Project description:Radiation therapy (RT) is an important component of cancer therapy, with >50% of cancer patients receiving RT. As the number of cancer survivors increases, the short- and long-term side effects of cancer therapy are of growing concern. Side effects of RT for thoracic tumors, notably cardiac and pulmonary toxicities, can cause morbidity and mortality in long-term cancer survivors. An understanding of the biological pathways and mechanisms involved in normal tissue toxicity from RT will improve future cancer treatments by reducing the risk of long-term side effects. Many of these mechanistic studies are performed in animal models of radiation exposure. In this area of research, the use of small animal image-guided RT with treatment planning systems that allow more accurate dose determination has the potential to revolutionize knowledge of clinically relevant tumor and normal tissue radiobiology. However, there are still a number of challenges to overcome to optimize such radiation delivery, including dose verification and calibration, determination of doses received by adjacent normal tissues that can affect outcomes, and motion management and identifying variation in doses due to animal heterogeneity. In addition, recent studies have begun to determine how animal strain and sex affect normal tissue radiation injuries. This review article discusses the known and potential benefits and caveats of newer technologies and methods used for small animal radiation delivery, as well as how the choice of animal models, including variables such as species, strain, and age, can alter the severity of cardiac radiation toxicities and impact their clinical relevance.
Project description:The rumen contains a multi-kingdom, commensal microbiome, including protozoa, bacteria, archaea, fungi and viruses, which enables ruminant herbivores to ferment and utilize plant feedstuffs that would be otherwise indigestible. Within the rumen, virus populations are diverse and highly abundant, often out-numbering the microbial populations that they both predate on and co-exist with. To date the research effort devoted to understanding rumen-associated viral populations has been considerably less than that given to the other microbial populations, yet their contribution to maintaining microbial population balance, intra-ruminal microbial lysis, fiber breakdown, nutrient cycling and genetic transfer may be highly significant. This review follows the technological advances which have contributed to our current understanding of rumen viruses and drawing on knowledge from other environmental and animal-associated microbiomes, describes the known and potential roles and impacts viruses have on rumen function and speculates on the future directions of rumen viral research.
Project description:Molecular flexibility over a wide time range is of central importance to the function of many proteins, both soluble and membrane. Revealing the modes of flexibility, their amplitudes, and time scales under physiological conditions is the challenge for spectroscopic methods, one of which is site-directed spin labeling EPR (SDSL-EPR). Here we provide an overview of some recent technological advances in SDSL-EPR related to investigation of structure, structural heterogeneity, and dynamics of proteins. These include new classes of spin labels, advances in measurement of long range distances and distance distributions, methods for identifying backbone and conformational fluctuations, and new strategies for determining the kinetics of protein motion.
Project description:Small cell lung cancer (SCLC) accounts for approximately 10-15% of all lung cancers. The prognosis is poor with median survival in the advanced stage remaining at around 12 months. Despite applying every known therapeutic approach, no major breakthrough has improved the overall survival in the last 30 years. Historically, experiments performed on conventional cell lines may have limitations of not accurately reflecting the complex biological and genomic heterogeneity of this disease. However, additional knowledge gained from recently developed genetically engineered mouse models (GEMMs) and patient derived xenografts (PDXs) have made encouraging inroads. Whole genome sequencing (WGS) data reveals a high mutational burden and a number of genetic alterations but low frequency of targetable mutations. Despite several failures, considerable therapeutic opportunities have recently emerged. Potentially promising therapies include those targeting DNA damage repair, stem cell/renewal and drug resistant mechanisms. Modest success has also been achieved with immune checkpoint inhibitors while therapeutic exploration of various other components of the immune system is underway. However, the complex heterogeneities reflect the need for accurate bio-markers to translate novel discoveries into clinical benefit. Additionally, the molecular mechanisms that differentiate chemo-sensitive from chemo-refractory disease remain unknown. Obtaining reliable tumour samples by utilising novel techniques such as endobronchial ultrasound guided needle aspiration or adopting to liquid biopsies are becoming popular. This review will focus on recent technological and therapeutic advancements to surmount this recalcitrant disease.
Project description:Silver nanoparticles (AgNPs) have been successfully applied in several areas due to their significant antimicrobial activity against several microorganisms. In dentistry, AgNP can be applied in disinfection, prophylaxis, and prevention of infections in the oral cavity. In this work, the use of silver nanoparticles in dentistry and associated technological innovations was analyzed. The scientific literature was searched using PubMed and Scopus databases with descriptors related to the use of silver nanoparticles in dentistry, resulting in 90 open-access articles. The search for patents was restricted to the A61K code (International Patent Classification), using the same descriptors, resulting in 206 patents. The results found were ordered by dental specialties and demonstrated the incorporation of AgNPs in different areas of dentistry. In this context, the search for patents reaffirmed the growth of this technology and the dominance of the USA pharmaceutical industry over AgNPs product development. It could be concluded that nanotechnology is a promising area in dentistry with several applications.
Project description:This paper forecasts the consequences of scientific progress in cancer for total Medicare spending between 2005 and 2030. Because technological advance is uncertain, widely varying scenarios are modeled. A baseline scenario assumes that year 2000 technology stays frozen. A second scenario incorporates recent cancer treatment advances and their attendant discomfort. Optimistic scenarios analyzed include the discovery of an inexpensive cure, a vaccine that prevents cancer, and vastly improved screening techniques. Applying the Future Elderly Model, we find that no scenario holds major promise for guaranteeing the future financial health of Medicare.
Project description:Site-specific phosphorylation is a fast and reversible covalent post-translational modification that is tightly regulated in cells. The cellular machinery of enzymes that write, erase and read these modifications (kinases, phosphatases and phospho-binding proteins) is frequently deregulated in different diseases, including cancer. Large-scale studies of phosphoproteins - termed phosphoproteomics - strongly rely on the use of high-performance mass spectrometric instrumentation. This powerful technology has been applied to study a great number of phosphorylation-based phenotypes. Nevertheless, many technical and biological challenges have to be overcome to identify biologically relevant phosphorylation sites in cells and tissues. This review describes different technological strategies to identify and quantify phosphorylation sites with high accuracy, without significant loss of analysis speed and reproducibility in tissues and cells. Moreover, computational tools for analysis, integration and biological interpretation of phosphorylation events are discussed.
Project description:Laminopathies are a group of rare disorders due to mutation in LMNA gene. Depending on the mutation, they may affect striated muscles, adipose tissues, nerves or are multisystemic with various accelerated ageing syndromes. Although the diverse pathomechanisms responsible for laminopathies are not fully understood, several therapeutic approaches have been evaluated in patient cells or animal models, ranging from gene therapies to cell and drug therapies. This review is focused on these therapies with a strong focus on striated muscle laminopathies and premature ageing syndromes.
Project description:To what extent are academics entrepreneurial, and to what extent does an entrepreneurial orientation contribute to higher research productivity in higher education? According to some schools of thought, academic research is conducted within 'paradigms' or circumscribed areas of study, with the implication that certain research might not be inherently innovative. This research sought to investigate the extent to which individuals with higher self-reported levels of entrepreneurial orientation (EO), as well as the propensity to apply novel technological methods (such as crowdfunding and crowdsourced R&D) in their research, have higher levels of research productivity. Applying a comprehensive purposive sampling process, a large South African university was sampled. A total of 292 usable responses were obtained, and these were analysed using ordinary least squares. In order to test the robustness of results, two further tests were applied, namely bootstrapping and negative binomial regression analysis. Findings suggest that individuals with higher endowments of entrepreneurial orientation may be more research productive. Interestingly, innovativeness is not found to be significantly related to academic research productivity. It is concluded that further synthesis between educational and entrepreneurship theory might offer useful insights for the improvement of societally important research productivity. It is also concluded, however, that novel technological methods such as crowdfunding may be underutilised in the academic context. Given the resource constraints faced by those in higher education, particularly in the developing-country context of this study, this underutilisation may point to important opportunities in the sector.
Project description:RNA-sequencing data across a large number of tissues in mouse, rat, dog, and monkey to evaluate baseline expression levels and establish a preclinical gene expression body atlas