Biologically active fibroblast growth factor 1 tagged with various epitopes

<p>Abstract</p> <p>Background</p> <p>Fibroblast growth factor (FGF) family members are involved in the regulation of a variety of biological phenomena. Because most of their activity is exerted via a signaling complex composed of FGF, heparin/heparan sulfate and FGF receptor tyrosine kinase, it is important to study the dynamic behavior of all the molecules in the complex without disturbing their interaction or activity.</p> <p>Findings</p> <p>We used <it>E. coli </it>to express biologically active human FGF1 tagged at its C-terminus with myc-(His)₆, V5-(His)₆or 3xFLAG-(His)₆. We found that the tagged FGF1s had affinities for heparin that were similar to that of the native form. The tagged FGF1s also exhibited mitogenic activity similar to that of the native form. Apparently, the tags do not interfere with the formation of the three-member complex involving FGF1, FGF receptor and heparan sulfate/heparin.</p> <p>Conclusion</p> <p>Tagged FGF1s should be useful for investigating the dynamic behavior of FGF1 in the context of its three-member signaling complex and other molecular complexes.</p

Bulge- and Basal Layer-Specific Expression of Fibroblast Growth Factor-13 (FHF-2) in Mouse Skin

A variety of polypeptide growth factors are involved in the dynamic maintenance of the skin and hair. Here, we demonstrate the presence of high levels of fibroblast growth factor (FGF)-13 in the bulge region of hair follicles. Using real-time PCR, we found that expression of FGF-13 mRNA is comparable to, or higher than, that of other FGF known to regulate hair growth and wound healing. To gain additional insight into the function of FGF-13, we evaluated its distribution using in situ hybridization and immunohistochemical staining. Unlike other FGF, the distribution of FGF-13 mRNA and protein in adult mice was mainly restricted to cells in the bulge region of hair follicles, although lower levels were detected with less frequency in keratinocytes in the basal layer of the epidermis. FGF-13 protein was detectable in the bulge region throughout the hair growth cycle, but its distribution was especially wide during telogen and early anagen. During hair follicle morphogenesis in newborn mice, FGF-13 protein was first detected in the bulge region and basal layer keratinocytes 3 d after birth. These findings suggest that FGF-13 may play a role in regulating the function of cells in the bulge region and basal layer of the epidermis

Comparison of FGF1 (aFGF) Expression between the Dorsal Motor Nucleus of Vagus and the Hypoglossal Nucleus of Rat

Neurons in the dorsal motor nucleus of the vagus (DMNV) are more severely affected by axonal injury than most other nerves, such as those of the hypoglossal nucleus. However, the mechanism underlying such a response remains unclear. In this study, we compared the expression of fibroblast growth factor 1 (FGF1), a neurotrophic factor, between the DMNV and the hypoglossal nucleus by RT-PCR and immunohistochemical analyses. RT-PCR showed that the level of FGF1 mRNA expression in the DMNV was lower than that in the hypoglossal nucleus (P<0.01). Immunohistochemistry revealed that FGF1 was localized to neurons. FGF1-positive neurons in large numbers were evenly distributed in the hypoglossal nucleus, whereas FGF1-positive neurons were located in the lateral part of the DMNV. Double immunostaining for FGF1 and choline acetyltransferase demonstrated that 22.7% and 78% of cholinergic neurons were positive for FGF1 in the DMNV and hypoglossal nucleus, respectively. A tracing study with cholera toxin B subunit (CTb) demonstrated that cholinergic neurons sending their axons from the DMNV to the superior laryngeal nerve were FGF1-negative. The results suggest that the low expression of FGF1 in the DMNV is due to severe damage of neurons in the DMNV

