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

Stimulus- en goal-driven control of eye movements: Action videogame players are faster not better

Action videogame players (AVGPs) have been shown to outperform nongamers (NVGPs) in covert visual attention tasks. These advantages have been attributed to improved top-down control in this population. The time course of visual selection, which permits researchers to highlight when top-down strategies start to control performance, has rarely been investigated in AVGPs. Here, we addressed specifically this issue through an oculomotor additional-singleton paradigm. Participants were instructed to make a saccadic eye movement to a unique orientation singleton. The target was presented among homogeneous nontargets and one additional orientation singleton that was more, equally, or less salient than the target. Saliency was manipulated in the color dimension. Our results showed similar patterns of performance for both AVGPs and NVGPs: Fast-initiated saccades were saliency-driven, whereas later-initiated saccades were more goal-driven. However, although AVGPs were faster than NVGPs, they were also less accurate. Importantly, a multinomial model applied to the data revealed comparable underlying saliency-driven and goal-driven functions for the two groups. Taken together, the observed differences in performance are compatible with the presence of a lower decision bound for releasing saccades in AVGPs than in NVGPs, in the context of comparable temporal interplay between the underlying attentional mechanisms. In sum, the present findings show that in both AVGPs and NVGPs, the implementation of top-down control in visual selection takes time to come about, and they argue against the idea of a general enhancement of top-down control in AVGPs

Finding the balance between capture and control: oculomotor selection in early deaf adults

Previous work investigating the consequence of bilateral deafness on attentional selection suggests that experience-dependent changes in this population may result in increased automatic processing of stimulus-driven visual information (e.g., saliency). However, adaptive behavior also requires observers to prioritize goal-driven information relevant to the task at hand. In order to investigate whether auditory deprivation alters the balance between these two components of attentional selection, we assessed the time-course of overt visual selection in deaf adults. Twenty early-deaf adults and twenty hearing controls performed an oculomotor additional singleton paradigm. Participants made a speeded eye-movement to a unique orientation target, embedded among homogenous non-targets and one additional unique orientation distractor that was more, equally or less salient than the target. Saliency was manipulated through color. For deaf participants proficiency in sign language was assessed. Overall, results showed that fast initiated saccades were saliency-driven, whereas later initiated saccades were goal-driven. However, deaf participants were overall slower than hearing controls at initiating saccades and also less captured by task-irrelevant salient distractors. The delayed oculomotor behavior of deaf adults was not explained by any of the linguistic measures acquired. Importantly, a multinomial model applied to the data revealed a comparable evolution over time of the underlying saliency- and goal-driven processes between the two groups, confirming the crucial role of saccadic latencies in determining the outcome of visual selection performance. The present findings indicate that prioritization of saliency-driven information is not an unavoidable phenomenon in deafness. Possible neural correlates of the documented behavioral effect are also discussed