Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency.

Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent in situ hybridization (flow-FISH) approach for direct ex vivo reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies.

Integration of Stromal Cells and Hydrogel Below Epithelium Results in Optimal Barrier Properties of Small Intestine Organoid Models.

: The barrier properties of the human small intestine play a crucial role in regulating digestion, nutrient absorption and drug metabolism. Current in vitro organotypic models consist only of an epithelium, which does not take into account the possible role of stromal cells such as fibroblasts or the extracellular matrix (ECM) which could contribute to epithelial barrier properties. Therefore, the aim of this study was to determine whether these stromal cells or ECM were beneficial or detrimental to barrier function when incorporated into an organotypic human small intestine model.

Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection.

Introduction: Upon infection, T cell-driven B cell responses in GC reactions induce memory B cells and antibody-secreting cells that secrete protective antibodies. How formation of specifically long-lived plasma cells is regulated via the interplay between specific B and CD4+ T cells is not well understood. Generally, antibody levels decline over time after clearance of the primary infection.

Exploring the dynamics of T-cell responses: a combined approach using EdU incorporation and proliferation dye dilution assay.

Understanding antigen-specific T-cell responses is crucial for advancing immunotherapies and vaccine development. This study proposes a novel approach combining two complementary assays: the 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay (tracking proliferation over 0-48 h) and the VPD450 dye dilution assay (tracking proliferation over 4-6 days). Integrating these techniques provides additional insights into T-cell proliferation kinetics.

Distinct transcriptional changes distinguish efficient and poor remyelination in multiple sclerosis.

Multiple sclerosis (MS) is a highly heterogeneous disease with varying remyelination potential across individuals and between lesions. However, the molecular mechanisms underlying the potential to remyelinate remain poorly understood. In this study, we aimed to take advantage of the intrinsic heterogeneity in remyelinating capacity between MS donors and lesions to uncover known and novel pro-remyelinating molecules for MS therapies.

Influence of the COVID-19 Pandemic on Influenza and SARS-CoV-2 Vaccination Willingness Among Dutch Nursing Home Health Care Workers.

Objectives: To explore the influenza and COVID-19 vaccination status among Dutch nursing home (NH) health care workers (HCWs), factors associated with vaccination including the influence of the pandemic, and the facilitators and barriers to vaccination willingness.

Design: An explanatory sequential mixed methods study.

Setting And Participants: HCWs providing direct care to residents in Dutch NHs.

An adenoviral vector encoding an inflammation-inducible antagonist, HMGB1 Box A, as a novel therapeutic approach to inflammatory diseases.

Influenza, as well as other respiratory viruses, can trigger local and systemic inflammation resulting in an overall "cytokine storm" that produces serious outcomes such as acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We hypothesized that gene therapy platforms could be useful in these cases if the production of an anti-inflammatory protein reflects the intensity and duration of the inflammatory condition. The recombinant protein would be produced and released only in the presence of the inciting stimulus, avoiding immunosuppression or other unwanted side effects that may occur when treating infectious diseases with anti-inflammatory drugs.

Changes in AXL and/or MITF melanoma subpopulations in patients receiving immunotherapy.

Background: Tumor heterogeneity is a hurdle to effective therapy, as illustrated by the 'mixed responses' frequently seen in immunotherapy-treated patients. Previously, AXL+ tumor cells were identified to be highly resistant to targeted therapy, whereas more differentiated MITF+ tumor cells do respond to RAF and MEK inhibitors.

Patients And Methods: In this study, we analyzed tumor heterogeneity and explored the presence of the previously described AXL+ or MITF+ melanoma subpopulations in metastatic tissues by NanoString gene expression analysis, single-cell RNA sequencing and multiplex immunofluorescence.

Shrimp allergy leading to severe transfusion reaction: A case report.

Background: Transfusion reactions occur at an estimated incidence of 2 per 1.000 transfused products. Anaphylactic transfusion reactions are rarer, and seen in 1 per 10.

Phenotypic antibiotic resistance of Mycoplasma genitalium and its variation between different macrolide resistance-associated mutations.

Objectives: Mycoplasma genitalium, a sexually transmitted bacterium, faces increasing antibiotic resistance, particularly to azithromycin. However, presence of macrolide resistance-associated mutations (MRAMs) does not evidently implicate azithromycin treatment failure. This study aimed to establish an in vitro co-culture system of M.

Polyfunctionality and breadth of HIV-1 antibodies are associated with delayed disease progression.

HIV-1 infection leads to chronic disease requiring life-long treatment and therefore alternative therapeutics, a cure and/or a protective vaccine are needed. Antibody-mediated effector functions could have a role in the fight against HIV-1. However, the properties underlying the potential beneficial effects of antibodies during HIV-1 infection are poorly understood.

A biomarker profile reflective of preserved thymic function is associated with reduced comorbidities in ageing people with HIV: an AGEhIV Cohort analysis.

Background: People with HIV (PWH) experience a higher burden of ageing-associated comorbidities, the underlying mechanisms of which remain to be fully elucidated. We aimed to identify profiles based on immune, inflammatory, and ageing biomarkers in blood from PWH and controls, and explore their association with total comorbidities over time.

Methods: Latent profile analysis was used to construct biomarker profiles in AGEhIV cohort participants (94 with well-controlled HIV on antiretroviral therapy (ART) and 95 controls without HIV) using baseline measurements of selected biomarkers.

Lymph nodes as gatekeepers of autoimmune diseases.

Secondary lymphoid organs such as lymph nodes (LNs) are the home of peripheral tolerance mechanisms which control autoreactive T cells and prevent immune responses to self-antigen. In systemic autoimmunity, there is a clear failure of these peripheral tolerance mechanisms that leads to chronic inflammation and tissue destruction, highlighting the role for LNs as possible gatekeepers of autoimmunity. In recent years there has been a shift in research focus towards tissue sites in autoimmune diseases ranging from type 1 diabetes to rheumatoid arthritis in an effort to better characterise pathogenesis and guide diagnostic and therapeutic decisions.

Synthetic mismatches enable specific CRISPR-Cas12a-based detection of genome-wide SNVs tracked by ARTEMIS.

Detection of pathogenic DNA variants is vital in cancer diagnostics and treatment monitoring. While CRISPR-based diagnostics (CRISPRdx) offer promising avenues for cost-effective, rapid, and point-of-care testing, achieving single-nucleotide detection fidelity remains challenging. We present an in silico pipeline that scans the human genome for targeting pathogenic mutations in the seed region (ARTEMIS), the most stringent crRNA domain.

Plant-produced SARS-CoV-2 antibody engineered towards enhanced potency and in vivo efficacy.

Prevention of severe COVID-19 disease by SARS-CoV-2 in high-risk patients, such as immuno-compromised individuals, can be achieved by administration of antibody prophylaxis, but producing antibodies can be costly. Plant expression platforms allow substantial lower production costs compared to traditional bio-manufacturing platforms depending on mammalian cells in bioreactors. In this study, we describe the expression, production and purification of the originally human COVA2-15 antibody in plants.

Antimicrobial Peptide SAAP-148-Functionalized Hydrogels from Photocrosslinkable Polymers with Broad Antibacterial Activity.

Antimicrobial peptides (AMPs) are promising alternatives to traditional antibiotics for treating skin wound infections. Nonetheless, their short half-life in biological environments restricts clinical applicability. Covalent immobilization of AMPs onto suitable substrates offers a comprehensive solution, creating contact-killing surfaces with long-term functionality.

Development of a Versatile Cancer Vaccine Format Targeting Antigen-Presenting Cells Using Proximity-Based Sortase A-Mediated Ligation of T-Cell Epitopes.

Cancer vaccines are a promising strategy to increase tumor-specific immune responses in patients who do not adequately respond to checkpoint inhibitors. Cancer vaccines that contain patient-specific tumor antigens are most effective but also necessitate the production of patient-specific vaccines. This study aims to develop a versatile cancer vaccine format in which patient-specific tumor antigens can be site-specifically conjugated by a proximity-based Sortase A (SrtA)-mediated ligation (PBSL) approach to antibodies that specifically bind to antigen-presenting cells to stimulate immune responses.

Spatial multiplex analysis of lung cancer reveals that regulatory T cells attenuate KRAS-G12C inhibitor-induced immune responses.

Kirsten rat sarcoma virus (KRAS)-G12C inhibition causes remodeling of the lung tumor immune microenvironment and synergistic responses to anti-PD-1 treatment, but only in T cell infiltrated tumors. To investigate mechanisms that restrain combination immunotherapy sensitivity in immune-excluded tumors, we used imaging mass cytometry to explore cellular distribution in an immune-evasive KRAS mutant lung cancer model. Cellular spatial pattern characterization revealed a community where CD4 and CD8 T cells and dendritic cells were gathered, suggesting localized T cell activation.

An epidemiological and spatiotemporal analysis of visceral leishmaniasis in West Pokot, Kenya, between 2018 and 2022.

Background: Visceral leishmaniasis (VL) remains a significant public health concern in West Pokot County, Kenya, where a large outbreak between 2020 and 2022 emphasised the need for improved VL control strategies. However, these measures are partially hampered by limited insight into the geographical distribution of cases and localised outbreaks of the disease. This study aimed to describe the epidemiology and spatiotemporal patterns of VL in West Pokot between 2018 and 2022, in order to map the spread of VL transmission and identify regions that should be prioritised for control interventions.

Bridging the gap: Insights in the immunopathology of Lyme borreliosis.

Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl) genospecies transmitted by Ixodes spp. ticks, is a significant public health concern in the Northern Hemisphere. This review highlights the complex interplay between Bbsl infection and host-immune responses, impacting clinical manifestations and long-term immunity.