Coronavirus malware is sweeping the online world with hackers taking advantage of the borderline panic that is gripping the world in the wake of COVID-19. The new threats themed after COVID-19 and preying on people's fears range from ransomware to info-stealer Trojans and are spread through every infection vector imaginable.

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TORONTO – The Ontario Securities Commission (OSC) is warning the public about aggressive promotion of Crestview Exploration Inc.

An ongoing threat campaign dubbed VEILDrive has been observed taking advantage of legitimate services from Microsoft, including Teams, SharePoint, Quick Assist, and OneDrive, as part of its modus operandi. "Leveraging Microsoft SaaS services — including Teams, SharePoint, Quick Assist, and OneDrive — the attacker exploited the trusted infrastructures of previously compromised organizations to

An ongoing phishing campaign is employing copyright infringement-related themes to trick victims into downloading a newer version of the Rhadamanthys information stealer since July 2024. Cybersecurity firm Check Point is tracking the large-scale campaign under the name CopyRh(ight)adamantys. Targeted regions include the United States, Europe, East Asia, and South America. "The campaign

Cybersecurity researchers have flagged a new ransomware family called Ymir that was deployed in an attack two days after systems were compromised by a stealer malware called RustyStealer. "Ymir ransomware introduces a unique combination of technical features and tactics that enhance its effectiveness," Russian cybersecurity vendor Kaspersky said. "Threat actors leveraged an unconventional blend

Deeply worried about Beijing's insatiable desire for land and the way its military has occupied areas by stealth, Washington has sent three warships to the region.

Deeply worried about Beijing's insatiable desire for land and the way its military has occupied areas by stealth, Washington has sent three warships to the region.

HAMPSHIRE racing starlet Brody Crockford has followed in his father’s tyre marks after completing his debut MiniGP50 Motorcycle British Championship in spectacular style.

There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor–targeted therapies. In this study, we exploit context-dependent differences in RNA polymerase II processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1–targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels insufficient to inhibit EWS-FLI1. In this study, we perform an siRNA screen of the druggable genome followed by a matrix drug screen to identify mithramycin potentiators and a synergistic "class" effect with cyclin-dependent kinase 9 (CDK9) inhibitors. These CDK9 inhibitors enhanced the mithramycin-mediated suppression of the EWS-FLI1 transcriptional program leading to a shift in the IC₅₀ and striking regressions of Ewing sarcoma xenografts. To determine whether these compounds may also be liver protective, we performed a qPCR screen of all known liver toxicity genes in HepG2 cells to identify mithramycin-driven transcriptional changes that contribute to the liver toxicity. Mithramycin induces expression of the BTG2 gene in HepG2 but not Ewing sarcoma cells, which leads to a liver-specific accumulation of reactive oxygen species (ROS). siRNA silencing of BTG2 rescues the induction of ROS and the cytotoxicity of mithramycin in these cells. Furthermore, CDK9 inhibition blocked the induction of BTG2 to limit cytotoxicity in HepG2, but not Ewing sarcoma cells. These studies provide the basis for a synergistic and less toxic EWS-FLI1–targeted combination therapy for Ewing sarcoma.

Pseudomonas aeruginosa exploits intrinsic and acquired resistance mechanisms to resist almost every antibiotic used in chemotherapy. Antimicrobial resistance in P. aeruginosa isolates recovered from cystic fibrosis (CF) patients is further enhanced by the occurrence of hypermutator strains, a hallmark of chronic infections in CF patients. However, the within-patient genetic diversity of P. aeruginosa populations related to antibiotic resistance remains unexplored. Here, we show the evolution of the mutational resistome profile of a P. aeruginosa hypermutator lineage by performing longitudinal and transversal analyses of isolates collected from a CF patient throughout 20 years of chronic infection. Our results show the accumulation of thousands of mutations, with an overall evolutionary history characterized by purifying selection. However, mutations in antibiotic resistance genes appear to have been positively selected, driven by antibiotic treatment. Antibiotic resistance increased as infection progressed toward the establishment of a population constituted by genotypically diversified coexisting sublineages, all of which converged to multidrug resistance. These sublineages emerged by parallel evolution through distinct evolutionary pathways, which affected genes of the same functional categories. Interestingly, ampC and ftsI, encoding the β-lactamase and penicillin-binding protein 3, respectively, were found to be among the most frequently mutated genes. In fact, both genes were targeted by multiple independent mutational events, which led to a wide diversity of coexisting alleles underlying β-lactam resistance. Our findings indicate that hypermutators, apart from boosting antibiotic resistance evolution by simultaneously targeting several genes, favor the emergence of adaptive innovative alleles by clustering beneficial/compensatory mutations in the same gene, hence expanding P. aeruginosa strategies for persistence.

Infinity Ward is rolling out a new update for Call of Duty: Modern Warfare and Warzone.

Ronaldo, a five-time Ballon d'Or winner, scored four times during Portugal's 5-1 victory over Lithuania to break Robbie Keane's record for most goals in European Championship qualifiers.

Dewey Library - HQ77.9.C44 2019