TLR4 signaling is coupled to SRC family kinase activation, tyrosine phosphorylation of zonula adherens proteins, and opening of the paracellular pathway in human lung microvascular endothelia

Bacterial lipopolysaccharide (LPS) is a key mediator in the vascular leak syndromes associated with Gram-negative bacterial infections. LPS opens the paracellular pathway in pulmonary vascular endothelia through protein tyrosine phosphorylation. We now have identified the protein-tyrosine kinases (PTKs) and their substrates required for LPS-induced protein tyrosine phosphorylation and opening of the paracellular pathway in human lung microvascular endothelial cells (HMVEC-Ls). LPS disrupted barrier integrity in a dose- and time-dependent manner, and prior broad spectrum PTK inhibition was protective. LPS increased tyrosine phosphorylation of zonula adherens proteins, VE-cadherin, gamma-catenin, and p120(ctn). Two SRC family PTK (SFK)-selective inhibitors, PP2 and SU6656, blocked LPS-induced increments in tyrosine phosphorylation of VE-cadherin and p120(ctn) and paracellular permeability. In HMVEC-Ls, c-SRC, YES, FYN, and LYN were expressed at both mRNA and protein levels. Selective small interfering RNA-induced knockdown of c-SRC, FYN, or YES diminished LPS-induced SRC Tyr(416) phosphorylation, tyrosine phosphorylation of VE-cadherin and p120(ctn), and barrier disruption, whereas knockdown of LYN did not. For VE-cadherin phosphorylation, knockdown of either c-SRC or FYN provided total protection, whereas YES knockdown was only partially protective. For p120(ctn) phosphorylation, knockdown of FYN, c-SRC, or YES each provided comparable but partial protection. Toll-like receptor 4 (TLR4) was expressed both on the surface and intracellular compartment of HMVEC-Ls. Prior knockdown of TLR4 blocked both LPS-induced SFK activation and barrier disruption. These data indicate that LPS recognition by TLR4 activates the SFKs, c-SRC, FYN, and YES, which, in turn, contribute to tyrosine phosphorylation of zonula adherens proteins to open the endothelial paracellular pathway.     

Evaluation of swollenin from <Emphasis Type="Italic">Trichoderma pseudokoningii</Emphasis> as a potential synergistic factor in the enzymatic hydrolysis of cellulose with low cellulase loadings

Swollenin is a novel plant expansin-like protein that has been proposed to have a cellulose disruption activity. In this study, the recombinant swollenin (SWO2) from Trichoderma pseudokoningii S38 was successfully produced and purified in Aspergillus niger with a final yield of up to 10 mg of purified protein from 1 l of fermentation supernatant. The recombinant protein was found to exhibit very low level of endoglucanase activity and caused a slight increase in the crystallinity when treating cellulose. Simultaneous incubation of SWO2 with low-dose cellulases resulted in a significant synergistic activity in cellulose hydrolysis. Specifically, an even greater increase in the synergistic activity was obtained when cellulose was pretreated with swollenin followed by cellulase hydrolysis. Our results, therefore, provide a novel approach for the potential application of swollenin in the efficient saccharification of cellulosic materials.     

Mass spectrometric U-series dating of Huanglong Cave in Hubei Province,central China: Evidence for early presence of modern humans in eastern Asia

Most researchers believe that anatomically modern humans (AMH) first appeared in Africa 160-190 ka ago, and would not have reached eastern Asia until ∼50 ka ago. However, the credibility of these scenarios might have been compromised by a largely inaccurate and compressed chronological framework previously established for hominin fossils found in China. Recently there has been a growing body of evidence indicating the possible presence of AMH in eastern Asia ca. 100 ka ago or even earlier. Here we report high-precision mass spectrometric U-series dating of intercalated flowstone samples from Huanglong Cave, a recently discovered Late Pleistocene hominin site in northern Hubei Province, central China. Systematic excavations there have led to the in situ discovery of seven hominin teeth and dozens of stone and bone artifacts. The U-series dates on localized thin flowstone formations bracket the hominin specimens between 81 and 101 ka, currently the most narrow time span for all AMH beyond 45 ka in China, if the assignment of the hominin teeth to modern Homo sapiens holds. Alternatively this study provides further evidence for the early presence of an AMH morphology in China, through either independent evolution of local archaic populations or their assimilation with incoming AMH. Along with recent dating results for hominin samples from Homo erectus to AMH, a new extended and continuous timeline for Chinese hominin fossils is taking shape, which warrants a reconstruction of human evolution, especially the origins of modern humans in eastern Asia.     

