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Soft condensed matter is challenging to study due to the vast time and length scales that are necessary to accurately represent complex systems and capture their underlying physics. Multiscale simulations are necessary to study processes that have disparate time and/or length scales, which abound throughout biology and other complex systems. Herein we present ezAlign, an open-source software for converting coarse-grained molecular dynamics structures to atomistic representation, allowing multiscale modeling of biomolecular systems. The ezAlign v1.1 software package is publicly available for download at github.com/LLNL/ezAlign. Its underlying methodology is based on a simple alignment of an atomistic template molecule, followed by position-restraint energy minimization, which forces the atomistic molecule to adopt a conformation consistent with the coarse-grained molecule. The molecules are then combined, solvated, minimized, and equilibrated with position restraints. Validation of the process was conducted on a pure POPC membrane and compared with other popular methods to construct atomistic membranes. Additional examples, including surfactant self-assembly, membrane proteins, and more complex bacterial and human plasma membrane models, are also presented. By providing these examples, parameter files, code, and an easy-to-follow recipe to add new molecules, this work will aid future multiscale modeling efforts.
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Thermochromic wood (TW), a smart material that can respond to temperature changes and store thermal energy, holds broad potential for application in the construction industry. This study fabricated thermochromic poplar (TP) by encapsulating a thermochromic phase change material (TPCM), consisting of tetradecyl myristate and methyl red, within a full poplar-based cellulose/lignin/SiO2 framework. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses indicate that the poplar matrix and the incorporated SiO2 formed an integrated cellulose/lignin/SiO2 framework, which encapsulated the TPCM within the poplar ducts. The TP exhibits a color change from light purple to dark purple within the temperature range of 30-48 °C, with a pronounced shift at approximately 42 °C, correlating with the sensation of scalding. Thus, TP-based products can alert users to the risk of scalding through a noticeable color change. The full poplar-based framework mitigates the impact of ultraviolet (UV) radiation on the TP and prevents the loss of TPCM during thermal processing. The mechanical properties of TP are enhanced to a strength grade comparable to that of Manchurian ash wood, making it suitable for load-bearing components in wooden structures. Additionally, the average temperature of TP is around 10 °C higher than that of untreated poplar within 25 min after the same thermal treatment. Consequently, TP can serve as a building material with capabilities for temperature response, thermal energy storage, and structural load-bearing.
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Celulosa , Lignina , Populus , Dióxido de Silicio , Temperatura , Madera , Lignina/química , Madera/química , Celulosa/química , Populus/química , Dióxido de Silicio/química , Color , Compuestos Azo/químicaRESUMEN
Exploring new electrode structures and co-doped composite biomass material electrodes is considered to be an effective way of developing cheap, efficient carbon-based supercapacitors. A bamboo-based sandwich-structured matrix was prepared from thin bamboo veneer and bamboo fiber by pretreatment with H3PO4 and Co2+-catalyzed graphitization. The pore structure was modulated by hydrothermal activation with NaOH and electrodeposition of carbon nanotubes (CNTs) to obtain CNTs modified, Co/P co-doped sandwich-structured woodceramics electrode (CNT@Co/P). It not only has an obvious sandwich structure, but also retains the natural structural characteristics of bamboo. The specific capacitance of the resulting electrode (CNT@Co/P-20) is as high as 453.72F/g using 1 wt% of carboxylated multi-walled carbon nanotubes (CMWCNT) solution as the deposition electrolyte at a current density of 0.2 A/g for 20 min at room temperature. When the power density is 500 W/kg, the energy density reaches 21.3Wh /kg, showing a good electrochemical performance.
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Nanotubos de Carbono , Nanotubos de Carbono/química , Galvanoplastia , Electrodos , Capacidad Eléctrica , BiomasaRESUMEN
Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.
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Cerebelo , Imagen por Resonancia Magnética , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/patología , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/diagnóstico por imagen , Cerebelo/patología , Cerebelo/diagnóstico por imagen , Femenino , Masculino , Adulto , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Sustancia Blanca/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Gris/patología , Tamaño de los Órganos , Aprendizaje ProfundoRESUMEN
Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.
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Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/psicología , Imagen por Resonancia Magnética , Encéfalo , Emociones , Corteza PrefrontalRESUMEN
Genetic contributions to human cortical structure manifest pervasive pleiotropy. This pleiotropy may be harnessed to identify unique genetically-informed parcellations of the cortex that are neurobiologically distinct from functional, cytoarchitectural, or other cortical parcellation schemes. We investigated genetic pleiotropy by applying genomic structural equation modeling (SEM) to map the genetic architecture of cortical surface area (SA) and cortical thickness (CT) for the 34 brain regions recently reported in the ENIGMA cortical GWAS. Genomic SEM uses the empirical genetic covariance estimated from GWAS summary statistics with LD score regression (LDSC) to discover factors underlying genetic covariance, which we are denoting genetically informed brain networks (GIBNs). Genomic SEM can fit a multivariate GWAS from summary statistics for each of the GIBNs, which can subsequently be used for LD score regression (LDSC). We found the best-fitting model of cortical SA identified 6 GIBNs and CT identified 4 GIBNs. The multivariate GWASs of these GIBNs identified 74 genome-wide significant (GWS) loci (p<5×10-8), including many previously implicated in neuroimaging phenotypes, behavioral traits, and psychiatric conditions. LDSC of GIBN GWASs found that SA-derived GIBNs had a positive genetic correlation with bipolar disorder (BPD), and cannabis use disorder, indicating genetic predisposition to a larger SA in the specific GIBN is associated with greater genetic risk of these disorders. A negative genetic correlation was observed with attention deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), and insomnia, indicating genetic predisposition to a larger SA in the specific GIBN is associated with lower genetic risk of these disorders. CT GIBNs displayed a negative genetic correlation with alcohol dependence. Jointly modeling the genetic architecture of complex traits and investigating multivariate genetic links across phenotypes offers a new vantage point for mapping the cortex into genetically informed networks.
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BACKGROUND: Neuropathic pain impairs quality of life, is widely prevalent, and incurs significant costs. Current pharmacological therapies have poor/no efficacy and significant adverse effects; safe and effective alternatives are needed. Hyperpolarisation-activated cyclic nucleotide-regulated (HCN) channels are causally implicated in some forms of peripherally mediated neuropathic pain. Whilst 2,6-substituted phenols, such as 2,6-di-tert-butylphenol (26DTB-P), selectively inhibit HCN1 gating and are antihyperalgesic, the development of therapeutically tolerable, HCN-selective antihyperalgesics based on their inverse agonist activity requires that such drugs spare the cardiac isoforms and do not cross the blood-brain barrier. METHODS: In silico molecular dynamics simulation, in vitro electrophysiology, and in vivo rat spared nerve injury methods were used to test whether 'hindered' variants of 26DTB-P (wherein a hydrophilic 'anchor' is attached in the para-position of 26DTB-P via an acyl chain 'tether') had the desired properties. RESULTS: Molecular dynamics simulation showed that membrane penetration of hindered 26DTB-Ps is controlled by a tethered diol anchor without elimination of head group rotational freedom. In vitro and in vivo analysis showed that BP4L-18:1:1, a variant wherein a diol anchor is attached to 26DTB-P via an 18-carbon tether, is an HCN1 inverse agonist and an orally available antihyperalgesic. With a CNS multiparameter optimisation score of 2.25, a >100-fold lower drug load in the brain vs blood, and an absence of adverse cardiovascular or CNS effects, BP4L-18:1:1 was shown to be poorly CNS penetrant and cardiac sparing. CONCLUSIONS: These findings provide a proof-of-concept demonstration that anchor-tethered drugs are a new chemotype for treatment of disorders involving membrane targets.
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Agonismo Inverso de Drogas , Neuralgia , Ratas , Animales , Calidad de Vida , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/uso terapéutico , Neuralgia/tratamiento farmacológico , Fenómenos ElectrofisiológicosRESUMEN
Previous studies have shown that rewards weaken visual inhibition of return (IOR). However, the specific mechanisms underlying the influence of rewards on cross-modal IOR remain unclear. Based on the Posner exogenous cue-target paradigm, the present study was conducted to investigate the effect of rewards on exogenous spatial cross-modal IOR in both visual cue with auditory target (VA) and auditory cue with visual target (AV) conditions. The results showed the following: in the AV condition, the IOR effect size in the high-reward condition was significantly lower than that in the low-reward condition. However, in the VA condition, there was no significant IOR in either the high- or low-reward condition and there was no significant difference between the two conditions. In other words, the use of rewards modulated exogenous spatial cross-modal IOR with visual targets; specifically, high rewards may have weakened IOR in the AV condition. Taken together, our study extended the effect of rewards on IOR to cross-modal attention conditions and demonstrated for the first time that higher motivation among individuals under high-reward conditions weakened the cross-modal IOR with visual targets. Moreover, the present study provided evidence for future research on the relationship between reward and attention.
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Atención , Desempeño Psicomotor , Humanos , Tiempo de Reacción/fisiología , Atención/fisiología , Desempeño Psicomotor/fisiología , Inhibición Psicológica , Estimulación Luminosa/métodos , Señales (Psicología)RESUMEN
Thermochromic wood is an important research direction for wood modification in recent years, and a red poplar-based thermochromic composite (R-PTC) had been prepared in our previous study by compositing a mixture of phase change reagents (tetradecyl ester: C28H56O2 and methyl red: C15H15N3O2) and full poplar wood. In order to improve the heating storage ability of R-PTC and encapsulating phase change reagents to prevent leakage, a new R-PTC composite (PS-R-PTC) was prepared by encapsulated R-PTC with polyethylene glycol 400 (PEG400)-SiO2 in this work. Compared to the original R-PTC samples, the cell walls of PS-R-PTC were not significantly changed by the SiO2 film and we also found that PS-R-PTC with PEG400 (90%)-silica solutions (10%) mixture had better heat storage performance and PS-R-PTC (90%) has better enthalpy change value (R-PTC: 43.01 J g-1; PS-R-PTC (90%): 71.82 J g-1). The PS-R-PTC can show the function of thermal energy storage, which is used in wooden buildings and can be a feasible insulating material for reducing thermal energy losses and hence reducing energy usage. In PS-R-PTC, SiO2 combines with the -OH of the R-PTC and the -OH of PEG400 (HO(CH2CH2O) n H), and these -OH lose hydrogen ions too.
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Introduction: Cortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCNs) are represented as graphs with brain regions as nodes and correlations between nodes as edges. Methods: We built SCNs for PTSD and control groups using 148 CT and SA measures that were harmonized for site in n = 3439 subjects from Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium (PGC) PTSD. We compared centrality between PTSD and controls as well as interactions of diagnostic group with age, sex, and comorbid major depressive disorder (MDD) status. We investigated associations between network modularity and diagnostic grouping. Results: Nodes with higher CT-based centrality in PTSD compared with controls included the left inferior frontal sulcus, left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. Children (<10 years) and adolescents (10-21) with PTSD showed greater centrality in frontotemporal areas compared with young (22-39) and middle-aged adults (40-59) with PTSD, who showed higher centrality in occipital areas. The PTSD diagnostic group interactions with sex and comorbid MDD showed altered centrality in occipital regions, along with greater visual network (VN) modularity in PTSD subjects compared with controls. Conclusion: Structural covariance in PTSD is associated with centrality differences in occipital areas and VN modularity differences in a large well-powered sample. In the context of extensive structural covariance remodeling taking place before and during adolescence, the present findings suggest a process of cortical remodeling that commences with trauma and/or the onset of PTSD but may also predate these events. Impact statement Centrality is a graph theory measure that offers insights into a node's relationship with all other nodes in the brain. Centrality pinpoints the drivers of brain communication within networks and nodes and may be a promising target for treatments such as neuromodulation. Modularity can pinpoint modules that exist within larger networks and quantify the connections between these modules. Centrality and modularity complement functional and structural connectivity measurements within specific brain networks.
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Trastorno Depresivo Mayor , Trastornos por Estrés Postraumático , Adolescente , Niño , Persona de Mediana Edad , Humanos , Encéfalo , Imagen por Resonancia Magnética/métodos , Trastorno Depresivo Mayor/diagnóstico por imagen , Lóbulo TemporalRESUMEN
PURPOSE: Although paclitaxel is a promising first-line chemotherapeutic drug for ovarian cancer, acquired resistance to paclitaxel is one of the leading causes of treatment failure, limiting its clinical application. Asparagus officinalis has been shown to have anti-tumorigenic effects on cell growth, apoptosis, cellular stress and invasion of various types of cancer cells and has also been shown to synergize with paclitaxel to inhibit cell proliferation in ovarian cancer. METHODS: Human ovarian cancer cell lines MES and its PTX-resistant counterpart MES-TP cell lines were used and were treated with Asparagus officinalis and paclitaxel alone as well as in combination. Cell proliferation, cellular stress, invasion and DMA damage were investigated and the synergistic effect of a combined therapy analyzed. RESULTS: In this study, we found that Asparagus officinalis combined with low-dose paclitaxel synergistically inhibited cell proliferation, induced cellular stress and apoptosis and reduced cell invasion in paclitaxel-sensitive and -resistant ovarian cancer cell lines. The combined treatment effects were dependent on DNA damage pathways and suppressing microtubule dynamics, and the AKT/mTOR pathway and microtubule-associated proteins regulated the inhibitory effect through different mechanisms in paclitaxel-sensitive and -resistant cells. CONCLUSION: These findings suggest that the combination of Asparagus officinalis and paclitaxel have potential clinical implications for development as a novel ovarian cancer treatment strategy.
