Protocol to study CCT-mediated folding of Gβ by single-particle cryo-EM.

The chaperonin CCT mediates folding of many cytosolic proteins, including G protein β subunits (Gβs). Here, we present a protocol for isolating Gβ bound to CCT and its co-chaperone PhLP1 and determining the CCT-mediated folding trajectory of Gβ using single-particle cryoelectron microscopy (cryo-EM) techniques. We describe steps for purifying CCT-Gβ-PhLP1 from human cells, stabilizing the closed CCT conformation, preparing and imaging cryo-EM specimens, and processing data to recover multiple Gβ folding intermediates.

Liraglutide 3.0 mg once daily for the treatment of overweight and obesity in patients hospitalised at a forensic psychiatric department: A 26-week open-label feasibility study.

Introduction: Overweight and obesity constitute a major concern among patients treated at forensic psychiatric departments. The present clinical feasibility study aimed at investigating the extent to which glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with once-daily liraglutide 3.0 mg could be a feasible pharmacological treatment of these conditions in patients with schizophrenia spectrum disorders hospitalised in forensic psychiatry.

Visualizing the chaperone-mediated folding trajectory of the G protein β5 β-propeller.

The Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with β-propeller domains. Here, we determine the structures of human CCT in complex with its accessory co-chaperone, phosducin-like protein 1 (PhLP1), in the process of folding Gβ, a component of Regulator of G protein Signaling (RGS) complexes. Cryoelectron microscopy (cryo-EM) and image processing reveal an ensemble of distinct snapshots that represent the folding trajectory of Gβ from an unfolded molten globule to a fully folded β-propeller.

Visualizing the chaperone-mediated folding trajectory of the G protein β5 β-propeller.

The cytosolic Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with β-propeller domains. Here, we determined structures of CCT in complex with its accessory co-chaperone, phosducin-like protein 1 (PhLP1), in the process of folding Gβ, a component of Regulator of G protein Signaling (RGS) complexes. Cryo-EM and image processing revealed an ensemble of distinct snapshots that represent the folding trajectory of Gβ from an unfolded molten globule to a fully folded β-propeller.

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry).

Introduction: Clozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited effects counteracting these adverse effects. Semaglutide, a glucagon-like peptide 1 receptor agonist, is approved for the treatment of type 2 diabetes and obesity.

But I have no time to read this article! A meta-analytic review of the consequences of employee time management behaviors.

Time management is a beneficial tool for both individuals and their organizations. In this study, we conduct a meta-analytic review of the consequences of employee time management behaviors. Our results suggest that time management is associated with a variety of beneficial employee outcomes such as increased job satisfaction, job performance, and lower levels of stress and burnout.

SARS-CoV-2 seroprevalence among patients with severe mental illness: A cross-sectional study.

Patients with severe mental illness (SMI) i.e. schizophrenia, schizoaffective disorder, and bipolar disorder are at increased risk of severe outcomes if infected with coronavirus disease 2019 (COVID-19).

Impact of EGFR and EGFR ligand expression on treatment response in patients with metastatic colorectal cancer.

Up to 50% of patients with colorectal cancer (CRC) have either synchronous or metachronous hepatic metastases in the course of their disease. Patients with metastatic CRC (mCRC) whose tumors express wild-type KRAS benefit from treatment with monoclonal antibodies (such as cetuximab or panitumumab) that target the epidermal growth factor receptor (EGFR). However, the therapeutic response to these antibodies is variable, and further predictive models are required.

Condition-dependent functional shift of two Mtmr lipid phosphatases in autophagy control.

Myotubularin (MTM) and myotubularin-related (MTMR) lipid phosphatases catalyze the removal of a phosphate group from certain phosphatidylinositol derivatives. Because some of these substrates are required for macroautophagy/autophagy, during which unwanted cytoplasmic constituents are delivered into lysosomes for degradation, MTM and MTMRs function as important regulators of the autophagic process. Despite its physiological and medical significance, the specific role of individual MTMR paralogs in autophagy control remains largely unexplored.

[Fracture of the posterior malleolus : A paradigm shift].

Ankle fractures with involvement of the posterior malleolus have a poor prognosis. The traditional concept of addressing the posterior fragment as the final step in the surgical reconstruction depending on the fragment size manifest in the lateral X‑ray, does not do justice to the anatomic and biomechanical relevance of the posterior malleolus. Intra-articular step-offs and fragment displacement ≥ 2 mm, impacted intercalary fragments, involvement of the fibular notch and instability of the syndesmosis, represent parameters relevant for the surgical reconstruction and the functional and radiomorphological outcome independent of fragment size.

Secretion of parathyroid hormone may be coupled to insulin secretion in humans.

