Waterloo Research

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Environmental bonds and public liability for resource extraction site cleanup
(University of Waterloo, 2024) Insley, Margaret
Governments have been left with large liabilities for cleanup at natural resource extraction sites after firms have declared bankruptcy. This research studies the impact of different forms of financial assurance on a firm's optimal actions over the full life cycle of a hypothetical natural gas well, in a world of uncertain natural gas prices, when firm bankruptcy may shift cleanup costs to the government. A firm's stochastic optimal control problem is described by an HJB equation with the natural gas price modelled as a stochastic differential equation. The impact of financial assurance is examined in relation to firm investment decisions, the cleanup liability imposed on government and resource taxation revenue. A Cash Deposit and Surety Bond are contrasted with the case of no financial assurance requirement. The "fair" fee (assuming the absence of arbitrage opportunities) is determined for the Surety Bond issued by a third party. Numerical results demonstrate that in the presence of distortionary taxes, there is a trade off between indemnifying the government against cleanup costs versus maintaining government tax and royalty revenues. A numerically plausible case is presented in which the total value of the natural gas well (to the firm and the government) is not increased by the imposition of a strict form of financial surety.
Canada's racialized immigrant women
(University of Waterloo, 2024) Ferrer, Ana; Dhatt, Sumeet Singh
Immigrants have traditionally lagged behind labour outcomes of Canadian born workers, a fact that is more obvious for immigrant women and for recent arrivals (those entering Canada within the last five years). In this report we explore the barriers and challenges faced by racialized newcomer women in the Canadian labour market and how differences in their characteristics are (or aren't) related to differences in labour market outcomes. We use a specially designed survey to capture the experiences of a sample of racialized newcomer women regarding integration into the labour market and what resources and strategies have been most helpful in achieving career success and improving their quality of life. We follow with an in-depth analysis of the labour market environment of immigrant women to Canada using data from the Labour Force Survey and the O*Net database. This allows us to quantify to what extent immigrant women may be facing barriers and challenges in the labour market, not only along many standard measures of job quality, such as employment, pay, or type or contract, but also examining other non-standard measures of job quality that are informative of the resilience of the jobs immigrants hold, such as the tasks they perform in their jobs.
The economics of Canadian immigration levels
(University of Waterloo, 2024) Doyle, Matthew; Skuterud, Mikal; Worswick, Christopher
In the hope of addressing chronic labour shortages and sluggish economic growth, the Canadian government plans to increase immigration in the coming years to per capita levels not reached since the 1920s. We argue that economic immigration in the Canadian context should aim to boost GDP per capita in the full population including the newcomers. We then examine the potential for increases in Canadian immigration levels to achieve this objective. Our analysis suggests that Canada is not well-positioned to leverage heightened immigration to boost GDP per capita owing primarily to weak capital investment and quantity-quality tradeoffs in immigrant selection. We conclude by providing a framework for identifying the optimal level of economic immigration.
Establishing a FAIR, CARE, and efficient synthetic health data sharing ecosystem for Canada
(University of Waterloo, 2024) Chen, Helen; Grossman, Maura R.; Sen, Anindya; Tsao, Shu-Feng
Obtaining access to real-world health data is a significant challenge, mainly due to privacy and security implications. Consequently, researchers and technology innovators - particularly those operating in the health data science and AI technology development spaces - increasingly resort to synthetic health data to bridge the data gap. High-quality synthetic data has the potential to expedite research and development of novel technologies. However, synthetic health datasets in Canada are scarce, and no existing synthetic health datasets conform to the Findable, Accessible, Interoperable, and Reusable (FAIR) standards. Moreover, while federated learning with synthetic health data. This paper explores the ethical considerations and value proposition of generating and sharing synthetic health data. Our goal is to facilitate the development of a reliable and sustainable synthetic data infrastructure that supports the ethical, responsible, and efficient use of synthetic health data. An important contribution of this research is the establishment of a framework that balances the social benefits of innovation from data sharing with the social costs that occur when individual privacy is compromised. The use of synthetic data significantly reduces the potential for individual harm and is a cost-effective means to lower data-sharing costs. We believe that this framework will pave the way for a more robust and secure synthetic data ecosystem, enabling the generation of valuable insights that can drive positive health outcomes for Canadians.
