Visualization of the entire differentiation process of murine M cells : suppression of their maturation in cecal patches

The microfold (M) cell residing in the follicle-associated epithelium is a specialized epithelial cell that initiates mucosal immune responses by sampling lumina! antigens. The differentiation process of M cells remains unclear due to limitations of analytical methods. Here we found that M cells were classified into two functionally different subtypes based on the expression of Glycoprotein 2 (GP2) by newly developed image cytometric analysis. GP2-high M cells actively took up luminal microbeads, whereas GP2-negative or low cells scarcely ingested them, even though both subsets equally expressed the other M-cell signature genes, suggesting that GP2-high M cells represent functionally mature M cells. Further, the GP2-high mature M cells were abundant in Peyer's patch but sparse in the cecal patch: this was most likely due to a decrease in the nuclear translocation of RelB, a downstream transcription factor for the receptor activator of nuclear factor-kappa B signaling. Given that murine cecum contains a protrusion of beneficial commensals, the restriction of M-cell activity might contribute to preventing the onset of any excessive immune response to the commensals through decelerating the M-cell-dependent uptake of microorganisms

Distinct Roles for the N- and C-terminal Regions of M-Sec in Plasma Membrane Deformation during Tunneling Nanotube Formation

The tunneling nanotube (TNT) is a structure used for intercellular communication, and is a thin membrane protrusion mediating transport of various signaling molecules and cellular components. M-Sec has potent membrane deformation ability and induces TNT formation in cooperation with the Ral/exocyst complex. Here, we show that the N-terminal polybasic region of M-Sec directly binds phosphatidylinositol (4,5)-bisphosphate for its localization to the plasma membrane during the initial stage of TNT formation. We further report a crystal structure of M-Sec, which consists of helix bundles arranged in a straight rod-like shape, similar to the membrane tethering complex subunits. A positively charged surface in the C-terminal domains is required for M-Sec interaction with active RalA to extend the plasma membrane protrusions. Our results suggest that the membrane-associated M-Sec recruits active RalA, which directs the exocyst complex to form TNTs

Crystallization and preliminary neutron diffraction studies of HIV-1 protease cocrystallized with inhibitor KNI-272

In order to determine the protonation states of the residues within the active site of an HIV-1 protease–inhibitor complex, a crystal of HIV-1 protease complexed with inhibitor (KNI-272) was grown to a size of 1.4 mm3 for neutron diffraction study. The crystal diffracted to 2.3 Å resolution with sufficient quality for further structure determination

Pionic atom unveils hidden structure of QCD vacuum

Modern theories of physics tell that the vacuum is not an empty space. Hidden in the vacuum is a structure of anti-quarks $\bar{q}$ and quarks $q$. The $\bar{q}$ and $q$ pair has the same quantum number as the vacuum and condensates in it since the strong interaction of the quantum chromodynamics (QCD) is too strong to leave it empty. The $\bar{q}q$ condensation breaks the chiral symmetry of the vacuum. The expectation value $$ is an order parameter. For higher temperature or higher matter-density, $||$ decreases reflecting the restoration of the symmetry. In contrast to these clear-cut arguments, experimental evidence is so far limited. First of all, the $\bar{q}q$ is nothing but the vacuum itself. It is neither visible nor perceptible. In this article, we unravel this invisible existence by high precision measurement of pionic atoms, $\pi^-$-meson-nucleus bound systems. Using the $\pi^-$ as a probe, we demonstrate that $||$ is reduced in the nucleus by a factor of 58 $\pm$ 4% compared with that in the vacuum. This reduction indicates that the chiral symmetry is partially restored due to the extremely high density of the nucleus. The present experimental result clearly exhibits the existence of the hidden structure, the chiral condensate, in the vacuum