Project description:Genetics evolved as a field of science after 1900 with new theories being derived from experiments obtained in fruit flies, bacteria, and viruses. This personal account suggests that the origins of human genetics can best be traced to the years 1949 to 1959. Several genetic scientific advances in genetics in 1949 yielded results directly relating to humans for the first time, except for a few earlier observations. In 1949 the first textbook of human genetics was published, the American Journal of Human Genetics was founded, and in the previous year the American Society of Human Genetics. In 1940 in Britain a textbook entitled Introduction to Medical Genetics served as a foundation for introducing genetic aspects into medicine. The introduction of new methods for analyzing chromosomes and new biochemical assays using cultured cells in 1959 and subsequent years revealed that many human diseases, including cancer, have genetic causes. It became possible to arrive at a precise cause-related genetic diagnosis. As a result the risk of occurrence or re-occurrence of a disease within a family could be assessed correctly. Genetic counseling as a new concept became a basis for improved patient care. Taken together the advances in medically orientated genetic research and patient care since 1949 have resulted in human genetics being both, a basic medical and a basic biological science. Prior to 1949 genetics was not generally viewed in a medical context. Although monogenic human diseases were recognized in 1902, their occurrence and distribution were considered mainly at the population level.
Project description:Introduction: Krabbe disease (KD) or globoid cell leukodystrophy (GLD) is one of the lysosomal disorders affecting central and peripheral nervous systems (CNS and PNS). It is caused by mutations on the galactocerebrosidase (GALC) gene. Affected individuals accumulate undegraded substrates and suffer from neuroinflammation. Methods: Hematopoietic stem cell transplantation (HSCT) has been partially successful in treating patients with KD when accomplished prior to the onset of symptoms. The success is credited to the ability of the hematopoietic stem cells in providing some GALC enzyme to the CNS and eradicating potential neuroinflammation. Combination of the HSCT with some other GALC-providing strategies has shown synergistic effects in the treatment of the mouse model of this disease. Results: Here, the possibility of eliminating HSCT in the treatment of human patients and replacing it with a single therapy that will provide sufficient GALC enzyme to the nervous systems is suggested. Such treatment, if started during the asymptomatic stage of the disease, not only may eradicate the enzyme deficiency, but may also keep any neuroinflammation at bay. Conclusion: Successful treatment of the KD may be possible by restoring consistent and sufficient GALC expression in CNS and PNS.
Project description:This is a historical account on the development of capillary LC from its beginning to the present day. The first investigations into the viability of capillary LC date back to the late 1970s, a decade after the pioneering efforts in HPLC. The drastically reduced column dimensions were required to counter the slow solute diffusion in liquids. There were numerous instrumental difficulties with sample introduction and detection in the picoliter or even femtoliter volumes. High-efficiency separations were needed in the analysis of complex biological mixtures. Miniaturization brought distinct advantages in spectroscopic and electrochemical detection. Since the 1980s, column technologies underwent significant changes: (a) from glass-drawn microcapillaries to slurry-packed, small-diameter fused silica columns; and (b) in microcapillaries packed alternatively with sub-2-?m particles or monoliths. The viability of LC-MS combination has dramatically promoted the use of small-diameter capillaries. Through "omics technologies", capillary LC/tandem MS accounts for most applications in proteomics, glycomics and metabolomics.
Project description:In this mini review, we discuss how our understanding of ribonucleic acid (RNA) properties becomes significantly deepened when a broad range of modern chemical and biophysical methods is applied. We span our perspective from RNA solid-phase synthesis and site-specific labeling to single-molecule fluorescence-resonance-energy-transfer imaging and NMR spectroscopy approaches to explore the dynamics of RNA over a broad timescale. We then move on to Fourier-transform-ion-cyclotron-resonance mass spectrometry (FT-ICR-MS) as a powerful technique for RNA sequencing and modification analysis. The novel methodological developments are discussed for selected biological systems that include the thiamine-pyrophosphate riboswitch, HIV and ribosomal A-site RNA, and transfer RNA.
Project description:The diverse members of the CCN family now designated as CCN1(CYR61), CCN2 (CTGF), CCN3(NOV), CCN4(WISP1), CCN5(WISP2), CCN6(WISP3) are a conserved matricellular family of proteins exhibiting a spectrum of functional properties throughout all organs in the body. Interaction with cell membrane receptors such as integrins trigger intracellular signaling pathways. Proteolytically cleaved fragments (constituting the active domains) can be transported to the nucleus and perform transcriptional relevant functional activities. Notably, as also found in other protein families some members act opposite to others creating a system of functionally relevant checks and balances. It has become apparent that these proteins are secreted into the circulation, are quantifiable, and can serve as disease biomarkers. How they might also serve as homeostatic regulators is just becoming appreciated. In this review I have attempted to highlight the most recent evidence under the subcategories of cancer and non-cancer relevant that could lead to potential therapeutic approaches or ideas that can be factored into clinical advances. I have added my own personal perspective on feasibility.
