Genes

MYC regulates a complex biological program by transcriptionally activating and repressing its numerous target genes. As such, MYC is a master regulator of many processes, including cell cycle entry, ribosome biogenesis, and metabolism. In cancer, the activity of the MYC transcriptional network is frequently deregulated, contributing to the initiation and maintenance of disease. Deregulation often leads to constitutive overexpression of MYC, which can be achieved through gross genetic abnormalities, including copy number alterations, chromosomal translocations, increased enhancer activity, or through aberrant signal transduction leading to increased MYC transcription or increased MYC mRNA and protein stability. Herein, we summarize the frequency and modes of MYC deregulation and describe both well-established and more recent findings in a variety of cancer types. Notably, these studies have highlighted that with an increased appreciation for the basic mechanisms deregulating MYC in cancer, new therapeutic vulnerabilities can be discovered and potentially exploited for the inhibition of this potent oncogene in cancer.

DNA methylation is a major epigenetic mark with important roles in genetic regulation. Methylated cytosines are found primarily at CpG dinucleotides, but are also found at non-CpG sites (CpA, CpT, and CpC). The general functions of CpG and non-CpG methylation include gene silencing or activation depending on the methylated regions. CpG and non-CpG methylation are found throughout the whole genome, including repetitive sequences, enhancers, promoters, and gene bodies. Interestingly, however, non-CpG methylation is restricted to specific cell types, such as pluripotent stem cells, oocytes, neurons, and glial cells. Thus, accumulation of methylation at non-CpG sites and CpG sites in neurons seems to be involved in development and disease etiology. Here, we provide an overview of CpG and non-CpG methylation and their roles in neurological diseases.

Being the most common musculoskeletal progressive condition, osteoarthritis is an interesting target for research. It is estimated that the prevalence of knee osteoarthritis (OA) among adults 60 years of age or older is approximately 10% in men and 13% in women, making knee OA one of the leading causes of disability in elderly population. Today, we know that osteoarthritis is not a disease characterized by loss of cartilage due to mechanical loading only, but a condition that affects all of the tissues in the joint, causing detectable changes in tissue architecture, its metabolism and function. All of these changes are mediated by a complex and not yet fully researched interplay of proinflammatory and anti-inflammatory cytokines, chemokines, growth factors and adipokines, all of which can be measured in the serum, synovium and histological samples, potentially serving as biomarkers of disease stage and progression. Another key aspect of disease progression is the epigenome that regulates all the genetic expression through DNA methylation, histone modifications, and mRNA interference. A lot of work has been put into developing non-surgical treatment options to slow down the natural course of osteoarthritis to postpone, or maybe even replace extensive surgeries such as total knee arthroplasty. At the moment, biological treatments such as platelet-rich plasma, bone marrow mesenchymal stem cells and autologous microfragmented adipose tissue containing stromal vascular fraction are ordinarily used. Furthermore, the latter two mentioned cell-based treatment options seem to be the only methods so far that increase the quality of cartilage in osteoarthritis patients. Yet, in the future, gene therapy could potentially become an option for orthopedic patients. In the following review, we summarized all of the latest and most important research in basic sciences, pathogenesis, and non-operative treatment.

Charcot-Marie-Tooth (CMT) neuropathies comprise a group of monogenic disorders affecting the peripheral nervous system. CMT is characterized by a clinically and genetically heterogeneous group of neuropathies, involving all types of Mendelian inheritance patterns. Over 1,000 different mutations have been discovered in 80 disease-associated genes. Genetic research of CMT has pioneered the discovery of genomic disorders and aided in understanding the effects of copy number variation and the mechanisms of genomic rearrangements. CMT genetic study also unraveled common pathomechanisms for peripheral nerve degeneration, elucidated gene networks, and initiated the development of therapeutic approaches. The reference genome, which became available thanks to the Human Genome Project, and the development of next generation sequencing tools, considerably accelerated gene and mutation discoveries. In fact, the first clinical whole genome sequence was reported in a patient with CMT. Here we review the history of CMT gene discoveries, starting with technologies from the early days in human genetics through the high-throughput application of modern DNA analyses. We highlight the most relevant examples of CMT genes and mutation mechanisms, some of which provide promising treatment strategies. Finally, we propose future initiatives to accelerate diagnosis of CMT patients through new ways of sharing large datasets and genetic variants, and at ever diminishing costs.

Mitogen-activated protein kinase (MAPK) pathways are implicated in several cellular processes including proliferation, differentiation, apoptosis, cell survival, cell motility, metabolism, stress response and inflammation. MAPK pathways transmit and convert a plethora of extracellular signals by three consecutive phosphorylation events involving a MAPK kinase kinase, a MAPK kinase, and a MAPK. In turn MAPKs phosphorylate substrates, including other protein kinases referred to as MAPK-activated protein kinases (MAPKAPKs). Eleven mammalian MAPKAPKs have been identified: ribosomal-S6-kinases (RSK1-4), mitogen- and stress-activated kinases (MSK1-2), MAPK-interacting kinases (MNK1-2), MAPKAPK-2 (MK2), MAPKAPK-3 (MK3), and MAPKAPK-5 (MK5). The role of these MAPKAPKs in inflammation will be reviewed.

