Giant spin polarization and a pair of antiparallel spins in a chiral superconductor.

Chiral molecules can exhibit spin-selective charge emission, which is known as chirality-induced spin selectivity1,2. Despite the constituent light elements of the molecules, their spin polarization can approach or even exceed that of typical ferromagnets. This powerful capability may lead to applications in the chiral spintronics2 field. Although the origin of spin selectivity is elusive, two microscopic phenomena have been suggested based on experimental results: effective enhancement of spin-orbit interactions3 and chirality represented by a pair of oppositely polarized spins4,5. However, the hypotheses remain to be verified. Here we report the simultaneous observation of these two phenomena in an organic chiral superconductor by magnetoresistance measurements in the vicinity of the superconducting transition temperature. A pair of oppositely polarized spins is demonstrated by spatially mapping the spin polarity in an electric alternating current excitation. The obtained spin polarization exceeds that of the Edelstein effect6-10 by several orders of magnitude, which indicates an effective enhancement of the spin-orbit interaction. Our results demonstrate a solid-state analogue of spin accumulations assumed for chiral molecules, and may provide clues to the origin of their molecular counterparts. In addition, the innovative capability of spin-current sourcing will invigorate superconducting spintronics research11.

Contribution of Noncanonical Antigens to Virulence and Adaptive Immunity in Human Infection with Enterotoxigenic E. coli.

Enterotoxigenic Escherichia coli (ETEC) contributes significantly to the substantial burden of infectious diarrhea among children living in low- and middle-income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as nondiarrheal sequelae related to these infections, including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches defined by a subset of ETEC pathovar-specific antigens known as colonization factors (CFs). To identify additional conserved immunogens unique to this pathovar, we employed an "open-aperture" approach to capture all potential conserved ETEC surface antigens, in which we mined the genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n = 118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n = 52) and toxin subunits. These arrays were then used to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this approach, we found that immune responses were largely constrained to a small number of antigens, including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children <2 years of age, both EtpA and a second antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for antigens not presently targeted by vaccines (noncanonical) in virulence and the development of adaptive immune responses during ETEC infections. These findings may inform vaccine design efforts to complement existing approaches.

Myositis with sarcoplasmic inclusions in Nakajo-Nishimura syndrome: a genetic inflammatory myopathy.

AIMS: Nakajo-Nishimura syndrome (NNS) is an autosomal recessive disease caused by biallelic mutations in the PSMB8 gene that encodes the immunoproteasome subunit ß5i. There have been only a limited number of reports on the clinicopathological features of the disease in genetically confirmed cases. METHODS: We studied clinical and pathological features of three NNS patients who all carry the homozygous p.G201V mutations in PSMB8. Patients' muscle specimens were analysed with histology and immunohistochemistry. RESULTS: All patients had episodes of typical periodic fever and skin rash, and later developed progressive muscle weakness and atrophy, similar to previous reports. Oral corticosteroid was used for treatment but showed no obvious efficacy. On muscle pathology, lymphocytes were present in the endomysium surrounding non-necrotic fibres, as well as in the perimysium perivascular area. Nearly all fibres strongly expressed MHC-I in the sarcolemma. In the eldest patient, there were abnormal protein aggregates in the sarcoplasm, immunoreactive to p62, TDP-43 and ubiquitin antibodies. CONCLUSIONS: These results suggest that inflammation, inclusion pathology and aggregation of abnormal proteins underlie the progressive clinical course of the NNS pathomechanism.

Interleukin-25 is involved in cutaneous T-cell lymphoma progression by establishing a T helper 2-dominant microenvironment.

BACKGROUND: Interleukin (IL)-25 is a member of the IL-17 family, which can promote and augment T-helper (Th) type 2 responses. The expression of IL-25 and its cognate receptor, IL-25 receptor (IL-25R), is upregulated and correlated with disease activity in Th2-associated diseases. OBJECTIVES: To examine the expression and function of IL-25 in cutaneous T-cell lymphoma (CTCL). METHODS: Expression and location of IL-25 in lesional skin was investigated with immunohistochemistry. The effect of various cytokines on IL-25 production from normal human epidermal keratinocytes was assessed by quantitative reverse-transcription real-time polymerase chain reaction. Serum IL-25 levels were measured by enzyme-linked immunosorbent assay. The direct effect of IL-25 on tumour cells was also examined using CTCL cell lines and peripheral blood mononuclear cells in patients with Sézary syndrome. RESULTS: IL-25 expression was increased in epidermal keratinocytes in lesional skin of CTCL. Th2 cytokines, IL-4 and IL-13, and periostin induced IL-25 expression by normal human epidermal keratinocytes. Serum IL-25 levels were increased in patients with advanced CTCL and correlated with serum lactate dehydrogenase levels. MyLa cells expressed IL-25R and its expression was augmented by stimulation with IL-25. IL-25 enhanced IL-13 production from MyLa cells via phosphorylation of signal transducer and activator of transcription 6. Peripheral blood mononuclear cells from one patient with Sézary syndrome expressed IL-25R and showed increase of IL-13 production by IL-25. CONCLUSIONS: Th2 cytokines highly expressed in CTCL lesional skin induce IL-25 production by epidermal keratinocytes, which may, in turn, lead to formation of a Th2-dominant microenvironment through the direct induction of IL-13 by tumour cells.

