The Wnt/β-catenin signaling pathway is one of several key conserved intercellular signaling pathways in animals, and plays fundamental roles in the proliferation, regeneration, differentiation, and ...function of many cell and tissue types. This pathway is activated in a dynamic manner during the morphogenesis of oral organs, including teeth, taste papillae, and taste buds, and is essential for these processes to occur normally. Conversely, forced activation of Wnt/β-catenin signaling promotes the formation of ectopic teeth and taste papillae. In this review, we discuss our current understanding of the roles of Wnt/β-catenin signaling in oral tissue development and in related human diseases, and the potential of manipulating this pathway for therapeutic purposes.
The Human Gene Mutation Database (HGMD
®
) constitutes a comprehensive collection of published germline mutations in nuclear genes that are thought to underlie, or are closely associated with human ...inherited disease. At the time of writing (June 2020), the database contains in excess of 289,000 different gene lesions identified in over 11,100 genes manually curated from 72,987 articles published in over 3100 peer-reviewed journals. There are primarily two main groups of users who utilise HGMD on a regular basis; research scientists and clinical diagnosticians. This review aims to highlight how to make the most out of HGMD data in each setting.
Nicotinic acetylcholine receptors (nAChRs) are pentameric neurotransmitter receptors. They are members of the Cys-loop family of ligand-gated ion channels which also include ionotropic receptors for ...5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA) and glycine. Nicotinic receptors are expressed in both the nervous system and at the neuromuscular junction and have been implicated in several neurological and neuromuscular disorders. In vertebrates, seventeen nAChR subunits have been identified (α1–α10, β1–β4, γ, δ and ɛ) which can co-assemble to generate a diverse family of nAChR subtypes. This review will focus on vertebrate nAChRs and will provide an overview of the extent of nAChR diversity based on studies of both native and recombinant nAChRs.
Stressed out symbiotes Millar, Niall S.; Bennett, Alison E.
Oecologia,
11/2016, Volume:
182, Issue:
3
Journal Article
Peer reviewed
Open access
Abiotic stress is a widespread threat to both plant and soil communities. Arbuscular mycorrhizal (AM) fungi can alleviate effects of abiotic stress by improving host plant stress tolerance, but the ...direct effects of abiotic stress on AM fungi are less well understood. We propose two hypotheses predicting how AM fungi will respond to abiotic stress. The stress exclusion hypothesis predicts that AM fungal abundance and diversity will decrease with persistent abiotic stress. The mycorrhizal stress adaptation hypothesis predicts that AM fungi will evolve in response to abiotic stress to maintain their fitness. We conclude that abiotic stress can have effects on AM fungi independent of the effects on the host plant. AM fungal communities will change in composition in response to abiotic stress, which may mean the loss of important individual species. This could alter feedbacks to the plant community and beyond. AM fungi will adapt to abiotic stress independent of their host plant. The adaptation of AM fungi to abiotic stress should allow the maintenance of the plant-AM fungal mutualism in the face of changing climates.
Distributed Denial of Service (DDoS) attacks are one of the most harmful threats in today's Internet, disrupting the availability of essential services. The challenge of DDoS detection is the ...combination of attack approaches coupled with the volume of live traffic to be analysed. In this paper, we present a practical, lightweight deep learning DDoS detection system called Lucid, which exploits the properties of Convolutional Neural Networks (CNNs) to classify traffic flows as either malicious or benign. We make four main contributions; (1) an innovative application of a CNN to detect DDoS traffic with low processing overhead, (2) a dataset-agnostic preprocessing mechanism to produce traffic observations for online attack detection, (3) an activation analysis to explain Lucid's DDoS classification, and (4) an empirical validation of the solution on a resource-constrained hardware platform. Using the latest datasets, Lucid matches existing state-of-the-art detection accuracy whilst presenting a 40x reduction in processing time, as compared to the state-of-the-art. With our evaluation results, we prove that the proposed approach is suitable for effective DDoS detection in resource-constrained operational environments.
Aims
Cannabidiol (CBD) is a cannabis‐derived medicinal product with potential application in a wide‐variety of contexts; however, its effective dose in different disease states remains unclear. This ...review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of CBD in a variety of medical contexts.
Methods
Publications involving administration of CBD alone were collected by searching PubMed, EMBASE and ClinicalTrials.gov.
