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1.
Cell ; 184(25): 6067-6080.e13, 2021 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-34852238

RESUMEN

The human monoclonal antibody (HmAb) C10 potently cross-neutralizes Zika virus (ZIKV) and dengue virus. Analysis of antibody fragment (Fab) C10 interactions with ZIKV and dengue virus serotype 2 (DENV2) particles by cryoelectron microscopy (cryo-EM) and amide hydrogen/deuterium exchange mass spectrometry (HDXMS) shows that Fab C10 binding decreases overall ZIKV particle dynamics, whereas with DENV2, the same Fab causes increased dynamics. Testing of different Fab C10:DENV2 E protein molar ratios revealed that, at higher Fab ratios, especially at saturated concentrations, the Fab enhanced viral dynamics (detected by HDXMS), and observation under cryo-EM showed increased numbers of distorted particles. Our results suggest that Fab C10 stabilizes ZIKV but that with DENV2 particles, high Fab C10 occupancy promotes E protein dimer conformational changes leading to overall increased particle dynamics and distortion of the viral surface. This is the first instance of a broadly neutralizing antibody eliciting virus-specific increases in whole virus particle dynamics.


Asunto(s)
Anticuerpos Neutralizantes , Virus del Dengue , Dengue , Proteínas del Envoltorio Viral , Infección por el Virus Zika , Virus Zika , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/inmunología , Reacciones Cruzadas , Dengue/inmunología , Dengue/virología , Virus del Dengue/inmunología , Virus del Dengue/fisiología , Humanos , Unión Proteica , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/metabolismo , Virus Zika/inmunología , Virus Zika/fisiología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/virología
2.
J Cell Sci ; 136(12)2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37259855

RESUMEN

The mammalian epidermis undergoes constant renewal, replenished by a pool of stem cells and terminal differentiation of their progeny. This is accompanied by changes in gene expression and morphology that are orchestrated, in part, by epigenetic modifiers. Here, we define the role of the histone acetyltransferase KAT2A in epidermal homeostasis and provide a comparative analysis that reveals key functional divergence with its paralog KAT2B. In contrast to the reported function of KAT2B in epidermal differentiation, KAT2A supports the undifferentiated state in keratinocytes. RNA-seq analysis of KAT2A- and KAT2B- depleted keratinocytes revealed dysregulated epidermal differentiation. Depletion of KAT2A led to premature expression of epidermal differentiation genes in the absence of inductive signals, whereas loss of KAT2B delayed differentiation. KAT2A acetyltransferase activity was indispensable in regulating epidermal differentiation gene expression. The metazoan-specific N terminus of KAT2A was also required to support its function in keratinocytes. We further showed that the interplay between KAT2A- and KAT2B-mediated regulation was important for normal cutaneous wound healing in vivo. Overall, these findings reveal a distinct mechanism in which keratinocytes use a pair of highly homologous histone acetyltransferases to support divergent functions in self-renewal and differentiation processes.


Asunto(s)
Histona Acetiltransferasas , Queratinocitos , Animales , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Queratinocitos/metabolismo , Diferenciación Celular/genética , Piel/metabolismo , Epidermis/metabolismo , Mamíferos/metabolismo
3.
Cardiovasc Diabetol ; 23(1): 303, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39152461

