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991.
We report on the synthesis of 2-deoxyglycosyl derivatives of uridine as potential donor substrates for glycosyltransferases. The totally stereoselective synthesis is accomplished by two sequential addition reactions of uridine derivatives to glycals promoted by triphenylphosphine-hydrogen bromide. 相似文献
992.
993.
Neuzil J Dong LF Ramanathapuram L Hahn T Chladova M Wang XF Zobalova R Prochazka L Gold M Freeman R Turanek J Akporiaye ET Dyason JC Ralph SJ 《Molecular aspects of medicine》2007,28(5-6):607-645
Mitochondria have recently emerged as new and promising targets for cancer prevention and therapy. One of the reasons for this is that mitochondria are instrumental to many types of cell death and often lie downstream from the initial actions of anti-cancer drugs. Unlike the tumour suppressor gene encoding p53 that is notoriously prone to inactivating mutations but whose function is essential for induction of apoptosis by DNA-targeting agents (such as doxorubicin or 5-fluorouracil), mitochondria present targets that are not so compromised by genetic mutation and whose targeting overcomes problems with mutations of upstream targets such as p53. We have recently proposed a novel class of anti-cancer agents, mitocans that exert their anti-cancer activity by destabilising mitochondria, promoting the selective induction of apoptotic death in tumour cells. In this communication, we review recent findings on mitocans and propose a common basis for their mode of action in inducing apoptosis of cancer cells. We use as an example the analogues of vitamin E that are proving to be cancer cell-specific and may soon be developed into efficient anti-cancer drugs. 相似文献
994.
《Endocrinología y nutrición》2014,61(3):153-159
Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens. 相似文献
995.
East Asian pollen database: modern pollen distribution and its quantitative relationship with vegetation and climate 总被引:1,自引:0,他引:1
996.
Arthur C. Durband 《American journal of physical anthropology》2014,155(1):173-178
The crania from Kow Swamp and Cohuna have been important for a number of debates in Australian paleoanthropology. These crania typically have long, flat foreheads that many workers have cited as evidence of genetic continuity with archaic Indonesian populations, particularly the Ngandong sample. Other scientists have alleged that at least some of the crania from Kow Swamp and the Cohuna skull have been altered through artificial modification, and that the flat foreheads possessed by these individuals are not phylogenetically informative. In this study, several Kow Swamp crania and Cohuna are compared to known modified and unmodified comparative samples. Canonical variates analyses and Mahalanobis distances are generated, and random expectation statistics are used to calculate statistical significance for these tests. The results of this study agree with prior work indicating that a portion of this sample shows evidence for artificial modification of the cranial vault. Many Kow Swamp crania and Cohuna display shape similarities with a population of known modified individuals from New Britain. Kow Swamp 1, 5, and Cohuna show the strongest evidence for modification, but other individuals from this sample also show evidence of culturally manipulated changes in cranial shape. This project provides added support for the argument that at least some Pleistocene Australian groups were practicing artificial cranial modification, and suggests that caution should be used when including these individuals in phylogenetic studies. Am J Phys Anthropol 155:173–178, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
997.
Relethford JH 《American journal of physical anthropology》2001,115(1):95-98
The recent extraction of mitochondrial DNA sequences from three European Neandertal fossils has led many to the conclusion that ancient DNA analysis supports the African replacement model of modern human origins and rejects models of multiregional evolution that propose some Neandertal ancestry in living humans. This conclusion is based, in part, on the lack of regional affinity of Neandertal DNA to that from living Europeans. Consideration of migration matrix models shows that this conclusion is premature, since under a model of interregional gene flow we expect to see similar levels of Neandertal ancestry in all contemporary regions, and living Europeans should not necessarily show closer affinity. The absence of regional affinity in Neandertal DNA does not distinguish between replacement and multiregional models. 相似文献
998.
