The why, when, and how of computing in biology classrooms [version 1; peer review: 2 approved]

Many biologists are interested in teaching computing skills or using computing in the classroom, despite not being formally trained in these skills themselves. Thus biologists may find themselves researching how to teach these skills, and therefore many individuals are individually attempting to discover resources and methods to do so. Recent years have seen an expansion of new technologies to assist in delivering course content interactively. Educational research provides insights into how learners absorb and process information during interactive learning. In this review, we discuss the value of teaching foundational computing skills to biologists, and strategies and tools to do so. Additionally, we review the literature on teaching practices to support the development of these skills. We pay special attention to meeting the needs of diverse learners, and consider how different ways of delivering course content can be leveraged to provide a more inclusive classroom experience. Our goal is to enable biologists to teach computational skills and use computing in the classroom successfully

Clinical and Molecular Characterisation Of Hyperinsulinaemic Hypoglycaemia In Infants Born Small-For-Gestational Age

OBJECTIVE: To characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH). METHODS: Clinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8. RESULTS: There was no correlation between the maximum glucose requirement and serum insulin levels. Serum insulin level was undetectable in five infants (19%) during hypoglycaemia. Six infants (22%) required diazoxide treatment >6 months. Normoglycaemia on diazoxide <5 mg/kg/day was a safe predictor of resolved HH. Sequencing of KCNJ11/ABCC8 did not identify any mutations. CONCLUSIONS: Serum insulin levels during hypoglycaemia taken in isolation can miss the diagnosis of HH. SGA infants may continue to have hypofattyacidaemic hypoketotic HH beyond the first few weeks of life. Recognition and treatment of this group of patients are important and may have important implications for neurodevelopmental outcome of these patients

Coincidence of a Novel KCNJ11 Missense Variant R365H With a Paternally Inherited 6q24 Duplication in a Patient With Transient Neonatal Diabetes

OBJECTIVE—Neonatal diabetes is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent neonatal diabetes is mutations of the ATP-sensitive K+ channel subunits; in transient neonatal diabetes, chromosome 6q24 abnormalities are the most common cause

Structured Observations Reveal Slow HIV-1 CTL Escape

The existence of viral variants that escape from the selection pressures imposed by cytotox- ic T-lymphocytes (CTLs) in HIV-1 infection is well documented, but it is unclear when they arise, with reported measures of the time to escape in individuals ranging from days to years. A study of participants enrolled in the SPARTAC (Short Pulse Anti-Retroviral Thera- py at HIV Seroconversion) clinical trial allowed direct observation of the evolution of CTL es- cape variants in 125 adults with primary HIV-1 infection observed for up to three years. Patient HLA-type, longitudinal CD8+ T-cell responses measured by IFN- γ ELISpot and lon- gitudinal HIV-1 gag , pol , and nef sequence data were used to study the timing and preva- lence of CTL escape in the participants whilst untreated. Results showed that sequence variation within CTL epitopes at the first time point (within six months of the estimated date of seroconversion) was consistent with most mutations being transmitted in the infecting viral strain rather than with escape arising within the first few weeks of infection. Escape arose throughout the first three years of infection, but slowly and steadily. Approximately one third of patients did not drive any new escape in an HLA-restricted epitope in just under two years. Patients driving several escape mutations during these two years were rare and the median and modal numbers of new escape events in each patient were one and zero re- spectively. Survival analysis of time to escape found that possession of a protective HLA type significantly reduced time to first escape in a patient (p = 0.01), and epitopes escaped faster in the face of a measurable CD8+ ELISpot response (p = 0.001). However, even in an HLA matched host who mounted a measurable, specific, CD8+ response the average time before the targeted epitope evolved an escape mutation was longer than two year

Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and hyperinsulinism

K(ATP) channels regulate insulin secretion from pancreatic beta-cells. Loss- and gain-of-function mutations in the genes encoding the Kir6.2 and SUR1 subunits of this channel cause hyperinsulinism of infancy and neonatal diabetes, respectively. We report two novel mutations in the gating loop of Kir6.2 which cause neonatal diabetes with developmental delay (T293N) and hyperinsulinism (T294M). These mutations increase (T293N) or decrease (T294M) whole-cell K(ATP) currents, accounting for the different clinical phenotypes. The T293N mutation increases the intrinsic channel open probability (Po((0))), thereby indirectly decreasing channel inhibition by ATP and increasing whole-cell currents. T294M channels exhibit a dramatically reduced Po((0)) in the homozygous but not in the pseudo-heterozygous state. Unlike wild-type channels, hetT294M channels were activated by MgADP in the absence but not in the presence of MgATP; however, they are activated by MgGDP in both the absence and presence of MgGTP. These mutations demonstrate the importance of the gating loop of Kir channels in regulating Po((0)) and further suggest that Mg-nucleotide interaction with SUR1 may reduce ATP inhibition at Kir6.2.We thank the Wellcome Trust (076436/Z/05/Z and 081188/A/06/Z), the Royal Society and the European Union (EuroDia, SHM‐CT‐2006‐518513 and EDICT, 201924) for support. FMA is a Royal Society Research Professor. Brittany Zadek was supported by an OXION studentship and Sarah Flanagan by a Sir Graham Wilkins Research Fellowship

Development of the iCook 4-H Curriculum for Youth and Adults: Cooking, Eating, and Playing Together for Childhood Obesity Prevention

The objective was to describe the development process of a curriculum (iCook 4-H) targeted to low-income, rural, and/or diverse youths and their adult primary meal preparer to promote cooking, eating, and playing together. Lessons learned highlighted the importance of grounding the curriculum in Social Cognitive Theory and applying the experiential 4-H learning model using a multiphased, community-based participatory approach with cyclical development and evaluation, and key modifications made for dissemination and distribution. Findings across 4 testing phases over 6 years and 5 states demonstrated the time-intensive, cyclical process that required flexibility with fidelity to form a hands-on, interactive curriculum

'Reaching the hard to reach' - lessons learned from the VCS (voluntary and community Sector). A qualitative study.

