Complications Dawn for Kinetochore Regulation by Aurora

Organisms must faithfully segregate their chromosomes during cell division; mistakes in this process can be costly and even fatal to the organism (1, 2). During mitosis, replicated chromosomes attach to the spindle, a dynamic system of microtubules organized around two poles. Chromosomes attach to the spindle via kinetochores, structures that form on centromeres and bind the ends of microtubules. For accurate segregation, kinetochores on sister chromosomes must attach to microtubules from opposite poles; incorrect attachments lead to missegregation (3). In PNAS, Umbreit et al. (4) expand our understanding of how kinetochore–microtubule interactions can be regulated to correct improper attachments. The authors use in vitro studies to demonstrate that a component of the kinetochore, the Ndc80 complex, can directly influence the dynamics of the microtubules it is bound to and how the complex can be regulated to correct errors in chromosome attachment. Kinetochores are complicated machines. They can stay attached to microtubule ends as they grow and shrink, regulate the dynamics of microtubules, regulate their own activity, and signal to the remainder of the cell. The outer layer of the kinetochore contains the dumbbell-shaped Ndc80 complex (5): One globular domain [the N-terminal domains of Hec1 (Ndc80 in budding yeast) and Nuf2] binds microtubules (6) and is connected by a long coiled coil to the other globular domain (composed of the C-terminal domains of Spc24/Spc25), which connects to other kinetochore components (7) (Fig. 1A). Hec1 contains a conserved calponin homology domain and an unstructured N-terminal tail: Both regions can bind to microtubules independently, but they must act together to produce high-affinity binding (5⇓⇓–8). When sister kinetochores attach...(see full text).Molecular and Cellular Biolog

Tethering Sister Centromeres to Each Other Suggests the Spindle Checkpoint Detects Stretch within the Kinetochore

The spindle checkpoint ensures that newly born cells receive one copy of each chromosome by preventing chromosomes from segregating until they are all correctly attached to the spindle. The checkpoint monitors tension to distinguish between correctly aligned chromosomes and those with both sisters attached to the same spindle pole. Tension arises when sister kinetochores attach to and are pulled toward opposite poles, stretching the chromatin around centromeres and elongating kinetochores. We distinguished between two hypotheses for where the checkpoint monitors tension: between the kinetochores, by detecting alterations in the distance between them, or by responding to changes in the structure of the kinetochore itself. To distinguish these models, we inhibited chromatin stretch by tethering sister chromatids together by binding a tetrameric form of the Lac repressor to arrays of the Lac operator located on either side of a centromere. Inhibiting chromatin stretch did not activate the spindle checkpoint; these cells entered anaphase at the same time as control cells that express a dimeric version of the Lac repressor, which cannot cross link chromatids, and cells whose checkpoint has been inactivated. There is no dominant checkpoint inhibition when sister kinetochores are held together: cells expressing the tetrameric Lac repressor still arrest in response to microtubule-depolymerizing drugs. Tethering chromatids together does not disrupt kinetochore function; chromosomes are successfully segregated to opposite poles of the spindle. Our results indicate that the spindle checkpoint does not monitor inter-kinetochore separation, thus supporting the hypothesis that tension is measured within the kinetochore

Balancing the COVID-19 disruption to undergraduate learning and assessment with an academic student support package: implications for student achievement and engagement

In response to the COVID-19 pandemic-induced emergency pivot to online teaching and assessment, an Academic Safety Net was implemented at a regional Australian university to provide academic student support. Bayesian hierarchical models were used to compare student performance between 2019 and 2020. More students withdrew from subjects in 2020, while fewer students remained enrolled but failed. While there was no overall year effect for overall student achievement, exam achievement increased and on-course assessment achievement decreased in 2020. When achievement was analysed according to an assessment task change, a year effect emerged, with the magnitude and direction of the effect dependent on the task changes. The results indicate that the enrolment component of the Academic Safety Net was an effective equity measure that enabled students an extended opportunity to self-withdraw in response to general impacts of the pandemic; while the results component protected the integrity of results awarded during the emergency pivot

Invasive Species Handbook: A Resource for Educators - Grades 3-8

This handbook includes six chapters that discuss invasive species and their environmental, economic, and health impacts. It also reviews pathways of invasive species spread and prevention, monitoring, and control. The handbook is a resource for educators teaching children in grades 3 through 8. Learning objectives, activities, and vocabulary are also included

Expansion of the ligand knowledge base for chelating P,P-donor ligands (LKB-PP)

[Image: see text] We have expanded the ligand knowledge base for bidentate P,P- and P,N-donor ligands (LKB-PP, Organometallics2008, 27, 1372–1383) by 208 ligands and introduced an additional steric descriptor (nHe(8)). This expanded knowledge base now captures information on 334 bidentate ligands and has been processed with principal component analysis (PCA) of the descriptors to produce a detailed map of bidentate ligand space, which better captures ligand variation and has been used for the analysis of ligand properties

