A Computational Systems Biology Approach Identifies SLUG as a Mediator of Partial Epithelial-Mesenchymal Transition (EMT).

Epithelial-mesenchymal plasticity comprises reversible transitions among epithelial, hybrid epithelial/mesenchymal (E/M) and mesenchymal phenotypes, and underlies various aspects of aggressive tumor progression such as metastasis, therapy resistance, and immune evasion. The process of cells attaining one or more hybrid E/M phenotypes is termed as partial epithelial mesenchymal transition (EMT). Cells in hybrid E/M phenotype(s) can be more aggressive than those in either fully epithelial or mesenchymal state.

NanoClick: A High Throughput, Target-Agnostic Peptide Cell Permeability Assay.

Macrocyclic peptides open new opportunities to target intracellular protein-protein interactions (PPIs) that are often considered nondruggable by traditional small molecules. However, engineering sufficient membrane permeability into these molecules is a central challenge for identifying clinical candidates. Currently, there is a lack of high-throughput assays to assess peptide permeability, which limits our capacity to engineer this property into macrocyclic peptides for advancement through drug discovery pipelines.

Intracellular Ionic Strength Sensing Using NanoLuc.

Intracellular ionic strength regulates myriad cellular processes that are fundamental to cellular survival and proliferation, including protein activity, aggregation, phase separation, and cell volume. It could be altered by changes in the activity of cellular signaling pathways, such as those that impact the activity of membrane-localized ion channels or by alterations in the microenvironmental osmolarity. Therefore, there is a demand for the development of sensitive tools for real-time monitoring of intracellular ionic strength.

Antibiotic Treatment for Chronic Rhinosinusitis: Prescription Patterns and Associations With Patient Outcome and the Sinus Microbiota.

Background: Chronic rhinosinusitis (CRS) is a common and debilitating inflammatory condition of the sinuses, afflicting 5% of the general population. Although antibiotics are frequently prescribed for the medical management of CRS, there is surprisingly little evidence to support their efficacy. In this study, we aimed to establish associations between medication usage, the sinus microbiota and patients' clinical outcomes.

Metal-free multicomponent approach for the synthesis of propargylamine: a review.

Propargylamines are important classes of alkyne coupled amine compounds used in heterocyclic chemistry and pharmaceuticals chemistry and have a large impact as a pharmacophore used in medicinal chemistry. One of the straightforward approaches for the synthesis of this class of compound is A3 coupling, a three-component coupling reaction among aldehyde, alkyne (terminal acetylene) and amine. However, there are many methods other than conventional three component alkyne-aldehyde-amine (A3) coupling which have also been reported for the synthesis of propargylamine.

Phosphodiesterase 5 (PDE5): Structure-function regulation and therapeutic applications of inhibitors.

Phosphodiesterase 5 (PDE5) is one of the most well-studied phosphodiesterases (PDEs) that specifically targets cGMP typically generated by nitric oxide (NO)-mediated activation of the soluble guanylyl cyclase. Given the crucial role of cGMP generated through the activation of this cellular signaling pathway in a variety of physiologically processes, pharmacological inhibition of PDE5 has been demonstrated to have several therapeutic applications including erectile dysfunction and pulmonary arterial hypertension. While they are designed to inhibit PDE5, the inhibitors show different affinities and specificities against all PDE subtypes.

Epidemiological and ES cell-based functional evaluation of BRCA2 variants identified in families with breast cancer.

The discovery of high-risk breast cancer susceptibility genes, such as Breast cancer associated gene 1 (BRCA1) and Breast cancer associated gene 2 (BRCA2) has led to accurate identification of individuals for risk management and targeted therapy. The rapid decline in sequencing costs has tremendously increased the number of individuals who are undergoing genetic testing world-wide. However, given the significant differences in population-specific variants, interpreting the results of these tests can be challenging especially for novel genetic variants in understudied populations.

A computational model for classification of BRCA2 variants using mouse embryonic stem cell-based functional assays.

Sequencing-based genetic tests to identify individuals at increased risk of hereditary breast and ovarian cancers have resulted in the identification of more than 40,000 sequence variants of BRCA1 and BRCA2. A majority of these variants are considered to be variants of uncertain significance (VUS) because their impact on disease risk remains unknown, largely due to lack of sufficient familial linkage and epidemiological data. Several assays have been developed to examine the effect of VUS on protein function, which can be used to assess their impact on cancer susceptibility.

Two Decades of Gla-100-Reflections from the Pivotal Clinical Trials.

The progressive nature of type 2 diabetes mellitus (T2DM) renders the shifting of patients from oral drugs to insulin therapy an inevitability in most patients especially in those with long duration of diabetes. At the turn of the last millennium, neutral protamine Hagedorn (NPH) insulin was still the only long-acting insulin available for people with diabetes. The advent of the first truly long-acting basal insulin, i.

Multiomic analysis identifies natural intrapatient temporal variability and changes in response to systemic corticosteroid therapy in chronic rhinosinusitis.

