A new and large monofenestratan reveals the evolutionary transition to the pterodactyloid pterosaurs.

For over a century, there was a major gap in our understanding of the evolution of the flying Mesozoic reptiles, the pterosaurs, with a major morphological gap between the early forms and the derived pterodactyloids. Recent discoveries have found a cluster of intermediate forms that have the head and neck of the pterodactyloids but the body of the early grade, yet this still leaves fundamental gaps between these intermediates and both earlier and more derived pterosaurs. Here, we describe a new and large Jurassic pterosaur, Skiphosoura bavarica gen.

Cerebrospinal Fluid and Brain Proteoforms of the Granin Neuropeptide Family in Alzheimer's Disease.

The granin neuropeptide family is composed of acidic secretory signaling molecules that act throughout the nervous system to help modulate synaptic signaling and neural activity. Granin neuropeptides have been shown to be dysregulated in different forms of dementia, including Alzheimer's disease (AD). Recent studies have suggested that the granin neuropeptides and their protease-cleaved bioactive peptides (proteoforms) may act as both powerful drivers of gene expression and as a biomarker of synaptic health in AD.

Tryptophan metabolism is inversely regulated in the tumor and blood of patients with glioblastoma.

Tryptophan (Trp)-catabolic enzymes (TCEs) produce metabolites that activate the aryl hydrocarbon receptor (AHR) and promote tumor progression and immunosuppression in glioblastoma. As therapies targeting TCEs or AHR become available, a better understanding of Trp metabolism is required. The combination of LC-MS/MS with chemical isobaric labeling enabled the simultaneous quantitative comparison of Trp and its amino group-bearing metabolites in multiple samples.

TMTpro: Design, Synthesis, and Initial Evaluation of a Proline-Based Isobaric 16-Plex Tandem Mass Tag Reagent Set.

The design and synthesis of a proline-based reporter isobaric Tandem Mass Tag structure (TMTpro) is presented. An analysis is made of the performance of the new TMTpro tags in comparison with the current commercially available dimethylpiperidine-reporter-based TMT10/11 reagents. The new reporter structure provides a set of 16 tags for use with resolution of 6.

Low-pH Solid-Phase Amino Labeling of Complex Peptide Digests with TMTs Improves Peptide Identification Rates for Multiplexed Global Phosphopeptide Analysis.

We present a novel tandem mass tag solid-phase amino labeling (TMT-SPAL) protocol using reversible immobilization of peptides onto octadecyl-derivatized (C18) solid supports. This method can reduce the number of steps required in complex protocols, saving time and potentially reducing sample loss. In our global phosphopeptide profiling workflow (SysQuant), we can cut 24 h from the protocol while increasing peptide identifications (20%) and reducing side reactions.

Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

Objective: LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application.

Methods: Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis.

Pharmacoproteomic investigation into antidepressant response in two mouse inbred strains.

In this study, we present a pharmacoproteomic investigation of response to antidepressants two inbred strains. Our aim was to uncover molecular mechanisms underlying antidepressant action and identify new biomarkers to determine therapeutic response to two antidepressants with proven efficacy in the treatment of depression but divergent mechanisms of action. Mice were treated with the pro-noradrenergic drug nortriptyline, the pro-serotonergic drug escitalopram or saline.

Breast Cancer Proteomics - Differences in Protein Expression between Estrogen Receptor-Positive and -Negative Tumors Identified by Tandem Mass Tag Technology.

BACKGROUND: Proteomic analysis has become an effective tool in breast cancer research. In this study, we applied the new gel-free tandem mass tag (TMT) reference method for the first time in breast cancer. MATERIALS AND METHODS: Proteomic analysis was used to compare 10 estrogen receptor (ER)-positive and 10 ER-negative samples.