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Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. Synthesis of plasmalogens is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of patients with deficiency in peroxisome biogenesis suggests that de novo synthesis of plasmalogens contributes significantly to plasmalogen homeostasis in humans. Plasmalogen biosynthesis is spatiotemporally regulated by a feedback mechanism that senses the amount of plasmalogens in the inner leaflet of the plasma membrane and regulates the stability of fatty acyl-CoA reductase 1 (FAR1), the rate-limiting enzyme for plasmalogen biosynthesis. Dysregulation of plasmalogen synthesis impairs cholesterol synthesis in cells and brain, resulting in the reduced expression of genes such as mRNA encoding myelin basic protein, a phenotype found in the cerebellum of plasmalogen-deficient mice. In this review, we summarize the current knowledge of molecular mechanisms underlying the regulation of plasmalogen biosynthesis and the link between plasmalogen homeostasis and cholesterol biosynthesis, and address the pathogenesis of impaired plasmalogen homeostasis in rodent and humans. [ABSTRACT FROM AUTHOR]

The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid -oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Because CNS integrity is coordinately established and maintained by neural cell interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact coculture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid -oxidation in the astrocytes. Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function. [ABSTRACT FROM AUTHOR]

Ether glycerolipids, plasmalogens are found in various mammalian cells and tissues. However, physiological role of plasmalogens in epithelial cells remains unknown. We herein show that synthesis of ethanolamine-containing plasmalogens, plasmenylethanolamine (PlsEtn), is deficient in MCF7 cells, an epithelial cell line, with severely reduced expression of alkyl-dihydroxyacetonephosphate synthase (ADAPS), the second enzyme in the PlsEtn biosynthesis. Moreover, expression of ADAPS or supplementation of PlsEtn containing C18-alkenyl residue delays the migration of MCF7 cells as compared to that mock-treated MCF7 and C16-alkenyl-PlsEtn-supplemented MCF7 cells. Localization of E-cadherin to cell–cell junctions is highly augmented in cells containing C18-alkenyl-PlsEtn. Together, these results suggest that PlsEtn containing C18-alkenyl residue plays a distinct role in the integrity of E-cadherin-mediated adherens junction. [ABSTRACT FROM AUTHOR]

Synthesis of ethanolamine plasmalogen (PlsEtn) is regulated by modulating the stability of fatty acyl-CoA reductase 1 (Far1) on peroxisomal membrane, a rate-limiting enzyme in plasmalogen synthesis. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis in cultured cells by altering the stability of squalene epoxidase (SQLE). However, regulation of PlsEtn synthesis and physiological consequences of plasmalogen homeostasis in tissues remain unknown. In the present study, we found that the protein but not the transcription level of Far1 in the cerebellum of the Pex14 mutant mouse expressing Pex14p lacking its C-terminal region (Pex14ΔC/ΔC) is higher than that from wild-type mouse, suggesting that Far1 is stabilized by the lowered level of PlsEtn. The protein level of SQLE was increased, whereas the transcriptional activity of the liver X receptors (LXRs), ligand-activated transcription factors of the nuclear receptor superfamily, is lowered in the cerebellum of Pex14ΔC/ΔC and the mice deficient in dihydroxyacetonephosphate acyltransferase, the initial enzyme for the synthesis of PlsEtn. These results suggest that the reduction of plasmalogens in the cerebellum more likely compromises the cholesterol homeostasis, thereby reducing the transcriptional activities of LXRs, master regulators of cholesterol homeostasis. [ABSTRACT FROM AUTHOR]

One of the important issues on the GPS‐acoustic (GPS‐A) observation for sea bottom positioning is how to address the horizontal heterogeneity of the sound speed in oceans. This study presents an analysis method of GPS‐A data in the presence of a sloping sound speed structure. By applying this method and revising the analysis scheme to make full use of existing data, we reevaluated the horizontal postseismic deformations occurring ~1.5–5 years after the 2011 Tohoku earthquake. The revised horizontal movements have more uniform directions and rates between neighboring sites, suggesting enhancement of the array positioning accuracy. The revised displacement rate of the site on the incoming Pacific plate, located ~100 km northeast of the main rupture zone, was decreased significantly; it was only slightly, by 1.4 cm/year larger than the global motion of the Pacific plate, suggesting a relatively small effect of viscoelastic relaxation. The horizontal movements of the near‐trench sites above the main rupture zone were generally landward and were significantly faster than the Pacific plate motion, indicating a viscoelastic relaxation of 5–10 cm/year. The distribution of the fast landward movements peaked near 38°N at an updip of the mainshock hypocenter and extended significantly farther to the north than to the south. This implies the existence of a secondary coseismic slip patch in the northern area in addition to a primary slip patch at ~38°N. The occurrence of episodic slow slip in early 2015 to the north of the main rupture zone was also verified from the GPS‐A analyses. Key Points: We present a new analysis method of GPS‐acoustic observation data for seafloor positioning in the presence of sloping sound speed structureThe application to the 2011 Tohoku earthquake demonstrate enhanced position accuracy by the spatially coherent postseismic movementsThe occurrence of episodic slow slip in 2015, which has been inferred from repeating earthquakes, was also verified from our observations [ABSTRACT FROM AUTHOR]

• Peat pots and peat pellets were tested for the rooting of 'MKR1' softwood cuttings. • Peat pots produced a similar rooting percentage as those in plastic pots. • Leaf trimming affected the rooting percentage and root growth of the cuttings. • Mixing peat with perlite increased rooting percentages and root growth. • Cuttings treated with 2000 mg L−1 K-NAA quick-dip had highest peat pellet rooting. Peat pots and peat pellets soaked in different concentrations of auxin were tested as an alternative to plastic pots and to improve propagation efficiency by eliminating the laborious work involved in softwood cutting propagation of 'MKR1' persimmon dwarfing rootstock. Cuttings in peat pots produced similar rooting percentages to those in plastic pots. The roots of cutting in pots placed on water-saturated trays were significantly longer than those placed on perforated, drained trays. Compared to intact leaves and 1/4 leaf trimming, cuttings with 1/2 of the leaf blade decreased the rooting percentage. Perlite produced 15% rooting, but when mixed with peat (1:1), it enhanced rooting to 91%. Cuttings planted in pellets soaked in 100, 250, 500, 1000, and 2000 mg L−1 K-IBA or K-NAA produced ≤ 50% rooting, while those quickly dipped in 2000 mg L−1 K-NAA and planted in hormone-free pellets achieved 83% rooting. Peat pots appear to be a potential alternative to plastic pots, and the laborious work of pot filling can be eliminated by planting cuttings in peat pellets after a quick dip in 2000 mg L−1 K-NAA. [ABSTRACT FROM AUTHOR]

