SANT proteins modulate gene expression by coordinating histone H3KAc and Khib levels and regulate plant heat tolerance.

Histone post-translational modifications (PTMs), such as acetylation and recently identified lysine 2-hydroxyisobutyrylation (Khib), act as active epigenomic marks in plants. SANT domain-containing proteins SANT1, SANT2, SANT3 and SANT4 (SANT1/2/3/4), derived from PIF/Harbinger transposases, form a complex with HISTONE DEACETYLASE 6 (HDA6) to regulate gene expression via histone deacetylation. However, whether SANT1/2/3/4 coordinate different types of PTMs to regulate transcription and mediate responses to specific stresses in plants remains unclear. Here, in addition to modulating histone deacetylation, we found that SANT1/2/3/4 proteins acted like HDA6 or HDA9 in regulating the removal of histone Khib in Arabidopsis (Arabidopsis thaliana). Histone H3 lysine acetylation (H3KAc) and histone Khib were coordinated by SANT1/2/3/4 to regulate gene expression, with H3KAc playing a predominant role and Khib acting complementarily to H3KAc. SANT1/2/3/4 mutation significantly increased the expression of heat-inducible genes with concurrent change of H3KAc levels under normal and heat stress conditions, resulting in enhanced thermotolerance. This study revealed the critical roles of Harbinger transposon-derived SANT domain-containing proteins in transcriptional regulation by coordinating different types of histone PTMs and in the regulation of plant thermotolerance by mediating histone acetylation modification.

The relationship between volcanism and global climate changes in the Tropical Western Pacific over the mid-Pleistocene transition: Evidence from mercury concentration and isotopic composition.

Volcanoes are a significant component of the Earth system, influencing the interaction between oceans and the atmosphere over large spatial and temporal scales. Being a volcanically dynamic region, the Tropical Western Pacific (TWP) can significantly impact variations in global climate. However, high-resolution continuous records of volcanic activity in this region are lacking, resulting in significant uncertainties regarding the coupling between the deep earth, climate changes, and atmospheric CO2 in the TWP. To address this issue, mercury (Hg) levels, isotopic compositions, and Hg/total organic carbon (Hg/TOC) ratios were determined at site U1486 to track volcanic activity throughout the mid-Pleistocene transition (MPT) from 1.3 Myr to 0.6 Myr. Our results of anomalously high Hg concentrations and Hg/TOC ratios provide evidence of time-varying volcanism throughout the MPT. Mercury isotopes in the Hg-enriched sediments were characterized by near-zero Δ199Hg values, which is consistent with volcanism acting as the primary source of Hg to the sediments. Spectral analysis of the Hg/TOC ratio showed significant periodicity at ~100 kyr and ~ 23 kyr as well as a weaker signal at ~41 kyr consistent with Milankovitch cycles. A cross spectral analysis of Hg/TOC and the LR04 δ18O stack record suggests that the peak in volcanism lags the temperature minimum by ~6 kyr, and occurs prior to the δ18O minimum known as the glacial termination by ~14 ± 2 kyr. The records of volcanic activity in this site are also consistent with a prominent rise in atmospheric CO2 and negative excursion of benthic carbon isotopes throughout the MPT. This study provides direct sedimentary evidence in the TWP of the feedback between volcanic activity, climate change and atmospheric CO2.

An epidemiologic survey of pediatric sepsis in regional hospitals in China.

OBJECTIVE: To determine the prevalence, treatment, and outcomes of sepsis at regional hospitals in Huai'an, Jiangsu, China. DESIGN: Prospective data registry using a descriptive clinical epidemiologic approach through a collaborative network. SETTING: Pediatric departments in 11 regional city and county referral hospitals serving 843,000 children (exclusive of neonates). SUBJECTS: All admissions (n = 27,836) of patients from 28 days to 15 years old from September 1, 2010, to August 31, 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,530 patients met the 2005 international consensus definition of sepsis, corresponding to an estimated incidence of 181/100,000 children, with 80% under 5 years old, and in 10% (153), severe sepsis or septic shock developed. The overall case fatality rate for sepsis was 3.5% (53/1,530) or 34.6% (53/153) in those in whom severe sepsis or septic shock developed. Treatment varied widely and in many instances did not conform to international guidelines as reflected by inadequate use of antibiotics, corticosteroids, vasoactive agents, and inotropes. CONCLUSIONS: We first report the prevalence and outcome of pediatric sepsis based on a regional hospital network in China. The diverse treatment approaches and practice at low-level clinics suggest the need for clinical implementation of internationally recognized strategy to improve the care standard in resource-limited regional hospitals.

Mitofusin2 decreases intracellular cholesterol of oxidized LDL-induced foam cells from rat vascular smooth muscle cells.

Mitofusin2 (Mfn2) plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the effects of Mfn2 on the trafficking of intracellular cholesterol in the foam cells derived from rat VSMCs (rVSMCs) and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 (ABCA1), adenosine triphosphate-binding cassette subfamily G member 1 (ABCG1) and peroxisome proliferator-activated receptor gamma (PPARγ). The rVSMCs were co-cultured with oxidized low density lipoprotein (LDL, 80 µg/mL) to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers (20, 40 and 60 pfu/cell) of recombinant adenovirus containing Mfn2 gene (Adv-Mfn2) were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group (P<0.05), and the expression levels significantly increased when the titer of Adv-Mfn2 increased (P<0.05). At 24 or 48 h after oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased (P<0.05), but it was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group (P<0.05), and it also significantly decreased when the titer of Adv-Mfn2 increased (P<0.05). The mRNA and protein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group (P<0.05). Though the mRNA and protein expression levels of PPARγ was not significantly increased (P>0.05), the phosporylation levels of PPARγ were significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group (P<0.05). These results suggest that the transfection of Adv-Mfn2 can significantly reduce intracellular cholesterol in oxidized LDL-induced rVSMCs possibly by decreasing PPARγ phosporylation and then increasing protein expression levels of ABCA1 and ABCG1, which may be helpful to suppress the formation of foam cells.