Notes on Cynipid Galls, Ground Beetles and Ground-dwelling Spiders Collected at Fort Severn, Ontario

A brief collecting trip to Fort Severn, Ontario (55°59' N, 87°38' W), in May 2001 revealed galls of three species of cynipid wasps (Hymenoptera: Cynipidae) on the wild rose Rosa acicularis. Roses and cynipid galls occur along the banks of the Severn River above the tree line because of clay deposits, heat, and rafts of vegetation carried north by the river. Ground beetles and spiders were collected with pitfall traps. Our identification of 15 species of ground beetles (Coleoptera: Carabidae), two of them new records for Ontario, and 11 species of ground spiders (Araneae: Lycosidae), all new records for northwestern Ontario, indicates that the invertebrate fauna in the area has been poorly studied. Roads and trails away from Fort Severn, regularly scheduled airline service, and convenient accommodations make the area ideal for biological studies.Une brève sortie de prélèvement à Fort Severn, en Ontario (55° 59' de lat. N., 87° 38' de long. O.), effectuée en mai 2001 a révélé l'existence de galles de trois espèces de cynips du rosier (hyménoptères: cynipidés) sur le rosier aciculaire Rosa acicularis. On trouve ce dernier et les galles du rosier le long des rives de la Severn au-dessus de la limite forestière en raison des dépôts d'argile, de la chaleur et de la végétation flottante que transporte la rivière en direction du Nord. On a prélevé des carabes et des araignées terricoles à l'aide de pièges à fosse. Notre identification de 15 espèces de carabes (coléoptères: carabidés), dont deux représentaient deux nouvelles espèces pour l'Ontario, et de 11 espèces d'araignées terricoles (aranéides: lycosidés), dont toutes étaient nouvelles pour le nord-ouest de l'Ontario, révèle que la faune invertébrée de la région n'a pas encore fait l'objet d'une étude approfondie. Les routes et les pistes menant à l'extérieur de Fort Severn, le service régulier de transport aérien et l'hébergement à proximité font de la région un emplacement idéal pour des études biologiques

Quantifying institutional reach through the human network in natural history collections

Through the Bloodhound proof-of-concept, https://bloodhound-tracker.net an international audience of collectors and determiners of natural history specimens are engaged in the emotive act of claiming their specimens and attributing other specimens to living and deceased mentors and colleagues. Behind the scenes, these claims build links between Open Researcher and Contributor Identifiers (ORCID, https://orcid.org) or Wikidata identifiers for people and Global Biodiversity Information Facility (GBIF) specimen identifiers, predicated by the Darwin Core terms, recordedBy (collected) and identifiedBy (determined). Here we additionally describe the socio-technical challenge in unequivocally resolving people names in legacy specimen data and propose lightweight and reusable solutions. The unique identifiers for the affiliations of active researchers are obtained from ORCID whereas the unique identifiers for institutions where specimens are actively curated are resolved through Wikidata. By constructing closed loops of links between person, specimen, and institution, an interesting suite of potential metrics emerges, all due to the activities of employees and their network of professional relationships. This approach balances a desire for individuals to receive formal recognition for their efforts in natural history collections with that of an institutional-level need to alter budgets in response to easily obtained numeric trends in national and international reach. If handled in a coordinating fashion, this reporting technique may be a significant new driver for specimen digitization efforts on par with Altmetric, https://www.altmetric.com, an important new tool that tracks the impact of publications and delights administrators and authors alike

Heterogeneity of the cancer cell line metabolic landscape

The unravelling of the complexity of cellular metabolism is in its infancy. Cancer-associated genetic alterations may result in changes to cellular metabolism that aid in understanding phenotypic changes, reveal detectable metabolic signatures, or elucidate vulnerabilities to particular drugs. To understand cancer-associated metabolic transformation, we performed untargeted metabolite analysis of 173 different cancer cell lines from 11 different tissues under constant conditions for 1,099 different species using mass spectrometry (MS). We correlate known cancer-associated mutations and gene expression programs with metabolic signatures, generating novel associations of known metabolic pathways with known cancer drivers. We show that metabolic activity correlates with drug sensitivity and use metabolic activity to predict drug response and synergy. Finally, we study the metabolic heterogeneity of cancer mutations across tissues, and find that genes exhibit a range of context specific, and more general metabolic control

