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Frontiers in Plant Science 2020Plants dedicate a high amount of energy and resources to the production of ribosomes. Historically, these multi-protein ribosome complexes have been considered static...
Plants dedicate a high amount of energy and resources to the production of ribosomes. Historically, these multi-protein ribosome complexes have been considered static protein synthesis machines that are not subject to extensive regulation but only read mRNA and produce polypeptides accordingly. New and increasing evidence across various model organisms demonstrated the heterogeneous nature of ribosomes. This heterogeneity can constitute specialized ribosomes that regulate mRNA translation and control protein synthesis. A prominent example of ribosome heterogeneity is seen in the model plant, , which, due to genome duplications, has multiple paralogs of each ribosomal protein (RP) gene. We support the notion of plant evolution directing high RP paralog divergence toward functional heterogeneity, underpinned in part by a vast resource of ribosome mutants that suggest specialization extends beyond the pleiotropic effects of single structural RPs or RP paralogs. Thus, Arabidopsis is a highly suitable model to study this phenomenon. Arabidopsis enables reverse genetics approaches that could provide evidence of ribosome specialization. In this review, we critically assess evidence of plant ribosome specialization and highlight steps along ribosome biogenesis in which heterogeneity may arise, filling the knowledge gaps in plant science by providing advanced insights from the human or yeast fields. We propose a data analysis pipeline that infers the heterogeneity of ribosome complexes and deviations from canonical structural compositions linked to stress events. This analysis pipeline can be extrapolated and enhanced by combination with other high-throughput methodologies, such as proteomics. Technologies, such as kinetic mass spectrometry and ribosome profiling, will be necessary to resolve the temporal and spatial aspects of translational regulation while the functional features of ribosomal subpopulations will become clear with the combination of reverse genetics and systems biology approaches.
PubMed: 32670337
DOI: 10.3389/fpls.2020.00948 -
Annals of Biomedical Engineering Aug 2020Here we demonstrate a technique to generate proteomic signatures of specific cell types within heterogeneous populations. While our method is broadly applicable across... (Meta-Analysis)
Meta-Analysis
Here we demonstrate a technique to generate proteomic signatures of specific cell types within heterogeneous populations. While our method is broadly applicable across biological systems, we have limited the current work to study neural cell types isolated from human, post-mortem Alzheimer's disease (AD) and aged-matched non-symptomatic (NS) brains. Motivating the need for this tool, we conducted an initial meta-analysis of current, human AD proteomics studies. While the results broadly corroborated major neurodegenerative disease hypotheses, cell type-specific predictions were limited. By adapting our Formaldehyde-fixed Intracellular Target-Sorted Antigen Retrieval (FITSAR) method for proteomics and applying this technique to characterize AD and NS brains, we generated enriched neuron and astrocyte proteomic profiles for a sample set of donors (available at www.fitsarpro.appspot.com ). Results showed the feasibility for using FITSAR to evaluate cell-type specific hypotheses. Our overall methodological approach provides an accessible platform to determine protein presence in specific cell types and emphasizes the need for protein-compatible techniques to resolve systems complicated by cellular heterogeneity.
Topics: Alzheimer Disease; Astrocytes; Brain; Neurons; Proteomics
PubMed: 32303872
DOI: 10.1007/s10439-020-02507-y -
Developmental Neurobiology Jul 2019Down syndrome (DS) occurs due to triplication of chromosome 21. Individuals with DS face an elevated risk for development of Alzheimer's disease (AD) due to increased...
Down syndrome (DS) occurs due to triplication of chromosome 21. Individuals with DS face an elevated risk for development of Alzheimer's disease (AD) due to increased amyloid beta (Aβ) resulting from the over-expression of the amyloid precursor protein found on chromosome 21. Diagnosis of AD among individuals with DS poses particular challenges resulting in an increased focus on alternative diagnostic methods such as blood-based biomarkers. The aim of this review was to evaluate the current state of the literature of blood-based biomarkers found in individuals with DS and particularly among those also diagnosed with AD or in prodromal stages (mild cognitive impairment [MCI]). A systematic review was conducted utilizing a comprehensive search strategy. Twenty-four references were identified, of those, 22 fulfilled inclusion criteria were selected for further analysis with restriction to only plasma-based biomarkers. Studies found Aβ to be consistently higher among individuals with DS; however, the link between Aβ peptides (Aβ1-42 and Aβ1-40) and AD among DS was inconsistent. Inflammatory-based proteins were more reliably found to be elevated leading to preliminary work focused on an algorithmic approach with predominantly inflammatory-based proteins to detect AD and MCI as well as predict risk of incidence among DS. Separate work has also shown remarkable diagnostic accuracy with the use of a single protein (NfL) as compared to combined proteomic profiles. This review serves to outline the current state of the literature and highlights the potential plasma-based biomarkers for use in detecting AD and MCI among this at-risk population.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Biomarkers; Down Syndrome; Humans; Prodromal Symptoms
PubMed: 31389185
DOI: 10.1002/dneu.22714 -
Nature Communications Jun 2019Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and...
