Proteomics: a paradigm shift

Proteome--the protein complement of a genome--has become the protein renaissance and a key research tool in the post-genomic era. The basic technology involves the routine usage of gel electrophoresis and spectrometry procedures for deciphering the primary protein sequence/structure as well as knowing certain unique post-translational modifications that a particular protein has undergone to perform a specific function in the cell. However, the recent advancements in protein analysis have ushered this science to provide deeper, bigger and more valuable perspectives regarding performance of subtle protein-protein interactions. Applications of this branch of molecular biology are as vast as the subject is and include clinical diagnostics, pharmaceutical and biotechnological industries. The 21st century hails the use of products, procedures and advancements of this science as finer touches required for the grooming of fast-paced technology.     

Social science and a post-genomic future: alternative readings of genomic agency

Abstract

This paper explores competing discourses that envision different socio-technical landscapes opened up by the completion of the map of the human genome in 2003. It examines the ways in which the map, and its organising principle and very rationale—the gene as the sole or prime agent through which to understand the body and its disordering (as disease)—has been interpreted in quite distinct ways. It suggests how the sequences of a genomic map have post-genomic con-sequences that depend on a social rather than simply biological reading of genomic agency. Various accounts of the map and genetic agency or described, within science, science policy and social science, especially across science and technology studies (STS). The paper concludes with a comparative summary of these positions and asks whether a deconstructive reading of genomic agency by STS analysts might be the basis for a critical re-constructive engagement with post-genomic policy discourse that avoids the over-determination of agency one often finds in the latter.     

The use of calorimetry in the biophysical characterization of small molecule alkaloids binding to RNA structures

BackgroundRNA has now emerged as a potential target for therapeutic intervention. RNA targeted drug design requires detailed thermodynamic characterization that provides new insights into the interactions and this together with structural data, may be used in rational drug design. The use of calorimetry to characterize small molecule–RNA interactions has emerged as a reliable and sensitive tool after the recent advancements in biocalorimetry.Scope of the reviewThis review summarizes the recent advancements in thermodynamic characterization of small molecules, particularly some natural alkaloids binding to various RNA structures. Thermodynamic characterization provides information that can supplement structural data leading to more effective drug development protocols.Major conclusionsThis review provides a concise report on the use of isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) techniques in characterizing small molecules, mostly alkaloids–RNA interactions with particular reference to binding of tRNA, single stranded RNA, double stranded RNA, poly(A), triplex RNA.General significanceIt is now apparent that a combination of structural and thermodynamic data is essential for rational design of specific RNA targeted drugs. Recent advancements in biocalorimetry instrumentation have led to detailed understanding of the thermodynamics of small molecules binding to various RNA structures paving the path for the development of many new natural and synthetic molecules as specific binders to various RNA structures. RNA targeted drug design, that remained unexplored, will immensely benefit from the calorimetric studies leading to the development of effective drugs for many diseases. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah.     

New perspectives in radiation oncology: Young radiation oncologist point of view and challenges

AimTo assess the role of the young radiation oncologist in the context of important recent advancements in the field of radiation oncology, and to explore new perspectives and competencies of the young radiation oncologist.BackgroundRadiation oncology is a field that has rapidly advanced over the last century. It holds a rich tradition of clinical care and evidence-based practice, and more recently has advanced with revolutionary innovations in technology and computer science, as well as pharmacology and molecular biology.Materials and methodsSeveral young radiation oncologists from different countries evaluated the current status and future directions of radiation oncology.ResultsFor young radiation oncologists, it is important to reflect on the current practice and future directions of the specialty as it relates to the role of the radiation oncologist in the comprehensive management of cancer patients. Radiation oncologists are responsible for the radiation treatment provided to patients and its subsequent impact on patients’ quality of life. Young radiation oncologists must proactively master new clinical, biological and technical information, as well as lead radiation oncology teams consisting of physicists, dosimetrists, nurses and technicians.ConclusionsThe role of the young radiation oncologist in the field of oncology should be proactive in developing new competencies. Above all, it is important to remember that we are dealing with the family members and loved ones of many individuals during the most difficult part of their lives.     

Small insecticidal molecules against crop pests

ABSTRACT

Previous decades have seen excessive use of chemical insecticides to control insect-mediated crop losses. However, toxicological and ecological concerns lead to the quest for more sustainable biological molecules as an alternative. Advent of Bt technology witnessed its supersession over chemical control measures and reinvigorated the potential of bioinsecticides as a commercially viable option. But the development of Bt-resistance in insect populations has raised concerns and entails the invention of alternate measures. In this review, we discuss the recent advancements in the field of Bt toxins and evaluate the potential of other insecticidal proteins and RNAi as the next generation insecticidal technologies.     

