Unraveling the layers of epigenetic control in respiratory antiviral defense

Decoding the Epigenetic Language of Neuronal Plasticity

Mammalian cortical development is a multifaceted process that is under the control of precise transcriptional programs. During embryonic neurogenesis, neural progenitor cells undergo defined steps of differentiation to generate functional neurons at distinct stages of development. It is becoming increasingly clear that epigenetic mechanisms, including histone modifications, DNA methylation, chromatin remodeling and noncoding RNAs, play critical roles in specifying and maintaining cell-fates during neurogenesis. Furthermore, these mechanisms function in concert with each other and with sequence-specific transcription factors, emphasizing the collaboration between genetic and epigenetic mechanisms in driving neuronal fate. In this chapter, a comprehensive overview is provided of the epigenetic layers that underlie neurogenesis, along with prospective for future challenges in this exciting field. Keywords: histones; chromatin; post-translational modification of histones; DNA methylation; noncoding RNA; epigenetics; corticogenesis; neural progenitors; neurons

Infections, Immunity & their Effects on Asthma

A community-based, time-matched, case-control study of respiratory viruses and exacerbations of COPD

Epigenetics for crop adaptation to climate change

Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus–host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype. Epigenetic modifications, such as histone modifications, DNA methylation, chromatin remodeling, and non-coding RNAs, function as important regulators that remodel host chromatin, altering host expression patterns and networks in a highly flexible manner. For most of the past two and a half decades, research has focused on the molecular mechanisms by which RNA viruses antagonize the signaling and sensing components that regulate induction of the host innate immune and antiviral defense programs upon infection. More recently, a growing body of evidence supports the hypothesis that viruses, even lytic RNA viruses that replicate in the cytoplasm, have developed intricate, highly evolved, and well-coordinated processes that are designed to regulate the host epigenome, and control host innate immune antiviral defense processes, thereby promoting robust virus replication and pathogenesis. In this article, we discuss the strategies that are used to evaluate the mechanisms by which viruses regulate the host epigenome, especially focusing on highly pathogenic respiratory RNA virus infections as a model. By combining measures of epigenome reorganization with RNA and proteomic datasets, we articulate a spatial-temporal data integration approach to identify regulatory genomic clusters and regions that play a crucial role in the host’s innate immune response, thereby defining a new viral antagonism mechanism following emerging coronavirus infection.

Viral respiratory tract infections and asthma: The course ahead

DNA (cytosine-5) methylation represents one of the most widely used mechanisms of enduring cellular memory. Stable patterns of DNA methylation are established during development, resulting in creation of persisting cellular phenotypes. There is growing evidence that the nervous system has co-opted a number of cellular mechanisms used during development to subserve the formation of long term memory. In this study, we examined the role DNA (cytosine-5) methyltransferase (DNMT) activity might play in regulating the induction of synaptic plasticity. We found that the DNA within promoters for reelin and brain-derived neurotrophic factor, genes implicated in the induction of synaptic plasticity in the adult hippocampus, exhibited rapid and dramatic changes in cytosine methylation when DNMT activity was inhibited. Moreover, zebularine and 5-aza-2-deoxycytidine, inhibitors of DNMT activity, blocked the induction of long term potentiation at Schaffer collateral synapses. Activation of protein kinase C in the hippocampus decreased reelin promoter methylation and increased DNMT3A gene expression. Interestingly, DNMT activity is required for protein kinase C-induced increases in histone H3 acetylation. Considered together, these results suggest that DNMT activity is dynamically regulated in the adult nervous system and that DNMT may play a role in regulating the induction of synaptic plasticity in the mature CNS.

Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms.

