Disruption of the sialic acid/Siglec-9 axis improves antibody-mediated neutrophil cytotoxicity towards tumor cells.

Upregulation of surface expressed sialoglycans on tumor cells is one of the mechanisms which promote tumor growth and progression. Specifically, the interactions of sialic acids with sialic acid-binding immunoglobulin-like lectins (Siglecs) on lymphoid or myeloid cells transmit inhibitory signals and lead to suppression of anti-tumor responses. Here, we show that neutrophils express among others Siglec-9, and that EGFR and HER2 positive breast tumor cells express ligands for Siglec-9.

Enterosignatures define common bacterial guilds in the human gut microbiome.

The human gut microbiome composition is generally in a stable dynamic equilibrium, but it can deteriorate into dysbiotic states detrimental to host health. To disentangle the inherent complexity and capture the ecological spectrum of microbiome variability, we used 5,230 gut metagenomes to characterize signatures of bacteria commonly co-occurring, termed enterosignatures (ESs). We find five generalizable ESs dominated by either Bacteroides, Firmicutes, Prevotella, Bifidobacterium, or Escherichia.

Towards optimised extracellular vesicle proteomics from cerebrospinal fluid.

The proteomic profile of extracellular vesicles (EVs) from cerebrospinal fluid (CSF) can reveal novel biomarkers for diseases of the brain. Here, we validate an ultrafiltration combined with size-exclusion chromatography (UF-SEC) method for isolation of EVs from canine CSF and probe the effect of starting volume on the EV proteomics profile. First, we performed a literature review of CSF EV articles to define the current state of art, discovering a need for basic characterisation of CSF EVs.

Shared genetic loci between Alzheimer's disease and multiple sclerosis: Crossroads between neurodegeneration and immune system.

Background: Neuroinflammation is involved in the pathophysiology of Alzheimer's disease (AD), including immune-linked genetic variants and molecular pathways, microglia and astrocytes. Multiple Sclerosis (MS) is a chronic, immune-mediated disease with genetic and environmental risk factors and neuropathological features. There are clinical and pathobiological similarities between AD and MS.

Antibody blockade of Jagged1 attenuates choroidal neovascularization.

Antibody-based blocking of vascular endothelial growth factor (VEGF) reduces choroidal neovascularization (CNV) and retinal edema, rescuing vision in patients with neovascular age-related macular degeneration (nAMD). However, poor response and resistance to anti-VEGF treatment occurs. We report that targeting the Notch ligand Jagged1 by a monoclonal antibody reduces neovascular lesion size, number of activated phagocytes and inflammatory markers and vascular leakage in an experimental CNV mouse model.

Brain-wide associations between white matter and age highlight the role of fornix microstructure in brain ageing.

Unveiling the details of white matter (WM) maturation throughout ageing is a fundamental question for understanding the ageing brain. In an extensive comparison of brain age predictions and age-associations of WM features from different diffusion approaches, we analyzed UK Biobank diffusion magnetic resonance imaging (dMRI) data across midlife and older age (N = 35,749, 44.6-82.

OnTarget: in silico design of MiniPromoters for targeted delivery of expression.

MiniPromoters, or compact promoters, are short DNA sequences that can drive expression in specific cells and tissues. While broadly useful, they are of high relevance to gene therapy due to their role in enabling precise control of where a therapeutic gene will be expressed. Here, we present OnTarget (http://ontarget.

Associations Between Symptoms of Premenstrual Disorders and Polygenic Liability for Major Psychiatric Disorders.

Importance: Premenstrual disorders are heritable, clinically heterogenous, with a range of affective spectrum comorbidities. It is unclear whether genetic predispositions to affective spectrum disorders or other major psychiatric disorders are associated with symptoms of premenstrual disorders.

Objective: To assesss whether symptoms of premenstrual disorders are associated with the genetic liability for major psychiatric disorders, as indexed by polygenic risk scores (PRSs).

T cell receptor repertoire sequencing reveals chemotherapy-driven clonal expansion in colorectal liver metastases.