Implicit incentive provision with misspecified learning
(University of Waterloo, 2025) Echenique, Federico; Li, Anqi
We study misspecified Bayesian learning in principal-agent relationships, where an agent is assessed by an evaluator and rewarded by the market. The agent's outcome depends on their innate ability, costly effort - whose effectiveness is governed by a productivity parameter - and noise. The market infers the agent's ability from observed outcomes and rewards them accordingly. The evaluator conducts costly assessments to reduce outcome noise, which shapes the market's inferences and provide implicit incentives for effort. Society - including the evaluator and the market - holds dogmatic, inaccurate beliefs about ability, which distort learning about effort productivity and effort choice. This, in turn, shapes the evaluator's choice of assessment. We describe a feedback loop linking misspecified ability, biased learning about effort, and distorted assessment. We characterize outcomes that arise in stable steady states and analyze their robust comparative statistics and learning foundations. Applications to education and labor market reveal how stereotypes can reinforce across domains - sometimes disguised as narrowing or even reversals of outcome gaps - and how policy interventions targeting assessment can help.
The impact of infection on population health: Results of the Ontario burden of infectious diseases study
(Public Library of Science, 2012-09-04) Kwong, Jeffrey C.; Ratnasingham, Sujitha; Campitelli, Michael A.; Daneman, Nick; Deeks, Shelley L.; Manuel, Douglas G.; Allen, Vanessa G.; Bayoumi, Ahmed M.; Fazil, Aamir; Fisman, David N.; Gershon, Andrea S.; Gournis, Effie; Heathcote, E. Jenny; Jamieson, Frances B.; Jha, Prabhat; Khan, Kamran M.; Majowicz, Shannon E.; Mazzulli, Tony; McGeer, Allison J.; Muller, Matthew P.; Raut, Abhishek; Rea, Elizabeth; Remis, Robert S.; Shahin, Rita; Wright, Alissa J.; Zagorski, Brandon; Crowcroft, Natasha S.
Background Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. Methodology/Principal Findings We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005–2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. Conclusions/Significance Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.
Pharmacokinetics of peptide mediated delivery of anticancer drug ellipticine
(Public Library of Science, 2012-08-31) Ma, Weina; Lu, Sheng; Pan, Pei; Sadatmousavi, Parisa; Yuan, Yongfang; Chen, P.
The amino acid pairing peptide EAK16-II (EAK) has shown the ability to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, we investigate pharmacokinetics of the formulation of EAK-EPT complexes in vivo. The developed formulation can achieve a sufficiently high drug concentration required in vivo animal models. The nanostructure and surface properties of EAK-EPT complexes or nanoparticle were characterized by transmission electron microscopy (TEM) and zeta potential measurements, respectively. 12 healthy male SD rats were divided into EPT group and EAK-EPT group randomly. Rats in EPT group were tail intravenously injected with the EPT (20 mg/kg); rats in EAK-EPT group were injected with EAK-EPT complexes (EPT's concentration is 20 mg/kg). EPT was extracted from rat plasma with dexamethasone sodium phosphate as internal standards (IS). The pharmacokinetic parameters were obtained using high pressure liquid chromatography (HPLC). Significant differences in main pharmacokinetic parameters between EPT and EAK-EPT complexes were observed, demonstrating that the complexation with EAK prolongs the residence time of the drug and enlarges the area under the concentration-time curve (AUC). This means that EAK can serve as a suitable carrier to increase the bioavailability of EPT.
Random mutagenesis reveals residues of JAK2 critical in evading inhibition by a tyrosine kinase inhibitor
(Public Library of Science, 2012-08-16) Marit, Michael R.; Chohan, Manprit; Matthew, Natasha; Huang, Kai; Kuntz, Douglas A.; Rose, David R.; Barber, Dwayne L.