RESUMEN

BACKGROUND: Patients with diabetes have an increased risk of developing heart failure with preserved ejection fraction (HFpEF). This study aimed to compare indices of myocardial deformation and perfusion between patients with type 2 diabetes mellitus (T2DM) with and without HFpEF and to investigate the relationship between myocardial strain and perfusion reserve. METHODS: This study included 156 patients with T2DM without obstructive coronary artery disease (CAD) and 50 healthy volunteers who underwent cardiac magnetic resonance (CMR) examination at our center. Patients with T2DM were subdivided into the T2DM-HFpEF (n = 74) and the T2DM-non-HFpEF (n = 82) groups. The parameters of left ventricular (LV) and left atrial (LA) strain as well as stress myocardial perfusion were compared. The correlation between myocardial deformation and perfusion parameters was also assessed. Mediation analyses were used to evaluate the direct and indirect effects of T2DM on LA strain. RESULTS: Patients with T2DM and HFpEF had reduced LV radial peak systolic strain rate (PSSR), LV circumferential peak diastolic strain rate (PDSR), LA reservoir strain, global myocardial perfusion reserve index (MPRI), and increased LA booster strain compared to patients with T2DM without HFpEF (all P < 0.05). Furthermore, LV longitudinal PSSR, LA reservoir, and LA conduit strain were notably impaired in patients with T2DM without HFpEF compared to controls (all P < 0.05), but LV torsion, LV radial PSSR, and LA booster strain compensated for these alterations (all P < 0.05). Multivariate linear regression analysis demonstrated that LA reservoir and LA booster strain were independently associated with global MPRI (ß = 0.259, P < 0.001; ß = - 0.326, P < 0.001, respectively). Further, the difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI. Global stress PI, LA booster, global rest PI, and global MPRI showed high accuracy in diagnosing HFpEF among patients with T2DM (areas under the curve [AUC]: 0.803, 0.790, 0.740, 0.740, respectively). CONCLUSIONS: Patients with T2DM and HFpEF exhibited significant LV systolic and diastolic deformation, decreased LA reservoir strain, severe impairment of myocardial perfusion, and elevated LA booster strain that is a compensatory response in HFpEF. Global MPRI was identified as an independent influencing factor on LA reservoir and LA booster strain. The difference in LA reservoir and LA booster strain between patients with T2DM with and without HFpEF was totally mediated by global MPRI, suggesting a possible mechanistic link between microcirculation impairment and cardiac dysfunction in diabetes. Myocardial perfusion and LA strain may prove valuable for diagnosing and managing HFpEF in the future.


Asunto(s)
Función del Atrio Izquierdo , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Imagen por Resonancia Cinemagnética , Imagen de Perfusión Miocárdica , Valor Predictivo de las Pruebas , Volumen Sistólico , Función Ventricular Izquierda , Humanos , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Imagen de Perfusión Miocárdica/métodos , Anciano , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/diagnóstico , Circulación Coronaria , Estudios de Casos y Controles , Contracción Miocárdica
4.
Mol Cell ; 62(4): 603-17, 2016 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-27184079

RESUMEN

Identifying pairwise RNA-RNA interactions is key to understanding how RNAs fold and interact with other RNAs inside the cell. We present a high-throughput approach, sequencing of psoralen crosslinked, ligated, and selected hybrids (SPLASH), that maps pairwise RNA interactions in vivo with high sensitivity and specificity, genome-wide. Applying SPLASH to human and yeast transcriptomes revealed the diversity and dynamics of thousands of long-range intra- and intermolecular RNA-RNA interactions. Our analysis highlighted key structural features of RNA classes, including the modular organization of mRNAs, its impact on translation and decay, and the enrichment of long-range interactions in noncoding RNAs. Additionally, intermolecular mRNA interactions were organized into network clusters and were remodeled during cellular differentiation. We also identified hundreds of known and new snoRNA-rRNA binding sites, expanding our knowledge of rRNA biogenesis. These results highlight the underexplored complexity of RNA interactomes and pave the way to better understanding how RNA organization impacts biology.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , ARN de Hongos/genética , ARN Mensajero/genética , ARN Neoplásico/genética , ARN Ribosómico/genética , ARN Nucleolar Pequeño/genética , Saccharomyces cerevisiae/genética , Transcriptoma , Sitios de Unión , Diferenciación Celular , Biología Computacional , Reactivos de Enlaces Cruzados/química , Bases de Datos Genéticas , Células Madre Embrionarias/metabolismo , Ficusina/química , Regulación Fúngica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Estudio de Asociación del Genoma Completo , Células HeLa , Humanos , Conformación de Ácido Nucleico , Estabilidad del ARN , ARN de Hongos/química , ARN de Hongos/metabolismo , ARN Mensajero/química , ARN Mensajero/metabolismo , ARN Neoplásico/química , ARN Neoplásico/metabolismo , ARN Ribosómico/química , ARN Ribosómico/metabolismo , ARN Nucleolar Pequeño/química , ARN Nucleolar Pequeño/metabolismo , Ribosomas/genética , Ribosomas/metabolismo , Saccharomyces cerevisiae/metabolismo
5.
Neurol Sci ; 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-39472362

RESUMEN

INTRODUCTION: Sexual dysfunction manifests as various challenges during sexual activity and is a prevalent condition that significantly impacts quality of life. Post stroke sexual dysfunction (PSSD) is particularly concerning, yet it is often overlooked by both healthcare providers and patients. METHODS: We conducted a comprehensive literature review, examining research and reports related to sexual dysfunction following stroke. Our aim is to synthetize an extensive, detailed and up-to-date overview of its prevalence, underlying mechanisms, and interventions. RESULTS AND CONCLUSION: PSSD, often underestimated among stroke survivors, has a high incidence but remains poorly understood in terms of its neurobiological mechanisms. Swift and accurate diagnosis, coupled with timely rehabilitative intervention, is crucial. However, the development of comprehensive guidelines is impeded by a lack of high-quality literature. This review seeks to present recent advances in understanding PSSD, and to advocate for a structured strategy in terms of the long-term rehabilitation of stroke survivors.

