Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition.

Cell competition has recently emerged as an important tumor suppressor mechanism in the thymus that inhibits autonomous thymic maintenance. Here, we show that the oncogenic transcription factor Lmo2 causes autonomous thymic maintenance in transgenic mice by inhibiting early T cell differentiation. This autonomous thymic maintenance results in the development of self-renewing preleukemic stem cells (pre-LSCs) and subsequent leukemogenesis, both of which are profoundly inhibited by restoration of thymic competition or expression of the antiapoptotic factor BCL2. Genomic analyses revealed the presence of Notch1 mutations in pre-LSCs before subsequent loss of tumor suppressors promotes the transition to overt leukemogenesis. These studies demonstrate a critical role for impaired cell competition in the development of pre-LSCs in a transgenic mouse model of T cell acute lymphoblastic leukemia (T-ALL), implying that this process plays a role in the ontogeny of human T-ALL.

Adsorption of Mn(ii) ions from wastewater using an AgNPs/GO/chitosan nanocomposite material.

Water contaminated with heavy metal ions is extremely poisonous and threatens living organisms. Therefore, scientists place a premium on removing heavy metal ions from water that has already been contaminated. Removing metal ions from water typically involves the use of nanomaterials. Chitosan was made by extracting it from shrimp shells and combining it with a 3 : 1 ratio of synthetically produced AgNPs/GO. Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) with transmission electron microscopy (TEM), and X-ray diffraction were used to investigate an AgNPs/GO/chitosan nanocomposite (XRD). A number of studies must be run to determine the optimal pH, adsorbent quantity, retention period, stirring speed, temperature, and initial concentration. The studies were conducted in a variety of ways. The isotherms of Langmuir, Freundlich, and Dubinin-Radushkevich were utilized. The industrial wastewater was used in the column adsorption experiment, and the flow rates and column bed heights were varied. An optimum contact time, pH, and adsorbent dosage for Mn(ii) were determined. At 30 minutes, pH 6, and 0.05 grams of Mn(ii) adsorbent per 100 ml, with agitation at 250 rpm, room temperature of 30 °C, and an initial concentration of 40 ppm, the best conditions were discovered. A positive correlation coefficient finding (R 2 = 0.925) indicates a good fit for Mn, according to equilibrium studies (II). The pseudo-second-order active model was connected to data that suited the pseudo-first and pseudo-second-order models. In the intra-particle diffusion model, the mechanism must proceed through four phases before equilibrium is reached. In an industrial adsorbent column, the adsorbent was put to the test. The periodicity test demonstrates that the nanocomposite's adsorption capability can be recovered by washing it with 0.1 M HCl. Mn(ii) adsorbed on AgNPs/GO/Chitosan after four cycles was only 20%, insufficient for additional adsorption tests. The repeated cycles that led to the partial loss of the adsorbate may have reduced the adsorbent material's efficacy.

Fe(iii) and Cr(vi) ions' removal using AgNPs/GO/chitosan nanocomposite as an adsorbent for wastewater treatment.

Heavy metal ions in water refer to significant risks to the biological system due to their high toxicity. Therefore, the decontamination of water polluted by heavy metal ions attracts significant interest of researchers. Adsorption by nanomaterials has been a widely used technique for removing heavy metal ions from water. Chitosan was extracted from shrimp shellfish and mixed with laboratory-prepared AgNPs/GO in the ratio of 3 : 1. A series of tests evaluates the best condition of pH, amount of adsorbent, retention time, stirring speed, temp, and initial concentration. The research was conducted under various conditions. Langmuir, Freundlich, Tempkin, and Dubinin-Radushkevich isotherms were also tested. Also, the column adsorption experiment was carried out on industrial wastewater at different flow rates and column bed heights. The optimal values of the contact time, pH, and adsorbent dose of Cr(vi) were found to be 80 min, 4, and 0.1 g 100 mL-1, respectively, at room temperature (30 °C), agitation at 150 rpm, and initial concentration of 50 ppm. On the other hand, the optimal value of contact time, pH, and adsorbent dose of Fe(iii) were found to be 30 min, 6, and 0.02 g 100 mL-1, respectively, at room temp (30 °C) with a stirring speed of 250 rpm and an initial concentration of 40 ppm. For Cr(vi) and Fe(iii), equilibrium studies show that the data fit the Freundlich isotherm well (correlation coefficient, R 2 = 0.98) (III). A link between the pseudo-second order active model and data fitting the pseudo-first order active models were made. Within the intraparticle diffusion model, there are four stages that the mechanism must go through before it is at equilibrium. The adsorbent was tested in an industrial adsorbent column. This test proves that the nanocomposite's adsorption capacity can be restored by washing it with 0.1 M HCl, as shown by the periodicity test. After four cycles, the amount of Cr(vi) adsorbed on AgNPs/GO/chitosan was just 20%, which is insufficient for further adsorption experiments. Cr(vi) removal rates (%R) decreased slightly.

Protocol for SARS-CoV-2 post-vaccine surveillance study in Australian adults and children with cancer: an observational study of safety and serological and immunological response to SARS-CoV-2 vaccination (SerOzNET).

BACKGROUND: Cancer is associated with excess morbidity and mortality from coronavirus disease 2019 (COVID-19) following infection by the novel pandemic coronavirus SARS-CoV-2. Vaccinations against SARS-CoV-2 have been rapidly developed and proved highly effective in reducing the incidence of severe COVID-19 in clinical trials of healthy populations. However, patients with cancer were excluded from pivotal clinical trials. Early data suggest that vaccine response is less robust in patients with immunosuppressive conditions or treatments, while toxicity and acceptability of COVID-19 vaccines in the cancer population is unknown. Unanswered questions remain about the impact of various cancer characteristics (such as treatment modality and degree of immunosuppression) on serological response to and safety of COVID-19 vaccinations. Furthermore, as the virus and disease manifestations evolve, ongoing data is required to address the impact of new variants. METHODS: SerOzNET is a prospective observational study of adults and children with cancer undergoing routine SARS-CoV-2 vaccination in Australia. Peripheral blood will be collected and processed at five timepoints (one pre-vaccination and four post-vaccination) for analysis of serologic responses to vaccine and exploration of T-cell immune correlates. Cohorts include: solid organ cancer (SOC) or haematological malignancy (HM) patients currently receiving (1) chemotherapy, (2) immune checkpoint inhibitors (3) hormonal or targeted therapy; (4) patients who completed chemotherapy within 6-12 months of vaccination; (5) HM patients with conditions associated with hypogammaglobulinaemia or immunocompromise; (6) SOC or HM patients with allergy to PEG or polysorbate 80. Data from healthy controls already enrolled on several parallel studies with comparable time points will be used for comparison. For children, patients with current or prior cancer who have not received recent systemic therapy will act as controls. Standardised scales for quality-of-life assessment, patient-reported toxicity and vaccine hesitancy will be obtained. DISCUSSION: The SerOzNET study was commenced in June 2021 to prospectively study immune correlates of vaccination in specific cancer cohorts. The high proportion of the Australian population naïve to COVID-19 infection and vaccination at study commencement has allowed a unique window of opportunity to study vaccine-related immunity. Quality of life and patient-reported adverse events have not yet been reported in detail post-vaccination for cancer patients. Trial registration This trial is registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001004853. Submitted for registration 25 June 2021. Registered 30 July 2021 (Retrospectively registered). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382281&isReview=true.

Bio-cleaning Efficiency of Rhamnolipids Produced from Native Pseudomonas aeruginosa Grown on Agro-industrial By-products for Liquid Detergent Formulation.

The cleaning activity of surface-active agents such as rhamnolipids (RLs) requires utmost effectiveness and is employed abundantly in various industries, particularly laundry cleaning, detergents, and cosmetics. In the current study, RLs were produced from Pseudomonas aeruginosa isolated from oil-contaminated soil using a minimal medium amended with agro-industrial by-products of refinery vegetable oil wastes (comprising of unsaturated types of fatty acids as determined by GC analysis) and dairy whey. The results showed that an amount of 5.72 g/L of RLs were obtained, while lower concentrations were obtained using chemically defined carbon sources. Ten congeners of mono- and di-RLs were detected by LC-MS, and they reduced the surface tension of water to 26 mN/m with a critical micelle concentration of 33 mg/L. Furthermore, the produced RLs showed promising cleaning and detergency properties in the removal of different stains on tested fabrics with a Stain Removal Index (SRI) of 17.45%. Moreover, an efficient cleaning was obtained when RLs were applied to a liquid detergent formulation model, and a cleaning power (∆E) of 245.95 and SRI of 36.28% were achieved. The present work showed that the produced RLs could be exploited as a powerful and alternative eco-friendly cleaning agent in many industries.

