The synthesis of 15-methyl or 15,16-dimethyl prostaglandins

The synthesis of 15-methyl or 15,16-dimethyl prostaglandins has been accomplished starting from the lactone 1, the intermediate for the synthesis of natural prostaglandins.     

Fenofibrate reduces cisplatin-induced apoptosis by inhibiting the p53/Puma/Caspase-9 pathway and the MAPK/Caspase-8 pathway rather than by promoting autophagy in murine renal proximal tubular cells

The main lesion of cisplatin nephrotoxicity is damage to proximal tubular cells due to increased apoptosis via the mitochondrial and death receptor pathways, which may be alleviated by appropriate promotion of autophagy. Fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-α) activator, is recently reported to promote autophagy as well as protect against cisplatin nephrotoxicity, although the mechanisms were only partially analyzed. Here, the detailed mechanisms of these putative protective effects were investigated in a murine renal proximal tubular (mProx) cell line. Fenofibrate attenuated cisplatin-induced apoptosis of mProx cells based on flow cytometry. As for the mitochondrial apoptotic pathway, the reagent reduced cisplatin-stimulated caspase-3 activation by decreasing the phosphorylation of p53, JNK, and 14-3-3, cytosolic and mitochondrial Puma accumulation, cytochrome C release to the cytosol, and resulting cytosolic caspase-9 activation. Fenofibrate also decreased cisplatin-stimulated activation of caspases-8 by suppressing MAPK and NFkB pathways and reducing the gene expression of TNF-α, TL1A, and Fas, main mediators of the death receptor apoptotic pathway. Autophagy defined by p62 reduction and an increase in LC3 II/I was promoted by fenofibrate in mProx cells under starvation. Autophagy inhibition using 3-MA further increased basal and cisplatin-induced caspase-3 and -8 activation, but had no influence on the inhibitory effects of fenofibrate on caspase activation. In conclusion, our study suggests fenofibrate to be a candidate agent to mitigate cisplatin nephrotoxicity by inhibiting the mitochondrial and death apoptotic pathways rather than by promoting autophagy.     

Nicotiana suaveolens accessions with different ploidy levels exhibit different reproductive isolation mechanisms in interspecific crosses with Nicotiana tabacum

Journal of Plant Research - Reproductive isolation, including prezygotic and postzygotic barriers, is a mechanism that separates species. Many species in the Nicotiana section Suaveolentes exhibit...     

Japanese Rice Wine can reduce psychophysical stress-induced depression-like behaviors and Fos expression in the trigeminal subnucleus caudalis evoked by masseter muscle injury in the rats

We determined if Japanese Rice Wine (Sake) had inhibitory effects on stress-induced enhancement of masseter muscle (MM) nociception in the rats. Male rats were subjected to the repeated forced swim stress (FS) or sham conditionings from Day ?3 to ?1. Daily administration of Sake or saline was conducted after each stress conditioning. At Day 0 the number of Fos positive cells, a marker for neural activity, was quantified at the trigeminal subnucleus caudalis (Vc) region by MM injury with formalin. FS increased MM-evoked Fos expression in the Vc region, which was inhibited by Sake compared to saline administration. Sake did not alter the number of Fos positive cells under sham conditions, indicating that inhibitory roles of Sake on neural activity in the Vc region were seen under FS conditions. These findings indicated that Sake had inhibitory roles on stress-induced MM nociception at the Vc region in our experimental conditions.     

Development of an anti-hepatitis B virus (HBV) agent through the structure-activity relationship of the interferon-like small compound CDM-3008

Hepatitis B, a viral infectious disease caused by hepatitis B virus (HBV), is a life-threatening disease that leads liver cirrhosis and liver cancer. Because the current treatments for HBV, such as an interferon (IFN) formulation or nucleoside/nucleotide analogues, are not sufficient, the development of a more effective agent for HBV is urgent required.CDM-3008 (1, 2-(2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl)-1,3,4-oxadiazole) (RO8191)) is a small molecule with an imidazo[1,2-a][1,8]naphthyridine scaffold that shows anti-HCV activity with an IFN-like effect. Here, we report that 1 was also effective for HBV, although the solubility and metabolic stability were insufficient for clinical use. Through the structure-activity relationship (SAR), we discovered that CDM-3032 (11, N-(piperidine-4-yl)-2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridine-8-carboxamide hydrochloride) was more soluble than 1 (>30?mg/mL for 11 versus 0.92?mg/mL for 1). In addition, the half-life period of 11 was dramatically improved in both mouse and human hepatic microsomes (T1/2, >120?min versus 58.2?min in mouse, and >120?min versus 34.1?min in human, for 11 and 1, respectively).     

