York University Libraries' Open Access Author Fund

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York University Libraries have directed a small portion of their collections budget in support of an open access author fund to cover Author Processing Charges for York researchers who wish to publish their work in open access journals. Please apply as early as possible as once the annual allocation has been expended, no further requests can be considered until the following fiscal year.

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Open Access
A 212-nt long RNA structure in the Tobacco necrosis virus-D RNA genome is resistant to Xrn degradation
(Oxford University Press, 2019) White, K. Andrew; Chaminda, Gunawardene D.; Newburn, Laura R.
Plus-strand RNA viruses can accumulate viral RNA degradation products during infections. Some of these decay intermediates are generated by the cytosolic 5′-to-3′ exoribonuclease Xrn1 (mammals and yeast) or Xrn4 (plants) and are formed when the enzyme stalls on substrate RNAs upon encountering inhibitory RNA structures. Many Xrn-generated RNAs correspond to 3′-terminal segments within the 3′-UTR of viral genomes and perform important functions during infections. Here we have investigated a 3′-terminal small viral RNA (svRNA) generated by Xrn during infections with Tobacco necrosis virus-D (family Tombusviridae). Our results indicate that (i) unlike known stalling RNA structures that are compact and modular, the TNV-D structure encompasses the entire 212 nt of the svRNA and is not functionally transposable, (ii) at least two tertiary interactions within the RNA structure are required for effective Xrn blocking and (iii) most of the svRNA generated in infections is derived from viral polymerase-generated subgenomic mRNA1. In vitro and in vivo analyses allowed for inferences on roles for the svRNA. Our findings provide a new and distinct addition to the growing list of Xrn-resistant viral RNAs and stalling structures found associated with different plant and animal RNA viruses.
Open Access
An adiponectin-S1P axis protects against lipid induced insulin resistance and cardiomyocyte cell death via reduction of oxidative stress
(Biomed Central, 2019-02-21) Botta, Amy; Liu, Ying; Wannaiampikul, Sivaporn; Tungtrongchitr, Rungsunn; Dadson, Keith; Park, Tae-Sik; Sweeney, Gary
Background: Adiponectin exerts several beneficial cardiovascular effects, however their specific molecular mechanisms require additional understanding. This study investigated the mechanisms of adiponectin action in the heart during high fat diet (HFD) feeding or in palmitate (PA) treated H9c2 cardiomyoblasts. Methods: 6-week-old male adiponectin knock out (Ad-KO) mice were fed chow or 60% HFD for 6 weeks then received saline or recombinant adiponectin (3μg/g body weight) for an additional 2 weeks. After acute insulin stimulation (4 U/kg), tissue and serum samples were collected for analysis. H9c2 cardiomyocytes were treated ±0.1 mM PA, the adiponectin receptor agonist AdipoRon, or the antioxidant MnTBAP then assays to analyze reactive oxygen species (ROS) production and cell death were conducted. To specifically determine the mechanistic role of S1P, gain and loss of function studies were conducted with adding S1P to cells or the inhibitors THI and SKI-II, respectively. Results: HFD feeding induced cardiac insulin resistance in Ad-KO mice, which was reversed following replenishment of normal circulating adiponectin levels. In addition, myocardial total triglyceride was elevated by HFD and lipidomic analysis showed increased levels of ceramides and sphingosine-1 phosphate (S1P), with only the latter being corrected by adiponectin administration. Similarly, treatment of H9C2 cardiomyoblasts with PA led to a significant increase of intracellular S1P but not in conditioned media whereas AdipoRon significantly increased S1P production and secretion from cells. AdipoRon or the antioxidant MnTBAP significantly reduced PA-induced cell death. Gain and loss of function studies suggested S1P secretion and autocrine receptor activation mediated the effect of AdipoRon to attenuate PA-induced ROS production and cell death. Conclusion: Our data establish adiponectin signaling-mediated increase in S1P secretion as a mechanism via which HFD or PA induced cardiomyocyte lipotoxicity, leading to insulin resistance and cell death, is attenuated. Keywords: Adiponectin, Sphingosine-1-phosphate, Ceramide, Cardiomyocyte apoptosis, High fat diet, Palmitate, ROS
