Genome‐wide association studies (GWAS) have identified numerous disease‐associated variants; however, these variants have a minor effect on disease and explain only a small amount of the heritability ...of complex disorders. The search for the missing heritability has shifted attention to rare variants, copy number variants, copy neutral variants and epigenetic modifications. The central role of epigenetics, and specifically DNA methylation, in disease susceptibility and progression has become more apparent in recent years. Epigenetic mechanisms facilitate the response to environmental changes and challenges by regulating gene expression. This makes the study of DNA methylation in psychiatric disorders such as posttraumatic stress disorder (PTSD) highly salient, as the environment plays such a vital role in disease aetiology. The epigenome is dynamic and can be modulated by numerous factors, including learning and memory, which are important in the context of PTSD. Numerous studies have shown the effects of early life events, such as maternal separation and traumas during adulthood, on DNA methylation patterns and subsequent gene expression profiles. Aberrations in adaptive DNA methylation contribute to disease susceptibility when an organism is unable to effectively respond to environmental demands. Epigenetic mechanisms are also involved in higher order brain functions. Dysregulation of methylation is associated with neurodevelopmental and neurodegenerative cognitive disorders, affective disorders, addictive behaviours and altered stress responses. A thorough understanding of how the environment, methylome and transcriptome interact and influence each other in the context of fear and anxiety is integral to our understanding and treatment of stress‐related disorders such as PTSD.
This article provides an extensive review of the involvement of DNA methylation in complex disorders, such as PTSD, and how this epigenetic mechanism can help to better understand and treat such disorders.
Alzheimer's Disease (AD) is a neurodegenerative disease characterized by central nervous system insults with progressive cognitive (memory, attention) and non-cognitive (anxiety, depression) ...impairments. Pathophysiological events affect predominantly cholinergic neuronal loss and dysfunctions of the dopaminergic system. The aim of the current study was to design multi-targeted directed lead structures based on the coumarin scaffold with inhibitory properties at two key enzymes in disease relevant systems, i.e. acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Conventional and microwave synthetic methods were utilized to synthesize coumarin scaffold-based novel morpholino, piperidino, thiophene and erucic acid conjugates. Biological assays indicated that the coumarin-morpholine ether conjugate BPR 10 was the most potent hMAO-B inhibitor. The coumarin-piperidine conjugates BPR 13 and BPR 12 were the most potent inhibitors of eeAChE at 100 μM and 1 μM, respectively. Molecular modelling studies were conducted with Accelrys
®
Discovery Studio
®
V3.1.1 utilising the published hMAO-B (2V61) and hAChE (4EY7) crystal structures. Compound BPR 10 occupies both the entrance and substrate cavities of the active site of MAO-B. BPR 13 resides in both the peripheral anionic site (PAS) and the catalytic anionic site (CAS) of hAChE. This study demonstrated that the coumarin scaffold serves as a promising pharmacophore for MTDLs design.
In the study of complex, heterogeneous disorders, such as anxiety and stress-related disorders, epigenetic factors provide an additional level of heritable complexity. MicroRNAs (miRNAs) are a class ...of small, noncoding RNAs that function as epigenetic modulators of gene expression by binding to target messenger RNAs (mRNAs) and subsequently blocking translation or accelerating their degradation. In light of their abundance in the central nervous system (CNS) and their involvement in synaptic plasticity and neuronal differentiation, miRNAs represent an exciting frontier to be explored in the etiology and treatment of anxiety and stress-related disorders. This chapter will present a thorough review of miRNAs, their functions, and mRNA targets in the CNS, focusing on their role in anxiety and stress-related disorders as described by studies performed in animals and human subjects.
To the Editor: We the undersigned, a collective of pharmacy researchers, practitioners and academics, call on the Minister to consider the following points in response to the input made by the South ...African Medical Association (SAMA) in relation to pharmacist-initiated management of antiretroviral therapy (PIMART), dated 9 September 2021. We wish to highlight the expertise of pharmacists in all matters relating to the design, production and use of quality, safe and affordable medicines. Furthermore, we need to stress the increasing importance of and role played by pharmacists in primary care teams, which has been further reinforced during the COVID-19 pandemic and subsequent vaccination efforts.