Background The non-receptor tyrosine kinase JAK2 is implicated in a group of myeloproliferative neoplasms including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. JAK2-selective inhibitors are currently being evaluated in clinical trials. Data from drug-resistant chronic myeloid leukemia patients demonstrate that treatment with a small-molecule inhibitor generates resistance via mutation or amplification of BCR-ABL. We hypothesize that treatment with small molecule inhibitors of JAK2 will similarly generate inhibitor-resistant mutants in JAK2. Methodology In order to identify inhibitor-resistant JAK2 mutations a priori, we utilized TEL-JAK2 to conduct an in vitro random mutagenesis screen for JAK2 alleles resistant to JAK Inhibitor-I. Isolated mutations were evaluated for their ability to sustain cellular growth, stimulate downstream signaling pathways, and phosphorylate a novel JAK2 substrate in the presence of inhibitor. Conclusions Mutations were found exclusively in the kinase domain of JAK2. The panel of mutations conferred resistance to high concentrations of inhibitor accompanied by sustained activation of the Stat5, Erk1/2, and Akt pathways. Using a JAK2 substrate, enhanced catalytic activity of the mutant JAK2 kinase was observed in inhibitor concentrations 200-fold higher than is inhibitory to the wild-type protein. When testing the panel of mutations in the context of the Jak2 V617F allele, we observed that a subset of mutations conferred resistance to inhibitor, validating the use of TEL-JAK2 in the initial screen. These results demonstrate that small-molecule inhibitors select for JAK2 inhibitor-resistant alleles, and the design of next-generation JAK2 inhibitors should consider the location of mutations arising in inhibitor-resistant screens.
Metagenomic annotation networks: Construction and applications
(Public Library of Science, 2012-08-07) Vey, Gregory; Moreno-Hagelsieb, Gabriel
The derivation and comparison of biological interaction networks are vital for understanding the functional capacity and hierarchical organization of integrated microbial communities. In the current work we present metagenomic annotation networks as a novel taxonomy-free approach for understanding the functional architecture of metagenomes. Specifically, metagenomic operon predictions are exploited to derive functional interactions that are translated and categorized according to their associated functional annotations. The result is a collection of discrete networks of weighted annotation linkages. These networks are subsequently examined for the occurrence of annotation modules that portray the functional and organizational characteristics of various microbial communities. A variety of network perspectives and annotation categories are applied to recover a diverse range of modules with different degrees of annotative cohesiveness. Applications to biocatalyst discovery and human health issues are discussed, as well as the limitations of the current implementation.
Intrinsic breaking of internal solitary waves in a deep lake
(Public Library of Science, 2012-07-23) Preusse, Martina; Stastna, Marek; Freistuhler, Heinrich; Peeters, Frank
Based on simulations with the Dubreil-Jacotin-Long (DJL) equation, the limiting amplitude and the breaking mechanisms of internal solitary waves of depression (ISWs) are predicted for different background stratifications. These theoretical predictions are compared to the amplitude and the stability of the leading internal solitary waves of more than 200 trains of ISWs observed in the centre of a sub-basin of Lake Constance. The comparison of the model results with the field observations indicates that the simulated limiting amplitude of the ISWs provides an excellent prediction of the critical wave height above which ISWs break in the field. Shear instabilities and convective instabilities are each responsible for about half of the predicted wave breaking events. The data suggest the presence of core-like structures within the convectively unstable waves, but fully developed and stable cores were not observed. The lack of stable trapped cores in the field can be explained by the results from dynamic simulations of ISWs with trapped cores which demonstrate that even slight disturbances of the background stratification cause trapped cores to become unstable.
Novel nongenomic signaling by glucocorticoid may involve changes to liver membrane order in rainbow trout
(Public Library of Science, 2012-10-08) Dindia, Laura; Murray, Josh; Faught, Erin; Davis, Tracy L.; Leonenko, Zoya; Vijayan, Mathilakath M.
