Analyzing the Impact of the Highest Expressed Epstein-Barr Virus-Encoded microRNAs on the Host Cell Transcriptome.

The Epstein-Barr virus (EBV) has a very high prevalence (>90% in adults), establishes a lifelong latency after primary infection, and exerts an oncogenic potential. This dsDNA virus encodes for various molecules, including microRNAs (miRs), which can be detected in the latent and lytic phases with different expression levels and affect, among others, immune evasion and malignant transformation. In this study, the different EBV miRs are quantified in EBV-positive lymphomas, and the impact on the host cell transcriptome of the most abundant EBV miRs will be analyzed using comparative RNA sequencing analyses.

Evolutionary adaptation of an HP1-protein chromodomain integrates chromatin and DNA sequence signals.

Members of the diverse heterochromatin protein 1 (HP1) family play crucial roles in heterochromatin formation and maintenance. Despite the similar affinities of their chromodomains for di- and tri-methylated histone H3 lysine 9 (H3K9me2/3), different HP1 proteins exhibit distinct chromatin-binding patterns, likely due to interactions with various specificity factors. Previously, we showed that the chromatin-binding pattern of the HP1 protein Rhino, a crucial factor of the PIWI-interacting RNA (piRNA) pathway, is largely defined by a DNA sequence-specific CH zinc finger protein named Kipferl (Baumgartner et al.

Mechanistic Insights into the Function of 14-3-3 Proteins as Negative Regulators of Brassinosteroid Signaling in Arabidopsis.

Brassinosteroids (BRs) are vital plant steroid hormones sensed at the cell surface by a membrane signaling complex comprising the receptor kinase BRI1 and a SERK family co-receptor kinase. Activation of this complex lead to dissociation of the inhibitor protein BKI1 from the receptor and to differential phosphorylation of BZR1/BES1 transcription factors by the glycogen synthase kinase 3 protein BIN2. Many phosphoproteins of the BR signaling pathway, including BRI1, SERKs, BKI1 and BZR1/BES1 can associate with 14-3-3 proteins.

Elucidation of GPR55-Associated Signaling behind THC and LPI Reducing Effects on Ki67-Immunoreactive Nuclei in Patient-Derived Glioblastoma Cells.

GPR55 is involved in many physiological and pathological processes. In cancer, GPR55 has been described to show accelerating and decelerating effects in tumor progression resulting from distinct intracellular signaling pathways. GPR55 becomes activated by LPI and various plant-derived, endogenous, and synthetic cannabinoids.

A toolbox to analyze collective cell migration, proliferation and cellular organization simultaneously.

Background: Analyses of collective cell migration and orientation phenomena are needed to assess the behavior of multicellular clusters. While some tools to the authors' knowledge none is capable to analyze collective migration, cellular orientation and proliferation in phase contrast images simultaneously.

Methods: We provide a tool based to analyze phase contrast images of dense cell layers.

[Advanced practice nurses in geriatric traumatology : A scoping review].

Background: Older and very old persons have an increased risk of traumatic injuries as well as comorbidities and multimorbidities. The standardized workflow in hospitals can increase the occurrence of typical geriatric complications, such as challenging behavior and delirium, which can result in highly complex care situations. The application of advanced practice nurses (APN) is an international response to such challenges.

MACC1-induced migration in tumors: Current state and perspective.

Malignant tumors are still a global, heavy health burden. Many tumor types cannot be treated curatively, underlining the need for new treatment targets. In recent years, metastasis associated in colon cancer 1 (MACC1) was identified as a promising biomarker and drug target, as it is promoting tumor migration, initiation, proliferation, and others in a multitude of solid cancers.

BRASSINOSTEROID INSENSITIVE1 internalization can occur independent of ligand binding.

The brassinosteroid (BR) hormone and its plasma membrane (PM) receptor BR INSENSITIVE1 (BRI1) are one of the best-studied receptor-ligand pairs for understanding the interplay between receptor endocytosis and signaling in plants. BR signaling is mainly determined by the PM pool of BRI1, whereas BRI1 endocytosis ensures signal attenuation. As BRs are ubiquitously distributed in the plant, the tools available to study the BRI1 function without interference from endogenous BRs are limited.

Jamming Transitions in Astrocytes and Glioblastoma Are Induced by Cell Density and Tension.

Collective behavior of cells emerges from coordination of cell-cell-interactions and is important to wound healing, embryonic and tumor development. Depending on cell density and cell-cell interactions, a transition from a migratory, fluid-like unjammed state to a more static and solid-like jammed state or vice versa can occur. Here, we analyze collective migration dynamics of astrocytes and glioblastoma cells using live cell imaging.

MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics.

Metastasis-associated in colon cancer 1 (MACC1) is a marker for metastasis, tumor cell migration, and increased proliferation in colorectal cancer (CRC). Tumors with high MACC1 expression show a worse prognosis and higher invasion into neighboring structures. Yet, many facets of the pro-migratory effects are not fully understood.

Microglia-Dependent and Independent Brain Cytoprotective Effects of Mycophenolate Mofetil During Neuronal Damage.

Acute lesions of the central nervous system often lead to permanent limiting deficits. In addition to the initial primary damage, accompanying neuroinflammation is responsible for progression of damage. Mycophenolate mofetil (MMF) as a selective inhibitor of inosine 5-monophosphate dehydrogenase (IMPDH) was shown to modulate the inflammatory response and promote neuronal survival when applied in specific time windows after neuronal injury.

Nimodipine Exerts Time-Dependent Neuroprotective Effect after Excitotoxical Damage in Organotypic Slice Cultures.

