Clusterin/ApoJ enhances central leptin signaling through Lrp2‐mediated endocytosis

Hypothalamic leptin signaling plays a central role in maintaining body weight homeostasis. Here, we show that clusterin/ApoJ, recently identified as an anorexigenic neuropeptide, is an important regulator in the hypothalamic leptin signaling pathway. Coadministration of clusterin potentiates the anorexigenic effect of leptin and boosts leptin‐induced hypothalamic Stat3 activation. In cultured neurons, clusterin enhances receptor binding and subsequent endocytosis of leptin. These effects are mainly mediated through the LDL receptor‐related protein‐2 (Lrp2). Notably, inhibition of hypothalamic clusterin, Lrp2 or endocytosis abrogates anorexia and hypothalamic Stat3 activation caused by leptin. These findings propose a novel regulatory mechanism in central leptin signaling pathways.     

Molecule-level imaging of Pax6 mRNA distribution in mouse embryonic neocortex by molecular interaction force microscopy

Detection of the cellular and tissue distributions of RNA species is critical in our understanding of the regulatory mechanisms underlying cellular and tissue differentiation. Here, we show that an atomic force microscope tip modified with 27-acid dendron, a cone shaped molecule with 27 monomeric units forming its base, can be successfully used to map the spatial distribution of mouse Pax6 mRNA on sectioned tissues of the mouse embryonic neocortex. Scanning of the sectioned tissue with a 30-mer DNA probe attached to the apex of the dendron resulted in detection of the target mRNA on the tissue section, permitting mapping of the mRNA distribution at nanometer resolution. The unprecedented sensitivity and resolution of this process should be applicable to identification of molecular level distribution of various RNAs in a cell.     

Succession of rudistid lithosomes along the western coastal margin of the Iberian Basin (Coniacian,Castrojimeno Section,central Spain)

Rudistid lithosomes cropping out near Castrojimeno, at the northern margin of the Central System in north-central Spain, provide detailed information on their composition and structure, on their development and succession, and about their relationship with the Coniacian sequence stratigraphy framework of the Iberian Basin. Most rudist assemblages are oligospecific, with a dominant species, or monospecific. The radiolitids Biradiolites angulosus, Praeradiolites requieni, and Radiolites sauvagesi and the hippuritids Hippurites incisus and Vaccinites giganteus were identified. Radiolitids demonstrate wide intraspecific morphological variability. The following Riding’s structural categories of organic reefs are represented: segment reefs, spaced and close cluster reefs, and close cluster/frame reefs. Bioclastic beds of reworked rudist fragments occur below or in between the rudist reefs. The vertical succession of all five types of rudistid lithosomes distinguished evidences a shallowing-upward trend. Rudistid lithosomes developed on the coastal margin during the superposition of the highstand sea-level stage of third- and fourth-order depositional sequences.     

Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity

The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan ≥ 92 years (y), mean ± standard deviation (SD) = 95.3 ± 2.2y) and 603 average-lifespan controls (lifespan ≤ 79y, mean = 75.7 ± 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1 , rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95%CI = 0.68–0.89, adjusted P  = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95%CI = 1.15–1.57, adjusted P  = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan.     

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

Microsatellite analysis of the silkworm strains (Bombyx mori): high variability and potential markers for strain identification

The silkworm (Bombyx mori) is of great economic value from an industrial perspective. Casual discrimination and accumulation of genetic information from a diverse variety of silkworms are essential for practical utilization and longterm conservation. In this study, a total of 54 silkworm strains preserved in Korea were typed for nine polymorphic microsatellite loci. We determined per-locus numbers of alleles ranging from 3 to 17 with an average value of 7.5, per-locus observed heterozygosity ranging from 0.04 to 0.98, and per-locus polymorphic information content (PIC) ranging from 0.06 to 0.86, thereby indicating that some of these loci are profoundly variable. Phylogenetic analysis using the nine concatenated microsatellite loci showed no clustering on the basis of known strain characteristics and origin. A total of 17 strain-specific apomorphic alleles, which discriminate 14 among 54 silkworm strains, were obtained from eight loci. These strain-specific alleles can, therefore, be casually utilized to discriminate between applicable strains, without any further typing of other loci. Furthermore, a substantial number of homozygote strains, represented by 24 among 67 alleles in nine loci, were also detected. These results collectively implicate silkworm microsatellite DNA as useful and potentially important molecular markers for the eventual discrimination of silkworm strains, hundreds of which are currently preserved in Korea.     

Bile acids regulate hepatic gluconeogenic genes and farnesoid X receptor via G��i-protein-coupled receptors and the AKT pathway

Bile acids are important regulatory molecules that can activate specific nuclear receptors and cell signaling pathways in the liver and gastrointestinal tract. In the current study, the chronic bile fistula (CBF) rat model and primary rat hepatocytes (PRH) were used to study the regulation of gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) and the gene encoding short heterodimeric partner (SHP) by taurocholate (TCA). The intestinal infusion of TCA into the CBF rat rapidly (1 h) activated the AKT (∼9-fold) and ERK1/2 (3- to 5-fold) signaling pathways, downregulated (∼50%, 30 min) the mRNA levels of PEPCK and G-6-Pase, and induced (14-fold in 3 h) SHP mRNA. TCA rapidly (∼50%, 1–2 h) downregulated PEPCK and G-6-Pase mRNA levels in PRH. The downregulation of these genes by TCA was blocked by pretreatment of PRH with pertussis toxin (PTX). In PRH, TCA plus insulin showed a significantly stronger inhibition of glucose secretion/synthesis from lactate and pyruvate than either alone. The induction of SHP mRNA in PRH was strongly blocked by inhibition of PI3 kinase or PKCζ by specific chemical inhibitors or knockdown of PKCζ by siRNA encoded by a recombinant lentivirus. Activation of the insulin signaling pathway appears to be linked to the upregulation of farnesoid X receptor functional activity and SHP induction.