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71.
72.
A purification process for heparin and precursor polysaccharides using the pH responsive behavior of chitosan 下载免费PDF全文
Ujjwal Bhaskar Anne M. Hickey Guoyun Li Ruchir V. Mundra Fuming Zhang Li Fu Chao Cai Zhimin Ou Jonathan S. Dordick Robert J. Linhardt 《Biotechnology progress》2015,31(5):1348-1359
The contamination crisis of 2008 has brought to light several risks associated with use of animal tissue derived heparin. Because the total chemical synthesis of heparin is not feasible, a bioengineered approach has been proposed, relying on recombinant enzymes derived from the heparin/HS biosynthetic pathway and Escherichia coli K5 capsular polysaccharide. Intensive process engineering efforts are required to achieve a cost‐competitive process for bioengineered heparin compared to commercially available porcine heparins. Towards this goal, we have used 96‐well plate based screening for development of a chitosan‐based purification process for heparin and precursor polysaccharides. The unique pH responsive behavior of chitosan enables simplified capture of target heparin or related polysaccharides, under low pH and complex solution conditions, followed by elution under mildly basic conditions. The use of mild, basic recovery conditions are compatible with the chemical N‐deacetylation/N‐sulfonation step used in the bioengineered heparin process. Selective precipitation of glycosaminoglycans (GAGs) leads to significant removal of process related impurities such as proteins, DNA and endotoxins. Use of highly sensitive liquid chromatography‐mass spectrometry and nuclear magnetic resonance analytical techniques reveal a minimum impact of chitosan‐based purification on heparin product composition. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1348–1359, 2015 相似文献
73.
Unreported yet massive deforestation driving loss
of endemic biodiversity in Indian Himalaya 总被引:1,自引:0,他引:1
M. K. Pandit Navjot S. Sodhi Lian Pin Koh Arun Bhaskar Barry W. Brook 《Biodiversity and Conservation》2007,16(1):153-163
Deforestation is a primary driver of biotic extinctions in the tropics. The impacts of deforestation in tropical biodiversity
hotspots are of particular concern because these regions contain high concentrations of globally endemic species. However,
the effects of large-scale deforestation on native biotas within the biodiversity hotspot of Himalaya remain poorly documented.
Here we report on an alarming trend of deforestation in the Indian Himalaya and project the likely consequential extinctions
of endemic taxa (species and subspecies) by 2100 across a broad range of taxonomic groups, including gymnosperms, angiosperms,
fishes, amphibians, reptiles, birds, and mammals. With the current level of deforestation, by 2100 only about 10% of the land
area of the Indian Himalaya will be covered by dense forest (>40% canopy cover)—a scenario in which almost a quarter of the
endemic species could be wiped out, including 366 endemic vascular plant taxa and 35 endemic vertebrate taxa. We also show
that inaccurate reporting of forest cover data by governmental institutions can result in underestimations of the biological
impacts of deforestation, as well as potential miscalculations in land-use decisions (e.g., the construction of hydroelectric
dams). Large-scale conservation efforts, including forest protection and reforestation, are urgently needed to avoid the impending
deforestation-driven biodiversity losses in the Himalaya. 相似文献
74.
Nicodemus KK Kolachana BS Vakkalanka R Straub RE Giegling I Egan MF Rujescu D Weinberger DR 《Human genetics》2007,120(6):889-906
Catechol-O-methyltransferase (COMT) regulates dopamine degradation and is located in a genomic region that is deleted in a syndrome
associated with psychosis, making it a promising candidate gene for schizophrenia. COMT also has been shown to influence prefrontal
cortex processing efficiency. Prefrontal processing dysfunction is a common finding in schizophrenia, and a background of
inefficient processing may modulate the effect of other candidate genes. Using the NIMH sibling study (SS), a non-independent
case-control set, and an independent German (G) case-control set, we performed conditional/unconditional logistic regression
to test for epistasis between SNPs in COMT (rs2097603, Val158Met (rs4680), rs165599) and polymorphisms in other schizophrenia
susceptibility genes. Evidence for interaction was evaluated using a likelihood ratio test (LRT) between nested models. SNPs
in RGS4, G72, GRM3, and DISC1 showed evidence for significant statistical epistasis with COMT. A striking result was found
in RGS4: three of five SNPs showed a significant increase in risk [LRT P-values: 90387 = 0.05 (SS); SNP4 = 0.02 (SS), 0.02 (G); SNP18 = 0.04 (SS), 0.008 (G)] in interaction with COMT; main effects
for RGS4 SNPs were null. Significant results for SNP4 and SNP18 were also found in the German study. We were able to detect
statistical interaction between COMT and polymorphisms in candidate genes for schizophrenia, many of which had no significant
main effect. In addition, we were able to replicate other studies, including allelic directionality. The use of epistatic
models may improve replication of psychiatric candidate gene studies. 相似文献
75.