Background: Colorectal liver metastasis (CLM) is a leading cause of colorectal cancer mortality, and the response to immune checkpoint inhibition (ICI) in microsatellite-stable CRC has been disappointing. Administration of cytotoxic chemotherapy may cause increased density of tumor-infiltrating T cells, which has been associated with improved response to ICI. This study aimed to quantify and characterize T-cell infiltration in CLM using T-cell receptor (TCR) repertoire sequencing.

Polygenic overlap with body-mass index improves prediction of treatment-resistant schizophrenia.

Treatment resistant schizophrenia (TRS) is characterized by repeated treatment failure with antipsychotics. A recent genome-wide association study (GWAS) of TRS showed a polygenic architecture, but no significant loci were identified. Clozapine is shown to be the superior drug in terms of clinical effect in TRS; at the same time it has a serious side effect profile, including weight gain.

Effects of non-compulsory and mandatory COVID-19 interventions on travel distance and time away from home, Norway, 2021.

BackgroundGiven the societal, economic and health costs of COVID-19 non-pharmaceutical interventions (NPI), it is important to assess their effects. Human mobility serves as a surrogate measure for human contacts and compliance with NPI. In Nordic countries, NPI have mostly been advised and sometimes made mandatory.

Risk of recurrent cardiovascular events in coronary artery disease patients with Type D personality.

Introduction: Data on the association between Type D personality, its traits negative affectivity (NA) and social inhibition (SI), and risk of major adverse cardiac events (MACE) in coronary outpatients is sparse. Furthermore, the associations between Type D subgroups and cardiovascular risk factors are largely unknown.

Methods: We investigated i) Type D personality, NA and SI and risk of recurrent MACE, and ii) the relationship between Type D subgroups and risk factors in a coronary population.

Contrast Enhanced Magnetic Resonance Imaging of Amyloid-β Plaques in a Murine Alzheimer's Disease Model.

Background: Early detection of amyloid-β (Aβ) aggregates is a critical step to improve the treatment of Alzheimer's disease (AD) because neuronal damage by the Aβ aggregates occurs before clinical symptoms are apparent. We have previously shown that luminescent conjugated oligothiophenes (LCOs), which are highly specific towards protein aggregates of Aβ, can be used to fluorescently label amyloid plaque in living rodents.

Objective: We hypothesize that the LCO can be used to target gadolinium to the amyloid plaque and hence make the plaque detectable by T1-weighted magnetic resonance imaging (MRI).

Mitochondria hormesis delays aging and associated diseases in impacting on key ferroptosis players.

Excessive iron accumulation or deficiency leads to a variety of pathologies in humans and developmental arrest in the nematode . Instead, sub-lethal iron depletion extends lifespan. Hypoxia preconditioning protects against severe hypoxia-induced neuromuscular damage across species but it has low feasible application.

SENP2 knockdown in human adipocytes reduces glucose metabolism and lipid accumulation, while increases lipid oxidation.

Adipose tissue is one of the main regulative sites for energy metabolism. Excess lipid storage and expansion of white adipose tissue (WAT) is the primary contributor to obesity, a strong predisposing factor for development of insulin resistance. Sentrin-specific protease (SENP) 2 has been shown to play a role in metabolism in murine fat and skeletal muscle cells, and we have previously demonstrated its role in energy metabolism of human skeletal muscle cells.

Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models.

Aggregates of the protein tau are proposed to drive pathogenesis in neurodegenerative diseases. Tau can be targeted by using passively transferred antibodies (Abs), but the mechanisms of Ab protection are incompletely understood. In this work, we used a variety of cell and animal model systems and showed that the cytosolic Ab receptor and E3 ligase TRIM21 (T21) could play a role in Ab protection against tau pathology.

Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults.

Importance: The prevalence and baseline risk factors of post-COVID-19 condition (PCC) remain unresolved among the large number of young people who experienced mild COVID-19.

Objectives: To determine the point prevalence of PCC 6 months after the acute infection, to determine the risk of development of PCC adjusted for possible confounders, and to explore a broad range of potential risk factors.

Design, Setting, And Participants: This cohort study included nonhospitalized individuals from 2 counties in Norway between ages 12 and 25 years who underwent reverse transcription-polymerase chain reaction (RT-PCR) testing.