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1.
S J Richman M Goodman T M Nguyen P W Schiller 《International journal of peptide and protein research》1985,25(6):648-662
As part of our continuing effort to define structure-activity relationships for enkephalin and design enzymatically resistant analogs, we report the synthesis and biological activities of linear and cyclic enkephalin analogs modified at the Gly3-Phe4 amide bond. The partial retro-inverso enkephalin analog Tyr-D-Ala-gGly-(R,S)-mPhe-Leu-NH2 and its cyclic counterpart, Tyr-cyclo[D-A2 bu-gGly-(R,S)-mPhe-Leu-], were synthesized as diastereomeric mixtures using solution methodology. The racemic benzylmalonate allowed the linear analog to be synthesized by fragment coupling at the reversed bond. Cyclization of the second analog was carried out at high concentration, eliminating formation of polymer by the use of an insoluble base. All gem-diaminoalkyl residues were prepared by conversion of peptidyl amides with benzene iodonium bis(trifluoroacetate). Diastereomers of both compounds were separable by reverse phase HPLC but those of the linear compound racemized rapidly under conditions of testing and were therefore tested together. All analogs tested had activities ranging from 6 to 14% of the activity of Leu enkephalin, indicating that the Gly3-Phe4 amide bond is important, though not crucial, for receptor binding. 相似文献
2.
Dr. Josef Schiller 《Plant Systematics and Evolution》1907,57(6):235-237
Ohne Zusammenfassung 相似文献
3.
4.
HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. 总被引:111,自引:11,他引:100 下载免费PDF全文
P Hawley-Nelson K H Vousden N L Hubbert D R Lowy J T Schiller 《The EMBO journal》1989,8(12):3905-3910
The human papillomavirus types (HPVs) most often associated with cancer of the cervix, such as HPV16, have been reported previously to immortalize normal human foreskin keratinocytes in vitro, while the types that are primarily associated with benign cervical lesions failed to do so. In this study we have determined the HPV16 genes that are responsible for the immortalizing activity of the viral genome. Transfection with a plasmid in which E6 and E7 were the only intact open reading frames (ORFs) induced an indefinite life-span in the keratinocytes with an efficiency similar to that of the entire early region of the viral DNA. Mutants in the E6E7 clone with inactivating lesions in E6 or E7 failed to induce immortalization. When transfected alone, E7 could induce hyperproliferation, but these cells eventually senesced. By itself, E6 exhibited no activity, Co-transfection of a plasmid with an intact E6 ORF and a second plasmid with an intact E7 ORF generated keratinocyte lines with indefinite growth potential. The E6 and E7 proteins were detected in the lines induced by the E6E7 DNA and by co-transfection of the E6 and E7 plasmids. Therefore, we conclude that HPV16 E6 and E7 cooperative to immortalize human keratinocytes in vitro. Changes in cellular gene expression are probably also required for immortalization since all of the keratinocyte lines examined were aneuploid. Serum and calcium resistant sublines were isolated from the E6E7 induced lines, indicating that other HPV genes do not play an obligatory role in the generation of resistance to differentiation.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
5.
Wheat dwarf virus, a geminivirus of graminaceous plants needs splicing for replication. 总被引:20,自引:3,他引:17
By analysing mRNAs with the polymerase chain reaction (PCR) and by studying in vitro generated mutants we have identified an intron in the genome of wheat dwarf virus (WDV), a geminivirus of cereals. Polypeptides whose expression is essential for the replication of the viral DNA have been defined. They are encoded by two distinct overlapping open reading frames (ORFs). The joining of these two ORFs by deletion of the intron as well as the introduction of a frameshift mutation within the intron do not prevent replication of the viral genome in suspension culture cells. In contrast to WDV, the geminiviruses of dicotyledonous plants possess a single continuous ORF, highly homologous to the two individual ones of WDV. We propose that mRNA splicing is a common feature of all geminiviruses of the Gramineae and might contribute to their host class specificity. The existence of a functional intron is a novel finding for the plant viruses. 相似文献
6.
Zusammenfassung Anhand einer 16jährigen Untersuchung im Raum Ostwestfalen/Bielefeld wird der Bruterfolg des Turmfalken anhand von 439 Gelegen und 2256 Eiern beschrieben. Drei Brutplatztypen können unterschieden werden: A. Baumbruten in Nestern; B1. Baumbruten in Nistkästen; B2. Gebäudebruten in Nischen oder Nistkästen. Zwischen Baumbruten (A) und Nistkastenbruten (B1/2) werden signifikante Unterschiede beschrieben, die für Nistkästen größere Gelege (ca. ein Ei mehr) und größeren Ausfliegeerfolg belegen. Zwischen Nistkästen in Bäumen (B1) oder an Gebäuden (B2) konnten keine signifikanten Unterschiede festgestellt werden. Weiterhin werden Lege- und Schlupftermine, Legerhythmus und oologische Daten aus dem Untersuchungsgebiet angegeben.
