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1.
Physiol Rev ; 102(3): 1327-1383, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35166161

RESUMEN

During the past three decades, mice, zebrafish, fruit flies, and Caenorhabditis elegans have been the primary model organisms used for the study of various biological phenomena. These models have also been adopted and developed to investigate the physiological roles of carbonic anhydrases (CAs) and carbonic anhydrase-related proteins (CARPs). These proteins belong to eight CA families and are identified by Greek letters: α, ß, γ, δ, ζ, η, θ, and ι. Studies using model organisms have focused on two CA families, α-CAs and ß-CAs, which are expressed in both prokaryotic and eukaryotic organisms with species-specific distribution patterns and unique functions. This review covers the biological roles of CAs and CARPs in light of investigations performed in model organisms. Functional studies demonstrate that CAs are not only linked to the regulation of pH homeostasis, the classical role of CAs, but also contribute to a plethora of previously undescribed functions.


Asunto(s)
Anhidrasas Carbónicas , Equilibrio Ácido-Base , Animales , Humanos , Ratones , Especificidad de la Especie , Pez Cebra
2.
Proc Natl Acad Sci U S A ; 120(28): e2219543120, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37406092

RESUMEN

Although HIV-1 Gag is known to drive viral assembly and budding, the precise mechanisms by which the lipid composition of the plasma membrane is remodeled during assembly are incompletely understood. Here, we provide evidence that the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) interacts with HIV-1 Gag and through the hydrolysis of sphingomyelin creates ceramide that is necessary for proper formation of the viral envelope and viral maturation. Inhibition or depletion of nSMase2 resulted in the production of noninfectious HIV-1 virions with incomplete Gag lattices lacking condensed conical cores. Inhibition of nSMase2 in HIV-1-infected humanized mouse models with a potent and selective inhibitor of nSMase2 termed PDDC [phenyl(R)-(1-(3-(3,4-dimethoxyphenyl)-2, 6-dimethylimidazo[1,2-b]pyridazin-8-yl) pyrrolidin-3-yl)-carbamate] produced a linear reduction in levels of HIV-1 in plasma. If undetectable plasma levels of HIV-1 were achieved with PDDC treatment, viral rebound did not occur for up to 4 wk when PDDC was discontinued. In vivo and tissue culture results suggest that PDDC selectively kills cells with actively replicating HIV-1. Collectively, this work demonstrates that nSMase2 is a critical regulator of HIV-1 replication and suggests that nSMase2 could be an important therapeutic target with the potential to kill HIV-1-infected cells.


Asunto(s)
VIH-1 , Esfingomielina Fosfodiesterasa , Ratones , Animales , Esfingomielina Fosfodiesterasa/metabolismo , VIH-1/metabolismo , Esfingomielinas/metabolismo , Membrana Celular/metabolismo
3.
Proc Natl Acad Sci U S A ; 120(28): e2219475120, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37406093

RESUMEN

HIV-1 assembly occurs at the inner leaflet of the plasma membrane (PM) in highly ordered membrane microdomains. The size and stability of membrane microdomains is regulated by activity of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) that is localized primarily to the inner leaflet of the PM. In this study, we demonstrate that pharmacological inhibition or depletion of nSMase2 in HIV-1-producer cells results in a block in the processing of the major viral structural polyprotein Gag and the production of morphologically aberrant, immature HIV-1 particles with severely impaired infectivity. We find that disruption of nSMase2 also severely inhibits the maturation and infectivity of other primate lentiviruses HIV-2 and simian immunodeficiency virus, has a modest or no effect on nonprimate lentiviruses equine infectious anemia virus and feline immunodeficiency virus, and has no effect on the gammaretrovirus murine leukemia virus. These studies demonstrate a key role for nSMase2 in HIV-1 particle morphogenesis and maturation.


