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91.
GROmaρs: A GROMACS-Based Toolset to Analyze Density Maps Derived from Molecular Dynamics Simulations
Rodolfo Briones Christian Blau Carsten Kutzner Bert L. de Groot Camilo Aponte-Santamaría 《Biophysical journal》2019,116(1):4-11
We introduce a computational toolset, named GROmaρs, to obtain and compare time-averaged density maps from molecular dynamics simulations. GROmaρs efficiently computes density maps by fast multi-Gaussian spreading of atomic densities onto a three-dimensional grid. It complements existing map-based tools by enabling spatial inspection of atomic average localization during the simulations. Most importantly, it allows the comparison between computed and reference maps (e.g., experimental) through calculation of difference maps and local and time-resolved global correlation. These comparison operations proved useful to quantitatively contrast perturbed and control simulation data sets and to examine how much biomolecular systems resemble both synthetic and experimental density maps. This was especially advantageous for multimolecule systems in which standard comparisons like RMSDs are difficult to compute. In addition, GROmaρs incorporates absolute and relative spatial free-energy estimates to provide an energetic picture of atomistic localization. This is an open-source GROMACS-based toolset, thus allowing for static or dynamic selection of atoms or even coarse-grained beads for the density calculation. Furthermore, masking of regions was implemented to speed up calculations and to facilitate the comparison with experimental maps. Beyond map comparison, GROmaρs provides a straightforward method to detect solvent cavities and average charge distribution in biomolecular systems. We employed all these functionalities to inspect the localization of lipid and water molecules in aquaporin systems, the binding of cholesterol to the G protein coupled chemokine receptor type 4, and the identification of permeation pathways through the dermicidin antimicrobial channel. Based on these examples, we anticipate a high applicability of GROmaρs for the analysis of molecular dynamics simulations and their comparison with experimentally determined densities. 相似文献
92.
A change of mind in response to social influence could be driven by informational conformity to increase accuracy, or by normative conformity to comply with social norms such as reciprocity. Disentangling the behavioural, cognitive, and neurobiological underpinnings of informational and normative conformity have proven elusive. Here, participants underwent fMRI while performing a perceptual task that involved both advice-taking and advice-giving to human and computer partners. The concurrent inclusion of 2 different social roles and 2 different social partners revealed distinct behavioural and neural markers for informational and normative conformity. Dorsal anterior cingulate cortex (dACC) BOLD response tracked informational conformity towards both human and computer but tracked normative conformity only when interacting with humans. A network of brain areas (dorsomedial prefrontal cortex (dmPFC) and temporoparietal junction (TPJ)) that tracked normative conformity increased their functional coupling with the dACC when interacting with humans. These findings enable differentiating the neural mechanisms by which different types of conformity shape social changes of mind.When we change our mind in response to other people’s opinion, we may be motivated to be correct or to have a good relationship with others. This fMRI study disentangles the neurobiological underpinnings of these two different motives in the human brain, and shows that the second motive is absent when we interact with computers. 相似文献
93.
Manabu Yamamoto Satoshi Okumura Carsten Schwencke Junichi Sadoshima Yoshihiro Ishikawa 《The Histochemical journal》1999,31(4):241-243
A high efficiency transfection protocol employing a common polycationic lipid is described. Using LipofectAMINE, a widely used transfection reagent, we transfected 293T cells with a plasmid harboring the -galactosidase (-gal) gene. The transfection efficiency was determined by direct staining for X-gal. The conventional transfection protocol achieved an efficiency of <40% while our protocol, which employs the repetition of transfection a few times, achieved an efficiency of approximately 80%. Thus, a dramatic increase in transfection efficiency can be obtained by simply repeating transfection with the use of a common polycationic lipid. This method will be useful in many molecular biological experiments. 相似文献
94.
Carlberg C 《The Journal of steroid biochemistry and molecular biology》2004,(1-5):227-232
The central element of the molecular switch of nuclear 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) signaling is the ligand-binding domain (LBD) of the Vitamin D receptor (VDR), which can be stabilized by 1alpha,25(OH)(2)D(3) or its analogues in to agonistic, antagonistic or inverse agonistic conformations. The positioning of helix 12 of the LBD is of most critical importance for these conformations, because it determines the distance between the charge clamp amino acids K246 and E420 that are essential for VDR-coactivator (CoA) interaction. Most VDR ligands have been identified as agonists and only a few (e.g., ZK168281 and TEI-9647) as pure or partial antagonists. Antagonists induce corepressor (CoR) dissociation from the VDR but prevent completely or partially CoA interaction and thus transactivation. Gemini is a 1alpha,25(OH)(2)D(3) analogue with two identical side chains that despite its significantly increased volume binds to the VDR and acts under most conditions as an agonist. Interestingly, supramolar CoR concentrations shift Gemini from an agonist to an inverse agonist, which actively recruits CoR to the VDR and thus mediates repression of 1alpha,25(OH)(2)D(3) target genes. Gemini is the first described (conditional) inverse agonist to an endocrine nuclear receptor (NR) and may function as a sensor for cell-specific CoA/CoR ratios. 相似文献
95.
96.