Strategies for successful designing of immunocontraceptive vaccines and recent updates in vaccine development against sexually transmitted infections - A review

BackgroundThe world population is continuously growing. It has been estimated that half of the world’s population is from the Asian continent, mainly from China and India. Overpopulation may lead to many societal problems as well as to changes in the habitat. Birth control measures are thus needed to control this growth. However, for the last 50–60 years, there have not been any improvements in the field of contraception. Nevertheless, the immunocontraceptive vaccine is an emerging field, and it might be the only replacement for the existing mode of contraception for the next millennium. Sexually transmitted infections (STIs) are frequent, and their transmission rate increases yearly. As antibiotics are the prevailing treatment for this kind of infections, resistance in humans has increased; therefore, having effective antibiotic treatments for STIs is now a concern. Vaccines against STIs are now needed. It is thought that the improvements in the fields of proteomics, immunomics, metabolomics, and other omics will help in the successful development of vaccines.ObjectiveTo collect and review the literature about recent advancements in immunocontraception and vaccines against sexually transmitted diseases/infections.MethodsReliable scientific databases, such as PubMed Central, PubMed, Scopus, Science Direct, and Goggle Scholar, were consulted. Publications bearing important information on targeted antigens/immunogens for contraceptive vaccine design and advancements in vaccine development for STIs were gathered and tabulated, and details were analyzed as per the theme of each study.ResultsImportant antigens that have a specific role in fertility have been studied extensively for their contraceptive nature. Additionally, the advancements in the screening for the best antigens, according to their antigenic nature and how they elicit immune responses for an extended period were also studied. Herd immunity for STIs and advancements in the development of vaccines for syphilis, gonorrhea, and herpes simplex virus were also studied and tabulated in this review. An extensive knowledge on STIs vaccines was gained.ConclusionThis extensive review is aimed to provide insights for active researchers in vaccinology, immunology, and reproductive biology. Advancements in the development of vaccines for different STIs can be gathered as a wholesome report.     

Blood and sputum protein biomarkers for chronic obstructive pulmonary disease (COPD)

ABSTRACT

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous set of disorders, characterized by airflow limitation, and reduced lung function. Despite increasing knowledge regarding its pathophysiology, there has been limited advancement in therapeutics and the current treatment strategy is symptom management and prevention of exacerbations.

Areas covered: Biomarkers represent important tools for the implementation of precision medicine. As fundamental molecules of all living processes, proteins could provide crucial information about how genes interact with the environment. Proteomics studies could act as important tools in identifying reliable biomarkers to enable a more precise therapeutic approach. In this review, we will explore the most promising blood and sputum protein biomarkers in COPD that have been consistently reported in the literature.

Expert commentary: Given the complexity of COPD, no single protein biomarker has been able to improve the outcomes of COPD patients. According to preliminary studies, precision medicine in COPD will likely require a combination of different proteins in a biomarker panel for clinical translation. With advancements in current mass spectrometry techniques, an enhancement in the identification of new biomarkers will be observed, and improvements in sequence database search can fill in potential gaps between biomarker discovery and patient care.     

蛋白质纯化技术研究进展

蛋白质组学研究的基础就是蛋白质的分离。对于天然蛋白来说,可能需要一系列的纯化步骤才能获得纯度满足研究要求的蛋白质,但是蛋白质在分离过程中常常由于溶液环境变化或外力作用造成构象变化而引起失活。本文首先介绍了常用的蛋白质分离纯化技术及其研究进展,包括膜分离技术、沉淀分离技术、电泳分离技术以及层析分离技术等常用的蛋白质纯化技术,总结了现有技术存在的问题,并对近年来发展的新型蛋白质分离技术--非对称流场流分离技术进行了介绍和展望。     

Quantification of manganese and mercury in toenail in vivo using portable X-ray fluorescence (XRF)

Background and objective: Toenail is an advantageous biomarker to assess exposure to metals such as manganese and mercury. Toenail Mn and Hg are in general analyzed by chemical methods such as inductively coupled plasma mass spectrometry and atomic absorption spectrophotometry. In this project, a practical and convenient technology—portable X-ray florescence (XRF)—is studied for the noninvasive in vivo quantification of manganese and mercury in toenail.

