Miracle-dz/UniFAR-FTUs huggingface dataset:
HSV-1 ICP22 Is a Selective Viral Repressor of Cellular RNA Polymerase II-Mediated Transcription Elongation

The Herpes Simplex Virus (HSV-1) immediate early protein ICP22 interacts with cellular proteins to inhibit host cell gene expression and promote viral gene expression. ICP22 inhibits phosphorylation of Ser2 of the RNA polymerase II (pol II) carboxyl-terminal domain (CTD) and productive elongation of pol II. Here we show that ICP22 affects elongation of pol II through both the early-elongation checkpoint and the poly(A)-associated elongation checkpoint on a protein-coding gene model. Coimmunoprecipitation assays using tagged ICP22 expressed in human cells and pulldown assays with recombinant ICP22 in vitro coupled with mass spectrometry identify transcription elongation factors, including P-TEFb, additional CTD kinases and the FACT complex as interacting cellular factors. Using a photoreactive amino acid incorporated into ICP22, we found that L191, Y230 and C225 crosslink to both subunits of the FACT complex in cells. Our findings indicate that ICP22 physically interacts with critical elongation regulators to inhibit transcription elongation of cellular genes, which may be vital for HSV-1 pathogenesis. We also show that the HSV viral activator, VP16 has a region of structural similarity to the ICP22 region that interacts with elongation factors, suggesting a model where VP16 competes with ICP22 to deliver elongation factors to viral genes.
Conservation and diversity in transcriptional responses among host plants forming distinct arbuscular mycorrhizal morphotypes

The morphotype of arbuscular mycorrhizal (AM) roots is distinct mostly depending on AM host species: Arum, Paris, and Intermediate types. We previously reported that gibberellin (GA) promotes the establishment of Paris-type AM symbiosis in Eustoma grandiflorum despite its negative effects on Arum-type AM symbiosis in model plants. However, the molecular mechanisms underlying the differential effects of GA on different morphotypes, including Intermediate-type AM symbiosis, remain elusive. Comparative transcriptomics revealed that several symbiosis-related genes were transcriptionally promoted upon AM fungal colonization in Lotus japonicus (Arum-type), Daucus carota (Intermediate-type), and E. grandiflorum (Paris-type). Interestingly, upon GA treatment, the fungal colonization levels and expression of symbiosis-related genes were suppressed in L. japonicus and D. carota but were promoted in E. grandiflorum. Exogenous GA transcriptionally inhibited the biosynthetic process of a host-derived signal molecule involved in AM symbiosis, strigolactone, in L. japonicus and E. grandiflorum. Additionally, disaccharides mainly metabolized in AM roots would be different between L. japonicus and D. carota/E. grandiflorum. This study uncovered the conserved transcriptional responses during mycorrhization and diverse responses to GA in AM roots with distinct morphotypes among phylogenetically distant host plants.
How perception and attention participate in reading skill?

Reading creates accessibility to the outer world information and is an integral skill for academic achievement. It involves visual perception, reasoning at symbolic level (text reading) and phonological processing. But does perception, visuospatial processing at pre-symbolic level affect reading skill? To understand and untangle the mechanism fifty children with reading problem (developmental dyslexia, DDC) and twentyfive age-matched typical readers (healthy controls, HC) were studied. In DDC, the variable-performance of non-symbolic visual search (pictorial-level) was associated with bilateral brain activity (functional MRI) of ventral stream (inferior occipital and fusiform) and greater involvement of frontal-prefrontal regions, suggesting the modified dorsal route-gating for figure-ground filtering. Performance variability in picture-concept reasoning (71.9% and significant group mean difference) and visuospatial-organization (51.3%) of DDC children indicate attentional or executive differences at nonsymbolic level. In symbolic discrimination performance, no significant difference observed for single alphabet or number (digit) reading but significant differences at word level for visual and phonological performance (considering orthographic differences), attributes to distractor-inhibition problems. Nonsymbolic to symbolic coding/decoding speed and writing error (copying) differences are suggestive of execution variability rather than motor coordination in DDC. In HC, the top-down dorsal route gating and hypoactivity induced in right frontal-anterior cingulate cortices, play a major role in reading by allocating spatial attention and inhibiting distractors. It has been elaborated in the “neurobiological model”. How perception and attention participate in reading skill? Research Highlights Visuospatial attention, executive control (nonsymbolic level) and visual discrimination (symbolic level) performance contribute to reading. In children with reading problems (dyslexia) pictorial visual processing task (fMRI) recruited higher activation in right hemispheric frontal, inferior parietal and anterior cingulate regions. Bilateral activation of occipital-striate, extra-striate, fusiform for nonsymbolic is associated with significantly more errors at bigger-symbol-string, in dyslexia. Auditory discrimination differences in shallow-deep orthography. Correlation of non-symbolic executive and symbolic performances. Role of the prelexical visual perception and dorsal-route gating in reading skill explained as neurobiological model.
(Invited) Oxygen Reduction Reaction at Cathodes on Proton Conducting Oxide Electrolytes: Contribution from Three Phase Boundary Compared to Bulk Path

The required protonic conductivity of cathodes on proton conducting electrolytes to extend the oxygen reduction reaction beyond the three phase boundary is explored. Experimental results for Ba0.5Sr0. 5Fe0.8Zn0. 2O3-δ (BSFZ) are discussed in this context. While for thin-film electrodes the effective rate constant kq of the surface reaction is the most important parameter, for porous thick cathodes kq and the electrode's proton conductivity are equally influential. The low activation energy of the latter quantity turns out to be particularly advantageous for the targeted lower operation temperatures.
Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis

Innate lymphoid cells (ILCs) comprise a heterogeneous population of immune cells that maintain barrier function and can initiate a protective or pathological immune response upon infection. Here we show the involvement of IL-17A-producing ILCs in microbiota-driven immunopathology in cutaneous leishmaniasis. IL-17A-producing ILCs were RORγt+ and were enriched in Leishmania major infected skin, and topical colonization with Staphylococcus epidermidis before L. major infection exacerbated the skin inflammatory responses and IL-17A-producing RORγt+ ILC accumulation without impacting type 1 immune responses. IL-17A responses in ILCs were directed by Batf3 dependent CD103+ dendritic cells, and experiments using ILC deficient Rag1-/- mice established that IL-17A+ ILCs were sufficient in driving the inflammatory responses. As depletion of ILCs or neutralization of IL-17A diminished the microbiota mediated immunopathology. Taken together, this study indicates that the skin microbiota promotes RORγt+ IL-17A-producing ILCs, which augment the skin inflammation in cutaneous leishmaniasis.
Asexual freshwater snails make poor mate choice decisions

Once-useful traits that no longer contribute to fitness tend to decay over time. Here, we address whether the expression of mating-related traits that increase the fitness of sexually reproducing individuals but are likely less useful or even costly to asexual counterparts seems to exhibit decay in the latter. Potamopyrgus antipodarum is a New Zealand freshwater snail characterized by repeated transitions from sexual to asexual reproduction. The frequent coexistence of sexual and asexual lineages makes P. antipodarum an excellent model for the study of mating-related trait loss. We used a mating choice assay including sexual and asexual P. antipodarum females and conspecific (presumed better choice) vs. heterospecific (presumed worse choice) males to evaluate the loss of behavioral traits related to sexual reproduction. We found that sexual females engaged in mating behaviors with conspecific mating partners more frequently and for a greater duration than with heterospecific mating partners. By contrast, asexual females mated at similar frequency and duration as sexual females, but did not mate more often or for longer duration with conspecific vs. heterospecific males. These results are consistent with a scenario where selection acting to maintain mate choice in asexual P. antipodarum is weak or ineffective relative to sexual females and, thus, where asexual reproduction contributes to the evolutionary decay of mating-related traits in this system.
Student Practice In 3D Design and Printing for Promoting Analytical and Applied Mathematical Thinking Skills