A Toolbox for Discrete Modelling of Cell Signalling Dynamics

In an age where the volume of data regarding biological systems exceeds our ability to analyse it, many researchers are looking towards systems biology and computational modelling to help unravel the complexities of gene and protein regulatory networks. In order to make such techniques more accessible to mainstream researchers, tools such as the BioModelAnalyzer (BMA) have been developed to provide a user-friendly graphical interface for discrete modelling of biological systems. Here we use the BMA to build a library of target functions of known molecular interactions, translated from ordinary differential equations (ODEs). We then show that these BMA target functions can be used to reconstruct complex networks, which can correctly predict many known genetic perturbations. This new library supports the accessibility ethos behind the creation of BMA, providing a toolbox for the construction of complex cell signalling models without the need for extensive experience in computer programming or mathematical modelling, and allows for construction and simulation of complex biological systems with only small amounts of quantitative data.Royal Societ

Preferential MGMT hypermethylation in SDH-deficient wild-type GIST

AIMS: Wild-type gastrointestinal stromal tumours (wtGIST) are frequently caused by inherited pathogenic variants, or somatic alterations in the succinate dehydrogenase subunit genes (SDHx). Succinate dehydrogenase is a key enzyme in the citric acid cycle. SDH deficiency caused by SDHx inactivation leads to an accumulation of succinate, which inhibits DNA and histone demethylase enzymes, resulting in global hypermethylation. Epigenetic silencing of the DNA repair gene MGMT has proven utility as a positive predictor of the therapeutic efficacy of the alklyating drug temozolomide (TMZ) in tumours such as glioblastoma multiforme. The aim of this study was to examine MGMT promoter methylation status in a large cohort of GIST. METHODS: MGMT methylation analysis was performed on 65 tumour samples including 47 wtGIST (33 SDH-deficient wtGIST and 11 SDH preserved wtGIST) and 21 tyrosine kinase (TK) mutant GIST. RESULTS: MGMT promoter methylation was detected in 8 cases of SDH-deficient (dSDH) GIST but in none of the 14 SDH preserved wild-type GIST or 21 TK mutant GIST samples analysed. Mean MGMT methylation was significantly higher (p 0.0449) and MGMT expression significantly lower (p<0.0001) in dSDH wtGIST compared with TK mutant or SDH preserved GIST. No correlation was identified between SDHx subunit gene mutations or SDHC epimutation status and mean MGMT methylation levels. CONCLUSION: MGMT promoter hypermethylation occurs exclusively in a subset of dSDH wtGIST. Data from this study support testing of tumour MGMT promoter methylation in patients with dSDH wtGIST to identify those patients who may benefit from most from TMZ therapy

A botanical demonstration of the potential of linking data using unique identifiers for people

Natural history collection data available digitally on the web have so far only made limited use of the potential of semantic links among themselves and with cross-disciplinary resources. In a pilot study, botanical collections of the Consortium of European Taxonomic Facilities (CETAF) have therefore begun to semantically annotate their collection data, starting with data on people, and to link them via a central index system. As a result, it is now possible to query data on collectors across different collections and automatically link them to a variety of external resources. The system is being continuously developed and is already in production use in an international collection portal

