The role of SARS-CoV-2 ORF8 protein ARKS motif on novobiocin binding

The discovery of the SARS-CoV-2 virus during the COVID-19 pandemic required scientists to develop medical solutions to reduce infectivity, severity of symptoms, and death. Although vaccines and drugs provided urgent assistance, the need to continue developing better drugs is necessary long term, and understanding the structure of the virus and finding potential inhibitors would prove vital to discovering solutions to this worldwide health problem. This experimental project focuses on targeting the unique accessory protein, Open Reading Frame 8 (ORF8) in SARS-CoV-2 through studying its interactions with a repurposable drug, novobiocin. Importantly, ORF8 specializes in helping evade immune system checks by downregulating major histocompatibility complex I (MHC-I) after infection, and is also involved in inflammatory responses from the cytokine storm, the most prominent cause of fatalities from the virus. Additionally, the ORF8 protein has been proposed to act as a histone mimic at the histone-H3 ARKS motif that causes post-translational changes in chromatin, further worsening these problems through gene transcription. Previous in silico and in vitro work from our lab has shown that novobiocin [Kd = 54.5 ± 3.14 μM] and three other computationally verified ligands (iohexol [Kd = 1185 ± 193 μM], kaempferol-7-O-glucoside [Kd = 135 ± 10.9 μM] & lercanidipine hydrochloride [Kd = 52.7 ± 5.71 μM]) bind to. To probe the role of Arg in the histone-H3 ARKS motif, specific mutation was done in position 52 from Arg to Met, Glu and Leu respectively. The above results in drastic changes in intermolecular forces such as opposing charge, polarity and different sizes of these side chains that negatively affect novobiocin’s ability to bind to the ORF8 pocket , which this research aims to experimentally prove this hypothesis. In silico analyses for the mutagenic ORF8 were initially found to require more energy to bind novobiocin to the ARKS motif than wild-type, but was still possible to dock according to Swissdock. Primers for the ORF8 R52 mutants were then designed and mutagenic plasmids were constructed and sequence verified. Each of the mutant ORF8 proteins was overexpressed, purified, and Kd values for binding to novobiocin were determined via intrinsic fluorescence spectroscopy and compared with wild-type binding. This data will help further understand the role of SARS-CoV-2 ORF8 protein ARKS motif and how its interactions affected novobiocin binding, potentially benefitting future studies attempting to repurpose novobiocin and other ligands for treatment of the spreading virus

Differential cross sections of electron silver scattering at varying energies

The differential scattering cross sections of electron - silver atom are calculated using the Eikonal approximation at incident energies of 50 eV,60 eV and 70 eV, with the Lenz-Jensen potential. Results obtained are ingood agreement with the NIST SRD 64 at scattering angles of about 80 to180 degrees; and are in very good agreement with the Born approximationbetween 30 to 180 degrees.Keywords: Differential cross section, Silver, Eikonal, Born approximatio

AN INVESTIGATION INTO DIFFICULTIES IN ENGLISH LISTENING OF FRESHMEN MAJORING IN ENGLISH AT A UNIVERSITY IN THE MEKONG DELTA, VIETNAM

English is a very popular language in the world. However, learning a foreign language is not an easy process for learners, especially the English listening process. In fact, most learners believe that it is hard for them to master this skill. Therefore, the research “An Investigation into Difficulties in English Listening of Freshmen Majoring in English at a University in the Mekong Delta” was conducted with the purpose of helping these students to recognize clearly their own problems in English listening. Statistical data were collected from eighty-five English-majored freshmen. The main instrument of the study was a questionnaire. The findings of the research would point out the students’ difficulties in linguistics, including vocabulary, grammar, pronunciation, intonation and accent; background knowledge; and difficulties from their own minds. One more notable purpose of this research is that thanks to the results, students can now solve their own problems, so that they can study better. Article visualizations

GC/MS determination of bioactive components and antibacterial properties of Goniothalamus umbrosusextracts

