BACKGROUND & AIMS: :Gene duplication and gene loss as well as other biological events can result in multiple copies of genes in a given species. Because of these gene duplication and loss dynamics, in addition to variation in sequence evolution and other sources of uncertainty, different gene trees ultimately present different evolutionary histories. All of this together results in gene trees that give different topologies from each other, making consensus species trees ambiguous in places. Other sources of data to generate species trees are also unable to provide completely resolved binary species trees. However, in addition to gene duplication events, speciation events have provided some underlying phylogenetic signal, enabling development of algorithms to characterize these processes. Therefore, a soft parsimony algorithm has been developed that enables the mapping of gene trees onto species trees and modification of uncertain or weakly supported branches based on minimizing the number of gene duplication and loss events implied by the tree. The algorithm also allows for rooting of unrooted trees and for removal of in-paralogues (lineage-specific duplicates and redundant sequences masquerading as such). The algorithm has also been made available for download as a software package, Softparsmap.

背景与目标： 基因复制和基因丢失以及其他生物学事件可导致给定物种中基因的多个拷贝。由于这些基因的复制和丢失动态，除了序列进化的变化和其他不确定性来源外，不同的基因树最终呈现出不同的进化历史。所有这些共同导致基因树相互提供不同的拓扑结构，从而使共有物种树在某些地方变得模棱两可。用于生成物种树的其他数据源也无法提供完全解析的二元物种树。但是，除了基因复制事件外，物种形成事件还提供了一些潜在的系统发育信号，从而能够开发出表征这些过程的算法。因此，已经开发了一种软简约算法，该算法可以基于使树隐含的基因重复和丢失事件的数量最小化，将基因树映射到树种上，并对不确定或弱支持的分支进行修改。该算法还允许无根树木生根，并删除旁系同源物（特定于谱系的重复片段和伪装成这样的冗余序列）。该算法还可以作为软件包Softparsmap下载。

BACKGROUND & AIMS: :Pyelonephritis-associated pili (Pap) are important in the pathogenesis of ascending, unobstructive Escherichia coli-caused renal infections because these surface bacterial organelles mediate digalactoside-specific binding to host uroepithelial cells. Pap are composed of many different polypeptides, of which only the tip proteins mediate specific binding. The PapA moiety polymerizes to form the bulk of the pilus structure and has been employed in vaccines despite its lack of Gal alpha(1-4)Gal receptor specificity. Animal recipients of PapA pilus-based vaccines are protected against experimental pyelonephritis caused by homologous and heterologous Gal-Gal-binding uropathogenic E. coli strains. Specific PapA immunoglobulin G antibodies in urine are correlated with protection in these infection models. The nucleotide sequences of the gene encoding PapA were determined for three E. coli clones expressing F7(1), F7(2), and F9 pili and were compared with corresponding sequences for other F serotypes. Specific rabbit antisera were employed in enzyme-linked immunosorbent assays to study the cross-reactivity between Gal-Gal pili purified from recombinant strains expressing F7(1), F7(2), F9, or F13 pili and among 60 Gal-Gal-binding wild-type strains. We present data which corroborate the concept that papA genes are highly homologous and encode proteins which exhibit greater than 70% homology among pili of different serotypes. The differences primarily occur in the cysteine-cysteine loop and variable regions and constitute the basis for serological diversity of these pili. Although there are differences in primary structures among these pili, antisera raised against pili of one serotype cross-reacted frequently with many other Gal-Gal pili of different serotypes. Furthermore, antisera raised against pili of the F13 serotype cross-reacted strongly or moderately with 52 (86%) of 60 wild-type Gal-Gal-binding E. coli strains. These data suggest that there are common immunogenic domains among these proteins. These additional data further support the hypothesis that broadly cross-protective PapA pilus vaccines for the immunoprophylaxis of pyelonephritis might be developed.