We have developed a comprehensive inversion scheme to analyze traveltime data collected through GPS-acoustic observations on a campaign basis. Our method uses a quantity called the 'nadir total delay' (NTD), which is analogous to the zenith total delay in Global Navigation Satellite Systems analyses, to represent the time variation of the sound speed. The observation equation using the NTD is an approximated formulation. We examine its applicable scope using numerical experiments and demonstrate that the approximation holds well enough in practice. Traveltime data from all our observation campaigns were utilized together for inversion calculation to determine the following: (1) the positions of individual precision acoustic transponders at the time of a particular reference campaign, (2) the displacement from these positions of a rigid array at the time of each campaign, and (3) the time variation of the NTD during each campaign. We applied this method to actual data to fix the array geometry more precisely. Also, we have made a first step in detecting vertical motions as well as horizontal motions, though further enhancement of the accuracy will be required. In performing linear regression of array displacements obtained from the inversion, their error covariance has a significant effect on the resulting velocities. When the covariance is taken into account, nearly the same velocities are obtained no matter what campaign is taken as reference in the inversion. [ABSTRACT FROM AUTHOR]

Plasmalogens, mostly ethanolamine-containing alkenyl ether phospholipids, are a major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of peroxisome biogenesis-defective patients suggests that the de novo synthesis of plasmalogens plays a pivotal role in its homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the stability of fatty acyl-CoA reductase 1 on peroxisomal membranes, a rate-limiting enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of plasma membranes. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis by altering the stability of squalene monooxygenase, a key enzyme in cholesterol biosynthesis, implying physiological consequences of plasmalogen homeostasis with respect to cholesterol metabolism in cells, as well as in organs such as the liver. [ABSTRACT FROM AUTHOR]

The durability of a water electrolysis cell against wind power voltage fluctuations was evaluated by developing an accelerated potential fluctuation test protocol based on wind power voltage fluctuations over an actual 24 h period of operation. Accelerating potential protocol tests corresponding to 160 d of actual operation were performed. The current loss during the test is mostly recovered if rest time was included during the operation. Reversible loss is most likely related to gas stagnation, suppression of oxygen reduction reaction activity owing to the formation less active Ir(V) species, and suppression of gas evolution owing to the increased hydrophilic surface. This irreversible loss can be attributed to the dissolution of IrO 2 and the loss of Nafion® ionomer. Even though the potential fluctuation itself was not a problem if the lowest potential was 1.0 V, the upper limit of the potential was rather problematic. When the upper potential is increased to 2.3 V, the oxidation of IrO 2 is enhanced, leading to the partial dissolution of IrO 2 , followed by the formation of a dense structure, a decrease in the oxygen evolution reaction activity, and an increase in the surface hydrophilicity. • The durability of a water electrolyzer against wind power fluctuation was evaluated. • A protocol evaluating the long-term durability was investigated. • Most of the current density loss was recovered after the rest time. • Suppression of gas evolution due to the increased hydrophilic surface was suggested. • A small portion of the irreversible loss was related to the loss of Ir and ionomer. [ABSTRACT FROM AUTHOR]

Key message : 2n pollen formed by FDR in citrus. Abstract: The Japanese local citrus cultivar, Nishiuchi Konatsu ( Citrus tamurana hort. ex Tanaka; NK hereafter), has the ability to produce unreduced 2n pollen grains, allowing generation of polyploid progenies via sexual polyploidization. In this study, we developed a method of single-pollen genotyping for citrus and applied it to the analysis of transmission of heterozygosity in NK 2n pollen grains. Heterozygosity transmission was expressed as the percentage inheritance of a set of heterozygous alleles from the parent to the 2n gamete. The pathway of 2n pollen development was investigated by applying the observed heterozygosity transmission and genetic distance to two different map functions, for first division restitution (FDR) and second division restitution (SDR). The fit of the values observed for both functions was calculated, while virtually moving the centromere position. We screened for six heterozygous SSR (codominant microsatellite marker loci) in NK, all of which were expected to lie within the same linkage group. Pollen germination prior to DNA extraction was essential for this work, and 6-h incubation proved to be optimal for subsequent PCR amplification. Single-pollen genotyping unreduced NK 2n pollen grains revealed that heterozygosity transmission exceeded 50 % in all six alleles, and fitness tests indicated that the FDR map function better fitted the heterozygosity transmission observed rather than the SDR function. Our data thus strongly indicate that 2n pollen in NK is a result of first division restitution. [ABSTRACT FROM AUTHOR]

Peroxisome number and quality are maintained by its biogenesis and turnover and are important for the homeostasis of peroxisomes. Peroxisomes are increased in number by division with dynamic morphological changes including elongation, constriction, and fission. In the course of peroxisomal division, peroxisomal morphogenesis is orchestrated by Pex11β, dynamin-like protein 1 (DLP1), and mitochondrial fission factor (Mff). Conversely, peroxisome number is reduced by its degradation. Peroxisomes are mainly degraded by pexophagy, a type of autophagy specific for peroxisomes. Upon pexophagy, an adaptor protein translocates on peroxisomal membrane and connects peroxisomes to autophagic machineries. Molecular mechanisms of pexophagy are well studied in yeast systems where several specific adaptor proteins are identified. Pexophagy in mammals also proceeds in a manner dependent on adaptor proteins. In this review, we address the recent progress in studies on peroxisome morphogenesis and pexophagy. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the birefringent properties of the cornea and examine the supraorganizational aspects of collagen fibers in cats with tropical keratopathy. Procedure: In this study, 10‐micrometer‐thick sections of corneal tissue from cats with tropical keratopathy were examined, both in the opaque and transparent areas of the anterior stroma. Control samples were obtained from healthy cat corneas. Polarized light microscopy was employed to evaluate the birefringent properties using two distinct methods. The first method involved measuring the optical retardation associated with corneal birefringence, while the second method assessed the alignment/waviness of the birefringent collagen fibers. Differences were significant when p <.05. Results: Tropical keratopathy resulted in a significant rise (p <.05) in optical retardation in both opaque and transparent regions of the cat cornea. In the anterior stroma, both the opaque zones and transparent tissue exhibited a higher degree of collagen fiber packing than the control corneas. However, no significant differences (p >.05) in alignment were observed between the transparent tissue of the diseased cornea and the healthy corneas. Conclusion: Supraorganizational changes in collagen fiber packing are not restricted to lesion zones in cat corneas affected by tropical keratopathy. Such alterations also occur in the corneal tissue of the anterior stroma adjoining the lesions. Therefore, it is plausible that the transparent tissue of the anterior stroma in corneas affected by the disease may have functional abnormalities, despite its macroscopic healthy appearance. Additional investigations are required to clarify the implications of these potential defects and their conceivable contribution to tropical keratopathy. [ABSTRACT FROM AUTHOR]

