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1.
Biophys J ; 123(15): 2312-2327, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-38321740

RESUMEN

We report herein that the anti-CD20 therapeutic antibody, rituximab, is rearranged into microclusters within the phagocytic synapse by macrophage Fcγ receptors (FcγR) during antibody-dependent cellular phagocytosis. These microclusters were observed to potently recruit Syk and to undergo rearrangements that were limited by the cytoskeleton of the target cell, with depolymerization of target-cell actin filaments leading to modest increases in phagocytic efficiency. Total internal reflection fluorescence analysis revealed that FcγR total phosphorylation, Syk phosphorylation, and Syk recruitment were enhanced when IgG-FcγR microclustering was enabled on fluid bilayers relative to immobile bilayers in a process that required Arp2/3. We conclude that on fluid surfaces, IgG-FcγR microclustering promotes signaling through Syk that is amplified by Arp2/3-driven actin rearrangements. Thus, the surface mobility of antigens bound by IgG shapes the signaling of FcγR with an unrecognized complexity beyond the zipper and trigger models of phagocytosis.


Asunto(s)
Complejo 2-3 Proteico Relacionado con la Actina , Fagocitosis , Receptores de IgG , Transducción de Señal , Quinasa Syk , Receptores de IgG/metabolismo , Complejo 2-3 Proteico Relacionado con la Actina/metabolismo , Quinasa Syk/metabolismo , Animales , Ratones , Rituximab/farmacología , Inmunoglobulina G/metabolismo , Inmunoglobulina G/química , Fosforilación , Humanos
2.
J Am Chem Soc ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258314

RESUMEN

We have discovered a strategy to synthesize reactive radical salts, effectively bottling up radicals in space and time for future use. We apply this new principle to electrochemiluminescence (ECL) through the simultaneous electro-reduction of peroxydisulfate, S2O82-, and tris(bipyridine)ruthenium(II), [Ru(bpy)3]2+ in a water/acetonitrile mixture. The electrode generates a concentration profile exceeding the solubility of the cation and anion pair, promoting precipitation. After the application of a potential, leads are disconnected, and the crystals electrolessly chemiluminesce during dissolution and can be transported to other solutions for later chemiluminescence uses. Our method extends ECL hundreds of micrometers from the electrode surface and increases the ECL lifetime by orders of magnitude. Control experiments, including electron spin resonance, validate the crystallization of SO4•-, allowing detailed mechanistic insight. We demonstrate platform generalizability by precipitating a radical salt made of calcium and SO4•-, and we demonstrate the salt's ability to drive chemiluminescence. Our results emphasize the elegant chemical tenet that extremely reactive radicals can be bottled up as solids to be used as future reagents if precipitation occurs more quickly than the radical lifetime.

3.
J Am Chem Soc ; 146(1): 707-713, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38156610

RESUMEN

Several groups have reported on the curious chemistry and reaction acceleration in confined volumes. These complex multiphase systems most closely resemble natural processes, and new measurement tools are necessary to probe chemistry in such environments. Generally, electrochemiluminescence (ECL) reports on processes immediately near (within a few micrometers) the electrode surface. Here, we introduce through-space ECL, reporting on dynamics of processes far away (100s of µm) from the electrode surface. We achieved this by collecting reflected ECL light. During the heterogeneous oxidation of C2O42- in an aqueous phase adjacent to a 1,2-dichlorethane droplet, CO2 accumulates in the 1,2-dichloroethane droplet. Upon buildup, we demonstrate that a CO2 bubble forms in the nonaqueous phase and is surprisingly trapped at the water|1,2-dichloroethane interface and continues to grow. The co-oxidation of tris(bipyridine)ruthenium(II) in the aqueous phase lights up the electrode surface and reflects off the edges of the bubble, revealing the bubble growth over time even when the bubble is fractions of a millimeter from the surface. We extend our results to quantifying bubble forces at the water-oil interface at remote distances from the electrode surface.

