Tuning the Magnetic Quantum Criticality of Artificial Kondo Superlattices CeRhIn_{5}/YbRhIn_{5}.

The effects of reduced dimensions and the interfaces on antiferromagnetic quantum criticality are studied in epitaxial Kondo superlattices, with alternating n layers of heavy-fermion antiferromagnet CeRhIn_{5} and seven layers of normal metal YbRhIn_{5}. As n is reduced, the Kondo coherence temperature is suppressed due to the reduction of effective Kondo screening. The Néel temperature is gradually suppressed as n decreases and the quasiparticle mass is strongly enhanced, implying dimensional control toward a quantum critical point. Magnetotransport measurements reveal that a quantum critical point is reached for the n=3 superlattice by applying small magnetic fields. Remarkably, the anisotropy of the quantum critical field is opposite to the expectations from the magnetic susceptibility in bulk CeRhIn_{5}, suggesting that the Rashba spin-orbit interaction arising from the inversion symmetry breaking at the interface plays a key role for tuning the quantum criticality in the two-dimensional Kondo lattice.

Atmospheric Humidity Influences Oviposition Rate of Tetranychus urticae (Acari: Tetranychidae) Through Morphological Responses of Host Cucumis sativus Leaves.

We investigated the effects of morphology of host cucumber, Cucumis sativus L., leaves acclimatized to different atmospheric humidity levels on oviposition by adult females of the twospotted spider mite, Tetranychus urticae Koch. Cucumber seedlings were grown at a vapor pressure deficit (VPD) of 0.4, 1.9, or 3.0 kPa at 28°C (90%, 50%, or 20% relative humidity, respectively) in growth chambers until the second true leaves had expanded. Adult females of T. urticae were released on the adaxial surfaces of leaf squares cut from first and second true leaves in each treatment group, and held in the same humidity condition. Eggs were counted 2 d after release. The lower acclimatization humidity (higher VPD) increased trichome (leaf hair) density of the host leaves and oviposition rate, but the relationship between the trichome and oviposition differed between leaf positions. The leaf mass per area (LMA) was greater in first true leaves than in second true leaves, but was not influenced by VPD. A linear regression model with oviposition rate as the dependent variable and trichome density and LMA as independent variables showed that both variables influenced the oviposition rate approximately equally. We conclude that oviposition was accelerated under low humidity (high VPD) conditions indirectly probably through an increase in the trichome density of host leaves.

Carvedilol Suppresses Apoptosis and Ion Channel Remodelling of HL-1 Cardiac Myocytes Expressing E334K cMyBPC.

BACKGROUND: Besides its antiarrhythmic action, carvedilol has an activity to suppress cardiac tissue damage. However, it is unknown whether it has any effect on cellular apoptosis and ion channel remodelling. PURPOSE: To know whether carvedilol has any effect on apoptosis and ion channel remodeling of HL-1 cells expressing E334K MyBPC, and comparing it with bisoprolol. METHOD: We examined effects of carvedilol and bisoprolol on the levels of pro- and anti-apoptotic proteins and ion channels as well as apoptosis of HL-1 cells transfected with E334K MyBPC using Western blot and flow cytometry. RESULTS: Carvedilol decreased the protein levels of p53, Bax and cytochrome c and increased that of Bcl-2 in HL-1 cells expressing E334K MyBPC. Bisoprolol failed to affect the protein levels. Both carvedilol and bisoprolol increased the protein levels of Cav1.2 but not that of Nav1.5. Carvedilol was stronger than bisoprolol at decreasing the number of annexin-V positive cells in HL-1 cells expressing E334K MyBPC. CONCLUSION: Carvedilol suppressed apoptosis of HL-1 cells expressing E334K MyBPC through modification of pro- and anti-apoptotic proteins, whose was associated with an increase of Cav 1.2 protein expression.

Controllable Rashba spin-orbit interaction in artificially engineered superlattices involving the heavy-fermion superconductor CeCoIn5.

