5 research outputs found
Maximum likelihood estimation of locus-specific mutation rates in Y-chromosome short tandem repeats
Motivation: Y-chromosome short tandem repeats (Y-STRs) are widely used for population studies, forensic purposes and, potentially, the study of disease, therefore knowledge of their mutation rate is valuable. Here we show a novel method for estimation of site-specific Y-STR mutation rates from partial phylogenetic information, via the maximum likelihood framework
Expression profiles of acute lymphoblastic and myeloblastic leukemias with ALL-1 rearrangements
The ALL-1 gene is directly involved in 5-10% of ALLs and AMLs by fusion to
other genes or through internal rearrangements. DNA microarrays were utilized
to determine expression profiles of ALLs and AMLs with ALL-1 rearrangements.
These profiles distinguish those tumors from other ALLs and AMLs. The
expression patterns of ALL-1-associated tumors, in particular ALLs, involve
oncogenes, tumor suppressors, anti apoptotic genes, drug resistance genes etc.,
and correlate with the aggressive nature of the tumors. The genes whose
expression differentiates between ALLs with and without ALL-1 rearrangement
were further divided into several groups enabling separation of ALL-1-
associated ALLs into two subclasses. Further, AMLs with partial duplication of
ALL-1 vary in their expression pattern from AMLs in which ALL-1 had undergone
fusion to other genes. The extensive analysis described here draws attention to
genes which might have a direct role in pathogenesis
Neolithic patrilineal signals indicate that the Armenian plateau was repopulated by agriculturalists
mTOR signaling in proteostasis and its relevance to autism spectrum disorders
Proteins are extremely labile cellular components, especially at physiological temperatures. The appropriate regulation of protein levels, or proteostasis, is essential for all cells. In the case of highly polarized cells like neurons, proteostasis is also crucial at synapses, where quick confined changes in protein composition occur to support synaptic activity and plasticity. The accurate regulation of those cellular processes controlling protein synthesis and degradation is necessary for proteostasis, and its deregulation has deleterious consequences in brain function. Alterations in those cellular mechanisms supporting synaptic protein homeostasis have been pinpointed in autism spectrum disorders such as tuberous sclerosis, neurofibromatosis 1, PTEN-related disorders, fragile X syndrome, MECP2 disorders and Angelman syndrome. Proteostasis alterations in these disorders share the alterations in mechanistic/mammalian target of rapamycin (mTOR) signaling pathway, an intracellular pathway with key synaptic roles. The aim of the present review is to describe the recent literature on the major cellular mechanisms involved in proteostasis regulation in the synaptic context, and its association with mTOR signaling deregulations in various autism spectrum disorders. Altogether, the cellular and molecular mechanisms in synaptic proteostasis could be the foundation for novel shared therapeutic strategies that would take advantage of targeting common disorder mechanisms.This review was supported by grant BFU2015-68568-P (MINECO/FEDER, EU) to AO