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GATA2 at the mitosis-to-G1 transition is critical for definitive hematopoiesis

In mitosis, transcription factors (TFs) and RNA polymerase disperse across the cytoplasm leading to transcriptional silencing, but some TFs are retained on condensed chromatin and mark genomic sites, a mechanism termed mitotic bookmarking. In pluripotent and differentiated cells this mechanism is important for pluripotency maintenance, cell reprogramming and lineage inheritance. However, the role

Sick leave after arthroscopic meniscus repair vs. arthroscopic partial meniscectomy

Objective: To evaluate sick leave after meniscal repair vs arthroscopic partial meniscectomy (APM) and, for comparison, vs the general population. Method: Using Swedish register data we included all employed persons aged 19–49 years in the general population of Skåne region and identified those having had meniscus repair or APM in the period of 2005–2012. We retrieved data on sick leave during 1 y

Plasma proteomic changes in response to exercise training are associated with cardiorespiratory fitness adaptations

Regular exercise leads to widespread salutary effects, and there is increasing recognition that exercise-stimulated circulating proteins can impart health benefits. Despite this, limited data exist regarding the plasma proteomic changes that occur in response to regular exercise. Here, we perform large-scale plasma proteomic profiling in 654 healthy human study participants before and after a supe

A scoping review of how early-stage knee osteoarthritis has been defined

BACKGROUND: Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature.METHODS: We performed a scoping literature review in PubM

Pulmonary Hypertension Phenotype Can Be Identified in Heart Failure With Reduced Ejection Fraction Using Echocardiographic Assessment of Pulmonary Artery Pressure With Supportive Use of Pressure Reflection Variables

Background: Pulmonary hypertension (PH) is frequent in patients with heart failure and reduced ejection fraction (HFrEF) with 2 different phenotypes: isolated postcapillary PH (IpcPH) and, with the worst prognosis, combined pre- and postcapillary PH (CpcPH). The aims of the present echocardiography study were to investigate (1) the ability to identify PH phenotype in patients with HFrEF using the

Adipocyte size and function in the epididymal and inguinal fat depots

Nearly 60% of the worlds adult population is projected to be overweight or obese by 2030. The prevalence of obesity- related diseases, such as type 2 diabetes (T2D), has increased markedly in the past decades. The adipose tissue plays an important role in disease progression of T2D. Adipocyte insulin sensitivity, adipose tissue’s ability to expand, and accumulation of subcutaneous rather than visc

Transcription Factor-Forced Astrocytic Differentiation Impairs Human Glioblastoma Growth In Vitro and In Vivo

Direct cellular reprogramming has recently gained attention of cancer researchers for the possibility to convert undifferentiated cancer cells into more differentiated, postmitotic cell types. While a few studies have attempted reprogramming of glioblastoma (GBM) cells toward a neuronal fate, this approach has not yet been used to induce differentiation into other lineages and in vivo data on redu

Charge Regulation during Amyloid Formation of α-Synuclein

Electrostatic interactions play crucial roles in protein function. Measuring pKa value perturbations upon complex formation or self-assembly of e.g. amyloid fibrils gives valuable information about the effect of electrostatic interactions in those processes. Site-specific pKa value determination by solution NMR spectroscopy is challenged by the high molecular weight of amyloid fibrils. Here we rep

Preheart failure comorbidities and impact on prognosis in heart failure patients : a nationwide study

Background: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. Objectives: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. Methods: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities

Increased midlife triglycerides predict brain β-amyloid and tau pathology 20 years later

Objective To evaluate the effect of midlife lipid levels on Alzheimer brain pathology 20 years later in cognitively normal elderly individuals.Methods This is a longitudinal cohort study of 318 cognitively normal individuals with data on fasting lipid levels at midlife (mean age 54 years). Presence of β-amyloid (Aβ) and tau pathologies 20 years later (mean age 73 years) were detected by quantifyin

