Mass Spectrometry-Based Proteomics for the Masses: Peptide and Protein Identification in the Hunt Laboratory During the 2000's.

There has been a rapid increase in the number of individuals utilizing mass spectrometry-based proteomics to study complex biological systems and questions since the start of the 2000's. Building off the advancements in ionization and liquid chromatography scientists continued to push towards technology that would enable in-depth analysis of biological specimen. Donald F Hunt and the Hunt laboratory were major contributors to this effort with their work on improving upon existing Fourier Transform MS, development of electron transfer dissociation, and continued work on ion-ion reactions to improve intact protein analysis.

The core functions and forms paradigm throughout EPIS: designing and implementing an evidence-based practice with function fidelity.

There are numerous frameworks for implementing evidence-based practices (EBPs) in novel settings to achieve "fidelity." However, identifying appropriate referents for fidelity poses a challenge. The Core Functions and Forms paradigm offers a model that can inform adaptation decisions throughout all phases of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework.

Developing a meta-understanding of 'human aspects' of providing palliative care.

Objectives: Our intention was to develop a meta-understanding of the 'human aspects' of providing palliative care. Integral to developing this meta-understanding was recognising the individuality of people, their varied involvements, situations, understandings, and responses, and the difficulty in stepping back to get a whole view of this while being in the midst of providing palliative care. We intended for this meta-understanding to inform reflections and sense-making conversations related to people's changing situations and diverse needs.

Localized Peritumoral AL Amyloidosis Associated With Mantle Cell Lymphoma With Plasmacytic Differentiation.

Immunoglobulin light chain (AL) amyloidosis is characterized by the deposition of amyloid fibers derived from pathologic immunoglobulin light chains. Although systemic plasma cell neoplasms are the most common cause of AL amyloidosis, a subset of cases is caused by B-cell lymphoproliferative disorders such as lymphoplasmacytic lymphoma or extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Recently, SOX11-negative IGH hypermutated mantle cell lymphoma (MCL) is recognized to show frequent plasmacytic differentiation and indolent clinical course.

Proteomic analysis shows that the main constituent of subepidermal localised cutaneous amyloidosis is not galectin-7.

Lichen or macular localised cutaneous amyloidoses have long been described as keratinic amyloidoses and believed to be due to the deposition of cytokeratin peptides originating from epidermis in the dermal papillae. However, recently it was suggested that galectin-7 is the causative protein for this type of amyloidosis. This was based on the detection of galectin-7 in a biopsy from a patient diagnosed with Bowen's disease and localised cutaneous amyloidosis.

Tyrosine Phosphorylation of the Myosin Regulatory Light Chain Controls Non-muscle Myosin II Assembly and Function in Migrating Cells.

Active non-muscle myosin II (NMII) enables migratory cell polarization and controls dynamic cellular processes, such as focal adhesion formation and turnover and cell division. Filament assembly and force generation depend on NMII activation through the phosphorylation of Ser19 of the regulatory light chain (RLC). Here, we identify amino acid Tyr (Y) 155 of the RLC as a novel regulatory site that spatially controls NMII function.

Mass Spectrometry-Based Method Targeting Ig Variable Regions for Assessment of Minimal Residual Disease in Multiple Myeloma.

Multiple myeloma is a systemic malignancy of monoclonal plasma cells that accounts for 10% of hematologic cancers. With development of highly effective therapies for multiple myeloma, minimal residual disease (MRD) assessment has emerged as an important end point for management decisions. Currently, serologic assays lack the sensitivity for MRD assessment, and invasive bone marrow sampling with flow cytometry or molecular methods has emerged as the gold standard.

Tracking of low disease burden in multiple myeloma: Using mass spectrometry assays in peripheral blood.

Efforts over the last 5 years have demonstrated that it is technically feasible to detect low levels of monoclonal proteins in peripheral blood using mass spectrometry. These methods are based on the fact that an M-protein has a specific amino acid sequence, and therefore, a specific mass. This mass can be tracked over time and can serve as a surrogate marker of the presence of clonal plasma cells.

Fibrinogen alpha amyloidosis: insights from proteomics.

: Systemic amyloidosis is a diverse group of diseases that, although rare, pose a serious health issue and can lead to organ failure and death. Amyloid typing is essential in determining the causative protein and initiating proper treatment. Mass spectrometry-based proteomics is currently the most sensitive and accurate means of typing amyloid.

Chemical Generation of Hydroxyl Radical for Oxidative 'Footprinting'.

Background: For almost four decades, hydroxyl radical chemically generated by Fenton chemistry has been a mainstay for the oxidative 'footprinting' of macromolecules.

Objective: In this article, we start by reviewing the application of chemical generation of hydroxyl radical to the development of oxidative footprinting of DNA and RNA and the subsequent application of the method to oxidative footprinting of proteins. We next discuss a novel strategy for generating hydroxyl radicals by Fenton chemistry that immobilizes catalytic iron on a solid surface (Pyrite Shrink Wrap laminate) for the application of nucleic acid and protein footprinting.

Exosomes Shuttle TREX1-Sensitive IFN-Stimulatory dsDNA from Irradiated Cancer Cells to DCs.

Radiotherapy (RT) used at immunogenic doses leads to accumulation of cytosolic double-stranded DNA (dsDNA) in cancer cells, which activates type I IFN (IFN-I) via the cGAS/STING pathway. Cancer cell-derived IFN-I is required to recruit BATF3-dependent dendritic cells (DC) to poorly immunogenic tumors and trigger antitumor T-cell responses in combination with immune checkpoint blockade. We have previously demonstrated that the exonuclease TREX1 regulates radiation immunogenicity by degrading cytosolic dsDNA.

Responds to the Central Metabolite Pyruvate To Regulate Virulence.

is a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens, must adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environmental signals for pathogenicity, only a limited number of these signals have been investigated in detail for their ability to modulate virulence.

STING Senses Microbial Viability to Orchestrate Stress-Mediated Autophagy of the Endoplasmic Reticulum.

Constitutive cell-autonomous immunity in metazoans predates interferon-inducible immunity and comprises primordial innate defense. Phagocytes mobilize interferon-inducible responses upon engagement of well-characterized signaling pathways by pathogen-associated molecular patterns (PAMPs). The signals controlling deployment of constitutive cell-autonomous responses during infection have remained elusive.

Tobacco cessation in Vietnam: Exploring the role of village health workers.

The purpose of this study was to explore current tobacco use treatment (TUT) practice patterns, and attitudes and beliefs among Village Health Workers (VHWs) about expanding their role to include delivering smoking cessation interventions and the perceived barriers. We conducted a survey of 449 VHWs from 26 communes in Thai Nguyen province, Vietnam. We assessed TUT practice patterns including asking about tobacco use, advising smokers to quit, offering assistance (3As) and attitudes, self-efficacy, and norms related to TUT.

SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin-RING ubiquitin ligase function.

NEDD8 is a ubiquitin-like modifier most well-studied for its role in activating the largest family of ubiquitin E3 ligases, the cullin-RING ligases (CRLs). While many non-cullin neddylation substrates have been proposed over the years, validation of true NEDD8 targets has been challenging, as overexpression of exogenous NEDD8 can trigger NEDD8 conjugation through the ubiquitylation machinery. Here, we developed a deconjugation-resistant form of NEDD8 to stabilize the neddylated form of cullins and other non-cullin substrates.

Phosphoproteomics of Fibroblast Growth Factor 1 (FGF1) Signaling in Chondrocytes: Identifying the Signature of Inhibitory Response.

Fibroblast growth factor (FGF) signaling is vital for many biological processes, beginning with development. The importance of FGF signaling for skeleton formation was first discovered by the analysis of genetic FGFR mutations which cause several bone morphogenetic disorders, including achondroplasia, the most common form of human dwarfism. The formation of the long bones is mediated through proliferation and differentiation of highly specialized cells - chondrocytes.

Using Quantitative Spectrometry to Understand the Influence of Genetics and Nutritional Perturbations On the Virulence Potential of .

() is the leading cause of a variety of bacterial infections ranging from superficial skin infections to invasive and life threatening diseases such as septic bacteremia, necrotizing pneumonia, and endocarditis. The success of as a human pathogen is contributed to its ability to adapt to different environments by changing expression, production, or secretion of virulence factors. Although immune evasion is well-studied, the regulation of virulence factors under different nutrient and growth conditions is still not well understood.

A film set for the elicitation of emotion in research: A comprehensive catalog derived from four decades of investigation.

Emotions are highly influential to many psychological processes. Indeed, research employing emotional stimuli is rapidly escalating across the field of psychology. However, challenges remain regarding discrete evocation of frequently co-elicited emotions such as amusement and happiness, or anger and disgust.

Effectiveness of Delayed Cord Clamping in Reducing Postdelivery Complications in Preterm Infants: A Systematic Review.

This systematic review evaluates the effectiveness of delayed cord clamping in preterm infants on reducing postdelivery complications of anemia, hemodynamic instability, and the development of intraventricular hemorrhages. Interventions included varying durations of delayed cord clamping with and without cord milking as compared with immediate cord clamping, shorter delays in cord clamping, and delayed cord clamping without cord milking. A comprehensive search of randomized controlled trials, observational, cohort, and before-after studies was conducted between 1946 and 2015 in the electronic databases of Ovid MEDLINE, Embase, and Google Scholar.