Electron transfer in polysaccharide monooxygenase catalysis.

Polysaccharide monooxygenase (PMO) catalysis involves the chemically difficult hydroxylation of unactivated C-H bonds in carbohydrates. The reaction requires reducing equivalents and will utilize either oxygen or hydrogen peroxide as a cosubstrate. Two key mechanistic questions are addressed here: 1) How does the enzyme regulate the timely and tightly controlled electron delivery to the mononuclear copper active site, especially when bound substrate occludes the active site? and 2) How does this electron delivery differ when utilizing oxygen or hydrogen peroxide as a cosubstrate? Using a computational approach, potential paths of electron transfer (ET) to the active site copper ion were identified in a representative AA9 family PMO from (PMO9E).

A hybrid machine learning approach for the personalized prognostication of aggressive skin cancers.

Accurate prognostication guides optimal clinical management in skin cancer. Merkel cell carcinoma (MCC) is the most aggressive form of skin cancer that often presents in advanced stages and is associated with poor survival rates. There are no personalized prognostic tools in use in MCC.

COVID-19 vaccine effectiveness against SARS-CoV-2-confirmed hospitalisation in the eastern part of the WHO European Region (2022-2023): a test-negative case-control study from the EuroSAVE network.

Background: Understanding COVID-19 vaccine effectiveness (VE) in preventing severe disease is critical to inform vaccine policy. We used the test-negative design to estimate VE against SARS-CoV-2-confirmed hospitalisation in adults ≥18 years in the eastern WHO European Region.

Methods: We included patients hospitalised for severe acute respiratory infection (SARI) at sentinel surveillance sites in Albania, Georgia, Kyrgyzstan, North Macedonia, Serbia, and in Kosovo.

Spatiotemporal dynamics of geomorphology, landuse, and storm surge inundation of FDMN settled in Bhasan Char island using geo-spatial techniques.

Bhasan Char has undergone noteworthy transformations in its geographical characteristics since its emergence in 2003. Driven by sediment transported by the Ganges-Brahmaputra-Meghna river system, the island has gradually transitioned from a stretched-out configuration to a more rounded shape primarily due to continuous accretion, while erosion has been minimal since 2012. Currently, the island is being prepared to accommodate over 1 million Forcefully Displaced Myanmar Nationals (FDMN) refugees.

Phosphorylation of 'SDT-like' motifs in ATRX mediates its interaction with the MRN complex and is important for ALT pathway suppression.

Approximately 10-15% of human cancers are telomerase-negative and maintain their telomeres through a recombination-based process known as the alternative lengthening of telomeres (ALT) pathway. Loss of the alpha-thalassemia/mental retardation, X-linked (ATRX) chromatin remodeller is a common event in ALT-positive cancers, but is generally insufficient to drive ALT induction in isolation. We previously demonstrated that ATRX binds to the MRN complex, which is also known to be important in the ALT pathway, but the molecular basis of this interaction remained elusive.