6.
Neurocrit Care ; 40(2): 743-749, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37697126

RESUMEN

BACKGROUND: The objective of this study was to investigate the clinical, imaging, and outcome characteristics of intracerebral hemorrhage (ICH) caused by structural vascular lesions. METHODS: We retrospectively analyzed data from a prospective observational cohort study of patients with spontaneous ICH admitted to the First Affiliated Hospital of Chongqing Medical University between May 2016 and April 2021. Good outcome was defined as modified Rankin Scale score of 0-3 at 3 months. The clinical and imaging characteristics were compared between primary ICH and ICH caused by structural vascular lesions. Multivariable logistic regression analysis was performed to test the associations of etiology with clinical outcome. RESULTS: All patients enrolled in this study were Asian. Compared with patients with primary ICH, those with structural vascular lesions were younger (48 vs. 62 years, P < 0.001), had a lower incidence of hypertension (26.4% vs. 81.7%, P < 0.001) and diabetes (7.4% vs. 16.2%, P = 0.003), and had mostly lobar hemorrhages (49.1% vs. 22.8%). ICH from structural vascular lesions had smaller baseline hematoma volume (8.4 ml vs. 13.8 ml, P = 0.010), had lower mortality rate at 30 days and 3 months (5.8% vs. 12.0%, P = 0.020; 6.7% vs. 14.8%, P = 0.007), and are associated with better functional outcome at 3 months (88% vs.70.3%, P < 0.001). CONCLUSIONS: Compared with primary ICH, ICH due to vascular lesions has smaller hematoma volume and less severe neurological deficit at presentation and better functional outcomes.


Asunto(s)
Hemorragia Cerebral , Tomografía Computarizada por Rayos X , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Hemorragia Cerebral/complicaciones , Hematoma/diagnóstico por imagen , Hematoma/terapia , Hematoma/complicaciones
7.
J Stroke Cerebrovasc Dis ; 33(6): 107683, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38513767

RESUMEN

BACKGROUND AND OBJECTIVES: The prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. METHODS: We analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. RESULTS: The receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. CONCLUSIONS: Optimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.


Asunto(s)
Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Hemorragia Cerebral Intraventricular/diagnóstico por imagen , Hemorragia Cerebral Intraventricular/fisiopatología , Hemorragia Cerebral Intraventricular/terapia , Hemorragia Cerebral Intraventricular/diagnóstico , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/terapia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/fisiopatología , Factores de Riesgo , Factores de Tiempo , Anciano de 80 o más Años , Evaluación de la Discapacidad , Hematoma/diagnóstico por imagen , Hematoma/diagnóstico , Curva ROC
8.
PLoS Pathog ; 17(2): e1009331, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33621239

RESUMEN

Different strains within a dengue serotype (DENV1-4) can have smooth, or "bumpy" surface morphologies with different antigenic characteristics at average body temperature (37°C). We determined the neutralizing properties of a serotype cross-reactive human monoclonal antibody (HMAb) 1C19 for strains with differing morphologies within the DENV1 and DENV2 serotypes. We mapped the 1C19 epitope to E protein domain II by hydrogen deuterium exchange mass spectrometry, cryoEM and molecular dynamics simulations, revealing that this epitope is likely partially hidden on the virus surface. We showed the antibody has high affinity for binding to recombinant DENV1 E proteins compared to those of DENV2, consistent with its strong neutralizing activities for all DENV1 strains tested regardless of their morphologies. This finding suggests that the antibody could out-compete E-to-E interaction for binding to its epitope. In contrast, for DENV2, HMAb 1C19 can only neutralize when the epitope becomes exposed on the bumpy-surfaced particle. Although HMAb 1C19 is not a suitable therapeutic candidate, this study with HMAb 1C19 shows the importance of choosing a high-affinity antibody that could neutralize diverse dengue virus morphologies for therapeutic purposes.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Virus del Dengue/inmunología , Dengue/inmunología , Epítopos/inmunología , Proteínas del Envoltorio Viral/inmunología , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/metabolismo , Anticuerpos Neutralizantes/química , Anticuerpos Neutralizantes/metabolismo , Anticuerpos Antivirales/química , Anticuerpos Antivirales/metabolismo , Afinidad de Anticuerpos , Especificidad de Anticuerpos , Dengue/virología , Virus del Dengue/química , Virus del Dengue/metabolismo , Epítopos/metabolismo , Humanos , Simulación de Dinámica Molecular , Conformación Proteica , Serogrupo
9.
Cerebrovasc Dis ; 52(4): 471-479, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36509082

RESUMEN

INTRODUCTION: The objective of this study was to define prehospital ultra-early neurological deterioration (UND) and to investigate the association with functional outcomes in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a prospective cohort study of consecutive acute ICH patients. The stroke severity at onset and hospital admission was assessed using the Chongqing Stroke Scale (CQSS), and prehospital UND was defined as a CQSS increase of ≥2 points between symptoms onset and admission. Early neurological deterioration (END) was defined as the increase of ≥4 points in NIHSS score within the first 24 h after admission. Poor outcome was defined as a modified Rankin Scale (mRS) of 4-6 at 3 months. RESULTS: Prehospital UND occurred in 29 of 169 patients (17.2%). Patients with prehospital UND had a median admission NIHSS score of 17.0 as opposed to those without prehospital UND with a median NIHSS score of 8.5. There were three patterns of neurological deterioration: prehospital UND only in 21 of 169 patients (12.4%), END but without prehospital UND in 20 of 169 patients (11.8%), and continuous neurological deterioration in both phases in 8 patients (4.7%). Prehospital UND was associated with worse 3-month outcomes (median mRS score, 4.0 vs. 2.0, p = 0.002). After adjusting for age, time from onset to admission, END, and systolic blood pressure, prehospital UND was an independent predictor of poor outcome (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.26-8.48, p = 0.015). CONCLUSION: Prehospital UND occurs in approximately 1 in 7 patients between symptom onset and admission and is associated with poor functional outcome in patients with ICH. Further research is needed to investigate the prehospital UND in the prehospital phase in the triage of patients with ICH.


Asunto(s)
Servicios Médicos de Urgencia , Accidente Cerebrovascular , Humanos , Estudios Prospectivos , Prevalencia , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/terapia , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia
10.
Neuropediatrics ; 54(2): 139-146, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36473490

RESUMEN

BACKGROUND: To explore the neural difference between children with obstructive sleep apnea (OSA) and healthy controls, together with the relation between this difference and clinical severity indicator of children with OSA. METHODS: Twenty-seven children with OSA (7.6 ± 2.5 years, apnea hypopnea index [AHI]: 9.7 ± 5.3 events/h) and 30 healthy controls (7.8 ± 2.6 years, AHI: 1.7 ± 1.2 events/h) were recruited and matched with age, gender, and handedness. All children underwent 3.0 T magnetic resonance imaging of the brain and cognitive testing evaluating. Volumetric segmentation of cortical and subcortical structures and voxel-based morphometry were performed. Pearson's correlation analysis was performed between these features of gray matter volume (GMV) and obstructive apnea index (OAI) among children with OSA. RESULTS: In the comparison of children's Wechsler test scores of full-scale intelligence quotient and verbal intelligence quotient, the OSA group was significantly lower than the control group (p < 0.05). Compared with the control group, the GMV of many brain regions in the OSA group was significantly decreased (p < 0.05). In the correlation analysis of GMV and OAI in OSA group, right inferior frontal gyrus volume was significantly negatively correlated with OAI (r = - 0.49, p = 0.02). CONCLUSION: Children with OSA presented abnormal neural activities in some brain regions and impaired cognitive functions. This finding suggests an association between the OSA and decreased GMV in children.


