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Dendritic cells (DCs) play a crucial role in orchestrating immune responses, particularly in promoting IFNγ-producing-CD8 cytotoxic T lymphocytes (CTLs) and IFNγ-producing-CD4 T helper 1 (Th1) cells, which are essential for defending against viral infections. Additionally, the nuclear envelope protein lamin A/C has been implicated in T cell immunity. Nevertheless, the intricate interplay between innate and adaptive immunity in response to viral infections, particularly the role of lamin A/C in DC functions within this context, remains poorly understood. In this study, we demonstrate that mice lacking lamin A/C in myeloid LysM promoter-expressing cells exhibit a reduced capacity to induce Th1 and CD8 CTL responses, leading to impaired clearance of acute primary Vaccinia virus (VACV) infection. Remarkably, in vitro-generated granulocyte macrophage colony-stimulating factor bone marrow-derived DCs (GM-CSF BMDCs) show high levels of lamin A/C. Lamin A/C absence on GM-CSF BMDCs does not affect the expression of costimulatory molecules on the cell membrane but it reduces the cellular ability to form immunological synapses with naïve CD4 T cells. Lamin A/C deletion induces alterations in NFκB nuclear localization, thereby influencing NF-κB-dependent transcription. Furthermore, lamin A/C ablation modifies the gene accessibility of BMDCs, predisposing these cells to mount a less effective antiviral response upon TLR stimulation. This study highlights the critical role of DCs in interacting with CD4 T cells during antiviral responses and proposes some mechanisms through which lamin A/C may modulate DC function via gene accessibility and transcriptional regulation. [ABSTRACT FROM AUTHOR]

Clonal hematopoiesis of indeterminate potential (CHIP), defined as the presence of somatic mutations in cancer-related genes in blood cells in the absence of hematological cancer, has recently emerged as an important risk factor for several age-related conditions, especially cardiovascular disease. CHIP is strongly associated with normal aging, but its role in premature aging syndromes is unknown. Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare genetic condition driven by the accumulation of a truncated form of the lamin A protein called progerin. HGPS patients exhibit several features of accelerated aging and typically die from cardiovascular complications in their early teens. Previous studies have shown normal hematological parameters in HGPS patients, except for elevated platelets, and low levels of lamin A expression in hematopoietic cells relative to other cell types in solid tissues, but the prevalence of CHIP in HGPS remains unexplored. To investigate the potential role of CHIP in HGPS, we performed high-sensitivity targeted sequencing of CHIP-related genes in blood DNA samples from a cohort of 47 HGPS patients. As a control, the same sequencing strategy was applied to blood DNA samples from middle-aged and elderly individuals, expected to exhibit a biological age and cardiovascular risk profile similar to HGPS patients. We found that CHIP is not prevalent in HGPS patients, in marked contrast to our observations in individuals who age normally. Thus, our study unveils a major difference between HGPS and normal aging and provides conclusive evidence that CHIP is not frequent in HGPS and, therefore, is unlikely to contribute to the pathophysiology of this accelerated aging syndrome. [ABSTRACT FROM AUTHOR]

Here we explored the role of interleukin-1β (IL-1β) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent in acute myeloid leukemia (AML) patients and represents a prognostic marker of reduced survival. Treatments with IL-1RN and the IL-1β monoclonal antibody canakinumab reduce the expansion of leukemic cells, including CD34+ progenitors, in AML xenografts. In vivo deletion of IL-1rn induces hematopoietic stem cell (HSC) differentiation into the myeloid lineage and hampers B cell development via transcriptional activation of myeloid differentiation pathways dependent on NFκB. Low IL-1rn is present in an experimental model of pre-leukemic myelopoiesis, and IL-1rn deletion promotes myeloproliferation, which relies on the bone marrow hematopoietic and stromal compartments. Conversely, IL-1rn protects against pre-leukemic myelopoiesis. Our data reveal that HSC differentiation is controlled by balanced IL-1β/IL-1rn levels under steady-state, and that loss of repression of IL-1β signaling may underlie pre-leukemic lesion and AML progression. Enhanced IL-1β signaling pathway causes hematopoietic stem cell (HSC) to differentiate into myeloid cells and contributes to malignant hematopoiesis. Here the authors reveal that HSC differentiation is controlled by balanced levels of IL-1 receptor antagonist (IL-1rn) and IL-1β under steady-state, and that IL-1rn protects against pre-leukemic myelopoiesis by repressing IL-1β signaling. [ABSTRACT FROM AUTHOR]

Spinal extradural arteriovenous fistulas (SEDAVF) with intradural drainage are uncommon vascular lesions that cause venous congestive myelopathy. We present three SEDAVF with intradural drainage treated with surgical disconnection of the intradural drainage via a single level laminectomy, followed by transarterial embolization (TAE) with Onyx if spontaneous thrombosis of the extradural fistula did not occur spontaneously. All patients improved their neurological condition and no congestive myelopathy recurrence was noted after mean follow-up of 84 months. We believe that SEDAVF with intradural drainage constitute a specific entity that should be included in the classifications of spinal arteriovenous malformations. [ABSTRACT FROM AUTHOR]

The occupancy of nucleosomes governs access to the eukaryotic genomes and results from a combination of biophysical features and the effect of ATP-dependent remodelling complexes. Most promoter regions show a conserved pattern characterized by a nucleosome-depleted region (NDR) flanked by nucleosomal arrays. The conserved RSC remodeler was reported to be critical to establish NDR in vivo in budding yeast but other evidences suggested that this activity may not be conserved in fission yeast. By reanalysing and expanding previously published data, we propose that NDR formation requires, at least partially, RSC in both yeast species. We also discuss the most prominent biological role of RSC and the possibility that non-essential subunits do not define alternate versions of the complex. [ABSTRACT FROM AUTHOR]

The developing human brain requires high amounts of sialic acids. While human milk is very rich in sialic acids, cow’s milk based infant formulas provide lower amounts of sialic acids, and sialic acids are absent in soy milk based formulas. This has prompted interest in the supplementation of formulas with sialic acids, either free or bound to glycoconjugates. In order for fortification of infant formulas with sialic acids to be appropriate for the developmental needs of the infant, an accurate quantitation of sialic acid content of infant formulas through a reliable and easy-to-use method is, therefore, of great interest to industry. In the present method, we describe the application of one of the most widely used analytical techniques to the quantitation of sialic acids in infant formulas. Briefly, sialic acids are hydrolyzed from glycoconjugates, derivatized using 1,2-diamino-4,5-methylenedioxybenzene dihydrochloride (DMB), and separated using reversed-phase high-performance liquid chromatography. The method fulfilled the established criteria for validation, with an interassay standard deviation of less than 5%, accuracy greater than 97%, and surrogate recovery between 98 and 104%. An investigation of the ruggedness of the method identified two key criteria: both standards and samples must be subjected to the same temperature and pH conditions for an accurate quantitation; and prolonged storage (more than 2 days) of the DMB reagent and derivatives must be avoided. In conclusion, this method is specific, straightforward, and accurate and can be easily performed in a quality-assurance laboratory to track the level of sialic acid in formulas that contain both inherent and fortified amounts of sialic acids. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Lactose Does Not Interfere With the Analysis of Sialic Acids As Their 1,2-diamino-4,5-methylenedioxybenzene Derivatives," by Spichtig et al., published in the previous issue.