In this study, the antibacterial activity and chemical composition of Goniothalamus umbrosus leaves extracts were evaluated. The antibacterial activity was investigated using two gram-positive bacteria, Methicillin resistant Staphylococcus aureus (MRSA) and Bacillus subtilis B29, and two gram-negative bacteria, Pseudomonas aeruginosa 60690 and Salmonella choleraesuis. The activity was tested using disc diffusion and minimum inhibitory concentration assays. The chemical compositions of the ethyl acetate extract of G. umbrosus were investigated using Shimadzu gas chromatography–mass spectrometry (GC-17A) while the mass spectra of the compounds found in the extract was matched with the library. The results showed that the  extracts demonstrated broad spectrum antibacterial effects against all tested bacteria. GC/MS analysis of ethyl acetate extract of G. umbrosus revealed the existence of 1-butyl-2-cyclohexen-1-ol (46.84%), benzaldehyde (4.42%) and globulol (4.07%). The results of this study offer a platform of using G. umbrosus as herbal alternative for the current synthetic antimicrobial agents

Evaluations of Andrographolide-Rich Fractions of Andrographis paniculata with Enhanced Potential Antioxidant, Anticancer, Antihypertensive, and Anti-Inflammatory Activities

Abstract: Andrographis paniculata is widely used as a traditional medicine in Asian countries. It has been classified as a safe and non-toxic medicine by traditional Chinese medicine. The investigation of the biological activities of A. paniculata is still focused on the crude extract and isolation of its main active compound, andrographolide, and its derivatives. However, the use of andrographolide alone has been shown to exacerbate unwanted effects. This highlights the importance of developing a fraction of A. paniculata with enhanced efficacy as an herbal-based medicine. In this study, the extraction and fractionation of A. paniculata, followed by quantitative analysis using high-performance liquid chromatography coupled with a DAD detector, were established to quantify the andrographolide and its derivative in each fraction. Biological activities, such as antioxidant, anticancer, antihypertensive, and anti-inflammatory activities, were evaluated to study their correlations with the quantification of active substances of A. paniculata extract and its fractions. The 50% methanolic fraction of A. paniculata exhibited the best cytotoxic activities against CACO-2 cells, as well as the best anti-inflammatory and antihypertensive activities compared to other extracts. The 50% methanolic fraction also displayed the highest quantification of its main active compound, andrographolide, and its derivatives, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and andrograpanin, among other

Development of polymeric nanocomposite (Xyloglucan-co-Methacrylic acid/Hydroxyapatite/SiO 2 ) scaffold for bone tissue engineering applications—In-vitro antibacterial, cytotoxicity and cell culture evaluation

Advancement and innovation in bone regeneration, specifically polymeric composite scaffolds, are of high significance for the treatment of bone defects. Xyloglucan (XG) is a polysaccharide biopolymer having a wide variety of regenerative tissue therapeutic applications due to its biocompatibility, in-vitro degradation and cytocompatibility. Current research is focused on the fabrication of polymeric bioactive scaffolds by freeze drying method for nanocomposite materials. The nanocomposite materials have been synthesized from free radical polymerization using n-SiO2 and n-HAp XG and Methacrylic acid (MAAc). Functional group analysis, crystallinity and surface morphology were investigated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD) and scanning electron microscopy (SEM) techniques, respectively. These bioactive polymeric scaffolds presented interconnected and well-organized porous morphology, controlled precisely by substantial ratios of n-SiO2. The swelling analysis was also performed in different media at varying temperatures (27, 37 and 47 °C) and the mechanical behavior of the dried scaffolds is also investigated. Antibacterial activities of these scaffolds were conducted against pathogenic gram-positive and gram-negative bacteria. Besides, the biological behavior of these scaffolds was evaluated by the Neutral Red dye assay against the MC3T3-E1 cell line. The scaffolds showed interesting properties for bone tissue engineering, including porosity with substantial mechanical strength, biodegradability, biocompatibility and cytocompatibility behavior. The reported polymeric bioactive scaffolds can be aspirant biomaterials for bone tissue engineering to regenerate defecated bone