An evolutionary basis for protein design and structure prediction

Some 4 billion years ago, nature began the experiment that led to you, that bird on the branch, that branch, and everything else which is alive that you see around you. The generating process of all this splendid life is, of course, evolution. Evolution works not only on the macroscopic scale (think eyes, muscles, wings) but also on the molecular scale (think molecular antennas, nanoscale muscles,The sequence diversity of protein families is a result of the biophysical selection pressures that shaped their evolutionary history. Among the dominant pressures is selection for protein thermostability, which in itself is an attractive target in protein engineering because of its importance for various biopharmaceutical properties, the performance of industrial enzymes, and the ability to design

Postprandial Levels of Branch Chained and Aromatic Amino Acids Associate with Fasting Glycaemia

High fasting plasma concentrations of isoleucine, phenylalanine, and tyrosine have been associated with increased risk of hyperglycaemia and incidence of type 2 diabetes. Whether these associations are diet or metabolism driven is unknown. We examined how the dietary protein source affects the postprandial circulating profile of these three diabetes associated amino acids (DMAAs) and tested whethe

Neurotrophic Factor Receptors in the Normal and Injured Visual System : Focus on Retinal Ganglion Cells

The focus of this thesis is the life and death of adult retinal ganglion cells (RGCs). RGCs are neurons that convey visual information from the retina to higher centers in the brain. If the optic nerve is transected (ONT), adult RGCs die by a form of cell death called apoptosis, and a general hypothesis is that neurotrophic factors can support the survival of injured neurons.With the intention to The focus of this thesis is the life and death of adult retinal ganglion cells (RGCs). RGCs are neurons that convey visual information from the retina to higher centers in the brain. If the optic nerve is transected (ONT), adult RGCs die by a form of cell death called apoptosis, and a general hypothesis is that neurotrophic factors can support the survival of injured neurons. With the intention to

A low-spin Fe(iii) complex with 100-ps ligand-to-metal charge transfer photoluminescence

Transition-metal complexes are used as photosensitizers1, in light-emitting diodes, for biosensing and in photocatalysis2. A key feature in these applications is excitation from the ground state to a charge-transfer state3,4; the long charge-transfer-state lifetimes typical for complexes of ruthenium5 and other precious metals are often essential to ensure high performance. There is much interest

Modelling human rostro-caudal neural patterning with a microfluidic morphogenic gradient

The study of biological mechanisms involved in human fetal brain development requires suitable models. To date, most findings have been acquired from animal models that fail to account for human-specific developmental traits. To counteract this limitation, a novel in vitro model is proposed where human pluripotent stem cells are differentiated into a coherent fetal brain tissue in a gradient formi

Meniscus tear; Knee arthroscopy; clinical practice and sick leave

Knäleden är kroppens största led och är påtagligt komplicerad. Den utsätts dagligen för stora krafter vid såväl böj och vridrörelser som stötkrafter vid stegisättning. För att den skall fungera optimalt måste flera olika komponenter samverka. Brosket som bekläder benändarna bidrar med stötdämpning och ger en mycket låg friktion vid rörelse. Flera olika ligament och muskler som löper över leden bid

Infections are associated with increased risk of giant cell arteritis - a population-based case-control study from Southern Sweden

Objective To investigate the association of infections with the subsequent development of giant cell arteritis (GCA) in a large population-based cohort from a defined geographic area in Sweden.Methods Patients diagnosed with biopsy-confirmed GCA between 2000 and 2016 were identified through the database of the Department of Pathology in Skåne, the southernmost region of Sweden. For each GCA case,

Neoadjuvant breast cancer treatment response; tumor size evaluation through different conventional imaging modalities in the NeoDense study

Neoadjuvant chemotherapy (NACT) is offered to an increasing number of breast cancer (BC) patients, and comprehensive monitoring of treatment response is of utmost importance. Several imaging modalities are available to follow tumor response, although likely to provide different clinical information. We aimed to examine the association between early radiological response by three conventional imagi

Two-Step Acoustophoresis Separation of Live Tumor Cells from Whole Blood

There is an unmet clinical need to extract living circulating tumor cells (CTCs) for functional studies and in vitro expansion to enable drug testing and predict responses to therapy in metastatic cancer. Here, we present a novel two-step acoustophoresis (A2) method for isolation of unfixed, viable cancer cells from red blood cell (RBC) lysed whole blood. The A2 method uses an initial acoustofluid

Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study

Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynam