Telomerase-free cancer cells employ a recombination-based alternative lengthening of telomeres (ALT) pathway that depends on ALT-associated promyelocytic leukemia (PML) nuclear bodies (APBs), whose function is unclear. We find that APBs behave as liquid condensates in response to telomere DNA damage, suggesting two potential functions: condensation to enrich DNA repair factors and coalescence to cluster telomeres. To test these models, we developed a chemically-induced dimerization approach to induce de novo APB condensation in live cells without DNA damage. We show that telomere binding protein sumoylation nucleates APB condensation via SUMO-SIM (SUMO interaction motif) interactions, and that APB coalescence drives telomere clustering. The induced APBs lack DNA repair factors, indicating that APB functions in promoting telomere clustering can be uncoupled from enriching DNA repair factors. Indeed, telomere clustering relies only on liquid properties of the condensate, as an alternative condensation chemistry also induces clustering independent of sumoylation. Our findings introduce a chemical dimerization approach to manipulate phase separation and demonstrate how the material properties and chemical composition of APBs independently contribute to ALT, suggesting a general framework for how chromatin condensates promote cellular functions. [Media: see text] [Media: see text] [Media: see text] [Media: see text]

This paper describes an empirical assessment of several hypotheses associated with organization design in the context of new and flexible technologies. Three distinct technologies were examined in four different geographical locations in Sweden, France, and Canada. The hypotheses illustrate how workplaces are being organized within the context of flexible, new technology, and the movement toward an emerging new paradigm of work. Flexible, new technologies and this paradigm are entering organizations at the same time. The former are changing the ground on which assumptions underlying the emerging paradigm of organization have been built. Several of the hypotheses examined have been revised as a consequence. The data from twelve companies are plotted on a matrix of organization design principles against organization design implementation to illustrate changing organization design patterns as well as geographic differences between the companies.

The microprocessor revolution is the leading edge of a new "technology system" that in itself underlies a new paradigm of organization. While it is early to completely describe the emerging paradigm, some hypotheses can be advanced. They are presented in this paper. The hypotheses arise from studies of how new technologies have changed our understanding of the nature of jobs, the division of labor and the control and coordination of organizations. In the process of transition to the new paradigm, new professional skills will be required. It is postulated that skill in the design of organizations may be one of these.

Michel Liu : Технология, организация работы и поведение рабочих. Считают обычно, что технология и организация работы непосредственно влияют на поведение рабочих. Результаты исследования, длившегося четыре года, показывают, что это влияние всегда опосредовано возникновением микрокультуры предприятия или цеха. Отношения между технологией, цеховой культурой и поведением были изучены. Наряду с перспективами для новых изысканий о сюжете, были предложены различные процессы, объясняющие действие технологии на поведение рабочих. Résumé Michel Liu : Technologie, organisation du travail et comportement des salariés. On considère généralement que la technologie et l'organisation du travail influencent directement le comportement des salariés. Les résultats d'une étude longitudinale sur quatre années montrent que cette influence est toujours médiatisée par la création d'une micro-culture d'entreprise ou d'atelier. Les relations entre technologie, culture d'atelier et comportement sont étudiées. Divers processus expliquant l'action de la technologie sur les comportements sont proposés, ainsi que des perspectives pour de nouvelles recherches sur le sujet.

MEIS2 (Meis homeobox 2) encodes a homeobox protein in the three amino acid loop extension (TALE) family of highly conserved homeodomain-containing transcription regulators important for development. MEIS2 deletions/mutations have been associated with cleft lip/palate, dysmorphic facial features, cardiac defects, as well as intellectual disability at a variable severity. Here we report on one familial case that two affected siblings carry the same non-mosaic ~ 423 kb genomic deletion at 15q14 encompassing the entirety of CDIN1 and the last three exons (ex. 10, 11, 12) of the MEIS2 gene, while their unaffected father is mosaic for the same deletion in about 10% lymphocytes. Both siblings presented with mild developmental delay and bifid uvula, while no congenital cardiac abnormalities were identified. The elder sister also showed syncopal episodes and mild speech delay and the father had atrial septal defects. This is the first report showing multiple family members inherit a genomic deletion resulting in a MEIS2 partial truncation from a mosaic parent. Taken all together, this study has important implications for genetic counseling regarding recurrence risk and also points to the importance of offering MEIS2 gene tests covering both point mutations and microdeletions to individuals with milder bifid uvula and developmental delay.