Background The notion 'hard to reach' is a contested and ambiguous term that is commonly used within the spheres of social care and health, especially in discourse around health and social inequalities. There is a need to address health inequalities and to engage in services the marginalized and socially excluded sectors of society. Methods This paper describes a pilot study involving interviews with representatives from eight Voluntary and Community Sector (VCS) organisations . The purpose of the study was to explore the notion of 'hard to reach' and perceptions of the barriers and facilitators to accessing services for 'hard to reach' groups from a voluntary and community sector perspective. Results The 'hard to reach' may include drug users, people living with HIV, people from sexual minority communities, asylum seekers, refugees, people from black and ethnic minority communities, and homeless people although defining the notion of the 'hard to reach' is not straight forward. It may be that certain groups resist engaging in treatment services and are deemed hard to reach by a particular service or from a societal stance. There are a number of potential barriers for people who may try and access services, including people having bad experiences in the past; location and opening times of services and how services are funded and managed. A number of areas of commonality are found in terms of how access to services for 'hard to reach' individuals and groups could be improved including: respectful treatment of service users, establishing trust with service users, offering service flexibility, partnership working with other organisations and harnessing service user involvement. Conclusions: If health services are to engage with groups that are deemed 'hard to reach' and marginalised from mainstream health services, the experiences and practices for engagement from within the VCS may serve as useful lessons for service improvement for statutory health services

Genome-Wide Studies of Histone Demethylation Catalysed by the Fission Yeast Homologues of Mammalian LSD1

In order to gain a more global view of the activity of histone demethylases, we report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and SWIRM2), associate together in a complex. However, we find that this complex specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down-regulates expression of different groups of genes. Using chromatin-immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2 or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide changes in patterns of histone methylation, and their correlation with gene expression, upon deletion of the swm1+ gene. Using hyper-geometric probability comparisons we uncover genetic links between lysine-specific demethylases, the histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and Swm2 are associated in complexes that can remove methyl groups from lysine 9 methylated histone H3. In vitro, we show that bacterially expressed Swm1 also possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2 is observed at genes that are up-regulated in a swm1 deletion strain. In addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets that are down-regulated in the swm1¿ strain. The in vivo data indicate that Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to repress gene expression. In addition, our in vitro analyses suggest that the H3K9 demethylase activity requires an unidentified post-translational modification to allow it to act. Thus, our results highlight complex interactions between histone demethylase, deacetylase and chromatin remodelling activities in the regulation of gene expression

What are the type, direction, and strength of species, community, and ecosystem responses to warming in aquatic mesocosm studies and their dependency on experimental characteristics? A systematic review protocol

Background Mesocosm experiments have become increasingly popular in climate change research as they bridge the gap between small-scale, less realistic, microcosm experiments, and large-scale, more complex, natural systems. Characteristics of aquatic mesocosm designs (e.g., mesocosm volume, study duration, and replication) vary widely, potentially affecting the magnitude and direction of effect sizes measured in experiments. In this global systematic review we aim to identify the type, direction and strength of climate warming effects on aquatic species, communities and ecosystems in mesocosm experiments. Furthermore, we will investigate the context-dependency of the observed effects on several a priori determined effect moderators (ecological and methodological). Our conclusions will provide recommendations for aquatic scientists designing mesocosm experiments, as well as guidelines for interpretation of experimental results by scientists, policy-makers and the general public. Methods We will conduct a systematic search using multiple online databases to gather evidence from the scientific literature on the effects of warming experimentally tested in aquatic mesocosms. Data from relevant studies will be extracted and used in a random effects meta-analysis to estimate the overall effect sizes of warming experiments on species performance, biodiversity and ecosystem functions. Experimental characteristics (e.g., mesocosm size and shape, replication-level, experimental duration and design, biogeographic region, community type, crossed manipulation) will be further analysed using subgroup analyses

Unravelling the genetic causes of mosaic islet morphology in congenital hyperinsulinism

Congenital hyperinsulinism (CHI) causes dysregulated insulin secretion which can lead to life-threatening hypoglycaemia if not effectively managed. CHI can be sub-classified into three distinct groups: diffuse, focal and mosaic pancreatic disease. Whilst the underlying causes of diffuse and focal disease have been widely characterised, the genetic basis of mosaic pancreatic disease is not known. To gain new insights into the underlying disease processes of mosaic-CHI we studied the islet tissue histopathology derived from limited surgical resection from the tail of the pancreas in a patient with CHI. The underlying genetic aetiology was investigated using a combination of high depth next-generation sequencing, microsatellite analysis and p57kip2 immunostaining. Histopathology of the pancreatic tissue confirmed the presence of a defined area associated with marked islet hypertrophy and a cytoarchitecture distinct from focal CHI but compatible with mosaic CHI localised to a discrete region within the pancreas. Analysis of DNA extracted from the lesion identified a de novo mosaic ABCC8 mutation and mosaic paternal uniparental disomy which were not present in leukocyte DNA or the surrounding unaffected pancreatic tissue. This study provides the first description of two independent disease-causing somatic genetic events occurring within the pancreas of an individual with localised mosaic CHI. Our findings increase knowledge of the genetic causes of islet disease and provide further insights into the underlying developmental changes associated with β-cell expansion in CHI