Endoplasmic reticulum (ER) membrane resident P5A-ATPases broadly affect protein biogenesis and quality control, and yet their molecular function remains debated. Here, we report cryo-EM structures of a P5A-ATPase, CtSpf1, covering multiple transport intermediates of the E1 → E1-ATP → E1P-ADP → E1P → E2P → E2.Pi → E2 → E1 cycle. In the E2P and E2.Pi states a cleft spans the entire membrane, holding

Purpose: To translate, validate, and evaluate the psychometric properties of the German version of Keratoconus Outcomes Research Questionnaire (KORQ). Methods: This prospective study included 3 phases. In phase 1, the KORQ was translated in a standardized way; in phase 2, Rasch validation was performed; in phase 3, the validated questionnaire was evaluated in a separate patient cohort. All patient

The built environment is still, to a large extent, not accessible and usable for all. The awareness of people's different conditions and abilities sometimes seems to be far from the agenda for planning and architecture. Universal Desing (UD) is pointed out as a strategy to achieve a built environment for all people regardless of age and abilities. UD has a radical potential to bring about change a

In Swedish policy, Universal design (UD) is implemented as a guiding principle. This paper explores the conditions for co-creation when authorities and civil society collaborate. The empirical basis comes from qualitative analysis of interviews, go-alongs, group discussions, and change-oriented workshops in three urban development projects concerning the re-design of public spaces and buildings in

Lytic polysaccharide monooxygenases (LPMOs) form a copper-dependent family of enzymes classified under the auxiliary activity (AA) superfamily. The LPMOs are known for their boosting of polysaccharide degradation through oxidation of the glycosidic bonds that link the monosaccharide subunits. This oxidation has been proposed to be dependent on either O2 or H2O2 as cosubstrate. Theoretical investig

Observations of polarization position angle (θ) standards made from 2014 to 2023 with the High Precision Polarimetric Instrument (HIPPI) and other HIPPI-class polarimeters in both hemispheres are used to investigate their variability. Multiband data were first used to thoroughly recalibrate the instrument performance by bench-marking against carefully selected literature data. A novel co-ordinate

We study steady axisymmetric water waves with general vorticity and swirl, subject to the influence of surface tension. Explicit solutions to such a water wave problem are static configurations where the surface is an unduloid, that is, a periodic surface of revolution with constant mean curvature. We prove that to any such configuration there connects a global continuum of non-static solutions by

Antimicrobial peptides (AMPs), particularly host defense peptides (HDPs), have gained recognition for their role in host defense mechanisms, but they have also shown potential as a promising anticancer, antiviral, antiparasitic, antifungal and immunomodulatory agent. Research studies in recent years have shown HDPs play a crucial role in endothelial cell function and biology. The function of endot

Background: High gluten and low dietary fiber in pregnancy intake is associated with an increased risk of celiac disease (CeD) in the child. Early life higher dietary quality is suggested to reduce the subsequent risk of CeD. Objectives: The aim was to investigate associations of pregnancy dietary quality and diversity with child risk of CeD. Methods: In The Norwegian Mother, Father and Child Coho

The innate immune system shapes brain development and is implicated in neurodevelopmental diseases. It is critical to define the relevant immune cells and signals and their impact on brain circuits. In this work, we found that group 2 innate lymphoid cells (ILC2s) and their cytokine interleukin-13 (IL-13) signaled directly to inhibitory interneurons to increase inhibitory synapse density in the de

BACKGROUND: Lymphatic disorders such as protein-losing enteropathy, plastic bronchitis, and chylothorax are important complications of the Fontan circulation and ultimately result in an increased risk of early death. Several European centers are now performing lymphatic procedures. The aim of this study is to map the extent of these lymphatic disorders and treatments provided across European pedia

Background: Foot deformities, such as valgus and varus in the coronal plane and equinus in the sagittal plane, are common in children with cerebral palsy (CP). The purpose of this study was to describe the prevalence of coronal plane foot deformities and their association with the Gross Motor Function Classification System (GMFCS) level, age, CP subtype, and equinus in children with CP. Methods: A

A peptide corresponding to a 13-residue segment of the human protein semenogelin I has been shown to generate a hydrogel consisting of amyloid-like fibrils. The relative chemical diversity (compared to synthetic de novo sequences) with 11 distinct amino acids makes this peptide (P0) an ideal candidate for investigating the role of individual residues in gelation. Herein, the N-terminal residues ha

Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with breast cancer before, during and after neoadjuvant ch

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system xc- radiotracer, [18F]FSPG, provides a sensitive and specific marker of NRF

Benbarche, Pineda, Galvis, et al. delineate an essential role for the G-patch motif-containing protein GPATCH8 in mis-splicing associated with cancer-driving mutations of the splicing factor SF3B1. GPATCH8 cooperates with SF3B1 mutants, affecting the splicing machinery. Targeting GPATCH8 reveals therapeutic opportunities for SF3B1 mutant cancers and other splicing-related diseases.

Fifty-eight million individuals worldwide are affected by chronic hepatitis C virus (HCV) infection, a primary driver of liver cancer for which no vaccine is available1. The HCV envelope proteins E1 and E2 form a heterodimer (E1/E2), which is the target for neutralizing antibodies2. However, the higher-order organization of these E1/E2 heterodimers, as well as that of any Hepacivirus envelope prot

Background: Providing secondary prevention through structured and comprehensive cardiac rehabilitation programmes to patients after a myocardial infarction (MI) reduces mortality and morbidity and improves health-related quality of life. Cardiac rehabilitation has the highest recommendation in current guidelines. While treatment target attainment rates at Swedish cardiac rehabilitation centres is

Photocatalytic nanoparticles offer antimicrobial effects under illumination due to the formation of reactive oxygen species (ROS), capable of degrading bacterial membranes. ROS may, however, also degrade human cell membranes and trigger toxicity. Since antimicrobial peptides (AMPs) may display excellent selectivity between human cells and bacteria, these may offer opportunities to effectively “tar