Material and methods: The portable XRF method has advantages in that it does not require toenail clipping and it can be done in 3?min, which will greatly benefit human studies involving the assessment of manganese and mercury exposures. This study mainly focused on the methodology development and validation which includes spectral analysis, system calibration, the effect of toenail thickness, and the detection limit of the system. Manganese- and mercury-doped toenail phantoms were made. Calibration lines were established for these measurements.

Results: The results show that the detection limit for manganese is 3.65?μg/g (ppm) and for mercury is 0.55?μg/g (ppm) using 1?mm thick nail phantoms with 10?mm soft tissue underneath.

Discussion and conclusion: We conclude that portable XRF is a valuable and sensitive technology to quantify toenail manganese and mercury in vivo.     

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.     

Deciphering nasopharyngeal carcinoma pathogenesis via proteomics

Introduction: Nasopharyngeal carcinoma (NPC) is a distinct head and neck squamous cell carcinoma in its etiological association of Epstein–Barr virus (EBV) infection, hidden anatomical location, remarkable racial and geographical distribution, and high incidence of locoregional recurrence or metastasis. Thanks to the advancements in proteomics in recent decades, more understanding of the disease etiology, carcinogenesis, and progression has been gained, potentially deciphering the molecular characteristics of the malignancy.

Areas covered: In this review, we provide an overview of the proteomic aberrations that are likely involved or drive NPC development and progression, focusing on the contributions of major EBV-encoded factors, intercommunication with environment, protein features of high metastasis and therapy resistance, and protein–protein interactions that allow NPC cells to evade immune recognition and elimination. Finally, multistep carcinogenesis and subtypes of NPC from a proteomic perspective are inquired.

Expert commentary: Proteomic studies have covered various aspects involved in NPC pathogenesis, yet much remains to be uncovered. Coherent study designs, optimal conditions for obtaining high-quality data, and compelling interpretation are critical in ensuring the emergence of good science out of NPC proteomics. NPC proteogenomics and proteoform analysis are two promising fields to promote the application of the proteomic findings from bench to bedside.     

Heparin concentration is critical for cell culture with human platelet lysate

Background aimsCulture media for mesenchymal stromal cells (MSCs) are generally supplemented with fetal bovine serum. Human platelet lysate (hPL) has been proven to be a very effective alternative without the risk of xenogeneic infections or immune reactions. In contrast to fetal bovine serum, hPL comprises plasma, and anticoagulants—usually unfractionated heparin (UFH)—need to be added to prevent gel formation.MethodsCultures of MSCs in hPL media with various concentrations of UFH and enoxaparin, a low-molecular-weight heparin (LMWH), were systematically compared with regard to proliferation, fibroblastoid colony-forming unit frequency, immunophenotype and in vitro differentiation.ResultsAt least 0.61 IU/mL UFH or 0.024 mg/mL LMWH was necessary for reliable prevention of coagulation of hPL pools used in this study. Higher concentrations impaired cellular proliferation in a dose-dependent manner even without benzyl alcohol, which is commonly added to heparins as a bacteriostatic agent. Colony-forming unit frequency was also reduced at higher heparin concentrations, particularly with LMWH, whereas no significant effect was observed on cellular morphology or immunophenotype. High concentrations of heparins reduced the in vitro differentiation toward adipogenic and osteogenic lineages.ConclusionsHeparin concentration is critical for culture of MSCs in hPL media; this is of particular relevance for cellular therapy where cell culture procedures need to be optimized and standardized.     

Long-Range Interactions between Ligands Bound to a DNA Molecule Give Rise to Adsorption with the Character of Phase Transition of the First Kind

Abstract

Influence of long-range interactions between ligands bound to DNA molecule on the character of their adsorption is studied using computer modeling. For this investigation, two calculation procedures are developed. They are based upon the method of the free energy minimum and on the partition function method. The both procedures demonstrate that in the case of a strong enough attraction between all the bound ligands their binding to DNA has the character of phase transition of the first kind. There is a break in the binding curve c(c₀) where c—relative concentration of bound ligands, c ₀—molar concentration of free ligands. The break occurs because there is an interval of central degrees of binding (～50% of the maximum c value) that are prohibited for individual DNA molecules. Such a transition might be caused by some types of DNA condensation. Attraction between the neighboring ligands only, adjacent or/and separated by double helix regions, does not cause this effect.     

Plasma proteomics and the paediatric patient

Introduction: Plasma proteomics has been extensively utilized for studies that investigate various disease settings (e.g. cardiovascular disease), as well as to monitor the effect of pharmaceuticals on the plasma proteome (e.g. chemotherapy). However, plasma proteomic studies focusing on children represent a very small proportion of the plasma proteomic studies completed to date. Early disease detection and prevention is critical in pediatrics, as children must live with the disease outcomes for many years and often carry negative outcomes into adulthood. Pediatrics represents an area of plasma proteomics that is about to undergo a significant expansion.