T-ALL can evolve to oncogene independence.

The majority of cases of T-cell acute lymphoblastic leukemia (T-ALL) contain chromosomal abnormalities that drive overexpression of oncogenic transcription factors. However, whether these initiating oncogenes are required for leukemia maintenance is poorly understood. To address this, we developed a tetracycline-regulated mouse model of T-ALL driven by the oncogenic transcription factor Lmo2. This revealed that whilst thymus-resident pre-Leukemic Stem Cells (pre-LSCs) required continuous Lmo2 expression, the majority of leukemias relapsed despite Lmo2 withdrawal. Relapse was associated with a mature phenotype and frequent mutation or loss of tumor suppressor genes including Ikzf1 (Ikaros), with targeted deletion Ikzf1 being sufficient to transform Lmo2-dependent leukemias to Lmo2-independence. Moreover, we found that the related transcription factor TAL1 was dispensable in several human T-ALL cell lines that contain SIL-TAL1 chromosomal deletions driving its overexpression, indicating that evolution to oncogene independence can also occur in human T-ALL. Together these results indicate an evolution of oncogene addiction in murine and human T-ALL and show that loss of Ikaros is a mechanism that can promote self-renewal of T-ALL lymphoblasts in the absence of an initiating oncogenic transcription factor.

Anti-quorum sensing activity of some marine bacteria isolated from different marine resources in Egypt.

OBJECTIVES: To screen for a variety of marine bacteria with anti-quorum sensing and anti-biofilm activities. RESULTS: Among 188 bacterial isolates from water, sediment, and corals in the Red Sea region, approximately 35% (65 isolates) of the isolates displayed a significant degradation in the purple pigment of the bioreporter strain without affecting cell growth. The quorum quenching bacteria obtained from coral-associated bacteria were 66.2% out of the total isolates. The PCR amplification results revealed that the recorded Acyl Homoserine lactone (AHL) inhibition by 91% of the anti-QS marine bacteria was not due to lactonase activity. On the other hand, lactonase genes were recorded only in the remaining 9% (6 isolates) and those were belonging to genus Bacillus, Nocardiopsis, and Enterobacter based on 16S rRNA gene sequences. The results also showed that marine bacteria with anti-QS activity inhibited 67% of the biofilm formed by Aeromonas hydrophila, Pseudomonas aeruginosa, and Vibrio alginolyticus. The computational profiling analysis confirmed the presence of the functional region in the detected genes. CONCLUSION: Coral microbial communities are rich sources for pharmacologically important natural products with anti-quorum sensing and anti-biofilm activities.

An integrated bioaugmentation/electrocoagulation concept for olive mill wastewater management and the reuse in irrigation of biofuel plants: a pilot study.

A consortium of highly degrading microorganisms was used in an integrated bioaugmentation/electrocoagulation process for treating olive mill wastewater. The system was investigated for treating 1 m3 day-1, at a pilot scale, for 2 years; hydraulic loading rate and organic loading rate were 2880 l m-2 day-1 and 37,930 g COD m-2 day-1, respectively. Average removal efficiency for COD, oils, and total phenols was 63.9%, 85.2%, and 43.6%, respectively. The olive mill consortium, OMC, consisted of seven actinomycete strains. The strains were confirmed, by 16S rDNA analysis, to belong to five Streptomyces, one Kitasatospora, and one Micromonospora strains, at 100-99.06% similarities. Hydrolytic enzyme activities of OMC strains were remarkably higher for degrading cellulosic and lipid constituents (enzyme-cumulative indices, 14-16.1), than the phenolic constituents (indices, 4.1-6.5). The establishment of actinomycetes in the treatment system was indicated by their increased counts in the biofilm at the end of the biofilter, reaching 13-fold higher than that in the control bed. The treated effluent was toxic to the seedlings of Jatropha curcas (Jatropha) and Simmondsia chinensis (Jojoba). Though its application in irrigation of 3-year-old Jatropha shrubs, significantly, enhanced the fruit yield up to 1.85-fold higher than the control, without affecting the seed oil content, after 3-month application, the irrigated soil showed insignificant changes in its biochemical properties. This developed bioaugmentation/electrocoagulation process can treat wastewater with extremely high organic strength, while its approximate construction and operational costs are limited to 0.03 and 0.51 US$ m-3, respectively. It produces a treated effluent that can be reused in irrigation of specific plants. Graphical abstract.