Stress-induced glucocorticoid elevation is a highly conserved response among vertebrates. This facilitates stress adaptation and the mode of action involves activation of the intracellular glucocorticoid receptor leading to the modulation of target gene expression. However, this genomic effect is slow acting and, therefore, a role for glucocorticoid in the rapid response to stress is unclear. Here we show that stress levels of cortisol, the primary glucocorticoid in teleosts, rapidly fluidizes rainbow trout (Oncorhynchus mykiss) liver plasma membranes in vitro. This involved incorporation of the steroid into the lipid domains, as cortisol coupled to a membrane impermeable peptide moiety, did not affect membrane order. Studies confirmed that cortisol, but not sex steroids, increases liver plasma membrane fluidity. Atomic force microscopy revealed cortisol-mediated changes to membrane surface topography and viscoelasticity confirming changes to membrane order. Treating trout hepatocytes with stress levels of cortisol led to the modulation of cell signaling pathways, including the phosphorylation status of putative PKA, PKC and AKT substrate proteins within 10 minutes. The phosphorylation by protein kinases in the presence of cortisol was consistent with that seen with benzyl alcohol, a known membrane fluidizer. Our results suggest that biophysical changes to plasma membrane properties, triggered by stressor-induced glucocorticoid elevation, act as a nonspecific stress response and may rapidly modulate acute stress-signaling pathways.
Statistical conditional sampling for variable-resolution video compression
(Public Library of Science, 2012-10-08) Wong, Alexander; Shafiee, Mohammad Javad; Azimifar, Zohreh
In this study, we investigate a variable-resolution approach to video compression based on Conditional Random Field and statistical conditional sampling in order to further improve compression rate while maintaining high-quality video. In the proposed approach, representative key-frames within a video shot are identified and stored at full resolution. The remaining frames within the video shot are stored and compressed at a reduced resolution. At the decompression stage, a region-based dictionary is constructed from the key-frames and used to restore the reduced resolution frames to the original resolution via statistical conditional sampling. The sampling approach is based on the conditional probability of the CRF modeling by use of the constructed dictionary. Experimental results show that the proposed variable-resolution approach via statistical conditional sampling has potential for improving compression rates when compared to compressing the video at full resolution, while achieving higher video quality when compared to compressing the video at reduced resolution.
The mechanics of metastasis: Insights from a computational model
(Public Library of Science, 2012-09-28) Brodland, G. Wayne; Veldhuis, Jim H.
Although it may seem obvious that mechanical forces are required to drive metastatic cell movements, understanding of the mechanical aspects of metastasis has lagged far behind genetic and biochemical knowledge. The goal of this study is to learn about the mechanics of metastasis using a cell-based finite element model that proved useful for advancing knowledge about the forces that drive embryonic cell and tissue movements. Metastasis, the predominant cause of cancer-related deaths, involves a series of mechanical events in which one or more cells dissociate from a primary tumour, migrate through normal tissue, traverse in and out of a multi-layer circulatory system vessel and resettle. The present work focuses on the dissemination steps, from dissociation to circulation. The model shows that certain surface tension relationships must be satisfied for cancerous cells to dissociate from a primary tumour and that these equations are analogous to those that govern dissociation of embryonic cells. For a dissociated cell to then migrate by invadopodium extension and contraction and exhibit the shapes seen in experiments, the invadopodium must generate a contraction equal to approximately twice that produced by the interfacial tension associated with surrounding cells. Intravasation through the wall of a vessel is governed by relationships akin to those in the previous two steps, while release from the vessel wall is governed by equations that involve surface and interfacial tensions. The model raises a number of potential research questions. It also identifies how specific mechanical properties and the sub-cellular structural components that give rise to them might be changed so as to thwart particular metastatic steps and thereby block the spread of cancer.
Has Alberta oil sands development altered delivery of polycyclic aromatic compounds to the Peace-Athabasca delta?
