Re-organization of Pacific overturning circulation across the Miocene Climate Optimum.

The response of the ocean overturning circulation to global warming remains controversial. Here, we integrate a multiproxy record from International Ocean Discovery Program Site U1490 in the western equatorial Pacific with published data from the Pacific, Southern and Indian Oceans to investigate the evolution of deep water circulation during the Miocene Climate Optimum (MCO) and Middle Miocene Climate Transition (MMCT). We find that the northward export of southern-sourced deep waters was closely tied to high-latitude climate and Antarctic ice cover variations.

Enhanced Calculation of Property Distributions in Chemical Fragment Spaces.

Chemical fragment spaces exceed traditional virtual compound libraries by orders of magnitude, making them ideal search spaces for drug design projects. However, due to their immense size, they are not compatible with traditional analysis and search algorithms that rely on the enumeration of molecules. In this paper, we present SpaceProp2, an evolution of the SpaceProp algorithm, which enables the calculation of exact property distributions for chemical fragment spaces without enumerating them.

The immunological landscape of peripheral blood in glioblastoma patients and immunological consequences of age and dexamethasone treatment.

Background: Glioblastomas manipulate the immune system both locally and systemically, yet, glioblastoma-associated changes in peripheral blood immune composition are poorly studied. Age and dexamethasone administration in glioblastoma patients have been hypothesized to limit the effectiveness of immunotherapy, but their effects remain unclear. We compared peripheral blood immune composition in patients with different types of brain tumor to determine the influence of age, dexamethasone treatment, and tumor volume.

Sialic acid-modified der p 2 allergen exerts immunomodulatory effects on human PBMCs.

Background: House dust mite extract-based allergen immunotherapy (AIT) to treat house dust mite allergy is substantially effective but still presents some safety and efficacy concerns that warrant improvement. Several major allergen-based approaches to increase safety and efficacy of AIT have been proposed. One of them is the use of the group 2 allergen, Der p 2.

Lesion-symptom mapping of language impairments in people with brain tumours: The influence of linguistic stimuli.

People with tumours in specific brain sites might face difficulties in tasks with different linguistic material. Previous lesion-symptom mapping studies (VLSM) demonstrated that people with tumours in posterior temporal regions have more severe linguistic impairments. However, to the best of our knowledge, preoperative performance and lesion location on tasks with different linguistic stimuli have not been examined.

The effect of mindfulness-based cognitive therapy on rumination and a task-based measure of intrusive thoughts in patients with bipolar disorder.

Background: Preliminary evidence suggests that Mindfulness-Based Cognitive Therapy (MBCT) is a promising treatment for bipolar disorder (BD). A proposed working mechanism of MBCT in attenuating depressive symptoms is reducing depressive rumination. The primary aim of this study was to investigate the effect of MBCT on self-reported trait depressive rumination and an experimental state measure of negative intrusive thoughts in BD patients.

Mindfulness based cognitive therapy (MBCT) reduces depression-related self-referential processing in patients with bipolar disorder: an exploratory task-based study.

Negative self-referential processing has fruitfully been studied in unipolar depressed patients, but remarkably less in patients with bipolar disorder (BD). This exploratory study examines the relation between task-based self-referential processing and depressive symptoms in BD and their possible importance to the working mechanism of mindfulness-based cognitive therapy (MBCT) for BD. The study population consisted of a subsample of patients with BD ( = 49) participating in an RCT of MBCT for BD, who were assigned to MBCT + TAU ( = 23) or treatment as usual (TAU) ( = 26).

Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer.

Identification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103- CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells.

Combined STING levels and CD103+ T cell infiltration have significant prognostic implications for patients with cervical cancer.

Activation of STimulator of INterferon Genes (STING) is important for induction of anti-tumor immunity. A dysfunctional STING pathway is observed in multiple cancer types and associates with poor prognosis and inferior response to immunotherapy. However, the association between STING and prognosis in virally induced cancers such as HPV-positive cervical cancer remains unknown.