Retrospective and perspective of plant epigenetics in China

Oocyte maturation involves both nuclear and cytoplasmic processes that are critical for the acquisition of oocyte competence. Granulosa cells, surrounding the oocyte, play a pivotal role in the maturation process, with mechanisms such as cAMP signaling significantly influencing oocyte development. Epigenetic mechanisms – including DNA methylation and its oxidative derivatives, histone post-translational modifications and chromatin remodeling – interfere with the accessibility of transcription factors to regulatory regions of the genome, such as promoter regions of genes, hence generally regulating gene expression profiles; however, in oocytes, transcription is largely independent of DNA methylation patterns. Here we highlight epigenetic reprogramming events occurring during oocyte development and ageing, focusing on the establishment of gamete-specific epigenetic marks, including DNA modifications at imprinted regions, and age-related epigenetic changes. We focus on the mechanisms of DNA methylation and demethylation during mouse and human oocyte maturation, alongside an exploration of how ageing impacts the oocyte epigenome and its implications for reproductive success. By providing a comprehensive analysis of the role of epigenetics in oocyte development and maturation, this review addresses the importance of comprehending these processes to enhance in vitro fertilization treatments and improve reproductive outcomes.

Community-acquired respiratory viruses

Acute respiratory infections (ARIs) are common during the first two years of life, when infants and young children experience six to eight ARIs annually. In this age group, ARIs are the most commonly managed problems in general practice. Between 3 and 6% of infants are hospitalised in their first year of life with a severe ARI illness. Information about the epidemiology of ARI in children is based on historic community-based studies, cohorts of hospitalised patients, emergency department or primary healthcare presentations, and more recently from birth cohort studies principally involving children at high-risk of asthma. However, these studies do not completely identify the burden of mild-to-moderate ARIs in the community.Recent community-based cohort studies have used sensitive polymerase chain reaction (PCR) assays. However, they have had one or more methodological limitations, including subject selection, length of study, non-representative sample populations, variable sampling frequency, and the lack of a control population. Furthermore, frequent detection of respiratory viruses in asymptomatic individuals questions their clinical and public health significance. Studies reporting the causal effect of individual respiratory viruses in ARI are needed to help address this question.The Observational Research in Childhood Infectious Diseases (ORChID) study was a four year prospective, community-based, longitudinal birth cohort study of ARIs in 158 healthy children from birth to two years of age. ORChID sought to minimise some of the methodological limitations of previous studies. Parents completed a daily symptom diary and collected weekly nasal swabs, which were tested against 17 respiratory viruses. Healthcare-seeking behaviour was recorded in a separate ‘burden’ diary.I found that young children experienced 0.56 (95% confidence interval (CI): 0.54, 0.59) ARIs per child-month. This equated to almost five cumulative months of respiratory symptoms during the first two years. Forty-eight percent of ARIs where a burden diary was completed initiated a visit to a family doctor. ARIs were associated with increasing age, the winter season, and childcare attendance.Studies examining respiratory viruses in neonates have largely been from neonatal units or neonates presenting to hospital with respiratory symptoms. I was able to show that respiratory virus infections were common (0.25 episodes per neonatal period, 95% CI: 0.18, 0.34), with diverse human rhinovirus (HRV) genotypes dominating (21/29; 72% of neonates with positive swabs). Almost 50% of respiratory virus infections in this period were asymptomatic. This subclinical shedding of all respiratory virus types complicates estimates of the true community burden of viral ARI in infants and young children.To explore this further, I investigated the relative contribution of individual respiratory viruses to ARIs by calculating the virus-specific attributable fractions in exposed (AFE) children of ARIs and lower respiratory tract infections (LRTIs). The overall incidence of virus infections was 978 (95% CI: 930, 1029) per 100 child-years in the first two years of life. Viruses were detected in 75% of ARI episodes, while 23% of weekly swabs were positive for viruses during asymptomatic periods. RNA viruses, including HRV, influenza, parainfluenza, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), and human coronaviruses NL63 and OC43 were associated with a significantly increased risk of ARI symptoms. Support for causality was strongest for RSV (AFE 68%, 95% CI: 45%, 82%), and HMPV (AFE 69%, 95% CI: 43%, 83%) in children with LRTIs. In contrast, amongst the DNA viruses tested, only adenoviruses (AFE 29%, 95% CI; 12%, 42%) were significantly associated with an increased risk of ARI symptoms. Of HRV species, only HRV-C had a significant AFE result for LRTIs (AFE 22% (95% CI: 5%, 22%).I went on to examine the timing of detection for each of the 17 respiratory viruses tested for in the ORChID infant cohort. Determining timing of first virus detection episodes (fVDEs) for different respiratory viruses in infants and young children identifies risk periods and informs preventive interventions, including vaccination. The median age for first HRV infections was 2.9 months (25th–75th centiles: 1.6, 5.1), while for all other respiratory viruses combined the median age was >13.9 months. Overall 52% of first HRV detections were symptomatic, compared with 57-83% with the other first virus detections. Thus, infants and young children do not always experience respiratory symptoms with their first viral detection episode, and for some viruses, such as RSV, these commonly occur when maternal vaccines may no longer offer protection.Collectively, these findings highlight the important community-managed disease burden caused by respiratory viruses in early childhood. They also provide a wealth of information about the relationship between respiratory virus infection and symptoms of respiratory illness. The ORChID study uses modern molecular-based techniques over four respiratory seasons to address questions about respiratory virus acquisition and infection.

Influenza viruses, respiratory syncytial virus (RSV), and SARS-COV2 are among the most dangerous respiratory viruses. Zinc is one of the essential micronutrients and is very important in the immune system. The aim of this narrative review is to review the most interesting findings about the importance of zinc in the anti-viral immune response in the respiratory tract and defense against influenza, RSV, and SARS-COV2 infections. The most interesting findings on the role of zinc in regulating immunity in the respiratory tract and the relationship between zinc and acute respiratory distress syndrome (ARDS) are reviewed, as well. Besides, current findings regarding the relationship between zinc and the effectiveness of respiratory viruses’ vaccines are reviewed. The results of reviewed studies have shown that zinc and some zinc-dependent proteins are involved in anti-viral defense and immune regulation in the respiratory tract. It seems that zinc can reduce the viral titer following influenza infection. Zinc may reduce RSV burden in the lungs. Zinc can be effective in reducing the duration of viral pneumonia symptoms. Zinc may enhance the effectiveness of hydroxychloroquine in reducing mortality rate in COVID-19 patients. Besides, zinc has a positive effect in preventing ARDS and ventilator-induced lung damage. The relationship between zinc levels and the effectiveness of respiratory viruses’ vaccines, especially influenza vaccines, is still unclear, and the findings are somewhat contradictory. In conclusion, zinc has anti-viral properties and is important in defending against respiratory viral infections and regulating the immune response in the respiratory tract.

The roots of plants play multiple functions that are essential for growth and development, including anchoring to the soil as well as water and nutrient acquisition. These underground organs exhibit the plasticity to modify their root system architecture in response to environmental cues, allowing adaptation to change in water and nutrient availability. In addition, roots enter in mutualistic interactions with soil microorganisms, for example, the root nodule symbiosis (RNS) established between a limited group of plants and nitrogen-fixing soil bacteria and the arbuscular mycorrhiza symbiosis involving most land plants and fungi of the Glomeromycetes phylum. In the past 20 years, genetic approaches allowed the identification and functional characterization of genes required for the specific programs of root development, root nodule, and arbuscular mycorrhiza symbioses. These genetic studies provided evidence that the program of the RNS recruited components of the arbuscular mycorrhiza symbiosis and the root developmental programs. The execution of these programs is strongly influenced by epigenetic changes-DNA methylation and histone post-translational modifications-that alter chromatin conformation modifying the expression of key genes. In this review, we summarize recent advances that highlight how DNA methylation and histone post-translational modifications, as well as chromatin remodeling factors and long noncoding RNAs, shape the root system architecture and allow the successful establishment of both root nodule and arbuscular mycorrhiza symbioses. We anticipate that the analysis of dynamic epigenetic changes and chromatin 3D structure in specific single cells or tissue types of root organs will illuminate our understanding of how root developmental and symbiotic programs are orchestrated, opening exciting questions and new perspectives to modulate agronomical and ecological traits linked to nutrient acquisition.