背景与目标： ：肾盂肾炎相关菌毛（Pap）在上升，畅通无阻的大肠埃希菌引起的肾脏感染的发病机理中很重要，因为这些表面细菌细胞器介导洋半乳糖苷与宿主尿道上皮细胞的特异性结合。子宫颈癌由许多不同的多肽组成，其中只有末端蛋白才能介导特异性结合。 PapA部分聚合形成菌毛结构的大部分，尽管缺乏Gal alpha（1-4）Gal受体特异性，但已用于疫苗中。基于PapA菌毛的疫苗的动物接受者受到保护，可抵抗由同源和异源结合Gal-Gal的泌尿道致病性大肠杆菌菌株引起的实验性肾盂肾炎。在这些感染模型中，尿液中的特异性PapA免疫球蛋白G抗体与保护作用相关。确定三个表达F7（1），F7（2）和F9 pili的大肠杆菌克隆的编码PapA的基因的核苷酸序列，并将其与其他F血清型的相应序列进行比较。特定的兔抗血清用于酶联免疫吸附测定中，研究从表达F7（1），F7（2），F9或F13菌毛的重​​组菌株纯化的Gal-Gal菌毛与60个Gal-Gal结合蛋白之间的交叉反应性野生型菌株。我们提供的数据证实了papA基因高度同源并编码在不同血清型菌毛之间显示出大于70％同源性的蛋白质的概念。差异主要发生在半胱氨酸-半胱氨酸环和可变区，并构成这些菌毛的血清学多样性的基础。尽管这些菌毛的一级结构存在差异，但是针对一种血清型菌毛产生的抗血清通常会与许多其他血清型的Gal-Gal菌毛发生交叉反应。此外，针对F13血清型菌毛的抗血清与60种野生型Gal-Gal结合大肠杆菌菌株中的52种（86％）发生了强烈或中度交叉反应。这些数据表明这些蛋白质之间存在共同的免疫原性结构域。这些额外的数据进一步支持以下假设：可以开发出广泛的交叉保护性PapA菌毛疫苗，用于肾盂肾炎的免疫预防。

BACKGROUND & AIMS: UNLABELLED:The objective of this study was to develop an automatic image registration technique capable of compensating for kidney motion in renal perfusion MRI, to assess the effect of renal artery stenosis on the kidney parenchyma. MATERIALS AND METHODS:Images from 20 patients scheduled for a renal perfusion study were acquired using a 1.5 T scanner. A free-breathing 3D-FSPGR sequence was used to acquire coronal views encompassing both kidneys following the infusion of Gd-BOPTA. A two-step registration algorithm was developed, including a preliminary registration minimising the quadratic difference and a fine registration maximising the mutual information (MI) between consecutive image frames. The starting point for the MI-based registration procedure was provided by an adaptive predictor that was able to predict kidney motion using a respiratory movement model. The algorithm was validated against manual registration performed by an expert user. RESULTS:The mean distance between the automatically and manually defined contours was 2.95 ± 0.81 mm, which was not significantly different from the interobserver variability of the manual registration procedure (2.86 ± 0.80 mm, P = 0.80). The perfusion indices evaluated on the manually and automatically extracted perfusion curves were not significantly different. CONCLUSIONS:The developed method is able to automatically compensate for kidney motion in perfusion studies, which prevents the need for time-consuming manual image registration.

背景与目标： 取消标记：这项研究的目的是开发一种能够在肾脏灌注MRI中补偿肾脏运动的自动图像配准技术，以评估肾动脉狭窄对肾脏实质的影响。
材料与方法：使用1.5T扫描仪从计划进行肾脏灌注研究的20位患者中获取图像。自由呼吸的3D-FSPGR序列用于在注入Gd-BOPTA之后获取涵盖两个肾脏的冠状视图。开发了一种两步配准算法，包括使二次方差最小的预配准和使连续图像帧之间的互信息（MI）最大化的精细配准。基于MI的注册过程的起点由自适应预测器提供，该预测器能够使用呼吸运动模型预测肾脏运动。针对专家用户执行的手动注册对算法进行了验证。
结果：自动和手动定义的轮廓之间的平均距离为2.95±0.81 mm，与手动注册程序的观察者间差异（2.86±0.80 mm，P = 0.80）没有显着差异。在手动和自动提取的灌注曲线上评估的灌注指数没有显着差异。
结论：开发的方法能够在灌注研究中自动补偿肾脏运动，从而避免了耗时的手动图像配准。

BACKGROUND & AIMS: :Satellite laser-ranging is successfully used in space geodesy, geodynamics and Earth sciences; and to test fundamental physics and specific features of General Relativity. We present a confirmation to approximately one part in a billion of the fundamental weak equivalence principle ("uniqueness of free fall") in the Earth's gravitational field, obtained with three laser-ranged satellites, at previously untested range and with previously untested materials. The weak equivalence principle is at the foundation of General Relativity and of most gravitational theories.