Breeding biology of Kestrels (Falco tinnunculus) in Eastern Westfalia 1972–1987
Summary The 16 years of study gave 439 clutches with 2,256 eggs. We separated three types of breeding sites: the use of (a) stick nests, mostly built by corvids (cf. Tab., Fig. 3), (b1) nest boxes attached to trees or telegraph poles (Fig. 2) and (b2) nest boxes or cavities at or in buildings (Fig. 1). Within these different types of breeding places we found some significant differences. Stick nests had less eggs and though less breeding success, which was possibly caused by predation of corvids, especially magpies. Within the two types of places with nest boxes no significant differences could be established. We concluded, that stick nests were marginal in Kestrels and nest boxes were optimal despite of their placement in trees, at poles or in buildings. Furthermore, the timing of breeding cycle was described (Fig. 4) and laying interval was determind to an average value of approximately two days (Fig. 5). Mean egg size was and average volume 21.2 cm2. Two daily controlled clutches lost 15.5% and 16.1% of mass (Fig. 6) pressumably mostly due to water losses.相似文献
7.
8.
Morten Glasø Olav Hilmar Iversen Torstein Hovig 《Virchows Archiv. B, Cell pathology including molecular pathology》1988,56(1):221-235
The nature and significance of so-called dark keratinocytes in the epidermis during chemical carcinogenesis is still a matter
of concern and debate. Based on ultrastructural observations it has been suggested that dark cells most often are shrunken
cells. Reports on skin carcinogenesis, however, claim that dark cells are a sign of ongoing tumor promotion and represent
those stem cells in the epidermis from which the tumors originate. It is therefore important to find out whether these cells
are simply injured and shrunken cells, or vital cells of great importance for carcinogenesis. Dark cells are assumed to be
rich in ribosomes. There is evidence, however, that the observed number of dark cells is highly dependent on tissue fixation.
In the present ultrastructural study, morphometric methods were used to compare the effects of two different fixation procedures
on the amount of cytoplasmic ribosomes in dark cells from both untreated and carcinogen-treated hairless mouse epidermis.
The results show that the ultrastructural features of both dark and clear cells vary considerably with different fixation
procedures. In acetone-treated controls typical dark cells are only observed when the fixative has a lower osmotic activity
than the plasma. With iso-osmolal fixation typical dark cells are not observed. After an abortive two-stage carcinogenesis
treatment, in which a single application of 9,10-dimethyl-l,2-benzanthracene (DMBA) in acetone was followed by a single application
of 12-O-tetradecanoyl-13-acetate (TPA) in acetone, signs of cell injury could be found after both fixation procedures. With
DMBA/TPA and hypo-osmolal fixation the number of dark cells seemed to increase, whereas only signs of cell injury with occurrence
of some heavily altered “clear cells” dominated the picture with iso-osmolal fixation. Morphometry showed that both the numerical
and the volumetric densities of cytoplasmic ribosomes in basal keratinocytes varied most significantly with the fixation procedure
used. The cytoplasmic volumes did not vary in a way that could explain these differences. One might therefore assume that
the number of ribosomes depends on the fixative. Large swelling artifacts occurred when a fixative with low osmotic activity
was used, leading to compression of neighboring cells. Hence, an increased ribosomal density reported previously in dark cells
is probably related to such cell volume artifacts and does not reflect an actually increased quantity of ribosomes. With both
fixation procedures, a single application of DMBA followed by one of TPA appeared to produce an increased number of ribosomes
in basal keratinocytes. When hypo-osmolal fixation was used, however, treatment with DMBA/TPA did not influence the cytoplasmic
volume or the numerical density of ribosomes, in dark cells. This might indicate that so-called dark keratinocytes following
DMBA/TPA treatment are functionally inactive cells that appear more vulnerable than active cells to compression during hypo-osmolal
fixation. 相似文献
9.
P Schiller J Amin J Ananthan M E Brown W A Scott R Voellmy 《Journal of molecular biology》1988,203(1):97-105
10.
In vitro biological activities of the E6 and E7 genes vary among human papillomaviruses of different oncogenic potential. 总被引:27,自引:11,他引:16 下载免费PDF全文
Human papillomavirus type 16 (HPV-16) and HPV-18 are often detected in cervical carcinomas, while HPV-6, although frequently present in benign genital lesions, is only rarely present in cancers of the cervix. Therefore, infections with HPV-16 and HPV-18 are considered high risk and infection with HPV-6 is considered low risk. We found, by using a heterologous promoter system, that expression of the E7 transforming protein differs between high- and low-risk HPVs. In high-risk HPV-16, E7 is expressed from constructs containing the complete upstream E6 open reading frame. In contrast, HPV-6 E7 was efficiently translated only when E6 was deleted. By using clones in which the coding regions of HPV-6, HPV-16, and HPV-18 E7s were preceded by identical leader sequences, we found that the ability of the E7 gene products to induce anchorage-independent growth in rodent fibroblasts correlated directly with the oncogenic association of the HPV types. By using an immortalization assay of normal human keratinocytes that requires complementation of E6 and E7, we found that both E6 and E7 of HPV-18 could complement the corresponding gene from HPV-16. However, neither E6 nor E7 from HPV-6 was able to substitute for the corresponding gene of HPV-16 or HPV-18. Our results suggest that multiple factors, including lower intrinsic biological activity of E6 and E7 and differences in the regulation of their expression, account for the low activity of HPV-6, in comparison with HPV-16 and HPV-18, in in vitro assays. These same factors may, in part, account for the apparent difference in oncogenic potential between these viruses. 相似文献