Quantification routines for full 3D elemental distributions of homogeneous and layered samples obtained with laboratory confocal micro XRF spectrometers

Confocal micro X ray fluorescence spectroscopy can be performed with laboratory spectrometers for elemental imaging with 3D resolution. Due to self absorption inside a specimen and energy effects induced by the used polycapillary optics, interpretation of data can be challenging. Thus, quantification techniques to reconstruct sample composition and geometry are mandatory to widen the applicability of the technique to further fields of analytical chemistry. We present an analytical routine which facilitates the quantitative investigation of 3D data sets obtained with laboratory spectrometers. By fully calibrating the spectrometer parameters the procedure is generalized to be suitable for all spectrometers with known excitation spectra and polycapillary optics. Calibration and validation measurements on homogeneous and stratified samples are presented with a discussion on uncertainties and challenges. Finally, the localization of a goethite needle in a quartz matrix is presented as an example of a possible routine applicatio

dOCRL maintains immune cell quiescence in Drosophila by regulating endosomal traffic

Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, and is caused by mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles in endocytic and endolysosomal trafficking, cytokinesis, and ciliogenesis, but it is unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation of Drosophila OCRL causes cell-autonomous activation of hemocytes, which are macrophage-like cells of the innate immune system. Among many cell biological defects that we identified in docrl mutant hemocytes, we pinpointed the cause of innate immune cell activation to reduced Rab11-dependent recycling traffic and concomitantly increased Rab7-dependent late endosome traffic. Loss of docrl amplifies multiple immune-relevant signals, including Toll, Jun kinase, and STAT, and leads to Rab11-sensitive mis-sorting and excessive secretion of the Toll ligand Spåtzle. Thus, docrl regulation of endosomal traffic maintains hemocytes in a poised, but quiescent state, suggesting mechanisms by which endosomal misregulation of signaling may contribute to symptoms of Lowe syndrome

Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics

The assessment of oocyte quality in human in vitro fertilization (IVF) is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF) is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomic

Mutational hot spot in the DSPP gene causing dentinogenesis imperfecta type II

The current system for the classification of hereditary defects of tooth dentin is based upon clinical and radiographic findings and consists of two types of dentin dysplasia (DD) and three types of dentinogenesis imperfecta (DGI). However, whether DGI type III should be considered a distinct phenotype or a variation of DGI type II is debatable. In the 30 years since the classification system was first proposed, significant advances have been made regarding the genetic etiologies of inherited dentin defects. DGI type II is recognized as an autosomal dominant disorder with almost complete penetrance and a low frequency of de novo mutations. We have identified a mutation (c.52G→T, p.V18F) at the first nucleotide of exon 3 of the DSPP (dentin sialophosphoprotein) gene in a Korean family (de novo) and a Caucasian family. This mutation has previously been reported as causing DGI type II in a Chinese family. These findings suggest that this mutation site represents a mutational “hot spot” in the DSPP gene. The clinical and radiographic features of these two families include the classic phenotypes associated with both DGI type II and type III. Finding that a single mutation causes both phenotypic patterns strongly supports the conclusion that DGI type II and DGI type III are not separate diseases but rather the phenotypic variation of a single disease. We propose a modification of the current classification system such that the designation “hereditary opalescent dentin” or “DGI type II” should be used to describe both the DGI type II and type III phenotypes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47595/1/439_2004_Article_1223.pd

Revisiting the adaptive and maladaptive effects of crossmodal plasticity

One of the most striking demonstrations of experience-dependent plasticity comes from studies of sensorydeprived individuals (e.g., blind or deaf), showing that brain regions deprived of their natural inputs change their sensory tuning to support the processing of inputs coming from the spared senses. These mechanisms of crossmodal plasticity have been traditionally conceptualized as having a double-edged sword effect on behavior. On one side, crossmodal plasticity is conceived as adaptive for the development of enhanced behavioral skills in the remaining senses of early-deaf or blind individuals. On the other side, crossmodal plasticity raises crucial challenges for sensory restoration and is typically conceived as maladaptive since its presence may prevent optimal recovery in sensory-reafferented individuals. In the present review we stress that this dichotomic vision is oversimplified and we emphasize that the notions of the unavoidable adaptive/maladaptive effects of crossmodal reorganization for sensory compensation/restoration may actually be misleading. For this purpose we critically review the findings from the blind and deaf literatures, highlighting the complementary nature of these two fields of research. The integrated framework we propose here has the potential to impact on the way rehabilitation programs for sensory recovery are carried out, with the promising prospect of eventually improving their final outcomes