Relevance of Fluorodopa PET Scan in Dopamine Responsive Dystonia and Juvenile Parkinsonism: A Systematic Review.

BACKGROUND: Dopamine Responsive Dystonia (DRD) and Juvenile Parkinsonism (JP) are two diseases commonly presenting with parkinsonian symptoms in young patients. Current clinical guidelines offer a diagnostic approach based on molecular analysis. However, developing countries have limitations in terms of accessibility to these tests. We aimed to assess the utility of imaging equipment, usually more available worldwide, to help diagnose and improve patients' quality of life with these diseases. METHODS: We performed a systematic literature review in English using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and meta-analysis of observational studies in epidemiology (MOOSE) protocols. We only used human clinical trials about dopamine responsive dystonia and juvenile parkinsonism patients in which a fluorodopa (FD) positron emission tomography (PET) scan was performed to identify its use in these diseases. RESULTS: We included six studies that fulfilled our criteria. We found a clear pattern of decreased uptake in the putamen and caudate nucleus in JP cases. At the same time, the results in DRD were comparable to normal subjects, with only a slightly decreased marker uptake in the previously mentioned regions by the FD PET scan. CONCLUSIONS: We found a distinctive pattern for each of these diseases. Identifying these findings with FD PET scans can shorten the delay in making a definitive diagnosis when genetic testing is unavailable, a common scenario in developing countries.

CTDGFinder: A Novel Homology-Based Algorithm for Identifying Closely Spaced Clusters of Tandemly Duplicated Genes.

Closely spaced clusters of tandemly duplicated genes (CTDGs) contribute to the diversity of many phenotypes, including chemosensation, snake venom, and animal body plans. CTDGs have traditionally been identified subjectively as genomic neighborhoods containing several gene duplicates in close proximity; however, CTDGs are often highly variable with respect to gene number, intergenic distance, and synteny. This lack of formal definition hampers the study of CTDG evolutionary dynamics and the discovery of novel CTDGs in the exponentially growing body of genomic data. To address this gap, we developed a novel homology-based algorithm, CTDGFinder, which formalizes and automates the identification of CTDGs by examining the physical distribution of individual members of families of duplicated genes across chromosomes. Application of CTDGFinder accurately identified CTDGs for many well-known gene clusters (e.g., Hox and beta-globin gene clusters) in the human, mouse and 20 other mammalian genomes. Differences between previously annotated gene clusters and our inferred CTDGs were due to the exclusion of nonhomologs that have historically been considered parts of specific gene clusters, the inclusion or absence of genes between the CTDGs and their corresponding gene clusters, and the splitting of certain gene clusters into distinct CTDGs. Examination of human genes showing tissue-specific enhancement of their expression by CTDGFinder identified members of several well-known gene clusters (e.g., cytochrome P450s and olfactory receptors) and revealed that they were unequally distributed across tissues. By formalizing and automating CTDG identification, CTDGFinder will facilitate understanding of CTDG evolutionary dynamics, their functional implications, and how they are associated with phenotypic diversity.

Rapid evolutionary dynamics of structural disorder as a potential driving force for biological divergence in flaviviruses.

Protein structure is commonly regarded to be conserved and to dictate function. Most proteins rely on conformational flexibility to some degree. Are regions that convey conformational flexibility conserved over evolutionary time? Can changes in conformational flexibility alter protein function? Here, the evolutionary dynamics of structurally ordered and disordered (flexible) regions are investigated genome-wide in flaviviruses, revealing that the amount and location of structural disorder fluctuates highly among related proteins. Some regions are prone to shift between structured and flexible states. Increased evolutionary dynamics of structural disorder is observed for some lineages but not in others. Lineage-specific transitions of this kind could alter the conformational ensemble accessible to the same protein in different species, causing a functional change, even if the predominant function remains conserved. Thus, rapid evolutionary dynamics of structural disorder is a potential driving force for phenotypic divergence among flaviviruses.

Medicacion antigotosa para agresion refractaria en pacientes autistas / Adenosine for refractary aggression in autistc patients

Las conductas hetero y autoagresivas en pacientes con autismo pueden ser refractarias a los medicamentos comúnmente empleados; sin embargo, la adenosina, purina neuromoduladora, ha demostrado ser una sustancia con propiedades antíagresivas dentro de modelos animales. Las vías de purinas se encuentran modificadas en ciertas patologías que presentan automutilaciones. El alopurinol aumentaría de forma indirecta las concentraciones de adenosina, por lo cual sería efectiva en el manejo de la agresión. En consecuencia, la población de pacientes autistas con dichos comportamientos lesivos podría tener mejoría con este medicamento antigotoso