Objective: Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion.

Centrosome Amplification in Cancer Disrupts Autophagy and Sensitizes to Autophagy Inhibition.

Centrosome amplification (CA), or a numerical increase in centrosomes, is common in human cancers, particularly those with high-risk features. We have discovered that cells with CA have an increased burden of autophagy, a catabolic process whereby autophagosomes engulf damaged organelles and proteins and deliver these contents to the lysosome for degradation and subsequent recycling. Cells with CA demonstrate an accumulation of autophagosomes.

Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131).

The centrosome, consisting of two centrioles surrounded by a dense network of proteins, is the microtubule-organizing center of animal cells. Polo-like kinase 4 (PLK4) is a Ser/Thr protein kinase and the master regulator of centriole duplication, but it may play additional roles in centrosome function. To identify additional proteins regulated by PLK4, we generated an RPE-1 human cell line with a genetically engineered "analog-sensitive" PLK4, which genetically encodes chemical sensitivity to competitive inhibition via a bulky ATP analog.

Minimally invasive internal fixation of calcaneal fractures or subtalar joint arthrodesis using the Calcanail®.

Objective: A minimally invasive technique to prevent soft tissue problems using a calcaneal nail (Calcanail®, FH Orthopedics, Heimsbrunn, France) for calcaneal fractures or in subtalar joint arthrodesis is described.

Indications: Displaced extra-articular calcaneal fractures involving the tuberosity fragment and in displaced intra-articular calcaneal fractures with impression and/or displacement of the subtalar joint surface. Subtalar joint arthrodesis for posttraumatic subtalar osteoarthritis.

Developmentally regulated autophagy is required for eye formation in Drosophila.

Unlabelled: The compound eye of the fruit fly Drosophila melanogaster is one of the most intensively studied and best understood model organs in the field of developmental genetics. Herein we demonstrate that autophagy, an evolutionarily conserved selfdegradation process of eukaryotic cells, is essential for eye development in this organism. Autophagic structures accumulate in a specific pattern in the developing eye disc, predominantly in the morphogenetic furrow (MF) and differentiation zone.

Discriminating the hemolytic risk of blood type A plasmas using the complement hemolysis using human erythrocytes (CHUHE) assay.

Background: The agglutination-based cross-matching method is sensitive for antibody binding to red blood cells but is only partially predictive of complement-mediated hemolysis, which is important in many acute hemolytic transfusion reactions. Here, we describe complement hemolysis using human erythrocytes (CHUHE) assays that directly evaluate complement-mediated hemolysis between individual serum-plasma and red blood cell combinations. The CHUHE assay is used to evaluate correlations between agglutination titers and complement-mediated hemolysis as well as the hemolytic potential of plasma from type A blood donors.

[Joint-preserving treatment of medial femoral neck fractures with an angular stable implant].

Objective: Operative stabilization is recommended even for non-displaced or only slightly displaced femoral neck fractures. In addition to the known osteosynthetic procedures, an angular stabile implant system (Targon® FN) has been established since 2006 for treatment of such fractures.

Indications: Displaced femoral neck fractures (Garden III and IV) and non-displaced fractures (Garden I and II).

Retromer Ensures the Degradation of Autophagic Cargo by Maintaining Lysosome Function in Drosophila.

The retromer is an evolutionarily conserved coat complex that consists of Vps26, Vps29, Vps35 and a heterodimer of sorting nexin (Snx) proteins in yeast. Retromer mediates the recycling of transmembrane proteins from endosomes to the trans-Golgi network, including receptors that are essential for the delivery of hydrolytic enzymes to lysosomes. Besides its function in lysosomal enzyme receptor recycling, involvement of retromer has also been proposed in a variety of vesicular trafficking events, including early steps of autophagy and endocytosis.

Specialized Cortex Glial Cells Accumulate Lipid Droplets in Drosophila melanogaster.

Lipid droplets (LDs) are common organelles of the majority of eukaryotic cell types. Their biological significance has been extensively studied in mammalian liver cells and white adipose tissue. Although the central nervous system contains the highest relative amount and the largest number of different lipid species, neither the spatial nor the temporal distribution of LDs has been described.

Anti-stress effects of lemon balm-containing foods.

Lemon balm (Melissa officinalis) has been used historically and contemporarily as a modulator of mood and cognitive function, with anxiolytic effects following administration of capsules, coated tablets and topical application. Following a pilot study with lemon balm extract administered as a water based drink, which confirmed absorption of rosmarinic acid effects on mood and cognitive function, we conducted two similar double-blind, placebo-controlled, crossover studies. These evaluated the mood and cognitive effects of a standardised M.