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Neuronal ensemble activity entrained by local field potential (LFP) patterns underlies a variety of brain functions, including emotion, cognition, and pain perception. Recent advances in machine learning approaches may enable more effective methods for analyzing LFP patterns across multiple brain areas than conventional time-frequency analysis. In this study, we tested the performance of two machine learning algorithms, AlexNet and the Transformer models, to classify LFP patterns in eight pain-related brain regions before and during acetic acid-induced visceral pain behaviors. Over short time windows lasting several seconds, applying AlexNet to LFP power datasets, but not to raw time-series LFP traces from multiple brain areas, successfully achieved superior classification performance compared with simple LFP power analysis. Furthermore, applying the Transformer directly to the raw LFP traces achieved significantly superior classification performance than AlexNet when using LFP power datasets. These results demonstrate the utility of the Transformer in the analysis of neurophysiological signals, and pave the way for its future applications in the decoding of more complex neuronal activity patterns. [ABSTRACT FROM AUTHOR]

For mucociliary clearance of pathogens, tracheal multiciliated epithelial cells (MCCs) organize coordinated beating of cilia, which originate from basal bodies (BBs) with basal feet (BFs) on one side. To clarify the self-organizing mechanism of coordinated intracellular BB-arrays composed of a well-ordered BB-alignment and unidirectional BB-orientation, determined by the direction of BB to BF, we generated double transgenic mice with GFP-centrin2-labeled BBs and mRuby3-Cep128-labeled BFs for long-term, high-resolution, dual-color live-cell imaging in primary-cultured tracheal MCCs. At early timepoints of MCC differentiation, BB-orientation and BB-local alignment antecedently coordinated in an apical microtubule-dependent manner. Later during MCC differentiation, fluctuations in BB-orientation were restricted, and locally aligned BB-arrays were further coordinated to align across the entire cell (BB-global alignment), mainly in an apical intermediate-sized filament-lattice-dependent manner. Thus, the high coordination of the BB-array was established for efficient mucociliary clearance as the primary defense against pathogen infection, identifying apical cytoskeletons as potential therapeutic targets. Synopsis: High-resolution live-cell imaging reveals the stepwise organization of ciliary basal body (BB) arrays in mouse tracheal multiciliated cells (MCCs), regulated by the apical cytoskeleton networks. A high-resolution, dual-color, live-cell imaging system is developed to monitor the dynamic organization of ciliary basal bodies (BBs) and basal feet (BF) in primary cultured mouse tracheal epithelial cells (MTECs). The unidirectional orientation of BB-BF and the alignment of BBs from local to global scales during the differentiation of multiciliated cells (MCCs) exhibit a stepwise organizational process. Apical microtubules (MTs) and apical intermediate filaments (IFs) provide stage-specific contributions to the organization of the basal body (BB) array. High-resolution live-cell imaging reveals the stepwise organization of ciliary basal body (BB) arrays in mouse tracheal multiciliated cells (MCCs), regulated by the apical cytoskeleton networks. [ABSTRACT FROM AUTHOR]

Blood–brain barrier (BBB) disruption contributes to brain injury and neurological impairment. Tight junctions (TJs) and cell–cell adhesion complexes develop between endothelial cells in the brain to establish and maintain the BBB. Occludin, the first transmembrane protein identified in TJs, has received intense research interest because numerous in vitro studies have suggested its importance in maintaining BBB integrity. However, its role in maintaining BBB integrity after ischemic stroke is less clear owing to the lack of in vivo evidence. This study aimed to investigate the dynamics and function of occludin across the acute and chronic phases after stroke using occludin-deficient mice. By photochemically induced thrombosis model, the expression of occludin was decreased in brain endothelial cells from ischemic lesions. The neurological function of occludin-deficient mice was continuously impaired compared to that of wild-type mice. BBB integrity evaluated by Evans blue and 0.5-kDa fluorescein in the acute phase and by 10-kDa fluorescein isothiocyanate-labeled dextran in the chronic phase was decreased to a greater extent after stroke in occludin-deficient mice. Furthermore, occludin-deficient mice showed decreased claudin-5 and neovascularization after stroke. Our study reveals that occludin plays an important role from the acute to the chronic phase after ischemic stroke in vivo. [ABSTRACT FROM AUTHOR]

