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Mononuclear phagocyte regulation by the transcription factor Blimp-1 in health and disease

B lymphocyte-induced maturation protein-1 (Blimp-1), the transcription factor encoded by the gene Prdm1, plays a number of crucial roles in the adaptive immune system, which result in the maintenance of key effector functions of B- and T-cells. Emerging clinical data, as well as mechanistic evidence from mouse studies, have additionally identified critical functions of Blimp-1 in the maintenance o

Cancer and Risk of COVID-19 Through a General Community Survey

Individuals with cancer may be at high risk for coronavirus disease 2019 (COVID-19) and adverse outcomes. However, evidence from large population-based studies examining whether cancer and cancer-related therapy exacerbates the risk of COVID-19 infection is still limited. Data were collected from the COVID Symptom Study smartphone application since March 29 through May 8, 2020. Among 23,266 partic

Novel Methods for the Quantification of Dipeptidyl Peptidase 3 (DPP3) Concentration and Activity in Human Blood Samples

BACKGROUND: The ubiquitously expressed dipeptidyl peptidase 3 (DPP3) is involved in protein metabolism, blood pressure regulation, and pain modulation. These diverse functions of DPP3 are attributed to the degradation of bioactive peptides like angiotensin II. However, because of limitations in currently available assays for determination of active DPP3 in plasma, the exact physiological function

Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction

Plasma concentrations of many cardiovascular and inflammatory proteins are altered after ST-elevation myocardial infarction (STEMI) and may provide prognostic information. We conducted a large-scale proteomic analysis in patients with STEMI, correlating protein levels to infarct size and left ventricular ejection fraction (LVEF) determined with cardiac magnetic resonance imaging. We analysed 131 c

K369I Tau Mice Demonstrate a Shift Towards Striatal Neuron Burst Firing and Goal-directed Behaviour

Pathological forms of the microtubule-associated protein tau are involved in a large group of neurodegenerative diseases named tauopathies, including frontotemporal lobar degeneration (FTLD-tau). K369I mutant tau transgenic mice (K3 mice) recapitulate neural and behavioural symptoms of FTLD, including tau aggregates in the cortex, alterations to nigrostriatum, memory deficits and parkinsonism. The

Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a rare hematopoietic disease characterized by a block in red cell differentiation. Most DBA cases are caused by mutations in ribosomal proteins and characterized by higher than normal activity of the tumor suppressor p53. Higher p53 activity is thought to contribute to DBA phenotypes by inducing apoptosis during red blood cell differentiation. Currently, there are

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Background Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of thes

Lung regeneration : implications of the diseased niche and ageing

Most chronic and acute lung diseases have no cure, leaving lung transplantation as the only option. Recent work has improved our understanding of the endogenous regenerative capacity of the lung and has helped identification of different progenitor cell populations, as well as exploration into inducing endogenous regeneration through pharmaceutical or biological therapies. Additionally, alternativ

Pregnancy Complication History in 10-Year Cardiovascular Disease Risk Prediction: a Review of Recent Evidence

Purpose of ReviewWomen with prevalent pregnancy complications (including preterm birth and preeclampsia) have twice the risk of later cardiovascular disease (CVD) compared to unaffected women. Current prevention guidelines recommend that reproductive history should be part of a woman’s CVD risk assessment. This review synthesizes recent findings on the value of history of pregnancy complications i

A Biomimetic, Copolymeric Membrane for Cell-Stretch Experiments with Pulmonary Epithelial Cells at the Air-Liquid Interface

Chronic respiratory diseases are among the leading causes of death worldwide, but only symptomatic therapies are available for terminal illness. This in part reflects a lack of biomimetic in vitro models that can imitate the complex environment and physiology of the lung. Here, a copolymeric membrane consisting of poly(ε-)caprolactone and gelatin with tunable properties, resembling the main charac

Mammographic tumour appearance is related to clinicopathological factors and surrogate molecular breast cancer subtype

Mammographic tumour appearance may provide prognostic useful information. For example, spiculation indicates invasiveness, but also better survival compared to tumours with other appearances. We aimed to study the relationship between mammographic tumour appearance and established clinicopathological factors, including surrogate molecular breast cancer subtypes, in the large Malmö Diet and Cancer

Poly(ester amide) microspheres are efficient vehicles for long-term intracerebral growth factor delivery and improve functional recovery after stroke

Growth factors promote plasticity in injured brain and improve impaired functions. For clinical application, efficient approaches for growth factor delivery into the brain are necessary. Poly(ester amide) (PEA)-derived microspheres (MS) could serve as vehicles due to their thermal and mechanical properties, biocompatibility and biodegradability. Vascular endothelial growth factor (VEGF) exerts bot

Trajectory of excess healthcare consultations, medication use, and work disability in newly diagnosed knee osteoarthritis : a matched longitudinal register-based study

PURPOSE: To estimate the excess healthcare use and work disability attributable to knee osteoarthritis (OA) in the first five years following diagnosis.METHODS: Among individual aged 40-80 years who resided in Skåne on 31st December 2008, we identified those with a main diagnosis of knee OA during 2009-2014 and no previous diagnosis of any OA from 1998 (n=16,888). We created a comparison cohort ma

Hydroxysteroid 17-β dehydrogenase 13 variant increases phospholipids and protects against fibrosis in nonalcoholic fatty liver disease

Carriers of the hydroxysteroid 17-β dehydrogenase 13 (HSD17B13) gene variant (rs72613567:TA) have a reduced risk of NASH and cirrhosis but not steatosis. We determined its effect on liver histology, lipidome, and transcriptome using ultra performance liquid chromatography-mass spectrometry and RNA-seq. In carriers and noncarriers of the gene variant, we also measured pathways of hepatic fatty acid

PP038. Renal ETK/BMX activation decreased in preeclampsia

INTRODUCTION: Vascular endothelial growth factors (VEGF's) are essential to angiogenesis and play a central role in the pathophysiology of preeclampsia. Specifically, antagonists of VEGFR2 cause a preeclampsia-like syndrome, in humans and rats[1]. ETK/BMX is a receptor tyrosine kinase (RTK) which induces VEGF expression and forms a complex with VEGFR2, whereby VEGF and TNF can induce a reciprocal

A circular RNA generated from an intron of the insulin gene controls insulin secretion

Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-c

Extracellular Vesicles Released by Enterovirus-Infected EndoC-βH1 Cells Mediate Non-Lytic Viral Spread

While human enteroviruses are generally regarded as a lytic virus, and persistent non-cytolytic enterovirus infection in pancreatic beta cells has been suspected of playing a role in type 1 diabetes pathogenesis. However, it is still unclear how enteroviruses could exit the pancreatic beta cell in a non-lytic manner. This study aimed to investigate the role of beta cell-derived extracellular vesic

Topological Performance Measures as Surrogates for Physical Flow Models for Risk and Vulnerability Analysis for Electric Power Systems

Critical infrastructure systems must be both robust and resilient in order to ensure the functioning of society. To improve the performance of such systems, we often use risk and vulnerability analysis to nd and address system weaknesses. A critical component of such analyses is the ability to accurately determine the negative consequences of various types of failures in the system. Numerous mathe