The Interaction of Viruses with the Cellular Senescence Response

Cellular senescence is viewed as a mechanism to prevent malignant transformation, but when it is chronic, as occurs in age-related diseases, it may have adverse effects on cancer. Therefore, targeting senescent cells is a novel therapeutic strategy against senescence-associated diseases. In addition to its role in cancer protection, cellular senescence is also considered a mechanism to control virus replication. Both interferon treatment and some viral infections can trigger cellular senescence as a way to restrict virus replication. However, activation of the cellular senescence program is linked to the alteration of different pathways, which can be exploited by some viruses to improve their replication. It is, therefore, important to understand the potential impact of senolytic agents on viral propagation. Here we focus on the relationship between virus and cellular senescence and the reported effects of senolytic compounds on virus replicationThis research was funded by Ministry of Science, Innovation and Universities and FEDER (BFU-2017-88880-P) and Xunta de Galicia (ED431G 2019/02). RS and SV are predoctoral fellows funded by Xunta de Galicia-Consellería de Cultura, Educación y Ordenación Universitaria (ED481A-2020/160 and ED481A-2018/110, respectively)S

Sustainability of phytoremediation: Post-harvest stratagems and economic opportunities for the produced metals contaminated biomass

Heavy metals (HMs) are indestructible and non-biodegradable. Phytoremediation presents an opportunity to transfer HMs from environmental matrices into plants, making it easy to translocate from one place to another. The ornate features of HMs’ phytoremediation are biophilia and carbon neutrality, compared to the physical and chemical remediation methods. Some recent studies related to LCA also support that phytoremediation is technically more sustainable than competing technologies. However, one major post-application challenge associated with HMs phytoremediation is properly managing HMs contaminated biomass generated. Such a yield presents the problem of reintroducing HMs into the environment due to natural decomposition and release of plant sap from the harvested biomass. The transportation of high yields can also make phytoremediation economically inviable. This review presents the design of a sustainable phytoremediation strategy using an everevolving life cycle assessment tool. This review also discusses possible post-phytoremediation biomass management strategies for the HMs contaminated biomass management. These strategies include composting, leachate compaction, gasification, pyrolysis, torrefaction, and metal recovery. Further, the commercial outlook for properly utilizing HMs contaminated biomass was presented.Authors apologize to all authors whose research has supported this area of interest, and their relevant findings were left out during the preparation of this review. Funding sources: This work was financed by the GREENER project of the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 826312). It has also received funds from Board of Education of Junta de Castilla y Leon ´ and the European Social Fund

Limited Phosphorous Supply Improved Lipid Content of Chlorella vulgaris That Increased Phenol and 2-Chlorophenol Adsorption from Contaminated Water with Acid Treatment

Phenolic compounds are toxic and ominously present in industrial effluents, which can end up in water bodies, causing potential damage to living organisms. This study employed the dried biomass of freshwater green microalgae Chlorella vulgaris to remove phenol and 2-chlorophenol from an aqueous environment. C. vulgaris was grown under different phosphorus- (P) starved conditions, and biomass was treated with sulfuric acid. It was observed that reducing the P level enhanced the lipid content by 7.8 times while decreasing protein by 7.2 times. P-starved C. vulgaris dried biomass removed phenol and 2-chlorophenol by 69 and 57%, respectively, after 180 min from the contaminated water. Acid-treated P-starved C. vulgaris dried biomass removed phenol and 2-chlorophenol by 77 and 75%, respectively, after 180 min. Thus, an economical and eco-friendly P-starved and acid treated C. vulgaris biomass has better potential to remove phenol and 2-chlorophenol from contaminated ground water and industrial wastewater.This research has been funded by Scientific Research Deanship at University of Ha’il—Saudi Arabia through project number RG-21 105

Evaluation of biostimulation, bioaugmentation, and organic amendments application on the bioremediation of recalcitrant hydrocarbons of soil