This paper presents the 1000 ensemble flood simulations using ensemble rainfalls simulated by 4D LETKF. The number of ensemble rainfall members is large as 1000 compared to the operational rainfall products of two-digit numbers to avoid sampling errors in the three-dimensional meteorological simulation based on chaotic theory. Using the large data set, 1000 ensemble rainfall–runoff for dam catchments and high-resolution inundation simulations of large area are carried out focusing on the Kumagawa river catchment. Herewith, the comparisons were carried out with 21-member ensemble rainfalls of an operational forecast by Japan Meteorological Agency and 100-member 4D-LETKF ensemble rainfalls simulated independent of 1000-member 4D-LETKF. At the same time, the accuracy of selective 100-member ensembles out of 1000 members is investigated. As a result, although many previous research works show a large number of ensemble simulations are necessary for three-dimensional meteorological field, the number could be reduced in the catchment-average rainfall–runoff and 2.5-dimensional inundation simulations given that the rainfall prediction has a certain level of accuracy since improving the discharge prediction accuracy with lower dimension is sometimes possible by adjusting the horizontally/vertically integrated model parameters determined by topography and soil characteristics in advance against the observed rainfall. Also, the 1000 ensembles could be classified into several patterns in horizontally accumulated 2D rainfall field. Likewise, the flood flow moves toward the low elevation area and river; thus, the resultant 2.5-dimensional flood field does not show much variety as three-dimensional meteorological simulation. The paper summarizes these studies. [ABSTRACT FROM AUTHOR]

Cryptococcus deneoformans is an opportunistic fungal pathogen that infects the lungs via airborne transmission and frequently causes fatal meningoencephalitis. Claudins (Cldns), a family of proteins with 27 members found in mammals, form the tight junctions within epithelial cell sheets. Cldn-4 and 18 are highly expressed in airway tissues, yet the roles of these claudins in respiratory infections have not been clarified. In the present study, we analyzed the roles of Cldn-4 and lung-specific Cldn-18 (luCldn-18) in host defense against C. deneoformans infection. luCldn-18-deficient mice exhibited increased susceptibility to pulmonary infection, while Cldn-4-deficient mice had normal fungal clearance. In luCldn-18-deficient mice, production of cytokines including IFN-γ was significantly decreased compared to wild-type mice, although infiltration of inflammatory cells including CD4+ T cells into the alveolar space was significantly increased. In addition, luCldn-18 deficiency led to high K+ ion concentrations in bronchoalveolar lavage fluids and also to alveolus acidification. The fungal replication was significantly enhanced both in acidic culture conditions and in the alveolar spaces of luCldn-18-deficient mice, compared with physiological pH conditions and those of wild-type mice, respectively. These results suggest that luCldn-18 may affect the clinical course of cryptococcal infection indirectly through dysregulation of the alveolar space microenvironment. [ABSTRACT FROM AUTHOR]

The V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing. However, regulation of hair bundle arrangements has not been fully understood. Recently, defects in hair bundle arrangement were reported in postnatal Dishevelled-associating protein (ccdc88c, alias Daple)-deficient mice. In the present study, we found that adult Daple−/− mice exhibited hearing disturbances over a broad frequency range through auditory brainstem response testing. Consistently, distorted patterns of hair bundles were detected in almost all regions, more typically in the basal region of the cochlear duct. In adult Daple−/− mice, apical microtubules were irregularly aggregated, and the number of microtubules attached to plasma membranes was decreased. Similar phenotypes were manifested upon nocodazole treatment in a wild type cochlea culture without affecting the microtubule structure of the kinocilium. These results indicate critical role of Daple in hair bundle arrangement through the orchestration of apical microtubule distribution, and thereby in hearing, especially at high frequencies. [ABSTRACT FROM AUTHOR]