α2-3 Sialic acid binding and uptake by human monocyte-derived dendritic cells alters metabolism and cytokine release and initiates tolerizing T cell programming.

Unlabelled: Dendritic cells (DCs) are key in the initiation of the adaptive T cell responses to tailor adequate immunity that corresponds to the type of pathogen encountered. Oppositely, DCs control the resolution phase of inflammation and are able to induce tolerance after receiving anti-inflammatory cytokines or upon encounter of self-associated molecular patterns, such as α2-3 linked sialic acid (α2-3sia).

Objective: We here investigated whether α2-3sia, that bind immune inhibitory Siglec receptors, would alter signaling and reprogramming of LPS-stimulated human monocyte-derived DCs (moDCs).

The puzzling pathophysiology of frozen shoulders - a scoping review.

Purpose: The pathophysiology of frozen shoulders is a complex and multifactorial process. The purpose of this review is to scope the currently available knowledge of the pathophysiology of frozen shoulders.

Methods: A systematic search was conducted in Medline, Embase and the Cochrane library.

Association of homozygous variants of STING1 with outcome in human cervical cancer.

DNA-sensing receptor Cyclic GMP-AMP Synthase (cGAS) and its downstream signaling effector STimulator of INterferon Genes (STING) have gained significant interest in the field of tumor immunology, as a dysfunctional cGAS-STING pathway is associated with poor prognosis and worse response to immunotherapy. However, studies so far have not taken into account the polymorphic nature of the STING-encoding STING1 gene. We hypothesized that the presence of allelic variance in STING1 would cause variation between individuals as to their susceptibility to cancer development, cancer progression, and potential response to (immuno)therapy.

Deep immune profiling of ovarian tumors identifies minimal MHC-I expression after neoadjuvant chemotherapy as negatively associated with T-cell-dependent outcome.

Epithelial Ovarian cancer (EOC) is the most lethal gynecological malignancy and has limited curative therapeutic options. Immunotherapy for EOC is promising, but clinical efficacy remains restricted to a small percentage of patients. Several lines of evidence suggest that the low response rate might be improved by combining immunotherapy with carboplatin and paclitaxel, the standard-of-care chemotherapy for EOC.

Lipo-Based Vaccines as an Approach to Target Dendritic Cells for Induction of T- and iNKT Cell Responses.

In this study we developed a liposome-based vaccine containing palmitoylated synthetic long peptides (SLP) and alpha galactosylceramide (αGC) to specifically target dendritic cells (DC) for activation of both innate (invariant natural killer T-cells [iNKT]) and adaptive (CD8 T-cells) players of the immune system. Combination of model tumor specific antigens (gp100/MART-1) formulated as a SLP and αGC in one liposome results in strong activation of CD8 and iNKT, as measured by IFNγ secretion. Moreover, addition of lipo-Lewis Y (Le) to the liposomes for C-type lectin targeting increased not only uptake by monocyte-derived dendritic cells (moDC), dermal dendritic cells and Langerhans cells but also enhanced gp100-specific CD8 T- and iNKT cell activation by human skin-emigrated antigen presenting cells in an explant model.

Checklist, assemblage composition, and biogeographic assessment of Recent benthic foraminifera (Protista, Rhizaria) from São Vincente, Cape Verdes.

We describe for the first time subtropical intertidal foraminiferal assemblages from beach sands on São Vincente, Cape Verdes. Sixty-five benthic foraminiferal species were recognised, representing 47 genera, 31 families, and 8 superfamilies. Endemic species were not recognised.

Activation of the C-Type Lectin MGL by Terminal GalNAc Ligands Reduces the Glycolytic Activity of Human Dendritic Cells.

