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51.
In the production of monoclonal antibodies (mAbs) intended for use in humans, it is a global regulatory requirement that the manufacturing process includes unit operations that are proven to inactivate or remove adventitious agents to ensure viral safety. Viral inactivation by low pH hold (LPH) is typically used to ensure this viral safety in the purification process of mAbs and other biotherapeutics derived from mammalian cell lines. To ascertain the effectiveness of the LPH step, viral clearance studies have evaluated LPH under worst-case conditions of pH above the manufacturing set point and hold duration at or below the manufacturing minimum. Highly acidic conditions (i.e., pH < 3.60) provide robust and effective enveloped virus inactivation but may lead to reduced product quality of the therapeutic protein. However, when viral inactivation is operated above pH 3.60 to ensure product stability, effective (>4 log10 reduction factor) viral inactivation may not be observed under these worst-case pH conditions in viral clearance studies. A multivariate design of experiments was conducted to further characterize the operating space for low pH viral inactivation of a model retrovirus, xenotropic murine leukemia virus (X-MuLV). The statistically designed experiment evaluated the effect of mAb isotype, pH, temperature, acid titrant, sodium chloride (NaCl) concentration, virus spike timing, and post-spike filtration on X-MuLV inactivation. Data from the characterization study were used to generate predictive models to identify conditions that reliably achieve effective viral inactivation at pH ≥ 3.60. Results of the study demonstrated that NaCl concentration has the greatest effect on virus inactivation in the range studied, and pH has a large effect when the load material has no additional NaCl. Overall, robust and effective inactivation of X-MuLV at pH 3.65–3.80 can be achieved by manipulating either the pH or the NaCl concentration of the load material. This study contributes to the understanding of ionic strength as an influential parameter in low pH viral inactivation studies. 相似文献
52.
Monoclonal antibodies against chicken type V collagen: production, specificity, and use for immunocytochemical localization in embryonic cornea and other organs 总被引:23,自引:17,他引:6
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TF Linsenmayer JM Fitch TM Schmid Zak NB E Gibney RD Sanderson R Mayne 《The Journal of cell biology》1983,96(1):124-132
Two monoclonal antibodies have been produced against chick type V collagen and shown to be highly specific for separate, conformational dependent determinants within this molecule. When used for immunocytochemical tissue localization, these antibodies show that a major site for the in situ deposition of type V is within the extracellular matrices of many dense connective tissues. In these, however, it is largely in a form unavailable to the antibodies, thus requiring a specific “unmasking” treatment to obtain successful immunocytochemical staining. The specificity of these two IgG antibodies was determined by inhibition ELISA, in which only type V and no other known collagen shows inhibition. In ELISA, mixtures of the two antibodies give an additive binding reaction to the collagen, suggesting that each is against a different antigenic determinant. That both antigenic determinants are conformational dependent, being either in, or closely associated with, the collagen helix is demonstrated by the loss of antibody binding to molecules that have been thermally denatured. The temperature at which this occurs, as assayed by inhibition ELISA, is very similar to that at which the collagen helix melts, as determined by optical rotation. This gives strong additional evidence that the antibodies are directed against the collagen. The antibodies were used for indirect immunofluorescence analyses of cryostat sections of corneas and other organs from 17 to 18-day-old chick embryos. Of all tissues examined only Bowman’s membrane gave a strong staining reaction with cryostat sections of unfixed material. Staining in other areas of the cornea and in other tissues was very light or nonexistent. When, however, sections were pretreated with pepsin dissolved in dilute HAc or, surprisingly, with the dilute HAc itself dramatic new staining by the antibodies was observed in most tissues examined. The staining, which was specific for the anti-type V collagen antibodies, was largely confined to extracellular matrices of dense connective tissues. Experiments using protease inhibitors suggested that the “unmasking” did not involve proteolysis. We do not yet know the mechanism of this unmasking; however, one possibility is that the dilute acid causes swelling or conformational changes in a type-V collagen-containing supramolecular structure. Further studies should allow us to determine whether this is the case. 相似文献
53.
54.
Influence of day length and temperature on number of main stem leaves and time to flowering in lupin
A growth chamber experiment was carried out to investigate the influence of day length and temperature on the development of flowering in eight varieties of the three grain lupin species Lupinus albus (Wat and C3396), L. angustifolius (Gungurru, Polonez and W26) and L. luteus, (Juno, Radames and Teo). The plants were grown at two temperatures, 10°C and 18°C, in combination with five daylength regimes: 10, 14, 18, 24 h day at full light intensity and 10 h full light extended with 8 h low intensity light. Increased daylength decreased days from sowing to flowering in all varieties, but had little effect on thermal time to flowering in most varieties. However, C3396, W26 and Radames had a significantly longer thermal time to flowering at high, non‐vernalising temperature (18°C) at short daylengths. Low light intensity daylength extension did not significantly influence thermal time to flowering. For flower initiation, measured as number of leaves on the main stem three types of response were found. All varieties formed fewer leaves on the main stem at 10°C than at 18°C, although the two thermo‐neutral varieties of L. luteus, Juno and Teo, gave only a small response to temperature and daylength. In Polonez, Gungurru and Wat, low temperature decreased leaf number, but there was only a small response to changes in daylength. Three varieties, C3396, W26 and Radames, showed longer thermal time to flowering at 18°C with short daylengths. This could be explained by a greater number of main stem leaves formed at short daylength at non‐vernalising temperatures. Increased daylength decreased leaf number in these varieties, but never to a smaller number than for plants grown at 10°C. In these varieties, low intensity extension of the daylength had a similar (W26, Radames) or decreased (C3396) effect compared to full light extension. The hastening of time to flowering by long days could be separated into two effects: a high light energy effect hastened development by increasing the rate of leaf appearance in all varieties, while low light energy in thermo‐sensitive varieties was able to substitute for vernalisation by decreasing leaf number. 相似文献
55.
