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

The development of a quantification method for measuring iridescence using sexually selected traits in the Gulf pipefish (Syngnathus scovelli)

Reliably quantifying the strength of visual sexual signals, such as iridescence, has been challenging across the field of evolutionary biology, but is critically important for studying biologically relevant trait variation. To address this issue, we present the Iridescence Detection and Isolation Algorithm (IDIA), which was designed to isolate the iridescent signal from photographs for quantification of ornamentation. The Gulf pipefish, Syngnathus scovelli, served as a model system for testing the limits of the algorithm, and was an ideal test case due to their female-specific iridescent bands on their abdomens with a large degree of among-individual variation. Specifically, we tested the repeatability of iridescence estimates in a variety of settings, including manual versus automated measurements, a gradient of lighting intensities, observational data from multiple populations, and in detecting exposure to synthetic estrogen. Using the IDIA, female iridescence was quantified in two ways with results indicating a manual measurement of each individual band may be more reliable than the automated measurement taken by drawing a polygon around all bands. However, the intensity of the lighting the photographs were taken in did not significantly affect repeatability of the measurement of iridescence no matter how it was taken. The IDIA was able to detect geographical variation in female ornamentation of S. scovelli, demonstrating that our automated approach can potentially replicate previously-described population-level variation. Differences in the iridescent signal were significant when comparing female pipefish from the Florida coast to females collected from the Texas coast, indicating the possibility that external factors, such as differing environmental conditions, could affect the strength of female visual signals. Lastly, the IDIA was applied in an ecotoxicology application to detect the development of iridescence in male pipefish exposed to synthetic estrogen. Exposed males began expressing banding patterns with iridescence levels within the range of females. The results from this study confirm the feasibility of using the IDIA for measuring iridescence in fish across a variety of applications

The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia : A systematic review and meta-analysis

Background: Methylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN). Methods: We performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted in duplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effects binary regression model were applied to determine pooled effect estimates. Findings: 44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (>= CIN2/high-grade squamous intra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72.7% (47 8-92.2))) vs. low-grade CIN (= CIN2/HSIL vs. = CIN2/HSIL vs. Interpretation: Higher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use is limited by the need for a multi-genotype and standardised assays. Next-generation multiplex HPV sequencing assays are under development and allow potential for rapid, automated and low-cost methylation testing. (C) 2019 The Authors. Published by Elsevier B.V.Peer reviewe

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

'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

Melanocortin 1 Receptor Variants in an Irish Population

The identification of an association between variants in the human melanocortin 1 receptor (MC1R) gene and red hair and fair skin, as well as the relation between variants of this gene and coat color in animals, suggests that the MC1R is an integral control point in the normal pigmentation phenotype. In order to further define the contribution of MC1R variants to pigmentation in a normal population, we have looked for alterations in this gene in series of individuals from a general Irish population, in whom there is a preponderance of individuals with fair skin type. Seventy-five per cent contained a variant in the MC1R gene, with 30% containing two variants. The Arg151Cys, Arg160Trp, and Asp294His variants were significantly associated with red hair (p = 0.0015, p < 0.001, and p < 0.005, respectively). Importantly, no individuals harboring two of these three variants did not have red hair, although some red-haired individuals only showed one alteration. The same three variants were also over-represented in individuals with light skin type as assessed using a modified Fitzpatrick scale. Despite these associations many subjects with dark hair/darker skin type harbored MC1R variants, but there was no evidence of any particular association of variants with the darker phenotype. The Asp294His variant was similarly associated with red hair in a Dutch population, but was infrequent in red-headed subjects from Sweden. The Asp294His variant was also significantly associated with nonmelanoma skin cancer in a U.K. population. The results show that the Arg151Cys, Arg160Trp, and Asp294His variants are of key significance in determining the pigmentary phenotype and response to ultraviolet radiation, and suggest that in many cases the red-haired component and in some cases fair skin type are inherited as a Mendelian recessive

Partial diazoxide responsiveness in a neonate with hyperinsulinism due to homozygous ABCC8 mutation

We report a case of partial diazoxide responsiveness in a child with severe congenital hyperinsulinaemic hypoglycaemia (CHI) due to a homozygous ABCC8 mutation. A term baby, with birth weight 3.8 kg, born to consanguineous parents presented on day 1 of life with hypoglycaemia. Hypoglycaemia screen confirmed CHI. Diazoxide was commenced on day 7 due to ongoing elevated glucose requirements (15 mg/kg/min), but despite escalation to a maximum dose (15 mg/kg/day), intravenous (i.v.) glucose requirement remained high (13 mg/kg/min). Genetic testing demonstrated a homozygous ABCC8 splicing mutation (c.2041-1G>C), consistent with a diffuse form of CHI. Diazoxide treatment was therefore stopped and subcutaneous (s.c.) octreotide infusion commenced. Despite this, s.c. glucagon and i.v. glucose were required to prevent hypoglycaemia. A trial of sirolimus and near-total pancreatectomy were considered, however due to the significant morbidity potentially associated with these, a further trial of diazoxide was commenced at 1.5 months of age. At a dose of 10 mg/kg/day of diazoxide and 40 µg/kg/day of octreotide, both i.v. glucose and s.c. glucagon were stopped as normoglycaemia was achieved. CHI due to homozygous ABCC8 mutation poses management difficulties if the somatostatin analogue octreotide is insufficient to prevent hypoglycaemia. Diazoxide unresponsiveness is often thought to be a hallmark of recessively inherited ABCC8 mutations. This patient was initially thought to be non-responsive, but this case highlights that a further trial of diazoxide is warranted, where other available treatments are associated with significant risk of morbidity. Learning points: Homozygous ABCC8 mutations are commonly thought to cause diazoxide non-responsive hyperinsulinaemic hypoglycaemia. This case highlights that partial diazoxide responsiveness in homozygous ABCC8 mutations may be present. Trial of diazoxide treatment in combination with octreotide is warranted prior to considering alternative treatments, such as sirolimus or near-total pancreatectomy, which are associated with more significant side effects.This article is freely available via Open Access. Click on the Publisher's URL to access the full-text

Patterns of postmeal insulin secretion in individuals with sulfonylurea- treated KCNJ11 neonatal diabetes show predominance of non- KATP- channel pathways

Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-KATP-channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-rich foods. We aimed to assess the physiological response to carbohydrate and protein/fat in people with sulfonylurea-treated KCNJ11 PNDM.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

The driver landscape of sporadic chordoma.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike