Comparison of a SARS-CoV-2 mRNA booster immunization containing additional antigens to a spike-based mRNA vaccine against Omicron BA.5 infection in hACE2 mice.

The emergence of SARS-CoV-2 variants presents challenges to vaccine effectiveness, underlining the necessity for next-generation vaccines with multiple antigens beyond the spike protein. Here, we investigated a multiantigenic booster containing spike and a chimeric construct composed of nucleoprotein (N) and membrane (M) proteins, comparing its efficacy to a spike-only booster against Omicron BA.5 in K18-hACE2 mice.

Transcription factor TCF1 binds to RORγt and orchestrates a regulatory network that determines homeostatic Th17 cell state.

T helper (Th) 17 cells encompass a spectrum of cell states, including cells that maintain homeostatic tissue functions and pro-inflammatory cells that can drive autoimmune tissue damage. Identifying regulators that determine Th17 cell states can identify ways to control tissue inflammation and restore homeostasis. Here, we found that interleukin (IL)-23, a cytokine critical for inducing pro-inflammatory Th17 cells, decreased transcription factor T cell factor 1 (TCF1) expression.

BACH2 regulates diversification of regulatory and proinflammatory chromatin states in T17 cells.

Interleukin-17 (IL-17)-producing helper T (T17) cells are heterogenous and consist of nonpathogenic T17 (npT17) cells that contribute to tissue homeostasis and pathogenic T17 (pT17) cells that mediate tissue inflammation. Here, we characterize regulatory pathways underlying T17 heterogeneity and discover substantial differences in the chromatin landscape of npT17 and pT17 cells both in vitro and in vivo. Compared to other CD4 T cell subsets, npT17 cells share accessible chromatin configurations with regulatory T cells, whereas pT17 cells exhibit features of both npT17 cells and type 1 helper T (T1) cells.

Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease.

APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD), with increased odds ratios in female carriers. Targeting amyloid plaques shows modest improvement in male non-APOE4 carriers. Leveraging single-cell transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female carriers with AD, we identify a new subset of neutrophils interacting with microglia associated with cognitive impairment.

Pan-cancer mapping of single CD8 T cell profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity.

CD8 T cells must persist and function in diverse tumor microenvironments to exert their effects. Thus, understanding common underlying expression programs could better inform the next generation of immunotherapies. We apply a generalizable matrix factorization algorithm that recovers both shared and context-specific expression programs from diverse datasets to a single-cell RNA sequencing (scRNA-seq) compendium of 33,161 CD8 T cells from 132 patients with seven human cancers.

Bacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer's disease mouse models.

The gut microbiota and microglia play critical roles in Alzheimer's disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aβ plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression.

APOE4 impairs the microglial response in Alzheimer's disease by inducing TGFβ-mediated checkpoints.

The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration.

Tumor immunogenicity dictates reliance on TCF1 in CD8 T cells for response to immunotherapy.

Stem-like CD8 T cells are regulated by T cell factor 1 (TCF1) and are considered requisite for immune checkpoint blockade (ICB) response. However, recent findings indicate that reliance on TCF1CD8 T cells for ICB efficacy may differ across tumor contexts. We find that TCF1 is essential for optimal priming of tumor antigen-specific CD8 T cells and ICB response in poorly immunogenic tumors that accumulate TOX dysfunctional T cells, but is dispensable for T cell priming and therapy response in highly immunogenic tumors that efficiently expand transitory effectors.

Vγ1 and Vγ4 gamma-delta T cells play opposing roles in the immunopathology of traumatic brain injury in males.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality. The innate and adaptive immune responses play an important role in the pathogenesis of TBI. Gamma-delta (γδ) T cells have been shown to affect brain immunopathology in multiple different conditions, however, their role in acute and chronic TBI is largely unknown.

Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.

Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine.

Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination.

Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab.

Mapping Processes in the Emergency Department Using the Functional Resonance Analysis Method.

Emergency departments (EDs) are dynamic, complex, and demanding environments. Introducing changes that lead to improvements in EDs can be challenging owing to the high staff turnover and mix, high patient volume with different needs, and being the front door to the hospital for the sickest patients. Quality improvement is a methodology applied routinely in EDs to instigate change to improve several outcomes such as waiting times, time to definitive treatment, and patient safety.

microRNA-92a promotes CNS autoimmunity by modulating the regulatory and inflammatory T cell balance.