Multi-target-directed ligands (MTDLs) centered on β-secretase 1 (BACE-1) inhibition are emerging as innovative therapeutics in addressing the complexity of neurodegenerative diseases. A new series of donepezil analogues was designed, synthesized and evaluated as MTDLs against neurodegenerative diseases. Profiling of donepezil, a potent acetylcholinesterase (hAChE) inhibitor, into BACE-1 inhibition was achieved through introduction of backbone amide linkers to the designed compounds which are capable of hydrogen-bonding with BACE-1 catalytic site. In vitro assays and molecular modeling studies revealed the dual mode of action of compounds 4–6 against hAChE and BACE-1. Notably, compound 4 displayed potent hAChE inhibition (IC50 value of 4.11 nM) and BACE-1 inhibition (IC50 value of 18.3 nM) in comparison to donepezil (IC50 values of 6.21 and 194 nM against hAChE and BACE-1, respectively). Moreover, 4 revealed potential metal chelating property, low toxicity on SH-SY5Y neuroblastoma cells and ability to cross the blood–brain barrier (BBB) in PAMPA-BBB assay which renders 4 a potential lead for further optimization of novel small ligands for the treatment of Alzheimer's disease. 相似文献
999.
Richard Gawne Kenneth Z. McKenna H. Frederik Nijhout 《BioEssays : news and reviews in molecular, cellular and developmental biology》2018,40(1)
The question of whether the modern evolutionary synthesis requires an extension has recently become a topic of discussion, and a source of controversy. We suggest that this debate is, for the most part, not about the modern synthesis at all. Rather, it is about the extent to which genetic mechanisms can be regarded as the primary determinants of phenotypic characters. The modern synthesis has been associated with the idea that phenotypes are the result of gene products, while supporters of the extended synthesis have suggested that environmental factors, along with processes such as epigenetic inheritance, and niche construction play an important role in character formation. We argue that the methodology of the modern evolutionary synthesis has been enormously successful, but does not provide an accurate characterization of the origin of phenotypes. For its part, the extended synthesis has yet to be transformed into a testable theory, and accordingly, has yielded few results. We conclude by suggesting that the origin of phenotypes can only be understood by integrating findings from all levels of the organismal hierarchy. In most cases, parts and processes from a single level fail to accurately explain the presence of a given phenotypic trait. 相似文献
1000.
Atish Barua Pritha Choudhury Joy Krishna Maity Sukhendu Bikash Mandal Suvra Mandal 《Free radical research》2019,53(1):57-67
Therapeutic efficacy of nucleoside analogues (NAs) like Gemcitabine, 5-fluorouracil in cancer treatment is already well established. Most of the known NAs are highly toxic to normal cells due to its non-specific action; thus searching for non-toxic NAs are still going on. For that purpose we have synthesised nine different NAs by alteration of their structural and functional groups. The aim of present study is to investigate the therapeutic potential of NAs against mice bearing breast adenocarcinoma cells at IC50 dose for 10 days treatment schedule. Results of the present study showed that, among the seven nucleoside analogues, NA-7 and NA-9 showed maximum therapeutic efficacy in controlling cancer cells by inhibiting cell proliferation and inducing apoptosis without any adverse effects to normal host cells. Additionally, NAs significantly decreased the tumour burden and enhanced survivability of host through generation of reactive oxygen species in tumour cells. These ultimately led to DNA damage, depolarisation of mitochondrial membrane potential and apoptosis in tumour cells. To find out the molecular mechanisms, we showed that administration of NA-7 and NA-9, down- regulating the expression of Bcl-2, cyclin D1, C-myc, P-21 and up-regulating the expression of P-53, Cyt-c, Bax, caspase-3 and caspase-9. The results suggest that NA-7 and NA-9 exhibits significant antitumor activity than 5-fluorouracil by modulating the cell cycle checkpoints and inducing apoptosis in Ehrlich ascites carcinoma (EAC)-bearing mice. Additionally, NA-7 and NA-9 did not show any clastogenic effect on bone marrow cells at sub-lethal dose. Thus, the present study clearly suggested therapeutic benefit of NAs by augmenting anticancer efficacy and diminishing toxicity to the host. 相似文献