162 research outputs found
Future direction of pathogenesis and treatment for rheumatic disorders
After the breakthrough in the treatment of rheumatoid arthritis and numerous related disorders with biological therapies targeting TNFa at the Kennedy Institute in London Millions of patients have tremendously benefitted. However, we cannot cure these diseases yet and have to search for additional therapeutic targets. Since it was shown that synovial fibroblasts (SF) are not only effector cells responding to inflammatory stimuli, but appear endogenously activated and potentially involved into spreading the disease [1], we searched for the epigenetic modifications leading to the activated phenotype of these cells. Epigenetics in its scientific definition “is the study of all heritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA”, but might be considered in simpler terms as the regulation of gene expression. Epigenetic modifications include: Acetylation
Sampling Local Fungal Diversity in an Undergraduate Laboratory using DNA Barcoding
Traditional methods for fungal species identification require diagnostic morphological characters and are often limited by the availability of fresh fruiting bodies and local identification resources. DNA barcoding offers an additional method of species identification and is rapidly developing as a critical tool in fungal taxonomy. As an exercise in an undergraduate biology course, we identified 9 specimens collected from the Hendrix College campus in Conway, Arkansas, USA to the genus or species level using morphology. We report that DNA barcoding targeting the internal transcribed spacer (ITS) region supported several of our taxonomic determinations and we were able to contribute 5 ITS sequences to GenBank that were supported by vouchered collection information. We suggest that small-scale barcoding projects are possible and that they have value for documenting fungal diversity
Regional variation in health is predominantly driven by lifestyle rather than genetics
Health-related traits are known to vary geographically. Here, Amador and colleagues show that regional variation of obesity-related traits in a Scottish population is influenced more by lifestyle differences than it is by genetic differences
Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses
The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined
The Quality of Registration of Clinical Trials
BACKGROUND: Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. METHODS AND FINDINGS: A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. CONCLUSIONS: Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records
Strategic technology alignment roadmapping STAR® aligning R&D investments with business needs
Importance of incomplete lineage sorting and introgression in the origin of shared genetic variation between two closely related pines with overlapping distributions
Genetic variation shared between closely related species may be due to retention of ancestral polymorphisms because of incomplete lineage sorting (ILS) and/or introgression following secondary contact. It is challenging to distinguish ILS and introgression because they generate similar patterns of shared genetic diversity, but this is nonetheless essential for inferring accurately the history of species with overlapping distributions. To address this issue, we sequenced 33 independent intron loci across the genome of two closely related pine species (Pinus massoniana Lamb. and Pinus hwangshanensis Hisa) from Southeast China. Population structure analyses revealed that the species showed slightly more admixture in parapatric populations than in allopatric populations. Levels of interspecific differentiation were lower in parapatry than in allopatry. Approximate Bayesian computation suggested that the most likely speciation scenario explaining this pattern was a long period of isolation followed by a secondary contact. Ecological niche modeling suggested that a gradual range expansion of P. hwangshanensis during the Pleistocene climatic oscillations could have been the cause of the overlap. Our study therefore suggests that secondary introgression, rather than ILS, explains most of the shared nuclear genomic variation between these two species and demonstrates the complementarity of population genetics and ecological niche modeling in understanding gene flow history. Finally, we discuss the importance of contrasting results from markers with different dynamics of migration, namely nuclear, chloroplast and mitochondrial DNA
Asymmetrical Gene Flow in a Hybrid Zone of Hawaiian Schiedea (Caryophyllaceae) Species with Contrasting Mating Systems
Asymmetrical gene flow, which has frequently been documented in naturally occurring hybrid zones, can result from various genetic and demographic factors. Understanding these factors is important for determining the ecological conditions that permitted hybridization and the evolutionary potential inherent in hybrids. Here, we characterized morphological, nuclear, and chloroplast variation in a putative hybrid zone between Schiedea menziesii and S. salicaria, endemic Hawaiian species with contrasting breeding systems. Schiedea menziesii is hermaphroditic with moderate selfing; S. salicaria is gynodioecious and wind-pollinated, with partially selfing hermaphrodites and largely outcrossed females. We tested three hypotheses: 1) putative hybrids were derived from natural crosses between S. menziesii and S. salicaria, 2) gene flow via pollen is unidirectional from S. salicaria to S. menziesii and 3) in the hybrid zone, traits associated with wind pollination would be favored as a result of pollen-swamping by S. salicaria. Schiedea menziesii and S. salicaria have distinct morphologies and chloroplast genomes but are less differentiated at the nuclear loci. Hybrids are most similar to S. menziesii at chloroplast loci, exhibit nuclear allele frequencies in common with both parental species, and resemble S. salicaria in pollen production and pollen size, traits important to wind pollination. Additionally, unlike S. menziesii, the hybrid zone contains many females, suggesting that the nuclear gene responsible for male sterility in S. salicaria has been transferred to hybrid plants. Continued selection of nuclear genes in the hybrid zone may result in a population that resembles S. salicaria, but retains chloroplast lineage(s) of S. menziesii
Evolution of Genome Size and Complexity in Pinus
BACKGROUND: Genome evolution in the gymnosperm lineage of seed plants has given rise to many of the most complex and largest plant genomes, however the elements involved are poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: Gymny is a previously undescribed retrotransposon family in Pinus that is related to Athila elements in Arabidopsis. Gymny elements are dispersed throughout the modern Pinus genome and occupy a physical space at least the size of the Arabidopsis thaliana genome. In contrast to previously described retroelements in Pinus, the Gymny family was amplified or introduced after the divergence of pine and spruce (Picea). If retrotransposon expansions are responsible for genome size differences within the Pinaceae, as they are in angiosperms, then they have yet to be identified. In contrast, molecular divergence of Gymny retrotransposons together with other families of retrotransposons can account for the large genome complexity of pines along with protein-coding genic DNA, as revealed by massively parallel DNA sequence analysis of Cot fractionated genomic DNA. CONCLUSIONS/SIGNIFICANCE: Most of the enormous genome complexity of pines can be explained by divergence of retrotransposons, however the elements responsible for genome size variation are yet to be identified. Genomic resources for Pinus including those reported here should assist in further defining whether and how the roles of retrotransposons differ in the evolution of angiosperm and gymnosperm genomes
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