Deciphering bioactive peptides and their action mechanisms through proteomics

Introduction: Bioactive peptides such as antimicrobial peptides (AMPs), ribosomally synthesized and post translationally modified peptides (RiPPs) and the non-ribosomal peptides (NRPs) have emerged with promising applications in medicine, agriculture and industry. However, their development has been limited by several difficulties making it necessary to search for novel discovery methods. In this context, proteomics has been considered a reliable tool.

Areas covered: This review highlights recent developments in proteomic tools that facilitate the discovery of AMPs, RiPPs and NRPs as well as the elucidation of action mechanisms of AMPs and resistance mechanisms of pathogens to them.

Expert commentary: Proteomic approaches have emerged as useful tools for the study of bioactive peptides, especially mass spectrometry-based peptidomics profiling, a promising strategy for AMP discovery. Furthermore, the rapidly expanding fields of genome mining and genome sequencing techniques, as well as mass spectrometry, have revolutionized the discovery of novel RiPPs and NRPs from complex biological samples.     

A model of lipid rearrangements during pore formation in the DPPC lipid bilayer

Context: The molecular bases of pore formation in the lipid bilayer remain unclear, as do the exact characteristics of their sizes and distributions. To understand this process, numerous studies have been performed on model lipid membranes including cell-sized giant unilamellar vesicles (GUV). The effect of an electric field on DPPC GUV depends on the lipid membrane state: in the liquid crystalline phase the created pores have a cylinder-like shape, whereas in the gel phase a crack has been observed.

Objective: The aim of the study was to investigate the geometry of pores created in a lipid bilayer in gel and liquid crystalline phases in reference to literature experimental data.

Methods: A mathematical model of the pore in a DPPC lipid bilayer developed based on the law of conservation of mass and the assumption of constant volume of lipid molecules, independent of their conformation, allows for analysis of pore shape and accompanying molecular rearrangements.

Results: The membrane area occupied by the pore of a cylinder-like shape is greater than the membrane area occupied by lipid molecules creating the pore structure (before pore appearance). Creation of such pores requires more space, which can be achieved by conformational changes of lipid chains toward a more compact state. This process is impossible for a membrane in the most compact, gel phase.

Discussion and conclusions: We show that the geometry of the pores formed in the lipid bilayer in the gel phase must be different from the cylinder shape formed in the lipid bilayer in a liquid crystalline state, confirming experimental studies. Furthermore, we characterize the occurrence of the ‘buffer’ zone surrounding pores in the liquid crystalline phase as a mechanism of separation of neighbouring pores.     

Reduced Pesticide Use in Scandinavian Agriculture

In all industrialized countries, the use of individual pesticides has been regulated on the basis of the presumed hazard that each poses to health and the environment. In Sweden, Norway, and Denmark, programs aimed at reducing total pesticide use have been initiated as well.

In Swedish and Danish agriculture, the amount of active ingredients used has decreased steadily since around 1980; however, the area treated has increased during the same period. The reduction during the 1980s can be ascribed to several factors affecting pesticide use in agriculture. First, old pesticides have been replaced by new ones that are active at lower doses. A general decrease in herbicide doses applied has been possible because of decreased weed pressure. Improved spraying technique also is important.

Environmental concern and political ambitions to reduce pesticide use in Scandinavian agriculture must be understood primarily within the historical framework of societal values and political and social experiences. The success in the reduction of pesticide use, however, cannot be measured and evaluated without taking into account the specific technical and agroecological prerequisites existing in Scandinavian agriculture. As in many other areas of complex changes in modern society: Opinion proposes, Technology disposes.     

Understanding type 1 diabetes through proteomics

Introduction: Auto-immunity against pancreatic beta-cells leads to an absolute shortage of the hormone insulin, resulting in hyperglycemia and the onset of type 1 diabetes (T1D). Proteomic approaches have been used to elucidate the mechanisms of beta-cell dysfunction and death.

