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- Disease load at conception predicts survival in later epidemics in a historical French-canadian cohort, suggesting functional trans-generational effects in humans. [Journal Article]
- PLoS One 2014; 9(4):e93868.
Functional trans-generational and parental effects are potentially important determinants of health in several mammals. For humans, the existing evidence is weak. We investigate whether disease exposure triggers functional trans-generational response effects among humans by analyzing siblings who were conceived under different disease loads, and comparing their mortality in later epidemics. Under functional trans-generational response mechanisms, we expect that those who were conceived under high pathogenic stress load will have relatively low mortality during a later epidemic.We use data from the Registre de la Population du Québec Ancien, which covers the historical population living in St. Lawrence Valley, Québec, Canada. Children born in 1705-1724 were grouped according to their exposure during conception to the measles 1714-15 epidemic. The 1714-15 epidemic was followed by two mortality crises in 1729-1734. The cause of the first crises in 1729 is not exactly known. The second crisis in 1732 was caused by a smallpox epidemic. Using proportional hazard Cox regression models with multivariate adjustment and with fixed-effects approach that compare siblings, we analyze whether mortality in 1729-1734 is affected by exposure to the 1714-15 epidemic.Children who were conceived during the peak of the measles epidemic of 1714-15 exhibited significantly lower mortality during the 1729-1734 crisis than those who were born before the 1714-15 epidemic (mortality hazard ratio 0.106, p<.05 in multivariate adjusted models; 0.142 p<.1 in sibling comparison models).The results are consistent with a trans-generational mechanism that functionally responds to pathogen stress and suggest that early disease exposure may be protective later in life. Alternative explanations for the mortality patterns are discussed and shown to be problematic.
- Studying the immune response to human viral infections using zebrafish. [REVIEW]
- Dev Comp Immunol 2014 Apr 6.
Humans and viruses have a long co-evolutionary history. Viral illnesses have and will continue to shape human history: from smallpox, to influenza, to HIV, and beyond. Animal models of human viral illnesses are needed in order to generate safe and effective antiviral medicines, adjuvant therapies, and vaccines. These animal models must support the replication of human viruses, recapitulate aspects of human viral illnesses, and respond with conserved immune signaling cascades. The zebrafish is perhaps the simplest, most commonly used laboratory model organism in which innate and/or adaptive immunity can be studied. Herein, we will discuss the current zebrafish models of human viral illnesses and the insights they have provided. We will highlight advantages of early life stage zebrafish and the importance of innate immunity in human viral illnesses. We will also discuss viral characteristics to consider before infecting zebrafish with human viruses as well as predict other human viruses that may be able to infect zebrafish.
- Lipid Characteristics of Five Epinephelinae Fishes, Epinephelus fasciatus, Epinephelus retouti, Cephalopholis aurantia, Cephalopholis miniatus, and Variola louti, in the Coral Reef. [JOURNAL ARTICLE]
- J Oleo Sci 2014 Apr 9.
The lipid and fatty acid compositions of the muscle and liver of five Epinephelinae fishes (Epinephelus fasciatus, Epinephelus retouti, Cephalopholis aurantia, Cephalopholis miniatus, and Variola louti) in the coral reef were investigated. The major polyunsaturated fatty acid (PUFA) in the Epinephelinae fish triacylglycerols was 22:6n-3 (docosahexaenoic acid; DHA), which was similar to high levels of DHA in the depot triacylglycerols of highly migratory fishes. In the phospholipids of all specimens, unusually high levels of 20:4n-6 (arachidonic acid; ARA), 22:5n-6 (docosapentaenoic acid; n-6 DPA), and 20:5n-3 (icosapentaenoic acid; EPA) were found with markedly high levels of DHA. Noticeable levels of n-6 long-chain PUFA, such as ARA and n-6 DPA, were found in the muscle and liver polar lipids and suggested a typical profile of the fatty acid composition of coral demersal fishes. The five Epinephelinae fishes were healthful marine foods containing markedly high levels of DHA with noticeable levels of various n-3 and n-6 PUFA.
- The Smallpox Threat: A Time to Reconsider Global Policy. [JOURNAL ARTICLE]
- Biosecur Bioterror 2014 Apr 8.