Plasmalogen biosynthesis is regulated by modulating fatty acyl-CoA reductase 1 stability in a manner dependent on cellular plasmalogen level. However, physiological significance of the regulation of plasmalogen biosynthesis remains unknown. Here we show that elevation of the cellular plasmalogen level reduces cholesterol biosynthesis without affecting the isoprenylation of proteins such as Rab and Pex19p. Analysis of intermediate metabolites in cholesterol biosynthesis suggests that the first oxidative step in cholesterol biosynthesis catalyzed by squalene monooxygenase (SQLE), an important regulator downstream HMG-CoA reductase in cholesterol synthesis, is reduced by degradation of SQLE upon elevation of cellular plasmalogen level. By contrast, the defect of plasmalogen synthesis causes elevation of SQLE expression, resulting in the reduction of 2,3- epoxysqualene required for cholesterol synthesis, hence implying a novel physiological consequence of the regulation of plasmalogen biosynthesis. [ABSTRACT FROM AUTHOR]

Background: The squamous cell carcinoma (SCC) is the second most common cancer in the oral epithelium of dogs and rarely involves the retrobulbar area. The diagnosis is confirmed with cytological and histopathological exam. Faced with the unusual occurrence of retrobulbar tumors in dogs, we report a case of SCC in the left maxilla, with ipsilateral retrobulbar metastasis, and also highlight clinical aspects of the neoplasia, exams, early diagnosis and therapeutic possibilities. Case: A male dog, 17 years old, with a history of visual loss, enlargement of left eye and prostration after 25 days of a dental treatment. The patient had exophthalmia of the left eye with mild lateral deviation, meibomitis, lagophthalmos, moderate conjunctival hyperemia and episcleral congestion, protrusion of the third eyelid, epiphora, moderate purulent discharge, paracentral corneal degeneration, absence of pupillary reflex to light (direct and consensual) and presence of immature cataract. The Schirmer test and intraocular pressure were normal, as well as complete blood count and biochemical profile. Due to the testy temperament of the animal, the intraoral examination was limited to two-thirds of the jaw in the first appointment. Ocular vitreous ultrasound was performed showing moderate amount of membranous and punctate echoes, as well as medium-high reflectivity were present in all meridians evaluated, suggesting hemorrhagic-inflammatory process. In the retrobulbar space image of contours were poorly defined, measuring approximately 35.2 mm, with a heterogeneous echotexture and mixed echogenicity, suggestive of neoplasm or abscess. The animal was anesthetized for cytological evaluation. Absence of left maxillary molars teeth, ulceration area and a maxillae nodule was observed ipsilateral to abnormal eye. This node had one centimeter in diameter, was reddish, ulcerated, friable and adhered. The material was collected for histopathology, which confirmed the diagnosis of undifferentiated SCC, with a primary focus in the oral cavity. Discussion: Exophthalmia can be a common clinical sign for ophthalmic and oral neoplasias and should be differentiated from secondary exophthalmia glaucoma, injuries and abscesses, granulomas, cysts, orbital cellulitis. It may also be the source of oral or salivary glands infections and systemic diseases. In this case, the clinical signs and history of previous dental treatment, ocular ultrasonography was performed to differentiate abscess from neoplasia, and also to verify the affected area. It was conclude that the retrobulbar neoplasia was secondary to oral squamous cell carcinoma due to the malignant neoplasia had keratinocyte origin, which is normally found in oral epithelium cells, however this types of cells is not found in retrobulbar area. Additionally to support our statement primary retrobulbar neoplasia has frequently low metastatic capacity to surrounding organs. The loss of visual acuity, probably was consequence of optic nerve compression, which also may led to impairment of the pupillary reflex of afferent pathway. As most retrobulbar neoplasia results from metastasis, clinical examination of adjacent regions is essential, as well as the use of additional exams to assist in the search for primary tumor and exclusion disorders that can demonstrate the same clinical signs. [ABSTRACT FROM AUTHOR]

The occlusion of the inferior lacrimal punctum limits tear drainage and thus keeps it over the ocular surface, prolongs lubrication and minimizes the need of ocular lubricants. The aim of this study was to evaluate the effectiveness of n-butyl-cyanoacrylate and 2-octyl-cyanoacrylate adhesives in the occlusion of the inferior lacrimal punctum and canaliculi of dogs and their clinical repercussions over 180 days. Eleven dogs, were divided into two groups: occlusion with n-butyl-cyanoacrylate (GB, n=6) and with 2-octyl-cyanoacrylate (GO, n=5). Tear production, blepharospasm, ocular discharge, epiphora and conjunctival hyperemia were analyzed before the procedure and on days (T) 3,7,15, 30, 45, 60, 90, 120, 150 and 180 after the procedure. Tear production of GB was significantly higher at T90 (P=0.0282) than its control. Variations between days showed that T7 (P=0.0069) and T180 (P=0.0207) varied significantly from TO. In the GO group, when treatment was compared to control, T15 (P<0.001) was significantly different from the rest. Variations between days showed that T15 was significantly different than TO (P=0.0044), T3 (P=0.0234), T60 (P=0.0207) and T90 (P=0.0482). No significant difference was observed between the treatment groups at any given time. It was concluded that both adhesives were effective in occluding lacrimal drainage for long periods and could thus be considered as therapeutic options in treating animals with lacrimal deficiency. [ABSTRACT FROM AUTHOR]

Rhizomelic chondrodysplasia punctata (RCDP) is an autosomal recessive disorder due to the deficiency in ether lipid synthesis. RCDP type 1, the most prominent type, is caused by the dysfunction of the receptor of peroxisome targeting signal type 2, Pex7 (peroxisomal biogenesis factor 7), and the rest of the patients, RCDP types 2 and 3, have defects in peroxisomal enzymes catalyzing the initial two steps of alkyl-phospholipid synthesis, glyceronephosphate O-acyltransferase and alkylglycerone phosphate synthase (Agps). We herein investigated defects of two patients with RCDP type 3. Patient 1 had a novel missense mutation, T1533G, resulting in the I511M substitution in Agps. The plasmalogen level was mildly reduced, whereas the protein level and peroxisomal localization of Agps-I511M in fibroblasts were normal as in the control fibroblasts. Structure prediction analysis suggested that the mutated residue was located in the helix α15 on the surface of V-shaped active site tunnel in Agps, likely accounting for the mild defects of plasmalogen synthesis. These results strongly suggest that an individual with mildly affected level of plasmalogen synthesis develops RCDP. In fibroblasts from patient 2, the expression of AGPS mRNA and Agps protein was severely affected, thereby giving rise to the strong reduction of plasmalogen synthesis. [ABSTRACT FROM AUTHOR]