Multidrug resistant (MDR) Acinetobacter baumannii poses a growing threat to global health. Research on Acinetobacter pathogenesis has primarily focused on pneumonia and bloodstream infections, even though one in five A. baumannii strains are isolated from urinary sites. In this study, we highlight the role of A. baumannii as a uropathogen. We develop the first A. baumannii catheter-associated urinary tract infection (CAUTI) murine model using UPAB1, a recent MDR urinary isolate. UPAB1 carries the plasmid pAB5, a member of the family of large conjugative plasmids that represses the type VI secretion system (T6SS) in multiple Acinetobacter strains. pAB5 confers niche specificity, as its carriage improves UPAB1 survival in a CAUTI model and decreases virulence in a pneumonia model. Comparative proteomic and transcriptomic analyses show that pAB5 regulates the expression of multiple chromosomally-encoded virulence factors besides T6SS. Our results demonstrate that plasmids can impact bacterial infections by controlling the expression of chromosomal genes.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Animals; Bacterial Proteins; Catheter-Related Infections; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Humans; Mice; Plasmids; Pneumonia, Bacterial; Proteomics; Retrospective Studies; Type VI Secretion Systems; Urinary Catheters; Urinary Tract; Urinary Tract Infections; Virulence; Virulence Factors
PubMed: 31235751
DOI: 10.1038/s41467-019-10706-y -
PloS One 2019Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality worldwide. Although predictive multiparametric screening is being developed, it is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality worldwide. Although predictive multiparametric screening is being developed, it is not applicable to nulliparous women, and is not applied to low-risk women. As PE is considered a heterogenous disorder, it is unlikely that any single multiparametric screening protocol containing a small group of biomarkers could have the required accuracy to predict all PE subgroups. Given the etiology of PE is complex and not fully understood, it begs the question, whether the search for biomarkers based on the predominant view of impaired placentation involving factors predominately implicated in angiogenesis and inflammation, has been too limiting. Here we highlight the enormous potential of state-of-the-art, high-throughput proteomics, to provide a comprehensive and unbiased approach to biomarker identification.
METHODS AND FINDINGS
Our literature search identified 1336 articles; after review, 45 studies with proteomic data from PE women that were eligible for inclusion. From 710 proteins with altered abundance, we identified 13 common circulating proteins, some of which had not been previously considered as prospective biomarkers of PE. An additional search of the literature for original publications testing any of the 13 common proteins using non-proteomic techniques was also undertaken. Strikingly, 9 of these common proteins had been independently evaluated in PE studies as potential biomarkers.
CONCLUSION
This study highlights the potential of using high-throughput data sets, which are comprehensive and without bias, to identify a profile of proteins that may improve predictions of PE and understanding of its etiology. We bring to the attention of the medical and research communities that the strengths and advantages of using data from high-throughput studies for biomarker discovery would be increased dramatically, if first and second trimester samples were collected for proteomics, and if standardized guidelines for patient reporting and data collection were implemented.
Topics: Biomarkers; Databases, Factual; Female; Fetal Growth Retardation; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Proteome; Proteomics
PubMed: 30951540
DOI: 10.1371/journal.pone.0214671 -
Iranian Journal of Medical Sciences Sep 2018Chronic and abnormal increase of different types of dyslipidemia leads to some important diseases, such as constriction and abstraction of vessels in various parts of... (Review)
Review
BACKGROUND
Chronic and abnormal increase of different types of dyslipidemia leads to some important diseases, such as constriction and abstraction of vessels in various parts of the body, especially in the heart. High lipid profile, such as increased total cholesterol and LDL as well as decreased HDL are recognized as cardiovascular disease risk factors. The present study aimed to estimate the prevalence of different types of dyslipidemia in Iran by a meta-analysis method.
