Taxon sampling and the accuracy of phylogenetic analyses

Appropriate and extensive taxon sampling is one of the most important determinants of accurate phylogenetic estimation. In addition, accuracy of inferences about evolutionary processes obtained from phyloge-netic analyses is improved significantly by thorough taxon sampling efforts. Many recent efforts to improve phylogenetic estimates have focused instead on increasing sequence length or the number of overall characters in the analysis, and this often does have a beneficial effect on the accuracy of phylogenetic analyses. However, phylogenetic analyses of few taxa (but each represented by many characters) can be subject to strong systematic biases, which in turn produce high measures of repeatability (such as bootstrap proportions) in support of incor-rect or misleading phylogenetic results. Thus, it is important for phylogeneticists to consider both the sampling of taxa, as well as the sampling of characters, in designing phylogenetic studies. Taxon sampling also improves estimates of evolutionary parameters derived from phylogenetic trees, and is thus important for improved applica-tions of phylogenetic analyses. Analysis of sensitivity to taxon inclusion, the possible effects of long-branch attraction, and sensitivity of parameter estimation for model-based methods should be a part of any careful and thorough phylogenetic analysis. Furthermore, recent improvements in phylogenetic algorithms and in computa-tional power have removed many constraints on analyzing large, thoroughly sampled data sets. Thorough taxon sampling is thus one of the most practical ways to improve the accuracy of phylogenetic estimates, as well as the accuracy of biological inferences that are based on these phylogenetic trees.

Transcriptome and Functional Analysis of Fiber-related Gene Expression in Cotton

Fiber cell initiation is a complex process involving many pathways,including phytohormones and components for transcriptional and posttranscriptional regulation.Here we report expression

Sarve:synthetic data and local differential privacy for private frequency estimation

The collection of user attributes by service providers is a double-edged sword.They are instrumental in driving statistical analysis to train more accurate predictive models like recommenders.The analysis of the collected user data includes frequency estimation for categorical attributes.Nonetheless,the users deserve privacy guarantees against inadvertent identity disclosures.Therefore algorithms called frequency oracles were developed to randomize or perturb user attributes and estimate the frequencies of their values.We propose Sarve,a frequency oracle that used Randomized Aggregatable Privacy-Preserving Ordinal Response(RAPPOR)and Hadamard Response(HR)for randomization in combination with fake data.The design of a service-oriented architecture must consider two types of complexities,namely computational and communication.The functions of such systems aim to minimize the two complexities and therefore,the choice of privacy-enhancing methods must be a calculated decision.The variant of RAPPOR we had used was realized through bloom flters.A bloom filter is a memory-efficient data structure that offers time complexity of O(1).On the other hand,HR has been proven to give the best communication costs of the order of log(b)for b-bits communication.Therefore,Sarve is a step towards frequency oracles that exhibit how privacy provisions of existing methods can be combined with those of fake data to achieve statistical results comparable to the original data.Sarve also implemented an adaptive solution enhanced from the work of Arcolezi et al.The use of RAPPOR was found to provide better privacy-utility tradeoffs for specific privacy budgets in both high and general privacyregimes.

Rice Interploidy Crosses Disrupt Epigenetic Regulation, Gene Expression, and Seed Development

在被子植物的种子开发在内乳要求 2:1 maternal-to-paternal 染色体比率(2m:1p ) 。当比率被破坏时，种子发展被损害。瑞斯 interploidy 十字导致内乳失败，但是内在的分子的机制仍然保持不清楚。这里，我们报导在米饭 interploidy 十字的有缺点的内乳与小 RNA 和编码蛋白质的基因的 nonadditive 表示被联系。有趣地， 24-nt 小介入 RNA 被充实在 5 和 3 ? flanking 序列 nonadditively 在 interploidy 十字表示了基因并且否定地与印的基因的表示被联系。而且，一些 PRC2 家庭基因和 DNA 包括 OsMET1b 和 OsCMT3a 的 methylation 相关的基因是在 2 湡散愠摮椠据敲獡摥礠敩摬鵸?鵸 的 upregulated？？

Prostate-associated gene 4 （PAGE4）, an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer

联系前列腺的基因(PAGE4 ) 4 是是的显著地前列腺特定的癌症 / 睾丸抗原高度，在人的胎儿的前列腺和它的 diseased 的 upregulated 说然而并非在成年的正常的腺。PAGE4 是作为压力反应蛋白质工作压制反应的氧种类以及阻止 DNA 损坏的内在地混乱的蛋白质(IDP ) 。另外， PAGE4 也是加强的一个 transcriptional 管理者由 oncogene c-Jun.c6 月的 transactivation 与 Fos 家庭的成员一起由 heterodimerizing 形成 AP-1 建筑群并且在前列腺的发展和病理起一个重要作用，强调 PAGE4/c-Jun 相互作用的重要性。HIPK1，另外压力反应小径的一个部件，在为它的 transcriptional 活动批评的 T51 的 phosphorylates PAGE4。Phosphorylation 导致 conformational 并且在导致新细胞的功能的 PAGE4 整体的动态切换。最后，生物信息学证据建议 PAGE4 mRNA 能或者被拼接导致与潜伏的功能提到 conformational 整体的一个范围的可能性的多肽的四潜在的 isoforms。一起考虑了，数据建议 PAGE4 可以代表在应力和前列腺癌症(PCa ) 之间的第一个分子的连接。因此， pharmacologically 指向 PAGE4 可以是为与 PCa 对待并且设法病人的一个新奇机会，特别有低风险的疾病的病人。

An Epigenetic Role for Disrupted Paternal Gene Expression in Postzygotic Seed Abortion in Arabidopsis Interspecific Hybrids

种间的混血儿经常增加杂合现象和混合活力的层次，而是一些种间的混合种子立即在授精以后被放弃。在这 postzygotic 种子流产后面的机制糟糕被理解。这里，我们在在在 Arabidopsis thaliana (关口， Ler，或 C24 ) 和 Arabidopsis arenosa 之间的三个 F1 种间的十字开发 siliques 和种子报导突变而产生之遗传的表示变化的染色体宽的分析。似母亲的多数表示了基因(MEG ) 而 272 父亲一般地表示的基因(木钉) 的 ∼90% 仅仅在一或二个 F1 十字被发现，在所有三个 F1 种间的十字之中被分享，在在不同十字变化的种子流产为破坏父亲的基因表示建议一个角色。与这个观点一致，在不肥沃的种间的混血儿的 12 个木钉在肥沃的 intraspecific 混血儿匹配 MEG。在种间的混血儿的木钉的这混乱与在在一位双母亲和一位 hexaploid 父亲之间的父亲过量的 interploidy 十字(2X6 ) 的基因的 upregulation 一致，导致种子流产。而且，在种间的十字的木钉的一个子集也是在 intraspecific 混血儿 met1XWT 或 meaXWT 的 upregulated，在哪个 MET1 (DNA METHYLTRANSFERASE1 ) 的异种或美狄亚， Polycomb 压抑的 Complex2gene，被用作母亲的父母。这些数据建议母亲的 epigenetic 因素和父亲的基因表示在种间的混血儿或 neo-allopolyploids 在 postzygotic 种子流产起重要作用。

Distinct transcriptomic landscapes of cutaneous basal cell carcinomas and squamous cell carcinomas

The majority of non-melanoma skin cancer(NMSC)is cutaneous basal cell carcinoma(BCC)or squamous cell carcinoma(SCC),which are also called keratinocyte carcinomas,as both of them originate from keratinocytes.The incidence of keratinocyte carcinomas is over 5 million per year in the US,three-fold higher than the total incidence of all other types of cancer combined.While there are several reports on gene expression profiling of BCC and SCC,there are significant variations in the reported gene expression changes in different studies.One reason is that tumor-adjacent normal skin specimens were not included in many studies as matched controls.Furthermore,while numerous studies of skin stem cells in mouse models have been reported,their relevance to human skin cancer remains unknown.In this report,we analyzed gene expression profiles of paired specimens of keratinocyte carcinomas with their matched normal skin tissues as the control.Among several novel findings,we discovered a significant number of zinc finger encoding genes up-regulated in human BCC.In BCC,a novel link was found between hedgehog signaling,Wnt signaling,and the cilium.While the SCC cancerstem-cell gene signature is shared between human and mouse SCCs,the hair follicle stem-cell signature of mice was not highly represented in human SCC.Differential gene expression(DEG)in human BCC shares gene signature with both bulge and epidermal stem cells.We have also determined that human BCCs and SCCs have distinct gene expression patterns,and some of them are not fully reflected in current mouse models.

