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151.
Jean-Marc Bielser Leon Kraus Orlando Burgos-Morales Hervé Broly Jonathan Souquet 《Biotechnology progress》2020,36(5):e3026
Media preparation for perfusion cell culture processes contributes significantly to operational costs and the footprint of continuous operations for therapeutic protein manufacturing. In this study, definitions are given for the use of a perfusion equivalent nutrient feed stream which, when used in combination with basal perfusion medium, supplements the culture with targeted compounds and increases the medium depth. Definitions to compare medium and feed depth are given in this article. Using a concentrated nutrient feed, a 1.8-fold medium consumption (MC) decrease and a 1.67-fold increase in volumetric productivity (PR) were achieved compared to the initial condition. Later, this strategy was used to push cell densities above 100 × 106 cells/ml while using a perfusion rate below 2 RV/day. In this example, MC was also decreased 1.8-fold compared to the initial condition, but due to the higher cell density, PR was increased 3.1-fold and to an average PR value of 1.36 g L−1 day−1 during a short stable phase, and versus 0.46 g L−1 day−1 in the initial condition. Overall, the performance improvements were aligned with the given definitions. This multiple feeding strategy can be applied to gain some flexibility during process development and also in a manufacturing set-up to enable better control on nutrient addition. 相似文献
152.
Leon Green Jan Niemax Jens‐Peter Herrmann Axel Temming Charlotta Kvarnemo 《Ecology and evolution》2020,10(18):9981-9999
During male–male competition, evolution can favor alternative reproductive tactics. This often results in a dominant morph that holds a resource, such as a nest for egg laying, which competes with a smaller sneaker morph that reproduces by stealing fertilizations. The salinity environment can influence male growth rates, for example, via osmoregulatory costs, which in turn may influence the use of sneaker tactics for small males competing for mating opportunities. Salinity can also affect sperm directly; however, little is known of how salinity influences sneaker tactics through sperm performance. We sampled males of the invasive round goby (Neogobius melanostomus) from two environments, a freshwater river and a brackish estuary. This fish has two male morphs: nest‐holding dark males and non‐nest‐holding light males. We examined the role of water salinity of 0, 8, and 16 on sperm performance and found that for estuarine males, a salinity of 0 reduced sperm velocity compared to a salinity of 8 and 16. Riverine males had low velocity in all salinities. Sperm viability also decreased by over 30% in 0 salinity, compared to 8 and 16, for fish from both environments. Gobies produce ejaculate contents in specialized glands that could in theory shield sperm in an adverse environment. However, gland contents did not improve sperm performance in our tests. Body mass and age estimates indicate that riverine males invested more in somatic growth compared to estuarine males. Estuarine light morph males had a high enough gonadosomatic index to indicate sneaker tactics. We propose that when sperm performance is low, such as for the riverine males, sneaker tactics are ineffective and will be selected against or phenotypically suppressed. Instead, we interpret the increased investment in somatic growth found in riverine males as a life‐history decision that is advantageous when defending a nest in the next reproductive season. 相似文献
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154.
Desai Chirag S. Khan Aisha Bellio Michael A. Willis Micah L. Mahung Cressida Ma Xiaobo Baldwin Xavier Williams Brittney M. Baron Todd H. Coleman Leon G. Wallet Shannon M. Maile Robert 《Molecular and cellular biochemistry》2021,476(12):4331-4341
Molecular and Cellular Biochemistry - Plasma-derived extracellular vesicles (EV) can serve as markers of cell damage/disease but can also have therapeutic utility depending on the nature of their... 相似文献
155.
Temmink Ralph J. M. Dorenbosch Martijn Lamers Leon P. M. Smolders Alfons J. P. Rip Winnie Lengkeek Wouter Didderen Karin Fivash Gregory S. Bouma Tjeerd J. van der Heide Tjisse 《Hydrobiologia》2021,848(17):3987-3999
Hydrobiologia - Aquatic ecosystems provide vital services, and macrophytes play a critical role in their functioning. Conceptual models indicate that in shallow lakes, plants with different growth... 相似文献
156.