The educational literature emphasizes the key role of analytical thinking (AT) and applied mathematical skills (AMS) in solving engineering prob-lems and calls to nurture these skills in school STEM education. This study proposes and explores a strategy for fostering AT and AMS among middle school students and prospective teachers through practice in digital design and 3D printing. The study involved 32 seventh grade students and five prospective teachers of technology. Both groups learned a 10-hour work-shop, “Make a spinning-top. ” The participants designed spinning-tops that can fit into a Kinder Surprise egg and analysed their geometric and mechani-cal properties. We collected data from students’ worksheets, their designed artefacts, and in-class discussions. The results indicated that the assignment prompted the participants to apply AT and AMS. School students designed complex models, inquired into their geometry, and verified their designs through 3D printing. The worksheets were found to be an effective tool to frame and guide students’ thinking in the design tasks and the creation and testing of mathematical models. For the prospective teachers, the workshop, accompanied by lectures on the methodology of experiential learning, ena-bled to implement mathematical solutions in designs and develop instruc-tional units on the subject.
Clinical Outcomes of Tanezumab With Different Dosages for Patient With Osteoarthritis: Network Meta-Analysis

Background: Osteoarthritis (OA) high disability rate will increase as people getting older, and is the most prevalent form of arthritis in the future. This study identified the clinical effects of optimum doses of tanezumab for patients with OA. Method: Three electronic databases were searched up until January 15, 2021. The mean difference (MD) or odds ratio (OR) was considered an effect measure. The design-by-treatment interaction model was adopted for network meta-analyses. Analyses were conducted using WinBUGS 1.4. 3 and R 4.0. 5 software. Results: nine publications with 10 studies were included. Compared with placebo in network meta-analysis, except the outcomes of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) stiffness subscale and joints replaced, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. However, there was no statistical difference among all different doses of tanezumab. Compared with placebo, except the outcomes of adverse events (AEs) and AEs of abnormal peripheral sensation, all different dosages of tanezumab weren’t superior to placebo in the other effectiveness outcome, and the difference was statistically significant. The 10 mg of tanezumab with highest SUCRA had the best effect, but it was associated with a higher safety event. Compared with placebo, except the outcomes of WOMAC stiffness subscale and joints replaced, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. Compared with placebo, except for the outcomes of AEs and AEs of abnormal peripheral sensation, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. Other direct comparisons showed no statistical difference. Conclusion: This study recommended that clinicians should give priority to the treatment of OA patients with a low dose of 2.5 mg according to the patient’s condition and actual situation. If the effect using tanezumab with 2.5 mg is not satisfactory, the increase up to 10 mg should be carefully pondered, because of a more unbalanced risk/benefit ratio.
Elites Do Not Deplete – No Effect of Prior Mental Exertion on Subsequent Shooting Performance in Elite Shooters

In order to perform at the highest level, elite shooters have to remain focused during the whole course of a tournament, which regularly lasts multiple hours. Investing self-control over extended time periods is often associated with lower levels of perceived self-control strength (i.e., the subjective estimation of how much mental effort one is capable of investing in a given task) and impaired performance in several sports-related domains. However, previous findings on the effects of prior self-control efforts on shooting performance have been mixed, as elite shooters seem to be less affected by preceding self-control demanding tasks than sub-elite athletes. Therefore, the aim of the present study was to investigate the effects of self-control on shooting performance in elite shooters. Hence, we randomly assigned elite shooters to an experimental (n = 12) or a control condition (n = 11) and asked them to perform a series of 40 shots at baseline (T1) and again after a task which either did or did not require self-control (T2). Additionally, we continuously measured the shooters’ level of perceived self-control strength. We assumed that in elite athletes, shooting accuracy as well as the perceived level of self-control strength would not be significantly affected over time from T1 to T2 in both conditions. In line with our assumptions, Bayesian linear mixed effect models revealed that shooting performance remained relatively stable in both conditions over time and the conditions also did not differ significantly in their perceived levels of self-control strength. Contrary to resource-based theories of self-control, these results speak against the idea of a limited self-control resource as previous acts of self-control did not impair subsequent shooting performance in elite athletes.
Risks and Protective Factors Associated With Mental Health Symptoms During COVID-19 Home Confinement in Italian Children and Adolescents: The #Understandingkids Study