Abstract: Peroxisomes are subcellular organelles that function in multiple anabolic and catabolic processes, including β-oxidation of very-long-chain fatty acids (VLCFA) and biosynthesis of ether phospholipids. Peroxisomal disorders caused by defects in peroxisome biogenesis or peroxisomal β-oxidation manifest as severe neural disorders of the central nervous system. Abnormal peroxisomal metabolism is thought to be responsible for the clinical symptoms of these diseases, but their molecular pathogenesis remains to be elucidated. We performed lipidomic analysis to identify aberrant metabolites in fibroblasts from patients with Zellweger syndrome (ZS), acyl-CoA oxidase1 (AOx) deficiency, D-bifunctional protein (D-BP) and X-linked adrenoleukodystrophy (X-ALD), as well as in peroxisome-deficient Chinese hamster ovary cell mutants. In cells deficient in peroxisomal biogenesis, plasmenylethanolamine was remarkably reduced and phosphatidylethanolamine was increased. Marked accumulation of very-long-chain saturated fatty acid and monounsaturated fatty acids in phosphatidylcholine was observed in all mutant cells. Very-long-chain polyunsaturated fatty acid (VLC-PUFA) levels were significantly elevated, whilst phospholipids containing docosahexaenoic acid (DHA, C22:6n-3) were reduced in fibroblasts from patients with ZS, AOx deficiency, and D-BP deficiency, but not in fibroblasts from an X-ALD patient. Because patients with AOx deficiency suffer from more severe symptoms than those with X-ALD, accumulation of VLC-PUFA and/or reduction of DHA may be associated with the severity of peroxisomal diseases. [Copyright &y& Elsevier]

Peroxisomal fatty acyl-CoA reductase 1 (Far1) is essential for supplying fatty alcohols required for ether bond formation in ether glycerophospholipid synthesis. The stability of Far1 is regulated by a mechanism that is dependent on cellular plasmalogen levels. However, the membrane topology of Far1 and how Far1 is targeted to membranes remain largely unknown. Here, Far1 is shown to be a peroxisomal tail-anchored protein. The hydrophobic C terminus of Far1 binds to Pex19p, a cytosolic receptor harboring a C-terminal CAAX motif, which is responsible for the targeting of Far1 to peroxisomes. Far1, but not Far2, was preferentially degraded in response to the cellular level of plasmalogens. Experiments in which regions of Far1 or Far2 were replaced with the corresponding region of the other protein showed that the region flanking the transmembrane domain of Far1 is required for plasmalogen-dependent modulation of Far1 stability. Expression of Far1 increased plasmalogen synthesis in wild-type Chinese hamster ovary cells, strongly suggesting that Far1 is a rate-limiting enzyme for plasmalogen synthesis. [ABSTRACT FROM AUTHOR]

We have successfully designed the geometry of the microwave cavity and the thin metal electrode, achieving resonance of the microwave cavity with the metal-insulator-semiconductor (MIS) device structure. This very simple MIS device operates in the cavity, where charge carriers are injected quantitatively by an applied bias at the insulator-semiconductor interface. The local motion of the charge carriers was clearly probed through the applied external microwave field, also giving the quantitative responses to the injected charge carrier density and charge/discharge characteristics. By means of the present measurement system named field-induced time-resolved microwave conductivity (FI-TRMC), the pentacene thin film in the MIS device allowed the evaluation of the hole and electron mobility at the insulator-semiconductor interface of 6.3 and 0.34 cm2 V-1 s-1, respectively. This is the first report on the direct, intrinsic, non-contact measurement of charge carrier mobility at interfaces that has been fully experimentally verified. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the optical and electronic properties of three kinds of polycarbazole with linkages located at 2,7-, 3,6-, and alternating positions, corresponding to poly(N-dodecyl-2,7-carbazolediyl), poly(N-dodecyl-3,6-carbazolediyl), and poly(N-dodecyl-2,7-carbazolediyl-alt-N-dodecyl-3,6-carbazolediyl), respectively. Fluorescence from the latter two polymers in chloroform showed time-dependent changes, which were examined in terms of solvent, concentration, UV light irradiation, and the presence of oxygen. Flash photolysis time-resolved microwave conductivity (FP-TRMC) and space charge limited current (SCLC) measurements revealed that poly(3,6-carbazole) had the highest intra- and intermolecular charge carrier mobilities, at 0.3 and 1.8×10−5 cm2 V−1 s−1, respectively, which were higher than those of the copolymer (0.2 and 2.0×10−7 cm2 V−1 s−1) and poly(2,7-carbazole) (0.1 and 3.4×10−9 cm2 V−1 s−1). Although poly(2,7-carbazole) was expected to show superior electronic properties based on X-ray diffraction (XRD), it showed the lowest value among the polycarbazoles investigated. The surface roughness, based on atomic force microscope (AFM) images, indicated that the deterioration of charge carrier transport properties arose from an unusually high degree of crystallinity. This study underlines the importance of the balance between intermolecular interaction (crystallinity), solubility, and delocalization of radical cations along the conjugated backbone, which could be of help in designing the molecular structures of highly efficient organic electronic devices. [Copyright &y& Elsevier]

Abstract: Mango (Mangifera indica L.) is one of the most important evergreen fruit trees, but it has a high tendency of biennial bearing because of irregular flowering. In this study, a FLOWERING LOCUS T-like (FT-like) gene was isolated from mango (MiFT) and characterized. The deduced amino acid sequence of MiFT showed high identity of the gene to other plant FT-like genes, and further, MiFT expression increased only in the leaves under floral-inductive conditions. Comparison of heavy crop load (HC) and no crop load (NC) mango trees showed that MiFT expression strongly increased only in NC trees under cool temperature. In NC trees, almost all the apical buds formed panicles, whereas in HC trees, only a few panicles were produced in the next season of fruit set. Further, HC trees had lower starch content in the shoots than NC trees. Furthermore, application of 250-ppm gibberellin 3 (GA3) completely inhibited flowering and MiFT expression in both HC and NC trees. GA metabolism genes were also isolated from mango and their expression patterns were investigated. Gibberellin-3-oxidase (GA3-ox) controls the final step of biosynthesis of active GA, and its gene expression surged only in HC trees under cool temperature. In conclusion, MiFT is considered a key factor in mango flowering, and regulation of MiFT expression through GA metabolism was discussed. [Copyright &y& Elsevier]

Abstract: In the Fischer–Tropsch (FT) synthesis, the catalytic behavior of Co-loaded powdered oxidized diamond (O-Dia) catalyst having a surface area of 24m2/g was examined. The catalytic activity of 9wt% Co-loaded oxidized diamond catalyst exhibited a high CO conversion of 44.5% at 250°C with a total pressure of 1.0MPa containing 1:2 CO and H2 mixed gas, and a space velocity of 4500h−1. This conversion is much higher than that of Co-loaded SiO2 catalyst of two different surface areas, where CO conversions of 38.4% and 12.2% were obtained for SiO2 having a surface area of 190m2/g and 12m2/g, respectively. The effect of cobalt precursor salt was examined, and an increased CO conversion was obtained with the use of cobalt acetate as a source of Co. A much higher dispersion of Co with the use of cobalt acetate was observed by temperature-programmed reduction, CO adsorption, and TEM observations. A weaker interaction between the O-Dia surface and cobalt oxide seems to contribute to higher catalytic activity for the FT synthesis. [Copyright &y& Elsevier]

