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A study involving 50 rehabilitation professionals, 264 rehabilitation clients, 90 adults with blindness, and 267 employers, identified factors that lead to or impede competitive job placements for clients of a state blindness rehabilitation agency. Also identified were services that employers felt would assist them in hiring or retaining clients. (Author/CR)

Multiphoton ionization (MPI) time-of-flight mass spectroscopy (TOFMS) and photoelectron spectroscopy (PES) studies of UF6 are reported using focused light from the Nd:YAG laser fundamental (λ=1064 nm) and its harmonics (λ=532, 355, or 266 nm), as well as other wavelengths provided by a tunable dye laser. The MPI mass spectra are dominated by the singly and multiply charged uranium ions rather than by the UF+x fragment ions, even at the lowest laser power densities at which signal could be detected. In general, the doubly charged uranium ion (U2+) intensity is much greater than that of the singly charged uranium ion (U+). For the case of the tunable dye laser experiments, the Un+ (n=1–4) wavelength dependence is relatively unstructured and does not show observable resonance enhancement at known atomic uranium excitation wavelengths. The MPI-PES studies reveal only very slow electrons (≤0.5 eV) for all wavelengths investigated. The dominance of the U2+ ion, the absence or very small intensities of UF+x (x=1–3) fragments, the unstructured wavelength dependence, and the preponderance of slow electrons all indicate that mechanisms may exist other than ionization of bare U atoms following the stepwise photodissociation of F atoms from the parent molecule. The data also argue against stepwise photodissociation of UF+x (x=5,6) ions. Neither of the traditional MPI mechanisms (‘‘neutral ladder’’ or the ‘‘ionic ladder’’) are believed to adequately describe the ionization phenomena observed. We propose that the multiphoton excitation of UF6 under these experimental conditions results in a highly excited molecule, superexcited UF6**. The excitation of highly excited UF6** is proposed to be facilitated by the well known ‘‘giant resonance,’’ whose energy level lies in the range of 12–14 eV above that of ground state UF6. The highly excited molecule then... [ABSTRACT FROM AUTHOR]

Adult Neural Stem Cells (aNSCs) in the ventricular-subventricular zone (V-SVZ) are largely quiescent. Here, we characterize the mechanism underlying the functional role of a cell-signalling inhibitory protein, LRIG1, in the control of aNSCs proliferation. Using Lrig1 knockout models, we show that Lrig1 ablation results in increased aNSCs proliferation with no change in neuronal progeny and that this hyperproliferation likely does not result solely from activation of the epidermal growth factor receptor (EGFR). Loss of LRIG1, however, also leads to impaired activation of transforming growth factor beta (TGFβ) and bone morphogenic protein (BMP) signalling. Biochemically, we show that LRIG1 binds TGFβ/BMP receptors and the TGFβ1 ligand. Finally, we show that the consequences of these interactions are to facilitate SMAD phosphorylation. Collectively, these data suggest that unlike in embryonic NSCs where EGFR may be the primary mechanism of action, in aNSCs, LRIG1 and TGFβ pathways function together to fulfill their inhibitory roles., (© 2024. The Author(s).)

The Polycomb Repressive Complex 2 (PRC2) regulates corticogenesis, yet the consequences of mutations to this epigenetic modifier in the mature brain are poorly defined. Importantly, PRC2 core genes are haploinsufficient and causative of several human neurodevelopmental disorders. To address the role of PRC2 in mature cortical structure and function, we conditionally deleted the PRC2 gene Eed from the developing mouse dorsal telencephalon. Adult homozygotes displayed smaller forebrain structures. Single-nucleus transcriptomics revealed that glutamatergic neurons were particularly affected, exhibiting dysregulated gene expression profiles, accompanied by aberrations in neuronal morphology and connectivity. Remarkably, homozygous mice performed well on challenging cognitive tasks. In contrast, while heterozygous mice did not exhibit clear anatomical or behavioral differences, they displayed dysregulation of neuronal genes and altered neuronal morphology that was strikingly different from homozygous phenotypes. Collectively, these data reveal how alterations to PRC2 function shape the mature brain and reveal a dose-specific role for PRC2 in determining glutamatergic neuron identity., (© The Author(s) 2024. Published by Oxford University Press.)