Apical constriction is critical for epithelial morphogenesis, including neural tube formation. Vertebrate apical constriction is induced by di‐phosphorylated myosin light chain (ppMLC)‐driven contraction of actomyosin‐based circumferential rings (CRs), also known as perijunctional actomyosin rings, around apical junctional complexes (AJCs), mainly consisting of tight junctions (TJs) and adherens junctions (AJs). Here, we revealed a ppMLC‐triggered system at TJ‐associated CRs for vertebrate apical constriction involving microtubules, LUZP1, and myosin phosphatase. We first identified LUZP1 via unbiased screening of microtubule‐associated proteins in the AJC‐enriched fraction. In cultured epithelial cells, LUZP1 was found localized at TJ‐, but not at AJ‐, associated CRs, and LUZP1 knockout resulted in apical constriction defects with a significant reduction in ppMLC levels within CRs. A series of assays revealed that ppMLC promotes the recruitment of LUZP1 to TJ‐associated CRs, where LUZP1 spatiotemporally inhibits myosin phosphatase in a microtubule‐facilitated manner. Our results uncovered a hitherto unknown microtubule‐LUZP1 association at TJ‐associated CRs that inhibits myosin phosphatase, contributing significantly to the understanding of vertebrate apical constriction. Synopsis: Apical cell constriction drives epithelial morphogenesis and is mediated by junctional actomyosin ring constriction in vertebrates. Here, the leucine zipper motif‐containing protein LUZP1 is found as a new regulator of this process via inhibition of myosin phosphatase activity at tight junction (TJ)‐associated circumferential rings (CRs). The microtubule‐associated protein LUZP1 localizes at TJ‐associated CRs.Di‐phosphorylated myosin light chain (ppMLC) promotes recruitment of LUZP1 to TJ‐associated CRs.LUZP1 inhibits myosin phosphatase to increase myosin light chain phosphorylation and promote CR contraction during apical constriction.Microtubules facilitate LUZP1‐mediated inhibition of myosin phosphatase activity. [ABSTRACT FROM AUTHOR]

Background: Forest management strategies such as thinning have long been used to enhance ecosystem functions, especially in plantations. Thinning in plantations with high deer density, however, may not yield a desired increase in understory vegetation because deer graze on germinating plants after thinning. Here, we examine the changes in understory vegetation after thinning in plantations that have been overgrazed by sika deer to provide insight into the effects of thinning on ecosystem functions such as soil conservation and biological diversity. Methods: We conducted our survey in the Tanzawa Mountains of eastern Japan. We surveyed the change in understory vegetation within and outside of three deer exclosures on a single slope with three levels of understory vegetation cover: sparse (1%, exclosure 'US'), moderate (30%, exclosure 'MM'), and dense (80%, exclosure 'LD') over 10 years after a 30% thinning of an old-growth cedar and cypress plantation which was overgrazed by sika deer. Results: Understory vegetation cover, biomass and species richness increased within and outside the 'US' and 'MM' exclosures after thinning, and biomass was greater within than outside the exclosures at 10 years after thinning. Unpalatable species dominated both 'US' and 'MM' exclosures before thinning, and trees and shrubs dominated within the exclosures over time after thinning. In contrast, unpalatable, grazing-tolerant, perennial, and annual species increased outside the 'US' and 'MM' exclosures. No noticeable changes were observed within and outside the 'LD' exclosure when compared with the 'US' and 'MM' exclosures. Conclusions: Our results suggest that thinning a stand by 30% based on volume resulted in an increase in understory vegetation cover mainly composed of both unpalatable and grazing-tolerant species in a plantation forest where understory vegetation is sparse or moderate and sika deer density is high. We emphasize that establishing deer exclosures or controlling deer is essential to maintaining similar understory vegetation both within and outside exclosures. [ABSTRACT FROM AUTHOR]

There are difficulties in conducting worldwide medical device development simultaneously because each country and/or region has their own medical device regulations. However, to aid globalization of the medical device market, and to quickly provide innovative medical devices to patients, attempts have been made to encourage harmonization and convergence of medical device regulations. 'Harmonization by doing' is a bilateral effort from the United States and Japan to develop global clinical trials and address regulatory barriers that may be impediments to timely device approval. The Global Harmonization Task Force (GHTF) was conceived in 1992 in an effort to achieve greater uniformity between national medical device regulatory systems. Since 2012, the GHTF has been replaced by the International Medical Device Regulators Forum. [ABSTRACT FROM AUTHOR]

The development of drugs and medical devices is necessary for medical progress; however, safety measures need to be put in place to protect the health of the population. In order to ensure the safety of drugs and medical devices, it is important to determine measures for appropriate management of risks at any time during the development phase, the regulatory review and the post-marketing phase. Adverse events detected in clinical trials are limited due to the restricted numbers of patients enrolled in the trials. Therefore, it is almost impossible to predict rare serious adverse events during the post-marketing phase. The revised Pharmaceutical Affairs Act was established in Japan in November 20, 2013. The new act focuses on increased safety of drugs and medical devices. The Pharmaceuticals and Medical Devices Agency (PMDA) is the regulatory authority in Japan that promotes safety measures from the development phase through to the post-marketing phase. In the post-marketing phase, the PMDA collects information from the medical product companies and healthcare professionals, as well as instructing and advising them with regard to post-marketing safety measures for each drug and medical device. Since Japan has a national health insurance system, a new drug or a medical device is available throughout the country when the drug price or medical fee is listed in the National Health Insurance price list. Healthcare professionals in medical institutions must learn about the drugs and medical devices they handle, and should make an effort to maintain patient safety. The PMDA medi-navi is a very useful electronic mail delivery service that provides critical information for protecting patients from health hazards caused by adverse events. The 'risk management plan' is also important as it contains important information about safety profile and post-marketing measures of a new drug. [ABSTRACT FROM AUTHOR]

Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal trafficking disorder, in which the cholesterols are aβnormally accumulated in lysosomes. Recently, the β-cyclodextrin (CD) derivatives are revealed to show therapeutic effect for NPC disease through the removal of accumulated cholesterols in lysosomes. Herein, to enhance the therapeutic effect and reduce the toxicity of β-CD derivatives, βiocleavaβle Pluronic/β-CD-βased polyrotaxanes (PRXs) βearing terminal disulfide linkages that can release threaded β-CDs in lysosomes were developed. The βiocleavaβle PRXs show negligiβle interaction with the plasma memβrane, leading to avoiding the toxicity of β-CDs derived from their hydrophoβic cavity. Additionally, lysosomal release of threaded β-CDs from βiocleavaβle PRXs βy the intracellular cleavage of terminal disulfide linkages is found to achieve approximately 100-fold higher cholesterol removal aβility fromNPCdisease-derived cells than β-CD derivatives. Consequently, the βiocleavaβle PRXs is considered to βe a noninvasive and effective therapeutics for NPC disease. [ABSTRACT FROM AUTHOR]

Tricyrtis ishiiana is a relic endemic plant taxon of the Convallariaceae that inhabits two nearby gorges in Kanagawa Prefecture, Japan. The distribution range and number of populations are thought to have been reduced to the present refugial populations during the Quaternary climatic oscillations. Because of its showy flowers, this plant has faced illegal removal from its natural habitats for horticultural use and has been designated a critically endangered species (class IA). In this study, we analyzed the genetic structure of the relict populations of T. ishiiana in order to contribute to the conservation strategies of the prefectural government. Our analyses of nine nuclear microsatellite loci detected high genetic diversity ( H = 0.704 and H = 0.541) for the two populations. The two populations were slightly differentiated ( R = 0.032), accompanied by faint substructure across the populations ( K = 3). In addition, each population exhibited spatial genetic structuring. The relatively low inbreeding coefficient for both populations together ( F = 0.233) and each population separately ( F = 0.217-0.246) may be attributable to crossing among descendants within a population along with occasional gene flow between the populations. These results suggested that the extant populations have not experienced a severe bottleneck. The two extant populations were genetically differentiated at a very low level, accompanied by occasional pollen flow via pollinators and/or seed dispersal by gravity in the mountainous environment. Occasional gene exchange between the populations has allowed T. ishiiana to harbor high genetic diversity despite being a relic plant confined to two small refugial populations. [ABSTRACT FROM AUTHOR]

Tight junctions are the main intercellular junctions of podocytes of the renal glomerulus under nephrotic conditions. Their requisite components, claudins, still remain to be identified. We have measured the mRNA levels of claudin subtypes by quantitative real-time PCR using isolated rat glomeruli. Claudin-5 was found to be expressed most abundantly in glomeruli. Mass spectrometric analysis of membrane preparation from isolated glomeruli also confirmed only claudin-5 expression without any detection of other claudin subtypes. In situ hybridization and immunolocalization studies revealed that claudin-5 was localized mainly in glomeruli where podocytes were the only cells expressing claudin-5. Claudin-5 protein was observed on the entire surface of podocytes including apical and basal domains of the plasma membrane in the normal condition and was inclined to be concentrated on tight junctions in puromycin aminonucleoside nephrosis. Total protein levels of claudin-5 in isolated glomeruli were not significantly upregulated in the nephrosis. These findings suggest that claudin-5 is a main claudin expressed in podocytes and that the formation of tight junctions in the nephrosis may be due to local recruitment of claudin-5 rather than due to total upregulation of the claudin protein levels. [ABSTRACT FROM AUTHOR]