Open Access
Age- and sex- specific all-cause mortality risk greatest in metabolic syndrome combinations with elevated blood pressure from 7 U.S. cohorts
(PLoS One, 2019) Yu, Winnie; Randhawa, Arshdeep K.; Blair, Steven N.; Sui, Xuemei; Kuk, Jennifer
Background The association between metabolic syndrome (MetS) and all-cause mortality is well established but it is unclear if there are differences in mortality risk among the 32 possible MetS combinations. Hence, the purpose of this study is to evaluate the associations between different MetS combinations and its individual components with all-cause mortality, and to examine differences in the association by age and sex. Methods A merged sample of 82,717 adults from 7 U.S. cohorts was used. Results In our sample, MetS was present in 32% of men, 34% of women, 28% of younger adults (18–65 years) and 62% of older adults (>65 years) with 14,989 deaths over 14.6 ± 7.4 years of follow-up. Risk of all-cause mortality was higher in younger individuals with a greater number of MetS factors present, but in older adults having all 5 MetS factors was the only combination significantly associated with mortality. Regardless of age or sex, elevated blood pressure was the MetS factor most consistently present in MetS combinations that were significantly and most strongly associated with mortality. In fact, elevated blood pressure in the absence of other risk factors was significantly associated with mortality in men (HR, 95% CI = 1.56, 1.33–1.84), women (HR = 1.62, 1.44–1.81) and younger adults (HR = 1.61, 1.45–1.79). Conversely, waist circumference, glucose and triglycerides in isolation were not associated with mortality (p>0.05). Conclusion In a large U.S. population, different combinations of MetS components vary substantially in their associations with all-cause mortality. Men, women and younger individuals with MetS combinations including elevated blood pressure had stronger associations with greater mortality risk, with minimal associations between MetS and mortality risk in older adults. Thus, we suggest that future algorithms may wish to consider differential weighting of these common metabolic risk factors, particularly in younger populations.
Open Access
Altered anterior visual system development following early monocular enucleation
(Elsevier Inc., 01/11/2013) Kelly, Krista; McKetton, Larissa; Schneider, Keith; Gallie, Brenda; Steeves, Jennifer
Purpose Retinoblastoma is a rare eye cancer that generally occurs before 5 years of age and often results in enucleation (surgical removal) of the cancerous eye. In the present study, we sought to determine the consequences of early monocular enucleation on the morphological development of the anterior visual pathway including the optic chiasm and lateral geniculate nucleus. Methods A group of adults who had one eye enucleated early in life due to retinoblastoma was compared to binocularly intact controls. Although structural changes have previously been reported in late enucleation, we also collected data from one late enucleated participant to compare to our early enucleated participants. Measurements of the optic nerves, optic chiasm, optic tracts and lateral geniculate nuclei were evaluated from T1 weighted and proton density weighted images collected from each participant. Results The early monocular enucleation group exhibited overall degeneration of the anterior visual system compared to controls. Surprisingly, however, optic tract diameter and geniculate volume decreases were less severe contralateral to the remaining eye. Consistent with previous research, the late enucleated participant showed no asymmetry and significantly larger volume decreases in both geniculate nuclei compared to controls. Conclusions The novel finding of an asymmetry in morphology of the anterior visual system following long-term survival from early monocular enucleation indicates altered postnatal visual development. Possible mechanisms behind this altered development include recruitment of deafferented cells by crossing nasal fibres and/or geniculate cell retention via feedback from primary visual cortex. These data highlight the importance of balanced binocular input during postnatal maturation for typical anterior visual system morphology.
