The p300/CBP Inhibitor A485 Normalizes Psoriatic Fibroblast Gene Expression In Vitro and Reduces Psoriasis-Like Skin Inflammation In Vivo.

Psoriasis is a chronic inflammatory skin disease that often recurs at the same locations, indicating potential epigenetic changes in lesional skin cells. In this study, we discovered that fibroblasts isolated from psoriatic skin lesions retain an abnormal phenotype even after several passages in culture. Transcriptomic profiling revealed the upregulation of several genes, including the extra domain A splice variant of fibronectin and ITGA4 in psoriatic fibroblasts.

Virus Diversity, Abundance, and Evolution in Three Different Bat Colonies in Switzerland.

Bats are increasingly recognized as reservoirs for many different viruses that threaten public health, such as Hendravirus, Ebolavirus, Nipahvirus, and SARS- and MERS-coronavirus. To assess spillover risk, viromes of bats from different parts of the world have been investigated in the past. As opposed to most of these prior studies, which determined the bat virome at a single time point, the current work was performed to monitor changes over time.

Mechanisms of extracellular vesicle-mediated immune evasion in melanoma.

Melanoma-derived extracellular vesicles (EVs) have been found to promote tumor growth and progression, and to predict patient responsiveness to immunotherapy. Consequently, EVs have been implicated in tumor immune evasion, and multiple studies reported immune-regulatory activities of melanoma EVs and . This review highlights mechanistic insights in EV-mediated regulation of various immune cell types, including effects on inflammatory, apoptotic, stress-sensing and immune checkpoint pathways as well as antigen-dependent responses.

Factors associated with an unsuccessful fast-track course following minimally invasive surgical mitral valve repair.

Objectives: Analyses of fast-track (FT) processes demonstrated that low-risk cardiac surgical patients require minimal intensive care, with a low incidence of mortality or morbidity. We investigated perioperative factors and their association with fast-track failure (FTF) in a retrospective cohort study of patients undergoing minimally invasive mitral valve surgery.

Methods: Patients undergoing minimally invasive surgical mitral valve repair for Carpentier type I or type II mitral regurgitation between 2014 and 2020 were included in the study.

Benchmark problems for transcranial ultrasound simulation: Intercomparison of compressional wave models.

Computational models of acoustic wave propagation are frequently used in transcranial ultrasound therapy, for example, to calculate the intracranial pressure field or to calculate phase delays to correct for skull distortions. To allow intercomparison between the different modeling tools and techniques used by the community, an international working group was convened to formulate a set of numerical benchmarks. Here, these benchmarks are presented, along with intercomparison results.

Bipartite phosphoinositide-dependent modulation of auxin signaling during xylem differentiation in Arabidopsis thaliana roots.

Efficient root-to-shoot delivery of water and nutrients in plants relies on the correct differentiation of xylem cells into hollow elements. While auxin is integral to the formation of xylem cells, it remains poorly characterized how each subcellular pool of this hormone regulates this process. Combining genetic and cell biological approaches, we investigated the bipartite activity of nucleoplasmic vs plasma membrane-associated phosphatidylinositol 4-phosphate kinases PIP5K1 and its homolog PIP5K2 in Arabidopsis thaliana roots and uncovered a novel mechanism by which phosphoinositides integrate distinct aspects of the auxin signaling cascade and, in turn, regulate the onset of xylem differentiation.

Chemogenetic activation of noradrenergic A5 neurons increases blood pressure and visceral sympathetic activity in adult rats.

In mammals, the pontine noradrenergic system influences nearly every aspect of central nervous system function. A subpopulation of pontine noradrenergic neurons, called A5, are thought to be important in the cardiovascular response to physical stressors, yet their function is poorly defined. We hypothesized that activation of A5 neurons drives a sympathetically mediated increase in blood pressure (BP).

Transcatheter Aortic Valve Replacement in a Patient With Criss-Cross Heart.

This paper presents the first transcatheter management of severe aortic regurgitation in a 77-year-old woman with a criss-cross heart-an extremely rare and complex congenital heart disease. The procedure achieved an elimination of aortic regurgitation and resulted in a remarkable improvement of the patient's physical condition. ().

Unique expression of the atypical mitochondrial subunit NDUFA4L2 in cerebral pericytes fine tunes HIF activity in response to hypoxia.

A central response to insufficient cerebral oxygen delivery is a profound reprograming of metabolism, which is mainly regulated by the Hypoxia Inducible Factor (HIF). Among other responses, HIF induces the expression of the atypical mitochondrial subunit NDUFA4L2. Surprisingly, NDUFA4L2 is constitutively expressed in the brain in non-hypoxic conditions.

Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030.

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives.

Immunomodulatory Responses of Subcapsular Sinus Floor Lymphatic Endothelial Cells in Tumor-Draining Lymph Nodes.

Tumor-draining lymph nodes (LNs), composed of lymphocytes, antigen-presenting cells, and stromal cells, are highly relevant for tumor immunity and the efficacy of immunotherapies. Lymphatic endothelial cells (LECs) represent an important stromal cell type within LNs, and several distinct subsets of LECs that interact with various immune cells and regulate immune responses have been identified. In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize LECs from LNs draining B16F10 melanomas compared to non-tumor-draining LNs.

Periareolar endoscopic minimally invasive cardiac surgery: postoperative scar assessment analysis.

Objectives: The standard approach for minimally invasive cardiac surgery (MICS) for repair of the atrioventricular valves is a right lateral minithoracotomy. In this study, we report our experience with a periareolar endoscopic approach, which aims at an optimal cosmetic outcome while preserving optimal clinical outcomes.