Asunto(s)
VIH-1 , Virus de la Anemia Infecciosa Equina , Animales , Gatos , Caballos , Ratones , VIH-1/fisiología , Esfingomielina Fosfodiesterasa/metabolismo , Ensamble de Virus , Lentivirus
4.
Biol Reprod ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38910516

RESUMEN

In cattle, the endometrium during diestrus and early pregnancy displays cellular responses that are consequences of prior, transient stimuli. Goal was to establish a model to study cellular memory in the endometrium. The hypothesis is that stimuli given to endometrium in vivo are retained as a cellular memory that remains after bovine uterine epithelial cells (BUECs) are isolated, cultured, and further stimulated in vitro. Objectives were to measure BUEC proliferation/migration and responsiveness to recombinant bovine Interferon-tau (rbIFNT) in vitro: among cows that showed estrus (experiment 1 [Exp1]), cows that became or not pregnant to artificial insemination (Exp2), cows that received or not supplemental progesterone (P4; Exp3) and cows that received or not a COX-1/2 inhibitor (Exp4). Only cows that displayed estrus were included in studies. For all experiments endometrial cytology was collected 4 days after estrus, BUECs were cultured, propagated, and submitted to rbIFNT treatment and an in vitro scratch assay. In Exp1, different cows spontaneously grouped according to proliferative/migratory capacity and responsiveness to rbIFNT of their respective BUECs. In Exp2, BUECs from pregnant cows showed greater rbIFNT responsiveness and cellular proliferation. In Exp3, BUECs from cows supplemented with P4 presented inhibited proliferation and increased expression of RSAD2. In Exp4, Flunixin Meglumine modified rbIFNT responsiveness of BUECs in an IFN-signaling pathway-specific manner. In conclusion, physiological and pharmacological stimuli received by the endometrium in vivo were retained as cellular memory in BUECs, persisted in culture, and changed BUEC proliferation/migration and responsiveness to rbIFNT, which are characteristics associated with fertility in cattle.

5.
J Physiol ; 601(2): 257-274, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36464834

RESUMEN

Carbonic anhydrase V (CA V), a mitochondrial enzyme, was first isolated from guinea-pig liver and subsequently identified in mice and humans. Later, studies revealed that the mouse genome contains two mitochondrial CA sequences, named Car5A and Car5B. The CA VA enzyme is most highly expressed in the liver, whereas CA VB shows a broad tissue distribution. Car5A knockout mice demonstrated a predominant role for CA VA in ammonia detoxification, whereas the roles of CA VB in ureagenesis and gluconeogenesis were evident only in the absence of CA VA. Previous studies have suggested that CA VA is mainly involved in the provision of HCO3 - for biosynthetic processes. In children, mutations in the CA5A gene led to reduced CA activity, and the enzyme was sensitive to increased temperature. The metabolic profiles of these children showed a reduced supply of HCO3 - to the enzymes that take part in intermediary metabolism: carbamoylphosphate synthetase, pyruvate carboxylase, propionyl-CoA carboxylase and 3-methylcrotonyl-CoA carboxylase. Although the role of CA VB is still poorly understood, a recent study reported that it plays an essential role in human Sertoli cells, which sustain spermatogenesis. Metabolic disease associated with CA VA appears to be more common than other inborn errors of metabolism and responds well to treatment with N-carbamyl-l-glutamate. Therefore, early identification of hyperammonaemia will allow specific treatment with N-carbamyl-l-glutamate and prevent neurological sequelae. Carbonic anhydrase VA deficiency should therefore be considered a treatable condition in the differential diagnosis of hyperammonaemia in neonates and young children.


Asunto(s)
Anhidrasas Carbónicas , Hiperamonemia , Animales , Humanos , Inhibidores de Anhidrasa Carbónica/farmacología , Anhidrasas Carbónicas/genética , Anhidrasas Carbónicas/metabolismo , Ácido Glutámico , Hígado/metabolismo
6.
Environ Res ; 219: 114959, 2023 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-36535398