By using a molecular beam epitaxy technique, we fabricate a new type of superconducting superlattices with controlled atomic layer thicknesses of alternating blocks between the heavy-fermion superconductor CeCoIn5, which exhibits a strong Pauli pair-breaking effect, and nonmagnetic metal YbCoIn5. The introduction of the thickness modulation of YbCoIn5 block layers breaks the inversion symmetry centered at the superconducting block of CeCoIn5. This configuration leads to dramatic changes in the temperature and angular dependence of the upper critical field, which can be understood by considering the effect of the Rashba spin-orbit interaction arising from the inversion symmetry breaking and the associated weakening of the Pauli pair-breaking effect. Since the degree of thickness modulation is a design feature of this type of superlattices, the Rashba interaction and the nature of pair breaking are largely tunable in these modulated superlattices with strong spin-orbit coupling.

Selection of microalgae suitable for culturing with digestate from methane fermentation.

The effects ofdigestate on the growth rates of Euglena gracilis, Chlorella vulgaris, and Dunaliella tertiolecta were investigated to select suitable microalgae for culturing with digestate from methane fermentation. Microalgae were cultured in an aqueous solution containing digestate at concentrations of 5%, 10%, 13%, 20%, 40%, 50%, and 100%, and Cramer-Myers (CM) solution as a control, at photosynthetic photon flux densities (PPFDs) of 75-150 micromol m(-2) s(-1) with continuous illumination at 30 degrees C. The number of cells was monitored daily, and specific growth rates (mu) were calculated as cellular multiplication rates. The maximum mu values of these species were greater in appropriate concentrations of digestate than in CM medium. The maximum mu values were 0.047 h(-1) in 10% digestate for E. gracilis, 0.065 h(-1) in 20% digestate for C. vulgaris, and 0.052 h(-1) in 50% digestate for D. tertiolecta at a PPFD of 150 micromol m(-2) s(-1). The mu of D. tertiolecta were 2.5 and 1.1 times higher than those of E. gracilis and C. vulgaris, respectively, in 50% digestate. These results demonstrated that these species could be cultured at high growth rates with diluted methane fermentation sludge and that, among these species, Dunaliella sp. was suitable for culturing at higher concentration of digestate under relatively low-level light conditions.

DNA barcodes for species identification in the hyperdiverse ant genus Pheidole (Formicidae: Myrmicinae).

DNA sequencing is increasingly being used to assist in species identification in order to overcome taxonomic impediment. However, few studies attempt to compare the results of these molecular studies with a more traditional species delineation approach based on morphological characters. Mitochondrial DNA Cytochrome oxidase subunit 1 (CO1) gene was sequenced, measuring 636 base pairs, from 47 ants of the genus Pheidole (Formicidae: Myrmicinae) collected in the Brazilian Atlantic Forest to test whether the morphology-based assignment of individuals into species is supported by DNA-based species delimitation. Twenty morphospecies were identified, whereas the barcoding analysis identified 19 Molecular Operational Taxonomic Units (MOTUs). Fifteen out of the 19 DNA-based clusters allocated, using sequence divergence thresholds of 2% and 3%, matched with morphospecies. Both thresholds yielded the same number of MOTUs. Only one MOTU was successfully identified to species level using the CO1 sequences of Pheidole species already in the Genbank. The average pairwise sequence divergence for all 47 sequences was 19%, ranging between 0-25%. In some cases, however, morphology and molecular based methods differed in their assignment of individuals to morphospecies or MOTUs. The occurrence of distinct mitochondrial lineages within morphological species highlights groups for further detailed genetic and morphological studies, and therefore a pluralistic approach using several methods to understand the taxonomy of difficult lineages is advocated.

Simultaneous treatment with azelnidipine and olmesartan inhibits apoptosis of Hl-1 cardiac myocytes expressing E334k cMyBPC.

BACKGROUND: Apoptosis appears to play an important role in the pathogenesis of hypertrophic cardiomyopathy (HCM). We have previously reported 3 HCM patients carrying the E334K MYBPC3, and that heterologous expression of E334K cMyBPC in cultured cells induced apoptosis. The purpose of this study was to identify pharmacological agents that would inhibit apoptosis in HL-1 cardiomyocytes expressing E334K cMyBPC. METHODS AND RESULTS: E334K cMyBPC expression in cells increased levels of pro-apoptosis (p53, Bax and cytochrome c) and decreased levels of anti-apoptosis (Bcl-2 and Bcl-XL). While the beta blocker carvedilol (1 µM) normalized the level of p53 and Bcl-2 and the calcium channel blocker (CCB) bepridil (0.5 µM) normalized that of Bcl-2, both the CCB azelnidipine (1 µM) and the angiotensin receptor blocker (ARB) olmesartan (10 µM) normalized those of p53, Bax, cytochrome c, and Bcl-XL. Among those proteins, cytochrome c was the one which showed the highest degree of change. Both azelnidipine (0.1 µM) and olmesartan (1 µM) reduced the level of cytochrome c by 40.2 ± 4.3% and 31.3 ± 5.1%, respectively. The CCB amlodipine and the ARB valsartan reduced it only by 19.1 ± 2.1% and 20.1 ± 5.2%, respectively. Flow cytometric analysis and annexin V staining showed that treatment of cells with azelnidipine (0.1 µM) plus olmesartan (0.3 µM) or that with amlodipine (0.1 µM) plus valsartan (0.3 µM) reduced the number of apoptotic cells by 35.8 ± 10.5% and 18.4 ± 3.2%, respectively. CONCLUSION: Azelnidipine plus olmesartan or amlodipine plus valsartan inhibited apoptosis of HL-1 cells expressing E334K cMyBPC, and the former combination was more effective than the latter.

Synthesis and antibacterial activity of novel 1beta-methyl carbapenems with cycloalkylamine moiety at the C-2 position.

Novel 1beta-methyl carbapenems with a cycloalkylamine moiety as a side chain were synthesized and their structure-activity relationships were studied. These carbapenems showed potent antibacterial activities against a wide range of Gram-positive and Gram-negative bacteria, and moderate urinary recovery when administered intraperitoneally in mice.

The perineuronal proteoglycan surface coat in the adult rat brain, with special reference to its reactions to Gömöri's ammoniacal silver.

The present study showed that many neurons in the adult rat brain possessed a perineuronal sulfated proteoglycan surface coat which reacted to cationic iron colloid and aldehyde fuchsin. This surface coat was stained supravitally with Ehrlich's methylene blue and doubly stained with Ehrlich's methylene blue and aldehyde fuchsin. The surface coat was also stained with Gömöri's ammoniacal silver and doubly stained with Gömöri's ammoniacal silver and cationic iron colloid. The surface coat was usually expressed together with a nerve cell surface glycoprotein net detectable with lectin Wisteria floribunda agglutinin. These findings indicate that the perineuronal proteoglycan surface coat is identical to Cajal's superficial reticulum and contains some collagenous elements. It was further demonstrated that collagenase digestion erased Gömöri's ammoniacal silver impregnation within the perineuronal proteoglycan surface coat.

[Antitumor effect of the angiogenesis inhibitor, TNP470, on squamous cell carcinoma cells in head and neck cancer].