We have investigated the effect of the chain length of temperature-sensitive poly( N-isopropylacrylamide) (PIPAAm) on the dispersion of [60]fullerene (C) in aqueous media through an interaction between PIPAAm and C below the lower critical solution temperature (LCST) of PIPAAm. UV-vis absorption spectral measurements showed that the saturated amount of the dispersed C increased in proportion to the chain length of the PIPAAm. Additionally, an absorption band at around 430 nm was observed in the dispersed C solution and was assigned to a C/PIPAAm complex. The complex formed an amorphous molecular assembly between C molecules and PIPAAm chains, the structure of which was confirmed in a transmission electron microscopy image. Dynamic light scattering measurements indicated that the particle size of the C/PIPAAm complex increased with the chain length of the PIPAAm. From electrophoretic laser light scattering measurements, the zeta potential of the C/PIPAAm complex was found to be shifted from a negative value to zero with an increase in the chain length of PIPAAm. Longer PIPAAm chains, however, gave rise to a higher dispersion stability of the complex. Similar to the dispersion behavior of PIPAAm-C conjugates in aqueous solutions, the aqueous C dispersion with PIPAAm exhibited rapid, and reversible dispersion-aggregation changes in response to temperature alternation across the LCST. [ABSTRACT FROM AUTHOR]

Neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) are well-recognized symptoms although the pathophysiology of neuropsychiatric SLE (NPSLE) is unclear. Since an association with antiphospholipid antibodies has been reported, we examined the prevalence of antiphosphatidylserine–prothrombin antibodies (anti-PS/PT Abs), lupus anticoagulant (LA), anticardiolipin/β2-glycoprotein I antibodies (anti-β2-GPI Abs), and antiribosomal P protein antibodies (antiribosomal P Abs) in 68 SLE patients and analyzed their associations with neuropsychiatric manifestations. The prevalence of LA was significantly higher in the patients with neuropsychiatric (NP) features than those without NP features ( P < 0.02). The levels of anti-PS/PT antibody were also significantly higher in the patients with NP features than those without NP features ( P < 0.01). The results indicate that LA positivity and higher levels of anti-PS/PT antibody can be predictive markers for NPSLE. [ABSTRACT FROM AUTHOR]

We reported two patients with refractory eosinophilic fasciitis (EF) and provided a systematic review of the literature to determine the clinical variables associated with prognosis of EF. We enrolled 88 cases, whose clinical characteristics were analyzed by separating the patients into two or three groups based on outcome. The incidence of certain clinical and pathological features differed among the groups. In particular, the incidence of morphea-like skin lesions in patients with refractory fibrosis was significantly higher than in patients without refractory fibrosis ( p = 0.003). Patients with morphea-like skin lesions were 1.9 times more likely to develop persistent fibrosis than patients without these lesions (95% confidence intervals, 1.5–2.5). A younger age (under 12 years) at onset was associated with a 1.6 times greater risk of residual fibrosis (95% confidence interval, 1.1–2.2). Trunk involvement was associated with a 1.4 times greater risk of residual fibrosis (95% confidence interval, 1.0–2.0). Histopathologically, the presence of dermal fibrosclerosis was associated with a 1.4 times greater risk of refractory fibrosis (95% confidence interval, 1.0–2.1). We consider these clinical characteristics, notably the presence of morphea-like skin lesions may be an important risk factor for developing residual fibrosis in EF patients. [ABSTRACT FROM AUTHOR]

Mediastinal irradiation has been reported to induce cardiac diseases such as pericardial disease, accelerated arteriosclerosis of the coronary arteries, valvular disease, conduction abnormalities, and calcification of the aorta. We experienced four cases of radiation-induced valvular disease. All patients had histories of radiation therapy and had aortic valve disease. All patients had marked fibrosis of the mediastinum and hypertrophy of pericardium. The aortic valve leaflets were tricuspid and fibrotic with focal dystrophic calcification and markedly thickened. In the pathological findings, certain rheumatic endocarditis changes such as endocardial reduplication and vascularization were not found in all aortic valves. The mechanism of radiation-induced cardiac disease is not clear. However, those changes seem to progress very slowly. Thus, long-term follow-up care is particularly important for patients undergoing radiation therapy. Fortunately, today's irradiation techniques are much less harmful; therefore, radiation-induced cardiac disease will likely become more rare in the future. [ABSTRACT FROM AUTHOR]

