Seminal plasma protein networks and enriched functions in varicocele: Effect of smoking.

To verify a possible synergistic effect of smoking and varicocele on the seminal plasma proteome and biological functions, a cross-sectional study was performed in 25 smokers and 24 nonsmokers. Samples were used for conventional semen analysis, functional analysis (DNA fragmentation, acrosome integrity and mitochondrial activity) and proteomics by a shotgun approach. Functional enrichment of biological pathways was performed in differentially expressed proteins. Smokers presented lower ejaculate volume (p = .027), percentage of progressively motile spermatozoa (p = .002), total sperm count (p = .039), morphology (p = .001) and higher percentage of immotile spermatozoa (p = .03), round cell (p = .045) and neutrophil count (p = .009). Smokers also presented lower mitochondrial activity and acrosome integrity and higher DNA fragmentation. We identified and quantified 421 proteins in seminal plasma, of which one was exclusive, 21 were overexpressed and 70 were underexpressed in the seminal plasma of smokers. The proteins neprilysin, beta-defensin 106A and histone H4A were capable of predicting the smoker group. Enriched functions were related to immune function and sperm machinery in testis/epididymis. Based on our findings, we can conclude that cigarette smoking leads to the establishment of inflammatory protein pathways in the testis/epididymis in the presence of varicocele that seems to act in synergy with the toxic components of the cigarette.

Comparing Data-Independent Acquisition and Parallel Reaction Monitoring in Their Abilities To Differentiate High-Density Lipoprotein Subclasses.

High-density lipoprotein (HDL) is a diverse group of particles with multiple cardioprotective functions. HDL proteome follows HDL particle complexity. Many proteins were described in HDL, but consistent quantification of HDL protein cargo is still a challenge. To address this issue, the aim of this work was to compare data-independent acquisition (DIA) and parallel reaction monitoring (PRM) methodologies in their abilities to differentiate HDL subclasses through their proteomes. To this end, we first evaluated the analytical performances of DIA and PRM using labeled peptides in pooled digested HDL as a biological matrix. Next, we compared the quantification capabilities of the two methodologies for 24 proteins found in HDL2 and HDL3 from 19 apparently healthy subjects. DIA and PRM exhibited comparable linearity, accuracy, and precision. Moreover, both methodologies worked equally well, differentiating HDL subclasses' proteomes with high precision. Our findings may help to understand HDL functional diversity.

Prediction of protein architectures involved in the signaling-pathway initiating sporulation in Firmicutes.

OBJECTIVES: Like many other proteins, those belonging to the signal transduction cascade initiating sporulation (Spo0 pathway) have conserved protein domains (Capra and Laub in Annu Rev Microbiol 66:325-47, 2012). Improvements in bioinformatics applications to discover proteins involved in the initiation of the sporulating cascade in newly sequenced genomes is an important task that requires rigorous comparative genomic methods and manual curation to identify endospore-forming bacteria. This note aims to present a collection of predicted proteins involved in the Spo0 pathway found in the proteomes of fully sequenced and manually curated endospore-forming Firmicutes species. This collection may serve as a guide to conduct future experiments in endospore formers in genomic and metagenomic projects. DATA DESCRIPTION: Similar to the report of Davidson et al. (PLoS Genet 14:1-33, 2018), we used Pfam profiles (El-Gebali et al. in Nucleic Acids Res 47:D427-32, 2019) defining each protein and the genomic context surrounding the query gene to predict probable orthologs of the Spo0 pathway in Firmicutes. We present in this note a collection of 325 Firmicutes species organized by phylogenetic class and classified as spore formers, non-spore formers or unknown spore phenotype based on published literature, for which we predicted probable orthologs defining the signal transduction pathway initiating sporulation.

A time-series DDP for functional proteomics profiles.

Using a new type of array technology, the reverse phase protein array (RPPA), we measure time-course protein expression for a set of selected markers that are known to coregulate biological functions in a pathway structure. To accommodate the complex dependent nature of the data, including temporal correlation and pathway dependence for the protein markers, we propose a mixed effects model with temporal and protein-specific components. We develop a sequence of random probability measures (RPM) to account for the dependence in time of the protein expression measurements. Marginally, for each RPM we assume a Dirichlet process model. The dependence is introduced by defining multivariate beta distributions for the unnormalized weights of the stick-breaking representation. We also acknowledge the pathway dependence among proteins via a conditionally autoregressive model. Applying our model to the RPPA data, we reveal a pathway-dependent functional profile for the set of proteins as well as marginal expression profiles over time for individual markers.

