419 research outputs found
Assessing spatial and temporal variability of acid-extractable organics in oil sands process-affected waters
The acid-extractable organic compounds (AEOs), including naphthenic acids (NAs), present within oil sands process-affected water (OSPW) receive great attention due to their known toxicity. While recent progress in advanced separation and analytical methodologies for AEOs has improved our understanding of the composition of these mixtures, little is known regarding any variability (i.e., spatial, temporal) inherent within, or between, tailings ponds. In this study, 5 samples were collected from the same location of one tailings pond over a 2-week period. In addition, 5 samples were collected simultaneously from different locations within a tailings pond from a different mine site, as well as its associated recycling pond. In both cases, the AEOs were analyzed using SFS, ESI-MS, HRMS, GCΓGC-ToF/MS, and GC- & LC-QToF/MS (GC analyses following conversion to methyl esters). Principal component analysis of HRMS data was able to distinguish the ponds from each other, while data from GCΓGC-ToF/MS, and LC- and GC-QToF/MS were used to differentiate samples from within the temporal and spatial sample sets, with the greater variability associated with the latter. Spatial differences could be attributed to pond dynamics, including differences in inputs of tailings and surface run-off. Application of novel chemometric data analyses of unknown compounds detected by LC- and GC-QToF/MS allowed further differentiation of samples both within and between data sets, providing an innovative approach for future fingerprinting studies
Use of the distributions of adamantane acids to profile short-term temporal and pond-scale spatial variations in the composition of oil sands process-affected waters
Β© The Royal Society of Chemistry. Oil industry produced waters, such as the oils sands process-affected waters (OSPW) of Alberta, Canada, represent a challenge in terms of risk assessment and reclamation due to their extreme complexity, particularly of the organic chemical constituents, including the naphthenic acids (NA). The identification of numerous NA in single samples has raised promise for the use of NA distributions for profiling OSPW. However, monitoring of the success of containment is still difficult, due to the lack of knowledge of the homogeneity (or otherwise) of OSPW composition within, and between, different industry containments. Here we used GCΓGC-MS to compare the NA of five OSPW samples from each of two different industries. Short-term temporal and pond-scale spatial variations in the distributions of known adamantane acids and diacids and other unknown tricyclic acids were examined and a statistical appraisal of the replicate data made. The presence/absence of individual acids easily distinguished the OSPW NA of one industry from those of the other. The proportions of tricyclic acids with different carbon numbers also varied significantly between the OSPW of the two industries. The pond-scale spatial variation in NA in OSPW samples was higher than the short-term (2 weeks) temporal variations. An OSPW sample from an aged pond was exceptionally high in the proportion of C<inf>15,16,17</inf> compounds, possibly due to increased biotransformation. Such techniques could possibly also help to distinguish different sources of NA in the environment
Increasing the potential for malaria elimination by targeting zoophilic vectors
Countries in the Asia Pacific region aim to eliminate malaria by 2030. A cornerstone of malaria elimination is the effective management of Anopheles mosquito vectors. Current control tools such as insecticide treated nets or indoor residual sprays target mosquitoes in human dwellings. We find in a high transmission region in India, malaria vector populations show a high propensity to feed on livestock (cattle) and rest in outdoor structures such as cattle shelters. We also find evidence for a shift in vector species complex towards increased zoophilic behavior in recent years. Using a malaria transmission model we demonstrate that in such regions dominated by zoophilic vectors, existing vector control tactics will be insufficient to achieve elimination, even if maximized. However, by increasing mortality in the zoophilic cycle, the elimination threshold can be reached. Current national vector control policy in India restricts use of residual insecticide sprays to domestic dwellings. Our study suggests substantial benefits of extending the approach to treatment of cattle sheds, or deploying other tactics that target zoophilic behavior. Optimizing use of existing tools will be essential to achieving the ambitious 2030 elimination target
Differential protein profiling as a potential multi-marker approach for TSE diagnosis
Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177This "proof of concept" study, examines the use of differential protein expression profiling using surface enhanced laser desorption and ionisationtime of flight mass spectrometry (SELDI-TOF) for the diagnosis of TSE disease. Spectral output from all proteins selectively captured from individual murine brain homogenate samples, are compared as "profiles" in groups of infected and non-infected animals. Differential protein expression between groups is thus highlighted and statistically significant protein "peaks" used to construct a panel of disease specific markers.
Studies at both terminal stages of disease and throughout the time course of disease have shown a disease specific protein profile or "disease fingerprint" which could be used to distinguish between groups of TSE infected and uninfected animals at an early time point of disease.
Results
Our results show many differentially expressed proteins in diseased and control animals, some at early stages of disease. Three proteins identified by SELDI-TOF analysis were verified by immunohistochemistry in brain tissue sections. We demonstrate that by combining the most statistically significant changes in expression, a panel of markers can be constructed that can distinguish between TSE diseased and normal animals.