During injuries in the central nervous system, intrinsic protective processes become activated. However, cellular reactions, especially those of glia cells, are frequently unsatisfactory, and further exogenous protective mechanisms are necessary. Nimodipine, a lipophilic L-type calcium channel blocking agent is clinically used in the treatment of aneurysmal subarachnoid haemorrhage with neuroprotective effects in different models.

Interaction of Glia Cells with Glioblastoma and Melanoma Cells under the Influence of Phytocannabinoids.

Brain tumor heterogeneity and progression are subject to complex interactions between tumor cells and their microenvironment. Glioblastoma and brain metastasis can contain 30-40% of tumor-associated macrophages, microglia, and astrocytes, affecting migration, proliferation, and apoptosis. Here, we analyzed interactions between glial cells and LN229 glioblastoma or A375 melanoma cells in the context of motility and cell-cell interactions in a 3D model.

Assessment of Neuronal Damage in Brain Slice Cultures Using Machine Learning Based on Spatial Features.

Neuronal damage presents a major health issue necessitating extensive research to identify mechanisms of neuronal cell death and potential therapeutic targets. Commonly used models are slice cultures out of different brain regions extracted from mice or rats, excitotoxically, ischemic, or traumatically lesioned and subsequently treated with potential neuroprotective agents. Thereby cell death is regularly assessed by measuring the propidium iodide (PI) uptake or counting of PI-positive nuclei.

THC Reduces Ki67-Immunoreactive Cells Derived from Human Primary Glioblastoma in a GPR55-Dependent Manner.

Glioblastoma (GBM) is the most frequent malignant tumor of the central nervous system in humans with a median survival time of less than 15 months. ∆-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are the best-characterized components of plants with modulating effects on cannabinoid receptors 1 and 2 (CB and CB) and on orphan receptors such as GPR18 or GPR55. Previous studies have demonstrated anti-tumorigenic effects of THC and CBD in several tumor entities including GBM, mostly mediated via CB or CB.

Preparation and Culture of Organotypic Hippocampal Slices for the Analysis of Brain Metastasis and Primary Brain Tumor Growth.

Brain metastasis is a major challenge for therapy and defines the end stage of tumor progression with a very limited patients' prognosis. Experimental setups that faithfully mimic these processes are necessary to understand the mechanism of brain metastasis and to develop new improved therapeutic strategies. Here, we describe an in vitro model, which closely resembles the in vivo situation.

Signatures of antagonistic pleiotropy in a bacterial flagellin epitope.

Immune systems respond to "non-self" molecules termed microbe-associated molecular patterns (MAMPs). Microbial genes encoding MAMPs have adaptive functions and are thus evolutionarily conserved. In the presence of a host, these genes are maladaptive and drive antagonistic pleiotropy (AP) because they promote microbe elimination by activating immune responses.

Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex.

Nuclear Argonaute proteins, guided by their bound small RNAs to nascent target transcripts, mediate cotranscriptional silencing of transposons and repetitive genomic loci through heterochromatin formation. The molecular mechanisms involved in this process are incompletely understood. Here, we show that the SFiNX complex, a silencing mediator downstream from nuclear Piwi-piRNA complexes in , facilitates cotranscriptional silencing as a homodimer.

Structure of the human core transcription-export complex reveals a hub for multivalent interactions.

The export of mRNA from nucleus to cytoplasm requires the conserved and essential transcription and export (TREX) complex (THO-UAP56/DDX39B-ALYREF). TREX selectively binds mRNA maturation marks and licenses mRNA for nuclear export by loading the export factor NXF1-NXT1. How TREX integrates these marks and achieves high selectivity for mature mRNA is poorly understood.

Constitutive Activation of Leucine-Rich Repeat Receptor Kinase Signaling Pathways by BAK1-INTERACTING RECEPTOR-LIKE KINASE3 Chimera.

Receptor kinases with extracellular leucine-rich repeat domains (LRR-RKs) form the largest group of membrane signaling proteins in plants. LRR-RKs can sense small molecule, peptide, or protein ligands and may be activated by ligand-induced interaction with a shape complementary SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) coreceptor kinase. We have previously shown that SERKs can also form constitutive, ligand-independent complexes with the LRR ectodomains of BAK1-INTERACTING RECEPTOR-LIKE KINASE3 (BIR3) receptor pseudokinases, negative regulators of LRR-RK signaling.

MACC1 driven alterations in cellular biomechanics facilitate cell motility in glioblastoma.

Background: Metastasis-associated in colon cancer 1 (MACC1) is an established marker for metastasis and tumor cell migration in a multitude of tumor entities, including glioblastoma (GBM). Nevertheless, the mechanism underlying the increased migratory capacity in GBM is not comprehensively explored.

Methods: We performed live cell and atomic force microscopy measurements to assess cell migration and mechanical properties of MACC1 overexpressing GBM cells.

Molecular mechanism for the recognition of sequence-divergent CIF peptides by the plant receptor kinases GSO1/SGN3 and GSO2.

Plants use leucine-rich repeat receptor kinases (LRR-RKs) to sense sequence diverse peptide hormones at the cell surface. A 3.0-Å crystal structure of the LRR-RK GSO1/SGN3 regulating Casparian strip formation in the endodermis reveals a large spiral-shaped ectodomain.

Opposite Effects of Neuroprotective Cannabinoids, Palmitoylethanolamide, and 2-Arachidonoylglycerol on Function and Morphology of Microglia.

Various studies performed in cultured cells and in models of neuronal damage showed that cannabinoids exert a neuroprotective effect. The increase in cannabinoids and cannabinoid like substances after stroke has been postulated to limit the content of neuronal injury. As well-accepted, inflammation, and neuronal damage are coupled processes and microglial cells as the main intrinsic immunological effector within the brain play a central role in their regulation.