Serum neutralizing capacity and T-cell response against the omicron BA.1 variant in seropositive children and their parents one year after SARS-CoV-2 infection.

Introduction: Durability of immune protection against reinfection with SARS-CoV-2 remains enigmatic, especially in the pediatric population and in the context of immune-evading variants of concern. Obviously, this knowledge is required for measures to contain the spread of infection and in selecting rational preventive measures.

Methods: Here, we investigated the serum neutralization capacity of 36 seropositive adults and 34 children approximately one year after infection with the ancestral Wuhan strain of SARS-CoV-2 by using a pseudovirus neutralization assay.

Cell competition is a tumour suppressor mechanism in the thymus.

Cell competition is an emerging principle underlying selection for cellular fitness during development and disease. Competition may be relevant for cancer, but an experimental link between defects in competition and tumorigenesis is elusive. In the thymus, T lymphocytes develop from precursors that are constantly replaced by bone-marrow-derived progenitors.

In vivo fate mapping identifies pre-TCRα expression as an intra- and extrathymic, but not prethymic, marker of T lymphopoiesis.

Expression of the pre-T cell receptor α (pTα) gene has been exploited in previous studies as a molecular marker to identify tiny cell populations in bone marrow (BM) and blood that were suggested to contain physiologically relevant thymus settling progenitors (TSPs). But to what extent these cells genuinely contribute to thymopoiesis has remained obscure. We have generated a novel pTα(iCre) knockin mouse line and performed lineage-tracing experiments to precisely quantitate the contribution of pTα-expressing progenitors to distinct differentiation pathways and to the genealogy of mature hematopoietic cells under physiological in vivo conditions.

Targeting π-conjugated multiple donor-acceptor motifs exemplified by tetrathiafulvalene-linked quinoxalines and tetrabenz[bc,ef,hi,uv]ovalenes: synthesis, spectroscopic, electrochemical, and theoretical characterization.

An efficient synthetic approach to a symmetrically functionalized tetrathiafulvalene (TTF) derivative with two diamine moieties, 2-[5,6-diamino-4,7-bis(4-pentylphenoxy)-1,3-benzodithiol-2-ylidene]-4,7-bis(4-pentylphenoxy)-1,3-benzodithiole-5,6-diamine (2), is reported. The subsequent Schiff-base reactions of 2 afford large π-conjugated multiple donor-acceptor (D-A) arrays, for example, the triad 2-[4,9-bis(4-pentylphenoxy)-1,3-dithiolo[4,5-g]quinoxalin-2-ylidene]-4,9-bis(4-pentylphenoxy)-1,3-dithiolo[4,5-g]quinoxaline (8) and the corresponding tetrabenz[bc,ef,hi,uv]ovalene-fused pentad 1, in good yields and high purity. The novel redox-active nanographene 1 is so far the largest known TTF-functionalized polycyclic aromatic hydrocarbon (PAH) with a well-resolved (1)H NMR spectrum.

Versatile strategy to access fully functionalized benzodifurans: redox-active chromophores for the construction of extended pi-conjugated materials.

An efficient synthetic approach to construct a fully substituted benzo[1,2-b:4,5-b']difuran (BDF) 2a via base-catalyzed double annulations is presented. Compound 2a can readily undergo Suzuki, Heck, and Sonogashira coupling reactions to afford in good yields a manifold of extended pi-conjugated BDF derivatives, e.g.

Fate mapping reveals separate origins of T cells and myeloid lineages in the thymus.

The cellular differentiation pathway originating from the bone marrow leading to early T lymphocytes remains poorly understood. The view that T cells branch off from a lymphoid-restricted pathway has recently been challenged by a model proposing a common progenitor for T cell and myeloid lineages. We generated interleukin-7 receptor alpha (Il7r) Cre recombinase knockin mice and traced lymphocyte development by visualizing the history of Il7r expression.

Annulation of tetrathiafulvalene to the bay region of perylenediimide.

A tetrathiafulvalene donor has been annulated to the bay region of perylenediimide affording a new pi-conjugated molecular dyad. Various electronic excited charge-transfer states are generated in different oxidation states, leading to almost full absorption in the visible to near-IR region with a high extinction coefficient.

A compactly fused pi-conjugated tetrathiafulvalene-perylenediimide donor-acceptor dyad.

The synthesis and structural characterization of a tetrathiafulvalene-fused perylenediimide molecular dyad is presented. Its largely extended pi-conjugation provides intense optical absorption bands over a wide spectral range. The planar functional molecule exhibits a short-lived nonluminescent excited state attributed to intramolecular charge separation.

Isolable zwitterionic pyridinio-semiquinone pi-radicals. Mild and efficient single-step access to stable radicals.

A rational design based on the proton-coupled electron transfer (PCET) concept allows us to structurally characterize for the first time isolable, air- and moisture-stable semiquinone radicals in a zwitterionic neutral form. The presence of an alkoxy and the bulky pyridinio substituents causes only a minor perturbation of either the redox potentials or the spectral UV-vis characteristics of the semiquinone core but significantly stabilizes the new radicals.

The pluripotency-associated gene Dppa4 is dispensable for embryonic stem cell identity and germ cell development but essential for embryogenesis.

Dppa4 (developmental pluripotency-associated 4) has been identified in several high-profile screens as a gene that is expressed exclusively in pluripotent cells. It encodes a nuclear protein with an SAP-like domain and appears to be associated preferentially with transcriptionally active chromatin. Its exquisite expression pattern and results of RNA interference experiments have led to speculation that Dppa4, as well as its nearby homolog Dppa2, might play essential roles in embryonic stem (ES) cell function and/or germ cell development.

Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms.

Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion.

Impaired function of primitive hematopoietic cells in mice lacking the Mixed-Lineage-Leukemia homolog MLL5.

The human Mixed-Lineage-Leukemia-5 (MLL5) gene is located in a genomic region frequently deleted in patients with myeloid malignancies and encodes a widely expressed nuclear protein most closely related to MLL1, a Trithorax transcriptional regulator with established involvement in leukemogenesis. Although the physiologic function of MLL5 is completely unknown, domain structure and homology to transcriptional regulators with histone methyltransferase activity suggest a role in epigenetic gene regulation. To investigate physiologic functions of Mll5, we have generated a knockout mouse mutant using Cre/loxP technology.

Neural crest origin of perivascular mesenchyme in the adult thymus.

The endodermal epithelial thymus anlage develops in tight association with neural crest (NC)-derived mesenchyme. This epithelial-NC interaction is crucial for thymus development, but it is not known how NC supports thymus development or whether NC cells or their progeny make any significant contribution to the adult thymus. By nude mouse blastocyst complementation and by cell surface phenotype, we could previously separate thymus stroma into Foxn1-dependent epithelial cells and a Foxn1-independent mesenchymal cell population.

Regulation of T cell survival through coronin-1-mediated generation of inositol-1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering.

T cell homeostasis is essential for the functioning of the vertebrate immune system, but the intracellular signals required for T cell homeostasis are largely unknown. We here report that the WD-repeat protein family member coronin-1, encoded by the gene Coro1a, is essential in the mouse for T cell survival through its promotion of Ca2+ mobilization from intracellular stores. Upon T cell receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5-trisphosphate from phosphatidylinositol-4,5-bisphosphate.

An efficient and facile synthesis of highly substituted 2,6-dicyanoanilines.

A one-pot procedure for the synthesis of substituted 2,6-dicyanoanilines starting from readily available ynones and malononitrile has been developed. For instance, penta-1,4-diyn-3-one is converted into the acetylene-substituted aniline derivative 1 in good yield. Upon photoexcitation, this chromophore shows a strong blue emission with a high quantum yield.

Faithful activation of an extra-bright red fluorescent protein in "knock-in" Cre-reporter mice ideally suited for lineage tracing studies.

The considerable potential of Cre recombinase as a tool for in vivo fate-mapping studies depends on the availability of reliable reporter mice. By targeting a tandem-dimer red fluorescent protein (tdRFP) with advanced spectral and biological properties into the ubiquitously expressed ROSA26 locus of C57BL/6-ES cells, we have generated a novel inbred Cre-reporter mouse with several unique characteristics. We directly demonstrate the usefulness of our reporter strain in inter-crosses with a "universal Cre-deleter" strain and with mice expressing Cre recombinase in a T lineage-specific manner.

Evidence for a functional second thymus in mice.

The thymus organ supports the development of T cells and is located in the thorax. Here, we report the existence of a second thymus in the mouse neck, which develops after birth and grows to the size of a small lymph node. The cervical thymus had a typical medulla-cortex structure, was found to support T cell development, and could correct T cell deficiency in athymic nude mice upon transplantation.

Gene targeting of VEGF-A in thymus epithelium disrupts thymus blood vessel architecture.

The thymus harbors an organ-typical dense network of branching and anastomosing blood vessels. To address the molecular basis for morphogenesis of this thymus-specific vascular pattern, we have inactivated a key vascular growth factor, VEGF-A, in thymus epithelial cells (TECs). Both Vegf-A alleles were deleted in TECs by a complementation strategy termed nude mouse [mutated in the transcription factor Foxn1 (forkhead box N1)] blastocyst complementation.

Loss of histochemical identity in mast cells lacking carboxypeptidase A.

Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease. The onset of expression in mast cell progenitors and lineage specificity suggest an important role for Mc-cpa in mast cells. To address the function of Mc-cpa, we generated Mc-cpa-null mice.

Mutational analysis of Ctnnb1 and Apc in tumors from rats given 1,2-dimethylhydrazine or 2-amino-3-methylimidazo[4,5-f]quinoline: mutational 'hotspots' and the relative expression of beta-catenin and c-jun.

There is growing interest in beta-catenin and its role in various human cancers. We recently reported that 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)- and 1,2-dimethylhydrazine (DMH)-induced colon tumors in the rat contain mutations in Ctnnb1, the gene for beta-catenin, but the mutation spectrum was influenced by postinitiation exposure to chlorophyllin (CHL) and indole-3-carbinol (I3C) [Blum et al., Carcinogenesis 2001;22:315-320].

Promotion versus suppression of rat colon carcinogenesis by chlorophyllin and chlorophyll: modulation of apoptosis, cell proliferation, and beta-catenin/Tcf signaling.

The carcinogens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 1,2-dimethylhydrazine (DMH) induce colon tumors in the rat that contain mutations in beta-catenin, but the mutation pattern can be influenced by exposure to dietary phytochemicals, such as the water-soluble derivative of chlorophyll called chlorophyllin. Whereas chlorophyllin is an effective blocking agent during the initiation phase, post-initiation responses depend upon the exposure protocol, and can be influenced by the initiating agent and the concentration of chlorophyllin. Post-initiation treatment with 0.

Beta cell-specific CD80 (B7-1) expression disrupts tissue protection from autoantigen-specific CTL-mediated diabetes.

T cell responses toward pancreatic beta cell autoantigens arise spontaneously or on immunization in many mouse strains, yet sustained islet infiltration and progressive diabetes rarely ensues. Most mouse diabetes models overcome the innocuous coexistence of anti-islet specific T cells and endogenous islets via incompletely understood mechanisms (e.g.