Genomic DNA is organized three-dimensionally in the nucleus, and is thought to form compact chromatin domains. Although chromatin compaction is known to be essential for mitosis, whether it confers other advantages, particularly in interphase cells, remains unknown. Here, we report that chromatin compaction protects genomic DNA from radiation damage. Using a newly developed solid-phase system, we found that the frequency of double-strand breaks (DSBs) in compact chromatin after ionizing irradiation was 5–50-fold lower than in decondensed chromatin. Since radical scavengers inhibited DSB induction in decondensed chromatin, condensed chromatin had a lower level of reactive radical generation after ionizing irradiation. We also found that chromatin compaction protects DNA from attack by chemical agents. Our findings suggest that genomic DNA compaction plays an important role in maintaining genomic integrity.
To determine the subunit composition of high-affinity kainate receptors in native neurons is a challenging problem because of the expression of more than one GluR subunit. In the present study the question of whether GluR5 and/or GluR6 subunits combine with KA-1 or KA-2 subunits in vivo is addressed by performing detailed physiological, pharmacological, and molecular characterization of functional kainate receptor channels in acutely dissociated trigeminal ganglion (TG) neurons. The results show that (1) smaller diameter TG neurons (Ͻ30 m) respond to L-glutamate and kainate, and the currents gated by kainate desensitize with prolonged agonist exposure; (2) all kainate receptor subunits are detected to some extent by reverse transcriptase-PCR, whereas glutamate receptor subunits GluR5 and KA-2 are expressed at high levels in the TG; (3) there is an obvious similarity between the features of native kainate receptor channels in TG neurons and of heteromeric recombinant GluR5(R)/KA-2 channels in pharmacological properties, desensitization, rectification, ion permeability, and mean channel conductance; and (4) the age-dependent increase in GluR5 and KA-2 RNA levels in the TG is correlated well with an increased number of kainate-sensitive cells during postnatal development. Our data suggest that the heteromeric GluR5/ KA2 combination actually occurs in TG neurons and give a clue as to the subunit composition of native kainate receptor channels.
Magnetic resonance (MR) imaging was performed in eight healthy volunteers and 30 patients with histologically and endocrinologically proved thyroid diseases. The use of a surface coil greatly improved spatial resolution, and normal anatomic structures were well demonstrated. In thyroid tumors, the margin, pseudocapsule, and lymph nodes were easily detected. Smooth margins, lobulated margins, and pseudocapsules were found in both adenoma and papillary carcinoma, whereas unclear margins were found only in papillary carcinoma. An unclear margin between the tumor and adjacent normal thyroid tissue seemed to reflect an ill-defined tumor border on gross pathologic examination. Metastatic lymph nodes as small as 3 mm were seen. Identification of small vessels enabled detection of dilated vessels in thyroid parenchyma in patients with Graves disease. Hemorrhage (hemorrhagic degeneration) was often found in adenoma, papillary carcinoma, and adenomatous goiter, resulting in variable signal intensity.
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