生物科技快报

生生物物科科技技快快报报 Bulletin of Biological Science . Q. Y. Cao, State Forestry Administration Press Conference in Chinese, /xwfbh/xwfbh070912.asp UNECE Timber Committee, Statement on Forest Products Markets in 2006 and Prospects for 2007 (Report ECE/TIM/06/N01, UNECE Timber Committee, Geneva, 2006). State Forestry Administration, Enhancing Forestry Ecological Improvement and Accelerating Development of the Industry (State Forestry Administration, Beijing, 2006). State Forestry Administration, China Forestry Development Report (China Forestry Publishing House, Beijing, 2005-07). State Forestry Administration, The Sixth National Survey on Forestry Resources, Progress Reports (China Forestry Publishing House, Beijing, 2005). State Forestry Administration, A Report for Monitoring and Assessment of the Social-Economic Impacts of Chinas Key Forestry Programs (China Forestry Publishing House, Beijing, 2003-06). Six Joint-Departmental Investigation Task Force, Investigation Report on Jiangxi Forest Ownership Reform (State Forestry Administration, Beijing, 2007). X. X. Sun, “Fujian forest-ownership reform on-the-spot report,“ Chinanews, 6 July 2007, p. 15 in Chinese; /cj/kong/news/2007/07-06/973437.shtml Central Committee of the Communist Party of China and China State Council, 2003, “Directive to enhance forestry development,“ issued 25 June 2003; Xinhua News Agency, Beijing, 11 September 2003 in Chinese, /zhengfu/2003-09/11/content_1075042.htm. 栖息地分离导致生物多样性下降栖息地分离导致生物多样性下降 6 一项在巴西大西洋森林中做的研究发现，在水陆两栖动物需要从成体阶段 生活的森林栖息地迁移到水栖繁殖地、再返回森林的过程中，物种的多样性在 减少。巴西大西洋森林是许多两栖类生活的地方。Carlos Guilherme Becker 和 巴西的同事解释说，这个被称为栖息地分离的状况通常是人类干预的后果。两 栖类种群和物种数量的下降正在发生着，栖息地的减少、真菌疾病、气候变化、 以及农用化学品的污染等被认为是造成两栖多样性减少的重要因素。为了更好 地了解栖息地如何影响多样性的减少，Becker 和文章共同作者对世界上生物 多样性受到最大威胁的“热点地区”进行了研究，这个地区有几千种两栖动物， 大多数的有水栖幼体。研究人员确定，栖息地分离是物种丰富程度最好的预测， 其次是栖息地减少和分裂。研究人员提出，栖息地分离也许能解释为什么两栖 动物减少通常发生在有水栖幼体的物种，他们呼吁恢复分离的栖息地来降低两 栖动物的减少。 英文摘要：Habitat Split and the Global Decline of Amphibians,Carlos Guilherme Becker, Carlos Roberto Fonseca,el al. Science 14 December 2007: Vol. 318. no. 5857, pp. 1775 1777 Fig. 1. Effect of habitat split on species richness of leaf-litter amphibians with aquatic larvae and with terrestrial development across 12 Brazilian Atlantic Forest landscapes. Habitat split is calculated as the percentage of the total stream length that does not overlap with natural forest cover. Linear regression lines are shown. Fig. 2. Path analysis models showing the relative strength of habitat split, habitat loss, and habitat fragmentation on species richness of Brazilian Atlantic Forest leaf-litter amphibians (N = 12 study sites). (A) Species with 7 aquatic larvae. (B) Species with terrestrial development. Numbers are standardized path coefficients (*P 0.001). The thickness of the arrows represents the relative strength of the relationship. 心脏病细胞疗法的新希望心脏病细胞疗法的新希望 细胞疗法被认为对治疗心肌疾病有很大潜力。当前的临床实验目标是通 过移植衰竭心脏中的自体骨胳肌或骨髓细胞来恢复收缩力，但这种方法迄今为 止只取得有限的成功。现在，用患有实验诱导的心肌梗塞的小鼠所做的研究获 得的发现表明，植入胎儿心肌细胞可很好地防止发生“室性心律失常” （心脏 病患者的一个常见死因） 。植入的细胞被心脏正常活动势激活，这些电耦合的 细胞的植入为增加向梗塞心脏中的导入建立了通道。另外，conexin 43一 种在相邻细胞之间的“间隙部”所发现的蛋白也被发现与这种保护作用有关。 令人吃惊的是，现在这种蛋白在骨骼肌细胞中的表达也能产生与胎儿心肌细胞 相似 的性质。这些结果让我们看到了基于细胞来治疗心脏病的一个新方法。 Nature 450, 819-824 (6 December 2007) FIGURE 1. VT in control, sham-injected and SM-engrafted hearts. a, Surface ECG from a control mouse including magnified inset of the burst stimulation (asterisks) protocol. Arrows indicate ventricular response; VT is not evoked. b, Sirius red staining proves transmural fibrotic scar 2 weeks after sham injection (left) or engraftment of SMs into the scar (right; inset shows EGFP-positive SMs). c, Burst stimulation induces self-terminating VT with atrio-ventricular dissociation in sham-injected mouse. Top trace, surface ECG; middle trace, ventricular apex electrogram; bottom trace, His- level electrogram. A, atrium; V, ventricle; a, atrial farfield; v, ventricular farfield. d, ECG recording from sham-injected mouse and SM-engrafted mouse. e, Burst pacing induces sustained VT in SM-engrafted mouse; note constant atrio-ventricular dissociation. Upper trace, surface ECG; lower trace, His-level electrogram. f, Engrafted EGFP-positive (green) SMs; 8 native myocardium is marked by yellow autofluorescence. g, Engrafted SM fibres are elongated and multinucleate with central nuclei (inset). h, Transplanted EGFP-positive SMs (green in inset); double cross-striation shown with nebulin staining (red). Scale bar, 1.3 mm (b), 150 m (f), 13 m (g), 16 m (g, inset), 7 m (h), 18 m (h, inset). FIGURE 2. VT protection in eCM-engrafted hearts. a, Sirius red staining. b, EGFP-positive eCMs engraft in the infarct and extend to the border zone. c, ECG recording of eCM-engrafted mouse. d, Ventricular burst stimulation does not induce VT. Upper trace, surface ECG; lower trace, His-level electrogram. e, EGFP-positive eCMs integrate into the infarct. f, EGFP-positive eCMs are striated ( - actinin staining, red) and are in direct contact with EGFP-negative host cardiomyocytes. g, Cx43 staining (red) illustrates gap-junction formation between engrafted EGFP-positive eCMs (arrows) and with native cardiomyocytes (arrowheads). h, Summary of VT inducibility. Note strongly elevated susceptibility to VT induction in sham- injected group (Sh) compared with control group (Con, P 0.0001); eCM engraftment reduces VT inducibility compared with sham injection (P 0.0001). Conversely, VT remain frequent after transplantation of SMs, BM and cardiac myofibroblasts (cFib) (P = 0.0011 and 0.0005; 0.015 and 0.008; 0.019 and 0.016 versus control and eCMs, respectively). i, Improvement of left ventricular ejection fraction after eCM or SM transplantation. Asterisk, P 0.005. Numbers above bars indicate n; error bars show s.d. Scale bar, 1.6 mm (a, b), 60 m (e), 5 m (f), 11 m (g). FIGURE 3. Entrainment of engrafted eCMs in vivo. a, Image of a heart (taken ex vivo) with engrafted GCaMP2+ cells in the infarct (dark area). b, Magnified view of the yellow box in a. c, Combined in vivo recordings (left) of ECG (black) and Ca2+ transients (red, area marked in b) reveal 2:1 coupling of native myocardium with engrafted cells. 