Genomic organization and comparative chromosome mapping of the U1 snRNA gene in cichlid fish, with an emphasis in Oreochromis niloticus.

To better understand genomic and chromosomal organization and evolutionary patterns of the U1 snRNA gene in cichlid fish, the gene was cytogenetically mapped and comparatively analyzed in 19 species belonging to several clades of the group. Moreover, the distribution and organization of U1 snRNA gene was analyzed in the Oreochromis niloticus genome. The results indicated high conservation of one chromosomal cluster of U1 snRNA in the African, Asian, and South American species, with few variations in the chromosomal position of the clusters in the South American species. The genomic analysis of U1 revealed a distinct scenario from that observed under the cytogenetic mapping. An enrichment of the U1 gene on linkage group (LG) 14 was observed that did not correspond to the same chromosome that harbors the U1 cluster identified by cytogenetic mapping. Moreover, it was revealed that the presence of several distinct transposable elements in the U1 gene flanking regions could be involved in the spreading of this sequence, but the generation of new, large snRNA clusters (detectable by fluorescent in situ hybridization, FISH) is apparently hampered. These results contribute to the understanding of multigene families' evolution and reinforce the utility of integrative analysis and the use of cytogenetic and bioinformatic methods to address the genomic and chromosomal evolutionary patterns of repeated DNAs among vertebrates. Moreover, the U1 gene represents a useful new chromosomal marker for cytogenetic studies.

T-helper 17 cells mediate the osteo/odontoclastogenesis induced by excessive orthodontic forces.

OBJECTIVE: The aim of this study was to investigate how T-helper 17 cells (Th17 cells), interleukin (IL)-17, and interleukin-6 contribute to root resorption during orthodontic tooth movement. MATERIALS AND METHODS: Fifteen male 6-week-old Wistar rats were subjected to orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars for 7 days. The expression levels of TRAP, IL-17, the IL-17 receptor (IL-17R), and IL-6 proteins were determined in periodontal ligament (PDL) by immunohistochemical analysis. Moreover, the fluorescent localization immunoassay was performed to detect Th17 cells. Furthermore, the effects of IL-17 on IL-6 release were investigated using human PDL cells in vitro. The effect of IL-17 on osteoclastogenesis was evaluated by TRAP staining, actin ring staining, and the pit formation assay. RESULTS: The immunoreactivity for Th17, IL-17, IL-17R, and IL-6 was detected in PDL tissue subjected to the orthodontic force on day 7. IL-17 increased the release of IL-6 from human periodontal ligament cells in a time-dependent manner. Moreover, IL-17 stimulated osteoclastogenesis from human osteoclast precursor cells, and these effects were partially suppressed by an anti-IL-6 antibody. CONCLUSION: These results suggest that Th17 cells may aggravate the process of orthodontically induced inflammatory root resorption.

IL-8 and MCP-1 induced by excessive orthodontic force mediates odontoclastogenesis in periodontal tissues.

OBJECTIVE: The aim of this study was to investigate how interleukin (IL)-8 (cytokine-induced neutrophil chemoattractant; CINC-1) and monocyte chemotactic protein (MCP)-1/CCL2 contribute to root resorption during orthodontic tooth movement. MATERIALS AND METHODS: Forty 6-week-old male Wistar rats were subjected to orthodontic force of 10 or 50 g to induce a mesially tipping movement of the upper first molars for 7 days. We determined the expressions of CINC-1, CXCR2, and MCP-1 proteins in root resorption area using immunohistochemistry. Furthermore, we investigated the effects of compression forces (CF) on IL-8 and MCP-1 production by human periodontal ligament (hPDL) cells. We observed an effect of chemokine treatment on rat odonto/osteoclasts in dentin slices that recapitulated root resorption. RESULTS: The immunoreactivity for CINC-1/CXCR2 and MCP-1 was detected in odontoclasts and PDL fibroblasts by the orthodontic force of 50 g on day 7. CF increased the secretion and the expression of mRNA of IL-8 and MCP-1 from PDL cells in a magnitude-dependent manner. Moreover, CINC-1 and MCP-1 stimulated osteoclastogenesis from rat osteoclast precursor cells. CONCLUSION: IL-8 (CINC-1) and MCP-1 may therefore facilitate the process of root resorption because of excessive orthodontic force.

Effects of relaxin on collagen type I released by stretched human periodontal ligament cells.

OBJECTIVES: Relapse of teeth that have moved during orthodontic treatment is a major clinical issue with respect to the goals of successful treatment. Such relapse is a physiologic response of the supporting tissues to application of force, and is mainly attributed to occlusal instability and increased mechanical tension exerted by the periodontal ligament (PDL). Relaxin, a member of the insulin/relaxin family of structurally related hormones, has an influence on many physiologic processes, such as collagen turnover, angiogenesis, and antifibrosis. Therefore, relaxin may also affect orthodontic tooth movement through alterations of the PDL, though little is known regarding the relationship between relaxin and stretched human PDL (hPDL) cells. In the present study, we investigated the effects of relaxin on the expression of collagen type I (Col-I) and matrix metalloproteinase 1 (MMP-1) in stretched hPDL cells in vitro. MATERIALS AND METHODS: The release and gene expression of Col-I, as well as those of MMP-1 in stretched hPDL cells treated with relaxin were investigated using enzyme-linked immunosorbent assay and real-time PCR methods. RESULTS: Relaxin decreased the release and gene expression of Col-I, and increased those of MMP-1 by stretched hPDL cells in a magnitude-dependent manner. CONCLUSION: Our results indicate that relaxin modulates collagen metabolism in stretched hPDL cells via the release and expression of Col-I and MMP-1. This hormone may be useful to prevent orthodontic relapse following orthodontic treatment.

Effects of compression force on fibroblast growth factor-2 and receptor activator of nuclear factor kappa B ligand production by periodontal ligament cells in vitro.

BACKGROUND AND OBJECTIVE: Mechanical stress by an orthodontic appliance induces biologically active substances. Fibroblast growth factor is a multifunctional cytokine that has various effects on fibroblast cells, and fibroblast growth factor-2 plays an important role in remodeling of the periodontal ligament. The receptor activator of nuclear factor kappa B ligand (RANKL) is an important protein involved in osteoclastogenesis and we recently reported that RANKL levels were increased by compression force in vitro. In the present study, we investigated the effects of compression force on fibroblast growth factor-2 and RANKL production by human periodontal ligament cells. MATERIAL AND METHODS: Compression force (0.5-4.0 g/cm2) was applied to human periodontal ligament cells for 0-24 h. The amounts of soluble RANKL (sRANKL) and fibroblast growth factor-2 were measured using an enzyme-linked immunosorbent assay, whereas mRNA levels were determined by the reverse transcription-polymerase chain reaction. Furthermore, anti-fibroblast growth factor-2 was added to the cell culture media and we measured the release of sRANKL and fibroblast growth factor-2 by enzyme-linked immunosorbent assay. RESULTS: Compression force induced higher levels of sRANKL and fibroblast growth factor-2 in both a time- and magnitude-dependent manner. Treatment with anti-fibroblast growth factor-2 inhibited the release of sRANKL. CONCLUSION: Fibroblast growth factor-2 may be partly involved in osteoclastogenesis during orthodontic tooth movement.

Alterations of the p53 tumor suppressor gene and its association with activation of the c-K-ras-2 protooncogene in premalignant and malignant lesions of the human uterine endometrium.

