Página 18 dos resultados de 20101 itens digitais encontrados em 0.007 segundos

‣ Movement and Crevices Around a Sodium Channel S3 Segment

Nguyen, Thao P.; Horn, Richard
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em /09/2002 Português
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Voltage sensing is due mainly to the movement of positively charged S4 segments through the membrane electric field during changes of membrane potential. The roles of other transmembrane segments are under study. The S3 segment of domain 4 (D4/S3) in the sodium channel Nav1.4 carries two negatively charged residues and has been implicated in voltage-dependent gating. We substituted cysteines into nine putative “high impact” sites along the complete length of D4/S3 and evaluated their accessibilities to extracellular sulfhydryl reagents. Only the four outermost substituted cysteines (L1433C, L1431C, G1430C, and S1427C) are accessible to extracellular sulfhydryl reagents. We measured the voltage-dependent modification rates of the two cysteines situated at the extreme ends of this accessible region, L1433C and S1427C. Independent of the charge on the sulfhydryl reagents, depolarization increases the reactivity of both of these residues. Thus, the direction of the voltage dependence is opposite to that expected for a negatively charged voltage sensor, namely an inward translational movement in response to depolarization. Intrinsic electrostatic potentials were probed by charged sulfhydryl reagents and were either negative or positive...

‣ Substrate entropy in enzyme enantioselectivity: An experimental and molecular modeling study of a lipase

Ottosson, Jenny; Fransson, Linda; Hult, Karl
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em /06/2002 Português
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The temperature dependence of the enantioselectivity of Candida antarctica lipase B for 3-hexanol, 2-butanol, 3-methyl-2-butanol, 3,3-dimethyl-2-butanol, and 1-bromo-2-butanol revealed that the differential activation entropy, ΔR−SΔS‡, was as significant as the differential activation enthalpy, ΔR−SΔH‡, to the enantiomeric ratio, E. 1-Bromo-2-butanol, with isosteric substituents, displayed the largest ΔR−SΔS‡. 3-Hexanol displayed, contrary to other sec-alcohols, a positive ΔR−SΔS‡. In other words, for 3-hexanol the preferred R-enantiomer is not only favored by enthalpy but also by entropy. Molecular dynamics (MD) simulations and systematic search calculations of the substrate accessible volume within the active site revealed that the (R)-3-hexanol transition state (TS) accessed a larger volume within the active site than the (S)-3-hexanol TS. This correlates well with the higher TS entropy of (R)-3-hexanol. In addition, this enantiomer did also yield a higher number of allowed conformations, N, from the systematic search routines, than did the S-enantiomer. The substrate accessible volume was greater for the enantiomer preferred by entropy also for 2-butanol. For 3,3-dimethyl-2-butanol, however, neither MD-simulations nor systematic search calculations yielded substrate accessible volumes that correlate to TS entropy. Ambiguous results were achieved for 3-methyl-2-butanol.

‣ THE BACON not the bacon: How children and adults understand accented and unaccented noun phrases

Arnold, Jennifer E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Two eye-tracking experiments examine whether adults and 4 and 5 year old children use the presence or absence of accenting to guide their interpretation of noun phrases (e.g., the bacon) with respect to the discourse context. Unaccented nouns tend to refer to contextually accessible referents, while accented variants tend to be used for less accessible entities. Experiment 1 confirms that accenting is informative for adults, who show a bias toward previously-mentioned objects beginning 300 msec after the onset of unaccented nouns and pronouns. But contrary to findings in the literature, accented words produced no observable bias. In Experiment 2, 4 and 5 year olds were also biased toward previously-mentioned objects with unaccented nouns and pronouns. This builds on findings of limits on children’s on-line reference comprehension (Arnold, Brown-Schmidt, & Trueswell, in press), showing that children’s interpretation of unaccented nouns and pronouns is constrained in contexts with one single highly accessible object.

‣ A Schiff base connectivity switch in sensory rhodopsin signaling

Sineshchekov, Oleg A.; Sasaki, Jun; Phillips, Brian J.; Spudich, John L.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Sensory rhodopsin I (SRI) in Halobacterium salinarum acts as a receptor for single-quantum attractant and two-quantum repellent phototaxis, transmitting light stimuli via its bound transducer HtrI. Signal-inverting mutations in the SRI–HtrI complex reverse the single-quantum response from attractant to repellent. Fast intramolecular charge movements reported here reveal that the unphotolyzed SRI–HtrI complex exists in two conformational states, which differ by their connection of the retinylidene Schiff base in the SRI photoactive site to inner or outer half-channels. In single-quantum photochemical reactions, the conformer with the Schiff base connected to the cytoplasmic (CP) half-channel generates an attractant signal, whereas the conformer with the Schiff base connected to the extracellular (EC) half-channel generates a repellent signal. In the wild-type complex the conformer equilibrium is poised strongly in favor of that with CP-accessible Schiff base. Signal-inverting mutations shift the equilibrium in favor of the EC-accessible Schiff base form, and suppressor mutations shift the equilibrium back toward the CP-accessible Schiff base form, restoring the wild-type phenotype. Our data show that the sign of the behavioral response directly correlates with the state of the connectivity switch...

‣ In Vivo Imaging of Presynaptic Terminals and Postsynaptic Sites in the Mouse Submandibular Ganglion

McCann, Corey M.; Lichtman, Jeff W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/2008 Português
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Much of what is currently known about the behavior of synapses in vivo has been learned at the mammalian neuromuscular junction, because it is large and accessible and also its postsynaptic acetylcholine receptors (AChRs) are readily labeled with a specific, high-affinity probe, α-bungarotoxin (BTX). Neuron–neuron synapses have thus far been much less accessible. We therefore developed techniques for imaging interneuronal synapses in an accessible ganglion in the peripheral nervous system. In the submandibular ganglion, individual preganglionic axons establish large numbers of axo-somatic synapses with postganglionic neurons. To visualize these sites of synaptic contact, presynaptic axons were imaged by using transgenic mice that express fluorescent protein in preganglionic neurons. The postsynaptic sites were visualized by labeling the acetylcholine receptor (AChR) α7 subunit with fluorescently tagged BTX. We developed in vivo methods to acquire three-dimensional image stacks of the axons and postsynaptic sites and then follow them over time. The submandibular ganglion is an ideal site to study the formation, elimination, and maintenance of synaptic connections between neurons in vivo.

‣ Surface Accessibility and Conformational Changes in the N-terminal Domain of Type I Inositol Trisphosphate Receptors: STUDIES USING CYSTEINE SUBSTITUTION MUTAGENESIS*S⃞

Anyatonwu, Georgia; Joseph, Suresh K.
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
Publicado em 20/03/2009 Português
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To identify surface-accessible residues and monitor conformational changes of the type I inositol 1,4,5-trisphosphate receptor protein in membranes, we have introduced 10 cysteine substitutions into the N-terminal ligand-binding domain. The reactivity of these mutants with progressively larger maleimide-polyethylene glycol derivatives (MPEG) was measured using a gel shift assay of tryptic fragments. The results indicate that the mutations fall into four categories as follows: sites that are highly accessible based on reactivity with the largest 20-kDa MPEG (S2C); sites that are moderately accessible based on reactivity only with 5-kDa MPEG (S6C, S7C, A189C, and S277C); sites whose accessibility is markedly enhanced by Ca2+ (S171C, S277C, and A575C); and sites that are inaccessible irrespective of incubation conditions (S217C, A245C, and S436C). The stimulation of accessibility induced by Ca2+ at the S277C site occurred with an EC50 of 0.8 μm and was mimicked by Sr2+ but not Ba2+. Inositol 1,4,5-trisphosphate alone did not affect reactivity of any of the mutants in the presence or absence of Ca2+. The data are interpreted using crystal structures and EM reconstructions of the receptor. Our data identify N-terminal regions of the protein that become exposed upon Ca2+ binding and suggest possible orientations of the suppressor and ligand-binding domains that have implications for the mechanism of gating of the channel.

‣ Relation of Structure to Performance Characteristics of Monolithic and Perfusive Stationary Phases

Trilisky, Egor I.; Koku, Harun; Czymmek, Kirk J.; Lenhoff, Abraham M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Commercially available polymer-based monolithic and perfusive stationary phases were evaluated for their applicability in chromatography of biologics. Information on bed geometry, including that from electron microscopy (EM), was used to interpret and predict accessible volumes, binding capacities, and pressure drops. For preparative purification of biologics up to at least 7 nm in diameter, monoliths and perfusive resins are inferior to conventional stationary phases due to their low binding capacities (20–30 g/L for BSA). For larger biologics, up to several hundred nanometers in diameter, calculations from EM images predict a potential increase in binding capacity to nearly 100 g/L. The accessible volume for adenovirus calculated from the EM images matched the experimental value. While the pores of perfusive resins are essentially inaccessible to adenovirus under binding conditions, under non-adsorbing conditions the accessible intrabead porosity is almost as large as the interbead porosity. Modeling of breakthrough curves showed that the experimentally observed slow approach to full saturation can be explained by the distribution of pore sizes.

‣ Transcranial Magnetic Stimulation and Connectivity Mapping: Tools for Studying the Neural Bases of Brain Disorders

Hampson, M.; Hoffman, R. E.
Fonte: Frontiers Research Foundation Publicador: Frontiers Research Foundation
Tipo: Artigo de Revista Científica
Publicado em 12/08/2010 Português
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There has been an increasing emphasis on characterizing pathophysiology underlying psychiatric and neurological disorders in terms of altered neural connectivity and network dynamics. Transcranial magnetic stimulation (TMS) provides a unique opportunity for investigating connectivity in the human brain. TMS allows researchers and clinicians to directly stimulate cortical regions accessible to electromagnetic coils positioned on the scalp. The induced activation can then propagate through long-range connections to other brain areas. Thus, by identifying distal regions activated during TMS, researchers can infer connectivity patterns in the healthy human brain and can examine how those patterns may be disrupted in patients with different brain disorders. Conversely, connectivity maps derived using neuroimaging methods can identify components of a dysfunctional network. Nodes in this dysfunctional network accessible as targets for TMS by virtue of their proximity to the scalp may then permit TMS-induced alterations of components of the network not directly accessible to TMS via propagated effects. Thus TMS can provide a portal for accessing and altering neural dynamics in networks that are widely distributed anatomically. Finally, when long-term modulation of network dynamics is induced by trains of repetitive TMS...

‣ Identification of Potential Sites for Tryptophan Oxidation in Recombinant Antibodies Using tert-Butylhydroperoxide and Quantitative LC-MS

Hensel, Miriam; Steurer, Rebecca; Fichtl, Juergen; Elger, Carsten; Wedekind, Frank; Petzold, Andreas; Schlothauer, Tilman; Molhoj, Michael; Reusch, Dietmar; Bulau, Patrick
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 03/03/2011 Português
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Amino acid oxidation is known to affect the structure, activity, and rate of degradation of proteins. Methionine oxidation is one of the several chemical degradation pathways for recombinant antibodies. In this study, we have identified for the first time a solvent accessible tryptophan residue (Trp-32) in the complementary-determining region (CDR) of a recombinant IgG1 antibody susceptible to oxidation under real-time storage and elevated temperature conditions. The degree of light chain Trp-32 oxidation was found to be higher than the oxidation level of the conserved heavy chain Met-429 and the heavy chain Met-107 of the recombinant IgG1 antibody HER2, which have already been identified as being solvent accessible and sensitive to chemical oxidation. In order to reduce the time for simultaneous identification and functional evaluation of potential methionine and tryptophan oxidation sites, a test system employing tert-butylhydroperoxide (TBHP) and quantitative LC-MS was developed. The optimized oxidizing conditions allowed us to specifically oxidize the solvent accessible methionine and tryptophan residues that displayed significant oxidation in the real-time stability and elevated temperature study. The achieved degree of tryptophan oxidation was adequate to identify the functional consequence of the tryptophan oxidation by binding studies. In summary...

‣ Genome-Wide Evolutionary Conservation of N-Glycosylation Sites

Park, Chungoo; Zhang, Jianzhi
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
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Although posttranslational protein modifications are generally thought to perform important cellular functions, recent studies showed that a large fraction of phosphorylation sites are not evolutionarily conserved. Whether the same is true for other protein modifications, such as N-glycosylation is an open question. N-glycosylation is a form of cotranslational and posttranslational modification that occurs by enzymatic addition of a polysaccharide, or glycan, to an asparagine (N) residue of a protein. Examining a large set of experimentally determined mouse N-glycosylation sites, we find that the evolutionary rate of glycosylated asparagines is significantly lower than that of nonglycosylated asparagines of the same proteins. We further confirm that the conservation of glycosylated asparagines is accompanied by the conservation of the canonical motif sequence for glycosylation, suggesting that the above substitution rate difference is related to glycosylation. Interestingly, when solvent accessibility is considered, the substitution rate disparity between glycosylated and nonglycosylated asparagines is highly significant at solvent accessible sites but not at solvent inaccessible sites. Thus, although the solvent inaccessible glycosylation sites were experimentally identified...

