New lines in tree ring research

Natural archives, and tree-rings in particular, are fundamental tools to investigate on pre-instrumental climate variability. Tree-ring research, indeed, covers a wide field of applications, however several woody species are still overlooked and investigating just at yearly resolution, we might miss important intra-annual information. To fill these gaps, the main objective of this thesis is to undertake new lines in tree-ring research testing i) the dendrochronological potential of a marginal species to detect different climatic signal respect the usual tree species and ii) a quantitative wood anatomy approach to investigate whether with multiple cell traits is possible to extract information not visible at annual level in tree-ring series. With the new species, the common juniper (Juniperus communis, L.), I found a clear winter precipitation signal in ring-width series in the Alps, and a decoupling in the tree-ring to climate responses and growth between trees and shrubs across all the biomes investigated (Mediterranean, Alpine and Polar). With wood anatomy, I assessed the importance to use several related proxies as a diagnostic tool to detect hydraulic deterioration and mortality due to drought stress in Scots pine (Pinus sylvestris L.) and Silver fir (Abies alba) in Spain. In addition, at high latitudes, still on Scots pine I was built a 1000-year long chronology with anatomical parameters which could permit to investigate long-term temperature fluctuations. This work highlights the importance to use different species and different approaches to extract new information out of the tree-ring series. These first analysis show the possibility to reconstruct winter precipitation in the Alps and to adopt anatomical data as a surrogate of densitometric measurements or as a valid diagnostic tool for a retrospective assessment of trees health. Prediction on the future status of our forests would benefit from such an information

Winter precipitation effect in a mid-latitude temperature-limited environment: the case of common juniper at high elevation in the Alps

Common juniper (Juniperus communis L.) is by far the most widespread conifer in the world. However, tree-ring research dealing with this species is still scarce, mainly due to the difficulty in crossdating associated with the irregular stem shape with strip-bark growth form in older individuals and the high number of missing and wedging rings. Given that many different species of the same genus have been successfully used in tree-ring investigations and proved to be reliable climate proxies, this study aims to (i) test the possibility to successfully apply dendrochronological techniques on common juniper growing above the treeline and (ii) verify the climate sensitivity of the species with special regard to winter precipitation, a climatic factor that generally does not affect tree-ring growth in all Alpine high-elevation tree species. Almost 90 samples have been collected in three sites in the central and eastern Alps, all between 2100 and 2400 m in elevation. Despite cross-dating difficulties, we were able to build a reliable chronology for each site, each spanning over 200 years. Climate-growth relationships computed over the last century highlight that juniper growth is mainly controlled by the amount of winter precipitation. The high variability of the climate-growth associations among sites, corresponds well to the low spatial dependence of this meteorological factor. Fairly long chronologies and the presence of a significant precipitation signal open up the possibility to reconstruct past winter precipitation. S Online supplementary data available from stacks.iop.org/ERL/9/104021/mmedi

In vitro and in vivo efficacy of 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) on human melanoma

6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX) is a powerful inhibitor of the glutathione transferase P1-1 (GSTP1-1) and causes the disruption of the complex between GSTP1-1 and c-Jun N-terminal Kinase (JNK). This induces JNK activation and apoptosis in tumour cells. in the present work we assess the in vitro and in vivo effectiveness of NBDHEX on two human melanoma cell lines, Me501 and A375. NBDHEX shows IC50 values in the low micromolar range (IC50 of 1.2 +/- 0.1 mu M and 2.0 +/- 0.2 mu M for Me501 and A375, respectively) and is over 100 times more cytotoxic to these cell lines than temozolomide. Apoptosis is observed in Me501 cells within 3 h of the addition of NBDHEX, while in A375 cells the apoptotic event is rather late, and is preceded by a G2/M phase arrest. In both melanoma cell lines, INK activity is required for the ability of NBDHEX to trigger apoptosis, confirming that the JNK pathway is an important therapeutic target for this tumour. NBDHEX is also both effective and well tolerated in in vivo tumour models. A tumour inhibition of 70% is observed in vivo against Me501 human melanoma and a similar result is obtained on A375 model, with 63% of turnout inhibition. These findings indicate that the activation of the JNK pathway, through a selective GSTP1-1 targeting, could prove to be a promising new strategy for treating melanoma, which responds poorly to conventional therapies. (C) 2009 Elsevier Ltd. All rights reserved

Impalement injuries of the shoulder: a case report with literature review

The management of penetrating skeletal extremity trauma is a clinical challenge even for experienced surgeons. While the treatment of associated vascular injuries should be prioritized, there is still a lack of evidence regarding the management of foreign bodies in case of bone fractures or neurological injuries. Here we present a case of impalement of the right proximal humerus with a construction steel rod. The 54-year-old man was successfully treated without vascular, neurological, and thoracic sequelae. A review of the current literature about the most appropriate extrication sequences and soft tissue reconstruction following massive foreign body injuries was carried out

In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol

ObjectiveThere is poor evidence to determine the superiority of combination regimens versus monotherapy against infections due to carbapenem-resistant (CR) Gram-negative bacteria. In vivo models can simulate the pathophysiology of infections in humans and assess antibiotic efficacy. We aim to investigate in vivo effects of antibiotic combination on mortality and disease burden for infections due to CR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae and provide an unbiased overview of existing knowledge. The results of the study can help prioritising future research on the most promising therapies against CR bacteria.Methods and analysisThis protocol was formulated using the Systematic Review Protocol for Animal Intervention Studies (SYRCLE) Checklist. Publications will be collected from PubMed, Scopus, Embase and Web of Science. Quality checklists adapted by Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies and SYRCLE's risk of bias tool will be used. If the meta-analysis seems feasible, the ES and the 95% CI will be analysed. The heterogeneity between studies will be assessed by I2 test. Subgroup meta-analysis will be performed when possible to assess the impact of the studies on efficacy of the treatments. Funnel plotting will be used to evaluate the risk of publication bias.DisseminationThis systematic review and meta-analysis is part of a wider research collaboration project, the COmbination tHErapy to treat sepsis due to carbapenem-Resistant bacteria in adult and paediatric population: EvideNCE and common practice (COHERENCE) study that includes also the analyses of in vitro and human studies. Data will be presented at international conferences and the results will be published in peer-reviewed journals.PROSPERO registration numberCRD42019128104(available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019128104)

