25 research outputs found

    Gate Switchable Transport and Optical Anisotropy in 90° Twisted Bilayer Black Phosphorus

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    Anisotropy describes the directional dependence of a material’s properties such as transport and optical response. In conventional bulk materials, anisotropy is intrinsically related to the crystal structure and thus not tunable by the gating techniques used in modern electronics. Here we show that, in bilayer black phosphorus with an interlayer twist angle of 90°, the anisotropy of its electronic structure and optical transitions is tunable by gating. Using first-principles calculations, we predict that a laboratory-accessible gate voltage can induce a hole effective mass that is 30 times larger along one Cartesian axis than along the other axis, and the two axes can be exchanged by flipping the sign of the gate voltage. This gate-controllable band structure also leads to a switchable optical linear dichroism, where the polarization of the lowest-energy optical transitions (absorption or luminescence) is tunable by gating. Thus, anisotropy is a tunable degree of freedom in twisted bilayer black phosphorus

    Ta3 interacts with Cep120 in the cell. FLAG-Cep120 was coexpressed with Ta3 (A) or various Ta3 mutants (B, C) in HEK293 cells as indicated.

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    <p>The protein lysates made from the cells were subjected to immunoblot (IB) or immunoprecipitation (IP) followed by immunoblot with the indicated antibodies. Note that the interaction of Cep120 with Ta3 requires the coil-coiled (CC) domain of Ta3 (B, C).</p

    Loss of Cep120 results in early embryonic lethality, hydrocephalus, and cerebellar hypoplasia in mice.

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    <p>(A) The gene targeting strategy used to create mouse <i>Cep120<sup>-</sup></i> and <i>Cep120<sup>f</sup></i> mutant alleles. Open rectangles refer to exons (which are numbered), lines to introns, grey rectangles to Frt sites, and triangles to loxP sites. BglII (Bg) restriction sites and a probe for Southern blot are indicated. Neo, neomycin gene; DTA, diphtheria toxin A gene. (B) Southern blot analysis shows a representative mutant and wild type (wt) ES cell clones. (C) Lateral view of wild type and <i>Cep120<sup>-/-</sup></i> embryos. Note that the development of Cep120 mutant embryos is delayed and the heart loops in the opposite direction (indicated by the arrow). (D–G) Morphology of two-week-old (P14) unskinned mouse heads (D), brains (E, F), and cerebellums (G), with indicated genotypes. The lines are in the same length for both wt and mutant, thus indicating the relative brain size or the extent of hydrocephalus in the mutant. Hematoxylin and eosin (H&E) staining of sagittal brain sections (E) confirms that the mutant ventricles of the brain are severely dilated. The boxed area in F is enlarged in (G). Cerebellums are outlined. The mutant cerebellum is significantly smaller (F).</p

    The Cep120 mutation results in cerebellar hypoplasia.

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    <p>Sagittal sections of P1, P7, and P14 wild type and <i>Cep120<sup>f/-</sup></i>; <i>nes-Cre</i> mutant cerebellums were stained with cresyl violet. Framed areas are enlarged in the corresponding lower panels. EGL, external granule cell layer; PCL, Purkinje cell layer; ML, molecular layer; and IGL, inner granule layer.</p

    Loss of Cep120 results in failed expansion of granule neuron progenitors (GNPs), due to lack of a response to Hedgehog signaling.

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    <p>(A–F) Sagittal sections of P1, P7, and P14 wild type and mutant cerebellums were coimmunostained for Pax6 (red), Calb1 (green), and nuclei (DAPI, blue). Pax6 and Calb1 label GNPs and Purkinje cells, respectively. Framed areas in panels A–F are enlarged in A′–F′. EGL, external granule cell layer; PCL, Purkinje cell layer; ML, molecular layer; IGL, inner granule layer. Genotypes are shown to the left. (G–H) LacZ staining of the P7 cerebellum is positive in wild type animals (G), but negative in the Cep120 mutant (H). Genotypes are indicated on both sides. Cerebellums are outlined, and cerebellar posterior lobes are indicated by asterisks.</p

    Site-Specific Quantification of Protein Ubiquitination on MS2 Fragment Ion Level via Isobaric Peptide Labeling

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    Proteome-wide quantitative analysis of protein ubiquitination is important to gain insight into its various cellular functions. However, it is still challenging to monitor how ubiquitination at each individual lysine residue is independently regulated, especially the whereabouts of peptides containing more than one ubiquitination site. In recent years, isobaric peptide termini labeling has been considered a promising strategy in quantitative proteomics, benefiting from its high accuracy by quantifying with a series of b, y fragment ion pairs. Herein, we extended the concept of isobaric peptide termini labeling to large-scale quantitative analysis of protein ubiquitination. A novel MS2 fragment ion based quantitative approach was developed, allowing the quantification of ubiquitination at site level via isobaric K-ε-GG peptide labeling, which combined metabolic labeling, K-ε-GG immunoaffinity enrichment, and site-selective N-terminus dimethylation. The feasibility of this proposed strategy was demonstrated through the ubiquitin proteome analysis of differently labeled MCF-7 cell digests. As a result, 2970 unique K-ε-GG peptides of 1383 proteins containing 2874 ubiquitinated sites were confidently quantified with high accuracy and sensitivity. In addition, we demonstrated that quantification on MS2 fragment ion level makes it possible to precisely quantify each individual ubiquitinated lysine residue in 39 K-ε-GG peptides bearing two ubiquitination sites by the use of specific ubiquitinated b, y ion pairs. It is expected that this proposed approach will serve as a powerful tool to quantify ubiquitination at the site level, especially for those multiubiquitinated peptides

    Failed centriole duplication, maturation, and ciliogenesis in cerebellar granule neuron progenitors (CGNPs) and ependymal cells in the Cep120 mutant.

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    <p>(A–D) Sagittal brain sections of P14 mice with the indicated genotypes were coimmunostained for acetylated α ˜tubulin and Arl13b, cilia markers. The fourth ventricular choroid plexus is circled. Framed areas in panels A and B are enlarged in A′/A″ and B′/B″. Panels A″ and B″ show representative areas of ependyma near the fourth ventricle. Panels C and D show representative areas of CGNPs. Arrowheads indicate representative cilia. Note that cilia develop in the <i>Cep120<sup>f/-</sup></i>; <i>nes-Cre</i> choroid plexus, but not in ependymal cells and CGNPs. (G–L) Sagittal cerebellar sections of P14 mice with the indicated genotypes were coimmunostained for γ ˜tubulin and Cep120, Odf2, or Ta3, as shown. Note that very few centrioles are present in <i>Cep120<sup>f/-</sup></i>; <i>nes-Cre</i> CGNPs, relative to wild type CGNPs. Arrowheads indicate one or two representative centrioles in each panel.</p

    Ta3 is required for asymmetrical localization of Cep120 to the daughter centriole.

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    <p>Wild type and <i>Ta3</i> mutant primary mouse embryonic fibroblasts (pMEFs) were coimmunostained for Cep120 and γ ˜tubulin (A) or Odf2 and Cep120 (B), together with DAPI (for nuclei). Arrowheads indicate the specific staining at centrioles. The Cep120 signal at the daughter and mother centrioles (DC and MC, respectively) was quantified for 21 randomly chosen cells, using NIH image J. Cep120 signal ratios were then calculated, specifically the DC to MC ratio and the wild type to Ta3 mutant ratio (average + standard deviation) (C). (D) No significant changes in Cep120 levels in <i>Ta3</i> mutant MEFs. Immunoblots show the expression of endogenous Ta3 and Cep120 in wild type and <i>Ta3</i> mutant MEFs, with tubulin as a loading control.</p

    Table_3_Histone Deacetylase Inhibitor Alleviates the Neurodegenerative Phenotypes and Histone Dysregulation in Presenilins-Deficient Mice.pdf

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    <p>Histone acetylation has been shown to play a crucial role in memory formation, and histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) has been demonstrated to improve memory performance and rescue the neurodegeneration of several Alzheimer’s Disease (AD) mouse models. The forebrain presenilin-1 and presenilin-2 conditional double knockout (cDKO) mice showed memory impairment, forebrain degeneration, tau hyperphosphorylation and inflammation that closely mimics AD-like phenotypes. In this article, we have investigated the effects of systemic administration of NaB on neurodegenerative phenotypes in cDKO mice. We found that chronic NaB treatment significantly restored contextual memory but did not alter cued memory in cDKO mice while such an effect was not permanent after treatment withdrawal. We further revealed that NaB treatment did not rescue reduced synaptic numbers and cortical shrinkage in cDKO mice, but significantly increased the neurogenesis in subgranular zone of dentate gyrus (DG). We also observed that tau hyperphosphorylation and inflammation related protein glial fibrillary acidic protein (GFAP) level were decreased in cDKO mice by NaB. Furthermore, GO and pathway analysis for the RNA-Seq data demonstrated that NaB treatment induced enrichment of transcripts associated with inflammation/immune processes and cytokine-cytokine receptor interactions. RT-PCR confirmed that NaB treatment inhibited the expression of inflammation related genes such as S100a9 and Ccl4 found upregulated in the brain of cDKO mice. Surprisingly, the level of brain histone acetylation in cDKO mice was dramatically increased and was decreased by the administration of NaB, which may reflect dysregulation of histone acetylation underlying memory impairment in cDKO mice. These results shed some lights on the possible molecular mechanisms of HDAC inhibitor in alleviating the neurodegenerative phenotypes of cDKO mice and provide a promising target for treating AD.</p

    Cep120 is required for centriole duplication and ciliogenesis.

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    <p>Wild type and <i>Cep120<sup>-/-</sup></i> pMEFs were coimmunostained for the indicated proteins. Most Cep120 mutant cells lacked either one or both centrioles, as indicated by γ ˜tubulin staining. Staining for Cep164, Ta3, and Odf2 showed that the missing centriole was the mother centriole. Staining for Arl13b and acetylated α ˜tubulin indicated no cilia being formed in Cep120 mutant cells. Arrowheads point to the staining of γ ˜tubulin (a centriole marker), the indicated proteins, or cilia.</p
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