Metals Toxic Effects in Aquatic Ecosystems: Modulators of Water Quality

The topic of this work was based on the assessment of aquatic systems quality related to the persistent metal pollution. The use of aquatic organisms as bioindicators of metal pollution allowed the obtaining of valuable information about the acute and chronic toxicity on common Romanian aquatic species and the estimation of the environment quality. Laboratory toxicity results showed that Cd, As, Cu, Zn, Pb, Ni, Zr, and Ti have toxic to very toxic effects on Cyprinus carpio, and this observation could raise concerns because of its importance as a fishery resource. The benthic invertebrates’ analysis showed that bioaccumulation level depends on species, type of metals, and sampling sites. The metal analysis from the shells of three mollusk species showed that the metals involved in the metabolic processes (Fe, Mn, Zn, Cu, and Mg) were more accumulated than the toxic ones (Pb, Cd). The bioaccumulation factors of metals in benthic invertebrates were subunitary, which indicated a slow bioaccumulation process in the studied aquatic ecosystems. The preliminary aquatic risk assessment of Ni, Cd, Cr, Cu, Pb, As, and Zn on C. carpio revealed insignificant to moderate risk considering the measured environmental concentrations, acute and long-term effects and environmental compartment

Evaluating the ecotoxicity of different pharmaceuticals using Aliivibrio fischeri bioassays

An endless list of companies have produced a large amount of pharmaceutical compounds in a year-on-year growth trend. Due to the excessive consumption of these substances and the inappropriate disposal, the environment was contaminated, especially aquatic ecosystems, with quantities of pharmaceuticals (PHACs) so that they have affected the living organisms, leading to decreased biodiversity and ecological degradation. Many studies on PHACs environmental presence and toxic effects were performed, but unfortunately, no limit was establish for discharging into environment, especially into the aquatic systems. The aim of this study was to use the bioluminescence of Aliivibrio fischeri bacteria as an indicator of toxically effect of different PHACs in simulated marine medium. The Microtox® bioassay is based on the PHACs inhibitory effect on the metabolism of bacteria which induced changes in their bacterial bioluminescence. The test organisms were exposed to analgesics and anti-inflammatories such as Diclofenac, Ketoprofen, Naproxen and Ibuprofen. The results showed that based on EC50 values, Naproxen had a very low toxicity but Diclofenac, Ketoprofen and Ibuprofen had a harmful effect on the aquatic organisms

Fast Flux-Activated Leakage Reduction for Superconducting Quantum Circuits

Quantum computers will require quantum error correction to reach the low error rates necessary for solving problems that surpass the capabilities of conventional computers. One of the dominant errors limiting the performance of quantum error correction codes across multiple technology platforms is leakage out of the computational subspace arising from the multi-level structure of qubit implementations. Here, we present a resource-efficient universal leakage reduction unit for superconducting qubits using parametric flux modulation. This operation removes leakage down to our measurement accuracy of $7\cdot 10^{-4}$ in approximately $50\, \mathrm{ns}$ with a low error of $2.5(1)\cdot 10^{-3}$ on the computational subspace, thereby reaching durations and fidelities comparable to those of single-qubit gates. We demonstrate that using the leakage reduction unit in repeated weight-two stabilizer measurements reduces the total number of detected errors in a scalable fashion to close to what can be achieved using leakage-rejection methods which do not scale. Our approach does neither require additional control electronics nor on-chip components and is applicable to both auxiliary and data qubits. These benefits make our method particularly attractive for mitigating leakage in large-scale quantum error correction circuits, a crucial requirement for the practical implementation of fault-tolerant quantum computation

Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement

Ontogenetic Profile of the Expression of Thyroid Hormone Receptors in Rat and Human Corpora Cavernosa of the Penis

Introduction. In the last few years, various studies have underlined a correlation between thyroid function and male sexual function, hypothesizing a direct action of thyroid hormones on the penis. Aim. To study the spatiotemporal distribution of mRNA for the thyroid hormone nuclear receptors (TR) alpha 1, alpha 2 and beta in the penis and smooth muscle cells (SMCs) of the corpora cavernosa of rats and humans during development. Methods. We used several molecular biology techniques to study the TR expression in whole tissues or primary cultures from human and rodent penile tissues of different ages. Main Outcome Measure. We measured our data by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) amplification, Northern blot and immunohistochemistry. Results. We found that TR alpha 1 and TR alpha 2 are both expressed in the penis and in SMCs during ontogenesis without development-dependent changes. However, in the rodent model, TR beta shows an increase from 3 to 6 days post natum (dpn) to 20 dpn, remaining high in adulthood. The same expression profile was observed in humans. While the expression of TR beta is strictly regulated by development, TR alpha 1 is the principal isoform present in corpora cavernosa, suggesting its importance in SMC function. These results have been confirmed by immunohistochemistry localization in SMCs and endothelial cells of the corpora cavernosa. Conclusions. The presence of TRs in the penis provides the biological basis for the direct action of thyroid hormones on this organ. Given this evidence, physicians would be advised to investigate sexual function in men with thyroid disorders. Carosa E, Di Sante S, Rossi S, Castri A, D'Adamo F, Gravina GL, Ronchi P, Kostrouch Z, Dolci S, Lenzi A, and Jannini EA. Ontogenetic profile of the expression of thyroid hormone receptors in rat and human corpora cavernosa of the penis. J Sex Med 2010;7:1381-1390

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN