Further delineation of the rare GDACCF (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies syndrome): genotype and phenotype of 22 patients with ZNF148 mutations.

BACKGROUND Pathogenic variants in the zinc finger protein coding genes are rare causes of intellectual disability and congenital malformations. Mutations in the ZNF148 gene causing GDACCF syndrome (global developmental delay, absent or hypoplastic corpus callosum, dysmorphic facies; MIM #617260) have been reported in five individuals so far. METHODS As a result of an international collaboration using GeneMatcher Phenome Central Repository and personal communications, here we describe the clinical and molecular genetic characteristics of 22 previously unreported individuals. RESULTS The core clinical phenotype is characterised by developmental delay particularly in the domain of speech development, postnatal growth retardation, microcephaly and facial dysmorphism. Corpus callosum abnormalities appear less frequently than suggested by previous observations. The identified mutations concerned nonsense or frameshift variants that were mainly located in the last exon of the ZNF148 gene. Heterozygous deletion including the entire ZNF148 gene was found in only one case. Most mutations occurred de novo, but were inherited from an affected parent in two families. CONCLUSION The GDACCF syndrome is clinically diverse, and a genotype-first approach, that is, exome sequencing is recommended for establishing a genetic diagnosis rather than a phenotype-first approach. However, the syndrome may be suspected based on some recurrent, recognisable features. Corpus callosum anomalies were not as constant as previously suggested, we therefore recommend to replace the term 'GDACCF syndrome' with 'ZNF148-related neurodevelopmental disorder'

Differences in adherence and virulence gene expression between two outbreak strains of enterohaemorrhagic Escherichia coli O157 : H7

The Escherichia coli O157 : H7 TW14359 strain was implicated in a multi-state outbreak in North America in 2006, which resulted in high rates of severe disease. Similarly, the O157 : H7 RIMD0509952 (Sakai) strain caused the largest O157 : H7 outbreak to date. Both strains were shown to represent divergent phylogenetic lineages. Here we compared global gene expression patterns before and after epithelial cell exposure, as well as the ability to adhere to and invade epithelial cells, between the two outbreak strains. Epithelial cell assays demonstrated a 2.5-fold greater adherence of the TW14359 strain relative to Sakai, while whole-genome microarrays detected significant differential expression of 914 genes, 206 of which had a fold change ≥1.5. Interestingly, most locus of enterocyte effacement (LEE) genes were upregulated in TW14359, whereas flagellar and chemotaxis genes were primarily upregulated in Sakai, suggesting discordant expression of these genes between the two strains. The Shiga toxin 2 genes were also upregulated in the TW14359 strain, as were several pO157-encoded genes that promote adherence, including type II secretion genes and their effectors stcE and adfO. Quantitative RT-PCR confirmed the expression differences detected in the microarray analysis, and expression levels were lower for a subset of LEE genes before versus after exposure to epithelial cells. In all, this study demonstrated the upregulation of major and ancillary virulence genes in TW14359 and of flagellar and chemotaxis genes in Sakai, under conditions that precede intimate bacterial attachment to epithelial cells. Differences in the level of adherence to epithelial cells were also observed, implying that these two phylogenetically divergent O157 : H7 outbreak strains vary in their ability to colonize, or initiate the disease process

Measurement of neutrino oscillation parameters with the first six detection units of KM3NeT/ORCA

International audienceKM3NeT/ORCA is a water Cherenkov neutrino detector under construction and anchored at the bottom of the Mediterranean Sea. The detector is designed to study oscillations of atmospheric neutrinos and determine the neutrino mass ordering. This paper focuses on an initial configuration of ORCA, referred to as ORCA6, which comprises six out of the foreseen 115 detection units of photo-sensors. A high-purity neutrino sample was extracted, corresponding to an exposure of 433 kton-years. The sample of 5828 neutrino candidates is analysed following a binned log-likelihood method in the reconstructed energy and cosine of the zenith angle. The atmospheric oscillation parameters are measured to be $\sin^2\theta_{23}= 0.51^{+0.04}_{-0.05}$, and $\Delta m^2_{31} = 2.14^{+0.25}_{-0.35}\times 10^{-3}~\mathrm{eV^2} \cup \{-2.25,-1.76\}\times 10^{-3}~\mathrm{eV^2}$ at 68% CL. The inverted neutrino mass ordering hypothesis is disfavoured with a p-value of 0.25

Search for quantum decoherence in neutrino oscillations with six detection units of KM3NeT/ORCA

International audienceNeutrinos described as an open quantum system may interact with the environment which introduces stochastic perturbations to their quantum phase. This mechanism leads to a loss of coherence along the propagation of the neutrino $-$ a phenomenon commonly referred to as decoherence $-$ and ultimately, to a modification of the oscillation probabilities. Fluctuations in space-time, as envisaged by various theories of quantum gravity, are a potential candidate for a decoherence-inducing environment. Consequently, the search for decoherence provides a rare opportunity to investigate quantum gravitational effects which are usually beyond the reach of current experiments. In this work, quantum decoherence effects are searched for in neutrino data collected by the KM3NeT/ORCA detector from January 2020 to November 2021. The analysis focuses on atmospheric neutrinos within the energy range of a few GeV to $100\,\mathrm{GeV}$. Adopting the open quantum system framework, decoherence is described in a phenomenological manner with the strength of the effect given by the parameters $\Gamma_{21}$ and $\Gamma_{31}$. Following previous studies, a dependence of the type $\Gamma_{ij} \propto (E/E_0)^n$ on the neutrino energy is assumed and the cases $n = -2,-1$ are explored. No significant deviation with respect to the standard oscillation hypothesis is observed. Therefore, $90\,\%$ CL upper limits are estimated as $\Gamma_{21} < 4.6\cdot 10^{-21}\,$GeV and $\Gamma_{31} < 8.4\cdot 10^{-21}\,$GeV for $n = -2$, and $\Gamma_{21} < 1.9\cdot 10^{-22}\,$GeV and $\Gamma_{31} < 2.7\cdot 10^{-22}\,$GeV for $n = -1$, respectively

Measurement of neutrino oscillation parameters with the first six detection units of KM3NeT/ORCA

International audienceKM3NeT/ORCA is a water Cherenkov neutrino detector under construction and anchored at the bottom of the Mediterranean Sea. The detector is designed to study oscillations of atmospheric neutrinos and determine the neutrino mass ordering. This paper focuses on an initial configuration of ORCA, referred to as ORCA6, which comprises six out of the foreseen 115 detection units of photo-sensors. A high-purity neutrino sample was extracted, corresponding to an exposure of 433 kton-years. The sample of 5828 neutrino candidates is analysed following a binned log-likelihood method in the reconstructed energy and cosine of the zenith angle. The atmospheric oscillation parameters are measured to be $\sin^2\theta_{23}= 0.51^{+0.04}_{-0.05}$, and $\Delta m^2_{31} = 2.14^{+0.25}_{-0.35}\times 10^{-3}~\mathrm{eV^2} \cup \{-2.25,-1.76\}\times 10^{-3}~\mathrm{eV^2}$ at 68% CL. The inverted neutrino mass ordering hypothesis is disfavoured with a p-value of 0.25

Measurement of neutrino oscillation parameters with the first six detection units of KM3NeT/ORCA

International audienceKM3NeT/ORCA is a water Cherenkov neutrino detector under construction and anchored at the bottom of the Mediterranean Sea. The detector is designed to study oscillations of atmospheric neutrinos and determine the neutrino mass ordering. This paper focuses on an initial configuration of ORCA, referred to as ORCA6, which comprises six out of the foreseen 115 detection units of photo-sensors. A high-purity neutrino sample was extracted, corresponding to an exposure of 433 kton-years. The sample of 5828 neutrino candidates is analysed following a binned log-likelihood method in the reconstructed energy and cosine of the zenith angle. The atmospheric oscillation parameters are measured to be $\sin^2\theta_{23}= 0.51^{+0.04}_{-0.05}$, and $\Delta m^2_{31} = 2.14^{+0.25}_{-0.35}\times 10^{-3}~\mathrm{eV^2} \cup \{-2.25,-1.76\}\times 10^{-3}~\mathrm{eV^2}$ at 68% CL. The inverted neutrino mass ordering hypothesis is disfavoured with a p-value of 0.25

Measurement of neutrino oscillation parameters with the first six detection units of KM3NeT/ORCA

International audienceKM3NeT/ORCA is a water Cherenkov neutrino detector under construction and anchored at the bottom of the Mediterranean Sea. The detector is designed to study oscillations of atmospheric neutrinos and determine the neutrino mass ordering. This paper focuses on an initial configuration of ORCA, referred to as ORCA6, which comprises six out of the foreseen 115 detection units of photo-sensors. A high-purity neutrino sample was extracted, corresponding to an exposure of 433 kton-years. The sample of 5828 neutrino candidates is analysed following a binned log-likelihood method in the reconstructed energy and cosine of the zenith angle. The atmospheric oscillation parameters are measured to be $\sin^2\theta_{23}= 0.51^{+0.04}_{-0.05}$, and $\Delta m^2_{31} = 2.14^{+0.25}_{-0.35}\times 10^{-3}~\mathrm{eV^2} \cup \{-2.25,-1.76\}\times 10^{-3}~\mathrm{eV^2}$ at 68% CL. The inverted neutrino mass ordering hypothesis is disfavoured with a p-value of 0.25

Measurement of neutrino oscillation parameters with the first six detection units of KM3NeT/ORCA

International audienceKM3NeT/ORCA is a water Cherenkov neutrino detector under construction and anchored at the bottom of the Mediterranean Sea. The detector is designed to study oscillations of atmospheric neutrinos and determine the neutrino mass ordering. This paper focuses on an initial configuration of ORCA, referred to as ORCA6, which comprises six out of the foreseen 115 detection units of photo-sensors. A high-purity neutrino sample was extracted, corresponding to an exposure of 433 kton-years. The sample of 5828 neutrino candidates is analysed following a binned log-likelihood method in the reconstructed energy and cosine of the zenith angle. The atmospheric oscillation parameters are measured to be $\sin^2\theta_{23}= 0.51^{+0.04}_{-0.05}$, and $\Delta m^2_{31} = 2.14^{+0.25}_{-0.35}\times 10^{-3}~\mathrm{eV^2} \cup \{-2.25,-1.76\}\times 10^{-3}~\mathrm{eV^2}$ at 68% CL. The inverted neutrino mass ordering hypothesis is disfavoured with a p-value of 0.25