Geraniol and Geranial Dehydrogenases Induced in Anaerobic Monoterpene Degradation by Castellaniella defragrans

Castellaniella defragrans is a Betaproteobacterium capable of coupling the oxidation of monoterpenes with denitrification. Geraniol dehydrogenase (GeDH) activity was induced during growth with limonene in comparison to growth with acetate. The N-terminal sequence of the purified enzyme directed the cloning of the corresponding open reading frame (ORF), the first bacterial gene for a GeDH (geoA, for geraniol oxidation pathway). The C. defragrans geraniol dehydrogenase is a homodimeric enzyme that affiliates with the zinc-containing benzyl alcohol dehydrogenases in the superfamily of medium-chain-length dehydrogenases/reductases (MDR). The purified enzyme most efficiently catalyzes the oxidation of perillyl alcohol (k cat/K m = 2.02 × 106 M−1 s−1), followed by geraniol (k cat/K m = 1.57 × 106 M−1 s−1). Apparent K m values of <10 μM are consistent with an in vivo toxicity of geraniol above 5 μM. In the genetic vicinity of geoA is a putative aldehyde dehydrogenase that was named geoB and identified as a highly abundant protein during growth with phellandrene. Extracts of Escherichia coli expressing geoB demonstrated in vitro a geranial dehydrogenase (GaDH) activity. GaDH activity was independent of coenzyme A. The irreversible formation of geranic acid allows for a metabolic flux from β-myrcene via linalool, geraniol, and geranial to geranic acid

Delivery of Rapamycin Using In Situ Forming Implants Promotes Immunoregulation and Vascularized Composite Allograft Survival.

Vascularized composite allotransplantation (VCA), such as hand and face transplantation, is emerging as a potential solution in patients that suffered severe injuries. However, adverse effects of chronic high-dose immunosuppression regimens strongly limit the access to these procedures. In this study, we developed an in situ forming implant (ISFI) loaded with rapamycin to promote VCA acceptance. We hypothesized that the sustained delivery of low-dose rapamycin in proximity to the graft may promote graft survival and induce an immunoregulatory microenvironment, boosting the expansion of T regulatory cells (T). In vitro and in vivo analysis of rapamycin-loaded ISFI (Rapa-ISFI) showed sustained drug release with subtherapeutic systemic levels and persistent tissue levels. A single injection of Rapa-ISFI in the groin on the same side as a transplanted limb significantly prolonged VCA survival. Moreover, treatment with Rapa-ISFI increased the levels of multilineage mixed chimerism and the frequency of T both in the circulation and VCA-skin. Our study shows that Rapa-ISFI therapy represents a promising approach for minimizing immunosuppression, decreasing toxicity and increasing patient compliance. Importantly, the use of such a delivery system may favor the reprogramming of allogeneic responses towards a regulatory function in VCA and, potentially, in other transplants and inflammatory conditions

Uncovering the care setting–turnover intention relationship of geriatric nurses

In times of global demographic changes, strategies are needed for improving nursing staff retention. We examined the association of care setting (nursing homes and home care) with geriatric nurses' intention to leave their job and their profession. Thus far, it is unclear why nurses' turnover intention and behaviour do not differ between care settings, although working conditions tend to be better in home care. We used the Job Demands-Resources model to explain indirect and buffering effects by job demands (time pressure, social conflicts) and resources (task identity, supervisor support, and co-worker support) via nurses' perceived health and job satisfaction on nurses' leaving intentions. The present cross-sectional questionnaire study was conducted with a sample of N = 278 registered nurses and nursing aides in German geriatric care. As expected, there was no direct relationship between care setting and leaving attitudes. Demands and resources predicted the intention to leave with job satisfaction as mediator. We found more demands in nursing homes but no differences in resources. Serial mediation effects of care setting on intentions to leave via demands/resources and health/job satisfaction as mediators were found only for time pressure and social conflicts. Unexpectedly, there were no clear differences between intention to leave the job and the profession. As hypotheses were only partly confirmed, other buffering and detrimental effects on leaving intentions are discussed. The present data suggest that detailed concepts for personnel and career planning in geriatric care are needed