The ezrin-radixin-moesin (ERM) family of proteins crosslink actin filaments and integral membrane proteins. Radixin (encoded by Rdx) is the dominant ERM protein in the liver of wildtype mice and is concentrated at bile canalicular membranes (BCMs). Here we show that Rdx[sup -/-] mice are normal at birth, but their serum concentrations of conjugated bilirubin begin to increase gradually around 4 weeks, and they show mild liver injury after 8 weeks. This phenotype is similar to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury. In wildtype mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile. In the BCMs of Rdx[sup -/-] mice, Mrp2 is decreased compared with other BCM proteins such as dipeptidyl peptidase IV (CD26) and P-glycoproteins. In vitro binding studies show that radixin associates directly with the carboxy-terminal cytoplasmic domain of human MRP2. These findings indicate that radixin is required for secretion of conjugated bilirubin through its support of Mrp2 localization at BCMs. [ABSTRACT FROM AUTHOR]

The antibacterial activity of 2″-amino-2″-deoxyarbekacin (AmABK) and 2″-amino-5,2″-dideoxy-5-epiaminoarbekacin (AmABK) was comparable to, or slightly less than, that of arbekacin (ABK) against gram-positive and gram-negative bacteria, including 60 stock cultures and 50 clinical isolates of Pseudomonas aeruginosa, but more potent against 31 isolates of MRSA possessing an aminoglycoside-modifying enzyme APH(2″)/AAC(6'). AmABK and AmABK showed in vivo activity which paralleled in vitro MICs, and were less toxic than ABK in acute toxicity in mice and nephrotoxicity in rats. These results indicate that the 2″-amino group introduced to ABK confers high stabilization to the aminoglycoside-modifying enzymes, while reducing acute and renal toxicities. [ABSTRACT FROM AUTHOR]

Nine microsatellite loci were isolated and characterized for the endangered and tertiary relict perennial herb, Tricyrtis ishiiana. The number of alleles ranged from 2 to 33. The expected (HE) and observed (HO) heterozygosities were 0.207-0.944 and 0.215-0.813, respectively, from 96 individuals on one population. Five loci exhibited significantly fewer heterozygotes than expected under Hardy-Weinberg equilibrium (P<0.05). These primers amplifying microsatellites in this species may provide a useful tool for population genetics to establish conservation strategy. [ABSTRACT FROM AUTHOR]

Supermolecules such as rotaxanes and catenanes have recently attracted considerable attention due to their potential widespread applications in areas such as molecular machines and switches. Moreover, the development of polyrotaxanes and polycatenanes, comprising multiple cyclic compounds, has allowed the fabrication of structures with novel properties. Although rotaxanes and polyrotaxanes have been extensively prepared from cyclodextrins as building blocks, very few studies have considered the syntheses of cyclodextrin-based polycatenanes. Here we report the one-pot syntheses and isolation of cyclodextrin-based radial polycatenanes with large numbers of cyclic components (>10) attached to a poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) copolymer core, with characterization performed using Raman spectroscopy, gel permeation chromatography, 1H-NMR spectroscopy, and other techniques. Overall, the results presented herein may be used to develop advanced supramolecular structures and materials, such as molecular machines, molecular actuators, molecular switches, biomaterials, and drug carriers. There are several structural motifs commonly reported for polycatenanes although radial polycatenanes remain poorly studied. Here, the authors report the facile synthesis of cyclodextrin based radial polycatenanes composed of more than ten rings via a polypseudorotaxane intermediate. [ABSTRACT FROM AUTHOR]

Tight junction is a cell adhesion apparatus functioning as barrier and/or channel in the paracellular spaces of epithelia. Claudin is the major component of tight junction and polymerizes to form tight junction strands with various morphologies that may correlate with their functions. Here we present the crystal structure of mammalian claudin-3 at 3.6 Å resolution. The third transmembrane helix of claudin-3 is clearly bent compared with that of other subtypes. Structural analysis of additional two mutants with a single mutation representing other subtypes in the third helix indicates that this helix takes a bent or straight structure depending on the residue. The presence or absence of the helix bending changes the positions of residues related to claudin-claudin interactions and affects the morphology and adhesiveness of the tight junction strands. These results evoke a model for tight junction strand formation with different morphologies - straight or curvy strands - observed in native epithelia. The main components of tight junctions (TJ) are claudins that polymerize and form meshwork architectures called TJ strands. Here the authors present the 3.6 Å crystal structure of murine claudin-3 and show that residue P134 causes a bending of the third transmembrane helix which affects the morphology and adhesiveness of the TJ strands. [ABSTRACT FROM AUTHOR]