【点评】
点评：通过不休提供LIF成长因子和持续表白5个重新编程因子，能够节造人体诱导多能干细（iPSC）维持在更原始的多能干细胞状态，该技术最大的用处就是便于成立iPSC细胞系，但是还不能扭转基因重新编程的iPSC没有临床利用价值的情景。

【原文摘录】Cell Stem Cell, Volume 6, Issue 6, 535-546, 4 June 2010
A Murine ESC-like State Facilitates Transgenesis and Homologous Recombination in Human Pluripotent Stem Cells
Christa Buecker, Hsu-Hsin Chen, Jose Maria Polo, Laurence Daheron, Lei Bu, Tahsin Stefan Barakat, Patricia Okwieka, Andrew Porter, Joost Gribnau, Konrad Hochedlinger and Niels Geijsen
Murine pluripotent stem cells can exist in two functionally distinct states, LIF-dependent embryonic stem cells (ESCs) and bFGF-dependent epiblast stem cells (EpiSCs). However, human pluripotent cells so far seemed to assume only an epiblast-like state. Here we demonstrate that human iPSC reprogramming in the presence of LIF yields human stem cells that display morphological, molecular, and functional properties of murine ESCs. We termed these hLR5 iPSCs because they require the expression of five ectopic reprogramming factors, Oct4, Sox2, Klf4, cMyc, and Nanog, to maintain this more naive state. The cells are metastable and upon ectopic factor withdrawal they revert to standard human iPSCs. Finally, we demonstrate that the hLR5 state facilitates gene targeting, and as such provides a powerful tool for the generation of recombinant human pluripotent stem cell lines.

2. 节造流感病毒复造的“开关”
【提要】科技日报 2010-6-7 10:31:18
　　据报路，美国科学家初次发现流感病毒的复造存在一个节造“开关”——幼病毒核糖核酸（svRNA），并有望据此研发出可能医治所有类型流感的药物。甲型流感病毒蕴含8个单体RNA片段，每个片段都有两个工作：通过转录过程造作蛋白；通过复造过程造作出新的病毒片段。由于每个单体必须执行两个职能，病毒必须让某一个过程优先实现，先转录而后振兴头复造。通过使用超高通量测序技术，纽约西奈山医学院的钻研人员初次找到了甲型流感病毒中的一个svRNA，并确定它就是节造病毒从转录过渡到复造的“开关”。超高通量测序技术是对传统测序伎俩的一次革命性扭转，它一次就可对几十万到几百万条DNA分子进行序列测定，使得对一个物种的转录组和基因组进行详细全貌的分析成为可能，所以又被称为深度测序。该钻研的辅导者之一、西奈山医学院微生物学家本杰明·腾奥弗暗示，这项钻研的意思极度重大。在流感病毒中，svRNA始终如一职位于病毒RNA片段之间，并且在每种流感病毒中都出现。若是我们可能阻止svRNA的活性，就能节造病毒不要转向复造过程，从而阻止其扩散。另表的一个益处是，若是病毒只能转录，那它就只能不休产生蛋白，反而最终会强化抗体的反映能力。
　　腾奥弗指出，理论上讲，通过抑造svRNA就能够阻止病毒片段的复造，但此刻的问题是，我们还不相识svRNA的“工作细节”，我们也但愿可能找到一种步骤，让基于RNA的匹敌剂进入人体中，用来抑造svRNA的职能，让病毒不转向复造过程。不外，这个问题可能还必要几年能力解决。由于乙型流感和丙型流感病毒的复造战术和甲型流感病毒的一样，这个发现也就意味着我们将最终可能研造出一种可能医治所有流感病毒的药物。固然甲型H1N1流感的阴影在消散，但我们从来没有健忘，仅季节性流感每年就要夺去全世界25万人的性命。一说到流感，你可能顿时想起疫苗。然而，流感病毒的进化和变异非？，疫苗也必须随之不休更新，并且还不见得有效。所以，科学家们一方口试图造就出全能流感疫苗，另一方面也从医治的角度致力开发通用抗流感药物，从而对流感病毒形成前后夹击之势。腾奥弗和他的团队今天带给恒峰g22正是后者的但愿。
【点评】
点评：从理论上发现了能够研造出匹敌所有流感病毒习染的药物的战术。

【原文摘录】Published online before print June 1, 2010, doi: 10.1073/pnas.1001984107
Influenza A virus-generated small RNAs regulate the switch from transcription to replication
Jasmine T. Perez, Andrew Varble, Ravi Sachidanandam, Ivan Zlatev, Muthiah Manoharan,
Adolfo García-Sastre, and Benjamin R. tenOever

The discovery of regulatory small RNAs continues to reshape paradigms in both molecular biology and virology. Here we describe examples of influenza A virus-derived small viral RNAs (svRNAs). svRNAs are 22–27 nt in length and correspond to the 5′ end of each of the viral genomic RNA (vRNA) segments. Expression of svRNA correlates with the accumulation of vRNA and a bias in RNA-dependent RNA polymerase (RdRp) activity from transcription toward genome replication. Synthesis of svRNA requires the RdRp, nucleoprotein and the nuclear export protein NS2. In addition, svRNA is detectable during replication of various influenza A virus subtypes across multiple host species and associates physically with the RdRp. We demonstrate that depletion of svRNA has a minimal impact on mRNA and complementary vRNA (cRNA) but results in a dramatic loss of vRNA in a segment-specific manner. We propose that svRNA triggers the viral switch from transcription to replication through interactions with the viral polymerase machinery. Taken together, the discovery of svRNA redefines the mechanistic switch of influenza virus transcription/replication and provides a potential target for broad-range, anti-influenza virus-based therapeutics.
3. T细胞基因刷新造作癌细胞杀手
　　

【提要】 《科学》期刊新颁发的一项钻研发现通过敲除T细胞必须基因Bcl11b可能获得类似NK细胞的ITNK细胞，在体表尝试和老鼠动物模型上这种细胞可能扑灭癌细胞和预防肿瘤的形成和转移。并且能够维持存活至少3个月，没有发现携带该细胞的老鼠出现异常。【点评】
点评：该发现为癌症的免疫疗法提供了新的线索。

【原文摘录】Published Online June 10, 2010  Science DOI: 10.1126/science.1188063
Reprogramming of T cells to Natural Killer-like cells upon Bcl11b deletion.
Peng Li, Shannon Burke, Juexuan Wang, Xiongfeng Chen, Mariaestela Ortiz, Song-Choon Lee, Dong Lu, Lia Campos, David Goulding, Bee Ling Ng, Gordon Dougan, Brian Huntly, Bertie Gottgens, Nancy A. Jenkins, Neal G. Copeland, Francesco Colucci, and Pentao Liu.

T cells develop in the thymus and are critical for adaptive immunity. Natural killer (NK) lymphocytes constitute an essential component of the innate immune system in tumor surveillance and defense against microbes and viruses. Here, we show that the transcription factor Bcl11b was expressed in all T cell compartments and was indispensable for T-lineage development. When Bcl11b was deleted, T cells from all developmental stages acquired NK cell properties and concomitantly lost or decreased T cell–associated gene expression. These induced T-to-natural-killer (ITNK) cells, which were morphologically and genetically similar to conventional NK cells, killed tumor cells in vitro and effectively prevented tumor metastasis in vivo. Therefore, ITNKs may represent a new cell source for cell-based therapies.
4. 红酒和绿茶中多酚类化合物抗癌的机理
　　

【提要】SphK1/S1P信号通路是与很多癌症的进展及医治抵抗有关的，最新的钻研证明绿茶里的儿茶素（ＥＧＣＧ），红酒中的白藜芦醇（Ｒｅｓｖｅｒａｔｒｏｌ），或者各自提取的混合多酚类都能在体内表尝试中抑造前列腺癌细胞的成长，是通过抑造SphK1/S1P信号通路实现的，第一次闯辗视生物学解读诠氏缢此类食品中多酚化合物在癌症预防和医治中的分子靶标。
【点评】
点评：该钻研提供了确定的证据，有助于理解绿茶和红酒的抗癌保健职能，也为抗癌药物的钻研提供了新靶点。

【原文摘录】The FASEB Journal, 2010; DOI: 10.1096/fj.10-160838
The sphingosine kinase-1 survival pathway is a molecular target for the tumor-suppressive tea and wine polyphenols in prostate cancer
Leyre Brizuela, Audrey Dayon, Nicolas Doumerc, Isabelle Ader, Muriel Golzio, Jean-Claude Izard, Yukihiko Hara, Bernard Malavaud, and Olivier Cuvillier

