Immune response to SARS-CoV-2 Omicron variant in patients and vaccinees following homologous and heterologous vaccinations

Antibodies elicited by a triple homologous or heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1.The SARS-CoV-2 Omicron variant has rapidly replaced the Delta variant of concern. This new variant harbors worrisome mutations on the spike protein, which are able to escape the immunity elicited by vaccination and/or natural infection. To evaluate the impact and susceptibility of different serum samples to the Omicron variant BA.1, samples from COVID-19 patients and vaccinated individuals were tested for their ability to bind and neutralize the original SARS-CoV-2 virus and the Omicron variant BA.1. COVID-19 patients show the most drastic reduction in Omicron-specific antibody response in comparison with the response to the wild-type virus. Antibodies elicited by a triple homologous/heterologous vaccination regimen or following natural SARS-CoV-2 infection combined with a two-dose vaccine course, result in highest neutralization capacity against the Omicron variant BA.1. Overall, these findings confirm that vaccination of COVID-19 survivors and booster dose to vaccinees with mRNA vaccines is the correct strategy to enhance the antibody cross-protection against Omicron variant BA.1

Functional analysis of the protein phosphatase activity of PTEN

In vitro, the tumour suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) displays intrinsic phosphatase activity towards both protein and lipid substrates. In vivo, the lipid phosphatase activity of PTEN, through which it dephosphorylates the 3 position in the inositol sugar of phosphatidylinositol derivatives, is important for its tumour suppressor function; however, the significance of its protein phosphatase activity remains unclear. Using two-photon laser-scanning microscopy and biolistic gene delivery of GFP (green fluorescent protein)-tagged constructs into organotypic hippocampal slice cultures, we have developed an assay of PTEN function in living tissue. Using this bioassay, we have demonstrated that overexpression of wild-type PTEN led to a decrease in spine density in neurons. Furthermore, it was the protein phosphatase activity, but not the lipid phosphatase activity, of PTEN that was essential for this effect. The ability of PTEN to decrease neuronal spine density depended upon the phosphorylation status of serine and threonine residues in its C-terminal segment and the integrity of the C-terminal PDZ-binding motif. The present study reveals a new aspect of the function of this important tumour suppressor and suggest that, in addition to dephosphorylating the 3 position in phosphatidylinositol phospholipids, the critical protein substrate of PTEN may be PTEN itself

Search for heavy neutral lepton production in K+ decays

A search for heavy neutral lepton production in K + decays using a data sample collected with a minimum bias trigger by the NA62 experiment at CERN in 2015 is reported. Upper limits at the 10−7 to 10−6 level are established on the elements of the extended neutrino mixing matrix |Ue4| 2 and |Uμ4| 2 for heavy neutral lepton mass in the ranges 170–448 MeV/c2 and 250–373 MeV/c2, respectively. This improves on the previous limits from HNL production searches over the whole mass range considered for |Ue4|2 and above 300 MeV/c2 for |Uμ4|2

Finding New Genes for Non-Syndromic Hearing Loss through an In Silico Prioritization Study

At present, 51 genes are already known to be responsible for Non-Syndromic hereditary Hearing Loss (NSHL), but the knowledge of 121 NSHL-linked chromosomal regions brings to the hypothesis that a number of disease genes have still to be uncovered. To help scientists to find new NSHL genes, we built a gene-scoring system, integrating Gene Ontology, NCBI Gene and Map Viewer databases, which prioritizes the candidate genes according to their probability to cause NSHL. We defined a set of candidates and measured their functional similarity with respect to the disease gene set, computing a score () that relies on the assumption that functionally related genes might contribute to the same (disease) phenotype. A Kolmogorov-Smirnov test, comparing the pair-wise distribution on the disease gene set with the distribution on the remaining human genes, provided a statistical assessment of this assumption. We found at a p-value that the former pair-wise is greater than the latter, justifying a prioritization strategy based on the functional similarity of candidate genes respect to the disease gene set. A cross-validation test measured to what extent the ranking for NSHL is different from a random ordering: adding 15% of the disease genes to the candidate gene set, the ranking of the disease genes in the first eight positions resulted statistically different from a hypergeometric distribution with a p-value and a power. The twenty top-scored genes were finally examined to evaluate their possible involvement in NSHL. We found that half of them are known to be expressed in human inner ear or cochlea and are mainly involved in remodeling and organization of actin formation and maintenance of the cilia and the endocochlear potential. These findings strongly indicate that our metric was able to suggest excellent NSHL candidates to be screened in patients and controls for causative mutations

Collective decision-making in rehabilitation teams: practices of talking work

Nell'articolo vengono comparate le pratiche discorsive di due gruppi di lavoro all'interno della medesima istituzione (un servizio socio-psichiatrico) in rapporto all'attività di formulazione dei problemi che avviene durante le riunioni. Dal punto di vista metodologico lo studio combina una indagine etnografica con un'analisi qualitativa di otto riunioni che sono state registrate e trascritte; l'analisi qualitativa è stata condotta sulla base di tre dimensioni: la cornice di partecipazione, la polifonia, e la memoria condivisa. L'analisi mostra come i due gruppi – nonostante si muovano all'interno dello stesso quadro istituzionale – realizzino differenti organizzazioni dell'attività discorsiva. Da un lato la cornice istituzionale dà forma al lavoro discorsivo; dall'altro lato ciascun gruppo di lavoro sviluppa un repertorio di pratiche unico, in risposta ad un insieme di vincoli che includono quelli istituzionali, ma non sono da questi stessi esauriti

Narrative activity within an institutional framework: how a rehabilitation team constructs problems that can be solved

This is a study about discursive practices of problem solving within a team of professionals who rehabilitate people with psycho-social problems. The study community is the team of Centro a.D., an organization located in the South of Switzerland. The research combines an ethnographic study of Centro a.D. with a qualitative analysis of recorded talk during team meetings. In particular, narrative analysis has been applied to study problem solving. An extensive history of team meetings has been considered; it was possible to recognize that some operations systematically occur in problem solving. The set of these operations is the corpus of Centro a.D’s working practices in relation to problem solving activity, i.e. layered narratives, old narratives as resources, contextualization, discursive simplification of the rehabilitation project, centralization of interaction. Examining the relationship between the problem solving activity and the institutional framework of Centro a.D., the research illustrates the extent to which problem solving is shaped by such a framework. Namely, planned solutions necessarily belong to a set of possible actions enabled by the institution and problem description must enable the planning of those kind of solutions that can be implemented within the institution. Therefore we can speak in terms of institutional narratives and non-institutional narratives: institutional narratives construct problems that open possibilities for action within a specific fragment of social reality

Driving AMPA Receptors into Synapses by LTP and CaMKII: Requirement for GluR1 and PDZ Domain Interaction

To elucidate mechanisms that control and execute activity-dependent synaptic plasticity, a-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPA-Rs) with an electrophysiological tag were expressed in rat hippocampal neurons. Long-term potentiation (LTP) or increased activity of the calcium/ calmodulin-dependent protein kinase II (CaMKII) induced delivery of tagged AMPA-Rs into synapses. This effect was not diminished by mutating the CaMKII phosphorylation site on the GluR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site. These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein.Y.H. was supported by Japan Society for the Promotion of Science and Uehara Memorial Foundation, J.A.E. by Alzheimer Association and National Alliance for Research on Schizophrenia and Depression, and J.-C.P. by the Human Frontier Science Program Organization. This study was supported by NIH and the Mathers Foundation (to R.M).Peer reviewe

β-Amyloid Is Different in Normal Aging and in Alzheimer Disease

The mechanism of neurodegeneration caused by beta-amyloid in Alzheimer disease is controversial. Neuronal toxicity is exerted mostly by various species of soluble beta-amyloid oligomers that differ in their N- and C-terminal domains. However, abundant accumulation of beta-amyloid also occurs in the brains of cognitively normal elderly people, in the absence of obvious neuronal dysfunction. We postulated that neuronal toxicity depends on the molecular composition, rather than the amount, of the soluble beta-amyloid oligomers. Here we show that soluble beta-amyloid aggregates that accumulate in Alzheimer disease are different from those of normal aging in regard to the composition as well as the aggregation and toxicity properties

The neutralizing response to SARS-CoV-2 Omicron variants BA.1 and BA.2 in COVID-19 patients and homologous and heterologous vaccinees

The rapid replacement of Omicron BA.1 by BA.2 sublineage is very alarming, raising the question of whether BA.2 can escape the immunity acquired after BA.1 infection. We compared the neutralizing activity toward the Omicron BA.1 and BA.2 sub-lineages in five groups: COVID-19 patients; subjects who had received two doses of mRNA vaccine; subjects naturally infected with SARS-CoV-2 who had received two doses of mRNA; and subjects who had received three doses of homologous or heterologous vaccine. The results obtained highlight the importance of vaccine boosters in eliciting neutralizing antibody responses against Omicron sub-lineages, and suggest that the adenovirus vectored vaccine elicits a lower response against BA.1 than against BA.2 sub-lineage