背景与目标： ：卫星激光测距技术已成功用于太空大地测量学，地球动力学和地球科学中；并测试广义相对论的基本物理学和特定特征。我们对地球引力场中十亿分之一的基本弱当量原理（“自由落体的唯一性”）进行了确认，该原理是由三颗激光测距卫星，以前未经测试的范围和未经测试的材料获得的。弱等价原理是广义相对论和大多数引力论的基础。

BACKGROUND & AIMS: :Chromosome-specific regulatory mechanisms provide a model to understand the coordinated regulation of genes on entire chromosomes or on larger genomic regions. In fruit flies, two chromosome-wide systems have been characterized: The male-specific lethal (MSL) complex, which mediates dosage compensation and primarily acts on the male X-chromosome, and Painting of fourth (POF), which governs chromosome-specific regulation of genes located on the 4th chromosome. How targeting of one specific chromosome evolves is still not understood; but repeated sequences, in forms of satellites and transposable elements, are thought to facilitate the evolution of chromosome-specific targeting. The highly repetitive 1.688 satellite has been functionally connected to both these systems. Considering the rapid evolution and the necessarily constant adaptation of regulatory mechanisms, such as dosage compensation, we hypothesised that POF and/or 1.688 may still show traces of dosage-compensation functions. Here, we test this hypothesis by transcriptome analysis. We show that loss of Pof decreases not only chromosome 4 expression but also reduces the X-chromosome expression in males. The 1.688 repeat deletion, Zhr1(Zygotic hybrid rescue), does not affect male dosage compensation detectably; however, Zhr1 in females causes a stimulatory effect on X-linked genes with a strong binding affinity to the MSL complex (genes close to high-affinity sites). Lack of pericentromeric 1.688 also affected 1.688 expression in trans and was linked to the differential expression of genes involved in eggshell formation. We discuss our results with reference to the connections between POF, the 1.688 satellite and dosage compensation, and the role of the 1.688 satellite in hybrid lethality.

背景与目标： ：特定于染色体的调控机制提供了一个模型，以了解整个染色体或更大基因组区域上基因的协调调控。在果蝇中，已鉴定出两个染色体全系统：雄性特异性致死（MSL）复合物，其介导剂量补偿并主要作用于雄性X染色体，以及第四种绘画（POF），其控制染色体特异性调节位于第4条染色体上的基因。仍然不了解靶向某一特定染色体的进化方式。但是卫星和转座因子形式的重复序列被认为有助于染色体特异性靶向的进化。高度重复的1.688卫星已在功能上连接到这两个系统。考虑到诸如剂量补偿之类的调节机制的迅速发展和必然不断的适应，我们假设POF和/或1.688可能仍显示出痕量的剂量补偿功能。在这里，我们通过转录组分析来检验该假设。我们显示，Pof的丧失不仅降低了4号染色体的表达，而且还降低了男性的X染色体表达。 1.688重复缺失Zhr1（合子杂种抢救）不会明显影响男性的剂量补偿；然而，雌性中的Zhr1对X连锁基因产生刺激作用，对MSL复合物具有很强的结合亲和力（基因靠近高亲和力位点）。缺乏着丝粒的1.688也影响反式1.688的表达，并且与蛋壳形成相关基因的差异表达有关。我们参考POF，1.688卫星和剂量补偿之间的联系以及1.688卫星在混合杀伤力中的作用来讨论我们的结果。

BACKGROUND & AIMS: :The c-fos proto-oncogene provides a good system to study the processes underlying messenger RNA degradation. After growth factor stimulation of susceptible cells, the c-fos transcription rate transiently increases from a low basal level by as much as 50-fold, producing a large amount of exceedingly unstable c-fos mRNA that is rapidly degraded. Here, we investigate the c-fos mRNA degradation process, and find that: (1) ongoing translation of the c-fos mRNA itself is required for its degradation; (2) after synthesis, the mRNA poly(A) tail is rapidly removed, in a translation-dependent manner, leading to accumulation of apparently deadenylated RNA; (3) deletion or replacement of an AU-rich sequence at the mRNA 3' end significantly stabilizes the mRNA; (4) deletion of the 3' AU-rich sequences dramatically slows the poly(A) shortening rate. These results suggest that the 3' AU-rich sequences act to destabilize the mRNA by directing rapid removal of the mRNA poly(A) tract.

背景与目标： ：c-fos原癌基因提供了一个很好的系统，用于研究信使RNA降解的基础过程。在易感细胞的生长因子刺激后，c-fos转录速率从低基础水平瞬时增加了多达50倍，从而产生了大量极其不稳定的c-fos mRNA，并迅速降解。在这里，我们研究了c-fos mRNA的降解过程，发现：（1）c-fos mRNA本身的持续翻译对其降解是必需的； （2）合成后，以翻译依赖性方式快速去除mRNA poly（A）尾巴，导致明显的去腺苷酸化的RNA积累。 （3）在mRNA 3'末端缺失或替换富含AU的序列可显着稳定mRNA； （4）删除富含3'AU的序列会大大减慢poly（A）的缩短速度。这些结果表明，富含3'AU的序列通过指导快速去除mRNA poly（A）束而使mRNA不稳定。

