Mouse Escape Behaviors and mPFC-BLA Activity Dataset: Understanding Flexible Defensive Strategies Under Threat

Responding to threats in the real world demands a sophisticated orchestration of freeze and flight behaviors dynamically modulated by the neural activity. While the medial prefrontal cortex-basolateral amygdala (mPFC-BLA) network is known to play a pivotal role in coordinating these responses, the mechanisms underlying its population dynamics remain vague. As traditional Pavlovian fear conditioning models fall short in encapsulating the breadth of natural escape behaviors, we introduce a novel dataset to bridge this gap, capturing the defensive strategies of mice against a spider robot in a natural-like environment. The adaptive escape behaviors and concurrent mPFC-BLA activity in eight mice were monitored using wireless local field potential (LFP) and video recordings, both individually and in groups. Our data offers a unique avenue to explore the neural dynamics that govern fear- and vigilance-induced threat responses in isolated and social contexts. Supplemented by detailed methodologies and validation, the dataset allows for the analysis of the transient neural oscillatory dynamics, with prospective implications for the fields of neuroscience, robotics, and artificial intelligence

Critical Incidents in Ways of Experiencing Ethical Engineering Practice

Background: Ethics is a required outcome for engineering education programs, but few studies focus on how workforce experiences lead to changes in how engineers experience ethics in practice. By identifying what incidents influence the ways that engineers come to experience ethical engineering practice, we can more effectively design post-secondary pedagogy based on these experiences. Purpose: We address the research question, What types of critical incidents influence engineers ways of experiencing ethical engineering practice? By identifying and categorizing critical incidents, we aim to provide the engineering education community with strategies and stories that they can embed in post-secondary engineering ethics curriculums. Design/Method: We employed a semi-structured interview protocol to solicit experiences with ethical engineering practice among 43 engineers from a variety of engineering disciplines and who were all currently working in the health products industry. While the interviews focused on ways of experiencing ethical engineering practice, many participants discussed critical change-inducing incidents therein. Thus, we used critical incident technique to identify and synthesize influential workforce experiences in their ethical practice. Results We identified 106 critical incidents, or workforce experiences that led to a change in how engineers viewed or practiced ethical engineering. We grouped incidents into 17 critical incident types, which represent patterns of events or behaviors that led to a change or reinforcement in ethical practice. We grouped incident types into five categories: (1) Cultural Immersions, (2) Interpersonal Encounters; (3) Ethical Actions, (4) Ethical Failures, and (5) Mentorship Events. Conclusion: This study can inform educational change efforts by ensuring that such efforts are grounded in and based on the lived experiences of practicing engineers. We found that Cultural Immersions was the most prominent type of critical incident among participants, and thus we emphasize the import of supporting student awareness of organizational culture, including how it informs ones ethical views and practices. Based on the range of incident types, we also emphasize how instructors might consider and build the multitude of incident types and categories to implement pedagogy aligned with workforce experiences

Metabolic determination of decursinol using human liver microsome

Purpose: To determine new metabolites of the main components of Angelica gigas known to give anti-inflammation and pain relief Methods: Decursinol and blank sample were metabolized in human liver microsomes. The metabolized samples were centrifuged and deproteinated by adding 3 mL acetonitrile. The acetonitrile layer was concentrated and reconstituted in methanol. Finally, the prepared sample was injected into the LC-Q- TOF-MS. Results: Four new metabolites of decursinol with m/z ranging from 263.0912 ~ 263.0920 were identified as hydroxylated forms of decursinol, and the hydroxylated position of each metabolite was characterized using TOF mass spectrum. Their error values of detected m/z were 0.38 ~ 2.29 ppm, which indicates high accuracy of analysis. Conclusion: Previously unreported decursinol metabolites have been identified in this study. The findings provide athe basis for further pharmaceutical studies and functional food development using decursinol

Applying Phenomenography to Develop a Comprehensive Understanding of Ethics in Engineering Practice

This Work-in-Progress Research paper describes (1) the contemporary research space on ethics education in engineering; (2) our long-term research plan; (3) the theoretical underpinnings of Phase 1 of our research plan (phenomenography); and (4) the design and developmental process of a phenomenographic interview protocol to explore engineers' experiences with ethics. Ethical behavior is a complex phenomenon that is complicated by the institutional and cultural contexts in which it occurs. Engineers also have varied roles and often work in a myriad of capacities that influence their experiences with and understanding of ethics in practice. We are using phenomenography, a qualitative research approach, to explore and categorize the ways engineers experience and understand ethical engineering practice. Specifically, phenomenography will allow us to systematically investigate the range and complexity of ways that engineers experience ethics in professional practice in the health products industry. Phenomenographic data will be obtained through a specialized type of semi-structured interview. Here we introduce the design of our interview protocol and its four sections: Background, Experience, Conceptual, and Summative. We also describe our iterative process for framing questions throughout each section

Rapid Real-Time Polymerase Chain Reaction for Salmonella Serotyping Based on Novel Unique Gene Markers by Pangenome Analysis