RESUMEN

A ceramic-polymeric membrane was fabricated through in-situ oxidative polymerization of pyrrole (Py) on alumina (Al2O3) ceramic ultrafiltration support. The establishment of polypyrrole (PPy) active layer on the ceramic support led to a new PPy coated ceramic-polymeric membrane. Various salient features such as surface wettability, surface morphology, composition and functional goups of PPy coated ceramic-polymeric membrane were determined by various characterization techniques water contact angle (WCA), scanning electron microscopy (SEM), energy dispersive x-ray (EDX) analysis and attenuated total reflectance fourier transform infrared (ATR-FTIR). The PPy coated ceramic-polymeric membrane showed superhydrophilic nature owing to its under water oil contact angle of ≥160° (superoleophobic). Thanks to stable deposition of PPy active layer on ceramic support, the membrane retained a separation efficiency of >99% for O/W emulsions at varied transmembrane pressures ranging from 0.5 bar to 2 bar with a feed concentration of 125 ppm of oil in water. Moreover, the PPy coated ceramic-polymeric membrane exhibited an ideal behaviour to the applied transmembrane pressure with a linear increase from 380 LMH to 2112 LMH in permeate flux as the pressure increased from 0.5 bar to 2 bar. As the concentration of oil was raised from 50 ppm to 250 ppm, the separation efficeincy separation remained at >99%. From among the different types of oils (Motor oil, Diesel oil and Crude oil) to mimic the oily waste water streams, the permeate flux was found to be highest in case of motor oil with a value reaching to 1690 LMH at 1 bar. The stability test revealed that the PPy coated ceramic-polymeric membrane was able to separate >99% of 125 ppm O/W surfactant stabilized emulsion for a period of 420 min.


Asunto(s)
Petróleo , Purificación del Agua , Aguas Residuales , Polímeros , Pirroles , Porosidad , Membranas Artificiales , Purificación del Agua/métodos , Aceites , Cerámica , Emulsiones
7.
Environ Res ; 238(Pt 2): 117282, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37783329

RESUMEN

Plant diseases pose a severe threat to modern agriculture, necessitating effective and lasting control solutions. Environmental factors significantly shape plant ecology. Human-induced greenhouse gas emissions have led to global temperature rise, impacting various aspects, including carbon dioxide (CO2) concentration, temperature, ozone (O3), and ultraviolet-B, all of which influence plant diseases. Altered pathogen ranges can accelerate disease transmission. This review explores environmental effects on plant diseases, with climate change affecting fungal biogeography, disease incidence, and severity, as well as agricultural production. Moreover, we have discussed how climate change influences pathogen development, host-fungal interactions, the emergence of new races of fungi, and the dissemination of emerging fungal diseases across the globe. The discussion about environment-mediated impact on pattern-triggered immunity (PTI), effector-triggered immunity (ETI), and RNA interference (RNAi) is also part of this review. In conclusion, the review underscores the critical importance of understanding how climate change is reshaping plant-fungal interactions. It highlights the need for continuous research efforts to elucidate the mechanisms driving these changes and their ecological consequences. As the global climate continues to evolve, it is imperative to develop innovative strategies for mitigating the adverse effects of fungal pathogens on plant health and food security.


Asunto(s)
Biodiversidad , Cambio Climático , Humanos , Temperatura , Plantas , Enfermedades de las Plantas/microbiología
8.
J Med Genet ; 59(5): 453-461, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34059554

RESUMEN

BACKGROUND: Minichromosomal maintenance (MCM) complex components 2, 4, 5 and 6 have been linked to human disease with phenotypes including microcephaly and intellectual disability. The MCM complex has DNA helicase activity and is thereby important for the initiation and elongation of the replication fork and highly expressed in proliferating neural stem cells. METHODS: Whole-exome sequencing was applied to identify the genetic cause underlying the neurodevelopmental disease of the index family. The expression pattern of Mcm7 was characterised by performing quantitative real-time PCR, in situ hybridisation and immunostaining. To prove the disease-causative nature of identified MCM7, a proof-of-principle experiment was performed. RESULTS: We reported that the homozygous missense variant c.793G>A/p.A265T (g.7:99695841C>T, NM_005916.4) in MCM7 was associated with autosomal recessive primary microcephaly (MCPH), severe intellectual disability and behavioural abnormalities in a consanguineous pedigree with three affected individuals. We found concordance between the spatiotemporal expression pattern of Mcm7 in mice and a proliferative state: Mcm7 expression was higher in early mouse developmental stages and in proliferative zones of the brain. Accordingly, Mcm7/MCM7 levels were detectable particularly in undifferentiated mouse embryonal stem cells and human induced pluripotent stem cells compared with differentiated neurons. We further demonstrate that the downregulation of Mcm7 in mouse neuroblastoma cells reduces cell viability and proliferation, and, as a proof-of-concept, that this is counterbalanced by the overexpression of wild-type but not mutant MCM7. CONCLUSION: We report mutations of MCM7 as a novel cause of autosomal recessive MCPH and intellectual disability and highlight the crucial function of MCM7 in nervous system development.


