goCluster integrates statistical analysis and functional interpretation of microarray expression data

Motivation: Several tools that facilitate the interpretation of transcriptional profiles using gene annotation data are available but most of them combine a particular statistical analysis strategy with functional information. goCluster extends this concept by providing a modular framework that facilitates integration of statistical and functional microarray data analysis with data interpretation. Results: goCluster enables scientists to employ annotation information, clustering algorithms and visualization tools in their array data analysis and interpretation strategy. The package provides four clustering algorithms and GeneOntology terms as prototype annotation data. The functional analysis is based on the hypergeometric distribution whereby the Bonferroni correction or the false discovery rate can be used to correct for multiple testing. The approach implemented in goCluster was successfully applied to interpret the results of complex mammalian and yeast expression data obtained with high density oligonucleotide microarrays (GeneChips). Availability: goCluster is available via the BioConductor portal at www.bioconductor.org. The software package, detailed documentation, user- and developer guides as well as other background information are also accessible via a web portal at http://www.bioz.unibas.ch/gocluster. Contact: [email protected]

The Ashbya Genome Database (AGD)—a tool for the yeast community and genome biologists

The Ashbya Genome Database (AGD) is a comprehensive online source of information covering genes from the filamentous fungus Ashbya gossypii. The database content is based upon comparative genome annotation between A.gossypii and the closely related budding yeast Saccharomyces cerevisiae taking both sequence similarity and synteny (conserved order and orientation) into account. Release 2 of AGD contains 4718 protein-encoding loci located across seven chromosomes. Information can be retrieved using systematic or standard locus names from A.gossypii as well as budding and fission yeast. Approximately 90% of the genes in the genome of A.gossypii are homologous and syntenic to loci of budding yeast. Therefore, AGD is a useful tool not only for the various yeast communities in general but also for biologists who are interested in evolutionary aspects of genome research and comparative genome annotation. The database provides scientists with a convenient graphical user interface that includes various locus search and genome browsing options, data download and export functionalities and numerous reciprocal links to external databases including SGD, MIPS, GeneDB, KEGG, GermOnline and Swiss-Prot/TrEMBL. AGD is accessible at http://agd.unibas.c

Cross-platform gene expression signature of human spermatogenic failure reveals inflammatory-like response

BACKGROUND The molecular basis of human testicular dysfunction is largely unknown. Global gene expression profiling of testicular biopsies might reveal an expression signature of spermatogenic failure in azoospermic men. METHODS Sixty-nine individual testicular biopsy samples were analysed on two microarray platforms; selected genes were validated by quantitative real-time PCR and immunohistochemistry. RESULTS A minimum of 188 transcripts were significantly increased on both platforms. Their levels increased with the severity of spermatogenic damage and reached maximum levels in samples with Sertoli-cell-only appearance, pointing to genes expressed in somatic testicular cells. Over-represented functional annotation terms were steroid metabolism, innate defence and immune response, focal adhesion, antigen processing and presentation and mitogen-activated protein kinase K signalling pathway. For a considerable proportion of genes included in the expression signature, individual transcript levels were in keeping with the individual mast cell numbers of the biopsies. When tested on three disparate microarray data sets, the gene expression signature was able to clearly distinguish normal from defective spermatogenesis. More than 90% of biopsy samples clustered correctly into the corresponding category, emphasizing the robustness of our data. CONCLUSIONS A gene expression signature of human spermatogenic failure was revealed which comprised well-studied examples of inflammation-related genes also increased in other pathologies, including autoimmune disease

Global human tissue profiling and protein network analysis reveals distinct levels of transcriptional germline-specificity and identifies target genes for male infertility

BACKGROUND Mammalian spermatogenesis is a process that involves a complex expression program in both somatic and germ cells present in the male gonad. A number of studies have attempted to define the transcriptome of male meiosis and gametogenesis in rodents and primates. Few human transcripts, however, have been associated with testicular somatic cells and germ cells at different post-natal developmental stages and little is known about their level of germline-specificity compared with non-testicular tissues. METHODS We quantified human transcripts using GeneChips and a total of 47 biopsies from prepubertal children diagnosed with undescended testis, infertile adult patients whose spermatogenesis is arrested at consecutive stages and fertile control individuals. These results were integrated with data from enriched normal germ cells, non-testicular expression data, phenotype information, predicted regulatory DNA-binding motifs and interactome data. RESULTS Among 3580 genes for which we found differential transcript concentrations in somatic and germ cells present in human testis, 933 were undetectable in 45 embryonic and adult non-testicular tissues, including many that were corroborated at protein level by published gene annotation data and histological high-throughput protein immunodetection assays. Using motif enrichment analyses, we identified regulatory promoter elements likely involved in germline development. Finally, we constructed a regulatory disease network for human fertility by integrating expression signals, interactome information, phenotypes and functional annotation data. CONCLUSIONS Our results provide broad insight into the post-natal human testicular transcriptome at the level of cell populations and in a global somatic tissular context. Furthermore, they yield clues for genetic causes of male infertility and will facilitate the identification of novel cancer/testis genes as targets for cancer immunotherapie

