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Cancer genomes are rife with genetic variants; one key outcome of this variation is widespread gain-of-cysteine mutations. These acquired cysteines can be both driver mutations and sites targeted by precision therapies. However, despite their ubiquity, nearly all acquired cysteines remain unidentified via chemoproteomics; identification is a critical step to enable functional analysis, including assessment of potential druggability and susceptibility to oxidation. Here, we pair cysteine chemoproteomics-a technique that enables proteome-wide pinpointing of functional, redox sensitive, and potentially druggable residues-with genomics to reveal the hidden landscape of cysteine genetic variation. Our chemoproteogenomics platform integrates chemoproteomic, whole exome, and RNA-seq data, with a customized two-stage false discovery rate (FDR) error controlled proteomic search, which is further enhanced with a user-friendly FragPipe interface. Chemoproteogenomics analysis reveals that cysteine acquisition is a ubiquitous feature of both healthy and cancer genomes that is further elevated in the context of decreased DNA repair. Reference cysteines proximal to missense variants are also found to be pervasive, supporting heretofore untapped opportunities for variant-specific chemical probe development campaigns. As chemoproteogenomics is further distinguished by sample-matched combinatorial variant databases and is compatible with redox proteomics and small molecule screening, we expect widespread utility in guiding proteoform-specific biology and therapeutic discovery.

An electrophilic arginine mimetic, 2-chloroacetamidine (CAM), was deployed to enable trypsin-mediated proteolysis at cysteine residues and to enhance mass spectrometry-based proteomic detection of cysteine-containing peptides. Illustrating the value of the CAM-capping strategy, proteogenomic analysis using a two-stage false discovery rate (FDR) search revealed 450% enhanced coverage of missense variants, when compared to established workflows. [ABSTRACT FROM AUTHOR]

This paper is devoted to characterizing the boundedness of the Riemann-Stieltjes operators from analytic Morrey spaces to Bloch-type spaces. Moreover, the boundedness of the superposition operator and weighted composition operator on analytic Morrey spaces is discussed, respectively.

Among the several threats to the conservation of mangrove ecosystems in most South Asian countries, shrimp farming is predominant. Since the introduction of shrimp farming in Sri Lanka in the 1980s, mangroves on the island's north‐western coast have been continually cleared to create new shrimp farms, leading to a decline in the social‐ecological services provided by the mangrove ecosystems.Using aerial (1973) and satellite (1996–2020) images, this study assessed areal changes in mangroves and shrimp farms in the Pambala‐Chilaw lagoon complex and Ihala Mahawewa, as well as the ecological footprint of shrimp farming in the study area.Mangroves around the Chilaw lagoon had decreased in areal extent by 45% from 1973 to 2020 of which 92% of this change was attributed to shrimp farming. There was, however, a decrease in the areal extent of shrimp farms from 2001 to 2020, and a corresponding increase in mangroves from 2006 to 2020.The ecological footprint of shrimp farming was assessed by comparing the expected surface ratios with those recorded for shrimp farms with mangroves and surface water bodies in the study area from 1973 to 2020. The results showed that the current shrimp farming was unsustainable (i.e. high ecological footprint).While the results support the current view that there is cause for cautious optimism with mangrove conservation (as evidenced by an increase in mangrove areal extent), it also reveals that semi‐intensive shrimp farming in Sri Lanka and probably other similar tropical countries is unsustainable.If immediate actions such as effective regulation of shrimp farming activities and mangrove restoration are not taken, the mangrove ecosystem will continue to decline. [ABSTRACT FROM AUTHOR]