Asunto(s)
Células Madre Pluripotentes Inducidas , Discapacidad Intelectual , Microcefalia , Malformaciones del Sistema Nervioso , Animales , Humanos , Discapacidad Intelectual/genética , Ratones , Microcefalia/complicaciones , Microcefalia/genética , Componente 7 del Complejo de Mantenimiento de Minicromosoma/genética , Mutación/genética , Linaje
9.
Proc Natl Acad Sci U S A ; 117(17): 9537-9545, 2020 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-32273392

RESUMEN

P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric, mucin-like, 120-kDa glycoprotein that binds to P-, E-, and L-selectins. PSGL-1 is expressed primarily on the surface of lymphoid and myeloid cells and is up-regulated during inflammation to mediate leukocyte tethering and rolling on the surface of endothelium for migration into inflamed tissues. Although it has been reported that PSGL-1 expression inhibits HIV-1 replication, the mechanism of PSGL-1-mediated anti-HIV activity remains to be elucidated. Here we report that PSGL-1 in virions blocks the infectivity of HIV-1 particles by preventing the binding of particles to target cells. This inhibitory activity is independent of the viral glycoprotein present on the virus particle; the binding of particles bearing the HIV-1 envelope glycoprotein or vesicular stomatitis virus G glycoprotein or even lacking a viral glycoprotein is impaired by PSGL-1. Mapping studies show that the extracellular N-terminal domain of PSGL-1 is necessary for its anti-HIV-1 activity, and that the PSGL-1 cytoplasmic tail contributes to inhibition. In addition, we demonstrate that the PSGL-1-related monomeric E-selectin-binding glycoprotein CD43 also effectively blocks HIV-1 infectivity. HIV-1 infection, or expression of either Vpu or Nef, down-regulates PSGL-1 from the cell surface; expression of Vpu appears to be primarily responsible for enabling the virus to partially escape PSGL-1-mediated restriction. Finally, we show that PSGL-1 inhibits the infectivity of other viruses, such as murine leukemia virus and influenza A virus. These findings demonstrate that PSGL-1 is a broad-spectrum antiviral host factor with a unique mechanism of action.


Asunto(s)
VIH-1/fisiología , Glicoproteínas de Membrana/metabolismo , Acoplamiento Viral , Capa Leucocitaria de la Sangre , Linfocitos T CD4-Positivos , Regulación de la Expresión Génica , Células HeLa , Humanos
10.
Int J Mol Sci ; 24(24)2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38139031

RESUMEN

The conversion of lignocellulosic biomass to second-generation biofuels through enzymes is achieved at a high cost. Filamentous fungi through a combination of oxidative enzymes can easily disintegrate the glycosidic bonds of cellulose. The combination of cellobiose dehydrogenase (CDH) with lytic polysaccharide monooxygenases (LPMOs) enhances cellulose degradation in many folds. CDH increases cellulose deconstruction via coupling the oxidation of cellobiose to the reductive activation of LPMOs by catalyzing the addition of oxygen to C-H bonds of the glycosidic linkages. Fungal LPMOs show different regio-selectivity (C1 or C4) and result in oxidized products through modifications at reducing as well as nonreducing ends of the respective glucan chain. T. reesei LPMOs have shown great potential for oxidative cleavage of cellobiose at C1 and C4 glucan bonds, therefore, the incorporation of heterologous CDH further increases its potential for biofuel production for industrial purposes at a reduced cost. We introduced CDH of Phanerochaete chrysosporium (PcCDH) in Trichoderma reesei (which originally lacked CDH). We purified CDH through affinity chromatography and analyzed its enzymatic activity, electron-donating ability to LPMO, and the synergistic effect of LPMO and CDH on cellulose deconstruction. The optimum temperature of the recombinant PcCDH was found to be 45 °C and the optimum pH of PcCDH was observed as 4.5. PcCDH has high cello-oligosaccharide kcat, Km, and kcat/Km values. The synergistic effect of LPMO and cellulase significantly improved the degradation efficiency of phosphoric acid swollen cellulose (PASC) when CDH was used as the electron donor. We also found that LPMO undergoes auto-oxidative inactivation, and when PcCDH is used an electron donor has the function of a C1-type LPMO electron donor without additional substrate increments. This work provides novel insights into finding stable electron donors for LPMOs and paves the way forward in discovering efficient CDHs for enhanced cellulose degradation.


