Bridging the gap: Leveraging telemedicine and IT infrastructure to connect outpatient oncology practices with specialized expert teams in the management of rare tumors.

Objectives: The treatment of rare tumors often necessitates the involvement of highly specialized teams, typically based in larger medical centers or university hospitals, which are often lacking in rural areas. The German TARGET (the Trans-sectoral Personalized Care Concept for Patients with Rare Cancers) project aims to improve the network between outpatient oncology practices and more centralized expert teams via telemedicine.

Methods: The primary work involved conceptualizing the implementation of project requirements based on feedback from various TARGET project teams, and ultimately, the method of implementation using the software CentraXX.

Profiling of ERBB receptors and downstream pathways reveals selectivity and hidden properties of ERBB4 antagonists.

ERBB receptor tyrosine kinases are involved in development and diseases like cancer, cardiovascular, neurodevelopmental, and mental disorders. Although existing drugs target ERBB receptors, the next generation of drugs requires enhanced selectivity and understanding of physiological pathway responses to improve efficiency and reduce side effects. To address this, we developed a multilevel barcoded reporter profiling assay, termed 'ERBBprofiler', in living cells to monitor the activity of all ERBB targets and key physiological pathways simultaneously.

Deconstructing depression by machine learning: the POKAL-PSY study.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care.

A prospective longitudinal cohort study on risk factors for COVID-19 vaccination failure (RisCoin): methods, procedures and characterization of the cohort.

The primary objective of the RisCoin study was to investigate the interplay of genetic, metabolic, and lifestyle factors as well as stress levels on influencing the humoral immune response after at least two COVID-19 vaccinations, primarily with mRNAs, and the risk of SARS-CoV-2 breakthrough infections during follow-up. Here, we describe the study design, procedures, and study population. RisCoin is a prospective, monocentric, longitudinal, observational cohort study.

The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research.

Introduction: Treatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking.

Biobanking in everyday clinical practice in psychiatry-The Munich Mental Health Biobank.

Translational research on complex, multifactorial mental health disorders, such as bipolar disorder, major depressive disorder, schizophrenia, and substance use disorders requires databases with large-scale, harmonized, and integrated real-world and research data. The Munich Mental Health Biobank (MMHB) is a mental health-specific biobank that was established in 2019 to collect, store, connect, and supply such high-quality phenotypic data and biosamples from patients and study participants, including healthy controls, recruited at the Department of Psychiatry and Psychotherapy (DPP) and the Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany. Participants are asked to complete a questionnaire that assesses sociodemographic and cross-diagnostic clinical information, provide blood samples, and grant access to their existing medical records.

Neuronal cholesterol synthesis is essential for repair of chronically demyelinated lesions in mice.

Astrocyte-derived cholesterol supports brain cells under physiological conditions. However, in demyelinating lesions, astrocytes downregulate cholesterol synthesis, and the cholesterol that is essential for remyelination has to originate from other cellular sources. Here, we show that repair following acute versus chronic demyelination involves distinct processes.

Correction to: Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays.

The article Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays, written by Jan P. Wintgens, Sven P. Wichert, Luksa Popovic, Moritz J.

Monitoring activities of receptor tyrosine kinases using a universal adapter in genetically encoded split TEV assays.

Receptor tyrosine kinases (RTKs) play key roles in various aspects of cell biology, including cell-to-cell communication, proliferation and differentiation, survival, and tissue homeostasis, and have been implicated in various diseases including cancer and neurodevelopmental disorders. Ligand-activated RTKs recruit adapter proteins through a phosphotyrosine (p-Tyr) motif that is present on the RTK and a p-Tyr-binding domain, like the Src homology 2 (SH2) domain found in adapter proteins. Notably, numerous combinations of RTK/adapter combinations exist, making it challenging to compare receptor activities in standardised assays.

Pathway sensor-based functional genomics screening identifies modulators of neuronal activity.

Neuronal signal transduction shapes brain function and malfunction may cause mental disorders. Despite the existence of functional genomics screens for proliferation and toxicity, neuronal signalling has been difficult to address so far. To overcome this limitation, we developed a pooled screening assay which combines barcoded activity reporters with pooled genetic perturbation in a dual-expression adeno-associated virus (AAV) library.

Multiplexed profiling of GPCR activities by combining split TEV assays and EXT-based barcoded readouts.

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors and are implicated in the physiological regulation of many biological processes. The high diversity of GPCRs and their physiological functions make them primary targets for therapeutic drugs. For the generation of novel compounds, however, selectivity towards a given target is a critical issue in drug development as structural similarities between members of GPCR subfamilies exist.

Spironolactone is an antagonist of NRG1-ERBB4 signaling and schizophrenia-relevant endophenotypes in mice.

Enhanced NRG1-ERBB4 signaling is a risk pathway in schizophrenia, and corresponding mouse models display several endophenotypes of the disease. Nonetheless, pathway-directed treatment strategies with clinically applicable compounds have not been identified. Here, we applied a cell-based assay using the split TEV technology to screen a library of clinically applicable compounds to identify modulators of NRG1-ERBB4 signaling for repurposing.

A neuronal PI(3,4,5)P-dependent program of oligodendrocyte precursor recruitment and myelination.

The molecular trigger of CNS myelination is unknown. By targeting Pten in cerebellar granule cells and activating the AKT1-mTOR pathway, we increased the caliber of normally unmyelinated axons and the expression of numerous genes encoding regulatory proteins. This led to the expansion of genetically wild-type oligodendrocyte progenitor cells, oligodendrocyte differentiation and de novo myelination of parallel fibers.

Molecular Signatures of Psychosocial Stress and Cognition Are Modulated by Chronic Lithium Treatment.

Chronic psychosocial stress is an important environmental risk factor of psychiatric diseases such as schizophrenia. Social defeat in rodents has been shown to be associated with maladaptive cellular and behavioral consequences including cognitive impairments. Although gene expression changes upon psychosocial stress have been described, a comprehensive transcriptome profiling study at the global level in precisely defined hippocampal subregions which are associated with learning has been lacking.

Neurodegeneration in Autoimmune Optic Neuritis Is Associated with Altered APP Cleavage in Neurons and Up-Regulation of p53.

Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the central nervous system (CNS). Histopathological and radiological analysis revealed that neurodegeneration occurs early in the disease course. However, the pathological mechanisms involved in neurodegeneration are poorly understood.

Mice lacking the circadian modulators SHARP1 and SHARP2 display altered sleep and mixed state endophenotypes of psychiatric disorders.

Increasing evidence suggests that clock genes may be implicated in a spectrum of psychiatric diseases, including sleep and mood related disorders as well as schizophrenia. The bHLH transcription factors SHARP1/DEC2/BHLHE41 and SHARP2/DEC1/BHLHE40 are modulators of the circadian system and SHARP1/DEC2/BHLHE40 has been shown to regulate homeostatic sleep drive in humans. In this study, we characterized Sharp1 and Sharp2 double mutant mice (S1/2-/-) using online EEG recordings in living animals, behavioral assays and global gene expression profiling.

Progesterone antagonist therapy in a Pelizaeus-Merzbacher mouse model.

Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disease, characterized by ataxia, intellectual disability, epilepsy, and premature death. In the majority of cases, PMD is caused by duplication of PLP1 that is expressed in myelinating oligodendrocytes. Despite detailed knowledge of PLP1, there is presently no curative therapy for PMD.

Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting.

For decades, neuroscientists have used enriched preparations of synaptic particles called synaptosomes to study synapse function. However, the interpretation of corresponding data is problematic as synaptosome preparations contain multiple types of synapses and non-synaptic neuronal and glial contaminants. We established a novel Fluorescence Activated Synaptosome Sorting (FASS) method that substantially improves conventional synaptosome enrichment protocols and enables high-resolution biochemical analyses of specific synapse subpopulations.

The multispecific thyroid hormone transporter OATP1C1 mediates cell-specific sulforhodamine 101-labeling of hippocampal astrocytes.

Sulforhodamine 101 (SR101) is widely used for astrocyte identification, though the labeling mechanism remains unknown and the efficacy of labeling in different brain regions is heterogeneous. By combining region-specific isolation of astrocytes followed by transcriptome analysis, two-photon excitation microscopy, and mouse genetics, we identified the thyroid hormone transporter OATP1C1 as the SR101-uptake transporter in hippocampus and cortex.

Neuronal basic helix-loop-helix proteins Neurod2/6 regulate cortical commissure formation before midline interactions.

Establishment of long-range fiber tracts by neocortical projection neurons is fundamental for higher brain functions. The molecular control of axon tract formation, however, is still poorly understood. Here, we have identified basic helix-loop-helix (bHLH) transcription factors Neurod2 and Neurod6 as key regulators of fasciculation and targeted axogenesis in the mouse neocortex.

Structural synaptic elements are differentially regulated in superior temporal cortex of schizophrenia patients.

Inaccurate wiring and synaptic pathology appear to be major hallmarks of schizophrenia. A variety of gene products involved in synaptic neurotransmission and receptor signaling are differentially expressed in brains of schizophrenia patients. However, synaptic pathology may also develop by improper expression of intra- and extra-cellular structural elements weakening synaptic stability.

Systematic approaches to central nervous system myelin.

Rapid signal propagation along vertebrate axons is facilitated by their insulation with myelin, a plasma membrane specialization of glial cells. The recent application of 'omics' approaches to the myelinating cells of the central nervous system, oligodendrocytes, revealed their mRNA signatures, enhanced our understanding of how myelination is regulated, and established that the protein composition of myelin is much more complex than previously thought. This review provides a meta-analysis of the > 1,200 proteins thus far identified by mass spectrometry in biochemically purified central nervous system myelin.

Regulation of the EGF transcriptional response by endocytic sorting.

Ligand binding to the epidermal growth factor receptor (EGFR) on the cell surface activates the extracellular signal-regulated kinase (ERK) cascade. Activated, ligand-bound receptors are internalized, and this process may contribute to termination of signaling or enable signaling from intracellular sites. ESCRT (endosomal sorting complex required for transport) complexes may contribute to termination of signaling by sorting receptors into intraluminal vesicles of multivesicular endosomes from which the receptors continue into lysosomes for degradation.

A rat model of Charcot-Marie-Tooth disease 1A recapitulates disease variability and supplies biomarkers of axonal loss in patients.

Charcot-Marie-Tooth disease is the most common inherited neuropathy and a duplication of the peripheral myelin protein 22 gene causes the most frequent subform Charcot-Marie-Tooth 1A. Patients develop a slowly progressive dysmyelinating and demyelinating peripheral neuropathy and distally pronounced muscle atrophy. The amount of axonal loss determines disease severity.