Bioweathering and biotransformation of granitic rock minerals by actinomycetes.

Actinomycetes inhabiting granitic rocks at St. Katherine, Egypt were investigated for their bioweathering potential. Actinomycete counts ranged between 174 and 360 colony forming units per gram. Counts were positively correlated to rock porosity (r = 0.65) and negatively correlated to rock salinity (r = -0.56). Sixty-six actinomycete isolates originating from rocks could be assigned into eight genera, with a high frequency of Nocardioides and Streptomyces. Organic acids were produced by 97% of the isolates. Strains belonging to Actinopolyspora, Actinomadura, Kitasatospora, Nocardioides, and Kibdelosporangium showed the highest acid production indices. Representatives from all eight genera could precipitate metals Cu, Fe, Zn, Cd, and Ag up to concentrations of 2.5 mM each. An actinomycete consortium of two Nocardioides strains and one Kibdelosporangium strain was studied for its potential to cause rock weathering in batch experiments. Results indicated a high ability of the consortium to leach the metals Cu, Zn, and Fe up to 2.6-, 2.1-, and 1.3-fold, respectively, compared to the control after 4 weeks. The pH significantly decreased after 1 week, which was parallel to an increased release of phosphate and sulfate reaching a 2.2- and 2.5-fold increase, respectively, compared to control. Highly significant weight loss (p = 0.005) was achieved by the consortium, indicating a potential multiple role of actinomycetes in weathering by acid production, metal leaching, and solubilization of phosphate and sulfate. This study emphasizes the diverse and unique abilities of actinomycetes inhabiting rock surfaces which could be of potential biotechnological applications, such as in the bioremediation of metal-contaminated environments and metal biorecovery.

Characterisation of actinomycetes isolated from ancient stone and their potential for deterioration.

Actinomycetes have been isolated from decayed and sound stone samples taken from a tomb site at Tell Basta, Zagazig City, Egypt. A total of 160 isolates have been characterised. The numbers and distribution of actinomycetes were studied during different seasons; during the winter months (18-20 degrees C), actinomycete numbers ranged from 10(3) to 10(4) cfu/g; in the summer (28-38 degrees C) lower counts were recorded. The actinomycete isolates were assigned to 4 different taxonomic groups: 54% belonged to the Streptomyces group, 26% to the Nocardia group, 14% showed the characteristics of the Micromonospora group, while the rest of the isolates analyzed (6%) were assigned to the sporangiate-type group of actinomycetes. The ability of the isolates to produce pigments as well as tolerance to high salinity were determined. It was shown that about 88% of the strains studied had the ability to produce extracellular pigments. Only 25% of the studied isolates showed tolerance to high salinity. The significance of actinomycetes to attack and degrade building stone was shown in laboratory experiments: actinomycetes recovered both from sound and decayed stones were capable of damaging stone under laboratory conditions as an up to 4% weight loss was recorded for some isolates.

Actinomycetes in rice straw decomposition.

Actinomycetes are well known as lignocellulose decomposers. Forty-two cellulolytic actinomycete isolates have been recovered from soil. Those were identified to the genus level as: Streptomyces (26 isolates), Nocardiopsis (5 isolates), Micromonospora (4 isolates), Nocardioides (4 isolates) in addition to three isolates tentatively identified as Nocardia, Kibdelosporangium and Saccharomonospora. These actinomycetes were examined for their cellulolytic activity using filter paper strips and rice straw pieces. Four isolates of the four genera Kibdelosporangium, Micromonospora, Streptomyces and Nocardioides were able to efficiently degrade rice straw pieces in minimal medium causing significant weight loss between 50 and 61%. Application of this knowledge may improve the management of waste rice straw.