Peroxisome division is regulated by several factors, termed fission factors, as well as the conditions of the cellular environment. Over the past decade, the idea of metabolic control of peroxisomal morphogenesis has been postulated, but remains largely undefined to date. In the current study, docosahexaenoic acid (DHA, C22:6n-3) was identified as an inducer of peroxisome division. In fibroblasts isolated from patients that carry defects in peroxisomal fatty acid β-oxidation, peroxisomes are much less abundant than normal cells. Treatment of these patient fibroblasts with DHA induced the proliferation of peroxisomes to the level seen in normal fibroblasts. DHA-induced peroxisomal proliferation was abrogated by treatment with a small inhibitory RNA (siRNA) targeting dynamin-like protein 1 and with dynasore, an inhibitor of dynamin-like protein 1, which suggested that DHA stimulates peroxisome division. DHA augmented the hyperoligomerization of Pex11pb and the formation of Pex11pb-enriched regions on elongated peroxisomes. Time-lapse imaging analysis of peroxisomal morphogenesis revealed a sequence of steps involved in peroxisome division, including elongation in one direction followed by peroxisomal fission. DHA enhanced peroxisomal division in a microtubule-independent manner. These results suggest that DHA is a crucial signal for peroxisomal elongation, a prerequisite for subsequent fission and peroxisome division. [ABSTRACT FROM AUTHOR]

Intramolecular mobility of positive charge carriers in conjugated polymer films based on dithieno [2,3-b: 2', 3'-d] pyrrole (DTP) is studied by time-resolved microwave conductivity (TRMC). A series of DTP homopolymer and copolymers combined with phenyl, 2,2'-biphenyl, thiophene, 2,2'-bithiophene, and 9,9'-dioctylfluorene were synthesized by Suzuki-Miyaura and Yamamoto coupling reactions. Polymers containing DTP unit are reported to show high value of hole mobility measured by FET method, and this type of polymers is expected to have stable HOMO orbitals which are important for hole transportation. Among these copolymers, DTP coupled with 9,9'-dioctylfluorene copolymer showed the highest charge carrier mobility as high as 1.7 cm2/Vs, demonstrating an excellent electrical property on rigid copolymer backbones. [ABSTRACT FROM AUTHOR]

We earlier isolated peroxisome biogenesis-defective Chinese hamster ovary (CHO) cell mutants, ZPEG241, by the 9-(1′-pyrene)nonanol/ultraviolet selection method, from TKaEG2, the wild-type CHO-K1 cells transformed with two cDNAs encoding rat Pex2p and peroxisome targeting signal type 2 (PTS2)-tagged enhanced green fluorescent protein (EGFP). Peroxisomal localization of PTS2-EGFP was specifically impaired in ZPEG241 due to the failure of Pex5pL expression. Analysis of partial genomic sequence of PEX5 revealed one-point nucleotide-mutation from G to A in the 3′-acceptor splice site located at 1 nt upstream of exon 7 encoding Pex5pL specific 37-amino acid insertion, thereby generating 21-nt deleted mRNA of PEX5L in ZPEG241. When ZPEG241-derived Pex5pL was ectopically expressed in ZPEG241, PTS2 import was not restored because of no interaction with Pex7p. Together, we confirm the pivotal role of Pex5pL in PTS2 import, showing that the N-terminal 7-amino acid residues in the 37-amino acid insertion of Pex5pL are essential for the binding to Pex7p. [ABSTRACT FROM PUBLISHER]

The molecular design of light-harvesting antennae requires not only the segregation of a large number of chromophore units in a confined nanospace but also the cooperation of these units in achieving highly efficient energy transduction. This article describes the synthesis and functions of a polyphenylene-based conjugated microporous polymer (PP-CMP). PP-CMP was recently designed and synthesized by Suzuki polycondensation reaction and used as an antenna for the noncovalent construction of a light-harvesting system. In contrast to linear polyphenylene, PP-CMP consists of conjugated three-dimensional polyphenylene scaffolds and holds inherent porous structure with uniform pore size (1.56 nm) and large surface area (1083 m² g-1). It emits blue photoluminescence, is capable of excitation energy migration over the framework, and enables rapid transportation of charge carrier with intrinsic mobility as high as 0.04 cm² V-1 s-1. The microporous structure of PP-CMP allows for the spatial confinement of energy-accepting coumarin 6 molecules in the pores and makes the high-throughput synthesis of light-harvesting systems with designable donor-acceptor compositions possible. Excitation of the PP-CMP skeleton leads to brilliant green emission from coumarin 6, with an intensity 21-fold as high as that upon direct excitation of coumarin 6 itself, while the fluorescence from PP-CMP itself is wholly quenched as a result of energy transfer from the light-harvesting PP-CMP framework to coumarin 6. The PP-CMP skeleton is highly cooperative, with an average of 176 phenylene units working together to channel the excitation energy to one coumarin 6 molecule, and features the energy-transfer process with quick, efficient, and vectorial character. These unique characteristics clearly originate from the conjugated porous structure and demonstrate the usefulness of CMPs in the exploration of p-electronic functions, in addition to their gas adsorption properties thus far reported. [ABSTRACT FROM AUTHOR]

Plasmalogens are a major subclass of ethanolamine and choline glycerophospholipids in which a long chain fatty alcohol is attached at the sn-1 position through a vinyl ether bond. This ether-linked alkyl bond is formed in peroxisomes by replacement of a fatty acyl chain in the intermediate 1-acyl-dihydroxy-acetone phosphate with a fatty alcohol in a reaction catalyzed by alkyl dihydroxyacetone phosphate synthase. Here, we demonstrate that the enzyme fatty acyl-CoA reductase 1 (Fan) supplies the fatty alcohols used in the formation of ether-linked alkyl bonds. Far1 activity is elevated in plasmalogen-deficient cells, and conversely, the levels of this enzyme are restored to normal upon plasmalogen supplementation. Down-regulation of Fan activity in response to plasmalogens is achieved by increasing the rate of degradation of peroxisomal Far1 protein. Supple- mentation of normal cells with ethanolamine and 1-O-hexadecyl- glycerol, which are intermediates in plasmalogen biosynthesis, accelerates degradation of Fan. Taken together, our results indicate that ether lipid biosynthesis in mammalian cells is regulated by a negative feedback mechanism that senses cellular plasmalogen levels and appropriately increases or decreases Far1. [ABSTRACT FROM AUTHOR]