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Asparagus , Neoplasias Ováricas , Humanos , Femenino , Paclitaxel , Resistencia a Antineoplásicos , Línea Celular Tumoral , Neoplasias Ováricas/patología , ApoptosisRESUMEN
Cortical thickness changes dramatically during development and is associated with adolescent drinking. However, previous findings have been inconsistent and limited by region-of-interest approaches that are underpowered because they do not conform to the underlying spatially heterogeneous effects of alcohol. In this study, adolescents (n = 657; 12-22 years at baseline) from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study who endorsed little to no alcohol use at baseline were assessed with structural magnetic resonance imaging and followed longitudinally at four yearly intervals. Seven unique spatial patterns of covarying cortical thickness were obtained from the baseline scans by applying an unsupervised machine learning method called non-negative matrix factorization (NMF). The cortical thickness maps of all participants' longitudinal scans were projected onto vertex-level cortical patterns to obtain participant-specific coefficients for each pattern. Linear mixed-effects models were fit to each pattern to investigate longitudinal effects of alcohol consumption on cortical thickness. We found in six NMF-derived cortical thickness patterns, the longitudinal rate of decline in no/low drinkers was similar for all age cohorts. Among moderate drinkers the decline was faster in the younger adolescent cohort and slower in the older cohort. Among heavy drinkers the decline was fastest in the younger cohort and slowest in the older cohort. The findings suggested that unsupervised machine learning successfully delineated spatially coordinated patterns of vertex-level cortical thickness variation that are unconstrained by neuroanatomical features. Age-appropriate cortical thinning is more rapid in younger adolescent drinkers and slower in older adolescent drinkers, an effect that is strongest among heavy drinkers.
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Consumo de Alcohol en Menores , Adolescente , Humanos , Anciano , Aprendizaje Automático no Supervisado , Adelgazamiento de la Corteza Cerebral , Consumo de Bebidas Alcohólicas , Imagen por Resonancia Magnética , Etanol , Estudios LongitudinalesRESUMEN
OBJECTIVE: The variety of instruments used to assess posttraumatic stress disorder (PTSD) allows for flexibility, but also creates challenges for data synthesis. The objective of this work was to use a multisite mega analysis to derive quantitative recommendations for equating scores across measures of PTSD severity. METHOD: Empirical Bayes harmonization and linear models were used to describe and mitigate site and covariate effects. Quadratic models for converting scores across PTSD assessments were constructed using bootstrapping and tested on hold out data. RESULTS: We aggregated 17 data sources and compiled an n = 5,634 sample of individuals who were assessed for PTSD symptoms. We confirmed our hypothesis that harmonization and covariate adjustments would significantly improve inference of scores across instruments. Harmonization significantly reduced cross-dataset variance (28%, p < .001), and models for converting scores across instruments were well fit (median R² = 0.985) with an average root mean squared error of 1.46 on sum scores. CONCLUSIONS: These methods allow PTSD symptom severity to be placed on multiple scales and offers interesting empirical perspectives on the role of harmonization in the behavioral sciences. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Trastornos por Estrés Postraumático , Veteranos , Humanos , Trastornos por Estrés Postraumático/diagnóstico , Teorema de Bayes , Índice de Severidad de la EnfermedadRESUMEN
Shanghai style furniture (SSF) was the classic case of Chinese furniture culture, we have researched on the teaching content of SSF design for the furniture design course in Chinese art design speciality, and carried out the teaching practice of SSF design for some students. According to this teaching practice, the students' design attitude towards SSF was summarized, which will provide a basis for inheriting SSF design and developing SSF design teaching. In our teaching practice, 132 students had learned the design experiences of SSF, carried on the design practice of SSF, and summarized their SSF design. In the process of students' redesign of SSF, generally speaking, the SSF style was characterized by the combination of China and the European and modern simplicity. Modern elements were added to the SSF design, and fine works were refined in the traditional Chinese modeling, so as to make SSF more in line with the trend of modern design and better carry forward the concept of design service life. After studying this course, these students had basically mastered the design method of SSF. Excavating the practical value of SSF culture and designing new SSF, which are not to copy traditional art style, but the recreation and redesign basing on modern cultures.
