3 research outputs found

    Nanoindentation of Isometric Viruses on Deterministically Corrugated Substrates

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    It has been just over 100 years since inventor Joseph Coyle perfected the egg cartona package format that has known very little changes since its first appearance (Dhillon, S. B. C. Inventor Created Better Way to Carry Eggs. In The Globe and Mail Vancouver, 2013). In this article, we extend Coyle’s old idea to the study of mechanical properties of viruses. Virus stiffness, strength, and breaking force obtained by force spectroscopy atomic force microscopy (AFM) provide the knowledge required for designing nanocontainers for applications in biotechnology and medicine, and for understanding the fundamentals of virus–host interaction such as virus translocation from one cellular compartment to another. In previous studies, virus particles adsorbed on flat surfaces from a physiological buffer were subjected to directional deformation by a known force exerted via a microscopic probe. The affinity between the virus shell and surface is required to be strong enough to anchor particles on the substrate while they are indented or imaged, yet sufficiently weak to preserve the native structure and interactions prior deformation. The specific question addressed here is whether an experimental scheme characterized by increased contact area and stable mechanical equilibrium under directional compression would provide a more reliable characterization than the traditional flat substrate approach

    Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

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    Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015. Study Selection: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. Data Extraction and Synthesis: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. Main Outcomes and Measures: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. Results: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]). Conclusions and Relevance: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases
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