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Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics.

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell-cell interactions that initiate and regulate the host response and modulates the effects of antibodies and soluble immune mediators. This perspective reports on a workshop organized jointly by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research in May 2020. The conference addressed the use of emerging glycoscience tools and resources to advance investigation of glycans and their roles in microbe-host interactions, immune-mediated diseases, and immune cell recognition and function. Future discoveries in these areas will increase fundamental scientific understanding and have the potential to improve diagnosis and treatment of infections and immune dysregulation.

C-Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging-related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide susceptibility to C-terminal cyclic imide formation or their effect on protein stability have not been explored in detail. Here, we characterize the primary and secondary structures of peptides and proteins that promote intrinsic formation of C-terminal cyclic imides in comparison to deamidation, a related form of protein damage. Extrinsic effects from solution properties and stressors on the cellular proteome additionally promote C-terminal cyclic imide formation on proteins like glutathione synthetase that are susceptible to aggregation if the protein damage products are not removed by CRBN. This systematic investigation provides insight into the regions of the proteome that are prone to these unexpectedly frequent modifications, the effects of this form of protein damage on protein stability, and the biological role of CRBN. [ABSTRACT FROM AUTHOR]

This form, used at UCI from September 2005 through September 2012, was based on the form used at UCLA. The form was opened as part of the morning's login at the reference desks. Reference activitives were recorded throughout the day; the form was closed when the reference desk closed. Langson Library reference had separate forms for ON and OFF the desk statistics, as did the reference desks in the other UCI Libraries,

All libraries confront the three Uh-Ohs of collections: overcrowding, out-of-date, out-of-scope. Instead of weeding in response to crises, we weed year-round. With little foreseeable growth in shelf space and a chronic need for more space, we are complementing collection growth with ongoing deselection.To formulate sustainable and acceptable solutions to librarians and constituents across disciplines, UCI Libraries use a combination of technology and disciplinary knowledge to identify low-use and duplicate-format material. We developed and shared our different strategies for overcoming obstacles and unforeseen challenges. We created a unique and coordinated approach to rotate weeding among librarians. We show how organizations might replicate our success through communication and coordination among bibliographers and technical services. We will share the issues and the solutions, including planning, matching weeding styles to client needs, disciplinary strategies of viewing colletions, scheduling, and workflows.

In this issue of Molecular Cell , Yoshida et al. 1 report an unconventional sugar-dependent ubiquitination event on Nrf1 that disrupts Nrf1 transcriptional activation. In this issue of Molecular Cell , Yoshida et al.1 report an unconventional sugar-dependent ubiquitination event on Nrf1 that disrupts Nrf1 transcriptional activation. [ABSTRACT FROM AUTHOR]

The University of California, Irvine ADD Center recently conducted a synthesis of the literature on the use of stimulants with children with attention deficit disorder (ADD), using a unique “review of reviews” methodology. In this article, we compare three reviews from each of three review types (traditional, meta-analytic, general audience) and illustrate how coding variables can highlight sources of divergence. In general, divergent conclusions stemmed from variations in goal rather than from variations in the sources selected to review. Across quantitative reviews, the average effect size for symptomatic improvement (.83) was twice that for benefits on IQ and achievement measures (.35). A summary of what should and should not be expected of the use of stimulants with ADD children, derived from the literature synthesis, is provided. © 1993, Council for Exceptional Children. All rights reserved.

Photoaffinity labeling (PAL) is one of the few biochemical techniques that can give direct evidence of biomolecular interactions in cells. Several photoactivatable functional groups have been adapted for use in PAL since its first implementation. The diversity of these chemistries has expanded the scope and fidelity of PAL experiments, but also increased the considerations during PAL probe design. In this review, we describe the major chemistries used in PAL experiments and their relative benefits and disadvantages. We additionally discuss recent examples of PAL experiments and provide recommendations on how to design a PAL probe. [ABSTRACT FROM AUTHOR]