Asunto(s)
Sustancia Gris , Apnea Obstructiva del Sueño , Humanos , Niño , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Apnea Obstructiva del Sueño/diagnóstico por imagen , Apnea Obstructiva del Sueño/patología , Encéfalo/patología , Imagen por Resonancia Magnética , Cognición
11.
Macromol Rapid Commun ; 44(24): e2300382, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37703910

RESUMEN

Organic-inorganic hybrid perovskites have garnered significant attention in optoelectronics owing to their outstanding tunable optical characteristics. Controlled growth of perovskite nanocrystals from solutions is key for controlling the emission intensity and photoluminescence lifetime of perovskites. In particular, most studies have focused on controlling the crystallization of perovskite through chemical treatment using chelating ligands or physical treatment via antisolvent diffusion, and there exists a trade-off between the photoluminescence intensity and lifetime of perovskites. Herein, a selective solvent vapor-assisted crystallization with the aid of a functional polymer, which nanoscale perovskite crystals are grown andante from precursor solution, is presented for tuning the crystallization and optical properties of a common halide perovskite, methylammonium lead bromide (MAPbBr3 ). The proposed method here produces perovskite nanocrystals in the range of 200-300 nm. The spin-coated thin film formed from the perovskite solution exhibits strong green photoluminescence with a long lifetime. The effects of the functional group and polymer dosage on the crystallization of MAPbBr3 are systematically investigated, and the crystallization mechanism is explained based on a modified LaMer model. This study provides an advanced solution process for precisely controlling perovskite crystallization to enhance their optical properties for next-generation optoelectronic devices.


Asunto(s)
Compuestos de Calcio , Gases , Cristalización , Difusión
12.
BMC Med Educ ; 23(1): 900, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38012606

RESUMEN

To keep up with the contemporary health landscape, there is an imperative need for healthcare professionals to practise health advocacy through health promotion on the individual, population, and systems levels. In the Academic Year of 2020/2021, the National University of Singapore (NUS) Department of Pharmacy implemented a new spiral curriculum integrating basic, clinical, and systems sciences with one of its aims to deepen students' health advocacy internalisation and prepare them as future health advocates. A mixed-methods approach was adopted. Questionnaires were disseminated across three time-points to elicit students' levels of internalisation of health advocacy, which were then categorised into levels, and a Mann-Whitney U test was conducted. In comparison with prematriculation, no significant difference was found after students underwent the first year of the curriculum, while a significant difference was found after students underwent two years of the curriculum. Semi-structured interviews were also conducted after each Academic Year to gain deeper insights into the questionnaire results. Thematic analysis of the interviews revealed that curricular integration in the first year was perceived to be lacking. However, with learnt knowledge constantly reinforced and more experiential learning opportunities incorporated throughout the second year, students found the integrated curriculum beneficial in instilling confidence to practise health advocacy. This study offers insights into the prospects of a spiral integrated curriculum in imparting health advocacy, and may even suggest its potential to be applied to other educational settings. Future follow-up studies can also be conducted on the same study population to evaluate long-term impacts and areas for improvement of the curriculum.


Asunto(s)
Educación en Farmacia , Farmacia , Estudiantes de Farmacia , Humanos , Farmacéuticos , Curriculum , Aprendizaje , Educación en Farmacia/métodos
13.
Int J Mol Sci ; 24(9)2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-37175867

RESUMEN

Dengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11 kb genomic RNA with capsid (C) proteins. Whereas the structure of the envelope is clearly defined, the structure of the packaged genome in complex with C proteins remains elusive. Here, we investigated the interactions of C proteins with viral RNA, in solution and inside mature virions, via footprinting and cross-linking experiments. We demonstrated that C protein interaction with DENV genomes saturates at an RNA:C protein ratio below 1:250. Moreover, we also showed that the length of the RNA genome interaction sites varies, in a multimodal distribution, consistent with the C protein binding to each RNA site mostly in singlets or pairs (and, in some instances, higher numbers). We showed that interaction sites are preferentially sites with low base pairing, as previously measured by 2'-acetylation analyzed by primer extension (SHAPE) reactivity indicating structuredness. We found a clear association pattern emerged: RNA-C protein binding sites are strongly associated with long-range RNA-RNA interaction sites, particularly inside virions. This, in turn, explains the need for C protein in viral genome packaging: the protein has a chief role in coordinating these key interactions, promoting proper packaging of viral RNA. Such sites are, thus, highly consequential for viral assembly, and, as such, may be targeted in future drug development strategies against these and related viruses.