Results
A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. Twenty‐three studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 and 50 mg/kg/d. Plasma concentrations were not provided in any publication. CBD was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of CBD on reducing seizure frequency or severity (average 15 mg/kg/d within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n = 6–62) assessing diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/kg/d) were used in these studies.
Conclusion
This review highlights that CBD has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.
Body condition can have important fitness consequences, but measuring body condition of live animals from wild populations has been the subject of much recent debate. Using the residuals from a ...regression of body mass on a linear measure of body size is one of the most common methods of measuring condition and has been used in many vertebrate taxa. Recently, the use of this method has been criticized because assumptions are likely violated. We tested several assumptions regarding the use of this method with body composition and morphometric data from five species of small mammals and with statistical simulations. We tested the assumptions that the relationship between body mass and body size is linear, and that the proportion of mass associated with energy reserves is independent of body size. In addition, we tested whether the residuals from reduced major axis (RMA) regression or major axis (MA) regression performed better than the residuals from ordinary least squares (OLS) regression as indices of body condition. We found no evidence of nonlinear relationships between body mass and body size. Relative energy reserves (fat and lean dry mass) were generally independent or weakly dependent on body size. Residuals from MA and RMA regression consistently explained less variation in body composition than OLS regression. Using statistical simulations, we compared the effects of violations of the assumption that true condition and residual indices are independent of body size on the OLS, MA, and RMA procedures and found that OLS performed better than the RMA and MA procedures. Despite recent criticisms of residuals from mass-size OLS regressions, these indices of body condition appear to satisfy critical assumptions. Although some caution is warranted when using residuals, especially when both inter-individual variation in body size and measurement error are high, we found no reason to reject OLS residuals as legitimate indices of body condition.
In order to realize probabilistically shaped signaling within the probabilistic amplitude shaping (PAS) framework, a shaping device outputs sequences that follow a certain nonuniform distribution. In ...case of constant-composition (CC) distribution matching (CCDM), the sequences differ only in the ordering of their constituent symbols, whereas the number of occurrences of each symbol is constant in every output block. Recent results by Amari et al. have shown that the CCDM block length can have a considerable impact on the effective signal-to-noise ratio (SNR) after fiber transmission. So far, no explanation for this behavior has been presented. Furthermore, the block-length dependence of the SNR seems not to be fully aligned with previous results in the literature. This paper is devoted to a detailed analysis of the nonlinear fiber interactions for CC sequences. We confirm in fiber simulations the inverse proportionality of SNR with CCDM block length and present two explanations. The first one, which only holds in the short-length regime, is based on how two-dimensional symbols are generated from shaped amplitudes in the PAS framework. The second, more general explanation relates to an induced shuffling within a sequence, or equivalently a limited concentration of identical symbols, that is an inherent property for short CC blocks, yet not necessarily present in case of long blocks. This temporal property results in weaker nonlinear interactions, and thus higher SNR, for short CC sequences. For a typical multi-span fiber setup, the SNR difference is numerically demonstrated to be up to 0.7 dB. Finally, we evaluate a heuristic figure of merit that captures the number of runs of identical symbols in a concatenation of several CC sequences. For moderate block lengths up to approximately 100 symbols, this metric suggests that limiting the number identical-symbol runs can be beneficial for reducing fiber nonlinearities and thus, for increasing SNR.
In 2004 a large focus of Plasmodium knowlesi malaria was reported in the human population in Sarawak, Malaysian Borneo. Plasmodium knowlesi, a parasite of the South-East Asian macaques (Macaca ...fascicularis and Macaca nemestrina), had entered the human population. Plasmodium knowlesi is transmitted by the leucosphyrus group of Anopheline mosquitoes and transmission is largely zoonotic and restricted to the jungle setting. Humans entering jungle transmission sites are at risk. Since 2004, human cases of P. knowlesi have been continuously reported in local communities and in travellers returning from South East Asia. Plasmodium knowlesi is the most common type of indigenous malaria reported in Malaysia. Infections are most often uncomplicated but at least 10% of patients report with severe malaria and 1–2% of cases have a fatal outcome. Parasitaemia is positively associated with the clinical and laboratory markers of severe malaria. The current literature on P. knowlesi, including epidemiology, natural hosts and vectors, pathogenesis, clinical descriptions, treatment and diagnosis, is reviewed. There are many gaps in our understanding of this disease that are highlighted here with suggestions for further research to inform pre-emptive control measures that would be required to prevent a full emergence of this parasite into the human population.
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