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Saliva has gained increasing attention in the quest for disease biomarkers. Because it is a biological fluid that can be collected is an easy, painless, and safe way, it has been increasingly studied for the identification of oral cancer biomarkers. This is particularly important because oral cancer is often diagnosed at late stages with a poor prognosis. The review addresses the evolution of the experimental approaches used in salivary proteomics studies of oral cancer over the years and outlines advantages and pitfalls related to each one. In addition, examines the current landscape of oral cancer biomarker discovery and translation focusing on salivary proteomic studies. This discussion is based on an extensive literature search (PubMed, Scopus and Google Scholar). The introduction of mass spectrometry has revolutionized the study of salivary proteomics. In the future, the focus will be on refining existing methods and introducing powerful experimental techniques such as mass spectrometry with selected reaction monitoring, which, despite their effectiveness, are still underutilized due to their high cost. In addition, conducting studies with larger cohorts and establishing standardized protocols for salivary proteomics are key challenges that need to be addressed in the coming years. [ABSTRACT FROM AUTHOR]

Fertility rates in developing countries have declined over the past decades, and the trend of delayed fatherhood is rising as societies develop. The reasons behind the decline in male fertility with advancing age remain mysterious, making it a compelling and crucial area for further research. However, the limited number of studies dedicated to unraveling this enigma poses a challenge. Thus, our objective is to illuminate some of the upregulated and downregulated mechanisms in the male testis during the aging process. Herein, we present a critical overview of the studies addressing the alterations of testicular proteome through the aging process, starting from sexually matured young males to end-of-life-expectancy aged males. The comparative studies of the proteomic testicular profile of men with and without spermatogenic impairment are also discussed and key proteins and pathways involved are highlighted. The difficulty of making age-comparative studies, especially of advanced-age study subjects, makes this topic of study quite challenging. Another topic worth mentioning is the heterogeneous nature and vast cellular composition of testicular tissue, which makes proteome data interpretation tricky. The cell type sorting and comorbidities testing in the testicular tissue of the studied subjects would help mitigate these problems. [ABSTRACT FROM AUTHOR]

The implementation of Building Information Modelling (BIM) in the Architecture, Engineering, Construction and Operations (AECO) industry requires multidisciplinary teams equipped with new technical and managerial skills. Professionals that are inexperienced or unfamiliar with the BIM design process face difficulties in transposing complex concepts into BIM modelling and coordination practices, despite governments, industry bodies, and academia's efforts. With this issue in mind, this article's objective is to present the teaching-learning strategies and tools adopted in a practical case of modelling an existing building on a BIM platform. In terms of method, a phenomenological approach has been taken to report on an exploratory didactic experience. The Cognitive Load Theory (CLT) was used to assess learning based on the authors' perceptions. The research has been structured into the following five stages: Literature Review; Analysis of Brazilian and International BIM Standards and Guides; Didactic exercise; Experience Assessment; and Conclusions. The results reveal aspects of BIM processes that can be widely investigated in an academic environment, such as the BIM design and coordination process model, which can be explored as a tool in the BIM teaching-learning process. Also, difficulties related to teaching BIM management processes were identified, thus calling for different didactic approaches. The contributions made by the research come from reporting and analysing the process of learning complex BIM content from the perspective of inexperienced professionals. The work also contributes to the field through the BIM learning assessment proposal and the BIM process model resulted from the authors' practical experience. [ABSTRACT FROM AUTHOR]

Periodontitis is a complex immune-inflammatory condition characterized by the disruption of the periodontal ligament and subsequent formation of periodontal pockets, and by alveolar bone loss, often resulting in tooth loss. A myriad of factors, namely, genetic, metabolic, immunological, and inflammatory, is associated with progression of periodontitis. Periodontitis is also associated with systemic conditions such as neoplastic disorders, obesity, and diabetes. The current diagnosis of this disease relies on clinical measurements such as clinical attachment loss and probing depth, which have poor precision due to patient, operator and probe-related factors. Thus, there is a need to develop reliable, objective, and reproducible biomarkers for early diagnosis of periodontitis. In this regard, saliva, with contributions from the gingival crevicular fluid, holds great potential. However, most of the information on biomarkers of periodontium-related salivary proteins has come from studies on the molecular pathogenesis of periodontitis. In periodontitis, a more holistic approach, such as the use of -omics technologies, for biomarker discovery, is needed. Herein, we review the biomarkers proposed to date for the assessment of periodontitis, with emphasis on the role of salivary peptides in periodontitis and their assessment by high-throughput saliva proteomics. We also discuss the challenges pertaining to the identification of new periodontitis biomarkers in saliva. [ABSTRACT FROM AUTHOR]

With available genomic data and related information, it is becoming possible to better highlight mutations or genomic alterations associated with a particular disease or disorder. The advent of high-throughput sequencing technologies has greatly advanced diagnostics, prognostics, and drug development. Peptidomics and proteogenomics are the two post-genomic technologies that enable the simultaneous study of peptides and proteins/transcripts/genes. Both technologies add a remarkably large amount of data to the pool of information on various peptides associated with gene mutations or genome remodeling. Literature search was performed in the PubMed database and is up to date. This article lists various techniques used for peptidomic and proteogenomic analyses. It also explains various bioinformatics workflows developed to understand differentially expressed peptides/proteins and their role in disease pathogenesis. Their role in deciphering disease pathways, cancer research, and biomarker discovery using biofluids is highlighted. Finally, the challenges and future requirements to overcome the current limitations for their effective clinical use are also discussed. [ABSTRACT FROM AUTHOR]

The increasing prevalence of periodontal and cardiovascular diseases is the result of a sedentary lifestyle associated with poor diet, obesity, hypercholesterolaemia, smoking habits, alcohol consumption and stress. The present study aims to uncover molecular associations between periodontitis and coronary heart disease using an unbiased strategy of automatic text mining traditionally applied to bibliometric studies. A total of 1590 articles on these diseases were retrieved from the Web of knowledge database and searched using the VOS viewer to create a network of keywords associated with both diseases. These data were supplemented with data from DisGeNET, which stores known associations to either periodontitis or coronary heart disease. Overall, the automated text mining approach presented here highlighted inflammatory molecules as common associations between periodontitis and coronary heart disease. Specifically, this study showed that molecules such as C-reactive protein, interleukins 6 and 1-β, myeloperoxidase, and matrix metalloproteinase 9 are simultaneously associated with periodontitis and coronary artery disease by both text mining and DisGeNET analyses. This association validates the multiplex assessment of salivary inflammatory markers as a tool to assess cardiovascular disease risk and could become an important tool to identify common molecular targets to monitor both diseases simultaneously. In addition, the text mining protocol and subsequent data processing and methods using bioinformatics tools could be useful to uncover links between other diseases. [ABSTRACT FROM AUTHOR]

Peptidomics is an emerging field of omics sciences using advanced isolation, analysis, and computational techniques that enable qualitative and quantitative analyses of various peptides in biological samples. Peptides can act as useful biomarkers and as therapeutic molecules for diseases The use of therapeutic peptides can be predicted quickly and efficiently using data-driven computational methods, particularly artificial intelligence (AI) approach. Various AI approaches are useful for peptide-based drug discovery, such as support vector machine, random forest, extremely randomized trees, and other more recently developed deep learning methods. AI methods are relatively new to the development of peptide-based therapies, but these techniques already become essential tools in protein science by dissecting novel therapeutic peptides and their functions (Figure 1). Researchers have shown that AI models can facilitate the development of peptidomics and selective peptide therapies in the field of peptide science. Biopeptide prediction is important for the discovery and development of successful peptide-based drugs. Due to their ability to predict therapeutic roles based on sequence details, many AI-dependent prediction tools have been developed (Figure 1). [ABSTRACT FROM AUTHOR]

