RESUMEN
Human vitronectin (hVN) is a glycoprotein that functions as a cell adhesion molecule and a regulator of coagulation in blood plasma and the extracellular matrix. In vitro, hVN is added to serum-free media in order to promote the adhesion of animal cells to tissue culture surfaces and the proliferation of undifferentiated stem cells. Here, we report the production of hVN in Nicotiana benthamiana using the inducible In Plant ACTivation (INPACT) hyperexpression platform. N. benthamiana plants were transformed with an INPACT expression cassette encoding hVN, and both the Tobacco yellow dwarf virus Rep/RepA activator and Tomato bushy stunt virus p19 gene under the transcriptional control of the ethanol-inducible AlcR:alcA gene switch. hVN expression was maximal 4-5 days postactivation of the INPACT platform with a dilute ethanol solution, and crude yields of the recombinant protein reached a maximum of 643 ± 78 mg/kg fresh weight. A three-stage purification protocol was developed using heparin and polyhistidine tag affinity binding and size exclusion filtration, resulting in a plant-made hVN product of >90% purity. Storage conditions for plant-made hVN were identified that maximized the capacity of the recombinant protein to promote cell adhesion. Critically, plant-made hVN was shown to be functionally equivalent to commercial, plasma-derived hVN at promoting one-half maximal attachment of murine fibroblast cells (BALB-C/3T3) in serum-free medium at <0.1 µg/cm2 to tissue culture plasticware. The INPACT platform represents an attractive means of producing large quantities of functional, animal-free hVN for in vitro applications.
Asunto(s)
Nicotiana/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Vitronectina/metabolismo , Regulación de la Expresión Génica de las Plantas , Humanos , Plantas Modificadas Genéticamente/genética , Nicotiana/genética , Vitronectina/genéticaRESUMEN
Toll-like receptor 7 and Myd88 are required for antiretroviral antibody and germinal center responses, but whether somatic hypermutation and class-switch recombination are required for antiretroviral immunity has not been examined. Mice deficient in activation-induced cytidine deaminase (AID) resisted Friend virus infection, produced virus-neutralizing antibodies, and controlled viremia. Passive transfer demonstrated that immune IgM from AID-deficient mice contributes to Friend virus control in the presence of virus-specific CD4+ T cells.
Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Virus de la Leucemia Murina de Friend/inmunología , Leucemia Experimental/inmunología , Infecciones por Retroviridae/inmunología , Hipermutación Somática de Inmunoglobulina , Infecciones Tumorales por Virus/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Citidina Desaminasa/deficiencia , Inmunización Pasiva , Cambio de Clase de Inmunoglobulina , Inmunoglobulina M/inmunología , Leucemia Experimental/virología , Ratones , Infecciones por Retroviridae/virología , Infecciones Tumorales por Virus/virologíaRESUMEN
In chronic viral infections, persistent antigen presentation causes progressive exhaustion of virus-specific CD8+ T cells. It has become clear, however, that virus-specific naïve CD8+ T cells newly generated from the thymus can be primed with persisting antigens. In the setting of low antigen density and resolved inflammation, newly primed CD8+ T cells are preferentially recruited into the functional memory pool. Thus, continual recruitment of naïve CD8+ T cells from the thymus is important for preserving the population of functional memory CD8+ T cells in chronically infected animals. Friend virus (FV) is the pathogenic murine retrovirus that establishes chronic infection in adult mice, which is bolstered by the profound exhaustion of virus-specific CD8+ T cells induced during the early phase of infection. Here we show an additional evasion strategy in which FV disseminates efficiently into the thymus, ultimately leading to clonal deletion of thymocytes that are reactive to FV antigens. Owing to the resultant lack of virus-specific recent thymic emigrants, along with the above exhaustion of antigen-experienced peripheral CD8+ T cells, mice chronically infected with FV fail to establish a functional virus-specific CD8+ T cell pool, and are highly susceptible to challenge with tumor cells expressing FV-encoded antigen. However, FV-specific naïve CD8+ T cells generated in uninfected mice can be primed and differentiate into functional memory CD8+ T cells upon their transfer into chronically infected animals. These findings indicate that virus-induced central tolerance that develops during the chronic phase of infection accelerates the accumulation of dysfunctional memory CD8+ T cells.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Tolerancia Inmunológica/inmunología , Memoria Inmunológica/inmunología , Infecciones por Retroviridae/inmunología , Timo/virología , Envejecimiento , Animales , Linfocitos T CD8-positivos/citología , Diferenciación Celular/inmunología , Enfermedad Crónica , Femenino , Citometría de Flujo , Virus de la Leucemia Murina de Friend/inmunología , Inmunohistoquímica , Masculino , Ratones , Ratones Transgénicos , Timo/inmunologíaRESUMEN