An Early Arising Role of the MicroRNA156/529-SPL Module in Reproductive Development Revealed by the Liverwort Marchantia polymorpha

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Ecosystem engineering by a canopy‐forming kelp facilitates the recruitment of native oysters

Ecosystem engineers are species that influence the abiotic and biotic environment around them and may assist the restoration of associated species, including other habitat‐forming species. We deployed an array of 28 artificial reefs with transplanted Ecklonia radiata, the dominant canopy‐forming kelp species across southern Australia, to investigate how the patch size and density of E. radiata influenced the establishment of the associated communities of plants and animals. Many of the reefs were rapidly colonized by Ostrea angasi, a critically depleted reef‐forming oyster. Over the 24‐month deployment of the reefs, thick oyster mats formed across the entire surface of many of the reefs with estimated biomass densities exceeding 5 kg of live oysters/m²; however, oyster density was dependent on E. radiata patch size and density. Increasing patch size and the presence of kelp resulted in significantly higher densities of oysters 5 months after the reefs were deployed and at the end of the experiment, where oysters were approximately three times more numerous on reefs with kelp compared to those without kelp. E. radiata appeared to facilitate the establishment of O. angasi largely through its capacity to reduce benthic light and thus suppress competition from turfing algae. These results may inform the development of novel approaches to tackle recruitment bottlenecks affecting the restoration of O. angasi reefs.     

Tumor suppressor CYLD regulates JNK-induced cell death in Drosophila

CYLD encodes a tumor suppressor that is mutated in familial cylindromatosis. Despite biochemical and cell culture studies, the physiological functions of CYLD in animal development and tumorigenesis remain poorly understood. To address these questions, we generated Drosophila CYLD (dCYLD) mutant and transgenic flies expressing wild-type and mutant dCYLD proteins. Here we show that dCYLD is essential for JNK-dependent oxidative stress resistance and normal lifespan. Furthermore, dCYLD regulates TNF-induced JNK activation and cell death through dTRAF2, which acts downstream of the TNF receptor Wengen and upstream of the JNKK kinase dTAK1. We show that dCYLD encodes a deubiquitinating enzyme that deubiquitinates dTRAF2 and prevents dTRAF2 from ubiquitin-mediated proteolytic degradation. These data provide a molecular mechanism for the tumor suppressor function of this evolutionary conserved molecule by indicating that dCYLD plays a critical role in modulating TNF-JNK-mediated cell death.     

Physiological significance of cyclic changes in room temperature around dusk and dawn for circadian rhythms of core and skin temperature, urinary 6-hydroxymelatonin sulfate, and waking sensation just after rising

The present study investigated whether room temperature (T(a)) cycles around dusk and dawn could influence the circadian rhythm of rectal temperature (T(core)), urinary 6-hydroxymelatonin sulfate during nocturnal sleep, and subjective assessments of sleep in humans. Six female and two male students served as participants. Two different T(a) conditions, cyclic and constant, were established. Two kinds of room temperature were provided to subjects: cyclic T(a) (gradual decrease from 27 degrees C to 24 degrees C between 1800 and 2200 h and gradual increase from 24 degrees C to 27 degrees C between 0300 and 0700 h) and constant T(a) (27 degrees C over 24 h). At cyclic T(a), the circadian nadir of T(core) rhythm was significantly advanced, while T(core) was significantly lower from 2300 to 0200 h and significantly higher from 0600 to 1000 h. The nocturnal concentration of 6-hydroxymelatonin sulfate in the urine during sleep was significantly higher during cyclic T(a). Waking sensation just after rising was significantly better with cyclic T(a). (Skin temperatures in the extremities-T(a)) were significantly higher with cyclic T(a) especially during the evening and night. Our results suggest that gradual change of room temperature in the evening and early morning is important in terms of sleep promotion and fresh awakening. It seems probable that mankind has been evolved to have deeper sleep under the influence of cyclic T(a) around dusk and dawn.     

Group 3 sigma factor gene, sigJ, a key regulator of desiccation tolerance, regulates the synthesis of extracellular polysaccharide in cyanobacterium Anabaena sp. strain PCC 7120.

The changes in the expression of sigma factor genes during dehydration in terrestrial Nostoc HK-01 and aquatic Anabaena PCC 7120 were determined. The expression of the sigJ gene in terrestrial Nostoc HK-01, which is homologous to sigJ (alr0277) in aquatic Anabaena PCC 7120, was significantly induced in the mid-stage of dehydration. We constructed a higher-expressing transformant of the sigJ gene (HE0277) in Anabaena PCC 7120, and the transformant acquired desiccation tolerance. The results of Anabaena oligonucleotide microarray experiments showed that a comparatively large number of genes relating to polysaccharide biosynthesis were upregulated in the HE0277 cells. The extracellular polysaccharide released into the culture medium of the HE0277 cells was as much as 3.2-fold more than that released by the control cells. This strongly suggests that the group 3 sigma factor gene sigJ is fundamental and conducive to desiccation tolerance in these cyanobacteria.