Asunto(s)
Celobiosa , Oxigenasas de Función Mixta , Oxigenasas de Función Mixta/metabolismo , Electrones , Polisacáridos/metabolismo , Celulosa/metabolismo
11.
Molecules ; 28(8)2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37110639

RESUMEN

Iron oxide nanoparticles (NPs) have attracted substantial interest due to their superparamagnetic features, biocompatibility, and nontoxicity. The latest progress in the biological production of Fe3O4 NPs by green methods has improved their quality and biological applications significantly. In this study, the fabrication of iron oxide NPs from Spirogyra hyalina and Ajuga bracteosa was conducted via an easy, environmentally friendly, and cost-effective process. The fabricated Fe3O4 NPs were characterized using various analytical methods to study their unique properties. UV-Vis absorption peaks were observed in algal and plant-based Fe3O4 NPs at 289 nm and 306 nm, respectively. Fourier transform infrared (FTIR) spectroscopy analyzed diverse bioactive phytochemicals present in algal and plant extracts that functioned as stabilizing and capping agents in the fabrication of algal and plant-based Fe3O4 NPs. X-ray diffraction of NPs revealed the crystalline nature of both biofabricated Fe3O4 NPs and their small size. Scanning electron microscopy (SEM) revealed that algae and plant-based Fe3O4 NPs are spherical and rod-shaped, averaging 52 nm and 75 nm in size. Energy dispersive X-ray spectroscopy showed that the green-synthesized Fe3O4 NPs require a high mass percentage of iron and oxygen to ensure their synthesis. The fabricated plant-based Fe3O4 NPs exhibited stronger antioxidant properties than algal-based Fe3O4 NPs. The algal-based NPs showed efficient antibacterial potential against E. coli, while the plant-based Fe3O4 NPs displayed a higher zone of inhibition against S. aureus. Moreover, plant-based Fe3O4 NPs exhibited superior scavenging and antibacterial potential compared to the algal-based Fe3O4 NPs. This might be due to the greater number of phytochemicals in plants that surround the NPs during their green fabrication. Hence, the capping of bioactive agents over iron oxide NPs improves antibacterial applications.


Asunto(s)
Ajuga , Nanopartículas del Metal , Spirogyra , Nanopartículas del Metal/química , Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Espectroscopía Infrarroja por Transformada de Fourier , Extractos Vegetales/farmacología , Extractos Vegetales/química , Difracción de Rayos X , Pruebas de Sensibilidad Microbiana
12.
Trop Anim Health Prod ; 55(4): 276, 2023 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-37500805

RESUMEN

This study aimed to utilize the XGBoost and MARS algorithms to predict present weight from body measurements. The algorithms have the potential to model nonlinear relationships between body measurements and weight, and this study attempted to find a model that provided the most accurate predictions of present weight. The current study was conducted with 152 animals in order to achieve a certain goal. To compare the model performances, goodness-of-fit criteria such as R2, r, RMSE, CV, SDratio, PI, MAPE, AIC were used. According to the results of this study, the XGBoost algorithm was the most reliable model for predicting present weight from body measurement. Even if the XGBoost algorithm was the most accurate model, the MARS algorithm was the reliable model for the same aim. In addition, it is hoped that the results of this study will help researchers and breeders better understand the relationship between body measurements and weight and ultimately be able to help individuals better manage their weight. As a conclusion, in the current study, the XGBoost algorithm is an effective, efficient, and reliable tool for accurately estimating present weight from body measurements. This makes it an invaluable tool in rural areas, where traditional weighing scales may not be available or reliable.


Asunto(s)
Algoritmos , Animales , Ovinos , Peso Corporal
13.
J Clean Prod ; 389: 135888, 2023 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-36687279

RESUMEN

COVID-19 is a viral disease also comprehended as a coronavirus pandemic that has compelled the world to revisit business strategies to encounter COVID-19 challenges. Over the last decade, ample research has been accomplished on corporate social responsibility (CSR) and circular economy. Nevertheless, a key research gap requires to be filled that how CSR can perform a foremost role in engaging stakeholders like consumers during the COVID-19 era. Drawing from the stakeholder theory, this research endeavors to probe CSR's impact on green purchase intention (GPI) with mediating role of green psychology (GP). Data for the study were gathered from mainland China employing convenience sampling and examined by utilizing SEM (Structural Equation Model). First, the study indicated a direct relationship between CSR and GPI as well as between CSR and GP within three streams, i.e., green trust (GT), green satisfaction (GS), and green perceived value (GPV). It is found that GT, GS, and GPV positively influence GPI whereas the positive mediating relationships of each GP factor were autonomously observed between CSR and GPI, respectively. This research can improve the understanding of the enterprises about consumers and how incorporating green activities may enhance consumers' GPI and GP during the COVID-19 pandemic. This study addresses numerous interesting and insightful implications for strategic management together with certain possibilities for prospective researchers.

14.
Environ Res ; 215(Pt 2): 114282, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36122702

RESUMEN

Drought is common in most regions of the world, and it has a significant impact on plant growth and development. Plants, on the other hand, have evolved their own defense systems to deal with the extreme weather. The reprogramming of gene expression by microRNAs (miRNAs) is one of these defense mechanisms. miRNAs are short noncoding RNAs that have emerged as key post-transcriptional gene regulators in a variety of species. Drought stress modulates the expression of certain miRNAs that are functionally conserved across plant species. These characteristics imply that miRNA-based genetic changes might improve drought resistance in plants. This study highlights current knowledge of plant miRNA biogenesis, regulatory mechanisms and their role in drought stress responses. miRNAs functions and their adaptations by plants during drought stress has also been explained that can be exploited to promote drought-resistance among economically important crops.


Asunto(s)
Sequías , MicroARNs , Productos Agrícolas/metabolismo , Regulación de la Expresión Génica de las Plantas , MicroARNs/genética , Estrés Fisiológico
15.
Proc Natl Acad Sci U S A ; 116(12): 5705-5714, 2019 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-30842281

RESUMEN

The T cell Ig and mucin domain (TIM) proteins inhibit release of HIV-1 and other enveloped viruses by interacting with cell- and virion-associated phosphatidylserine (PS). Here, we show that the Nef proteins of HIV-1 and other lentiviruses antagonize TIM-mediated restriction. TIM-1 more potently inhibits the release of Nef-deficient relative to Nef-expressing HIV-1, and ectopic expression of Nef relieves restriction. HIV-1 Nef does not down-regulate the overall level of TIM-1 expression, but promotes its internalization from the plasma membrane and sequesters its expression in intracellular compartments. Notably, Nef mutants defective in modulating membrane protein endocytic trafficking are incapable of antagonizing TIM-mediated inhibition of HIV-1 release. Intriguingly, depletion of SERINC3 or SERINC5 proteins in human peripheral blood mononuclear cells (PBMCs) attenuates TIM-1 restriction of HIV-1 release, in particular that of Nef-deficient viruses. In contrast, coexpression of SERINC3 or SERINC5 increases the expression of TIM-1 on the plasma membrane and potentiates TIM-mediated inhibition of HIV-1 production. Pulse-chase metabolic labeling reveals that the half-life of TIM-1 is extended by SERINC5 from <2 to ∼6 hours, suggesting that SERINC5 stabilizes the expression of TIM-1. Consistent with a role for SERINC protein in potentiating TIM-1 restriction, we find that MLV glycoGag and EIAV S2 proteins, which, like Nef, antagonize SERINC-mediated diminishment of HIV-1 infectivity, also effectively counteract TIM-mediated inhibition of HIV-1 release. Collectively, our work reveals a role of Nef in antagonizing TIM-1 and highlights the complex interplay between Nef and HIV-1 restriction by TIMs and SERINCs.


Asunto(s)
Infecciones por VIH/metabolismo , Receptor Celular 1 del Virus de la Hepatitis A/fisiología , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/fisiología , Membrana Celular/metabolismo , Regulación hacia Abajo , Células HEK293 , Seropositividad para VIH , VIH-1/metabolismo , VIH-1/patogenicidad , Receptor Celular 1 del Virus de la Hepatitis A/antagonistas & inhibidores , Receptor Celular 1 del Virus de la Hepatitis A/metabolismo , Interacciones Huésped-Patógeno/fisiología , Humanos , Leucocitos Mononucleares/metabolismo , Glicoproteínas de Membrana , Proteínas de la Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Transporte de Proteínas , Receptores de Superficie Celular/metabolismo , Virión/metabolismo , Replicación Viral/efectos de los fármacos , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/metabolismo
16.
Sensors (Basel) ; 22(11)2022 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-35684901

RESUMEN

In Distributed Hash Table (DHT)-based Mobile Ad Hoc Networks (MANETs), a logical structured network (i.e., follows a tree, ring, chord, 3D, etc., structure) is built over the ad hoc physical topology in a distributed manner. The logical structures guide routing processes and eliminate flooding at the control and the data plans, thus making the system scalable. However, limited radio range, mobility, and lack of infrastructure introduce frequent and unpredictable changes to network topology, i.e., connectivity/dis-connectivity, node/link failure, network partition, and frequent merging. Moreover, every single change in the physical topology has an associated impact on the logical structured network and results in unevenly distributed and disrupted logical structures. This completely halts communication in the logical network, even physically connected nodes would not remain reachable due to disrupted logical structure, and unavailability of index information maintained at anchor nodes (ANs) in DHT networks. Therefore, distributed solutions are needed to tolerate faults in the logical network and provide end-to-end connectivity in such an adversarial environment. This paper defines the scope of the problem in the context of DHT networks and contributes a Fault-Tolerant DHT-based routing protocol (FTDN). FTDN, using a cross-layer design approach, investigates network dynamics in the physical network and adaptively makes arrangements to tolerate faults in the logically structured DHT network. In particular, FTDN ensures network availability (i.e., maintains connected and evenly distributed logical structures and ensures access to index information) in the face of failures and significantly improves performance. Analysis and simulation results show the effectiveness of the proposed solutions.

17.
Sensors (Basel) ; 22(7)2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35408338

RESUMEN

The defocus or motion effect in images is one of the main reasons for the blurry regions in digital images. It can affect the image artifacts up to some extent. However, there is a need for automatic defocus segmentation to separate blurred and sharp regions to extract the information about defocus-blur objects in some specific areas, for example, scene enhancement and object detection or recognition in defocus-blur images. The existence of defocus-blur segmentation algorithms is less prominent in noise and also costly for designing metric maps of local clarity. In this research, the authors propose a novel and robust defocus-blur segmentation scheme consisting of a Local Ternary Pattern (LTP) measured alongside Pulse Coupled Neural Network (PCNN) technique. The proposed scheme segments the blur region from blurred fragments in the image scene to resolve the limitations mentioned above of the existing defocus segmentation methods. It is noticed that the extracted fusion of upper and lower patterns of proposed sharpness-measure yields more noticeable results in terms of regions and edges compared to referenced algorithms. Besides, the suggested parameters in the proposed descriptor can be flexible to modify for performing numerous settings. To test the proposed scheme's effectiveness, it is experimentally compared with eight referenced techniques along with a defocus-blur dataset of 1000 semi blurred images of numerous categories. The model adopted various evaluation metrics comprised of Precision, recall, and F1-Score, which improved the efficiency and accuracy of the proposed scheme. Moreover, the proposed scheme used some other flavors of evaluation parameters, e.g., Accuracy, Matthews Correlation-Coefficient (MCC), Dice-Similarity-Coefficient (DSC), and Specificity for ensuring provable evaluation results. Furthermore, the fuzzy-logic-based ranking approach of Evaluation Based on Distance from Average Solution (EDAS) module is also observed in the promising integrity analysis of the defocus blur segmentation and also in minimizing the time complexity.


Asunto(s)
Algoritmos , Redes Neurales de la Computación , Lógica Difusa , Movimiento (Física)
18.
Sensors (Basel) ; 22(1)2022 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-35009878

