Conformational stability of PCID2 upon DSS1 binding with molecular dynamics simulation

DSS1 is a small acidic intrinsically disordered protein (IDP) that can fold upon binding with PCID2 TREX-2. The resulting complex plays a key role in mRNA export. However, the binding mechanism between DSS1 and PCID2 is unsolved. Here, three independent 500-ns molecular dynamics (MD) simulations were performed to study the DSS1–PCID2 binding mechanism by comparing apo-PCID2 and bound PCID2. The results show that the conformational variation of bound PCID2 is smaller than that of apo-PCID2, especially in the binding domain of two helices (helix IV and VIII). The probability of coil formation between helix III and helix IV of bound PCID2 increases, and a short anti-parallel β-sheet forms upon DSS1 binding. The decomposition of binding free energy into protein and residue pairs suggests that electrostatic and hydrophobic interactions play key roles in the recognition between DSS1 and PCID2. There is a hydrophobic core of seven residues in DSS1 favorable to the binding of PCID2. These analytical methods can be used to reveal the recognition mechanisms of other IDPs and their partners.

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Figure Differences of second structure of PCID2 in bound and unbound states. The interaction surface between the helix VIII of PCID2 and helix of DSS1

     

Shifts and plasticity of plant leaf mass per area and leaf size among slope aspects in a subalpine meadow

The composition of vegetation on a slope frequently changes substantially owing to the different micro‐environments of various slope aspects. To understand how the slope aspect affects the vegetation changes, we examined the variations in leaf mass per area (LMA) and leaf size (LS) within and among populations for 66 species from 14 plots with a variety of slope aspects in a subalpine meadow. LMA is a leaf economic trait that is tightly correlated with plant physiological traits, while the LS shows a tight correlation with leaf temperature, indicating the strategy of plants to self‐adjust in different thermal and hydraulic conditions. In this study, we compared the two leaf traits between slope aspects and between functional types and explored their correlation with soil variables and heat load. Our results showed that high‐LMA, small‐leaved species were favored in south‐facing slopes, while the reverse was true in north‐facing areas. In detail, small dense‐leaved graminoids dominated the south slopes, while large thin‐leaved forbs dominated the north slopes. Soil moisture and the availability of soil P were the two most important soil factors that related to both LMA and LS, and heat load also contributed substantially. Moreover, we disentangled the relative importance of intraspecific trait variation and species turnover in the trait variation among plots and found that the intraspecific variation contributed 98% and 56% to LMA and LS variation among communities, respectively, implying a large contribution of intraspecific trait plasticity. These results indicate that LMA and LS are two essential leaf traits that affect the adaptation or acclimation of plants underlying the vegetation composition changes in different slope aspects in the subalpine meadow.     

Asialoglycoprotein receptor and liposome synergistically mediate the gene transfer into primary rat hepatocytes

Gene transfer into primary rat hepatocytes was performed by employing cationic liposome as DNA carrier and the specific ligand of hepatic asialoglycopmtein receptor (ASGPR), asialofetuin, as liver-targeting ligand. The results showed that asialofetuin, when added to the gene transfer complexes, could significantly increase the hepatocyte transfection efficiency, and alleviate the cellular toxicity of Lipofectin. Several synthetic ligands of ASGPR (galactosyl albumin) could also increase the transfection efficiency of hepatocyte like asialofetuin. It was proved that ASGPR and cationic liposome could synergistically mediate the gene transfer into primary rat hepatocytes. This novel gene delivery system provided a safer, more simple and efficient gene transfer method for primary hepatocytes, and showed prospecting application in hepatic gene therapy.     

N6-methyladenosine demethylase FTO promotes growth and metastasis of gastric cancer via m6A modification of caveolin-1 and metabolic regulation of mitochondrial dynamics

Gastric cancer (GC) is the fifth most common tumor and the third most deadly cancer worldwide. N6-methyladenosine (m⁶A) modification has been reported to play a regulatory role in human cancers. However, the exact role of m⁶A in GC remains largely unknown, and the dysregulation of m⁶A on mitochondrial metabolism has never been studied. In the present study, we demonstrated that FTO, a key demethylase for RNA m⁶A modification, was up-regulated in GC tissues, especially in tissues with liver metastasis. Functionally, FTO acted as a promoter for the proliferation and metastasis in GC. Moreover, FTO enhanced the degradation of caveolin-1 mRNA via its demethylation, which regulated the mitochondrial fission/fusion and metabolism. Collectively, our current findings provided some valuable insights into FTO-mediated m⁶A demethylation modification and could be used as a new strategy for more careful surveillance and aggressive therapeutic intervention.Subject terms: Cancer genomics, Gastrointestinal diseases     

