GSK3β phosphorylation catalyzes the aggregation of tau into Alzheimer's disease-like filaments.

The pathological deposition of proteins is a hallmark of several devastating neurodegenerative diseases. These pathological deposits comprise aggregates of proteins that adopt distinct structures named strains. However, the molecular factors responsible for the formation of distinct aggregate strains are unknown.

Ice thickness control and measurement in the VitroJet for time-efficient single particle structure determination.

Embedding biomolecules in vitreous ice of optimal thickness is critical for structure determination by cryo-electron microscopy. Ice thickness assessment and selection of suitable holes for data collection are currently part of time-consuming preparatory routines performed on expensive electron microscopes. To address this challenge, a routine has been developed to measure ice thickness during sample preparation using an optical camera integrated in the VitroJet.

Exploring global and local processes underlying alterations in resting-state functional connectivity and dynamics in schizophrenia.

Introduction: We examined changes in large-scale functional connectivity and temporal dynamics and their underlying mechanisms in schizophrenia (ScZ) through measurements of resting-state functional magnetic resonance imaging (rs-fMRI) data and computational modelling.

Methods: The rs-fMRI measurements from patients with chronic ScZ (n=38) and matched healthy controls (n=43), were obtained through the public schizConnect repository. Computational models were constructed based on diffusion-weighted MRI scans and fit to the experimental rs-fMRI data.

Evaluation of post-transfusion RBC alloimmunization in dogs using a gel-column crossmatch with and without anti-canine globulin enhancement.

A blood crossmatch is essential to ensure RBC compatibility for previously transfused dogs. There is no gold standard crossmatch method for dogs, although the standards used most commonly by academic institutions and reference laboratories are the tube and gel-column crossmatches. Addition of anti-canine globulin (ACG) has been suggested to increase detection of RBC incompatibilities.

Atg18 oligomer organization in assembled tubes and on lipid membrane scaffolds.

Autophagy-related protein 18 (Atg18) participates in the elongation of early autophagosomal structures in concert with Atg2 and Atg9 complexes. How Atg18 contributes to the structural coordination of Atg2 and Atg9 at the isolation membrane remains to be understood. Here, we determined the cryo-EM structures of Atg18 organized in helical tubes, Atg18 oligomers in solution as well as on lipid membrane scaffolds.

Computational mechanisms of belief updating in relation to psychotic-like experiences.

Introduction: Psychotic-like experiences (PLEs) may occur due to changes in weighting prior beliefs and new evidence in the belief updating process. It is still unclear whether the acquisition or integration of stable beliefs is altered, and whether such alteration depends on the level of environmental and belief precision, which reflects the associated uncertainty. This motivated us to investigate uncertainty-related dynamics of belief updating in relation to PLEs using an online study design.

The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services.

Our understanding of protein synthesis has been conceptualised around the structure and function of the bacterial ribosome. This complex macromolecular machine is the target of important antimicrobial drugs, an integral line of defence against infectious diseases. Here, we describe how open access to cryo-electron microscopy facilities combined with bespoke user support enabled structural determination of the translating ribosome from Escherichia coli at 1.

Belief Updating in Subclinical and Clinical Delusions.

Background And Hypothesis: Current frameworks propose that delusions result from aberrant belief updating due to altered prediction error (PE) signaling and misestimation of environmental volatility. We aimed to investigate whether behavioral and neural signatures of belief updating are specifically related to the presence of delusions or generally associated with manifest schizophrenia.

Methods: Our cross-sectional design includes human participants ([female/male] = 66[25/41]), stratified into four groups: healthy participants with minimal ( = 22) or strong delusional-like ideation ( = 18), and participants with diagnosed schizophrenia with minimal ( = 13) or strong delusions ( = 13), resulting in a 2 × 2 design, which allows to test for the effects of delusion and diagnosis.

Effect of donor blood storage on gel column crossmatch in dogs.

Background: Compared with fresh blood, stored equine donor blood results in spurious tube crossmatch incompatibilities. Interpretation of blood crossmatch results is considered subjective.

Objectives: We aimed to determine if the duration of canine donor blood storage impacts compatibility testing using a standard gel column crossmatch and evaluate interobserver variation in the interpretation of crossmatch results.

Structural basis for FLCN RagC GAP activation in MiT-TFE substrate-selective mTORC1 regulation.

The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth and catabolism in response to nutrients through phosphorylation of key substrates. The tumor suppressor folliculin (FLCN) is a RagC/D guanosine triphosphatase (GTPase)-activating protein (GAP) that regulates mTORC1 phosphorylation of MiT-TFE transcription factors, controlling lysosome biogenesis and autophagy. We determined the cryo-electron microscopy structure of the active FLCN complex (AFC) containing FLCN, FNIP2, the N-terminal tail of SLC38A9, the RagA:RagC GTPase dimer, and the Ragulator scaffold.

Models of Dynamic Belief Updating in Psychosis-A Review Across Different Computational Approaches.

To understand the dysfunctional mechanisms underlying maladaptive reasoning of psychosis, computational models of decision making have widely been applied over the past decade. Thereby, a particular focus has been on the degree to which beliefs are updated based on new evidence, expressed by the learning rate in computational models. Higher order beliefs about the stability of the environment can determine the attribution of meaningfulness to events that deviate from existing beliefs by interpreting these either as noise or as true systematic changes (volatility).

Neuromelanin-Sensitive Magnetic Resonance Imaging in Schizophrenia: A Meta-Analysis of Case-Control Studies.

