RESUMEN
We report a 40-year-old man who was found to have profound hypocalcaemia and hypoparathyroidism when investigated for multiple, generalized, tonic/clonic seizures and a chest infection. Computed tomography scan of the brain revealed extensive symmetric bilateral calcification within the cerebellum, thalamus and basal ganglia. Molecular cytogenetic testing by fluorescent in situ hybridization using the commercial Vysis LSI DiGeorge/VCFS dual colour probe set showed a deletion of 22q11.2. The extraordinary feature of this case is the adult presentation of hypocalcaemia, hypoparathyroidism and basal ganglia calcification due to 22q11.2 deletion.
Asunto(s)
Ganglios Basales/patología , Calcinosis/genética , Deleción Cromosómica , Cromosomas Humanos Par 22/ultraestructura , Síndrome de DiGeorge/diagnóstico , Epilepsia Tónico-Clónica/etiología , Hipocalcemia/genética , Hipoparatiroidismo/genética , Adulto , Edad de Inicio , Anticonvulsivantes/uso terapéutico , Ganglios Basales/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Síndrome de DiGeorge/clasificación , Síndrome de DiGeorge/epidemiología , Síndrome de DiGeorge/genética , Epilepsia Tónico-Clónica/tratamiento farmacológico , Humanos , Hiperfosfatemia/genética , Hipocalcemia/complicaciones , Hipoparatiroidismo/complicaciones , Masculino , Hormona Paratiroidea/deficiencia , Fenotipo , Neumonía Bacteriana/complicaciones , Tomografía Computarizada por Rayos X , Ácido Valproico/uso terapéuticoRESUMEN
The number of Tasmanian devils in the wild is rapidly declining owing to a transmissible cancer, devil facial tumor disease (DFTD). Although progress has been made to understand the spread of this disease, crucial research on the pathogenesis of DFTD has been limited because of the threatened status of the host species. Here, the authors describe the development of a NOD/SCID (nonobese diabetic / severe combined immunodeficiency) mouse model that reproduces DFTD and provides a much-needed model to undertake studies into this intriguing transmissible cancer. Histologically, the DFTD produced in NOD/SCID mice (xenografted DFTD) was indistinguishable from the DFTD identified in Tasmanian devils. At the protein level, all xenografted DFTD tumors expressed periaxin, a marker that confirmed the diagnosis of DFTD. The karyotype of DFTD in NOD/SCID mice reproduced similar chromosomal alterations as seen in diseased devils. Furthermore, each NOD/SCID mouse inoculated with cultured DFTD tumor cells developed tumors, whereas DFTD did not develop in any of the inoculated immune-competent BALB/c mice.
Asunto(s)
Modelos Animales de Enfermedad , Transmisión de Enfermedad Infecciosa/veterinaria , Especies en Peligro de Extinción , Neoplasias Faciales/patología , Neoplasias Faciales/veterinaria , Marsupiales , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias Faciales/genética , Inmunohistoquímica/veterinaria , Cariotipificación , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones SCID , Trasplante de Neoplasias/veterinariaRESUMEN
Chromosome microarrays are an essential tool for investigation of copy number changes in children with congenital anomalies and intellectual deficit. Attempts to standardise microarray testing have focused on establishing technical and clinical quality criteria, however external quality assessment programs are still needed. We report on a microarray proficiency testing program for Australasian laboratories. Quality metrics evaluated included analytical accuracy, result interpretation, report completeness, and laboratory performance data: sample numbers, success and abnormality rate and reporting times. Between 2009 and 2014 nine samples were dispatched with variable results for analytical accuracy (30-100%), correct interpretation (32-96%), and report completeness (30-92%). Laboratory performance data (2007-2014) showed an overall mean success rate of 99.2% and abnormality rate of 23.6%. Reporting times decreased from >90 days to <30 days for normal results and from >102 days to <35 days for abnormal results. Data trends showed a positive correlation with improvement for all these quality metrics, however only 'report completeness' and reporting times reached statistical significance. Whether the overall improvement in laboratory performance was due to participation in this program, or from accumulated laboratory experience over time, is not clear. Either way, the outcome is likely to assist referring clinicians and improve patient care.