4.
Epidemiology ; 35(4): 542-555, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38534176

RESUMEN

BACKGROUND: Spatial epidemiology has emerged as an important subfield of epidemiology over the past quarter century. We trace the origins of spatial epidemiology and note that its emergence coincided with technological developments in spatial statistics and geography. We hypothesize that spatial epidemiology makes important contributions to descriptive epidemiology and analytic risk-factor studies but is not yet aligned with epidemiology's current focus on causal inference and intervention. METHODS: We conducted a systematic review of studies indexed in PubMed that used the term "spatial epidemiolog*" in the title, abstract, or keywords. Excluded articles were not written in English, examined disease in animals, or reported biologic pathogen distribution only. We coded the included papers into five categories (review, demonstration of method, descriptive, analytic, and intervention) and recorded the unit of analysis (i.e., individual vs. ecological). We additionally examined articles coded as analytic ecologic studies using scales for lexical content. RESULTS: A total of 482 articles met the inclusion criteria, including 76 reviews, 117 demonstrations of methods, 122 descriptive studies, 167 analytic studies, and 0 intervention studies. Demonstration studies were most common from 2006 to 2014, and analytic studies were most common after 2015. Among the analytic ecologic studies, those published in later years used more terms relevant to spatial statistics (incidence rate ratio =1.3; 95% confidence interval [CI] = 1.1, 1.5) and causal inference (incidence rate ratio =1.1; 95% CI = 1.1, 1.2). CONCLUSIONS: Spatial epidemiology is an important and growing subfield of epidemiology. We suggest a re-orientation to help align its practice with the goals of contemporary epidemiology.


Asunto(s)
Análisis Espacial , Humanos , Métodos Epidemiológicos , Epidemiología
5.
Mem Cognit ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38865077

RESUMEN

Memory for words that are drawn or sketched by the participant, rather than written, during encoding is typically superior. While this drawing benefit has been reliably demonstrated in recent years, there has yet to be an investigation of its neural basis. Here, we asked participants to either create drawings, repeatedly write, or list physical characteristics depicting each target word during encoding. Participants then completed a recognition memory test for target words while undergoing functional magnetic resonance imaging (fMRI). Behavioural results showed memory was significantly higher for words drawn than written, replicating the typical drawing effect. Memory for words whose physical characteristics were listed at encoding was also higher than for those written repeatedly, but lower than for those drawn. Voxel-wise analyses of fMRI data revealed two distributed sets of brain regions more active for items drawn relative to written, the left angular gyrus (BA 39) and bilateral frontal (BA 10) regions, suggesting integration and self-referential processing during retrieval of drawn words. Brain-behaviour correlation analyses showed that the size of one's memory benefit for words drawn relative to written at encoding was positively correlated with activation in brain regions linked to visual representation and imagery (BA 17 and cuneus) and motor planning (premotor and supplementary motor areas; BA 6). This study suggests that drawing benefits memory by coactivating multiple sensory traces. Target words drawn during encoding are subsequently remembered by re-engaging visual, motoric, and semantic representations.

6.
Mem Cognit ; 52(1): 57-72, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37440162

RESUMEN

The production effect-that reading aloud leads to better memory than does reading silently-has been defined narrowly with reference to memory; it has been explored largely using word lists as the material to be read and remembered. But might the benefit of production extend beyond memory and beyond individual words? In a series of four experiments, passages from reading comprehension tests served as the study material. Participants read some passages aloud and others silently. After each passage, they completed multiple-choice questions about that passage. Separating the multiple-choice questions into memory-focused versus comprehension-focused questions, we observed a consistent production benefit only for the memory-focused questions. Production clearly improves memory for text, not just for individual words, and also extends to multiple-choice testing. The overall pattern of findings fits with the distinctiveness account of production-that information read aloud stands out at study and at test from information read silently. Only when the tested information is a very close match to the studied information, as is the case for memory questions but not for comprehension questions, does production improve accuracy.


