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Transient molecules in the gastrointestinal tract such as nitric oxide and hydrogen sulfide are key signals and mediators of inflammation. Owing to their highly reactive nature and extremely short lifetime in the body, these molecules are difficult to detect. Here we develop a miniaturized device that integrates genetically engineered probiotic biosensors with a custom-designed photodetector and readout chip to track these molecules in the gastrointestinal tract. Leveraging the molecular specificity of living sensors1, we genetically encoded bacteria to respond to inflammation-associated molecules by producing luminescence. Low-power electronic readout circuits2 integrated into the device convert the light emitted by the encapsulated bacteria to a wireless signal. We demonstrate in vivo biosensor monitoring in the gastrointestinal tract of small and large animal models and the integration of all components into a sub-1.4 cm3 form factor that is compatible with ingestion and capable of supporting wireless communication. With this device, diseases such as inflammatory bowel disease could be diagnosed earlier than is currently possible, and disease progression could be more accurately tracked. The wireless detection of short-lived, disease-associated molecules with our device could also support timely communication between patients and caregivers, as well as remote personalized care.
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Biomarcadores , Técnicas Biosensibles , Sulfuro de Hidrógeno , Inflamación , Óxido Nítrico , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/metabolismo , Modelos Animales , Tracto Gastrointestinal/metabolismo , Tracto Gastrointestinal/microbiología , Cápsulas/administración & dosificación , Probióticos/metabolismo , Bacterias/metabolismo , Luminiscencia , Progresión de la Enfermedad , Inflamación/diagnóstico , Inflamación/metabolismo , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Sulfuro de Hidrógeno/análisis , Sulfuro de Hidrógeno/metabolismo , Tecnología Inalámbrica/instrumentación , Administración Oral , Tecnología de Sensores Remotos/instrumentación , Tecnología de Sensores Remotos/métodos , Factores de Tiempo , Humanos , Tamaño CorporalRESUMEN
Epigenetic regulation of chromatin states is crucial for proper gene expression programs and progression during development, but precise mechanisms by which epigenetic factors influence differentiation remain poorly understood. Here we find that the histone variant H2A.Z accumulates at Sox motif-containing promoters during zebrafish gastrulation while neighboring genes become transcriptionally active. These changes coincide with reduced expression of anp32e, the H2A.Z histone removal chaperone, suggesting that loss of Anp32e may lead to increases in H2A.Z binding during differentiation. Remarkably, genetic removal of Anp32e in embryos leads to H2A.Z accumulation prior to gastrulation and developmental genes become precociously active. Accordingly, H2A.Z accumulation occurs most extensively at Sox motif-associated genes, including many which are normally activated following gastrulation. Altogether, our results provide compelling evidence for a mechanism in which Anp32e preferentially restricts H2A.Z accumulation at Sox motifs to regulate the initial phases of developmental differentiation in zebrafish.
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Histonas , Pez Cebra , Animales , Histonas/genética , Histonas/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo , Gastrulación/genética , Epigénesis Genética , Cromatina , NucleosomasRESUMEN
During sea-level exercise, blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) in humans without a patent foramen ovale (PFO) is negatively correlated with pulmonary pressure. Yet, it is unknown whether the superior exercise capacity of Tibetans well adapted to living at high altitude is the result of lower pulmonary pressure during exercise in hypoxia, and whether their cardiopulmonary characteristics are significantly different from lowland natives of comparable ancestry (e.g. Han Chinese). We found a 47% PFO prevalence in male Tibetans (n = 19) and Han Chinese (n = 19) participants. In participants without a PFO (n = 10 each group), we measured heart structure and function at rest and peak oxygen uptake ( V Ì O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ ), peak power output ( W Ì p e a k ${{\dot{W}}_{peak}}$ ), pulmonary artery systolic pressure (PASP), blood flow through IPAVA and cardiac output ( Q Ì T ${{\dot{Q}}_{\mathrm{T}}} $ ) at rest and during recumbent cycle ergometer exercise at 760 Torr (SL) and at 410 Torr (ALT) barometric pressure in a pressure chamber. Tibetans achieved a higher W peak ${W}_{\textit{peak}}$ than Han, and a higher V Ì O 2 peak ${{\dot{V}}_{{{{\mathrm{O}}}_{\mathrm{2}}}{\mathrm{peak}}}}$ at ALT without differences in heart rate, stroke volume or Q Ì T ${{\dot{Q}}_{\mathrm{T}}} $ . Blood flow through IPAVA was generally similar between groups. Increases in PASP and total pulmonary resistance at ALT were comparable between the groups. There were no differences in the slopes of PASP plotted