METHODS
A literature search for studies published during 1998-2015 was carried out using both Persian and English databases (SID, Magiran, IranMedex, MedLib, PubMed, and Scopus). Keywords such as lipid, dyslipidemia, CVD, cardiovascular risk factors, hypercholesterolemia, high LDL-C, low HDL-C, and prevalence were used in the search. Random-effects model was used for the analysis using STATA (version 11.2).
RESULTS
In total, 163 articles were identified of which 49 articles fulfilled the inclusion criteria. The estimated prevalence (95% confidence interval) of eligible articles for high cholesterol ≥200 mg/dl and ≥240 mg/dl was 42% (95% CI: 38-45) and 17% (95% CI: 14-20), respectively. Moreover, the prevalence (95% confidence interval) for high LDL-C ≥130 mg/dl and ≥160 mg/dl was 40% (95% CI: 32-48) and 19% (95% CI: 16-23), respectively. The pooled prevalence estimate for low HDL-C (<40 among males, <50 among females) was 43% (95% CI: 33-53) in both sexes of the Iranian people. All types of lipid component abnormalities (hypercholesterolemia, high LDL-C, and low HDL-C) were more prevalent in women.
CONCLUSION
The results indicate that the prevalence of different types of dyslipidemia in Iran is substantial. Given the risk of complications (e.g. cardiovascular disease and control of different types of dyslipidemia) in Iranian people, it is important to reduce the burden of cardiovascular diseases.
PubMed: 30214097
DOI: No ID Found -
Frontiers in Bioscience (Landmark... Jan 2018Elevated levels of low density lipoproteins (LDLs) cause atherosclerotic disease, and proteomic analyses have found that these lipoproteins are endowed with... (Review)
Review
Elevated levels of low density lipoproteins (LDLs) cause atherosclerotic disease, and proteomic analyses have found that these lipoproteins are endowed with prenylcysteine lyase. This systematic review summarizes current understanding of this enzyme, now known as prenylcysteine oxidase 1 (PCYOX1), which hydrolyzes the thioether bond of prenylcysteines in the final step in the degradation of prenylated proteins, releasing hydrogen peroxide, cysteine and the isoprenoid aldehyde. Despite the high variability of the gene, no polymorphism has yet been associated with any disease. The liver, which is responsible for vehiculization of the enzyme in lipoproteins, is one of the main organs responsible for its expression, together with the gastrointestinal tract, kidney, male reproductive tissue and muscle. Moreover, although hepatic mRNA expression is sensitive to diet and hormones, the repercussion of these changes in LDLs containing PCYOX1 has not been addressed. One consequence of its elevated activity could be an increase in hydrogen peroxide, which might help to propagate the oxidative burden of LDLs, thus making PCYOX1 a potential pharmacological target and a new biomarker in cardiovascular disease.
Topics: Animals; Carbon-Sulfur Lyases; Cardiovascular Diseases; Gene Expression Profiling; Humans; Lipoproteins, LDL; Liver; Neoplasms; Neurodegenerative Diseases; Polymorphism, Single Nucleotide
PubMed: 28930587
DOI: 10.2741/4631 -
BMC Genomics Sep 2017Pancreatic β-cells require a constant supply of zinc to maintain normal insulin secretory function. Following co-exocytosis with insulin, zinc is replenished via the... (Review)
Review
BACKGROUND
Pancreatic β-cells require a constant supply of zinc to maintain normal insulin secretory function. Following co-exocytosis with insulin, zinc is replenished via the Zrt- and Irt-like (ZIP; SLC39A) family of transporters. However the ZIP paralogues of particular importance for zinc uptake, and associations with β-cell function and Type 2 Diabetes remain largely unexplored. We retrieved and statistically analysed publically available microarray and RNA-seq datasets to perform a systematic review on the expression of β-cell SLC39A paralogues. We complemented results with experimental data on expression profiling of human islets and mouse β-cell derived MIN6 cells, and compared transcriptomic and proteomic sequence conservation between human, mouse and rat.
RESULTS
The 14 ZIP paralogues have 73-98% amino sequence conservation between human and rodents. We identified 18 datasets for β-cell SLC39A analysis, which compared relative expression to non-β-cells, and expression in response to PDX-1 activity, cytokines, glucose and type 2 diabetic status. Published expression data demonstrate enrichment of transcripts for ZIP7 and ZIP9 transporters within rodent β-cells and of ZIP6, ZIP7 and ZIP14 within human β-cells, with ZIP1 most differentially expressed in response to cytokines and PDX-1 within rodent, and ZIP6 in response to diabetic status in human and glucose in rat. Our qPCR expression profiling data indicate that SLC39A6, -9, -13, and - 14 are the highest expressed paralogues in human β-cells and Slc39a6 and -7 in MIN6 cells.
CONCLUSIONS
Our systematic review, expression profiling and sequence alignment reveal similarities and potentially important differences in ZIP complements between human and rodent β-cells. We identify ZIP6, ZIP7, ZIP9, ZIP13 and ZIP14 in human and rodent and ZIP1 in rodent as potentially biologically important for β-cell zinc trafficking. We propose ZIP6 and ZIP7 are key functional orthologues in human and rodent β-cells and highlight these zinc importers as important targets for exploring associations between zinc status and normal physiology of β-cells and their decline in Type 2 Diabetes.
Topics: Animals; Cation Transport Proteins; Gene Expression Profiling; Humans; Insulin-Secreting Cells
PubMed: 28893192
DOI: 10.1186/s12864-017-4119-2 -
Scientific Reports Aug 2017Pelvic organ prolapse (POP) is a highly disabling condition common for a vast number of women worldwide. To contribute to existing knowledge in POP pathogenesis, we...
Pelvic organ prolapse (POP) is a highly disabling condition common for a vast number of women worldwide. To contribute to existing knowledge in POP pathogenesis, we performed a systematic review of expression studies on both specific gene and whole-genome/proteome levels and an in silico analysis of publicly available datasets related to POP development. The most extensively investigated genes in individual studies were related to extracellular matrix (ECM) organization. Three premenopausal and two postmenopausal sets from two Gene Expression Omnibus (GEO) studies (GSE53868 and GSE12852) were analyzed; Gene Ontology (GO) terms related to tissue repair (locomotion, biological adhesion, immune processes and other) were enriched in all five datasets. Co-expression was higher in cases than in controls in three premenopausal sets. The shared between two or more datasets up-regulated genes were enriched with those related to inflammatory bowel disease (IBD) in the NHGRI GWAS Catalog. ECM-related genes were not over-represented among differently expressed genes. Up-regulation of genes related to tissue renewal probably reflects compensatory mechanisms aimed at repair of damaged tissue. Inefficiency of this process may have different origins including age-related deregulation of gene expression.
Topics: Computational Biology; Computer Simulation; Databases, Genetic; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Humans; Pelvic Organ Prolapse; Proteomics; Transcriptome
PubMed: 28794464
DOI: 10.1038/s41598-017-08185-6 -
Journal of Proteome Research Jul 2017Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of... (Review)
Review
Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis. A systematic review of the diversity and outcomes of existing AAA metabonomic research has been performed. Original research studies applying metabonomics to human aneurysmal disease are included. Seven relevant articles were identified: four studies were based on plasma/serum metabolite profiling, and three studies examined aneurysmal tissue. Aminomalonic acid, guanidinosuccinic acid, and glycerol emerge as potential plasma biomarkers of large aneurysm. Lipid profiling improves predictive models of aneurysm presence. Patterns of metabolite variation associated with AAA relate to carbohydrate and lipid metabolism. Perioperative perturbations in metabolites suggest differential systemic inflammatory responses to surgery, generating hypotheses for adjunctive perioperative therapy. Significant limitations include small study sizes, lack of correction for multiple testing false discovery rates, and single time-point sampling. Metabolic profiling carries the potential to identify biomarkers of AAA and elucidate pathways underlying aneurysmal disease. Statistically and methodologically robust studies are required for validation, addressing the hiatus in understanding mechanisms of aneurysm growth and developing effective treatment strategies.
Topics: Aortic Aneurysm, Abdominal; Biomarkers; Disease Progression; Glycerol; Guanidines; Humans; Lipoxins; Malonates; Metabolome; Metabolomics; Prognosis; Succinates; Thromboxane B2
PubMed: 28287739
DOI: 10.1021/acs.jproteome.6b00894