Aedes koreicus, a vector on the rise: Pan-European genetic patterns, mitochondrial and draft genome sequencing.

Background: The mosquito Aedes koreicus (Edwards, 1917) is a recent invader on the European continent that was introduced to several new places since its first detection in 2008. Compared to other exotic Aedes mosquitoes with public health significance that invaded Europe during the last decades, this species' biology, behavior, and dispersal patterns were poorly investigated to date.

Methodology/principal Findings: To understand the species' population relationships and dispersal patterns within Europe, a fragment of the cytochrome oxidase I (COI or COX1) gene was sequenced from 130 mosquitoes, collected from five countries where the species has been introduced and/or established.

"Endothelial Antibody Factory" at the Blood Brain Barrier: Novel Approach to Therapy of Neurodegenerative Diseases.

The failures of anti-β-amyloid immunotherapies suggested that the very low fraction of injected antibodies reaching the brain parenchyma due to the filtering effect of the BBB may be a reason for the lack of therapeutic effect. However, there is no treatment, as yet, for the amyotrophic lateral sclerosis (ALS) despite substantial evidence existing of the involvement of TDP-43 protein in the evolution of ALS. To circumvent this filtering effect, we have developed a novel approach to facilitate the penetration of antibody fragments (Fabs) into the brain parenchyma.

The metabolic stress response: Adaptation to acute-, repeated- and chronic challenges in mice.

There is a strong relationship between stress and metabolism. Because acute traumatic- and chronic stress events are often accompanied with metabolic pathophysiology, it is important to understand the details of the metabolic stress response. In this study we directly compared metabolic effects of acute stress with chronic repeated- and chronic unpredictable stress in mouse models.

Complement Levels at Admission Reflecting Progression to Severe Acute Kidney Injury (AKI) in Coronavirus Disease 2019 (COVID-19): A Multicenter Prospective Cohort Study.

Background: Dysregulation of complement system is thought to be a major player in development of multi-organ damage and adverse outcomes in patients with coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement system activity and development of severe acute kidney injury (AKI) among hospitalized COVID-19 patients.

Materials And Methods: In this multicenter, international study, complement as well as inflammatory and thrombotic parameters were analyzed in COVID-19 patients requiring hospitalization at one US and two Hungarian centers.

tea protects against diabetes-induced cardiac dysfunction in rats without affecting glucose tolerance.

Background And Aim: Common chickweed () tea has traditionally been applied for treatment of various metabolic diseases including diabetes in folk medicine; however, experimental evidence to support this practice is lacking. Therefore, we aimed to assess the effect of tea on glucose homeostasis and cardiac performance in a rat model of diabetes.

Experimental Procedure: Hot water extract of herb were analyzed and used in this study, where diabetes was induced by fructose-enriched diet supplemented with a single injection of streptozotocin.

Nonlinear electric response of the diffuse double layer to an abrupt charge displacement inside a biological membrane.

In order to elucidate the old, still unsolved problem of how the diffuse electric double layer responds to an abrupt, intramolecular charge displacement inside a biological membrane, we investigated the fastest components of the light-induced electric signals of bacteriorhodopsin and its mutants, in numerous ionic and buffer solutions. The obtained data for temperature and solute concentration dependence were interpreted as a consequence of changes in the capacity of the diffuse double layer surrounding the purple membrane. The possible physiological consequences of this so far not demonstrated phenomenon are discussed.

Proteome-wide landscape of solubility limits in a bacterial cell.

Proteins are prone to aggregate when expressed above their solubility limits. Aggregation may occur rapidly, potentially as early as proteins emerge from the ribosome, or slowly, following synthesis. However, in vivo data on aggregation rates are scarce.

Review of Label-Free Monitoring of Bacteria: From Challenging Practical Applications to Basic Research Perspectives.

Novel biosensors already provide a fast way to detect the adhesion of whole bacteria (or parts of them), biofilm formation, and the effect of antibiotics. Moreover, the detection sensitivities of recent sensor technologies are large enough to investigate molecular-scale biological processes. Usually, these measurements can be performed in real time without using labeling.

Folic Acid Treatment Directly Influences the Genetic and Epigenetic Regulation along with the Associated Cellular Maintenance Processes of HT-29 and SW480 Colorectal Cancer Cell Lines.