Dietary alteration of the gut microbiome is an important target in the treatment of obesity. Animal and human studies have shown bidirectional weight modulation based on the probiotic formulation used. In this study, we systematically reviewed the literature and performed a meta-analysis to assess the impact of prebiotics, probiotics and synbiotics on body weight, body mass index (BMI) and fat mass in adult human subjects. We searched Medline (PubMed), Embase, the Cochrane Library and the Web of Science to identify 4721 articles, of which 41 were subjected to full-text screening, yielding 21 included studies with 33 study arms. Probiotic use was associated with significant decreases in BMI, weight and fat mass. Studies of subjects consuming prebiotics demonstrated a significant reduction in body weight, whereas synbiotics did not show an effect. Overall, when the utilization of gut microbiome-modulating dietary agents (prebiotic/probiotic/synbiotic) was compared to placebo, there were significant decreases in BMI, weight and fat mass. In summary, dietary agents for the modulation of the gut microbiome are essential tools in the treatment of obesity and can lead to significant decreases in BMI, weight and fat mass. Further studies are needed to identify the ideal dose and duration of supplementation and to assess the durability of this effect.

Biosensors are enabling major advances in the field of analytics that are both facilitating and being facilitated by advances in synthetic biology. The ability of biosensors to rapidly and specifically detect a wide range of molecules makes them highly relevant to a range of industrial, medical, ecological, and scientific applications. Approaches to biosensor design are as diverse as their applications, with major biosensor classes including nucleic acids, proteins, and transcription factors. Each of these biosensor types has advantages and limitations based on the intended application, and the parameters that are required for optimal performance. Specifically, the choice of biosensor design must consider factors such as the ligand specificity, sensitivity, dynamic range, functional range, mode of output, time of activation, ease of use, and ease of engineering. This review discusses the rationale for designing the major classes of biosensor in the context of their limitations and assesses their suitability to different areas of biotechnological application.

Air quality depends on the various gases and particles present in it. Both natural phenomena and human activities affect the cleanliness of air. In the last decade, many countries experienced an unprecedented industrial growth, resulting in changing air quality values, and correspondingly, affecting our life quality. Air quality can be accessed by employing microchips that qualitatively and quantitatively determine the present gases and dust particles. The so-called particular matter 2.5 (PM2.5) values are of high importance, as such small particles can penetrate the human lung barrier and enter the blood system. There are cancer cases related to many air pollutants, and especially to PM2.5, contributing to exploding costs within the healthcare system. We focus on various current and potential future air pollutants, and propose solutions on how to protect our health against such dangerous substances. Recent developments in the Organ-on-Chip (OoC) technology can be used to study air pollution as well. OoC allows determination of pollutant toxicity and speeds up the development of novel pharmaceutical drugs.

The basic region/leucine zipper motif (bZIP) transcription factor family is one of the largest families of transcriptional regulators in plants. bZIP genes have been systematically characterized in some plants, but not in rapeseed (Brassica napus). In this study, we identified 247 BnbZIP genes in the rapeseed genome, which we classified into 10 subfamilies based on phylogenetic analysis of their deduced protein sequences. The BnbZIP genes were grouped into functional clades with Arabidopsis genes with similar putative functions, indicating functional conservation. Genome mapping analysis revealed that the BnbZIPs are distributed unevenly across all 19 chromosomes, and that some of these genes arose through whole-genome duplication and dispersed duplication events. All expression profiles of 247 bZIP genes were extracted from RNA-sequencing data obtained from 17 different B. napus ZS11 tissues with 42 various developmental stages. These genes exhibited different expression patterns in various tissues, revealing that these genes are differentially regulated. Our results provide a valuable foundation for functional dissection of the different BnbZIP homologs in B. napus and its parental lines and for molecular breeding studies of bZIP genes in B. napus.

Tandem DNA repeats derived from the ancestral (TTAGGG)n run were first detected at chromosome ends of the majority of living organisms, hence the name telomeric DNA repeats. Subsequently, it has become clear that telomeric motifs are also present within chromosomes, and they were suitably called interstitial telomeric sequences (ITSs). It is well known that telomeric DNA repeats play a key role in chromosome stability, preventing end-to-end fusions and precluding the recurrent DNA loss during replication. Recent data suggest that ITSs are also important genomic elements as they confer its karyotype plasticity. In fact, ITSs appeared to be among the most unstable microsatellite sequences as they are highly length polymorphic and can trigger chromosomal fragility and gross chromosomal rearrangements. Importantly, mechanisms responsible for their instability appear to be similar to the mechanisms that maintain the length of genuine telomeres. This review compares the mechanisms of maintenance and dynamic properties of telomeric repeats and ITSs and discusses the implications of these dynamics on genome stability.