We previously reported (T. Enomoto et al., Cancer Res., 50: 6139-6145, 1990; T. Enomoto et al., Cancer Res., 51: 5308-5314, 1991) a significant frequency of activating point mutations in codon 12 of the c-K-ras-2 protooncogene in endometrial adenocarcinoma and its premalignant precursor lesions (series 1 and 2). To reveal the role of the p53 tumor suppressor gene in the development of endometrial adenocarcinoma and to study the association of p53 alterations with K-ras activation, an additional 28 endometrial adenocarcinomas and an additional 11 premalignant atypical uterine hyperplasias (series 3), as well as 12 cases of endometrial adenocarcinoma (10 having K- or N-ras activation) and 2 cases of atypical hyperplasia from series 1 and 2, were screened for the presence of p53 alterations. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 6 of 19 (32%) informative cases of endometrial adenocarcinoma and 1 of 4 (25%) informative cases of endometrial atypical hyperplasia by restriction fragment length polymorphism analysis and by single-strand conformation polymorphism analysis of polymerase chain reaction (PCR)-amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by single-strand conformation polymorphism analysis of PCR-amplified DNA fragments. Mutations were found in 9 of 40 (23%) endometrial adenocarcinomas and 1 of 13 (8%) atypical hyperplasias that were studied. Mutations in p53 were significantly more frequently found in clinical grade 3 (G3) cancers (6 of 14, 43%) than in G1-G2 cancers (3 of 26, 12%) (P = 0.033). Mutations were subsequently confirmed by direct sequencing. Single missense base substitutions were detected in 6 cases of endometrial carcinoma and in one case of atypical hyperplasia. Deletions of a single base and of 2 bases were each detected in single cases of endometrial carcinoma, and a single base insertion was found in a third case. Point mutations in K-ras were also identified in tumors of series 3 by direct sequencing of PCR-amplified DNA fragments of exons 1 and 2. Point mutations in codons 12 and 13 in K-ras were detected by direct sequencing of PCR-amplified DNA in 7 of 28 adenocarcinomas in series 3, but none were found in exon 2 (codons 59.63. The spectrum of point mutations in p53 in endometrial adenocarcinomas was almost identical to what we found in K-ras in series 1 and 2 and in series 3, suggesting the possible role of a mutagen that might be responsible for mutations in both K-ras and p53.(ABSTRACT TRUNCATED AT 400 WORDS)

Colonic hamartoma development by anomalous duplication in Cdx2 knockout mice.

To determine the biological role of caudal-like homeobox gene CDX2, we constructed knockout mice in which its mouse homologue Cdx2 was inactivated by homologous recombination, placing a bacterial lacZ gene under the control of the Cdx2 promoter. Although the homozygous mutants died in utero around implantation, the heterozygotes were viable and fertile and expressed lacZ in the caudal region in early embryos and in the gut tissues in adults. The heterozygotes developed cecal and colonic villi by anteriorization and formed hamartomatous polyps in the proximal colon. The hamartoma started to develop at 11.5 days of gestation as an outpocket of the gut epithelium, which ceased to express the remaining Cdx2 allele. The outpocket then expanded as a partially duplicated gut but was contained as a hamartoma after birth. In adult mice, these hamartomas grew very slowly and took a benign course. None of them progressed into invasive adenocarcinomas, even at 1.5 years of age. Whereas the cecal and colonic villi expressed lacZ, the hamartoma epithelium did not, nor did it express Cdx2 mRNA from the wild-type allele. However, genomic DNA analysis of the polyp epithelium did not show a loss of heterozygosity of the Cdx2 gene, suggesting a mechanism of biallelic Cdx2 inactivation other than loss of heterozygosity. These results indicate that the Cdx2 haploin-sufficiency caused cecal and colonic villi, whereas the biallelic inactivation of Cdx2 triggered anomalous duplications of the embryonic gut epithelium, which were contained as hamartomas after birth.

Perforated appendicitis causing thigh emphysema: a case report.

We report a case of thigh emphysema resulting from perforated appendicitis. The patient was an 83-year-old man who had no apparent abdominal signs and was initially misdiagnosed as having psoas abscess. Magnetic resonance imaging of the pelvis revealed appendicitis, and a barium enema showed a leakage of enhanced contrast material from the appendix region down into the thigh. A retroperitoneal perforation of the retrocaecal appendix without peritonitis was diagnosed. The patient underwent an appendectomy and curettage of the retroperitoneal and psoas muscle spaces, as well as the thigh. He recovered gradually, though the abscess had extended into the hip joint and resulted in osteomyelitis, requiring an additional procedure of resection arthroplasty. The patient fully recovered with no signs of infection one year postoperatively.

Oxygen exchange between the Fe(IV) = O heme and bulk water for the A2 isozyme of horseradish peroxidase.

Resonance Raman spectra were observed for compound II of horseradish peroxidase A2, and the Fe(IV) = O stretching Raman line was identified at 775 cm-1. This Raman line shifted to 741 cm-1 upon a change of solvent from H2(16)O to H2(18)O, indicating occurrence of the oxygen exchange between the Fe(IV) = O heme and bulk water. The oxygen exchange took place only at the acidic side of the heme-linked ionization with pKa = 6.9.

Resonance Raman characterization of hog thyroid peroxidase. An SERRS study.