The reproductive characteristics of 'Nishiuchi Konatsu, a bud mutation of Hyuganatsu that is self-incompatible, were examined. A pollination experiment resulted in Hyuganatsu x 'Nishiuchi Konatsu' and 'Nishiuchi Konatsu' self-pollination produced their fruit, whereas 'Nishiuchi Konatsu' x Hyuganatsu cannot produce fruit as a result of early dropping of premature fruits within the first 10 weeks after pollination. Considering the self-incompatible nature of Hyuganatsu, this result implies a mutation of the pollen-expressed gene(s) associated with the self-incompatibility occurring in 'Nishiuchi Konatsu'. When 'Nishiuchi Konatsu' pollen was used for several citrus accessions (Hyuganatsu, 'Nishiuchi Konatsu', Hassaku, and 'Sweet Spring'), it was observed that the number of normal seeds decreased and that of aborted seeds increased. Interestingly, the extent of seed abortion differed among seed parents. Hyuganatsu and 'Nishiuchi Konatsu' lost most of their normal seeds. In contrast, Hassaku lost relatively lesser seeds, and 'Sweet Spring' lost only a few seeds. Moreover, Hassaku fruits obtained by pollination with 'Nishiuchi Konatsu' pollen showed various proportions of normal and aborted seeds even among individual fruits. 'Nishiuchi Konatsu' pollen did not affect the fruit characteristics, with some exceptions in Hyuganatsu, 'Nishiuchi Konatsu', and Hassaku. All the characteristics were superior in Hyuganatsu-pollinated fruits compared with 'Nishiuchi Konatsu'-pollinated ones in 'Sweet Spring'. In conclusion, it was demonstrated that 'Nishiuchi Konatsu' has two agriculturally important traits: self-compatibility and seed abortion. It can be useful for elucidating the mechanisms and as the genetic resources that introduce these traits. [ABSTRACT FROM AUTHOR]

Abstract: Intra-molecular mobility of positive charge carriers in poly(n-hexyl-[S]-2-methylbutylsilane) (PHMBS) films doped with N,N′-bis(2,5-di-tert-buthylphenyl)-3,4,9,10-perylenedicarboximide (PDI) is studied by time-resolved microwave conductivity (TRMC) measurements. PHMBS with optically active side chains has a rod-like tightly locked Si catenation with unlikely long persistence length compared with conventional dialkyl-substituted polysilanes. It was found that PDI is a suitable electron acceptor for PHMBS as it provides the high product of photo carrier generation yield ϕ as ∼0.08% under an excitation at 355nm. The efficient electron transfer reaction from PHMBS to PDI gives clear conductivity transients ascribed to the positive charges on the Si catenation of PHMBS by TRMC measurements. The estimated value of isotropic mobility along the tightly locked Si catenation is 0.36cm2 V−1 s−1, suggesting the presence of mobile holes on the backbones of PHMBS. [Copyright &y& Elsevier]

Abstract: We herein isolated plasmalogen-deficient Chinese hamster ovary (CHO) mutant, ZPEG251, with a phenotype of normal import of peroxisomal matrix and membrane proteins. In ZPEG251, plasmenylethanolamine (PlsEtn) was severely reduced. Complementation analysis by expression of genes responsible for the plasmalogen biogenesis suggested that alkyl-dihydroxyacetonephosphate synthase (ADAPS), catalyzing the second step of plasmalogen biogenesis, was deficient in ZPEG251. ADAPS mRNA was barely detectable as verified by Northern blot and reverse transcription-PCR analyses. Defect of ADAPS expression was also assessed by immunoblot. As a step toward delineating functional roles of PlsEtn, we investigated its subcellular localization. PlsEtn was localized to post-Golgi compartments and enriched in detergent-resistant membranes. Transport of PlsEtn to post-Golgi compartments was apparently affected by lowering cellular ATP, but not by inhibitors of microtubule assembly and vesicular transport. Partitioning of cholesterol and sphingomyelin, a typical feature of lipid rafts, was not impaired in plasmalogen-deficient cells, including peroxisome assembly-defective mutants, hence suggesting that PlsEtn was not essential for lipid-raft architecture in CHO cells. [Copyright &y& Elsevier]

Abstract: The effective pollination period (EPP) of durian was determined by both delayed and bud pollination, during which reproductive factors affecting the EPP, e.g., stigma receptivity, pollen tube growth in the style, and ovule longevity were studied histologically. This study was conducted in three distinct locations in Thailand, namely, the Chantaburi Horticultural Research Center and two private orchards in Chantaburi and Trat provinces. Results from artificial pollination revealed that at anthesis, the durian flower is receptive and has a high fruit set ratio. A mean fruit set of 50% was obtained at anthesis in the private orchard in Chantaburi province. However, the EPP of durian was found to be very short, lasting for only one night; the fruit set from pollination on the morning after anthesis ranged from 0% to 3.4%. No fruit set occurred following pollination 24 or more hours after anthesis. When compared with the flowers of other fruit species, the durian flower has a unique feature in that it blooms overnight; the following morning, there is abscission of all parts of the flower, except the gynoecium. Thus, EPP appears to be synchronized with flower longevity. On the other hand, the durian flower was receptive several hours before anthesis. The results of chemical tests, including the hydrogen peroxide test and Perex-Test®, for the evaluation of stigma receptivity appeared to be in agreement with the EPP. However, fluorescent microscopy revealed that pollen could germinate even in the stigmas pollinated 48h after anthesis, but the number of pollen tubes at the top of the style rapidly decreased from 34.6 (at anthesis) to 0.5 (48h after anthesis). A correlation test demonstrated a higher correlation coefficient between the fruit set and the number of pollen than that between the fruit set and the result of Perex-Test®. This indicated that pollen tube penetration or elongation in the style was inhibited, probably due to the deterioration of nutritional support from the pistil to the pollen tubes; this can be a limiting factor of the EPP in durian. [Copyright &y& Elsevier]

Although the exact etiology of Alzheimer's disease (AD) is a topic of debate, the consensus is that the accumulation of β-amyloid (Aβ) peptides in the senile plaques is one of the hallmarks of the progression of the disease. The Aβ peptide is formed by the amyloidogenic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. The endocytic system has been implicated in the cleavages leading to the formation of Aβ. However, the identity of the intracellular compartment where the amyloidogenic secretases cleave and the mechanism by which the intracellularly generated Aβ is released into the extracellular milieu are not clear. Here, we show that β-cleavage occurs in early endosomes followed by routing of Aβ to multivesicular bodies (MVBs) in HeLa and N2a cells. Subsequently, a minute fraction of Aβ peptides can be secreted from the cells in association with exosomes, intraluminal vesicles of MVBs that are released into the extracellular space as a result of fusion of MVBs with the plasma membrane. Exosomal proteins were found to accumulate in the plaques of AD patient brains, suggesting a role in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Artificial self-pollination and cross-pollination were performed in addition to open pollination in four Thai durian cultivars, ‘Mon Thong’, ‘Chanee’, ‘Kradum Thong’ and ‘Phaung Manee’, for investigating the efficiency of pollination to fruit set. In all cultivars, open pollination treatment resulted in the lowest fruit set, ranging from 0 to 1.4% at harvest. This may be due to lack of pollination. Self-pollination treatment also resulted in lower fruit set, especially in ‘Mon Thong’ (7.7%), ‘Chanee’ (3.6%) and ‘Phaung Manee’ (0%), indicating a self-incompatibility in durian. When ‘Kradum Thong’ was used as pollen parent, fruit set percentage was significantly high in ‘Mon Thong’ (27.2%), which is a leading cultivar in Thailand. High fruit set was also achieved in ‘Chanee’ (16.3%) by ‘Kradum Thong’ pollen, although its value was not significantly separated from values of other pollen parents tested. Artificial cross-pollination using ‘Kradum Thong’ as a pollinizer was strongly recommended for commercial durian cultivation. The observation of pollen-tube growth in vivo revealed that pollen germination on stigma and pollen-tube elongation in style were not inhibited by self-pollination. Thus, durian seems to have a late-acting self-incompatibility. [Copyright &y& Elsevier]

