GATA transcription factors drive initial Xist upregulation after fertilization through direct activation of a distal enhancer element

To ensure dosage compensation for X-linked genes between the sexes, one X chromosome is silenced during early embryonic development of female mammals. This process of X-chromosome inactivation (XCI) is initiated through upregulation of the RNA Xist from one X chromosome shortly after fertilization. Xist then mediates chromosome-wide gene silencing in cis and remains expressed in all cell types except the germ line and the pluripotent state, where XCI is reversed. The factors that drive Xist upregulation and thereby initiate XCI remain however unknown. We identify GATA transcription factors as potent Xist activators and demonstrate that they are essential for the activation of Xist in mice following fertilization. Through a pooled CRISPR activation screen we find that GATA1 can drive ectopic Xist expression in murine embryonic stem cells (mESCs). We demonstrate that all GATA factors can activate Xist directly via a GATA-responsive regulatory element (RE79) positioned 100 kb upstream of the Xist promoter. Additionally, GATA factors are essential for the induction of XCI in mouse preimplantation embryos, as simultaneous deletion of three members of the GATA family (GATA1/4/6) in mouse zygotes effectively prevents Xist upregulation. Thus, initiation of XCI and possibly its maintenance in distinct lineages of the preimplantation embryo is ensured by the combined activity of different GATA family members, and the absence of GATA factors in the pluripotent state likely contributes to X reactivation. We thus describe a form of regulation in which the combined action of numerous tissue-specific factors can achieve near-ubiquitous expression of a target gene

Global mobility of professionals and the transfer of tacit knowledge in multinational service firms

Purpose: The use of expatriates to transfer individual and organizational know-how and knowledge is a practice widely used by multinational enterprises (MNEs). However, for service firms, the mobility of employees across national borders depends on the commitments made by countries under the General Agreement on Trade in Services (GATS). In particular, the Mode 4 form of supply under GATS can limit the ability of professionals to enter a particular country and can restrict the intra-organizational transfer of knowledge in multinational service firms. The purpose of this paper is to investigate how MNEs attempt to overcome these barriers and transfer knowledge through their global network. Design/methodology/approach: Using Nonaka and Takeuchi’s SECI model of knowledge transfer, the authors study the intra-organizational knowledge transfer practices of an Indian multinational service firm. Semi-structured interviews were conducted with 20 key informants involved with the organization. Findings: The company uses global teams to transfer tacit knowledge and facilitates inpatriation through an internship program that helps the firm overcome nationality requirement that restricts the movement of their managers to other countries, which in turn limits their ability to transfer knowledge in the intra-organizational setting. The company uses the services of a not-for-profit youth organization that helps recruit interns for the program and also facilitates the relationship with the Indian Government, which provides support for this initiative by reducing barriers to entry for the interns. Originality/value: This study takes the unique approach of studying barriers to movement of professionals and a firm’s strategic response. It identifies the pressures and barriers that companies face in the global economy and highlights the role of government agencies and other stakeholders in facilitating or restricting the transfer of knowledge within a firm’s international network. The paper articulates the implications for policy and practice, and a future research agenda

Interpretation and Visualization of Non-Linear Data Fusion in Kernel Space: Study on Metabolomic Characterization of Progression of Multiple Sclerosis

Contains fulltext : 93904.pdf (publisher's version ) (Open Access

Progressive Focusing and Trustworthiness in Qualitative Research: The Enabling Role of Computer-Assisted Qualitative Data Analysis Software (CAQDAS)

* The business and management community increasingly recognises that qualitative research is a ‘messy’, non-linear and often unpredictable undertaking. Yet, a considerable proportion of the qualitative research published in top journals is still presented as the result of a linear, predictable research process, thus wrongly suggesting deductive reasoning. * In this paper, we focus on a particular type of ‘messiness’ where during fieldwork, the research context is revealed to be more complex than anticipated, forcing the researcher to gradually refine/shift their focus to reflect ‘what really matters’. We adopt Stake’s notion of progressive focusing for this gradual approach. * Progressive focusing is well-suited to qualitative research in international business requiring complex iteration between theory and data, and the truthful yet coherent presentation of the research process. We propose that this dual challenge of complexity and trustworthiness may be addressed by using computer-assisted qualitative data analysis software (CAQDAS). * We present conceptual considerations and guidelines and offer a view on a ‘messy’, non-linear doctoral research project conducted using a progressive focusing approach, to demonstrate how CAQDAS can help to develop and re-negotiate insights from theory and interview data, as well as enhance trustworthiness, transparency and publication potential

An interdisciplinary approach to characterize peanut-allergic patients - first data from the FOOD@ consortium