Areas covered: In the present review, we discuss discoveries in the beta-cell proteome that have contributed to better insights in the role of the beta-cell in T1D. Techniques, such as 2D-DIGE and MALDI imaging, together with new approaches for sample preparation, including laser capture microdissection and immunopeptidomics, have resulted in novel mechanistic insights in the pathogenesis of T1D. We describe how proteomic studies in beta-cell lines as well as isolated islets from animal models and humans have discovered intracellular signaling pathways leading to beta-cell destruction, the generation of neo-antigens through post-translational modifications of beta-cell antigens as well as better biomarkers of disease progression.

Expert commentary: Proteomics has contributed to the discovery of beta-cell neo-autoantigen generation through post-translational modifications, hybrid insulin peptide formation and the generation of defective ribosomal gene products. These concepts are revolutionizing our insights in the pathogenesis of T1D, acknowledging a central role for the beta-cell in its own destruction.     

Updates on Sjögren’s syndrome: from proteomics to protein biomarkers

Introduction: Primary Sjögren’s syndrome (pSS) is a complex heterogeneous autoimmune disorder, typically affecting exocrine glands. Recently, a great interest has arisen in searching for novel biomarkers able to improve the diagnostic work-up of the disease as well as the general assessment and the prognostic stratification of pSS patients. From this perspective, salivary proteomics has appeared as a promising tool considering that salivary proteins may closely reflect the underlying disease processes in the salivary glands.

Areas covered: Here we will provide an update on the state of the art of proteomics in pSS, focusing in particular on putative novel biomarkers for the disease. There is a special focus on candidate salivary protein and their role in non-invasive diagnosis of pSS.

Expert commentary: Proteomics represents an emerging throughput omics-based approach for use in diagnosis of pSS. The studies that have been presented in this review have provided major contributions towards the identification of putative protein biomarkers, that once validated, could be able not only to contribute to a non-invasive diagnosis of pSS but also to the stratification of different disease subsets, ultimately allowing a better comprehension of the disease.     

Structural insights into the inhibitor binding and new inhibitor design to Polo-like kinase-1 Polo-box domain using computational studies

Polo box domain (PBD) from Polo-Like Kinase-1 (PLK-1) a cell cycle regulator is one of the important non-kinase targets implicated in various cancers. The crystal structure of PLK-1 PBD bound to phosphopeptide inhibitor is available and acylthiourea derivatives have been reported as potent PBD inhibitors. In this work, structure and ligand-based pharmacophore methods have been used to identify new PBD inhibitors. The binding of acylthiourea analogs and new inhibitors to PBD were assessed using molecular docking and molecular dynamics simulations to understand their binding interactions, investigate the complex stability and reveal the molecular basis for inhibition. This study provides the binding free energies and residue-wise contributions to decipher the essential interactions in the protein-inhibitor complementarity for complex formation and the design of new PBD inhibitors with better binding.

Communicated by Ramaswamy H. Sarma     

Protein interactions study through proximity-labeling

Introduction: The proteome is a dynamic system in which protein-protein interactions play a crucial part in shaping the cell phenotype. However, given the current limitations of available technologies to describe the dynamic nature of these interactions, the identification of protein-protein interactions has long been a major challenge in proteomics. In recent years, the development of BioID and APEX, two proximity-tagging technologies, have opened-up new perspectives and have already started to change our conception of protein-protein interactions, and more generally, of the proteome. With a broad range of application encompassing health, these new technologies are currently setting milestones crucial to understand fine cellular mechanisms.

Area covered: In this article, we describe both the recent and the more conventional available tools to study protein-protein interactions, compare the advantages and the limitations of these techniques, and discuss the recent advancements led by the proximity tagging techniques to refine our conception of the proteome.

Expert opinion: The recent development of proximity labeling techniques emphasizes the growing importance of such technologies to decipher cellular mechanism. Although several challenges still need to be addressed, many fields can benefit from these tools and notably the detection of new therapeutic targets for patient care     

Mass spectrometry based proteomics analyses in kallikrein-related peptidase research: implications for cancer research and therapy

Introduction: Kallikrein-related peptidases (KLKs) are a family of serine peptidases that are deregulated in numerous pathological conditions, with a multitude of KLK-mediated functional roles implicated in the progression of cancer. Advances in multidimensional mass spectrometry (MS)-based proteomics have facilitated the quantitative measurement of deregulated KLK expression in cancer, identifying certain KLKs, as well as their substrates, as potential cancer biomarkers.

