2-(Trimethylammonium) Ethyl (R)-3-Methoxy-3-oxo-2-Stearamidopropyl Phosphate Suppresses Osteoclast Maturation and Bone Resorption by Targeting Macrophage-Colony Stimulating Factor Signaling

2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity.     

Sleep-related daytime consequences mediated the neuroticism–depression link

Sleep and Biological Rhythms - Neuroticism has been found to predispose individuals to depression, but the underlying mechanism is not well studied. The current study sought to delineate the...     

CsBAFF,a Teleost B Cell Activating Factor,Promotes Pathogen-Induced Innate Immunity and Vaccine-Induced Adaptive Immunity

B cell activating factor (BAFF) is a member of the tumor necrosis factor family that is known to play an important role in B cell activation, proliferation, and differentiation in mammals. However, studies of BAFF in teleosts are very limited and its function, in particular that under in vivo conditions, is essentially unknown. In this study, we conducted in vivo as well as in vitro functional analyses of a BAFF homologue (CsBAFF) from the teleost fish tongue sole (Cynoglossus semilaevis). CsBAFF is composed of 261 residues and shares moderate sequence identities with known BAFFs of other teleosts. CsBAFF expression was most abundant in immune organs and was upregulated during bacterial infection. Purified recombinant CsBAFF (rCsBAFF) bound to tongue sole lymphocytes and promoted cellular proliferation and survival. The results of an in vivo study showed that CsBAFF overexpression in tongue sole significantly enhanced macrophage activation and reduced bacterial infection in fish tissues, whereas knockdown of CsBAFF expression resulted in increased bacterial dissemination and colonization in fish tissues. Furthermore, vaccination studies showed that CsBAFF enhanced the immunoprotection of a DNA vaccine and augmented the production of specific serum antibodies. Taken together, these results provide the first in vivo evidence to indicate that teleost BAFF is an immunostimulator that significantly contributes to the innate antibacterial immune response and vaccine-induced adaptive immune response.     

利用回交导入系剖析水稻苗期和分蘖期耐盐性的遗传重叠

以籼稻品种IR64为受体，来自伊朗的粳稻农家品种Binam为供体培育的99个BC2F8回交导入系为材料，定位了水稻在2叶1心期和分蘖期控制耐盐相关性状的数量性状基因座（QTL）．共检测到影响苗期叶片盐害级别、幼苗存活天数和地上部钾、钠离子浓度的QTL 13个，影响分蘖期株高、分蘖数和地上部鲜重的QTL 22个．多数分蘖期QTL对盐胁迫表现出明显的表达差异，根据表达情况将这些QTL分成3组，第1组为在对照条件下表达的11个QTL；第2组为在对照和盐胁迫条件下共同表达的5个QTL，其中有3个（QPh5，QPh8，QTn9）在两种环境下的基因效应大小和方向一致，其表达受盐胁迫影响较小；第3组为受盐胁迫诱导表达的6个QTL．检测到13个影响胁迫与对照差值即性状稳定性的QTL，除QPh4，QTn2和QFw2a外，其余10个基因座增加性状稳定性或提高耐盐性的等位基因均来自Binam．上述受盐胁迫影响较小的3个QTL和影响性状稳定性的13个QTL对耐盐性有贡献，属耐盐QTL．比较苗期和分蘖期耐盐QTL的分布，发现多数（69％）影响苗期和分蘖期的耐盐QTL在遗传上相互独立，仅在第1，2，8和11染色体的4个相同或相邻区域定位到影响两个时期的耐盐QTL，表明苗期和分蘖期的耐盐性存在部分的遗传重叠．通过标记辅助选择将苗期和分蘖期的重要耐盐QTL进行累加，或针对苗期和分蘖期的重叠耐盐QTL进行选择，有可能培育出苗期和分蘖期均耐盐的水稻品种．     

siRNA介导的NFBD1表达沉默对HeLa细胞增殖与凋亡的影响

NFBD1，也称MDC1，是1个参与细胞内DNA损伤后细胞应答反应的重要分子．为探讨NFBD1在细胞增殖和凋亡中的作用及其作为分子靶点用于肿瘤治疗的潜在价值，本研究采用siRNA技术抑制NFBD1的表达，并观察了其对人宫颈癌细胞HeLa细胞增殖和细胞凋亡的影响．半定量RT-PCR和蛋白质印迹分析结果表明，筛选到的短链NFBD1 siRNA能有效抑制内源NFBD1的表达，抑制程度约100％．细胞生长曲线分析结果表明，siRNA介导的NFBD1表达沉默导致HeLa细胞生长增殖的显著抑制．FACS分析结果表明，NFBD1表达抑制导致sub-G₁峰的出现，同时蛋白质印迹分析观察到了caspase 3和PARP（poly-ADP-ribose polymerase）的剪接激活，表明NFBD1表达抑制诱发了细胞凋亡．在该凋亡过程中，P-53及其下游靶分子Bax和Puma的表达水平均没有发生明显变化，但Noxa的表达在mRNA和蛋白质水平上均显著上调，强烈提示该凋亡过程很可能是1个不依赖P53的凋亡途径，且Noxa的转录激活在该凋亡过程中可能起着重要作用．这些结果表明，NFBD1参与细胞生长增殖和凋亡的调节，是一个潜在的肿瘤治疗新靶点．     

Characteristics of von Willebrand Factor multimer adhesion and its bio-inspired applications

The von Willebrand Factor (vWF) is a large multimeric protein that aids blood clotting. Hydrodynamic force triggers elongation of vWF; this regulates its activity by exposing binding sites for platelets and collagen. To investigate mechanisms of vWF multimer adhesion to relevant biological entities, a coarse grain molecular model is used to explore vWF interaction with collagen-coated surfaces. The vWF multimer model incorporates observed mechanical properties of vWF monomers in that the model A2 domain in each monomer is capable of significant elongation with sufficient applied force on the molecule. Brownian dynamics simulations have been performed to understand a single vWF multimer adhesion process in both free-draining and hydrodynamic interactions (HI) cases. Results show the configuration at the moment of adhesion is critical, as this dictates the configuration of vWF thereafter. The presence of the collagen-coated surface increases the stretching of vWF multimers and the elongation of model A2 domains. HI effect plays a hindering role in unfolding of vWF multimer and elongation of model A2 domains. The adhesion is impeded by HI, and results in hydrodynamic lift leading to vWF multimer migration away from the wall.     

Pulmonary Toxocariasis Mimicking Invasive Aspergillosis in a Patient with Ulcerative Colitis

A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.     

Continuous production of fructooligosaccharides using fructosyltransferase immobilized on ion exchange resin

A continuous production of fructooligosaccharides from sucrose was investigated by fructosyltransferase immobilized on a high porous resin, Diaion HPA 25. The optimum pH (5.5) and temperature (55°C) of the enzyme for activity was unaltered by immobilization, and the immobilized enzyme became less sensitive to the pH change. The optimal operation conditions of the immobilized enzyme column for maximizing the productivity were as follows: 600 g/L of sucrose feed concentration, flow rate of superficial space velocity 2.7 h^?1. When the enzyme column was run at 50°C, about 8% loss of the initial activity of immobilized enzyme was observed after 30 days of continuous operation, during which high productivity of 1174 g/L·h was achieved. The kinds of products obtained using the immobilized enzyme were almost the same as those using soluble enzymes or free cells.