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Generalized immune activation as a direct result of activated CD4+ T cell killing. 作为CD4+ T细胞杀伤激活的直接结果的全身免疫激活。
Pub Date : 2009-01-01 DOI: 10.1186/jbiol194
Rute Marques, Adam Williams, Urszula Eksmond, Andy Wullaert, Nigel Killeen, Manolis Pasparakis, Dimitris Kioussis, George Kassiotis

Background: In addition to progressive CD4(+) T cell immune deficiency, HIV infection is characterized by generalized immune activation, thought to arise from increased microbial exposure resulting from diminishing immunity.

Results: Here we report that, in a virus-free mouse model, conditional ablation of activated CD4(+) T cells, the targets of immunodeficiency viruses, accelerates their turnover and produces CD4(+) T cell immune deficiency. More importantly, activated CD4(+) T cell killing also results in generalized immune activation, which is attributable to regulatory CD4(+) T cell insufficiency and preventable by regulatory CD4(+) T cell reconstitution. Immune activation in this model develops independently of microbial exposure. Furthermore, microbial translocation in mice with conditional disruption of intestinal epithelial integrity affects myeloid but not T cell homeostasis.

Conclusions: Although neither ablation of activated CD4(+) T cells nor disruption of intestinal epithelial integrity in mice fully reproduces every aspect of HIV-associated immune dysfunction in humans, ablation of activated CD4(+) T cells, but not disruption of intestinal epithelial integrity, approximates the two key immune alterations in HIV infection: CD4(+) T cell immune deficiency and generalized immune activation. We therefore propose activated CD4(+) T cell killing as a common etiology for both immune deficiency and activation in HIV infection.

背景:除了进行性CD4(+) T细胞免疫缺陷外,HIV感染的特点是全身性免疫激活,这被认为是由于免疫力下降导致微生物暴露增加引起的。结果:在无病毒小鼠模型中,有条件地消融活化的CD4(+) T细胞(免疫缺陷病毒的靶标),加速其周转并产生CD4(+) T细胞免疫缺陷。更重要的是,活化的CD4(+) T细胞杀伤也会导致全身性免疫激活,这是由于调节性CD4(+) T细胞功能不全,可通过调节性CD4(+) T细胞重构来预防。该模型中的免疫激活与微生物暴露无关。此外,肠道上皮完整性条件性破坏小鼠的微生物易位影响髓细胞而不影响T细胞稳态。结论:虽然小鼠体内激活的CD4(+) T细胞的消融和肠上皮完整性的破坏都不能完全再现人类HIV相关免疫功能障碍的各个方面,但激活的CD4(+) T细胞的消融,而不是肠上皮完整性的破坏,近似于HIV感染中的两个关键免疫改变:CD4(+) T细胞免疫缺陷和全身免疫激活。因此,我们提出活化的CD4(+) T细胞杀伤是HIV感染中免疫缺陷和激活的常见病因。
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引用次数: 18
Parasite immunomodulation and polymorphisms of the immune system. 寄生虫免疫调节和免疫系统的多态性。
Pub Date : 2009-01-01 Epub Date: 2009-08-05 DOI: 10.1186/jbiol166
Rick M Maizels

Parasites are accomplished evaders of host immunity. Their evasion strategies have shaped every facet of the immune system, driving diversity within gene families and immune gene polymorphisms within populations. New studies published recently in BMC Biology and Journal of Experimental Medicine document parasite-associated immunosuppression in natural populations and suggest that host genetic variants favoring resistance to parasites may be detrimental in the absence of infection.

寄生虫是宿主免疫的成功逃避者。它们的逃避策略塑造了免疫系统的方方面面,推动了基因家族的多样性和群体内免疫基因的多态性。最近发表在《BMC生物学》和《实验医学杂志》上的新研究记录了自然种群中与寄生虫相关的免疫抑制,并表明在没有感染的情况下,有利于抵抗寄生虫的宿主遗传变异可能是有害的。
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引用次数: 81
The gene complement of the ancestral bilaterian - was Urbilateria a monster? 祖先双侧龙的基因补充——双侧龙是怪物吗?
Pub Date : 2009-01-01 DOI: 10.1186/jbiol192
David J Miller, Eldon E Ball

Expressed sequence tag analyses of the annelid Pomatoceros lamarckii, recently published in BMC Evolutionary Biology, are consistent with less extensive gene loss in the Lophotrochozoa than in the Ecdysozoa, but it would be premature to generalize about patterns of gene loss on the basis of the limited data available.

