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Monogenic syndromes are associated with neurodevelopmental changes that result in cognitive impairments, neurobehavioral phenotypes including autism and attention deficit hyperactivity disorder (ADHD), and seizures. Limited studies and resources are available to make meaningful headway into the underlying molecular mechanisms that result in these symptoms. One such example is DeSanto-Shinawi Syndrome (DESSH), a rare disorder caused by pathogenic variants in the WAC gene. Individuals with DESSH syndrome exhibit a recognizable craniofacial gestalt, developmental delay/intellectual disability, neurobehavioral symptoms that include autism, ADHD, behavioral difficulties and seizures. However, no thorough studies from a vertebrate model exist to understand how these changes occur. To overcome this, we developed both murine and zebrafish Wac/wac deletion mutants and studied whether their phenotypes recapitulate those described in individuals with DESSH syndrome. We show that the two Wac models exhibit craniofacial and behavioral changes, reminiscent of abnormalities found in DESSH syndrome. In addition, each model revealed impacts to GABAergic neurons and further studies showed that the mouse mutants are susceptible to seizures, changes in brain volumes that are different between sexes and relevant behaviors. Finally, we uncovered transcriptional impacts of Wac loss of function that will pave the way for future molecular studies into DESSH. These studies begin to uncover some biological underpinnings of DESSH syndrome and elucidate the biology of Wac, with advantages in each model.
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Entheses are classified into three types: fibrocartilaginous, fibrous, and periosteal insertions. However, the mechanism behind the development of fibrous entheses and periosteal insertions remains unclear. Since both entheses are part of the temporomandibular joint (TMJ), this study analyzes the TMJ entheses. Here, we show that SOX9 expression is negatively regulated during TMJ enthesis development, unlike fibrocartilage entheses which are modularly formed by SCX and SOX9 positive progenitors. The TMJ entheses was adjacent to the intramembranous bone rather than cartilage. SOX9 expression was diminished during TMJ enthesis development. To clarify the functional role of Sox9 in the development of TMJ entheses, we examined these structures in TMJ using Wnt1Cre;Sox9flox/+ reporter mice. Wnt1Cre;Sox9flox/+ mice showed enthesial deformation at the TMJ. Next, we also observed a diminished SOX9 expression area at the enthesis in contact with the clavicle's membranous bone portion, similar to the TMJ entheses. Together, these findings reveal that the timing of SOX9 expression varies with the ossification development mode.
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Osteogénesis , Factor de Transcripción SOX9 , Articulación Temporomandibular , Factor de Transcripción SOX9/metabolismo , Factor de Transcripción SOX9/genética , Animales , Ratones , Articulación Temporomandibular/metabolismo , Articulación Temporomandibular/crecimiento & desarrollo , Osteogénesis/genética , Regulación hacia Abajo , Fibrocartílago/metabolismo , Ratones TransgénicosRESUMEN
The Society for Craniofacial Genetics and Developmental Biology (SCGDB) held its 46th Annual Meeting at Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio on October 10th-12th, 2023. On the first day of the meeting, Drs. Sally Moody and Justin Cotney were each honored with the SCGDB Distinguished Scientist Awards for their exceptional contributions to the field of craniofacial biology. The following two days of the meeting featured five sessions that highlighted new discoveries in signaling and genomic mechanisms regulating craniofacial development, human genetics, translational and regenerative approaches, and clinical management of craniofacial differences. Interactive workshops on spatial transcriptomics and scientific communication, as well as a poster session facilitated meaningful interactions among the 122 attendees representing diverse career stages and research backgrounds in developmental biology and genetics, strengthened the SCGDB community.