Methods: All patients underwent periareolar endoscopic MICS using high-definition three-dimensional endoscopic visualization without additional rib-spreading.

Competition for pollinators destabilizes plant coexistence.

Mounting concern over the global decline of pollinators has fuelled calls for investigating their role in maintaining plant diversity. Theory predicts that competition for pollinators can stabilize interactions between plant species by providing opportunities for niche differentiation, while at the same time can drive competitive imbalances that favour exclusion. Here we empirically tested these contrasting effects by manipulating competition for pollinators in a way that predicts its long-term implications for plant coexistence.

Poxviruses package viral redox proteins in lateral bodies and modulate the host oxidative response.

All poxviruses contain a set of proteinaceous structures termed lateral bodies (LB) that deliver viral effector proteins into the host cytosol during virus entry. To date, the spatial proteotype of LBs remains unknown. Using the prototypic poxvirus, vaccinia virus (VACV), we employed a quantitative comparative mass spectrometry strategy to determine the poxvirus LB proteome.

The arch remodelling stent for DeBakey I acute aortic dissection: experience with 100 implantations.

Objectives: A novel hybrid non-covered stent was developed to treat malperfusion and prevent aneurysm formation following hemiarch procedure for DeBakey I acute aortic dissection (AAD). The present analysis investigates the performance of the device in 100 consecutive implantations.

Methods: Between 2018 and 2021, 100 patients underwent surgical repair of DeBakey I AAD with implantation of a non-covered stent in the arch and descending aorta.

Mediators of Capillary-to-Venule Conversion in the Chronic Inflammatory Skin Disease Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal hyperplasia and hyperkeratosis, immune cell infiltration and vascular remodeling. Despite the emerging recognition of vascular normalization as a potential strategy for managing psoriasis, an in-depth delineation of the remodeled dermal vasculature has been missing. In this study, we exploited 5' single-cell RNA sequencing to investigate the transcriptomic alterations in different subpopulations of blood vascular and lymphatic endothelial cells directly isolated from psoriatic and healthy human skin.

Lymphatic vessels in cancer.

The lymphatic system, composed of initial and collecting lymphatic vessels as well as lymph nodes that are present in almost every tissue of the human body, acts as an essential transport system for fluids, biomolecules, and cells between peripheral tissues and the central circulation. Consequently, it is required for normal body physiology but is also involved in the pathogenesis of various diseases, most notably cancer. The important role of tumor-associated lymphatic vessels and lymphangiogenesis in the formation of lymph node metastasis has been elucidated during the last two decades, whereas the underlying mechanisms and the relation between lymphatic and peripheral organ dissemination of cancer cells are incompletely understood.

Meiosis in allopolyploid Arabidopsis suecica.

Polyploidy is a major force shaping eukaryote evolution but poses challenges for meiotic chromosome segregation. As a result, first-generation polyploids often suffer from more meiotic errors and lower fertility than established wild polyploid populations. How established polyploids adapt their meiotic behaviour to ensure genome stability and accurate chromosome segregation remains an active research question.

Glacier melt-down changes habitat characteristics and unique microbial community composition and physiology in alpine lake sediments.

Glacial melt-down alters hydrological and physico-chemical conditions in downstream aquatic habitats. In this study, we tested if sediment-associated microbial communities respond to the decrease of glaciers and associated meltwater flows in high-alpine lakes. We analyzed 16 lakes in forefield catchments of three glaciers in the Eastern Swiss Alps on physico-chemical and biological parameters.

Small Animals, Big Impact? Early Farmers and Pre- and Post-Harvest Pests from the Middle Neolithic Site of Les Bagnoles in the South-East of France (L'Isle-sur-la-Sorgue, Vaucluse, Provence-Alpes-Côte-d'Azur).

Pests appear to have accompanied humans and their crops since the beginning of farming. Nevertheless, their study is only rarely integrated into research on farming in prehistory. An assemblage of invertebrates and small mammals was recovered from the waterlogged layers of three wells at the Middle Neolithic site (4250-3700 cal B.

Protein Tyrosine Phosphatase SHP2 Controls Interleukin-8 Expression in Breast Cancer Cells.

Treatment of metastasis remains a clinical challenge and the majority of breast cancer-related deaths are the result of drug-resistant metastases. The protein tyrosine phosphatase SHP2 encoded by the proto-oncogene PTPN11 promotes breast cancer progression. Inhibition of SHP2 has been shown to decrease metastases formation in various breast cancer models, but specific downstream effectors of SHP2 remain poorly characterized.

The metastatic spread of breast cancer accelerates during sleep.

The metastatic spread of cancer is achieved by the haematogenous dissemination of circulating tumour cells (CTCs). Generally, however, the temporal dynamics that dictate the generation of metastasis-competent CTCs are largely uncharacterized, and it is often assumed that CTCs are constantly shed from growing tumours or are shed as a consequence of mechanical insults. Here we observe a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep.

A genetic framework for proximal secondary vein branching in the Arabidopsis thaliana embryo.

Over time, plants have evolved flexible self-organizing patterning mechanisms to adapt tissue functionality for continuous organ growth. An example of this process is the multicellular organization of cells into a vascular network in foliar organs. An important, yet poorly understood component of this process is secondary vein branching, a mechanism employed to extend vascular tissues throughout the cotyledon surface.

Sodium-calcium exchanger-3 regulates pain "wind-up": From human psychophysics to spinal mechanisms.

Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is "wind-up," in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up in healthy human volunteers and found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3).