Chromosome congression is promoted by CENP-Q- and CENP-E-dependent pathways

A key step of mitosis is the congression of chromosomes to the spindle equator. Congression is driven by at least two distinct mechanisms: (1) kinetochores slide along the microtubule lattice using the plus-end directed CENP-E motor, and (2) kinetochores biorientating near the pole move to the equator through microtubule depolymerisation-coupled pulling. Here, we show that CENP-Q - a subunit of the CENP-O complex (comprising CENP-O, CENP-P, CENP-Q and CENP-U) that targets polo-like kinase (Plk1) to kinetochores - is also required for the recruitment of CENP-E to kinetochores. We further reveal a CENP-E recruitment-independent role for CENP-Q in depolymerisation-coupled pulling. Both of these functions are abolished by a single point mutation in CENP-Q (S50A) - a residue that is phosphorylated in vivo. Importantly, the S50A mutant does not affect the loading of Plk1 onto kinetochores and leaves the CENP-O complex intact. Thus, the functions of CENP-Q in CENP-E loading and depolymerisation-coupled pulling are independent from its role in Plk1 recruitment and CENP-O complex stabilisation. Taken together, our data provide evidence that phosphoregulation of CENP-Q plays a central function in coordinating chromosome congression mechanisms

Body Size and Bite Force of Stray and Feral Cats - Are Bigger or Older Cats Taking the Largest or More Difficult to Handle Prey

As carnivorans rely heavily on their head and jaws for prey capture and handling, skull morphology and bite force can therefore reflect their ability to take larger or more difficult-to-handle prey. For 568 feral and stray cats (Felis catus), we recorded their demographics (sex and age), source location (feral or stray) and morphological measures (body mass, body condition); we estimated potential bite force from skull measurements for n = 268 of these cats, and quantified diet composition from stomach contents for n = 358. We compared skull measurements to estimate their bite force and determine how it varied with sex, age, body mass, body condition. Body mass had the strongest influence of bite force. In our sample, males were 36.2% heavier and had 20.0% greater estimated bite force (206.2 ± 44.7 Newtons, n = 168) than females (171.9 ± 29.3 Newtons, n = 120). However, cat age was the strongest predictor of the size of prey that they had taken, with older cats taking larger prey. The predictive power of this relationship was poor though (r2 \u3c 0.038, p \u3c 0.003), because even small cats ate large prey and some of the largest cats ate small prey, such as invertebrates. Cats are opportunistic, generalist carnivores taking a broad range of prey. Their ability to handle larger prey increases as the cats grow, increasing their jaw strength, and improving their hunting skills, but even the smallest cats in our sample had tackled and consumed large and potentially ‘dangerous’ prey that would likely have put up a defence

Mistaken-for-Game Hunting Accidents: A Human Factors Review

Hunting accidents can have devastating consequences. One of the most common causes of hunting fatalities in this country, and others, are target identification failures—mistaking people for game. A golden rule in firearm safety is to identify your target beyond all doubt. Despite this message being constantly repeated, accidents are still occurring. Hunter education and awareness about high visibility clothing have reduced accident rates, but these statistics have since plateaued. Contrary to what most people think, the hunters committing these accidents are often experienced and considered to be safe and competent. Crucially, they often believe they have, 100%, correctly identified their target. Psychology and human factors can provide insight into how these situations might occur. When interpreting information, we rely heavily upon mental rules of thumb called heuristics. Heuristics operate outside of our conscious awareness and are utilised even more in stressful or emotionally charged situations. However, they can also make us susceptible to cognitive biases which may lead us astray—we underestimate the impact heuristics will have on our decisions. Attempts to manage heuristics and cognitive biases are often futile because we normally cannot detect them when they occur. Hunters are constantly told that they need to treat every sound or movement as human in an attempt to change their mind-set. However, given the difficulty in detecting cognitive biases, it is unlikely a hunter’s conscious management of heuristics would be consistently possible in the long term. Cognitive biases undoubtedly occur in hunting as in most activities we do. Analyses of accidents and anecdotal reports point to their involvement, as does research showing their involvement in other critical environments, including firearms operations in the military and the police. Given the impracticality of preventing heuristics and cognitive biases from affecting a hunter’s target identification, an additional approach is required. One method to prevent mistaken-for-game hunting accidents may involve the use of objective warning systems, such as those used to prevent friendly fire in the military. This white paper discusses four key cognitive biases which we believe play a role in mistaken-for-game hunting accidents: the availability heuristic, expectancy, confirmation bias, and optimism bias. We also present the assertion that experience may not safeguard a hunter, and may in fact do the opposite. Other contributing factors—buck fever, poor choice of clothing, and snap shooting—are discussed in relation to cognitive biases. However, there is currently a notable lack of research on the role of cognitive biases in hunting accidents per se. As a result, more work needs to be conducted to verify the conclusions of this white paper, for which a human factors approach must be taken

'There and Back Again'-Forward Genetics and Reverse Phenotyping in Pulmonary Arterial Hypertension.

