Allosteric inhibition of IgE-FcεRI interactions by simultaneous targeting of IgE F(ab')2 epitopes.

Immunoglobulin E (IgE) plays pivotal roles in allergic diseases through interaction with a high-affinity receptor (FcεRI). We established that Fab fragments of anti-IgE antibodies (HMK-12 Fab) rapidly dissociate preformed IgE-FcεRI complexes in a temperature-dependent manner and inhibit IgE-mediated anaphylactic reactions, even after allergen challenge. X-ray crystallographic studies revealed that HMK-12 Fab interacts with each of two equivalent epitopes on the Cε2 homodimer domain involved in IgE F(ab')2.

Impact of maternal dietary gut microbial metabolites on an offspring's systemic immune response in mouse models.

The gut microbiota has a great impact on the host immune systems. Recent evidence suggests that the maternal gut microbiota affects the immune systems of offspring. Metabolites produced by the gut microbiota play crucial roles in the immune system.

A fast and convenient solid phase preparation method for releasing N-glycans from glycoproteins using trypsin- and peptide-N-glycosidase F (PNGase F)-impregnated polyacrylamide gels fabricated in a pipette tip.

An efficient deglycosylation process is a key requirement for the identification and characterization of glycosylation during the production and purification of therapeutic antibodies. PNGase F is widely used for the deglycosylation of N-linked glycans. The commonly-used in-solution deglycosylation method is relatively time-consuming and requires several hours up to overnight for complete removal of all N-linked glycans.

The Fab fragment of anti-IgE Cε2 domain prevents allergic reactions through interacting with IgE-FcεRIα complex on rat mast cells.

Immunoglobulin E (IgE) plays a central role in the pathogenesis of Type I hypersensitivity through interaction with a high-affinity receptor (FcεRIα). For therapeutic applications, substantial attention has been focused recently on the blockade of the IgE interaction with FcεRIα. While exploring better options for preventing allergic diseases, we found that the Fab fragment of the rat anti-murine IgE antibody (Fab-6HD5) strongly inhibited passive cutaneous anaphylaxis (PCA) in vivo, as well as spleen tyrosine kinase (Syk) activity and β-hexosaminidase release from basophilic leukemia cells in vitro.

Mesenchymal cell differentiation and diseases: involvement of translin/TRAX complexes and associated proteins.

Translin and translin-associated factor X (translin/TRAX) proteins have been implicated in a variety of cellular activities central to nucleic acid metabolism. Accumulating evidence indicates that translin/TRAX complexes participate in processes ensuring the replication of DNA, as well as cell division. Significant progress has been made in understanding the roles of translin/TRAX complexes in RNA metabolism, such as through RNA-induced silencing complex activation or the microRNA depletion that occurs in Dicer deficiency.

Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation.

A specialized bone marrow microenvironment (niche) regulates hematopoietic stem cell (HSC) self-renewal and commitment. For successful donor-HSC engraftment, the niche must be emptied via myeloablative irradiation or chemotherapy. However, myeloablation can cause severe complications and even mortality.

The zinc finger transcription factor RP58 negatively regulates Rnd2 for the control of neuronal migration during cerebral cortical development.

The zinc finger transcription factor RP58 (also known as ZNF238) regulates neurogenesis of the mouse neocortex and cerebellum (Okado et al. 2009; Xiang et al. 2011; Baubet et al.

RP58 regulates the multipolar-bipolar transition of newborn neurons in the developing cerebral cortex.

Accumulating evidence suggests that many brain diseases are associated with defects in neuronal migration, suggesting that this step of neurogenesis is critical for brain organization. However, the molecular mechanisms underlying neuronal migration remain largely unknown. Here, we identified the zinc-finger transcriptional repressor RP58 as a key regulator of neuronal migration via multipolar-to-bipolar transition.

RP58 controls neuron and astrocyte differentiation by downregulating the expression of Id1-4 genes in the developing cortex.

Appropriate number of neurons and glial cells is generated from neural stem cells (NSCs) by the regulation of cell cycle exit and subsequent differentiation. Although the regulatory mechanism remains obscure, Id (inhibitor of differentiation) proteins are known to contribute critically to NSC proliferation by controlling cell cycle. Here, we report that a transcriptional factor, RP58, negatively regulates all four Id genes (Id1-Id4) in developing cerebral cortex.

Dendritic trafficking of brain-derived neurotrophic factor mRNA: regulation by translin-dependent and -independent mechanisms.

Dendritic trafficking and translation of brain-derived neurotrophic factor (BDNF) transcripts play a key role in mediating synaptic plasticity. Recently, we demonstrated that siRNA-mediated knockdown of translin, an RNA-binding protein, impairs KCl-induced dendritic trafficking of BDNF mRNA in cultured hippocampal neurons. We have now assessed whether translin deletion impairs dendritic trafficking of BDNF mRNA in hippocampal neurons in vivo.

A systems approach reveals that the myogenesis genome network is regulated by the transcriptional repressor RP58.

We created a whole-mount in situ hybridization (WISH) database, termed EMBRYS, containing expression data of 1520 transcription factors and cofactors expressed in E9.5, E10.5, and E11.

The transcriptional repressor RP58 is crucial for cell-division patterning and neuronal survival in the developing cortex.

The neocortex and the hippocampus comprise several specific layers containing distinct neurons that originate from progenitors at specific development times, under the control of an adequate cell-division patterning mechanism. Although many molecules are known to regulate this cell-division patterning process, its details are not well understood. Here, we show that, in the developing cerebral cortex, the RP58 transcription repressor protein was expressed both in postmitotic glutamatergic projection neurons and in their progenitor cells, but not in GABAergic interneurons.

Contribution of Translin to hematopoietic regeneration after sublethal ionizing irradiation.

The integrity of the genome is threatened by DNA damaging events such as radiation, viral infection and chemicals. Ionizing irradiation is known to cause genotoxic damage through the generation of reactive oxygen species (ROS) and nitrogen species (RNS) and we have found that a signaling pathway for the nuclear translocation of Translin is initiated in association and efficiently blocked by a specific inhibitor of nitric oxide synthase (NOS). This suggests the involvement of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) in the nuclear translocation of Translin.

Spatial and temporal expression of RP58, a novel zinc finger transcriptional repressor, in mouse brain.

RP58, a novel zinc finger protein containing a POZ domain, is a sequence-specific transcriptional repressor. To understand the role of this protein, we examined RP58 gene expression in the developing mouse brain by quantitative polymerase chain reaction (PCR) and in situ hybridization. RP58 mRNA expression was detected at embryonic day (E) 10 in the neuroepithelium, and subsequently in the ventricular zones of the cerebral cortex in the E12 embryo.

Immunological detection of severe acute respiratory syndrome coronavirus by monoclonal antibodies.

In order to establish immunological detection methods for severe acute respiratory syndrome coronavirus (SARS-CoV), we established monoclonal antibodies directed against structural components of the virus. B cell hybridomas were generated from mice that were hyper-immunized with inactivated SARS-CoV virion. By screening 2,880 generated hybridomas, we established three hybridoma clones that secreted antibodies specific for nucleocapsid protein (N) and 27 clones that secreted antibodies specific for spike protein (S).

A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice.

The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant.

Structure of human translin at 2.2 A resolution.

The structure of human translin at 2.2 A resolution is reported in space group C222(1). Translin forms a tetramer in the asymmetric unit.

A role for the octameric ring protein, Translin, in mitotic cell division.

The octameric ring protein, Translin, demonstrates marked similarities to the family of helicase enzymes regarding its quaternary organization and dimerization of subunits. Here we show that the level of Translin closely parallels the proliferative state in various cell types. Expression is periodic during the cell cycle, with protein synthesis becoming maximal in the S and mitosis phases, consistent with a role in cell division.