Asunto(s)
Comprensión , Reconocimiento en Psicología , Humanos , Lectura , Recuerdo Mental , Proyectos de Investigación
7.
Prev Med ; 165(Pt A): 107207, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36027991

RESUMEN

Firearm violence is a major cause of morbidity, mortality, and racial health disparities in the United States. Previous studies have identified associations between historically racist housing discrimination (i.e., redlining practices) and firearm violence; however, these studies generally have been limited to a single city and have yet to provide sufficient evidence through which to determine the extent and dynamics of the impact of this relationship across the country. The aim of our study was (1) to estimate the association of historical redlining on both violent and firearm death across the country in nested models; and (2) to examine spatial non-stationarity to determine whether the impact of historical redlining on violent and firearm death was the same across the U.S. We used multilevel Bayesian conditional autoregressive Poisson models to determine the relationship between redlining as illustrated through Home Owners' Loan Corporation maps and 2019 violent and firearm deaths at the ZIP code-level nested within 21 cities across the U.S. We found that at the ZIP code level, there was a dose-responsive relationship between HOLC grading and the incidence of present-day firearm deaths. In general, redlined ZIP codes had higher relative incidence of firearm deaths. Associations were not stable across cities. For example, associations were relatively stronger in Baltimore, MD and weaker in Los Angeles, CA. This research reinforces the findings of previous studies examining the impact of redlining on firearm death across the extent of the entire country in 21 cities and claim that HOLC grades are associated with present-day violence.


Asunto(s)
Armas de Fuego , Humanos , Estados Unidos/epidemiología , Ciudades/epidemiología , Teorema de Bayes , Violencia , Vivienda
8.
Phys Chem Chem Phys ; 24(39): 24076-24088, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36172791

RESUMEN

We present an ab initio study of the rovibronic spectra of sulphur monoxide (32S16O) using internally contracted multireference configuration interaction (ic-MRCI) method and aug-cc-pV5Z basis sets. It covers 13 electronic states X3Σ-, a1Δ, b1Σ+, c1Σ-, A''3Σ+, A'3Δ, A3Π, B3Σ-, C3Π, d1Π, e1Π, C'3Π, and (3)1Π ranging up to 66 800 cm-1. The ab initio spectroscopic model includes 13 potential energy curves, 23 dipole and transition dipole moment curves, 23 spin-orbit curves, and 14 electronic angular momentum curves. A diabatic representation is built by removing the avoided crossings between the spatially degenerate pairs C3Π-C'3Π and e1Π-(3)1Π through a property-based diabatisation method. We also present non-adiabatic couplings and diabatic couplings for these avoided crossing systems. All phases for our coupling curves are defined, and consistent, providing the first fully reproducible spectroscopic model of SO covering the wavelength range longer than 147 nm. Finally, an ab initio rovibronic spectrum of SO is computed.

9.
Sensors (Basel) ; 22(12)2022 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-35746368

RESUMEN

Quantitative dynamic strain measurements of the ground would be useful for engineering scale problems such as monitoring for natural hazards, soil-structure interaction studies, and non-invasive site investigation using full waveform inversion (FWI). Distributed acoustic sensing (DAS), a promising technology for these purposes, needs to be better understood in terms of its directional sensitivity, spatial position, and amplitude for application to engineering-scale problems. This study investigates whether the physical measurements made using DAS are consistent with the theoretical transfer function, reception patterns, and experimental measurements of ground strain made by geophones. Results show that DAS and geophone measurements are consistent in both phase and amplitude for broadband (10 s of Hz), high amplitude (10 s of microstrain), and complex wavefields originating from different positions around the array when: (1) the DAS channels and geophone locations are properly aligned, (2) the DAS cable provides good deformation coupling to the internal optical fiber, (3) the cable is coupled to the ground through direct burial and compaction, and (4) laser frequency drift is mitigated in the DAS measurements. The transfer function of DAS arrays is presented considering the gauge length, pulse shape, and cable design. The theoretical relationship between DAS-measured and pointwise strain for vertical and horizontal active sources is introduced using 3D elastic finite-difference simulations. The implications of using DAS strain measurements are discussed including directionality and magnitude differences between the actual and DAS-measured strain fields. Estimating measurement quality based on the wavelength-to-gauge length ratio for field data is demonstrated. A method for spatially aligning the DAS channels with the geophone locations at tolerances less than the spatial resolution of a DAS system is proposed.

10.
Biomacromolecules ; 22(5): 2010-2019, 2021 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-33881308

RESUMEN

Rational protein design requires understanding the contribution of each amino acid to a targeted protein fold. For a subset of protein structures, namely, α-helical coiled coils (CCs), knowledge is sufficiently advanced to allow the rational de novo design of many structures, including entirely new protein folds. Current CC design rules center on using aliphatic hydrophobic residues predominantly to drive the folding and assembly of amphipathic α helices. The consequences of using aromatic residues-which would be useful for introducing structural probes, and binding and catalytic functionalities-into these interfaces are not understood. There are specific examples of designed CCs containing such aromatic residues, e.g., phenylalanine-rich sequences, and the use of polar aromatic residues to make buried hydrogen-bond networks. However, it is not known generally if sequences rich in tyrosine can form CCs, or what CC assemblies these would lead to. Here, we explore tyrosine-rich sequences in a general CC-forming background and resolve new CC structures. In one of these, an antiparallel tetramer, the tyrosine residues are solvent accessible and pack at the interface between the core and the surface. In another more complex structure, the residues are buried and form an extended hydrogen-bond network.


Asunto(s)
Pliegue de Proteína , Proteínas , Secuencia de Aminoácidos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Secundaria de Proteína
11.
Ann Bot ; 125(2): 365-376, 2020 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-31532484

RESUMEN

BACKGROUND AND AIMS: Coastal wetlands have evolved to withstand stressful abiotic conditions through the maintenance of hydrologic feedbacks between vegetation production and flooding. However, disruption of these feedbacks can lead to ecosystem collapse, or a regime shift from vegetated wetland to open water. To prevent the loss of critical coastal wetland habitat, we must improve understanding of the abiotic-biotic linkages among flooding and wetland stability. The aim of this research was to identify characteristic landscape patterns and thresholds of wetland degradation that can be used to identify areas of vulnerability, reduce flooding threats and improve habitat quality. METHODS: We measured local- and landscape-scale responses of coastal wetland vegetation to flooding stress in healthy and degrading coastal wetlands. We hypothesized that conversion of Spartina patens wetlands to open water could be defined by a distinct change in landscape configuration pattern, and that this change would occur at a discrete elevation threshold. KEY RESULTS: Despite similarities in total land and water cover, we observed differences in the landscape configuration of vegetated and open water pixels in healthy and degrading wetlands. Healthy wetlands were more aggregated, and degrading wetlands were more fragmented. Generally, greater aggregation was associated with higher wetland elevation and better drainage, compared with fragmented wetlands, which had lower elevation and poor drainage. The relationship between vegetation cover and elevation was non-linear, and the conversion from vegetated wetland to open water occurred beyond an elevation threshold of hydrologic stress. CONCLUSIONS: The elevation threshold defined a transition zone where healthy, aggregated, wetland converted to a degrading, fragmented, wetland beyond an elevation threshold of 0.09 m [1988 North American Vertical Datum (NAVD88)] [0.27 m mean sea level (MSL)], and complete conversion to open water occurred beyond 0.03 m NAVD88 (0.21 m MSL). This work illustrates that changes in landscape configuration can be used as an indicator of wetland loss. Furthermore, in conjunction with specific elevation thresholds, these data can inform restoration and conservation planning to maximize wetland stability in anticipation of flooding threats.