Indari is one of the coastal areas in the West Bacan Subdistrict, Regency of South Halmahera, Province of North Mollucas. Fisheries business activities that are quite popular in this region are ...aquaculture with seaweed commodities. Indari waters is also one of the areas designated as seaweed cultivation development zones in Province of North Mollucas. One of the factors that determine the success of a seaweed cultivation business is production. This is because production is the final result obtained from a cultivation business. The purpose of this research was to determine the production of seaweed K.alvarezii cultivation based on seasons. The method used in the survey is a method of interviewing using questionnaires to seaweed farmers as many as 30 people. Production data collected is wet and dry production data by season. Production data collected is wet and dry production data by season. The results showed that the highest seaweed K.alvarezii production was found in the dry season with wet production of 9.320 kg and dry production of 852.5 kg, whereas in the rainy season, wet production was 898.125 kg and dry production was 718.5 kg.
During an Ebola outbreak, the WHO recommends that health professionals consider people as suspect cases (SCs) when they show key signs such as the sudden onset of high fever or specific symptoms ...after having had contact with a suspect or confirmed Ebola case. SCs should then get care, be isolated and be reported to health authorities until the Ebola virus disease is confirmed through a lab test. This exploratory study aims to understand this identification process in the field based on a qualitative analysis of the diagnosis and therapeutic itineraries of 19 SCs in Cote d'Ivoire and Senegal (2014-2015). Results indicate that the main criteria for SC identification at the field level were fever (understood broadly) and provenance from a highly affected country (applied indiscriminately). WHO criteria were not followed in at least 9 of the 19 cases. Several medical, social and cultural factors favour over-identification of people as SCs, including relativism in defining 'high fever', placism, humanitarian or securitarian bias, issues in categorising SC's contact cases, and the context of fear. To avoid undue categorisation and its possible harmful social effects, the WHO definition should be implemented more carefully in various contexts and with greater consideration for ethical issues, while prioritising diagnosis strategies with higher specificity.
Over the past two decades fruit symptoms resembling a marbling pattern on the fruit skin or corking of the fruit flesh was observed on Japanese plums in South Africa resulting in unmarketable fruit. ...The ability of high-throughput sequencing (HTS) to detect known and unknown pathogens was exploited, by assaying affected and unaffected fruit tree accessions to identify the potential aetiological agent of marbling and/or corky flesh disease. In this study it is shown that the disease is associated with a previously undescribed small RNA with typical viroid structural features . The potential viroid was the only pathological agent consistently detected in all symptomatic trees by HTS and the association with the symptoms was confirmed in field surveys over two seasons. To date this RNA was not detectable by RT-PCR in seedlings raised from seeds collected from infected trees. Although the autonomous replication of this viroid-like RNA was not proven, it was shown to be transmissible by grafting and associated with a range of symptoms that include marbling on the fruit skin, corky flesh, reduced fruit size and irregular shaped and uneven fruit surface depending on the cultivar. Moreover, the circular RNA genome, consisting of 317 nucleotides, strongly supports that this viroid-like RNA is most likely a viroid for which the name plum viroid I (PVd-I) is proposed. The primary structure of this viroid showed a less than 90% nucleotide sequence identity to viroids of the genus
, with which it has close phylognetic relationships and shares conserved structural motifs.
Pinus patula is the most intensively planted conifer in the tropics and subtropics. The increased proportion of corewood that results when rotation ages of pine plantations are shortened has become a ...wood quality factor of growing concern worldwide. The purpose of this study was to develop empirically based models for predicting the flexural properties of the wood produced from relatively young P. patula trees. Models were based on the properties of standing trees, and their effectiveness was evaluated at board, tree, and compartment levels. Sample material was obtained from 170 P. patula trees, 16–20 years old, established in 17 compartments on the Mpumalanga escarpment of South Africa. Multiple regression models were developed, which managed to explain 68, 60, and 95 % of the variation in the dynamic modulus of elasticity (MOE) on individual boards, trees, and compartments levels, respectively. At compartment level, 80 % of the variation in the 5th percentile MOR value could be explained by the model. Sensitivity analyses showed that site index at base age of 10 years, acoustic time of flight, wood density, and ring width were influential variables in the MOE models. The models indicated that tree slenderness during early growth seems to play a major role in determining the dynamic MOE and MOR of lumber. This is in agreement with Euler’s buckling theory and the bending stress theory. The results from this study indicated that the MOEdyₙand MOR of lumber can be accurately predicted on especially a compartment level. The predictive models developed can be used as management tools to improve operational decisions around tree breeding, silvicultural practices, and rotation ages.
In this paper we present the most innovative aspects of the EC-FP7 EcoThermo project. The main aim of the project consists on innovating the technique of heat cost allocation in buildings with a ...centralized heating system, overcoming the heat cost allocator drawbacks for reliability, measurement reproducibility and traceability and contexts of applications. Given the complexity of the project, we will focus on its main aspects, such as the use of a virtual sensor to estimate the radiators heating power, the design of electronic valves fitted out with an energy harvesting system and the original wireless communication protocol.
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