TE Willnow C Antignac AW Br?ndli EI Christensen RD Cox D Davidson JA Davies O Devuyst G Eichele ND Hastie PJ Verroust A Schedl IC Meij 《Organogenesis》2005,2(2):42-47
Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a three-dimensional reconstruction of the organ. We will seek proof of concept for the organ atlas by elucidating genetic pathways involved in development and pathophysiology of the kidney. Such a kidney atlas may provide a paradigm for a new systems-biology approach in functional genome research aimed at understanding the genetic bases of organ development, physiology and disease.Key Words: EuReGene, kidney, genome, development, pathophysiology, genetics 相似文献
56.
57.
Prevalence of nontuberculous mycobacteria in water supplies of hemodialysis centers. 总被引:5,自引:1,他引:4
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L A Carson L A Bland L B Cusick M S Favero G A Bolan A L Reingold R C Good 《Applied microbiology》1988,54(12):3122-3125
Infection of hemodialysis patients with nontuberculous mycobacteria (NTM) has been associated with water used in reprocessing hemodialyzers. This study was conducted to determine the prevalence of NTM and other bacteria in water samples collected over a 13-week period from 115 randomly selected dialysis centers in the United States. Total viable counts were determined by membrane filter assays; increased recovery of NTM was obtained by dosing a portion of each water sample with 1% formaldehyde (HCHO) before filtering. NTM were widely distributed and occurred with a high frequency in water supplies in dialysis centers. NTM were detected in water from 95 centers (83%), and 50% of all samples examined contained NTM. The results of this study support recommendations to use 4% HCHO or a chemical germicidal equivalent for disinfecting dialyzers that are to be reused. 相似文献
58.
Tong Hao Yang Wang Roberto Mosca Jörg Menche Mikko Taipale Murat Taşan Changyu Fan Xinping Yang Patrick Haley Ryan R Murray Flora Mer Fana Gebreab Stanley Tam Andrew MacWilliams Amélie Dricot Patrick Reichert Balaji Santhanam Lila Ghamsari Michael A Calderwood Thomas Rolland Benoit Charloteaux Susan Lindquist Albert‐László Barabási David E Hill Patrick Aloy Michael E Cusick Yu Xia Frederick P Roth Marc Vidal 《Molecular systems biology》2016,12(4)
In cellular systems, biophysical interactions between macromolecules underlie a complex web of functional interactions. How biophysical and functional networks are coordinated, whether all biophysical interactions correspond to functional interactions, and how such biophysical‐versus‐functional network coordination is shaped by evolutionary forces are all largely unanswered questions. Here, we investigate these questions using an “inter‐interactome” approach. We systematically probed the yeast and human proteomes for interactions between proteins from these two species and functionally characterized the resulting inter‐interactome network. After a billion years of evolutionary divergence, the yeast and human proteomes are still capable of forming a biophysical network with properties that resemble those of intra‐species networks. Although substantially reduced relative to intra‐species networks, the levels of functional overlap in the yeast–human inter‐interactome network uncover significant remnants of co‐functionality widely preserved in the two proteomes beyond human–yeast homologs. Our data support evolutionary selection against biophysical interactions between proteins with little or no co‐functionality. Such non‐functional interactions, however, represent a reservoir from which nascent functional interactions may arise. 相似文献
59.
Wandrille Duchemin Pierre-Yves Dupont Matthew A Campbell Austen RD Ganley Murray P Cox 《BMC bioinformatics》2014,16(1)
Background
Forming a new species through the merger of two or more divergent parent species is increasingly seen as a key phenomenon in the evolution of many biological systems. However, little is known about how expression of parental gene copies (homeologs) responds following genome merger. High throughput RNA sequencing now makes this analysis technically feasible, but tools to determine homeolog expression are still in their infancy.Results
Here we present HyLiTE – a single-step analysis to obtain tables of homeolog expression in a hybrid or allopolyploid and its parent species directly from raw mRNA sequence files. By implementing on-the-fly detection of diagnostic parental polymorphisms, HyLiTE can perform SNP calling and read classification simultaneously, thus allowing HyLiTE to be run as parallelized code. HyLiTE accommodates any number of parent species, multiple data sources (including genomic DNA reads to improve SNP detection), and implements a statistical framework optimized for genes with low to moderate expression.Conclusions
HyLiTE is a flexible and easy-to-use program designed for bench biologists to explore patterns of gene expression following genome merger. HyLiTE offers practical advantages over manual methods and existing programs, has been designed to accommodate a wide range of genome merger systems, can identify SNPs that arose following genome merger, and offers accurate performance on non-model organisms.Electronic supplementary material
The online version of this article (doi:10.1186/s12859-014-0433-8) contains supplementary material, which is available to authorized users. 相似文献60.
Maria A Trainer David Capstick Alicja Zachertowska Kathy N Lam Scott RD Clark Trevor C Charles 《BMC microbiology》2010,10(1):92