CMV-IgG pre-allogeneic hematopoietic stem cell transplantation and the risk for CMV reactivation and mortality.

Cytomegalovirus (CMV) represents one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, a common diagnostic test used to stratify the risk for CMV infection in allo-HSCT recipients is the qualitative CMV serology of donor and recipient. A positive serostatus of the recipient is the most important risk factor for CMV reactivation and associated with reduced overall survival post-transplantation (TX). Direct and indirect effects of CMV are involved in the poorer survival outcome. The present study investigated if the quantitative interpretation of anti-CMV IgG before allo-HSCT might serve as a novel parameter for the identification of patients at risk for CMV reactivation and worse outcome post-TX. For this purpose, a cohort of 440 allo-HSCT recipients over a period of 10 years was retrospectively analyzed. Our findings indicated that patients with high CMV IgG pre-allo-HSCT had a higher risk to develop CMV reactivation, including clinically relevant infections, and a worse prognosis 36 months post-allo-HSCT as compared to recipients with low CMV IgG values. In the letermovir (LMV) era, this group of patients might benefit from a closer CMV monitoring, and hence, earlier intervention if needed, especially after discontinuation of prophylaxis.

Adeno-associated viral-mediated insulin-like growth factor delivery protects motor neurons in vitro.

Recent work has demonstrated that adeno-associated viral (AAV) vector-mediated delivery of the insulin-like growth factor (IGF-I) gene through retrograde axonal transport can prolong survival and delay disease onset in the superoxide dismutase mutant mouse model of motor neuron (MN) disease. The present experiment examines IGF-I gene transfer in vitro. Adenoviral and AAV vectors for IGF-I infect neurons triggering expression and secretion of biologically active IGF-I. AAV-mediated IGF-I expression in SH-SY5Y neurons protects both cells expressing the transgene, and bystanders without transgene expression from glutamate-induced apoptosis. Similarly, AAV-mediated IGF-I delivery in primary E15 MN culture provides a titer-dependent neuroprotection from glutamate-induced DNA fragmentation. Both infected and noninfected neurons are equally protected. These observations argue that vector-mediated IGF-I gene transfer induces secretion of active IGF-I that acts through direct effects on spinal cord MNs. This mechanism may explain the therapeutic effects observed in vivo despite relatively low affinity AAV spinal cord uptake.

Intracellular compartmentation in the biosynthesis of caulerpenyne: study on intact macroalgae using stable-isotope-labeled precursors.

The biosynthesis of caulerpenyne 1 was studied in the invasive green alga Caulerpa taxifolia. The investigation was performed on intact algae with stable-isotope-labeled precursors administered under mixotrophic growth conditions. According to the labeling pattern, after incorporation of 1-(13)C-acetate and (13)CO(2), respectively, the biosynthesis of the sesquiterpene backbone occurs in the chloroplast and follows the methyl-erythritol-4-phosphate (MEP) pathway. In contrast, the acetyl residues of caulerpenyne 1 are derived from a cytosolic resource. [structure: see text]

Comparison of the wound-activated transformation of caulerpenyne by invasive and noninvasive Caulerpa species of the Mediterranean.

The invasive green alga, Caulerpa taxifolia, that has spread rapidly after its introduction into the Mediterranean and the North American Pacific, reacts to wounding by transforming its major metabolite caulerpenyne. This wound-activated reaction involves the transformation of the bis-enol acetate moiety of 1, releasing reactive 1,4-dialdehydes. The ability to perform this transformation is found also in both the noninvasive Mediterranean C. prolifera and the invasive C. racemosa. Trapping experiments, as well as transformation of the model substrate geranyl acetate, suggest that all three investigated Caulerpa spp. rely on esterases that act upon wounding of the algae by subsequently removing the three acetate residues of caulerpenyne. The resulting reactive 1,4-dialdehyde oxytoxin 2 can be identified by liquid chromatography-mass spectrometry and is unstable in the wounded tissue. Caulerpenyne transformation occurs rapidly, and severe tissue damage caused degradation of more than 50% of the stored caulerpenyne within 1 min in all three algae. Prevention of the enzymatic reaction before extraction, by shock freezing the tissue with liquid nitrogen, was used for the determination of the caulerpenyne content in intact algae. It gives about twofold higher values compared to an established methanol extraction protocol. The speed and mechanism of the wound-activated transformation, as well as the caulerpenyne content in intact tissue of invasive and noninvasive Caulerpa spp., are comparable. Thus, this enzymatic transformation, despite being fast and efficient, is likely not the key for the success of the investigated invasive species.