Areas covered: In this review, we discuss how these approaches have been utilized for KLK biomarker discovery and unbiased substrate determination in complex protein pools that mimic the in vivo extracellular microenvironment.

Expert commentary: Although a limited number of studies have been performed, the quantity of information generated has greatly improved our understanding of the functional roles of KLKs in cancer progression. In addition, these data suggest additional means through which deregulated KLK expression may be targeted in cancer treatment, highlighting the potential therapeutic value of these state-of-the-art MS-based studies.     

Genomic database resources for Dictyostelium discoideum

Dictyostelium is an attractive model system for the study of mechanisms basic to cellular function or complex multicellular developmental processes. Recent advances in Dictyostelium genomics have generated a wide spectrum of resources. However, much of the current genomic sequence information is still not currently available through GenBank or related databases. Thus, many investigators are unaware that extensive sequence data from Dictyostelium has been compiled, or of its availability and access. Here, we discuss progress in Dictyostelium genomics and gene annotation, and highlight the primary portals for sequence access, manipulation and analysis (http://genome.imb-jena.de/dictyostelium/; http://dictygenome.bcm.tmc.edu/; http://www.sanger. ac.uk/Projects/D_discoideum/; http://www.csm.biol. tsukuba.ac.jp/cDNAproject.html).     

Global profiling of protein complexes: current approaches and their perspective in biomedical research

Introduction: Despite the rapid evolution of proteomic methods, protein interactions and their participation in protein complexes – an important aspect of their function – has rarely been investigated on the proteome-wide level. Disease states, such as muscular dystrophy or viral infection, are induced by interference in protein-protein interactions within complexes. The purpose of this review is to describe the current methods for global complexome analysis and to critically discuss the challenges and opportunities for the application of these methods in biomedical research.

Areas covered: We discuss advancements in experimental techniques and computational tools that facilitate profiling of the complexome. The main focus is on the separation of native protein complexes via size exclusion chromatography and gel electrophoresis, which has recently been combined with quantitative mass spectrometry, for a global protein-complex profiling. The development of this approach has been supported by advanced bioinformatics strategies and fast and sensitive mass spectrometers that have allowed the analysis of whole cell lysates. The application of this technique to biomedical research is assessed, and future directions are anticipated.

Expert commentary: The methodology is quite new, and has already shown great potential when combined with complementary methods for detection of protein complexes.     

Fatty acids from oleaginous yeasts and yeast-like fungi and their potential applications

Purpose: Oleaginous yeasts, fatty acids biosynthesis and regulation in the oleaginous yeasts and the fatty acids from the oleaginous yeasts and their applications are reviewed in this article.

Results: Oleaginous yeasts such as Rhodosporidium toruloides, Yarrowia lipolytica, Rhodotorula mucilaginosa, and Aureobasidium melanogenum, which can accumulate over 50% lipid of their cell dry weight, have many advantages over other oleaginous microorganisms. The fatty acids from the oleaginous yeasts have many potential applications. Many oleaginous yeasts have now been genetically modified to over-produce fatty acids and their derivatives. The most important features of the oleaginous yeasts are that they have special enzymatic systems for enhanced biosynthesis and regulation of fatty acids in their lipid particles. Recently, some oleaginous yeasts such as R. toruloides have been found to have a unique fatty acids synthetase and other oleaginous yeasts such as A. melanogenum have a unique highly reducing polyketide synthase (HR-PKS) involved in the biosynthesis of hydroxyl fatty acids.

Conclusions: It is necessary to further enhance lipid biosynthesis using metabolic engineering and explore new applications of fatty acids in biotechnology.     

A new rodent (Caviomorpha: Dinomyidae) from the upper Miocene of southwestern Brazilian Amazonia

Recently, the fossil record of rodents from southwestern Brazilian Amazonia has been reviewed with regards to its diversity as well as its ecological relationships. In the reviews, the necessity to report new specimens collected with stratigraphic control was stated. Here, a new dinomyid specimen collected during a 2015 expedition to the Niterói locality, Acre River, is reported. The material is a fragment of skull with the right P4–M1 and the left P4–M2 preserved. The cheek teeth are protohypsodont, a characteristic employed to differentiate Potamarchinae dinomyids from the euhypsodont dinomyids Eumegamyinae and Tetrastylinae. The occlusal surface of the cheek teeth is composed of lophs with interruptions, showing little wear, which suggests that the specimen is not fully ontogenetically developed. The specimen has a unique combination of characters (protohypsodont and pentalophodont cheek teeth, with the leading edges of similar thickness to the trailing edges, and presence of a groove on the bottom of the infraorbital foramen) not present in other known dinomyids, which led us to erect a new taxon. The abundant and diverse fossil record of protohypsodont dinomyids suggests that an important radiative event may have occurred during the middle–late Miocene of northern South America.

http://zoobank.org/urn:lsid:zoobank.org:pub:E082C3C6-47B6-4D83-9009-A64879AAFC7A

http://www.zoobank.org/NomenclaturalActs/16235A7B-A261-445E-8DD4-940AB21DCB06     

RETRACTED ARTICLE: A review of 45 candidate genes: Association of single nucleotide polymorphism to schizophrenia Risk

The following article has been retracted from publication in the Taylor & Francis journal New Genetics and Society. I. Priya, S. Sharma, I. Sharma, R. Mahajan and N. Kapoor, A review of 45 candidate genes: association of single nucleotide polymorphism to schizophrenia risk, New Genetics and Society https://doi.org/10.1080/14636778.2018.1481740. Version of Record published online 13 July 2018.

The editorial office of the journal inadvertently processed the paper through the online submission system without proper peer review or requisite checks. This has now been remedied and the journal and publishers apologise to the authors that this occurred. Journal processes and checks have now been reviewed and updated so that all best efforts are made to ensure this does not occur again.

© Taylor & Francis/Journal owner     

Molecular Data and the Dynamic Nature of Polyploidy

During the past decade, molecular techniques have provided a wealth of data that have facilitated the resolution of several controversial questions in polyploid evolution. Herein we have focused on several of these issues: (1) the frequency of recurrent formation of polyploid species; (2) the genetic consequences of multiple polyploidizations within a species; (3) the prevalence and genetic attributes of autopolyploids; and (4) the genetic changes that occur in polyploid genomes following their formation.

Molecular data provide a more dynamic picture of polyploid evolution than has been traditionally espoused. Numerous studies have demonstrated multiple origins of both allopolyploids and autopolyploids. In several polyploid species studied in detail, multiple origins were found to be frequent on a local geographic scale, as well as during a short span of time. Molecular data strongly suggest that recurrent formation of polyploid species is the rule, rather than the exception. In addition, molecular data indicate that recurrent formation of polyploids has important genetic consequences, introducing considerable genetic variation from diploid progenitors into polyploid derivatives.

Molecular data also suggest a much more important role for natural autopolyploids than has been historically envisioned. In contrast to the longstanding view of autopolyploidy as being rare, molecular data continue to reveal steadily increasing numbers of well-documented autoploids having tetrasomic or higher-level polysomic inheritance. Although autopolyploidy undoubtedly occurs much less frequently than allopolyploidy in natural populations, it nonetheless has been a significant evolutionary mechanism. Molecular data also provide compelling genetic evidence that contradicts the traditional view of autopolyploidy as being maladaptive. Electrophoretic studies have revealed three important attributes of autopolyploids compared to their diploid progenitors: (1) enzyme multiplicity, (2) increased heterozygosity, and (3) increased allelic diversity. Genetic variability is, in fact, typically substantially higher in autopoloids than in their diploid progenitors. These genetic attributes of autopolyploids are due to polysomic inheritance and provide strong genetic arguments for the potential success of autopolyploids in nature.

