De novo expression of parvalbumin in ependymal cells in response to brain injury promotes ependymal remodeling and wound repair

The calcium-binding protein parvalbumin (PV) hallmarks subpopulations of interneurons in the murine brain. We serendipitously observed the de novo expression of PV in ependymal cells of the lateral ventricle wall following in vivo lesioning and brain slicing for the preparation of organotypic hippocampal slice cultures (OHSCs). In OHSCs, de novo PV-expression begins shortly after the onset of culturing, and the number of ependymal cells implicated in this process increases with time. PV-immunopositive ependymal cells aggregate and form compact cell clusters, which are characterized by lumen-formation and beating cilia. Scratches inflicted on such clusters with a sharp knife are rapidly closed. Exposure of OHSCs to NF-КB-inhibitors and to antioxidants reduces PV-expression in ependymal cells, thereby implicating injury-induced inflammation in this process. Indeed, in vivo stab injury enhances PV-expression in ependymal cells adjacent to the lesion, whereas neuraminidase denudation is without effect. PV-knock-out mice manifest an impaired wound-healing response to in vivo injury, and a reduced scratch-wound reparation capacity in OHSCs. Whole-transcriptome analysis of ependymal-cell clusters in OHSCs revealed down-regulation of genes involved in cytoskeletal rearrangement, cell motility and cell adhesion in PV-knock out mice as compared with wild-type mice. Our data indicate that the injury-triggered up-regulation of PV-expression is mediated by inflammatory cytokines, and promotes the motility and adhesion of ependymal cells, thereby contributing to leakage closure by the re-establishment of a continuous ependymal layer

Parvalbumin-neurons of the ventrolateral hypothalamic parvafox nucleus receive a glycinergic input: a gene-microarray study

The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis and, armed with the forthcoming data, controlled the results with the Allen databases and the murine BrainStars (B*) database. The parvafox nucleus was specifically sampled by laser-capture microdissection and the transcriptome was subjected to a microarray analysis on Affymetrix chips. Eighty-two relevant genes were found to be potentially more expressed in this brain region than in either the cerebral cortex or the hippocampus. When the expression patterns of these genes were counterchecked in the Allen-Database of in-situ hybridizations and in the B*-microarray database, their localization in the parvafox region was confirmed for thirteen. For nine novel genes, which are particularly interesting because of their possible involvement in neuromodulation, the expression was verified by quantitative real time-PCR. Of particular functional importance may be the occurrence of glycine receptors, the presence of which indicates that the activity of the parvafox nucleus is under ascending inhibitory control

Parvalbumin-expressing ependymal cells in rostral lateral ventricle wall adhesions contribute to aging-related ventricle stenosis in mice

Aging-associated ependymal-cell pathologies can manifest as ventricular gliosis, ventricle enlargement, or ventricle stenosis. Ventricle stenosis and fusion of the lateral ventricle (LV) walls is associated with a massive decline of the proliferative capacities of the stem cell niche in the affected subventricular zone (SVZ) in aging mice. We examined the brains of adult C57BL/6 mice and found that ependymal cells located in the adhesions of the medial and lateral walls of the rostral LVs upregulated parvalbumin (PV) and displayed reactive phenotype, similarly to injury-reactive ependymal cells. However, PV+ ependymal cells in the LV-wall adhesions, unlike injury-reactive ones, did not express glial fibrillary acidic protein. S100B+/PV+ ependymal cells found in younger mice diminished in the LV-wall adhesions throughout aging. We found that periventricular PV-immunofluorescence showed positive correlation to the grade of LV stenosis in nonaged mice (10-month-old) PV-knock out (PV-KO) mice. This suggests an involvement of PV+ ependymal cells in aging-associated ventricle stenosis. Additionally, we observed a time-shift in microglial activation in the LV-wall adhesions between age-grouped PV- KO and wild-type mice, suggesting a delay in microglial activation when PV is absent from ependymal cells. Our findings implicate that compromised ependymal cells of the adhering ependymal layers upregulate PV and display phenotype shift to “reactive” ependymal cells in aging-related ventricle stenosis; moreover, they also contribute to the progression of LV-wall fusion associated with a decline of the affected SVZ-stem cell niche in aged mice

Prediction and Simulator Verification of Roll/Lateral Adverse Aeroservoelastic Rotorcraft–Pilot Couplings