9 Averaging of coupled QRS (green lines) and Ca2+ signals yields their temporal correlation (middle). Pseudocolour images of GCaMP2 fluorescence at time points indicated by numbers (right). d, e, High-resolution Ca2+ fluorescence from engrafted GCaMP2+ cells (d, left) in a Langendorff-perfused heart. Image series (d, middle) demonstrates coupling of engrafted cells, with sequential activation (e) of individual regions (d, right). f, Entrainment of Ca2+ fluorescence in vivo to 2-Hz stimulation from electrode in normal myocardium (intrinsic heart rate slowed with the use of deep anaesthesia). Scale bar, 1.5 mm (a), 360 m (b, d), 3.2 mm (c). 抗抗 Bv8Bv8 抗体抑制肿瘤的作用抗体抑制肿瘤的作用 来自骨髓的细胞已知能帮助肿瘤中 血管的形成。现在，血管生成肽 Bv8（亦称为 prokineticin-2）被发现 可能与这一过程有关。移植进免疫缺陷 小鼠体内的肿瘤分泌 G-CSF，它是一个 通常与血细胞形成有关的因子，能增加 骨髓中 Bv8 的生成。然后 Bv8 会将“喜 中性”类的白血细胞引导到肿瘤上。抗 Bv8 抗体会阻断血管生成，抑制某些肿 瘤的生长，说明它也许是一种有效的抗 肿瘤试剂， 尤其是当与细胞毒性化疗结合起来使用 时。 Nature 450, 825-831 (6 December 2007) FIGURE 1. Regulation of Bv8 expression in vitro and in vivo. a, Beige nude mice were implanted with A673 10 (n = 6) or HM7 (n = 6) cells, and Bv8 was measured in the bone marrow by ELISA. b, Beige nude mice were implanted (n = 5) with A673, HM7, HPAC, Calu6 or Jurkat cells. Bv8 expression in BMMNC CD11b+Gr1+ and CD11bGr1 subsets was determined by Taqman. Gapdh, glyceraldehyde-3-phosphate dehydrogenase. c, Whole BMNNCs, CD11b+Gr1+ and CD11bGr1 populations were treated with Sdf1 , IL-6, IL-10, G-CSF or GM-CSF, and Bv8 expression was measured (n = 4). d, BMMNCs were treated with aliquots of HM7 tumour lysates, pre-incubated with various concentrations of anti-G-CSF or control IgG. Bv8 expression was monitored by Taqman (n = 4). Rpl19, ribosomal protein L19. e, Anti-G-CSF reduces the level of Bv8 in the bone marrow of HM7-tumour-bearing mice (n = 6).Clear bars, control IgG; filled bars, anti-G-CSF. f, Bv8 has a role in bone marrow cell mobilization induced by G-CSF (n = 5). See Methods for details. All mice were bled 6 h after final injection, and the frequency of CD11b+Gr1+ cells was determined. Single asterisk, P 0.05; error bars represent standard deviation (s.d.). FIGURE 2. Expression of Bv8 in tumour-associated myeloid cells, and effects of anti-Bv8 antibodies on tumour growth. a, CD11b+ cells are the main source of Bv8 in the tumours. Beige nude mice (n = 5) were implanted with A673, Calu6, HM7, HPAC or Jurkat cells and were killed ten days after tumour cell transplantation. Populations of cells enriched for CD11b+ were isolated and the expression of mouse Bv8 or human BV8 was analysed. be, Balb/c nude mice (n = 10) were implanted with A673 (b), HM7 (c), HPAC (d) or Jurkat (e) cells and were treated as described. Asterisks indicate significant difference in anti-Bv8 or anti-Vegf compared to control-treated groups (P 0.05). C, control; AB, anti-Bv8; AV, anti-Vegf. Insets show tumour weights. f, Anti-Bv8 and anti-Vegf have additive effects to inhibit tumour growth. Beige nude mice (n = 10) were implanted with 11 TIB42 cells and were treated with control, anti-Bv8, anti-Vegf or a combination (anti-Bv8 plus anti-Vegf). The inset shows the terminal tumour weights in all treatments. Error bars represent s.e.m. FIGURE 3. Anti-Bv8 treatment reduces CD11b+Gr1+ cells in the peripheral blood and the tumours. a, b, Nude mice (n = 5) were implanted with A673, Calu6, HM7, HPAC or Jurkat cells and were treated with anti-Bv8 or control monoclonal antibodies, as described. Mice were analysed ten days after tumour cell inoculation and the frequency of CD11b+, Gr1+ and CD11b+Gr1+ cells was measured in peripheral blood (a) and in tumours (b). The inset in a shows the frequency of circulating CD11b+, Gr1+ and CD11b+Gr1+ cells in Matrigel-implanted mice. Error bars represent s.d. Asterisks denote significant differences (P 0.05) when comparing CD11b+, Gr1+ and CD11b+Gr1+ cells in each tumour in anti- Bv8 treated mice compared to control treated animals. FIGURE 4. Bv8 regulates tumour angiogenesis. HM7-tumour-bearing mice were injected with 107 p.f.u. of Av-Bv8, Av-Vegf or Av-LacZ (each group, n = 10) five days after cell inoculation. a, Shown is the terminal tumour volume measurement in Av-Bv8 and Av-Vegf compared to Av-LacZ group. b, FACS data show the frequency of circulating CD11b+Gr1+ cells in the treatment groups. c, d, Micro-CT analysis revealed increased vascular volume (c) and vascular density (d) in Av-Bv8- and Av-Vegf- 12 injected tumours. e, Representative images of vascular networks and tumours (shown in red and grey, respectively) from all treatment groups. f, Nude mice (n = 10) were implanted with HM7 cells and were treated with monoclonal antibodies. Data represent tumour volume measurement at day ten. g, FACS data represent the percentage of circulating CD11b+Gr1+ cells in treatment groups. h, i, The micro-CT analysis showed a significant decrease in vascular volume (h) and vascular density (i) in anti-Bv8- versus control-treated mice. j, Representative images of tumours from the three treatment groups. Error bars represent s.e.m. Asterisks denote significant differences (P 100). Scale bar, 10 m. c, S. typhimurium growth in LB or a medium mimicking endosomal conditions (MGM) in the presence or absence of 10 M H-89 at pH 7.5 or pH 4.5 was measured at a wavelength of 595 nm. 15 FIGURE 2. Chemical profiling for antibiotic activity of kinase inhibitors. a, The building block H-89 was selectively modified. For synthesis see Supplementary Fig. 2. b, Chemical profiling for S. typhimurium infection. Primary human macrophages infected with S. typhimurium SL1344 were cultured in the presence of 10 M of the compounds for 18 h. Intracellular growth was determined in c.f.u. assays. Shown is the mean of quadruplicate c.f.u. counts s.e.m. (*P 