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Anomalías Craneofaciales , Biología Evolutiva , Humanos , Anomalías Craneofaciales/genética , Anomalías Craneofaciales/patologíaRESUMEN
The calvaria (top part of the skull) is made of pieces of bone as well as multiple soft tissue joints called sutures. The latter is crucial to the growth and morphogenesis of the skull, and thus a loss of calvarial sutures can lead to severe congenital defects in humans. During embryogenesis, the calvaria develops from the cranial mesenchyme covering the brain, which contains cells originating from the neural crest and the mesoderm. While the mechanism that patterns the cranial mesenchyme into bone and sutures is not well understood, function of Lmx1b, a gene encoding a LIM-domain homeodomain transcription factor, plays a key role in this process. In the current study, we investigated a difference in the function of Lmx1b in different parts of the calvaria using neural crest-specific and mesoderm-specific Lmx1b mutants. We found that Lmx1b was obligatory for development of the interfrontal suture and the anterior fontanel along the dorsal midline of the skull, but not for the posterior fontanel over the midbrain. Also, Lmx1b mutation in the neural crest-derived mesenchyme, but not the mesoderm-derived mesenchyme, had a non-cell autonomous effect on coronal suture development. Furthermore, overexpression of Lmx1b in the neural crest lineage had different effects on the position of the coronal suture on the apical part and the basal part. Other unexpected phenotypes of Lmx1b mutants led to an additional finding that the coronal suture and the sagittal suture are of dual embryonic origin. Together, our data reveal a remarkable level of regional specificity in regulation of calvarial development.
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Myostatin (Myo) is known to suppress skeletal muscle growth, and was recently reported to control tendon homeostasis. The purpose of the present study was to investigate the regulatory involvement of Myo in the myotendinous junction (MTJ) in vivo and in vitro. After Achilles tendon injury in mice, we identified unexpected cell accumulation on the tendon side of the MTJ. At postoperative day 7 (POD7), the nuclei had an egg-like profile, whereas at POD28 they were spindle-shaped. The aspect ratio of nuclei on the tendon side of the MTJ differed significantly between POD7 and POD28 (p = 4.67 × 10-34). We then investigated Myo expression in the injured Achilles tendon. At the MTJ, Myo expression was significantly increased at POD28 relative to POD7 (p = 0.0309). To investigate the action of Myo in vitro, we then prepared laminated sheets of myoblasts (C2C12) and fibroblasts (NIH3T3) (a pseudo MTJ model). Myo did not affect the expression of Pax7 and desmin (markers of muscle development), scleraxis and temonodulin (markers of tendon development), or Sox9 (a common marker of muscle and tendon development) in the cell sheets. However, Myo changed the nuclear morphology of scleraxis-positive cells arrayed at the boundary between the myoblast sheet and the fibroblast sheet (aspect ratio of the cell nuclei, myostatin(+) vs. myostatin(-): p = 0.000134). Myo may strengthen the connection at the MTJ in the initial stages of growth and wound healing.
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Tendón Calcáneo , Unión Miotendinosa , Ratones , Animales , Miostatina/genética , Células 3T3 NIH , Músculos/fisiología , Músculo EsqueléticoRESUMEN
We report a proteogenomic analysis of pancreatic ductal adenocarcinoma (PDAC). Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. Messenger RNA-protein abundance correlations revealed potential prognostic biomarkers correlated with patient survival. Integrated clustering of mRNA, protein and phosphorylation data identified six PDAC subtypes. Cellular pathways represented by mRNA and protein signatures, defining the subtypes and compositions of cell types in the subtypes, characterized them as classical progenitor (TS1), squamous (TS2-4), immunogenic progenitor (IS1) and exocrine-like (IS2) subtypes. Compared with the mRNA data, protein and phosphorylation data further classified the squamous subtypes into activated stroma-enriched (TS2), invasive (TS3) and invasive-proliferative (TS4) squamous subtypes. Orthotopic mouse PDAC models revealed a higher number of pro-tumorigenic immune cells in TS4, inhibiting T cell proliferation. Our proteogenomic analysis provides significantly mutated genes/biomarkers, cellular pathways and cell types as potential therapeutic targets to improve stratification of patients with PDAC.