as a function of Q Ì T ${{\dot{Q}}_{\mathrm{T}}} $ during exercise. In those without PFO, our data indicate that the superior aerobic exercise capacity of Tibetans over Han Chinese is independent of cardiopulmonary features and more probably linked to differences in local muscular oxygen extraction. KEY POINTS: Patent foramen ovale (PFO) prevalence was 47% in Tibetans and Han Chinese living at 2 275 m. Subjects with PFO were excluded from exercise studies. Compared to Han Chinese, Tibetans had a higher peak workload with acute compression to sea level barometric pressure (SL) and acute decompression to 5000 m altitude (ALT). Comprehensive cardiac structure and function at rest were not significantly different between Han Chinese and Tibetans. Tibetans and Han had similar blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) during exercise at SL. Peak pulmonary artery systolic pressure (PASP) and total pulmonary resistance were different between SL and ALT, with significantly increased PASP for Han compared to Tibetans at ALT. No differences were observed between groups at acute SL and ALT.
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Ejercicio Físico , Hemodinámica , Descanso , Humanos , Masculino , Ejercicio Físico/fisiología , Tibet , Adulto , Hemodinámica/fisiología , Descanso/fisiología , Pueblo Asiatico , Adulto Joven , Consumo de Oxígeno/fisiología , Gasto Cardíaco/fisiología , Altitud , Arteria Pulmonar/fisiología , Pueblos del Este de AsiaRESUMEN
RESEARCH HIGHLIGHTS: IDS presented pathognomonic dilatation of the jejunum up to Meckel's diverticulum.IDS caused weight loss, decreased egg production, and increased culling and mortality.Chicken parvovirus (ChPV) was consistently detected through PCR assays.Chicken megrivirus (ChMV) was consistently detected through viral metagenomics.
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Plastic surgeons routinely use 3D-models in their clinical practice, from 3D-photography and surface imaging to 3D-segmentations from radiological scans. However, these models continue to be viewed on flattened 2D screens that do not enable an intuitive understanding of 3D-relationships and cause challenges regarding collaboration with colleagues. The Metaverse has been proposed as a new age of applications building on modern Mixed Reality headset technology that allows remote collaboration on virtual 3D-models in a shared physical-virtual space in real-time. We demonstrate the first use of the Metaverse in the context of reconstructive surgery, focusing on preoperative planning discussions and trainee education. Using a HoloLens headset with the Microsoft Mesh application, we performed planning sessions for 4 DIEP-flaps in our reconstructive metaverse on virtual patient-models segmented from routine CT angiography. In these sessions, surgeons discuss perforator anatomy and perforator selection strategies whilst comprehensively assessing the respective models. We demonstrate the workflow for a one-on-one interaction between an attending surgeon and a trainee in a video featuring both viewpoints as seen through the headset. We believe the Metaverse will provide novel opportunities to use the 3D-models that are already created in everyday plastic surgery practice in a more collaborative, immersive, accessible, and educational manner.
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BACKGROUND: Microsurgical breast reconstruction using abdominal tissue is a complex procedure, in part, due to variable vascular/perforator anatomy. Preoperative computed tomography angiography (CTA) has mitigated this challenge to some degree; yet it continues to pose certain challenges. The ability to map perforators with Mixed Reality has been demonstrated in case studies, but its accuracy has not been studied intraoperatively. Here, we compare the accuracy of "HoloDIEP" in identifying perforator location (vs. Doppler ultrasound) by using holographic 3D models derived from preoperative CTA. METHODS: Using a custom application on HoloLens, the deep inferior epigastric artery vascular tree was traced in 15 patients who underwent microsurgical breast reconstruction. Perforator markings were compared against the 3D model in a coordinate system centered on the umbilicus. Holographic- and Doppler-identified markings were compared using a perspective-corrected photo technique against the 3D model along with measurement of duration of perforator mapping for each technique. RESULTS: Vascular points in HoloDIEP skin markings were -0.97 ± 6.2 mm (perforators: -0.62 ± 6.13 mm) away from 3D-model ground-truth in radial length from the umbilicus at a true distance of 10.81 ± 6.14 mm (perforators: 11.40 ± 6.15 mm). Absolute difference in radial distance was twice as high for Doppler markings compared with Holo-markings (9.71 ± 6.16 and 4.02 ± 3.20 mm, respectively). Only in half of all cases (7/14), more than 50% of the Doppler-identified points were reasonably close (<30 mm) to 3D-model ground-truth. HoloDIEP was twice as fast as Doppler ultrasound (76.9s vs. 150.4 s per abdomen). CONCLUSION: HoloDIEP allows for faster and more accurate intraoperative perforator mapping than Doppler ultrasound.
