Abstract Some clinical case reports have shown that immature permanent teeth with periradicular periodontitis or abscess can undergo apexogenesis after conservative endodontic treatment. A call for a ...paradigm shift and new protocol for the clinical management of these cases has been brought to attention. Concomitantly, a new population of mesenchymal stem cells residing in the apical papilla of permanent immature teeth recently has been discovered and was termed stem cells from the apical papilla (SCAP). These stem cells appear to be the source of odontoblasts that are responsible for the formation of root dentin. Conservation of these stem cells when treating immature teeth may allow continuous formation of the root to completion. This article reviews current findings on the isolation and characterization of these stem cells. The potential role of these stem cells in the following respects will be discussed: (1) their contribution in continued root maturation in endodontically treated immature teeth with periradicular periodontitis or abscess and (2) their potential utilization for pulp/dentin regeneration and bioroot engineering.
Abstract Mesenchymal stem cells (MSCs) have been isolated from the pulp tissue of permanent teeth (dental pulp stem cells or DPSCs) and deciduous teeth (stem cells from human exfoliated deciduous ...teeth). We recently discovered another type of MSCs in the apical papilla of human immature permanent teeth termed stem cells from the apical papilla (SCAP). Here, we further characterized the apical papilla tissue and stem cell properties of SCAP using histologic, immunohistochemical, and immunocytofluorescent analyses. We found that the apical papilla is distinctive to the pulp in terms of containing less cellular and vascular components than those in the pulp. Cells in the apical papilla proliferated 2- to 3-fold greater than those in the pulp in organ cultures. Both SCAP and DPSCs were as potent in osteo/dentinogenic differentiation as MSCs from bone marrows, whereas they were weaker in adipogenic potential. The immunophenotype of SCAP is similar to that of DPSCs on the osteo/dentinogenic and growth factor receptor gene profiles. Double-staining experiments showed that STRO-1 coexpressed with dentinogenic markers such as bone sialophosphoprotein, osteocalcin, and growth factors FGFR1 and TGFβRI in cultured SCAP. Additionally, SCAP express a wide variety of neurogenic markers such as nestin and neurofilament M upon stimulation with a neurogenic medium. We conclude that SCAP are similar to DPSCs but a distinct source of potent dental stem/progenitor cells. Their implications in root development and apexogenesis are discussed.
Cervical human papillomavirus (HPV) infection may increase HIV risk. Since other genital infections enhance HIV susceptibility by inducing inflammation, we assessed the impact of HPV infection and ...clearance on genital immunology and the cervico-vaginal microbiome. Genital samples were collected from 65 women for HPV testing, immune studies and microbiota assessment; repeat HPV testing was performed after 6 months. All participants were HIV-uninfected and free of bacterial STIs. Cytobrush-derived T cell and dendritic cell subsets were assessed by multiparameter flow cytometry. Undiluted cervico-vaginal secretions were used to determine cytokine levels by multiplex ELISA, and to assess bacterial community composition and structure by 16S rRNA gene sequence analysis. Neither HPV infection nor clearance were associated with broad differences in cervical T cell subsets or cytokines, although HPV clearance was associated with increased Langerhans cells and HPV infection with elevated IP-10 and MIG. Individuals with HPV more frequently had a high diversity cervico-vaginal microbiome (community state type IV) and were less likely to have an L. gasseri predominant microbiome. In summary, HPV infection and/or subsequent clearance was not associated with inflammation or altered cervical T cell subsets, but associations with increased Langerhans cells and the composition of the vaginal microbiome warrant further exploration.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the novel coronavirus disease 2019 (COVID-19), has caused a global pandemic on a scale not seen for over a ...century. Increasing evidence suggests that respiratory droplets and aerosols are likely the most common route of transmission for SARS-CoV-2. Since the virus can be spread by presymptomatic and asymptomatic individuals, universal face masking has been recommended as a straightforward and low-cost strategy to mitigate virus transmission. Numerous governments and public health agencies around the world have advocated for or mandated the wearing of masks in public settings, especially in situations where social distancing is not possible. However, the efficacy of wearing a mask remains controversial. This interdisciplinary review summarizes the current, state-of-the-art understanding of mask usage against COVID-19. It covers three main aspects of mask usage amid the pandemic: quality standards for various face masks and their fundamental filtration mechanisms, empirical methods for quantitatively determining mask integrity and particle filtration efficiency, and decontamination methods that allow for the reuse of traditionally disposable N95 and surgical masks. The focus is given to the fundamental physicochemical and engineering sciences behind each aspect covered in this review, providing novel insights into the current understanding of mask usage to curb COVID-19 spread.
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•Universal face masking as a low-cost strategy to mitigate virus transmission•Interdisciplinary systematic review on face masking against COVID-19•Standards for various face masks and their fundamental filtration mechanisms•Empirical methods for determining mask integrity and particle filtration efficiency•Decontamination methods that allow for the reuse of traditionally disposable masks
Inconel 718 samples were fabricated by selective laser melting (SLM). The effects of line laser energy densities in the range 0.1–0.3 J/mm on the microstructure, mechanical properties, and ...deformation of these samples were investigated. The fewest pores and best mechanical properties were realized at 0.2 J/mm with a yield strength of 775 MPa, ultimate tensile strength of 1055 MPa, and elongation of 29.5%. Fine dimples were uniformly distributed on the fracture surface under 0.2 J/mm. An Electron Backscatter Diffraction (EBSD) test revealed a mixture of fine columnar and equiaxed grains that promote strength while maintaining high plasticity. The prisms cut from these samples bent outwards, indicating great residual stresses in the samples. Their deformation increased with increasing laser energy density. Therefore, stress release treatment is necessary for SLM parts.
•The tensile strength and elongation reached 1055 MPa and 29.5%, respectively.•The best mechanical properties were achieved at 0.2 J/mm, instead of 0.3 J/mm.•Orderly stacking of melt pools without stagger caused tiny pores at the overlapping.•Prisms cut from specimens bent, the bigger energy density, the bigger deformation.
Abstract Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, ...muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in CD39 expression or Treg number.
Abstract
We present an analysis of the global stellar populations of galaxies in the SAMI (Sydney-AAO Multi-object Integral field spectrograph) Galaxy Survey. Our sample consists of 1319 galaxies ...spanning four orders of magnitude in stellar mass and includes all morphologies and environments. We derive luminosity-weighted, single stellar population equivalent stellar ages, metallicities and alpha enhancements from spectra integrated within one effective radius apertures. Variations in galaxy size explain the majority of the scatter in the age–mass and metallicity–mass relations. Stellar populations vary systematically in the plane of galaxy size and stellar mass, such that galaxies with high stellar surface mass density are older, more metal rich and alpha enhanced than less dense galaxies. Galaxies with high surface mass densities have a very narrow range of metallicities; however, at fixed mass, the spread in metallicity increases substantially with increasing galaxy size (decreasing density). We identify residual correlations with morphology and environment. At fixed mass and size, galaxies with late-type morphologies, small bulges and low Sérsic n are younger than early type, high n, high bulge-to-total galaxies. Both age and metallicity show small residual correlations with environment; at fixed mass and size, galaxies in denser environments or more massive haloes are older and somewhat more metal rich than those in less dense environments. We connect these trends to evolutionary tracks within the size–mass plane.
The four R-spondins (RSPO1-4) and their three related receptors LGR4, 5 and 6 (LGR4-6) have emerged as a major ligand-receptor system with critical roles in development and stem cell survival through ...modulation of Wnt signaling. Recurrent, gain-of-expression gene fusions of RSPO2 (to EIF3E) and RSPO3 (to PTPRK) occur in a subset of human colorectal cancer. However, the exact roles and mechanisms of the RSPO-LGR system in oncogenesis remain largely unknown. We found that RSPO3 is aberrantly expressed at high levels in approximately half of Keap1-mutated lung adenocarcinomas (ADs). This high RSPO3 expression is driven by a combination of demethylation of its own promoter region and deficiency in Keap1 instead of gene fusion as in colon cancer. Patients with RSPO3-high tumors (~9%, 36/412) displayed much poorer survival than the rest of the cohort (median survival of 28 vs 163 months, log-rank test P<0.0001). Knockdown (KD) of RSPO3, LGR4 or their signaling mediator IQGAP1 in lung cancer cell lines with Keap1 deficiency and high RSPO3-LGR4 expression led to reduction in cell proliferation and migration in vitro, and KD of LGR4 or IQGAP1 resulted in decrease in tumor growth and metastasis in vivo. These findings suggest that aberrant RSPO3-LGR4 signaling potentially acts as a driving mechanism in the aggressiveness of Keap1-deficient lung ADs.
Background. Genital inflammation is a key determinant of human immunodeficiency virus (HIV) transmission, and may increase HIV-susceptible target cells and alter epithelial integrity. Several genital ...conditions that increase HIV risk are more prevalent in African, Caribbean, and other black (ACB) women, including bacterial vaginosis and herpes simplex virus type-2 (HSV-2) infection. Therefore, we assessed the impact of the genital microbiota on mucosal immunology in ACB women and microbiome-HSV-2 interactions. Methods. Cervicovaginal secretions and endocervical cells were collected by cytobrush and Instead Softcup, respectively. T cells and dendritic cells were assessed by flow cytometry, cytokines by multiplex enzyme-linked immunosorbent assay (ELISA), and the microbiota by 16S ribosomal ribonucleic acid gene sequencing. Results. The cervicovaginal microbiota of 51 participants were composed of community state types (CSTs) showing diversity (20/51; 39%) or predominated by Lactobacillus iners (22/51; 42%), L. crispatus (7/51; 14%), or L. gasseri (2/51; 4%). High-diversity CSTs and specific bacterial phyla (Gardnerella vaginalis and Prevotella bivia) were strongly associated with cervicovaginal inflammatory cytokines, but not with altered endocervical immune cells. However, cervical CD4+ T-cell number was associated with HSV-2 infection and a distinct cytokine profile. Conclusions. This suggests that the genital microbiota and HSV-2 infection may influence HIV susceptibility through independent biological mechanisms.
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