RESUMEN
Many critical biological processes take place at hydrophobic:hydrophilic interfaces, and a wide range of organisms produce surface-active proteins and peptides that reduce surface and interfacial tension and mediate growth and development at these boundaries. Microorganisms produce both small lipid-associated peptides and amphipathic proteins that allow growth across water:air boundaries, attachment to surfaces, predation, and improved bioavailability of hydrophobic substrates. Higher-order organisms produce surface-active proteins with a wide variety of functions, including the provision of protective foam environments for vulnerable reproductive stages, evaporative cooling, and gas exchange across airway membranes. In general, the biological functions supported by these diverse polypeptides require them to have an amphipathic nature, and this is achieved by a diverse range of molecular structures, with some proteins undergoing significant conformational change or intermolecular association to generate the structures that are surface active.
Asunto(s)
Caseínas/química , Glicoproteínas/química , Proteínas de la Membrana/química , Proteínas de Neoplasias/química , Fosfoproteínas/química , Surfactantes Pulmonares/química , Tensoactivos/química , Animales , Bacterias/química , Bacterias/genética , Bacterias/metabolismo , Caseínas/genética , Caseínas/metabolismo , Hongos/química , Hongos/genética , Hongos/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Mamíferos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Conformación Proteica , Surfactantes Pulmonares/metabolismo , Propiedades de Superficie , Tensoactivos/metabolismo , Agua/química , Agua/metabolismoRESUMEN
The RIP homotypic interaction motif (RHIM) is an essential protein motif in inflammatory signaling and certain cell death pathways. RHIM signaling occurs following the assembly of functional amyloids, and while the structural biology of such higher-order RHIM complexes has started to emerge, the conformations and dynamics of nonassembled RHIMs remain unknown. Here, using solution NMR spectroscopy, we report the characterization of the monomeric form of the RHIM in receptor-interacting protein kinase 3 (RIPK3), a fundamental protein in human immunity. Our results establish that the RHIM of RIPK3 is an intrinsically disordered protein motif, contrary to prediction, and that exchange dynamics between free monomers and amyloid-bound RIPK3 monomers involve a 20-residue stretch outside the RHIM that is not incorporated within the structured cores of the RIPK3 assemblies determined by cryo-EM or solid-state NMR. Thus, our findings expand on the structural characterization of RHIM-containing proteins, specifically highlighting conformational dynamics involved in assembly processes.
Asunto(s)
Amiloide , Proteínas Amiloidogénicas , Humanos , Amiloide/química , Muerte Celular , Proteínas Amiloidogénicas/metabolismo , Transducción de Señal , Espectroscopía de Resonancia Magnética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
The purpose of this study was to evaluate the feasibility and accuracy of remote Video Plethysmography (VPPG) for contactless measurements of blood pressure (BP) and heart rate (HR) in adult surgical patients in a hospital setting. An iPad Pro was used to record a 1.5-minute facial video of the participant's face and VPPG was used to extract vital signs measurements. A standard medical device (Welch Allyn) was used for comparison to measure BP and HR. Trial registration: NCT05165381. Two-hundred-sixteen participants consented and completed the contactless BP and HR monitoring (mean age 54.1 ± 16.8 years, 58% male). The consent rate was 75% and VPPG was 99% successful in capturing BP and HR. VPPG predicted SBP, DBP, and HR with a measurement bias ± SD, -8.18 ± 16.44 mmHg, - 6.65 ± 9.59 mmHg, 0.09 ± 6.47 beats/min respectively. Pearson's correlation for all measurements between VPPG and standard medical device was significant. Correlation for SBP was moderate (0.48), DBP was weak (0.29), and HR was strong (0.85). Most patients were satisfied with the non-contact technology with an average rating of 8.7/10 and would recommend it for clinical use. VPPG was highly accurate in measuring HR, and is currently not accurate in measuring BP in surgical patients. The VPPG BP algorithm showed limitations in capturing individual variations in blood pressure, highlighting the need for further improvements to render it clinically effective across all ranges. Contactless vital signs monitoring was well-received and earned a high satisfaction score.