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Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.
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Imagen por Resonancia Magnética , Trastornos por Estrés Postraumático , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuroimagen , Adulto JovenRESUMEN
Characterizing the biophysical properties of bacterial membranes is critical for understanding the protective nature of the microbial envelope, interaction of biological membranes with exogenous materials, and designing new antibacterial agents. Presented here are molecular dynamics simulations for two cationic quaternary ammonium compounds, and the anionic and nonionic form of a fatty acid molecule interacting with a Staphylococcus aureus bacterial inner membrane. The effect of the tested materials on the properties of the model membranes are evaluated with respect to various structural properties such as the lateral pressure profile, lipid tail order parameter, and the bilayer's electrostatic potential. Conducting asymmetric loading of molecules in only one leaflet, it was observed that anionic and cationic amphiphiles have a large impact on the Staphylococcus aureus membrane's electrostatic potential and lateral pressure profile as compared to a symmetric distribution. Nonintuitively, we find that the cationic and anionic molecules induce a similar change in the electrostatic potential, which points to the complexity of membrane interfaces, and how asymmetry can induce biophysical consequences. Finally, we link changes in membrane structure to the rate of electroporation for the membranes, and again find a crucial impact of introducing asymmetry to the system. Understanding these physical mechanisms provides critical insights and viable pathways for the rational design of membrane-active molecules, where controlling the localization is key.
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BACKGROUND: Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). METHODS: Neuroimaging and clinical data were aggregated from 29 research sites in >1300 PTSD cases and >2000 trauma-exposed control subjects (ages 6.2-85.2 years) by the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta Analysis-Psychiatric Genomics Consortium) PTSD working group. Cortical regions in the network were rank ordered by the effect size of PTSD-related cortical differences in CT and SA. The top-n (n = 2-148) regions with the largest effect size for PTSD > non-PTSD formed hypertrophic networks, the largest effect size for PTSD < non-PTSD formed atrophic networks, and the smallest effect size of between-group differences formed stable networks. The mean structural covariance (SC) of a given n-region network was the average of all positive pairwise correlations and was compared with the mean SC of 5000 randomly generated n-region networks. RESULTS: Patients with PTSD, relative to non-PTSD control subjects, exhibited lower mean SC in CT-based and SA-based atrophic networks. Comorbid depression, sex, and age modulated covariance differences of PTSD-related structural networks. CONCLUSIONS: Covariance of structural networks based on CT and cortical SA are affected by PTSD and further modulated by comorbid depression, sex, and age. The SC networks that are perturbed in PTSD comport with converging evidence from resting-state functional connectivity networks and networks affected by inflammatory processes and stress hormones in PTSD.
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Conectoma , Trastornos por Estrés Postraumático , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Conectoma/métodos , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Neuroimagen , Adulto JovenRESUMEN
Mild Traumatic brain injury (mTBI) is a signature wound in military personnel, and repetitive mTBI has been linked to age-related neurogenerative disorders that affect white matter (WM) in the brain. However, findings of injury to specific WM tracts have been variable and inconsistent. This may be due to the heterogeneity of mechanisms, etiology, and comorbid disorders related to mTBI. Non-negative matrix factorization (NMF) is a data-driven approach that detects covarying patterns (components) within high-dimensional data. We applied NMF to diffusion imaging data from military Veterans with and without a self-reported TBI history. NMF identified 12 independent components derived from fractional anisotropy (FA) in a large dataset (n = 1,475) gathered through the ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Military Brain Injury working group. Regressions were used to examine TBI- and mTBI-related associations in NMF-derived components while adjusting for age, sex, post-traumatic stress disorder, depression, and data acquisition site/scanner. We found significantly stronger age-dependent effects of lower FA in Veterans with TBI than Veterans without in four components (q < 0.05), which are spatially unconstrained by traditionally defined WM tracts. One component, occupying the most peripheral location, exhibited significantly stronger age-dependent differences in Veterans with mTBI. We found NMF to be powerful and effective in detecting covarying patterns of FA associated with mTBI by applying standard parametric regression modeling. Our results highlight patterns of WM alteration that are differentially affected by TBI and mTBI in younger compared to older military Veterans.