A disequilibrium between immunosuppressive Tregs and inflammatory IL-17-producing Th17 cells is a hallmark of autoimmune diseases, including multiple sclerosis (MS). However, the molecular mechanisms underlying the Treg and Th17 imbalance in CNS autoimmunity remain largely unclear. Identifying the factors that drive this imbalance is of high clinical interest.

Myeloid cell subsets that express latency-associated peptide promote cancer growth by modulating T cells.

Myeloid suppressor cells promote tumor growth by a variety of mechanisms which are not fully characterized. We identified myeloid cells (MCs) expressing the latency-associated peptide (LAP) of TGF-β on their surface and LAP MCs that stimulate Foxp3 Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-β inhibits the tolerogenic ability of LAP MCs.

Subdiaphragmatic Renal Ectopia: Case Report and Review of the Literature.

Background. We report the case of a male infant whose right kidney migrated to an ectopic position after birth. The migration of a kidney in postnatal life without any symptoms has not been reported in literature so far.

Positive trends in paediatric renal biopsy service provision in the UK: a national survey and re-audit of paediatric renal biopsy practice.

Background: Paediatric renal biopsy standards introduced in the UK in 2010 were intended to reduce variation and improve practice. A concurrent national drive was aimed at building robust paediatric nephrology networks to ensure services cater for the needs of the family and minimise time away from home. We aimed to identify current national practice since these changes on behalf of the British Association for Paediatric Nephrology.

Hydrophilic polyurethane matrix promotes chondrogenesis of mesenchymal stem cells.

Segmental polyurethanes exhibit biphasic morphology and can control cell fate by providing distinct matrix guided signals to increase the chondrogenic potential of mesenchymal stem cells (MSCs). Polyethylene glycol (PEG) based hydrophilic polyurethanes can deliver differential signals to MSCs through their matrix phases where hard segments are cell-interactive domains and PEG based soft segments are minimally interactive with cells. These coordinated communications can modulate cell-matrix interactions to control cell shape and size for chondrogenesis.

Hybrid cross-linking characteristics of hydrogel control stem cell fate.

Controlling hydrogel structures by combination of physical and chemical cross-links provides a novel system to regulate (stem) cell fate. In this study, we designed a polyethylene glycol (PEG)-based hydrogel where the polymer chains contain both physical and chemical cross-linking units in the same chain with self-assembling L-tyrosine-based dipeptides and photopolymerizable polyacrylate groups, respectively. It is shown that hydrogel architectures derived from this polymer are correlated to the cross-linking mechanisms.

Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest.

While many antibody therapeutics are formulated at low concentration (~10-20 mg/mL) for intravenous administration, high concentration (> 100 mg/mL) formulations may be required for subcutaneous delivery in certain clinical indications. For such high concentration formulations, product color is more apparent due to the higher molecular density across a given path-length. Color is therefore a product quality attribute that must be well-understood and controlled, to demonstrate process consistency and enable clinical trial blinding.

Cell-material interactions on biphasic polyurethane matrix.

Cell-matrix interaction is a key regulator for controlling stem cell fate in regenerative tissue engineering. These interactions are induced and controlled by the nanoscale features of extracellular matrix and are mimicked on synthetic matrices to control cell structure and functions. Recent studies have shown that nanostructured matrices can modulate stem cell behavior and exert specific role in tissue regeneration.

Batchwise and continuous nanofiltration of POSS-tagged Grubbs-Hoveyda-type olefin metathesis catalysts.

New molecular-weight-enlarged metathesis catalysts, which bear polyhedral oligomeric silsesquioxane (POSS) tags, were synthesized and characterized. The catalysts can be recovered from the reaction mixture by using nanofiltration techniques and can be reused. It was found that the membranes Starmem 228 and PuraMem 280 successfully separate the catalyst from the post-reaction mixtures to below 3 ppm.

Urinary concentration defects and mechanisms underlying nephronophthisis.

The cystic kidney disease nephronophthisis (NPHP) is the commonest genetic cause of end-stage renal failure in young people and children. Histologically the disease is characterized by interstitial fibrosis, tubular atrophy with corticomedullary cyst development and disruption of the tubular basement membrane. Affected children present with polydipsia and polyuria, secondary to a urinary concentration defect, before these structural changes develop.

Minimising changes in plasma calcium and magnesium concentrations during plasmapheresis.

Hypocalcaemic tetany is a known complication of plasmapheresis. It has two causes. Intravenously administered 4.