Conclusion
Differential protein expression profiling has the potential to be used for the detection of disease in TSE infected animals. Having established that a "training set" of potential markers can be constructed, more work would be required to further test the specificity and sensitivity of the assay in a "testing set". Based on these promising results, further studies are being performed using blood samples from infected sheep to assess the potential use of SELDI-TOF as a pre-mortem blood based diagnostic.https://doi.org/10.1186/1471-2334-9-1889pubpub
Beating the blues after Cancer: randomised controlled trial of a tele-based psychological intervention for high distress patients and carers
Background: The diagnosis and treatment of cancer is a major life stress such that approximately 35% of patients experience persistent clinically significant distress and carers often experience even higher distress than patients. This paper presents the design of a two arm randomised controlled trial with patients and carers who have elevated psychological distress comparing minimal contact self management vs. an individualised tele-based cognitive behavioural intervention. Methods/design: 140 patients and 140 carers per condition (560 participants in total) will been recruited after being identified as high distress through caller screening at two community-based cancer helplines and randomised to 1) a single 30-minute telephone support and education session with a nurse counsellor with self management materials 2) a tele-based psychologist delivered five session individualised cognitive behavioural intervention. Session components will include stress reduction, problem-solving, cognitive challenging and enhancing relationship support and will be delivered weekly. Participants will be assessed at baseline and 3, 6 and 12 months after recruitment. Outcome measures include: anxiety and depression, cancer specific distress, unmet psychological supportive care needs, positive adjustment, overall Quality of life. Discussion: The study will provide recommendations about the efficacy and potential economic value of minimal contact self management vs. tele-based psychologist delivered cognitive behavioural intervention to facilitate better psychosocial adjustment and mental health for people with cancer and their carers
Bovine Herpesvirus Type 1 (BHV-1) UL49.5 Luminal Domain Residues 30 to 32 Are Critical for MHC-I Down-Regulation in Virus-Infected Cells
Bovine herpesvirus type 1 (BHV-1) UL49.5 inhibits transporter associated with antigen processing (TAP) and down-regulates cell-surface expression of major histocompatibility complex (MHC) class I molecules to promote immune evasion. We have constructed a BHV-1 UL49.5 cytoplasmic tail (CT) null and several UL49.5 luminal domain mutants in the backbone of wild-type BHV-1 or BHV-1 UL49.5 CT- null viruses and determined their relative TAP mediated peptide transport inhibition and MHC-1 down-regulation properties compared with BHV-1 wt. Based on our results, the UL49.5 luminal domain residues 30β32 and UL49.5 CT residues, together, promote efficient TAP inhibition and MHC-I down-regulation functions. In vitro, BHV-1 UL49.5 Ξ30β32 CT-null virus growth property was similar to that of BHV-1 wt and like the wt UL49.5, the mutant UL49.5 was incorporated in the virion envelope and it formed a complex with gM in the infected cells
Deciphering von Hippel-Lindau (VHL/Vhl)-Associated Pancreatic Manifestations by Inactivating Vhl in Specific Pancreatic Cell Populations
The von Hippel-Lindau (VHL) syndrome is a pleomorphic familial disease characterized by the development of highly vascularized tumors, such as hemangioblastomas of the central nervous system, pheochromocytomas, renal cell carcinomas, cysts and neuroendocrine tumors of the pancreas. Up to 75% of VHL patients are affected by VHL-associated pancreatic lesions; however, very few reports in the published literature have described the cellular origins and biological roles of VHL in the pancreas. Since homozygous loss of Vhl in mice resulted in embryonic lethality, this study aimed to characterize the functional significance of VHL in the pancreas by conditionally inactivating Vhl utilizing the Cre/LoxP system. Specifically, Vhl was inactivated in different pancreatic cell populations distinguished by their roles during embryonic organ development and their endocrine lineage commitment. With Cre recombinase expression directed by a glucagon promoter in Ξ±-cells or an insulin promoter in Ξ²-cells, we showed that deletion of Vhl is dispensable for normal functions of the endocrine pancreas. In addition, deficiency of VHL protein (pVHL) in terminally differentiated Ξ±-cells or Ξ²-cells is insufficient to induce pancreatic neuroendocrine tumorigenesis. Most significantly, we presented the first mouse model of VHL-associated pancreatic disease in mice lacking pVHL utilizing Pdx1-Cre transgenic mice to inactivate Vhl in pancreatic progenitor cells. The highly vascularized microcystic adenomas and hyperplastic islets that developed in Pdx1-Cre;Vhl f/f homozygous mice exhibited clinical features similar to VHL patients. Establishment of three different, cell-specific Vhl knockouts in the pancreas have allowed us to provide evidence suggesting that VHL is functionally important for postnatal ductal and exocrine pancreas, and that VHL-associated pancreatic lesions are likely to originate from progenitor cells, not mature endocrine cells. The novel model systems reported here will provide the basis for further functional and genetic studies to define molecular mechanisms involved in VHL-associated pancreatic diseases
Recommended from our members
Applying an extended theory of planned behaviour to predict breakfast consumption in adolescents