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Carcinoma Ductal Pancreático , Carcinoma de Células Escamosas , Neoplasias Pancreáticas , Proteogenómica , Animales , Ratones , Humanos , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , Biomarcadores , Neoplasias PancreáticasRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year overall survival rate. Patients with PDAC display limited benefits after undergoing chemotherapy or immunotherapy modalities. Herein, we reveal that chemotherapy upregulates placental growth factor (PlGF), which directly activates cancer-associated fibroblasts (CAFs) to induce fibrosis-associated collagen deposition in PDAC. Patients with poor prognosis have high PIGF/VEGF expression and an increased number of PIGF/VEGF receptor-expressing CAFs, associated with enhanced collagen deposition. We also develop a multi-paratopic VEGF decoy receptor (Ate-Grab) by fusing the single-chain Fv of atezolizumab (anti-PD-L1) to VEGF-Grab to target PD-L1-expressing CAFs. Ate-Grab exerts anti-tumor and anti-fibrotic effects in PDAC models via the PD-L1-directed PlGF/VEGF blockade. Furthermore, Ate-Grab synergizes with gemcitabine by relieving desmoplasia. Single-cell RNA sequencing identifies that a CD141+ CAF population is reduced upon Ate-Grab and gemcitabine combination treatment. Overall, our results elucidate the mechanism underlying chemotherapy-induced fibrosis in PDAC and highlight a combinatorial therapeutic strategy for desmoplastic cancers.
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Antineoplásicos , Fibroblastos Asociados al Cáncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Anticuerpos de Cadena Única , Femenino , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de Crecimiento Placentario/genética , Factor de Crecimiento Placentario/metabolismo , Anticuerpos de Cadena Única/metabolismo , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/genética , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Antineoplásicos/farmacología , Fibrosis , Neoplasias PancreáticasRESUMEN
The standard analysis pipeline for single-cell RNA-seq data consists of sequential steps initiated by clustering the cells. An innate limitation of this pipeline is that an imperfect clustering result can irreversibly affect the succeeding steps. For example, there can be cell types not well distinguished by clustering because they largely share the global structure, such as the anterior primitive streak and mid primitive streak cells. If one searches differentially expressed genes (DEGs) solely based on clustering, marker genes for distinguishing these types will be missed. Moreover, clustering depends on many parameters and can often be subjective to manual decisions. To overcome these limitations, we propose MarcoPolo, a method that identifies informative DEGs independently of prior clustering. MarcoPolo sorts out genes by evaluating if the distributions are bimodal, if similar expression patterns are observed in other genes, and if the expressing cells are proximal in a low-dimensional space. Using real datasets with FACS-purified cell labels, we demonstrate that MarcoPolo recovers marker genes better than competing methods. Notably, MarcoPolo finds key genes that can distinguish cell types that are not distinguishable by the standard clustering. MarcoPolo is built in a convenient software package that provides analysis results in an HTML file.
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Análisis de la Célula Individual , Programas Informáticos , Algoritmos , Biomarcadores , Análisis por Conglomerados , Perfilación de la Expresión Génica/métodos , RNA-Seq , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Secuenciación del ExomaRESUMEN
Craniofacial development is controlled by a large number of genes, which interact with one another to form a complex gene regulatory network (GRN). Key components of GRN are signaling molecules and transcription factors. Therefore, identifying targets of core transcription factors is an important part of the overall efforts toward building a comprehensive and accurate model of GRN. LHX6 and LHX8 are transcription factors expressed in the oral mesenchyme of the first pharyngeal arch (PA1), and they are crucial regulators of palate and tooth development. Previously, we performed genome-wide transcriptional profiling and chromatin immunoprecipitation to identify target genes of LHX6 and LHX8 in PA1, and described a set of genes repressed by LHX. However, there has not been any discussion of the genes positively regulated by LHX6 and LHX8. In this paper, we revisited the above datasets to identify candidate positive targets of LHX in PA1. Focusing on those with known connections to craniofacial development, we performed RNA in situ hybridization to confirm the changes in expression in Lhx6;Lhx8 mutant. We also confirmed the binding of LHX6 to several putative enhancers near the candidate target genes. Together, we have uncovered novel connections between Lhx and other important regulators of craniofacial development, including Eya1, Barx1, Rspo2, Rspo3, and Wnt11.
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Regulación del Desarrollo de la Expresión Génica , Factores de Transcripción , Proteínas con Homeodominio LIM/genética , Proteínas con Homeodominio LIM/metabolismo , Maxilar/metabolismo , Hueso Paladar/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45+ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2negative AGC.
