Combinational Inhibition of MEK and AKT Synergistically Induces Melanoma Stem Cell Apoptosis and Blocks NRAS Tumor Growth.

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MICs), implicated in tumorigenesis, invasion, and drug resistance, and characterized by an elevated expression of stem cell markers, including CD133. siRNA knockdown of CD133 has been previously shown to enhance apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133's anti-apoptotic activity in patient-derived BAKP melanoma, harboring the difficult-to-treat NRAS driver mutation, after CRISPR-Cas9 CD133 knockout or Doxycycline (Dox)-inducible re-expression of CD133.

Temperature Is a Key Factor Governing the Toxic Impact of Ultra-Violet Radiation-Emitting Nail Dryers When Used on Human Skin Cells.

The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400 nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth's surface causing the majority of the visible signs of skin photoaging.

Automated Method for Intracranial Aneurysm Classification Using Deep Learning.

Intracranial aneurysm (IA) is now a common term closely associated with subarachnoid hemorrhage. IA is the bulging of a blood vessel caused by a weakening of its wall. This bulge can rupture and, in most cases, cause internal bleeding.

CD133 Stimulates Cell Proliferation via the Upregulation of Amphiregulin in Melanoma.

CD133, a cancer stem cell (CSC) marker in tumors, including melanoma, is associated with tumor recurrence, chemoresistance, and metastasis. Patient-derived melanoma cell lines were transduced with a Tet-on vector expressing CD133, generating doxycycline (Dox)-inducible cell lines. Cells were exposed to Dox for 24 h to induce CD133 expression, followed by RNA-seq and bioinformatic analyses, revealing genes and pathways that are significantly up- or downregulated by CD133.

TRIP12 governs DNA Polymerase β involvement in DNA damage response and repair.

The multitude of DNA lesion types, and the nuclear dynamic context in which they occur, present a challenge for genome integrity maintenance as this requires the engagement of different DNA repair pathways. Specific 'repair controllers' that facilitate DNA repair pathway crosstalk between double strand break (DSB) repair and base excision repair (BER), and regulate BER protein trafficking at lesion sites, have yet to be identified. We find that DNA polymerase β (Polβ), crucial for BER, is ubiquitylated in a BER complex-dependent manner by TRIP12, an E3 ligase that partners with UBR5 and restrains DSB repair signaling.

Prevalence of SARS-CoV-2 variants in Prague wastewater determined by nanopore-based sequencing.

The early detection of upcoming disease outbreaks is essential to avoid both health and economic damage. The last four years of COVID-19 pandemic have proven wastewater-based epidemiology is a reliable system for monitoring the spread of SARS-CoV-2, a causative agent of COVID-19, in an urban population. As this monitoring enables the identification of the prevalence of spreading variants of SARS-CoV-2, it could provide a critical tool in the fight against this viral disease.

Monitoring of monkeypox viral DNA in Prague wastewater.

Monkeypox virus (Mpxv) is a dsDNA virus that has become a global concern for human health in 2022. As both infected people and non-human hosts can shed the virus from their skin, faeces, urine and other body fluids, and the resulting sewage contains viral load representative of the whole population, it is highly promising to detect the spread of monkeypox virus in municipal wastewater. We established a methodology for sewage-based monitoring of Mpxv in Prague and analysed samples (n = 24) already early August-October of 2022 in a municipality with 1.

Skin Immuno-CometChip in 3D vs. 2D Cultures to Screen Topical Toxins and Skin-Specific Cytochrome Inducers.

The targets of topical genotoxic agents are basal and stem cells of the skin. These cells may misrepair DNA lesions, resulting in deleterious mutations of tumor suppressors or oncogenes. However, the genotoxicity of many compounds has not as yet been determined and needs to be tested using a relevant skin model.

A New Deep-Learning Method for Human Activity Recognition.

Currently, three-dimensional convolutional neural networks (3DCNNs) are a popular approach in the field of human activity recognition. However, due to the variety of methods used for human activity recognition, we propose a new deep-learning model in this paper. The main objective of our work is to optimize the traditional 3DCNN and propose a new model that combines 3DCNN with Convolutional Long Short-Term Memory (ConvLSTM) layers.

Monitoring COVID-19 spread in selected Prague's schools based on the presence of SARS-CoV-2 RNA in wastewater.

The COVID-19 pandemic has demanded a broad range of techniques to better monitor its extent. Owing to its consistency, non-invasiveness, and cost effectiveness, wastewater-based epidemiology has emerged as a relevant approach to monitor the pandemic's course. In this work, we analyzed the extent of the COVID-19 pandemic in five primary schools in Prague, the Czech Republic, and how different preventive measures impact the presence of SARS-CoV-2 RNA copy numbers in wastewaters.

Methodology for clinical research.

A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Indeed, selecting an inappropriate study type, an error that cannot be corrected after the beginning of a study, results in flawed methodology. The results of clinical research studies enhance the repertoire of knowledge regarding a disease pathogenicity, an existing or newly discovered medication, surgical or diagnostic procedure or medical device.