In addition to providing numerous important insights into the formation of polyploids and the immediate genetic consequences of polyploidy, molecular data also have been used to study the subsequent evolution of polyploid genomes. Common hypotheses on the subsequent evolution of polyploid genomes include (1) gene silencing, eventually leading to extensively diploidized polyploid genomes; (2) gene diversification, resulting in regulatory or functional divergence of duplicate genes; and (3) genome diversification, resulting in chromosomal repatterning. Compelling, but limited, genetic evidence for all of these factors has been obtained in molecular analyses of polyploid species. The occurrence of these processes in polyploid genomes indicates that polyploid genomes are plastic and susceptible to evolutionary change.

In summary, molecular data continue to demonstrate that polyploidization and the subsequent evolution of polyploid genomes are very dynamic processes.     

The progress and potential of proteomic biomarkers for type 1 diabetes in children

Introduction: Although it is possible to identify the genetic risk for type 1 diabetes (T1D), it is not possible to predict who will develop the disease. New biomarkers are needed that would help understand the mechanisms of disease onset and when to administer targeted therapies and interventions.

Areas covered: An overview is presented of international study efforts towards understanding the cause of T1D, including the collection of several extensive temporal sample series that follow the development of T1D in at risk children. The results of the proteomics analysis of these materials are presented, which have included bodily fluids, such as serum or plasma and urine, as well as tissue samples from the pancreas.

Expert commentary: Promising recent reports have indicated detection of early proteomic changes in the serum of patients prior to diagnosis, potentially providing new measures for risk assessment. Similarly, there has been evidence that post-translational modification (PTM) may result in the recognition of islet cell proteins as autoantigens; modified proteins could thus be used as targets for immunomodulation to overcome the threat of the autoimmune response.     

Proteomic profiling of the cancer cell secretome: informing clinical research

Introduction: Cancer represents one of the major causes of human deaths. Identification of proteins as biomarkers for early detection of cancer and therapeutic targets for cancer treatment are important issues in precision medicine. Secretome of cancer cells represents the collection of proteins secreted or shed from cancer cells. Proteomic profiling of the cancer cell secretome has been proven to be a convenient and efficient way to discover cancer biomarker and/or therapeutic targets.

Areas covered: There have been numerous reviews describing the history and application of secretome analysis in cancer biomarker/therapeutic target research. The present review focuses on the technological advancement for profiling low-molecular-mass proteins in secretome, the latest information regarding the new candidate biomarkers and molecular mechanisms discovered on the basis of cancer cell secretome analysis, as well as the previously discovered candidate biomarkers that enter into clinical trials.

Expert commentary: Current technologies for protein sample preparation/separation and MS-based protein identification have allowed in-depth analysis of cancer cell secretome. Future efforts should focus on the comprehensiveness of cancer cell secretome, meta-analysis of different secretome datasets and integrated analysis via combining other omics datasets, as well as the incorporation of MS-based biomarker verification pipeline into both preclinical studies and clinical trials.     

Proteomic investigations into hypertension: what’s new and how might it affect clinical practice?

Introduction: Hypertension is a multifactorial disease that has, thus far, proven to be a difficult target for pharmacological intervention. The application of proteomic strategies may help to identify new biomarkers for the early diagnosis and prompt treatment of hypertension, in order to control blood pressure and prevent organ damage.

Areas covered: Advances in proteomics have led to the discovery of new biomarkers to help track the pathophysiological processes implicated in hypertension. These findings not only help to better understand the nature of the disease, but will also contribute to the clinical needs for a timely diagnosis and more precise treatment. In this review, we provide an overview of new biomarkers identified in hypertension through the application of proteomic techniques, and we also discuss the difficulties and challenges in identifying biomarkers in this clinical setting. We performed a literature search in PubMed with the key words ‘hypertension’ and ‘proteomics’, and focused specifically on the most recent literature on the utility of proteomics in hypertension research.

Expert opinion: There have been several promising biomarkers of hypertension identified by proteomics, but too few have been introduced to the clinic. Thus, further investigations in larger cohorts are necessary to test the feasibility of this strategy for patients. Also, this emerging field would profit from more collaboration between clinicians and researchers.