Computational Tools and Methods for the Study of Systemic Amyloidosis at the Clinical and Molecular Level.

Amyloidosis diseases are characterized by protein misfolding, which forms insoluble beta-sheet fibrils progressively deposited in tissues. Deposition in the form of amyloid aggregates can occur in various organs, damaging their structure and function. The hallmark of amyloidosis is aberrant interactions leading to protein aggregation and proteotoxicity.

Seminal proteoforms from bulls with contrasting semen freezability: a story deciphered by top-down mass spectrometry.

Top-down proteomics was employed to construct proteoform atlas of sperm and seminal plasma (SP) from bulls with low (LF) and high (HF) semen freezability. Sperm and seminal proteins were fractionated by tandem size exclusion chromatography (< 30 kDa) and analyzed by reversed-phase liquid chromatography-tandem mass spectrometry. This approach enabled the identification of 299 SP (from 46 families) and 267 sperm proteoforms (from 139 families).

Integration of Omics Data and Network Models to Unveil Negative Aspects of SARS-CoV-2, from Pathogenic Mechanisms to Drug Repurposing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 health emergency, affecting and killing millions of people worldwide. Following SARS-CoV-2 infection, COVID-19 patients show a spectrum of symptoms ranging from asymptomatic to very severe manifestations. In particular, bronchial and pulmonary cells, involved at the initial stage, trigger a hyper-inflammation phase, damaging a wide range of organs, including the heart, brain, liver, intestine and kidney.

Early Foliar Proteome Response to Root Exposure to the Rhizobacterium WCS417.

WCS417 is a plant growth-promoting rhizobacterium that improves plant health and development. In this study, we investigate the early leaf responses of to WCS417 exposure and the possible involvement of formate dehydrogenase (FDH) in such responses. In vitro-grown seedlings expressing an FDH::GUS reporter show a significant increase in FDH promoter activity in their roots and shoots after 7 days of indirect exposure (without contact) to WCS417.

Reduced G protein signaling despite impaired internalization and β-arrestin recruitment in patients carrying a CXCR4Leu317fsX3 mutation causing WHIM syndrome.

WHIM syndrome is an inherited immune disorder caused by an autosomal dominant heterozygous mutation in CXCR4. The disease is characterized by neutropenia/leukopenia (secondary to retention of mature neutrophils in bone marrow), recurrent bacterial infections, treatment-refractory warts, and hypogammaglobulinemia. All mutations reported in WHIM patients lead to the truncations in the C-terminal domain of CXCR4, R334X being the most frequent.

Natural history of type 1 diabetes on an immunodysregulatory background with genetic alteration in B-cell activating factor receptor: A case report.

The immunological events leading to type 1 diabetes (T1D) are complex and heterogeneous, underscoring the necessity to study rare cases to improve our understanding. Here, we report the case of a 16-year-old patient who showed glycosuria during a regular checkup. Upon further evaluation, stage 2 T1D, autoimmune thrombocytopenic purpura (AITP), and common variable immunodeficiency (CVID) were diagnosed.

Characterization of Circulating Extracellular Vesicle Surface Antigens in Patients With Primary Aldosteronism.

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Thymic Epithelial Cell Alterations and Defective Thymopoiesis Lead to Central and Peripheral Tolerance Perturbation in MHCII Deficiency.

Major Histocompatibility Complex (MHC) class II (MHCII) deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules. MHCII deficiency results in impaired cellular and humoral immune responses, leading to severe infections and autoimmunity. Abnormal cross-talk with developing T cells due to the absence of MHCII expression likely leads to defects in thymic epithelial cells (TEC).

Premature Senescence and Increased Oxidative Stress in the Thymus of Down Syndrome Patients.

Down syndrome (DS) patients prematurely show clinical manifestations usually associated with aging. Their immune system declines earlier than healthy individuals, leading to increased susceptibility to infections and higher incidence of autoimmune phenomena. Clinical features of accelerated aging indicate that trisomy 21 increases the biological age of tissues.

Immune profiling of plasma-derived extracellular vesicles identifies Parkinson disease.

Objective: To develop a diagnostic model based on plasma-derived extracellular vesicle (EV) subpopulations in Parkinson disease (PD) and atypical parkinsonism (AP), we applied an innovative flow cytometric multiplex bead-based platform.

Methods: Plasma-derived EVs were isolated from PD, matched healthy controls, multiple system atrophy (MSA), and AP with tauopathies (AP-Tau). The expression levels of 37 EV surface markers were measured by flow cytometry and correlated with clinical scales.

Are In Silico Approaches Applicable As a First Step for the Prediction of e-Liquid Toxicity in e-Cigarettes?

Recent studies have raised concerns about e-cigarette liquid inhalation toxicity by reporting the presence of chemicals with European Union CLP toxicity classification. In this scenario, the regulatory context is still developing and is not yet up to date with vaping current reality. Due to the paucity of toxicological studies, robust data regarding which components in e-liquids exhibit potential toxicities, are still inconsistent.

Heparin and heparan sulfate proteoglycans promote HIV-1 p17 matrix protein oligomerization: computational, biochemical and biological implications.

p17 matrix protein released by HIV+ cells interacts with leukocytes heparan sulfate proteoglycans (HSPGs), CXCR1 and CXCR2 exerting different cytokine-like activities that contribute to AIDS pathogenesis. Since the bioactive form of several cytokines is represented by dimers/oligomers and oligomerization is promoted by binding to heparin or HSPGs, here we evaluated if heparin/HSPGs also promote p17 oligomerization. Heparin favours p17 dimer, trimer and tetramer assembly, in a time- and biphasic dose-dependent way.

