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The thymic tissue revealed homogeneous decrease in intensity on opposed-phase MR images relative to that seen on in-phase images in 15 healthy volunteers and two patients with hyperplastic thymus. Chemical-shift MR imaging may be useful in identifying normal thymic tissue and the hyperplastic thymus in early adulthood.

Purpose: To clarify the influences of age and gender on normal fatty replacement of the thymus in childhood, adolescence, and early adulthood using chemical-shift MRI. Materials and Methods:A total of 95 normal subjects (52 males and 43 females, mean age ϭ 15.6 years, range ϭ 7-25 years) who underwent chemical-shift MRI of the thymus were assessed prospectively. Signal intensity loss (SIL) of the thymus was determined by dividing the thymus/ muscle ratio on the opposed-phase image by that on the in-phase image. We evaluated SIL for its correlation with age and gender, and assessed SIL of the thymus with uncommon morphological features.Results: A significant correlation was found between SIL and age (r ϭ 0.750, P Ͻ 0.001). There was no significant difference in SIL between the genders. No significant SIL was identified in any of the subjects aged 10 years or less. However, significant SIL was found in 70.8% of those aged 11-20 years, 100% of those aged 21 years or more, and 46.2% of subjects with uncommon morphological features of the thymus. Conclusion:Chemical-shift MRI can depict physiologic fatty infiltration within the normal thymus in subjects over 11 years of age. It is crucial to correlate these normal agerelated findings with clinical cases in order to avoid misinterpretation.

Misfolding of Cu,Zn-superoxide dismutase (SOD1) is a pathological change in the familial form of amyotrophic lateral sclerosis caused by mutations in the SOD1 gene. SOD1 is an enzyme that matures through the binding of copper and zinc ions and the formation of an intramolecular disulfide bond. Pathogenic mutations are proposed to retard the post-translational maturation, decrease the structural stability, and hence trigger the misfolding of SOD1 proteins. Despite this, a misfolded and potentially pathogenic conformation of immature SOD1 remains obscure. Here, we show significant and distinct conformational changes of apoSOD1 that occur only upon reduction of the intramolecular disulfide bond in solution. In particular, loop regions in SOD1 lose their restraint and become significantly disordered upon dissociation of metal ions and reduction of the disulfide bond. Such drastic changes in the solution structure of SOD1 may trigger misfolding and fibrillar aggregation observed as pathological changes in the familial form of amyotrophic lateral sclerosis.Mutations in Cu,Zn-superoxide dismutase (SOD1) 2 are linked to familial forms of amyotrophic lateral sclerosis (fALS) (1). A major pathological change observed in SOD1-related fALS is the abnormal accumulation of misfolded mutant SOD1 proteins in affected motor neurons (2). Actually, many in vivo as well as in vitro studies have supported that pathogenic mutations facilitate the misfolding of SOD1 proteins (3); however, the molecular mechanism triggering the misfolding of SOD1 remains controversial.SOD1 is known as one of the most stable proteins to the extent that its melting temperature (T m ) is Ͼ90°C (4); therefore, a misfolding event appears quite unlikely for SOD1. Nonetheless, SOD1 was found to have acquired such high stability through several post-translational processes including copper and zinc binding and disulfide bond formation (Fig. 1A). Actually, disulfide-reduced apoSOD1 exhibits significantly decreased stability (T m ϳ 42°C) and is susceptible to unfolding/ misfolding at physiological temperatures (5, 6). Intracellular deregulation of metal binding and/or disulfide formation will, hence, be a key event triggering the misfolding of SOD1.Notably, many pathogenic mutations are found to disturb the post-translational control of SOD1 maturation (7, 8) and thereby increase intracellular fractions of the apo-(9) and/or disulfide-reduced state (10). Only when both metal ions and disulfide bond are absent, SOD1 forms fibrillar aggregates (11). Given that SOD1 fibrillation is a pathological hallmark in SOD1-related fALS patients (12) as well as model mice (13), the most immature form of SOD1 will provide a clue to understand the molecular pathomechanism of this devastating disease. In a number of previous studies, the roles of metal binding and disulfide formation in the misfolding of SOD1 have been suggested by a variety of experimental methods (6, 8, 11, 14 -19); however, conformational information on SOD1 in solution lacking both metal ions and the disulfi...

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TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA-binding protein containing two consecutive RNA recognition motifs (RRM1 and RRM2) in tandem. Functional abnormality of TDP-43 has been proposed to cause neurodegeneration, but it remains obscure how the physiological functions of this protein are regulated. Here, we show distinct roles of RRM1 and RRM2 in the sequence-specific substrate recognition of TDP-43. RRM1 was found to bind a wide spectrum of ssDNA sequences, while no binding was observed between RRM2 and ssDNA. When two RRMs are fused in tandem as in native TDP-43, the fused construct almost exclusively binds ssDNA with a TG-repeat sequence. In contrast, such sequence-specificity was not observed in a simple mixture of RRM1 and RRM2. We thus propose that the spatial arrangement of multiple RRMs in DNA/RNA binding proteins provides steric effects on the substrate-binding site and thereby controls the specificity of its substrate nucleotide sequences.

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It is difficult to preoperatively diagnose early carcinoma of the vermiform appendix because of its rarity and few specific clinical features. In the present study, we report a preoperatively diagnosed mucosal carcinoma of the vermiform appendix.