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41.
Vugmeyster Y Xu X Theil FP Khawli LA Leach MW 《World journal of biological chemistry》2012,3(4):73-92
Significant progress has been made in understanding pharmacokinetics (PK),pharmacodynamics (PD),as well as toxicity profiles of therapeutic proteins in animals and humans,which have been in commercial development for more than three decades.However,in the PK arena,many fundamental questions remain to be resolved.Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans,and from in vitro assays to in vivo readouts,which would ultimately lead to a higher success rate in drug development.In toxicology,it is known,in general,what studies are needed to safely develop therapeutic proteins,and what studies do not provide relevant information.One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity.In this review,we will highlight the emerging science and technology,as well as the challenges around the pharmacokinetic-and safety-related issues in drug development of mAbs and other therapeutic proteins. 相似文献
42.
Ekaterina V. Madyarova Renat V. Adelshin Mariya D. Dimova Denis V. Axenov-Gribanov Yulia A. Lubyaga Maxim A. Timofeyev 《PloS one》2015,10(6)
At present, approximately 187 genera and over 1300 species of Microsporidia have been described, among which almost half infect aquatic species and approximately 50 genera potentially infect aquatic arthropods. Lake Baikal is the deepest and one of the oldest lakes in the world, and it has a rich endemic fauna with a predominance of arthropods. Among the arthropods living in this lake, amphipods (Crustacea) are the most dominant group and are represented by more than 350 endemic species. Baikalian amphipods inhabit almost all depths and all types of substrates. The age and geographical isolation of this group creates excellent opportunities for studying the diversity, evolution and genetics of host-parasite relationships. However, despite more than 150 years of study, data investigating the microsporidia of Lake Baikal remain incomplete. In this study, we used molecular genetic analyses to detect microsporidia in the hemolymph of several endemic species of amphipods from Lake Baikal. We provide the first evidence that microsporidian species belonging to three genera (Microsporidium, Dictyocoela and Nosema) are present in the hemolymph of Baikalian endemic amphipods. In the hemolymph of Eulimnogammarus verrucosus, we detected SSU rDNA of microsporidia belonging to the genus Nozema. In the hemolymph of Pallasea cancellous, we found the DNA of Microsporidium sp. similar to that in other Baikalian endemic amphipods; Dictyocoela sp. was found in the hemolymph of Eulimnogammarus marituji and Acanthogammarus lappaceus longispinus. 相似文献
43.
Tyurina YY Tungekar MA Jung MY Tyurin VA Greenberger JS Stoyanovsky DA Kagan VE 《FEBS letters》2012,586(3):235-241
Peroxidation of cardiolipin in mitochondria is essential for the execution of apoptosis. We suggested that integration of oleic acid into cardiolipin generates non-oxidizable cardiolipin species hence protects cells against apoptosis. We synthesized mitochondria-targeted triphenylphosphonium oleic acid ester. Using lipidomics analysis we found that pretreatment of mouse embryonic cells with triphenylphosphonium oleic acid ester resulted in decreased contents of polyunsaturated cardiolipins and elevation of its species containing oleic acid residues. This caused suppression of apoptosis induced by actinomycin D. Triacsin C, an inhibitor of acyl-CoA synthase, blocked integration of oleic acid into cardiolipin and restored cell sensitivity to apoptosis. 相似文献
44.
45.
Natalia A. Mikhailova Yulia A. Gracheva Thierry Backeljau Andrey I. Granovitch 《Genetica》2009,137(3):333-340
Three sister species of rough periwinkles, viz. Littorina saxatilis (Olivi 1792), L. arcana (Hannaford Ellis 1978) and L. compressa (Jeffreys 1865) from the Barents Sea (Russia), the White Sea (Russia) and the Norwegian Sea (Norway) were studied. The identification
of two sibling species L. saxatilis and L. arcana is often difficult as both species have extremely similar shell morphology and reproductive systems. Only mature females
can be unambiguously distinguished, with a jelly gland present in female L. arcana, but which is replaced by a brood pouch containing developing embryos in L. saxatilis. No clear-cut diagnostic features have been found to discriminate between males or juveniles of the two species. The very
first diagnostic DNA marker (DNA fragment A2.8, 271 bp length) for L. arcana and L. saxatilis separation was developed. The marker was derived from apparently species-specific L. arcana DNA fragments obtained via Random Amplified Polymorphic DNA (RAPD) analysis. This fragment was cloned and sequenced, whereupon
specific primers were designed and the amplification was surveyed in a large number of morphologically well-identified females
of both species. Subsequently, the specific DNA marker was used for the identification of male L. arcana and partners in copulating pairs. In this way, we obtained evidence of possible interspecific hybridization between the sibling
species L. arcana and L. saxatilis living in sympatry in natural populations: the presence of A2.8 fragment in 12% of morphologically well identified L. saxatilis females and its absence in 14% of morphologically well identified L. arcana females. The A2.8 fragment never amplified in L. saxatilis from sites without L. arcana. The A2.8 fragment did not amplify in L. compressa, not even in microsympatric populations, and we did not observe interspecific copulations between L. arcana and L. compressa. 相似文献
46.
