RESUMEN
Medical images such as CT and X-ray have been widely used for the detection of several chest infections and lung diseases. However, these images are susceptible to different types of noise, and it is hard to remove these noises due to their complex distribution. The presence of such noise significantly deteriorates the quality of the images and significantly affects the diagnosis performance. Hence, the design of an effective de-noising technique is highly essential to remove the noise from chest CT and X-ray images prior to further processing. Deep learning methods, mainly, CNN have shown tremendous progress on de-noising tasks. However, existing CNN based models estimate the noise from the final layers, which may not carry adequate details of the image. To tackle this issue, in this paper a deep multi-level semantic fusion network is proposed, called DMF-Net for the removal of noise from chest CT and X-ray images. The DMF-Net mainly comprises of a dilated convolutional feature extraction block, a cascaded feature learning block (CFLB) and a noise fusion block (NFB) followed by a prominent feature extraction block. The CFLB cascades the features from different levels (convolutional layers) which are later fed to NFB to attain correct noise prediction. Finally, the Prominent Feature Extraction Block(PFEB) produces the clean image. To validate the proposed de-noising technique, a separate and a mixed dataset containing high-resolution CT and X-ray images with specific and blind noise are used. Experimental results indicate the effectiveness of the DMF-Net compared to other state-of-the-art methods in the context of peak signal-to-noise ratio (PSNR) and structural similarity measurement (SSIM) while drastically cutting down on the processing power needed.
Asunto(s)
Semántica , Tomografía Computarizada por Rayos X , Humanos , Rayos X , Relación Señal-Ruido , Procesamiento de Imagen Asistido por ComputadorRESUMEN
Post translational modifications, ubiquitination and its reversal by deubiquitination play an important role in regulating innate immune system. USP12 is a poorly studied deubiquitinase reported to regulate T-cell receptor signalling however the functional role of USP12 in macrophages, the principal architects of inflammation, is unknown. Thus, in this study we probed the involvement of USP12 in macrophage mediated inflammatory responses using bacterial endotoxin, LPS, as the model system. Here, we observed that the expression of USP12 was altered in time dependent manner in LPS stimulated RAW 264.7 macrophages at both mRNA and protein levels as revealed by qPCR and western blot analysis, respectively. Further analysis showed that LPS reduced the levels of Sp1 which enhanced the transcriptional levels of USP12. We observed that siRNA mediated ablation of USP12 expression in mouse macrophages suppressed the induction of LPS-induced iNOS and IL-6 expression but failed to alter IFN-ß synthesis, oxidative stress and phagocytic ability of macrophages. Mechanistic analysis suggest that USP12 may be required for the activation of NFκB pathway as knockdown of USP12 reduced the inhibitory phosphorylation of IκBα, a well characterized inhibitor of NFκB nuclear translocation. Further, USP12 was observed to be required for LPS elicited phosphorylation of ERK1/2 and p38. Collectively, our data suggest that USP12 may be a key mediator of LPS stimulated macrophage responses.
Asunto(s)
Endopeptidasas/metabolismo , Lipopolisacáridos/toxicidad , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Inhibidor NF-kappaB alfa/antagonistas & inhibidores , Animales , Endopeptidasas/deficiencia , Endopeptidasas/genética , Expresión Génica , Técnicas de Silenciamiento del Gen , Inflamación/metabolismo , Interferón gamma/farmacología , Activación de Macrófagos/efectos de los fármacos , Activación de Macrófagos/inmunología , Activación de Macrófagos/fisiología , Macrófagos/inmunología , Ratones , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación , Células RAW 264.7 , ARN Interferente Pequeño/genética , Ubiquitina TiolesterasaRESUMEN
Chronic inflammatory diseases such as insulin resistance, Type 2 diabetes, neurodegenerative diseases etc., are shown to be caused due to imbalanced activation states of macrophages. MicroRNAs which are transcriptional/post-transcriptional regulators of gene expression drive several pathophysiological processes including macrophage polarization. However the functional role of microRNAs in regulating inflammation induced insulin resistance is ill defined. In our current study we observed that the expression of miR-712 was reduced in macrophages exposed to LPS and IFN-γ. Ectopic expression of miR-712 in RAW 264.7 mouse macrophages impaired the expression of iNOS protein and secretion of pro-inflammatory cytokines such as TNF-α, IL-6 and IFN-ß which in turn led to improved insulin stimulated glucose uptake in co-cultured L6 myoblasts. Mechanistically, we identified that miR-712 targets the 3'UTR of a potent inflammatory gene LRRK2 and dampens the phosphorylation of p38 and ERK1/2 kinases. Taken together, our data underscore the regulatory role of miR-712 in restoring insulin stimulated glucose uptake by myoblasts through down-regulating macrophage mediated inflammatory responses.
