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151.
Dr. Louise M. Sternicki Dr. Jim Nonomiya Dr. Miaomiao Liu Dr. Melinda M. Mulvihill Dr. Ronald J. Quinn 《ChemMedChem》2021,16(14):2206-2210
PRO teolysis TA rgeting C himeras (PROTACs) promote the degradation, rather than inhibition, of a drug target as a mechanism for therapeutic treatment. Bifunctional PROTAC molecules allow simultaneous binding of both the target protein and an E3-Ubiquitin ligase, bringing the two proteins into close spatial proximity to allow ubiquitinylation and degradation of the target protein via the cell's endogenous protein degradation pathway. We utilized native mass spectrometry (MS) to study the ternary complexes promoted by the previously reported PROTAC GNE-987 between Brd4 bromodomains 1 and 2, and Von Hippel Lindeau E3-Ubiquitin Ligase. Native MS at high resolution allowed us to measure ternary complex formation as a function of PROTAC concentration to provide a measure of complex affinity and stability, whilst simultaneously measuring other intermediate protein species. Native MS provides a high-throughput, low sample consumption, direct screening method to measure ternary complexes for PROTAC development. 相似文献
152.
Dr. Yuteng Wu Dr. M. Teresa Bertran James Rowley Dr. Ewen D. D. Calder Dhira Joshi Dr. Louise J. Walport 《ChemMedChem》2021,16(20):3185-3188
The major obstacle in applying peptides to intracellular targets is their low inherent cell permeability. Standard approaches to attach a fluorophore (e. g. FITC, TAMRA) can change the physicochemical properties of the parent peptide and influence their ability to penetrate and localize in cells. We report a label-free strategy for evaluating the cell permeability of cyclic peptide leads. Fluorescent tryptophan analogues 4-cyanotryptophan (4CNW) and β-(1-azulenyl)-L-alanine (AzAla) were incorporated into in vitro translated macrocyclic peptides by initiator reprogramming. We then demonstrate these efficient blue fluorescent emitters are good tools for monitoring peptide penetration into cells. 相似文献
153.
Louise L. Sousa 《Fuel Processing Technology》2010,91(2):194-196
This paper evaluates the production of methyl esters from castor oil and methanol after neutralization of castor oil with glycerol. The reaction was carried out under atmospheric pressure and ambient temperature in a batch reactor, employing potassium hydroxide as catalyst. Results showed high yield of castor oil into methyl esters after neutralization of castor oil with glycerol. The highest yield observed was of 92.5% after 15 min of reaction. The best operating condition was obtained applying an alcohol to oil molar ratio of 6.0 and 0.5% w/w of catalyst. 相似文献
154.
Nicole M. van Dam Bao-Li Qiu Cornelis A. Hordijk Louise E. M. Vet Jeroen J. Jansen 《Journal of chemical ecology》2010,36(9):1006-1016
Plants under attack by aboveground herbivores emit complex blends of volatile organic compounds (VOCs). Specific compounds in these blends are used by parasitic wasps to find their hosts. Belowground induction causes shifts in the composition of aboveground induced VOC blends, which affect the preference of parasitic wasps. To identify which of the many volatiles in the complex VOC blends may explain parasitoid preference poses a challenge to ecologists. Here, we present a case study in which we use a novel bioinformatics approach to identify biologically relevant differences between VOC blends of feral cabbage (Brassica oleracea L.). The plants were induced aboveground or belowground with jasmonic acid (JA) and shoot feeding caterpillars (Pieris brassicae or P. rapae). We used Partial Least Squares—Discriminant Analysis (PLSDA) to integrate and visualize the relation between plant-emitted VOCs and the preference of female Cotesia glomerata. Overall, female wasps preferred JA-induced plants over controls, but they strongly preferred aboveground JA-induced plants over belowground JA-induced plants. PLSDA revealed that the emission of several monoterpenes was enhanced similarly in all JA-treated plants, whereas homoterpenes and sesquiterpenes increased exclusively in aboveground JA-induced plants. Wasps may use the ratio between these two classes of terpenes to discriminate between aboveground and belowground induced plants. Additionally, it shows that aboveground applied JA induces different VOC biosynthetic pathways than JA applied to the root. Our bioinformatic approach, thus, successfully identified which VOCs matched the preferences of the wasps in the various choice tests. Additionally, the analysis generated novel hypotheses about the role of JA as a signaling compound in aboveground and belowground induced responses in plants. 相似文献
155.
Ingrid M le Roux Karl le Roux W Scott Comulada Erin M Greco Katherine A Desmond Nokwanele Mbewu Mary Jane Rotheram-Borus 《Nutrition journal》2010,9(1):56
Background
Child and infant malnourishment is a significant and growing problem in the developing world. Malnourished children are at high risk for negative health outcomes over their lifespans. Philani, a paraprofessional home visiting program, was developed to improve childhood nourishment. The objective of this study is to evaluate whether the Philani program can rehabilitate malnourished children in a timely manner. 相似文献156.
High-fat ketogenic diets are used to treat intractable seizures in children, but little is known of the mechanism by which
these diets work or whether fats rich in n−3 polyunsaturates might be beneficial. Tissue lipid and fatty acid profiles were
determined in rats consuming very high fat (80 weight%), low-carbohydrate ketogenic diets containing either medium-chain triglyceride,
flaxseed oil, butter, or an equal combination of these three fat sources. Ketogenic diets containing butter markedly raised
liver triglyceride but had no effect on plasma cholesterol. Unlike the other fats, flaxseed oil in the ketogenic diet did
not raise brain cholesterol. Brain total and free fatty acid profiles remained similar in all groups, but there was an increase
in the proportion of arachidonate in brain total lipids in the medium-chain triglyceride group, while the two groups consuming
flaxseed oil had significantly lower arachidonate in brain, liver, and plasma. The very high dietary intake of α-linolenate
in the flaxseed group did not change docosahexaenoate levels in the brain. Our previous report based on these diets showed
that although ketosis is higher in rats consuming a ketogenic diet based on medium-chain triglyceride oil, seizure resistance
in the pentylenetetrazol model is not clearly related to the degree of ketosis achieved. In combination with our present data
from the same seizure study, it appears that ketogenic diets with widely differing effects on tissue lipids and fatty acid
profiles can confer a similar amount of seizure protection. 相似文献
157.
High-performance liquid chromatography of human milk triacylglycerols and gas chromatography of component fatty acids 总被引:1,自引:0,他引:1
Human milk triacylglycerols were separated by high-performance liquid chromatography. A 5-μ Supelcosil LC-18 column (Supelco,
Inc., Bellefonte, PA) was used with acetone/acetonitrile (64∶36, vol/vol) as mobile phase. Triacylglycerols were tentatively
identified based on theoretical carbon number and relative retention time. Despite changes resulting from dietary fat variation,
the major component triacylglycerols were those composed of palmitic, oleic and linoleic acids. Triacylglycerols with palmitic,
stearic and oleic acids were present as minor components. Fatty acids were quantified by gas chromatography relative to an
internal standard. Ratios of n−6/n−3 fatty acids were found to be high than previously reported.
Based on a paper presented at the Symposium on Milk Lipids held at the AOCS Annual Meeting, Baltimore, MD, April 1990. 相似文献
158.
A. Weller and L. Weller (see record 1997-06365-004) claimed to report "the definitive study of menstrual synchrony" (p. 148). To allow for cycle variability, they used the following criterion for synchrony: It occurred in 2 out of 3 months. The underlying assumption of the state of menstrual synchrony is that cycle length variability is minimal. The present article uses a random selection of cycle lengths from a distribution described by R. F. Vollman (1977) to illustrate how variable cycle lengths cause a fluctuation from synchrony to asynchrony. A. Weller and L. Weller's study is not, therefore, conclusive, and future studies of menstrual synchrony should include an assessment of cycle variability as well as onset difference. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
159.
Green Bonnie L.; Grace Mary C.; Lindy Jacob D.; Titchener James L.; Lindy Joanne G. 《Canadian Metallurgical Quarterly》1983,51(4):573
117 individuals (mean age 37.77 yrs) who were at the fire and 30 individuals (mean age 40.72 yrs) who were not at the fire (bereaved families and rescue workers) were assessed regarding objective stressfulness of their fire experience, subjective stressfulness, and intensity of psychological symptoms (the Psychiatric Evaluation Form, PEF) in a structured clinical interview approximately 1 yr after the fire. Ss also filled out the Symptom Checklist-90, Revised Version (SCL-90R). 88 Ss were followed-up at 2 yrs. The group as a whole was more impaired than comparison samples of normals but less impaired than outpatients. Ss at the fire were less impaired than those not at the fire, who were similar to outpatients on the PEF. The latter group improved significantly on several measures from 1 to 2 yrs postfire, whereas the group at the fire showed little change. Results are discussed in the context of the specific instruments and methodology used in the present study, impairment levels of other samples, and the nature of the particular disaster. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
160.
Examined responses to depressive interpersonal behavior. 30 undergraduates interacted with a same-sex confederate for 7 min in the context of waiting together for an experiment to begin. Confederates employed either a depressed role (depressive interpersonal behavior and reporting serious deficits in functioning), a normal role (normal interpersonal behavior and reporting minimal deficits in functioning), or a physically ill role (normal interpersonal behavior and reporting serious deficits in functioning). Ss who interacted with a "depressive" responded with a higher rate of silences and directly negative comments and a lower rate of overall verbal responding. Their expressions of direct support were equivalent to those made to the "physically ill" confederates and greater than those in the normal condition. Ss also were more rejecting of partners who behaved in a depressed manner and described them in more negative terms and as having greater interpersonal impact than confederates in other roles. There were no induced mood differences. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献