The Influence of Media Trust and Normative Role Expectations on the Credibility of Fact Checkers

Fact-checking has been granted a pivotal role in mitigating the effects of online disinformation, but its effectiveness has nonetheless been questioned (Lee and Shin Citation2019). Like any persuasive communication, fact checkers depend on their recipients perceiving both their messages and them as credible (Lombardi, Seyranian, and Sinatra Citation2014; Lombardi, Nussbaum, and Sinatra Citation2016). This study investigates the role of the perceived credibility of the fact checker as possible detriment to the effectiveness of fact-checking efforts by means of an online survey-embedded experiment. Results show that the perceived credibility of the fact checker and fact-checking messages is best explained by normative expectations of the roles of fact checkers and trust in traditional media. Some users perceive fact checkers as elite power structures in journalism or, in other words, as collaborative-facilitators for state propaganda (Hanitzsch and Vos Citation2018; see also Fawzi Citation2020). Further, low trust in media and politics predicts perceived credibility of disinformation better than political partisanship. The findings suggest that fact checkers should be more transparent and proactive in communicating their motives and identities. Further implications are discussed

Die epistemische Krise und der Aufstieg des Rechtsextremismus: Zur Konzeptualisierung von Gegenwissensordnungen in der digitalen Wissensgesellschaft

Years of global crises since the turn of the millennium and recently the coronavirus pandemic have made the opening fault lines of rationality in digital knowledge society more visible. This paper draws from work on the digital transformation of knowledge societies. It considers how the conditions of this transformation have not only profoundly influenced the established knowledge order but also facilitated the emergence of counter-knowledge orders. Counter-knowledge orders dissolve knowledge contexts, reorganize hierarchies and claim roles in digitalized knowledge societies to create and maintain subversive alternatives freed of the established order’s rules and impositions. To exemplify the analytical power of counter-knowledge orders as a concept, this paper considers the far right as a counter-knowledge order. This approach is shown to help reconcile the apparent contradictions and inadequacies that are criticized in the dominant counterpublic framework for studying the far right from a knowledge centered perspective. For the far right, the allure of counter-knowledge orders lies in the simultaneous assumption of different social power positions that the established order grants and withholds. The paper concludes that the far-right struggle for hegemony can ultimately be understood as an attempt to (re-) gain control over the entire knowledge process. The anti-democratic, illiberal and exclusionary presuppositions of far-right ideology at the basis of all dimensions of the far-right counter-knowledge order are well-documented in the literature. From a social-epistemologist perspective, however, it is important to stress that counter-knowledge orders are not a‑priori assuming any illiberal ideology per se and may, in different contexts, even be seen as a necessity for a more just knowledge order. The simultaneous danger and necessity of counter-knowledge orders in liberal democracy merit further exploration in the future. Moreover, it is important to scrutinize the societal conditions that uniquely enable the far-right counter-knowledge order to capitalize on these dynamics.Die globalen Krisen seit der Jahrtausendwende, zuletzt die Coronapandemie und Kriege in Nahost sowie der Ukraine, haben Bruchlinien digitaler Wissensgesellschaften deutlicher sichtbar gemacht, die nicht nur entlang von Überzeugungen zum jeweiligen Gegenstand verlaufen, sondern die gesellschaftlichen Systeme und Ordnungen sowie die Mechanismen deren Etablierung selbst in Frage stellen. Dieser Text befasst sich damit, wie die digitale Transformation der Wissensgesellschaft und deren Bedingungen die Entstehung von Gegenwissensordnungen begünstigen. Gegenwissensordnungen nutzen die Bedingungen einer digitalisierten Wissensgesellschaft zur Auflösung von Wissenskontexten, zur Reorganisation von Hierarchien und zur Beanspruchung von Rollen innerhalb dieser Kontexte. Gegenwissensordnungen konstruieren so eine subversive Alternative, die nicht an die Regeln und Zumutungen der etablierten Ordnung gebunden ist. Zur Veranschaulichung des Konzepts der Gegenwissensordnungen, wird hier die extreme Rechte (far right) betrachtet und gezeigt, wie dieser Ansatz unter anderem hilft, scheinbare Widersprüche und Unzulänglichkeiten in der Analyse der Far Right in der politischen Kommunikationsforschung aufzulösen. Die Anziehungskraft einer Gegenwissensordnung für die extreme Rechte liegt in der Gleichzeitigkeit der Inanspruchnahme verschiedener Positionen sozialer Macht, die von der herrschenden Ordnung zugestanden und vorenthalten werden, d. h. in der Verknüpfung von Widerstand und Defensivität. Abschließend wird betont, wie wichtig es ist, die extreme Rechte als eine Gegenwissensordnung zu untersuchen, um ihre potenziellen Auswirkungen auf die liberale Demokratie zu verstehen. Die antidemokratischen, illiberalen und ausgrenzenden Voraussetzungen der rechtsextremen Ideologie, die allen Dimensionen der rechtsextremen Gegenwissensordnung zugrunde liegen, sind in der Literatur gut dokumentiert. Aus einer sozialepistemologischen Perspektive ist es jedoch wichtig zu betonen, dass Gegenwissensordnungen nicht von vornherein eine illiberale Ideologie voraussetzen und in verschiedenen Kontexten sogar als Notwendigkeit für eine gerechtere Wissensordnung angesehen werden können. Die gleichzeitige Gefahr und Notwendigkeit von Gegenwissensordnungen in der liberalen Demokratie verdienen es, in Zukunft weiter erforscht zu werden. Darüber hinaus ist es wichtig, die gesellschaftlichen Bedingungen zu untersuchen, die es der rechtsextremen Gegenwissensordnung ermöglichen, aus dieser Dynamik Kapital zu schlagen

Thinking different as an act of resistance: Reconceptualizing the German protests in the COVID-19 pandemic as an emergent counter-knowledge order

Massive anti-government protests erupted during the COVID-19 pandemic in Germany. The crisis activated a potential for resistance that has been simmering under the impositions of late-modern knowledge society. Made salient by the pandemic conditions of sudden extreme reliance on scientific (non) knowledge, the corona protestors activated this potential for resistance and constructed their own counter-knowledge order bound by shared resentment of and distrust in the established order and facilitated by digital platforms. Utilising social network analysis and structural topic modeling for digital critical discourse analysis, in this paper I explore how the corona protest counter-knowledge order is constructed with a particular focus on its contexts, roles, and hierarchies. I find that far-right and conspiracy imaginations are used to level out hierarchies and detach epistemic roles from their contexts to reinstate a superior self into interpretative power. The counter-knowledge order’s inherent construction of unwarranted omnipotence points to a more fundamental resistance to the established normative orders of our society that should be addressed more effectively if we want to be prepared for future crises and not lose common ground for making sense of them

Database model and specification of GermOnline Release 2.0, a cross-species community annotation knowledgebase on germ cell differentiation

Summary: GermOnline is a web-accessible relational database that enables life scientists to make a significant and sustained contribution to the annotation of genes relevant for the fields of mitosis, meiosis, germ line development and gametogenesis across species. This novel approach to genome annotation includes a platform for knowledge submission and curation as well as microarray data storage and visualization hosted by a global network of servers. Availability: The database is accessible at http://www.germonline.org/. For convenient world-wide access we have set up a network of servers in Europe (http://germonline.unibas.ch/; http://germonline.igh.cnrs.fr/), Japan (http://germonline.biochem.s.u-tokyo.ac.jp/) and USA (http://germonline.yeastgenome.org/). Supplementary information: Extended documentation of the database is available through the link ‘About GermOnline' at the website

Chemical origins of β-Ti stabilization via B<inf>4</inf>C additions in metastable β-Ti alloys and composites

The aerospace industry relies on Ti alloys owing to their strength-to-weight ratio and corrosion resistance. In metastable β-Ti alloys, slow cooling from the β-transus leads to partial transformation into coarse α laths, which is detrimental to the mechanical properties. A refinement and decrease of α laths has been previously achieved in β-Ti alloys with B4C additions. In these materials, the ductility of β-Ti is preserved, and the TiB and TiC particles promote strengthening. However, the mechanism of the β-Ti stabilization remains unclear. Using atom probe tomography, we propose that Mo enrichment in the α-phase limits its growth by reducing the influx of Al from the β-phase. The complex chemical environment near eutectic TiB is enriched in Al and TiO, promoting heterogeneous nucleation of fine α-phase. Increased TiO concentration is observed with the introduction of B4C. A fundamental understanding of the α-refinement mechanism in Ti-alloys is critical for aerospace applications demanding high performance and reliability