Cranial bone morphometric study among mouse strains

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Little is known about the molecular mechanism which regulates how the whole cranium is shaped. Mouse models currently available for genetic research include several hundreds of unique inbred strains and genetically engineered mutants. By cross comparing their genomic structures, we can elucidate the cause of any differences in the phenotype between two strains. The craniometry of subspecies, or closely related species, of mice provide a good systemic model to study the relationship between genetic variance and cranial shape evolution. The lack of a quantified framework for comparing and analyzing mouse cranial shape has been a problem. For this reason, we performed quantitative analysis of cranial shape morphology between several mouse strains. Results: This article reports on a craniometric assay of seven mouse strains: four inbred strains (C57BL/6J, BALB/cA, C3H/HeJ, and CBA/JNCr) from Mus musculus domesticus (M. m. domesticus); one closed colony strain (ICR) from M. m. domesticus; one inbred strain (MSM/Ms) from Mus musculus molossinus; and, Mus spretus as a strain from a species other than M. m. domesticus. W

Stability of topologically protected edge states in nonlinear quantum walks: Additional bifurcations unique to Floquet systems

Recently, effects of nonlinearity on topologically nontrivial systems have attracted attention and the stability of topologically protected edge states has been studied for a quantum walk with nonlinear effects, which is akin to time-periodically driven systems (Floquet systems). In the previous work, it has been found that the edge states can be stable attractors or unstable repellers depending on their intrinsic topological property, while the stability is not affected by the strength of nonlinearity. In the present work, we find additional bifurcations at which edge states change from stable attractors to unstable repellers with increasing the strength of nonlinearity in nonlinear quantum walks, for the first time. The new bifurcations are unique to Floquet systems, since we take dynamical properties of Floquet systems into consideration by directly applying the time-evolution operator of the quantum walks to the linear stability analysis. Our results shed new light on nonlinear effects on topological edge states in Floquet systems.Comment: 28 pages, 11 figure

A Validity Perspective on Evaluating the Justified Use of Data-driven Decision-making Algorithms

Recent research increasingly brings to question the appropriateness of using predictive tools in complex, real-world tasks. While a growing body of work has explored ways to improve value alignment in these tools, comparatively less work has centered concerns around the fundamental justifiability of using these tools. This work seeks to center validity considerations in deliberations around whether and how to build data-driven algorithms in high-stakes domains. Toward this end, we translate key concepts from validity theory to predictive algorithms. We apply the lens of validity to re-examine common challenges in problem formulation and data issues that jeopardize the justifiability of using predictive algorithms and connect these challenges to the social science discourse around validity. Our interdisciplinary exposition clarifies how these concepts apply to algorithmic decision making contexts. We demonstrate how these validity considerations could distill into a series of high-level questions intended to promote and document reflections on the legitimacy of the predictive task and the suitability of the data.Comment: in IEEE Conference on Secure and Trustworthy Machine Learning (SaTML) 202

Novel migrating mouse neural crest cell assay system utilizing P0-Cre/EGFP fluorescent time-lapse imaging

<p>Abstract</p> <p>Background</p> <p>Neural crest cells (NCCs) are embryonic, multipotent stem cells. Their long-range and precision-guided migration is one of their most striking characteristics. We previously reported that <it>P0-Cre/CAG-CAT-lacZ </it>double-transgenic mice showed significant lacZ expression in tissues derived from NCCs.</p> <p>Results</p> <p>In this study, by embedding a <it>P0-Cre/CAG-CAT-EGFP </it>embryo at E9.5 in collagen gel inside a culture glass slide, we were able to keep the embryo developing <it>ex vivo </it>for more than 24 hours; this development was with enough NCC fluorescent signal intensity to enable single-cell resolution analysis, with the accompanying NCC migration potential intact and with the appropriate NCC response to the extracellular signal maintained. By implantation of beads with absorbed platelet-derived growth factor-AA (PDGF-AA), we demonstrated that PDGF-AA acts as an NCC-attractant in embryos.</p> <p>We also performed assays with NCCs isolated from <it>P0-Cre/CAG-CAT-EGFP </it>embryos on culture plates. The neuromediator 5-hydroxytryptamine (5-HT) has been known to regulate NCC migration. We newly demonstrated that dopamine, in addition to 5-HT, stimulated NCC migration <it>in vitro</it>. Two NCC populations, with different axial levels of origins, showed unique distribution patterns regarding migration velocity and different dose-response patterns to both 5-HT and dopamine.</p> <p>Conclusions</p> <p>Although avian species predominated over the other species in the NCC study, our novel system should enable us to use mice to assay many different aspects of NCCs in embryos or on culture plates, such as migration, division, differentiation, and apoptosis.</p

Elevated expression of interleukin-6 (IL-6) and serum amyloid A (SAA) in the skin and the serum of recessive dystrophic epidermolysis bullosa: Skin as a possible source of IL-6 through Toll-like receptor ligands and SAA