Suppression of monosodium urate crystal-induced inflammation by inhibiting TGF-β-activated kinase 1-dependent signaling:role of the ubiquitin proteasome system

Monosodium urate(MSU)crystals activate inflammatory pathways that overlap with interleukin-1β(IL-1β)signaling.However,the post-translational mechanisms involved and the role of signaling proteins in this activation are unknown.In the present study,we investigated the intracellular signaling mechanisms involved in MSU-induced activation of THP-1 macrophages and human nondiseased synovial fibroblasts(NLSFs)and the in vivo efficacy of an inhibitor of tumor grovArth factor-β(TGF-β)-activated kinase 1(TAK1),5Z-7-oxozeaenoI,in MSU-induced paw inflammation in C57BL76 mice.THP-1 macrophage activation with MSU crystals(25-200 ng/ml)resulted in the rapid and sustained phosphorylation of interleukin-1 receptor-activated kinase 1(IRAK1 Thr^(209))and TAK1(Thr^(184/187))and their association with the E3 ubiquitin ligase TRAF6.At the cellular level,MSU inhibited the deubiquitinases A20 and UCHL2 and increased 20s proteasomal activity,leading to a global decrease in K^(63)-linked ubiquitination and increase in K^(48)-linked ubiquitination in THP-1 macrophages.While MSU did not stimulate cytokine produaion in NLSFs,it significantly amplified IL-1β-induced IL-6,IL-8,and ENA-78/CXCL5 production.Docking studies and MD simulations followed by TAK1 in vitro kinase assays revealed that uric acid molecules are capable of arresting TAK1 in an active-state conformation,resulting in sustained TAK1 kinase activation.Importantly,MSU-induced proinflammatory cytokine production was completely inhibited by 5Z-7-oxozeaenol but not IRAK1/4 or TRAF6 inhibitors.Administration of 5Z-7-oxozeaenol(5 or 15 mg/kg;orally)significantly inhibited MSU-induced paw inflammation in C57BL/6 mice.Our study identifies a novel post-translational mechanism of TAK1 activation by MSU and suggests the therapeutic potential of TAK1 in regulating MSU-induced Inflammation.

Differential Splicing of Skipped Exons Predicts Drug Response in Cancer Cell Lines

Alternative splicing of pre-mRNA transcripts is an important regulatory mechanism that increases the diversity of gene products in eukaryotes.Various studies have linked specific transcript isoforms to altered drug response in cancer;however,few algorithms have incorporated splicing information into drug response prediction.In this study,we evaluated whether basal-level splicing information could be used to predict drug sensitivity by constructing doxorubicin-sensitivity classification models with splicing and expression data.We detailed splicing differences between sensitive and resistant cell lines by implementing quasi-binomial generalized linear modeling(QBGLM)and found altered inclusion of 277 skipped exons.We additionally conducted RNA-binding protein(RBP)binding motif enrichment and differential ex-pression analysis to characterize cis-and trans-acting elements that potentially influence doxorubicin response-mediating splicing alterations.Our results showed that a classification model built with skipped exon data exhibited strong predictive power.We discovered an association between differentially spliced events and epithelial-mesenchymal transition(EMT)and observed motif enrichment,as well as differential expression of RBFOX and ELAVL RBP family members.Our work demonstrates the potential of incorporating splicing data into drug response algorithms and the utility of a QBGLM approach for fast,scalable identification of relevant splicing differences between large groups of samples.

Model-based Comparative Prediction of Transcription-Factor Binding Motifs in Anabolic Responses in Bone

Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm,a biologically-inspired computational technique for microarray data,and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software,Ant Modeler,and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both "anabolic responses of mechanical loading" and "BMP-mediated osteogenic signaling"? Although there is no significant overlap among genes in the two responses,a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs,such as a stress responsive element and a motif for peroxisome proliferator-activated recep-tor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells sup-ported involvements of the predicted TFBMs such as PPAR,Ikaros 3,and LMO2 in response to mechanical loading. Taken together,the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.