最近发表在《BMC进化生物学》杂志上的对环节动物Pomatoceros lamarckii的表达序列标签分析表明,光栖动物的基因丢失范围小于外生动物,但根据现有的有限数据,对基因丢失模式进行概括还为时过早。
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引用次数: 13
Life and death as a T lymphocyte: from immune protection to HIV pathogenesis. 作为T淋巴细胞的生与死:从免疫保护到HIV发病机制。
Pub Date : 2009-01-01 DOI: 10.1186/jbiol198
Nienke Vrisekoop, Judith N Mandl, Ronald N Germain

Detailed analysis of T cell dynamics in humans is challenging and mouse models can be important tools for characterizing T cell dynamic processes. In a paper just published in Journal of Biology, Marques et al. suggest that a mouse model with its activated CD4(+) T cells are deleted has relevance for HIV infection.

人体T细胞动力学的详细分析具有挑战性,小鼠模型可以成为表征T细胞动力学过程的重要工具。在刚刚发表在《生物学杂志》上的一篇论文中,Marques等人认为,一个被激活的CD4(+) T细胞被删除的小鼠模型与HIV感染有关。
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引用次数: 11
Coordinated gene expression by post-transcriptional regulons in African trypanosomes. 非洲锥虫转录后调控的协调基因表达。
Pub Date : 2009-01-01 Epub Date: 2009-12-14 DOI: 10.1186/jbiol203
Marc Ouellette, Barbara Papadopoulou

The regulation of gene expression in trypanosomes is unique. In the absence of transcriptional control at the level of initiation, a subset of Trypanosoma brucei genes form post-transcriptional regulons in which mRNAs are co-regulated in response to differentiation signals. See research articles http://www.biomedcentral.com/1471-2164/10/427, http://www.biomedcentral.com/1471-2164/10/482 and http://www.biomedcentral.com/1471-2164/10/495.

锥虫的基因表达调控是独特的。在起始水平缺乏转录控制的情况下,布鲁氏锥虫基因的一个子集形成转录后调控,其中mrna在响应分化信号时被共同调控。参见研究文章http://www.biomedcentral.com/1471-2164/10/427, http://www.biomedcentral.com/1471-2164/10/482和http://www.biomedcentral.com/1471-2164/10/495。
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引用次数: 59
Sperm dumping as a defense against meiotic drive. 精子倾倒作为对减数分裂驱动的防御。
Pub Date : 2009-01-01 Epub Date: 2009-01-20 DOI: 10.1186/jbiol109
Tom Price, Zenobia Lewis, Nina Wedell

Sperm from Drosophila simulans that carry a sex-ratio distorter is preferentially lost from females' sperm-storage organs. This suggests that sperm dumping is a major factor affecting sperm competition in this species, and may have evolved in response to sex-ratio distorters.

携带性别比例扭曲的果蝇精子会优先从雌性精子储存器官中丢失。这表明,精子倾倒是影响该物种精子竞争的主要因素,可能是为了应对性别比例扭曲而进化出来的。
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引用次数: 7
Happy together: genomic insights into the unique Nanoarchaeum/Ignicoccus association. 快乐在一起:对独特的纳米古菌/火苗球菌关联的基因组见解。
Pub Date : 2009-01-01 Epub Date: 2009-01-23 DOI: 10.1186/jbiol110
Patrick Forterre, Simonetta Gribaldo, Céline Brochier-Armanet

The complete genome sequence of the crenarchaeon Ignicoccus hospitalis published recently in Genome Biology provides a great leap forward in the dissection of its unique association with another hyperthermophilic archaeon, Nanoarchaeum equitans.

最近发表在《基因组生物学》杂志上的医院绿古菌的完整基因组序列为解剖它与另一种超嗜热古菌——马纳米古菌的独特联系提供了一个巨大的飞跃。
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引用次数: 24
Genome degeneration affects both extracellular and intracellular bacterial endosymbionts. 基因组退化影响细胞外和细胞内细菌的内共生体。
Pub Date : 2009-01-01 Epub Date: 2009-04-06 DOI: 10.1186/jbiol129
Heike Feldhaar, Roy Gross

The obligate intracellular bacterial endosymbionts of insects are a paradigm for reductive genome evolution. A study published recently in BMC Biology demonstrates that similar evolutionary forces shaping genome structure may also apply to extracellular endosymbionts.

昆虫的专性细胞内细菌共生体是还原性基因组进化的范例。最近发表在《BMC生物学》上的一项研究表明,形成基因组结构的类似进化力量也可能适用于细胞外内共生生物。
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引用次数: 8
Reconstructing prokaryotic transcriptional regulatory networks: lessons from actinobacteria. 重建原核生物转录调控网络:来自放线菌的教训。
Pub Date : 2009-01-01 Epub Date: 2009-04-15 DOI: 10.1186/jbiol132
Thiago M Venancio, L Aravind

Reconstruction of transcriptional regulatory networks of uncharacterized bacteria is a main challenge for the post-genomic era. Recent studies, including one in BMC Systems Biology, address this problem in the relatively underexplored actinobacteria clade, which includes major pathogenic and economically relevant taxa.

重建未表征细菌的转录调控网络是后基因组时代的主要挑战。最近的研究,包括BMC系统生物学的一项研究,在相对未被开发的放线菌分支中解决了这个问题,其中包括主要的致病和经济相关的分类群。
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引用次数: 20
Conservation of core gene expression in vertebrate tissues. 脊椎动物组织中核心基因表达的一致性。
Pub Date : 2009-01-01 Epub Date: 2009-04-16 DOI: 10.1186/jbiol130
Esther T Chan, Gerald T Quon, Gordon Chua, Tomas Babak, Miles Trochesset, Ralph A Zirngibl, Jane Aubin, Michael J H Ratcliffe, Andrew Wilde, Michael Brudno, Quaid D Morris, Timothy R Hughes

Background: Vertebrates share the same general body plan and organs, possess related sets of genes, and rely on similar physiological mechanisms, yet show great diversity in morphology, habitat and behavior. Alteration of gene regulation is thought to be a major mechanism in phenotypic variation and evolution, but relatively little is known about the broad patterns of conservation in gene expression in non-mammalian vertebrates.

Results: We measured expression of all known and predicted genes across twenty tissues in chicken, frog and pufferfish. By combining the results with human and mouse data and considering only ten common tissues, we have found evidence of conserved expression for more than a third of unique orthologous genes. We find that, on average, transcription factor gene expression is neither more nor less conserved than that of other genes. Strikingly, conservation of expression correlates poorly with the amount of conserved nonexonic sequence, even using a sequence alignment technique that accounts for non-collinearity in conserved elements. Many genes show conserved human/fish expression despite having almost no nonexonic conserved primary sequence.

Conclusions: There are clearly strong evolutionary constraints on tissue-specific gene expression. A major challenge will be to understand the precise mechanisms by which many gene expression patterns remain similar despite extensive cis-regulatory restructuring.

背景:脊椎动物具有相同的身体结构和器官,拥有相关的基因集,依赖类似的生理机制,但在形态、栖息地和行为方面却表现出极大的多样性。基因调控的改变被认为是表型变异和进化的主要机制,但人们对非哺乳类脊椎动物基因表达的广泛保护模式知之甚少:我们测量了鸡、青蛙和河豚 20 种组织中所有已知和预测基因的表达。通过将结果与人类和小鼠的数据相结合,并只考虑十种常见组织,我们发现有证据表明三分之一以上的独特同源基因的表达是保守的。我们发现,平均而言,转录因子基因表达的保守性既不高于也不低于其他基因。令人吃惊的是,表达的保守性与非共轭序列的保守性关系不大,即使是使用考虑保守元素非共轭性的序列比对技术也是如此。许多基因尽管几乎没有非共轭的保守主序列,但却显示出人类/鱼类表达的保守性:结论:组织特异性基因表达显然受到了强大的进化限制。一项重大挑战将是了解许多基因表达模式在广泛的顺式调控重组后仍然保持相似的确切机制。
{"title":"Conservation of core gene expression in vertebrate tissues.","authors":"Esther T Chan, Gerald T Quon, Gordon Chua, Tomas Babak, Miles Trochesset, Ralph A Zirngibl, Jane Aubin, Michael J H Ratcliffe, Andrew Wilde, Michael Brudno, Quaid D Morris, Timothy R Hughes","doi":"10.1186/jbiol130","DOIUrl":"10.1186/jbiol130","url":null,"abstract":"<p><strong>Background: </strong>Vertebrates share the same general body plan and organs, possess related sets of genes, and rely on similar physiological mechanisms, yet show great diversity in morphology, habitat and behavior. Alteration of gene regulation is thought to be a major mechanism in phenotypic variation and evolution, but relatively little is known about the broad patterns of conservation in gene expression in non-mammalian vertebrates.</p><p><strong>Results: </strong>We measured expression of all known and predicted genes across twenty tissues in chicken, frog and pufferfish. By combining the results with human and mouse data and considering only ten common tissues, we have found evidence of conserved expression for more than a third of unique orthologous genes. We find that, on average, transcription factor gene expression is neither more nor less conserved than that of other genes. Strikingly, conservation of expression correlates poorly with the amount of conserved nonexonic sequence, even using a sequence alignment technique that accounts for non-collinearity in conserved elements. Many genes show conserved human/fish expression despite having almost no nonexonic conserved primary sequence.</p><p><strong>Conclusions: </strong>There are clearly strong evolutionary constraints on tissue-specific gene expression. A major challenge will be to understand the precise mechanisms by which many gene expression patterns remain similar despite extensive cis-regulatory restructuring.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28113335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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