Resonance Raman (RR) spectra of hog thyroid peroxidase (TPO) were observed for the first time and compared with those of lactoperoxidase (LPO) and horseradish peroxidase (HRP). Since TPO purified by monoclonal antibody-assisted immunoaffinity chromatography was strongly fluorescent, the surface enhancement technique using Ag colloid adsorption was used for the oxidized form, but ordinary RR spectra could be obtained for the reduced form. The RR spectra of TPO were distinct from those of HRP in both the oxidized and reduced states and indicated the presence of six-coordinated iron-protoporphyrin.

Physiological aspects of free-radical reactions.

Enzymes which catalyze the formation of free radicals in vitro will catalyze similar reactions in vivo. We believe that the formation of some kinds of free radicals has definite physiological meanings in metabolism. In this sense, the enzymes forming such free radicals are concluded to be in evolutionally advanced states. Elaborated structure and function of enzymes such as horseradish peroxidase and microsomal flavoproteins support the idea. Deleterious and side reactions caused by free radicals are assumed to be minimized in vivo by localizing the reactions, but this assumption should be verified by future studies.

Increased cyclooxygenase 2 (COX-2) expression occurs frequently in precursor lesions of human adenocarcinoma of the lung.

A low incidence of lung carcinoma has been reported in cases of prolonged use of aspirin. Cyclooxygenase (COX) 2 expression is frequently seen in adenocarcinoma of the lung, but COX-2 expression in atypical adenomatous hyperplasia (AAH), a possible precursor lesion of adenocarcinoma of the lung, is not known. COX-2 expression was immunohistochemically evaluated in a cohort of 20 cuboidal cell hyperplasias (CCH), 81 atypical adenomatous hyperplasias (AAH), 18 bronchioloalveolar carcinomas (BAC), and 88 invasive adenocarcinomas (I-Ad). The relationship between COX-2 expression and clinicopathologic factors and survival was examined. COX-2 overexpression was detected in over 80% of CCH, AAH, BAC, and I-Ad. However, overexpression was diffuse in AAH (71.6%) and BAC (66.7%). No relationship was found between COX-2 expression and clinicopathological factors or survival. COX-2 expression was most frequently detected in AAH. These findings, taken with previous reports that treatment with COX-2 inhibitor suppresses human colon carcinogenesis, suggest that inhibition of COX-2 may reduce the incidence of human adenocarcinoma of the lung.

The effect of polymerization of horseradish peroxidase on the peroxidase activity in the presence of excess H2O2: a background for a homogeneous enzyme immunoassay.

The phenol oxidation catalyzed by horseradish peroxidase (HRP) is slowed down by the presence of excess H2O2. This inhibition is due to accumulation of Compound III, which is a catalytically sluggish form of HRP. When HRP is polymerized through covalent bonds, Compound III becomes unstable and the peroxidase activity is less sensitive to excess H2O2. Under suitable experimental conditions, the phenol oxidation is increased by about 20-fold upon polymerization of the enzyme. This fact represents the principle of a homogeneous enzyme immunoassay reported by Hoshino et al. (J. Biochem. 97, 113-118 (1985)). The ratio of the peroxidase activities of monomeric and polymerized HRPs is 1 : 4 when phenol is replaced by resorcinol, and the difference is no larger when guaiacol and catechol are used as electron donors.

A facile preparation of exo-cyclic conjugated dienes fused to lactams or lactones via intramolecular coupling of acetylenes and their behavior in Diels-Alder reactions.

[reaction: see text] Treatment of bis-acetylenic amides or esters 3 with (eta(2)-propene)Ti(O-i-Pr)(2) generates functionalized titanacyclopentadienes which, upon hydrolytic workup, give exo, exo-cyclic conjugated dienes 4 in good yields. Some regio- and stereochemical aspects of their Diels-Alder reaction with dienophiles are also disclosed.

Synthesis and antifungal activity of rhodopeptin analogues. 1. Modification of the east and south amino acid moieties.

Structure-activity relationships of the east and south amino acid modified analogues of rhodopeptins, novel antifungal cyclic tetrapeptides isolated from Rhodococcus species Mer-N1033, have been investigated. It was observed that a basic amino acid moiety (lysine or ornithine) as the east amino acid and a hydrophobic and bulky neutral amino acid (i.e., gamma-methylleucine) as the south amino acid were indispensable structure motifs for antifungal activity of rhodopeptin analogues.

Synthesis and antifungal activity of rhodopeptin analogues. 2. Modification of the west amino acid moiety.

Structure-activity relationships of the west amino acid modified analogues of rhodopeptins, novel antifungal tetrapeptide isolated from Rhodococcus species Mer-N1033, have been investigated. Among the analogues synthesized, 2,2-difluoro and 2-hydroxy derivatives retained the antifungal activity with better physical properties, i.e., solubility or acute toxicity.