‣ Differences in the substrate binding regions of renal organic anion transporters 1 (OAT1) and 3 (OAT3)

Astorga, Bethzaida; Wunz, Theresa M.; Morales, Mark; Wright, Stephen H.; Pelis, Ryan M.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
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This study examined the selectivity of organic anion transporters OAT1 and OAT3 for structural congeners of the heavy metal chelator 2,3-dimercapto-1-propanesulfonic acid (DMPS). Thiol-reactive reagents were also used to test structural predictions based on a homology model of OAT1 structure. DMPS was near equipotent in its ability to inhibit OAT1 (IC50 = 83 μM) and OAT3 (IC50 = 40 μM) expressed in Chinese hamster ovary cells. However, removal of a thiol group (3-mercapto-1-propanesulfonic acid) resulted in a 2.5-fold increase in IC50 toward OAT1 vs. a ∼55-fold increase in IC50 toward OAT3. The data suggested that compound volume/size is important for binding to OAT1/OAT3. The sensitivity to HgCl2 of OAT1 and OAT3 was also dramatically different, with IC50 values of 104 and 659 μM, respectively. Consistent with cysteines of OAT1 being more accessible from the external medium than those of OAT3, thiol-reactive reagents reacted preferentially with OAT1 in cell surface biotinylation assays. OAT1 was less sensitive to HgCl2 inhibition and less reactive toward membrane-impermeant thiol reactive reagents following mutation of cysteine 440 (C440) to an alanine. These data indicate that C440 in transmembrane helix 10 of OAT1 is accessible from the extracellular space. Indeed...

‣ Disassembly of Simian Virus 40 during Passage through the Endoplasmic Reticulum and in the Cytoplasm

Kuksin, Dmitry; Norkin, Leonard C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2012 Português
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The nonenveloped polyomavirus simian virus 40 (SV40) is taken up into cells by a caveola-mediated endocytic process that delivers the virus to the endoplasmic reticulum (ER). Within the ER lumen, the capsid undergoes partial disassembly, which exposes its internal capsid proteins VP2 and VP3 to immunostaining with antibodies. We demonstrate here that the SV40 genome does not become accessible to detection while the virus is in the ER. Instead, the genome becomes accessible two distinct detection procedures, one using anti-bromodeoxyuridine antibodies and the other using a 5-ethynyl-2-deoxyuridine-based chemical reaction, only after the emergence of partially disassembled SV40 particles in the cytoplasm. These cytoplasmic particles retain some of the SV40 capsid proteins, VP1, VP2, and VP3, in addition to the viral genome. Thus, SV40 particles undergo discrete disassembly steps during entry that are separated temporally and topologically. First, a partial disassembly of the particles occurs in the ER, which exposes internal capsid proteins VP2 and VP3. Then, in the cytoplasm, disassembly progresses further to also make the genomic DNA accessible to immune detection.

‣ Development of Lead Hammerhead Ribozyme Candidates against Human Rod Opsin mRNA for Retinal Degeneration Therapy

Abdelmaksoud, Heba E.; Yau, Edwin H.; Zuker, Michael; Sullivan, Jack M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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To identify lead candidate allele-independent hammerhead ribozymes (hhRz) for the treatment of autosomal dominant mutations in the human rod opsin (RHO) gene, we tested a series of hhRzs for potential to significantly knockdown human RHO gene expression in a human cell expression system. Multiple computational criteria were used to select target mRNA regions likely to be single stranded and accessible to hhRz annealing and cleavage. Target regions are tested for accessibility in a human cell culture expression system where the hhRz RNA and target mRNA and protein are coexpressed. The hhRz RNA is embedded in an adenoviral VAI RNA chimeric RNA of established structure and properties which are critical to the experimental paradigm. The chimeric hhRz-VAI RNA is abundantly transcribed so that the hhRzs are expected to be in great excess over substrate mRNA. HhRz-VAI traffics predominantly to the cytoplasm to colocalize with the RHO mRNA target. Colocalization is essential for second-order annealing reactions. The VAI chimera protects the hhRz RNA from degradation and provides for a long half life. With cell lines chosen for high transfection efficiency and a molar excess of hhRz plasmid over target plasmid, the conditions of this experimental paradigm are specifically designed to evaluate for regions of accessibility of the target mRNA in cellulo. Western analysis was used to measure the impact of hhRz expression on RHO protein expression. Three lead candidate hhRz designs were identified that significantly knockdown target protein expression relative to control (p < 0.05). Successful lead candidates (hhRz CUC↓ 266...

