Genomic structure of human lysosomal glycosylasparaginase

AbstractThe gene structure of the human lysosomal enzyme glycosylasparaginase was determined. The gene spans 13 kb and consists of 9 exons. Both 5′ and 3′ untranslated regions of the gene are uninterrupted by introns. A number of transcriptional elements were identified in the 5′ upstream sequence that includes two putative CAAT boxes followed by TATA-like sequences together with two AP-2 binding sites and one for Sp1. A 100 bp CpG island and several ETF binding sites were also found. Additional AP-2 and Sp1 binding sites are present in the first intron. Two polyadenylation sites are present and appear to be functional. The major known glycosylasparaginase gene defect G488→C, which causes the lysosomal storage disease aspartylglycosaminuria (AGU) in Finland, is located in exon 4. Exon 5 encodes the post-translational cleavage site for the formation of the mature α/β subunits of the enzyme as well as a recently proposed active site threonine, Thr206

Cardiac and renal expression of TLR4 is increased in Aldo-salt-treated rats.

<p>(A and B) Rats were infused with Aldo-salt at 1 mg/kg/day for 4weeks, and cardiac mRNA levels (A) and protein levels (B) of TLR4 were assayed using qPCR and western blot, respectively. Rats were infused with Aldo-salt at 1 mg/kg/day for 4weeks, and renal mRNA levels (C) and protein levels (D) of TLR4 were assayed using qPCR and western blot, respectively. *<i>p</i>< 0.05.</p

Histological findings.

<p>Cardiac (A) or renal (B) mRNA levels of Col I and TGF-β in rats treated with Aldo-salt or with Aldo-salt plus TAK-242. *<i>p</i>< 0.05 vs control, #<i>p</i>< 0.05 vs Aldo-salt. (C)Representative images and quantitation of perivascular fibrosis in left ventricles of rats treated with Aldo-salt or with Aldo-salt plus TAK-242. *<i>p</i>< 0.05 vs control, #<i>p</i>< 0.05 vs Aldo-salt. (D) Histological staining with periodic acid Schiff (PAS), also showing tubulointerstitial damage of rats treated with Aldo-salt or with Aldo-salt plus TAK-242. *<i>p</i>< 0.05 vs control, #<i>p</i>< 0.05 vs Aldo-salt. n = 9, 200× magnification.</p

Physiological and renal parameters in Aldo-salt–treated rats.

<p>Aldo = aldosterone; KW = kidney weight; BW = body weight.</p><p>Values are presented as mean ± SEM.</p><p>*<i>p</i><0.05 vs. control</p><p>^#<i>p</i><0.05 vs. Aldo-salt group.</p><p>Physiological and renal parameters in Aldo-salt–treated rats.</p

TAK-242 suppresses renal inflammation and fibrosis caused by Aldo-salt <i>in vivo</i>.

<p>(A-C) Renal mRNA levels of TNF-α, MCP-1 and IL-1β in rats treated with Aldo-salt or with Aldo-salt plus TAK-242. *<i>p</i>< 0.05 vs control, #<i>p</i>< 0.05 vs Aldo-salt. (D) Renal protein levels of TNF-α, MCP-1 and IL-1β in rats treated with Aldo-salt or with Aldo-salt plus TAK-242 were assayed using ELISA. *<i>p</i>< 0.05 vs control, #<i>p</i>< 0.05 vs Aldo-salt.</p

TAK-242 suppresses Aldo-salt-induced EMT.

<p>Renal mRNA (A) and protein (B) expression of E-cadherin (an epithelial marker), and Fibronectin and a-SMA (mesenchymal markers) were assayed in rats treated with Aldo-salt or with Aldo-salt plus TAK-242. TAK-242 reversed the Aldo-salt–induced renal epithelial-mesenchymal transition. *<i>p</i>< 0.05 vs control, #<i>p</i>< 0.05 vs Aldo-salt.</p

Rational Design of Cobalt–Iron Selenides for Highly Efficient Electrochemical Water Oxidation

Exploring active, stable, earth-abundant, low-cost, and high-efficiency electrocatalysts is highly desired for large-scale industrial applications toward the low-carbon economy. In this study, we apply a versatile selenizing technology to synthesize Se-enriched Co_1–<i>x</i>Fe_<i>x</i>Se₂ catalysts on nickel foams for oxygen evolution reactions (OERs) and disclose the relationship between the electronic structures of Co_1–<i>x</i>Fe_<i>x</i>Se₂ (via regulating the atom ratio of Co/Fe) and their OER performance. Owing to the fact that the electron configuration of the Co_1–<i>x</i>Fe_<i>x</i>Se₂ compounds can be tuned by the incorporated Fe species (electron transfer and lattice distortion), the catalytic activity can be adjusted according to the Co/Fe ratios in the catalyst. Moreover, the morphology of Co_1–<i>x</i>Fe_<i>x</i>Se₂ is also verified to strongly depend on the Co/Fe ratios, and the thinner Co_0.4Fe_0.6Se₂ nanosheets are obtained upon selenization treatment, in which it allows more active sites to be exposed to the electrolyte, in turn promoting the OER performance. The Co_0.4Fe_0.6Se₂ nanosheets not only exhibit superior OER performance with a low overpotential of 217 mV at 10 mA cm^–2 and a small Tafel slope of 41 mV dec^–1 but also possess ultrahigh durability with a dinky degeneration of 4.4% even after 72 h fierce water oxidation test in alkaline solution, which outperforms the commercial RuO₂ catalyst. As expected, the Co_0.4Fe_0.6Se₂ nanosheets have shown great prospects for practical applications toward water oxidation

HS worsen and CCL20 antibody improves lung damage in IgAN mice.

<p>Representative images of HE stained lungs from mice as indicated (200×).</p

HS increases and CCL20 antibody decreases Th17-related cytokines in IgAN mice.

<p>(A): Renal CCL20 concentrations of each groups; (B): Renal IL-17A concentrations of each groups; (C): Renal IL-21 concentrations of each groups; (D): Renal IL-6 concentrations of each groups. ^#<i>vs</i> control group, <i>P</i><0.05; ^*<i>vs</i> IgAN group, ^&<i>vs</i> HS-IgAN group <i>P</i><0.05.</p

HS increases and CCL20 antibody decreases abnormal glomeruli in IgAN mice.

<p>PAS-stained kidney sections were evaluated for the presence of abnormal glomeruli. ^#<i>vs</i> control group, <i>P</i><0.05; * <i>vs</i> IgAN group, <i>P</i><0.05; ^&<i>vs</i> HS-IgAN group, <i>P</i><0.05.</p