Asunto(s)
Resistencia a la Insulina/genética , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina/inmunología , Activación de Macrófagos/genética , MicroARNs/inmunología , Mioblastos/metabolismo , Animales , Ensayo de Inmunoadsorción Enzimática , Regulación de la Expresión Génica/inmunología , Glucosa/metabolismo , Immunoblotting , Inflamación/inmunología , Activación de Macrófagos/inmunología , Macrófagos/inmunología , Ratones , Mioblastos/inmunología , Células RAW 264.7 , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Adult-type nicotinic acetylcholine receptors (AChRs) mediate signalling at mature neuromuscular junctions and fetal-type AChRs are necessary for proper synapse development. Each AChR has two neurotransmitter binding sites located at the interface of a principal and a complementary subunit. Although all agonist binding sites have the same core of five aromatic amino acids, the fetal site has â¼30-fold higher affinity for the neurotransmitter ACh. Here we use molecular dynamics simulations of adult versus fetal homology models to identify complementary-subunit residues near the core that influence affinity, and use single-channel electrophysiology to corroborate the results. Four residues in combination determine adult versus fetal affinity. Simulations suggest that at lower-affinity sites, one of these unsettles the core directly and the others (in loop E) increase backbone flexibility to unlock a key, complementary tryptophan from the core. Swapping only four amino acids is necessary and sufficient to exchange function between adult and fetal AChRs.
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Potenciales Postsinápticos Excitadores/fisiología , Subunidades de Proteína/química , Receptores Nicotínicos/química , Factores de Edad , Secuencias de Aminoácidos , Animales , Aplysia/química , Sitios de Unión , Cristalografía por Rayos X , Expresión Génica , Células HEK293 , Humanos , Ratones , Simulación de Dinámica Molecular , Datos de Secuencia Molecular , Unión Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alineación de Secuencia , Transducción de Señal , Homología Estructural de ProteínaAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Receptores de Interleucina-6/antagonistas & inhibidores , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados/farmacología , Femenino , Humanos , Masculino , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Efficient intracellular transport is essential for healthy cellular function and structural integrity, and problems in this pathway can lead to neuronal cell death and disease. To spatially and temporally evaluate how transport defects are initiated, we adapted a primary neuronal culture system from Drosophila larval brains to visualize the movement dynamics of several cargos/organelles along a 90 micron axonal neurite over time. All six vesicles/organelles imaged showed robust bi-directional motility at both day 1 and day 2. Reduction of motor proteins decreased the movement of vesicles/organelles with increased numbers of neurite blocks. Neuronal growth was also perturbed with reduction of motor proteins. Strikingly, we found that all blockages were not fixed, permanent blocks that impeded transport of vesicles as previously thought, but that some blocks were dynamic clusters of vesicles that resolved over time. Taken together, our findings suggest that non-resolving blocks may likely initiate deleterious pathways leading to death and degeneration, while resolving blocks may be benign. Therefore evaluating the spatial and temporal characteristics of vesicle transport has important implications for our understanding of how transport defects can affect other pathways to initiate death and degeneration.
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Transporte Axonal , Animales , Axones/metabolismo , Encéfalo/citología , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citología , Dineínas/metabolismo , Cinesinas/metabolismo , Larva/citología , Análisis Espacio-TemporalRESUMEN
A 36-year-old man presented to the emergency department with a history of trauma to genitalia during intercourse. The patient reported the forceful collision between his penis and the bed and audible clicking sound with swollen penis thereafter. On examination, the genitalia was swollen with an 'S' shaped deformity. The skin over the swelling was apparently normal, with no local rise of temperature. A provisional diagnosis was made after clinical evaluation. Scrotum and testes examination revealed no abnormality. A subcoronal circumferential incision with de-gloving of penile skin was used to access the tunica. A rent in tunica albuginea and corpora cavernosa identified and the defect repaired with absorbable suture material after removal of clot and properly maintaining haemostasis. The patient's postoperative recovery was uneventful. The following case report demonstrates a typical case of fracture penis.
Asunto(s)
Enfermedades del Pene/diagnóstico , Pene/lesiones , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Enfermedades del Pene/cirugía , Resultado del TratamientoRESUMEN
UNLABELLED: Ion channels are fundamental molecules in the nervous system that catalyze the flux of ions across the cell membrane. Ion channel flux activity is comparable to the catalytic activity of enzyme molecules. Saturating concentrations of substrate induce "dynamic disorder" in the kinetic rate processes of single-enzyme molecules and consequently, develop correlative "memory" of the previous history of activities. Similarly, binding of ions as substrate alone or in presence of agonists affects the catalytic turnover of single-ion channels. Here, we investigated the possible existence of dynamic disorder and molecular memory in the single human-TREK1-channel due to binding of substrate/agonist using the excised inside-out patch-clamp technique. Our results suggest that the single-hTREK1-channel behaves as a typical Michaelis-Menten enzyme molecule with a high-affinity binding site for K(+) ion as substrate. But, in contrast to enzyme, dynamic disorder in single-hTREK1-channel was not induced by substrate K(+) binding, but required allosteric modification of the channel molecule by the agonist, trichloroethanol. In addition, interaction of trichloroethanol with hTREK1 induced strong correlation in the waiting time and flux intensity, exemplified by distinct mode-switching between high and low flux activities. This suggested the induction of molecular memory in the channel molecule by the agonist, which persisted for several decades in time. Our mathematical modeling studies identified the kinetic rate processes associated with dynamic disorder. It further revealed the presence of multiple populations of distinct conformations that contributed to the "heterogeneity" and consequently, to the molecular memory phenomenon that we observed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12154-010-0053-3) contains supplementary material, which is available to authorized users.