Psychiatry is in urgent need of reliable biomarkers. Novel neuromelanin-sensitive magnetic resonance imaging (NM-MRI) sequences provide a time-efficient and non-invasive way to investigate the human brain . This gives insight into the metabolites of dopaminergic signaling and may provide further evidence for potential dopaminergic alterations in patients with schizophrenia (SCZ).

Structural Differences Between Healthy Subjects and Patients With Schizophrenia or Schizoaffective Disorder: A Graph and Control Theoretical Perspective.

The coordinated dynamic interactions of large-scale brain circuits and networks have been associated with cognitive functions and behavior. Recent advances in network neuroscience have suggested that the anatomical organization of such networks puts fundamental constraints on the dynamical landscape of brain activity, i.e.

Structural basis for the ARF GAP activity and specificity of the C9orf72 complex.

Mutation of C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontal temporal degeneration (FTD), which is attributed to both a gain and loss of function. C9orf72 forms a complex with SMCR8 and WDR41, which was reported to have GTPase activating protein activity toward ARF proteins, RAB8A, and RAB11A. We determined the cryo-EM structure of ARF1-GDP-BeF bound to C9orf72:SMCR8:WDR41.

Fat and Carbohydrate Interact to Potentiate Food Reward in Healthy Weight but Not in Overweight or Obesity.

Prior work suggests that actual, but not estimated, energy density drives the reinforcing value of food and that energy from fat and carbohydrate can interact to potentiate reward. Here we sought to replicate these findings in an American sample and to determine if the effects are influenced by body mass index (BMI). Thirty participants with healthy weight (HW; BMI 21.

Development of MacroPics: A novel food picture set to dissociate the effects of carbohydrate and fat on eating behaviors.

Emerging evidence suggests that fat and carbohydrate interact to potentiate the reward value of food (DiFeliceantonio et al., 2018). The primary goal of the current study was to develop a novel picture set to facilitate research into the effects of macronutrient composition on food choice and eating behavior.

Structural mechanism for amino acid-dependent Rag GTPase nucleotide state switching by SLC38A9.

The Rag GTPases (Rags) recruit mTORC1 to the lysosomal membrane in response to nutrients, where it is then activated in response to energy and growth factor availability. The lysosomal folliculin (FLCN) complex (LFC) consists of the inactive Rag dimer, the pentameric scaffold Ragulator, and the FLCN:FNIP2 (FLCN-interacting protein 2) GTPase activating protein (GAP) complex, and prevents Rag dimer activation during amino acid starvation. How the LFC is disassembled upon amino acid refeeding is an outstanding question.

Structure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD.

Mutation of C9orf72 is the most prevalent defect associated with amyotrophic lateral sclerosis and frontotemporal degeneration. Together with hexanucleotide-repeat expansion, haploinsufficiency of C9orf72 contributes to neuronal dysfunction. Here we determine the structure of the C9orf72-SMCR8-WDR41 complex by cryo-electron microscopy.

Municipal waste incineration fly ashes: from a multi-element approach to market potential evaluation.

Background: Fly ashes from municipal solid waste incineration contain significant amounts of (technology critical) elements. Processes to recover Cu or Zn are already in practice, but it still remains difficult to evaluate the full secondary resource potential of the ashes. One reason is the absence of a worldwide comparable analytical basis for detailed market analyses.

No evidence for an association between obesity and milkshake liking.

Background: Prevailing models of obesity posit that hedonic signals override homeostatic mechanisms to promote overeating in today's food environment. What researchers mean by "hedonic" varies considerably, but most frequently refers to an aggregate of appetitive events including incentive salience, motivation, reinforcement, and perceived pleasantness. Here we define hedonic as orosensory pleasure experienced during eating and set out to test whether there is a relationship between adiposity and the perceived pleasure of a palatable and energy-dense milkshake.

Enhanced angiogenic function in response to fibroblasts from psoriatic arthritis synovium compared to rheumatoid arthritis.

Introduction: Angiogenesis is an early event in the pathogenesis of both psoriatic arthritis (PsA) and rheumatoid arthritis (RA); however, there are striking differences in blood vessel morphology and activation between the two arthropathies. The aim of this study was to assess if the PsA and RA joint microenvironments differentially regulate endothelial cell function.

Methods: PsA and RA primary synovial fibroblasts (SFC) were isolated from synovial biopsies, grown to confluence, and supernatants harvested and termed 'conditioned media' (CM).

Structural mechanism of a Rag GTPase activation checkpoint by the lysosomal folliculin complex.

The tumor suppressor folliculin (FLCN) enables nutrient-dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1) protein kinase via its guanosine triphosphatase (GTPase) activating protein (GAP) activity toward the GTPase RagC. Concomitant with mTORC1 inactivation by starvation, FLCN relocalizes from the cytosol to lysosomes. To determine the lysosomal function of FLCN, we reconstituted the human lysosomal FLCN complex (LFC) containing FLCN, its partner FLCN-interacting protein 2 (FNIP2), and the RagA:RagC GTPases as they exist in the starved state with their lysosomal anchor Ragulator complex and determined its cryo-electron microscopy structure to 3.

Psychometric Evaluation of the German Version of the Dietary Fat and Free Sugar-Short Questionnaire.

Background: The Dietary Fat and Free Sugar-Short Questionnaire (DFS) is a cost- and time-efficient self-report screening instrument to estimate dietary intake of saturated fat and free sugar. To date, only the English version has been psychometrically evaluated. We assessed the psychometric characteristics of the German version of the DFS in individuals with normal weight, overweight, and obesity.