Molecular and chemical genetic approaches to developmental origins of aging and disease in zebrafish

AbstractThe incidence of diseases increases rapidly with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but mostly inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states in response to different environmental or genetic perturbations. On the one hand, we hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds of adaptive plasticity by chemical genetic approaches, we have been investigating whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during embryogenesis (“embryonic senescence”), subsequently showing shortened lifespan in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes and small molecular compounds that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins of aging in vertebrates. This article is part of a Special Issue entitled: Animal Models of Disease

Room-Temperature Electron Spin Transport in a Highly Doped Si Channel

We report on the first demonstration of generating a spin current and spin transport in a highly doped Si channel at room temperature (RT) using a four-terminal lateral device with a spin injector and a detector consisting of an Fe/MgO tunnel barrier. Spin current was generated using a nonlocal technique, and spin injection signals and Hanle-type spin precession were successfully detected at 300 K, thus proving spin injection with the elimination of spurious signals. The spin diffusion length and its lifetime at RT were estimated to be 0.6 \"im and 1.3 ns by the Hanle-type spin precession, respectively.Comment: 14 pages, 4 Figure

Note on the spectrum of discrete Schrodinger operators

The spectrum of discrete Schrödinger operator L + V on the d-dimensional lattice is considered, where L denotes the discrete Laplacian and V a delta function with mass at a single point. Eigenvalues of L + V are specified and the absence of singular continuous spectrum is proven. In particular it is shown that an embedded eigenvalue does appear for d ≥ 5 but does not for 1 ≤ d ≤ 4.ArticleJournal of Math-for-Industry. 4(2012B-4):105-108 (2012)journal articl

Suppression of Borna Disease Virus Replication during Its Persistent Infection Using the CRISPR/Cas13b System

Borna disease virus (BoDV-1) is a bornavirus that infects the central nervous systems of various animal species, including humans, and causes fatal encephalitis. BoDV-1 also establishes persistent infection in neuronal cells and causes neurobehavioral abnormalities. Once neuronal cells or normal neural networks are lost by BoDV-1 infection, it is difficult to regenerate damaged neural networks. Therefore, the development of efficient anti-BoDV-1 treatments is important to improve the outcomes of the infection. Recently, one of the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) systems, CRISPR/Cas13, has been utilized as antiviral tools. However, it is still unrevealed whether the CRISPR/Cas13 system can suppress RNA viruses in persistently infected cells. In this study, we addressed this question using persistently BoDV-1-infected cells. The CRISPR/Cas13 system targeting viral mRNAs efficiently decreased the levels of target viral mRNAs and genomic RNA (gRNA) in persistently infected cells. Furthermore, the CRISPR/Cas13 system targeting viral mRNAs also suppressed BoDV-1 infection if the system was introduced prior to the infection. Collectively, we demonstrated that the CRISPR/Cas13 system can suppress BoDV-1 in both acute and persistent infections. Our findings will open the avenue to treat prolonged infection with RNA viruses using the CRISPR/Cas13 system

Spin Drift in Highly Doped n-type Si

A quantitative estimation of spin drift velocity in highly doped n-type silicon (Si) at 8 K is presented in this letter. A local two-terminal Hanle measurement enables the detection of a modulation of spin signals from the Si as a function of an external electric field, and this modulation is analyzed by using a spin drift-diffusion equation and an analytical solution of the Hanle-type spin precession. The analyses reveal that the spin drift velocity is linearly proportional to the electric field. The contribution of the spin drift effect to the spin signals is crosschecked by introducing a modified nonlocal four-terminal method.Comment: 16 pages, 3 figure