Addressing the needs of children with disabilities experiencing disaster or terrorism

Purpose of review: This paper reviews the empirical literature on psychosocial factors relating to children with disabilities in the context of disaster or terrorism. Recent findings: Research indicates individuals with disabilities experience increased exposure to hazards due to existing social disparities and barriers associated with disability status. However, studies on the psychological effects of disaster/terrorism on children with preexisting disabilities are exceedingly few and empirical evidence of the effectiveness of trauma-focused therapies for this population is limited. Secondary adversities, including social stigma and health concerns, also compromise the recovery of these children post-disaster/terrorism. Schools and teachers appear to be particularly important in the recovery of children with disabilities to disaster. Disasters, terrorism, and war all contribute to the incidence of disability, as well as disproportionately affect children with preexisting disabilities. Summary: Disaster preparedness interventions and societal changes are needed to decrease the disproportionate environmental and social vulnerability of children with disabilities to disaster and terrorism

The Reelin Receptors Apoer2 and Vldlr Coordinate the Patterning of Purkinje Cell Topography in the Developing Mouse Cerebellum

The adult cerebellar cortex is comprised of reproducible arrays of transverse zones and parasagittal stripes of Purkinje cells. Adult stripes are created through the perinatal rostrocaudal dispersion of embryonic Purkinje cell clusters, triggered by signaling through the Reelin pathway. Reelin is secreted by neurons in the external granular layer and deep cerebellar nuclei and binds to two high affinity extracellular receptors on Purkinje cells-the Very low density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (Apoer2). In mice null for either Reelin or double null for Vldlr and Apoer2, Purkinje cell clusters fail to disperse. Here we report that animals null for either Vldlr or Apoer2 individually, exhibit specific and parasagittally-restricted Purkinje cell ectopias. For example, in mice lacking Apoer2 function immunostaining reveals ectopic Purkinje cells that are largely restricted to the zebrin II-immunonegative population of the anterior vermis. In contrast, mice null for Vldlr have a much larger population of ectopic Purkinje cells that includes members from both the zebrin II-immunonegative and -immunopositive phenotypes. HSP25 immunoreactivity reveals that in Vldlr null animals a large portion of zebrin II-immunopositive ectopic cells are probably destined to become stripes in the central zone (lobules VI–VII). A small population of ectopic zebrin II-immunonegative Purkinje cells is also observed in animals heterozygous for both receptors (Apoer2+/−: Vldlr+/−), but no ectopia is present in mice heterozygous for either receptor alone. These results indicate that Apoer2 and Vldlr coordinate the dispersal of distinct, but overlapping subsets of Purkinje cells in the developing cerebellum

Cell Type–Specific Transcriptome Analysis Reveals a Major Role for Zeb1 and miR-200b in Mouse Inner Ear Morphogenesis

Cellular heterogeneity hinders the extraction of functionally significant results and inference of regulatory networks from wide-scale expression profiles of complex mammalian organs. The mammalian inner ear consists of the auditory and vestibular systems that are each composed of hair cells, supporting cells, neurons, mesenchymal cells, other epithelial cells, and blood vessels. We developed a novel protocol to sort auditory and vestibular tissues of newborn mouse inner ears into their major cellular components. Transcriptome profiling of the sorted cells identified cell type–specific expression clusters. Computational analysis detected transcription factors and microRNAs that play key roles in determining cell identity in the inner ear. Specifically, our analysis revealed the role of the Zeb1/miR-200b pathway in establishing epithelial and mesenchymal identity in the inner ear. Furthermore, we detected a misregulation of the ZEB1 pathway in the inner ear of Twirler mice, which manifest, among other phenotypes, malformations of the auditory and vestibular labyrinth. The association of misregulation of the ZEB1/miR-200b pathway with auditory and vestibular defects in the Twirler mutant mice uncovers a novel mechanism underlying deafness and balance disorders. Our approach can be employed to decipher additional complex regulatory networks underlying other hearing and balance mouse mutants

Cerebellar Zones: A Personal History

Cerebellar zones were there, of course, before anyone noticed them. Their history is that of young people, unhindered by preconceived ideas, who followed up their observations with available or new techniques. In the 1960s of the last century, the circumstances were fortunate because three groups, in Leiden, Lund, and Bristol, using different approaches, stumbled on the same zonal pattern in the cerebellum of the cat. In Leiden, the Häggqvist myelin stain divulged the compartments in the cerebellar white matter that channel the afferent and efferent connections of the zones. In Lund, the spino-olivocerebellar pathways activated from individual spinal funiculi revealed the zonal pattern. In Bristol, charting the axon reflex of olivocerebellar climbing fibers on the surface of the cerebellum resulted in a very similar zonal map. The history of the zones is one of accidents and purposeful pursuit. The technicians, librarians, animal caretakers, students, secretaries, and medical illustrators who made it possible remain unnamed, but their contributions certainly should be acknowledged