Mitochondrial fatty acid β-oxidation disorders (FAOD) are among the diseases detected by newborn screening in most developed countries. Alterations of mitochondrial functionality are characteristic of these metabolic disorders. However, many questions remain to be clarified, namely how the interplay between the signaling pathways harbored in mitochondria contributes to the disease-related phenotype. Herein, we overview the role of mitochondria on the regulation of cell homeostasis through the production of ROS, mitophagy, apoptosis, and mitochondrial biogenesis. Emphasis is given to the signaling pathways involving MnSOD, sirtuins and PGC-1α, which seem to contribute to FAOD phenotype, namely to multiple acyl-CoA dehydrogenase deficiency (MADD). The association between phenotype and genotype is not straightforward, suggesting that specific molecular mechanisms may contribute to MADD pathogenesis, making MADD an interesting model to better understand this interplay. However, more work needs to be done envisioning the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: With the worldwide decline on male fertility potential, the importance of the insight of the spermatogenic process has been increasing. In recent years, proteomic methodologies have been applied to seminal fluid of infertile men to search for infertility potential biomarkers. However, to understand the spermatogenic event and to search for treatment to spermatogenic impairment, comparative analysis of testicular proteomics is considered a powerful methodology. Areas covered: Herein, we present a critical overview of the studies addressing proteomic alterations in the development of spermatogenesis during puberty, as well as during the different phases of the spermatogenic event. The comparative studies of the proteomic testicular profile of men with and without spermatogenic impairment are also discussed and key proteins and pathways involved highlighted. Expert opinion: The usage of whole human testicular tissue with its heterogeneous cellular composition makes proteome data interpretation particularly challenging. This may be minimized by controlled experiments involving the collection of testicular tissue and sperm from the same individuals, integrated in a clinically characterized cohort of healthy and infertile men. The analysis of specific subcellular proteomes can add more information to the proteomic puzzle, opening new treatment possibilities for infertile/subfertile men. [ABSTRACT FROM AUTHOR]

This paper exhibits an outline of the piston rings operational characteristics and consequently, of their main functional challenges. The basic geometrical shapes, materials and manufacturing technologies used to produce compression rings for up to date diesel engines are summarized. Based on this description, each technological solution to enhance the behavior of the piston rings is fully described and explained. The state-of-the-art solutions such as a DLC (diamond-like carbon) layer, multi-layered coatings and compound coatings are tersely presented and discussed. New approaches suggest surface textures, which are expected to be a major improvement in the development of optimized surface coatings of the piston rings, and the latest progress in that area is examined and debated. Also, a novel solution for the enhancement of the behavior of ring coatings is presented, using a proposed and previously tested solution for a different application. This solution attempts to optimize most of the properties in relation to friction, wear, mechanical stresses, heat dissipation and self-lubrication. The overall idea is to use specific materials in specified positions over the surface to individually enhance the referred properties, creating a multifunctional surface. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) is an excellent source of biological information regarding the nervous system, once it is in close contact and accurately reflects alterations in this system. Several studies have analyzed differential protein profiles of CSF samples between healthy and diseased human subjects. However, the pathophysiological mechanisms and how CSF proteins relate to diseases are still poorly known. By applying bioinformatics tools, we attempted to provide new insights on the biological and functional meaning of proteomics data envisioning the identification of putative disease biomarkers. Bioinformatics analysis of data retrieved from 99 mass spectrometry (MS)-based studies on CSF profiling highlighted 1985 differentially expressed proteins across 49 diseases. A large percentage of the modulated proteins originate from exosome vesicles, and the majority are involved in either neuronal cell growth, development, maturation, migration, or neurotransmitter-mediated cellular communication. Nevertheless, some diseases present a unique CSF proteome profile, which were critically analyzed in the present study. For instance, 48 proteins were found exclusively upregulated in the CSF of patients with Alzheimer’s disease and are mainly involved in steroid esterification and protein activation cascade processes. A higher number of exclusively upregulated proteins were found in the CSF of patients with multiple sclerosis (76 proteins) and with bacterial meningitis (70 proteins). Whereas in multiple sclerosis, these proteins are mostly involved in the regulation of RNA metabolism and apoptosis, in bacterial meningitis the exclusively upregulated proteins participate in inflammation and antibacterial humoral response, reflecting disease pathogenesis. The exploration of the contribution of exclusively upregulated proteins to disease pathogenesis will certainly help to envision potential biomarkers in the CSF for the clinical management of nervous system diseases. [ABSTRACT FROM PUBLISHER]

