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711.
Jayati Sarkar Lalita Kanwar Shekhawat Varun Loomba Anurag S. Rathore 《Biotechnology progress》2016,32(3):613-628
Mixing in bioreactors is known to be crucial for achieving efficient mass and heat transfer, both of which thereby impact not only growth of cells but also product quality. In a typical bioreactor, the rate of transport of oxygen from air is the limiting factor. While higher impeller speeds can enhance mixing, they can also cause severe cell damage. Hence, it is crucial to understand the hydrodynamics in a bioreactor to achieve optimal performance. This article presents a novel approach involving use of computational fluid dynamics (CFD) to model the hydrodynamics of an aerated stirred bioreactor for production of a monoclonal antibody therapeutic via mammalian cell culture. This is achieved by estimating the volume averaged mass transfer coefficient (kLa) under varying conditions of the process parameters. The process parameters that have been examined include the impeller rotational speed and the flow rate of the incoming gas through the sparger inlet. To undermine the two‐phase flow and turbulence, an Eulerian‐Eulerian multiphase model and k‐ε turbulence model have been used, respectively. These have further been coupled with population balance model to incorporate the various interphase interactions that lead to coalescence and breakage of bubbles. We have successfully demonstrated the utility of CFD as a tool to predict size distribution of bubbles as a function of process parameters and an efficient approach for obtaining optimized mixing conditions in the reactor. The proposed approach is significantly time and resource efficient when compared to the hit and trial, all experimental approach that is presently used. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:613–628, 2016 相似文献
712.
713.
Sebastiano Bellanca Robert L. Summers Max Meyrath Anurag Dave Megan N. Nash Martin Dittmer Cecilia P. Sanchez Wilfred D. Stein Rowena E. Martin Michael Lanzer 《The Journal of biological chemistry》2014,289(52):36336-36351
Mutations in the “chloroquine resistance transporter” (PfCRT) are a major determinant of drug resistance in the malaria parasite Plasmodium falciparum. We have previously shown that mutant PfCRT transports the antimalarial drug chloroquine away from its target, whereas the wild-type form of PfCRT does not. However, little is understood about the transport of other drugs via PfCRT or the mechanism by which PfCRT recognizes different substrates. Here we show that mutant PfCRT also transports quinine, quinidine, and verapamil, indicating that the protein behaves as a multidrug resistance carrier. Detailed kinetic analyses revealed that chloroquine and quinine compete for transport via PfCRT in a manner that is consistent with mixed-type inhibition. Moreover, our analyses suggest that PfCRT accepts chloroquine and quinine at distinct but antagonistically interacting sites. We also found verapamil to be a partial mixed-type inhibitor of chloroquine transport via PfCRT, further supporting the idea that PfCRT possesses multiple substrate-binding sites. Our findings provide new mechanistic insights into the workings of PfCRT, which could be exploited to design potent inhibitors of this key mediator of drug resistance. 相似文献
714.
Salil Varshney Kripa Shankar Muheeb Beg Vishal M. Balaramnavar Sunil Kumar Mishra Pankaj Jagdale Shishir Srivastava Yashpal S. Chhonker Vijai Lakshmi Bhushan P. Chaudhari Rabi Shankar Bhatta Anil Kumar Saxena Anil Nilkanth Gaikwad 《Journal of lipid research》2014,55(6):1019-1032
We developed a common feature pharmacophore model using known antiadipogenic compounds (CFPMA). We identified rohitukine, a reported chromone anticancer alkaloid as a potential hit through in silico mapping of the in-house natural product library on CFPMA. Studies were designed to assess the antiadipogenic potential of rohitukine. Rohitukine was isolated from Dysoxylum binacteriferum Hook. to ⬧95% purity. As predicted by CFPMA, rohitukine was indeed found to be an antiadipogenic molecule. Rohitukine inhibited lipid accumulation and adipogenic differentiation in a concentration- and exposure-time-dependent manner in 3T3-L1 and C3H10T1/2 cells. Rohitukine downregulated expression of PPARγ, CCAAT/enhancer binding protein α, adipocyte protein 2 (aP2), FAS, and glucose transporter 4. It also suppressed mRNA expression of LPL, sterol-regulatory element binding protein (SREBP) 1c, FAS, and aP2, the downstream targets of PPARγ. Rohitukine arrests cells in S phase during mitotic clonal expansion. Rohitukine was bioavailable, and 25.7% of orally administered compound reached systemic circulation. We evaluated the effect of rohitukine on dyslipidemia induced by high-fat diet in the hamster model. Rohitukine increased hepatic expression of liver X receptor α and decreased expression of SREBP-2 and associated targets. Rohitukine decreased hepatic and gonadal lipid accumulation and ameliorated dyslipidemia significantly. In summary, our strategy to identify a novel antiadipogenic molecule using CFPMA successfully resulted in identification of rohitukine, which confirmed antiadipogenic activity and also exhibited in vivo antidyslipidemic activity. 相似文献
715.
Silpi Chatterjee Minti Kumari Anurag Rai Tanoj Kumar Akash Tripathi Shruti Gupta 《Bioinformation》2021,17(1):53
It is of interest to report data on periodontal Health among elderly people in Bushland, Jharkhand, Magadha and Patna, India. The sample comprised of a 130 elderly people. The studies device comprised of a semi-structured survey with thirteen questions. Data shows that old people in Jharkhand suffered from advanced periodontal ailment (47.6%) with easy gingivitis (33.8%). Data also shows that grownups (88.2% grownup males, 64.5% girls in Jharkhand and 34.5% grownup males and 88.9% girls in Bihar) used toothpaste and toothbrush as their primary style for tooth cleansing. These data help in providing improved dental service to rural population in India. 相似文献
716.
Sharon Barone Stacey L. Fussell Anurag Kumar Singh Fred Lucas Jie Xu Charles Kim Xudong Wu Yiling Yu Hassane Amlal Ursula Seidler Jian Zuo Manoocher Soleimani 《The Journal of biological chemistry》2009,284(8):5056-5066
The identity of the transporter responsible for fructose absorption in the
intestine in vivo and its potential role in fructose-induced
hypertension remain speculative. Here we demonstrate that Glut5 (Slc2a5)
deletion reduced fructose absorption by ∼75% in the jejunum and decreased
the concentration of serum fructose by ∼90% relative to wild-type mice on
increased dietary fructose. When fed a control (60% starch) diet,
Glut5-/- mice had normal blood pressure and displayed normal weight
gain. However, whereas Glut5+/+ mice showed enhanced salt
absorption in their jejuna in response to luminal fructose and developed
systemic hypertension when fed a high fructose (60% fructose) diet for 14
weeks, Glut5-/- mice did not display fructose-stimulated salt
absorption in their jejuna, and they experienced a significant impairment of
nutrient absorption in their intestine with accompanying hypotension as early
as 3–5 days after the start of a high fructose diet. Examination of the
intestinal tract of Glut5-/- mice fed a high fructose diet revealed
massive dilatation of the caecum and colon, consistent with severe
malabsorption, along with a unique adaptive up-regulation of ion transporters.
In contrast to the malabsorption of fructose, Glut5-/- mice did not
exhibit an absorption defect when fed a high glucose (60% glucose) diet. We
conclude that Glut5 is essential for the absorption of fructose in the
intestine and plays a fundamental role in the generation of fructose-induced
hypertension. Deletion of Glut5 results in a serious nutrient-absorptive
defect and volume depletion only when the animals are fed a high fructose diet
and is associated with compensatory adaptive up-regulation of ion-absorbing
transporters in the colon.Fructose is a monosaccharide and is one of the three most important blood
sugars along with glucose and galactose
(1–3).
It plays an essential role in vital metabolic functions in the body, including
glycolysis and gluconeogenesis
(4–6).
Fructose is predominantly metabolized in the liver. A high flux of fructose to
the liver perturbs glucose metabolism and leads to a significantly enhanced
rate of triglyceride synthesis. In addition, fructose can be metabolized in
the liver to uric acid, a potent antioxidant
(7,
8).The classic model of sugar absorption indicates that sodium glucose
cotransporter 1
(Sglt1)3 and Glut5
absorb glucose and fructose, respectively, from intestinal lumen to cytosol,
and Glut2 transports both glucose and fructose from the cytosol to the blood
(9–19).
Glut2 has high affinity for glucose and a moderate affinity for fructose,
whereas Glut5 predominantly transports fructose with very low affinity for
glucose
(9–19;
reviews in Refs. 14,
17–19).
