Significance Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and one deadly types, with a 5-y survival rate below 10%. One reason for this high mortality that PDAC cells have an enhanced ability to survive proliferate despite existing in nutrient-deprived environments. Understanding metabolic rewiring enables nutrient scavenging rapid processing can provide new strategies develop effective treatment options intractable disease. In study, convergent...

Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we showed that lectibody consisting the high-mannose glycan-binding lectin Avaren and human immunoglobulin G1 (IgG1) Fc (AvFc) selectively recognizes range cell lines derived from lung, breast, colon, blood cancers at nanomolar concentrations. Binding AvFc to non-small lung (NSCLC) A549 H460 was characterized in detail. Co-immunoprecipitation proteomics...

Summary Phytochrome A (phyA) plays a primary role in initiating seedling de‐etiolation and is the only plant photoreceptor known to be activated by far‐red light (FR). The signaling intermediate FHY1 appears either participate directly relaying phyA signal or positively regulate critical event(s) downstream of activation. Here we identify homolog named FHL (FHY1‐like) as novel factor essential for complete responsiveness phyA. possesses functional nuclear localization export signals. Lines...

Brh2, the BRCA2 homolog in Ustilago maydis, functions recombinational repair of DNA damage by regulating Rad51 and is, turn, regulated Dss1. Dss1 is not required for Brh2 stability vivo, nor to associate with Rad51, but formation green fluorescent protein (GFP)-Rad51 foci following gamma radiation. To understand more about interplay between Dss1, we isolated mutant variants able bypass requirement These were found lack entire C-terminal DNA-Dss1 binding domain maintain N-terminal region...

Abstract Introduction There is an increased need for the development of novel blood‐based biomarkers early detection, prevention, or intervention in Alzheimer's disease (AD). This study sought to determine whether serum glycopeptide analysis holds potential identifying diagnostics and prognostics AD. Methods The involved 195 participants, including 96 patients with AD diagnosis 99 controls no cognitive deficit. Utilizing a validated analytical mass spectrometry method, we monitored...

The molecular complexity of the carbohydrates consumed by humans has been deceptively oversimplified due to a lack analytical methods that possess throughput, sensitivity, and resolution required provide quantitative structural information. However, such information is becoming an integral part understanding how specific glycan structures impact health through their interaction with gut microbiome host physiology. This work presents detailed catalogue glycans present in complementary foods...

Brh2, the BRCA2 ortholog in Ustilago maydis, enables recombinational repair of DNA by controlling Rad51 and is turn regulated Dss1. Interplay with conducted via BRC element located N-terminal region protein through an unrelated domain, CRE, at C terminus. Mutation either or CRE severely reduces functional activity, but deficiency brh2 mutant can be complemented expressing on different molecules. This intermolecular complementation dependent upon presence Brh2 molecules associate overlapping...

Summary Plants use the family of phytochrome photoreceptors to sense their light environment in red/far‐red region spectrum. Phytochrome A (phyA) is primary photoreceptor that regulates germination and early seedling development. This mediates de‐etiolation for developmental transition from heterotrophic photoauxotrophic growth. High intensity far‐red provides a way specifically assess role phyA this process was used isolate phyA‐signaling intermediates. fhy1 pat3 (renamed fhy1‐3 ) are...

Brh2 is the Ustilago maydis ortholog of BRCA2 tumor suppressor. It functions in repair DNA by homologous recombination controlling action Rad51. A critical aspect control appears to be recruitment Rad51 single-stranded regions exposed as lesions after damage or following a disturbance synthesis. In previous experimentation, was shown nucleate formation nucleoprotein filament that becomes active element promoting pairing and strand exchange. Nucleation found initiated at junctions...

Cancer progression is linked to aberrant protein glycosylation due the overexpression of several enzymes. These enzymes are underexploited as potential anticancer drug targets and development rapid-screening methods identification inhibitors highly sought. An integrated bioinformatics mass spectrometry-based glycomics-driven glycoproteomics analysis pipeline was performed identify an N-glycan inhibitor against lung cancer cells. Combined network pharmacology in silico screening approaches...

Lung cancer is the leading cause of death and non-small cell lung carcinoma (NSCLC) accounting for majority cancers. Thus, it important to find potential biomarkers, such as glycans glycoproteins, which can be used diagnostic tools against NSCLC. Here, N-glycome, proteome, N-glycosylation distribution maps tumor peritumoral tissues Filipino patients (n = 5) were characterized. We present several case studies with varying stages development (I−III), mutation status (EGFR, ALK), biomarker...