- The personal touch: strategies toward personalized vaccines and predicting immune responses to them. [Journal Article]
- Expert Rev Vaccines 2014 May; 13(5):657-69.
The impact of vaccines on public health and wellbeing has been profound. Smallpox has been eradicated, polio is nearing eradication, and multiple diseases have been eliminated from certain areas of the world. Unfortunately, we now face diseases such as hepatitis C, malaria or tuberculosis, as well as new and re-emerging pathogens for which we lack effective vaccines. Empirical approaches to vaccine development have been successful in the past, but may not be up to the current infectious disease challenges facing us. New, directed approaches to vaccine design, development, and testing need to be developed. Ideally these approaches will capitalize on cutting-edge technologies, advanced analytical and modeling strategies, and up-to-date knowledge of both pathogen and host. These approaches will pay particular attention to the causes of inter-individual variation in vaccine response in order to develop new vaccines tailored to the unique needs of individuals and communities within the population.
- Smallpox and globalization or the first achieved plannetary goal. [Journal Article, Research Support, Non-U.S. Gov't]
- Vojnosanit Pregl 2014 Mar; 71(3):301-6.
- Activation Of Stress Response Pathways Promote Formation Of Antiviral Granules And Restrict Virus Replication. [JOURNAL ARTICLE]
- Mol Cell Biol 2014 Mar 24.
The formation of protein-RNA granules is a part of both natural cellular function (P-bodies and nuclear HNRNPs) and a response to cellular stress (stress granules and ND10 bodies). To better understand the role of stress-induced granules on viral infection we have studied the ability of cells to restrict poxvirus replication through the formation of antiviral granules (AVGs). In cells infected with a wild-type poxvirus, a small number of infected cells spontaneously formed AVGs. In these AVG-positive cells, viral gene expression was inhibited. Adding compounds that altered RNA helicase activity, induced oxidative stress or stimulated translation initiation factor phosphorylation significantly increased the number of AVGs-positive cells. When AVGs formed, both viral translation and titers were decreased even when host translation persisted. Treatment with the antiviral compound IBT, a compound that was used to treat smallpox infections, induced AVGs, suggesting a role for these structures in the pharmacological inhibition of poxvirus replication. These findings provide evidence that AVGs are an innate host response to combat virus infection that can be exogenously stimulated to combat virus infection. Since small molecules are able to stimulate AVG formation, it is a potential target for new antiviral development.
- Smallpox vaccination, colonial Sydney and serendipity. [Journal Article]
- Med J Aust 2014 Mar 17; 200(5):295-7.
- Nanoporous titanium surfaces for sustained elution of proteins and antibiotics. [Journal Article]
- PLoS One 2014; 9(3):e92080.
Current medically relevant metals for prosthetic reconstructions enjoy a relatively good success rate, but their performance drops significantly in patients with compromised health status, and post-surgical infections still remain an important challenge. To address these problems, different nanotechnology-based strategies have been exploited to create implantable metals with an enhanced bioactivity and antibacterial capacities. Among these, oxidative nanopatterning has emerged as a very effective approach to engender nanoporous surfaces that stimulate and guide the activity of adhering cells. The resulting nanoporosity is also attractive because it offers nanoconfined volumes that can be exploited to load bioactive compounds and modulate their release over time. Such extended elution is needed since a single exposure to growth factors and/or antibiotics, for instance, may not be adequate to further sustain bone regeneration and/or to counteract bacterial colonization. In this article, we assessed the capacities of nanoporous titanium surfaces generated by oxidative nanopatterning to provide controlled and sustained elution of proteins and antibiotic molecules. To this end, we have selected bovine serum albumin (BSA) and vancomycin to reflect commonly used compounds, and investigated their adsorption and elution by Fourier-transform infrared (FT-IR) and ultraviolet-visible (UV-VIS) spectroscopy. Our results demonstrate that while the elution of albumin is not significantly affected by the nanoporosity, in the case of vancomycin, nanoporous surfaces provided an extended release. These findings were successively correlated to the establishment of interactions with the surface and physical-entrapment effects exerted by the nanopores, ultimately highlighting their synergistic contribution to the release profiles and thus their importance in the design of nanostructured eluting platforms for applications in medicine.
- Prediction of steps in the evolution of variola virus host range. [Journal Article]
- PLoS One 2014; 9(3):e91520.
Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox.