Role of TAK1 and TAB1 in BMP signaling in early Xenopus development

Transforming growth factor-beta (TGF-beta) superfamily members elicit signals through stimulation of serine/threonine kinase receptors. Recent studies of this signaling pathway have identified two types of novel mediating molecules, the Smads and TGF-beta activated kinase 1 (TAK1). Smads were shown to mimic the effects of bone morphogenetic protein (BMP), activin and TGF-beta. TAK1 and TAB1 were identified as a MAPKKK and its activator, respectively, which might be involved in the up-regulation of TGF-beta superfamily-induced gene expression, but their biological role is poorly understood. Here, we have examined the role of TAK1 and TAB1 in the dorsoventral patterning of early Xenopus embryos. Ectopic expression of Xenopus TAK1 (xTAK1) in early embryos induced cell death. Interestingly, however, concomitant overexpression of bcl-2 with the activated form of xTAK1 or both xTAK1 and xTAB1 in dorsal blastomeres not only rescued the cells but also caused the ventralization of the embryos. In addition, a kinase-negative form of xTAK1 (xTAK1KN) which is known to inhibit endogenous signaling could partially rescue phenotypes generated by the expression of a constitutively active BMP-2/4 type IA receptor (BMPR-IA). Moreover, xTAK1KN could block the expression of ventral mesoderm marker genes induced by Smad1 or 5. These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner.     

Synthesis and biological activities of indolactone-V, the lactone analogue of the tumor promoter (-)-indolactam-V

The tumor promoter (-)-indolactam-V (1) exists in two stable conformers (twist and sofa) due to isomerization of the amide group. Indolactone-V (2), the lactone analogue of 1, has been synthesized to investigate the effects of the amide group on its conformation and biological activities. Indolactone-V (2) existed only as the inactive sofa-like conformer, indicating that the amide group of 1 plays a critical role in formation of the active twist conformation.     

Varying effects of cyclodextrin derivatives on aggregation and thermal behavior of insulin in aqueous solution

Brain invasion prevents complete surgical extirpation of malignant gliomas; however, invasive cells from distant, histologically normal brain previously have not been isolated, cultured, and characterized. To evaluate invasive human malignant glioma cells, the authors established cultures from gross tumor and histologically normal brain. Three men and one woman, with a mean age of 67 years, underwent two frontal and two temporal lobectomies for tumors, which yielded specimens of both gross tumor and histologically normal brain. Each specimen was acquired a minimum of 4 cm from the gross tumor. The specimens were split: a portion was sent for neuropathological evaluation (three glioblastomas multiforme and one oligodendroglioma) and a portion was used to establish cell lines. Morphologically, the specimens of gross tumor and histologically normal brain were identical in three of the four cell culture pairs. Histochemical staining characteristics were consistent both within each pair and when compared with the specimens sent for neuropathological evaluation. Cultures demonstrated anchorage-independent growth in soft agarose and neoplastic karyotypes. Growth rates in culture were greater for histologically normal brain than for gross tumor in three of the four culture pairs. Although the observed increases in growth rates of histologically normal brain cultures do not correlate with in vivo behavior, these findings corroborate the previously reported stem cell potential of invasive glioma cells. Using the radial dish assay, no significant differences in motility between cultures of gross tumor and histologically normal brain were found. In summary, tumor cells were cultured from histologically normal brain acquired from a distance greater than 4 cm from the gross tumor, indicating the relative insensitivity of standard histopathological identification of invasive glioma cells (and hence the inadequacy of frozen-section evaluation of resection margins). Cell lines derived from gross tumor and histologically normal brain were usually histologically identical and demonstrated equivalent motility, but had different growth rates.     

A T‐LCLC type immittance converter

“Immittance converter” is short for “impedance–admittance converter.” The immittance converter has an input impedance that is proportional to the admittance of the load connected across output terminals. In this converter, the output current is proportional to the input voltage and the input current is proportional to the output voltage. Consequently, it converts a constant voltage source into a constant current source and a constant current source into a constant voltage source. It is well known that the quarter‐wavelength transmission line shows immittance conversion characteristics. However, it has very long line length for the switching frequency, and is not suitable for power electronics application. Thus, we proposed immittance converters that consist of lumped elements L, C and show improved immittance conversion characteristics at a resonant frequency. In this paper, we propose a T‐LCLC‐type immittance converter, which has the transitive configuration and both advantages of T‐LCL‐ and π‐CLC‐type immittance converters. We show voltage–current transformation characteristics and frequency characteristics and efficiency characteristics of the T‐LCLC immittance converter. These characteristics were determined analytically and experimentally. © 2002 Wiley Periodicals, Inc. Electr Eng Jpn, 142(3): 57–63, 2003; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.10095     

A new method to improve in-bore middle cerebral artery occlusion in rats: demonstration with diffusion- and perfusion-weighted imaging

