ABSTRACT
The SNO+ Collaboration reports the first evidence of reactor antineutrinos in a Cherenkov detector. The nearest nuclear reactors are located 240 km away in Ontario, Canada. This analysis uses events with energies lower than in any previous analysis with a large water Cherenkov detector. Two analytical methods are used to distinguish reactor antineutrinos from background events in 190 days of data and yield consistent evidence for antineutrinos with a combined significance of 3.5σ.
ABSTRACT
Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate a mutant form of the TARP family member stargazin, described in an ID patient. Molecular dynamics analyses predicted that the ID-associated stargazin variant, V143L, weakens the overall interface of the AMPAR:stargazin complex and impairs the stability of the complex. Knock-in mice harboring the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects, resembling phenotypes displayed by ID patients. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation, abnormal synaptic transmission and long-term potentiation specifically in basal dendrites, and synaptic ultrastructural alterations. These data suggest a causal role for mutated stargazin in the pathogenesis of ID and unveil a new role for stargazin in the development and function of hippocampal synapses.
Subject(s)
Calcium Channels , Intellectual Disability , Receptors, AMPA , Animals , Calcium Channels/genetics , Calcium Channels/metabolism , Hippocampus/metabolism , Humans , Intellectual Disability/genetics , Intellectual Disability/metabolism , Mice , Mutation/genetics , Receptors, AMPA/genetics , Receptors, AMPA/metabolism , Synapses/metabolism , Synaptic Transmission/geneticsABSTRACT
1. In this study, classical and molecular microbiological methods for detection and quantification of Campylobacter spp. were used to estimate their prevalence in faecal samples and skin swabs collected from 31 broiler flocks (20 farms) in Portugal, and measure the impact of transport-related factors on the expected rising excretion rates from the farm to the slaughterhouse. 2. Data on husbandry practices and transport conditions were gathered, including time in transit, distance travelled or ante-mortem plant-holding time. 3. A generalised linear mixed model was used to evaluate the significance of a potential post-transport rise in Campylobacter spp. counts and to assess risk determinants. 4. At least one flock tested positive for Campylobacter spp. in 80% of the sampled farms. At the slaughterhouse, Campylobacter spp. were detected in all faecal samples, C. jejuni being the most commonly isolated. 5. A post-transport rise of Campylobacter spp. counts from skin swabs was observed using classical microbiological methods (from a mean of 1.43 to 2.40 log10 CFU/cm2) and molecular techniques (from a mean of 2.64 to 3.31 log10 genome copies/cm2). 6. None of the husbandry practices or transport-related factors were found to be associated with Campylobacter spp. counts. 7. This study highlights the need for more research to better understand the multi-factorial nature of Campylobacter spp., a public health threat that was found to be highly prevalent in a sample of Portuguese poultry farms.