BACKGROUND & AIMS: BACKGROUND:Immune checkpoint inhibitors are effective in some cases of lung adenocarcinoma (LUAD). Whole-exome sequencing has revealed that the tumour mutation burden (TMB) is associated with clinical benefits among patients from immune checkpoint inhibitors. Several commercial mutation panels have been developed for estimating the TMB regardless of the cancer type. However, different cancer types have different mutational landscapes; hence, this study aimed to develop a small cancer-type-specific mutation panel for high-accuracy estimation of the TMB of LUAD patients. METHODS:We developed a small cancer-type-specific mutation panel based on coding sequences (CDSs) rather than genes, for LUAD patients. Using somatic CDSs mutation data from 486 LUAD patients in The Cancer Genome Atlas (TCGA) database, we pre-selected a set of CDSs with mutation states significantly correlated with the TMB, from which we selected a CDS mutation panel with a panel-score most significantly correlated with the TMB, using a genetic algorithm. RESULTS:A mutation panel containing 106 CDSs of 100 genes with only 0.34 Mb was developed, whose length was much shorter than current commercial mutation panels of 0.80-0.92 Mb. The correlation of this panel with the TMB was validated in two independent LUAD datasets with progression-free survival data for patients treated with nivolumab plus ipilimumab and pembrolizumab immunotherapies, respectively. In both test datasets, survival analyses revealed that patients with a high TMB predicted via the 106-CDS mutation panel with a cut-point of 6.20 mutations per megabase, median panel score in the training dataset, had a significantly longer progression-free survival than those with a low predicted TMB (log-rank p = 0.0018, HR = 3.35, 95% CI 1.51-7.42; log-rank p = 0.0020, HR = 5.06, 95% CI 1.63-15.69). This small panel better predicted the efficacy of immunotherapy than current commercial mutation panels. CONCLUSIONS:The small-CDS mutation panel of only 0.34 Mb is superior to current commercial mutation panels and can better predict the efficacy of immunotherapy for LUAD patients, and its low cost and time-intensiveness make it more suitable for clinical applications.

背景与目标： 背景：免疫检查点抑制剂在某些肺腺癌（LUAD）病例中有效。全外显子组测序显示，肿瘤突变负担（TMB）与免疫检查点抑制剂对患者的临床益处相关。已经开发了几种商业突变专家组来估计TMB，而与癌症类型无关。然而，不同类型的癌症具有不同的突变态势。因此，本研究旨在开发一种小型的癌症类型特异性突变检测板，用于对LUAD患者的TMB进行高精度估算。
方法：我们为LUAD患者开发了一个基于编码序列（CDS）而非基因的小型癌症类型特异性突变组。利用癌症基因组图谱（TCGA）数据库中486位LUAD患者的体细胞CDS突变数据，我们预先选择了一组突变状态与TMB显着相关的CDS，我们从中选择了得分最高的CDS突变专家组使用遗传算法，与TMB显着相关。
结果：开发了一个包含100个基因的106个CDS的突变小组，仅0.34 Mb，其长度比目前的商业突变小组0.80-0.92 Mb短得多。在两个独立的LUAD数据集中验证了该面板与TMB的相关性，分别针对了用nivolumab联合ipilimumab和pembrolizumab免疫疗法治疗的患者提供无进展生存数据。在这两个测试数据集中，生存分析表明，通过106-CDS突变小组预测的TMB高的患者，每百万碱基的切入点为6.20突变，训练数据集中的中位小组得分，其无进展生存期显着长于无进展生存期。那些预测的TMB较低的人（对数排名p = 0.0018，HR ^ = 3.35，95％CI 1.51-7.42; log-rank p = 0.0020，HR = 5.06，95％CI 1.63-15.69）。这个小小组比目前的商业突变小组更好地预测了免疫疗法的功效。
结论：仅0.34 Mb的小CDS突变面板优于当前的商业突变面板，并且可以更好地预测LUAD患者的免疫疗法的疗效，其低成本和费时的特性使其更适合于临床应用。

BACKGROUND & AIMS: :A differentiation, based on morphological characters, between Stylonychia mytilus and Stylonychia lemnae is very difficult, especially for non-specialists. These two sibling species were considered as one species, S. mytilus, until detailed cytological and genetic studies could show the existence of two genetically isolated varieties. Further morphological and biochemical analyses verified the separation and finally in 1983 a new species S. lemnae was described. The examination of several isoenzymes revealed unambiguous differences in the banding pattern of isocitrate dehydrogenase (IDH) between these two species. Therefore, the IDH gene of 30 isolates of S. lemnae and S. mytilus coming from various regions all over the world were amplified and sequenced. The sequence analyses revealed intraspecific as well as interspecific substitutions, which were used for the development of species-specific PCR primers for both species. Application of these species-specific primer pairs now allows a very easy and clear identification of both sibling species.