In this study, we describe a novel protein production platform that provides both activation and amplification of transgene expression in planta. The In Plant Activation (INPACT) system is based on the replication machinery of tobacco yellow dwarf mastrevirus (TYDV) and is essentially transient gene expression from a stably transformed plant, thus combining the advantages of both means of expression. The INPACT cassette is uniquely arranged such that the gene of interest is split and only reconstituted in the presence of the TYDV-encoded Rep/RepA proteins. Rep/RepA expression is placed under the control of the AlcA:AlcR gene switch, which is responsive to trace levels of ethanol. Transgenic tobacco (Nicotiana tabacum cv Samsun) plants containing an INPACT cassette encoding the ß-glucuronidase (GUS) reporter had negligible background expression but accumulated very high GUS levels (up to 10% total soluble protein) throughout the plant, within 3 d of a 1% ethanol application. The GUS reporter was replaced with a gene encoding a lethal ribonuclease, barnase, demonstrating that the INPACT system provides exquisite control of transgene expression and can be adapted to potentially toxic or inhibitory compounds. The INPACT gene expression platform is scalable, not host-limited, and has been used to express both a therapeutic and an industrial protein.
Asunto(s)
Expresión Génica/genética , Plantas/genética , Proteínas Recombinantes/genética , Transgenes/genética , Secuencia de Aminoácidos , Animales , Proteínas Bacterianas , Secuencia de Bases , Bovinos , Caulimovirus/genética , Etanol/farmacología , Geminiviridae/genética , Expresión Génica/efectos de los fármacos , Vectores Genéticos/genética , Glucuronidasa/genética , Glucuronidasa/metabolismo , Humanos , Immunoblotting , Datos de Secuencia Molecular , Plantas/metabolismo , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas/genética , Proteínas Recombinantes/metabolismo , Ribonucleasas/genética , Ribonucleasas/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/virología , Tripsinógeno/genética , Tripsinógeno/metabolismo , Proteínas Virales/genética , Vitronectina/genética , Vitronectina/metabolismoRESUMEN
In December 2019, a new infectious pathogen named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China. Transmitted through respiratory droplets, SARS-CoV-2 is the causative pathogen of coronavirus disease 2019 (COVID-19). Although this new COVID-19 infection is known to cause primarily interstitial pneumonia and respiratory failure, it is often associated with cutaneous manifestations as well. These manifestations with COVID-19 can be classified into seven categories: (i) chilblain-like skin eruption (e.g., COVID toes), (ii) urticaria-like skin eruption, (iii) maculopapular lesions, (iv) vesicular eruptions, (v) purpura, (vi) livedo reticularis and necrotic lesions, (vii) urticarial vasculitis, and others such as alopecia and herpes zoster. The pathogenesis of skin eruptions can be broadly divided into vasculitic and inflammatory skin eruptions. Various cutaneous adverse reactions have also been observed after COVID-19 mRNA vaccination. The major cutaneous adverse reactions are type I hypersensitivity (urticaria and anaphylaxis) and type IV hypersensitivity (COVID arm and erythema multiform). Autoimmune-mediated reactions including bullous pemphigus, vasculitis, vitiligo, and alopecia areata have also been reported. Several cases with chilblain-like lesions and herpes zoster after COVID-19 mRNA vaccination have been published. Various skin diseases associated with COVID-19 and COVID-19 vaccination have been reported, and the mechanism has been partly elucidated. In the process, for example, some papers have reported that it is not related to COVID-19 infection, although it was initially called COVID-toe and considered a COVID-19-associated cutaneous eruption. In fact, some COVID-19-associated skin reactions are indistinguishable from drug eruptions. In the future, the mechanisms of COVID-19- or COVID-19 vaccine-associated skin reactions need to be elucidated and verification of causal relationships is required.
