PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?

BACKGROUND: Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders. CASE PRESENTATION: We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing. CONCLUSION: Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation

Motion Deblurring in the Wild

The task of image deblurring is a very ill-posed problem as both the image and the blur are unknown. Moreover, when pictures are taken in the wild, this task becomes even more challenging due to the blur varying spatially and the occlusions between the object. Due to the complexity of the general image model we propose a novel convolutional network architecture which directly generates the sharp image.This network is built in three stages, and exploits the benefits of pyramid schemes often used in blind deconvolution. One of the main difficulties in training such a network is to design a suitable dataset. While useful data can be obtained by synthetically blurring a collection of images, more realistic data must be collected in the wild. To obtain such data we use a high frame rate video camera and keep one frame as the sharp image and frame average as the corresponding blurred image. We show that this realistic dataset is key in achieving state-of-the-art performance and dealing with occlusions

Toxicity assessment of modified Cry1Ac1 proteins and genetically modified insect-resistant Agb0101 rice

Insect-resistant Agb0101 rice was recently developed by modifying the cry1ac1 gene by changing codon usage changes relative to the native truncated cry1ac1 gene. To assess the toxicity of genetically modified Agb0101 rice, we conducted bioinfomational comparisons of the amino acid sequences that are not similar to known toxic proteins. Sufficient quantities of mCry1Ac1 protein were produced in Escherichia coli for in vitro evaluation and animal study. We compared the amino acid sequences and molecular mass. There have the same amino acid sequences and molecular masses after purifying the modified Cry1Ac1 (mCry1Ac1) protein from highly expressed bacteria and genetically modified rice were identical. We also investigated the acute and 90-days oral toxicities. No adverse effects were observed in mice following acute oral exposure to 2,000 mg/ kg body weight mCry1Ac1 protein of body weight and 90 days oral exposure to Agb0101. These results indicate that mCry1Ac1 proteins and Agb0101 rice demonstrate no adverse effects in these tests when applied via gavage and feed, respectively.Key words: Modified Cry1Ac1, food safety assessment, toxicity, insect- resistant rice Agb0101

Characterization of Fine Particulate Matter and Associations between Particulate Chemical Constituents and Mortality in Seoul, Korea

Background: Numerous studies have linked fine particles [≤ 2.5 µm in aerodynamic diameter (PM2.5)] and health. Most studies focused on the total mass of the particles, although the chemical composition of the particles varies substantially. Which chemical components of fine particles that are the most harmful is not well understood, and research on the chemical composition of PM2.5 and the components that are the most harmful is particularly limited in Asia

Multi-step self-guided pathways for shape-changing metamaterials

Multi-step pathways, constituted of a sequence of reconfigurations, are central to a wide variety of natural and man-made systems. Such pathways autonomously execute in self-guided processes such as protein folding and self-assembly, but require external control in macroscopic mechanical systems, provided by, e.g., actuators in robotics or manual folding in origami. Here we introduce shape-changing mechanical metamaterials, that exhibit self-guided multi-step pathways in response to global uniform compression. Their design combines strongly nonlinear mechanical elements with a multimodal architecture that allows for a sequence of topological reconfigurations, i.e., modifications of the topology caused by the formation of internal self-contacts. We realized such metamaterials by digital manufacturing, and show that the pathway and final configuration can be controlled by rational design of the nonlinear mechanical elements. We furthermore demonstrate that self-contacts suppress pathway errors. Finally, we demonstrate how hierarchical architectures allow to extend the number of distinct reconfiguration steps. Our work establishes general principles for designing mechanical pathways, opening new avenues for self-folding media, pluripotent materials, and pliable devices in, e.g., stretchable electronics and soft robotics.Comment: 16 pages, 3 main figures, 10 extended data figures. See https://youtu.be/8m1QfkMFL0I for an explanatory vide

Multiphoton Absorption Stimulated Metal Chalcogenide Quantum Dot Solar Cells under Ambient and Concentrated Irradiance

Colloidal metal chalcogenide quantum dots (QDs) have excellent quantum efficiency in light–matter interactions and good device stability. However, QDs have been brought to the forefront as viable building blocks in bottom‐up assembling semiconductor devices, the development of QD solar cell (QDSC) is still confronting considerable challenges compared to other QD technologies due to their low performance under natural sunlight, as a consequence of untapped potential from their quantized density‐of‐state and inorganic natures. This report is designed to address this long‐standing challenge by accessing the feasibility of using QDSC for indoor and concentration PV (CPV) applications. This work finds that above bandgap photon energy irradiation of QD solids can generate high densities of excitons via multi‐photon absorption (MPA), and these excitons are not limited to diffuse by Auger recombination up to 1.5 × 1019 cm−3 densities. Based on these findings, a 19.5% (2000 lux indoor light) and an 11.6% efficiency (1.5 Suns) have been facilely realized from ordinary QDSCs (9.55% under 1 Sun). To further illustrate the potential of the MPA in QDSCs, 21.29% efficiency polymer lens CPVs (4.08 Suns) and viable sensor networks powered by indoor QDSCs matrix have been demonstrated