Asunto(s)
Proteínas de la Cápside , Virus del Dengue , Animales , Humanos , Proteínas de la Cápside/química , Virus del Dengue/genética , Virus del Dengue/metabolismo , Genoma Viral , Cápside/química , ARN Viral/metabolismo
14.
Org Biomol Chem ; 20(44): 8623-8627, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36314887

RESUMEN

A base-catalyzed divergent synthesis of multisubstituted imidazoles through TosMIC-based [3 + 2] cyclization reaction has been developed. In the presence of ketenimines and tBuONa, 1,4,5-trisubstituted imidazoles were obtained. Nonetheless, in the absence of ketenimines, 1,4-disubstituted imidazole was produced through cyclodimerization of TosMIC.


Asunto(s)
Cianuros , Imidazoles , Ciclización , Catálisis
15.
Environ Res ; 204(Pt A): 111966, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34450156

RESUMEN

Microalgae are drawing attentions among researchers for their biorefinery use or value-added products. The high production rate of biomasses produced are attractive for conversion into volatile biochar. Torrefaction, pyrolysis and hydrothermal carbonization are the recommended thermochemical conversion techniques that could produce microalgal-based biochar with desirable physiochemical properties such as high surface area and pore volume, abundant surface functional groups, as well as functionality such as high adsorption capacity. The characterizations of the biochar significantly influence the mechanisms in adsorption of pollutants from wastewaters. Specific adsorption of the organic and inorganic pollutants from the effluent are reviewed to examine the adsorption capacity and efficiency of biochar derived from different microalgae species. Last but not least, future remarks over the challenges and improvements are discussed accordingly. Overall, this review would discuss the synthesis, characterization and application of the microalgal-based biochar in wastewater.


Asunto(s)
Microalgas , Aguas Residuales , Adsorción , Carbón Orgánico
16.
PLoS Pathog ; 15(9): e1007996, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31536610

RESUMEN

The ability of DENV2 to display different morphologies (hence different antigenic properties) complicates vaccine and therapeutics development. Previous studies showed most strains of laboratory adapted DENV2 particles changed from smooth to "bumpy" surfaced morphology when the temperature is switched from 29°C at 37°C. Here we identified five envelope (E) protein residues different between two alternative passage history DENV2 NGC strains exhibiting smooth or bumpy surface morphologies. Several mutations performed on the smooth DENV2 infectious clone destabilized the surface, as observed by cryoEM. Molecular dynamics simulations demonstrated how chemically subtle substitution at various positions destabilized dimeric interactions between E proteins. In contrast, three out of four DENV2 clinical isolates showed a smooth surface morphology at 37°C, and only at high fever temperature (40°C) did they become "bumpy". These results imply vaccines should contain particles representing both morphologies. For prophylactic and therapeutic treatments, this study also informs on which types of antibodies should be used at different stages of an infection, i.e., those that bind to monomeric E proteins on the bumpy surface or across multiple E proteins on the smooth surfaced virus.


Asunto(s)
Virus del Dengue/clasificación , Virus del Dengue/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Animales , Antígenos Virales/química , Antígenos Virales/genética , Línea Celular , Microscopía por Crioelectrón , Virus del Dengue/ultraestructura , Humanos , Modelos Moleculares , Simulación de Dinámica Molecular , Mutación , Dominios y Motivos de Interacción de Proteínas , Homología de Secuencia de Aminoácido , Serogrupo , Temperatura , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunología
17.
Curr Neurol Neurosci Rep ; 21(5): 22, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33710468

RESUMEN

PURPOSE OF REVIEW: Hematoma expansion (HE) is strongly associated with poor clinical outcome and is a compelling target for improving outcome after intracerebral hemorrhage (ICH). Non-contrast computed tomography (NCCT) is widely used in clinical practice due to its faster acquisition at the presence of acute stroke. Recently, imaging markers on NCCT are increasingly used for predicting HE. We comprehensively review the current evidence on HE prediction using NCCT and provide a summary for assessment of these markers in future research studies. RECENT FINDINGS: Predictors of HE on NCCT have been described in reports of several studies. The proposed markers, including swirl sign, blend sign, black hole sign, island sign, satellite sign, and subarachnoid extension, were all significantly associated with HE and poor outcome in their small sample studies after ICH. In summary, the optimal management of ICH remains a therapeutic dilemma. Therefore, using NCCT markers to select patients at high risk of HE is urgently needed. These markers may allow rapid identification and provide potential targets for anti-HE treatments in patients with acute ICH.