Asunto(s)
Ecosistema , Humedales , Conservación de los Recursos Naturales , Poaceae
12.
J Am Chem Soc ; 141(22): 8787-8797, 2019 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-31066556

RESUMEN

The association of amphipathic α helices in water leads to α-helical-bundle protein structures. However, the driving force for this-the hydrophobic effect-is not specific and does not define the number or the orientation of helices in the associated state. Rather, this is achieved through deeper sequence-to-structure relationships, which are increasingly being discerned. For example, for one structurally extreme but nevertheless ubiquitous class of bundle-the α-helical coiled coils-relationships have been established that discriminate between all-parallel dimers, trimers, and tetramers. Association states above this are known, as are antiparallel and mixed arrangements of the helices. However, these alternative states are less well understood. Here, we describe a synthetic-peptide system that switches between parallel hexamers and various up-down-up-down tetramers in response to single-amino-acid changes and solution conditions. The main accessible states of each peptide variant are characterized fully in solution and, in most cases, to high resolution with X-ray crystal structures. Analysis and inspection of these structures helps rationalize the different states formed. This navigation of the structural landscape of α-helical coiled coils above the dimers and trimers that dominate in nature has allowed us to design rationally a well-defined and hyperstable antiparallel coiled-coil tetramer (apCC-Tet). This robust de novo protein provides another scaffold for further structural and functional designs in protein engineering and synthetic biology.


Asunto(s)
Proteínas/química , Secuencia de Aminoácidos , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformación Proteica en Hélice alfa , Pliegue de Proteína , Agua/química
13.
Proc Biol Sci ; 286(1902): 20190655, 2019 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-31088271

RESUMEN

Evolutionary biologists have long sought to identify phenotypic traits whose evolution enhances an organism's performance in its environment. Diversification of traits related to resource acquisition can occur owing to spatial or temporal resource heterogeneity. We examined the ability to capture light in the Cryptophyta, a phylum of single-celled eukaryotic algae with diverse photosynthetic pigments, to better understand how acquisition of an abiotic resource may be associated with diversification. Cryptophytes originated through secondary endosymbiosis between an unknown eukaryotic host and a red algal symbiont. This merger resulted in distinctive pigment-protein complexes, the cryptophyte phycobiliproteins, which are the products of genes from both ancestors. These novel complexes may have facilitated diversification across environments where the spectrum of light available for photosynthesis varies widely. We measured light capture and pigments under controlled conditions in a phenotypically and phylogenetically diverse collection of cryptophytes. Using phylogenetic comparative methods, we found that phycobiliprotein characteristics were evolutionarily associated with diversification of light capture in cryptophytes, while non-phycobiliprotein pigments were not. Furthermore, phycobiliproteins were evolutionarily labile with repeated transitions and reversals. Thus, the endosymbiotic origin of cryptophyte phycobiliproteins provided an evolutionary spark that drove diversification of light capture, the resource that is the foundation of photosynthesis.


Asunto(s)
Evolución Biológica , Criptófitas/fisiología , Fotosíntesis/fisiología , Ficobiliproteínas/fisiología , Simbiosis
14.
Br J Surg ; : 1611-1616, 2019 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-31577372

RESUMEN

BACKGROUND: Patients are increasingly taking an active role in the design and delivery of surgical research. Public communication of results should also be encouraged, but this is often limited to non-expert commentary. This study assessed the role of plain English abstracts disseminated via social media in engaging patients and clinicians in the communication of surgical research. METHODS: A three-arm randomized controlled trial with crossover of two intervention arms was performed. Manuscripts accepted for publication in BJS were allocated to one of three arms and disseminated via Twitter: plain English abstracts, visual abstracts and standard tweets. The primary outcome was online engagement (a composite of tweets, replies and likes) by members of the public within 14 days. The secondary outcome was online engagement by healthcare professionals. RESULTS: Forty-one manuscripts were randomized to plain English abstracts (14), visual abstracts (14) and standard tweets (13). The number of public engagements was low, with a mean of 1·8 (range 0-8), 2·5 (0-11), and 1·2 (0-4) for plain English abstracts, visual abstracts and standard tweets respectively. The mean number of engagements by healthcare professionals was 29·4 (6-66), 45·3 (6-161) and 28·8 (10-52) respectively. Overall, visual abstracts attracted a significantly greater number of engagements than plain English ones (P < 0·001). CONCLUSION: Online, public engagement with surgical research was low. Overall engagement (predominantly from healthcare professionals) was enhanced by the use of visual abstracts.


