Hagfish: champions of CO2 tolerance question the origins of vertebrate gill function

The gill is widely accepted to have played a key role in the adaptive radiation of early vertebrates by supplanting the skin as the dominant site of gas exchange. However, in the most basal extant craniates, the hagfishes, gills play only a minor role in gas exchange. In contrast, we found hagfish gills to be associated with a tremendous capacity for acid-base regulation. Indeed, Pacific hagfish exposed acutely to severe sustained hypercarbia tolerated among the most severe blood acidoses ever reported (1.2 pH unit reduction) and subsequently exhibited the greatest degree of acid-base compensation ever observed in an aquatic chordate. This was accomplished through an unprecedented increase in plasma [HCO3−] (>75 mM) in exchange for [Cl−]. We thus propose that the first physiological function of the ancestral gill was acid-base regulation, and that the gill was later co-opted for its central role in gas exchange in more derived aquatic vertebrates

Installation instructions for GLiMR version 1.pdf

Here, we describe and demonstrate a geographic information systems-based lithic morphometric research (GLiMR) software approach. GLiMR accurately and rapidly handles a sequence of ArcGIS procedures to extract geometric morphometric data from 2D and 3D scan files of lithic artifacts. GLiMR generates three main types of geometric properties: shape data, topographic data and domain aggregate data. These data can be extracted in ways that support other analyses of artifact form, including Generalized Procrustes Analysis, Principal Components Analysis and Cluster Analyses. We illustrate the use of GLiMR by presenting a basic case study that compares the geometric morphometry of Western Stemmed Tradition projectile points found in two cache features at Idaho’s Cooper’s Ferry site and from other sites in the Columbia River Plateau region of the Pacific Northwest. This collection also includes the XYZ scan files for artifacts used for case study analysis

PhenomiR: a knowledgebase for microRNA expression in diseases and biological processes

PhenomiR is a comprehensive database of 542 studies reporting deregulation of miRNAs allowing large-scale statistical analysis of miRNA expression changes

A Cross-Sectional Survey of the Association between Bilateral Topical Prostaglandin Analogue Use and Ocular Adnexal Features

We studied the relation between prostaglandin analogue use and ocular adnexal features. We used a prospective, cross-sectional study involving 157 current, 15 past, and 171 never users of prostaglandin analogues. Patients 50 years of age or older and without conditions affecting ocular adnexal anatomy underwent glaucoma medication use history, external digital photography and systematic external adnexal exam. Two masked readers assessed the digital photos for upper lid dermatochalasis and lower lid steatoblepharon using a validated grading scheme. Another masked clinical examiner also assessed upper lid ptosis, levator muscle function, and inferior scleral show. We performed ordinal logistic regression analysis accounting for multiple covariates to assess the relation between prostaglandin analogue use and adnexal features. Multivariable analyses indicated there was a 230-fold increased risk of incremental involution of dermatochalasis (odds ratio (OR) = 2.30; 95% confidence interval (CI) 1.43–3.69; p = 5.44E-04) and a 249-fold increased risk of incremental loss of lower lid steatoblepharon (OR = 2.49; 95% CI, 1.54–4.03; p = 1.98E-04) associated with current prostaglandin analogue use (bimatoprost 0.03%, travoprost 0.005%, or latanoprost 0.004%) versus prostaglandin analogue never or past users. Upper lid ptosis (OR = 4.04; 95% CI, 2.43–6.72; p = 7.37E-08), levator dysfunction (OR = 7.51; 95% CI, 3.39–16.65; p = 6.74E-07) and lower lid retraction (OR = 2.60; 95% CI, 1.58–4.28; p = 1.72E-04) were highly associated with current prostaglandin analogue use versus prostaglandin analogue never or past users. The associations between prostaglandin analogue use and deepening of the upper lid sulci and between prostaglandin analogue use and loss of inferior periorbital fat are confirmed in this multivariable analysis. The associations between prostaglandin analogue use and levator muscle dysfunction and between prostaglandin analogue use and upper lid ptosis represent significant side effects that could impact visual function in glaucoma patients

Extensional and Intensional Strategies

This paper is a contribution to the theoretical foundations of strategies. We first present a general definition of abstract strategies which is extensional in the sense that a strategy is defined explicitly as a set of derivations of an abstract reduction system. We then move to a more intensional definition supporting the abstract view but more operational in the sense that it describes a means for determining such a set. We characterize the class of extensional strategies that can be defined intensionally. We also give some hints towards a logical characterization of intensional strategies and propose a few challenging perspectives