‣ 2-[Hy­droxy(2-meth­oxy­phenyl)methyl]acrylonitrile

Bakthadoss, M.; Selvakumar, R.; Madhanraj, R.; Murugavel, S.
Fonte: International Union of Crystallography Publicador: International Union of Crystallography
Tipo: Artigo de Revista Científica
Publicado em 18/07/2012 Português
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In the title compound, C11H11NO2, the mean planes formed by the benzene ring and the C and N atoms of the acryl group are almost orthogonal to each other, with a dihedral angle of 85.7 (1)°. During the structure analysis, it was observed that the unit cell contains large accessible voids, with a volume of 186.9 Å3, which may host disordered solvent mol­ecules. This affects the diffraction pattern, mostly at low scattering angles. Density identified in these solvent-accessible areas was calculated and corrected for using the SQUEEZE routine in PLATON [Spek (2009 ▶), Acta Cryst. D65, 148–155]. Despite the presence of the hy­droxy group in the mol­ecule, no classical or nonclassical hydrogen bonds are observed in the structure. This may reflect the fact that the O—H group points towards the solvent-accessible void.

‣ Barriers and Facilitators to Community Mobility for Assistive Technology Users

Layton, Natasha
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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Mobility is frequently described in terms of individual body function and structures however contemporary views of disability also recognise the role of environment in creating disability. Aim. To identify consumer perspectives regarding barriers and facilitators to optimal mobility for a heterogeneous population of impaired Victorians who use assistive technology in their daily lives. Method. An accessible survey investigated the impact of supports or facilitators upon actual and desired life outcomes and health-related quality of life, from 100 AT users in Victoria, Australia. This paper reports upon data pertaining to community mobility. Results. A range of barriers and enablers to community mobility were identified including access to AT devices, environmental interventions, public transport, and inclusive community environs. Substantial levels of unmet need result in limited personal mobility and community participation. Outcomes fall short of many principles enshrined in current policy and human rights frameworks. Conclusion. AT devices as well as accessible and inclusive home and community environs are essential to maximizing mobility for many. Given the impact of the environment upon the capacity of individuals to realise community mobility...

‣ Prediction of phenotypes of missense mutations in human proteins from biological assemblies

Wei, Qiong; Xu, Qifang; Dunbrack, Roland L.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Single nucleotide polymorphism (SNPs) are the most frequent variation in the human genome. Non-synonymous SNPs that lead to missense mutations can be neutral or deleterious, and several computational methods have been presented that predict the phenotype of human missense mutations. These methods employ sequence-based and structure-based features in various combinations, relying on different statistical distributions of these features for deleterious and neutral mutations. One structure-based feature that has not been studied significantly is the accessible surface area within biologically relevant oligomeric assemblies. These assemblies are different from the crystallographic asymmetric unit for more than half of X-ray crystal structures. We find that mutations in the core of proteins or in the interfaces in biological assemblies are significantly more likely to be disease-associated than those on the surface of the biological assemblies. For structures with more than one protein in the biological assembly (whether the same sequence or different), we find the accessible surface area from biological assemblies provides a statistically significant improvement in prediction over the accessible surface area of monomers from protein crystal structures (p=6e-5). When adding this information to sequence-based features such as the difference between wildtype and mutant position-specific profile scores...

‣ Construction and validation of a homology model of the human voltage-gated proton channel hHV1

Kulleperuma, Kethika; Smith, Susan M.E.; Morgan, Deri; Musset, Boris; Holyoake, John; Chakrabarti, Nilmadhab; Cherny, Vladimir V.; DeCoursey, Thomas E.; Pomès, Régis
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em /04/2013 Português
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The topological similarity of voltage-gated proton channels (HV1s) to the voltage-sensing domain (VSD) of other voltage-gated ion channels raises the central question of whether HV1s have a similar structure. We present the construction and validation of a homology model of the human HV1 (hHV1). Multiple structural alignment was used to construct structural models of the open (proton-conducting) state of hHV1 by exploiting the homology of hHV1 with VSDs of K+ and Na+ channels of known three-dimensional structure. The comparative assessment of structural stability of the homology models and their VSD templates was performed using massively repeated molecular dynamics simulations in which the proteins were allowed to relax from their initial conformation in an explicit membrane mimetic. The analysis of structural deviations from the initial conformation based on up to 125 repeats of 100-ns simulations for each system reveals structural features consistently retained in the homology models and leads to a consensus structural model for hHV1 in which well-defined external and internal salt-bridge networks stabilize the open state. The structural and electrostatic properties of this open-state model are compatible with proton translocation and offer an explanation for the reversal of charge selectivity in neutral mutants of Asp112. Furthermore...

