A novel unconventional T cell population enriched in Crohn's disease

Objective One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls. Design We performed bulk TCR repertoire profiling of both the TCR alpha and beta chains using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. We further characterised specific T cell clonotypes via single-cell RNAseq. Results We identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn's disease (CD) and particularly expanded in the CD8+ T cell population. Single-cell RNAseq data showed an innate-like phenotype of these cells, with a comparable gene expression to unconventional T cells such as mucosal associated invariant T and natural killer T (NKT) cells, but with distinct TCRs. Conclusions We identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Innvandrerfamilier med barn med spesielle behov – mødres tilknytning til arbeidslivet

Artikkelen belyser hvordan mødre med innvandrerbakgrunn som har barn med spesielle behov, reflekterer over egne forventninger og muligheter til det å være yrkesaktive. Analysen er basert på kvalitative intervjuer med i alt 27 foreldre. De fleste mødrene ønsker å være i arbeid, men flere opplever likevel at dette er vanskelig å realisere. Mange familier kommer inn i en negativ spiral som begrenser mødrenes arbeidsdeltakelse, gjennom at fedre må arbeide stadig lengre dager, mens mødrene blir utslitt av det ekstra omsorgsarbeidet. Analysen viser at avlastnings- tilbud, begrenset relevant utdanning, språk og arbeidserfaring har stor betydning for arbeidsmulighetene

Innvandrerfamilier med barn med spesielle behov – mødres tilknytning til arbeidslivet

Sammendrag Artikkelen belyser hvordan mødre med innvandrerbakgrunn som har barn med spesielle behov, reflekterer over egne forventninger og muligheter til det å være yrkesaktive. Analysen er basert på kvalitative intervjuer med i alt 27 foreldre. De fleste mødrene ønsker å være i arbeid, men flere opplever likevel at dette er vanskelig å realisere. Mange familier kommer inn i en negativ spiral som begrenser mødrenes arbeidsdeltakelse, gjennom at fedre må arbeide stadig lengre dager, mens mødrene blir utslitt av det ekstra omsorgsarbeidet. Analysen viser at avlastningstilbud, begrenset relevant utdanning, språk og arbeidserfaring har stor betydning for arbeidsmulighetene. Nøkkelord: kvinner, innvandrerbakgrunn, barn med spesielle behov, arbeidsdeltakels

High-Frequency Vibrations of the Simplest Benzylic Amide [2]Catenane

Infrared and Raman spectroscopies along with molecular orbital calculations are used to study-for the first time-the vibrational motions of a topologically complicated chemical system, namely a [2]catenane of the benzylic amide type. Because of the intrinsic line width of the spectra, comparison of experiments and theory is only partially successful. The insight given by the simulations-which show that the C=O normal modes are delocalized while the N-H modes are localized-is, however, useful and makes us propose a simple model that explains both the larger line width of the spectra of the catenane with respect to those of the parent macrocycle and the great sensitivity of the infrared spectrum of the catenane to the environment. Examples of such sensitivity are the frequency shifts observed upon going from KBr to CsI, features not present in the case of the macrocycle.

Experimental and theoretical studies of the low-lying electronic states of the simplest benzylic amide [2]catenane

The lowest electronically excited states of the simplest benzylic amide [2]catenane have been studied by a combination of experimental and theoretical techniques. Experimentally, steady-state and transient absorption spectra, emission spectra, and the optoacoustic response in solution have been recorded for the catenane and a model compound (N,N'-dibenzylisophthalic diamide), as well as the electron energy loss spectrum of the catenane deposited on the Au(111) surface. The theoretical picture builds on the results of semiempirical quantum chemical calculations and shows that partial delocalisation of the electronic states over the many chromophores of the catenanes can occur.