RESUMEN
The obligate biotrophic chytrid species Synchytrium endobioticum is the causal agent of potato wart disease. Currently, 39 pathotypes have been described based on their interaction with a differential set of potato varieties. Wart resistance and pathotyping is performed using bioassays in which etiolated tuber sprouts are inoculated. Here, we describe an alternative method in which aboveground plant parts are inoculated. Susceptible plants produced typical wart symptoms in developing but not in fully expanded aboveground organs. Colonization of the host by S. endobioticum was verified by screening for resting spores by microscopy and by molecular techniques using TaqMan polymerase chain reaction and RNAseq analysis. When applied to resistant plants, none of these symptoms were detectable. Recognition of S. endobioticum pathotypes by differentially resistant potato varieties was identical in axillary buds and the tuber-based bioassays. This suggests that S. endobioticum resistance genes are expressed in both etiolated "belowground" sprouts and green aboveground organs. RNAseq analysis demonstrated that the symptomatic aboveground materials contain less contaminants compared with resting spores extracted from tuber-based assays. This reduced microbial contamination in the aboveground bioassay could be an important advantage to study this obligate biotrophic plant-pathogen interaction. Because wart resistance is active in both below- and aboveground organs, the aboveground bioassay can potentially speed up screening for S. endobioticum resistance in potato breeding programs because it omits the requirement for tuber formation. In addition, possibilities arise to express S. endobioticum effectors in potato leaves through agroinfiltration, thereby providing additional phenotyping tools for research and breeding. Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Asunto(s)
Quitridiomicetos , Enfermedades de las Plantas/microbiología , Solanum tuberosum , Verrugas , BioensayoRESUMEN
A heterogeneous group of neurological disorders known as the spinocerebellar ataxias (SCA) are characterized by degeneration of the cerebellum, spinal cord and brainstem. We describe linkage analysis in four unusual SCA families revealing a distinct disease locus on chromosome 3p14-21.1. The disease in these families is distinguished from other forms of SCA by concomitant retinal degeneration. Initial visual problems leading to blindness, disabling ataxia and anticipation are seen in all kindreds. The anticipation in these families suggests a dynamic mutation at this locus. Eventual molecular characterization of this disease may provide valuable insights into the processes of both neural and retinal degeneration.
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Cromosomas Humanos Par 3 , Degeneración Retiniana/genética , Degeneraciones Espinocerebelosas/genética , Adolescente , Adulto , Edad de Inicio , Alelos , Población Negra/genética , Niño , Preescolar , Defectos de la Visión Cromática/complicaciones , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Linaje , Degeneración Retiniana/complicaciones , Degeneración Retiniana/diagnóstico , Población Blanca/genéticaAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Neumonía Bacteriana/microbiología , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa , Adulto , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/etiología , Resultado Fatal , Enfermedad de Hodgkin/terapia , Humanos , Huésped Inmunocomprometido , MasculinoRESUMEN
The autosomal dominant cerebellar ataxias (ADCA) comprise a heterogeneous group of neurologic disorders characterized by degeneration of the cerebellum, spinal cord, and brainstem. Genetic analysis has revealed two loci, SCA1 on chromosome 6p, and SCA2 on chromosome 12q, responsible for some ADCA. We present a four-generation kindred of 42 individuals, 12 of whom were clinically affected with ADCA and an associated cone dystrophy. Early loss of color discrimination with retinal and macular signs is followed by gradual progression of cerebellar dysfunction and development of pyramidal signs. Pathology shows degeneration of cerebellum, basis pontis, inferior olive, and retinal ganglion cells. For genetic analysis, we used polymorphic markers D6S89 and D12S79; linkage analysis gave negative results, excluding linkage to both SCA1 and SCA2. The data strongly support genetic heterogeneity consistent with the unique clinicopathologic features of the form of ADCA displayed in this large family.
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Ataxia Cerebelosa/genética , Ataxia Cerebelosa/patología , Degeneración Retiniana/genética , Adolescente , Adulto , Encéfalo/patología , Ataxia Cerebelosa/complicaciones , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Escala de Lod , Masculino , Persona de Mediana Edad , Linaje , Reacción en Cadena de la Polimerasa , Degeneración Retiniana/etiologíaRESUMEN
Ewing's sarcoma is a highly malignant tumor of children and young adults. The molecular mechanisms that underlie Ewing's Sarcoma development are beginning to be understood. For example, most cases of this disease harbor somatic chromosomal translocations that fuse the EWSR1 gene on chromosome 22 with members of the ETS family. While some cooperative genetic events have been identified, such as mutations in TP53 or deletions of the CDKN2A locus, these appear to be absent in the vast majority of cases. It is therefore uncertain whether EWS/ETS translocations are the only consistently present alteration in this tumor, or whether there are other recurrent abnormalities yet to be discovered. One method to discover such mutations is to identify familial cases of Ewing's sarcoma and to then map the susceptibility locus using traditional genetic mapping techniques. Although cases of sibling pairs with Ewing's sarcoma exist, familial cases of Ewing's sarcoma have not been reported. While Ewing's sarcoma has been reported as a 2nd malignancy after retinoblastoma, significant associations of Ewing's sarcoma with classic tumor susceptibility syndromes have not been identified. We will review the current evidence, or lack thereof, regarding the potential of a heritable condition predisposing to Ewing's sarcoma.
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Activation of primary resting T cells requires costimulation which can be delivered by the B7 molecules (CD80 and CD86) expressed on activated antigen-presenting cells (APC). In the present study, we examined in vitro effects of immunotoxins (ITs) composed of gelonin conjugated to mAbs against CD80 or CD86 (alphaCD80-IT and alphaCD86-IT). The specificity of both ITs was demonstrated using CD80 and CD86 transfected cell lines. In primary mixed lymphocyte cultures (MLCs), it was found that the average inhibitory capacity of alphaCD86-IT (72%) and alphaCD80-IT (30%) was significantly higher than alphaCD86 (54%) and alphaCD80 (11%). In reculture MLC experiments it was found that peripheral blood mononuclear cells pretreated with alphaCD86/alphaCD80 regained full stimulatory capacity whereas alphaCD86-IT/alphaCD80-IT pretreatment induced >95% loss of stimulatory capacity. Our results therefore demonstrate that these alphaB7-ITs functionally block B7-CD28 costimulatory signaling and eliminate activated APC.
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Antígenos CD/metabolismo , Antígeno B7-1/metabolismo , Inmunidad Celular/efectos de los fármacos , Inmunotoxinas/farmacología , Glicoproteínas de Membrana/metabolismo , Linfocitos T/efectos de los fármacos , Reacciones Antígeno-Anticuerpo , Células Presentadoras de Antígenos/metabolismo , Antígenos CD/inmunología , Antígeno B7-1/biosíntesis , Antígeno B7-1/inmunología , Antígeno B7-2 , Células Cultivadas , Desoxirribonucleasas/farmacología , Humanos , Inmunidad Celular/inmunología , Inmunotoxinas/inmunología , Prueba de Cultivo Mixto de Linfocitos , Glicoproteínas de Membrana/inmunología , Proteínas de Plantas/farmacología , Inhibidores de la Síntesis de la Proteína/farmacología , Proteínas Inactivadoras de Ribosomas Tipo 1 , Linfocitos T/citología , Linfocitos T/inmunologíaRESUMEN
Clinical and electrophysiological data have outlined a spectrum of similar yet distinct periodic paralyses, including potassium-sensitive (hyperkalemic periodic paralysis [HYPP]) and temperature-sensitive (paramyotonia congenita [PC]) forms. Recent work has revealed that these disorders result from allelic defects in the alpha-subunit of the adult, human skeletal muscle sodium channel. We report an additional mutation, a leucine-->arginine substitution in the S3 segment of domain 4 (L1433R), that results in the PC phenotype. Five other HYPP and PC families have been ascertained, and previously reported sodium channel mutations have been identified in each. Characterization of these mutations and phenotypic variations in such families will contribute to the understanding of sodium channel structure and function relationships, as well as channel malfunction in the periodic paralyses.
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Hiperpotasemia/genética , Mutación , Miotonía Congénita/genética , Parálisis/genética , Canales de Sodio/genética , Adulto , Secuencia de Aminoácidos , ADN/análisis , Femenino , Humanos , Masculino , Datos de Secuencia Molecular , Polimorfismo GenéticoRESUMEN
The gene for spinocerebellar ataxia 7 (SCA7) includes a transcribed, translated CAG tract that is expanded in SCA7 patients. We have determined expansions in 73 individuals from 17 SCA7 kindreds and compared them with repeat lengths of 180 unaffected individuals. Subjects with abnormal expansions comprise 59 clinically affected individuals and 14 at-risk currently unaffected individuals predicted to carry the mutation by haplotype analysis. For expanded alleles, CAG repeat length correlates with disease progression and severity and correlates inversely with age of onset. Increased repeat lengths are seen in generational transmission of the disease allele, consistent with the pattern of clinical anticipation seen in these kindreds. Repeat lengths in expanded alleles show somatic mosaicism in leukocyte DNA, suggesting that these alleles are unstable within individuals as well as between generations. Although dynamic repeat expansions from paternal transmissions are greater than those from maternal transmissions, maternal transmission of disease is more common, suggesting germline or embryonic effects of the repeat expansion.