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51.
Lipid protein interactions: the assembly of CD1d1 with cellular phospholipids occurs in the endoplasmic reticulum. 总被引:7,自引:0,他引:7
A Dharshan De Silva J-June Park Naoto Matsuki Aleksandar K Stanic Randy R Brutkiewicz M Edward Medof Sebastian Joyce 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(2):723-733
CD1d1 is a member of a family of lipid Ag-presenting molecules. The cellular ligands associated with CD1d1 were isolated and characterized by biochemical means as an approach to elucidate the mechanism by which CD1 molecules assemble in vivo. Natural ligands of mouse CD1d1 included cellular phosphatidylinositol and phosphatidylinositol-glycans that are synthesized in the endoplasmic reticulum. Further biochemical data revealed that the two CD1d1 mutants, one defective in recycling from-and-to the plasma membrane and the other in efficiently negotiating the secretory pathway, associated with phosphatidylinositol. Thus phosphatidylinositol associated with CD1d1 in the early secretory pathway. Phosphatidylinositol also associated with CD1d1 in Pig-A-deficient cells that are defective in the first glycosylation step of glycosylphosphatidylinositol biosynthesis. Moreover, cellular phosphatidylinositol-glycans are not Valpha14Jalpha15 natural T cell Ags. Therefore, we predict that cellular lipids occlude the hydrophobic Ag-binding groove of CD1 during assembly until they are exchanged for a glycolipid Ag(s) within the recycling compartment for display on the plasma membrane. In this manner, cellular lipids might play a chaperone-like role in the assembly of CD1d1 in vivo, akin to the function of invariant chain in MHC class II assembly. 相似文献
52.
Xiaoling Tong Steven Hrycaj Ondrej Podlaha Aleksandar Popadic Antónia Monteiro 《Developmental biology》2014
In insects, forewings and hindwings usually have different shapes, sizes, and color patterns. A variety of RNAi experiments across insect species have shown that the hox gene Ultrabithorax (Ubx) is necessary to promote hindwing identity. However, it remains unclear whether Ubx is sufficient to confer hindwing fate to forewings across insects. Here, we address this question by over-expressing Ubx in the butterfly Bicyclus anynana using a heat-shock promoter. Ubx whole-body over-expression during embryonic and larvae development led to body plan changes in larvae but to mere quantitative changes to adult morphology, respectively. Embryonic heat-shocks led to fused segments, loss of thoracic and abdominal limbs, and transformation of head limbs to larger appendages. Larval heat-shocks led to reduced eyespot size in the expected homeotic direction, but neither additional eyespots nor wing shape changes were observed in forewings as expected of a homeotic transformation. Interestingly, Ubx was found to be expressed in a novel, non-characteristic domain – in the hindwing eyespot centers. Furthermore, ectopic expression of Ubx on the pupal wing activated the eyespot-associated genes spalt and Distal-less, known to be directly repressed by Ubx in the fly?s haltere and leg primordia, respectively, and led to the differentiation of black wing scales. These results suggest that Ubx has been co-opted into a novel eyespot gene regulatory network, and that it is capable of activating black pigmentation in butterflies. 相似文献
53.
Mathieu Arminjon Amer Chamseddine Vladimir Kopta Aleksandar Paunovi? Christine Mohr 《PloS one》2015,10(9)
We quickly form first impressions about newly encountered people guiding our subsequent behaviour (approach, avoidance). Such instant judgments might be innate and automatic, being performed unconsciously and independently to other cognitive processes. Lying detection might be subject to such a modular process. Unfortunately, numerous studies highlighted problems with lying detection paradigms such as high error rates and learning effects. Additionally, humans should be motivated doing both detecting others’ lies and disguising own lies. Disguising own lies might even be more challenging than detecting other people’s lies. Thus, when trying to disguise cheating behaviour, liars might display a mixture of disguising (fake) trust cues and uncontrolled lying cues making the interpretation of the expression difficult (perceivers are guessing). In two consecutive online studies, we tested whether seeing an increasing amount (range 0–4) of lying cues (LC) and non-lying cues (NLC) on a standard face results in enhanced guessing behaviour (studies 1 and 2) and that enhanced guessing is accompanied by slower responding (study 2). Results showed that pronounced guessing and slowest responding occurred for faces with an intermediate number and not with the highest number of LC and NLC. In particular, LC were more important than NLC to uncertain lying decisions. Thus, only a few LC may interfere with automatic processing of lying detection (irrespective of NLC), probably because too little lying cue information is yet available. 相似文献
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Mirjana Lenhardt Goran Markovic Aleksandar Hegedis Stevan Maletin Miroslav Cirkovic Zoran Markovic 《Reviews in Fish Biology and Fisheries》2011,21(3):407-421
A total of 22 fish species have been introduced into the inland waters of Serbia, either intentionally or accidentally. This
paper provides a summary of data concerning time and reason of introduction, mode of expansion, degree of acclimatization,
impact on native fish and estimated area of recent distribution. Four of the non-native fish species currently occupy more
than 51% of Serbian territory while 5 of them occupy between 21–50% of territory. This paper reviews impacts of introduced
freshwater fish in Serbia based on collected data. 相似文献
57.
