"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction".

Background: Patient-derived organoids (PDOs) from advanced colorectal cancer (CRC) patients could be a key platform to predict drug response and discover new biomarkers. We aimed to integrate PDO drug response with multi-omics characterization beyond genomics.

Methods: We generated 29 PDO lines from 22 advanced CRC patients and provided a morphologic, genomic, and transcriptomic characterization.

Cetylpyridinium chloride promotes disaggregation of SARS-CoV-2 virus-like particles.

Background: SARS-CoV-2 is continuously disseminating worldwide. The development of strategies to break transmission is mandatory.

Aim Of The Study: To investigate the potential of cetylpyridinium chloride (CPC) as a viral inhibitor.

Dissecting the individual contribution of conserved cysteines to the redox regulation of RubisCO.

Oxidation of the cysteines from ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) leads to inactivation and promotes structural changes that increase the proteolytic sensitivity and membrane association propensity related to its catabolism. To uncover the individual role of the different cysteines, the sequential order of modification under increasing oxidative conditions was determined using chemical labeling and mass spectrometry. Besides, site-directed RubisCO mutants were obtained in Chlamydomonas reinhardtii replacing single conserved cysteines (Cys84, Cys172, Cys192, Cys247, Cys284, Cys427, Cys459 from the large and sCys41, sCys83 from the small subunit) and the redox properties of the mutant enzymes were determined.

In-Depth Proteomic Characterization of Classical and Non-Classical Monocyte Subsets.

Monocytes are bone marrow-derived leukocytes that are part of the innate immune system. Monocytes are divided into three subsets: classical, intermediate and non-classical, which can be differentiated by their expression of some surface antigens, mainly CD14 and CD16. These cells are key players in the inflammation process underlying the mechanism of many diseases.

Proteomic composition of Nipah virus-like particles.

Unlabelled: Virions are often described as virus-only entities with no cellular components with the exception of the lipids in their membranes. However, advances in proteomics are revealing substantial amounts of host proteins in the viral particles. In the case of Nipah virus (NiV), the viral components in the virion have been known for some time.

A multicentric study to evaluate the use of relative retention times in targeted proteomics.

Unlabelled: Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII).

Detection of Missing Proteins Using the PRIDE Database as a Source of Mass Spectrometry Evidence.

The current catalogue of the human proteome is not yet complete, as experimental proteomics evidence is still elusive for a group of proteins known as the missing proteins. The Human Proteome Project (HPP) has been successfully using technology and bioinformatic resources to improve the characterization of such challenging proteins. In this manuscript, we propose a pipeline starting with the mining of the PRIDE database to select a group of data sets potentially enriched in missing proteins that are subsequently analyzed for protein identification with a method based on the statistical analysis of proteotypic peptides.

Data set of interactomes and metabolic pathways of proteins differentially expressed in brains with Alzheimer׳s disease.

Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease.

Identification of proteins that are differentially expressed in brains with Alzheimer's disease using iTRAQ labeling and tandem mass spectrometry.

Unlabelled: Alzheimer's disease is one of the leading causes of dementia in the elderly. It is considered the result of complex events involving both genetic and environmental factors. To gain further insights into this complexity, we quantitatively analyzed the proteome of cortex region of brains from patients diagnosed with Alzheimer's disease, using a bottom-up proteomics approach.

Data set of the protein expression profiles of Luminal A, Claudin-low and overexpressing HER2(+) breast cancer cell lines by iTRAQ labelling and tandem mass spectrometry.

Breast cancer is the most common and the leading cause of mortality in women worldwide. There is a dire necessity of the identification of novel molecules useful in diagnosis and prognosis. In this work we determined the differentially expression profiles of four breast cancer cell lines compared to a control cell line.

Determination of the protein expression profiles of breast cancer cell lines by quantitative proteomics using iTRAQ labelling and tandem mass spectrometry.

Unlabelled: Breast cancer is the principal cancer in women worldwide. Although there are serum tumor markers such as CEA and HER2, they are detected in advanced stages of the disease and used as progression and recurrence markers. Therefore, there is a necessity for the identification of new markers that might lead to an early detection and also provide evidence of an effective treatment.

Prediction of a missing protein expression map in the context of the human proteome project.

Experimental evidence for the entire human proteome has been defined in the Human Proteome Project, and it is publicly available in the neXtProt database. However, there are still human proteins for which reliable experimental evidence does not exist, and the identification of such information has become one of the overriding objectives in the chromosome-centric study of the human proteome. With this aim and considering the complexity of protein detection using shotgun and targeted proteomics, the research community has addressed the integration of transcriptomics and proteomics landscapes.

Unveiling novel interactions of histone chaperone Asf1 linked to TREX-2 factors Sus1 and Thp1.

Anti-silencing function 1 (Asf1) is a conserved key eukaryotic histone H3/H4 chaperone that participates in a variety of DNA and chromatin-related processes. These include the assembly and disassembly of histones H3 and H4 from chromatin during replication, transcription, and DNA repair. In addition, Asf1 is required for H3K56 acetylation activity dependent on histone acetyltransferase Rtt109.

Surfing transcriptomic landscapes. A step beyond the annotation of chromosome 16 proteome.

The Spanish team of the Human Proteome Project (SpHPP) marked the annotation of Chr16 and data analysis as one of its priorities. Precise annotation of Chromosome 16 proteins according to C-HPP criteria is presented. Moreover, Human Body Map 2.

Identification of polypeptides in neurofibrillary tangles and total homogenates of brains with Alzheimer's disease by tandem mass spectrometry.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD brains are characterized by the presence of neurofibrillary tangles (NFTs) and neuritic plaques. NFTs are constituted of paired helical filaments, which are structurally composed by assembled hyperphosphorylated and truncated tau polypeptides.

Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells.

The study of host-parasite interactions has increased considerably in the last decades, with many studies focusing on the identification of parasite molecules (i.e. surface or excretory/secretory proteins (ESP)) as potential targets for new specific treatments and/or diagnostic tools.

Decoding the folding of Burkholderia glumae lipase: folding intermediates en route to kinetic stability.

The lipase produced by Burkholderia glumae folds spontaneously into an inactive near-native state and requires a periplasmic chaperone to reach its final active and secretion-competent fold. The B. glumae lipase-specific foldase (Lif) is classified as a member of the steric-chaperone family of which the propeptides of α-lytic protease and subtilisin are the best known representatives.

Zygocotyle lunata: proteomic analysis of the adult stage.

The somatic extract of Zygocotyle lunata (Trematoda: Paramphistomidae) adults collected from experimentally infected mice was investigated using a proteomic approach to separate and identify tryptic peptides from the somatic extract of Z. lunata adult worms. A shot-gun liquid chromatography/tandem mass spectrometry procedure was used.

Simple chemical tools to expand the range of proteomics applications.

Proteomics is an expanding technology with potential applications in many research fields. Even though many research groups do not have direct access to its main analytical technique, mass spectrometry, they can interact with proteomics core facilities to incorporate this technology into their projects. Protein identification is the analysis most frequently performed in core facilities and is, probably, the most robust procedure.

Excretory/secretory proteome of the adult stage of Echinostoma caproni.

The excretory/secretory proteome of Echinostoma caproni (Trematoda: Echinostomatidae) adults collected from experimentally infected mice was investigated using a proteomic approach. We performed a shot-gun liquid chromatography/tandem mass spectrometry for the separation and identification of tryptic peptides from the excretory/secretory products of E. caproni adult worms.

Proteomic analysis of phosphorylated nuclear proteins underscores novel roles for rapid actions of retinoic acid in the regulation of mRNA splicing and translation.

Retinoic acid (RA) signaling is mediated by the retinoic acid receptor (RAR), belonging to the nuclear hormone receptor superfamily. In addition to its classical transcriptional actions, RAR also mediates rapid transcription-independent (nongenomic) actions, consisting in the activation of signal transduction pathways, as the phosphatidyl-inositol-3-kinase or the ERK MAPK-signaling pathways. RA-induced rapid transcription-independent actions play a role in different physiological contexts.

Redox regulation of methylthioadenosine phosphorylase in liver cells: molecular mechanism and functional implications.

MTAP (5'-methylthioadenosine phosphorylase) catalyses the reversible phosphorolytic cleavage of methylthioadenosine leading to the production of methylthioribose-1-phosphate and adenine. Deficient MTAP activity has been correlated with human diseases including cirrhosis and hepatocellular carcinoma. In the present study we have investigated the regulation of MTAP by ROS (reactive oxygen species).

Solvent-exposed residues located in the beta-sheet modulate the stability of the tetramerization domain of p53--a structural and combinatorial approach.

The role of hydrophobic amino acids in the formation of hydrophobic cores as one of the major driving forces in protein folding has been extensively studied. However, the implication of neutral solvent-exposed amino acids is less clear and available information is scarce. We have used a combinatorial approach to study the structural relevance of three solvent-exposed residues (Tyr(327), Thr(329), and Gln(331)) located in thebeta-sheet of the tetramerization domain of the tumor suppressor p53 (p53TD).

Importance of a deficiency in S-adenosyl-L-methionine synthesis in the pathogenesis of liver injury.

One of the features of liver cirrhosis is an abnormal metabolism of methionine--a characteristic that was described more than a half a century ago. Thus, after an oral load of methionine, the rate of clearance of this amino acid from the blood is markedly impaired in cirrhotic patients compared with that in control subjects. Almost 15 y ago we observed that the failure to metabolize methionine in cirrhosis was due to an abnormally low activity of the enzyme methionine adenosyltransferase (EC 2.

Regulation of mammalian liver methionine adenosyltransferase.

S-adenosylmethionine (SAM) is an essential metabolite in all cells. SAM is the most important biological methyl group donor and is a precursor in the synthesis of polyamines. Methionine adenosyltransferase (MAT; EC 2.