背景与目标： ：在形态特征上，Mytilus和Stylonychia lemnae之间的区分是非常困难的，特别是对于非专业人士而言。直到详细的细胞学和遗传学研究表明存在两个遗传分离的变种之前，这两个兄弟姐妹种才被认为是一种S. mytilus。进一步的形态学和生化分析证实了分离，最后在1983年描述了一个新种S. lemnae。对几种同工酶的检查表明，这两个物种之间的异柠檬酸脱氢酶（IDH）的带谱模式无明显差异。因此，扩增并测序了来自世界各地的30株柠檬肉链球菌和枯草链球菌的IDH基因。序列分析揭示了种内和种间取代，这些被用于开发两个物种的物种特异性PCR引物。现在，这些物种特异性引物对的应用可以非常轻松，清晰地鉴定两个同胞物种。

BACKGROUND & AIMS: :The reconstruction of relationships within recently radiated groups is challenging even when massive amounts of sequencing data are available. The use of restriction site-associated DNA sequencing (RAD-Seq) to this end is promising. Here, we assessed the performance of RAD-Seq to infer the species-level phylogeny of the rapidly radiating genus Cereus (Cactaceae). To examine how the amount of genomic data affects resolution in this group, we used datasets and implemented different analyses. We sampled 52 individuals of Cereus, representing 18 of the 25 species currently recognized, plus members of the closely allied genera Cipocereus and Praecereus, and other 11 Cactaceae genera as outgroups. Three scenarios of permissiveness to missing data were carried out in iPyRAD, assembling datasets with 30% (333 loci), 45% (1440 loci), and 70% (6141 loci) of missing data. For each dataset, Maximum Likelihood (ML) trees were generated using two supermatrices, i.e., only SNPs and SNPs plus invariant sites. Accuracy and resolution were improved when the dataset with the highest number of loci was used (6141 loci), despite the high percentage of missing data included (70%). Coalescent trees estimated using SVDQuartets and ASTRAL are similar to those obtained by the ML reconstructions. Overall, we reconstruct a well-supported phylogeny of Cereus, which is resolved as monophyletic and composed of four main clades with high support in their internal relationships. Our findings also provide insights into the impact of missing data for phylogeny reconstruction using RAD loci.

背景与目标： ：即使有大量的测序数据，重建最近受辐射的群体之间的关系也具有挑战性。为此目的，与限制性酶切位点相关的DNA测序（RAD-Seq）的使用是有希望的。在这里，我们评估了RAD-Seq的性能，以推断快速辐射的仙影属（Ceraceae）的物种水平的系统发育。为了检查基因组数据的数量如何影响该组的分离度，我们使用了数据集并进行了不同的分析。我们抽样了52头蜡菊个体，代表了目前公认的25个物种中的18种，另外还有紧密联系的Cipocereus和Praecereus属以及其他11个Cactaceae属的成员。在iPyRAD中执行了三种允许丢失数据的方案，组装了30％（333个基因座），45％（1440个基因座）和70％（6141个基因座）的数据集。对于每个数据集，使用两个超矩阵（即仅SNP和SNP加上不变位点）生成最大似然（ML）树。尽管使用了丢失数据的百分比很高（70％），但使用了具有最高基因座数量的数据集（6141个基因座）时，准确性和分辨率得到了改善。使用SVDQuartets和ASTRAL估计的合并树与通过ML重建获得的合并树相似。总体而言，我们重建了一个良好支持的仙影猴的系统发育系统，将其解析为单系统的，由四个主要进化枝组成，这些进化枝在其内部关系中具有高度支持。我们的发现还提供了有关缺失数据对使用RAD基因座进行系统发育重建的影响的见解。

BACKGROUND & AIMS: :Centriolar satellites are dynamic, membraneless granules composed of over 200 proteins. They store, modify, and traffic centrosome and primary cilium proteins, and help to regulate both the biogenesis and some functions of centrosomes and cilium. In most cell types, satellites cluster around the perinuclear centrosome, but their integrity and cellular distribution are dynamically remodeled in response to different stimuli, such as cell cycle cues. Dissecting the specific and temporal functions and mechanisms of satellites and how these are influenced by their cellular positioning and dynamics has been challenging using genetic approaches, particularly in ciliated and proliferating cells. To address this, we developed a chemical-based trafficking assay to rapidly and efficiently redistribute satellites to either the cell periphery or center, and fuse them into stable clusters in a temporally controlled way. Induced satellite clustering at either the periphery or center resulted in antagonistic changes in the pericentrosomal levels of a subset of proteins, revealing a direct and selective role for their positioning in protein targeting and sequestration. Systematic analysis of the interactome of peripheral satellite clusters revealed enrichment of proteins implicated in cilium biogenesis and mitosis. Importantly, induction of peripheral satellite targeting in ciliated cells revealed a function for satellites not just for efficient cilium assembly but also in the maintenance of steady-state cilia and in cilia disassembly by regulating the structural integrity of the ciliary axoneme. Finally, perturbing satellite distribution and dynamics inhibited their mitotic dissolution, and mitotic progression was perturbed only in cells with centrosomal satellite clustering. Collectively, our results for the first time showed a direct link between satellite functions and their pericentrosomal clustering, suggested new mechanisms underlying satellite functions during cilium assembly, and provided a new tool for probing temporal satellite functions in different contexts.