(Public Library of Science, 2012-09-26) Hall, Roland I.; Wolfe, Brent B.; Wiklund, Johan A.; Edwards, Thomas W. D.; Farwell, Andrea J.; Dixon, D. George
Background The extend to which Alberta oil sands mining and upgrading operations have enhanced delivery of bitumen-derived contaminants via the Athabasca River and atmosphere to the Peace-Athabasca Delta (200 km to the north) is a pivotal question that has generated national and international concern. Accounts of rare health disorders in residents of Fort Chipewyan and deformed fish in downstream ecosystems provided impetus for several recent expert-panel assessments regarding the societal and environmental consequences of this multi-billion-dollar industry. Deciphering relative contributions of natural versus industrial processes on downstream supply of polycyclic aromatic compounds (PACs) has been identified as a critical knowledge gap. But, this remains a formidable scientific challenge because loading from natural processes remains unknown. And, industrial activity occurs in the same locations as the natural bitumen deposits, which potentially confounds contemporary upstream-downstream comparisons of contaminant levels. Methods/Principal Findings Based on analysis of lake sediment cores, we provide evidence that the Athabasca Delta has been a natural repository of PACs carried by the Athabasca River for at least the past two centuries. We detect no measureable increase in the concentration and proportion of river-transported bitumen-associated indicator PACs in sediments deposited in a flood-prone lake since onset of oil sands development. Results also reveal no evidence that industrial activity has contributed measurably to sedimentary concentration of PACs supplied by atmospheric transport. Conclusions/Significance Findings that suggest that natural erosion of exposed bitumen in banks of the Athabasca River and its tributaries is a major process delivering PACs to the Athabasca Delta, and the spring freshet is a key period for contaminant mobilization and transport. This baseline environmental information is essential for informed management of natural resources and human-health concerns by provincial and federal regulatory agencies and industry, and for designing effective long-term monitoring programs for the lower Athabasca River watershed.
Does it really matter where you look when walking on stairs? Insights from a dual-task study
(Public Library of Science, 2012-09-06) Miyasike-daSilva, Veronica; McIlroy, William E.
Although the visual system is known to provide relevant information to guide stair locomotion, there is less understanding of the specific contributions of foveal and peripheral visual field information. The present study investigated the specific role of foveal vision during stair locomotion and ground-stairs transitions by using a dual-task paradigm to influence the ability to rely on foveal vision. Fifteen healthy adults (26.9±3.3 years; 8 females) ascended a 7-step staircase under four conditions: no secondary tasks (CONTROL); gaze fixation on a fixed target located at the end of the pathway (TARGET); visual reaction time task (VRT); and auditory reaction time task (ART). Gaze fixations towards stair features were significantly reduced in TARGET and VRT compared to CONTROL and ART. Despite the reduced fixations, participants were able to successfully ascend stairs and rarely used the handrail. Step time was increased during VRT compared to CONTROL in most stair steps. Navigating on the transition steps did not require more gaze fixations than the middle steps. However, reaction time tended to increase during locomotion on transitions suggesting additional executive demands during this phase. These findings suggest that foveal vision may not be an essential source of visual information regarding stair features to guide stair walking, despite the unique control challenges at transition phases as highlighted by phase-specific challenges in dual-tasking. Instead, the tendency to look at the steps in usual conditions likely provides a stable reference frame for extraction of visual information regarding step features from the entire visual field.
Suppression of cancer progression by MGAT1 shRNA knockdown
(Public Library of Science, 2012-09-05) Zavareh, Reza Beheshti; Sukhai, Mahadeo A.; Hurren, Rose; Gronda, Marcela; Wang, Xiaoming; Simpson, Craig D.; Maclean, Neil; Zih, Francis; Ketela, Troy; Swallow, Carol J.; Moffat, Jason; Rose, David R.; Schachter, Harry; Schimmer, Aaron D.; Dennis, James W.