0.001) c, Chemical profiling for M. tuberculosis infection. Primary human macrophages infected with M. tuberculosis were cultured as in b for 6 days with daily renewal of medium, and intracellular growth determined. Shown is the mean of quadruplicate c.f.u. counts s.e.m. (*P 100). Scale bar, 10 m. b, GFP-labelled PAK4 or constitutively active PAK4(S445N) expressed in MCF7 cells were infected and cultured with DsRed-S.typhimurium for 18 h with AKTi1/2. DsRed-S. typhimurium were quantified by FACS and related to the infection of GFP PAK4-transfected cells, set at 100%. Shown is the mean of triplicate experiments. c, MCF7 cells were transfected with MycRAB14, AS160 or the shRNAi AS160.2 construct for AS160, and infected with GFP-S. typhimurium in the presence or absence of AKTi1/2. Intracellular S. typhimurium was quantified by FACS 18 h later and compared to untreated AS160-transfected MCF7 cells (set at 100%). Shown is the mean of triplicate experiments. d, S. typhimurium effector SopB activates AKT. AKT1 targets PAK4, which phosphorylates GEF-H1, thus controlling RHOA, RAC1 and actin. AKT1 also phosphorylates the RAB14-GAP, AS160. This prevents AS160 binding to phagosomal membranes, thus activating RAB14 and inhibiting phagosomal maturation. 天然人体激素可作为新一代抗抑郁药物天然人体激素可作为新一代抗抑郁药物 论文作者：Kamilla Miskowiak 期刊：生物精神病学 发布时间：2007-12-13 根据发表在 12 月 1 日的爱思唯尔期刊生物精神病学 （Biological Psychiatry）上的文章，人体的一种天然 激素促红细胞生成素（erythropoietin Epo）会影响认 17 知及相关神经反应，并有望用于抑郁症的治疗。该方法将对公共健康产生巨大 影响，因为它的成功率高，且起效快速。 文章第一作者、牛津大学的 Kamilla Miskowiak 表示：“尽管抑郁通常和脑 部化学问题相关，但最近有证据显示结构问题同样会引起抑郁，结构问题可能 是由于神经细胞再生速度不够，或是压力激素导致的毒性作用产生的。 ”正是以 上发现促使科学家分析促红细胞生成素的作用。 促红细胞生成素是肾脏产生的一种激素，它能促进红细胞生成，可被用 于治疗贫血。文章作者表示，新证据显示促红细胞生成素对于动物神经系统存 在保护和营养作用，这会影响人类认知和相关的神经反应，因此它可能成为治 疗抑郁症的药物。 在研究中，Miskowiak 与同事向 23 名健康的志愿者展示快乐或者恐惧的 面部表情图片，并用功能磁共振成像来跟踪脑部的神经加工和认知处理过程， 由此来评估红细胞生成素对此过程的影响。恐惧表情是人类基本情感中最显著 的一种，它可能表示危险的存在。研究人员重点研究了红细胞生成素对这种 “危险信息”的影响。 结果表明，红细胞生成素药剂降低了人对危险信息的认知和神经反应， 这与现有的抗抑郁药物的作用惊人相似。同时，即使在使用红细胞生成素 7 天 后，这种抑制作用依然存在。Miskowiak 表示，以上发现意味着促红细胞生成 素能影响神经功能，并可能成为未来治疗抑郁症的手段。 生物神经病学编辑，来自耶鲁大学医学院和康涅狄格卫生保健系统 的 John H. Krystal 同意以上观点，他表示：“促红细胞生成素对于动物大脑有 营养作用。现有数据证实它能调节人类大脑情绪过程。现在已经能评估人类促 红细胞生成素和其它相关物质的抗抑郁效果。 ” （生物精神病学 （Biological Psychiatry） ， doi:10.1016/j.biopsych.2007.01.011，Kamilla Miskowiak, Catherine J. Harmera） 18 杂志简介： 生物精神病学 （Biological Psychiatry）由世界 最大的科学、技术和医学出版商 Elsevier 出版发行，是美 国生物精神病学会的官方杂志。发表的文章涉及精神病学 病理及治疗的广泛领域，接收发表的文章包括精神疾病的 病理及治疗的基础和临床研究，此外，对相关领域有一定 影响、反映研究动态的文章或简报、评论、有意义的病例 分析、通讯等投稿将也被接收发表。该杂志尤其欢迎涉及遗传因素和环境因素、 神经网络、神经化学、新的治疗方法的文章。 生物精神病学2006 年的影响 因子为 7.154，在 95 种精神病学杂志中排名第 4。 抗丙肝药物研究新进展抗丙肝药物研究新进展 论文作者：Takaji Wakita 期刊：先进药物输送评论 发布时间：2007-12-12 丙肝病毒（HCV）最初是在受感染的黑猩猩血液中发 现的，它会持续感染宿主细胞，引发丙型肝炎，肝硬化， 最终导致肝癌。所以科学家们一直致力于抗 HCV 药物的 研发以及 HCV 疫苗的研究。当前抗 HCV 病毒有效的药物 是干扰素（IFN）和病毒唑，但疗效并不令人满意，抗 HCV 特异性药物只能在临床前和临床实验中进行，因为 HCV 在培养细胞中繁 殖很困难，而且实验缺乏合适的病毒培养系统和动物模型。 随着研究的深入，科学家们发现了 HCV 亚基因组复制系统，使用了 JFH- 1 克隆的病毒培养系统，移植了人体肝细胞的 Alb-uPA/SCID 的小鼠作为实验 动物模型，以此设计出了抗 HCV 药物如 NS53 和 NS5B 抑制剂。在抗 HCV 药 19 物的研究中，HCV 生活史中的每一步都可能成为开发反 HCV 药物的靶点。 