Paracrine interleukin-8 affects mesenchymal stem cells through the Akt pathway and enhances human umbilical vein endothelial cell proliferation and migration

Interleukin-8 (IL-8) promotes cell homing and angiogenesis, but its effects on activating human bone marrow mesenchymal stem cells (BMSCs) and promoting angiogenesis are unclear. We used bioinformatics to predict these processes. In vitro, BMSCs were stimulated in a high-glucose (HG) environment with 50 or 100 μg/ml IL-8 was used as the IL-8 group. A total of 5 μmol/l Triciribine was added to the two IL-8 groups as the Akt inhibitor group. Cultured human umbilical vein endothelial cells (HUVECs) were cultured in BMSCs conditioned medium (CM). The changes in proliferation, apoptosis, migration ability and levels of VEGF and IL-6 in HUVECs were observed in each group. Seventy processes and 26 pathways were involved in vascular development, through which IL-8 affected BMSCs. Compared with the HG control group, HUVEC proliferation absorbance value (A value), Gap closure rate, and Transwell cell migration rate in the IL-8 50 and IL-8 100 CM groups were significantly increased (P<0.01, n=30). However, HUVEC apoptosis was significantly decreased (P<0.01, n=30). Akt and phospho-Akt (P-Akt) protein contents in lysates of BMSCs treated with IL-8, as well as VEGF and IL-6 protein contents in the supernatant of BMSCs treated with IL-8, were all highly expressed (P<0.01, n=15). These analyses confirmed that IL-8 promoted the expression of 41 core proteins in BMSCs through the PI3K Akt pathway, which could promote the proliferation and migration of vascular endothelial cells. Therefore, in an HG environment, IL-8 activated the Akt signaling pathway, promoted paracrine mechanisms of BMSCs, and improved the proliferation and migration of HUVECs.     

海南省鼻咽癌三个高发家系报告

本文调查了鼻咽癌聚集的10个家系。在3个高发家族中,家系1两代11人中有4 人患鼻咽癌;家系2同代6人中有3人患鼻咽癌;家系3同胞5人中有3人患鼻咽癌。我们从肿瘤流行病学、病理类型及其血缘关系作了分析,认为鼻咽癌具有垂直和水平的家族发生 倾向,支持鼻咽癌有遗传倾向的看法。 Abstract:We studied the genealogy with nasopharyngeal carcinoma(NPC)and found 25 patients (18 males,7 females)with NPC in 10 families,aged from 13 to 60.The bron of the same parents were 12 patients,accounting for 48% among these patients.Both male and female patients were found in five families;the patients in four families were all male;there were all female patients in the only one family;At the sametime,21 patients with NPC were the first kinsfolk in 8 families,accounting for 84%.Besides,we looked into 3 families with high incidence;there were 4 out of 11 family members suffering from NPC in the first genealogy in 2 generations;3 of 6 brons of the same parents were ill with NPC in the third genealogy.Based on the studies of cancer epidemiology,pathology and genealogy,our results suggested that the family incidence of NPC had vertical and horizontal thndency,and that genetic factors played a decisive role in NPC incidence.     

Environmental temperature during early life affects the personality of mosquitofish in adulthood

Personality has been observed in a variety of animal taxa with important implications in ecology and evolution. Exploring the influence of environmental temperature during early life on personality could help to understand the ontogeny of this phenotypic trait in animals. In this study, we reared newborn mosquitofish Gambusia affinis at high (30°C) and low (25°C) water temperatures and measured their shyness and exploration upon sexual maturity. We tested the repeatability of each behavioral trait; the correlation between them; and the effects of rearing temperature, sex, and body length on the behaviors. When growing up at low temperatures, female fish exhibited repeatability in shyness and exploration, and males exhibited marginal repeatability in shyness. However, neither of the 2 behaviors were repeatable when the fish were reared at high temperatures. There was a negative correlation between shyness and exploration, indicating that the 2 behaviors comprise a behavioral syndrome in this species. Mosquitofish reared at high temperatures were more explorative than those reared at low temperatures, while there was no difference in shyness between the 2 treatments. Body length and sex had no significant effects on the average values of the 2 behaviors. The results indicate that environmental temperature during early life could shape the personality of mosquitofish and modify the average of the behavioral traits. These findings might provide insights to understand the ontogeny of animal personality and how changes in environmental temperature influence animal dispersal by shaping their personality.     

重组人血清白蛋白表达研究进展

本文综述了重组人血清白蛋白在细菌,酵母,植物和动物等表达系统中表达的研究进展。用酵母表达系统,尤其是毕赤酵母,表达的重组白蛋白产量高且提取工艺简单,是其产业化最具有前途的表达系统。同时在转基因动物、植物中培养表达也具有诱人的前景。