Folic acid (FA) is a synthetic form of vitamin B9, generally used as a nutritional supplement and an adjunctive medication in cancer therapy. FA is involved in genetic and epigenetic regulation; therefore, it has a dual modulatory role in established neoplasms. We aimed to investigate the effect of short-term (72 h) FA supplementation on colorectal cancer; hence, HT-29 and SW480 cells were exposed to different FA concentrations (0, 100, 10,000 ng/mL).

Identifying Novel Inhibitors for Hepatic Organic Anion Transporting Polypeptides by Machine Learning-Based Virtual Screening.

Integration of statistical learning methods with structure-based modeling approaches is a contemporary strategy to identify novel lead compounds in drug discovery. Hepatic organic anion transporting polypeptides (OATP1B1, OATP1B3, and OATP2B1) are classical off-targets, and it is well recognized that their ability to interfere with a wide range of chemically unrelated drugs, environmental chemicals, or food additives can lead to unwanted adverse effects like liver toxicity and drug-drug or drug-food interactions. Therefore, the identification of novel (tool) compounds for hepatic OATPs by virtual screening approaches and subsequent experimental validation is a major asset for elucidating structure-function relationships of (related) transporters: they enhance our understanding about molecular determinants and structural aspects of hepatic OATPs driving ligand binding and selectivity.

Selective Enrichment of Munc13-2 in Presynaptic Active Zones of Hippocampal Pyramidal Cells That Innervate mGluR1α Expressing Interneurons.

Selective distribution of proteins in presynaptic active zones (AZs) is a prerequisite for generating postsynaptic target cell type-specific differences in presynaptic vesicle release probability (P) and short-term plasticity, a characteristic feature of cortical pyramidal cells (PCs). In the hippocampus of rodents, somatostatin and mGluR1α expressing interneurons (mGluR1α+ INs) receive small, facilitating excitatory postsynaptic currents (EPSCs) from PCs and express Elfn1 that trans-synaptically recruits mGluR7 into the presynaptic AZ of PC axons. Here we show that Elfn1 also has a role in the selective recruitment of Munc13-2, a synaptic vesicle priming and docking protein, to PC AZs that innervate mGluR1α+ INs.

Tissue miRNA Combinations for the Differential Diagnosis of Adrenocortical Carcinoma and Adenoma Established by Artificial Intelligence.

The histological analysis of adrenal tumors is difficult and requires great expertise. Tissue microRNA (miRNA) expression is distinct between benign and malignant tumors of several organs and can be useful for diagnostic purposes. MiRNAs are stable and their expression can be reliably reproduced from archived formalin-fixed, paraffin-embedded (FFPE) tissue blocks.

Blood-brain barrier dysfunction in L-ornithine induced acute pancreatitis in rats and the direct effect of L-ornithine on cultured brain endothelial cells.

Background: In severe acute pancreatitis (AP) the CNS is affected manifesting in neurological symptoms. Earlier research from our laboratory showed blood-brain barrier (BBB) permeability elevation in a taurocholate-induced AP model. Here we aimed to further explore BBB changes in AP using a different, non-invasive in vivo model induced by L-ornithine.

Syndecan-4 affects myogenesis via Rac1-mediated actin remodeling and exhibits copy-number amplification and increased expression in human rhabdomyosarcoma tumors.

Skeletal muscle demonstrates a high degree of regenerative capacity repeating the embryonic myogenic program under strict control. Rhabdomyosarcoma is the most common sarcoma in childhood and is characterized by impaired muscle differentiation. In this study, we observed that silencing the expression of syndecan-4, the ubiquitously expressed transmembrane heparan sulfate proteoglycan, significantly enhanced myoblast differentiation, and fusion.

In vivo and cellular antiarrhythmic and cardiac electrophysiological effects of desethylamiodarone in dog cardiac preparations.

Background And Purpose: The aim of the present study was to study the antiarrhythmic effects and cellular mechanisms of desethylamiodarone (DEA), the main metabolite of amiodarone (AMIO), following acute and chronic 4-week oral treatments (25-50 mg·kg ·day ).

Experimental Approach: The antiarrhythmic effects of acute iv. (10 mg·kg ) and chronic oral (4 weeks, 25 mg·kg ·day ) administration of DEA were assessed in carbachol and tachypacing-induced dog atrial fibrillation models.