An accurate diagnostic method for Salmonella serovars is fundamental to preventing the spread of associated diseases. A diagnostic polymerase chain reaction (PCR)-based method has proven to be an effective tool for detecting pathogenic bacteria. However, the gene markers currently used in real-time PCR to detect Salmonella serovars have low specificity and are developed for only a few serovars. Therefore, in this study, we explored the novel unique gene markers for 60 serovars that share similar antigenic formulas and show high prevalence using pangenome analysis and developed a real-time PCR to detect them. Before exploring gene markers, the 535 Salmonella genomes were evaluated, and some genomes had serovars different from the designated serovar information. Based on these analyses, serovar-specific gene markers were explored. These markers were identified as genes present in all strains of target serovar genomes but absent in strains of other serovar genomes. Serovar-specific primer pairs were designed from the gene markers, and a real-time PCR method that can distinguish between 60 of the most common Salmonella serovars in a single 96-well plate assay was developed. As a result, real-time PCR showed 100% specificity for 199 Salmonella and 29 non-Salmonella strains. Subsequently, the method developed was applied successfully to both strains with identified serovars and an unknown strain, demonstrating that real-time PCR can accurately detect serovars of strains compared with traditional serotyping methods, such as antisera agglutination. Therefore, our method enables rapid and economical Salmonella serotyping compared with the traditional serotyping method.</p&gt

Distinct features of B cell receptors in neuromyelitis optica spectrum disorder among CNS inflammatory demyelinating diseases

Background Neuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing. Methods From a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups. Results Blood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups. Conclusions NMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individuals lifetime.This study was supported by grants from the National Research Foundation of Korea (NRF) (2023R1A2C2007798); Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HR18C0016, HR21C0198); and Asan Institute for Life Science (2022IF0019, 2019IP0853-1), Asan Medical Center, Seoul, South Korea. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI22C0553). This study was supported by a Medical Scientist Training Program from the Ministry of Science & ICT of Korea

Serology assays used in SARS-CoV-2 seroprevalence surveys worldwide: a systematic review and meta-analysis of assay features, testing algorithms, and performance

Many serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested. We conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between 1 January 2020, and 19 November 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment. Among 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [-0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence. The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays

GPR105 Ablation Prevents Inflammation and Improves Insulin Sensitivity in Mice with Diet-Induced Obesity

GPR105, a G-protein coupled receptor for UDP-glucose, is highly expressed in several human tissues and participates in the innate immune response. Since inflammation has been implicated as a key initial trigger for type 2 diabetes, we hypothesized that GPR105 (official gene name: P2RY14) might play a role in the initiation of inflammation and insulin resistance in obesity. To this end, we investigated glucose metabolism in GPR105 knockout (KO) and wild-type (WT) mice fed a high-fat diet (HFD). We also examined whether GPR105 regulates macrophage recruitment to liver or adipose tissues by in vivo monocyte tracking and in vitro chemotaxis experiments, followed by transplantation of bone marrow from either KO or WT donors to WT recipients. Our data show that genetic deletion of GPR105 confers protection against HFD-induced insulin resistance, with reduced macrophage infiltration and inflammation in liver, and increased insulin-stimulated Akt phosphorylation in liver, muscle and adipose tissue. By tracking monocytes from either KO or WT donors, we found that fewer KO monocytes were recruited to the liver of WT recipients. Furthermore, we observed that UDP-Glc enhanced the in vitro migration of bone marrow-derived macrophages from WT but not KO mice, and that plasma UDP-Glc levels were significantly higher in obese versus lean mice. Finally, we confirmed that insulin sensitivity improved in HFD mice with a myeloid cell-specific deletion of GPR105. These studies indicate that GPR105 ablation mitigates HFD-induced insulin resistance by inhibiting macrophage recruitment and tissue inflammation. Hence, GPR105 provides a novel link between innate immunity and metabolism

DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity

<p>Abstract</p> <p>Background</p> <p>Histone modifications and DNA methylation are two major factors in epigenetic phenomenon. Unlike the histone deacetylase inhibitors, which are known to exert radiosensitizing effects, there have only been a few studies thus far concerning the role of DNA methyltransferase (DNMT) inhibitors as radiosensitizers. The principal objective of this study was to evaluate the effects of DNMT inhibitors on the radiosensitivity of human cancer cell lines, and to elucidate the mechanisms relevant to that process.</p> <p>Methods</p> <p>A549 (lung cancer) and U373MG (glioblastoma) cells were exposed to radiation with or without six DNMT inhibitors (5-azacytidine, 5-aza-2'-deoxycytidine, zebularine, hydralazine, epigallocatechin gallate, and psammaplin A) for 18 hours prior to radiation, after which cell survival was evaluated via clonogenic assays. Cell cycle and apoptosis were analyzed via flow cytometry. Expressions of DNMT1, 3A/3B, and cleaved caspase-3 were detected via Western blotting. Expression of γH2AX, a marker of radiation-induced DNA double-strand break, was examined by immunocytochemistry.</p> <p>Results</p> <p>Pretreatment with psammaplin A, 5-aza-2'-deoxycytidine, and zebularine radiosensitized both A549 and U373MG cells. Pretreatment with psammaplin A increased the sub-G1 fraction of A549 cells, as compared to cells exposed to radiation alone. Prolongation of γH2AX expression was observed in the cells treated with DNMT inhibitors prior to radiation as compared with those treated by radiation alone.</p> <p>Conclusions</p> <p>Psammaplin A, 5-aza-2'-deoxycytidine, and zebularine induce radiosensitivity in both A549 and U373MG cell lines, and suggest that this effect might be associated with the inhibition of DNA repair.</p