Our framework offers a comprehensive yet flexible approach for identifying genomic regions of biological interest in large epidemiological studies using quantitative high-throughput methods.

Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Hematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. While DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs1, a comprehensive DNA methylation map of hematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Dramatic epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, suggesting a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome appears to be important in hematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions.

Computed tomography (CT) and ultrasonography (US) are ideally suited for demonstrating urachal remnant diseases. A patent urachus is demonstrated at longitudinal US and occasionally at CT as a tubular connection between the anterosuperior aspect of the bladder and the umbilicus. An umbilical-urachal sinus manifests at US as a thickened tubular structure along the midline below the umbilicus. A vesicourachal diverticulum is usually discovered incidentally at axial CT, appearing as a midline cystic lesion just above the anterosuperior aspect of the bladder. At US, it manifests as an extraluminally protruding, fluid-filled sac that does not communicate with the umbilicus. Urachal cysts manifest at both modalities as a noncommunicating, fluid-filled cavity in the midline lower abdominal wall located just beneath the umbilicus or above the bladder. Both infected urachal cysts and urachal carcinomas commonly display increased echogenicity at US and thick-walled cystic or mixed attenuation at CT, making it difficult to differentiate between them. Percutaneous needle biopsy or fluid aspiration is usually needed for diagnosis and therapeutic planning. Nevertheless, CT and US can help identify most disease entities originating from the urachal remnant in the anterior abdominal wall. Understanding the anatomy and the imaging features of urachal remnant diseases is essential for correct diagnosis and proper management.

Tai Chi Qigong training appears to have beneficial effects in terms of the quality of life and physical functioning of elderly subjects with knee osteoarthritis. However, more rigorous trials are needed to confirm the efficacy of this training for patients with osteoarthritis of the knee.

No abstract