Right-wing authoritarianism and perceptions that minoritized groups pose a threat: The moderating roles of individual- and country-level religiosity and marginalization.

Right-wing authoritarianism (RWA) refers to an adherence to conventional values and authorities with the power to penalize groups that are perceived to challenge the cohesion of ingroup norms. Correspondingly, RWA has repeatedly been linked to negative perceptions of minoritized groups, such as refugees or religious minorities. To investigate whether and how sociocultural factors add to and moderate how RWA influences perceptions that minoritized groups pose a threat (i.

Structure-function relationship of dynorphin B variants using naturally occurring amino acid substitutions.

Dynorphins (Dyn) represent the subset of endogenous opioid peptides with the highest binding affinity to kappa opioid receptors (KOPrs). Activation of the G-protein-coupled pathway of KOPrs has strong anticonvulsant effects. Dyn also bind to mu (MOPrs) and delta opioid receptors (DOPrs) with lower affinity and can activate the β-arrestin pathway.

Does the gender of emergency physicians have an impact on the prehospital care of psychiatric emergencies? a retrospective cohort analysis.

Background: Psychiatric emergencies pose a special challenge for emergency physicians. It is known from other areas of medicine that the influence of a doctor's gender can have an impact on the type of treatment and quality of patient care. However, this has not yet been investigated in the context of prehospital care in psychiatric emergencies.

Evaluation of the SH-SY5Y cell line as an model for potency testing of a neuropeptide-expressing AAV vector.

Viral vectors have become important tools for basic research and clinical gene therapy over the past years. However, testing of vector-derived transgene function can be challenging when specific post-translational modifications are needed for biological activity. Similarly, neuropeptide precursors need to be processed to yield mature neuropeptides.

Mechanisms underlying the health benefits of intermittent hypoxia conditioning.

Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender.

Dimethyl sulfoxide's impact on epileptiform activity in a mouse model of chronic temporal lobe epilepsy.

In the quest for novel treatments for patients with drug-resistant seizures, poor water solubility of potential drug candidates is a frequent obstacle. Literature indicated that the highly efficient solvent dimethyl sulfoxide (DMSO) may have a confounding influence in epilepsy research, reporting both pro- and antiepileptic effects. In this study, we aim to clarify the effects of DMSO on epileptiform activity in one of the most frequently studied models of chronic epilepsy, the intrahippocampal kainic acid (IHKA) mouse model, and in a model of acute seizures.

A reversible SRC-relayed COX2 inflammatory program drives resistance to BRAF and EGFR inhibition in BRAF colorectal tumors.

BRAF mutation confers a poor prognosis in metastatic colorectal cancer (CRC) despite combinatorial targeted therapies based on the latest understanding of signaling circuitry. To identify parallel resistance mechanisms induced by BRAF-MEK-EGFR co-targeting, we used a high-throughput kinase activity mapping platform. Here we show that SRC kinases are systematically activated in BRAF CRC following targeted inhibition of BRAF ± EGFR and that coordinated targeting of SRC with BRAF ± EGFR increases treatment efficacy in vitro and in vivo.

Factors Associated With Postoperative Delirium in Patients Undergoing Complex Head and Neck Flap Surgery.

Purpose: Postoperative delirium (PD) is a common and severe complication, following extensive surgery and prolonged stays in intensive care units (ICU). The study aimed to estimate the frequency of and identify risk factors for PD in a unified sample of head and neck surgery patients.

Methods: The investigators implemented a retrospective cohort study composing of patients undergoing free flap reconstructive surgery over 1 year.

Knockout of Ca1.3 L-type calcium channels in a mouse model of retinitis pigmentosa.

Retinitis Pigmentosa is a genetically heterogeneous, degenerative retinal disorder characterized by gradual dysfunction and death of photoreceptors, first rods and later cones, and progressive blindness. Studies suggested that application of L-type calcium channel blockers rescues photoreceptors in paradigms related to Ca overflow. To investigate whether Cav1.

Physical Activity Reduces Clinical Symptoms and Restores Neuroplasticity in Major Depression.

Major depressive disorder (MDD) is the most common mental disorder and deficits in neuroplasticity are discussed as one pathophysiological mechanism. Physical activity (PA) enhances neuroplasticity in healthy subjects and improves clinical symptoms of MDD. However, it is unclear whether this clinical effect of PA is due to restoring deficient neuroplasticity in MDD.

Considerations on Using Antibodies for Studying the Dynorphins/Kappa Opioid Receptor System.

Antibodies are important tools for protein and peptide research, including for the kappa opioid receptor (KOR) and dynorphins (Dyns). Well-characterized antibodies are essential for rigorous and reproducible research. However, lack of validation of antibody specificity has been thought to contribute significantly to the reproducibility crisis in biomedical research.

Improved Protein and PTM Characterization with a Practical Electron-Based Fragmentation on Q-TOF Instruments.

Electron-based dissociation (ExD) produces uncluttered mass spectra of intact proteins while preserving labile post-translational modifications. However, technical challenges have limited this option to only a few high-end mass spectrometers. We have developed an efficient ExD cell that can be retrofitted in less than an hour into current LC/Q-TOF instruments.

