Stabilizing Nitroxide Spin Labels for Structural and Conformational Studies of Biomolecules by Maleimide Treatment.

Nitroxide (NO) spin radicals are effective in characterizing structures, interactions and dynamics of biomolecules. The EPR applications in cell lysates or intracellular milieu require stable spin labels, but NO radicals are unstable in such conditions. We showed that the destabilization of NO radicals in cell lysates or even in cells is caused by NADPH/NADH related enzymes, but not by the commonly believed reducing reagents such as GSH. Maleimide stabilizes the NO radicals in the cell lysates by consumption of the NADPH/NADH that are essential for the enzymes involved in destabilizing NO radicals, instead of serving as the solo thiol scavenger. The maleimide treatment retains the crowding properties of the intracellular components and allows to perform long-time EPR measurements of NO labeled biomolecules close to the intracellular conditions. The strategy of maleimide treatment on cell lysates for the EPR applications has been demonstrated on double electron-electron resonance (DEER) measurements on a number of NO labeled protein samples. The method opens a broad application range for the NO labeled biomolecules by EPR in conditions that resemble the intracellular milieu.

Epigenetic Dysregulation Induces Translocation of Histone H3 into Cytoplasm.

In eukaryote cells, core components of chromatin, such as histones and DNA, are packaged in nucleus. Leakage of nuclear materials into cytosol will induce pathological effects. However, the underlying mechanisms remain elusive. Here, cytoplasmic localization of nuclear materials induced by chromatin dysregulation (CLIC) in mammalian cells is reported. H3K9me3 inhibition by small chemicals, HP1α knockdown, or knockout of H3K9 methylase SETDB1, induces formation of cytoplasmic puncta containing histones H3.1, H4 and cytosolic DNA, which in turn activates inflammatory genes and autophagic degradation. Autophagy deficiency rescues H3 degradation, and enhances the activation of inflammatory genes. MRE11, a subunit of MRN complex, enters cytoplasm after heterochromatin dysregulation. Deficiency of MRE11 or NBS1, but not RAD50, inhibits CLIC puncta in cytosol. MRE11 depletion represses tumor growth enhanced by HP1α deficiency, suggesting a connection between CLIC and tumorigenesis. This study reveals a novel pathway that heterochromatin dysregulation induces translocation of nuclear materials into cytoplasm, which is important for inflammatory diseases and cancer.

Promotional effect of nonalcoholic fatty liver disease on Gallstone disease: A systematic review and meta-analysis.

BACKGROUND/AIMS: Growing evidence indicates that nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) share the same risk factors, and that NAFLD may be associated with the occurrence of GD. However, overall results remain controversial. The aim of this study is to perform a meta-analysis to assess the relationship between GD and NAFLD. MATERIALS AND METHODS: Five databases (PubMed, Medline, Embase, Web of Science, and Cochrane Library) were queried, and observational studies that assessed the association between GD and NAFLD were selected. We pooled the prevalence of GD in participants with NAFLD, and compared the prevalence of GD in NAFLD and non-NAFLD groups in four trials. RESULTS: Twelve studies met our inclusion criteria. The pooled prevalence of GD in cases with NAFLD was 17% (95% CI: 0.12-0.23). Compared with the non-NAFLD group, NAFLD was significantly correlated with GD (OR: 1.40, 95% CI: 1.23-1.59). Additional analyses reveal that participants in the GD group included more females (OR: 1.95, 95% CI: 1.36-2.79), were older (WMD: 6.61, 95% CI: 3.80-9.42), and had higher BMIs (WMD: 1.63, 95% CI: 0.62-2.65) in the population with NAFLD, compared to the non-GD group. CONCLUSION: GD prevalence in NAFLD patients is higher than that in the general population. Furthermore, the occurrence of GD is significantly associated with the female sex, age and BMI in NAFLD patients.

[Speciation and distribution characters of rare earth elements in the Baotou Section of the Yellow River].

As a whole of water column, suspended matter and surface sediment in the mainstream and the branch taking up industry wastewater, speciation and distribution characters of rare earth elements (REEs) were investigated systemically in the Baotou section of the Yellow River. This study shows that rare earth elements in the mainstream of the Baotou section of the Yellow River mainly exist in suspended particles, and the dissolved contents are in extremely minute quantities. REEs mainly exist in dissolved particles in the branch taking up industry wastewater, and suspended sigma REE and dissolved sigma REE are obviously higher than those in the mainstream. The change of sigma REE of dissolved particles in water phase along the Baotou section of the Yellow River is very similar to that of sigma REE of suspended particles, and consistent along the main river, it is that sigma REE increase appreciably from the control profile to the keystone discharged section, come to a head in the D site and reduce in the E site. This distribution pattern indicates pile industry wastewater of Baotou to rare earth elements in the mainstream of the Yellow River, particularly LREE. The REE distribution in the mainstream of the Baotou section of the Yellow River is the same, with LREE enrichment and Eu depletion. But LREE origin of D site is different from the other sites by excursion of LREE distribution curve and other geochemical parameters, they are origin of industry wastewater piled, otherwise the other four sites are origin of loess altiplano. And HREE are origin of loess altiplano in all the sites. The speciation characteristics of REE in the sediments and suspended matter are quite similar with the amount in as follows: residual >> bound to carbonates, bound to Fe-Mn oxides > bound to organic matter >> exchangeable. REEs exchangeable in surface sediment and suspended matter in the branch taking up industry wastewater are higher than those in the mainstream, it confirms that REEs in the mainstream mainly exist in suspended particles, and mainly exist in dissolved particles in the branch.