Kelly E. Leon Raquel Buj Elizabeth Lesko Erika S. Dahl Chi-Wei Chen Naveen Kumar Tangudu Yuka Imamura-Kawasawa Andrew V. Kossenkov Ryan P. Hobbs Katherine M. Aird 《The Journal of cell biology》2021,220(8)
Oncogene-induced senescence (OIS) is a stable cell cycle arrest that occurs in normal cells upon oncogene activation. Cells undergoing OIS express a wide variety of secreted factors that affect the senescent microenvironment termed the senescence-associated secretory phenotype (SASP), which is beneficial or detrimental in a context-dependent manner. OIS cells are also characterized by marked epigenetic changes. We globally assessed histone modifications of OIS cells and discovered an increase in the active histone marks H3K79me2/3. The H3K79 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) was necessary and sufficient for increased H3K79me2/3 occupancy at the IL1A gene locus, but not other SASP genes, and was downstream of STING. Modulating DOT1L expression did not affect the cell cycle arrest. Together, our studies establish DOT1L as an epigenetic regulator of the SASP, whose expression is uncoupled from the senescence-associated cell cycle arrest, providing a potential strategy to inhibit the negative side effects of senescence while maintaining the beneficial inhibition of proliferation. 相似文献
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159.
Melanie Köllmer Carmen Popescu Prashanth Manda Leon Zhou Richard A. Gemeinhart 《AAPS PharmSciTech》2013,14(4):1333-1340
Pharmaceutical excipients contain reactive groups and impurities due to manufacturing processes that can cause decomposition of active drug compounds. The aim of this investigation was to determine if commercially available oral disintegrating tablet (ODT) platforms induce active pharmaceutical ingredient (API) degradation. Benzocaine was selected as the model API due to known degradation through ester and primary amino groups. Benzocaine was either compressed at a constant pressure, 20 kN, or at pressure necessary to produce a set hardness, i.e., where a series of tablets were produced at different compression forces until an average hardness of approximately 100 N was achieved. Tablets were then stored for 6 months under International Conference on Harmonization recommended conditions, 25°C and 60% relative humidity (RH), or under accelerated conditions, 40°C and 75% RH. Benzocaine degradation was monitored by liquid chromatography–mass spectrometry. Regardless of the ODT platform, no degradation of benzocaine was observed in tablets that were kept for 6 months at 25°C and 60% RH. After storage for 30 days under accelerated conditions, benzocaine degradation was observed in a single platform. Qualitative differences in ODT platform behavior were observed in physical appearance of the tablets after storage under different temperature and humidity conditions. 相似文献
160.
Jessica Cruz de Leon Nicole Scheumann Wandy Beatty Josh R. Beck Johnson Q. Tran Candace Yau Peter J. Bradley Keith Gull Bill Wickstead Naomi S. Morrissette 《Eukaryotic cell》2013,12(7):1009-1019
SAS-6 is required for centriole biogenesis in diverse eukaryotes. Here, we describe a novel family of SAS-6-like (SAS6L) proteins that share an N-terminal domain with SAS-6 but lack coiled-coil tails. SAS6L proteins are found in a subset of eukaryotes that contain SAS-6, including diverse protozoa and green algae. In the apicomplexan parasite Toxoplasma gondii, SAS-6 localizes to the centriole but SAS6L is found above the conoid, an enigmatic tubulin-containing structure found at the apex of a subset of alveolate organisms. Loss of SAS6L causes reduced fitness in Toxoplasma. The Trypanosoma brucei homolog of SAS6L localizes to the basal-plate region, the site in the axoneme where the central-pair microtubules are nucleated. When endogenous SAS6L is overexpressed in Toxoplasma tachyzoites or Trypanosoma trypomastigotes, it forms prominent filaments that extend through the cell cytoplasm, indicating that it retains a capacity to form higher-order structures despite lacking a coiled-coil domain. We conclude that although SAS6L proteins share a conserved domain with SAS-6, they are a functionally distinct family that predates the last common ancestor of eukaryotes. Moreover, the distinct localization of the SAS6L protein in Trypanosoma and Toxoplasma adds weight to the hypothesis that the conoid complex evolved from flagellar components. 相似文献