Despite WT1 binding sites in the promoter region of human and mouse nucleoporin glycoprotein 210, WT1 does not influence expression of GP210

BACKGROUND: Glycoprotein 210 (GP210) is a transmembrane component of the nuclear pore complex of metazoans, with a short carboxyterminus protruding towards the cytoplasm. Its function is unknown, but it is considered to be a major structural component of metazoan nuclear pores. Yet, our previous findings showed pronounced differences in expression levels in embryonic mouse tissues and cell lines. In order to identify factors regulating GP210, the genomic organization of human GP210 was analyzed in silico. RESULTS: The human gene was mapped to chromosome 3 and consists of 40 exons spread over 102 kb. The deduced 1887 amino acid showed a high degree of alignment homology to previously reported orthologues. Experimentally we defined two transcription initiation sites, 18 and 29 bp upstream of the ATG start codon. The promoter region is characterized by a CpG island and several consensus binding motifs for gene regulatory transcription factors, including clustered sites associated with Sp1 and the Wilms' tumor suppressor gene zinc finger protein (WT1). In addition, distal to the translation start we found a (GT)n repetitive sequence, an element known for its ability to bind WT1. Homologies for these motifs could be identified in the corresponding mouse genomic region. However, experimental tetracycline dependent induction of WT1 in SAOS osteosarcoma cells did not influence GP210 transcription. CONCLUSION: Although mouse GP210 was identified as an early response gene during induced metanephric kidney development, and WT1 binding sites were identified in the promoter region of the human GP210 gene, experimental modulation of WT1 expression did not influence expression of GP210. Therefore, WT1 is probably not regulating GP210 expression. Instead, we suggest that the identified Sp binding sites are involved

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

JWST Low-resolution MIRI Spectral Observations of SN 2021aefx: High-density Burning in a Type Ia Supernova

We present a JWST/MIRI low-resolution mid-infrared (MIR) spectroscopic observation of the normal Type Ia supernova (SN Ia) SN 2021aefx at +323 days past rest-frame B-band maximum light. The spectrum ranges from 4 to 14 μm and shows many unique qualities, including a flat-topped [Ar iii] 8.991 μm profile, a strongly tilted [Co iii] 11.888 μm feature, and multiple stable Ni lines. These features provide critical information about the physics of the explosion. The observations are compared to synthetic spectra from detailed non-local thermodynamic equilibrium multidimensional models. The results of the best-fitting model are used to identify the components of the spectral blends and provide a quantitative comparison to the explosion physics. Emission line profiles and the presence of electron capture elements are used to constrain the mass of the exploding white dwarf (WD) and the chemical asymmetries in the ejecta. We show that the observations of SN 2021aefx are consistent with an off-center delayed detonation explosion of a near-Chandrasekhar mass (M Ch) WD at a viewing angle of −30° relative to the point of the deflagration to detonation transition. From the strengths of the stable Ni lines, we determine that there is little to no mixing in the central regions of the ejecta. Based on both the presence of stable Ni and the Ar velocity distributions, we obtain a strict lower limit of 1.2 M ⊙ for the initial WD, implying that most sub-M Ch explosions models are not viable models for SN 2021aefx. The analysis here shows the crucial importance of MIR spectra in distinguishing between explosion scenarios for SNe Ia

JWST MIRI /Medium Resolution Spectrograph (MRS) Observations and Spectral Models of the Underluminous Type Ia Supernova 2022xkq

We present a JWST mid-infrared spectrum of the under-luminous Type Ia Supernova (SN Ia) 2022xkq, obtained with the medium-resolution spectrometer on the Mid-Infrared Instrument (MIRI) ~ 130 days post-explosion. We identify the first MIR lines beyond 14 um in SN Ia observations. We find features unique to under luminous SNe Ia, including: isolated emission of stable Ni, strong blends of [Ti II], and large ratios of singly ionized to doubly ionized species in both [Ar] and [Co]. Comparisons to normal-luminosity SNe Ia spectra at similar phases show a tentative trend between the width of the [Co III] 11.888 um feature and the SN light curve shape. Using non-LTE-multi-dimensional radiation hydro simulations and the observed electron capture elements we constrain the mass of the exploding white dwarf. The best-fitting model shows that SN 2022xkq is consistent with an off-center delayed-detonation explosion of a near-Chandrasekhar mass WD (Mej ≈ 1.37 M⊙) of high-central density (ρc≥2.0×109 g cm−3) seen equator on, which produced M(56Ni) =0.324 M⊙ and M(58Ni) ≥0.06 M⊙. The observed line widths are consistent with the overall abundance distribution; and the narrow stable Ni lines indicate little to no mixing in the central regions, favoring central ignition of sub-sonic carbon burning followed by an off-center DDT beginning at a single point. Additional observations may further constrain the physics revealing the presence of additional species including Cr and Mn. Our work demonstrates the power of using the full coverage of MIRI in combination with detailed modeling to elucidate the physics of SNe Ia at a level not previously possible

Expression of the beta 2-subunit and apical localization of Na+-K+-ATPase in metanephric kidney

During kidney organogenesis, the Na+-K+-ATPase pump is not restricted to the basolateral plasma membrane of the renal epithelial cell but is instead either localized to the apical and lateral membrane sites of the early nephron or expressed in a nonpolarized distribution in the newly formed collecting ducts. The importance of Na+-K+-ATPase beta-subunit expression in the translocation of the Na+-K+-ATPase to the plasma membrane raises the question as to which beta-subunit isoform is expressed during kidney organogenesis. Immunocytochemical, Western analysis and RNase protection studies showed that both beta 1-subunit protein and beta 2 mRNA are expressed in the early gestation to midgestation human metanephric kidney. In contrast, although beta 1 mRNA abundance is equivalent to that of the beta 2-subunit in the metanephric kidney, the beta 1-subunit protein was not detected in early to midgestation metanephric kidney samples. Immunocytochemical analysis revealed that both alpha 1- and beta 2-subunits were present in the apical epithelial plasma membranes of distal nephron segments of early stage nephrons, maturing loops of Henle, and collecting ducts during kidney development. We also detected a significant increase in alpha 1 and beta 1 mRNA after birth with a marked reduction in beta 2 mRNA abundance associated with an increase in alpha 1- and beta 1-subunit proteins and loss of beta 2 protein expression. These studies support the conclusion that the expression of the beta 2-subunit in the fetal kidney may be an important mechanism controlling polarization of the Na+-K+-ATPase pump in the epithelia of the developing nephron during kidney organogenesis