In the present work, the operational conditions for improving the degradation rates of Total Petroleum Hydrocarbons (TPHs) in contaminated soil from a machinery park were optimized at a microcosms scale along a 90- days incubation period. In this study, bioremediation strategies and an organic amendment have been tested to verify the remediation of soil contaminated with different hydrocarbons, mineral oils, and heavy metals. Specifically, designed biostimulation and bioaugmentation strategies were compared with and without adding vermicompost. The polluted soil harboring multiple contaminants, partially attenuated for years, was used. The initial profile showed enrichment in heavy linear alkanes, suggesting a previous moderate weathering. The application of vermicompost increased five and two times the amounts of available phosphorus (P) and exchangeable potassium (K), respectively, as a direct consequence of the organic amendment addition. The microbial activity increased due to soil acidification, which influenced the solubility of P and other micronutrients. It also impacted the predominance and variability of the different microbial groups and the incubation, as reflected by phospholipid fatty acid (PLFA) results. An increase in the alkaline phosphatases and proteases linked to bacterial growth was displayed. This stimulation of microbial metabolism correlated with the degradation rates since TPHs degradation’ efficiency after vermicompost addition reached 32.5% and 34.4% of the initial hydrocarbon levels for biostimulation and bioaugmentation, respectively. Although Polycyclic Aromatic Hydrocarbons (PAHs) were less abundant in this soil, results also decreased, especially for the most abundant, the phenanthrene. Despite improving the degradation rates, results revealed that recalcitrant and hydrophobic petroleum compounds remained unchanged, indicating that mobility, linked to bioavailability, probably represents the limiting step for further soil recovery.This work is funded by the GREENER project of the European Union’s Horizon 2020 research and innovation program (Grant Agreement No. 826312). S. Curiel pre-doctoral contract was funded by Junta de Castilla y Leon ´ (ORDEN EDU/1508/2020, de 15 de diciembre)

Epstein-Barr Virus (EBV) detection and typing by PCR: a contribution to diagnostic screening of EBV-positive Burkitt's lymphoma

BACKGROUND: Epstein-Barr virus (EBV) is associated to the etio-pathogenesis of an increasing number of tumors. Detection of EBV in pathology samples is relevant since its high prevalence in some cancers makes the virus a promising target of specific therapies. RNA in situ hybridization (RISH) is the standard diagnostic procedure, while polymerase chain reaction (PCR)-based methods are used for strain (EBV type-1 or 2) distinction. We performed a systematic comparison between RISH and PCR for EBV detection, in a group of childhood B-cell Non-Hodgkin lymphomas (NHL), aiming to validate PCR as a first, rapid method for the diagnosis of EBV-associated B-cell NHL. METHODS: EBV infection was investigated in formalin fixed paraffin-embedded tumor samples of 41 children with B-cell NHL, including 35 Burkitt's lymphoma (BL), from Rio de Janeiro, Brazil, by in situ hybridization of EBV-encoded small RNA (EBER-RISH) and PCR assays based on EBNA2 amplification. RESULTS: EBV genomes were detected in 68% of all NHL. Type 1 and 2 accounted for 80% and 20% of EBV infection, respectively. PCR and RISH were highly concordant (95%), as well as single- and nested-PCR results, allowing the use of a single PCR round for diagnostic purposes. PCR assays showed a sensitivity and specificity of 96% and 100%, respectively, with a detection level of 1 EBV genome in 5,000–10,000 EBV-negative cells, excluding the possibility of detecting low-number EBV-bearing memory cells. CONCLUSION: We describe adequate PCR conditions with similar sensitivity and reliability to RISH, to be used for EBV diagnostic screening in high grade B-NHL, in "at risk" geographic regions

Different prognostic impact of recurrent gene mutations in chronic lymphocytic leukemia depending on IGHV gene somatic hypermutation status: a study by ERIC in HARMONY

Recent evidence suggests that the prognostic impact of gene mutations in patients with chronic lymphocytic leukemia (CLL) may differ depending on the immunoglobulin heavy variable (IGHV) gene somatic hypermutation (SHM) status. In this study, we assessed the impact of nine recurrently mutated genes (BIRC3, EGR2, MYD88, NFKBIE, NOTCH1, POT1, SF3B1, TP53, and XPO1) in pre-treatment samples from 4580 patients with CLL, using time-to-first-treatment (TTFT) as the primary end-point in relation to IGHV gene SHM status. Mutations were detected in 1588 (34.7%) patients at frequencies ranging from 2.3-9.8% with mutations in NOTCH1 being the most frequent. In both univariate and multivariate analyses, mutations in all genes except MYD88 were associated with a significantly shorter TTFT. In multivariate analysis of Binet stage A patients, performed separately for IGHV-mutated (M-CLL) and unmutated CLL (U-CLL), a different spectrum of gene alterations independently predicted short TTFT within the two subgroups. While SF3B1 and XPO1 mutations were independent prognostic variables in both U-CLL and M-CLL, TP53, BIRC3 and EGR2 aberrations were significant predictors only in U-CLL, and NOTCH1 and NFKBIE only in M-CLL. Our findings underscore the need for a compartmentalized approach to identify high-risk patients, particularly among M-CLL patients, with potential implications for stratified management

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation