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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

Resonant X-ray photo-oxidation of light-harvesting iron (II/III) N-heterocyclic carbene complexes

Two photoactive iron N-heterocyclic carbene complexes [FeII(btz)2(bpy)]2+ and [FeIII(btz)3]3+, where btz is 3,3’-dimethyl-1,1’-bis(p-tolyl)-4,4’-bis(1,2,3-triazol-5-ylidene) and bpy is 2,2’-bipyridine, have been investigated by Resonant Photoelectron Spectroscopy (RPES). Tuning the incident X-ray photon energy to match core-valence excitations provides a site specific probe of the electronic struc

Consensus statement on the definition of orthostatic hypertension endorsed by the American Autonomic Society and the Japanese Society of Hypertension

We propose a consensus definition of "an exaggerated orthostatic pressor response" in subjects in whom systolic blood pressure increases ≥ 20 mmHg when going from supine to standing posture. This definition can be extended for seated to standing measurements. We reserve the term "orthostatic hypertension" for when this pressor response leads to an upright systolic blood pressure ≥ 140 mmHg. We bel

Proteogenomic Profiling of Treatment-Naïve Metastatic Malignant Melanoma

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

Interval Cancers in a Large, Prospective Breast Tomosynthesis Screening Trial

PURPOSETo assess interval cancer rate in a large, prospective digital breast tomosynthesis (DBT) screening trial in comparison with a concurrent screening population and to assess tumor characteristics of interval cancers in DBT-screening.METHOD AND MATERIALSThe prospective ****Trial, comparing digital breast tomosynthesis (DBT) with digital mammography (DM) in 14,848 women has shown a significant

Dual-Band Infrared Scheimpflug Lidar Reveals Insect Activity in a Tropical Cloud Forest

We describe an entomological dual-band 808 and 980 nm lidar system which has been implemented in a tropical cloud forest (Ecuador). The system was successfully tested at a sample rate of 5 kHz in a cloud forest during challenging foggy conditions (extinction coefficients up to 20 km–1). At times, the backscattered signal could be retrieved from a distance of 2.929 km. We present insect and bat obs

Bacterial Pathogenesis : Methods and Protocols

This detailed volume presents a diverse set of methodological approaches designed to improve our understanding of bacterial infections from a wide range of bacterial species. Beginning with biofilms and subcellular compartments, the book explores transcriptional analysis, methods for studying plasmid dynamics, and tools for phylogenetic analysis of bacterial genomes, as well as bacterial effector

Environmental determinants of body mass index trajectories: results from a longitudinal Swedish study

Exposure to natural environments is thought to benefit mental and physical health. A better understanding of the interplay between the individual and the environment in relation to public health is imperative in light of the joint biodiversity, climate, and health crises. This study aimed to 1) identify Body Mass Index (BMI) trajectories in the Scania Public Health Cohort (SPHC), 2) characterise t

Radiolabeled antibodies in prostate cancer: A case study showing the effect of host immunity on antibody bio-distribution.

Human tumors xenografted in immunodeficient mice are crucial models in nuclear medicine to evaluate the effectiveness of candidate diagnostic and therapeutic compounds. However, little attention has been focused on the biological profile of the host model and its potential effects on the bio-distribution and tumor targeting of the tracer compound under study. We specifically investigated the dissi

Identification of stage-specific surface markers in early B cell development provides novel tools for identification of progenitor populations

Whereas the characterization of B lymphoid progenitors has been facilitated by the identification of lineage-and stage-specific surface markers, the continued identification of differentially expressed proteins increases our capacity to explore normal and malignant B cell development. To identify novel surface markers with stage-specific expression patterns, we explored the reactivity of CD19+ B c

Changes in dietary intake following a culturally adapted lifestyle intervention among Iraqi immigrants to Sweden at high risk of type 2 diabetes : a randomised trial

Objective: To investigate the effectiveness of a culturally adapted lifestyle intervention for changing dietary intake, particularly energy, fat and fibre intakes, in the intervention group (IG) compared with the control group (CG). Design: Randomised controlled trial. Setting: IG (n 50) and CG (n 46). The IG was offered seven group sessions, including one cooking class, over a period of 4 months.

An Artificial Intelligence-based Support Tool for Automation and Standardisation of Gleason Grading in Prostate Biopsies

BACKGROUND: Gleason grading is the standard diagnostic method for prostate cancer and is essential for determining prognosis and treatment. The dearth of expert pathologists, the inter- and intraobserver variability, as well as the labour intensity of Gleason grading all necessitate the development of a user-friendly tool for robust standardisation.OBJECTIVE: To develop an artificial intelligence

Agonistic targeting of TLR1/TLR2 induces p38 MAPK-dependent apoptosis and NFκB-dependent differentiation of AML cells

Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34+CD38-cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 inMLL-AF9-driv

X-Ray Dark-Field Imaging of Lung Cancer in Mice

Lung cancer accounts for 1.6 million deaths per year worldwide. The majority of patients are diagnosed at advanced stages of the disease and often present with metastasis. Thus, the 5-year survival rate of lung cancer remains around 15%. Early diagnosis of lung cancer allows for better control of the disease with 5-year survival rates up to around 70%. Chest radiography is the most common techniqu

A new genetic tool to improve immune-compromised mouse models : Derivation and CRISPR/Cas9-mediated targeting of NRG embryonic stem cell lines

Development of human hematopoietic stem cells and differentiation of embryonic stem (ES) cells/induced pluripotent stem (iPS) cells to hematopoietic stem cells are poorly understood. NOD (Non-obese diabetic)-derived mouse strains, such as NSG (NOD-Scid-il2Rg) or NRG (NOD-Rag1-il2Rg), are the best available models for studying the function of fetal and adult human hematopoietic cells as well as ES/