Asunto(s)
Atención Perioperativa , Pletismografía , Adulto , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Presión Sanguínea/fisiología , Frecuencia CardíacaRESUMEN
The accurate recording of respiratory rate (RR) without contact is important for patient care. The current methods for RR measurement such as capnography, pneumography, and plethysmography require patient contact, are cumbersome, or not accurate for widespread clinical use. Video Plethysmography (VPPG) is a novel automated technology that measures RR using a facial video without contact. The objective of our study was to determine whether VPPG can feasibly and accurately measure RR without contact in surgical patients at a clinical setting. After research ethics approval, 216 patients undergoing ambulatory surgery consented to the study. Patients had a 1.5 min video of their faces taken via an iPad preoperatively, which was analyzed using VPPG to obtain RR information. The RR prediction by VPPG was compared to 60-s manual counting of breathing by research assistants. We found that VPPG predicted RR with 88.8% accuracy and a bias of 1.40 ± 1.96 breaths per minute. A significant and high correlation (0.87) was observed between VPPG-predicted and manually recorded RR. These results did not change with the ethnicity of patients. The success rate of the VPPG technology was 99.1%. Contactless RR monitoring of surgical patients at a hospital setting using VPPG is accurate and feasible, making this technology an attractive alternative to the current approaches to RR monitoring. Future developments should focus on improving reliability of the technology.
Asunto(s)
Pletismografía , Frecuencia Respiratoria , Humanos , Reproducibilidad de los Resultados , Monitoreo Fisiológico/métodos , RespiraciónRESUMEN
OBJECTIVES: This study aims to determine the malnutrition status among Vietnamese patients newly diagnosed with gastric cancer (GC). BACKGROUND: GC remains the top rank of common and deadly diseases. With limited clinical manifestation, most GC patients were diagnosed at late stages when tumor is not radically resected. Malnutrition was associated with poor prognosis of GC, such as prolonged hospitalization, limited treatment efficacy and low survival rate. METHODS: The cross-sectional descriptive study recruited 77 patients newly diagnosed with GC and 90 healthy individuals (HC). The data used for this study were approved by the local Ethical Committee. The data were analysed on STATA 14.0 and GraphPad Prism 8.0. RESULTS: We observed the male dominant distribution in GC cohort and over 65% of GC were firstly diagnosed at advanced stages (III and IV). Anemia was detected in about 50% of GC patients. Hyponutrition was prevalent in newly diagnosed GC. We found the decreased tendency of anemia related indexes from HC to early stages (I and II) and advanced stages (III and IV) of GC patients. CONCLUSION: Anemia and hypoproteinemia occurred frequently among Vietnamese newly diagnosed GC. The nutrition therapy would benefit GC patients (Tab. 4, Fig. 4, Ref. 20).
Asunto(s)
Anemia , Desnutrición , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Masculino , Femenino , Estudios Transversales , Persona de Mediana Edad , Vietnam/epidemiología , Anemia/diagnóstico , Anemia/etiología , Desnutrición/diagnóstico , Desnutrición/epidemiología , Anciano , Adulto , Estadificación de NeoplasiasRESUMEN
Chimeric antigen receptor (CAR) T cells and PD-1 antibodies (PD-1 Ab) are emergent immunotherapies with unprecedented efficacy. The presence of PD-1 on T cells contributes to hypofunction of CAR-T therapy and inhibition of PD-1 enhances anti-cancer effect of CAR-T cells. Therefore, the combination of CAR-T cells and PD-1 antibody is a promissing strategy for cancer treatment. This study aims to establish our in-house CAR-T cells and evaluate the safety of CAR-T cells in combination with PD-1 antibody in animals. The toxicity of CD19-CAR-T cells was examined using Swiss Webster mice. Four mouse groups were treated with control, CAR-T, PD-1 antibody or CAR-T + PD-1 antibody. Mice's overall status was monitored and recorded. At the end-point, hematological and biochemical indices were quantified, histopathology of liver and kidney was evaluated by pathologists. The relative abnormal ratio and absolute values were compared between groups. We generated our in-house CAR-T cells and used them for safety evaluation in mice. The increase in mouse weight was observed in all groups after treatment and the weight was comparable between groups. The hematological, biochemical and histopathological parameters were equivalent between groups, except for liver grain degeneration occurred in treatment groups. Thus, CAR-T cells, PD-1 Ab and their combination were safe in mice. We successfully produced our in-house CAR-T cells and the combination of our CAR-T cells and PD-1 antibody was safe in mice with comparable values of hematopoietic indices, liver and kidney functions. Longer follow-up might be necessary to evaluate their effect on the liver.
Asunto(s)
Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Ratones , Animales , Receptor de Muerte Celular Programada 1 , Línea Celular Tumoral , Linfocitos T , Anticuerpos , Inmunoterapia Adoptiva , Modelos TeóricosRESUMEN
Hydrophobins are remarkable proteins due to their ability to self-assemble into amphipathic coatings that reverse surface wettability. Here, the versatility of the Class I hydrophobins EASΔ15 and DewY in diverse nanosuspension and coating applications is demonstrated. The hydrophobins are shown to coat or emulsify a range of substrates including oil, hydrophobic drugs, and nanodiamonds and alter their solution and surface behavior. Surprisingly, while the coatings confer new properties, only a subset is found to be resistant to hot detergent treatment, a feature previously thought to be characteristic of the functional amyloid form of Class I hydrophobins. These results demonstrate that substrate surface properties can influence the molecular structures and physiochemical properties of hydrophobin and possibly other functional amyloids. Functional amyloid assembly with different substrates and conditions may be analogous to the propagation of different polymorphs of disease-associated amyloid fibrils with distinct structures, stability, and clinical phenotypes. Given that amyloid formation is not required for Class I hydrophobins to serve diverse applications, our findings open up new opportunities for their use in applications requiring a range of chemical and physical properties. In hydrophobin nanotechnological applications where high stability of assemblies is required, simultaneous structural and functional characterization should be carried out. Finally, while results in this study pertain to synthetic substrates, they raise the possibility that at least some members of the pseudo-Class I and Class III hydrophobins, reported to form assemblies with noncanonical properties, may be Class I hydrophobins adopting alternative structures in response to environmental cues.
Asunto(s)
Amiloide , Proteínas Fúngicas , Proteínas Fúngicas/química , Humectabilidad , Interacciones Hidrofóbicas e Hidrofílicas , Propiedades de Superficie , Secuencia de Aminoácidos , Amiloide/química , Proteínas AmiloidogénicasRESUMEN
BACKGROUND: In clinical obstetrics, many guidelines recommended the use of Doppler fetal ductus venosus blood flow to monitor and to manage fetal growth restriction (FGR). The ductus venosus and the pulmonary venous flow pattern of fetuses are similar. Umbilical artery pH (UA pH) is essential in identifying adverse pregnancy outcomes, particularly in fetal growth restriction cases. Nevertheless, the literature indicates that the relationship between pulmonary vein pulsatility index (PVPI) and UA pH in FGR cases has not been well investigated. This study aimed to identify the alteration in PVPI in FGR cases and evaluate the correlation between PVPI and UA pH in FGR newborns. METHODS: This matched cohort study of singleton pregnancies from 28+ 0 to 40+ 0 weeks of gestation without congenital abnormalities included 135 cases of FGR (disease group) and 135 cases of normal growth (control group). The PVPI was measured at the proximal segment of the right or left pulmonary vein, approximately 5 mm from the left atrium wall. The umbilical artery pulsatility index (UAPI) was measured on the free umbilical cord. An elective cesarean section or labor induction are both options for ending the pregnancy, depending on the condition of the mother or fetus. Umbilical artery blood samples were collected within 5 min of delivery for UA pH measurement. SPSS version 20 and Medcalc version 20.1 were used for data analysis. RESULTS: FGR cases had a significantly higher mean fetal PVPI than the control group (1.16 ± 0.26 vs. 0.84 ± 0.16; p < 0.01), and PVPI and UAPI were positively correlated (r = 0.63; p < 0.001). PVPI and UA pH were negatively correlated in FGR patients, with r = -0.68; p < 0.001. The PVPI value on the 95th percentile had a prognostic value of UA pH < 7.20 with a sensitivity of 88.2%, specificity of 66.3%, positive predictive value of 46.9%, and negative predictive value of 94.3%. CONCLUSIONS: There was a statistically significant difference in PVPI values in FGR cases compared to the normal growth group, a positive correlation between PVPI and UAPI, and a negative correlation between PVPI and UA pH. PVPI might have a prognostic meaning in predicting UA pH at birth.