The Kappa Opioid Receptor System in Temporal Lobe Epilepsy.

Temporal lobe epilepsy is considered to be one of the most common and severe forms of focal epilepsies. Patients frequently develop cognitive deficits and emotional blunting along progression of the disease. The high incidence of refractoriness to antiepileptic drugs and a frequent lack of admissibility to surgery pose an unmet medical challenge.

Phenotypic Characterization and Brain Structure Analysis of Calcium Channel Subunit αδ-2 Mutant (Ducky) and αδ Double Knockout Mice.

Auxiliary αδ subunits of voltage-gated calcium channels modulate channel trafficking, current properties, and synapse formation. Three of the four isoforms (αδ-1, αδ-2, and αδ-3) are abundantly expressed in the brain; however, of the available knockout models, only αδ-2 knockout or mutant mice display an obvious abnormal neurological phenotype. Thus, we hypothesize that the neuronal αδ isoforms may have partially specific as well as redundant functions.

Genetic Diversity and Connectivity in Plant Species Differing in Clonality and Dispersal Mechanisms in Wetland Island Habitats.

In plants, long-distance dispersal is both attenuated and directed by specific movement vectors, including animals, wind, and/or water. Hence, movement vectors partly shape metapopulation genetic patterns that are, however, also influenced by other life-history traits such as clonal growth. We studied the relationship between area, isolation, plant-species richness, reproduction, and dispersal mechanisms with genetic diversity and divergence in 4 widespread wetland plant-species in a total of 20 island-like kettle-hole habitats surrounded by an intensive agricultural landscape.

A Rationale for Hypoxic and Chemical Conditioning in Huntington's Disease.

Neurodegenerative diseases are characterized by adverse cellular environments and pathological alterations causing neurodegeneration in distinct brain regions. This development is triggered or facilitated by conditions such as hypoxia, ischemia or inflammation and is associated with disruptions of fundamental cellular functions, including metabolic and ion homeostasis. Targeting intracellular downstream consequences to specifically reverse these pathological changes proved difficult to translate to clinical settings.

Biallelic mutations in the death domain of PIDD1 impair caspase-2 activation and are associated with intellectual disability.

PIDD1 encodes p53-Induced Death Domain protein 1, which acts as a sensor surveilling centrosome numbers and p53 activity in mammalian cells. Early results also suggest a role in DNA damage response where PIDD1 may act as a cell-fate switch, through interaction with RIP1 and NEMO/IKKg, activating NF-κB signaling for survival, or as an apoptosis-inducing protein by activating caspase-2. Biallelic truncating mutations in CRADD-the protein bridging PIDD1 and caspase-2-have been reported in intellectual disability (ID), and in a form of lissencephaly.

Mitochondrial Respiration Changes in R6/2 Huntington's Disease Model Mice during Aging in a Brain Region Specific Manner.

Mitochondrial dysfunction is crucially involved in aging and neurodegenerative diseases, such as Huntington's Disease (HD). How mitochondria become compromised in HD is poorly understood but instrumental for the development of treatments to prevent or reverse resulting deficits. In this paper, we investigate whether oxidative phosphorylation (OXPHOS) differs across brain regions in juvenile as compared to adult mice and whether such developmental changes might be compromised in the R6/2 mouse model of HD.

Neuroinflammatory alterations in trait anxiety: modulatory effects of minocycline.

High trait anxiety is a substantial risk factor for developing anxiety disorders and depression. While neuroinflammation has been identified to contribute to stress-induced anxiety, little is known about potential dysregulation in the neuroinflammatory system of genetically determined pathological anxiety or high trait anxiety individuals. We report microglial alterations in various brain regions in a mouse model of high trait anxiety (HAB).

Impaired chloride homeostasis in epilepsy: Molecular basis, impact on treatment, and current treatment approaches.

Epilepsies represent one of the most common neurological diseases worldwide. They are characterized by recurrent spontaneous seizures with severe impact on a patient's life. An imbalance in excitatory and inhibitory signalling is considered the main underlying pathophysiological mechanism.

Dynorphin-based "release on demand" gene therapy for drug-resistant temporal lobe epilepsy.

Focal epilepsy represents one of the most common chronic CNS diseases. The high incidence of drug resistance, devastating comorbidities, and insufficient responsiveness to surgery pose unmet medical challenges. In the quest of novel, disease-modifying treatment strategies of neuropeptides represent promising candidates.

Functional characterization of novel bumetanide derivatives for epilepsy treatment.

Temporal lobe epilepsy (TLE) is the most common type of focal epilepsies, affecting approximately 35 million people worldwide. Despite the introduction of numerous novel antiepileptic drugs during the last decades, the proportion of patients with therapy-resistant TLE is still high. As an impaired cellular chloride homeostasis appears involved in disease pathophysiology, bumetanide, an antagonist to Na-K-Cl cotransporters, gained interest as potential therapeutic option.