Interspecific hybridization of <Emphasis Type="Italic">Prunus persica</Emphasis> with <Emphasis Type="Italic">P. armeniaca</Emphasis> and <Emphasis Type="Italic">P. salicina</Emphasis> using embryo rescue

Embryo rescue technique was used successfully to produce interspecific hybrids by crossing peach (P. persica) as a female parent with apricot (P. armeniaca) and plum (P. salicica). In those crosses that had ‘Yuhualu’ or ‘Zhonghuashoutao’ as female parents, hybrid embryos aborted from the 7th or 8th week after pollination mainly due to post-pollination incompatibility. An embryo rescue protocol was established to rescue such embryos and recover hybrid plants. Modified half-strength MS medium containing 4 mg l⁻¹ 6-BA and 0.5 mg l⁻¹ IBA produced up to 90% germination in the embryos. Modified MS medium with 1.0 mg l⁻¹ 6-BA and 1.0 mg l⁻¹ IBA gave the highest bud induction and multiplication whereas modified MS medium containing 0.5 mg l⁻¹ IAA and 0.2 mg l⁻¹ NAA gave the best rooting percentage. All the hybrids obtained using this embryo rescue technique were verified using simple sequence repeat (SSR) markers. A series of pollen treatments were carried out to partially overcome pre-pollination incompatibility, and it was found accidentally that pollen treatment with electrostatic field not only improved pollen germination but also increased the multiplication coefficient of embryo-induced shoots.     

Identification of a diverse synthetic abietane diterpenoid library and insight into the structure-activity relationships for antibacterial activity

A diverse natural product-like (NPL) synthetic abietane diterpenoid library containing 86 compounds were obtained and the SARs were studied based on their antibacterial potential. Further in vitro cytotoxic and in silico drug-like properties evaluation showed that the potent antibacterial compound 84 had good drug-like properties and displayed low cytotoxicity toward noncancerous mammalian cells, indicating the study of AA and DHAA might be a good starting point for the search of novel antimicrobial molecules. Future work should be focused on the optimization of their potency and selectivity.     

湖泊湿地土壤有机碳形成、周转及稳定性研究进展

湖泊湿地生态系统作为重要的陆地碳汇之一,其土壤有机碳(SOC)储量变化将对全球气候产生显著影响。当前全球变化背景下,湖泊湿地经历的水位降低、水域面积缩小等生态问题使其碳汇功能面临严重威胁。尽管已有大量文献研究了湖泊湿地SOC的动态变化,但由于研究地点、实验方法和关注重点的不同,难以形成一致的结论,因此详细阐明湖泊湿地SOC存储和转化过程的演化趋势尤为重要。综述国内外湖泊湿地SOC的研究成果,从其形成、周转及稳定性三个方面进行归纳,总结现阶段湖泊湿地SOC的研究热点和不足,并结合当前湖泊湿地面临的现状,阐述影响其有机碳动态变化的因素。现有研究表明,植物源碳尤其是凋落物碳是湖泊湿地SOC的主要来源,但微生物碳在湖泊湿地SOC形成中的作用不容忽视,且植物和微生物碳对湖泊湿地碳储量的贡献比可能具有空间异质性。湿地SOC周转主要受微生物的调控,但中小型区系的土壤动物也扮演着重要的角色,它们可能既是驱动者也是贡献者,研究提示将土壤动物纳入湿地SOC的周转模型才可更准确地评估湖泊湿地的碳周转过程。有机物-矿物化学结合态保护是维持湖泊湿地SOC稳定的最重要机制,多种生物和非生物(气候、水环境等)因素会直接或间接影响SOC的稳定储存。目前维持湖泊湿地SOC稳定性的机制仍延用陆地或海洋生态系统的理论模型,需进一步评估其在湖泊湿地中的适用性。研究旨在总结湖泊湿地中SOC形成和转化的研究进展,为研究提供文献参考和思路。     

Position chronologique des sites de l’Homme moderne en Chine d’après la datation U-Th

The origin and evolution of modern Homo sapiens has been the subject of an intensive debate between exponents of two competing hypotheses, multiregional origins and “recent out of Africa”. This paper presents a synthesis of the chronological studies on seven hominid sites in China based on the U-series dating, five of them of intercalated speleothem calcites and other two of fossil materials. The results show that modern humans were present in China about 100 ka ago, much earlier than previously estimated, and that the so-called “temporal gap” of human presence in China between 40 and 100 ka is most probably nothing but an artifact caused by systematic errors of the dating methods. Further multidisciplinary studies on hominid sites in China may provide important evidence for resolving the hotly debated issues concerning the origin of modern humans.