We report studies of the fission yeast fimbrin-like protein Fim1, which contains two EF-hand domains and two actin-binding domains (ABD1 and ABD2). Fim1 is a component of both F-actin patches and the F-actin ring, but not of F-actin cables. Fim1 cross-links F-actin in vitro, but a Fim1 protein lacking either EF-hand domains (Fim1A12) or both the EF-hand domains and ABD1 (Fim1A2) has no actin cross-linking activity. Overexpression of Fim1 induced the formation of F-actin patches throughout the cell cortex, whereas the F-actin patches disappear in cells overexpressing Fim1A12 or Fim1A2. Thus, the actin cross-linking activity of Fim1 is probably important for the formation of F-actin patches. The overexpression of Fim1 also excluded the actin-depolymerizing factor Adf1 from the F-actin patches and inhibited the turnover of actin in these structures. Thus, Fim1 may function in stabilizing the F-actin patches. We also isolated the gene encoding Acp1, a subunit of the heterodimeric F-actin capping protein. fim1 acp1 double null cells showed more severe defects in the organization of the actin cytoskeleton than those seen in each single mutant. Thus, Fim1 and Acp1 may function in a similar manner in the organization of the actin cytoskeleton. Finally, genetic studies suggested that Fim1 may function in cytokinesis in cooperation with Cdc15 (PSTPIP) and Rng2 (IQGAP), respectively.
Background: Elongation factor 1␣ (EF1␣), an essential component of the eukaryotic translational machinery, has been shown to possess various biochemical and biological activities, including F-actin-binding and -bundling, microtubulesevering, and the activity of making fibroblasts highly susceptible to transformation. However, our understanding of the biological significance of EF1␣ with respect to these various biochemical or biological activities remains limited. Here we report the identification of EF1␣-encoding genes as genes whose over-expression causes aberrant cell morphology in fission yeast.
n Abstract: Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations. The association between dermatomyositis and malignancy is becoming more clearly delineated. A sort of dermatomyositis is thought to be paraneoplastic syndrome and dermatomyositis may follow clinical course of malignancy. We report a 68-yearold woman with dermatomyositis, whose clinical onset of dermatomyositis was apparently concomitant with breast cancer. Dermatomyositis had settled down and oral steroid could be tapered after the resection of breast cancer. Creatine kinase value was elevated before the detection of the first and second recurrence and in the terminal state. At the second recurrence, skin lesions and creatine kinase value had flared up and immediate metastatic check-up revealed the recurrence. Our case shows dermatomyositis, which was thought to be paraneoplastic syndrome, that followed clinical course of malignancy and suggests immediate check-up is needed for early detection of recurrence when dermatomyositis flares up after the resection of the malignancy. n
An X-ray-induced protein in human T cell leukemia MOLT-4 cells is described. It was detected 4 hrs after irradiation by two dimensional gel electrophoresis and silver staining. The location is 41 kDa in the mass and 4.0 of pI. Its spots were collected from the gels and microsequenced. The protein was identified from its partial sequences as a set gene product, whose gene translocation previously was found in a case of acute undifferentiated leukemia. Polyclonal rabbit antibodies stained two spots, the 41 kDa (p 41) and the 42 kDa (p 42) proteins. Photoimage analyses of the silver-stained gels and Western blots indicated that the induction of p 41 was time dependent, starting 4 hrs after irradiation and reaching a plateau by 10 hrs, and was dose dependent between 1 and 10 Gy. p 41 appeared somewhat ahead of cell death, as determined by the dye exclusion test, but the role in that cell process has yet to be clarified.
Metaiodobenzylguanidine (MIBG) myocardial scintigraphy is widely accepted as a beneficial tool for differentiating Parkinson's disease (PD) from other Parkinson-related disorders (PRD). In Japan, dopamine transporter (DAT) imaging, which can evaluate presynaptic degeneration of dopamine neurons, has been applied in clinics since 2014. The present study investigated the utility of [(123)I]-Ioflupane single photon emission computed tomography (SPECT) combined with MIBG myocardial scintigraphy for the diagnosis of PD. We performed [(123)I]-Ioflupane SPECT and MIBG myocardial scintigraphy in 63 PD patients, 8 PRD patients and 1 essential tremor patient, and obtained the specific binding ratio (SBR [cut-off: 4.5]) and the heart-to-mediastinum ratio (H/M [cut-off: 2.2]). In 70% of the PD patients, both parameters were significantly reduced. In 22% of the PD patients, the SBR was smaller than 4.5 with normal H/M, and H/M was less than 2.2 with normal SBR in 5% of all subjects. Either the SBR or H/M was significantly reduced in 97% of the study population. The SBR showed low disease specificity to PD (11%), and the SBR and H/M negatively correlated with disease duration. These findings indicate that [(123)I]-Ioflupane SPECT combined with MIBG myocardial scintigraphy can improve the detection rate of PD. However, careful interpretation of these results is required because [(123)I]-Ioflupane SPECT poorly differentiates PD from PRD. Progression of PD may reflect the gradual reduction of isotope accumulation, hence, both [(123)I]-Ioflupane SPECT and MIBG myocardial scintigraphy should be tested repeatedly even in clinically suspected PD cases showing negative results.
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