Partial resistance of cell membranes to solubilization with mild detergents and the analysis of isolated detergent-resistant membranes (DRMs) have been used operationally to define membrane domains. Given the multitude of detergents used for this purpose, we sought to investigate whether extraction with different detergents might reflect the same underlying principle of domain formation. We therefore compared the protein and lipid content of DRMs prepared with a variety of detergents from two cell lines. We found that the detergents differ considerably in their ability to selectively solubilize membrane proteins and to enrich sphingolipids and cholesterol over glycerophospholipids as well as saturated over unsaturated phosphatidylcholine. In addition, we observed cell type-dependent variations of the molecular characteristics of DRMs and the effectiveness of particular detergents. These results make it unlikely that different detergents reflect the same aspects of membrane organization and underscore both the structural complexity of cell membranes and the need for more sophisticated analytical tools to understand their architecture. [ABSTRACT FROM AUTHOR]

Caveolins have been identified as key components of caveolae, specialized cholesterol-enriched raft domains visible as small flask-shaped invaginations of the plasma membrane. In polarized MDCK cells caveolin-1 and -2 are found together on basolateral caveolae whereas the apical membrane, where only caveolin-1 is present, lacks caveolae. Expression of a caveolin mutant prevented the formation of the large caveolin-1/-2 hetero-oligomeric complexes, and led to intracellular retention of caveolin-2 and disappearance of caveolae from the basolateral membrane. Correspondingly, in MDCK cells over-expressing caveolin-2 the basolateral membrane exhibited an increased number of caveolae. These results indicate the involvement of caveolin-2 in caveolar biogenesis. [Copyright &y& Elsevier]

This paper describes a direct drawing method for a microfabrication based on a selective metal plating technology. The selective metal plating technology allows metal plating where a seed material is drawn. It becomes possible to combine various materials, so that the proposed method may cover a classical micromachining at the rather large scale.The direct drawing method can be applied to various surfaces where it is not suitable for a conventional micromachining based on a photolithography technology. A specific drawing system has been constructed in order to apply the proposed method to three-dimensional structures in this study. A fabrication of a multi-layer circuit will be reported as the first example of applications. Next, plating metal patterns on various three-dimensional structures will be demonstrated. Furthermore, plating metal patterns on a ball will be reported. This result promises a possibility that the direct selective metal plating technology can also be applied to the so-called ball semiconductor technology at the rather large scale. [Copyright &y& Elsevier]

Examines the role of PEX3 in peroxisome biogenesis disorders (PBD). Restoration of peroxisome biogenesis by morphology and biochemistry; Deletion of all exon 11; Influence of PEX3 as a pathogenic gene responsible for complementation group G PBD.

We envisioned that the rumen of Kitasato Yakumo beef cattle would contain unique microorganisms which produce bioactive compounds as their defense response to the external environment. The variety of microorganisms were collected from the feces of Kitasato Yakumo beef cattle. We evaluated the biological activity of the culture broth of the isolated strains, proving the utility of our approach. [ABSTRACT FROM AUTHOR]

In this paper, we describe our discovery of burnettiene A (1) as an antimalarial compound from the culture broth of Lecanicillium primulinum (current name: Flavocillium primulinum) FKI-6715 strain utilizing our original multidrug-sensitive yeast system. This polyene-decalin polyketide natural product was originally isolated as an antifungal active compound from Aspergillus burnettii. However, the antifungal activity of 1 has been revealed in only one fungal species, and the mechanism of action of 1 remains unknown. After the validation of mitochondrial function inhibitory of 1 , we envisioned a new antimalarial drug discovery platform based on mitochondrial function inhibitory activity. We evaluated antimalarial activity and 1 showed antimalarial activity against Plasmodium falciparum FCR3 (chloroquine sensitive) and the K1 strain (chloroquine resistant). Our study revealed the utility of our original screening system based on a multidrug-sensitive yeast and mitochondrial function inhibitory activity for the discovery of new antimalarial drug candidates. [ABSTRACT FROM AUTHOR]

Herein, we report on a self-threading polythiophene whose conjugated molecular wire is sheathed within its own cyclic side chains. The defect-free insulating layer prevents electronic cross-communication between the adjacent polythiophene back- bone even in the solid film. Notably, the covalently linked cyclic side chains extend the effective conjugation length of the interior polythiophene backbone, which results in an excellent intra wire hole mobility of 0.9 cm2 V-1 s-1. [ABSTRACT FROM AUTHOR]

Peroxisomes proliferate by sequential processes comprising elongation, constriction, and scission of peroxisomal membrane. It is known that the constriction step is mediated by a GTPase named dynamin-like protein 1 (DLP1) upon efficient loading of GTP. However, mechanism of fuelling GTP to DLP1 remains unknown in mammals. We earlier show that nucleoside diphosphate (NDP) kinase-like protein, termed dynamin-based ring motive-force organizer 1 (DYNAMO1), generates GTP for DLP1 in a red alga, Cyanidioschyzon merolae. In the present study, we identified that nucleoside diphosphate kinase 3 (NME3), a mammalian homologue of DYNAMO1, localizes to peroxisomes. Elongated peroxisomes were observed in cells with suppressed expression of NME3 and fibroblasts from a patient lacking NME3 due to the homozygous mutation at the initiation codon of NME3. Peroxisomes proliferated by elevation of NME3 upon silencing the expression of ATPase family AAA domain containing 1, ATAD1. In the wild-type cells expressing catalytically-inactive NME3, peroxisomes were elongated. These results suggest that NME3 plays an important role in peroxisome division in a manner dependent on its NDP kinase activity. Moreover, the impairment of peroxisome division reduces the level of ether-linked glycerophospholipids, ethanolamine plasmalogens, implying the physiological importance of regulation of peroxisome morphology. [ABSTRACT FROM AUTHOR]