Incidence, Risks, and Types of Infections in Pediatric Long-term Care Facilities

Importance: The population of infants, children, and adolescents cared for at pediatric long-term care facilities is increasing in complexity and size and thus consumes substantial health care resources. Infections are a significant cause of morbidity and mortality in this population, but few recent data describe their incidence and effects. Objectives: To describe the types of infections diagnosed in residents of pediatric long-term care facilities, calculate infection rates, and identify risk factors for respiratory tract infections (RTIs). Design, Setting, and Participants: This prospective cohort study, which was part of a larger trial called Keep It Clean for Kids, was conducted from September 1, 2012, to December 31, 2015, at 3 pediatric long-term care facilities in New York. Residents of the facilities who were 21 years or younger and either residents or admitted during the study period (n = 717) were enrolled in the study. Medical records were reviewed to identify infections diagnosed by site clinicians. Main Outcomes and Measures: Incidence of infections, such as RTIs; skin and soft-tissue infections; chronic comorbid conditions, including neurologic and respiratory disorders; and device use, including gastrostomy tubes and tracheostomies, was determined. Risk factors for RTIs were assessed by generalized linear mixed method regression modeling. Results: The 717 residents had a median (interquartile range) age at enrollment of 2.6 (0.4-9.1) years; 358 (49.9%) were male. Four hundred twenty-eight residents (59.7%) had feeding tubes and 215 (30.0%) had tracheostomies. Most chronic comorbid conditions were musculoskeletal or ambulation (532 residents [74.2%]), neurologic (505 [70.4%]), respiratory (361 [50.3%]), and gastrointestinal (230 [32.1%]) disorders, and 460 residents (64.2%) had 4 or more chronic comorbid conditions. Site clinicians diagnosed 2052 infections during the 3-year study period. Respiratory tract infections were most common and were diagnosed in 1291 residents (62.9%). The overall infection rate was 5.3 infections per 1000 resident-days, and RTI rates were 3.3 infections per 1000 resident-days. Overall infection rates and rates of RTI, skin and soft-tissue infection, urinary tract infection, and bloodstream infection varied among the 3 sites. In the multivariable model, younger age (incidence rate ratio [IRR], 1.05; 95% CI, 1.03-1.06), increased number of chronic comorbid conditions (IRR, 1.12; 95% CI, 1.06-1.19), and the use of feeding tubes (IRR, 1.34; 95% CI, 1.03-1.64) and tracheostomies (IRR, 1.40; 95% CI, 1.17-1.69) were associated with RTIs. Conclusions and Relevance: In this study, RTIs were the most common infections diagnosed, but modifiable risk factors for RTIs were not identified. Future work should focus on optimizing infection prevention and control strategies to reduce infections, particularly RTIs, in the pediatric long-term care population

Dressing changes in a burns unit for children under the age of five:a qualitative study of mothers’ experiences

This study aimed to investigate the experiences of mothers who had attended their child’s burn dressing changes. Participants were recruited from a burns unit based within a children’s hospital. Face-to-face interviews were conducted with five mothers of children under the age of five who had undergone a series of dressing changes taking place on the burns unit. The interview guide explored parents’ experience of initial and subsequent dressing changes. Participants were prompted to explore their expectations, thoughts, feelings and behaviours associated with these experiences. The interviews were recorded and transcribed verbatim. Transcripts were analysed using interpretative phenomenological analysis. The analysis identified four themes: ‘needing to fulfil the responsibilities associated with being a mother’; ‘emotional synchrony between mother and child’; ‘being informed and knowing what to expect’; and ‘the importance of establishing rapport with nurses performing dressing changes’. Findings from this research can inform services to help optimise mothers’ experiences of dressing changes in this stage of pediatric burn care

Defining thresholds of sustainable impact on benthic communities in relation to fishing disturbance

AbstractWhile the direct physical impact on seabed biota is well understood, no studies have defined thresholds to inform an ecosystem-based approach to managing fishing impacts. We addressed this knowledge gap using a large-scale experiment that created a controlled gradient of fishing intensity and assessed the immediate impacts and short-term recovery. We observed a mosaic of taxon-specific responses at various thresholds. The lowest threshold of significant lasting impact occurred between 1 and 3 times fished and elicited a decrease in abundance of 39 to 70% for some sessile epifaunal organisms (cnidarians, bryozoans). This contrasted with significant increases in abundance and/or biomass of scavenging species (epifaunal echinoderms, infaunal crustaceans) by two to four-fold in areas fished twice and more. In spite of these significant specific responses, the benthic community structure, biomass and abundance at the population level appeared resilient to fishing. Overall, natural temporal variation in community metrics exceeded the effects of fishing in this highly dynamic study site, suggesting that an acute level of disturbance (fished over six times) would match the level of natural variation. We discuss the implications of our findings for natural resources management with respect to context-specific human disturbance and provide guidance for best fishing practices.</jats:p

Patient experience and satisfaction with symptomatic Faecal Immunochemical Testing: An explanatory sequential mixed-methods evaluation

Background: Recent evidence suggests that faecal immunochemical testing (FIT) can rule out colorectal cancer in symptomatic adults. To date, there is little research exploring experiences of FIT for this population. Aim: To explore patient experience and satisfaction with FIT in an ‘early adopter’ site in England. Design: We used an explanatory sequential mixed-methods approach combining mailed quantitative surveys with semi-structured telephone interviews. Methods: Multivariate logistic regression was used to analyse quantitative data. Thematic analysis was used to assess qualitative transcripts. Results: The survey had 260 respondents and found satisfaction with FIT was high (88.7%). Compared with test satisfaction, the proportion of respondents satisfied with GP consultation, and how they received their results, was lower (74.4% and 76.2%, respectively). Multivariate analysis showed increased area-level deprivation and not receiving an explanation of the purpose of the test were associated with lower satisfaction with GP consultation (both P-values&lt;0.05), while increased area-level deprivation and not receiving results from the GP were associated with lower satisfaction with receiving results (both P-values&lt;0.05). Interviews with respondents (n=20) helped explain the quantitative results. They revealed that “not knowing the purpose of the test” caused “anxiety” and “confusion”, which led to dissatisfaction. “Not receiving results from GP” was considered “unacceptable”, as this left patients with a “niggling doubt” and lack of diagnosis, or assurance that they did not have cancer. Conclusion: Patient satisfaction with symptomatic FIT is high. Efforts to improve satisfaction should focus on ensuring patients understand the purpose of the test and always receive their test results