Human cancers over express genes that are specific to a variety of normal human tissues

We have analyzed gene expression data from 3 different kinds of samples: normal human tissues, human cancer cell lines and leukemic cells from lymphoid and myeloid leukemia pediatric patients. We have searched for genes that are over expressed in human cancer and also show specific patterns of tissue-dependent expression in normal tissues. Using the expression data of the normal tissues we identified 4346 genes with a high variability of expression, and clustered these genes according to their relative expression level. Of 91 stable clusters obtained, 24 clusters included genes preferentially expressed either only in hematopoietic tissues or in hematopoietic and 1-2 other tissues; 28 clusters included genes preferentially expressed in various non-hematopoietic tissues such as neuronal, testis, liver, kidney, muscle, lung, pancreas and placenta. Analysis of the expression levels of these 2 groups of genes in the human cancer cell lines and leukemias, identified genes that were highly expressed in cancer cells but not in their normal counterparts, and were thus over expressed in the cancers. The different cancer cell lines and leukemias varied in the number and identity of these over expressed genes. The results indicate that many genes that are over expressed in human cancer cells are specific to a variety of normal tissues, including normal tissues other than those from which the cancer originated. It is suggested that this general property of cancer cells plays a major role in determining the behavior of the cancers, including their metastatic potential.Comment: To appear in PNA

Language impairment in bilingual children: state of the art 2017

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A Minimum-Labeling Approach for Reconstructing Protein Networks across Multiple Conditions

The sheer amounts of biological data that are generated in recent years have driven the development of network analysis tools to facilitate the interpretation and representation of these data. A fundamental challenge in this domain is the reconstruction of a protein-protein subnetwork that underlies a process of interest from a genome-wide screen of associated genes. Despite intense work in this area, current algorithmic approaches are largely limited to analyzing a single screen and are, thus, unable to account for information on condition-specific genes, or reveal the dynamics (over time or condition) of the process in question. Here we propose a novel formulation for network reconstruction from multiple-condition data and devise an efficient integer program solution for it. We apply our algorithm to analyze the response to influenza infection in humans over time as well as to analyze a pair of ER export related screens in humans. By comparing to an extant, single-condition tool we demonstrate the power of our new approach in integrating data from multiple conditions in a compact and coherent manner, capturing the dynamics of the underlying processes.Comment: Peer-reviewed and presented as part of the 13th Workshop on Algorithms in Bioinformatics (WABI2013

Enrichment and aggregation of topological motifs are independent organizational principles of integrated interaction networks

Topological network motifs represent functional relationships within and between regulatory and protein-protein interaction networks. Enriched motifs often aggregate into self-contained units forming functional modules. Theoretical models for network evolution by duplication-divergence mechanisms and for network topology by hierarchical scale-free networks have suggested a one-to-one relation between network motif enrichment and aggregation, but this relation has never been tested quantitatively in real biological interaction networks. Here we introduce a novel method for assessing the statistical significance of network motif aggregation and for identifying clusters of overlapping network motifs. Using an integrated network of transcriptional, posttranslational and protein-protein interactions in yeast we show that network motif aggregation reflects a local modularity property which is independent of network motif enrichment. In particular our method identified novel functional network themes for a set of motifs which are not enriched yet aggregate significantly and challenges the conventional view that network motif enrichment is the most basic organizational principle of complex networks.Comment: 12 pages, 5 figure

‘L’homosexualité? ça n’existe pas en banlieue’: the indigènes de la république and gay marriage, between intersectionality and homophobia

Since its founding in 2005, the anti-racist organisation Les Indigènes de la République has acquired a certain notoriety in the French public eye as a fresh voice of the anti-racist Left. The Indigènes combined postcolonial and intersectional analysis with more traditional forms of anti-racist activism. This article examines how the Indigènes engaged with LGBTQ minorities as they tried to articulate ‘intersectional’ views of the Republic. While the intersection of gender and race was central to the emergence of the organisation in 2004, the Indigènes have mostly avoided addressing issues relevant to the LGBTQ communities. The one exception to this rule occurred in the wake of the Marriage pour tous protests against the legalisation of same-sex marriage, where the organisation equated ‘homosexual identity’ with colonial oppression. Using interviews and publication material, this article explores the gestation of the Indigènes’ position on the issue of same-sex marriage, with its contradictions between a left-wing discourse that prioritised an idea of social justice through inclusion of all oppressed minorities and the desire to represent a marginalised constituency that was often unsympathetic to LGBTQ issues. Their choice highlights the difficulties of analysing the volatile political reality in contemporary France through abstract notions of social justice

Between Resistance and the State: Caribbean Activism and the Invention of a National Memory of Slavery in France

Between 1998 and 2006, the memory of slavery in France developed from a marginalized issue into a priority of the state. This article examines the process in which community activists and state actors interacted with and against one another to integrate remembrance and the commemoration of slavery and its abolitions into a Republican national narrative. It focuses on a series of actions from the protests against the 150th anniversary of the abolition of slavery in 1998 to the creation of the 10 May National Memorial Day to Slavery and Its Abolitions in 2006. Basing its analysis on oral-history interviews and various publications, this article argues that “memory activists” – and particularly new anti-racist groups – mobilized the memory of slavery to address issues of community identity and resistance within the context of 21st-century Republicanism. In so doing, they articulated a new kind of black identity in France

ResponseNet: revealing signaling and regulatory networks linking genetic transcriptomic screening data