Objective: To identify risk and protective factors for mental health symptoms associated with lifestyle changes caused by home confinement in pediatric subjects and in children and adolescents with a neuropsychiatric disorder. Study design: This was a prospective, cross-sectional study conducted from May 10 to May 31, 2020. Two online anonymous surveys were developed: population-based and clinical-based (children with neuropsychiatric disorders). Outcomes included emotional and behavioral symptoms, as assessed by psychometric scales (BPSC, PPSC, PSC, CES-DC and SCARED, respectively), and lifestyle changes during home confinement (i.e., physical activity, screen time, home schooling, reading). Results: The sample included 9,688 pediatric subjects, and 289 children and adolescents with a neuropsychiatric disorder. The presence of siblings was a protective factor in all ages. In pre- and school children: male sex, a diagnosis of autism, residency in highly affected areas, high parental educational level or job loss, and screen time (>2 h/day) were risk factors. Physical activity, home-schooling, reading, talking with other people were protective factors. Residency in highly affected areas, a diagnosis of mood disorder, parental job loss, and screen time, were associated with a worsening of the depressive symptoms, whereas physical activity, talking with other people, playing with parents were protective activities. Screen time was also a risk factor for anxiety symptoms, while physical activity, reading and talking with other people were protective factors. Conclusions: This study identified risk and protective factors for mental health symptoms associated with lifestyle changes caused by COVID-19 home confinement to promote mental well-being in pediatrics during pandemic times.
Highly Sensitive Flow Cytometry Allows Monitoring of Changes in Circulating Immune Cells in Blood After Tdap Booster Vaccination

Antigen-specific serum immunoglobulin (Ag-specific Ig) levels are broadly used as correlates of protection. However, in several disease and vaccination models these fail to predict immunity. In these models, in-depth knowledge of cellular processes associated with protective versus poor responses may bring added value. We applied high-throughput multicolor flow cytometry to track over-time changes in circulating immune cells in 10 individuals following pertussis booster vaccination (Tdap, Boostrix®, GlaxoSmithKline). Next, we applied correlation network analysis to extensively investigate how changes in individual cell populations correlate with each other and with Ag-specific Ig levels. We further determined the most informative cell subsets and analysis time points for future studies. Expansion and maturation of total IgG1 plasma cells, which peaked at day 7 post-vaccination, was the most prominent cellular change. Although these cells preceded the increase in Ag-specific serum Ig levels, they did not correlate with the increase of Ig levels. In contrast, strong correlation was observed between Ag-specific IgGs and maximum expansion of total IgG1 and IgA1 memory B cells at days 7 to 28. Changes in circulating T cells were limited, implying the need for a more sensitive approach. Early changes in innate immune cells, i.e. expansion of neutrophils, and expansion and maturation of monocytes up to day 5, most likely reflected their responses to local damage and adjuvant. Here we show that simultaneous monitoring of multiple circulating immune subsets in blood by flow cytometry is feasible. B cells seem to be the best candidates for vaccine monitoring.
A Cross-Sectional Study Comparing Two Opt-Out HIV Testing Strategies in the Out-Patient Setting