Open Access
Altered white matter connectivity associated with visual hallucinations following occipital stroke
(Wiley, 2018-05-21) Rafique, Sara; Richards, John R.; Steeves, Jennifer
Introduction: Visual hallucinations that arise following vision loss stem from aberrant functional activity in visual cortices and an imbalance of activity across associated cortical and subcortical networks subsequent to visual pathway damage. We sought to determine if structural changes in white matter connectivity play a role in cases of chronic visual hallucinations associated with visual cortical damage. Methods: We performed diffusion tensor imaging (DTI) and probabilistic fiber tractography to assess white matter connectivity in a patient suffering from continuous and disruptive phosphene (simple) visual hallucinations for more than 2 years following right occipital stroke. We compared these data to that of healthy age-matched controls. Results: Probabilistic tractography to reconstruct white matter tracts suggests regeneration of terminal fibers of the ipsilesional optic radiations in the patient. However, arrangement of the converse reconstruction of these tracts, which were seeded from the ipsilesional visual cortex to the intrahemispheric lateral geniculate body, remained disrupted. We further observed compromised structural characteristics, and changes in diffusion (measured using diffusion tensor indices) of white matter tracts in the patient connecting the visual cortex with frontal and temporal regions, and also in interhemispheric connectivity between visual cortices. Conclusions: Cortical remapping and the disruption of communication between visual cortices and remote regions are consistent with our previous functional magnetic resonance imaging (fMRI) data showing imbalanced functional activity of the same regions in this patient (Rafique et al, 2016, Neurology, 87, 1493–1500). Long-term adaptive and disruptive changes in white matter connectivity may account for the rare nature of cases presenting with chronic and continuous visual hallucinations.
Open Access
Altered white matter structure in auditory tracts following early monocular enucleation
(Elsevier, 2019) Wong, Nikita; Rafique, Sara; Moro, Stefania S.; Kelly, Krista; Steeves, Jennifer
Purpose: Similar to early blindness, monocular enucleation (the removal of one eye) early in life results in crossmodal behavioral and morphological adaptations. Previously it has been shown that partial visual deprivation from early monocular enucleation results in structural white matter changes throughout the visual system (Wong et al., 2018). The current study investigated structural white matter of the auditory system in adults who have undergone early monocular enucleation compared to binocular control participants. Methods: We reconstructed four auditory and audiovisual tracts of interest using probabilistic tractography and compared microstructural properties of these tracts to binocularly intact controls using standard diffusion indices. Results: Although both groups demonstrated asymmetries in indices in intrahemispheric tracts, monocular enucleation participants showed asymmetries opposite to control participants in the auditory and A1-V1 tracts. Monocularenucleation participants also demonstrated significantly lower fractional anisotropy in the audiovisual projections contralateral to the enucleated eye relative to control participants. Conclusions: Partial vision loss from early monocular enucleation results in altered structural
Open Access
Amino acid-induced impairment of insulin sensitivity in healthy and obese rats is reversible
(Physiological Reports, 2014-07-04) Jeganathan, Senthure; Abdullahi, Abdikarim; Zargar, Sana; Maeda, Naomi; Riddell, Michael; ADEGOKE, OLASUNKANMI
High-protein diets (HPDs) promote weight loss but other studies implicate these diets and their constituent amino acids (AAs) in insulin resistance. We hypothesized that AA-induced insulin resistance is a temporal and reversible metabolic event. L6 myotubes were serum deprived for 4 h and then incubated in AA and/or insulin (100 nmol/L). Another group of cells was incubated overnight in AA + insulin, starved again, and then reincubated with AA and insulin. Mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) signaling and glucose uptake were then measured. Healthy or insulin-resistant rats were gavaged with leucine (0.48 g/kg) and insulin sensitivity was examined. In myotubes, incubation with AA and insulin significantly (P < 0.05) increased the phosphorylation of the mTORC1 substrate ribosomal protein S6 kinase 1 (S6K1, T389) and of insulin receptor substrate 1 (IRS-1, serine residues), but suppressed insulinstimulated glucose uptake by 40% (P < 0.01). These modifications were mTORC1-dependent and were reversible. In vivo, leucine gavage reversibly increased S6K1 phosphorylation and IRS-1 serine phosphorylation 5- to 12- fold in skeletal muscle and impaired insulin tolerance of glucose (P < 0.05) in lean rats. In insulin-resistant rats, the impairment of whole blood glucose and AA metabolism induced by leucine gavage (0.001 < P < 0.05) was more severe than that observed in lean rats; however, the impairment was reversible within 24 h of treatment. If these data are confirmed in long-term studies, it would imply that the use of leucine/HPD in treating metabolic diseases is unlikely to have lasting negative effects on insulin sensitivity.