RESUMEN

The ever-growing ecosystem of the Internet of Things (IoT) integrating with the ever-evolving wireless communication technology paves the way for adopting new applications in a smart society. The core concept of smart society emphasizes utilizing information and communication technology (ICT) infrastructure to improve every aspect of life. Among the variety of smart services, eHealth is at the forefront of these promises. eHealth is rapidly gaining popularity to overcome the insufficient healthcare services and provide patient-centric treatment for the rising aging population with chronic diseases. Keeping in view the sensitivity of medical data, this interfacing between healthcare and technology has raised many security concerns. Among the many contemporary solutions, attribute-based encryption (ABE) is the dominant technology because of its inherent support for one-to-many transfer and fine-grained access control mechanisms to confidential medical data. ABE uses costly bilinear pairing operations, which are too heavy for eHealth's tiny wireless body area network (WBAN) devices despite its proper functionality. We present an efficient and secure ABE architecture with outsourcing intense encryption and decryption operations in this work. For practical realization, our scheme uses elliptic curve scalar point multiplication as the underlying technology of ABE instead of costly pairing operations. In addition, it provides support for attribute/users revocation and verifiability of outsourced medical data. Using the selective-set security model, the proposed scheme is secure under the elliptic curve decisional Diffie-Hellman (ECDDH) assumption. The performance assessment and top-ranked value via the help of fuzzy logic's evaluation based on distance from average solution (EDAS) method show that the proposed scheme is efficient and suitable for access control in eHealth smart societies.


Asunto(s)
Seguridad Computacional , Telemedicina , Anciano , Confidencialidad , Ecosistema , Humanos , Tecnología Inalámbrica
19.
Sensors (Basel) ; 22(1)2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-35009941

RESUMEN

Software-defined network (SDN) and vehicular ad-hoc network (VANET) combined provided a software-defined vehicular network (SDVN). To increase the quality of service (QoS) of vehicle communication and to make the overall process efficient, researchers are working on VANET communication systems. Current research work has made many strides, but due to the following limitations, it needs further investigation and research: Cloud computing is used for messages/tasks execution instead of fog computing, which increases response time. Furthermore, a fault tolerance mechanism is used to reduce the tasks/messages failure ratio. We proposed QoS aware and fault tolerance-based software-defined V vehicular networks using Cloud-fog computing (QAFT-SDVN) to address the above issues. We provided heuristic algorithms to solve the above limitations. The proposed model gets vehicle messages through SDN nodes which are placed on fog nodes. SDN controllers receive messages from nearby SDN units and prioritize the messages in two different ways. One is the message nature way, while the other one is deadline and size way of messages prioritization. SDN controller categorized in safety and non-safety messages and forward to the destination. After sending messages to their destination, we check their acknowledgment; if the destination receives the messages, then no action is taken; otherwise, we use a fault tolerance mechanism. We send the messages again. The proposed model is implemented in CloudSIm and iFogSim, and compared with the latest models. The results show that our proposed model decreased response time by 50% of the safety and non-safety messages by using fog nodes for the SDN controller. Furthermore, we reduced the execution time of the safety and non-safety messages by up to 4%. Similarly, compared with the latest model, we reduced the task failure ratio by 20%, 15%, 23.3%, and 22.5%.

20.
Telemed J E Health ; 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35349350

RESUMEN

Introduction: Back pain is among the most common presentations in primary care offices. National organizations have standardized the appropriate use of imaging for acute low-back pain (LBP). The objective of this study was to evaluate the use of imaging in LBP between telemedicine and in-person clinical encounters. Methods: This retrospective cohort compared secondary data from 20,624 telemedicine and office encounters in a large nonprofit health system from July 1, 2019, to June 30, 2021. The proportion of patients aged 18-50 years who did not receive imaging for acute LBP (X-ray, computed tomography, or magnetic resonance imaging) within 28 days of the provider encounter was measured according to Healthcare Effectiveness Data and Information Set specifications. Performance was compared across race, ethnicity, age, body mass index, overall risk score, and insurance type. Chi-squared tests determined significant differences between cohorts (p < 0.05). Results: Patients seen via telemedicine had significantly lower rates of imaging within 28 days of their physician encounter (office: 16.32%, telemedicine: 11.20%; difference: 5.12%; p < 0.01). This was consistent across racial, ethnic, and risk score subgroups. Discussion: For practices and health systems, telemedicine might be a higher value approach for initial evaluation of acute LBP in primary care. For policy makers, telemedicine can save on health care costs without negatively impacting quality performance measures. Conclusions: Telemedicine is unlikely to compromise quality of acute LBP care, supporting this virtual space as an alternative care venue. The most beneficial use of telemedicine might be triaging initial encounters of acute LBP in primary care. Stronger evidence could support its long-term potential for driving value through cost savings.

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