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Acute bilateral vision loss (ABVL) is a rare and challenging diagnostic issue that is most often caused by a neurological disorder. Since it can be the presenting symptom of potentially life-threatening diseases, priority should be given to excluding such diagnoses. Special caution is required if ABVL symptoms result after an intracranial intervention. This article reports on a diagnostic approach for a patient suffering from ABVL due to vitreous hemorrhage related to a subarachnoid hemorrhage (SAH) after endovascular intracranial aneurysm treatment. This case study highlights the importance of imaging interpretation and its consequences.
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Aneurisma Intracraneal , Hemorragia Subaracnoidea , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/cirugía , Hemorragia Vítrea/complicaciones , Hemorragia Vítrea/diagnósticoRESUMEN
We assess the theoretical feasibility of percutaneous posterior sacral foramen (pSF) needle puncture of the sacral dural sac (DS) by studying the three-dimensional imaging anatomy of pSFs relative to the sacral canal (SC). On CT images of 40 healthy subjects, we retrospectively studied sacral alae passageways from SC to pSFs in all three planes to determine if an imaginary spinal needle could theoretically traverse S1 or S2 pSFs in a straight path toward DS. If not straight, we measured multiplane angulations and morphometrics of this route. We found no straight connections between S1 or S2 pSFs and SC. Instead, there were bilateral spatially complex dorsoventral M-shaped "foraminal conduits" (FCs; common, ventral, and dorsal) from SC to anterior SFs and pSFs that would prevent percutaneous straight needle puncture of the DS. This detailed knowledge of the sacral FCs will be useful for accurate imaging interpretation and interventional procedures on the sacrum.
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Región Sacrococcígea , Sacro , Humanos , Sacro/diagnóstico por imagen , Sacro/cirugía , Estudios Retrospectivos , Estudios de Factibilidad , Tomografía Computarizada por Rayos X/métodosRESUMEN
The caudolenticular (or transcapsular) gray bridges (CLGBs) connect the caudate nucleus (CN) and putamen across the internal capsule. The CLGBs function as the main efferent terminus from premotor and supplementary motor area cortex to the basal ganglia (BG). We conjectured if inherent variations in numbers and sizes of CLGBs could contribute to abnormal cortical-subcortical connectivity in Parkinson's disease (PD), a neurodegenerative disorder featuring a hindrance of BG processing. However, there are no literature accounts of normative anatomy and morphometry of CLGBs. We therefore retrospectively analyzed axial and coronal 3T fast spoiled gradient-echo magnetic resonance images (MRIs) of 34 healthy individuals for bilateral CLGBs symmetry, their numbers, dimensions of thickest and longest bridge, and axial surface areas of CN head and putamen. We calculated Evans' index (EI) to account for any brain atrophy. We statistically tested associations between sex or age and measured dependent variables, and linear correlations between all measured variables (significance at p < 0.05). Study subjects were F:M = 23:11 with mean age 49.9 years. All EI's were normal (<0.3). All but three CLGBs were bilaterally symmetrical with a mean 7.4 CLGBs per side. Mean CLGBs thickness and lengths were 1.0 and 4.6 mm, respectively; CN head and putamen areas were 205 and 382.0 mm2 , respectively. Females had thicker CLGBs (p = 0.02) but we found no significant interactions between sex or age and measured dependent variables, and no correlations between CN head or putamen areas and CLGBs dimensions. These normative MRI dimensions of the CLGBs will help guide future studies on the possible role of CLGBs morphometry in PD predisposition.