Asunto(s)
Ensayos de Aptitud de Laboratorios/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/normas , Australasia , Dosificación de Gen , Humanos , Laboratorios/normasRESUMEN
We have recently cloned a cDNA encoding sucrose:fructan 6-fructosyltransferase (6-SFT), a key enzyme of fructan synthesis forming the beta-2,6 linkages typical of the grass fructans, graminans and phleins [Sprenger et al. (1995) Proc. Natl. Acad. Sci. USA 92, 11652-11656]. Here we report functional expression of 6-SFT from barley in transgenic tobacco and chicory. Transformants of tobacco, a plant naturally unable to form fructans, synthesized the trisaccharide kestose and a series of unbranched fructans of the phlein type (beta-2,6 linkages). Transformants of chicory, a plant naturally producing only unbranched fructans of the inulin type (beta-2,1 linkages), synthesized in addition branched fructans of the graminan type, particularly the tetrasaccharide bifurcose which is also a main fructan in barley leaves.
Asunto(s)
Fructanos/biosíntesis , Hexosiltransferasas/metabolismo , Hordeum/enzimología , Nicotiana/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Plantas Tóxicas , Hexosiltransferasas/genética , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente/enzimología , Nicotiana/enzimología , Transformación GenéticaRESUMEN
Background and objectives: We provide a case analysis for a 28-year-old, native Dutch-speaking lady who developed Foreign Accent Syndrome (FAS), a few weeks after falling down the staircase. In addition to FAS, which gave the impression she spoke with a German accent, German(-like) words and structures occurred. Speech symptoms were aggravated by increased stress, fatigue or emotional pressure, and this triggered jargon speech. It was hypothesized her FAS and jargon developed on a functional basis.MethodsIn-depth analyses of the patients medical background, neuropsychological and neurolinguistic tests and psychodiagnostic exams were done. The patient participated in an fMRI experiment. In a syllable repetition paradigm, motor speech activations were compared to those of healthy individuals, to see whether they were altered, which would be expected in case of a neurological etiology.ResultsMedical history disclosed prior traumatic experiences for which she sought help, but no neurological incidents. Repeated neuropsychological and neurolinguistic tests showed deficits in recent memory and executive functioning. The patient demonstrated great difficulties with picture naming. Clinically, language switching and mixing as well as recurring jargon speech was found. Formal psychodiagnostic tests did not identify a clear disorder, but psychodiagnostic interviews were consistent with a DSM-5 conversion disorder. The fMRI study demonstrated that speech network activations corresponded to those found in healthy participants.ConclusionThe clinical neurolinguistic characteristics, outcome of the fMRI experiment, together with the clinical psychodiagnostic findings were strongly indicative for an underlying functional etiology for the FAS and jargon speech, presenting as symptoms of conversion disorder. (AU)
Asunto(s)
Humanos , Femenino , Adulto , Trastornos del Habla , Fatiga , Neurología , Trastornos de ConversiónAsunto(s)
Linfoma/veterinaria , Enfermedades de las Ovejas/patología , Neoplasias Cutáneas/veterinaria , Animales , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/veterinaria , Diagnóstico Diferencial , Linfoma/diagnóstico , Linfoma/patología , Masculino , Ovinos , Enfermedades de las Ovejas/diagnóstico , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/veterinaria , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patologíaAsunto(s)
Aborto Veterinario/epidemiología , Infecciones por Escherichia coli/veterinaria , Escherichia coli/clasificación , Enfermedades Placentarias/veterinaria , Complicaciones Infecciosas del Embarazo/veterinaria , Enfermedades de las Ovejas/epidemiología , Aborto Veterinario/etiología , Aborto Veterinario/microbiología , Animales , Brotes de Enfermedades/veterinaria , Inglaterra/epidemiología , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/epidemiología , Femenino , Enfermedades Placentarias/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Ovinos , Enfermedades de las Ovejas/etiología , Enfermedades de las Ovejas/microbiología , Toxinas Shiga/biosíntesisRESUMEN
It has long been thought that the biosynthesis of trehalose, a sugar present in all kingdoms, is absent from the vast majority of higher plants. However, recent experiments have indicated that genes from Arabidopsis are able to complement yeast strains deficient in trehalose metabolism. In yeast, trehalose has been suggested as a regulatory component in the control of glycolytic flux and in a variety of stress survival strategies. Thus, the occurrence of complimentary genes in Arabidopsis and yeast might lead to the development of strategies and applications for improvement of crop plants.
RESUMEN
Fructan (polyfructosylsucrose) is an important storage carbohydrate in many plant families. fructan:fructan 6G-fructosyltransferase (6G-FFT) is a key enzyme in the formation of the inulin neoseries, a type of fructan accumulated by members of the Liliales. We have cloned the 6G-FFT from onion by screening a cDNA library using barley sucrose:fructan 6-fructosyltransferase (6-SFT) as a probe. The deduced amino acid sequence showed a high homology with plant invertases and 6-SFT. Incubation of protein extracts from transgenic tobacco plants with the trisaccharide 1-kestose and sucrose resulted in the formation of neokestose and fructans of the inulin neoseries with a degree of polymerization up to six. Introduction of the onion 6G-FFT into chicory resulted in the synthesis of fructan of the inulin neoseries, in addition to the synthesis of linear inulin.
Asunto(s)
Allium/enzimología , Fructanos/biosíntesis , Hexosiltransferasas/metabolismo , Inulina/biosíntesis , Plantas Modificadas Genéticamente/metabolismo , Secuencia de Aminoácidos , Cichorium intybus , Biblioteca de Genes , Hexosiltransferasas/biosíntesis , Hexosiltransferasas/química , Hordeum/enzimología , Datos de Secuencia Molecular , Plantas Tóxicas , Protoplastos/enzimología , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Homología de Secuencia de Aminoácido , Nicotiana/enzimología , Vacuolas/enzimologíaRESUMEN
The question whether sucrose (Suc) is present inside plastids has been long debated. Low Suc levels were reported to be present inside isolated chloroplasts, but these were argued to be artifacts of the isolation procedures used. We have introduced Suc-metabolizing enzymes in plastids and our experiments suggest substantial Suc entry into plastids. The enzyme levansucrase from Bacillus subtilis efficiently synthesizes fructan from Suc. Targeting of this enzyme to the plastids of tobacco (Nicotiana tabacum) and potato (Solanum tuberosum) plants leads to high-level fructan accumulation in chloroplasts and amyloplasts, respectively. Moreover, introduction of this enzyme in amyloplasts leads to an altered starch structure. Expression of the yeast invertase in potato tuber amyloplasts results in an 80% reduction of total Suc content, showing efficient hydrolysis of Suc by the plastidic invertase. These observations suggest that Suc can enter plastids efficiently and they raise questions as to its function and metabolism in this organelle.
Asunto(s)
Nicotiana/metabolismo , Plastidios/metabolismo , Sacarosa/metabolismo , beta-Fructofuranosidasa/metabolismo , Cloroplastos/metabolismo , Fructosa/metabolismo , Microscopía Electrónica de Rastreo , Protoplastos/metabolismo , Nicotiana/ultraestructuraRESUMEN
As a first step toward the exploitation of the disaccharide trehalose as a stress-protective and preservative agent in plants, we engineered trehalose biosynthesis in tobacco (Nicotiana tabacum) and potato (Solanum tuberosum) by introducing the otsA and otsB genes from Escherichia coli, which encode trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase, respectively. In leaves of transgenic tobacco plants, very low levels of trehalose accumulation were obtained (0.11 mg g-1 fresh weight), whereas in transgenic potato tubers, no trehalose accumulated at all. Plant trehalase activity was shown to affect the accumulation of trehalose in these plants. An increase in trehalose accumulation, up to 0.41 and 4.04 mg g-1 fresh weight in tobacco leaves and potato micro-tubers, respectively, was noted when the potent trehalase inhibitor validamycin A was added to in vitro plants and to hydroponically grown greenhouse plants. Stunted growth and the formation of lancet-shaped leaves by trehalose-accumulating tobacco plants suggest a negative effect of trehalose biosynthesis on N. tabacum development. It is surprising that experiments with wild-type plants cultured in the presence of validamycin A indicate that, despite current belief, the capacity to synthesize trehalose may not be restricted to primitive phyla of vascular plants and certain "resurrection plants," but may exist throughout the angiosperms.