Oncogenic signaling promotes tumor invasion and metastasis, in part, by increasing the expression of tri- and tetra- branched N-glycans. The branched N-glycans bind to galectins forming a multivalent lattice that enhances cell surface residency of growth factor receptors, and focal adhesion turnover. N-acetylglucosaminyltransferase I (MGAT1), the first branching enzyme in the pathway, is required for the addition of all subsequent branches. Here we have introduced MGAT1 shRNA into human HeLa cervical and PC-3-Yellow prostate tumor cells lines, generating cell lines with reduced transcript, enzyme activity and branched N-glycans at the cell surface. MGAT1 knockdown inhibited HeLa cell migration and invasion, but did not alter cell proliferation rates. Swainsonine, an inhibitor of α-mannosidase II immediately downstream of MGAT1, also inhibited cell invasion and was not additive with MGAT1 shRNA, consistent with a common mechanism of action. Focal adhesion and microfilament organization in MGAT1 knockdown cells also indicate a less motile phenotype. In vivo, MGAT1 knockdown in the PC-3-Yellow orthotopic prostate cancer xenograft model significantly decreased primary tumor growth and the incidence of lung metastases. Our results demonstrate that blocking MGAT1 is a potential target for anti-cancer therapy.
Influenza forecasting with Google Flu Trends
(Public Library of Science, 2013-02-14) Dugas, Andrea Freyer; Jalalpour, Mehdi; Gel, Yulia; Levin, Scott; Torcaso, Fred; Igusa, Takeru; Rothman, Richard E.
Background We developed a practical influenza forecast model based on real-time, geographically focused, and easy to access data, designed to provide individual medical centers with advanced warning of the expected number of influenza cases, thus allowing for sufficient time to implement interventions. Secondly, we evaluated the effects of incorporating a real-time influenza surveillance system, Google Flu Trends, and meteorological and temporal information on forecast accuracy. Methods Forecast models designed to predict one week in advance were developed from weekly counts of confirmed influenza cases over seven seasons (2004-2011) divided into seven training and out-of-sample verification sets. Forecasting procedures using classical Box-Jenkins, generalized linear models (GLM), and generalized linear autoregressive moving average (GARMA) methods were employed to develop the final model and assess the relative contribution of external variables such as, Google Flu Trends, meteorological data, and temporal information. Results A GARMA(3,0) forecast model with Negative Binomial distribution integrating Google Flu Trends information provided the most accurate influenza case predictions. The model, on the average, predicts weekly influenza cases during 7 out-of-sample outbreaks within 7 cases for 83% of estimates. Google Flu Trend data was the only source of external information to provide statistically significant forecast improvements over the base model in four of the seven out-of-sample verification sets. Overall, the p-value of adding this external information to the model is 0.0005. The other exogenous variables did not yield a statistically significant improvement in any of the verification sets. Conclusions Integer-valued autoregression of influenza cases provides a strong base forecast model, which is enhanced by the addition of Google Flu Trends confirming the predictive capabilities of search query based syndromic surveillance. This accessible and flexible forecast model can be used by individual medical centers to provide advanced warning of future influenza cases.
Multi-parametric clustering for sensor mode coordination in cognitive wireless sensor networks
(Public Library of Science, 2013-02-13) Wang, Xiao Yu; Wong, Alexander
The deployment of wireless sensor networks for healthcare applications have been motivated and driven by the increasing demand for real-time monitoring of patients in hospital and large disaster response environments. A major challenge in developing such sensor networks is the need for coordinating a large number of randomly deployed sensor nodes. In this study, we propose a multi-parametric clustering scheme designed to aid in the coordination of sensor nodes within cognitive wireless sensor networks. In the proposed scheme, sensor nodes are clustered together based on similar network behaviour across multiple network parameters, such as channel availability, interference characteristics, and topological characteristics, followed by mechanisms for forming, joining and switching clusters. Extensive performance evaluation is conducted to study the impact on important factors such as clustering overhead, cluster joining estimation error, interference probability, as well as probability of reclustering. Results show that the proposed clustering scheme can be an excellent candidate for use in large scale cognitive wireless sensor network deployments with high dynamics.
