‘Locked nucleic acids’ (LNAs) are known to introduce enhanced bio- and thermostability into natural nucleic acids rendering them powerful tools for diagnostic and therapeutic applications. We present the 1.9 Å X-ray structure of an ‘all LNA’ duplex containing exclusively modified β-d-2′-O-4′C-methylene ribofuranose nucleotides. The helix illustrates a new type of nucleic acid geometry that contributes to the understanding of the enhanced thermostability of LNA duplexes. A notable decrease of several local and overall helical parameters like twist, roll and propeller twist influence the structure of the LNA helix and result in a widening of the major groove, a decrease in helical winding and an enlarged helical pitch. A detailed structural comparison to the previously solved RNA crystal structure with the corresponding base pair sequence underlines the differences in conformation. The surrounding water network of the RNA and the LNA helix shows a similar hydration pattern.

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Can the boss take the heat? Is he or she tough enough for the job? Can they take it, endure the pressure, tolerate or stand up to it? Although we know that resilient leaders are essential for a healthy and efficient workforce, the resilience of leaders itself is still largely unexplored. Our study aims to identify distinctive resilience factors in leadership and help close this research gap. We interviewed 27 leaders from various industrial sectors, German regions and leadership positions. In a qualitative content analysis, we identified 77 individual, situational and behavioural factors that seem to impact on the resilience of leaders. We divided these factors into meaningful categories and integrated them into a framework appropriate for leadership. This framework shows that in addition to individual traits and abilities, situational factors (private and work environment) and behavioural factors (personal and interpersonal behaviour) are highly important and that leaders' resilience results from an interaction of these factors. As most of the identified factors can be directly influenced by the leader or the organization, our study provides important insights into the effective development and nurturing of leaders' resilience. Furthermore, the findings can be a helpful starting point for future empirical studies.

Selenocysteine-incorporating tRNA(Sec)(UCA), the product of selC, was isolated from E.coli and aminoacylated with serine. The equilibrium dissociation constant for the interaction of Ser-tRNA(Sec)(UCA) with elongation factor Tu.GTP was determined to be 5.0 +/- 2.5 x 10(-8) M. Compared with the dissociation constants of the two elongator Ser-tRNA(Ser) species (Kd = 7 x 10(-10) M), the selenocysteine-incorporating UGA suppressor tRNA has an almost hundred fold weaker affinity for EF-Tu.GTP. This suggests a mechanism by which the Ser-tRNA(Sec) is prevented in recognition of UGA codons. This tRNA is not bound to EF-Tu.GTP and is converted to selenocysteinyl-tRNA(Sec). We also demonstrate the lack of an efficient interaction of Sec-tRNA(Sec)(UCA) with EF-Tu.GTP. The results of this work are in support of a mechanism by which the selenocysteine incorporation at UGA nonsense codons is mediated by an elongation factor other than EF-Tu.GTP.

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Protein-protein interactions are well recognized as therapeutic targets and therefore interfering peptides (IP) that block these interactions are receiving increasing attention. Four different tumor-penetrating peptides (TPPs) (iRGD, RPARPAR, Linear TT1 (LinTT1), and cyclic TT1 (TT1)) are associated to an IP that blocks the interaction between the protein phosphatase PP2A and its binding protein SET, generating new bifunctional peptides able to intracellularly target the PP2A/SET interaction in malignant B cells and tumoral hepatocytes. The TPPs are able to penetrate into B cells of patients suffering chronic lymphocytic leukemia (CLL) and into tumoral hepatocytes but not into B cells from healthy donors and healthy hepatocytes. The association of cargo does not affect the penetration of the TPPs in CLL B cells. All the bifunctional peptides induce apoptosis in human CLL B cells and tumoral hepatocytes, and stability tests reveal that iRGD-IP, RPARPAR-IP, and TT1-IP are stable after 24 h incubation in human serum. The iRGD associated with the IP significantly increases the survival of mice bearing xenograft models of CLL without any symptom of toxicity, suggesting that the bifunctional peptides may have a therapeutic application for selective tumoral targeting of PP2A/SET interaction, which is deregulated in several cancers, including CLL.

Living and operating in a global world, the risk for a global economic crisis has never been greater. As ongoing events, such as the COVID-19 pandemic, the recent war in Ukraine or the sharply increasing inflation have shown, organizations need to be highly resilient to persevere in a crisis-prone world. Even though we know that crises serve as a focal lens on leadership behavior and leaders play a crucial role in these scenarios, little is known as to how leaders handle an existence-threatening organizational crisis. Using an inductive analysis of 32 interviews on crisis leadership, we show that in the case of an acute crisis, leaders apply different paradoxical behaviors to cope effectively with the situation and navigate their organizations through these events. More specifically, our study contributes to existing literature by, first, showing that the distinctiveness of crises results from the fact that leaders are confronted with paradoxes that they can otherwise smoothly separate in terms of time or organization, second, revealing that the leader’s paradoxical behaviors as a respond are derived from their mindset to consciously recognize the contradictory demands of the crisis, and third, from their action in terms of a compressed situational leadership. By identifying six pairs of paradoxical behaviors, we demonstrate how leaders effectively deal with the unsolvable contradictions that arise from the crisis, and thus contribute to the organizations’ ability to cope with crises.