A comparison of SNPs and microsatellites as linkage mapping markers: lessons from the zebra finch (Taeniopygia guttata)

Background: Genetic linkage maps are essential tools when searching for quantitative trait loci (QTL). To maximize genome coverage and provide an evenly spaced marker distribution a combination of different types of genetic marker are sometimes used. In this study we created linkage maps of four zebra finch (Taeniopygia guttata) chromosomes (1, 1A, 2 and 9) using two types of marker, Single Nucleotide Polymorphisms (SNPs) and microsatellites. To assess the effectiveness and accuracy of each kind of marker we compared maps built with each marker type separately and with both types of marker combined. Linkage map marker order was validated by making comparisons to the assembled zebra finch genome sequence. Results: We showed that marker order was less reliable and linkage map lengths were inflated for microsatellite maps relative to SNP maps, apparently due to differing error rates between the two types of marker. Guidelines on how to minimise the effects of error are provided. In particular, we show that when combining both types of marker the conventional process of building linkage maps, whereby the most informative markers are added to the map first, has to be modified in order to improve map accuracy. Conclusions: When using multiple types and large numbers of markers to create dense linkage maps, the least error prone loci (SNPs) rather than the most informative should be used to create framework maps before the addition of other potentially more error prone markers (microsatellites). This raises questions about the accuracy of marker order and predicted recombination rates in previous microsatellite linkage maps which were created using the conventional building process, however, provided suitable error detection strategies are followed microsatellite-based maps can continue to be regarded as reasonably reliable

Long-Term Data Reveal a Population Decline of the Tropical Lizard Anolis apletophallus, and a Negative Affect of El Nino Years on Population Growth Rate

Climate change threatens biodiversity worldwide, however predicting how particular species will respond is difficult because climate varies spatially, complex factors regulate population abundance, and species vary in their susceptibility to climate change. Studies need to incorporate these factors with long-term data in order to link climate change to population abundance. We used 40 years of lizard abundance data and local climate data from Barro Colorado Island to ask how climate, total lizard abundance and cohort-specific abundance have changed over time, and how total and cohort-specific abundance relate to climate variables including those predicted to make the species vulnerable to climate change (i.e. temperatures exceeding preferred body temperature). We documented a decrease in lizard abundance over the last 40 years, and changes in the local climate. Population growth rate was related to the previous years’ southern oscillation index; increasing following cooler-wetter, la niña years, decreasing following warmer-drier, el nino years. Within-year recruitment was negatively related to rainfall and minimum temperature. This study simultaneously identified climatic factors driving long-term population fluctuations and climate variables influencing short-term annual recruitment, both of which may be contributing to the population decline and influence the population’s future persistence

Mining protein function from text using term-based support vector machines

<p>Abstract</p> <p>Background</p> <p>Text mining has spurred huge interest in the domain of biology. The goal of the BioCreAtIvE exercise was to evaluate the performance of current text mining systems. We participated in Task 2, which addressed assigning Gene Ontology terms to human proteins and selecting relevant evidence from full-text documents. We approached it as a modified form of the document classification task. We used a supervised machine-learning approach (based on support vector machines) to assign protein function and select passages that support the assignments. As classification features, we used a protein's co-occurring terms that were automatically extracted from documents.</p> <p>Results</p> <p>The results evaluated by curators were modest, and quite variable for different problems: in many cases we have relatively good assignment of GO terms to proteins, but the selected supporting text was typically non-relevant (precision spanning from 3% to 50%). The method appears to work best when a substantial set of relevant documents is obtained, while it works poorly on single documents and/or short passages. The initial results suggest that our approach can also mine annotations from text even when an explicit statement relating a protein to a GO term is absent.</p> <p>Conclusion</p> <p>A machine learning approach to mining protein function predictions from text can yield good performance only if sufficient training data is available, and significant amount of supporting data is used for prediction. The most promising results are for combined document retrieval and GO term assignment, which calls for the integration of methods developed in BioCreAtIvE Task 1 and Task 2.</p

A Qualitative Study of How Adolescents’ Use of Coping Strategies and Support Varies in Line With Their Experiences of Adversity

BACKGROUND: Adolescence is associated with a rise in the incidence of mental health issues. Thus, the factors, processes, and contexts that protect and promote positive mental health in adolescence are of key interest to policymakers. OBJECTIVE: Our aim was twofold: First, to explore the coping strategies and sources of support that adolescents identify as protective (or not) in the face of difficulty over a three-year period; second, to examine how and why this may vary in line with the levels of adversity that they report experiencing in life. METHODS: Participants were attending schools in England implementing a mental health prevention programme called HeadStart. 93 semi-structured interviews were conducted with 31 adolescents (age 11–12 at the outset of the study; 58% female) once per year over three years. The interviews were analysed using thematic analysis. RESULTS: Six coping strategy themes (e.g., ‘Disengaging from problems’) and five support themes (e.g., ‘Parents as a source of comfort and advice’) were derived from the interviews. The types, quality, and consistency of reported coping strategies and support varied in line with whether adolescents were experiencing higher or lower levels of adversity in life over time, and according to the resources that they had available within their physical and social contexts. CONCLUSIONS: Our findings underscore the importance for mental health prevention programmes of bolstering both individual-level coping strategies and the resources available within adolescents’ environments to help them to manage adversity

Sufficient exercise for Australians living with dementia in residential aged care facilities is lacking: An exploration of policy incoherence

Along with cognitive decline, dementia is characterised by changes in emotional control, social behaviour and physical performance.1 Individuals living with dementia often require assistance with their activities of daily living as dementia progresses.2 Requirements for higher levels of care result in more individuals with dementia living in residential aged care facilities (RACFs); up to 52% of all individuals living in RACFs have a diagnosis of dementia

Investigating the role of SLFN14 mutations in inherited thrombocytopenia and haematopoiesis

Schlafen 14 (SLFN14) has recently been identified as an endoribonuclease responsible for cleaving RNA to regulate and inhibit protein synthesis. Early studies revealed members of the SLFN family are capable of altering lineage commitment during T-cell differentiation, using cell cycle arrest as a means of translational control. SLFN14 mutations have been previously reported as causing inherited macrothrombocytopenia and bleeding in patients. The aim of this thesis was to uncover potential mechanisms for how SLFN14 and its mutations contribute to inherited thrombocytopenia and altered haematopoiesis. A novel CRISPR knock-in mouse of SLFN14-K208N and platelet specific knock-out mouse using the PF4Cre loxP system were used to better understand the involvement of SLFN14 in haematopoiesis and platelet function. Gross haematological analysis, in vitro and in vivo studies of platelet and erythrocyte function, as well as analysis of spleen and bone marrow progenitors were used. Homozygous mice for the K208N mutation do not survive to weaning age due to severe anaemia. Heterozygotes exhibit microcytic erythrocytosis, haemolytic anaemia, splenomegaly and abnormal thrombus formation examined by intravital microscopy although in vitro platelet function and morphology remain unchanged. RT-PCR of transcription factor GATA1 in SLFN14-K208N mice revealed significant reduction in GATA1 mRNA from whole bone marrow suggesting the SLFN14 endoribonuclease is active in haematopoiesis. In addition, SLFN14 PF4Cre mice show macrothrombocytopenia with reduced proportion of megakaryocytes in the bone marrow although platelet function was retained. This suggests SLFN14 is a key regulator in mammalian haematopoiesis and a species-specific mediator in platelet and erythrocyte production and function

Examining the concordance of retinal ganglion cell counts generated using measures of structure and function