Open Access
Anaphase Chromosomes in Crane-Fly Spermatocytes Treated With Taxol (Paclitaxel) Accelerate When Their Kinetochore Microtubules Are Cut: Evidence for Spindle Matrix Involvement With Spindle Forces
(Frontiers, 2018-07-24) Forer, Arthur; Sheykhani, Rozhan; Berns, Michael
Various experiments have indicated that anaphase chromosomes continue to move after their kinetochore microtubules are severed. The chromosomes move poleward at an accelerated rate after the microtubules are cut but they slow down 1–3 min later and move poleward at near the original speed. There are two published interpretations of chromosome movements with severed kinetochore microtubules. One interpretation is that dynein relocates to the severed microtubule ends and propels them poleward by pushing against non kinetochore microtubules. The other interpretation is that components of a putative “spindle matrix” normally push kinetochore microtubules poleward and continue to do so after the microtubules are severed from the pole. In this study we distinguish between these interpretations by treating cells with taxol. Taxol eliminates microtubule dynamics, alters spindle microtubule arrangements, and inhibits dynein motor activity in vivo. If the dynein interpretation is correct, taxol should interfere with chromosome movements after kinetochore microtubules are severed because it alters the arrangements of spindle microtubules and because it blocks dynein activity. If the “spindle matrix” interpretation is correct, on the other hand, taxol should not interfere with the accelerated movements. Our results support the spindle matrix interpretation: anaphase chromosomes in taxol-treated crane-fly spermatocytes accelerated after their kinetochore microtubules were severed.
Open Access
Antiviral Strategies for Emerging Influenza Viruses in Remote Communities
(PLoS ONE, 2013-04-22) Marek, Laskowski; Amy L., Greer; Moghadas, Seyed
Background: Due to the lack of timely access to resources for critical care, strategic use of antiviral drugs is crucial for mitigating the impact of novel influenza viruses with pandemic potential in remote and isolated communities. We sought to evaluate the effect of antiviral treatment and prophylaxis of close contacts in a Canadian remote northern community. Methods: We used an agent-based, discrete-time simulation model for disease spread in a remote community, which was developed as an in-silico population using population census data. Relative and cumulative age-specific attack rates, and the total number of infections in simulated model scenarios were obtained. Results: We found that early initiation of antiviral treatment is more critical for lowering attack rates in a remote setting with a low population-average age compared to an urban population. Our results show that a significant reduction in the relative, age-specific attack rates due to increasing treatment coverage does not necessarily translate to a significant reduction in the overall arrack rate. When treatment coverage varies from low to moderate, targeted prophylaxis has a very limited impact in reducing attack rates and should be offered at a low level (below 10%) to avoid excessive waste of drugs. Conclusions: In contrast to previous work, for conservative treatment coverages, our results do not provide any convincing evidence for the implementation of targeted prophylaxis. The findings suggest that public health strategies in remote communities should focus on the wider availability (higher coverage) and timely distribution of antiviral drugs for treatment of clinically ill individuals.