Many tumors display alterations in the biosynthetic pathways of glycosylation, resulting in increased expression of specific tumor-associated glycan structures. Expression of these altered glycan structures is associated with metastasis and poor prognosis. Antigen presenting cells can recognize tumor-associated glycan structures, including the truncated -glycan Tn antigen, via specific glycan receptors.

Increased prevalence of ECG suspicious for Brugada Syndrome in recent onset schizophrenia spectrum disorders.

Background: Schizophrenia is associated with an increased risk of sudden cardiac death, traditionally attributed to prolonged QTc interval and increased prevalence of cardiovascular risk factors. However, defective ion channels implicated in both schizophrenia and Brugada Syndrome (BrS) may be associated with an increased risk of cardiac arrhythmias. Moreover, these cardiac arrhythmias can be provoked by various drugs, including psychotropic drugs.

A Transcriptionally Distinct CXCL13CD103CD8 T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer.

The chemokine CXCL13 mediates recruitment of B cells to tumors and is essential for the formation of tertiary lymphoid structures (TLSs). TLSs are thought to support antitumor immunity and are associated with improved prognosis. However, it remains unknown whether TLSs are formed in response to the general inflammatory character of the tumor microenvironment, or rather, are induced by (neo)antigen-specific adaptive immunity.

Modulation of Immune Tolerance via Siglec-Sialic Acid Interactions.

One of the key features of the immune system is its extraordinary capacity to discriminate between self and non-self and to respond accordingly. Several molecular interactions allow the induction of acquired immune responses when a foreign antigen is recognized, while others regulate the resolution of inflammation, or the induction of tolerance to self-antigens. Post-translational signatures, such as glycans that are part of proteins (glycoproteins) and lipids (glycolipids) of host cells or pathogens, are increasingly appreciated as key molecules in regulating immunity vs.

Late Miocene climate cooling and intensification of southeast Asian winter monsoon.

The late Miocene offers the opportunity to assess the sensitivity of the Earth's climate to orbital forcing and to changing boundary conditions, such as ice volume and greenhouse gas concentrations, on a warmer-than-modern Earth. Here we investigate the relationships between low- and high-latitude climate variability in an extended succession from the subtropical northwestern Pacific Ocean. Our high-resolution benthic isotope record in combination with paired mixed layer isotope and Mg/Ca-derived temperature data reveal that a long-term cooling trend was synchronous with intensification of the Asian winter monsoon and strengthening of the biological pump from ~7 Ma until ~5.

Acetylated Histones in Apoptotic Microparticles Drive the Formation of Neutrophil Extracellular Traps in Active Lupus Nephritis.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of autoantibodies against nuclear components. Lupus nephritis (LN) is the major cause of morbidity and mortality in patients with SLE. Central to the pathogenesis of SLE is the accumulation of cellular waste, especially apoptotic microparticles (MPs), which stimulates diverse immune reactions including the formation of neutrophil extracellular traps (NETs).

Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy.

Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S.

Satisfaction and self-confidence with nursing clinical simulation: Novice learners, medium-fidelity, and community settings.

Background: Simulation is fast becoming a normative pedagogy for a portion of clinical time in undergraduate nursing programs in the U.S. Studies have shown positive outcomes in increasing self-confidence and satisfaction with simulation.

Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced inflammation in COPD.

Cigarette smoke (CS) exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). We investigated whether CS-induced damage-associated molecular pattern (DAMP) release or DAMP-mediated inflammation contributes to susceptibility for COPD. Samples, including bronchial brushings, were collected from young and old individuals, susceptible and nonsusceptible for the development of COPD, before and after smoking, and used for gene profiling and airway epithelial cell (AEC) culture.

Changes in peripheral blood lymphocyte subsets during arthritis development in arthralgia patients.

Background: Multiple lymphocyte subsets like T and B cells have been connected to joint infiltration and inflammation in rheumatoid arthritis (RA). Identification of leucocyte subsets that are dysregulated in arthritis development could provide insight into the aetiology of RA. This study aimed to investigate the composition of the peripheral blood components, i.