Circulating cardiomyocyte-derived extracellular vesicles reflect cardiac injury during systemic inflammatory response syndrome in mice.

The release of extracellular vesicles (EVs) is increased under cellular stress and cardiomyocyte damaging conditions. However, whether the cardiomyocyte-derived EVs eventually reach the systemic circulation and whether their number in the bloodstream reflects cardiac injury, remains unknown. Wild type C57B/6 and conditional transgenic mice expressing green fluorescent protein (GFP) by cardiomyocytes were studied in lipopolysaccharide (LPS)-induced systemic inflammatory response syndrome (SIRS).

Hippocampal sharp wave-ripples and the associated sequence replay emerge from structured synaptic interactions in a network model of area CA3.

Hippocampal place cells are activated sequentially as an animal explores its environment. These activity sequences are internally recreated ('replayed'), either in the same or reversed order, during bursts of activity (sharp wave-ripples [SWRs]) that occur in sleep and awake rest. SWR-associated replay is thought to be critical for the creation and maintenance of long-term memory.

Surprising genetic and pathological findings in a patient with giant bilateral periadrenal tumours: PEComas and mutations of in Gorlin-Goltz syndrome.

Gorlin-Goltz syndrome (GGS) or nevoid basal cell carcinoma syndrome is a rare tumour-overgrowth syndrome associated with multiple developmental anomalies and a wide variety of tumours. Here, we describe a case of a man aged 23 years with GGS with bilateral giant tumours adjacent to both adrenals that raised the suspicion of malignancy on imaging. Histological analysis of both surgically resected tumours revealed perivascular epitheloid cell tumours (PEComas) that were independent of the adrenals.

Novel Assay Platform to Evaluate Intracellular Killing of : and Validation.

One of the main hallmarks of tuberculosis (TB) is the ability of the causative agent to transform into a stage of dormancy and the capability of long persistence in the host phagocytes. It is believed that approximately one-third of the population of the world is latently infected with (), and 5%-10% of these individuals can develop clinical manifestations of active TB even decades after the initial infection. In this latent, intracellular form, the is shielded by an extremely robust cell wall and becomes phenotypically resistant to most antituberculars.

Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats.

The centrally-projecting Edinger-Westphal nucleus (EWcp) hosts a large population of neurons expressing urocortin 1 (Ucn1) and about half of these neurons also express the leptin receptor (LepRb). Previously, we have shown that the peripheral adiposity hormone leptin signaling energy surfeit modulates EWcp neurons' activity. Here, we hypothesized that Ucn1/LepRb neurons in the EWcp would act as a crucial neuronal node in the brain-white adipose tissue (WAT) axis modulating efferent sympathetic outflow to the WAT.

Combination of multifunctional ursolic acid with kinase inhibitors for anti-cancer drug carrier vesicles.

A sterically stabilized unilamellar nanocarrier vesicle (SSV) system containing dipalmitoylphosphatidylcholine, cholesterol, ursolic acid and PEGylated phospholipid has been developed by exploiting the structural advantages of ursolic acid: by spontaneously attaching to the lipid head groups, it induces curvature at the outer side of the bilayers, allowing the preparation of size-limited vesicles without extrusion. Ursolic acid (UA) also interacts with the PEG chains, supporting steric stabilization even when the amount of PEGylated phospholipid is reduced. Using fluorescence immunohistochemistry, vesicles containing ursolic acid (UA-SSVs) were found to accumulate in the tumor in 3 h on xenografted mouse, suggesting the potential use of these vesicles for passive tumor targeting.

PharmacoSTORM nanoscale pharmacology reveals cariprazine binding on Islands of Calleja granule cells.

Immunolabeling and autoradiography have traditionally been applied as the methods-of-choice to visualize and collect molecular information about physiological and pathological processes. Here, we introduce PharmacoSTORM super-resolution imaging that combines the complementary advantages of these approaches and enables cell-type- and compartment-specific nanoscale molecular measurements. We exploited rational chemical design for fluorophore-tagged high-affinity receptor ligands and an enzyme inhibitor; and demonstrated broad PharmacoSTORM applicability for three protein classes and for cariprazine, a clinically approved antipsychotic and antidepressant drug.