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Heterochromatin is characterized by an inaccessibility to the transcriptional machinery and is associated with the histone mark H3K9me3. However, studying the functional consequences of heterochromatin loss in human cells has been challenging. Here, we used CRISPRi-mediated silencing of the histone methyltransferase SETDB1 to remove H3K9me3 heterochromatin in human neural progenitor cells. Despite
Background: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) enables sensitive detection and staging of prostate cancer, yet its relationship with long-term survival remains unclear. This study aimed to assess whether total lesion volume (TLV) measured on [18F]PSMA-1007 PET/CT predicts overall survival (OS) in prostate cancer patients. Methods: A co
Denna berättelse om Synergi mellan Strål- och Immun-Terapi har sitt ursprung i resultaten av försök som utfördes år 2001 vilka avsåg att kombinera tumörvaccin-behandling med strålterapi av Fischer-344 råttor med gliom-tumörer inokulerade i hjärnan.Med 3 omgångar tumörvaccin kombinerat med endast en fraktion strålterapi á 5Gy, överlevde sex av åtta behandlade djur (ca.75%). Detta dramatiska re
The proline-rich domain (PRD) of the tumor suppressor p53 plays a central role in modulating conformational dynamics and molecular interactions, yet its intrinsic structural behavior remains incompletely understood. Here, we combine extensive all-atom molecular dynamics simulations with biophysical validation to characterize the conformational ensemble of the p53 PRD. The domain behaves as an intr
Histatin 5 (Hst5) is a histidine-rich intrinsically disordered protein (IDP) whose biological function arises from a highly heterogeneous conformational ensemble and environmental sensitivity. Unlike structured antimicrobial peptides that rely on persistent secondary motifs, Hst5 remains disordered across a wide range of conditions, enabling continuous adaptation to changes in pH, ionic strength,
The human influence on Earth's ecosystems is omnipresent. Artificial light at night (ALAN), anthropogenic noise, and air pollution are inherent features of human activities and infrastructure and pose novel environmental challenges to urban-dwelling wildlife. So far, most of the studies investigating the impacts of exposure to urban pollutants on animals have either investigated the effects of urb
Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation. We report a genome-wide association study and multi-trait analysis of DCM (14,256 cases) and three left ventricular traits (36,203 UK Biobank participants). We identified 80 genomic risk loci and prioritized 62 putative effector genes, including several with rare variant DCM associations (MAP3K7, NEDD4L a
Chaperone proteins are essential for maintaining proteostasis. Their main role is to assist with the folding of other proteins and to prevent the aggregation of misfolded proteins. The molecular chaperone DNAJB6b efficiently suppresses amyloid formation of several peptides. This activity may rely on the same physicochemical properties as those driving chaperone self-assembly into large micellar-li
The unprecedented x-ray flux density provided by modern x-ray sources offers new spatiotemporal possibilities for x-ray imaging of fast dynamic processes. Approaches to exploit such possibilities often result in either (i) a limited number of projections or spatial information due to limited scanning speed, as in time-resolved tomography, or (ii) a limited number of time points, as in stroboscopic
Purpose: The Paleolithic Diet Fraction (PDF) estimates the proportion of absolute dietary intake derived from food groups included in the Paleolithic diet. In the Malmö Diet and Cancer Study (MDCS), higher PDF and lower systemic low-grade chronic inflammation (SLGCI) have been associated with lower cardiometabolic morbidity and mortality. We examined associations between PDF and SLGCI in the MDCS.
Migratory birds have evolved a multitude of physiological and behavioural adaptations to reach their population-specific wintering areas during their first migration. The endogenous program encodes distance, direction and fuelling, and involves species-specific adaptations leading naïve migratory birds along highly diverse routes. While daylength has been extensively studied in relation to the ons
Individuals with rapidly progressing atherosclerotic plaques are at higher risk of experiencing acute complications. Currently, we lack knowledge regarding factors in human plaque that cause rapid progression. Using the 14C bomb-pulse dating method, we assessed the physical age of atherosclerotic plaques and which biological processes were associated with rapidly progressing plaques. Interestingly
Background: Several studies indicate increasing hospitalisation rates for specific infectious diseases (IDs). Studies describing the entire ID spectrum are scarcer. Our aim was to describe hospital use with ID diagnoses in Swedish adults from 1998 to 2019. Methods: All four-position codes in ICD-10 were reclassified as ID or non-ID diagnoses. Using data from the National Patient Register, age-stan
Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition caused by deposition of transthyretin amyloid fibrils in the heart and is associated with poor quality of life and a shortened lifespan. This study aimed to describe the prevalence, clinical characteristics, and mortality of patients with ATTR-CM, using multiple national health registers in Denmark, Finland, Norway, an
Aim: This randomised controlled trial evaluated changes in parental self-efficacy and children's weight, after a Child-Centred Health Dialogue about preventing obesity. Methods: We randomly assigned 37 Child Health Centres in Skåne county Sweden to provide usual care or the dialogue intervention. They included centres from high and low socioeconomic areas. The outcomes were changes in parental sel
Background Elevated troponin levels are a sensitive biomarker for cardiac injury. The quick and reliable prediction of troponin elevation for patients with chest pain from readily available ECGs may pose a valuable time-saving diagnostic tool during decision-making concerning this patient population. Methods and results The data used included 15 856 ECGs from patients presenting to the emergency r
Despite the anticipated benefits of smart home technology (SHT) to support older adults' engagement in meaningful activities, barriers to the adoption of SHT have been identified. While research in the field of technology is surging, research on older adults playing an active role in designing and developing SHT to enhance usability is lacking. It is important to co-develop solutions to place olde
Background: Emerging evidence suggests that artificial intelligence (AI) can increase cancer detection in mammography screening while reducing screen-reading workload, but further understanding of the clinical impact is needed. Methods: In this randomised, controlled, parallel-group, non-inferiority, single-blinded, screening-accuracy study, done within the Swedish national screening programme, wo
Background: Arterial stiffness, measured using carotid-femoral pulse wave velocity (c-f PWV) and heart rate-corrected augmentation index (Aix75), is associated with cardiovascular disease, and in some studies incident atrial fibrillation (AF). In this cross-sectional study, we aimed to investigate whether arterial stiffness is associated with markers of atrial myopathy, which refers to structural
BACKGROUND: Melanoma is a highly heterogeneous disease, and a deeper molecular classification is essential for improving patient stratification and treatment approaches. Here, we describe the histopathology-driven proteogenomic landscape of 142 treatment-naïve metastatic melanoma samples to uncover molecular subtypes and clinically relevant biomarkers.METHODS: We performed an integrative proteogen