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Encéfalo , Enfermedad de Parkinson , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen , Enfermedad de Parkinson/patología , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Online supplemental material is available for this article.
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COVID-19 , Neumonía , COVID-19/diagnóstico por imagen , Humanos , SARS-CoV-2 , Tórax , Tomografía Computarizada por Rayos XRESUMEN
PAX6 haploinsufficiency related aniridia is characterized by disorder of limbal epithelial cells (LECs) and aniridia related keratopathy. In the limbal epithelial cells of aniridia patients, deregulated retinoic acid (RA) signaling components were identified. We aimed to visualize differentiation marker and RA signaling component expression in LECs, combining a differentiation triggering growth condition with a small interfering RNA (siRNA) based aniridia cell model (PAX6 knock down). Primary LECs were isolated from corneoscleral rims of healthy donors and cultured in serum free low Ca2+ medium (KSFM) and in KSFM supplemented with 0.9 mmol/L Ca2+. In addition, LECs were treated with siRNA against PAX6. DSG1, PAX6, KRT12, KRT 3, ADH7, RDH10, ALDH1A1, ALDH3A1, STRA6, CYP1B1, RBP1, CRABP2, FABP5, PPARG, VEGFA and ELOVL7 expression was determined using qPCR and western blot. DSG1, FABP5, ADH7, ALDH1A1, RBP1, CRABP2 and PAX6 mRNA and FABP5 protein expression increased (p ≤ 0.03), PPARG, CYP1B1 mRNA expression decreased (p ≤ 0.0003) and DSG1 protein expression was only visible after Ca2+ supplementation. After PAX6 knock down and Ca2+ supplementation, ADH7 and ALDH1A1 mRNA and DSG1 and FABP5 protein expression decreased (p ≤ 0.04), compared to Ca2+ supplementation alone. Using our cell model, with Ca2+ supplementation and PAX6 knockdown with siRNA treatment against PAX6, we provide evidence that haploinsufficiency of the master regulatory gene PAX6 contributes to differentiation defect in the corneal epithelium through alterations of RA signalling. Upon PAX6 knockdown, DSG1 differentiation marker and FABP5 RA signaling component mRNA expression decreases. A similar effect becomes apparent at protein level though differentiation triggering Ca2+ supplementation in the siRNA-based aniridia cell model. Expression data from this cell model and from our siRNA aniridia cell model strongly indicate that FABP5 expression is PAX6 dependent. These new findings may lead to a better understanding of differentiation processes in LECs and are able to explain the insufficient cell function in AAK.
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Aniridia , Desmogleína 1 , Proteínas de Unión a Ácidos Grasos , Factor de Transcripción PAX6 , Aniridia/genética , Antígenos de Diferenciación , Desmogleína 1/biosíntesis , Desmogleína 1/genética , Células Epiteliales/metabolismo , Proteínas de Unión a Ácidos Grasos/biosíntesis , Proteínas de Unión a Ácidos Grasos/genética , Proteínas de Unión a Ácidos Grasos/metabolismo , Humanos , Factor de Transcripción PAX6/genética , Factor de Transcripción PAX6/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Tretinoina/metabolismoRESUMEN
Mesostructured pillared zeolite materials in the form of lamellar phases with a crystal structure of mordenite (MOR) and ZSM-5 (MFI) were grown using CTAB as an agent that creates mesopores, in a one-pot synthesis; then into the CTAB layers separating the 2D zeolite plates were introduced by diffusion the TEOS molecules which were further hydrolyzed, and finally the material was annealed to remove the organic phase, leaving the 2D zeolite plates separated by pillars of silicon dioxide. To monitor the successive structural changes and the state of the atoms of the zeolite framework and organic compounds at all the steps of the synthesis of pillared MOR and MFI zeolites, the nuclear magnetic resonance method (NMR) with magic angle spinning (MAS) was applied. The 27Al and 29Si MAS NMR spectra confirm the regularity of the zeolite frameworks of the as synthetized materials. Analysis of the 1H and 13C MAS NMR spectra and an experiment with variable contact time evidence a strong interaction between the charged "heads" -[N(CH3)3]+ of CTAB and the zeolite framework at the place of [AlO4]- location. According to 27Al and 29Si MAS NMR the evacuation of organic cations leads to a partial but not critical collapse of the local zeolite structure.