Predicting Remaining Useful Life with Similarity-Based Priors

Prognostics is the area of research that is concerned with predicting the remaining useful life of machines and machine parts. The remaining useful life is the time during which a machine or part can be used, before it must be replaced or repaired. To create accurate predictions, predictive techniques must take external data into account on the operating conditions of the part and events that occurred during its lifetime. However, such data is often not available. Similarity-based techniques can help in such cases. They are based on the hypothesis that if a curve developed similarly to other curves up to a point, it will probably continue to do so. This paper presents a novel technique for similarity-based remaining useful life prediction. In particular, it combines Bayesian updating with priors that are based on similarity estimation. The paper shows that this technique outperforms other techniques on long-term predictions by a large margin, although other techniques still perform better on short-term predictions.</p

Use of Korean dramas to facilitate precision mental health understanding and discussion for Asian Americans

Precision mental health holds great potential for revolutionizing care and reducing the burden of mental illness. All races and ethnicities such as Asian Americans, the fastest growing racial group in the United States (U.S.), need to be engaged in precision mental health research. Owing to its global popularity, Korean drama ('K-drama') television shows may be an effective educational tool to increase precision mental health knowledge, attitudes and behaviors among Asian Americans. This qualitative study examined the participants' perspectives about and acceptance of using K-dramas to educate and engage Asian Americans about precision mental health. Twelve workshops were conducted in English, Vietnamese and Korean with a convenience sample in the San Francisco Bay Area in the U.S. (n = 122). Discussions were coded for themes. Findings revealed that all language groups reported positive reactions to using K-dramas to learn about precision health, genetics and mental health. Overall, participants shared that they learned about topics that are not generally talked about (e.g. precision health; genetic testing; mental health), from other people's perspectives, and the importance of mental health. Participants expressed how much they enjoyed the workshop, how they felt relieved due to the workshop, thought the workshop was interesting, and had an opportunity for self-reflection/healing. This pilot test demonstrated that K-dramas has promise to be used as a health educational tool in a workshop format focused on mental health among a diverse group of Asian Americans. Given the widespread access to K-dramas, they present a scalable opportunity for increasing awareness about specific health topics

Magnetism and its microscopic origin in iron-based high-temperature superconductors

High-temperature superconductivity in the iron-based materials emerges from, or sometimes coexists with, their metallic or insulating parent compound states. This is surprising since these undoped states display dramatically different antiferromagnetic (AF) spin arrangements and N$\rm \acute{e}$el temperatures. Although there is general consensus that magnetic interactions are important for superconductivity, much is still unknown concerning the microscopic origin of the magnetic states. In this review, progress in this area is summarized, focusing on recent experimental and theoretical results and discussing their microscopic implications. It is concluded that the parent compounds are in a state that is more complex than implied by a simple Fermi surface nesting scenario, and a dual description including both itinerant and localized degrees of freedom is needed to properly describe these fascinating materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in Nature Physic

Spin State Disproportionation in Insulating Ferromagnetic LaCoO3 Epitaxial Thin Films

The origin of insulating ferromagnetism in epitaxial LaCoO3 films under tensile strain remains elusive despite extensive research efforts have been devoted. Surprisingly, the spin state of its Co ions, the main parameter of its ferromagnetism, is still to be determined. Here, we have systematically investigated the spin state in epitaxial LaCoO3 thin films to clarify the mechanism of strain induced ferromagnetism using element-specific x-ray absorption spectroscopy and dichroism. Combining with the configuration interaction cluster calculations, we unambiguously demonstrate that Co3+ in LaCoO3 films under compressive strain (on LaAlO3 substrate) are practically a low spin state, whereas Co3+ in LaCoO3 films under tensile strain (on SrTiO3 substrate) have mixed high spin and low spin states with a ratio close to 1:3. From the identification of this spin state ratio, we infer that the dark strips observed by high-resolution scanning transmission electron microscopy indicate the position of Co3+ high spin state, i.e., an observation of a spin state disproportionation in tensile-strained LaCoO3 films. This consequently explains the nature of ferromagnetism in LaCoO3 films