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特集：弔いと想起・語

Pcdhβ deficiency affects hippocampal CA1 ensemble activity and contextual fear discrimination

Clustered protocadherins (Pcdhs), a large group of adhesion molecules, are important for axonal projections and dendritic spread, but little is known about how they influence neuronal activity. The Pcdhβ cluster is strongly expressed in the hippocampus, and in vivo Ca2+ imaging in Pcdhβ-deficient mice revealed altered activity of neuronal ensembles but not of individual cells in this region in freely moving animals. Specifically, Pcdhβ deficiency increased the number of large-size neuronal ensembles and the proportion of cells shared between ensembles. Furthermore, Pcdhβ-deficient mice exhibited reduced repetitive neuronal population activity during exploration of a novel context and were less able to discriminate contexts in a contextual fear conditioning paradigm. These results suggest that one function of Pcdhβs is to modulate neural ensemble activity in the hippocampus to promote context discrimination

Extracellular Release of ILEI/FAM3C and Amyloid-β Is Associated with the Activation of Distinct Synapse Subpopulations.

Background:Brain amyloid-β (Aβ) peptide is released into the interstitial fluid (ISF) in a neuronal activity-dependent manner, and Aβ deposition in Alzheimer\u27s disease (AD) is linked to baseline neuronal activity. Although the intrinsic mechanism for Aβ generation remains to be elucidated, interleukin-like epithelial-mesenchymal transition inducer (ILEI) is a candidate for an endogenous Aβ suppressor.Objective:This study aimed to access the mechanism underlying ILEI secretion and its effect on Aβ production in the brain.Methods:ILEI and Aβ levels in the cerebral cortex were monitored using a newly developed ILEI-specific ELISA and in vivo microdialysis in mutant human Aβ precursor protein-knockin mice. ILEI levels in autopsied brains and cerebrospinal fluid (CSF) were measured using ELISA.Results:Extracellular release of ILEI and Aβ was dependent on neuronal activation and specifically on tetanus toxin-sensitive exocytosis of synaptic vesicles. However, simultaneous monitoring of extracellular ILEI and Aβ revealed that a spontaneous fluctuation of ILEI levels appeared to inversely mirror that of Aβ levels. Selective activation and inhibition of synaptic receptors differentially altered these levels. The evoked activation of AMPA-type receptors resulted in opposing changes to ILEI and Aβ levels. Brain ILEI levels were selectively decreased in AD. CSF ILEI concentration correlated with that of Aβ and were reduced in AD and mild cognitive impairment.Conclusion:ILEI and Aβ are released from distinct subpopulations of synaptic terminals in an activity-dependent manner, and ILEI negatively regulates Aβ production in specific synapse types. CSF ILEI might represent a surrogate marker for the accumulation of brain Aβ

Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Turn allocation in Japanese business meetings : emergence of institutionality

Ph.D. University of Hawaii at Manoa 2012.Includes bibliographical references.This dissertation uses conversation analysis as a theoretical and methodological framework to examine the organization of in-house business meetings that are conducted in Japanese. In particular, this study focuses on how institutionality becomes apparent within the participants' interactions. The data consists of six videotaped in-house meetings: three departmental staff meetings (bukai) and three interdepartmental meetings (kaigi.) The members' distinction between the two types of meeting is found to be crucial in this study. Using video-recordings of the business meetings, this study provides a detailed description of the participants' moment-to-moment interactional practices, even when no verbal interaction is involved. The first objective of this study is twofold: (a) to investigate how participants orient to the boundaries that mark the beginnings and endings of meetings, and (b) to identify what members do (or do not do) during the pre-meeting period. It is common among the meetings in the data for the chairpersons to mark explicitly both a meeting's opening and closing. However, the patterns of premeeting organization differ between the two types of meetings. Meetings in institutional settings tend to have a pre-established turn allocation system. The second objective of the present study is to investigate how precisely a turn-allocation system is operated in Japanese business meetings, and where the institutionality of the interaction emerges in that process. Identifying how reporters acquire their report turns, this study examines turn-allocation patterns specific to the reporting activities at meetings. It is also shown that the patterns of turn-allocation differ between the two types of meetings and that they depend upon the way in which a topic is provided. Through close observation of the participants' interactional practices, including their gaze and bodily movements, this study highlights the interactional patterns that are either common to all the in-house business meetings or particular to a type of meeting in the data. It is hoped that this study will not only yield insights into how meetings are organized in a Japanese business context, but will also promote a multimodal approach (as typified by the use of video-recorded data) to research on business interaction in Japanese

Alcam-a and Pdgfr-α are essential for the development of sclerotome-derived stromal cells that support hematopoiesis

International audienceAbstract Mesenchymal stromal cells are essential components of hematopoietic stem and progenitor cell (HSPC) niches, regulating HSPC proliferation and fates. Their developmental origins are largely unknown. In zebrafish, we previously found that the stromal cells of the caudal hematopoietic tissue (CHT), a niche functionally homologous to the mammalian fetal liver, arise from the ventral part of caudal somites. We have now found that this ventral domain is the sclerotome, and that two markers of mammalian mesenchymal stem/stromal cells, Alcam and Pdgfr-α, are distinctively expressed there and instrumental for the emergence and migration of stromal cell progenitors, which in turn conditions the proper assembly of the vascular component of the CHT niche. Furthermore, we find that trunk somites are similarly dependent on Alcam and Pdgfr-α to produce mesenchymal cells that foster HSPC emergence from the aorta. Thus the sclerotome contributes essential stromal cells for each of the key steps of developmental hematopoiesis

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Alcam-a and Pdgfr-α are essential for the development of sclerotome derived stromal cells that support hematopoiesis in vivo.

Posté sur Research Square le 2 mars 2022Mesenchymal stromal cells are essential components of hematopoietic stem and progenitor cell (HSPC) niches, regulating HSPC proliferation and fate decisions. Their developmental origins are largely unknown. In zebrafish, we previously found that the stromal cells of the caudal hematopoietic tissue (CHT), a niche functionally homologous to the fetal liver in mammals, arise from the ventral part of caudal somites. We have now discovered that this ventral domain is actually the sclerotome, and that two typical markers of mammalian mesenchymal stem/stromal cells, Alcam and Pdgfr-α, are distinctively expressed there and instrumental for the emergence and migration of stromal cell progenitors, which in turn conditions the proper assembly of the vascular component of the CHT niche. Furthermore, we find that the trunk somites are similarly dependent on Alcam and Pdgfr-α to produce mesenchymal stromal cells that foster the initial emergence of HSPCs from the dorsal aorta. Thus the sclerotome contributes essential stromal cells for each of the key steps of developmental hematopoiesis, and likely is the embryological origin of most if not all mesenchymal stem/stromal cells found in non-cephalic tissues