Introduction:The proper folding of native proteins is critical and dynamic, but inherently unstable. Therefore, proteins eventually end up adopting misfolded conformations which compromise their function and may even trigger aggregation. Risk factors for neurodegenerative, metabolic and heart diseases compromise cellular protein quality-control systems, promoting protein aggregation. Multiple protein post-translational modifications dynamically regulate protein aggregation and disaggregation in a very complex, intricate and delicate balance. Areas covered:Herein, we overview the more promising techniques and approaches for the elucidation of the biological implications of protein aggregation. The particular insights provided by different techniques were discriminated and several examples of post-translational modifications together with their targets were pooled and critically discussed, representing promising future therapeutic targets. Expert commentary:In the years to come, differences between physiological and pathological protein aggregation will certainly become easier to determine. Techniques such as hydrogen/deuterium exchange, circular dichroism spectroscopy and novel mass spectrometry-based approaches are being optimized and are expected to introduce inhibitors of protein aggregation into the clinic. However, protein aggregation is not an isolated phenomenon, but rather influenced by multiple cellular components which complete knowledge is still far. [ABSTRACT FROM PUBLISHER]

A disparity in gender incidence has been reported in both papillary thyroid carcinoma (PTC) and chronic lymphocytic thyroiditis (CLT) diseases frequently associated and whose incidence has been increasing in parallel. We aimed to analyze differences in morphometric variables between male and female PTC patients and their relationship with the presence of concurrent CLT. The nuclear texture features of 100 hematoxylin-eosin stained nuclei from 100 consecutive classic PTC patients enrolled in our service were compared with their clinical and pathological features, including the presence of CLT. All patients were submitted to a standard management protocol and followed-up for 13-248 months (Mo = 117 months). Chromatin in women tended to present a denser and more homogeneous structure, in a less mottled pattern, with higher values of energy ( p = 0.008) and diagonal moment ( p = 0.032) than men. Concurrent CLT was more prevalent in women (41.42%) than in men (13.33%, p = 0.04) and was associated with higher cluster prominence values ( p = 0.027), a parameter that indicates a predominance of high nuclear contrasted heterochromatin. A multivariate logistic regression analysis showed that higher cluster prominence was independently correlated with chromatin in patients who presented CLT but did not demonstrate any association between concurrent CLT and gender. We were unable to demonstrate any association between gender and any characteristic of tumor aggressiveness or patients outcome. Our results suggest that chromatin texture of hematoxylin-eosin stained nuclei in paraffin sections of PTC cells is related to both gender and concurrent CLT. [ABSTRACT FROM AUTHOR]

Growing evidence suggests that a range of reversible protein post-translational modifications such as acetylation regulates mitochondria signalling, impacting cellular homeostasis. However, the extent of this type of regulation in the control of mitochondria functionality is just beginning to be discovered, aided by the availability of high-resolution mass spectrometers and bioinformatic tools. Data mining from literature on protein acetylation profiling focused on mitochondria isolated from tissues retrieved more than 1395 distinct proteins, corresponding to more than 4858 acetylation sites. ClueGo analysis of identified proteins highlighted oxidative phosphorylation, tricarboxylic acid cycle, fatty acid oxidation and amino acid metabolism as the biological processes more prone to regulation through acetylation. This review also examines the physiological relevance of protein acetylation on the molecular pathways harbored in mitochondria under distinct pathophysiological conditions as caloric restriction and alcohol-induced liver damage. This integrative perspective will certainly help to envisage future studies targeting the regulation of mitochondrial functionality. [ABSTRACT FROM AUTHOR]