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Silicatos de Aluminio/química , Resonancia Magnética Nuclear Biomolecular/métodos , Zeolitas/química , Aluminio , Rastreo Diferencial de Calorimetría , Cetrimonio/química , Cristalización , Isótopos , Microscopía Electrónica de Rastreo , Silicio , Espectrometría por Rayos X , Termogravimetría , Difracción de Rayos XRESUMEN
Chronic kidney disease (CKD) leads to increased skeletal muscle fatigue, weakness, and atrophy. Previous work has implicated mitochondria within the skeletal muscle as a mediator of muscle dysfunction in CKD; however, the mechanisms underlying mitochondrial dysfunction in CKD are not entirely known. The purpose of this study was to define the impact of uremic metabolites on mitochondrial energetics. Skeletal muscle mitochondria were isolated from C57BL/6N mice and exposed to vehicle (DMSO) or varying concentrations of uremic metabolites: indoxyl sulfate, indole-3-acetic-acid, l-kynurenine, and kynurenic acid. A comprehensive mitochondrial phenotyping platform that included assessments of mitochondrial oxidative phosphorylation (OXPHOS) conductance and respiratory capacity, hydrogen peroxide production (JH2O2), matrix dehydrogenase activity, electron transport system enzyme activity, and ATP synthase activity was employed. Uremic metabolite exposure resulted in a ~25-40% decrease in OXPHOS conductance across multiple substrate conditions (P < 0.05, n = 5-6/condition), as well as decreased ADP-stimulated and uncoupled respiratory capacity. ATP synthase activity was not impacted by uremic metabolites; however, a screen of matrix dehydrogenases indicated that malate and glutamate dehydrogenases were impaired by some, but not all, uremic metabolites. Assessments of electron transport system enzymes indicated that uremic metabolites significantly impair complex III and IV. Uremic metabolites resulted in increased JH2O2 under glutamate/malate, pyruvate/malate, and succinate conditions across multiple levels of energy demand (all P < 0.05, n = 4/group). Disruption of mitochondrial OXPHOS was confirmed by decreased respiratory capacity and elevated superoxide production in cultured myotubes. These findings provide direct evidence that uremic metabolites negatively impact skeletal muscle mitochondrial energetics, resulting in decreased energy transfer, impaired complex III and IV enzyme activity, and elevated oxidant production.
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Transporte de Electrón/fisiología , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Oxidorreductasas/metabolismo , Animales , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fosforilación Oxidativa , Consumo de Oxígeno/fisiología , Insuficiencia Renal Crónica/metabolismoRESUMEN
PAX6-related Aniridia is a sight-threatening disease involving progression of secondary glaucoma and aniridia related keratopathy (ARK). Change or loss of limbal epithelial progenitors causes epithelial surface defects. We analyzed the effect of PAX6 on mRNA expression changes with a two-step approach, as follows. First, we sequenced mRNA from limbal epithelial cells isolated from controls and aniridia patients. Second, we confirmed the bioinformatics and literature-based result list for a small interfering RNA (siRNA)-based primary aniridia cell model (PAX6 knockdown). With this approach, we expected that the genes directly influenced by PAX6 would be distinguishable from those affected secondarily by the ARK disease state. Therefore, epithelial cells were isolated from the limbus region of two patients with aniridia and cultured in keratinocyte serum-free medium. Normal control cells were obtained from the limbus region of corneal donors. For the siRNA-based aniridia cell model, cells were transfected with Lipofectamine and 5â¯nM siRNA against PAX6 or control treatment. All cells were lysed to yield DNA, RNA, and protein. Reduction of PAX6 protein was assessed by western blot. Aniridia and control Poly-A-enriched RNA libraries were subjected to next-generation sequencing. The differential analysis was a combination of quantification with RSEM and differential tests with edgeR. Gene lists were filtered by comparison to NCBI GEO datasets, annotated with DAVID, and manually annotated using a literature search. Based on the resulting filtered gene list, qPCR primers were purchased, and candidate genes (TP63, ABCG2, ADH7, ALDH1A1, PITX1, DKK1, DSG1, KRT12, KRT3, KRT13, SPINK6, SPINK7, CTSV, SERPINB1) were verified by qPCR on the siRNA-based aniridia cell model. We identified genes that might be regulated by PAX6 and showed that SPINK7 mRNA, which codes for a protease inhibitor, is downregulated in patients as well as in our primary aniridia cell model. ALDH1A1 and AHD7 mRNA levels were reduced in limbal epithelial cells of aniridia patients, and both transcripts were downregulated by PAX6 knockdown in our cell model. This siRNA-based aniridia cell model is a valuable tool for confirming identified PAX6-affected genes that might promote ARK pathogenesis. The model recapitulated expression changes for SPINK7, ADH7, and ALDH1A1 that were also observed in patient samples. These results provide evidence that PAX6 might drive corneal epithelial differentiation by direct or indirect control of retinoic acid signaling processes through ADH7 and ALDH1A1.
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Alcohol Deshidrogenasa/genética , Aldehído Deshidrogenasa/genética , Aniridia/genética , Epitelio Corneal/metabolismo , Limbo de la Córnea/metabolismo , Transducción de Señal/fisiología , Tretinoina/metabolismo , Familia de Aldehído Deshidrogenasa 1 , Western Blotting , Diferenciación Celular , Células Cultivadas , Enfermedades de la Córnea/genética , Enfermedades de la Córnea/metabolismo , Regulación de la Expresión Génica/fisiología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Modelos Biológicos , Factor de Transcripción PAX6/fisiología , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Retinal-Deshidrogenasa , Inhibidores de Serinpeptidasas Tipo Kazal/genética , TransfecciónRESUMEN
Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis. Since the UPR is strategically positioned to sense and integrate metabolic stress signals, it is likely that - apart from its adaptive response to restore proteostasis - it also directly affects metabolic pathways. Here we investigate the direct role of the UPR in glucose homeostasis. O-GlcNAc is a post-translational modification that is highly responsive to glucose fluctuations. We find that UPR activation results in decreased O-GlcNAc modification, in line with reduced glucose metabolism. Our data indicate that UPR activation has no direct impact on the upstream processes in glucose metabolism; glucose transporter expression, glucose uptake and hexokinase activity. In contrast, prolonged UPR activation decreases glycolysis and mitochondrial metabolism. Decreased mitochondrial respiration is not accompanied by apoptosis or a structural change in mitochondria indicating that the reduction in metabolic rate upon UPR activation is a physiological non-apoptotic response. Metabolic decrease is prevented if the IRE1 pathway of the UPR is inhibited. This indicates that activation of IRE1 signaling induces a reduction in glucose metabolism, as part of an adaptive response.
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Acetilglucosamina/metabolismo , Endorribonucleasas/genética , Glucosa/deficiencia , Neuronas/metabolismo , Procesamiento Proteico-Postraduccional , Proteínas Serina-Treonina Quinasas/genética , Respuesta de Proteína Desplegada , Adaptación Fisiológica , Transporte Biológico , Línea Celular Tumoral , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/ultraestructura , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico/genética , Endorribonucleasas/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Glucólisis/genética , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hexoquinasa/genética , Hexoquinasa/metabolismo , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Neuronas/citología , Fosforilación Oxidativa , Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Activación TranscripcionalRESUMEN
PAX6 is a master gene of ocular development and postnatal ocular equilibrium. Congenital aniridia is the hallmark of PAX6 gene haploinsufficiency (Chr. 11 p. 13), but PAX6-associated aniridia is a profound, progressive pan-ocular developmental disorder often leading to blindness. There is congenital visual impairment with advancing loss of vision mainly due to secondary glaucoma and to corneal blindness caused by limbal stem cell insufficiency (LSCI). LSCI leads to ARK (aniridia-related keratopathy), which typically develops in four stages. Incipient LSCI with vessels starting to grow into the cornea can be imaged by fluorescein anterior segment angiography, which enables fine vessels to be more easily detected than by routine slit lamp examination, especially in patients with nystagmus. Thus, clinical stage 1 ARK is often diagnosed at stage 2 by angiography. Corneal neovascularizations often start at the 12 and 6 positions and subsequently progress circumferentially, not at the 3 and 9 positions as previously believed. Anterior segment angiography can provide an easily standardizable tool for monitoring progress, treatment-induced regress or stabilization of ARK. Especially in children, angiography could be used to monitor new treatment regimens for reducing LSCI. Angiography could enable treatment to begin earlier to preserve corneal hemostasis. In addition, the fact that vascularization often starts at the subpalpebral 6 and 12 positions as opposed to the 3 and 9 positions raises more questions concerning factors that promote LSCI and related corneal injuries. Clin. Anat. 31:392-397, 2018. © 2018 Wiley Periodicals, Inc.
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Aniridia/diagnóstico por imagen , Angiografía , Aniridia/genética , Progresión de la Enfermedad , Humanos , Factor de Transcripción PAX6/genética , Nicho de Células MadreRESUMEN
The endoscope is thought to provide an improved exposure of the internal acoustic meatus after retrosigmoid craniotomy for microsurgical resection of intrameatal tumors. The aim of this study is to quantify the differences in internal acoustic meatus (IAM) exposure comparing microscopic and endoscopic visualization. A retrosigmoid approach was performed on 5 cadaver heads. A millimeter gauge was introduced into the internal acoustic meatus, and examinations with a surgical microscope and 0°, 30° and 70° rigid endoscopes were performed. The extent of IAM depth visualized with the microscope and the different angled endoscopes were analyzed. The microscopic view allowed an average IAM depth visualization of 2.8 mm. The endoscope allowed an improved exposure of IAM in all cases. The 0°, 30° and 70° endoscopes permitted an exposure that was respectively 96% (5.5 mm), 139% (6.7 mm) and 200% (8.4 mm) more lateral than the microscopic view. Angled optics, however, provided an image distortion, specifically the 70° endoscope. The endoscope provides a superior visualization of the IAM compared to the microscope when using a retrosigmoid approach. The 30° endoscope represented an ideal compromise of superior visualization with marginal image distortion. Additional implementation of the endoscope into microsurgery of intrameatal tumors likely facilitates complete tumor removal and might spare facial and vestibulocochlear function. Clin. Anat. 31:398-403, 2018. © 2017 Wiley Periodicals, Inc.
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Oído/cirugía , Oído/anatomía & histología , Endoscopía , Femenino , Humanos , Masculino , MicroscopíaRESUMEN
To provide insight into the clinical anatomy of Tenon's capsule and to describe a technique to manage sclerocorneal defects using autologous Tenon's tissue. A thin layer of Tenon's capsule harvested from the patient's own eye is used to seal the defect and act as a scaffold. The Tenon's flap is spread over the defect and held in place by Vicryl sutures. A bandage contact lens is then placed on the eye. Tenon's capsule is composed of thick fibrous tissue with smooth muscle fibers and a thin posterior capsule of orbital fat. It is rich in fibroblasts, which can accelerate wound healing and eventually lead to robust scarring without risk of immunogenicity and without cost. Tenonplasty uses easily-available autologous Tenon's tissue in patients with sclerocorneal defects to preserve globe morphology. The technique is a feasible alternative not limited by the availability of graft tissue. Clin. Anat. 31:72-76, 2018. © 2017 Wiley Periodicals, Inc.
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Perforación Corneal/cirugía , Cirugía Filtrante , Procedimientos Quirúrgicos Oftalmológicos/métodos , Procedimientos de Cirugía Plástica/métodos , Pterigion/cirugía , Enfermedades de la Esclerótica/cirugía , Cápsula de Tenon/trasplante , Córnea/cirugía , Humanos , Esclerótica/cirugía , Técnicas de Sutura , Trabeculectomía/métodos , Cicatrización de HeridasRESUMEN
Acanthameoba keratitis is a serious ophthalmological condition with a potentially vision-threatening prognosis. Early diagnosis and recognition of relapse, and the detection of persistent Acanthamoeba cysts, are essential for informing the prognosis and managing the condition. We suggest the use of in vivo confocal microscopy not only to identify the early signs of relapse after keratoplasty in patients with Acanthamoeba keratitis, but also as an additional follow-up tool after antimicrobial crosslinking. This study shows that in vivo confocal microscopy is, in experienced hands, a quick and reliable diagnostic tool. Clin. Anat. 31:60-63, 2018. © 2017 Wiley Periodicals, Inc.