The effect of persistent skin inflammation on extracutaneous organs and blood is not well studied. Patients with recessive dystrophic epidermolysis bullosa (RDEB), a severe form of the inherited blistering skin disorder, have widespread and persistent skin ulcers, and they develop various complications including anaemia, hyperglobulinaemia, hypoalbuminaemia and secondary amyloidosis. These complications are associated with the bioactivities of IL-6, and the development of secondary amyloidosis requires the persistent elevation of serum amyloid A (SAA) level. We found that patients with RDEB had significantly higher serum levels of IL-6 and SAA compared to healthy volunteers and patients with psoriasis or atopic dermatitis. Both IL-6 and SAA were highly expressed in epidermal keratinocytes and dermal fibroblasts of the skin ulcer lesions. Keratinocytes and fibroblasts surrounding the ulcer lesions are continuously exposed to Toll-like receptor (TLR) ligands, pathogen-associated and damage-associated molecular pattern molecules. In vitro, TLR ligands induced IL-6 expression via NF-κB in normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs). SAA further induced the expression of IL-6 via TLR1/2 and NF-κB in NHEKs and NHDFs. The limitation of this study is that NHEKs and NHDFs were not derived from RDEB patients. These observations suggest that TLR-mediated persistent skin inflammation might increase the risk of IL-6-related systemic complications, including RDEB

Discovery of a novel restriction endonuclease by genome comparison and application of a wheat-germ-based cell-free translation assay: PabI (5′-GTA/C) from the hyperthermophilic archaeon Pyrococcus abyssi

To search for restriction endonucleases, we used a novel plant-based cell-free translation procedure that bypasses the toxicity of these enzymes. To identify candidate genes, the related genomes of the hyperthermophilic archaea Pyrococcus abyssi and Pyrococcus horikoshii were compared. In line with the selfish mobile gene hypothesis for restriction–modification systems, apparent genome rearrangement around putative restriction genes served as a selecting criterion. Several candidate restriction genes were identified and then amplified in such a way that they were removed from their own translation signal. During their cloning into a plasmid, the genes became connected with a plant translation signal. After in vitro transcription by T7 RNA polymerase, the mRNAs were separated from the template DNA and translated in a wheat-germ-based cell-free protein synthesis system. The resulting solution could be directly assayed for restriction activity. We identified two deoxyribonucleases. The novel enzyme was denoted as PabI, purified and found to recognize 5′-GTAC and leave a 3′-TA overhang (5′-GTA/C), a novel restriction enzyme-generated terminus. PabI is active up to 90°C and optimally active at a pH of around 6 and in NaCl concentrations ranging from 100 to 200 mM. We predict that it has a novel 3D structure

Kinetics of Intraparenchymal Mononuclear Cells in A Murine Model of Pulmonary Fibrosis Induced by Bleomycin

Bleomycin (BLM), an anti-tumor drug, has been observed to cause interstitial pneumonia followed by subsequent fibrosis. In order to elucidate the cellular mechanism in the fibrotic process, we examined inflammatory cells in the lungs of mice after intratracheal administration of BLM. Microscopic observation of May-Giemsa-stained cells demonstrated that the number of macrophages remained at the basal level as of day 3, then increased and peaked on days 7 to 14, while the number of lymphocytes increased as early as day 1, peaked on day 7, and then gradually decreased. In flow cytometric analysis, the numbers of both B and T cells, including both CD4+ and CD8+ T cells, showed a rapid increase after administration of BLM. The T cells were activated, as indicated by the induction of IL-2 receptor (IL-2R) and the augmented expression on their surface of leukocyte function associated antigen-1 (LFA-1), which has also been regarded as a T cell activation marker. In addition, marked accumulation of γ δT cells was observed in the lungs of mice treated with BLM, although it has not been elucidated whether these cells were involved in the pathogenesis. These results suggest that the increase of intraparenchymal macrophages and lymphocytes and the activation of T cells are prerequisite for the development of pulmonary fibrosis

Imiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.

OBJECTIVE To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN), compared with placebo or no intervention. DATA SOURCES We searched Cochrane, PubMed, ISRCTN registry, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to November 23, 2022. METHODS OF STUDY SELECTION We included randomized controlled trials and prospective nonrandomized studies with control arms that investigated the efficacy of imiquimod for histologically confirmed CIN or VAIN. The primary outcomes were histologic regression of the disease (primary efficacy outcome) and treatment discontinuation due to side effects (primary safety outcome). We estimated pooled odds ratios (ORs) of imiquimod, compared with placebo or no intervention. We also conducted a meta-analysis of the proportions of patients with adverse events in the imiquimod arms. TABULATION, INTEGRATION, AND RESULTS Four studies contributed to the pooled OR for the primary efficacy outcome. An additional four studies were available for meta-analyses of proportions in the imiquimod arm. Imiquimod was associated with increased probability of regression (pooled OR 4.05, 95% CI 2.08-7.89). Pooled OR for CIN in the three studies was 4.27 (95% CI 2.11-8.66); results of one study were available for VAIN (OR, 2.67, 95% CI 0.36-19.71). Pooled probability for primary safety outcome in the imiquimod arm was 0.07 (95% CI 0.03-0.14). The pooled probabilities (95% CI) of secondary outcomes were 0.51 (0.20-0.81) for fever, 0.53 (0.31-0.73) for arthralgia or myalgia, 0.31 (0.18-0.47) for abdominal pain, 0.28 (0.09-0.61) for abnormal vaginal discharge or genital bleeding, 0.48 (0.16-0.82) for vulvovaginal pain, and 0.02 (0.01-0.06) for vaginal ulceration. CONCLUSION Imiquimod was found to be effective for CIN, whereas data on VAIN were limited. Although local and systemic complications are common, treatment discontinuation is infrequent. Thus, imiquimod is potentially an alternative therapy to surgery for CIN. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42022377982