‣ Conformity of Pediatric/Adolescent HIV Clinics to the Patient-Centered Medical Home Care Model

Yehia, Baligh R.; Agwu, Allison L.; Schranz, Asher; Korthuis, P. Todd; Gaur, Aditya H.; Rutstein, Richard; Sharp, Victoria; Spector, Stephen A.; Berry, Stephen A.; Gebo, Kelly A.
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica
Publicado em /05/2013 Português
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The patient-centered medical home (PCMH) has been introduced as a model for providing high-quality, comprehensive, patient-centered care that is both accessible and coordinated, and may provide a framework for optimizing the care of youth living with HIV (YLH). We surveyed six pediatric/adolescent HIV clinics caring for 578 patients (median age 19 years, 51% male, and 82% black) in July 2011 to assess conformity to the PCMH. Clinics completed a 50-item survey covering the six domains of the PCMH: (1) comprehensive care, (2) patient-centered care, (3) coordinated care, (4) accessible services, (5) quality and safety, and (6) health information technology. To determine conformity to the PCMH, a novel point-based scoring system was devised. Points were tabulated across clinics by domain to obtain an aggregate assessment of PCMH conformity. All six clinics responded. Overall, clinics attained a mean 75.8% [95% CI, 63.3–88.3%] on PCMH measures—scoring highest on patient-centered care (94.7%), coordinated care (83.3%), and quality and safety measures (76.7%), and lowest on health information technology (70.0%), accessible services (69.1%), and comprehensive care (61.1%). Clinics moderately conformed to the PCMH model. Areas for improvement include access to care...

‣ A DNA ‘Barcode Blitz’: Rapid Digitization and Sequencing of a Natural History Collection

Hebert, Paul D. N.; deWaard, Jeremy R.; Zakharov, Evgeny V.; Prosser, Sean W. J.; Sones, Jayme E.; McKeown, Jaclyn T. A.; Mantle, Beth; La Salle, John
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 10/07/2013 Português
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DNA barcoding protocols require the linkage of each sequence record to a voucher specimen that has, whenever possible, been authoritatively identified. Natural history collections would seem an ideal resource for barcode library construction, but they have never seen large-scale analysis because of concerns linked to DNA degradation. The present study examines the strength of this barrier, carrying out a comprehensive analysis of moth and butterfly (Lepidoptera) species in the Australian National Insect Collection. Protocols were developed that enabled tissue samples, specimen data, and images to be assembled rapidly. Using these methods, a five-person team processed 41,650 specimens representing 12,699 species in 14 weeks. Subsequent molecular analysis took about six months, reflecting the need for multiple rounds of PCR as sequence recovery was impacted by age, body size, and collection protocols. Despite these variables and the fact that specimens averaged 30.4 years old, barcode records were obtained from 86% of the species. In fact, one or more barcode compliant sequences (>487 bp) were recovered from virtually all species represented by five or more individuals, even when the youngest was 50 years old. By assembling specimen images...

‣ For Which Side the Bell Tolls: The Laterality of Approach-Avoidance Associative Networks

Fetterman, Adam K.; Ode, Scott; Robinson, Michael D.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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The two hemispheres of the brain appear to play different roles in emotion and/or motivation. A great deal of previous research has examined the valence hypothesis (left hemisphere = positive; right = negative), but an increasing body of work has supported the motivational hypothesis (left hemisphere = approach; right = avoidance) as an alternative. The present investigation (N = 117) sought to provide novel support for the latter perspective. Left versus right hemispheres were briefly activated by neutral lateralized auditory primes. Subsequently, participants categorized approach versus avoidance words as quickly and accurately as possible. Performance in the task revealed that approach-related thoughts were more accessible following left-hemispheric activation, whereas avoidance-related thoughts were more accessible following right-hemispheric activation. The present results are the first to examine such lateralized differences in accessible motivational thoughts, which may underlie more “downstream” manifestations of approach and avoidance motivation such as judgments, decision making, and behavior.