The antitumor effect of the angiogenesis inhibitor TNP470, O-(chloro-acetyl-carbamoyl) fumagillol, a synthetic analogue of fumagillin, was studied in vitro and in vivo on, cell line KB which produced interleukin (IL)-8. In vitro, TNP470 reduced the production of IL-8 from KB cells, the same as anti-IL-8 antibody (Ab.) The combination of anti-IL-8 Ab (10 micrograms/ml) and TNP470 (10 ng/ml) significantly inhibited the proliferation of KB cells, compared to no treatment (p < 0.05). Proliferation of KB cells was also significantly more suppressed by simultaneous treatment of cisplatin and TNP470 (1 mg/ml), than cisplatin alone. The in vivo antitumor effect of TNP470 was studied using anti-IL-8 Ab, anti-vascular endothel growth factor (VEGF) Ab, and TNP470, in administered by different routes, i.e., intratumoral (i.t.), intraperitoneal (i.p.), and intravenous. TNP470 (10 mg/ml) showed an antitumor effect, and intratumoral administration of TNP470 was the most effective route. Combined administration of anti-IL-8 Ab (i.p.) and TNP470 (i.t.) reduced tumor volume more than anti-IL-8 Ab alone did. These results suggest that the combination of TNP470, cisplatin, and anti-IL-8 Ab could be a beneficial treatment for solid tumors of the head and neck.

Effect of estrogen-progestogen hormonal replacement therapy on periurethral and bladder vessels.

This study assessed the effect of hormone replacement therapy using estrogens and/or progestogens on the number of vessels in the proximal and distal urethra, vesicourethral junction and bladder of castrated adult female rats. Forty-five virgin adult rats (Rattus norvegicus albinus) castrated for at least 30 days were used. They were assigned to five groups; group I (control) received no medication; the others received via the subcutaneous route, respectively, 17-beta-estradiol (group II), medroxyprogesterone acetate (group III), a maize oil and benzyl acid solution - placebo (group IV) and 17-beta-estradiol combined with medroxyprogesterone acetate (group V), for a minimum of 28 days. Increased vascularization throughout the urinary tract, except in the distal urethra, was found following estrogen replacement alone. In the group that received combined estrogens and progestogens, no increase was found. It was concluded that estrogen replacement in castrated rats significantly increased the number of vessels in the lower urinary tract.

Synthesis and structure-activity relationships of 1beta-methylcarbapenems with quaternary ammonium side chains.

The synthesis and antibacterial activity of 1beta-methylcarbapenems with quaternary ammonium groups at the C-2 position have been studied. Two types of new carbapenem derivatives have been synthesized. These 1beta-methylcarbapenems, one type having a (2S,4S)-2-[1,1-dimethyl-2-(1-piperazinyl)carbonyl]pyrrolidinio-4-+ ++ylthio group and the other type having a (2S,4S)-2-(4-carbamoylmethyl-4-methylhomopiperazinio-1-yl carbonyl)pyrrolidin-4-ylthio group, show potent and well balanced antibacterial activity as well as high stability against dehydropeptidase-I. The in vivo potency of these two carbapenems was compared with that of meropenem. The structure-activity relationships leading to these carbapenems are also described.

Complementation of a fibre mutant adenovirus by packaging cell lines stably expressing the adenovirus type 5 fibre protein.

Adenovirus-based gene therapy vectors now in use cannot be targeted to specific cell types in vivo and are immunogenic, properties which limit their clinical utility. Improved vectors lacking the genes for viral structural proteins may overcome these limitations. We have developed cell lines which stably express the adenovirus type 5 (Ad5) fibre protein in its native trimeric form. These cells can complement an Ad5 mutant with a defect in the fibre gene, and are capable of incorporating the Ad5 fibre into particles of a different Ad serotype. As the fibre protein is responsible for the initial binding of virus to cells, packaging cell lines expressing different or modified fibre proteins will be useful in studying the mechanism by which adenovirus infects different cell types.

Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion.

Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle alpha-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.

Synthesis and structure-activity relationships of a novel oral carbapenem, CS-834.

We have studied an ester prodrug of a carbapenem to develop a potent orally active beta-lactam antibiotic. A variety of 1 beta-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1R, 5S, 6S)-6-[(R)-1-hydroxyethyl]-l-methyl-2-[(R)-5-oxopyrrolidin-3-yl thio]- l-carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.

Identification of semaphorin E as a non-MDR drug resistance gene of human cancers.

To improve cancer chemotherapy, a better understanding of the molecular mechanisms of drug resistance is essential. To identify the molecules responsible for drug resistance that is unrelated to MDR1 or MRP gene products, a eukaryotic expression cDNA library of cis-diamminedichloroplatinum(II) (CDDP)-resistant ovarian cancer TYKnuR cells was introduced into Cos-7 cells. After repeated CDDP selection, cDNA homologous to murine semaphorin E was isolated from surviving cells. Human semaphorin E (H-sema E) was overexpressed in CDDP-resistant cell lines and was readily induced not only by diverse chemotherapeutic drugs but also by x-ray and UV irradiation. Transfection of H-sema E conferred a drug-resistant phenotype to CDDP-sensitive cells. In addition, the aberrant expression of H-sema E protein was detected immunohistochemically in 14 of 42 (33.3%) recurrent squamous cell carcinomas removed at autopsy after extensive radiochemotherapy. Recently, another member of the semaphorin family, CD100, was shown to significantly improve the viability of B lymphocytes. These results suggest the involvement of semaphorins in diverse cell survival mechanisms.

Aberrant expression of a hemidesmosomal protein, bullous pemphigoid antigen 2, in human squamous cell carcinoma.

Through yet unidentified mechanisms, squamous epithelial cells become committed to terminal differentiation after detachment from the basement membrane. In squamous cell carcinoma, these mechanisms seem to be disturbed. A murine monoclonal antibody, designated NCC-Lu-226 (IgG1, K), which recognizes an antigen expressed in basal cells of squamous epithelium at the epithelio-connective tissue border, was obtained. A cDNA clone encoding the antigen was isolated from a cDNA library by immunoselection. DNA sequencing and a database search revealed that this cDNA clone was identical to a hemidesmosomal transmembrane protein, bullous pemphigoid antigen 2 (BPA-2; also known as BPAG2, BP180, or type XVII collagen). Immunoelectron microscopy validated the specific reactivity of this monoclonal antibody with skin hemidesmosomes. Enhanced expression and abnormal distribution of BPA-2 was revealed immunohistochemically in various precancerous and cancerous tissues, including solar keratosis (4 of 5), Bowen's disease (3 of 5), invasive squamous cell carcinoma (7 of 7) of the skin, and squamous cell carcinoma of the lung (14 of 14), esophagus (12 of 13), and cervix (14 of 17). The specific expression of BPA-2 protein in squamous cell carcinoma was confirmed by RT-PCR and Northern hybridization. BPA-2 has possible phosphorylation sites and is actually phosphorylated in cultured keratinocytes and squamous cell carcinoma. The aberrant expression of BPA-2 may reflect dysfunction of the hemidesmosome that occurs as a relatively early event in multistep carcinogenesis of squamous epithelium.

[Histopathological and electron microscopic changes in mice treated with puffer fish toxin].

The histopathological examination of a male ddY mouse given an intraperitoneal injection of the crude extract containing 169 micrograms/ml of tetrodotoxin (TTX) prepared from the ovary of Takifugu porphyreus was carried out. Two crude extract solutions (0.42 and 0.21 microgram/ml) were prepared; one kills an animal in 10 min (group 1), and other kills it in 40 min (group 2) after the injection. As a result, a remarkable inflation of the gall bladder was observed macroscopically in both groups. By light microscopic observed, both groups showed the congestion in the brain, heart, liver, gall bladder, lung and kidneys, while nerve cells were characterized by the vacuolation and disappearance of Nissl's body only in group 2, probably because of the mitochondrial degeneration. Electron microscopically, a part of cristae of mitochondria and ribosome of endoplasmic reticulum disappeared or vacuolated in the nerve cells of group 2. This was also observed in a part of pre and postsynaptic mitochondria of synapse. However, little significant changes were observed in group 1 and in other tissues of group 2. These results show that a cytopathological change of mice by TTX is mainly detected in nerve tissues when a small amount of TTX is administered to the animals.