Introduction: The pathophysiology and temporal dynamics of affected tissues in chronic rhinosinusitis (CRS) remain poorly understood. Here, we present a multiomics-based time-series assessment of nasal polyp biopsies from three patients with CRS, assessing natural variability over time and local response to systemic corticosteroid therapy.

Methods: Polyp tissue biopsies were collected at three time points over two consecutive weeks.

Ultralow Thermal Conductivity, Enhanced Mechanical Stability, and High Thermoelectric Performance in (GeTe)(SnSe)(SnS).

Thermoelectric (TE) energy conversion demands high performance crystalline inorganic solids that exhibit ultralow thermal conductivity, high mechanical stability, and good TE device properties. Pb-free germanium telluride (GeTe)-based material has recently attracted significant attention in TE power generation in mid temperatures, but pristine GeTe possesses significantly higher lattice thermal conductivity (κ) compared to that of its theoretical minimum (κ) of ∼0.3 W/mK.

On-surface synthesis of doubly-linked one-dimensional pentacene ladder polymers.

On-surface synthesis has recently become an essential approach toward the formation of carbon-based nanostructures. Special emphasis is set on the synthesis of π-conjugated polymers taking into consideration their relevance and potential in organic electronics, optoelectronics and spintronics. Here, we report the on-surface synthesis of conjugated ladder polymers consisting of pentacene units doubly-linked via ethynylene-like bonds on the Au(111) surface under ultra-high vacuum conditions.

High Spin to Charge Conversion Efficiency in Electron Beam-Evaporated Topological Insulator BiSe.

BiSe is a well-established topological insulator (TI) having spin momentum locked Dirac surface states at room temperature and predicted to exhibit high spin to charge conversion efficiency (SCCE) for spintronics applications. The SCCE in TIs is characterized by an inverse Edelstein effect length (λ). We report an λ of ∼0.

Validation of Revised Baveno VI Criteria for Screening of Varices Needing Treatment in Children with Cirrhosis.

Background: Baveno VI criteria for screening varices needing treatment (VNT) have not yet been validated in an exclusive pediatric and adolescent set of the population, in whom baseline parameters differ in relation to adults. Therefore, our primary objective was to validate Baveno VI and its expanded form in children below 18 years of age. The secondary aim was to elicit whether any revision of the above criteria with a target of not missing more than 5% VNT could be more accurate for this age group.

COVID-19 Contact Tracing: Challenges and Future Directions.

Contact tracing has become a vital tool for public health officials to effectively combat the spread of new diseases, such as the novel coronavirus disease COVID-19. Contact tracing is not new to epidemiologist rather, it used manual or semi-manual approaches that are incredibly time-consuming, costly and inefficient. It mostly relies on human memory while scalability is a significant challenge in tackling pandemics.

Effect of tonsillectomy on antibiotic prescribing in children.

Introduction: Tonsillectomy is the second most common surgical procedure performed in pediatric otolaryngology. Multiple courses of antibiotics are usually prescribed prior to surgical intervention. Surgery is indicated when patients reach a certain number of infective episodes, or their obstructive symptoms warrant intervention.

Utility of global longitudinal strain to detect significant coronary artery disease, its extent and severity in patients with stable ischemic heart disease.

Background: Early changes in cardiac function due to ischemia may be detected by global longitudinal peak systolic strain (GLS). Till date, no Indian data exist regarding role of GLS in stable ischemic heart disease (SIHD) and data showing correlation of GLS and SYNTAX score (SS) is meager in world literature. Our aim was to ascertain the role of GLS in SIHD.

2D layered all-inorganic halide perovskites: recent trends in their structure, synthesis and properties.

Recently, halide perovskites have appeared as a superior class of materials for diverse applications, mainly in optoelectronics and photovoltaics. Perovskite halides are broadly classified as hybrid organic-inorganic and all-inorganic analogues depending on the chemical nature of the A cation in the ABX3-type structure. Immense progress has already been achieved in halide perovskites focusing mainly on the hybrid equivalents and all-inorganic three-dimensional (3D) structures, however all-inorganic two-dimensional (2D) layered halide perovskites are relatively new and their nanostructures have gained significant attention in the last few years.

Corrigendum: Anti-biofilm and Antibacterial Activities of Silver Nanoparticles Synthesized by the Reducing Activity of Phytoconstituents Present in the Indian Medicinal Plants.

[This corrects the article DOI: 10.3389/fmicb.2020.

NFATc Acts as a Non-Canonical Phenotypic Stability Factor for a Hybrid Epithelial/Mesenchymal Phenotype.

Metastasis remains the cause of over 90% of cancer-related deaths. Cells undergoing metastasis use phenotypic plasticity to adapt to their changing environmental conditions and avoid therapy and immune response. Reversible transitions between epithelial and mesenchymal phenotypes - epithelial-mesenchymal transition (EMT) and its reverse mesenchymal-epithelial transition (MET) - form a key axis of phenotypic plasticity during metastasis and therapy resistance.