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Changes in transcription factor binding sites (TFBSs) can alter the spatiotemporal expression pattern and transcript abundance of genes. Loss and gain of TFBSs were shown to cause shifts in expression patterns in numerous cases. However, we know little about the evolution of extended regulatory sequences incorporating many TFBSs. We compare, across the crucifers (Brassicaceae, cabbage family), the sequences between the translated regions of Arabidopsis Bsister (ABS)-like MADS-box genes (including paralogous GOA-like genes) and the next gene upstream, as an example of family-wide evolution of putative upstream regulatory regions (PURRs). ABS-like genes are essential for integument development of ovules and endothelium formation in seeds of Arabidopsis thaliana. A combination of motif-based gene ontology enrichment and reporter gene analysis using A. thaliana as common trans-regulatory environment allows analysis of selected Brassicaceae Bsister gene PURRs. Comparison of TFBS of transcriptionally active ABS-like genes with those of transcriptionally largely inactive GOA-like genes shows that the number of in silico predicted TFBS) is similar between paralogs, emphasizing the importance of experimental verification for in silico characterization of TFBS activity and analysis of their evolution. Further, our data show highly conserved expression of Brassicaceae ABS-like genes almost exclusively in the chalazal region of ovules. The Arabidopsis-specific insertion of a transposable element (TE) into the ABS PURRs is required for stabilizing this spatially restricted expression, while other Brassicaceae achieve chalaza-specific expression without TE insertion. We hypothesize that the chalaza-specific expression of ABS is regulated by cis-regulatory elements provided by the TE.

ZusammenfassungEin 96-jähriger Patient erlitt nach der TFNA©-Osteosynthese einer pertrochantären Femurfraktur trotz korrekter Reposition und Fixation einen vollständigen „cut-in“, d. h. eine Medialisierung der gesamten Schenkelhalsklinge im Nagel ins Hüftgelenk. Vor dem Hintergrund der Implantatentwicklung und anhand der aktuellen Literatur wird diese häufiger werdende Komplikationsart beschrieben bzw. vom Fixationsversagen des „cut-out“ unterschieden. Bisherige Erklärungsversuche und notwendige Forschungsansätze werden aufgezeigt und abschließend ein pragmatisches Vorgehen im Alltag dargelegt.

In this work we address the main issues of Information Technology (IT) consumerization that are related to security risks, and vulnerabilities of devices used within Bring Your Own Device (BYOD) strategy in particular. We propose a ‘soft’ mitigation strategy for user actions based on nudging, widely applied to health and social behavior influence. In particular, we propose a complementary, less strict, more flexible Information Security policies, based on risk assessment of device vulnerabilities and threats to corporate data and devices, combined with a strategy of influencing security behavior by nudging. We argue that nudging, by taking into account the context of the decision-making environment, and the fact that the employee may be in better position to make a more appropriate decision, may be more suitable than strict policies in situations of uncertainty of security-related decisions. Several examples of nudging are considered for different tested and potential scenarios in security context.

Gene editing strategies for cystic fibrosis are challenged by the complex barrier properties of airway epithelia. We previously reported that the amphiphilic S10 shuttle peptide non-covalently combined with CRISPR-associated (Cas) ribonucleoprotein (RNP) enabled editing of human and mouse airway epithelial cells. Here, to improve base editor RNP delivery, we optimized S10 to derive the S315 peptide. Following intratracheal aerosol of Cy5-labeled peptide cargo in rhesus macaques, we confirmed delivery throughout the respiratory tract. Subsequently, we targeted CCR5 with co-administration of ABE8e-Cas9 RNP and S315. We achieved editing efficiencies of up to 5.3% in rhesus airway epithelia. Moreover, we documented persistence of edited epithelia for up to 12 months in mice. Finally, delivery of ABE8e-Cas9 targeting the CFTR R553X mutation restored anion channel function in cultured human airway epithelial cells. These results demonstrate the therapeutic potential of base editor delivery with S315 to functionally correct the CFTR R553X mutation in respiratory epithelia.