87 research outputs found
Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease
We present the first application of the hypothesis-rich mathematical theory
to genome-wide association data. The Hamza et al. late-onset sporadic
Parkinson's disease genome-wide association study dataset was analyzed. We
found a rare, coding, non-synonymous SNP variant in the gene DZIP1 that confers
increased susceptibility to Parkinson's disease. The association of DZIP1 with
Parkinson's disease is consistent with a Parkinson's disease stem-cell ageing
theory.Comment: 14 page
A common root for coevolution and substitution rate variability in protein sequence evolution
We introduce a simple model that describes the average occurrence of point variations in a generic protein sequence. This model is based on the idea that mutations are more likely to be fixed at sites in contact with others that have mutated in the recent past. Therefore, we extend the usual assumptions made in protein coevolution by introducing a time dumping on the effect of a substitution on its surrounding and makes correlated substitutions happen in avalanches localized in space and time. The model correctly predicts the average correlation of substitutions as a function of their distance along the sequence. At the same time, it predicts an among-site distribution of the number of substitutions per site highly compatible with a negative binomial, consistently with experimental data. The promising outcomes achieved with this model encourage the application of the same ideas in the field of pairwise and multiple sequence alignment
MicroRNA Expression Profiling of the Porcine Developing Brain
BACKGROUND: MicroRNAs are small, non-coding RNA molecules that regulate gene expression at the post-transcriptional level and play an important role in the control of developmental and physiological processes. In particular, the developing brain contains an impressive diversity of microRNAs. Most microRNA expression profiling studies have been performed in human or rodents and relatively limited knowledge exists in other mammalian species. The domestic pig is considered to be an excellent, alternate, large mammal model for human-related neurological studies, due to its similarity in both brain development and the growth curve when compared to humans. Considering these similarities, studies examining microRNA expression during porcine brain development could potentially be used to predict the expression profile and role of microRNAs in the human brain. METHODOLOGY/PRINCIPAL FINDINGS: MicroRNA expression profiling by use of microRNA microarrays and qPCR was performed on the porcine developing brain. Our results show that microRNA expression is regulated in a developmentally stage-specific, as well as a tissue-specific manner. Numerous developmental stage or tissue-specific microRNAs including, miR-17, miR-18a, miR-29c, miR-106a, miR-135a and b, miR-221 and miR-222 were found by microarray analysis. Expression profiles of selected candidates were confirmed by qPCR. CONCLUSIONS/SIGNIFICANCE: The differential expression of specific microRNAs in fetal versus postnatal samples suggests that they likely play an important role in the regulation of developmental and physiological processes during brain development. The data presented here supports the notion that microRNAs act as post-transcriptional switches which may regulate gene expression when required
Mathematical Modelling as a Proof of Concept for MPNs as a Human Inflammation Model for Cancer Development
<p><b>Left:</b> Typical development in stem cells (top panel A) and mature cells (bottom panel B). Healthy hematopoietic cells (full blue curves) dominate in the early phase where the number of malignant cells (stipulated red curves) are few. The total number of cells is also shown (dotted green curves). When a stem cell mutates without repairing mechanisms, a slowly increasing exponential growth starts. At a certain stage, the malignant cells become dominant, and the healthy hematopoietic cells begin to show a visible decline. Finally, the composition between the cell types results in a takeover by the malignant cells, leading to an exponential decline in hematopoietic cells and ultimately their extinction. The development is driven by an approximately exponential increase in the MPN stem cells, and the development is closely followed by the mature MPN cells. <b>Right:</b> B)The corresponding allele burden (7%, 33% and 67% corresponding to ET, PV, and PMF, respectively) defined as the ratio of MPN mature cells to the total number of mature cells.</p
MicroRNA Dysregulation in the Spinal Cord following Traumatic Injury
Spinal cord injury (SCI) triggers a multitude of pathophysiological events that are tightly regulated by the expression levels of specific genes. Recent studies suggest that changes in gene expression following neural injury can result from the dysregulation of microRNAs, short non-coding RNA molecules that repress the translation of target mRNA. To understand the mechanisms underlying gene alterations following SCI, we analyzed the microRNA expression patterns at different time points following rat spinal cord injury
The self-organizing fractal theory as a universal discovery method: the phenomenon of life
A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy
QCD and strongly coupled gauge theories : challenges and perspectives
We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe
IMRT delivers lower radiation doses to dental structures than 3DRT in head and neck cancer patients
Lipopolysaccharide-induced memory impairment in rats is preventable using 7-nitroindazole
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