Proteínas do plasma seminal, funções espermáticas e marcadores moleculares da fertilidade / Seminal plasma proteins, sperm functions and molecular markers of fertility

Componentes moleculares dos espermatozoides, ou dos meios que os cercam, influenciam a capacidade fecundante destas células. Dado tal conceito, proteínas do plasma seminal modulam cruciais funções e processos da reprodução, como a motilidade e capacitação espermática, proteção celular, reação acrossômica e fertilização. As relações empíricas entre índices de fertilidade e proteínas seminais em determinadas espécies indicam que estas proteínas têm o potencial de serem identificadas como marcadores da capacidade reprodutiva do macho.(AU)

Molecular components of the sperm, or from the media that surround them, influence the fertilizing capacity of such cells. Given this concept, proteins of the seminal plasma modulate crucial functions and events of reproduction, such as sperm motility and capacitation, cell protection, acrosome reaction and fertilization. Empirical associations between some proteins and fertility indexes in certain species indicate that these proteins can be potentially identified as molecular markers of the male reproductive status.(AU)

Proteínas do plasma seminal, funções espermáticas e marcadores moleculares da fertilidade / Seminal plasma proteins, sperm functions and molecular markers of fertility

Componentes moleculares dos espermatozoides, ou dos meios que os cercam, influenciam a capacidade fecundante destas células. Dado tal conceito, proteínas do plasma seminal modulam cruciais funções e processos da reprodução, como a motilidade e capacitação espermática, proteção celular, reação acrossômica e fertilização. As relações empíricas entre índices de fertilidade e proteínas seminais em determinadas espécies indicam que estas proteínas têm o potencial de serem identificadas como marcadores da capacidade reprodutiva do macho.

Molecular components of the sperm, or from the media that surround them, influence the fertilizing capacity of such cells. Given this concept, proteins of the seminal plasma modulate crucial functions and events of reproduction, such as sperm motility and capacitation, cell protection, acrosome reaction and fertilization. Empirical associations between some proteins and fertility indexes in certain species indicate that these proteins can be potentially identified as molecular markers of the male reproductive status.

Proteometric study of ghrelin receptor function variations upon mutations using amino acid sequence autocorrelation vectors and genetic algorithm-based least square support vector machines.

Functional variations on the human ghrelin receptor upon mutations have been associated with a syndrome of short stature and obesity, of which the obesity appears to develop around puberty. In this work, we reported a proteometrics analysis of the constitutive and ghrelin-induced activities of wild-type and mutant ghrelin receptors using amino acid sequence autocorrelation (AASA) approach for protein structural information encoding. AASA vectors were calculated by measuring the autocorrelations at sequence lags ranging from 1 to 15 on the protein primary structure of 48 amino acid/residue properties selected from the AAindex database. Genetic algorithm-based multilinear regression analysis (GA-MRA) and genetic algorithm-based least square support vector machines (GA-LSSVM) were used for building linear and non-linear models of the receptor activity. A genetic optimized radial basis function (RBF) kernel yielded the optimum GA-LSSVM models describing 88% and 95% of the cross-validation variance for the constitutive and ghrelin-induced activities, respectively. AASA vectors in the optimum models mainly appeared weighted by hydrophobicity-related properties. However, differently to the constitutive activity, the ghrelin-induced activity was also highly dependent of the steric features of the receptor.

Dissecting the human spliceosome through bioinformatics and proteomics approaches.

The precise excision of introns from mRNAs is executed by the spliceosome, a cellular machinery composed by five small nuclear RNAs and hundreds of proteins. In the last few years, several groups have used proteomics and computational biology tools to characterize the components of the human spliceosome. These reports have identified basically all known splicing factors and several new proteins. The composition of the human spliceosome confirms the link between splicing and other steps in gene expression. Here we comment on these reports and discuss the perspectives for the coming years.