Open Access
Associations between mother-preschooler attachment and maternal depression symptoms: A systematic review and meta-analysis
(PLOS, 2018-10-02) Martin, Jodi; Guérin-Marion, Camille; O’Neill, Monica; Pillai Riddell, Rebecca; Bureau, Jean-François; Spiegel, Rebecca; Badovinac, Shaylea
The current study aimed to systematically review and meta-analyze concurrent and longitudinal associations between maternal depression symptoms and mother-child attachment during the preschool period (aged 2 to 7 years) as assessed using the coding systems by Cassidy and Marvin (1992) and Main and Cassidy (1988). The review was pre-registered with PROSPERO (International Prospective Register of Systematic Reviews; Registration number CRD42017073417) and was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 7,969 records were screened and 18 articles were deemed as eligible for inclusion in the review. Studies were reviewed using qualitative synthesis techniques and, where appropriate, meta-analysis. Qualitative synthesis indicated that mothers of disorganized/controlling children most consistently reported the highest levels of depressive symptoms, both concurrently and longitudinally. The association between disorganized/controlling child attachment and concurrent maternal depressive symptoms was significant (n = 1,787; g = 0.27, 95% CI [0.13,0.40]), and was not moderated by sample type, child gender, or risk of bias. Findings of a relationship between child attachment insecurity and maternal depressive symptoms must be qualified due to significant within-study heterogeneity and publication bias. Results suggest that maternal depressive symptoms may confer risk for disorganized/controlling attachment during the preschool period.
Open Access
Attention-deficit/hyperactivity disorder in relation to addictive behaviors: a moderated-mediation analysis of personality-risk factors and sex
(Frontiers, 2015-04-20) Davis, Caroline; Cohen, Alina; Davids, Mark; Rabindranath, Alex
Introduction: Research has shown that those with attention-deficit/hyperactivity disorder (ADHD) have an increased risk for addiction disorders like alcoholism and substance abuse. What is less clear is the mechanism(s) whereby ADHD gives rise to increased engagement in addictive behaviors, and whether there are sex differences in the ADHD-addiction propensity. Both ADHD and addictions have also been associated with personality traits such as impulsivity, reward seeking, anxiousness, and negative affect. In this study, we tested a moderator-mediation model, which predicted that both sex and ADHD-symptom status would make independent contributions to the variance in personality risk and in addictive behaviors, with males, and those with diagnosed ADHD, scoring higher on both dependent variables. Our model also predicted that the effect of sex and ADHD-symptom status on addictive behaviors would be via the mediating or intervening influence of personality-risk factors. Methods: A community-based sample of young men and women took part in the study. Among these individuals, 46 had received a lifetime diagnosis of ADHD. The nondiagnosed participants were dichotomized into a high-ADHD-symptom group (n D83) and a low-symptom group (nD84). Results: We found that a high-risk personality profile may, in part, account for the relationship between ADHD symptomatology and the use/abuse of a broad range of addictive behaviors. However, we found no sex differences in personality risk for addiction or in the use of addictive behaviors; nor did sex moderate the relationships we assessed. Conclusion: While ADHD status showed a strong relationship with both dependent variables in the model, we found no difference between those who had been diagnosed with ADHD and treated with stimulants, and their high-symptom non-diagnosed/ non-treated counterparts. These results add support to claims that the treatment of ADHD with stimulant medication neither protects nor fosters the risk for substance abuse disorders.
Open Access
Barriers to cardiac rehabilitation delivery in a low-resource setting from the perspective of healthcare administrators, rehabilitation providers, and cardiac patients
(Biomed Central, 2019-09-02) Sérvio, Thaianne Cavalcante; Britto, Raquel; Lima de Melo Ghisi, Gabriela; da Silva, Lilian Pinto; Duarte Novais Silva, Luciana; Lima, Márcia Maria Oliveira; Pereira, Danielle Aparecida Gomes; Grace, Sherry L.