背景与目标： ：卫星状卫星是由200多种蛋白质组成的动态无膜颗粒。它们存储，修饰和运输中心体和初级纤毛蛋白，并帮助调节中心体和纤毛的生物发生和某些功能。在大多数细胞类型中，卫星聚集在核周中心体周围，但是它们的完整性和细胞分布会根据不同的刺激（例如细胞周期提示）而动态重塑。使用遗传方法，尤其是在纤毛和增生细胞中，剖析卫星的特定和暂时的功能和机制以及它们如何受到其细胞定位和动力学的影响一直是具有挑战性的。为了解决这个问题，我们开发了一种基于化学物质的贩运测定法，可以快速有效地将卫星重新分配到细胞外围或中心，并以时间控制的方式将它们融合成稳定的簇。在外围或中心的诱导卫星簇集导致蛋白质亚群的中央体水平的拮抗变化，揭示了它们在蛋白质靶向和螯合中的定位的直接和选择性作用。对外围卫星簇的相互作用组的系统分析表明，与纤毛发生和有丝分裂有关的蛋白质富集。重要的是，在纤毛细胞中诱导外周卫星靶向揭示了卫星不仅具有有效的纤毛组装功能，而且还具有通过调节纤毛轴突的结构完整性来维持稳态纤毛和纤毛分解的功能。最后，扰动的卫星分布和动力学抑制了它们的有丝分裂溶解，有丝分裂的进展仅在具有中心体卫星簇的细胞中受到干扰。总的来说，我们的结果首次显示了卫星功能与其中心周围簇之间的直接联系，在纤毛组装过程中提出了卫星功能背后的新机制，并提供了一种在不同情况下探测时间卫星功能的新工具。

BACKGROUND & AIMS: :Suckers (Family Catostomidae) are holarctic in distribution and include 76 recent species in 14 genera, with 13 genera and 75 species occurring in North and Central America and Siberia. Although this group constitutes a significant component of many aquatic ecosystems, most historic systematic effort has been either alpha- or limited beta-level studies focusing on the two largest tribes within the family, the Catostomini and the Moxostomatini. A recent phylogenetic study based on morphological, biochemical, and early life history characters has advanced current understanding of relationships among catostomid fishes. To further examine phylogenetic relationships among basal lineages of catostomids, we sequenced the entire mitochondrial (mt) SSU and LSU rRNA genes from genera representing all subfamilies and tribes within Catostomidae. Phylogenetic analysis of gene sequences yielded monophyletic Catostomidae, Ictiobinae, and Catostominae and para- or polyphyletic Cycleptinae, with Myxocyprinus as the basal-most taxon and Cycleptus as either the next most-basal taxon or the taxon basal to the Catostominae. Relationships within the Catostominae were generally consistent with those proposed in the above-noted recent phylogenetic study although Thoburnia and Hypentelium were either a clade sister to or a grade group relative to Moxostoma and Scartomyzon. In all trees, Scartomyzon was paraphyletic and embedded within Moxostoma. Phylogenetic affinities of Erimyzon and Minytrema varied depending on data set and character weighting scheme employed. To better reflect phylogenetic relationships resolved in this extensive analysis, we propose the following changes to the classification of catostomids: formation of the new subfamily Myxocyprininae, containing Myxocyprinus from China; restriction of the Cycleptinae to the two species of Cycleptus from North America; restriction of the tribe Moxostomatini to Moxostoma and Scartomyzon; Erimyzon and Minytrema are incertae sedis within Catostominae; and resurrection of the tribe Thoburniini, containing Thoburnia and expanded to include Hypentelium.