BACKGROUND AND PURPOSE: In-bore middle cerebral artery occlusion (MCAO) enables investigators to acquire preischemic MRI data and to image ischemic changes immediately after occlusion. We have developed a highly successful in-bore MCAO method. This study describes the methods and pertinent techniques. METHODS: Sixty-seven Sprague-Dawley rats were subjected to temporary (n=36) or permanent (n=31) MCAO. The occluding device consisted of a supporting tubing, a driving line, and a silicone-coated 4-0 nylon suture occluder. Outside the magnet, the occluder was positioned in the carotid canal. MCAO was achieved in the magnet bore by remotely advancing the driving line until resistance was felt. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) were acquired before and immediately after occlusion and were used to document the presence of MCAO. RESULTS: Fifty-nine (88.1%) rats were successfully occluded, demonstrating hyperintensity on DWI, perfusion deficits on PWI, and no subarachnoid hemorrhage at postmortem examination. The average values of the apparent diffusion coefficient in both the frontoparietal cortex and the lateral caudoputamen significantly decreased as early as 3 minutes after the onset of ischemia. The failures included preocclusion damage (1/67), sliding out of the occluder during occlusion (1/67), no occlusion (2/67), and arterial perforation (4/67). CONCLUSIONS: Our in-bore MCAO method is easily performed and is as successful as MCAO induced outside the magnet.     

Blood pressure lowering effect of low intensity aerobic training in elderly hypertensive patients

OBJECTIVE: The prevalence and etiology of pre- and postpartum depressive symptoms in women in a variety of family forms have been well documented, but relatively little research has been conducted on the adjustment of their male partners. The authors' goals in this study were 1) to estimate rates of depression during the pregnancy and 8 weeks following the birth of a child in a large representative community sample of fathers in different family structures and 2) to explore the role of stressful life events, social and emotional support, the quality of the partner relationship, and socioeconomic circumstances. METHOD: This study describes the relations of family setting and other correlates to men's depressive symptoms during the pregnancies (18 weeks gestation, on average) and 8 weeks after the births of children for 7,018 partners of female participants in the Avon Longitudinal Study of Pregnancy and Childhood. RESULTS: Men living in stepfamilies had-significantly higher levels of depressive symptoms before and after the birth than did men in more traditional families. The effect of stepfamily status on depression was mediated by education, life events, social support, social network, and level of aggression in the partnership. CONCLUSIONS: There are similarities in the patterns and correlates of depression after the birth of a child for men and women. These findings point to the importance of family and partnership ecology in the adjustment of men before and after the birth of a child.     

The molecular basis for the absence of N-glycolylneuraminic acid in humans

N-Glycolylneuraminic acid (NeuGc) is abundantly expressed in most mammals, but it is not detectable in humans. The expression of NeuGc is controlled by cytidine monophospho-N-acetylneuraminic acid (CMP-NeuAc) hydroxylase activity. We previously cloned a cDNA for mouse CMP-NeuAc hydroxylase and found that the human genome contains a homologue. We report here the molecular basis for the absence of NeuGc in humans. We cloned a cDNA for human CMP-NeuAc hydroxylase from a HeLa cell cDNA library. The cDNA encodes a 486-amino acid protein, and its deduced amino acid sequence lacks a domain corresponding to the N-terminal 104 amino acids of the mouse CMP-NeuAc hydroxylase protein, although the human protein is highly identical (93%) to the rest of the mouse hydroxylase protein. The N-terminal truncation of the human hydroxylase is caused by deletion of a 92-base pair-long exon in human genomic DNA. The human hydroxylase expressed in COS-7 cells exhibited no enzymatic activity, and a mouse hydroxylase mutant, which lacks the N-terminal domain, was also inactive. A chimera composed of the human hydroxylase and the N-terminal domain of the mouse hydroxylase displayed the enzyme activity. These results indicate that the human homologue of CMP-NeuAc hydroxylase is inactive because it lacks an N-terminal domain that is essential for enzyme activity. The absence of NeuGc in human glycoconjugates is due to a partial deletion in the gene that encodes CMP-NeuAc hydroxylase.     

Coupling-current loss in a multifilamentary superconducting wire with a normal-metal core

Coupling-current losses in a multifilamentary superconducting wire with a normal metal core were calculated for the case of transverse magnetic fields. The results showed that the dependence of the coupling-current loss of such a wire on the rate of field variation is markedly different from that of a wire without the core, the former being characterized by two time constants while the latter by one. The theoretical result was confirmed experimentally. It was pointed out that in the case when a wire with Cu/CuNi matrices is to be used in a rapidly changing magnet field, Cu for a stabilization should be arranged at the centre of the wire rather than at the surface of the wire in order to reduce the loss.     

A Measurement of Efficiency for Internal Organization a Study of the Three Japanese Public Corporations

Behaviormetrika - This paper shows how one can measure the overall efficiency of organizational decision -making to yield maximum organizational outputs under many constraints of economic,...     

Multiple myeloma developing myelodysplastic syndrome with thrombocytosis

A 64-year-old woman with multiple myeloma, IgG lambda type Durie-Salmon Stage II, was admitted because of gradually developing anemia and increased blasts with abnormal karyotype in her bone marrow after 10 years of treatment. The chromosomal analysis showed 44, XX, del(5q), del(7q), -9, add(12p), -21, typical of secondary MDS due to the cumulative alkylating agents. Thrombocytosis concomitantly occurred with emergence of chromosomal abnormality, but the serum interleukin 6 level was not elevated, which suggested that it was related to development of secondary MDS.