The sphingosine kinase-1/sphingosine 1-phosphate (SphK1/S1P) pathway has been associated with cancer promotion and progression and resistance to treatments in a number of cancers, including prostate adenocarcinoma. Here we provide the first evidence that dietary agents, namely, epigallocatechin gallate (EGCg, IC5075 μM), resveratrol (IC5040 μM), or a mixture of polyphenols from green tea [polyphenon E (PPE), IC5070 μM] or grapevine extract (vineatrol, IC5030 μM), impede prostate cancer cell growth in vitro and in vivo by inhibiting the SphK1/S1P pathway. We establish that SphK1 is a downstream effector of the ERK/phospholipase D (PLD) pathway, which is inhibited by green tea and wine polyphenols. Enforced expression of SphK1 impaired the ability of green tea and wine polyphenols, as well as pharmacological inhibitors of PLD and ERK activities, to induce apoptosis in PC-3 and C4-2B cells. The therapeutic efficacy of these polyphenols on tumor growth and the SphK1/S1P pathway were confirmed in animals using a heterotopic PC-3 tumor in place model. PC-3/SphK1 cells implanted in animals developed larger tumors and resistance to treatment with polyphenols. Furthermore, using an orthotopic PC-3/GFP model, the chemopreventive effect of an EGCg or PPE diet was associated with SphK1 inhibition, a decrease in primary tumor volume, and occurrence and number of metastases. These results provide the first demonstration that the prosurvival, antiapoptotic SphK1/S1P pathway represents a target of dietary green tea and wine polyphenols in cancer.
5. 慢性习染使γ滋扰素激活休眠的造血干细胞

【提要】 全身习染会迅速亏损体内的淋巴细胞和中性粒细胞，造血系统的祖细胞会增产免疫细胞来复原体内平衡。最新的动物尝试钻研了造血干细胞在这一过程中的行为，发此刻鸡结核杆菌慢性习染大的老鼠中造血干细胞持久的增多的增殖反映必须有γ滋扰素的参加，这一结论也在γ滋扰素缺失的老鼠身上得到验证。
【点评】
点评：该钻研有助于更好的理解一些慢性习染病患的免疫系统重建身分，更深刻理解造血系统若何复原免疫细胞的数量。

【原文摘录】Nature, 2010; 465 (7299): 793 DOI: 10.1038/nature09135
Quiescent haematopoietic stem cells are activated by IFN-γ in response to chronic infection
Megan T. Baldridge, Katherine Y. King, Nathan C. Boles, David C. Weksberg, Margaret A. Goodell

Lymphocytes and neutrophils are rapidly depleted by systemic infection. Progenitor cells of the haematopoietic system, such as common myeloid progenitors and common lymphoid progenitors, increase the production of immune cells to restore and maintain homeostasis during chronic infection, but the contribution of haematopoietic stem cells (HSCs) to this process is largely unknown. Here we show, using an in vivo mouse model of Mycobacterium avium infection, that an increased proportion of long-term repopulating HSCs proliferate during M. avium infection, and that this response requires interferon-γ (IFN-γ) but not interferon-α (IFN-α) signalling. Thus, the haematopoietic response to chronic bacterial infection involves the activation not only of intermediate blood progenitors but of long-term repopulating HSCs as well. IFN-γ is sufficient to promote long-term repopulating HSC proliferation in vivo; furthermore, HSCs from IFN-γ-deficient mice have a lower proliferative rate, indicating that baseline IFN-γ tone regulates HSC activity. These findings implicate IFN-γ both as a regulator of HSCs during homeostasis and under conditions of infectious stress. Our studies contribute to a deeper understanding of haematological responses in patients with chronic infections such as HIV/AIDS or tuberculosis.
6. 肿瘤抑造因子ｐ５３在生殖细胞减数割裂中也有生理作用

【提要】 肿瘤抑造因子ｐ５３生物学作用不仅体此刻抑造肿瘤发生，最近的动物尝试批注生殖细胞的减数割裂过程，出格是拓扑异构酶Ｓｐｏ１１催化的ＤＮＡ双链解开激活了ｐ５３的职能，并一向存在于无法进行减数割裂ＤＮＡ建复的细胞中。这一发现确证了ｐ５３在减数割裂中有生理作用，也提醒了ｐ５３的抑造肿瘤发生的作用可能是在执行更原始的与基因重组有关的职能时辰派的。
【点评】
点评：ｐ５３抑造肿瘤天生的作用看来有可能是其最本原的职能的附带职能。

【原文摘录】Science, 2010; 328 (5983): 1278 DOI: 10.1126/science.1185640
Meiotic Recombination Provokes Functional Activation of the p53 Regulatory Network
Wan-Jin Lu, Joseph Chapo, Ignasi Roig, John M. Abrams