Cellular response to stimuli is typically complex and involves both regulatory and metabolic processes. Large-scale experimental efforts to identify components of these processes often comprise of genetic screening and transcriptomic profiling assays. We previously established that in yeast genetic screens tend to identify response regulators, while transcriptomic profiling assays tend to identify components of metabolic processes. ResponseNet is a network-optimization approach that integrates the results from these assays with data of known molecular interactions. Specifically, ResponseNet identifies a high-probability sub-network, composed of signaling and regulatory molecular interaction paths, through which putative response regulators may lead to the measured transcriptomic changes. Computationally, this is achieved by formulating a minimum-cost flow optimization problem and solving it efficiently using linear programming tools. The ResponseNet web server offers a simple interface for applying ResponseNet. Users can upload weighted lists of proteins and genes and obtain a sparse, weighted, molecular interaction sub-network connecting their data. The predicted sub-network and its gene ontology enrichment analysis are presented graphically or as text. Consequently, the ResponseNet web server enables researchers that were previously limited to separate analysis of their distinct, large-scale experiments, to meaningfully integrate their data and substantially expand their understanding of the underlying cellular response. ResponseNet is available at http://bioinfo.bgu.ac.il/respnet.Seventh Framework Programme (European Commission) (FP7-PEOPLE-MCA-IRG)United States-Israel Binational Science Foundation (Grant 2009323

Beyond memory wars: The indigènes de la république’s grass-roots anti-racism between the memory of colonialism and antisemitism

In the mid-2010s, the expression ‘memory wars’, which had been coined in debates about the role of various commemorations of France’s colonial history, became increasingly identified with an atmosphere of conflict between France’s Jewish population and other minority communities. Simultaneously, conflicts over remembrance of the Holocaust and France’s colonial past characterized a new dynamic of memorial anti-racism. This article examines the trajectory of the Indigènes de la République, an organization that was particularly identified with this kind of memorial anti-racism. Through oral history interviews as well as the organization’s publications and media appearances, this article outlines the role of memory in the growing atmosphere of conflict between Jews and other postcolonial minorities in France and ultimately questions the role of so-called memory wars in the growing conversation about race in the Fifth Republic

The potential of sentence imitation tasks for assessment of language abilities in sequential bilingual children

Sentence repetition tasks are increasingly recognised as a useful clinical tool for diagnosing language impairment in children. They are quick to administer, can be carefully targeted to elicit specific sentence structures, and are particularly informative about children’s lexical and morphosyntactic knowledge. This chapter exlores the theoretical potential of sentence repetition for assessment of sequential bilingual children, and presents three studies comparing performance of sequential bilingual children with monolingual children’s performance on standardised sentence repetition tests in Hebrew (children with L1 Russian, age 5-7 years, and L1 English, age 4½-6½ years), German (children with L1 Russian, age 4-7 years) and English (children with L1 Turkish, age 6-9 years). Results differed across studies: distribution of children in the Hebrew studies was in line with monolingual norms, while the majority of children in the English-Turkish study scored in a range that would be deemed impaired for monolingual children, and performance in the German-Russian study fell between these extremes. Analyses of performance within studies revealed similar discrepancies in effects of children’s exposure to L2, with significant effects of Age of Onset in the Hebrew-Russian and Hebrew-English groups and some indication of Length of Exposure effects, but no effects of either factor in the English-Turkish group. Multiple differences between these studies preclude direct inferences about the reasons for these different results: studies differed in content, methods and scoring of sentence repetition tests, and in ages, languages, language exposure, and socioeconomic status of participants. It is possible that socioeconomic differences are associated with differences in language experience that are equally or more important than onset and length of exposure. Collectively, these studies demonstrate that sentence repetition provides a measure of children’s proficiency in their L2, but that the use of sentence repetition in clinical assessment requires caution unless norms are available for the child’s bilingual community. As a next step, it is proposed that sentence repetition tests using early-acquired vocabulary and targeting aspects of sentence structure known to be difficult for monolingual children with language impairments should be developed in different target languages. This will allow us to explore further the factors that influence attainment of basic morphosyntax in sequential bilingual children, and the point at which sentence repetition, as a measure of morphosyntax, can help to identify children requiring clinical intervention

A game-theoretic model of interspecific brood parasitism with sequential decisions

The interaction between hosts and parasites in bird populations has been studied extensively. This paper uses game-theoretic methods to model this interaction. This has been done in previous papers but has not been studied taking into account the detailed sequential nature of this game. We introduce a model allowing the host and parasite to make a number of decisions which will depend on various natural factors. The sequence of events begins with the host forming a nest and laying a number of eggs, followed by the possibility that a parasite bird will arrive at the nest; if it does it can choose to destroy some of the host eggs and lay one of its own. A sequence of events follows, which is broken down into two key stages; firstly the interaction between the host and the parasite adult, and secondly that between the host and the parasite chick. The final decision involves the host choosing whether to raise or abandon the chicks that are in the nest. There are certain natural parameters and probabilities which are central to these various decisions; in particular the host is generally uncertain whether parasitism has taken place, but can assess the likelihood of parasitism based upon certain cues (e.g. how many eggs remain in its nest). We then use this methodology to model two real-world interactions, that of the Reed Warbler with the Common Cuckoo and also the Yellow Warbler with the Brown-headed Cowbird. These parasites have different methods in the way they parasitize the nests of their hosts, and the hosts can in turn have different reactions to these parasites. Our model predictions generally match the real results well, and the model also makes predictions of the effect of changes in various key parameters on the type of parasitic interactions that should occur