The involuntary interaction of a pilot with an aircraft can be described as pilot-assisted oscillations. Such phenomena are usually only addressed late in the design process when they manifest themselves during ground/flight testing. Methods to be able to predict such phenomena as early as possible are therefore useful. This work describes a technique to predict the adverse aeroservoelastic rotorcraft–pilot couplings, specifically between a rotorcraft’s roll motion and the resultant involuntary pilot lateral cyclic motion. By coupling linear vehicle aeroservoelastic models and experimentally identified pilot biodynamic models, pilot-assisted oscillations and no-pilot-assisted oscillation conditions have been numerically predicted for a soft-in-plane hingeless helicopter with a lightly damped regressive lead–lag mode that strongly interacts with the roll modeat a frequency within the biodynamic band of the pilots. These predictions have then been verified using real-time flight-simulation experiments. The absence of any similar adverse couplings experienced while using only rigid-body models in the flight simulator verified that the observed phenomena were indeed aeroelastic in nature. The excellent agreement between the numerical predictions and the observed experimental results indicates that the techniques developed in this paper can be used to highlight the proneness of new or existing designs to pilot-assisted oscillation

Experimental investigations of ambiguity: the case of most

In the study of natural language quantification, much recent attention has been devoted to the investigation of verification procedures associated with the proportional quantifier most. The aim of these studies is to go beyond the traditional characterization of the semantics of most, which is confined to explicating its truth-functional and presuppositional content as well as its combinatorial properties, as these aspects underdetermine the correct analysis of most. The present paper contributes to this effort by presenting new experimental evidence in support of a decompositional analysis of most according to which it is a superlative construction built from a gradable predicate many or much and the superlative operator -est (Hackl, in Nat Lang Semant 17:63–98, 2009). Our evidence comes in the form of verification profiles for sentences like Most of the dots are blue which, we argue, reflect the existence of a superlative reading of most. This notably contrasts with Lidz et al.’s (Nat Lang Semant 19:227–256, 2011) results. To reconcile the two sets of data, we argue, it is necessary to take important differences in task demands into account, which impose limits on the conclusions that can be drawn from these studies

A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: the Treat-OA consortium

To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genome-wide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81×10−5). The C allele conferred a reduced risk of 33% to 41% using a case–control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA

The orbitofrontal cortex projects to the parvafox nucleus of the ventrolateral hypothalamus and to its targets in the ventromedial periaqueductal grey matter

Although connections between the orbitofrontal cortex (OFC)—the seat of high cognitive functions—the lateral hypothalamus and the periaqueductal grey (PAG) have been recognized in the past, the precise targets of the descending fibres have not been identified. In the present study, viral tracer-transport experiments revealed neurons of the lateral (LO) and the ventrolateral (VLO) OFC (homologous to part of Area 13 in primates) to project to a circumscribed region in the ventrolateral hypothalamus, namely, the horizontally oriented, cylindrical parvalbumin- and Foxb1- expressing (parvafox) nucleus. The fine collaterals stem from coarse axons in the internal capsule and form excitatory synapses specifically with neurons of the parvafox nucleus, avoiding the rest of the hypothalamus. In its further caudal course, this contingent of LO/VLO-axons projects collaterals to the Su3- and the PV2 nuclei, which lie ventral to the aqueduct in the (PAG), where the terminals fields overlap those deriving from the parvafox nucleus itself. The targeting of the parvafox nucleus by the LO/VLO-projections, and the overlapping of their terminal fields within the PAG, suggest that the two cerebral sites interact closely. An involvement of this LO/VLO- driven circuit in the somatic manifestation of behavioural events is conceivable

The acquisition of asserted, presupposed, and pragmatically implied exhaustivity in Hungarian

The paper reports on three experiments in which the exhaustive interpretation of sentences containing the focus particle csak ‘only’, structural focus constructions, and sentences with neutral intonation and word order were investigated. The results obtained not only reveal the developmental trajectory of the adult-like comprehension of each sentence type, but also contribute to the discussion concerning the semantic or pragmatic nature of their exhaustive meaning component. As the three construction types were judged in different ways on a three-point scale, the findings appear to support the hypothesis according to which exhaustivity is part of the asserted content of sentences with csak ‘only’, it is context-independently presupposed in the case of structural focus, and in certain contexts it can arise as an implicature in the case of neutral utterances, as well