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Development of the teeth requires complex signaling interactions between the mesenchyme and the epithelium mediated by multiple pathways. For example, canonical WNT signaling is essential to many aspects of odontogenesis, and inhibiting this pathway blocks tooth development at an early stage. R-spondins (RSPOs) are secreted proteins, and they mostly augment WNT signaling. Although RSPOs have been shown to play important roles in the development of many organs, their role in tooth development is unclear. A previous study reported that mutating Rspo2 in mice led to supernumerary lower molars, while teeth forming at the normal positions showed no significant anomalies. Because multiple Rspo genes are expressed in the orofacial region, it is possible that the relatively mild phenotype of Rspo2 mutants is due to functional compensation by other RSPO proteins. We found that inactivating Rspo3 in the craniofacial mesenchyme caused the loss of lower incisors, which did not progress beyond the bud stage. A simultaneous deletion of Rspo2 and Rspo3 caused severe disruption of craniofacial development from early stages, which was accompanied with impaired development of all teeth. Together, these results indicate that Rspo3 is an important regulator of mammalian dental and craniofacial development.
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BACKGROUND/AIMS: Weather and air pollution are associated with the exacerbation of respiratory diseases. We investigated patterns of medical care use according to meteorological factors and air pollution in patients with asthma or chronic obstructive pulmonary disease (COPD). METHODS: We analyzed the medical care utilization patterns of patients with asthma or COPD registered in the Korea Health Insurance Review and Assessment database for the period 2007 to 2013. The patterns were divided into hospitalization and emergency department (ED) use. RESULTS: The medical care use of patients with asthma or COPD increased when the mean temperature and relative humidity were lower, and the temperature difference and atmospheric pressure were greater. Medical care use increased with the concentrations of particulate matter and ozone. Among age groups, sensitivity to pollutants was greatest in patients aged ≥ 65 years. The effect of being elderly was greater for asthma than for COPD, with a higher hospitalization rate. ED utilization affected by environmental factors was significantly greater for females and hospitalization was significantly more common for males. CONCLUSION: Meteorological factors and air pollutants were shown to contribute to increased medical care utilization by patients with asthma and COPD, particularly elderly patients. The overall effect was greater for COPD, but the effect in elderly patients was greater for asthma. In addition, the patterns of change in medical care use due to environmental factors differed according to sex.
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Contaminantes Atmosféricos , Contaminación del Aire , Asma , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Asma/diagnóstico , Asma/epidemiología , Asma/terapia , Femenino , Hospitalización , Humanos , Masculino , Material Particulado , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/terapiaRESUMEN
Currently, most biological research relies on conventional experimental techniques that allow only static analyses at certain time points in vitro or ex vivo. However, if one could visualize cellular dynamics in living organisms, that would provide a unique opportunity to study key biological phenomena in vivo. Intravital microscopy (IVM) encompasses diverse optical systems for direct viewing of objects, including biological structures and individual cells in live animals. With the current development of devices and techniques, IVM addresses important questions in various fields of biological and biomedical sciences. In this mini-review, we provide a general introduction to IVM and examples of recent applications in the field of immunology, oncology, and vascular biology. We also introduce an advanced type of IVM, dubbed real-time IVM, equipped with video-rate resonant scanning. Since the realtime IVM can render cellular dynamics with high temporal resolution in vivo, it allows visualization and analysis of rapid biological processes. [BMB Reports 2020; 53(7): 357-366].
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Microscopía Intravital/métodos , Análisis de la Célula Individual/métodos , Animales , HumanosRESUMEN
The musculoskeletal system, which comprises muscles, tendons, and bones, is an efficient tissue complex that coordinates body movement and maintains structural stability. The process of its construction into a single functional and complex organization is unclear. SRY-box containing gene 9 (Sox9) is expressed initially in pluripotent cells and subsequently in ectodermal, endodermal, and mesodermal derivatives. This study investigated how Sox9 controls the development of each component of the musculoskeletal system. Sox9 was expressed in MTJ, tendon, and bone progenitor cells at E13 and in bone at E16. We detected Sox9 expression in muscle progenitor cells using double-transgenic mice and myoblastic cell lines. However, we found no Sox9 expression in developed muscle. A decrease in Sox9 expression in muscle-associated connective tissues, tendons, and bones led to hypoplasia of the cartilage and its attachment to tendons and muscle. These results showed that switching on Sox9 expression in each component (muscle, tendon, and bone) is essential for the development of the musculoskeletal system. Sox9 is expressed in not only tendon and bone progenitor cells but also muscle progenitor cells, and it controls musculoskeletal system development.
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Desarrollo Óseo/fisiología , Desarrollo de Músculos/fisiología , Factor de Transcripción SOX9/metabolismo , Células Madre/metabolismo , Tendones/crecimiento & desarrollo , Animales , Desarrollo Óseo/genética , Huesos/metabolismo , Ratones , Ratones Transgénicos , Desarrollo de Músculos/genética , Músculos/metabolismo , Factor de Transcripción SOX9/genética , Tendones/metabolismoRESUMEN
The strains of inbred laboratory mice are isogenic and homogeneous for over 98.6% of their genomes. However, geometric morphometric studies have demonstrated clear differences among the skull shapes of various mice strains. The question now arises: why are skull shapes different among the mice strains? Epigenetic processes, such as morphological interaction between the muscles and bones, may cause differences in the skull shapes among various mice strains. To test these predictions, the objective of this study is to examine the morphological association between a specific part of the skull and its adjacent muscle. We examined C57BL6J, BALB/cA, and ICR mice on embryonic days (E) 12.5 and 16.5 as well as on postnatal days (P) 0, 10, and 90. As a result, we found morphological differences between C57BL6J and BALB/cA mice with respect to the inferior spine of the hypophyseal cartilage or basisphenoid (SP) and the tensor veli palatini muscle (TVP) during the prenatal and postnatal periods. There was a morphological correlation between the SP and the TVP in the C57BL6J, BALB/cA, and ICR mice during E15 and P0. However, there were not correlation between the TVP and the SP during P10. After discectomy, bone deformation was associated with a change in the shape of the adjacent muscle. Therefore, epigenetic modifications linked to the interaction between the muscles and bones might occur easily during the prenatal period, and inflammation seems to allow epigenetic modifications between the two to occur.
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Anatomía Comparada/métodos , Músculos Palatinos/embriología , Músculos Palatinos/crecimiento & desarrollo , Hueso Esfenoides/embriología , Hueso Esfenoides/crecimiento & desarrollo , Animales , Animales Recién Nacidos , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Músculos Palatinos/anatomía & histología , Embarazo , Hueso Esfenoides/anatomía & histologíaRESUMEN
Recent preclinical/clinical studies have underscored the significant impact of tumor microenvironment (TME) on tumor progression in diverse scenarios. Highly heterogeneous and complex, the tumor microenvironment is composed of malignant cancer cells and non-malignant cells including endothelial cells, fibroblasts, and diverse immune cells. Since immune compartments play pivotal roles in regulating tumor progression via various mechanisms, understanding of their multifaceted functions is crucial to developing effective cancer therapies. While roles of lymphoid cells in tumors have been systematically studied for a long time, the complex functions of myeloid cells have been relatively underexplored. However, constant findings on tumor-associated myeloid cells are drawing attention, highlighting the primary effects of innate immune cells such as monocytes and neutrophils in disease progression. This review focuses on hitherto identified contextual developments and functions of monocytes and neutrophils with a special interest in solid tumors. Moreover, ongoing clinical applications are discussed at the end of the review.
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Células Endoteliales/inmunología , Monocitos/inmunología , Neoplasias/inmunología , Neutrófilos/inmunología , Microambiente Tumoral/inmunología , Animales , Diferenciación Celular/inmunología , Células Dendríticas/inmunología , Progresión de la Enfermedad , Humanos , Inmunidad Innata/inmunología , Macrófagos/inmunología , Ratones , Monocitos/citologíaRESUMEN
In the head of an embryo, a layer of mesenchyme surrounds the brain underneath the surface ectoderm. This cranial mesenchyme gives rise to the meninges, the calvaria (top part of the skull), and the dermis of the scalp. Abnormal development of these structures, especially the meninges and the calvaria, is linked to significant congenital defects in humans. It has been known that different areas of the cranial mesenchyme have different fates. For example, the calvarial bone develops from the cranial mesenchyme on the baso-lateral side of the head just above the eye (supraorbital mesenchyme, SOM), but not from the mesenchyme apical to SOM (early migrating mesenchyme, EMM). However, the molecular basis of this difference is not fully understood. To answer this question, we compared the transcriptomes of EMM and SOM using high-throughput sequencing (RNA-seq). This experiment identified a large number of genes that were differentially expressed in EMM and SOM, and gene ontology analyses found very different terms enriched in each region. We verified the expression of about 40 genes in the head by RNA in situ hybridization, and the expression patterns were annotated to make a map of molecular markers for 6 subdivisions of the cranial mesenchyme. Our data also provided insights into potential novel regulators of cranial mesenchyme development, including several axon guidance pathways, lectin complement pathway, cyclic-adenosine monophosphate (cAMP) signaling pathway, and ZIC family transcription factors. Together, information in this paper will serve as a unique resource to guide future research on cranial mesenchyme development.
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Tipificación del Cuerpo/genética , Mesodermo/embriología , Cráneo/embriología , Animales , Orientación del Axón/genética , Moléculas de Adhesión Celular/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Inmunidad Innata , Hibridación in Situ , Masculino , Ratones , Ratones Endogámicos C57BL , Neoplasias/genética , RNA-Seq , Transducción de Señal , Cráneo/citología , Factores de Transcripción/metabolismo , TranscriptomaRESUMEN
The meninges are membranous layers surrounding the central nervous system. In the head, the meninges lie between the brain and the skull, and interact closely with both during development. The cranial meninges originate from a mesenchymal sheath on the surface of the developing brain, called primary meninx, and undergo differentiation into three layers with distinct histological characteristics: the dura mater, the arachnoid mater, and the pia mater. While genetic regulation of meningeal development is still poorly understood, mouse mutants and other models with meningeal defects have demonstrated the importance of the meninges to normal development of the calvaria and the brain. For the calvaria, the interactions with the meninges are necessary for the progression of calvarial osteogenesis during early development. In later stages, the meninges control the patterning of the skull and the fate of the sutures. For the brain, the meninges regulate diverse processes including cell survival, cell migration, generation of neurons from progenitors, and vascularization. Also, the meninges serve as a stem cell niche for the brain in the postnatal life. Given these important roles of the meninges, further investigation into the molecular mechanisms underlying meningeal development can provide novel insights into the coordinated development of the head.
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Meninges/embriología , Meninges/metabolismo , Meninges/fisiología , Animales , Aracnoides/embriología , Aracnoides/metabolismo , Encéfalo/embriología , Encéfalo/metabolismo , Diferenciación Celular , Biología Evolutiva/métodos , Duramadre/embriología , Duramadre/metabolismo , Humanos , Piamadre/embriología , Piamadre/metabolismo , Cráneo/embriología , Cráneo/metabolismoRESUMEN
BACKGROUND: Accurate, rapid, and cost-effective screening tests for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection may be useful in laboratories that cannot afford automated chemiluminescent immunoassays (CLIAs). We evaluated the diagnostic performance of a novel rapid automated fluorescent lateral flow immunoassay (LFIA). METHODS: A fluorescent LFIA using a small bench-top fluorescence reader, Automated Fluorescent Immunoassay System (AFIAS; Boditech Med Inc., Chuncheon, Korea), was developed for qualitative detection of hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), and antibody to HCV (anti-HCV) within 20 minutes. We compared the diagnostic performance of AFIAS with that of automated CLIAs-Elecsys (Roche Diagnostics GmbH, Penzberg, Germany) and ARCHITECT (Abbott Laboratories, Abbott Park, IL, USA)-using 20 seroconversion panels and 3,500 clinical serum samples. RESULTS: Evaluation with the seroconversion panels demonstrated that AFIAS had adequate sensitivity for HBsAg and anti-HCV detection. From the clinical samples, AFIAS sensitivity and specificity were 99.8% and 99.3% for the HBsAg test, 100.0% and 100.0% for the anti-HBs test, and 98.8% and 99.1% for the anti-HCV test, respectively. Its agreement rates with the Elecsys HBsAg, anti-HBs, and anti-HCV detection assays were 99.4%, 100.0%, and 99.0%, respectively. AFIAS detected all samples with HBsAg genotypes A-F and H and anti-HCV genotypes 1, 1a, 1b, 2a, 2b, 4, and 6. Cross-reactivity with other infections was not observed. CONCLUSIONS: The AFIAS HBsAg, anti-HBs, and anti-HCV tests demonstrated diagnostic performance equivalent to current automated CLIAs. AFIAS could be used for a large-scale HBV or HCV screening in low-resource laboratories or low-to middle-income areas.