58.
Maria Fesatidou Panagiotis Zagaliotis Charalampos Camoutsis Anthi Petrou Phaedra Eleftheriou Christophe Tratrat Micheline Haroun Athina Geronikaki Ana Ciric Marina Sokovic 《Bioorganic & medicinal chemistry》2018,26(16):4664-4676
In continuation of our efforts to develop new compounds with antimicrobial properties we describe design, synthesis, molecular docking study and evaluation of antimicrobial activity of seventeen novel 2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-arylidene-1,3-thiazolidin-4-ones. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. Twelve out of seventeen compounds were more potent than streptomycin and all compounds exhibited higher potency than ampicillin. Compounds were also tested against three resistant bacterial strains: MRSA, P. aeruginosa and E. coli. The best antibacterial potential against ATCC and resistant strains was observed for compound 8 (2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5-(4-nitrobenzylidene)-1,3thiazolidin-4-one). The most sensitive bacterium appeared to be S. typhimirium, followed by B. cereus while L. monocitogenes and M. flavus were the most resistant. Compounds were also tested for their antifungal activity against eight fungal species. All compounds exhibited antifungal activity better than the reference drugs bifonazole and ketokonazole (3-115 times). It was found that compound 8 appeared again to be the most potent. Molecular docking studies on E. coli MurB, MurA as well as C. albicans CYP 51 and dihydrofolate reductase were used for the prediction of mechanism of antibacterial and antifungal activities confirming the experimental results. 相似文献
59.
Braden T. Tierney Elizabeth Anderson Yingxuan Tan Kajal Claypool Sivateja Tangirala Aleksandar D. Kostic Arjun K. Manrai Chirag J. Patel 《PLoS biology》2021,19(9)
Hypothesis generation in observational, biomedical data science often starts with computing an association or identifying the statistical relationship between a dependent and an independent variable. However, the outcome of this process depends fundamentally on modeling strategy, with differing strategies generating what can be called “vibration of effects” (VoE). VoE is defined by variation in associations that often lead to contradictory results. Here, we present a computational tool capable of modeling VoE in biomedical data by fitting millions of different models and comparing their output. We execute a VoE analysis on a series of widely reported associations (e.g., carrot intake associated with eyesight) with an extended additional focus on lifestyle exposures (e.g., physical activity) and components of the Framingham Risk Score for cardiovascular health (e.g., blood pressure). We leveraged our tool for potential confounder identification, investigating what adjusting variables are responsible for conflicting models. We propose modeling VoE as a critical step in navigating discovery in observational data, discerning robust associations, and cataloging adjusting variables that impact model output.COVID positivity and vitamin D intake, red meat and heart disease; how can we discern when biomedical associations are reliable and when they are susceptible to our own arbitrary choices and assumptions? This study presents “quantvoe,” a software package for exploring the entirety of possible findings due to the multiverse of associations possible. 相似文献
60.
Oliver Allemann R. Matthew Cross Manuela M. Brütsch Aleksandar Radakovic Dale L. Boger 《Bioorganic & medicinal chemistry letters》2017,27(14):3055-3059
A key series of vinblastine analogs 7–13, which contain modifications to the C20′ ethyl group, was prepared with use of two distinct synthetic approaches that provide modifications of the C20′ side chain containing linear and cyclized alkyl groups or added functionalized substituents. Their examination revealed the unique nature of the improved properties of the synthetic vinblastine 6, offers insights into the origins of its increased tubulin binding affinity and 10-fold improved cell growth inhibition potency, and served to probe a small hydrophobic pocket anchoring the binding of vinblastine with tubulin. Especially noteworthy were the trends observed with substitution of the terminal carbon of the ethyl group that, with the exception of 9 (R = F vs H, equipotent), led to remarkably substantial reductions in activity (>10-fold): R = F (equipotent with H) > N3, CN (10-fold) > Me (50-fold) > Et (100-fold) > OH (inactive). This is in sharp contrast to the maintained (7) or enhanced activity (6) observed with its incorporation into a cyclic C20′/C15′-fused six-membered ring. 相似文献