Enriched biodiversity data as a resource and service

Background: Recent years have seen a surge in projects that produce large volumes of structured, machine-readable biodiversity data. To make these data amenable to processing by generic, open source “data enrichment” workflows, they are increasingly being represented in a variety of standards-compliant interchange formats. Here, we report on an initiative in which software developers and taxonomists came together to address the challenges and highlight the opportunities in the enrichment of such biodiversity data by engaging in intensive, collaborative software development: The Biodiversity Data Enrichment Hackathon. Results: The hackathon brought together 37 participants (including developers and taxonomists, i.e. scientific professionals that gather, identify, name and classify species) from 10 countries: Belgium, Bulgaria, Canada, Finland, Germany, Italy, the Netherlands, New Zealand, the UK, and the US. The participants brought expertise in processing structured data, text mining, development of ontologies, digital identification keys, geographic information systems, niche modeling, natural language processing, provenance annotation, semantic integration, taxonomic name resolution, web service interfaces, workflow tools and visualisation. Most use cases and exemplar data were provided by taxonomists. One goal of the meeting was to facilitate re-use and enhancement of biodiversity knowledge by a broad range of stakeholders, such as taxonomists, systematists, ecologists, niche modelers, informaticians and ontologists. The suggested use cases resulted in nine breakout groups addressing three main themes: i) mobilising heritage biodiversity knowledge; ii) formalising and linking concepts; and iii) addressing interoperability between service platforms. Another goal was to further foster a community of experts in biodiversity informatics and to build human links between research projects and institutions, in response to recent calls to further such integration in this research domain. Conclusions: Beyond deriving prototype solutions for each use case, areas of inadequacy were discussed and are being pursued further. It was striking how many possible applications for biodiversity data there were and how quickly solutions could be put together when the normal constraints to collaboration were broken down for a week. Conversely, mobilising biodiversity knowledge from their silos in heritage literature and natural history collections will continue to require formalisation of the concepts (and the links between them) that define the research domain, as well as increased interoperability between the software platforms that operate on these concepts

KCNQ potassium channels modulate Wnt activity in gastro-oesophageal adenocarcinomas

Voltage-sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. Through large-scale analysis of 897 patients with gastro-oesophageal adenocarcinomas (GOAs) coupled with in vitro models, we find KCNQ family genes are mutated in ∼30% of patients, and play therapeutically targetable roles in GOA cancer growth. KCNQ1 and KCNQ3 mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherin junctions. This also highlights novel roles of KCNQ3 in non-excitable tissues. We also discover that activity of KCNQ3 sensitises cancer cells to existing potassium channel inhibitors and that inhibition of KCNQ activity reduces proliferation of GOA cancer cells. These findings reveal a novel and exploitable role of potassium channels in the advancement of human cancer, and highlight that supplemental treatments for GOAs may exist through KCNQ inhibitors

People are essential to linking biodiversity data

People are one of the best known and most stable entities in the biodiversity knowledge graph. The wealth of public information associated with people and the ability to identify them uniquely open up the possibility to make more use of these data in biodiversity science. Person data are almost always associated with entities such as specimens, molecular sequences, taxonomic names, observations, images, traits and publications. For example, the digitization and the aggregation of specimen data from museums and herbaria allow us to view a scientist’s specimen collecting in conjunction with the whole corpus of their works. However, the metadata of these entities are also useful in validating data, integrating data across collections and institutional databases and can be the basis of future research into biodiversity and science. In addition, the ability to reliably credit collectors for their work has the potential to change the incentive structure to promote improved curation and maintenance of natural history collections

Lung tumors with distinct p53 mutations respond similarly to p53 targeted therapy but exhibit genotype-specific statin sensitivity

Lung adenocarcinoma accounts for ∼40% of lung cancers, the leading cause of cancer-related death worldwide, and current therapies provide only limited survival benefit. Approximately half of lung adenocarcinomas harbor mutations in TP53 (p53), making these mutants appealing targets for lung cancer therapy. As mutant p53 remains untargetable, mutant p53-dependent phenotypes represent alternative targeting opportunities, but the prevalence and therapeutic relevance of such effects (gain of function and dominant-negative activity) in lung adenocarcinoma are unclear. Through transcriptional and functional analysis of murine Kras(G12D) -p53(null) , -p53(R172H) (conformational), and -p53(R270H) (contact) mutant lung tumors, we identified genotype-independent and genotype-dependent therapeutic sensitivities. Unexpectedly, we found that wild-type p53 exerts a dominant tumor-suppressive effect on mutant tumors, as all genotypes were similarly sensitive to its restoration in vivo. These data show that the potential of p53 targeted therapies is comparable across all p53-deficient genotypes and may explain the high incidence of p53 loss of heterozygosity in mutant tumors. In contrast, mutant p53 gain of function and their associated vulnerabilities can vary according to mutation type. Notably, we identified a p53(R270H) -specific sensitivity to simvastatin in lung tumors, and the transcriptional signature that underlies this sensitivity was also present in human lung tumors, indicating that this therapeutic approach may be clinically relevant.This work was supported by the Medical Research Council