426 research outputs found
Using the Hands to Learn About the Brain: Testing Action-Based Instruction in Brain Anatomy
Brain anatomy is typically taught using static images. We asked participants to use their own hands to represent the brain and perform gestures during learning. We measured learning via a pretest/postest design. We compared five video trainings in which participants heard similar audio and repeated terminology aloud. Conditions were: (1) Image: Participants saw images of a physical model of the brain. (2) Physical model: Participants saw hands pointing to the physical model. (3) Physical model + action: Participants performed actions on the physical model. (4) Hand model: Participants saw images of hands being used to represent the brain. (5) Hand model + action: Participants performed gestures seen in the video. All trainings improved post-test performance. Performance in the hand model condition was worse compared to conditions with action. We connect these findings to the larger claim that gesture benefits learning
The Partial Molal Volumes of Potassium Salts of Certain Organic Acids at 25°C
This paper is a brief resume of a part of the work performed under the direction of Dr. J. N. Pearce in an attempt to determine from density measurements the partial molal volumes of the potassium salts of various organic acids at various concentrations. It was hoped that some indication might be found as to the influence upon the partial molal volumes of the nature and position of substituent groups in the anion
A single amino acid determines preference between phospholipids and reveals length restriction for activation ofthe S1P<sub>4</sub> receptor
Background<br/><br/>
Sphingosine-1-phosphate and lysophosphatidic acid (LPA) are ligands for two related families of G protein-coupled receptors, the S1P and LPA receptors, respectively. The lysophospholipid ligands of these receptors are structurally similar, however recognition of these lipids by these receptors is highly selective. A single residue present within the third transmembrane domain (TM) of S1P receptors is thought to determine ligand selectivity; replacement of the naturally occurring glutamic acid with glutamine (present at this position in the LPA receptors) has previously been shown to be sufficient to change the specificity of S1P<sub>1</sub> from S1P to 18:1 LPA.<br/><br/>
Results<br/><br/>
We tested whether mutation of this "ligand selectivity" residue to glutamine could confer LPA-responsiveness to the related S1P receptor, S1P<sub>4</sub>. This mutation severely affected the response of S1P<sub>4</sub> to S1P in a [<sup>35</sup>S]GTPγS binding assay, and imparted sensitivity to LPA species in the order 14:0 LPA > 16:0 LPA > 18:1 LPA. These results indicate a length restriction for activation of this receptor and demonstrate the utility of using LPA-responsive S1P receptor mutants to probe binding pocket length using readily available LPA species. Computational modelling of the interactions between these ligands and both wild type and mutant S1P<sub>4</sub> receptors showed excellent agreement with experimental data, therefore confirming the fundamental role of this residue in ligand recognition by S1P receptors.<br/><br/>
Conclusions<br/><br/>
Glutamic acid in the third transmembrane domain of the S1P receptors is a general selectivity switch regulating response to S1P over the closely related phospholipids, LPA. Mutation of this residue to glutamine confers LPA responsiveness with preference for short-chain species. The preference for short-chain LPA species indicates a length restriction different from the closely related S1P<sub>1</sub> receptor
Observers Use Gesture to Disambiguate Contrastive Expressions of Preference
We present two studies exploring how participants respond when a speaker contrasts two ideas, then expresses an ambiguous preference towards one of them. Study 1 showed that, when reading a speaker’s preference as text, participants tended to choose whatever was said last as matching the speaker’s preference, reflecting the recent-mention bias of anaphora resolution. In Study 2, we asked whether this pattern changed for audio versions of our stimuli. We found that it did not. We then asked whether observers used gesture to disambiguate the speaker’s preference. Participants watched videos in which two statements were spoken. Co-speech gestures were produced during each statement, in two different locations. Next, an ambiguous preference for one option was spoken. In ‘gesture disambiguating’ trials, this statement was accompanied by a gesture in the same spatial location as the gesture accompanying the first statement. In ‘gesture non-disambiguating’ trials, no third gesture occurred. Participants chose the first statement as matching the speaker’s preference more often for gesture disambiguating compared to non-disambiguating trials. Our findings add to the literature on resolution of ambiguous anaphoric reference involving concrete entities and discourse deixis, and we extend this literature to show that gestures indexing abstract ideas are also used during discourse comprehension
Computational identification and experimental characterization of substrate binding determinants of nucleotide pyrophosphatase/phosphodiesterase 7