Background: Despite clinical practice guideline recommendations that cardiovascular disease patients participate, cardiac rehabilitation (CR) programs are highly unavailable and underutilized. This is particularly true in low-resource settings, where the epidemic is at its’ worst. The reasons are complex, and include health system, program and patient-level barriers. This is the first study to assess barriers at all these levels concurrently, and to do so in a lowresource setting. Methods: In this cross-sectional study, data from three cohorts (healthcare administrators, CR coordinators and patients) were triangulated. Healthcare administrators from all institutions offering cardiac services, and providers from all CR programs in public and private institutions of Minas Gerais state, Brazil were invited to complete a questionnaire. Patients from a random subsample of 12 outpatient cardiac clinics and 11 CR programs in these institutions completed the CR Barriers Scale. Results: Thirty-two (35.2%) healthcare administrators, 16 (28.6%) CR providers and 805 cardiac patients (305 [37.9%] attending CR) consented to participate. Administrators recognized the importance of CR, but also the lack of resources to deliver it; CR providers noted referral is lacking. Patients who were not enrolled in CR reported significantly greater barriers related to comorbidities/functional status, perceived need, personal/family issues and access than enrollees, and enrollees reported travel/work conflicts as greater barriers than non-enrollees (all p < 0.01). Conclusions: The inter-relationship among barriers at each level is evident; without resources to offer more programs, there are no programs to which physicians can refer (and hence inform and encourage patients to attend), and patients will continue to have barriers related to distance, cost and transport. Advocacy for services is needed. Keywords: Health care services, Cardiac rehabilitation, Cardiac care facilities, Attitude of health personnel
Open Access
Bees collect polyurethane and polyethylene plastics as novel nest materials
(Ecological Society of America, 2013-12-31) MacIvor, Scott; Moore, Andrew E.
Plastic waste pervades the global landscape. Although adverse impacts on both species and ecosystems have been documented, there are few observations of behavioral flexibility and adaptation in species, especially insects, to increasingly plastic-rich environments. Here, two species of megachilid bee are described independently using different types of polyurethane and polyethylene plastics in place of natural materials to construct and close brood cells in nests containing successfully emerging brood. The plastics collected by each bee species resembled the natural materials usually sought; Megachile rotundata, which uses cut plant leaves, was found constructing brood cells out of cut pieces of polyethylene-based plastic bags, and Megachile campanulae, which uses plant and tree resins, had brood cells constructed out of a polyurethane-based exterior building sealant. Although perhaps incidentally collected, the novel use of plastics in the nests of bees could reflect ecologically adaptive traits necessary for survival in an increasingly human-dominated environment.
Open Access
CAPA neuropeptides and their receptor form an anti-diuretic hormone signalling system in the human disease vector, Aedes aegypti
(Nature, 2020) Sajadi, Farwa; Uyuklu, Ali; Paputsis, Christine; Lajevardi, Aryan; Wahedi, Azizia; Ber, Lindsay Taylor; Matei, Andreea; Paluzzi, Jean-Paul
Insect CAPA neuropeptides are homologs of mammalian neuromedin U and are known to influence ion and water balance by regulating the activity of the Malpighian ‘renal’ tubules (MTs). Several diuretic hormones are known to increase primary fluid and ion secretion by insect MTs and, in adult female mosquitoes, a calcitonin-related peptide (DH31) called mosquito natriuretic peptide, increases sodium secretion to compensate for the excess salt load acquired during blood-feeding. An endogenous mosquito anti-diuretic hormone was recently described, having potent inhibitory activity against select diuretic hormones, including DH31. Herein, we functionally deorphanized, both in vitro and in vivo, a mosquito anti-diuretic hormone receptor (AedaeADHr) with expression analysis indicating highest enrichment in the MTs where it is localized within principal cells. Characterization using a heterologous in vitro system demonstrated the receptor was highly sensitive to mosquito CAPA neuropeptides while in vivo, AedaeADHr knockdown abolished CAPA-induced anti-diuretic control of DH31-stimulated MTs. CAPA neuropeptides are produced within a pair of neurosecretory cells in each of the abdominal ganglia, whose axonal projections innervate the abdominal neurohaemal organs, where these neurohormones are released into circulation. Lastly, pharmacological inhibition of nitric oxide synthase (NOS) and protein kinase G (PKG) signaling eliminated anti-diuretic activity of CAPA, highlighting the role of the second messenger cGMP and NOS/PKG in this anti-diuretic signaling pathway.
Open Access
A checklist for choosing between R packages in ecology and evolution
(Wiley, 2020) Lortie, Christopher; Braun, Jenna; Filazzola, Alessandro; Miguel, Maria Florencia
The open source and free programming language R is a phenomenal mechanism to address a multiplicity of challenges in ecology and evolution. It is also a complex ecosystem because of the diversity of solutions available to the analyst. Packages for R enhance and specialize the capacity to explore both niche data/experiments and more common needs. However, the paradox of choice or how we select between many seemingly similar options can be overwhelming and lead to different potential outcomes. There is extensive choice in ecology and evolution between packages for both fundamental statistics and for more specialized domain‐level analyses. Here, we provide a checklist to inform these decisions based on the principles of resilience, need, and integration with scientific workflows for evidence. It is important to explore choices in any analytical coding environment—not just R—for solutions to challenges in ecology and evolution, and document this process because it advances reproducible science, promotes a deeper understand of the scientific evidence, and ensures that the outcomes are correct, representative, and robust.
Open Access
Conservation Conundrum: At-risk Bumble Bees (Bombus spp.) Show Preference for Invasive Tufted Vetch (Vicia cracca) While Foraging in Protected Areas
(Published by Oxford University Press on behalf of Entomological Society of America., 2019-03-02) Gibson, Shelby D; Liczner, Amanda R; Colla, Sheila R
In recent decades, some bumble bee species have declined, including in North America. Declines have been reported in species of bumble bees historically present in Ontario, including: yellow bumble bee (Bombus fervidus) (Fabricus, 1798), American bumble bee (Bombus pensylvanicus) (DeGeer, 1773), and yellow-banded bumble bee (Bombus terricola) (Kirby, 1837). Threats contributing to bumble bee population declines include: land-use changes, habitat loss, climate change, pathogen spillover, and pesticide use. A response to the need for action on pollinator preservation in North America has been to encourage ‘bee-friendly’ plantings. Previous studies show differences in common and at-risk bumble bee foraging; however, similar data are unavailable for Ontario. Our research question is whether there is a difference in co-occurring at-risk and common bumble bee (Bombus spp.) floral use (including nectar and pollen collection) in protected areas in southern Ontario. We hypothesize that common and at-risk species forage differently, predicting that at-risk species forage on a limited selection of host plants. We conducted a field survey of sites in southern Ontario, using observational methods to determine bumble bee foraging by species. The results of a redundancy analysis show a difference in foraging between common and at-risk bumblebee species. At-risk bumble bee species show a preference for foraging on invasive, naturalized Vicia cracca (tufted vetch). This finding raises the question of how to preserve or provide forage for at-risk bumble bees, when they show an association with an invasive species often subject to control in protected areas.
Open Access
Conservation Genomics of the Declining North American Bumblebee Bombus terricola Reveals Inbreeding and Selection on Immune Genes
(Frontiers Media, 2018-08-10) Kent, Clement; Dey, Alivia; Patel, Harshilkumar; Tsvetkov, Nadejda; Tiwari, Tanushree; MacPhail, Victoria J.; Gobeil, Yann; Harpur, Brock; Gurtowski, James; Schatz, Michael; Colla, Sheila R.; Zayed, Amro
The yellow-banded bumblebee Bombus terricola was common in North America but has recently declined and is now on the IUCN Red List of threatened species. The causes of B. terricola’s decline are not well understood. Our objectives were to create a partial genome and then use this to estimate population data of conservation interest, and to determine whether genes showing signs of recent selection suggest a specific cause of decline. First, we generated a draft partial genome (contig set) for B. terricola, sequenced using Pacific Biosciences RS II at an average depth of 35×. Second, we sequenced the individual genomes of 22 bumblebee gynes from Ontario and Quebec using Illumina HiSeq 2500, each at an average depth of 20×, which were used to improve the PacBio genome calls and for population genetic analyses. The latter revealed that several samples had long runs of homozygosity, and individuals had high inbreeding coefficient F, consistent with low effective population size. Our data suggest that B. terricola’s effective population size has decreased orders of magnitude from pre-Holocene levels. We carried out tests of selection to identify genes that may have played a role in ameliorating environmental stressors underlying B. terricola’s decline. Several immune-related genes have signatures of recent positive selection, which is consistent with the pathogen-spillover hypothesis for B. terricola’s decline. The new B. terricola contig set can help solve the mystery of bumblebee decline by enabling functional genomics research to directly assess the health of pollinators and identify the stressors causing declines.