Cells use many post-translational modifications (PTMs) to tailor proteins and transduce cellular signals. Recent years have witnessed the rapid growth of small molecule and enzymatic strategies to purposely manipulate one particular PTM, ubiquitination, on desired target proteins in cells. These approaches typically act by induced proximity between an E3 ligase and a target protein resulting in ubiquitination and degradation of the substrate in cells. In this review, we cover recent approaches to study molecular degraders and discover their induced substrates in vitro and in live cells. Methods that have been adapted and applied to the development of molecular degraders are described, including global proteomics, affinity-purification, chemical proteomics and enzymatic strategies. Extension of these strategies to edit additional PTMs in cells is also discussed. This review is intended to assist researchers who are interested in editing PTMs with new modalities to select suitable method(s) and guide their studies. [ABSTRACT FROM AUTHOR]

Zhu and Hart 1 use dual-specificity RNA aptamers to recruit cellular O-GlcNAc transferase (OGT) and induce O-GlcNAc on target proteins like β-catenin, revealing that O-GlcNAc stabilizes β-catenin and enhances its transcriptional activity. Zhu and Hart1 use dual-specificity RNA aptamers to recruit cellular O-GlcNAc transferase (OGT) and induce O-GlcNAc on target proteins like β-catenin, revealing that O-GlcNAc stabilizes β-catenin and enhances its transcriptional activity. [ABSTRACT FROM AUTHOR]

O-linked N-acetylglucosamine (O-GlcNAc) is a widespread reversible modification on nucleocytoplasmic proteins that plays an important role in many biochemical processes and is highly relevant to numerous human diseases. The O-GlcNAc modification has diverse functional impacts on individual proteins and glycosites, and methods for editing this modification on substrates are essential to decipher these functions. Herein, we review recent progress in developing methods for O-GlcNAc regulation, with a focus on methods for editing O-GlcNAc with protein- and site-selectivity in cells. The applications, advantages, and limitations of currently available strategies for writing and erasing OGlcNAc and future directions are also discussed. These emerging approaches to manipulate O-GlcNAc on a target protein in cells will greatly accelerate the development of functional studies and enable therapeutic interventions in the O-GlcNAc field. [ABSTRACT FROM AUTHOR]

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell–cell interactions that initiate and regulate the host response and modulates the effects of antibodies and soluble immune mediators. This perspective reports on a workshop organized jointly by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research in May 2020. The conference addressed the use of emerging glycoscience tools and resources to advance investigation of glycans and their roles in microbe-host interactions, immune-mediated diseases, and immune cell recognition and function. Future discoveries in these areas will increase fundamental scientific understanding and have the potential to improve diagnosis and treatment of infections and immune dysregulation. [ABSTRACT FROM AUTHOR]

Sanglifehrin A and B are immunosuppressive macrocyclic natural products endowed with and differentiated by a unique spirocyclic lactam. Herein, we report an enantioselective total synthesis and biological evaluation of sanglifehrin A and B and analogs. Access to the spirocyclic lactam was achieved through convergent assembly of a key pyranone intermediate followed by a stereo‐controlled spirocyclization. The 22‐membered macrocyclic core was synthesized by ring‐closing metathesis in the presence of 2,6‐bis(trifluoromethyl) benzeneboronic acid (BFBB). The spirocyclic lactam and macrocycle fragments were united by a Stille coupling to furnish sanglifehrin A and B. Additional sanglifehrin B analogs with variation at the C40 position were additionally prepared. Biological evaluation revealed that the 2‐CF3 analog of sanglifehrin B exhibited higher anti‐proliferative activity than the natural products sanglifehrin A and B in Jurkat cells. Both natural products induced higher‐order homodimerization of cyclophilin A (CypA), but only sanglifehrin A promoted CypA complexation with inosine‐5′‐monophosphate dehydrogenase 2 (IMPDH2). The synthesis reported herein will enable further evaluation of the spirolactam and its contribution to sanglifehrin‐dependent immunosuppressive activity. [ABSTRACT FROM AUTHOR]

Enantioselective synthetic route is described for the complex anticancer antimicrobial agent kinamycin F, where the success of the route is the development of a three-step sequence for construction of the diazonapthoquinone function of the natural product. Ortho-quinone methide intermediates, formed by the reduction and loss of dinitrogen from kinamycin F, are formed in vivo and the method has provided a synthetic pathway to these compounds.