Asunto(s)
Hemorragia Cerebral , Accidente Cerebrovascular , Biomarcadores , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Hematoma , Humanos , Tomografía Computarizada por Rayos X
18.
Neurocrit Care ; 35(2): 451-456, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33942209

RESUMEN

OBJECTIVES: Perihemorrhagic edema (PHE) growth has been gradually considered as predictor for outcome of Intracerebral hemorrhage (ICH) patients. The aim of our study was to investigate correlation between non-contrast computed tomography (CT) markers and early PHE growth. METHODS: ICH patients between July 2011 and March 2017 were included in this retrospective analysis. ICH and PHE volumes were measured by using a validated semiautomatic volumetric algorithm. Nonparametric test was used for comparing PHE volume at different time points of non-contrast computed tomography (NCCT) imaging markers. Multivariable linear regression was constructed to study the relationship between NCCT imaging markers and PHE growth over 36 h. RESULTS: A total of 214 patients were included. Nonparametric test showed that PHE volume was significantly different between patients with and without NCCT imaging markers. (all p < 0.05) In multivariable linear regression analysis adjusted for ICH characteristics, blend sign (p = 0.011), black hole sign (p = 0.002), island sign (p < 0.001), and expansion-prone hematoma (p < 0.001) were correlated with PHE growth. Follow-up PHE volume within 36 h after baseline CT scan was associated with blend sign (p = 0.001), island sign (p < 0.001), and expansion-prone hematoma (p < 0.001). CONCLUSION: NCCT imaging markers of hematoma expansion are associated with PHE growth. This suggests that early PHE growth can be predicted using radiology markers on admission CT scan.


Asunto(s)
Hemorragia Cerebral , Hematoma , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/diagnóstico por imagen , Edema , Hematoma/diagnóstico por imagen , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
19.
Neurocrit Care ; 35(1): 62-71, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33174150

RESUMEN

BACKGROUND/OBJECTIVES: To propose a novel definition for hydrocephalus growth and to further describe the association between hydrocephalus growth and poor outcome among patients with intracerebral hemorrhage (ICH). METHODS: We analyzed consecutive patients who presented within 6 h after ICH ictus between July 2011 and June 2017. Follow-up CT scans were performed within 36 h after initial CT scans. The degree of hydrocephalus were evaluated by the hydrocephalus score of Diringer et al. The optimal increase of the hydrocephalus scores between initial and follow-up CT scan was estimated to define hydrocephalus growth. Poor long-term outcome was defined as a modified Rankin Scale of 4-6 at 3 months. Multivariate logistic regression analysis was performed to investigate the hydrocephalus growth for predicting 30-day mortality, 90-day mortality, and poor long-term outcome. RESULTS: A total of 321 patients with ICH were included in the study. Of 64 patients with hydrocephalus growth, 34 (53.1%) patients presented with both concurrent hematoma expansion and intraventricular hemorrhage (IVH) growth. After adjusting for potential confounding factors, hydrocephalus growth independently predicted 30-day mortality, 90-day mortality, and 90-day poor long-term outcome in multivariate logistic regression analysis. Hydrocephalus growth showed higher accuracy for predicting 30-day mortality, 90-day mortality, and poor long-term outcome than IVH growth or hematoma expansion, respectively. CONCLUSIONS: Hydrocephalus growth is defined by strongly predictive of short- or long-term mortality and poor outcome at 90 days, and might be a potential indicator for assisting clinicians for clinical decision-making.


Asunto(s)
Hemorragia Cerebral , Hidrocefalia , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/epidemiología , Hematoma , Humanos , Hidrocefalia/diagnóstico por imagen , Hidrocefalia/epidemiología , Prevalencia , Tomografía Computarizada por Rayos X
20.
Omega (Westport) ; 84(2): 512-524, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32019387

RESUMEN

Suffering experiences are common phenomena in palliative care. In this study, we aim to explore the different patterns of suffering in palliative care. Adult palliative care patients were recruited from the University of Malaya Medical Centre. Suffering scores were charted 3 times a day for a week. The characteristics of the suffering charts were analyzed using SPSS. The patterns of suffering were analyzed using structural pattern recognition. A total of 53 patients participated. The overall trends of suffering were downward (64%), upward (19%), and stable (17%). Median minimum and maximum suffering scores were 2/10 and 6/10, with an average of 3.6/10. Nine patterns of suffering were recognized from categorizing two key characteristics of suffering (intensity and fluctuation)-named S1 to S9. Understanding the different patterns of suffering may lead to better suffering management.


Asunto(s)
Cuidados Paliativos , Estrés Psicológico , Adulto , Humanos
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