Nuclear factor one X (NFIX) is a transcription factor required for normal ependymal development. Constitutive loss of Nfix in mice ( Nfix -/- ) is associated with hydrocephalus and sloughing of the dorsal ependyma within the lateral ventricles. Previous studies have implicated NFIX in the transcriptional regulation of genes encoding for factors essential to ependymal development. However, the cellular and molecular mechanisms underpinning hydrocephalus in Nfix -/- mice are unknown. To investigate the role of NFIX in hydrocephalus, we examined ependymal cells in brains from postnatal Nfix -/- and control ( Nfix +/+ ) mice using a combination of confocal and electron microscopy. This revealed that the ependymal cells in Nfix -/- mice exhibited abnormal cilia structure and disrupted localisation of adhesion proteins. Furthermore, we modelled ependymal cell adhesion using epithelial cell culture and revealed changes in extracellular matrix and adherens junction gene expression following knockdown of NFIX . Finally, the ablation of Nfix from ependymal cells in the adult brain using a conditional approach culminated in enlarged ventricles, sloughing of ependymal cells from the lateral ventricles and abnormal localisation of adhesion proteins, which are phenotypes observed during development. Collectively, these data demonstrate a pivotal role for NFIX in the regulation of cell adhesion within ependymal cells of the lateral ventricles.

Members of the nuclear factor I (NFI) family are key regulators of stem cell biology during development, with well-documented roles for NFIA, NFIB, and NFIX in a variety of developing tissues, including brain, muscle, and lung. Given the central role these factors play in stem cell biology, we posited that they may be pivotal for spermatogonial stem cells or further developing spermatogonia during testicular development. Surprisingly, in stark contrast to other developing organ systems where NFI members are co-expressed, these NFI family members show discrete patterns of expression within the seminiferous tubules. Sertoli cells (spermatogenic supporting cells) express NFIA, spermatocytes express NFIX, round spermatids express NFIB, and peritubular myoid cells express each of these three family members. Further analysis of NFIX expression during the cycle of the seminiferous epithelium revealed expression not in spermatogonia, as we anticipated, but in spermatocytes. These data suggested a potential role for NFIX in spermatogenesis. To investigate, we analyzed mice with constitutive deletion of Nfix (Nfix-null). Assessment of germ cells in the postnatal day 20 (P20) testes of Nfix-null mice revealed that spermatocytes initiate meiosis, but zygotene stage spermatocytes display structural defects in the synaptonemal complex, and increased instances of unrepaired DNA double-strand breaks. Many developing spermatocytes in the Nfix-null testis exhibited multinucleation. As a result of these defects, spermatogenesis is blocked at early diplotene and very few round spermatids are produced. Collectively, these novel data establish the global requirement for NFIX in correct meiotic progression during the first wave of spermatogenesis., (© The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Within the adult mammalian central nervous system, the ventricular-subventricular zone (V-SVZ) lining the lateral ventricles houses neural stem cells (NSCs) that continue to produce neurons throughout life. Developmentally, the V-SVZ neurogenic niche arises during corticogenesis following the terminal differentiation of telencephalic radial glial cells (RGCs) into either adult neural stem cells (aNSCs) or ependymal cells. In mice, these two cellular populations form rosettes during the late embryonic and early postnatal period, with ependymal cells surrounding aNSCs. These aNSCs and ependymal cells serve a number of key purposes, including the generation of neurons throughout life (aNSCs), and acting as a barrier between the CSF and the parenchyma and promoting CSF bulk flow (ependymal cells). Interestingly, the development of this neurogenic niche, as well as its ongoing function, has been shown to be reliant on different aspects of lipid biology. In this review we discuss the developmental origins of the rodent V-SVZ neurogenic niche, and highlight research which has implicated a role for lipids in the physiology of this part of the brain. We also discuss the role of lipids in the maintenance of the V-SVZ niche, and discuss new research which has suggested that alterations to lipid biology could contribute to ependymal cell dysfunction in aging and disease., (Copyright © 2020 Elsevier Ltd. All rights reserved.)