UBC-Nepal Expedition: An experimental overview of the 2016 University of British Columbia Scientific Expedition to Nepal Himalaya

The University of British Columbia Nepal Expedition took place over several months in the fall of 2016 and was comprised of an international team of 37 researchers. This paper describes the objectives, study characteristics, organization and management of this expedition, and presents novel blood gas data during acclimatization in both lowlanders and Sherpa. An overview and framework for the forthcoming publications is provided. The expedition conducted 17 major studies with two principal goals—to identify physiological differences in: 1) acclimatization; and 2) responses to sustained high-altitude exposure between lowland natives and people of Tibetan descent. We performed observational cohort studies of human responses to progressive hypobaric hypoxia (during ascent), and to sustained exposure to 5050 m over 3 weeks comparing lowlander adults (n = 30) with Sherpa adults (n = 24). Sherpa were tested both with (n = 12) and without (n = 12) descent to Kathmandu. Data collected from lowlander children (n = 30) in Canada were compared with those collected from Sherpa children (n = 57; 3400–3900m). Studies were conducted in Canada (344m) and the following locations in Nepal: Kathmandu (1400m), Namche Bazaar (3440m), Kunde Hospital (3480m), Pheriche (4371m) and the Ev-K2-CNR Research Pyramid Laboratory (5050m). The core studies focused on the mechanisms of cerebral blood flow regulation, the role of iron in cardiopulmonary regulation, pulmonary pressures, intra-ocular pressures, cardiac function, neuromuscular fatigue and function, blood volume regulation, autonomic control, and micro and macro vascular function. A total of 335 study sessions were conducted over three weeks at 5050m. In addition to an overview of this expedition and arterial blood gas data from Sherpa, suggestions for scientists aiming to perform field-based altitude research are also presented. Together, these findings will contribute to our understanding of human acclimatization and adaptation to the stress of residence at high-altitude

How Plastic Can Phenotypic Plasticity Be? The Branching Coral Stylophora pistillata as a Model System

Phenotypic plasticity enables multicellular organisms to adjust morphologies and various life history traits to variable environmental challenges. Here, we elucidate fixed and plastic architectural rules for colony astogeny in multiple types of colonial ramets, propagated by cutting from genets of the branching coral Stylophora pistillata from Eilat, the Red Sea. We examined 16 morphometric parameters on 136 one-year old S. pistillata colonies (of seven genotypes), originating from small fragments belonging, each, to one of three single-branch types (single tips, start-up, and advanced bifurcating tips) or to structural preparative manipulations (representing a single or two growth axes). Experiments were guided by the rationale that in colonial forms, complexity of evolving phenotypic plasticity can be associated with a degree of structural modularity, where shapes are approached by erecting iterative growth patterns at different levels of coral-colony organization. Analyses revealed plastic morphometric characters at branch level, and predetermined morphometric traits at colony level (only single trait exhibited plasticity under extreme manipulation state). Therefore, under the experimental manipulations of this study, phenotypic plasticity in S. pistillata appears to be related to branch level of organization, whereas colony traits are controlled by predetermined genetic architectural rules. Each level of organization undergoes its own mode of astogeny. However, depending on the original ramet structure, the spherical 3-D colonial architecture in this species is orchestrated and assembled by both developmental trajectories at the branch level, and traits at the colony level of organization. In nature, branching colonial forms are often subjected to harsh environmental conditions that cause fragmentation of colony into ramets of different sizes and structures. Developmental traits that are plastic, responding to fragment structure and are not predetermine in controlling astogeny, allow formation of species-specific architecture product through integrated but variable developmental routes. This adaptive plasticity or regeneration is an efficient mechanism by which isolated fragments of branching coral species cope with external environmental forces

Wnt addiction of genetically defined cancers reversed by PORCN inhibition

Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Whether these mutations identify a clinical opportunity is an important question. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. We developed a novel potent, orally available PORCN inhibitor, ETC-1922159 (henceforth called ETC-159) that blocks the secretion and activity of all Wnts. ETC-159 is remarkably effective in treating RSPO-translocation bearing colorectal cancer (CRC) patient-derived xenografts. This is the first example of effective targeted therapy for this subset of CRC. Consistent with a central role of Wnt signaling in regulation of gene expression, inhibition of PORCN in RSPO3-translocated cancers causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell and proliferation genes, and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers

Skeletal carbonate mineralogy of Scottish bryozoans

This paper describes the skeletal carbonate mineralogy of 156 bryozoan species collected from Scotland (sourced both from museum collections and from waters around Scotland) and collated from literature. This collection represents 79% of the species which inhabit Scottish waters and is a greater number and proportion of extant species than any previous regional study. The study is also of significance globally where the data augment the growing database of mineralogical analyses and offers first analyses for 26 genera and four families. Specimens were collated through a combination of field sampling and existing collections and were analysed by X-ray diffraction (XRD) and micro-XRD to determine wt% MgCO3 in calcite and wt% aragonite. Species distribution data and phylogenetic organisation were applied to understand distributional, taxonomic and phylo-mineralogical patterns. Analysis of the skeletal composition of Scottish bryozoans shows that the group is statistically different from neighbouring Arctic fauna but features a range of mineralogy comparable to other temperate regions. As has been previously reported, cyclostomes feature low Mg in calcite and very little aragonite, whereas cheilostomes show much more variability, including bimineralic species. Scotland is a highly variable region, open to biological and environmental influx from all directions, and bryozoans exhibit this in the wide range of within-species mineralogical variability they present. This plasticity in skeletal composition may be driven by a combination of environmentally-induced phenotypic variation, or physiological factors. A flexible response to environment, as manifested in a wide range of skeletal mineralogy within a species, may be one characteristic of successful invasive bryozoans

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

The Molecular Origin and Taxonomy of Mucinous Ovarian Carcinoma

Mucinous ovarian carcinoma (MOC) is a unique subtype of ovarian cancer with an uncertain etiology, including whether it genuinely arises at the ovary or is metastatic disease from other organs. In addition, the molecular drivers of invasive progression, high-grade and metastatic disease are poorly defined. We perform genetic analysis of MOC across all histological grades, including benign and borderline mucinous ovarian tumors, and compare these to tumors from other potential extra-ovarian sites of origin. Here we show that MOC is distinct from tumors from other sites and supports a progressive model of evolution from borderline precursors to high-grade invasive MOC. Key drivers of progression identified are TP53 mutation and copy number aberrations, including a notable amplicon on 9p13. High copy number aberration burden is associated with worse prognosis in MOC. Our data conclusively demonstrate that MOC arise from benign and borderline precursors at the ovary and are not extra-ovarian metastases