at the two perinatal centers in Toronto, Ontario, Canada during the study period (January 1, 1990–December 31, 1996) were reviewed. Data were collected on obstetric, neonatal, and long-term neurodevelopmental outcomes. Follow up data were gathered regarding the presence of a severe deficit in four categories (vision, hearing, cognition, and motor skills). Statistical analysis was performed to determine a gestational age at which a significant decrease in deficit occurred. During the study period 165 multifetal pregnancies were delivered. This resulted in 511 fetuses, of which 496 were live births. Of these 496 infants, 453 survived to discharge. Follow up data were obtained on 332 (73.3 per cent) infants. Infant survival increased with gestational age, and was approximately 90 per cent or greater at 26 weeks or more. Of all infants followed, the proportion of those without deficit increased with increasing gestational age, such that the per cent without deficit was 96.9 at 31 weeks or greater. Of all infants followed, 301 (90.7 per cent) had no deficit. Statistical analysis revealed a significant difference in long-term neurodevelopmental outcome between infants born before and after 28 weeks gestation. The incidence of a major deficit was 44.1 per cent for those born earlier than and 5.4 per cent for those born later than this gestational age (p = 0.001). In our cohort, survival figures were high. Even in lower gestational groupings, survival was high, but not without serious concerns about severe morbidity. This information is useful when counseling parents of higher order multifetal pregnancies.

scholarly journals Experiences and Strategies Influencing Older Adults to Continue Playing Walking Football

2020 ◽  
pp. 1-13
Author(s):  
Rachel Cholerton ◽  
Helen Quirk ◽  
Jeff Breckon ◽  
Joanne Butt
Keyword(s):  
Physical Activity ◽  
Older Adults ◽  
Sport Participation ◽  
Higher Order ◽  
Perceived Benefits ◽  
Policy And Practice ◽  
Semistructured Interviews ◽  
Conscious Process ◽  
Adapted Sports

Adults aged 55+ years are most likely to be inactive, despite research suggesting that older adults experience multiple benefits when participating in physical activity and sport. Limited research focuses on long-term continuation of sport participation in this population, especially in “adapted sports” like walking football. This study explored the experiences of walking football maintenance in 55- to 75-year-old players. Semistructured interviews were conducted, with 17 older adults maintaining walking football play over 6 months. The inductive analysis revealed five higher-order themes representing maintenance influences and two higher-order themes relating to maintenance mechanisms (i.e., the conscious process by which players maintain). Influences when maintaining walking football included individual- and culture-level influences (e.g., perceived benefits of maintenance and ability acceptance). Maintenance mechanisms included cognitions and behaviors (e.g., scheduling sessions and redefining physical activity expectations). Findings highlight novel implications for policy and practice, which are important to consider when delivering walking football to older adults.

scholarly journals The mutational load in natural populations is significantly affected by high primary rates of retroposition

2021 ◽  
Vol 118 (6) ◽  
pp. e2013043118 ◽  
Author(s):  
Wenyu Zhang ◽  
Chen Xie ◽  
Kristian Ullrich ◽  
Yong E. Zhang ◽  
Diethard Tautz
Keyword(s):  
Gene Evolution ◽  
Natural Populations ◽  
Distribution Patterns ◽  
Mutational Load ◽  
Negative Effects ◽  
Single Nucleotide ◽  
Species Comparisons ◽  
The Impact ◽  
Profiling Analysis

Gene retroposition is known to contribute to patterns of gene evolution and adaptations. However, possible negative effects of gene retroposition remain largely unexplored since most previous studies have focused on between-species comparisons where negatively selected copies are mostly not observed, as they are quickly lost from populations. Here, we show for natural house mouse populations that the primary rate of retroposition is orders of magnitude higher than the long-term rate. Comparisons with single-nucleotide polymorphism distribution patterns in the same populations show that most retroposition events are deleterious. Transcriptomic profiling analysis shows that new retroposed copies become easily subject to transcription and have an influence on the expression levels of their parental genes, especially when transcribed in the antisense direction. Our results imply that the impact of retroposition on the mutational load has been highly underestimated in natural populations. This has additional implications for strategies of disease allele detection in humans.

scholarly journals Statistical concepts in the theory of bacterial mutation

1953 ◽  
Vol 51 (2) ◽  
pp. 162-184 ◽  
Author(s):  
P. Armitage
Keyword(s):  
Mutation Rate ◽  
Phenotypic Expression ◽  
Theoretical Distribution ◽  
Mutation Rates ◽  
Safe Procedure ◽  
Short Term ◽  
Mutant Type ◽  
Bacterial Populations ◽  
Long Term Experiment

This paper is a short exposition of the mathematical and statistical theory of the growth of bacterial populations subject to mutation.A mathematical model for the long-term development of a mixed population with two types of organism is proposed. The proportion of organisms which are of the mutant type eventually approaches an asymptotic value, which is independent of the initial composition of the population. A procedure is outlined for estimating the forward and backward mutation rates from a long-term experiment.The exact interpretation of the constants representing mutation rates requires some assumption about the point of time, during an individual life cycle, at which mutations occur. The usual assumption is that mutations can occur with equal frequency at all instants during the cycle.In short-term experiments, in which the proportion of mutants is at all times negligible, it is important to consider the variation between the numbers of mutants developing in replicate cultures. The theoretical distribution of Lea & Coulson may be disturbed by the failure of any one of a number of assumptions; the effects of such disturbances are considered in some detail.Various methods of estimating the mutation rate from an observed series of replicate cultures are examined. Two of the main sources of disturbance of the theoretical distribution may be delay of phenotypic expression, and the existence of multinucleate cells with dominant mutation. These factors affect particularly the lower tail of the distribution, and it is suggested that a fairly safe procedure may be to estimate the mutation rate from the upper quartile of the observed distribution. Tables 3 and 4 enable the estimate of the mutation rate, together with 95% confidence limits, to be readily calculated.

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