Lipidomic Analysis of Extracellular Vesicles from the Pathogenic Phase of Paracoccidioides brasiliensis

Background: Fungal extracellular vesicles are able to cross the cell wall and transport molecules that help in nutrient acquisition, cell defense, and modulation of the host defense machinery.Methodology/Principal Findings: Here we present a detailed lipidomic analysis of extracellular vesicles released by Paracoccidioides brasiliensis at the yeast pathogenic phase. We compared data of two representative isolates, Pb3 and Pb18, which have distinct virulence profiles and phylogenetic background. Vesicle lipids were fractionated into different classes and analyzed by either electrospray ionization- or gas chromatography-mass spectrometry. We found two species of monohexosylceramide and 33 phospholipid species, including phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid, phosphatidylserine, phosphatidylinositol, and phosphatidylglycerol. Among the phospholipid-bound fatty acids in extracellular vesicles, C181 predominated in Pb3, whereas C18:2 prevailed in Pb18. the prevalent sterol in Pb3 and Pb18 vesicles was brassicasterol, followed by ergosterol and lanosterol. Inter-isolate differences in sterol composition were observed, and also between extracellular vesicles and whole cells.Conclusions/Significance: the extensive lipidomic analysis of extracellular vesicles from two P. brasiliensis isolates will help to understand the composition of these fungal components/organelles and will hopefully be useful to study their biogenesis and role in host-pathogen interactions.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Institutes of Health (NIH)Universidade Federal de São Paulo, UNIFESP, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv Texas El Paso, Dept Biol Sci, Border Biomed Res Ctr, El Paso, TX 79968 USAUniversidade Federal de São Paulo, UNIFESP, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilFAPESP: 06/05095-6FAPESP: 07/04757-8FAPESP: 07/59768-4CNPq: 301666/2010-5National Institutes of Health (NIH): 5G12RR008124-16A1National Institutes of Health (NIH): 5G12RR008124-16A1S1National Institutes of Health (NIH): G12MD007592Web of Scienc

A Sensitive High-Throughput Assay for Evaluating Host-Pathogen Interactions in Cryptococcus neoformans Infection

Background: Cryptococcus neoformans causes serious disease in immunocompromised individuals, leading to over 600,000 deaths per year worldwide. Part of this impact is due to the organism’s ability to thwart what should be the mammalian hosts ’ first line of defense against cryptococcal infection: internalization by macrophages. Even when C. neoformans is engulfed by host phagocytes, it can survive and replicate within them rather than being destroyed; this ability is central in cryptococcal virulence. It is therefore critical to elucidate the interactions of this facultative intracellular pathogen with phagocytic cells of its mammalian host. Methodology/Principal Findings: To accurately assess initial interactions between human phagocytic cells and fungi, we have developed a method using high-throughput microscopy to efficiently distinguish adherent and engulfed cryptococci and quantitate each population. This method offers significant advantages over currently available means of assaying hostfungal cell interactions, and remains statistically robust when implemented in an automated fashion appropriate for screening. It was used to demonstrate the sensitivity of human phagocytes to subtle changes in the cryptococcal capsule, a major virulence factor of this pathogen. Conclusions/Significance: Our high-throughput method for characterizing interactions between C. neoformans and mammalian phagocytic cells offers a powerful tool for elucidating the relationship between these cell types durin

Evidence for link between modelled trends in Antarctic sea ice and underestimated westerly wind changes

Despite global warming, total Antarctic sea ice coverage increased over 1979-2013. However, the majority of Coupled Model Intercomparison Project phase 5 models simulate a decline. Mechanisms causing this discrepancy have so far remained elusive. Here we show that weaker trends in the intensification of the Southern Hemisphere westerly wind jet simulated by the models may contribute to this disparity. During austral summer, a strengthened jet leads to increased upwelling of cooler subsurface water and strengthened equatorward transport, conducive to increased sea ice. As the majority of models underestimate summer jet trends, this cooling process is underestimated compared with observations and is insufficient to offset warming in the models. Through the sea ice-albedo feedback, models produce a high-latitude surface ocean warming and sea ice decline, contrasting the observed net cooling and sea ice increase. A realistic simulation of observed wind changes may be crucial for reproducing the recent observed sea ice increase