Descriptions of Spatial Operations – Recent Approaches and Community Feedback

Progress in the technical provision of spatial operations as loosely-coupled interoperable web services requires a corresponding development of standardisation in their description. Operation discovery, usage and interpretation of results require more information on what a spatial operation does than just their input and output interface specifications. Geooperators and WPS profiles have been proposed for addressing operation descriptions for different operational perspectives. Geooperators have been developed mostly for supporting operation discovery through defining alternative perspectives such as a geodata, legacy GIS, formal or technical perspective. These act as filters in the discovery process. WPS profiles provide a hierarchical approach to define the concept underlying an operation and, in more specific profiles, the syntactic interface of the operation. Both approaches require community engagement for reaching an agreed set of documented operations. We report on a discussion of these approaches and the larger framework of a geoprocessing community platform from a workshop held at the AGILE International Conference on Geographic Information Science in Lisbon in 2015. At the workshop two presentations provided insights in different contexts of use of online geoprocessing. After detailed introductions to the two operation descriptions approaches, two breakout sessions were held. In the breakout sessions operation descriptions and technical developments in the field were discussed. This article summarizes the discussion that took place at the workshop with the intention to involve the extended community in the discourse on operation descriptions

A Novel Siglec-4 Derived Spacer Improves the Functionality of CAR T Cells Against Membrane-Proximal Epitopes

A domain that is often neglected in the assessment of chimeric antigen receptor (CAR) functionality is the extracellular spacer module. However, several studies have elucidated that membrane proximal epitopes are best targeted through CARs comprising long spacers, while short spacer CARs exhibit highest activity on distal epitopes. This finding can be explained by the requirement to have an optimal distance between the effector T cell and target cell. Commonly used long spacer domains are the CH2-CH3 domains of IgG molecules. However, CARs containing these spacers generally show inferior in vivo efficacy in mouse models compared to their observed in vitro activity, which is linked to unspecific Fcγ-Receptor binding and can be abolished by mutating the respective regions. Here, we first assessed a CAR therapy targeting membrane proximal CD20 using such a modified long IgG1 spacer. However, despite these mutations, this construct failed to unfold its observed in vitro cytotoxic potential in an in vivo model, while a shorter but less structured CD8α spacer CAR showed complete tumor clearance. Given the shortage of well-described long spacer domains with a favorable functionality profile, we designed a novel class of CAR spacers with similar attributes to IgG spacers but without unspecific off-target binding, derived from the Sialic acid-binding immunoglobulin-type lectins (Siglecs). Of five constructs tested, a Siglec-4 derived spacer showed highest cytotoxic potential and similar performance to a CD8α spacer in a CD20 specific CAR setting. In a pancreatic ductal adenocarcinoma model, a Siglec-4 spacer CAR targeting a membrane proximal (TSPAN8) epitope was efficiently engaged in vitro, while a membrane distal (CD66c) epitope did not activate the T cell. Transfer of the TSPAN8 specific Siglec-4 spacer CAR to an in vivo setting maintained the excellent tumor killing characteristics being indistinguishable from a TSPAN8 CD8α spacer CAR while outperforming an IgG4 long spacer CAR and, at the same time, showing an advantageous central memory CAR T cell phenotype with lower release of inflammatory cytokines. In summary, we developed a novel spacer that combines cytotoxic potential with an advantageous T cell and cytokine release phenotype, which make this an interesting candidate for future clinical applications

Identification of upper thermal thresholds during development in the endangered Nechako white sturgeon with management implications for a regulated river

Climate change-induced warming effects are already evident in river ecosystems, and projected increases in temperature will continue to amplify stress on fish communities. In addition, many rivers globally are impacted by dams, which have many negative effects on fishes by altering flow, blocking fish passage, and changing sediment composition. However, in some systems, dams present an opportunity to manage river temperature through regulated releases of cooler water. For example, there is a government mandate for Kenney dam operators in the Nechako river, British Columbia, Canada, to maintain river temperature <20°C in July and August to protect migrating sockeye salmon (Oncorhynchus nerka). However, there is another endangered fish species inhabiting the same river, Nechako white sturgeon (Acipenser transmontanus), and it is unclear if these current temperature regulations, or timing of the regulations, are suitable for spawning and developing sturgeon. In this study, we aimed to identify upper thermal thresholds in white sturgeon embryos and larvae to investigate if exposure to current river temperatures are playing a role in recruitment failure. We incubated embryos and yolk-sac larvae in three environmentally relevant temperatures (14, 18 and 21°C) throughout development to identify thermal thresholds across different levels of biological organization. Our results demonstrate upper thermal thresholds at 21°C across physiological measurements in embryo and yolk-sac larvae white sturgeon. Before hatch, both embryo survival and metabolic rate were reduced at 21°C. After hatch, sublethal consequences continued at 21°C because larval sturgeon had decreased thermal plasticity and a dampened transcriptional response during development. In recent years, the Nechako river has reached 21°C by the end of June, and at this temperature, a decrease in sturgeon performance is evident in most of the traits measured. As such, the thermal thresholds identified here suggest current temperature regulations may not be suitable for developing white sturgeon and future recruitment