Andrews PD Ovechkina Y Morrice N Wagenbach M Duncan K Wordeman L Swedlow JR 《Developmental cell》2004,6(2):253-268
Chromosome orientation and alignment within the mitotic spindle requires the Aurora B protein kinase and the mitotic centromere-associated kinesin (MCAK). Here, we report the regulation of MCAK by Aurora B. Aurora B inhibited MCAK's microtubule depolymerizing activity in vitro, and phospho-mimic (S/E) mutants of MCAK inhibited depolymerization in vivo. Expression of either MCAK (S/E) or MCAK (S/A) mutants increased the frequency of syntelic microtubule-kinetochore attachments and mono-oriented chromosomes. MCAK phosphorylation also regulates MCAK localization: the MCAK (S/E) mutant frequently localized to the inner centromere while the (S/A) mutant concentrated at kinetochores. We also detected two different binding sites for MCAK using FRAP analysis of the different MCAK mutants. Moreover, disruption of Aurora B function by expression of a kinase-dead mutant or RNAi prevented centromeric targeting of MCAK. These results link Aurora B activity to MCAK function, with Aurora B regulating MCAK's activity and its localization at the centromere and kinetochore. 相似文献
47.
Smol'kina ON Shishonkova NS Fedonenko YP Zdorovenko EL Konnova SA Ignatov VV 《Carbohydrate research》2012,347(1):161-163
A method is developed for the preparation of D-rhamnose from an O-polysaccharide (OPS) isolated by mild acid hydrolysis of Azospirillum brasilense SR75 cell mass. After the OPS hydrolysis, D-rhamnose was recovered by gel-permeation chromatography on Toyopearl TSK HW-40 and was crystallized. The sugar activity was demonstrated immunochemically. The advantages of the method are that it expedites and simplifies the extraction of D-rhamnose and increases its yield. 相似文献
48.
Renat V. Adelshin Olga V. Melnikova Yulia N. Trushina Alexander D. Botvinkin Tatyana I. Borisova Evgeny I. Andaev Dmitry B. Verzhutsky Albert S. Khangazhinov Sergey V. Balakhonov 《中国病毒学》2015,30(4):313
<正>Dear Editor,Lake Baikal and its neighboring territories are an intermediate zone for thesteppeandarctic-likerabies virus lineages in Russia.After the elimination of dog-mediated rabies during the early 1980s,this area remained rabies-free for over 25–30 years.A sudden reappearance of rabies occurred in this zone in the Republic of Buryatia in 2011–2012.A marginal part of the Mongolian steppe penetrates the Siberian taiga forests in this area,and human and animal rabies have been repeatedly recorded in the Republic of Buryatia from the end of the 相似文献
49.
A closed‐loop supply chain (CLSC) is considered not only an important solution for ensuring sustainable exploitation of materials, but also a promising strategy for securing long‐term availability of materials. The latter is especially highlighted in the materials criticality discourse. Critical raw materials (CRMs), being exposed to supply disruptions, create an uncertain operational environment for many industries, particularly for green energy technologies that employ multiple CRMs. However, recycling rates of CRMs are very low and engagement of companies in CLSC for CRM is limited. This study examines factors influencing CLSC for CRM development in photovoltaic panels and wind turbine technologies. The aim is to analyze how the factors manifest themselves in different companies along the supply chain and to identify enabling and bottleneck conditions for implementation of CLSC for CRM. The novelty of the study is twofold: the focus on material rather than product flows, and examination of factors from a multiactor perspective. The evidence obtained suggests that the manufacturing companies and reverse supply‐chain operators engaged in the study take different perspectives (product vs. material) regarding development of CLSC for CRM and thus emphasize different factors. The findings underline the need for interactions between supply‐chain actors, a sound competitive environment for recycling processes, and investment in technologies and infrastructure development if CLSC for CRM is to be developed. The paper provides implications for practitioners and policy makers for implementation of CLSC for CRM, and suggests prospects for further research. 相似文献
50.
Yulia Kundel Nicola J. Nasser Ofer Purim Rinat Yerushalmi Eyal Fenig Raphael M. Pfeffer Salomon M. Stemmer Shulamith Rizel Zvi Symon Bella Kaufman Aaron Sulkes Baruch Brenner 《PloS one》2013,8(7)