ANTECEDENTES: Los pacientes están tomando cada vez más un papel activo en el diseño y en la difusión de la investigación quirúrgica. También se debe fomentar la comunicación pública de los resultados, pero a menudo ésta se limita a comentarios de personas no expertas. Este estudio evaluó el papel de los resúmenes redactados en un inglés sencillo difundidos a través de las redes sociales para involucrar a pacientes y médicos en la comunicación de la investigación quirúrgica. MÉTODOS: Se realizó un ensayo aleatorizado y controlado de tres brazos con un diseño cruzado de los dos brazos de intervención. Los manuscritos aceptados para publicación en BJS se asignaron a tres brazos y se difundieron vía twitter: resúmenes redactados en un inglés sencillo, resúmenes visuales, y tweets estándar. El criterio de valoración principal fue la interacción online (variable compuesta de tweets, respuestas y me gusta) por parte del público durante los primeros 14 días. El criterio de valoración secundario fue la interacción online de los profesionales de la salud. RESULTADOS: Un total de 41 manuscritos se asignaron al azar a resúmenes redactados en un inglés sencillo (n = 14), resúmenes visuales (n = 14) y tweets estándar (n = 13). El número de interacciones por parte del público fue bajo, con una media de 1,8 (rango 0-8), 2,5 (rango 0-11) y 1,2 (rango 0-4) para resúmenes en inglés sencillo, resúmenes visuales y tweets estándar, respectivamente. El número medio de interacciones por profesionales de la salud fue de 29,4 (rango 6-66), 45,3 (6-161) y 28,8 (10-52). En general, los resúmenes visuales atrajeron un número significativamente mayor de interacciones que los de inglés sencillo (P = 0,001). CONCLUSIÓN: La interacción online del público con la investigación quirúrgica fue baja. La participación general (predominantemente de profesionales de la salud) mejoró mediante el uso de resúmenes visuales. Los próximos trabajos podrían considerar si el público desea interaccionar y de qué modo con resúmenes redactados en un inglés sencillo.

15.
J Phycol ; 55(3): 552-564, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30468692

RESUMEN

Phenotypic traits associated with light capture and phylogenetic relationships were characterized in 34 strains of diversely pigmented marine and freshwater cryptophytes. Nuclear SSU and partial LSU rDNA sequence data from 33 of these strains plus an additional 66 strains produced a concatenated rooted maximum likelihood tree that classified the strains into 7 distinct clades. Molecular and phenotypic data together support: (i) the reclassification of Cryptomonas irregularis NIES 698 to the genus Rhodomonas, (ii) revision of phycobiliprotein (PBP) diversity within the genus Hemiselmis to include cryptophyte phycocyanin (Cr-PC) 569, (iii) the inclusion of previously unidentified strain CCMP 2293 into the genus Falcomonas, even though it contains cryptophyte phycoerythrin 545 (Cr-PE 545), and (iv) the inclusion of previously unidentified strain CCMP 3175, which contains Cr-PE 545, in a clade with PC-containing Chroomonas species. A discriminant analysis-based model of group membership correctly predicted 70.6% of the clades using three traits: PBP concentration · cell-1 , the wavelength of PBP maximal absorption, and habitat. Non-PBP pigments (alloxanthin, chl-a, chl-c2 , α-carotene) did not contribute significantly to group classification, indicating the potential plasticity of these pigments and the evolutionary conservation of the PBPs. Pigment data showed evidence of trade-offs in investments in PBPs vs. chlorophylls (a +c2 ).