Project description:In nature, toxins have evolved as weapons to capture and subdue the prey or to counter predators or competitors. When they are inadvertently injected into humans, they cause symptoms ranging from mild discomfort to debilitation and death. Toxinology is the science of studying venoms and toxins that are produced by a wide variety of organisms. In the past, the structure, function and mechanisms of most abundant and/or most toxic components were characterized to understand and to develop strategies to neutralize their toxicity. With recent technical advances, we are able to evaluate and determine the toxin profiles using transcriptomes of venom glands and proteomes of tiny amounts of venom. Enormous amounts of data from these studies have opened tremendous opportunities in many directions of basic and applied research. The lower costs for profiling venoms will further fuel the expansion of toxin database, which in turn will provide greater exciting and bright opportunities in toxin research.
Project description:Bioinformatics is now intrinsic to life science research, but the past decade has witnessed a continuing deficiency in this essential expertise. Basic data stewardship is still taught relatively rarely in life science education programmes, creating a chasm between theory and practice, and fuelling demand for bioinformatics training across all educational levels and career roles. Concerned by this, surveys have been conducted in recent years to monitor bioinformatics and computational training needs worldwide. This article briefly reviews the principal findings of a number of these studies. We see that there is still a strong appetite for short courses to improve expertise and confidence in data analysis and interpretation; strikingly, however, the most urgent appeal is for bioinformatics to be woven into the fabric of life science degree programmes. Satisfying the relentless training needs of current and future generations of life scientists will require a concerted response from stakeholders across the globe, who need to deliver sustainable solutions capable of both transforming education curricula and cultivating a new cadre of trainer scientists.
Project description:Today, thanks to advances in cloud computing, it is possible for small teams of software developers to produce internet-scale products, a feat that was previously the preserve of large organizations. Herein, we describe how these advances in software engineering can be made more readily available to bioinformaticians. In the same way that cloud computing has democratized access to distributed systems engineering for generalist software engineers, access to scalable and reproducible bioinformatic engineering can be democratized for generalist bioinformaticians and biologists. We present solutions, based on our own efforts, to achieve this goal.
Project description:Previous studies describe the financial burden of chronic rhinosinusitis (CRS) from the perspective of third-party payers, but, to our knowledge, none analyze the costs borne by patients (i.e., out-of-pocket expenses [OOPE]). Furthermore, this burden has not been previously investigated in the context of a publicly funded health care system.The purpose of this study was to characterize the financial impact of CRS on patients, specifically by evaluating its associated OOPEs and the perceived financial burden. The secondary aim was to determine the factors predictive of OOPEs and perceived burden.Patients with CRS at a tertiary care sinus center completed a self-administered questionnaire that assessed their socioeconomic characteristics, disease-specific quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), workdays missed due to CRS, perceived financial burden, and direct medical and nonmedical OOPEs over a 12-month period. Total OOPEs were calculated from the sum of direct medical and nonmedical OOPEs. Regression analyses determined factors predictive of OOPEs and the perceived burden.A total of 84 patients completed the questionnaires. After accounting for health insurance coverage and the median direct medical, direct nonmedical, and total OOPEs per patient over a 12-month period were Canadian dollars (CAD) $336.00 (2011) [U.S. $339.85], CAD $129.87 [U.S. $131.86], and CAD $607.10 [U.S. $614.06], respectively. CRS resulted in an average of 20.6 workdays missed over a 12-month period. Factors predictive of a higher financial burden included younger age, a greater number of previous sinus surgeries, <80% health insurance coverage, residing out of town, and higher SNOT-22 scores.Total OOPEs incurred from the treatment of CRS may amount to CAD $607.10 [U.S. $614.06] per patient per year, within the context of a single-payer health care system. Managing clinicians should be aware of patient groups with a greater perceived financial burden and consider counseling them on strategies to offset expenses, including obtaining travel grants, using telemedicine for follow-up assessments, providing drug samples, and streamlining diagnostic testing with medical visits.
Project description:Personal pronouns have been shown to influence cognitive perspective taking during comprehension. Studies using single sentences found that 3rd person pronouns facilitate the construction of a mental model from an observer's perspective, whereas 2nd person pronouns support an actor's perspective. The direction of the effect for 1st person pronouns seems to depend on the situational context. In the present study, we investigated how personal pronouns influence discourse comprehension when people read fiction stories and if this has consequences for affective components like emotion during reading or appreciation of the story. We wanted to find out if personal pronouns affect immersion and arousal, as well as appreciation of fiction. In a natural reading paradigm, we measured electrodermal activity and story immersion, while participants read literary stories with 1st and 3rd person pronouns referring to the protagonist. In addition, participants rated and ranked the stories for appreciation. Our results show that stories with 1st person pronouns lead to higher immersion. Two factors-transportation into the story world and mental imagery during reading-in particular showed higher scores for 1st person as compared to 3rd person pronoun stories. In contrast, arousal as measured by electrodermal activity seemed tentatively higher for 3rd person pronoun stories. The two measures of appreciation were not affected by the pronoun manipulation. Our findings underscore the importance of perspective for language processing, and additionally show which aspects of the narrative experience are influenced by a change in perspective.