Specific Inhibitor of Placental Alkaline Phosphatase Isolated from a DNA-Encoded Chemical Library Targets Tumor of the Female Reproductive Tract.

Placental alkaline phosphatase (PLAP) is an abundant surface antigen in the malignancies of the female reproductive tract. Nevertheless, the discovery of PLAP-specific small organic ligands for targeting applications has been hindered by ligand cross-reactivity with the ubiquitous tissue non-specific alkaline phosphatase (TNAP). In this study, we used DNA-encoded chemical libraries to discover a potent (IC = 32 nM) and selective PLAP inhibitor, with no detectable inhibition of TNAP activity.

Mechanisms and Clinical Significance of Tumor Lymphatic Invasion.

Tumor-associated lymphatic vessels play an important role in tumor progression, mediating lymphatic dissemination of malignant cells to tumor-draining lymph nodes and regulating tumor immunity. An early, necessary step in the lymphatic metastasis cascade is the invasion of lymphatic vessels by tumor cell clusters or single tumor cells. In this review, we discuss our current understanding of the underlying cellular and molecular mechanisms, which include tumor-specific as well as normal, developmental and immunological processes "hijacked" by tumor cells to gain access to the lymphatic system.

Development and Clinical Validation of the LymphMonitor Technology to Quantitatively Assess Lymphatic Function.

Current diagnostic methods for evaluating the functionality of the lymphatic vascular system usually do not provide quantitative data and suffer from many limitations including high costs, complexity, and the need to perform them in hospital settings. In this work, we present a quantitative, simple outpatient technology named LymphMonitor to quantitatively assess lymphatic function. This method is based on the painless injection of the lymphatic-specific near-infrared fluorescent tracer indocyanine green complexed with human serum albumin, using MicronJet600 microneedles, and monitoring the disappearance of the fluorescence signal at the injection site over time using a portable detection device named LymphMeter.

Validation of a novel risk score to predict mortality after surgery for acute type A dissection.

Objectives: The aim of this study was to externally validate a lab-based risk score (lactate, creatinine, aspartate aminotransferase, alanine aminotransferase or bilirubin) by Ghoreishi et al. to predict perioperative mortality in patients undergoing surgical repair for acute type A aortic dissection.

Methods: The risk score to predict operative mortality was applied to a large and homogenous validation cohort that consisted of 632 patients undergoing surgery for acute type A aortic dissection in 2 centres.

Acoustofluidic medium exchange for preparation of electrocompetent bacteria using channel wall trapping.

Comprehensive integration of process steps into a miniaturised version of synthetic biology workflows remains a crucial task in automating the design of biosystems. However, each of these process steps has specific demands with respect to the environmental conditions, including in particular the composition of the surrounding fluid, which makes integration cumbersome. As a case in point, transformation, reprogramming of bacteria by delivering exogenous genetic material (such as DNA) into the cytoplasm, is a key process in molecular engineering and modern biotechnology in general.

Activities, Housing Situation and Other Factors Influencing Psychological Strain Experienced During the First COVID-19 Lockdown in Switzerland.

The Coronavirus disease 2019 (COVID-19) crisis and the corresponding first nationwide lockdown from mid-March to 10 May 2020 engendered considerable psychological strain among people in Switzerland. This study analyzes determinants of changes in subjective levels of psychological strain experienced during the lockdown. An online survey conducted as part of a larger mixed methods study examined the material and emotional aspects of individual reactions to the lockdown from a socio-ecological perspective.

Fibroblast growth factor receptor 3 in hepatocytes protects from toxin-induced liver injury and fibrosis.

The liver's remarkable regenerative capacity is orchestrated by several growth factors and cytokines. Fibroblast growth factor receptor 3 (Fgfr3) is frequently overexpressed in hepatocellular carcinoma and promotes cancer aggressiveness, whereas its role in liver homeostasis, repair and regeneration is unknown. We show here that Fgfr3 is expressed by hepatocytes in the healthy liver.

Neurovascular dysfunction and neuroinflammation in a Cockayne syndrome mouse model.

Cockayne syndrome (CS) is a rare, autosomal genetic disorder characterized by premature aging-like features, such as cachectic dwarfism, retinal atrophy, and progressive neurodegeneration. The molecular defect in CS lies in genes associated with the transcription-coupled branch of the nucleotide excision DNA repair (NER) pathway, though it is not yet clear how DNA repair deficiency leads to the multiorgan dysfunction symptoms of CS. In this work, we used a mouse model of severe CS with complete loss of NER (), which recapitulates several CS-related phenotypes, resulting in premature death of these mice at approximately 20 weeks of age.

An evaluation of multi-species empirical tree mortality algorithms for dynamic vegetation modelling.

Tree mortality is key for projecting forest dynamics, but difficult to portray in dynamic vegetation models (DVMs). Empirical mortality algorithms (MAs) are often considered promising, but little is known about DVM robustness when employing MAs of various structures and origins for multiple species. We analysed empirical MAs for a suite of European tree species within a consistent DVM framework under present and future climates in two climatically different study areas in Switzerland and evaluated their performance using empirical data from old-growth forests across Europe.

Missing the blind spot in a HeartMate 3 LVAD outflow graft obstruction caused by fungal infection.

A patient was admitted in cardiogenic shock and a constant decrease of pump flow requiring combined inotropic support. To evaluate the cause, echocardiography and a ramp test were performed. The results suggested a LVAD related problem - particularly a suspected outflow graft obstruction.

MorphoSONIC: A morphologically structured intramembrane cavitation model reveals fiber-specific neuromodulation by ultrasound.

Low-Intensity Focused Ultrasound Stimulation (LIFUS) holds promise for the remote modulation of neural activity, but an incomplete mechanistic characterization hinders its clinical maturation. Here we developed a computational framework to model intramembrane cavitation (a candidate mechanism) in multi-compartment, morphologically structured neuron models, and used it to investigate ultrasound neuromodulation of peripheral nerves. We predict that by engaging membrane mechanoelectrical coupling, LIFUS exploits fiber-specific differences in membrane conductance and capacitance to selectively recruit myelinated and/or unmyelinated axons in distinct parametric subspaces, allowing to modulate their activity concurrently and independently over physiologically relevant spiking frequency ranges.

A fatal affair: Circulating tumor cell relationships that shape metastasis.

Circulating tumor cells are metastatic precursors in several cancer types. Their biology and clinical utility are subject to numerous investigations, yet one aspect that is often neglected is their entanglement with the tumor microenvironment, namely the cross talk with stromal and immune cells and their relationships with other tumor-derived components such as circulating tumor DNA and extracellular vesicles in circulation. We will focus our short review specifically on these aspects, i.

The circle method for preoperative TAVI sizing in a Sievers type 0 stenotic bicuspid aortic valve.

The most common congenital cardiac anomaly, affecting an estimated 0.4-2.25% of the general population, is the bicuspid aortic valve.

Cooperation between melanoma cell states promotes metastasis through heterotypic cluster formation.

Melanomas can have multiple coexisting cell states, including proliferative (PRO) versus invasive (INV) subpopulations that represent a "go or grow" trade-off; however, how these populations interact is poorly understood. Using a combination of zebrafish modeling and analysis of patient samples, we show that INV and PRO cells form spatially structured heterotypic clusters and cooperate in the seeding of metastasis, maintaining cell state heterogeneity. INV cells adhere tightly to each other and form clusters with a rim of PRO cells.

The choice of negative control antisense oligonucleotides dramatically impacts downstream analysis depending on the cellular background.

Background: The lymphatic and the blood vasculature are closely related systems that collaborate to ensure the organism's physiological function. Despite their common developmental origin, they present distinct functional fates in adulthood that rely on robust lineage-specific regulatory programs. The recent technological boost in sequencing approaches unveiled long noncoding RNAs (lncRNAs) as prominent regulatory players of various gene expression levels in a cell-type-specific manner.

PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells.

Cancer cells frequently lack nutrients like glucose, due to insufficient vascular networks. Mitochondrial phosphoenolpyruvate carboxykinase, PCK2, has recently been found to mediate partial gluconeogenesis and hence anabolic metabolism in glucose starved cancer cells. Here we show that PCK2 acts as a regulator of mitochondrial respiration and maintains the redox balance in nutrient-deprived human lung cancer cells.

Physical Activity and Health-Related Quality of Life in Adults With a Neurologically-Related Mobility Disability During the COVID-19 Pandemic: An Exploratory Analysis.

During the coronavirus-19 (COVID-19) pandemic various containment strategies were employed. Their impact on individuals with neurological conditions, considered vulnerable to COVID-19 complications, remains to be determined. To investigate associations between physical activity and health-related quality of life outcomes in individuals with a neurological condition during government mandated COVID-19 restrictions.

Expression of immunoglobulin constant domain genes in neurons of the mouse central nervous system.

General consensus states that immunoglobulins are exclusively expressed by B lymphocytes to form the first line of defense against common pathogens. Here, we provide compelling evidence for the expression of two heavy chain immunoglobulin genes in subpopulations of neurons in the mouse brain and spinal cord. RNA isolated from excitatory and inhibitory neurons through ribosome affinity purification revealed and transcripts encoding for the constant (Fc), but not the variable regions of IgG3 and IgM.

Induced radiofrequency fields in patients undergoing MR examinations: insights for risk assessment.

. To characterize and quantify the induced radiofrequency (RF) electric ()-fields andfields in patients undergoing magnetic resonance (MR) examinations; to provide guidance on aspects of RF heating risks for patients with and without implants; and to discuss some strengths and limitations of safety assessments in current ISO, IEC, and ASTM standards to determine the RF heating risks for patients with and without implants..

Minimally invasive surgery versus sternotomy in native mitral valve endocarditis: a matched comparison.

Objectives: The present study compared the clinical outcomes between minimally invasive surgery (MIS) and median sternotomy (MS) in patients with native mitral valve infective endocarditis.

Methods: From 2009 to 2019, a total of 154 patients with acute (n = 131, 85%) or subacute (n = 23, 15%) native mitral valve infective endocarditis were included in the study. One-to-one nearest neighbour propensity score matching considering endocarditis severity using the dedicated De Feo score and 19 other clinically relevant baseline variables resulted in a population of 39 matched pairs.

Techniques for Robotic-Assisted Surgical Myocardial Revascularization.

The two current strategies for robotic-assisted, surgical myocardial revascularization are minimally invasive direct coronary artery bypass (MIDCAB) and totally endoscopic coronary artery bypass grafting (TECAB). We discuss the rationale underlying the benefits of robotic assistance in surgical myocardial revascularization, and detail the technical steps to safely and effectively perform these two procedures.

Presence of ethanol-sensitive and ethanol-insensitive glycine receptors in the ventral tegmental area and prefrontal cortex in mice.

Background And Purpose: Glycine receptors composed of α1 and β subunits are primarily found in the spinal cord and brainstem and are potentiated by ethanol (10-100 mM). However, much less is known about the presence, composition and ethanol sensitivity of these receptors in higher CNS regions. Here, we examined two regions of the brain reward system, the ventral tegmental area (VTA) and the prefrontal cortex (PFC), to determine their glycine receptor subunit composition and sensitivity to ethanol.

Exercise-induced angiogenesis is dependent on metabolically primed ATF3/4 endothelial cells.

Exercise is a powerful driver of physiological angiogenesis during adulthood, but the mechanisms of exercise-induced vascular expansion are poorly understood. We explored endothelial heterogeneity in skeletal muscle and identified two capillary muscle endothelial cell (mEC) populations that are characterized by differential expression of ATF3/4. Spatial mapping showed that ATF3/4 mECs are enriched in red oxidative muscle areas while ATF3/4 ECs lie adjacent to white glycolytic fibers.