Plasticity in dendroclimatic response across the distribution range of Aleppo pine (Pinus halepensis)

We investigated the variability of the climate-growth relationship of Aleppo pine across its distribution range in the Mediterranean Basin. We constructed a network of tree-ring index chronologies from 63 sites across the region. Correlation function analysis identified the relationships of tree-ring index to climate factors for each site. We also estimated the dominant climatic gradients of the region using principal component analysis of monthly, seasonal, and annual mean temperature and total precipitation from 1,068 climatic gridpoints. Variation in ring width index was primarily related to precipitation and secondarily to temperature. However, we found that the dendroclimatic relationship depended on the position of the site along the climatic gradient. In the southern part of the distribution range, where temperature was generally higher and precipitation lower than the regional average, reduced growth was also associated with warm and dry conditions. In the northern part, where the average temperature was lower and the precipitation more abundant than the regional average, reduced growth was associated with cool conditions. Thus, our study highlights the substantial plasticity of Aleppo pine in response to different climatic conditions. These results do not resolve the source of response variability as being due to either genetic variation in provenance, to phenotypic plasticity, or a combination of factors. However, as current growth responses to inter-annual climate variability vary spatially across existing climate gradients, future climate-growth relationships will also likely be determined by differential adaptation and/or acclimation responses to spatial climatic variation. The contribution of local adaptation and/or phenotypic plasticity across populations to the persistence of species under global warming could be decisive for prediction of climate change impacts across populations. In this sense, a more complex forest dynamics modeling approach that includes the contribution of genetic variation and phenotypic plasticity can improve the reliability of the ecological inferences derived from the climate-growth relationships.This work was partially supported by Spanish Ministry of Education and Science co-funded by FEDER program (CGL2012-31668), the European Union and the National Ministry of Education and Religion of Greece (EPEAEK- Environment – Archimedes), the Slovenian Research Agency (program P4-0015), and the USDA Forest Service. The cooperation among international partners was supported by the COST Action FP1106, STREeSS

Pediatric brainstem cavernous malformations: 2-center experience in 40 children

OBJECTIVE Brainstem cavernous malformations (BSCMs) are relatively uncommon, low-flow vascular lesions in children. Given the paucity of data, guidelines regarding the clinical management of BSCMs in children are lacking and the surgical indication is most commonly based on an individual surgeon's judgment and experience. The goal in this study was to evaluate the clinical behavior of BSCMs in childhood and the long-term outcome in children managed conservatively and surgically. METHODS This was an observational, retrospective study including all children with BSCMs who were followed at 2 institutions between 2008 and 2020. RESULTS The study population consisted of 40 children (27 boys, 67.5%) with a mean age of 11.4 years. Twenty-three children (57.5%) were managed conservatively, whereas 17 children (42.5%) underwent resection of BSCMs. An aggressive clinical course was observed in 13 children (32.5%), who experienced multiple hemorrhages with a progressive pattern of neurological decline. Multiple BSCMs were observed in 8 patients, of whom 3 patients presented with a complex of multiple tightly attached BSCMs and posed a significant therapeutic challenge. The overall long-term outcome was favorable (modified Rankin Scale [mRS] scores 0-2) in 36 patients (90%), whereas an unfavorable outcome (mRS scores 3 and 4) was seen in 4 children (10%). An mRS score of 5 or 6 was not observed. The mean (± SD) follow-up was 88.0 (± 92.6) months. CONCLUSIONS The clinical course of BSCMs in children is highly variable, with benign lesions on the one hand and highly aggressive lesions with repetitive hemorrhages on the other. Given the greater life expectancy and the known higher functional recovery in children, surgical treatment should be considered early in young patients presenting with surgically accessible lesions and an aggressive clinical course, and it should be performed in a high-volume center

The Amyloid Precursor Protein (APP) Does Not Have a Ferroxidase Site in Its E2 Domain

The ubiquitous 24-meric iron-storage protein ferritin and multicopper oxidases such as ceruloplasmin or hephaestin catalyze oxidation of Fe(II) to Fe(III), using molecular oxygen as oxidant. The ferroxidase activity of these proteins is essential for cellular iron homeostasis. It has been reported that the amyloid precursor protein (APP) also has ferroxidase activity. The activity is assigned to a ferroxidase site in the E2 domain of APP. A synthetic 22-residue peptide that carries the putative ferroxidase site of E2 domain (FD1 peptide) has been claimed to encompass the same activity. We previously tested the ferroxidase activity of the synthetic FD1 peptide but we did not observe any activity above the background oxidation of Fe(II) by molecular oxygen. Here we used isothermal titration calorimetry to study Zn(II) and Fe(II) binding to the natural E2 domain of APP, and we employed the transferrin assay and oxygen consumption measurements to test the ferroxidase activity of the E2 domain. We found that this domain neither in the presence nor in the absence of the E1 domain binds Fe(II) and it is not able to catalyze the oxidation of Fe(II). Binding of Cu(II) to the E2 domain did not induce ferroxidase activity contrary to the presence of redox active Cu(II) centers in ceruloplasmin or hephaestin. Thus, we conclude that E2 or E1 domains of APP do not have ferroxidase activity and that the potential involvement of APP as a ferroxidase in the pathology of Alzheimer's disease must be re-evaluated.BT/BiotechnologyApplied Science