Epigenetic control of multiple genes with a lentiviral vector encoding transcriptional repressors fused to compact zinc finger arrays.

Gene silencing without gene editing holds great potential for the development of safe therapeutic applications. Here, we describe a novel strategy to concomitantly repress multiple genes using zinc finger proteins fused to Krüppel-Associated Box repression domains (ZF-Rs). This was achieved via the optimization of a lentiviral system tailored for the delivery of ZF-Rs in hematopoietic cells. We showed that an optimal design of the lentiviral backbone is crucial to multiplex up to three ZF-Rs or two ZF-Rs and a chimeric antigen receptor. ZF-R expression had no impact on the integrity and functionality of transduced cells. Furthermore, gene repression in ZF-R-expressing T cells was highly efficient in vitro and in vivo during the entire monitoring period (up to 10 weeks), and it was accompanied by epigenetic remodeling events. Finally, we described an approach to improve ZF-R specificity to illustrate the path toward the generation of ZF-Rs with a safe clinical profile. In conclusion, we successfully developed an epigenetic-based cell engineering approach for concomitant modulation of multiple gene expressions that bypass the risks associated with DNA editing.

A theory of ventilation estimate over hypothetical urban areas.

Urban roughness is a major factor governing the flows and scalar transport in the atmospheric boundary layer (ABL) but our understanding is rather limited. The ventilation and pollutant removal of hypothetical urban areas consisting of various types of street canyons are examined using computational fluid dynamics (CFD). The aerodynamic resistance, ventilation efficiency, and pollutant removal are measured by the friction factor f, air exchange rate (ACH), and pollutant exchange rate (PCH), respectively. Two source configurations of passive tracer, ground-level-only (Tracer 0) and all-solid-boundary (Tracer 1) are employed to contrast their transport behavior. It is found that the ventilation and pollutant removal are largely attributed to their turbulent components (over 60%). Moreover, with a consistent support from analytical solution and CFD results, the turbulent ACH is a linear function of the square root of the friction factor (ACH'∝f(1/2)) regardless of building geometry. Tracer 0 and Tracer 1 exhibit diversified removal behavior as functions of friction factor so analytical parameterizations have not yet been developed. In view of the large portion of aged air removal by turbulence, it is proposed that the aerodynamic resistance can serve as an estimate to the minimum ventilation efficiency of urban areas.

International family therapy: a view from Kyoto, Japan.

"International family therapy" is an emergent field within (or overarching) the field of family therapy. At this stage, it can be described as the collecting and sharing of experiences by family therapists from different countries. Recent publications (7) gather information principally from Western cultures in which systemic family therapy has grown over the past thirty years. Japan is of particular interest to Western practitioners because it is a highly successful, post-industrial culture that differs markedly from the West. Familiar family therapy interventions often work for unfamiliar reasons, and different goals are often needed in order to respond to apparently similar family problems. An expanded sense of choice around strategies for family life and family therapy that such diversity implies is the primary contribution that this maturing, international family therapy movement can make to family therapy.

Hyperprolactinaemia in a patient with the McCune-Albright Syndrome.

A patient is presented with the syndrome of polyostotic fibrous dysplasia and precocious puberty (McCune-Albright Syndrome). In adult life she developed hyperprolactinaemia with galactorrhoea and amenorrhoea; there was also evidence of excessive secretion of growth hormone.