BACKGROUND: Peanut allergy is a frequent cause of food allergy and potentially life-threatening. Within this interdisciplinary research approach, we aim to unravel the complex mechanisms of peanut allergy. As a first step were applied in an exploratory manner the analysis of peanut allergic versus non-allergic controls. METHODS: Biosamples were studied regarding DNA methylation signatures, gut microbiome, adaptive and innate immune cell populations, soluble signaling molecules and allergen-reactive antibody specificities. We applied a scalable systems medicine computational workflow to the assembled data. RESULTS: We identified combined cellular and soluble biomarker signatures that stratify donors into peanut-allergic and non-allergic with high specificity. DNA methylation profiling revealed various genes of interest and stool microbiota differences in bacteria abundances. CONCLUSION: By extending our findings to a larger set of patients (e.g., children vs. adults), we will establish predictors for food allergy and tolerance and translate these as for example, indicators for interventional studies

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities.</p

EFEKTIVITAS PENGAWASAN UNIT KERJA ANTI FRAUD PADA BANK MUAMALAT INDONESIA

Perkembangan perbankan syari‟ah di Indonesia demikian pesat yang ditandai dengan berdirinya Bank Muamalat Indonesia. Perkembangan ini berimplikasi pada besarnya tantangan perbankan syari‟ah di Indonesia terutama dalam mempertahankan identitasnya sebagai perusahaan yang bergerak berlandaskan prinsip-prinsip syari‟ah. Sejak berdirinya perbankan syariah,berbagai kontroversi muncul dari masyarakat, masalah yang paling banyak disorot adalah pelekatan label syariah pada institusi keuangan Islam yang masih dianggap belum layak. Keraguan masyarakat tersebut seolah terjawab dengan munculnya kasus yang cukup menggemparkan yakni kasus fraud (tindak kecurangan) yang terjadi di lembaga syariah. Bank Muamalat Indonesia merupakan bank syari‟ah pertama yang muncul dengan gagasan bank murni syari‟ah. Akan tetapi, bank Muamalat Indonesia juga tak luput dari kasus fraud yang dilakukan oleh karyawan bank tersebut. Berdasarkan Laporan Tahunan BMI menyebutkan bahwa telah terjadi peningkatan kasus fraud dari tahun sebelumnya yang berjumlah 18 kasus menjadi 82 kasus pada tahun 2016. Padahal perusahaan yang menggunakan identitas syariah seharusnya dapat lebih meminimalisir bahkan meniadakan resiko terjadinya kasus fraud dengan adanya internal control perusahaan. Dari latar belakang tersebut, peneliti berusaha mendalami peran pengawasan Unit Kerja Anti Fraud dalam fraud preventive pada Bank Muamalat Indonesia. Penelitian ini merupakan penelitin pustaka yang bersifat deskriptif analisis dengan pendekatan kualitatif. Adapun sumber bahan hukum primer yang dipakai yaitu berdasarkan Laporan Tahunan Bank Muamalat Indonesia Tahun 2016. Sedangkan sumber bahan hukum sekunder berupa buku-buku, jurnal,karya ilmiah, artikel, terkait dengan strategi anti fraud perbankan syariah. Dari hasil penelitian dikemukakan bahwa peningkatan kasus fraud yang terjadi pada Bank Muamalat Indonesia disebabkan kurang efektifnya pengawasan Unit Kerja Anti Fraud. Hal ini dikarenakan kegiatan yang dilakukan selama tahun 2016 belum menujukkan adanya usaha preventif terhadap kasus fraud. Sedangkan pencegahan merupakan pilar penting dalam keefektivan sebuah pengawasan. Tujuan perusahaan dalam mencegah fraud dapat tercapai, jika fungsi pengawasan dilakukan sebelum terjadinya penyimpangan-penyimpangan sehingga lebih bersifat mencegah (prefentive control). Oleh karena itu, keefektivan pengawasan Unit Kerja Anti Fraud diharapkan dapat meminimalisir tindak kecurangan demi mewujudkan perusahaan yang patuh terhadap ketentuan syariah sesuai dengan identitas perusahaan. vii Usaha pencegahan terjadinya kasus pada Bank Muamalat Indonesia diharapkan dapat menjadi bukti terlaksananya tatakelola perusahaan (Good Corporate Governance) pada Bank Syari‟ah dengan baik. Hal ini berdasarkan dalam dalam perbankan syariah dikenal adanya prinsip-prinsip syariah yang mendukung bagi terlaksananya prinsip GCG yakni keharusan bagi subjek hukum termasuk bank untuk menerapkan prinsip kejujuran (shiddiq), edukasi kepada masyarakat (tabligh), kepercayaan (amanah), dan pengelolaan secara profesional (fathanah)

European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities