The transcription complex p52-ETS1 is essential for germinal center formation.

The NF-κB family comprises five transcription factors (RELA, RELB, C-REL, NF-κB1 (p50) and NF-κB2 (p52)) that form homo- or heterodimers among themselves to regulate gene expression by binding DNA. Here we show that p52 activates transcription without directly binding DNA but as a heterotetrameric complex with ETS1, a transcription factor outside the NF-κB family. By generating a knock-in mouse model (Nfkb2) with three mutated residues on p52 required for its interaction with ETS1, but not RELB, we demonstrate that the p52-ETS1 complex regulates the expression of transcription factors OCT1 and OBF1, which are known to be critical for the germinal center program.

Serotonin receptor 5-HT as a potential target for HCC immunotherapy.

Background: While recent clinical trials of combination immunotherapies for hepatocellular carcinoma (HCC) have shown promising clinical efficacy and survival improvements breakthroughs, there is still much room for further improvement. A key limiting factor for HCC immunotherapy is the intrinsic immunosuppression within the liver microenvironment, resulting in suboptimal priming of tumor-specific CD8 cytotoxic T cells and thus immune evasion by the tumor. Hence, identifying new key molecular pathways suppressing T-cell responses within the liver is critical for the rational design of more effective combination immunotherapies for HCC.

Crosstalk between CD64MHCII macrophages and CD4 T cells drives joint pathology during chikungunya.

Communications between immune cells are essential to ensure appropriate coordination of their activities. Here, we observed the infiltration of activated macrophages into the joint-footpads of chikungunya virus (CHIKV)-infected animals. Large numbers of CD64MHCII and CD64MHCII macrophages were present in the joint-footpad, preceded by the recruitment of their CD11bLy6C inflammatory monocyte precursors.

Palliative Sedation Therapy Practice Comparison - A Survey of Pediatric Palliative Care and Pain Management Specialists.

: Palliative sedation therapy (PST) can relieve suffering at end-of-life (EOL) in children with intolerable and refractory symptoms. However, updated and consistent guidance on PST practices are imperative. : We investigate current variations in clinical practice and PST implementation among pediatric palliative care (PPC) and pain management (PM) specialists.

Acute changes in handgrip strength, lung function and health-related quality of life following cardiac surgery.

Background: Handgrip strength (HGS), lung function and health-related quality of life (HRQoL) are relevant indicators of future cardiovascular risk and mortality. The impact of cardiac surgery on these predictive variables has been under-explored. The aim of this study was to determine the acute (within hospital) changes in HGS, lung function and HRQoL, and their relationships, in adults undergoing elective cardiac surgery.

Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined.

A subset of Kupffer cells regulates metabolism through the expression of CD36.

Tissue macrophages are immune cells whose phenotypes and functions are dictated by origin and niches. However, tissues are complex environments, and macrophage heterogeneity within the same organ has been overlooked so far. Here, we used high-dimensional approaches to characterize macrophage populations in the murine liver.

Prevalence of traumatic brain injury among the guests at a low-barrier homeless shelter.

Objective: This study aimed at determining the prevalence of traumatic brain injuries (TBI) among guests staying at a low-barrier homeless shelter who represent an especially vulnerable subset of individuals experiencing homelessness.

Results: A total of 21 out of 35 shelter guests participated in the survey. We found that 17 (81.

Combinatorial Single-Cell Analyses of Granulocyte-Monocyte Progenitor Heterogeneity Reveals an Early Uni-potent Neutrophil Progenitor.

Granulocyte-monocyte progenitors (GMPs) have been previously defined for their potential to generate various myeloid progenies such as neutrophils and monocytes. Although studies have proposed lineage heterogeneity within GMPs, it is unclear if committed progenitors already exist among these progenitors and how they may behave differently during inflammation. By combining single-cell transcriptomic and proteomic analyses, we identified the early committed progenitor within the GMPs responsible for the strict production of neutrophils, which we designate as proNeu1.

Midkine-a functions as a universal regulator of proliferation during epimorphic regeneration in adult zebrafish.

Zebrafish have the ability to regenerate damaged cells and tissues by activating quiescent stem and progenitor cells or reprogramming differentiated cells into regeneration-competent precursors. Proliferation among the cells that will functionally restore injured tissues is a fundamental biological process underlying regeneration. Midkine-a is a cytokine growth factor, whose expression is strongly induced by injury in a variety of tissues across a range of vertebrate classes.

Bystander CD8 T cells are abundant and phenotypically distinct in human tumour infiltrates.

Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown.