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05), indicating eccentric overload. That the quadriceps muscle activity was similar in squat and leg press, while rGRF and NJM about the knee were greater in squat than leg press, may, together with the finding of a propensity to perform leg press at deeper knee angle than squat, suggest that leg press is the preferable leg-extension resistance exercise, both from a training efficacy and injury risk perspective.This editorial summarizes the contributions to the Frontiers Research topic "Innovative Analysis Ecosystems for HEP Data", established under the Big Data and AI in High Energy Physics section and appearing under the Frontiers in Big Data and Frontiers in Artificial Intelligence journals.Understanding the order and progression of change in biomarkers of neurodegeneration is essential to detect the effects of pharmacological interventions on these biomarkers. In Huntington's disease (HD), motor, cognitive and MRI biomarkers are currently used in clinical trials of drug efficacy. Here for the first time we use directly compare data from three large observational studies of HD (total N = 532) using a probabilistic event-based model (EBM) to characterise the order in which motor, cognitive and MRI biomarkers become abnormal. We also investigate the impact of the genetic cause of HD, cytosine-adenine-guanine (CAG) repeat length, on progression through these stages. We find that EBM uncovers a broadly consistent order of events across all three studies; that EBM stage reflects clinical stage; and that EBM stage is related to age and genetic burden. Our findings indicate that measures of subcortical and white matter volume become abnormal prior to clinical and cognitive biomarkers. Importantly, CAG repeat length has a large impact on the timing of onset of each stage and progression through the stages, with a longer repeat length resulting in earlier onset and faster progression. Our results can be used to help design clinical trials of treatments for Huntington's disease, influencing the choice of biomarkers and the recruitment of participants.Well-curated datasets are essential to evidence based decision making and to the integration of artificial intelligence with human reasoning across disciplines. However, many sources of data remain siloed, unstructured, and/or unavailable for complementary and secondary research. Sysrev was developed to address these issues. First, Sysrev was built to aid in systematic evidence reviews (SER), where digital documents are evaluated according to a well defined process, and where Sysrev provides an easy to access, publicly available and free platform for collaborating in SER projects. Secondly, Sysrev addresses the issue of unstructured, siloed, and inaccessible data in the context of generalized data extraction, where human and machine learning algorithms are combined to extract insights and evidence for better decision making across disciplines. Sysrev uses FAIR - Findability, Accessibility, Interoperability, and Reuse of digital assets - as primary principles in design. Sysrev was developed primarily because of an observed need to reduce redundancy, reduce inefficient use of human time and increase the impact of evidence based decision making. This publication is an introduction to Sysrev as a novel technology, with an overview of the features, motivations and use cases of the tool. Methods Sysrev. com is a FAIR motivated web platform for data curation and SER. Sysrev allows users to create data curation projects called "sysrevs" wherein users upload documents, define review tasks, recruit reviewers, perform review tasks, and automate review tasks. Conclusion Sysrev is a web application designed to facilitate data curation and SERs. Thousands of publicly accessible Sysrev projects have been created, accommodating research in a wide variety of disciplines. Described use cases include data curation, managed reviews, and SERs.Herein, we describe the development of a paper-based device to detect nucleic acids of pathogens of interest in complex samples using loop-mediated isothermal amplification (LAMP) by producing a colorimetric response visible to the human eye. To demonstrate the utility of this device in emerging public health emergencies, we developed and optimized our device to detect SARS-CoV-2 in human saliva without preprocessing. The resulting device was capable of detecting the virus within 60 min and had an analytical sensitivity of 97% and a specificity of 100% with a limit of detection of 200 genomic copies/μL of patient saliva using image analysis. The device consists of a configurable number of reaction zones constructed of Grade 222 chromatography paper separated by 20 mil polystyrene spacers attached to a Melinex® backing via an ARclean® double-sided adhesive. The resulting device is easily configurable to detect multiple targets and has the potential to detect a variety of pathogens simply by changing the LAMP primer sets.DNA methylation is an important epigenetic mechanism involved in proper genome function. Bisulfite pyrosequencing (PSQ) is a commonly used technique to quantify DNA methylation. Although very accurate, bisulfite pyrosequencing can be expensive and time consuming for large-scale quantitative DNA methylation analysis at the single nucleotide level. High throughput DNA methylation sequencing has the potential to address these limitations, but its comparability to other methylation detection methods has not been well studied. We compared QIAseq Targeted Methyl Panel technologies (QMS) and PSQ by analyzing four CpG sites within four genes involved in neurodevelopment. QMS and PSQ had an average 5.6% difference in the detected level of DNA methylation for the same four CpG sites. Eganelisib research buy However, we observed a strong correlation in the levels of methylation across all four CpG sites between the two technologies. These findings demonstrate the comparability of QMS relative to PSQ in the ability to accurately quantify DNA methylation at specific CpG sites.The gpa-4 promoter-driven expression is described as specific for ASIL and ASIR chemosensory neurons in the nematode Caenorhabditis elegans, yet this was mostly examined in adult animals. Here we used a recombination-mediated reporter to test the previously used gpa-4 promoter expression. This reporter highlights all cells in which the gpa-4 promoter has been active at one point or another during development. We show that the gpa-4 promoter is indeed active in ASI, yet to our surprise, thispromoter drives also expression in many other cell types, including the somatic gonad, the seam cells, a subset of tail and head neurons, and muscle cells, demonstrating a widespread activity of this transgenic gpa-4 promoter during embryonic and post-embryonic development.Targeted protein degradation is a powerful approach to study and inhibit protein function in vivo. Introduction of the auxin-inducible degron (AID) system to the fission yeast Schizosaccharomyces pombe was previously reported, but, to the best of our knowledge, no plasmid for constructing AID-tagged fission yeast strains has been described so far. Here, we describe two plasmids that facilitate the introduction of the mini auxin-inducible degron (mAID) tag with a FLAG epitope or GFP by the conventional PCR-based gene targeting method. Our experimental verification indicated that PCR-based mAID tagging is straightforward and that the auxin-degron system is useful for studying essential proteins in S. pombe.During mating, C. elegans males whose tails have reached the head or tail of their intended mates are able to switch to scanning the other side by performing a turn during which the male's tail curls ventrally all the while keeping in contact with the hermaphrodite. The ability to execute turns efficiently is dependent upon serotonergic neurons in the posterior ventral nerve cord that stimulate diagonal muscles by activating a serotonin receptor, SER-1. Here we show that turning behavior is abnormal in males lacking a cGMP-dependent protein kinase, EGL-4. egl-4 mutant males are also resistant to ventral tail curling induced by exogenous serotonin.In response to a recent call to rid psychedelic science of the concept of mystical experience, we argue that acknowledging the varieties and weirdness of psychedelic experiences should be at the heart of any research program on this topic. We highlight the rich tradition and scientific tools for studying mystical-type experiences, their relevance for understanding the therapeutic effects of psychedelics, as well as the need for more diversity in the experiences and participants included in this research.In a recent Viewpoint, Sanders and Zijlmans call for the demystification of psychedelic science. However, they ignore the subjective aspect of psychedelic experiences. For the subject, mystical experiences are felt as real and can yield personally meaningful insights. It is a philosophical question whether they are true.The delivery of hydrophobic therapeutic agents to tumors is a challenge in the treatment of cancers. Here, we review recent advances in coiled-coil protein origami and discuss a proposed programmable protein origami structure, switchable by a protein kinase A/phosphatase switch, as an example of functionalization for designing future protein nanorobots.The DNA-damage-activated checkpoint protein CHK1 is required to prevent replication or mitosis in the presence of unrepaired DNA damage. Inhibitors of CHK1 (CHK1i) circumvent this checkpoint and enhance cell killing by DNA-damaging drugs. CHK1i also elicit single-agent cytotoxicity in a small subset of cell lines. Resolving the mechanisms underlying the single-agent activity may permit patient stratification and targeted therapy against sensitive tumors. Our recent comparison of three CHK1i demonstrated that they all inhibited protein synthesis only in sensitive cells. LY2606368, the most selective of these CHK1i, was used in the current study. Comparison across a panel of cell lines demonstrated that sensitive cells died upon incubation with LY2606368, whereas resistant cells underwent growth inhibition and/or cytostasis but failed to die. Sensitive cells exhibited inhibition of protein synthesis, elevated DNA damage, impaired DNA repair, and subsequently death. The consequence of CHK1 inhibition involved activation of cyclin A/CDK2 and MUS81, resulting in DNA damage. This damage led to activation of AMPK, dephosphorylation of 4E-BP1, and inhibition of protein synthesis. Inhibition of MUS81 prevented activation of AMPK, while inhibition of AMPK enhanced DNA repair and cell survival. The activation of AMPK may involve a combination of LKB1 and CaMKKβ. This study raises questions concerning the potential importance of the inhibition of protein synthesis in response to other drugs, alone or in combination with CHK1i. It also highlights the importance of clearly discriminating among growth inhibition, cytostasis, and cell death, as only the latter is likely to result in tumor regression.Nucleotide-binding domain leucine-rich repeat family pyrin domain containing 3 (NLRP3) inflammasome complex regulates the caspase-1 activity and subsequent processing of interleukin-1β (IL-1β). Various inflammatory diseases involve the activation of inflammasome complexes; thus, the intervention in complex formation via small molecules offers a new therapeutic opportunity. The structure-guided design and synthesis of a series of methoxystilbenes and methoxy-2-phenylnaphthalenes identified new inhibitors of NLRP3 inflammasome complex. The tetramethoxystilbene 4o and trimethoxy 2-phenylnaphthalene 1t inhibit the release of a mature form of IL-1β in J774A.1 cells with IC50 values of 1.39 and 2.07 μM, respectively. Mechanistic investigation revealed that tetramethoxystilbene 4o blocks the oligomerization of apoptosis-associated speck-like protein (ASC), which is the vital step in the formation of NLRP3 inflammasome assembly, thus preventing the activation of caspase-1 and the IL-1β release. Treatment of LPS+ATP challenged mice with 20 mg/kg of 4o significantly suppressed the levels of IL-1β.