Asunto(s)
Venas Pulmonares , Recién Nacido , Embarazo , Humanos , Femenino , Venas Pulmonares/diagnóstico por imagen , Arterias Umbilicales/diagnóstico por imagen , Cesárea , Estudios de Cohortes , Retardo del Crecimiento Fetal/diagnóstico por imagen , Pueblos del Sudeste AsiáticoRESUMEN
Nucleosome-nucleosome interactions drive the folding of nucleosomal arrays into dense chromatin fibers. A better physical account of the folding of chromatin fibers is necessary to understand the role of chromatin in regulating DNA transactions. Here, we studied the unfolding pathway of regular chromatin fibers as a function of single base pair increments in linker length, using both rigid base-pair Monte Carlo simulations and single-molecule force spectroscopy. Both computational and experimental results reveal a periodic variation of the folding energies due to the limited flexibility of the linker DNA. We show that twist is more restrictive for nucleosome stacking than bend, and find the most stable stacking interactions for linker lengths of multiples of 10 bp. We analyzed nucleosomes stacking in both 1- and 2-start topologies and show that stacking preferences are determined by the length of the linker DNA. Moreover, we present evidence that the sequence of the linker DNA also modulates nucleosome stacking and that the effect of the deletion of the H4 tail depends on the linker length. Importantly, these results imply that nucleosome positioning in vivo not only affects the phasing of nucleosomes relative to DNA but also directs the higher-order structure of chromatin.
Asunto(s)
Cromatina/química , ADN/química , Nucleosomas/química , Histonas/genética , Modelos Moleculares , Método de Montecarlo , Conformación de Ácido NucleicoRESUMEN
In recent years, the rapid development of deep learning approaches has paved the way to explore the underlying factors that explain the data. In particular, several methods have been proposed to learn to identify and disentangle these underlying explanatory factors in order to improve the learning process and model generalization. However, extracting this representation with little or no supervision remains a key challenge in machine learning. In this paper, we provide a theoretical outlook on recent advances in the field of unsupervised representation learning with a focus on auto-encoding-based approaches and on the most well-known supervised disentanglement metrics. We cover the current state-of-the-art methods for learning disentangled representation in an unsupervised manner while pointing out the connection between each method and its added value on disentanglement. Further, we discuss how to quantify disentanglement and present an in-depth analysis of associated metrics. We conclude by carrying out a comparative evaluation of these metrics according to three criteria, (i) modularity, (ii) compactness and (iii) informativeness. Finally, we show that only the Mutual Information Gap score (MIG) meets all three criteria.
RESUMEN
The Receptor-interacting protein kinase Homotypic Interaction Motif (RHIM) is an amino acid sequence that mediates multiple protein:protein interactions in the mammalian programmed cell death pathway known as necroptosis. At least one key RHIM-based complex has been shown to have a functional amyloid fibril structure, which provides a stable hetero-oligomeric platform for downstream signaling. RHIMs and related motifs are present in immunity-related proteins across nature, from viruses to fungi to metazoans. Necroptosis is a hallmark feature of cellular clearance of infection. For this reason, numerous pathogens, including viruses and bacteria, have developed varied methods to modulate necroptosis, focusing on inhibiting RHIM:RHIM interactions, and thus their downstream cell death effects. This review will discuss current understanding of RHIM:RHIM interactions in normal cellular activation of necroptosis, from a structural and cell biology perspective. It will compare the mechanisms by which pathogens subvert these interactions in order to maintain their replicative and infective cycles and consider the similarities between RHIMs and other functional amyloid-forming proteins associated with cell death and innate immunity. It will discuss the implications of the heteromeric nature and structure of RHIM-based amyloid complexes in the context of other functional amyloids.
Asunto(s)
Apoptosis/inmunología , Necroptosis/inmunología , Proteína Serina-Treonina Quinasas de Interacción con Receptores/inmunología , Animales , Humanos , Inmunidad Innata/inmunología , Unión Proteica , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismoRESUMEN
Herpesviruses are known to encode a number of inhibitors of host cell death, including RIP Homotypic Interaction Motif (RHIM)-containing proteins. Varicella zoster virus (VZV) is a member of the alphaherpesvirus subfamily and is responsible for causing chickenpox and shingles. We have identified a novel viral RHIM in the VZV capsid triplex protein, open reading frame (ORF) 20, that acts as a host cell death inhibitor. Like the human cellular RHIMs in RIPK1 and RIPK3 that stabilise the necrosome in TNF-induced necroptosis, and the viral RHIM in M45 from murine cytomegalovirus that inhibits cell death, the ORF20 RHIM is capable of forming fibrillar functional amyloid complexes. Notably, the ORF20 RHIM forms hybrid amyloid complexes with human ZBP1, a cytoplasmic sensor of viral nucleic acid. Although VZV can inhibit TNF-induced necroptosis, the ORF20 RHIM does not appear to be responsible for this inhibition. In contrast, the ZBP1 pathway is identified as important for VZV infection. Mutation of the ORF20 RHIM renders the virus incapable of efficient spread in ZBP1-expressing HT-29 cells, an effect which can be reversed by the inhibition of caspases. Therefore we conclude that the VZV ORF20 RHIM is important for preventing ZBP1-driven apoptosis during VZV infection, and propose that it mediates this effect by sequestering ZBP1 into decoy amyloid assemblies.