Asunto(s)
Criptófitas , Agua Dulce , ADN Ribosómico , Ficocianina , Filogenia
16.
Bioinformatics ; 33(19): 3043-3050, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28582565

RESUMEN

MOTIVATION: The rational design of biomolecules is becoming a reality. However, further computational tools are needed to facilitate and accelerate this, and to make it accessible to more users. RESULTS: Here we introduce ISAMBARD, a tool for structural analysis, model building and rational design of biomolecules. ISAMBARD is open-source, modular, computationally scalable and intuitive to use. These features allow non-experts to explore biomolecular design in silico. ISAMBARD addresses a standing issue in protein design, namely, how to introduce backbone variability in a controlled manner. This is achieved through the generalization of tools for parametric modelling, describing the overall shape of proteins geometrically, and without input from experimentally determined structures. This will allow backbone conformations for entire folds and assemblies not observed in nature to be generated de novo, that is, to access the 'dark matter of protein-fold space'. We anticipate that ISAMBARD will find broad applications in biomolecular design, biotechnology and synthetic biology. AVAILABILITY AND IMPLEMENTATION: A current stable build can be downloaded from the python package index (https://pypi.python.org/pypi/isambard/) with development builds available on GitHub (https://github.com/woolfson-group/) along with documentation, tutorial material and all the scripts used to generate the data described in this paper. CONTACT: d.n.woolfson@bristol.ac.uk or chris.wood@bristol.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Conformación Proteica , Programas Informáticos , Simulación por Computador , Modelos Moleculares , Pliegue de Proteína , Proteínas/química
17.
Phys Biol ; 15(3): 036005, 2018 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-29412191

RESUMEN

Weak external electric fields (EFs) polarize cellular structure and direct most migrating cells (galvanotaxis) toward the cathode, making it a useful tool during tissue engineering and for healing epidermal wounds. However, the biophysical mechanisms for sensing weak EFs remain elusive. We have reinvestigated the mechanism of cathode-directed water flow (electro-osmosis) in the boundary layer of cells, by reducing it with neutral, viscous polymers. We report that increasing viscosity with low molecular weight polymers decreases cathodal migration and promotes anodal migration in a concentration dependent manner. In contrast, increased viscosity with high molecular weight polymers does not affect directionality. We explain the contradictory results in terms of porosity and hydraulic permeability between the polymers rather than in terms of bulk viscosity. These results provide the first evidence for controlled reversal of galvanotaxis using viscous agents and position the field closer to identifying the putative electric field receptor, a fundamental, outside-in signaling receptor that controls cellular polarity for different cell types.


Asunto(s)
Movimiento Celular/fisiología , Polaridad Celular , Taxia/fisiología , Pez Cebra/fisiología , Animales , Polímeros/metabolismo , Viscosidad
18.
Colorectal Dis ; 20(5): O114-O118, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29509990

RESUMEN

AIM: Engagement by medical professionals with social media (SM) is increasing. Variation is noted in engagement between SM platforms and between surgical specialities and geographical regions. We aimed to study SM engagement by colorectal surgeons attending an international conference. METHOD: Surgeons were identified from the delegate list of the 2017 Annual Meeting of the American Society of Colon and Rectal Surgeons (ASCRS) and Tripartite Meeting (Seattle, Washington, USA). Delegates were searched on Twitter and LinkedIn for the presence of a matching profile. SM presence, activity, gender and geographical region were analysed. RESULTS: Two hundred and seventy (13.2%) surgeons had Twitter accounts and 994 (44.3%) had LinkedIn profiles. UK surgeons were more likely to be on Twitter than surgeons from elsewhere (23.4% vs 12.7%, P = 0.0072). Significant variation in SM membership between each geographical region was noted, with usage rates for Twitter of 18.1% in Europe, 14.4% in North America, 12.9% in South America, 4.3% in Oceania, 3.7% in Asia and 0% in Africa. A similar picture for LinkedIn is seen. The #ASCRS17 meeting saw the highest participation of users to date (979 participants, over 7000 individual tweets and nearly 14 million impressions). CONCLUSION: SM engagement by colorectal surgeons continues to increase. Significant geographical variation is noted, suggesting that SM's unique potential for education and networking may not yet be widely appreciated globally. Future work should include further analysis into tweet contents to gain insights and optimize the use of SM as an educational adjunct.