背景与目标： ：吸盘（Catastomidae科）分布呈甲状，包括14属中的76个近来种，其中13属和75种在北美洲，中美洲和西伯利亚。尽管该群体构成了许多水生生态系统的重要组成部分，但历史上最系统的研究还是集中于该家族中两个最大的部落Catostomini和Moxostomatini的alpha或有限的beta级研究。最近一项基于形态，生化和早期生命史特征的系统发育研究，已使目前对Catastomid鱼类之间的关系有了更深入的了解。为了进一步检查基础物种之间的系统发育关系，我们对整个线粒体（mt）SSU和LSU rRNA基因进行了测序，该基因来自代表该科的所有亚科和部落。基因序列的系统发育分析产生了单系的Catastomidae，Ictiobinae和Catostominae以及近系或多系的Cycleptina，其中粘液丝藻是最基础的分类群，而Cycleptus则是下一个最基础的分类群或基础的分类群。尽管Thoburnia和Hypentelium是Moxostoma和Scartomyzon的进化分支姐妹或等级组，但Catostotomae内的关系通常与上述最近的系统发育研究中提出的关系一致。在所有树木中，Scartomyzon具有共生能力，并嵌入到Moxostoma中。 Erimyzon和Minytrema的系统发生亲和力取决于数据集和使用的字符加权方案。为了更好地反映在广泛分析中解决的系统发育关系，我们建议对catostomids的分类进行以下更改：形成一个新的亚家族Myxocyprininae，该亚家族包含来自中国的Myxocyprinus。将Cycleptinae限制于来自北美的两种Cycleptus。 Moxostomatini部落对Moxostoma和Scartomyzon的限制； Erimyzon和Minytrema是Catostominae中的不动产。托本（Thoburniini）部落的复活，其中包括托本（Thoburnia），并扩大到包括Hypentelium。

BACKGROUND & AIMS: :Salmonella requires genes on the Salmonella pathogenicity island 1 (SPI1) for the intestinal phase of infection in several models of pathogenesis. In Salmonella enterica serovar Typhimurium, most SPI1 genes are arranged in operons that are coordinately regulated by the SPI1-encoded protein HilA. In the past, it has been shown that HilA directly activates two promoters on SPI1, P(invF-1) and P(prgH). P(invF-1) contains a HilA binding site, termed a HilA box, that is necessary and sufficient for activation by HilA. The HilA box is 17 nucleotides long and contains a direct repeat comprised of two hexamers separated by 5 nucleotides, centered at -45 relative to the start site of transcription. P(prgH) also contains a HilA box, and here we investigate its role at P(prgH). We have found that the HilA box is necessary, but not sufficient, for HilA-dependent activation of P(prgH). Instead, half-site-like hexamers outside the HilA box appear to be required for HilA-dependent activation of P(prgH), even though HilA binds to the HilA box in the absence of these hexamers. Thus, although HilA-dependent activation of P(invF-1) and P(prgH) coordinates the expression of the structural genes for a type III secretion apparatus and the effectors secreted by that apparatus, it is also possible that mechanisms not apparent under in vitro inducing conditions could separate the expression of invFGEABC-spaMNOPQRS-sicA-sipBCDA-iacP-sicP-sptP and prgHIJK-orgABC.

背景与目标： ：沙门氏菌在几种发病机理模型中都需要沙门氏菌致病岛1（SPI1）上的基因来感染肠道。在小肠沙门氏菌血清型鼠伤寒沙门氏菌中，大多数SPI1基因排列在操纵子中，这些操纵子由SPI1编码的蛋白HilA协调调控。在过去，已显示HilA直接激活SPI1上的两个启动子P（invF-1）和P（prgH）。 P（invF-1）包含一个HilA结合位点，称为HilA盒，对于HilA激活是必需的和足够的。 HilA盒长17个核苷酸，并包含直接重复，该直接重复由两个被5个核苷酸分隔的六聚体组成，相对于转录起始位点居中-45。 P（prgH）也包含一个HilA框，在这里我们研究其在P（prgH）中的作用。我们发现，HilA框对于P（prgH）的HilA依赖激活是必要的，但还不够。而是，HilA依赖的P（prgH）激活似乎需要HilA盒外的半位点状六聚体，即使在没有这些六聚体的情况下HilA结合到HilA盒上也是如此。因此，尽管HilA依赖的P（invF-1）和P（prgH）激活可协调III型分泌设备的结构基因的表达以及该设备分泌的效应子，但在体外诱导条件可以分离invFGEABC-spaMNOPQRS-sicA-sipBCDA-iacP-sicP-sptP和prgHIJK-orgABC的表达。

BACKGROUND & AIMS: :A plasmid library of small genomic fragments from the cyanobacterium Anabaena sp. strain PCC 7120 was screened for sequences whose transcripts increase in abundance during a heterocyst development time course. A total of 350 clones were analyzed, representing 1-2% of the Anabaena sp. strain PCC 7120 genome. Twenty-seven clones (8%) showed some degree of up-regulation after nitrogen starvation. The increase in transcript abundance ranged from 1.2-fold to 3.5-fold. Further analysis of the expression of some of the sequences using Northern blots suggested that the up-regulation values calculated from the screen are underestimates. The collection of up-regulated clones includes novel genes, previously characterized genes, and genes identifiable by similarity to known genes. One of the novel genes has been shown to be required for heterocyst function, and the sequence similarities and expression patterns of some of the others suggest that they may play a role in heterocyst development.

