Analysis of FAIMS for the Study of Affinity-Purified Protein Complexes Using the Orbitrap Ascend Tribrid Mass Spectrometer.

In this study, we analyzed the combination of affinity purification mass spectrometry (AP-MS) with high-field asymmetric waveform ion mobility spectrometry (FAIMS), integrated between nanoLC-MS and an Orbitrap Ascend Tribrid Mass Spectrometer. Our primary objective was to evaluate the application of the FAIMS interface for detecting affinity purified SAP25 protein complexes with enhanced sensitivity and robustness. As a result, we observed that nanoLC-FAIMS-MS (with FAIMS) significantly improved the sensitivity and detection limits at the protein level, peptide level and significantly reduced chemical contaminants compared to nanoLC-MS alone without FAIMS (No FAIMS).

An integrated structural model of the DNA damage-responsive H3K4me3 binding WDR76:SPIN1 complex with the nucleosome.

Serial capture affinity purification (SCAP) is a powerful method to isolate a specific protein complex. When combined with cross-linking mass spectrometry and computational approaches, one can build an integrated structural model of the isolated complex. Here, we applied SCAP to dissect a subpopulation of WDR76 in complex with SPIN1, a histone reader that recognizes trimethylated histone H3 lysine4 (H3K4me3).

Serial Capture Affinity Purification and Integrated Structural Modeling of the H3K4me3 Binding and DNA Damage Related WDR76:SPIN1 Complex.

Unlabelled: WDR76 is a multifunctional protein involved in many cellular functions. With a diverse and complicated protein interaction network, dissecting the structure and function of specific WDR76 complexes is needed. We previously demonstrated the ability of the Serial Capture Affinity Purification (SCAP) method to isolate specific complexes by introducing two proteins of interest as baits at the same time.

SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and caused the devastating global pandemic of coronavirus disease 2019 (COVID-19), in part because of its ability to effectively suppress host cell responses. In rare cases, viral proteins dampen antiviral responses by mimicking critical regions of human histone proteins, particularly those containing post-translational modifications required for transcriptional regulation. Recent work has demonstrated that SARS-CoV-2 markedly disrupts host cell epigenetic regulation.

Assessing the differences in operative and patient-reported outcomes between lateral approaches for lumbar fusion: a systematic review and indirect meta-analysis.

Objective: Anterior-to-psoas lumbar interbody fusion (ATP-LIF), more commonly referred to as oblique lateral interbody fusion, and lateral transpsoas lumbar interbody fusion (LTP-LIF), also known as extreme lateral interbody fusion, are the two commonly used lateral approaches for performing a lumbar fusion procedure. These approaches help overcome some of the technical challenges associated with traditional approaches for lumbar fusion. In this systematic review and indirect meta-analysis, the authors compared operative and patient-reported outcomes between these two select approaches using available studies.

Truncated titin proteins in dilated cardiomyopathy.

Truncating variants in (TTNtvs) are the most common known cause of nonischemic dilated cardiomyopathy (DCM), but how TTNtvs cause disease has remained controversial. Efforts to detect truncated titin proteins in affected human DCM hearts have failed, suggesting that disease is caused by haploinsufficiency, but reduced amounts of titin protein have not yet been demonstrated. Here, we leveraged a collection of 184 explanted posttransplant DCM hearts to show, using specialized electrophoretic gels, Western blotting, allelic phasing, and unbiased proteomics, that truncated titin proteins can quantitatively be detected in human DCM hearts.

Longitudinal Large-Scale Semiquantitative Proteomic Data Stability Across Multiple Instrument Platforms.

With the rapid developments in mass spectrometry (MS)-based proteomics methods, label-free semiquantitative proteomics has become an increasingly popular tool for profiling global protein abundances in an unbiased manner. However, the reproducibility of these data across time and LC-MS platforms is not well characterized. Here, we evaluate the performance of three LC-MS platforms (Orbitrap Elite, Q Exactive HF, and Orbitrap Fusion) in label-free semiquantitative analysis of cell surface proteins over a six-year period.

Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting.

Activating RAS missense mutations are among the most prevalent genomic alterations observed in human cancers and drive oncogenesis in the three most lethal tumor types. Emerging evidence suggests mutant KRAS (mKRAS) may be targeted immunologically, but mKRAS epitopes remain poorly defined. Here we employ a multi-omics approach to characterize HLA class I-restricted mKRAS epitopes.

Outcomes following surgical versus endovascular treatment of spinal dural arteriovenous fistula: a systematic review and meta-analysis.

Although surgical resection is associated with a complete cure in most cases of spinal dural arteriovenous fistulas (SDAVF), there has been an increasing trend towards embolisation. We performed a systematic review and meta-analysis comparing surgical resection with endovascular treatment in terms of success of treatment, rate of recurrence and complications. A literature search was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Comparing outcomes of fusion versus repeat discectomy for recurrent lumbar disc herniation: A systematic review and meta-analysis.

Objectives: Current surgical treatment options for one-time recurrent lumbar disc herniation (RLDH) include repeat discectomy or discectomy supplemented with fusion. Significant contention exists within the surgical spine community with regard to the most effective treatment modality. The objective of this study is to compare reoperation rates and patient reported outcomes following fusion versus repeat discectomy for RLDH.

Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus.

Background: Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia differentially impact males and females and are highly heritable. The ways in which sex and genetic vulnerability influence the pathogenesis of these disorders are not clearly understood. The n-methyl-d-aspartate (NMDA) receptor pathway has been implicated in schizophrenia and autism spectrum disorders and changes dramatically across postnatal development at the level of the GluN2B-GluN2A subunit "switch" (a shift from reliance on GluN2B-containing receptors to reliance on GluN2A-containing receptors).