<p>Abstract</p> <p>Background</p> <p>Nucleotide pyrophosphatase/phosphodiesterase 7 (NPP7) is the only member of the mammalian NPP enzyme family that has been confirmed to act as a sphingomyelinase, hydrolyzing sphingomyelin (SM) to form phosphocholine and ceramide. NPP7 additionally hydrolyzes lysophosphatidylcholine (LPC), a substrate preference shared with the NPP2/autotaxin(ATX) and NPP6 mammalian family members. This study utilizes a synergistic combination of molecular modeling validated by experimental site-directed mutagenesis to explore the molecular basis for the unique ability of NPP7 to hydrolyze SM.</p> <p>Results</p> <p>The catalytic function of NPP7 against SM, LPC, platelet activating factor (PAF) and para-nitrophenylphosphorylcholine (pNPPC) is impaired in the F275A mutant relative to wild type NPP7, but different impacts are noted for mutations at other sites. These results are consistent with a previously described role of F275 to interact with the choline headgroup, where all substrates share a common functionality. The L107F mutation showed enhanced hydrolysis of LPC, PAF and pNPPC but reduced hydrolysis of SM. Modeling suggests this difference can be explained by the gain of cation-pi interactions with the choline headgroups of all four substrates, opposed by increased steric crowding against the sphingoid tail of SM. Modeling also revealed that the long and flexible hydrophobic tails of substrates exhibit considerable dynamic flexibility in the binding pocket, reducing the entropic penalty that might otherwise be incurred upon substrate binding.</p> <p>Conclusions</p> <p>Substrate recognition by NPP7 includes several important contributions, ranging from cation-pi interactions between F275 and the choline headgroup of all substrates, to tail-group binding pockets that accommodate the inherent flexibility of the lipid hydrophobic tails. Two contributions to the unique ability of NPP7 to hydrolyze SM were identified. First, the second hydrophobic tail of SM occupies a second hydrophobic binding pocket. Second, the leucine residue present at position 107 contrasts with a conserved phenylalanine in NPP enzymes that do not utilize SM as a substrate, consistent with the observed reduction in SM hydrolysis by the NPP7-L107F mutant.</p
PDBTM: Protein Data Bank of transmembrane proteins after 8 years
The PDBTM database (available at http://pdbtm
.enzim.hu), the first comprehensive and up-to-date
transmembrane protein selection of the Protein
Data Bank, was launched in 2004. The database
was created and has been continuously updated
by the TMDET algorithm that is able to distinguish
between transmembrane and non-transmembrane
proteins using their 3D atomic coordinates only.
The TMDET algorithm can locate the spatial positions
of transmembrane proteins in lipid bilayer as
well. During the last 8 years not only the size of the
PDBTM database has been steadily growing from
~400 to 1700 entries but also new structural
elements have been identified, in addition to the
well-known a-helical bundle and b-barrel structures.
Numerous ‘exotic’ transmembrane protein structures
have been solved since the first release,
which has made it necessary to define these new
structural elements, such as membrane loops or
interfacial helices in the database. This article
reports the new features of the PDBTM database
that have been added since its first release, and
our current efforts to keep the database
up-to-date and easy to use so that it may continue
to serve as a fundamental resource for the scientific
community
Reconstruction and thermal stability of the cubic SiC(001) surfaces
The (001) surfaces of cubic SiC were investigated with ab-initio molecular
dynamics simulations. We show that C-terminated surfaces can have different
c(2x2) and p(2x1) reconstructions, depending on preparation conditions and
thermal treatment, and we suggest experimental probes to identify the various
reconstructed geometries. Furthermore we show that Si-terminated surfaces
exhibit a p(2x1) reconstruction at T=0, whereas above room temperature they
oscillate between a dimer row and an ideal geometry below 500 K, and sample
several patterns including a c(4x2) above 500 K.Comment: 12 pages, RevTeX, figures 1 and 2 available in gif form at
http://irrmawww.epfl.ch/fg/sic/fig1.gif and
http://irrmawww.epfl.ch/fg/sic/fig2.gi
Reactive organoallyl species generated from aryl halides and allene: allylation of alpha,beta-unsaturated aldehydes and cyclic ketones employing Pd/In transmetallation processes
Allylation of α,β-unsaturated aldehydes and cyclic ketones promoted by Pd/In transmetallation processes has been studied. The unsaturated aldehydes underwent regioselective 1,2-addition to afford secondary homoally alcohols. The reactions have been performed using Pd(OAc)2/PPh3 as catalytic system and metallic indium affording the products in good yields. The same transformation with unsaturated ketones proved to be less efficient, while saturated cyclic ketones delivered generally excellent yields in the presence of CuI. In these latter processes the presence of a distal heteroatom influences the reaction rate
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