Improved nitrogen removal efficiency by implementation of intermittent aeration.

The aim of the paper was to verify the possibility of using intermittent aeration to decrease outflow total nitrogen concentrations in municipal WWTPs of different capacities (15,780, 23,000 and 806,250 PE). A simple time-based intermittent aeration control was used in the experimental work. The results of WWTPs are compared with each other and with literature sources.

A New Approach for Abnormal Human Activities Recognition Based on ConvLSTM Architecture.

Recognizing various abnormal human activities from video is very challenging. This problem is also greatly influenced by the lack of datasets containing various abnormal human activities. The available datasets contain various human activities, but only a few of them contain non-standard human behavior such as theft, harassment, etc.

Monitoring COVID-19 spread in Prague local neighborhoods based on the presence of SARS-CoV-2 RNA in wastewater collected throughout the sewer network.

Many reports have documented that the presence of SARS-CoV-2 RNA in the influents of municipal wastewater treatment plants (WWTP) correlates with the actual epidemic situation in a given city. However, few data have been reported thus far on measurements upstream of WWTPs, i.e.

Employing CRISPR-Cas9 to Generate CD133 Synthetic Lethal Melanoma Stem Cells.

Malignant melanoma is a lethal skin cancer containing melanoma-initiating cells (MIC) implicated in tumorigenesis, invasion, and drug resistance, and is characterized by the elevated expression of stem cell markers, including CD133. The siRNA knockdown of CD133 enhances apoptosis induced by the MEK inhibitor trametinib in melanoma cells. This study investigates the underlying mechanisms of CD133's anti-apoptotic activity in patient-derived BAKP and POT cells, harboring difficult-to-treat NRAS and NRAS drivers, after CRISPR-Cas9 CD133 knockout or Dox-inducible expression of CD133.

Commissioning of the new water line of the Central wastewater treatment plant in Prague and its impact on the operation of the existing water line.

This paper describes the commissioning of the new water line (NWL) of the Central wastewater treatment plant in Prague and also the gradual reduction of the existing water line (EWL) loading. Concerning the NWL, the gradual start-up of the process without inoculation will be described. As to the EWL, the presentation describes the adaptation of the EWL operation to the relatively quick reduction of loading to approximately 35%.

Extracellular NAD enhances PARP-dependent DNA repair capacity independently of CD73 activity.

Changes in nicotinamide adenine dinucleotide (NAD) levels that compromise mitochondrial function trigger release of DNA damaging reactive oxygen species. NAD levels also affect DNA repair capacity as NAD is a substrate for PARP-enzymes (mono/poly-ADP-ribosylation) and sirtuins (deacetylation). The ecto-5'-nucleotidase CD73, an ectoenzyme highly expressed in cancer, is suggested to regulate intracellular NAD levels by processing NAD and its bio-precursor, nicotinamide mononucleotide (NMN), from tumor microenvironments, thereby enhancing tumor DNA repair capacity and chemotherapy resistance.

CRISPR-Cas9 Knockdown and Induced Expression of CD133 Reveal Essential Roles in Melanoma Invasion and Metastasis.

CD133, known as prominin1, is a penta-span transmembrane glycoprotein presumably a cancer stem cell marker for carcinomas, glioblastomas, and melanomas. We showed that CD133(+) 'melanoma-initiating cells' are associated with chemoresistance, contributing to poor patient outcome. The current study investigates the role(s) of CD133 in invasion and metastasis.

Camptothecin Efficacy to Poison Top1 Is Altered by Bisphenol A in Mouse Embryonic Fibroblasts.

Bisphenol A (BPA) is used heavily in the production of polycarbonate plastics, thermal receipt paper, and epoxies. Ubiquitous exposure to BPA has been linked to obesity, diabetes, and breast and reproductive system cancers. Resistance to chemotherapeutic agents has also been shown in cancer cell models.

Application of the CometChip platform to assess DNA damage in field-collected blood samples from turtles.

DNA damage has been linked to genomic instability and the progressive breakdown of cellular and organismal homeostasis, leading to the onset of disease and reduced longevity. Insults to DNA from endogenous sources include base deamination, base hydrolysis, base alkylation, and metabolism-induced oxidative damage that can lead to single-strand and double-strand DNA breaks. Alternatively, exposure to environmental pollutants, radiation or ultra-violet light, can also contribute to exogenously derived DNA damage.

Next generation high throughput DNA damage detection platform for genotoxic compound screening.

Methods for quantifying DNA damage, as well as repair of that damage, in a high-throughput format are lacking. Single cell gel electrophoresis (SCGE; comet assay) is a widely-used method due to its technical simplicity and sensitivity, but the standard comet assay has limitations in reproducibility and throughput. We have advanced the SCGE assay by creating a 96-well hardware platform coupled with dedicated data processing software (CometChip Platform).