Open Access
Considering the role of Murine double minute 2 in the cardiovascular system
(Frontiers, 2019) Roudier, Emile; Lam, Brian
The E3 ubiquitin ligase Murine double minute 2 (MDM2) is the main negative regulator of the tumor protein p53 (TP53). Extensive studies over more than two decades have confirmed MDM2 oncogenic role through mechanisms both TP53-dependent and TP53-independent oncogenic function. These studies have contributed to designate MDM2 as a therapeutic target of choice for cancer treatment and the number of patents for MDM2 antagonists has increased immensely over the last years. However, the question of the physiological functions of MDM2 has not been fully resolved yet, particularly when expressed and regulated physiologically in healthy tissue. Cardiovascular complications are almost an inescapable side-effect of anti-cancer therapies. While several MDM2 antagonists are entering phase I, II and even III of clinical trials, this review proposes to bring awareness on the physiological role of MDM2 in the cardiovascular system.
Open Access
Cost-effectiveness of a potential Zika vaccine candidate: a case study for Colombia
(Biomed Central, 2018-07-03) Shoukat, Affan; Vilches, Thomas; Moghadas, Seyed
Background: A number of Zika vaccine platforms are currently being investigated, some of which have entered clinical trials. We sought to evaluate the cost-effectiveness of a potential Zika vaccine candidate under the WHO Vaccine Target Product Profile for outbreak response, prioritizing women of reproductive age to prevent microcephaly and other neurological disorders. Methods: Using an agent-based simulation model of ZIKV transmission dynamics in a Colombian population setting, we conducted cost-effectiveness analysis with and without pre-existing herd immunity. The model was parameterized with estimates associated with ZIKV infection, risks of microcephaly in different trimesters, direct medical costs, and vaccination costs. We assumed that a single dose of vaccine provides a protection efficacy in the range 60% to 90% against infection. Cost-effectiveness analysis was conducted from a government perspective. Results: Under a favorable scenario when the reproduction number is relatively low (R0 = 2.2) and the relative transmissibility of asymptomatic infection is 10% compared with symptomatic infection, a vaccine is cost-saving (with negative incremental cost-effective ratio; ICER) for vaccination costs up to US$6 per individual without herd immunity, and up to US$4 per individual with 8% herd immunity. For positive ICER values, vaccination is highly cost-effective for vaccination costs up to US$10 (US$7) in the respective scenarios with the willingness-to-pay of US$6610 per disability-adjusted life-year, corresponding to the average per capita GDP of Colombia between 2013 and 2017. Our results indicate that the effect of other control measures targeted to reduce ZIKV transmission decreases the range of vaccination costs for cost-effectiveness due to reduced returns of vaccine-induced herd immunity. In all scenarios investigated, the median reduction of microcephaly exceeded 64% with vaccination. Conclusions: Our study suggests that a Zika vaccine with protection efficacy as low as 60% could significantly reduce the incidence of microcephaly. From a government perspective, Zika vaccination is highly cost-effective, and even cost-saving in Colombia if vaccination costs per individual is sufficiently low. Efficacy data from clinical trials and number of vaccine doses will be important requirements in future studies to refine our estimates, and conduct similar studies in other at-risk populations. Keywords: Zika, Microcephaly, Vaccination, Agent-based modeling, Cost-effectiveness
Open Access
The dark side of facilitation: native shrubs facilitate exotic annuals more strongly than native annuals in net abundance
(Pensoft, 2019-04) Lucero, Jacob; Noble, Taylor; Haas, Stephanie; Westphal, Michael; Butterfield, H. Scott; Lortie, Christopher