The expression of Glut5 or Glut2 in the small intestine increases in rats or
mice fed a diet high in fructose or perfused with increased fructose
concentration
(11–14,
18,
19).Glut2 is predominantly found on the basolateral membrane and in the
cytoplasm of enterocytes at basal state but is thought to be recruited to the
apical membrane in the presence of increased glucose or fructose in the
intestinal lumen (11,
19). Given the fact that both
Glut5 and Glut2 can transport fructose in vitro and given the ability
of Glut2 to traffic to the apical membrane, the contribution of Glut5 to the
absorption of fructose in vivo and systemic fructose homeostasis
remains speculative.The marked increase in dietary fructose consumption in the form of high
fructose corn syrup, a common sweetener used in the food industry, table
sugar, and fruits correlates with the increased incidence of metabolic
syndrome, which is reaching an epidemic proportion in developed countries and
is a major contributor to premature morbidity and mortality in our society
(20–22).
Increased dietary fructose intake recapitulates many aspects of metabolic
syndrome, including dyslipidemia, insulin resistance, and hypertension in rat
and mouse
(23–26).
Recent studies demonstrate that fructose-induced hypertension is initiated by
increased absorption of salt and fructose in the intestine
(27); however, the one or more
molecules (Glut2, Glut5, Glut7, or Sglt1) that are responsible for the
absorption of fructose in the intestine remain speculative. Further, although
Glut7, Glut5, and Glut2 can transport fructose in vitro, the role of
Glut5 in in vivo fructose absorption remains unknown. To ascertain
the role of Glut5 in fructose absorption in the intestine in vivo and
fructose-induced hypertension, mice lacking the Glut5 gene
(Glut5-/-) were placed on either high fructose or normal diet and
compared with their wild-type littermates (Glut5+/+). 相似文献
717.
PHYLOGENETIC TRENDS IN PHENOLIC METABOLISM OF MILKWEEDS (ASCLEPIAS): EVIDENCE FOR ESCALATION 总被引:1,自引:0,他引:1
Anurag A. Agrawal Juha-Pekka Salminen Mark Fishbein 《Evolution; international journal of organic evolution》2009,63(3):663-673
Although plant-defense theory has long predicted patterns of chemical defense across taxa, we know remarkably little about the evolution of defense, especially in the context of directional phylogenetic trends. Here we contrast the production of phenolics and cardenolides in 35 species of milkweeds ( Asclepias and Gomphocarpus ). Maximum-likelihood analyses of character evolution revealed three major patterns. First, consistent with the defense-escalation hypothesis, the diversification of the milkweeds was associated with a trend for increasing phenolic production; this pattern was reversed (a declining evolutionary trend) for cardenolides, toxins sequestered by specialist herbivores. Second, phylogenetically independent correlations existed among phenolic classes across species. For example, coumaric acid derivatives showed negatively correlated evolution with caffeic acid derivatives, and this was likely driven by the fact that the former are used as precursors for the latter. In contrast, coumaric acid derivatives were positively correlated with flavonoids, consistent with competition for the precursor p- coumaric acid. Finally, of the phenolic classes, only flavonoids showed correlated evolution (positive) with cardenolides, consistent with a physiological and evolutionary link between the two via malonate. Thus, this study presents a rigorous test of the defense-escalation hypothesis and a novel phylogenetic approach to understanding the long-term persistence of physiological constraints on secondary metabolism. 相似文献
718.
719.
720.
Ankita Varshney Basir Ahmad Gulam Rabbani Vijay Kumar Savita Yadav Rizwan Hasan Khan 《Amino acids》2010,39(3):899-910
Keyhole limpet hemocyanin (KLH) is widely used as an immune stimulant and hapten carrier derived from a marine mollusc Megathura crenulata. To provide details of the stability and equilibrium of KLH, different intermediate species were investigated with a series of biophysical techniques: circular dichroism, binding of hydrophobic dye, 1-anilino-8-naphthalene sulfonic acid, acrylamide-induced fluorescence quenching, thermal stability and dynamic light scattering. KLH in its native state at pH 7.4 exists in the stable didecameric form with hydrodynamic radii (R h) of 28.22 nm, which is approximately equal to a molecular mass of 8.8 ± 0.6 MDa. The experimental results demonstrated the presence of two structurally distinct species in the conformational transition of KLH under acidic conditions. One species populates at pH 2.8, characterized as decameric (4.8 ± 0.2 MDa; R h = 22.02 nm), molten globule-like state, while the other accumulates at pH 1.2 and is characterized as a tetramer (2.4 ± 0.8 MDa; R h = 16.47 nm) with more organized secondary and tertiary structures. Our experimental manipulation of the oligomeric states of KLH has provided data that correlate well with the known oligomeric forms obtained from total KLH formed in vivo and extends our understanding of multimer formation by KLH. The results are of particular interest in light of the important role of the mechanistic pathway of pH-dependent structural changes of Hc stability in the biochemical and medical applications of these respiratory proteins. 相似文献