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Alkylresorcinols (AR) are phenolic lipids found in the bran fraction of whole-grain wheat, rye, and barley. In intervention studies, plasma AR concentration increased in response to greater intakes of whole grain, wheat, and rye. This study examined the cross-sectional associations between plasma AR and habitual whole-grain intake, BMI, and metabolic risk factors in 407 free-living older adults (166 men and 241 women; aged 60-81y; median BMI: 27 kg/m(2)). Plasma AR were measured by liquid chromatography-tandem MS, and whole-grain intakes were estimated by using an FFQ. After adjustment for fasting TG concentrations, median plasma AR concentrations across quartile categories of AR were 5, 14, 27, and 62 nmol/L, respectively. Spearman correlation coefficients between plasma AR and whole-grain wheat-rich foods and total bran intake were 0.31 and 0.27, respectively (both P < 0.0001). After adjustment for multiple covariates, the geometric means of BMI in the lowest and highest quartile category of plasma AR were 27.6 and 26.7 kg/m(2), respectively (P-trend = 0.04). No associations were observed between plasma AR and glucose and insulin. Our study shows a dose-dependent relationship between whole-grain intake and plasma AR and confirms the previously observed inverse relationship between whole-grain intake and BMI using an independent biomarker of whole-grain wheat intake. [ABSTRACT FROM AUTHOR]

Alkylresorcinols (AR) are phenolic lipids found in the bran fraction of whole-grain wheat, rye, and barley. In intervention studies, plasma AR concentration increased in response to greater intakes of whole grain, wheat, and rye. This study examined the cross-sectional associations between plasma AR and habitual whole-grain intake, BMI, and metabolic risk factors in 407 free-living older adults (166 men and 241 women; aged 60-81 y; median BMI: 27 kg/m2). Plasma AR were measured by liquid chromatography-tandem MS, and whole-grain intakes were estimated by using an FFQ. After adjustment for fasting TG concentrations, median plasma AR concentrations across quartile categories of AR were 5, 14, 27, and 62 nmol/L, respectively. Spearman correlation coefficients between plasma AR and whole-grain wheat-rich foods and total bran intake were 0.31 and 0.27, respectively (both P < 0.0001). After adjustment for multiple covariates, the geometric means of BMI in the lowest and highest quartile category of plasma AR were 27.6 and 26.7 kg/m2, respectively (P-trend = 0.04). No associations were observed between plasma AR and glucose and insulin. Our study shows a dose-dependent relationship between whole-grain intake and plasma AR and confirms the previously observed inverse relationship between whole-grain intake and BMI using an independent biomarker of whole-grain wheat intake. [ABSTRACT FROM AUTHOR]

The bones of the vertebrate limb form by the process of endochondral ossification, whereby limb mesenchyme condenses to form an intermediate cartilage scaffold that is then replaced by bone. Although Indian hedgehog (IHH) is known to control hypertophic differentiation of chondrocytes during this process, the role of hedgehog signaling in the earlier stages of chondrogenesis is less clear. We have conditionally inactivated the hedgehog receptor Ptc1 in undifferentiated limb mesenchyme of the mouse limb using Prx1-Cre, thus inducing constitutively active ligand-independent hedgehog signaling. In addition to major patterning defects, we observed a marked disruption to the cartilage elements in the limbs of Prx1-Cre:Ptc1c/c embryos. Using an in vitro micromass culture system we show that this defect lies downstream of mesenchymal cell condensation and likely upstream of chondrocyte differentiation. Despite early increases in levels of chondrogenic genes, soon after mesenchymal condensation the stromal layer of Prx1-Cre:Ptc1c/c-derived micromass cultures is characterized by a loss of cell integrity, which is associated with increased cell death and a striking decrease in Alcian blue staining cartilage nodules. Furthermore, inhibition of the hedgehog pathway activation using cyclopamine was sufficient to essentially overcome this chondrogenic defect in both micromass and ex vivo explant assays of Prx1-Cre: Ptc1c/c limbs. These data demonstrate for the first time the inhibitory effect of cell autonomously activated hedgehog signaling on chondrogenesis, and stress the importance of PTC1 in maintaining strict control of signaling levels during this phase of skeletal development. [ABSTRACT FROM AUTHOR]

Embryonic stem (ES) cells have the capacity to differentiate into all cells of the developing embryo and may provide a renewable resource for future cell replacement therapies. The addition of bone morphogenetic protein 4 (BMP4) to serum-free ES cell culture has previously been shown to induce transcription factors, signaling molecules, and cell adhesion proteins expressed during mesoderm specification of the embryo. Here, we show the dynamics of primitive streak mesoderm differentiation in ES cells is comparable between serum and serum-free embryoid body (EB) cultures, supplemented with BMP4. Furthermore, we show a delayed wave of expression of a cohort of genes (Pax2, WT1, podocalyxin, pod-1, and nephrin), which play important roles during embryonic kidney development. The paired box transcription factor, Pax2, is one of the earliest genes expressed during kidney organogenesis and is required for normal urogenital development. ES cell lines containing either a modified Pax2 promoter- lacZ or bacterial artificial chromosome-green fluorescent protein (GFP) transgene were generated, which enabled the quantitative analysis of kidney rather than neuronal Pax2 expression within EBs. Both β-galactosidase activity and GFP expression were detected by immunohistochemical and flow cytometric analysis following 16 days of EB culture, which correlated with an increase in Pax2 transcript levels. Together, these results suggest a spontaneous kidney gene expression program develops in mature EBs grown in both serum and serum-free conditions, when supplemented with BMP4. Further, the recombinant growth factors BMP2, BMP4, and BMP7 strongly influence gene expression within mesoderm induced EBs. BMP4 promotes ventral (blood) and intermediate (kidney) mesoderm gene expression, whereas BMP2 and BMP7 promote kidney outcomes at the expense of hematopoietic commitment. This induction assay and these unique ES cell lines will be useful for the generation of mesoderm-derived cell populations with implications for future cell therapeutic/integration assays. [ABSTRACT FROM AUTHOR]