NALCN ion channels have alternative selectivity filters resembling calcium channels or sodium channels
(Public Library of Science, 2013-01-28) Senatore, Adriano; Monteil, Arnaud; van Minnen, Jan; Smit, August B.; Spafford, J. David
NALCN is a member of the family of ion channels with four homologous, repeat domains that include voltage-gated calcium and sodium channels. NALCN is a highly conserved gene from simple, extant multicellular organisms without nervous systems such as sponges and placozoans and mostly remains a single gene compared to the calcium and sodium channels which diversified into twenty genes in humans. The single NALCN gene has alternatively-spliced exons at exons 15 or exon 31 that splices in novel selectivity filter residues that resemble calcium channels (EEEE) or sodium channels (EKEE or EEKE). NALCN channels with alternative calcium, (EEEE) and sodium, (EKEE or EEKE) -selective pores are conserved in simple bilaterally symmetrical animals like flatworms to non-chordate deuterostomes. The single NALCN gene is limited as a sodium channel with a lysine (K)-containing pore in vertebrates, but originally NALCN was a calcium-like channel, and evolved to operate as both a calcium channel and sodium channel for different roles in many invertebrates. Expression patterns of NALCN-EKEE in pond snail, Lymnaea stagnalis suggest roles for NALCN in secretion, with an abundant expression in brain, and an up-regulation in secretory organs of sexually-mature adults such as albumen gland and prostate. NALCN-EEEE is equally abundant as NALCN-EKEE in snails, but is greater expressed in heart and other muscle tissue, and 50% less expressed in the brain than NALCN-EKEE. Transfected snail NALCN-EEEE and NALCN-EKEE channel isoforms express in HEK-293T cells. We were not able to distinguish potential NALCN currents from background, non-selective leak conductances in HEK293T cells. Native leak currents without expressing NALCN genes in HEK-293T cells are NMDG+ impermeant and blockable with 10 µM Gd3+ ions and are indistinguishable from the hallmark currents ascribed to mammalian NALCN currents expressed in vitro by Lu et al. in Cell. 2007 Apr 20;129(2):371-83.
Horizontal gene transfer contributed to the evolution of extracellular surface structures: The freshwater polyp Hydra is covered by a complex fibrous cuticle containing glycosaminoglucans and proteins of the PPOD and SWT (sweet tooth) families
(Public Library of Science, 2012-12-27) Bottger, Angelika; Doxey, Andrew C.; Hess, Michael W.; Pfaller, Kristian; Salvenmoser, Willi; Deutzmann, Rainer; Geissner, Andreas; Pauly, Barbara; Altstatter, Johannes; Munder, Sandra; Heim, Astrid; Gabius, Hans-Joachim; McConkey, Brendan J.; David, Charles N.
The single-cell layered ectoderm of the fresh water polyp Hydra fulfills the function of an epidermis by protecting the animals from the surrounding medium. Its outer surface is covered by a fibrous structure termed the cuticle layer, with similarity to the extracellular surface coats of mammalian epithelia. In this paper we have identified molecular components of the cuticle. We show that its outermost layer contains glycoproteins and glycosaminoglycans and we have identified chondroitin and chondroitin-6-sulfate chains. In a search for proteins that could be involved in organising this structure we found PPOD proteins and several members of a protein family containing only SWT (sweet tooth) domains. Structural analyses indicate that PPODs consist of two tandem β-trefoil domains with similarity to carbohydrate-binding sites found in lectins. Experimental evidence confirmed that PPODs can bind sulfated glycans and are secreted into the cuticle layer from granules localized under the apical surface of the ectodermal epithelial cells. PPODs are taxon-specific proteins which appear to have entered the Hydra genome by horizontal gene transfer from bacteria. Their acquisition at the time Hydra evolved from a marine ancestor may have been critical for the transition to the freshwater environment.

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