Although the invention of right heart catheterisation in the 1950s enabled accurate clinical diagnosis of pulmonary arterial hypertension (PAH), it was not until 2000 when the landmark discovery of the causative role of bone morphogenetic protein receptor type II (BMPR2) mutations shed new light on the pathogenesis of PAH. Since then several genes have been discovered, which now account for around 25% of cases with the clinical diagnosis of idiopathic PAH. Despite the ongoing efforts, in the majority of patients the cause of the disease remains elusive, a phenomenon often referred to as "missing heritability". In this review, we discuss research approaches to uncover the genetic architecture of PAH starting with forward phenotyping, which in a research setting should focus on stable intermediate phenotypes, forward and reverse genetics, and finally reverse phenotyping. We then discuss potential sources of "missing heritability" and how functional genomics and multi-omics methods are employed to tackle this problem

Adopt, adapt, and improve: Assessment of a new driver display in rail

This project evaluated the impact of a new enhanced information display intended as a cognitive aid on the operating performance of Locomotive Engineers (i.e. Train Drivers) within a large New Zealand freight rail network. The display previewed the upcoming route and presented information capable of optimising the performance of the locomotive. It did not exert any direct influence over the train and therefore did not take any decision-making capacity away from the driver. The addition of this technology represented a step-change for the organisation and a considerable investment for furthering safety and performance by improving the situation awareness of train drivers. Improving situation awareness is likely to lead to improved decision-making and hence performance and safety (Endsley, 1999) However, given the impact on ways of working for the train driver, and on the development of the organisation, acquiring insight into the cognitive, organisational and/or physical ergonomics impact of the technology was critical and attracted the need for a human factors assessment

Exploring patterns of recurrent melanoma in Northeast Scotland to inform the introduction a digital self-examination intervention

Peer reviewedPublisher PD

Recruitment, retention, and training of people with type 2 diabetes as diabetes prevention mentors (DPM) to support a healthcare professional-delivered diabetes prevention program: the Norfolk Diabetes Prevention Study (NDPS)

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement: Data are available upon reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.Objective: Intensive lifestyle interventions reduce the risk of type 2 diabetes in populations at highest risk, but staffing levels are usually unable to meet the challenge of delivering effective prevention strategies to a very large at-risk population. Training volunteers with existing type 2 diabetes to support healthcare professionals deliver lifestyle interventions is an attractive option. Methods: We identified 141 973 people at highest risk of diabetes in the East of England, screened 12 778, and randomized 1764 into a suite of type 2 diabetes prevention and screen detected type 2 diabetes management trials. A key element of the program tested the value of volunteers with type 2 diabetes, trained to act as diabetes prevention mentors (DPM) when added to an intervention arm delivered by healthcare professionals trained to support participant lifestyle change. Results: We invited 9951 people with type 2 diabetes to become DPM and 427 responded (4.3%). Of these, 356 (83.3%) were interviewed by phone, and of these 131 (36.8%) were interviewed in person. We then appointed 104 of these 131 interviewed applicants (79%) to the role (mean age 62 years, 55% (n=57) male). All DPMs volunteered for a total of 2895 months, and made 6879 telephone calls to 461 randomized participants. Seventy-six (73%) DPMs volunteered for at least 6 months and 66 (73%) for at least 1 year. Discussion: Individuals with type 2 diabetes can be recruited, trained and retained as DPM in large numbers to support a group-based diabetes prevention program delivered by healthcare professionals. This volunteer model is low cost, and accesses the large type 2 diabetes population that shares a lifestyle experience with the target population. This is an attractive model for supporting diabetes prevention efforts.National Institute for Health Research (NIHR

Recruitment, retention, and training of people with type 2 diabetes as diabetes prevention mentors (DPM) to support a healthcare professional-delivered diabetes prevention program:The Norfolk Diabetes Prevention Study (NDPS)

Objective: Intensive lifestyle interventions reduce the risk of type 2 diabetes in populations at highest risk, but staffing levels are usually unable to meet the challenge of delivering effective prevention strategies to a very large at-risk population. Training volunteers with existing type 2 diabetes to support healthcare professionals deliver lifestyle interventions is an attractive option. Methods: We identified 141 973 people at highest risk of diabetes in the East of England, screened 12 778, and randomized 1764 into a suite of type 2 diabetes prevention and screen detected type 2 diabetes management trials. A key element of the program tested the value of volunteers with type 2 diabetes, trained to act as diabetes prevention mentors (DPM) when added to an intervention arm delivered by healthcare professionals trained to support participant lifestyle change. Results: We invited 9951 people with type 2 diabetes to become DPM and 427 responded (4.3%). Of these, 356 (83.3%) were interviewed by phone, and of these 131 (36.8%) were interviewed in person. We then appointed 104 of these 131 interviewed applicants (79%) to the role (mean age 62 years, 55% (n=57) male). All DPMs volunteered for a total of 2895 months, and made 6879 telephone calls to 461 randomized participants. Seventy-six (73%) DPMs volunteered for at least 6 months and 66 (73%) for at least 1 year. Discussion: Individuals with type 2 diabetes can be recruited, trained and retained as DPM in large numbers to support a group-based diabetes prevention program delivered by healthcare professionals. This volunteer model is low cost, and accesses the large type 2 diabetes population that shares a lifestyle experience with the target population. This is an attractive model for supporting diabetes prevention efforts