PURPOSE: There are several indirect methods used to estimate retinal ganglion cell (RGC) count in an individual eye, but there is limited information as to the agreement between these methods. In this work, RGC receptive field (RGC‐RF) count underlying a spot stimulus (0.43°, Goldmann III) was calculated and compared using three different methods. METHODS: RGC‐RF count was calculated at a retinal eccentricity of 2.32 mm for 44 healthy adult participants (aged 18–58 years, refractive error −9.75 DS to +1.75 DS) using: (i) functional measures of achromatic peripheral grating resolution acuity (PGRA), (ii) structural measures of RGC‐layer thickness (OCT‐model, based on the method outlined by Raza and Hood) and (iii) scaling published histology density data to simulate a global expansion in myopia (Histology‐Balloon). RESULTS: Whilst average RGC‐RF counts from the OCT‐model (median 105.3, IQR 99.6–111.0) and the Histology‐Balloon model (median 107.5, IQR 97.7–114.6) were similar, PGRA estimates were approximately 65% lower (median 37.7, IQR 33.8–46.0). However, there was poor agreement between all three methods (Bland–Altman 95% limits of agreement; PGRA/OCT: 55.4; PGRA/Histology‐Balloon 59.3; OCT/Histology‐Balloon: 52.4). High intersubject variability in RGC‐RF count was evident using all three methods. CONCLUSIONS: The lower PGRA RGC‐RF counts may be the result of targeting only a specific subset of functional RGCs, as opposed to the coarser approach of the OCT‐model and Histology‐Balloon, which include all RGCs, and also likely displaced amacrine cells. In the absence of a ‘ground truth’, direct measure of RGC‐RF count, it is not possible to determine which method is most accurate, and each has limitations. However, what is clear is the poor agreement found between the methods prevents direct comparison of RGC‐RF counts between studies utilising different methodologies and highlights the need to utilise the same method in longitudinal work

Perspectives of paediatric hospital staff on factors influencing the sustainability and spread of a safety quality improvement programme

OBJECTIVE: Situation Awareness For Everyone (SAFE) is a quality improvement programme aiming to improve situation awareness in paediatric clinical teams. The aim of our study was to examine hospital staff perceptions of the facilitators and barriers/challenges to the sustaining and subsequent spread of the huddle, the key intervention of the SAFE programme. SETTING: Interviews were held on two wards in two children hospitals and on two children wards in two district general hospitals. METHOD: Semistructured interviews were conducted with 23 staff members from four National Health Service paediatric wards. A deductive thematic analysis was conducted, drawing on an existing framework, which groups the factors influencing programme sustainability into four categories: innovation, leadership, process and context. PARTICIPANTS: 23 staff in two children’s hospitals and two children’s wards across four UK hospitals, comprising of nurses and doctors, administration or housekeeping staff, ward managers and matrons, and allied professionals. PRIMARY OUTCOME: Understanding factors contributing to the sustaining and spread of a quality improvement intervention. RESULTS: Perceptions of the benefits, purpose and fit of the huddle, team commitment, sharing learning, adaptation of the method and senior leadership were identified as facilitators. High staff turnover, large multiple specialty medical staff teams, lack of senior leadership and dislike of change were identified as barriers/challenges. CONCLUSIONS: Sustaining and spreading quality improvement interventions in a complex clinical setting requires understanding of the interplay between the actual innovation and existing leadership, process and contextual factors. These must be considered at the planning stage of an innovation to maximise the potential for sustainability and spread to other settings

The effect of military clothing on gunshot wound patterns in a cadaveric animal limb model

The majority of injuries in survivors of gunshot wounds (GSW) are typically to the extremities. Novel wound ballistic research is encouraged to try and capture corporate knowledge on the management of these injuries gained during recent conflicts and understand the wounding patterns seen. With recent work examining the effect of UK military clothing on extremity GSW patterns in a synthetic model, a model with greater biofidelity is needed for ballistic testing. The aim of this study was to assess the effect of UK military clothing on GSW patterns within a cadaveric animal limb model using two types of ammunition commonly used in recent conflicts—7.62 × 39 mm and 5.45 × 39 mm. In total, 24 fallow deer hind limbs were shot, 12 by 7.62 mm projectiles and the remaining 12 shot by 5.45 mm projectiles, further divided into four with no clothing layers (Cnil), four with a single clothing layer (Cmin) and four with maximum clothing layers (Cmax) as worn on active duty by UK military personnel. Limbs were analysed after ballistic impact using contrast CT scanning to obtain measurements of permanent cavity damage, and results were compared using analysis of variance (ANOVA). Results showed significantly different damage measurements within limbs with Cmax for both ammunition types compared with the other clothing states. This may result in GSWs that require more extensive surgical management, and invites further study