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Background: Hearing preservation after large vestibular schwannoma (VS) removal is challenging and the long‑term outcomes of postoperatively preserved hearing have not been elucidated. Objective: We aimed to clarify long‑term outcomes of hearing preservation after the retrosigmoid large VS removal and to recommend a strategy for treating large VS. Materials and Methods: Hearing preservation with total/nearly total (T/NT) tumor removal was accomplished in six of 129 patients who underwent retrosigmoid large VS (≥3 cm) removal. We evaluated the long‑term outcomes of these six patients. Results: Preoperative hearing of these six patients was 15–68 dB by pure tone audiometry (PTA) (Class I: 2, II: 3, and III: 1 by the Gardner‑Robertson (GR) classification). Postoperatively, magnetic resonance imaging (MRI) with gadolinium administration confirmed T/NT removal, the preserved hearing was 36–88 dB (Class II: 4 and III: 2), and no facial palsy occurred. After long‑term follow‑up (8–16 [median: 11.5] years), five patients maintained hearing of 46–75 dB (Class II: 1 and III: 4) while one lost hearing. Three patients showed small tumor recurrence on MRI; two recurrences were controlled by gamma knife (GK) and one showed minimal change only by observation. Conclusions: Hearing preserved after T/NT removal of large VS is maintained for a long time (>10 years), though tumor recurrence on MRI is somewhat common. Detecting small recurrence early, and regular MRI follow‑up contributes to the long‑term maintenance of hearing. Hearing preservation with tumor removal is a challenging yet worthwhile strategy in large VS patients with preoperative hearing. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study which examines the role of fission yeast leucine-rich repeat protein Lrp1 in the morphogenesis of cell. The authors explained that cell morphogenesis is coordinately regulated in eukaryotes with cell cycle. They showed that Lrp1 is vital for cell growth and cell morphogenesis as a recognized component of morphogenesis Orb6 network. The localization of Lrp1 to the spindle pole bodies and its interaction with protein Nak1 are explained.

AbstractThe process of aging involves the accumulating changes in the microenvironment that lead to cell senescence or apoptosis, and subsequent tissue or organ dysfunction. Multiple extrinsic and intrinsic events that cause DNA instability are associated with aging. Cells containing unstable DNA are biologically vulnerable, and if the DNA damage is too great for the cell to repair, it becomes senescent or dies by apoptosis. Thus, the cell’s capacity to repair its DNA determines the progress of aging, at least in part. Here, we focus on the sirtuins, the mammalian homologs of the yeast life-span-extending molecule, Sir2. Among the sirtuin family proteins in mammals, the one most similar to yeast Sir2 is SIRT1, which is involved in multiple pathways, including the repair of DNA double-strand breaks. Although the role of SIRT1 in mammalian longevity is not clear, it is expressed throughout the retina, where it may suppress aging. In fact, a mutant mouse model of retinal degeneration shows an abnormal subcellular localization of SIRT1 protein and accelerated retinal cell apoptosis. Further analyses are required to elucidate the mechanism of DNA damage and repair, including the contributions of the sirtuins, in the aged or diseased retinas, which will help us understand the mechanisms of retinal aging.Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Leber congenital amaurosis type nine is an autosomal recessive retinopathy caused by mutations of the NAD+ synthesis enzyme NMNAT1. Despite the ubiquitous expression of NMNAT1, patients do not manifest pathologies other than retinal degeneration. Here we demonstrate that widespread NMNAT1 depletion in adult mice mirrors the human pathology, with selective loss of photoreceptors highlighting the exquisite vulnerability of these cells to NMNAT1 loss. Conditional deletion demonstrates that NMNAT1 is required within the photoreceptor. Mechanistically, loss of NMNAT1 activates the NADase SARM1, the central executioner of axon degeneration, to trigger photoreceptor death and vision loss. Hence, the essential function of NMNAT1 in photoreceptors is to inhibit SARM1, highlighting an unexpected shared mechanism between axonal degeneration and photoreceptor neurodegeneration. These results define a novel SARM1-dependent photoreceptor cell death pathway and identifies SARM1 as a therapeutic candidate for retinopathies. [ABSTRACT FROM AUTHOR]

Nicotinamide adenine dinucleotide (NAD+) is an enzyme cofactor or cosubstrate in many essential biological pathways. To date, the primary source of neuronal NAD+ has been unclear. NAD+ can be synthesized from several different precursors, among which nicotinamide is the substrate predominantly used in mammals. The rate-limiting step in the NAD+ biosynthetic pathway from nicotinamide is performed by nicotinamide phosphoribosyltransferase (Nampt). Here, we tested the hypothesis that neurons use intracellular Nampt-mediated NAD+ biosynthesis by generating and evaluating mice lacking Nampt in forebrain excitatory neurons (CaMKIIαNampt-/- mice). CaMKIIαNampt-/- mice showed hippocampal and cortical atrophy, astrogliosis, microgliosis, and abnormal CA1 dendritic morphology by 2-3 months of age. Importantly, these histological changes occurred with altered intrahippocampal connectivity and abnormal behavior; including hyperactivity, some defects in motor skills, memory impairment, and reduced anxiety, but in the absence of impaired sensory processes or long-term potentiation of the Schaffer collateral pathway. These results clearly demonstrate that forebrain excitatory neurons mainly use intracellular Nampt-mediated NAD+ biosynthesis to mediate their survival and function. Studying this particular NAD+ biosynthetic pathway in these neurons provides critical insight into their vulnerability to pathophysiological stimuli and the development of therapeutic and preventive interventions for their preservation. [ABSTRACT FROM AUTHOR]