Asunto(s)
Muerte Celular/fisiología , Herpesvirus Humano 3/metabolismo , Proteínas de Unión al ARN/metabolismo , Infección por el Virus de la Varicela-Zóster/metabolismo , Proteínas Virales/metabolismo , Animales , Humanos , RatonesRESUMEN
Pollution status and distribution characteristics of ten typical phthalic acid esters (PAEs) were investigated in 36 sediment samples collected from three rivers in Northern Vietnam from June to October 2020. The total concentrations of PAEs in sediment samples collected from the To Lich River (n = 9), the Nhue River (n = 12), and the Day River (n = 15) were in ranges of 11,000-125,000 ng/g-dwt (mean/median: 50,000/42,200 ng/g-dwt), 2140-89,900 ng/g-dwt (mean/median: 29,300/20,700 ng/g-dwt), and 1140-43,100 ng/g-dwt (mean/median: 13,800/10,400 ng/g-dwt), respectively. Among ten PAEs studied, di-(2-ethylhexyl) phthalate (DEHP) was found at the highest levels in all samples meanwhile dimethyl phthalate (DMP), diethyl phthalate (DEP), and dipropyl phthalate (DPP) were detected at low frequency and concentration. Significant correlations have existed between the median-chain (C4-C7) PAE pairs in sediment samples. Due to the high accumulation in the sediments, the median-chain PAEs had a higher ecological risk than the short-chain (C1-C3) PAEs. These contaminants may present a longstanding influence on organisms and ecosystems.
Asunto(s)
Ácidos Ftálicos , Contaminantes Químicos del Agua , China , Dibutil Ftalato , Ecosistema , Ésteres , Sedimentos Geológicos , Medición de Riesgo , Ríos , Vietnam , Contaminantes Químicos del Agua/análisisRESUMEN
The objective of this systematic review and meta-analysis was to analyze the effectiveness of contactless vital sign monitors that utilize a consumer-friendly camera versus medical grade instruments. A multiple database search was conducted from inception to September 2020. Inclusion criteria were as follows: studies that used a consumer-grade camera (smartphone/webcam) to examine contactless vital signs in adults; evaluated the non-contact device against a reference medical device; and used the participants' face for measurement. Twenty-six studies were included in the review of which 16 were included in Pearson's correlation and 14 studies were included in the Bland-Altman meta-analysis. Twenty-two studies measured heart rate (HR) (92%), three measured blood pressure (BP) (12%), and respiratory rate (RR) (12%). No study examined blood oxygen saturation (SpO2). Most studies had a small sample size (≤ 30 participants) and were performed in a laboratory setting. Our meta-analysis found that consumer-grade contactless vital sign monitors were accurate in comparison to a medical device in measuring HR. Current contactless monitors have limitations such as motion, poor lighting, and lack of automatic face tracking. Currently available consumer-friendly contactless monitors measure HR accurately compared to standard medical devices. More studies are needed to assess the accuracy of contactless BP and RR monitors. Implementation of contactless vital sign monitors for clinical use will require validation in a larger population, in a clinical setting, and expanded to encompass other vital signs including BP, RR, and SpO2.