Background: HIV infections are generally asymptomatic, leading to undetected infections and late-stage diagnoses. There are a lack of acceptable testing strategies for routine opt-out HIV screening. Our aim was to evaluate and compare the diagnostic yield of routine opt-out HIV testing strategies in two out-patient settings in a low HIV prevalence country: The public primary care and specialist out-patient care setting Methods: A cross-sectional study was conducted in a primary care clinic over a four-week period in 2016 to 2017 and in a specialist out-patient clinic over a concurrent 11-month period. Patients were invited to complete a questionnaire assessing demographic characteristics, acceptance of opt-out HIV testing as a policy in all out-patient clinics in Hong Kong and reasons if refusing the HIV test. All respondents were offered an HIV test. Results: This study included 648 and 1,603 patients in the primary care and specialist out-patient clinic, respectively. Test acceptability was 86 and 87% in the primary care and specialist out-patient setting, respectively. Test uptake was 35 and 68% in the primary care and specialist out-patient setting, respectively. No HIV infections were detected. Conclusion: Opt-out HIV testing during routine blood taking in the specialist out-patient setting achieved a high test uptake and acceptability. In contrast, opt-out HIV testing using rapid finger-prick tests in the primary care setting was not effective.
Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers

Tinnitus can be a burdensome condition on both individual and societal levels. Many aspects of this condition remain elusive, including its underlying mechanisms, ultimately hindering the development of a cure. Interdisciplinary approaches are required to overcome long-established research challenges. This review summarizes current knowledge in various tinnitus-relevant research fields including tinnitus generating mechanisms, heterogeneity, epidemiology, assessment, and treatment development, in an effort to highlight the main challenges and provide suggestions for future research to overcome them. Four common themes across different areas were identified as future research direction: (1) Further establishment of multicenter and multidisciplinary collaborations; (2) Systematic reviews and syntheses of existing knowledge; (3) Standardization of research methods including tinnitus assessment, data acquisition, and data analysis protocols; (4) The design of studies with large sample sizes and the creation of large tinnitus-specific databases that would allow in-depth exploration of tinnitus heterogeneity.
Screening for Anti-Inflammation Quality Markers of Lianhua Qingwen Capsule Based on Network Pharmacology, UPLC, and Biological Activity

Influenza is a common respiratory infectious disease. In China, Lianhua Qingwen capsule (LHQWC), a drug with significant clinical efficacy and few side effects, is commonly used to treat influenza. However, the composition of LHQWC is complicated, and currently used quality control methods cannot ensure its consistency. In this study, combined with its clinical efficacy, the targets of LHQWC were screened using network pharmacology. Then, anti-inflammation quality markers of LHQWC were screened and judged by combined chemical with biological evaluation. Cyclooxygenase-2 (COX-2) was identified as one of the main targets of the anti-inflammatory activity of LHQWC. The rate of inhibition of COX-2 by different batches of LHQWC was determined. Furthermore, seven components of LHQWC were identified. The potential quality markers were screened by spectral-effect relationship. As a result, chlorogenic acid, isochlorogenic acid B, and isochlorogenic acid C were identified and confirmed as anti-inflammatory quality markers of LHQWC. We hope that these findings provide a scientific basis for the accurate quality control of LHQWC and serve as a reference for the quality control of other drugs.
Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

Celastrol (also called tripterine) is a quinone methide triterpene isolated from the root extract of Tripterygium wilfordii (thunder god vine in traditional Chinese medicine). Over the past two decades, celastrol has gained wide attention as a potent anti-inflammatory, anti-autoimmune, anti-cancer, anti-oxidant, and neuroprotective agent. However, its clinical translation is very challenging due to its lower aqueous solubility, poor oral bioavailability, and high organ toxicity. To deal with these issues, various formulation strategies have been investigated to augment the overall celastrol efficacy in vivo by attempting to increase the bioavailability and/or reduce the toxicity. Among these, nanotechnology-based celastrol formulations are most widely explored by pharmaceutical scientists worldwide. Based on the survey of literature over the past 15 years, this mini-review is aimed at summarizing a multitude of celastrol nanoformulations that have been developed and tested for various therapeutic applications. In addition, the review highlights the unmet need in the clinical translation of celastrol nanoformulations and the path forward.