Like the beta-turns, which are characterized by a limiting distance between residues two positions apart (i, i+3), a distance criterion (involving residues at positions i and i+4) is used here to identify alpha-turns from a database of known protein structures. At least 15 classes of alpha-turns have been enumerated based on the location in the phi,psi space of the three central residues (i+1 to i+3)-one of the major being the class AAA, where the residues occupy the conventional helical backbone torsion angles. However, moving towards the C-terminal end of the turn, there is a shift in the phi,psi angles towards more negative phi, such that the electrostatic repulsion between two consecutive carbonyl oxygen atoms is reduced. Except for the last position (i+4), there is not much similarity in residue composition at different positions of hydrogen and non-hydrogen bonded AAA turns. The presence or absence of Pro at i+1 position of alpha- and beta-turns has a bearing on whether the turn is hydrogen-bonded or without a hydrogen bond. In the tertiary structure, alpha-turns are more likely to be found in beta-hairpin loops. The residue composition at the beginning of the hydrogen bonded AAA alpha-turn has similarity with type I beta-turn and N-terminal positions of helices, but the last position matches with the C-terminal capping position of helices, suggesting that the existence of a "helix cap signal" at i+4 position prevents alpha-turns from growing into helices. Our results also provide new insights into alpha-helix nucleation and folding. 相似文献
76.
77.
78.
Zhang H Berg JS Li Z Wang Y Lång P Sousa AD Bhaskar A Cheney RE Strömblad S 《Nature cell biology》2004,6(6):523-531
Unconventional myosins are actin-based motors with a growing number of attributed functions. Interestingly, it has been proposed that integrins are transported by unidentified myosins to facilitate cellular remodelling. Here we present an interaction between the unconventional myosin-X (Myo10) FERM (band 4.1/ezrin/radixin/moesin) domain and an NPXY motif within beta-integrin cytoplasmic domains. Importantly, knock-down of Myo10 by short interfering RNA impaired integrin function in cell adhesion, whereas overexpression of Myo10 stimulated the formation and elongation of filopodia in an integrin-dependent manner and relocalized integrins together with Myo10 to the tips of filopodia. This integrin relocalization and filopodia elongation did not occur with Myo10 mutants deficient in integrin binding or with a beta(1)-integrin point mutant deficient in Myo10 binding. Taken together, these results indicate that Myo10-mediated relocalization of integrins might serve to form adhesive structures and thereby promote filopodial extension. 相似文献
79.
Remote Sensing of Solar-excited Plant Fluorescence as a Measure of Photosynthetic Rate 总被引:1,自引:0,他引:1
Freedman A. Cavender-Bares J. Kebabian P.L. Bhaskar R. Scott H. Bazzaz F.A. 《Photosynthetica》2002,40(1):127-132
Leaf level net photosynthetic rates (P
N) of laurel oak (Quercus hemispherica) juveniles grown under contrasting nutrient and CO2 regimes were negatively correlated with red to far-red ratios, R/FR (690/760 nm), steady-state, solar-excited fluorescence ratios (r
2 = 0.66, n = 12) measured across 12 plant canopies. Laurel oak juveniles that had been subjected to nitrogen stress over a period of a year demonstrated higher R/FR than their counterparts that had been provided with sufficient nitrogen. Plants that had been grown at elevated CO2 concentrations, EC [700 mol (CO2) mol-1] also exhibited significantly higher R/FR when subjected to normal ambient carbon dioxide concentrations than their counterparts grown under ambient concentrations, AC [380 mol (CO2) mol-1]. All fluorescence measurements were obtained by observing a multi-plant canopy using a unique solar-blind passive sensor. This sensor, which utilizes Fraunhofer-line discrimination techniques, detects radiation at the cores of the lines comprising the atmospheric oxygen A- and B-bands, centered at 762 and 688 nm, respectively. These results support the use of solar-excited steady-state plant fluorescence as a potential tool for remote measurement of canopy radiation use efficiency. 相似文献
80.
The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function 总被引:54,自引:0,他引:54
Egan MF Kojima M Callicott JH Goldberg TE Kolachana BS Bertolino A Zaitsev E Gold B Goldman D Dean M Lu B Weinberger DR 《Cell》2003,112(2):257-269
Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity and hippocampal-dependent memory in cell models and in animals. We examined the effects of a valine (val) to methionine (met) substitution in the 5' pro-region of the human BDNF protein. In human subjects, the met allele was associated with poorer episodic memory, abnormal hippocampal activation assayed with fMRI, and lower hippocampal n-acetyl aspartate (NAA), assayed with MRI spectroscopy. Neurons transfected with met-BDNF-GFP showed lower depolarization-induced secretion, while constitutive secretion was unchanged. Furthermore, met-BDNF-GFP failed to localize to secretory granules or synapses. These results demonstrate a role for BDNF and its val/met polymorphism in human memory and hippocampal function and suggest val/met exerts these effects by impacting intracellular trafficking and activity-dependent secretion of BDNF. 相似文献