Asunto(s)
Frecuencia Respiratoria , Signos Vitales , Adulto , Frecuencia Cardíaca , Humanos , Monitoreo Fisiológico , OximetríaRESUMEN
One of the most significant limitations of oximeters is their performance under poor perfusion conditions. This systematic review examines pulse oximeter model accuracy in adults under poor perfusion conditions. A multiple database search was conducted from inception to December 2020. The inclusion criteria were as follows: (1) adult participants (> 18 years) with explicitly stated conditions that cause poor peripheral perfusion (conditions localized at the oximeter placement site; or systemic conditions, including critical conditions such as hypothermia, hypotension, hypovolemia, and vasoconstricting agents use; or experimental conditions) (2) a comparison of arterial oxygen saturation and arterial blood gas values. A total of 22 studies were included and assessed for reliability and agreement using a modified Guidelines for Reporting Reliability and Agreement Studies tool. We calculated the accuracy root mean square error from bias and precision we extracted from the studies. Most oximeters (75%) were deemed accurate in patients with poor perfusion. Modern oximeters utilizing more complex algorithms were more likely to be accurate than older models. Earlobe placement of oximeters seemed more sensitive, with greater measurement accuracy, than on fingertip placement. Only one study controlled for skin pigmentation, and none strictly followed Food and Drug Association recommendations for experiments to determine oximeter accuracy. Oximeters are accurate in poorly perfused patients, especially newer oximeter models and those placed on earlobes. Further studies are needed that examine multiple oximeter models used on a diverse selection of patients while following FDA recommendations to examine oximeter accuracy.
Asunto(s)
Oximetría , Saturación de Oxígeno , Adulto , Humanos , Oxígeno , Perfusión , Reproducibilidad de los ResultadosRESUMEN
TIR-domain-containing adapter-inducing interferon-ß (TRIF) is an innate immune protein that serves as an adaptor for multiple cellular signalling outcomes in the context of infection. TRIF is activated via ligation of Toll-like receptors 3 and 4. One outcome of TRIF-directed signalling is the activation of the programmed cell death pathway necroptosis, which is governed by interactions between proteins that contain a RIP Homotypic Interaction Motif (RHIM). TRIF contains a RHIM sequence and can interact with receptor interacting protein kinases 1 (RIPK1) and 3 (RIPK3) to initiate necroptosis. Here, we demonstrate that the RHIM of TRIF is amyloidogenic and supports the formation of homomeric TRIF-containing fibrils. We show that the core tetrad sequence within the RHIM governs the supramolecular organisation of TRIF amyloid assemblies, although the stable amyloid core of TRIF amyloid fibrils comprises a much larger region than the conserved RHIM only. We provide evidence that RHIMs of TRIF, RIPK1 and RIPK3 interact directly to form heteromeric structures and that these TRIF-containing hetero-assemblies display altered and emergent properties that likely underlie necroptosis signalling in response to Toll-like receptor activation.
Asunto(s)
Amiloide , Necroptosis , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras del Transporte Vesicular/genética , Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Amiloide/metabolismo , Apoptosis/fisiologíaRESUMEN
We report the observation of gravity-capillary waves on a torus of fluid. By means of an original technique, a stable torus is achieved by depositing water on a superhydrophobic groove with a shallow wedge-shaped channel running along its perimeter. Using a spatiotemporal optical measurement, we report the full dispersion relation of azimuthal waves propagating along the inner and outer torus borders, highlighting several branches modeled as varicose, sinuous, and sloshing modes. Standing azimuthal waves are also studied leading to polygonlike patterns arising on the two torus borders with a number of sides different when a tunable decoupling of the two interfaces occurs. The quantized nature of the dispersion relation is also evidenced.
RESUMEN
The murine cytomegalovirus protein M45 protects infected mouse cells from necroptotic death and, when heterologously expressed, can protect human cells from necroptosis induced by tumour necrosis factor receptor (TNFR) activation. Here, we show that the N-terminal 90 residues of the M45 protein, which contain a RIP homotypic interaction motif (RHIM), are sufficient to confer protection against TNFR-induced necroptosis. This N-terminal region of M45 drives rapid self-assembly into homo-oligomeric amyloid fibrils and interacts with the RHIMs of the human kinases RIPK1 and RIPK3, and the Z-DNA binding protein 1 (ZBP1), to form heteromeric amyloid fibrils in vitro Mutation of the tetrad residues in the M45 RHIM attenuates homo- and hetero-amyloid assembly by M45, suggesting that the amyloidogenic nature of the M45 RHIM underlies its biological activity. The M45 RHIM preferentially interacts with RIPK3 and ZBP1 over RIPK1 and alters the properties of the host RHIM protein assemblies. Our results indicate that M45 mimics the interactions made by RIPK1 or ZBP1 with RIPK3, thereby forming heteromeric amyloid structures, which may explain its ability to inhibit necroptosis.
Asunto(s)
Amiloide/metabolismo , Necroptosis , Agregación Patológica de Proteínas/metabolismo , Multimerización de Proteína , Ribonucleótido Reductasas/metabolismo , Proteínas Virales/metabolismo , Amiloide/química , Amiloide/ultraestructura , Amiloidosis/etiología , Amiloidosis/metabolismo , Amiloidosis/patología , Animales , Proteínas Portadoras/química , Proteínas Portadoras/metabolismo , Línea Celular , Humanos , Ratones , Modelos Moleculares , Unión Proteica , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Ribonucleótido Reductasas/química , Relación Estructura-Actividad , Proteínas Virales/químicaRESUMEN
PURPOSE: Obstructive sleep apnea (OSA) may increase the risk of severe COVID-19; however, the level of potential modulation has not yet been established. The objective of the study was to determine the association between high risk of OSA, comorbidities, and increased risk for COVID-19, hospitalization, and intensive care unit (ICU) treatment. METHODS: We conducted a cross-sectional population-based web survey in adults in 14 countries/regions. The survey included sociodemographic variables and comorbidities. Participants were asked questions about COVID-19, hospitalization, and ICU treatment. Standardized questionnaire (STOP questionnaire for high risk of OSA) was included. Multivariable logistic regression was conducted adjusting for various factors. RESULTS: Out of 26,539 respondents, 20,598 (35.4% male) completed the survey. Mean age and BMI of participants were 41.5 ± 16.0 years and 24.0 ± 5.0 kg/m2, respectively. The prevalence of physician-diagnosed OSA was 4.1% and high risk of OSA was 9.5%. We found that high risk of OSA (adjusted odds ratio (aOR) 1.72, 95% confidence interval (CI): 1.20, 2.47) and diabetes (aOR 2.07, 95% CI: 1.23, 3.48) were associated with reporting of a COVID-19 diagnosis. High risk for OSA (aOR 2.11, 95% CI: 1.10-4.01), being male (aOR: 2.82, 95% CI: 1.55-5.12), having diabetes (aOR: 3.93, 95% CI: 1.70-9.12), and having depression (aOR: 2.33, 95% CI: 1.15-4.77) were associated with increased risk of hospitalization or ICU treatment. CONCLUSIONS: Participants at high risk of OSA had increased odds of having COVID-19 and were two times more likely to be hospitalized or treated in ICU.
Asunto(s)
Prueba de COVID-19/estadística & datos numéricos , COVID-19/epidemiología , Estado de Salud , Apnea Obstructiva del Sueño/epidemiología , Adulto , COVID-19/diagnóstico , Comorbilidad , Estudios Transversales , Depresión/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Factores Sexuales , Apnea Obstructiva del Sueño/diagnóstico , Ronquido/epidemiologíaRESUMEN
AIM: This study aimed to evaluate the unique phenotype of the Vietnamese polycystic ovarian syndrome (PCOS) population. METHODS: In this multicenter cross-sectional descriptive study, a total of 901 reproductive-age women were recruited at three medical centers in Vietnam from June 2016 to May 2018. Group I included 479 patients with PCOS (Rotterdam 2003 consensus) and Group II included 422 non-PCOS women, consisted of women with regular menstrual cycle, collected at the same time of PCOS recruitment, without ovarian disease or ovarian failure. Main outcome measures were anthropomorphic, serum hormone, ultrasound and physical characteristics of PCOS. RESULTS: The Vietnamese PCOS population was lean, but with a higher weight and body mass index compared to controls. About 34.4% of PCOS subjects had hirsutism, primarily confined to the leg, arm and pubis. The PCOS population had higher serum luteinizing hormone (LH), LH : follicle stimulating hormone ratio, anti-Mullerian hormone and testosterone. The PCOS population had double the ovarian volume compared to controls. PCOS subjects had no increase in metabolic disease history and had on average optimal serum markers for low metabolic disease risk. Group D (O + polycystic ovary morphology [PCOM]) was the most prevalent phenotype noted in our Vietnamese PCOS cohort (67.6%). Modified Ferriman-Gallwey, levels of LH, testosterone and anti-Mullerian hormone were highest in Group A (O + H + PCOM) and lowest in Group D (O + PCOM). CONCLUSION: The Vietnamese PCOS population is characterized by a lean body type, nonfacial hirsutism, anovulatory, enlarged ovaries and typical PCOS serum hormone markers, low risk factors for metabolic syndrome. Nonclassical phenotypes for PCOS were more frequent than the classic phenotype.