Asunto(s)
Alopecia Areata , Vacunas contra la COVID-19 , COVID-19 , Eritema Pernio , Exantema , Herpes Zóster , Enfermedades de la Piel , Urticaria , Humanos , Alopecia Areata/complicaciones , COVID-19/complicaciones , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Exantema/etiología , Herpes Zóster/complicaciones , SARS-CoV-2 , Enfermedades de la Piel/etiología , Urticaria/complicaciones , Vacunación/efectos adversosRESUMEN
During chronic viral infection, persistent exposure to viral Ags leads to the overexpression of multiple inhibitory cell-surface receptors that cause CD8(+) T cell exhaustion. The severity of exhaustion correlates directly with the level of infection and the number and intensity of inhibitory receptors expressed, and it correlates inversely with the ability to respond to the blockade of inhibitory pathways. Friend virus (FV) is a murine retrovirus complex that induces acute high-level viremia, followed by persistent infection and leukemia development, when inoculated into immunocompetent adult mice. In this article, we provide conclusive evidence that FV infection results in the generation of virus-specific effector CD8(+) T cells that are terminally exhausted. Acute FV-induced disease is characterized by a rapid increase in the number of virus-infected erythroblasts, leading to massive splenomegaly. Most of the expanded erythroblasts strongly express programmed death ligand-1 and MHC class I, thereby creating a highly tolerogenic environment. Consequently, FV-specific effector CD8(+) T cells uniformly express multiple inhibitory receptors, such as programmed cell death 1 (PD-1), T cell Ig domain and mucin domain 3 (Tim-3), lymphocyte activation gene-3, and CTLA-4, rapidly become nonresponsive to restimulation and are no longer reinvigorated by combined in vivo blockade of PD-1 and Tim-3 during the memory phase. However, combined blockade of PD-1 and Tim-3 during the priming/differentiation phase rescued FV-specific CD8(+) T cells from becoming terminally exhausted, resulting in improved CD8(+) T cell functionality and virus control. These results highlight FV's unique ability to evade virus-specific CD8(+) T cell responses and the importance of an early prophylactic approach for preventing terminal exhaustion of CD8(+) T cells.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Virus de la Leucemia Murina de Friend/inmunología , Activación de Linfocitos/inmunología , Receptores KIR/biosíntesis , Animales , Antígeno B7-1/fisiología , Antígeno B7-H1 , Linfocitos T CD8-positivos/virología , Células Cultivadas , Epítopos de Linfocito T/inmunología , Eritroblastos/inmunología , Eritroblastos/patología , Eritroblastos/virología , Femenino , Receptor Celular 1 del Virus de la Hepatitis A , Receptor 2 Celular del Virus de la Hepatitis A , Evasión Inmune/inmunología , Masculino , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/fisiología , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/fisiología , Ratones , Ratones Endogámicos A , Ratones Endogámicos C57BL , Péptidos/antagonistas & inhibidores , Péptidos/fisiología , Receptores KIR/fisiología , Receptores Virales/antagonistas & inhibidores , Receptores Virales/fisiología , Infecciones por Retroviridae/inmunología , Infecciones por Retroviridae/patología , Infecciones por Retroviridae/virología , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/patología , Infecciones Tumorales por Virus/virologíaRESUMEN
Chloroplasts have their own DNA and gene expression systems. Transcription in chloroplasts is regulated by two types of RNA polymerase, nuclear-encoded plastid RNA polymerase (NEP) and plastid-encoded plastid RNA polymerase (PEP), and multiple sigma factors for PEP. To study transcriptional regulation in chloroplasts, a molecular genetic approach has extensively been used. However, this method may include indirect effects, and it cannot be applied to the analysis of factors essential to survival. These limitations make understanding specific regulation by transcription factors difficult. Chromatin immunoprecipitation (ChIP) is a powerful and useful tool for obtaining information on transcription-factor binding sites; it can directly detect dynamic changes in their interaction patterns in vivo. To further understand transcriptional regulation in chloroplasts, we here established a ChIP-based method in Arabidopsis thaliana and analyzed the binding pattern of a chloroplast sigma factor, SIG1. We found that SIG1 specifically binds to newly identified target promoters as well as to a set of promoters of genes whose mRNA expression is dependent on OsSIG1 in rice and that this binding changed in response to high-light stress. These results suggested that the ChIP-based approach is very useful in understanding transcriptional regulation of chloroplast genes and can overcome several problems posed by conventional methods.
Asunto(s)
Cloroplastos/genética , Cromosomas de las Plantas/genética , ADN de Plantas/metabolismo , ARN Polimerasas Dirigidas por ADN/genética , Factor sigma/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cloroplastos/enzimología , Inmunoprecipitación de Cromatina , ADN de Plantas/química , ARN Polimerasas Dirigidas por ADN/metabolismo , Regulación de la Expresión Génica de las Plantas , Luz , Oryza/metabolismo , Regiones Promotoras Genéticas , ARN Mensajero/metabolismo , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Plantones/metabolismo , Factor sigma/metabolismoRESUMEN
Several host genes control retroviral replication and pathogenesis through the regulation of immune responses to viral antigens. The Rfv3 gene influences the persistence of viremia and production of virus-neutralizing antibodies in mice infected with Friend mouse retrovirus complex (FV). This locus has been mapped within a narrow segment of mouse chromosome 15 harboring the APOBEC3 and BAFF-R loci, both of which show functional polymorphisms among different strains of mice. The exon 5-lacking product of the APOBEC3 allele expressed in FV-resistant C57BL/6 (B6) mice directly restricts viral replication, and mice lacking the B6-derived APOBEC3 exhibit exaggerated pathology and reduced production of neutralizing antibodies. However, the mechanisms by which the polymorphisms at the APOBEC3 locus affect the production of neutralizing antibodies remain unclear. Here we show that the APOBEC3 genotypes do not directly affect the B-cell repertoire, and mice lacking B6-derived APOBEC3 still produce FV-neutralizing antibodies in the presence of primed T helper cells. Instead, higher viral loads at a very early stage of FV infection caused by either a lack of the B6-derived APOBEC3 or a lack of the wild-type BAFF-R resulted in slower production of neutralizing antibodies. Indeed, B cells were hyperactivated soon after infection in the APOBEC3- or BAFF-R-deficient mice. In contrast to mice deficient in the B6-derived APOBEC3, which cleared viremia by 4 weeks after FV infection, mice lacking the functional BAFF-R allele exhibited sustained viremia, indicating that the polymorphisms at the BAFF-R locus may better explain the Rfv3-defining phenotype of persistent viremia.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Citidina Desaminasa/genética , Virus de la Leucemia Murina de Friend/inmunología , Polimorfismo Genético , Infecciones por Retroviridae/veterinaria , Enfermedades de los Roedores/genética , Enfermedades de los Roedores/inmunología , Viremia/genética , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Receptor del Factor Activador de Células B/genética , Receptor del Factor Activador de Células B/inmunología , Citidina Desaminasa/inmunología , Virus de la Leucemia Murina de Friend/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infecciones por Retroviridae/genética , Infecciones por Retroviridae/inmunología , Infecciones por Retroviridae/virología , Enfermedades de los Roedores/virología , Viremia/inmunología , Viremia/virologíaRESUMEN
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by a deficiency of arylsulfatase A. MLD is a heterogeneous disease with variable age at onset and variable clinical features. We evaluated a 33-year-old female patient who developed manifestations of disinhibitory behavior. She was diagnosed with MLD by genetic analysis, which revealed compound heterozygous ARSA missense mutations (p.G99D and p.T409I). The same combination of mutations was previously reported in a Japanese patient with similar symptoms. We performed additional, detailed neuropsychological tests with functional imaging on the current patient that demonstrated frontal lobe dysfunction. These results indicate that the mutations have important implications for genotype-phenotype correlation in MLD.
Asunto(s)
Cerebrósido Sulfatasa/genética , Leucodistrofia Metacromática/genética , Mutación Missense/genética , Adulto , Encéfalo/patología , Femenino , Estudios de Asociación Genética , Heterocigoto , Humanos , Leucodistrofia Metacromática/patología , Imagen por Resonancia MagnéticaRESUMEN
Peptides are attractive drug candidates, but their utility is greatly limited by their inherent susceptibility to proteolytic degradation and their inability to pass through the cell membrane. Here, we employ a strategy of temporary cyclization to develop a cell-active lysine-specific demethylase 1 (LSD1/KDM1A) inhibitor peptide. We first identified a highly potent LSD1-inhibitory linear peptide, with the assistance of X-ray crystal structure data of inhibitor peptide-bound LSD1·CoREST. The peptide was converted to a redox-activatable cyclic peptide incorporating cell-penetrating peptide (CPP), expecting selective activation under intracellular reducing conditions. The cyclic peptide moiety exhibited enhanced stability to protease and was converted to the linear, unmodified LSD1 inhibitor peptide under reducing conditions. The cyclic peptide with CPP inhibited the proliferation of human acute myeloid leukemia cells (HL-60) in the low micromolar concentration range.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Histona Demetilasas/antagonistas & inhibidores , Péptidos Cíclicos/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Péptidos de Penetración Celular/síntesis química , Péptidos de Penetración Celular/metabolismo , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/metabolismo , Histona Demetilasas/metabolismo , Humanos , Oxidación-Reducción , Péptidos Cíclicos/síntesis química , Péptidos Cíclicos/metabolismo , Unión Proteica , Estabilidad Proteica , RatasRESUMEN
Recent studies have identified autoantibodies against synaptic molecules in patients with encephalitis. Autoantibodies against the N-Methyl-d-Aspartate receptor have been reported in patients with schizophrenia; however, autoantibodies against other molecules are yet to be identified. This study used a cell-based assay to examine serum samples from individuals with schizophrenia and healthy controls. The results showed that 5 (8.6%) of 57 patients with schizophrenia harbor autoantibodies against the α1 subunit of the γ-aminobutyric acid A receptor (GABAARα1), which are currently not know to be linked to the pathology of this disease. Some patients showed markedly high antibody titers (i.e., 1:10,000-100,000). None of the heathy control subjects were positive for GABAARα1 antibodies. Therefore, these autoantibodies may form the basis of GABA-mediated pathology in a subgroup of patients with schizophrenia.
Asunto(s)
Encefalitis , Esquizofrenia , Autoanticuerpos , Humanos , Receptores de N-Metil-D-Aspartato , Ácido gamma-AminobutíricoRESUMEN
Geminiviruses and their diseases are a considerable economic threat to a vast number of crops worldwide. Investigating how and where these viruses replicate and accumulate in their hosts may lead to novel molecular resistance strategies. In this study, we used the Rep-inducible In Plant Activation (INPACT) expression platform, based on the genome of tobacco yellow dwarf virus (TYDV), to determine where this model mastrevirus replicates in its host tobacco. By developing an infectious clone of TYDV and optimizing its delivery by agroinfiltration, we first established an efficient artificial infection process. When delivered into transgenic tobacco plants containing a TYDV-based INPACT cassette encoding the ß-glucuronidase (GUS) reporter, we showed the virus activates GUS expression. Histology revealed that reporter gene expression was limited to phloem-associated cell types suggesting TYDV replication has a restricted tissue tropism.
Asunto(s)
Geminiviridae/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas/genética , Nicotiana/virología , Tropismo Viral/genética , Replicación Viral/fisiología , Geminiviridae/genética , Genoma Viral/genética , Glucuronidasa/genética , Interacciones Microbiota-Huesped/genética , Interacciones Microbiota-Huesped/fisiología , Enfermedades de las Plantas/virología , Plantas Modificadas Genéticamente/virología , Replicación Viral/genéticaAsunto(s)
Transmisión Vertical de Enfermedad Infecciosa , Linfoma de Células T/complicaciones , Células T Asesinas Naturales/patología , Complicaciones Neoplásicas del Embarazo/patología , Neoplasias Testiculares/etiología , Adulto , ADN de Neoplasias/análisis , Femenino , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Linfoma de Células T/patología , Masculino , Intercambio Materno-Fetal , Embarazo , Neoplasias Testiculares/patologíaRESUMEN
OBJECTIVE: For transplantation of cord blood (CB) cells, it is important to select a CB sample that can reconstitute not only myelo-erythropoiesis but also lymphopoiesis in recipients. However, until now the reconstitution ability of CB samples has been assessed by colony forming unit-culture (CFU-C) assay or by simply counting CD34+ cells. The present study aims at establishing a method capable of assessing the potential of T lymphopoieses of CB samples. METHODS: CD34+ CD38- cells sorted from CB were cultured on a monolayer of murine stromal cell line TSt-4, transduced with the human Delta-like 1 gene. RESULTS: Immature T cells expressing CD5 and/or CD7 were generated in the culture. As these immature T cells can easily be discriminated from mature T cells that are included in the mononuclear cell population (MNCs), we can use the MNCs as starting material for quantification of progenitors capable of generating T cells (TGP). By applying a limiting dilution analysis, we succeeded in determining the frequency of TGP in MNCs. It was found that the ratios for the number of TGP vs. that of CFU-C differ among CB samples maximally by 3.5 times. CONCLUSION: The present assay system provides a novel tool for the evaluation of CB samples, especially for their T-cell-generating potential.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Sangre Fetal/citología , Células Madre/citología , Linfocitos T/citología , ADP-Ribosil Ciclasa 1/biosíntesis , Animales , Antígenos CD34/biosíntesis , Antígenos CD7/biosíntesis , Antígenos CD5/biosíntesis , Proteínas de Unión al Calcio , Citometría de Flujo , Reordenamiento Génico , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Leucocitos Mononucleares/citología , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos C57BL , Células del Estroma/metabolismoRESUMEN
Clostridium butyricum MIYAIRI 588 (CBM 588), one of the probiotic bacterial strains used for humans and domestic animals, has been reported to exert a variety of beneficial health effects. The effect of this probiotic on lifespan, however, is unknown. In the present study, we investigated the effect of CBM 588 on lifespan and multiple-stress resistance using Caenorhabditis elegans as a model animal. When adult C. elegans were fed a standard diet of Escherichia coli OP50 or CBM 588, the lifespan of the animals fed CBM 588 was significantly longer than that of animals fed OP50. In addition, the animals fed CBM588 exhibited higher locomotion at every age tested. Moreover, the worms fed CBM 588 were more resistant to certain stressors, including infections with pathogenic bacteria, UV irradiation, and the metal stressor Cu2+. CBM 588 failed to extend the lifespan of the daf-2/insulin-like receptor, daf-16/FOXO and skn-1/Nrf2 mutants. In conclusion, CBM 588 extends the lifespan of C. elegans probably through regulation of the insulin/IGF-1 signaling (IIS) pathway and the Nrf2 transcription factor, and CBM 588 improves resistance to several stressors in C. elegans.
Asunto(s)
Caenorhabditis elegans/microbiología , Caenorhabditis elegans/fisiología , Clostridium butyricum/fisiología , Longevidad , Estrés Fisiológico , Animales , Clostridium butyricum/clasificación , Modelos Animales , ProbióticosRESUMEN
BACKGROUND: Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis that is caused by mutations in the VPS13A gene. There are only few reports that studied clinical status of the obligate carriers of ChAc. Clinical courses with follow-up neuroradiological and neuropsychological evaluations in individuals with ChAc have been rarely reported. METHODS: We followed an index patient with ChAc and evaluated the clinical features of the pedigree members. Genetic analyses of VPS13A and genes responsible for other neuroacanthocytotic and neurodegenerative diseases were performed. CONCLUSIONS: The index patient was homozygous for a 3889C>T nonsense mutation in the VPS13A gene and presented with a typical ChAc phenotype. Neuropsychological evaluation with brain imaging in the patient over 3 years revealed atrophy and a decrease in blood flow at the basal ganglia and frontal lobe, and impairment in cognitive function reflecting frontal lobe dysfunction in progressive manners. Four out of five heterozygous mutation carriers in the pedigree showed signs or symptoms potentially attributable to a heterozygous VPS13A mutation.
Asunto(s)
Predisposición Genética a la Enfermedad , Neuroacantocitosis/genética , Linaje , Proteínas de Transporte Vesicular/genética , Adulto , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN/métodos , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Humanos , Japón , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuroacantocitosis/fisiopatología , Pruebas Neuropsicológicas , Polimorfismo Genético , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodosAsunto(s)
Anemia Hemolítica Autoinmune/etiología , Anemia Hemolítica Autoinmune/inmunología , Herpesvirus Humano 6/inmunología , Neutropenia/etiología , Neutropenia/inmunología , Anemia Hemolítica Congénita/complicaciones , Anemia Hemolítica Congénita/etiología , Anemia Hemolítica Congénita/inmunología , Anemia Hemolítica Congénita/virología , Humanos , LactanteRESUMEN
AIM: To investigate the acute effects of the ingestion of a fructose-containing beverage combinedwith fat on postprandial lipoprotein metabolism. METHODS: Twelve young healthy Japanese women with apolipoprotein E phenotype 3/3 were enrolled in this study. At each of four sessions, the subjects ingested one of four sugar beverages containing fructose and/or glucose (total: 0.5g/kg body weight) combined with OFTT cream (1g/kg, 0.35g/kg as fat) in a randomized crossover design. The four sugar beverages were as follows: 100% (w/w) fructose (F100), 90% fructose+10% glucose (F90G10), 55% fructose+45% glucose (F55G45) and 100% glucose (G100). Venous blood samples were obtained at baseline and 0.5, one, two, four and six hours after ingestion. RESULTS: The serum concentrations of TG in the F100, F90G10 and F55G45 trials were significantlyhigher than each fasting value at two and four hours, and returned to baseline at six hours, except inthe F100 trial. The concentrations at four hours and the incremental areas under the curve for thehepatic triglyceride-rich lipoprotein-triglyceride (VLDL-TG(TM)) levels in the F100 and F90G10 trialswere significantly higher and larger, respectively, than those observed in the G100 trial. Meanwhile,the concentrations of RLP-TG and apolipoprotein B-48 peaked at two hours in the G100 trial, versusfour hours in the other trials, and did not return to baseline at six hours, except in the G100 trial.At four hours, the â¿apoB48 tended to be higher in the F100 trial than in the G100 trial. CONCLUSIONS: The ingestion of a high-fructose-containing beverage with fat cream delays the clearance of chylomicron and its remnant derived from the intestine and enhances the secretion of triglyceride-rich lipoprotein particles from the liver, thereby inducing postprandial lipidemia, even in young healthy women.
RESUMEN
AIM: To investigate the acute effects of the ingestion of a fructose-containing beverage combined with fat on postprandial lipoprotein metabolism. METHODS: Twelve young healthy Japanese women with apolipoprotein E phenotype 3/3 were enrolled in this study. At each of four sessions, the subjects ingested one of four sugar beverages containing fructose and/or glucose (total: 0.5 g/kg body weight) combined with OFTT cream (1 g/kg, 0.35 g/kg as fat) in a randomized crossover design. The four sugar beverages were as follows: 100% (w/w) fructose (F100), 90% fructose + 10% glucose (F90G10), 55% fructose + 45% glucose (F55G45) and 100% glucose (G100). Venous blood samples were obtained at baseline and 0.5, one, two, four and six hours after ingestion. RESULTS: The serum concentrations of TG in the F100, F90G10 and F55G45 trials were significantly higher than each fasting value at two and four hours, and returned to baseline at six hours, except in the F100 trial. The concentrations at four hours and the incremental areas under the curve for the hepatic triglyceride-rich lipoprotein-triglyceride (VLDL-TG(TM)) levels in the F100 and F90G10 trials were significantly higher and larger, respectively, than those observed in the G100 trial. Meanwhile, the concentrations of RLP-TG and apolipoprotein B-48 peaked at two hours in the G100 trial, versus four hours in the other trials, and did not return to baseline at six hours, except in the G100 trial. At four hours, the â¿apoB48 tended to be higher in the F100 trial than in the G100 trial. CONCLUSIONS: The ingestion of a high-fructose-containing beverage with fat cream delays the clearance of chylomicron and its remnant derived from the intestine and enhances the secretion of triglyceride-rich lipoprotein particles from the liver, thereby inducing postprandial lipidemia, even in young healthy women.