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Type 1 diabetes (T1D) is an autoimmune disease that results in the destruction of insulin producing pancreatic β-cells. One of the genes associated with T1D is TYK2, which encodes a Janus kinase with critical roles in type-Ι interferon (IFN-Ι) mediated intracellular signalling. To study the role of TYK2 in β-cell development and response to IFNα, we generated TYK2 knockout human iPSCs and directed
The fetal to adult switch in hematopoietic stem cell (HSC) behavior is characterized by alterations in lineage output and entry into deep quiescence. Here we identify the emergence of megakaryocyte (Mk) biased HSCs as an event coinciding with this developmental switch. Single-cell chromatin accessibility analysis reveals a ubiquitous acquisition of Mk lineage priming signatures in HSCs during the
Background and aimsData exploring normal values of different ventricular–arterial coupling (VAC) parameters and their association with anthropometric and cardiovascular (CV) factors are scarce. We aim to report values of two different methods of VAC assessment according to age and sex and explore their association with CV factors within a large population-based cohort of middle-aged individuals.Me
The brain is the key organ that orchestrates the stress response which translates to the retina. The retina is an extension of the brain and retinal symptoms in subjects with neurodegenerative diseases substantiated the eye as a window to the brain. The retina is used in this study to determine whether chronic stress reflects neurodegenerative signs indicative of neurodegenerative conditions. A 3-
Inflammatory mediators induce emergency myelopoiesis and cycling of adult hematopoietic stem cells (HSCs) through incompletely understood mechanisms. To suppress the unwanted effects of inflammation and preserve its beneficial outcomes, the mechanisms by which inflammation affects hematopoiesis need to be fully elucidated. Rather than focusing on specific inflammatory stimuli, we here investigated
BackgroundThe essential trace elements copper and zinc, and their ratio (copper/zinc), are important for maintaining redox homeostasis. Previous studies suggest that these elements may impact breast cancer survival. However, no epidemiological study has so far been conducted on the potential association between copper and copper/zinc levels and survival after breast cancer diagnosis. In this study
Previous reports of mortality and morbidity in pediatric severe traumatic brain injury (TBI) vary considerably, with few population-based studies. Mortality rates from 3-33 % and varying morbidity have been reported, most commonly using the Extended Glasgow Outcome Scale (eGOS). The Lund concept is a treatment algorithm for severe TBI aiming at controlling intracranial pressure (ICP) by reducing c
Ventricular-arterial coupling (VAC) has independent diagnostic and prognostic value for cardiovascular (CV) risk stratification, but studies on its association with anthropometric and CV factors are sparse in young individuals without overt CV disease. We aim to provide descriptive data regarding VAC and its associations with CV risk factors in young adults without overt CV disease. For 631 (mean
BACKGROUND: To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal COVID-19 among nursing homes residents.METHODS: We performed repeated capillary blood sampling with analysis of S-binding IgG in an open cohort of nursing home residents in Sweden. We analyzed immunological and registry data from 16
Due to desirable optical properties, such as efficient luminescence and large Stokes shift, DNA-templated silver nanoclusters (DNA-AgNCs) have received significant attention over the past decade. Nevertheless, the excited-state dynamics of these systems are poorly understood, as studies of the processes ultimately leading to a fluorescent state are scarce. Here we investigate the early time relaxa
Climate change affects the functioning of all of the components of food systems, often in ways that exacerbate existing predicaments and inequalities among regions of the world and groups in society. At the same time, food systems are a major cause of climate change, accounting for a third of all greenhouse gas (GHG) emissions. Therefore, food systems can and should play a much bigger role in clim
OBJECTIVE: Communication about patients' values, goals, and prognosis in serious illness (serious illness communication) is a cornerstone of person-centered care yet difficult to implement in practice. As part of Serious Illness Care Program implementation in five health systems, we studied the clinical culture-related factors that supported or impeded improvement in serious illness conversations.
Dysregulation of circulating lipids is a central element for the metabolic syndrome. However, it is not well established whether human subcutaneous adipose tissue is affected by or affect circulating lipids through epigenetic mechanisms. Hence, our aim was to investigate the association between circulating lipids and DNA methylation levels in human adipose tissue. DNA methylation and gene expressi
α-Synuclein (α-Syn), is an intrinsically disordered protein present in the substantia nigra part of the brain. α-Syn is commonly known to associate with lipid membranes containing anionic lipids. Hence, the protein is hypothesized to be involved in the vesicle trafficking at the synapses, but there are yet many unanswered questions regarding the full physiological role of the protein. During the d
Photo-induced cross-linking of unmodified proteins (PICUP) has been used in the past to study size distributions of protein assemblies. PICUP may, for example, overcome the significant experimental challenges related to the transient nature, heterogeneity, and low concentration of amyloid protein oligomers relative to monomeric and fibrillar species. In the current study, a reaction chamber was de
Amyloid fibrils may adopt different morphologies depending on the solution conditions and the protein sequence. Here, we show that two chemically identical but morphologically distinct α-synuclein fibrils can form under identical conditions. This was observed by nuclear magnetic resonance (NMR), circular dichroism (CD), and fluorescence spectroscopy, as well as by cryo-transmission electron micros
We theoretically investigate the extractable work in single molecule unfolding-folding experiments with applied feedback. Using a simple two-state model, we obtain a description of the full work distribution from discrete to continuous feedback. The effect of the feedback is captured by a detailed fluctuation theorem, accounting for the information aquired. We find analytical expressions for the a
Inflammation is a key factor in the development of plaque rupture and acute cardiovascular events. Although imaging techniques can be used to identify vulnerable atherosclerotic plaques, we are lacking non-invasive methods, such as plasma markers of plaque inflammation that could help to identify presence of vulnerable plaques. The aim of the present study was to investigate whether increased plas