An infrastructure for precision medicine through analysis of big data.

Background: Nowadays, the increasing availability of omics data, due to both the advancements in the acquisition of molecular biology results and in systems biology simulation technologies, provides the bases for precision medicine. Success in precision medicine depends on the access to healthcare and biomedical data. To this end, the digitization of all clinical exams and medical records is becoming a standard in hospitals.

Large Scale Proteomic Data and Network-Based Systems Biology Approaches to Explore the Plant World.

The investigation of plant organisms by means of data-derived systems biology approaches based on network modeling is mainly characterized by genomic data, while the potential of proteomics is largely unexplored. This delay is mainly caused by the paucity of plant genomic/proteomic sequences and annotations which are fundamental to perform mass-spectrometry (MS) data interpretation. However, Next Generation Sequencing (NGS) techniques are contributing to filling this gap and an increasing number of studies are focusing on plant proteome profiling and protein-protein interactions (PPIs) identification.

From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data.

The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory.

LAV-BPIFB4 isoform modulates eNOS signalling through Ca2+/PKC-alpha-dependent mechanism.

Aims: Ageing is associated with impairment of endothelial nitric oxide synthase (eNOS) and progressive reduction in endothelial function. A genetic study on long-living individuals-who are characterized by delays in ageing and in the onset of cardiovascular disease-previously revealed I229V (rs2070325) in bactericidal/permeability-increasing fold-containing-family-B-member-4 (BPIFB4) as a longevity-associated variant (LAV); the LAV protein enhanced endothelial NO production and vasorelaxation through a protein kinase R-like endoplasmic reticulum kinase/14-3-3/heat shock protein 90 signal. Here, we further characterize the molecular mechanisms underlying LAV-BPIFB4-dependent enhancement of vascular function.

Proteomics-based network analysis characterizes biological processes and pathways activated by preconditioned mesenchymal stem cells in cardiac repair mechanisms.

Background: We have demonstrated that intramyocardial delivery of human mesenchymal stem cells preconditioned with a hyaluronan mixed ester of butyric and retinoic acid (MSCp) is more effective in preventing the decay of regional myocardial contractility in a swine model of myocardial infarction (MI). However, the understanding of the role of MSCp in proteomic remodeling of cardiac infarcted tissue is not complete. We therefore sought to perform a comprehensive analysis of the proteome of infarct remote (RZ) and border zone (BZ) of pigs treated with MSCp or unconditioned stem cells.

myMIR: a genome-wide microRNA targets identification and annotation tool.

miRNA target genes prediction represents a crucial step in miRNAs functional characterization. In this context, the challenging issue remains predictions accuracy and recognition of false positive results. In this article myMIR, a web based system for increasing reliability of miRNAs predicted targets lists, is presented.

Separation of isomers L-alanine and sarcosine in urine by electrospray ionization and tandem differential mobility analysis-mass spectrometry.

Sarcosine, an isomer of L-alanine, has been proposed as a prostate cancer progression biomarker [1]. Both compounds are detected in urine, where the measured sarcosine/alanine ratio has been found to be higher in prostate biopsy-positive group versus controls. We present here preliminary evidence showing that urine samples spiked with sarcosine/alanine can be partially resolved in 3 min via tandem differential mobility analysis-mass spectrometry (DMA-MS).

In silico saturation mutagenesis and docking screening for the analysis of protein-ligand interaction: the Endothelial Protein C Receptor case study.

Background: The design of mutants in protein functional regions, such as the ligand binding sites, is a powerful approach to recognize the determinants of specific protein activities in cellular pathways. For an exhaustive analysis of selected positions of protein structure large scale mutagenesis techniques are often employed, with laborious and time consuming experimental set-up. 'In silico' mutagenesis and screening simulation represents a valid alternative to laboratory methods to drive the 'in vivo' testing toward more focused objectives.

BGBlast: a BLAST grid implementation with database self-updating and adaptive replication.

BLAST is probably the most used application in bioinformatics teams. BLAST complexity tends to be a concern when the query sequence sets and reference databases are large. Here we present BGBlast: an approach for handling the computational complexity of large BLAST executions by porting BLAST to the Grid platform, leveraging the power of the thousands of CPUs which compose the EGEE infrastructure.

Data handling strategies for high throughput pyrosequencers.

Background: New high throughput pyrosequencers such as the 454 Life Sciences GS 20 are capable of massively parallelizing DNA sequencing providing an unprecedented rate of output data as well as potentially reducing costs. However, these new pyrosequencers bear a different error profile and provide shorter reads than those of a more traditional Sanger sequencer. These facts pose new challenges regarding how the data are handled and analyzed, in addition, the steep increase in the sequencers throughput calls for much computation power at a low cost.

Identification of a region within SEL1L protein required for tumour growth inhibition.

The ectopic expression of the entire SEL1L cDNA significantly reduces the proliferate activity and aggressive behavior of the human breast carcinoma cell line MCF-7. However, the mechanism responsible for this biological effect remains unclear. A study was initiated to define those regions within SEL1L conferring such antiproliferative properties.