A single Rad52-related protein is evident by blast analysis of the Ustilago maydis genome database. Mutants created disruption structural gene exhibited few discernible defects in resistance to UV, ionizing radiation, chemical alkylating or cross-linking agents. No deficiency was noted spontaneous mutator activity, allelic recombination meiosis. GFP-Rad51 foci were formed rad52 cells following DNA damage, but initially less intense than normal suggesting a possible role for Rad52 formation...

The C-terminal region of Brh2 (Brh2(CT)), the BRCA2 homolog in Ustilago maydis, is highly conserved and aligns with DSS1/DNA-binding domain (DBD) mammalian BRCA2, while N-terminal (Brh2(NT)) poorly has no obvious functional except for single Rad51-interacting BRC element. Paradoxically, Brh2(NT), but not Brh2(CT), complements DNA repair recombination deficiency brh2 mutant. We show here that Brh2(NT) exhibits an unexpected binding activity properties similar to full-length protein. Deletion...

Aberrant glycosylation has been extensively reported in cancer, with fundamental changes the patterns of cell-surface and secreted proteins largely occurring during cancer progression. As such, serum glycan glycopeptide biomarkers have discovered using mass spectrometry proposed for detection. Here, we report first time potential N-glycan Philippine lung patients. The glycoprotein profiles a cohort (n = 26 patients, n 22 age- gender-matched) patients were analyzed compared to identify...

Brh2, the BRCA2 homologue in Ustilago maydis, plays a crucial role homologous recombination by controlling Rad51. In turn, Brh2 is governed Dss1, an intrinsically disordered protein that forms tight complex with C-terminal region of Brh2. This associating Dss1 highly conserved sequence and comparison mammalian corresponds to part DNA binding domain characteristic OB folds. The N-terminal harbors less-defined but powerful site, activity which revealed upon deletion region. Full-length...

Summary Brh2, a member of the BRCA2 family proteins, governs homologous recombination in fungus Ustilago maydis through interaction with Rad51. Brh2 serves at an early step to mediate Rad51 nucleoprotein filament formation and also has capability function later its inherent DNA annealing activity. Rec2, paralogue, Rad52 are additional components system, but absence either is less critical than for operational Here we tested variety mutant forms activity recombinational repair as measured by...

Rec2 is the single Rad51 paralog in Ustilago maydis. Here, we find that required for radiation-induced nuclear focus formation but foci form independently of and Brh2. Brh2 also absence Rec2. By coprecipitation from cleared extracts prepared Escherichia coli cells expressing proteins, found interacts physically not only with itself Transgenic expression rec2 mutants can effectively restore radiation resistance, frequencies spontaneous allelic recombination are elevated. The Dss1-independent...

Glycomic profiling methods were used to determine the effect of metabolic inhibitors on glycan production. These are commonly alter cell surface glycosylation. However, structural analysis released glycans has been limited. In this research, membranes enriched and obtain N-glycans glycocalyx. using liquid chromatography–mass spectrometry (LC–MS) with a PGC chip column was profile structures in membrane. Glycans untreated cells compared treated inhibitors, including kifunensine, which...

Brh2, the ortholog of BRCA2 tumor suppressor in Ustilago maydis, works hand with Rad51 to promote repair DNA by homologous recombination. Previous studies established that Brh2 can stimulate strand exchange enabling nucleoprotein filament formation on replication protein A-coated ssDNA. But, more recently, it was noted has an inherent annealing activity, raising notion might have roles recombination addition or beyond mediator function. Here, we found autonomously D-loops reactions plasmid...

N-Glycosylations are an important post-translational modification of proteins that can significantly impact cell function. Terminal sialic acid in hybrid or complex N-glycans has been shown to be relevant various types cancer, but its role non-malignant cells remains poorly understood. We have previously the motility human bone marrow derived mesenchymal stromal (MSCs) modified by altering N-glycoforms. The goal this study was determine sialylated MSCs. Here, we show IFN-gamma exposure...

Dss1 is an intrinsically unstructured polypeptide that partners with the much larger Brh2 protein, BRCA2 ortholog in Ustilago maydis, to form a tight complex. Mutants lacking have essentially same phenotype as mutants defective Brh2, implying through physical interaction serves positive activator of Brh2. associates surface carboxy-terminal region. Certain derivatives this remain highly competent DNA repair long DNA-binding domain present. However, Dss1-independent activity raises question...

A multi-glycomic method for characterizing the glycocalyx was employed to identify difference between 2-dimensional (2D) and 3-dimensional (3D) culture models with two human colorectal cancer cell lines, HCT116 HT29. 3D cultures are considered more representative of due their ability mimic microenvironment found in tumors. For this reason, they have become an important tool research. Cell-cell interactions increase compared 2D, indeed significant glycomic changes were observed each line....