25 research outputs found
Purkinje cell-specific ablation of CaV2.1 Channels is sufficient to cause cerebellar ataxia in mice
The Cacna1a gene encodes the α1A subunit of voltage-gated CaV2.1 Ca2+ channels that are involved in neurotransmission at central synapses. CaV2.1-α1- knockout (α1KO) mice, which lack CaV2.1 channels in all neurons, have a very severe phenotype of cerebellar ataxia and dystonia, and usually die around postnatal day 20. This early lethality, combined with the wide expression of CaV2.1 channels throughout the cerebellar cortex and nuclei, prohibited determination of the contribution of particular cerebellar cell types to the development of the severe neurobiological phenotype in Cacna1a mutant mice. Here, we crossed conditional Cacna1a mice with transgenic mice expressing Cre recombinase, driven by the Purkinje cell-specific Pcp2 promoter, to specifically ablate the CaV2.1- α1A subunit and thereby CaV2.1 channels in Purkinje cells. Purkinje cell CaV2.1-α1A-knockout (PCα1KO) mice aged without difficulties, rescuing the lethal phenotype seen in α1KO mice. PCα1KO mice exhibited cerebellar ataxia starting around P12, much earlier than the first signs of progressive Purkinje cell loss, which appears in these mice between P30 and P45. Secondary cell loss was observed in the granular and molecular layers of the cerebellum and the volume of all individual cerebellar nuclei was reduced. In this mouse model with a cell type-specific ablation of CaV2.1 channels, we show that ablation of CaV2.1 channels restricted to Purkinje cells is sufficient to cause cerebellar ataxia. We demonstrate that spatial ablation of CaV2.1 channels may help in unraveling mechanisms of human disease
The worldwide NORM production and a fully automated gamma-ray spectrometer for their characterization
Materials containing radionuclides of natural origin, which is modified by
human made processes and being subject to regulation because of their
radioactivity are known as NORM. We present a brief review of the main
categories of non-nuclear industries together with the levels of activity
concentration in feed raw materials, products and waste, including mechanisms
of radioisotope enrichments. The global management of NORM shows a high level
of complexity, mainly due to different degrees of radioactivity enhancement and
the huge amount of worldwide waste production. The future tendency of
guidelines concerning environmental protection will require both a systematic
monitoring based on the ever-increasing sampling and high performance of gamma
ray spectroscopy. On the ground of these requirements a new low background
fully automated high-resolution gamma-ray spectrometer MCA_Rad has been
developed. The design of Pb and Cu shielding allowed to reach a background
reduction of two order of magnitude with respect to laboratory radioactivity. A
severe lowering of manpower cost is obtained through a fully automation system,
which enables up to 24 samples to be measured without any human attendance. Two
coupled HPGe detectors increase the detection efficiency, performing accurate
measurements on sample volume (180 cc) with a reduction of sample transport
cost of material. Details of the instrument calibration method are presented.
MCA_Rad system can measure in less than one hour a typical NORM sample enriched
in U and Th with some hundreds of Bq/kg, with an overall uncertainty less than
5%. Quality control of this method has been tested. Measurements of certified
reference materials RGK-1, RGU-2 and RGTh-1 containing concentrations of K, U
and Th comparable to NORM have been performed, resulting an overall relative
discrepancy of 5% among central values within the reported uncertainty.Comment: 21 pages, 4 figures, 6 table
Can environment or allergy explain international variation in prevalence of wheeze in childhood?
Asthma prevalence in children varies substantially around the world, but the contribution of known risk factors to this international variation is uncertain. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two studied 8–12 year old children in 30 centres worldwide with parent-completed symptom and risk factor questionnaires and aeroallergen skin prick testing. We used multilevel logistic regression modelling to investigate the effect of adjustment for individual and ecological risk factors on the between-centre variation in prevalence of recent wheeze. Adjustment for single individual-level risk factors changed the centre-level variation from a reduction of up to 8.4% (and 8.5% for atopy) to an increase of up to 6.8%. Modelling the 11 most influential environmental factors among all children simultaneously, the centre-level variation changed little overall (2.4% increase). Modelling only factors that decreased the variance, the 6 most influential factors (synthetic and feather quilt, mother’s smoking, heating stoves, dampness and foam pillows) in combination resulted in a 21% reduction in variance. Ecological (centre-level) risk factors generally explained higher proportions of the variation than did individual risk factors. Single environmental factors and aeroallergen sensitisation measured at the individual (child) level did not explain much of the between-centre variation in wheeze prevalence
Human leukocyte antigen-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in an Albanian population from Kosovo
HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genotyping was performed in a sample of Albanian population from Kosovo. The comparison of the respective allele frequencies through Fst analysis resulted in a close relationship with the Albanians from Albania, the Bulgarians, FYROM Macedonians and Greeks, while the other neighbouring populations are slightly more distant
Plasma metabolic profiling after cortical spreading depression in a transgenic mouse model of hemiplegic migraine by capillary electrophoresis mass spectrometry
Paroxysmal Cerebral Disorder
Automatic Registration of Mass Spectrometry Imaging Data Sets to the Allen Brain Atlas
Proteomic