Disorder of Higher Brain Function in Myotonlc Dystrophy

筋強直性ジストロフィー(以下Mypとする)は第19番染色体長腕にあるMyD原因遺伝子のCTGリピート数の異常増大により発症する常染色体優性遺伝の疾患である。本症では高頻度に中枢神経障害を伴うことが知られており、記憶力や注意力、遂行機能能力、構成能力などの高次脳機能障害がみられる。今回、本症例7例について海馬領域が陳述記憶の中枢として重要であることから頭部MRIで海馬領域の計測を行い、その計測結果と日本語版ウェクスラー記憶検査との比較及び正常コントロール群の計測結果との比較を行った。同時に大脳萎縮についても計測、比較した。さらに知能検査、記憶検査、事象関連電位などとCTGリピート数との関連についも検討した。結論としてMyD群の海馬領域計測では記憶の様式特異性障害が示され、さらに海馬領域を含めた大脳全体の萎縮が示された。また事象関連電位P300とCTGリピートの増大との相関が新たに示された。Myotonic dystrophy (Myp) is an autosomaI dominantly inherited disease. This abnormal gepe for Myp is localized to chromosome 19ql3.3 as an expansion of CTG repeat. There is a correIation between the number of CTG repeats and the severity of clinical symptoms. MyD has been noticed accompanying CNS disorders such as disturbance of memory, attention, executive function and construction. We measured cerebral and hippocampal areas of 7 patients with MyD by MRI Hippocampus is one of important areas of declarative memory, therefore it was examined if there was a correlation between the hippocampaI areas of the patients and the scores of Wechsler Memory Scale-Revised (WMS-R). WechsIer Adult Intelligent Scale-Revised (WAIS-R) and event-related potentia1 P300 were also performed for the patients. Then we anaIyzed a correlation to the number of CTG repeats and each datum. In conclusion, an expansion of CTG repeat was correIated to onset, WMS-R andP300 in the patients. And diffuse brain atrophy was observed and correlated to WAIS-R. Also, the degree of hippocampaI atrophy was significantly correIated to the score of WMS-R, especially verbaI memory tests. It was first found that there was a significant correlation between the latency of P300 and the number of CTG repeats in MyD. These results suggest that CTG expansion and brain atrophy relate to disorder of higher brain function in MyD

Evidence for a Common Founder and Clinical Characteristics of Japanese Families with the MAPT R406W Mutation

Background/Aim: Mutations in MAPT cause frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Patients with the MAPT R406W mutation were reported to show phenotypic heterogeneity in different ethnic backgrounds. We here report the clinical and genetic characteristics of Japanese families with the R406W mutation. Methods: We examined the clinical and neuroimaging features of 6 patients from three families with the R406W mutation. We determined the genotypes of intragenic MAPT single-nucleotide polymorphisms (SNPs) and the flanking microsatellite markers to search for a common founder. Results: The initial symptom was memory loss with the average age at onset being 54 years. Anterograde amnesia with episodic memory impairment was the predominant phenotype. Behavioral and personality changes or parkinsonism is not a prominent feature. A brain MRI study revealed marked atrophy of the medial temporal lobe. Genetic analysis of SNPs and microsatellite markers revealed that the affected members of the three families share common genotypes. Conclusion: The findings of the affected members in this study, which corroborate previously reported findings of European families, suggest that the R406W mutation may represent a phenotype of predominant anterograde amnesia in FTLD-17. Our genetic data suggest that a founder effect may account for some families with the R406W mutation

Theoretical study on naphthobischalcogenadiazole conjugated polymer systems and C61 derivative as organic photovoltaic semiconductors

We investigated the charge-transfer reactions of solar cells including a quaterthiophene copolymer with naphtho-bis-thiadiazole (PNTz4T) and naphtho-bis-oxadiazole (PNOz4T) using constrained density functional theory (CDFT). According to our calculations, the high electron-transfer rate results in a highly efficient solar cell, and the stable charge-transfer state results in low energy loss. Our computations imply that the following three factors are crucial to improve the performance of semiconducting polymers: (i) large structural changes following charge-transfer, (ii) narrow band gap, and (iii) spatially delocalized lowest unoccupied molecular orbital (LUMO) of the ground state

Some Experimental Studies on Dissolving-processes between Water and Water-soluble Liquid

Dissolving processes at the interfacial laycrs between water and water-soluble1iquid have been studied by the photographic densitometry-method. Simple theoretical considerations about the phenomena are also given which showed a good agreement with the experimental data

Editorial: Conflicts

The Editorial Board reflects on the theme of 'conflict', as observed in the work published in this issue, and in the wider world