Paving Luteolin Therapeutic Potentialities and Agro-Food-Pharma Applications: Emphasis on in Vivo Pharmacological Effects and Bioavailability Traits

Luteolin is a naturally occurring secondary metabolite belonging to the class of flavones. As many other natural flavonoids, it is often found in combination with glycosides in many fruits, vegetables, and plants, contributing to their biological and pharmacological value. Many preclinical studies report that luteolin present excellent antioxidant, anticancer, antimicrobial, neuroprotective, cardioprotective, antiviral, and anti-inflammatory effects, and as a consequence, various clinical trials have been designed to investigate the therapeutic potential of luteolin in humans. However, luteolin has a very limited bioavailability, which consequently affects its biological properties and efficacy. Several drug delivery strategies have been developed to raise its bioavailability, with nanoformulations and lipid carriers, such as liposomes, being the most intensively explored. Pharmacological potential of luteolin in various disorders has also been underlined, but to some of them, the exact mechanism is still poorly understood. Given the great potential of this natural antioxidant in health, this review is aimed at providing an extensive overview on the in vivo pharmacological action of luteolin and at stressing the main features related to its bioavailability, absorption, and metabolism, while essential steps determine its absolute health benefits and safety profiles. In addition, despite the scarcity of studies on luteolin bioavailability, the different drug delivery formulations developed to increase its bioavailability are also listed here.This study was partially supported by Çanakkale Onsekiz Mart Üniversitesi (Scientific Research Projects, ID: FYL-2017-1339 and FBA-2017-1268)

Probing anomalous tbW couplings in single-top production using top polarization at the Large Hadron Collider

We study the sensitivity of the Large Hadron Collider (LHC) to anomalous tbW couplings in single-top production in association with a W^- boson followed by semileptonic decay of the top. We calculate top polarization and the effects of these anomalous couplings to it at two centre-of-mass (cm) energies of 7 TeV and 14 TeV. As a measure of top polarization, we look at various laboratory frame distributions of its decay products, viz., lepton angular and energy distributions and b-quark angular distributions, without requiring reconstruction of the rest frame of the top, and study the effect of anomalous couplings on these distributions. We construct certain asymmetries to study the sensitivity of these distributions to anomalous tbW couplings. We find that 1\sigma limits on real and imaginary parts of the dominant anomalous coupling Ref_{2R} which may be obtained by utilizing these asymmetries at the LHC with cm energy of 14 TeV and an integrated luminosity of 10 fb^{-1} will be significantly better than the expectations from direct measurements of cross sections and some other variables at the LHC and over an order of magnitude better than the indirect limits.Comment: 25 pages, 34 figure

Lasia spinosa Chemical Composition and Therapeutic Potential: A Literature-Based Review

Lasia spinosa (L.) is used ethnobotanically for the treatment of various diseases, including rheumatoid arthritis, inflammation of the lungs, bleeding cough, hemorrhoids, intestinal diseases, stomach pain, and uterine cancer. This review is aimed at summarizing phytochemistry and pharmacological data with their molecular mechanisms of action. A search was performed in databases such as PubMed, Science Direct, and Google Scholar using the keywords: "Lasia spinosa,"then combined with "ethnopharmacological use,""phytochemistry,"and "pharmacological activity."This updated review included studies with in vitro, ex vivo, and in vivo experiments with compounds of known concentration and highlighted pharmacological mechanisms. The research results showed that L. spinosa contains many important nutritional and phytochemical components such as alkanes, aldehydes, alkaloids, carotenoids, flavonoids, fatty acids, ketones, lignans, phenolics, terpenoids, steroids, and volatile oil with excellent bioactivity. The importance of this review lies in the fact that scientific pharmacological evidence supports the fact that the plant has antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antidiarrheal, antihelminthic, antidiabetic, antihyperlipidemic, and antinociceptive effects, while protecting the gastrointestinal system and reproductive. Regarding future toxicological and safety data, more research is needed, including studies on human subjects. In light of these data, L. spinosa can be considered a medicinal plant with effective bioactives for the adjuvant treatment of various diseases in humans.This work was supported by Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) PIA/APOYO CCTE AFB170007. N.C.-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017)