Six microsatellite loci that were isolated from a microsatellite-enriched genomic library of mango ( Mangifera indica) along with their specific primer sets were each characterized by using 36 cultivars collected mainly in Thailand. The observed and expected heterozygosities ranged from 0 to 0.83 and from 0.29 to 0.73, respectively. The number of putative alleles are two to six. Three of the six alleles have frequencies of over 75%. The high frequency may be attributed to the bias in the origin of cultivars. Among 36 mango cultivars tested, 29 cultivars showed a unique pattern by six primer sets, whereas seven cultivars cannot be identified because of genotype similarities. This suggests the potentials for identification of mango cultivars by microsatellite markers. [ABSTRACT FROM AUTHOR]

We found that the culture broth of fungi showed anti-fungal activity against multidrug-sensitive budding yeast. However, we could not identify the anti-fungal compound due to the small quantity. Therefore, we attempted to increase the productivity of the target compound by the introduction of a global secondary metabolism regulator, laeA to the strain, which led to the successful isolation of 10-folds greater amount of MS-347a (1) than Aspergillus sp. FKI-5362. Compound 1 was not effective against Candida albicans and the detailed anti-fungal activity of 1 remains unverified. After our anti-fungal activity screening, 1 was found to inhibit the growth of broad plant pathogenic fungal species belonging to the Ascomycota. It is noteworthy that 1 showed little insecticidal activity against silkworms, suggesting its selective biological activity against plant pathogenic fungi. Our study implies that the combination strategy of multidrug-sensitive yeast and the introduction of laeA is useful for new anti-fungal drug discovery. [ABSTRACT FROM AUTHOR]

Along the Japan trench, quasi-periodic slow slip was found from repeating earthquakes (repeaters) and on-land GPS data before the 2011 Tohoku-oki earthquake. After the earthquake, the occurrence of Very Low Frequency Earthquakes (VLFEs) was recognized and new GPS-Acoustic (GPS-A) stations were deployed along the shallow plate boundary. In this study, we examine the postseismic activity of the slow slip from repeater, GPS-A and VLFE data. The repeaters are selected form their inter-event waveform similarity and the VLFEs are selected by waveform similarity with template matching at low-frequency range (0.02 – 0.1 Hz). Both data analysis periods were extended from previous studies to until the end of 2016. The GPS-A data from 2012 to 2016 was also re-analyzed to obtain better positions by incorporating the effect of horizontal variations in the sound speed of the ocean. The repeater analysis shows that the plate-boundary slip rate in the area close to the trench off Sanriku (to the north of the coseismic slip area) has large temporal variations with overall decay after the Tohoku-oki earthquake. On the other hand, the slip rate decreased monotonically with time in the area close to the trench off Fukushima (to the south of the coseismic slip area). In the off-Sanriku area, a slip-rate peak in 2015 correlated well with an active period of the VLFEs and a period of trenchward movement of the GPS-A stations. These observations suggest the occurrence of episodic slow slip caused the surface trenchward movement and repeater and VLFE activities. The amount of the inferred fault slip from the repeater activity was ~27 cm for the 2015 event, consistent with the seafloor GPS-A station movements (7~16 cm). The largest 5 earthquakes in the region during the 2015 episode were M5.5 to 6.9, but the total surface deformation expected from these earthquakes is too small (~2 cm) to explain the GPS-A station movements. This suggests the event was mostly aseismic. We also found the distribution of the VLFEs and repeaters are spatially complementary, suggesting that variations in local fault material properties near the plate boundary control the differences in slip mode. [ABSTRACT FROM AUTHOR]

Anti-microbial resistance (AMR) is one of the greatest threats to global health. The continual battle between the emergence of AMR and the development of drugs will be extremely difficult to stop as long as traditional anti-biotic approaches are taken. In order to overcome this impasse, we here focused on the type III secretion system (T3SS), which is highly conserved in many Gram-negative pathogenic bacteria. The T3SS is known to be indispensable in establishing disease processes but not essential for pathogen survival. Therefore, T3SS inhibitors may be innovative anti-infective agents that could dramatically reduce the evolutionary selective pressure on strains resistant to treatment. Based on this concept, we previously identified a polyketide natural product, aurodox (AD), as a specific T3SS inhibitor using our original screening system. However, despite its promise as a unique anti-infective drug of AD, the molecular target of AD has remained unclear. In this paper, using an innovative chemistry and genetic biology-based approach, we show that AD binds to adenylosuccinate synthase (PurA), which suppresses the production of the secreted proteins from T3SS, resulting in the expression of bacterial virulence both in vitro and in vivo experiments. Our findings illuminate the potential of PurA as a target of anti-infective drugs and vaccination and could open a avenue for application of PurA in the regulation of T3SS. [ABSTRACT FROM AUTHOR]

Peroxisomal matrix proteins are imported into peroxisomes via membrane-bound docking/translocation machinery. One central component of this machinery is Pex14p, a peroxisomal membrane protein involved in the docking of Pex5p, the receptor for peroxisome targeting signal type 1 (PTS1). Studies in several yeast species have shown that Pex14p is phosphorylated in vivo, whereas no function has been assigned to Pex14p phosphorylation in yeast and mammalian cells. Here, we investigated peroxisomal protein import and its dynamics in mitotic mammalian cells. In mitotically arrested cells, Pex14p is phosphorylated at Ser-232, resulting in a lower import efficiency of catalase, but not the majority of proteins including canonical PTS1 proteins. Conformational change induced by the mitotic phosphorylation of Pex14p more likely increases homomeric interacting affinity and suppresses topological change of its N-terminal part, thereby giving rise to the retardation of Pex5p export in mitotic cells. Taken together, these data show that mitotic phosphorylation of Pex14p and consequent suppression of catalase import are a mechanism of protecting DNA upon nuclear envelope breakdown at mitosis. [ABSTRACT FROM AUTHOR]

Alkenyl ether phospholipids are a major sub-class of ethanolamine- and choline-phospholipids in which a long chain fatty alcohol is attached at the sn-1 position through a vinyl ether bond. Biosynthesis of ethanolamine-containing alkenyl ether phospholipids, plasmalogens, is regulated by modulating the stability of fatty acyl-CoA reductase 1 (Far1) in a manner dependent on the level of cellular plasmalogens. However, precise molecular mechanisms underlying the regulation of plasmalogen synthesis remain poorly understood. Here we show that degradation of Far1 is accelerated by inhibiting dynamin-, Src kinase-, or flotillin-1-mediated endocytosis without increasing the cellular level of plasmalogens. By contrast, Far1 is stabilized by sequestering cholesterol with nystatin. Moreover, abrogation of the asymmetric distribution of plasmalogens in the plasma membrane by reducing the expression of CDC50A encoding a β-subunit of flippase elevates the expression level of Far1 and plasmalogen synthesis without reducing the total cellular level of plasmalogens. Together, these results support a model that plasmalogens localised in the inner leaflet of the plasma membranes are sensed for plasmalogen homeostasis in cells, thereby suggesting that plasmalogen synthesis is spatiotemporally regulated by monitoring cellular level of plasmalogens. [ABSTRACT FROM AUTHOR]