Asunto(s)
Cirugía Colorrectal/estadística & datos numéricos , Medios de Comunicación Sociales/estadística & datos numéricos , Cirujanos/estadística & datos numéricos , Adulto , Congresos como Asunto , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Sociedades Médicas
19.
Colorectal Dis ; 20(2): 144-149, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28783240

RESUMEN

AIM: Engagement in social media is increasing. Medical professionals have been adapting LinkedIn, a professional networking site, and Twitter, a microblogging service, for a number of uses. This development has been described for a number of medical specialties, but there remains a paucity of European data. A study was undertaken to measure the engagement and activity of German visceral surgeons on social media platforms. METHOD: Visceral surgeons were identified from 15 regional Associations of Statutory Health Insurance Physicians (Kassenärztliche Vereinigungen) opt-in registers. A manual search was subsequently performed across key professional social media platforms. The presence of a profile and key markers of use were recorded. RESULTS: In total, 575 visceral surgeons were identified. 523 (93%) were men. 183 (31%) surgeons engaged in professional social media. 22 (3.8%) used Twitter, producing a mean of 16.43 tweets with a mean of 7.57 followers. 137 (24%) surgeons had a profile on LinkedIn with a mean of 46.36 connections. Female surgeons were less connected on LinkedIn (P < 0.005). 60 (10%) used Xing, with a mean of 27.95 connections. There were no significant differences in use of social media between surgeons from Eastern and Western Germany (P = 0.262) or male and female surgeons (P = 0.399). CONCLUSIONS: German visceral surgeons are less engaged and less active on social media than previously examined cohorts. Loco-regional, cultural, demographic and regulatory matters may have a significant influence on uptake. If this surgical cohort wishes to have a wider international presence then education on the potential benefits of these tools may be needed.


Asunto(s)
Gastroenterólogos/estadística & datos numéricos , Medios de Comunicación Sociales/estadística & datos numéricos , Cirujanos/estadística & datos numéricos , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad
20.
Br J Surg ; 104(11): 1470-1476, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28881004

RESUMEN

BACKGROUND: The use of social media platforms among healthcare professionals is increasing. A Twitter social media campaign promoting the hashtag #colorectalsurgery was launched with the aim of providing a specialty-specific forum to collate discussions and science relevant to an engaged, global community of coloproctologists. This article reviews initial experiences of the early adoption, engagement and utilization of this pilot initiative. METHODS: The hashtag #colorectalsurgery was promoted via the online microblogging service Twitter across a 180-day interval. Data on all tweets containing the #colorectalsurgery hashtag were analysed using online analytical tools. Data included total number of tweets, number of views, and user engagement since registration and launch of the campaign. Content of tweet and user demographic analysis was undertaken. RESULTS: The number of tweets using #colorectalsurgery grew rapidly following the launch on 24 April 2016; #colorectalsurgery was used in 15 708 tweets, which resulted in 65 398 696 impressions and involved 1863 individual Twitter accounts. Increased volumes of #colorectalsurgery tweets were noted in association with the timing of three major international colorectal surgical conferences, and geographical trends were noted. Some 88·4 per cent of all posts were by male users. The top 25 users by volume of #colorectalsurgery tweets had considerable influence and posted 8023 tweets (51·1 per cent). CONCLUSION: Online global communities formed via healthcare-related hashtags, such as #colorectalsurgery, unify social media posts, scientists, surgeons and authors who have an interest in coloproctology. Furthermore, they facilitate greater connectivity among geographically separate users.


Asunto(s)
Cirugía Colorrectal , Internet , Medios de Comunicación Sociales/estadística & datos numéricos , Estudios Transversales , Femenino , Humanos , Masculino
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