背景与目标： ：蓝藻鱼腥藻属小基因组片段的质粒文库筛选PCC 7120菌株中的转录本，该序列的转录本在异型囊发育时间过程中丰度增加。总共分析了350个克隆，占鱼腥藻的1-2％。株PCC 7120基因组。二十七个克隆（8％）在氮饥饿后表现出一定程度的上调。转录丰度的增加范围为1.2倍至3.5倍。使用Northern印迹对某些序列表达的进一步分析表明，从筛选中计算出的上调值被低估了。上调克隆的集合包括新基因，先前表征的基因以及可通过与已知基因的相似性鉴定的基因。已经显示出其中一个新基因是异型囊肿功能所必需的，而另一些基因的序列相似性和表达模式则表明它们可能在异型囊肿的发育中发挥作用。

BACKGROUND & AIMS: :DNA sequence comparisons of two mitochondrial DNA genes were used to infer phylogenetic relationships among four species of mullids. Approximately 238bp of the mitochondrial 16S ribosomal RNA (rRNA) and 261bp of the cytochrome b (cytb) genes were sequenced from representatives of three mullid genera (Mullus, Upeneus, Pseudopeneus), present in the Mediterranean Sea. Trees were constructed using three methods: maximum likelihood (ML), neighbor joining (NJ) and parsimony (MP). The results of the analyses of these data together with published data of the same mtDNA segments of two other perciform species (Sparus aurata, Perca fluviatilis), support the previous taxonomic classification of the three genera examined, as well as the classification of the two red mullet species in the same genus.

背景与目标： ：两个线粒体DNA基因的DNA序列比较被用来推断4种of科动物之间的系统发育关系。从存在于地中海中的三个mullid属（Mullus，Upeneus，Pseudopeneus）的代表对线粒体16S核糖体RNA（rRNA）的约238bp和细胞色素b（cytb）基因进行了测序。使用三种方法构造树：最大似然（ML），邻居加入（NJ）和简约（MP）。这些数据的分析结果以及其他两种perciform物种（Sparus aurata，Perca fluviatilis）的相同mtDNA片段的公开数据，支持先前对这三个属的分类学分类，以及对两种红色的分类。同一属的species鱼种。

BACKGROUND & AIMS: BACKGROUND:Sperm epigenetics is an emerging area of study supported by observations reporting that abnormal sperm DNA methylation patterns are associated with infertility. Here, we explore cytosine-guanine dinucleotides (CpGs) methylation in high (HM) and low motile (LM) Bos taurus sperm populations separated by Percoll gradient. HM and LM methylation patterns were investigated by bisulfite sequencing. RESULTS:Comparison between HM and LM sperm populations revealed that methylation variation affects genes involved in chromatin organization. CpG Islands (CGIs), were highly remodelled. A high proportion of CGIs was found to be methylated at low/intermediate level (20-60%) and associated to the repetitive element BTSAT4 satellite. The low/intermediate level of methylation in BTSAT4 was stably maintained in pericentric regions of chromosomes. BTSAT4 was hypomethylated in HM sperm populations. CONCLUSIONS:The characterization of the epigenome in HM and LM Bos taurus sperm populations provides a first step towards the understanding of the effect of methylation on sperm fertility. Methylation variation observed in HM and LM populations in genes associated to DNA structure remodelling as well as in a repetitive element in pericentric regions suggests that maintenance of chromosome structure through epigenetic regulation is probably crucial for correct sperm functionality.

背景与目标： 背景：精子表观遗传学是一个新兴的研究领域，其观察结果表明，精子DNA甲基化异常与不育有关。在这里，我们探索由Percoll梯度分离的高（HM）和低运动（LM）的金牛座精子群体中的胞嘧啶-鸟嘌呤二核苷酸（CpGs）甲基化。亚硫酸氢盐测序研究了HM和LM甲基化模式。
结果：HM和LM精子种群之间的比较表明，甲基化变异影响染色质组织所涉及的基因。 CpG岛（CGI）进行了高度重塑。发现高比例的CGI在低/中水平（20-60％）处被甲基化，并与重复元素BTSAT4卫星相关。 BTSAT4的甲基化水平处于低/中级水平，在染色体的外周中心区域保持稳定。 BTSAT4在HM精子群体中被低甲基化。
结论：HM和LM金牛座的精子群体的表观基因组的表征为迈向了解甲基化对精子繁殖力的影响迈出了第一步。在HM和LM种群中，与DNA结构重塑相关的基因以及周围中心区域的重复元件中观察到的甲基化变化表明，通过表观遗传调控来维持染色体结构可能对正确的精子功能至关重要。