The Fluctuating Phenotype of the Lymphohematopoietic Stem Cell with Cell Cycle Transit

The most primitive engrafting hematopoietic stem cell has been assumed to have a fixed phenotype, with changes in engraftment and renewal potential occurring in a stepwise irreversible fashion linked with differentiation. Recent work shows that in vitro cytokine stimulation of murine marrow cells induces cell cycle transit of primitive stem cells, taking 40 h for progression from G0 to mitosis and 12 h for subsequent doublings. At 48 h of culture, progenitors are expanded, but stem cell engraftment is markedly diminished. We have investigated whether this effect on engraftment was an irreversible step or a reversible plastic feature correlated with cell cycle progression. Long-term engraftment (2 and 6 mo) of male BALB/c marrow cells exposed in vitro to interleukin (IL)-3, IL-6, IL-11, and steel factor was assessed at 2–4-h intervals of culture over 24–48 h using irradiated female hosts; the engraftment phenotype showed marked fluctuations over 2–4-h intervals, with engraftment nadirs occurring in late S and early G2. These data show that early stem cell regulation is cell cycle based, and have critical implications for strategies for stem cell expansion and engraftment or gene therapy, since position in cell cycle will determine whether effective engraftment occurs in either setting

Genetics of coronary artery calcification among African Americans, a meta-analysis

Background: Coronary heart disease (CHD) is the major cause of death in the United States. Coronary artery calcification (CAC) scores are independent predictors of CHD. African Americans (AA) have higher rates of CHD but are less well-studied in genomic studies. We assembled the largest AA data resource currently available with measured CAC to identify associated genetic variants.Methods: We analyzed log transformed CAC quantity (ln(CAC + 1)), for association with ~2.5 million single nucleotide polymorphisms (SNPs) and performed an inverse-variance weighted meta-analysis on results for 5,823 AA from 8 studies. Heritability was calculated using family studies. The most significant SNPs among AAs were evaluated in European Ancestry (EA) CAC data; conversely, the significance of published SNPs for CAC/CHD in EA was queried within our AA meta-analysis.Results: Heritability of CAC was lower in AA (~30%) than previously reported for EA (~50%). No SNP reached genome wide significance (p < 5E-08). Of 67 SNPs with p < 1E-05 in AA there was no evidence of association in EA CAC data. Four SNPs in regions previously implicated in CAC/CHD (at 9p21 and PHACTR1) in EA reached

Implications of serial measurements of natriuretic peptides in heart failure: insights from BIOSTAT‐CHF

No abstract available

Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH

Buckling and vibration of rectangular laminates with cut off regions

The pure global buckling and vibration of four sides simply-supported as well as clamped orthotropic rectangular laminates having multiple rectangular cut off regions that are symmetric with respect to mid-plane have been studied by treating the remaining cut off regions as uniform plates with reduced stiffnesses. The variation of stiffness of the plate is represented by Fourier series. Some numerical results for the pure global buckling load prediction due to its reduced flexural stiffness for typical cases of rectangular middle-plane symmetric cut off regions are presented

Thermal bending analysis of laminated orthotropic plates by the generalized differential quadrature method

The interlaminar stresses in a thin laminated rectangular orthotropic plate with four sides simply supported edges under bending was determined by using the generalized differential quadrature (GDQ) method involving the effects of thermal expansion strain and transverse Load. The approximate stress and displacement solutions are obtained under the effects of thermal expansion force and uniform pressure load for eight-layer unidirectional laminates, symmetric cross-ply laminates. Numerical results on the dominant interlaminar stresses and displacement of bending analysis are compared to the Navier solution. The thermal induced forces have significant effect on the bending of plates

Shear deformation in thermal bending analysis of laminated plates by the GDQ method

The interlaminar stresses and deflections in a laminated rectangular plate under thermal bending were determined, by using the generalized differential quadrature method involving the effect of shear deformation. The approximate stress and deflection solutions are obtained under the bending of sinusoidal temperature of thermal load for layer in cross-ply laminates and angle-ply laminates. Numerical results show that the shear deformation has significant effects on the dominant interlaminar stresses and deflections in the laminated plate of thermal bending analysis. (C) 2002 Elsevier Science Ltd. All rights reserved

Shear deformation in thermal vibration analysis of laminated plates by the GDQ method

The interlaminar stresses and deflections in a laminated rectangular plate under thermal vibration were determined by using the generalized differential quadrature (GDQ) method involving the effect of shear deformation. The approximate stress and deflection solutions are obtained under the vibration of sinusoidal temperature of thermal load for layer in cross-ply laminate. Numerical results show that the maximum deflection and stresses at center position of laminate increasing with the side-to-thickness ratio a/h* value decreasing, especially in the region a/h* less than or equal to 20. The GDQ method provides an efficient method for calculating the interlaminar stresses and deflections in a multi-layered plate of cross-ply laminate subjected to thermal vibration of sinusoidal temperature including shear deformation with a few grid points. (C) 2003 Elsevier Science Ltd. All rights reserved