The Scl (Tal1) gene encodes a helix-loop-helix transcription factor essential for hematopoietic stem cell and erythroid development. The Scl +40 enhancer is situated downstream of Map17, the 3' flanking gene of Scl, and is active in transgenic mice during primitive and definitive erythropoiesis. To analyze the in vivo function of the Scl +40 enhancer within the Scl/Map17 transcriptional domain, we deleted this element in the germ line. SclΔ40/Δ40 mice were viable with reduced numbers of erythroid CFU in both bone marrow and spleen yet displayed a normal response to stress hematopoiesis. Analysis of SclΔ40/Δ40 embryonic stem (ES) cells revealed impaired erythroid differentiation, which was accompanied by a failure to upregulate Scl when erythropoiesis was initiated. Map17 expression was also reduced in hematopoietic tissues and differentiating ES cells, and the Scl +40 element was able to enhance activity of the Map17 promoter. However, only Scl but not Map17 could rescue the SclΔ40/Δ40 ES phenotype. Together, these data demonstrate that the Scl +40 enhancer is an erythroid cell-specific enhancer that regulates the expression of both Scl and Map17. Moreover, deletion of the +40 enhancer causes a novel erythroid phenotype, which can be rescued by ectopic expression of Scl but not Map17. [ABSTRACT FROM AUTHOR]

A fluorophore-anchor dye based on the 4-amino-1,8-naphthalimide chromophore was designed and characterised with respect to its ability of forming supramolecular host–guest complexes with cucurbit[6]uril (CB6) and cucurbit[7]uril (CB7) hosts. It was found that CB6 encapsulates the anchor of the dye with a high binding constant [K = (1.1–1.4) × 107 M− 1], which was independent of acidic or neutral pH conditions. The 1:1 binding was accompanied by fluorescence quenching (ca. 20%) and a bathochromic shift (Δλ = +22 nm) of the charge-transfer absorption band of the dye. This is indicative of the occurrence of hydrogen bonding between a carbonyl-lined host portal and the aromatic NH group of the guest dye. In comparison, CB7 encapsulated the dye much less efficiently (K = 4.8 × 104 M− 1) and showed a significant fluorescence enhancement (Φf = 0.15 versus 0.52 for free and CB7-complexed dye at pH 4, respectively). The occurrence of hydrogen bonding with the aromatic NH was much less evident for CB7 as judged by the only minor bathochromic shift (Δλ = +4 nm) of the charge-transfer absorption band of the dye. The dye–CB6 assembly has the potential for the detection of biogenic amines under physiological pH conditions and at low analyte concentrations. [ABSTRACT FROM PUBLISHER]

Focuses on the knowledge of the biological functions of the hematopoietic transcription factor GATA1 to determine its influence on the establishment of lineage-specific expression profiles. Development of mature blood cells of distinct lineages from the hematopoietic stem cells; Modulation of the expression of target genes; Use of GATA1 as a paradigm for hematopoietic transcription factors.

Development progresses through a sequence of cellular identities which are determined by the activities of networks of transcription factor genes. Alterations in cis-regulatory elements of these genes play a major role in evolutionary change, but little is known about the mechanisms responsible for maintaining conserved patterns of gene expression. We have studied the evolution of cis-regulatory mechanisms controlling the SCL gene, which encodes a key transcriptional regulator of blood, vasculature, and brain development and exhibits conserved function and pattern of expression throughout vertebrate evolution. SCL cis-regulatory elements are conserved between frog and chicken but accrued alterations at an accelerated rate between 310 and 200 million years ago, with subsequent fixation of a new cis-regulatory pattern at the beginning of the mammalian radiation. As a consequence, orthologous elements shared by mammals and lower vertebrates exhibit functional differences and binding site turnover between widely separated cis-regulatory modules. However, the net effect of these alterations is constancy of overall regulatory inputs and of expression pattern. Our data demonstrate remarkable cis-regulatory remodelling across the SCL locus and indicate that stable patterns of expression can mask extensive regulatory change. These insights illuminate our understanding of vertebrate evolution. [ABSTRACT FROM AUTHOR]

An abstract of the article "Characteristics and Limitations of the 2D Drawing in the Review of Design Plans," by Rita Cristina Ferreira and Eduardo Toledo Santos is presented.