Evidence that both G + C rich and G + C poor isochores are replicated early and late in the cell cycle

Since the G + C content of a gene is correlated to that of the isochore in which it resides, and early replicating isochores are thought to be relatively G + C rich, early replicating genes should also be rich in G + C. This hypothesis is tested on a sample of 44 mammalian genes for which replication time data and sequence information are available. Early replicating genes do not appear to be more G + C rich than late replicating genes, instead there is considerable variation in the G + C content of genes replicated during both halves of S phase. These results show that both G + C rich and poor fractions of the genome are replicated early and late in the cell cycle, and suggest that isochores are not maintained by the replication of DNA sequences in compositionally biased free nucleotide pools

How much of the variation in the mutation rate along the human genome can be explained?

It has been claimed recently that it may be possible to predict the rate of de novo mutation of each site in the human genome with a high degree of accuracy [Michaelson et al. (2012), Cell 151: 143121442]. We show that this claim is unwarranted. By considering the correlation between the rate of de novo mutation and the predictions from the model of Michaelson et al., we show there could be substantial unexplained variance in the mutation rate. We investigate whether the model of Michaelson et al. captures variation at the single nucleotide level that is not due to simple context. We show that the model captures a substantial fraction of this variation at CpG dinucleotides but fails to explain much of the variation at non-CpG sites

Cryptic Variation in the Human Mutation Rate

The mutation rate is known to vary between adjacent sites within the human genome as a consequence of context, the most well-studied example being the influence of CpG dinucelotides. We investigated whether there is additional variation by testing whether there is an excess of sites at which both humans and chimpanzees have a single-nucleotide polymorphism ( SNP). We found a highly significant excess of such sites, and we demonstrated that this excess is not due to neighbouring nucleotide effects, ancestral polymorphism, or natural selection. We therefore infer that there is cryptic variation in the mutation rate. However, although this variation in the mutation rate is not associated with the adjacent nucleotides, we show that there are highly nonrandom patterns of nucleotides that extend similar to 80 base pairs on either side of sites with coincident SNPs, suggesting that there are extensive and complex context effects. Finally, we estimate the level of variation needed to produce the excess of coincident SNPs and show that there is a similar, or higher, level of variation in the mutation rate associated with this cryptic process than there is associated with adjacent nucleotides, including the CpG effect. We conclude that there is substantial variation in the mutation that has, until now, been hidden from view

The impact of fire suppression tasks on firefighter hydration: A critical review with consideration of the utility of reported hydration measures

BACKGROUND: Firefighting is a highly stressful occupation with unique physical challenges, apparel and environments that increase the potential for dehydration. Dehydration leaves the firefighter at risk of harm to their health, safety and performance. The purpose of this review was to critically analyse the current literature investigating the impact of fighting ‘live’ fires on firefighter hydration. METHODS: A systematic search was performed of four electronic databases for relevant published studies investigating the impact of live fire suppression on firefighter hydration. Study eligibility was assessed using strict inclusion and exclusion criteria. The included studies were critically appraised using the Downs and Black protocol and graded according to the Kennelly grading system. RESULTS: Ten studies met the eligibility criteria for this review. The average score for methodological quality was 55 %, ranging from 50 % (‘fair’ quality) to 61 % (‘good’ quality) with a ‘substantial agreement’ between raters (k = .772). Wildfire suppression was considered in five studies and structural fire suppression in five studies. Results varied across the studies, reflecting variations in outcome measures, hydration protocols and interventions. Three studies reported significant indicators of dehydration resulting from structural fire suppression, while two studies found mixed results, with some measures indicating dehydration and other measures an unchanged hydration status. Three studies found non-significant changes in hydration resulting from wildfire firefighting and two studies found significant improvements in markers of hydration. Ad libitum fluid intake was a common factor across the studies finding no, or less severe, dehydration. CONCLUSIONS: The evidence confirms that structural and wildfire firefighting can cause dehydration. Ad libitum drinking may be sufficient to maintain hydration in many wildfire environments but possibly not during intense, longer duration, hot structural fire operations. Future high quality research better quantifying the effects of these influences on the degree of dehydration is required to inform policies and procedures that ensure firefighter health and safety

Visualising Network Traffic Data From AirTraffic Control Radio Systems

In recent years the aviation industry has begun to embrace digital technology forAir Traffic Control (ATC) radio systems. This change has created challenges not onlyfor the industry but also for personnel. However, this implementation offers manyimprovements over older systems; more precise control, straightforward integrationwith other ATC systems and a more efficient way to provide software updates. Thechallenge for personnel is to develop a new skillset enabling a learning transitionfrom analogue to digital systems, with a specific emphasis on computer networkingskills.This project was undertaken in collaboration between the University of Lincoln(UoL) and Park Air Systems (PAS), an industry-leading provider of Air-Space com-munication solutions. A system has been developed to find a mechanism to monitorand visualise network traffic. The use of graphs provides a direct interface for theend-users, enabling a mechanism for identifying performance issues to meet thetransitional challenges from analogue to digital. An easy to use interface has beendesigned, which will enable non-technical users to interact effectively with the sys-tem.Considerable testing was undertaken to investigate the system usability concern-ing the practical application for users with limited networking experience. A surveyprovided a range of quantitative and qualitative data which was further analysed toscrutinize user perspectives on system usability. This involved engineers from PASand postgraduate students from UoL to compare results between direct industrypersonnel and unaffiliated participants

Evidence of widespread degradation of gene control regions in hominid genomes

Although sequences containing regulatory elements located close to protein-coding genes are often only weakly conserved during evolution, comparisons of rodent genomes have implied that these sequences are subject to some selective constraints. Evolutionary conservation is particularly apparent upstream of coding sequences and in first introns, regions that are enriched for regulatory elements. By comparing the human and chimpanzee genomes, we show here that there is almost no evidence for conservation in these regions in hominids. Furthermore, we show that gene expression is diverging more rapidly in hominids than in murids per unit of neutral sequence divergence. By combining data on polymorphism levels in human noncoding DNA and the corresponding human¿chimpanzee divergence, we show that the proportion of adaptive substitutions in these regions in hominids is very low. It therefore seems likely that the lack of conservation and increased rate of gene expression divergence are caused by a reduction in the effectiveness of natural selection against deleterious mutations because of the low effective population sizes of hominids. This has resulted in the accumulation of a large number of deleterious mutations in sequences containing gene control elements and hence a widespread degradation of the genome during the evolution of humans and chimpanzees

Player Discipline in the NFL: Arbitration or Arbitrary?

Since the Houston Texans drafted him in 2017, Deshaun Watson has statistically been one of the best quarterbacks in the National Football League (“NFL”). Watson led the Texans to the playoffs in both the 2018 and 2019 seasons before internal organizational issues led to Watson requesting a trade after the 2020 season. By the end of March 2021, twenty-one women had filed civil lawsuits alleging Watson of sexual assault and sexual misconduct. Watson did not immediately face any discipline from the NFL, but the Texans made Watson inactive for every week of the 2021 season in light of the accusations and the rift between the organization and the quarterback. In June 2022, a twenty-fourth woman filed a lawsuit against Watson. By August 2022, Watson has settled twenty-three of the twenty-four lawsuits, and a Texas grand jury declined to criminally indict Watson