HCV 克隆后，新的感染就会持续增加，HCV 感染的高危人群仍然存在，比如 健康人和静脉药物使用者，所以研发预防 HCV 的疫苗一样重要。HCV 如何侵 入宿主免疫系统，保护性免疫如何抵御 HCV 感染，仍然是有效疫苗的研究重 点。除此之外，HCV 疫苗也可以用于慢性携带者的免疫治疗。 相关论文 10 月 10 日发表在爱思唯尔期刊先进药物输送评论 （Advanced Drug Delivery Reviews）上。 （先进药物输送评论（Advanced Drug Delivery Reviews），Volume 59, Issue 12, 10 October 2007, Pages 1196-1199，Takaji Wakita） 英文文摘：英文文摘： HCV research and anti-HCV drug discovery: Toward the next generation Takaji Wakita a, aDepartment of Virology II, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan Abstract Hepatitis C virus (HCV) causes persistent infection and induces chronic hepatitis, liver cirrhosis and finally hepatocellular carcinoma. Current therapies for HCV infection have not been satisfactory, and more effective anti-viral treatments are needed. In this regard, detailed analysis of HCV has been hampered by a lack of appropriate viral culture systems and small animal models of infection. However, rapid progress in HCV research has recently been achieved, such as a subgenomic replicon system, a viral culture system using JFH-1 clone and the Alb-uPA/SCID mouse transplanted with human liver cells. Such progress will propel HCV research and anti-HCV drug discovery toward the next generation. 关于关于 P-P-型型 ATPATP 酶的一组研究论文酶的一组研究论文 P-型 ATP 酶是对所有真核生物和很多原核生物具有根本重要性的阳离子泵。 20 本期 Nature 上三篇论文介绍了关于这一超级家族关键成员的结构及功能研究。 本期封面所示为钠离子和钾离子泵的结构，是由 Morth 等人在本期杂志上以 3.5 埃的分辨率描述的，同时还刊登了 J. C. Skou 关于其 50 年前发现依赖于钠离 子和钾离子的 ATP 酶活性的原始笔记。这篇论文显示了与钾相结合的状态，同 时还暗示了一种依赖于电压的调控基础。这些结果部分是通过与 Skou 所做实 验相似的动能实验获得的。Olesen 等人介绍了肌质网 Ca2+-ATP 酶（钙泵）的 新的晶体结构，同时还有关于功能的研究工作，并且最终呈现了关于钙运输的 一个完整机制。在植物和真菌中，细胞离子平衡状态和膜势是由胞质膜 H+- ATP 酶（另一种 P-型 ATP 酶）提供动力的。Pedersen 等人介绍了它的 X-射线 结构，提供了关于它是如何沿一个陡峭的电化学梯度来泵输质子的有关线索。 Nature 450, 1036-1042 (13 December 2007) FIGURE 1. Overall comparison of SERCA1a structures representing key states of the reaction cycle. The new structures of Ca2E1 P-AMPPN, E2-BeF3- and E2-AlF4- complexes form the basis of this report and the E2-BeF3- complex is increased in size to emphasize its critical importance. Cation- and nucleotide-exchange reactions are indicated. The structures are depicted by grey, transparent surfaces and by cartoon representations, with the A domain in yellow, N domain in red, P domain in blue, transmembrane segment M12 in purple, M34 in green, M56 in wheat and M710 in grey. The TGES motif is shown by pink space-filling, residues 309, 771 and 796 (mentioned in the text) as sticks, and bound Ca2+ ions as grey spheres. Here, and in the 21 following figures, structural representations were prepared with Pymol FIGURE 2. The Ca2E1P state obtained with AMPPNP. a, Refined structure (stick representation) of the Ca2E1 P- AMPPN complex. The unbiased (FO-FC) difference map of the nucleotide complex (green mesh, 5.5 ), and the experimental (FOAMPPNP-FOADP-AlF) difference map (-4 and 4 , red-brown and blue, respectively) show phosphoryl transfer to Asp 351. b, The upper panel shows Ca2+ accumulation by sarcoplasmic