Hölmich LR Vejborg IM Conrad C Sletting S Høier-Madsen M Fryzek JP McLaughlin JK Kjøller K Wiik A Friis S 《Plastic and reconstructive surgery》2004,114(1):204-14; discussion 215-6
Implant rupture is a well-known complication of breast implant surgery that can pass unnoticed by both patient and physician. To date, no prospective study has addressed the possible health implications of silicone breast implant rupture. The aim of the present study was to evaluate whether untreated ruptures are associated with changes over time in magnetic resonance imaging findings, serologic markers, or self-reported breast symptoms. A baseline magnetic resonance imaging examination was performed in 1999 on 271 women who were randomly chosen from a larger cohort of women having cosmetic breast implants for a median period of 12 years (range, 3 to 25 years). A follow-up magnetic resonance imaging examination was carried out in 2001, excluding women who underwent explantation in the period between the two magnetic resonance imaging examinations (n = 44). On the basis of these examinations, the authors identified 64 women who had at least one ruptured implant at the first magnetic resonance imaging examination and, for comparison, all women who had intact implants at both examinations (n = 98). Magnetic resonance images from the two examinations were compared and changes in rupture configuration were evaluated. Comparisons were also made for self-reported breast symptoms occurring during the study period and for changes in serum values of antinuclear antibodies, rheumatoid factor, and cardiolipin antibodies immunoglobulin G and immunoglobulin M. The majority of the women with implant rupture had no visible magnetic resonance imaging changes of their ruptured implants. For 11 implants (11 percent) in 10 women, the authors observed progression of silicone seepage, either as a conversion from intracapsular into extracapsular rupture (n = 7), as progression of extra-capsular silicone (n = 3), or as increasing herniation of the silicone within the fibrous capsule (n = 1); however, in most cases, these changes were minor. Some changes could be ascribed to trauma, but others seemed spontaneous. There was no increase in levels of autoantibodies during the study period in either study group. Women with untreated implant ruptures reported a significant increase in nonspecific breast changes (odds ratio, 2.1; 95 percent confidence interval, 1.2 to 3.8) compared with women without ruptures. On the basis of this first study of women with untreated silicone breast implant rupture, the authors conclude that implant rupture is a relatively harmless condition, which only rarely progresses and gives rise to notable symptoms. Even so, because of a small risk of silicone spread, the authors suggest that women with implant ruptures be followed clinically, if not operated on. Because implant ruptures often occur asymptomatically, any woman with silicone implants, regardless of rupture status, should be evaluated at regular intervals. 相似文献
97.
98.
Degradation of acrylic copolymers by white-rot fungi 总被引:4,自引:0,他引:4
Mai C Schormann W Majcherczyk A Hüttermann A 《Applied microbiology and biotechnology》2004,65(4):479-487
Various water-soluble homopolymers and copolymers of acrylamide (AAm) and acrylic acid (AA) which contained phenolic sites, such as guaiacol, lignin sulfonate (LS) and 3,4-dihydroxybenzoic acid (3,4-DHBA), were tested with regard to their degradability by white-rot fungi. Compared with Phanerochaete chrysosporium, Pleurotus ostreatus caused a significantly higher decrease in the average molecular weight (w) of most of the copolymers and the homopolymer under the applied culture conditions. However, the w of poly(guaiacol/AAm) increased significantly during incubation with Pl ostreatus. P. chrysosporium was able to reduce only the w of the poly(LS/AA) to a significant degree and not that of the other polymers. The mineralization rate of AAm and AA copolymers and terpolymers of AAm, AA and phenolics (LS, 3,4-DHBA, guiacol), which were tested with P. ostreatus and Trametes versicolor, turned out to be low (0.8–3.2%). While the rates of mineralization were similar among all polymers, the decrease in radioactivity from the culture media was higher with the terpolymers bearing phenolic sites. UV spectra of the culture media revealed that the phenolic sites in the terpolymers were significantly degraded by both fungi. Obviously, the degradation of phenolics within the polymer chain caused a higher decrease in w but did not significantly increase the mineralization rate. 相似文献
99.
Hocke C Prante O Löber S Hübner H Gmeiner P Kuwert T 《Bioorganic & medicinal chemistry letters》2004,14(15):3963-3966
Starting from FAUC 365, a series of iodine substituted heteroaryl carboxamides has been synthesized revealing high affinity and selectivity for the dopamine D3 receptor. Binding data showed a 15-560-fold selectivity for the dopamine D3 over D2. A 2,3-dichloro substitution pattern on the phenylpiperazine moiety led to the highest subtype selectivity, whereas the 2-methoxy substituted compounds showed superior D3 affinity. Suitable precursors were radioiodinated with high radiochemical yields (53-85%) leading to potential imaging agents for the D3 receptor by SPET. 相似文献
100.
Germline transformation systems for nearly 20 insect species have been derived from transposable elements, allowing the development of transgenic insects for basic and applied studies. These systems use a defective nonautonomous vector that results in stable vector integrations after the disappearance of transiently provided transposase helper plasmid, which is essential to maintain true breeding lines and consistent transgene expression that would otherwise be lost after vector remobilization. The risk of remobilization by an unintended transposase source has so far not been a concern for laboratory studies, but the prospective use of millions of transgenic insects in biocontrol programs will likely increase the risk, therefore making this a critical issue for the ecological safety of field release programs. Here we describe an efficient method that deletes a terminal repeat sequence of a transposon vector after genomic integration. This procedure prevents transposase-mediated remobilization of the other terminal sequence and associated genes, ensuring their genomic stability. 相似文献