BACKGROUND/OBJECTIVES: Breakfast skipping increases during adolescence and is associated with lower levels of physical activity and weight gain. Theory-based interventions promoting breakfast consumption in adolescents report mixed findings, potentially because of limited research identifying which determinants to target. This study aimed to: (i) utilise the Theory of Planned Behaviour (TPB) to identify the relative contribution of attitudes (affective, cognitive and behavioural) to predict intention to eat breakfast and breakfast consumption in adolescents and (ii) determine whether demographic factors moderate the relationship between TPB variables, intention and behaviour. SUBJECTS/METHODS: Questionnaires were completed by 434 students (mean 14+/-0.9 years) measuring breakfast consumption (0-2, 3-6 or 7 days), physical activity levels and TPB measures. Data were analysed by breakfast frequency and demographics using hierarchical and multinomial regression analyses. RESULTS: Breakfast was consumed everyday by 57% of students, with boys more likely to eat a regular breakfast, report higher activity levels and report more positive attitudes towards breakfast than girls (P<0.001). The TPB predicted 58% of the variation in intentions. Overall, the model was predictive of breakfast behaviours (P<0.001), but the relative contribution of TPB constructs varied depending on breakfast frequency. Interactions between gender and intentions were significant when comparing 0-2- and 3-6-day breakfast eaters only highlighting a stronger intention-behaviour relationship for girls. CONCLUSIONS: Findings confirm that the TPB is a successful model for predicting breakfast intentions and behaviours in adolescents. The potential for a direct effect of attitudes on behaviours should be considered in the implementation and design of breakfast interventions
Selective estrogen receptor modulators inhibit growth and progression of premalignant lesions in a mouse model of ductal carcinoma in situ
INTRODUCTION: Ductal carcinoma in situ (DCIS) is a noninvasive premalignant lesion and is considered a precursor to invasive carcinoma. DCIS accounts for nearly 20% of newly diagnosed breast cancer, but the lack of experimentally amenable in vivo DCIS models hinders the development of treatment strategies. Here, we demonstrate the utility of a mouse transplantation model of DCIS for chemoprevention studies using selective estrogen receptor modulators (SERMs). This model consists of a set of serially transplanted lines of genetically engineered mouse mammary intraepithelial neoplasia (MIN) outgrowth (MIN-O) tissue that have stable characteristics. We studied the ovarian-hormone-responsiveness of one of the lines with a particular focus on the effects of two related SERMs, tamoxifen and ospemifene. METHODS: The estrogen receptor (ER) status and ovarian-hormone-dependence of the mouse MIN outgrowth tissue were determined by immunohistochemistry and ovarian ablation. The effects of tamoxifen and ospemifene on the growth and tumorigenesis of MIN outgrowth were assessed at 3 and 10 weeks after transplantation. The effects on ER status, cell proliferation, and apoptosis were studied with immunohistochemistry. RESULTS: The MIN-O was ER-positive and ovarian ablation resulted in reduced MIN-O growth and tumor development. Likewise, tamoxifen and ospemifene treatments decreased the MIN growth and tumor incidence in comparison with the control (P < 0.01). Both SERMs significantly decreased cell proliferation. Between the two SERM treatment groups, there were no statistically significant differences in MIN-O size, tumor latency, or proliferation rate. In contrast, the ospemifene treatment significantly increased ER levels while tamoxifen significantly decreased them. CONCLUSION: Tamoxifen and ospemifene inhibit the growth of premalignant mammary lesions and the progression to invasive carcinoma in a transplantable mouse model of DCIS. The inhibitory effects of these two SERMs are similar except for their effects on ER modulation. These differences in ER modulation may suggest different mechanisms of action between the two related SERMs and may portend different long-term outcomes. These data demonstrate the value of this model system for preclinical testing of antiestrogen or other therapies designed to prevent or delay the malignant transformation of premalignant mammary lesions in chemoprevention
Vapor grown carbon nanofiber based cotton fabrics with negative thermoelectric power
Vapor grown carbon nanofiber (CNF)
based ink dispersions were used to dip-coat woven
cotton fabrics with different constructional parameters, and their thermoelectric (TE) properties studied
at room temperature. Unlike the positive thermoelectric power (TEP) observed in TE textile fabrics
produced with similar carbon-based nanostructures,
the CNF-based cotton fabrics showed negative TEP,
caused by the compensated semimetal character of the
CNFs and the highly graphitic nature of their outer
layers, which hinders the p-type doping with oxygen
groups onto them. A dependence of the electrical
conductivity (r) and TEP as a function of the woven
cotton fabric was also observed. The cotton fabric with
the largest linear density (tex) showed the best
performance with negative TEP values around
- 8 lV K-1
, a power factor of 1.65 9 10-3
lW m-1 K-2
, and a figure of merit of 1.14 9 10-6
.
Moreover, the possibility of a slight e- charge transfer
or n-doping from the cellulose onto the most external
CNF graphitic shells was also analysed by computer
modelling. This study presents n-type carbon-based
TE textile fabrics produced easily and without any
functionalization processes to prevent the inherent
doping with oxygen, which causes the typical p-type
character found in most carbon-based TE materialsFEDER funds through
COMPETE and by national funds through FCT β Foundation for
Science and Technology within the project POCI-01-0145-
FEDER-007136. E. M. F. Vieira is grateful for financial support
through FCT with CMEMS-UMinho Strategic Project UIDB/
04436/202
- β¦