B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma

New lines in tree ring research

Natural archives, and tree-rings in particular, are fundamental tools to investigate on pre-instrumental climate variability. Tree-ring research, indeed, covers a wide field of applications, however several woody species are still overlooked and investigating just at yearly resolution, we might miss important intra-annual information. To fill these gaps, the main objective of this thesis is to undertake new lines in tree-ring research testing i) the dendrochronological potential of a marginal species to detect different climatic signal respect the usual tree species and ii) a quantitative wood anatomy approach to investigate whether with multiple cell traits is possible to extract information not visible at annual level in tree-ring series. With the new species, the common juniper (Juniperus communis, L.), I found a clear winter precipitation signal in ring-width series in the Alps, and a decoupling in the tree-ring to climate responses and growth between trees and shrubs across all the biomes investigated (Mediterranean, Alpine and Polar). With wood anatomy, I assessed the importance to use several related proxies as a diagnostic tool to detect hydraulic deterioration and mortality due to drought stress in Scots pine (Pinus sylvestris L.) and Silver fir (Abies alba) in Spain. In addition, at high latitudes, still on Scots pine I was built a 1000-year long chronology with anatomical parameters which could permit to investigate long-term temperature fluctuations. This work highlights the importance to use different species and different approaches to extract new information out of the tree-ring series. These first analysis show the possibility to reconstruct winter precipitation in the Alps and to adopt anatomical data as a surrogate of densitometric measurements or as a valid diagnostic tool for a retrospective assessment of trees health. Prediction on the future status of our forests would benefit from such an information.Archivi naturali, in particolare gli anelli legnosi, sono strumenti fondamentali per studiare la variabilità climatica antecedente la strumentazione meteorologica. La ricerca sugli anelli legnosi, copre un ampio campo di applicazioni, ciononostante, molte specie vegetali non sono ancora state esplorate dal punto di vista dendrocronologico, e in aggiunta l’analisi solo a livello annuale, potrebbe non evidenziare diverse importanti informazioni intra-annuali. Per colmare queste mancanze, l’obbiettivo principale di questa tesi è di intraprendere nuove linee di ricerca dendrocronologica testando i) il potenziale di una specie marginale per individuare un segnale climatico differente e non identificato in altre specie arboree e ii) un approccio di dendro-anatomia quantitativa per verificare se attraverso molteplici tratti cellulari è possibile estrarre informazioni non visibili a livello annuale nelle serie di anelli legnosi. Con l’utilizzo di una nuova specie in dendrocronologia, il ginepro comune (Juniperus communis, L.), ho identificato un chiaro segnale di precipitazione invernale nelle serie anulari nella regione Alpina, e un disaccoppiamento negli incrementi sulla risposta clima-accrescimento tra alberi e arbusti in diversi biomi (Mediterraneo, Alpino e Polare). Attraverso l’anatomia del legno, ho definito l’importanza di utilizzare diversi “proxy” relativi a queste misure come strumenti diagnostici per individuare la deteriorazione idraulica e mortalità a causa di stress idrico e siccità su pino silvestre (Pinus sylvestris L.) e abete bianco (Abies alba, Mill) in Spagna. In aggiunta, ad elevate latitudini, sempre su pino silvestre ho costruito una cronologia lunga 1000 anni con parametri anatomici che potrebbero permettere di studiare fluttuazioni di lungo termine. Questo lavoro evidenzia l’importanza di utilizzare diverse specie in dendrocronologia e differenti approcci per estrarre nuove informazioni da serie di anelli legnosi. Queste prime analisi dimostrano la possibilità di ricostruire la precipitazione nevosa sulle Alpi e di adottare dati anatomici come sostituti di misure densitometriche o come validi strumenti diagnostici per un’analisi retrospettiva della salute degli alberi. Queste nuove informazioni possono essere di beneficio per comprendere il futuro status delle nostre foreste

Common Juniper: a challenge to seek a precipitation signal at high elevation in the Alps

Common juniper (Juniperus communis L.) is by far the most widespread conifer in the world. However, despite its wide distribution, tree-ring research dealing with this species is still scarce. The main reason is likely related to the hardness in crossdating not just comparing different samples, but also within the same plant due to irregular stem shape with strip-bark growth form in the older individuals and to the high number of missing, wedging and false rings. Considering that a precipitation signal is generally missing in the Alpine high-elevation tree species, here we present a pilot study aimed to i) test the dendrochronological potential of common juniper growing above the treeline and ii) verify the precipitation sensitivity of the species. We collected more than 200 samples from three sites in the central and eastern Alps, all between 2100 and 2400 m altitude. As expected, crossdating was exceptionally challenging. However, thanks to the conspicuous number of frost rings acting as pointer years, we were able to successfully date an adequate number of samples to produce a reliable chronology longer than 200 years in all three study sites. Chronology statistics (EPS, rbar, PC1, etc.) were significantly lower than the corresponding values for the high-elevation tree species (larch, stone pine, spruce), but were similar to other species of the same genus found in literature. Climate/growth relationships computed in the last century highlight a significant precipitation signal in winter months, with a high variability among sites that well corresponds to the low spatial dependence of this factor. Despite the difficulties encountered, the possibility of building fairly long chronologies and the likely presence of a significant precipitation signal seems a promising starting point to apply classical dendroclimatological approach on this creeping shrub

Trade-In Programs in the Context of Technological Innovation with Herding

We study optimal pricing strategies and consequent market shares’ dynamics in a transition from an old and established technology to a new one. We simulate an agent-based model, in which a large population of possible buyers decide whether to adopt or not depending on prices, private signals and herding behavior. The firm, on its part, sets prices to maximize revenues. We show that trade-in programs, in practice comparable to very aggressive discounts, are supported by a rational attitude