Areas covered: This review is based on a PubMed search focusing on five keywords that are plasma, biomarkers, pediatric, proteomics, and children. It is a comprehensive summary of plasma proteomic studies specific to the pediatric patient and discusses aspects such as the clinical setting, sample size, methodological approaches and outlines the significance of the findings.

Expert commentary: Plasma proteomics is expanding significantly as a result of major advancements in proteomic technology. This is in synergy with the growing focus on true early disease detection and prevention in early life. We are about to see a new era of advanced medical science built from pediatric proteomics.     

Chlorosome antenna complexes from green photosynthetic bacteria

Chlorosomes are the distinguishing light-harvesting antenna complexes that are found in green photosynthetic bacteria. They contain bacteriochlorophyll (BChl) c, d, e in natural organisms, and recently through mutation, BChl f, as their principal light-harvesting pigments. In chlorosomes, these pigments self-assemble into large supramolecular structures that are enclosed inside a lipid monolayer to form an ellipsoid. The pigment assembly is dictated mostly by pigment–pigment interactions as opposed to protein–pigment interactions. On the bottom face of the chlorosome, the CsmA protein aggregates into a paracrystalline baseplate with BChl a, and serves as the interface to the next energy acceptor in the system. The exceptional light-harvesting ability at very low light conditions of chlorosomes has made them an attractive subject of study for both basic and applied science. This review, incorporating recent advancements, considers several important aspects of chlorosomes: pigment biosynthesis, organization of pigments and proteins, spectroscopic properties, and applications to bio-hybrid and bio-inspired devices.     

Advances in understanding the role of disease-associated proteins in spinal muscular atrophy

Introduction: Spinal muscular atrophy (SMA) is a neurodegenerative disorder characterized by alpha motor neuron loss in the spinal cord due to reduced survival motor neuron (SMN) protein level. While the genetic basis of SMA is well described, the specific molecular pathway underlying SMA is still not fully understood.

Areas covered: This review discusses the recent advancements in understanding the molecular pathways in SMA using different omics approaches and genetic modifiers identified in both vertebrate and invertebrate systems. The findings that are summarized in this article were deduced from original articles and reviews with a particular focus on the latest advancements in the field.

Expert commentary: The identification of genetic modifiers such as PLS3 and NCALD in humans or of SMA modulators such as Elavl4 (HuD), Copa, Uba1, Mapk10 (Jnk3), Nrxn2 and Tmem41b (Stasimon) in various SMA animal models improved our knowledge of impaired cellular pathways in SMA. Inspiration from modifier genes and their functions in motor neuron and neuromuscular junctions may open a new avenue for future SMA combinatorial therapies.     

Boron removal and recovery from water and wastewater

Boron is an important element for plants, humans, and animals in limited amounts. However, excess amounts can cause adverse effects in both humans and plants, necessitating its removal from certain systems. Boron compounds are used in many industrial applications, including in developing sectors like alternative energy technology; as a result, the need for this element is increasing and industries are looking towards boron recovery for the sustained use of this element in their products. While the literature on boron removal strategies is abundant, there is a relative lack of studies on boron recovery, with no review papers having yet addressed this topic. In this review, both boron removal and recovery techniques involving conventional approaches and membrane processes are examined to juxtapose the states of the science in these two related—and increasingly important—processes.

Graphical abstract

     

Digital game design-based STEM activity: Biodiversity example

Abstract

The purpose of this study is to design a digital game design-based STEM activity for fifth-grade students learning about endangered organisms and significance of biodiversity for living. This activity was carried out with twenty students in a public school in Eastern Black Sea Region of Turkey during academic year of 2018–2019 spring term. This study planned as eight-lesson time (8?×?40?minutes) and completed at this lesson time. The students were given the digital game design challenge in real-life problem context that has been created based on design-based science learning and for which they shall use their knowledge and skills in each of the STEM disciplines. During this design challenge, students worked like a scientist and an engineer. They carried out scientific research and inquiry process in the science discipline, understood the engineering design process in the engineering discipline, established mathematical relations in the mathematics discipline, learned how to make coding in the technology discipline, and used this knowledge and skills thus acquired in their suggested solutions for the design challenge. They designed a digital game by coding and presented science knowledge and skills that acquired from inquiry process.