Sulfur transfer and activation by ubiquitin-like modifier system Uba4•Urm1 link protein urmylation and tRNA thiolation in yeast

Urm1 is a unique dual-function member of the ubiquitin protein family and conserved from yeast to man. It acts both as a protein modifier in ubiquitin-like urmylation and as a sulfur donor for tRNA thiolation, which in concert with the Elongator pathway forms 5-methoxy-carbonyl-methyl-2-thio (mcm5s2) modified wobble uridines (U34) in anticodons. Using Saccharomyces cerevisiae as a model to study a relationship between these two functions, we examined whether cultivation temperature and sulfur supply previously implicated in the tRNA thiolation branch of the URM1 pathway also contribute to proper urmylation. Monitoring Urm1 conjugation, we found urmylation of the peroxiredoxin Ahp1 is suppressed either at elevated cultivation temperatures or under sulfur starvation. In line with this, mutants with sulfur transfer defects that are linked to enzymes (Tum1, Uba4) required for Urm1 activation by thiocarboxylation (Urm1-COSH) were found to maintain drastically reduced levels of Ahp1 urmylation and mcm5s2U34 modification. Moreover, as revealed by site specific mutagenesis, the Stransfer rhodanese domain (RHD) in the E1-like activator (Uba4) crucial for Urm1-COSH formation is critical but not essential for protein urmylation and tRNA thiolation. In sum, sulfur supply, transfer and activation chemically link protein urmylation and tRNA thiolation. These are features that distinguish the ubiquitin-like modifier system Uba4•Urm1 from canonical ubiquitin family members and will help elucidate whether, in addition to their mechanistic links, the protein and tRNA modification branches of the URM1 pathway may also relate in function to one another.

Calibration of Grassmaster II to estimate green and dry matter yield in Mediterranean pastures: effects of pasture moisture content

Accurate assessment of standing pasture biomass in livestock production systems is a major factor for improving feed planning. Several tools are available to achieve this, including the GrassMaster II capacitance meter. This tool relies on an electrical signal, which is modified by the surrounding pasture. There is limited knowledge on how this capacitance meter performs in Mediterranean pastures. Therefore, we evaluated the GrassMaster II under Mediterranean conditions to determine (i) the effect of pasture moisture content (PMC) on the meter’s ability to estimate pasture green matter (GM) and dry matter (DM) yields, and (ii) the spatial variability and temporal stability of corrected meter readings (CMR) and DM in a bio-diverse pasture. Field tests were carried out with typical pastures of the southern region of Portugal (grasses, legumes, mixture and volunteer annual species) and at different phenological stages (and different PMC). There were significant positive linear relations between CMR and GM (r2 = 0.60, P < 0.01) and CMR and DM (r2 = 0.35, P < 0.05) for all locations (n = 347). Weak relationships were found for PMC (%) v. slope and coefficient of determination for both GM and DM. A significant linear relation existed for CMR v. GM and DM for PMC >80% (r2= 0.57, P < 0.01, RMSE = 2856.7 kg ha–1, CVRMSE=17.1% to GM; and r2= 0.51, P < 0.01,RMSE = 353.7 kg ha–1, CVRMSE = 14.3% to DM). Therefore, under the conditions of this current study there exists an optimum PMC (%) for estimating both GM and DM with the GrassMaster II. Repeated-measurements taken at the same location on different dates and conditions in a bio-diverse pasture showed similar and stable patterns between CMR and DM (r2= 0.67, P < 0.01, RMSE = 136.1 kg ha–1, CVRMSE = 6.5%). The results indicate that the GrassMaster II in-situ technique could play a crucial role in assessing pasture mass to improve feed planning under Mediterranean conditions.

Evaluation of DUALEM, OptRx and Grassmaster II sensors for monitoring the spatial variability and the temporal stability of a Mediterranean pasture

Site-specific management (SSM) is a form of precision agriculture whereby decisions on resource application and agronomic practices are improved to better match soil and crop requirements as they vary in the field. SSM enables the identification of regions (homogeneous management zones) within the area delimited by field boundaries. These subfield regions constitute areas that have similar permanent characteristics. Traditional soil and pasture sampling and the necessary laboratory analysis are time-consuming, labour-intensive and cost prohibitive, not viable from a SSM perspective because it needs a large number of soil and pasture samples in order to achieve a good representation of soil properties, nutrient levels and pasture quality and productivity. The main objective of this work was to evaluate technologies which have potential for monitoring aspects related to spatial and temporal variability of soil nutrients and pasture green and dry matter yield (respectively, GM and DM, in kg/ha) and support to decision making for the farmer. Three types of sensors were evaluated in a 7ha pasture experimental field: an electromagnetic induction sensor (“DUALEM 1S”, which measures the soil apparent electrical conductivity, ECa), an active optical sensor ("OptRx®", which measures the NDVI, “Normalized Difference Vegetation Index”) and a capacitance probe ("GrassMaster II" which estimates plant mass). The results indicate the possibility of using a soil electrical conductivity probe as, probably, the best tool for monitoring not only some of the characteristics of the soil, but also those of the pasture, which could represent an important help in simplifying the process of sampling and support SSM decision making, in precision agriculture projects. On the other hand, the significant and very strong correlations obtained between capacitance and NDVI and between any of these parameters and the pasture productivity shows the potential of these tools for monitoring the evolution of spatial and temporal patterns of the vegetative growth of biodiverse pasture, for identifying different plant species and variability in pasture yield in Alentejo dry-land farming systems. These results are relevant for the selection of an adequate sensing system for a particular application and open new perspectives for other works that would allow the testing, calibration and validation of the sensors in a wider range of pasture production conditions, namely the extraordinary diversity of botanical species that are characteristic of the Mediterranean region at the different periods of the year.

Era uma vez...As sete casas da infortuna: relação actor - marioneta : Relatório de estágio

O presente relatório tem como objectivo analisar a realidade de uma Companhia de Marionetas em Portugal, Teatro e Marionetas de Mandrágora, incidindo sobre a relação entre o actor, marioneta e meio envolvente (site specific) no contexto de uma prática teatral concreta, a produção do espectáculo Era uma vez ...As Sete Casas da Infortuna, no Castelo de Santa Maria da Feira. Os resultados apurados acompanham os moldes em que se procurou passar de um actor convencional para a especialização de um micromundo teatral onde a aprendizagem foi, fulcral desde o processo de construção até, à manipulação em cena num universo de trabalho particularmente árduo e específico. A minha trajectória no seio da companhia começou pela familiarização e aprendizagem informal da prática das marionetas através da observação directa dos espectáculos e de diferentes projectos da companhia. A formação feita no local de estágio (atelier da Companhia) foi outra das modalidades de formação que acompanhou o meu trajecto ao longo do estágio através da minha colaboração em projectos como Teatro nas Instituições, sempre sob a égide da divisão de tarefas e de alguma autoaprendizagem com a devida supervisão e orientação de artistas especialistas, como o Director Criativo, enVide neFelibata. O laboratório de aprendizagem prosseguiu pela mão da marionetista Clara Ribeiro que orientou a minha formação no sentido de absorver princípios teórico-práticos como o Foco, o Movimento e o Olhar para uma melhor consciencialização do universo do teatro de marionetas e formas animadas. Ainda nessa aprendizagem, a figura de alguns artistas especialistas foi fulcral, nomeadamente a da cenógrafa Marta Fernandes da Silva, que revelou ser de extrema importância ao longo do estágio pois permitiu uma verdadeira intersecção entre as componentes teórica e prática. Dessa forma pude acompanhar todo o processo de criação do Era uma vez ...As Sete Casas da Infortuna, e colaborar na construção das marionetas que iria manipular como actor - marionetista. Relativamente à questão da componente da interpretação no estágio, esta foi assumida pela encenadora - marionetista, Filipa Alexandre que, com a sua orientação, permitiu um enfoque do grupo de trabalho num processo de criação colectiva. Assim, a nível pessoal, fui movido por uma necessidade premente de descodificar o papel do actor na sua relação com a marioneta e o meio envolvente (site specific). ABSTRACT: This study aims to examine the reality of a Puppet Company in Portugal, the Puppet Theater of Mandrágora, focusing on the relationship between actor, puppet and environment (site specific) in the context of an actual theatrical practice, Once upon a time ...Seven houses of infortune, in the Castle of Santa Maria da Feira. The results obtained follow the way in which one seeks to move from one "conventional" actor to the specialization of a micro theater where learning was central from the building process to manipulation on the scene in a universe of work particularly hard and specific. My initial course within the company began with the familiarization and informal learning of the practice of puppetry through direct observation of performances and various projects of the company. The training done at the company (workshop of the Company) was one of the training arrangements that accompanied my way along the training through assistance on projects such as Teatro nas Instituições, always under the auspices of the division of tasks and due self-teaching with appropriate supervision and guidance of expert artists, such as the Creative Director, enVide neFelibata. The learning laboratory continued by the hand of the puppeteer Clara Ribeiro who supervised my training in order to absorb theoretical and practical principles as the Focus, the Movement and the Look for better awareness of the world of puppetry and animated forms. Also at this level, the figure of some specialist artists were central, such as the scenographer Marta Fernandes da Silva, who proved to be extremely important during this training, allowing a true intersection between the theoretical and the practical components. I could experience the surroundings of the creation notebook of Era uma vez ...As Sete Casas da Infortuna, and collaborate in the preparation of puppets that would handle as an actor - puppeteer. As to the question of the interpretation component on training, this was in charge of stage director - puppeteer, and the Artistic Director, Filipa Alexandre, whose instructions allowed a focus of the working group in a process of collective creation. Accordingly, to a personal level, I was urged to decode the role of the actor in relation to the puppet and the environment (site specific).

Sviluppo di processi di comunicazione aptici tra uomo e macchina

La ricerca si focalizza sul rapporto tra tecnologie abilitanti e corpo umano. La miniaturizzazione delle tecnologie, unita alla loro maggiore diffusione negli ambienti, porta ad interrogarsi sull’efficacia dell’integrazione di esse con corpo e attività ad esso connesse. Il contesto problematico della ricerca riguarda i dispositivi indossabili e il progetto di soluzioni destinate a risolvere inediti bisogni o potenziare i sensi umani. La letteratura scientifica e i casi studio circoscrivono il piede come efficace piattaforma per la sperimentazione di interfacce aptiche di comunicazione uomo/macchina, atte a connettere il corpo con informazioni referenziate all’ambiente. Il piede, elemento motorio duplice e simmetrico, ha un’elevata qualità percettiva ed è morfologicamente adeguato all’applicazione di tecnologie emergenti. La posizione di soglia, tra spazio e corpo, consente la raccolta di stimoli da entrambe le aree. La bibliografia evidenzia quanto la pressione, rispetto alla vibrazione, sia preferibile nella comunicazione aptica in quanto componente naturale dei linguaggi relazionali del corpo. Dall’analisi multidisciplinare emerge infine l’opportunità di sviluppo del ritmo come componente strutturale dei messaggi. I legami relazionali tra ritmo, corpo e comportamenti umani sono evidenti in molteplici meccanismi: trascinamento ritmico, mimesi ritmica, sincronia. La messa in relazione di piede, pressione e ritmo diventa affordance dello spazio, capace di suggerire, enfatizzare o attivare determinati comportamenti. L’unione di questi elementi è qui definita ritmica podotattile ed esplicitata nella tesi della descrizione delle sue caratteristiche, dalla circoscrizione di campi e azioni applicative e dalla raccolta dati sui test effettuati con i prototipi costruiti. Le analisi quantitative e qualitative dei dati di lettura del movimento e delle emozioni dimostrano quanto l’utilizzo di un linguaggio ritmico aptico nel piede esprima elevate potenzialità di integrazione con il corpo nel rispetto del comfort e dell’equilibrio attentivo nei flussi di azione preesistenti. I risultati aprono riflessioni su nuove applicazioni progettuali nel campo museale, lavorativo e urbano.

Metocean Climate Impact on the Fatigue Assessment of a Jacket-Type Offshore Platform

When the offshore oil and gas supplies exhaust, most offshore platforms are decommissioned and removed. The purpose of this paper is to evaluate the fatigue damage that will occur during the service life of a jacket-type offshore platform using different fatigue approaches in particular locations. The locations considered for this metocean climate impact study were Norway (North Sea), Portugal (Atlantic Ocean - Leixões) and Italy (Adriatic Sea). A finite element model was created by the means of Sesam and two different fatigue analysis, deterministic and spectral, were applied. For the fatigue assessment, an appropriate description of the site-specific wave environment, during the jacket platform service life, must be accomplished. This description is usually provided by a wave scatter diagram. Wave scatter diagrams usually represent the long-term wave environment during a (typical) year and are based on several years of site-specific data to ensure that they adequately represent the wave environment at the location of the structure. In this thesis, the comparison between these fatigue approaches will serve as a pilot study for planned reliability analysis in decommissioned offshore platforms in order to maximize the reuse of these platforms for future wind generation systems.

Adattamento morfologico e variazione dell'espressione genica dopo pneumonectomia: osservazioni su modello sperimentale animale

Introduzione La pneumonectomia su modello animale potrebbe essere un’utile piattaforma di studio per approfondire i meccanismi della risposta compensatoria al danno polmonare. Scopo dello studio è determinare la presenza di variazioni morfologiche e di espressione del trascrittoma dopo pneumonectomia. Materiali e metodi Undici suini sono stati sottoposti a pneumonectomia sinistra. Sono stati eseguiti prelievi sito-specifici intraoperatori su polmone sinistro e successivamente confrontati con prelievi sito-specifici su polmone destro dopo eutanasia a 60 giorni. I prelievi degli animali con decorso regolare sono stati sottoposti a RNA-sequencing e successiva analisi computazionale per valutare il peso funzionale del singolo gene o di clusters di geni. Risultati Un animale è stato escluso per insorgenza di ernia diaframmatica. In 7/10 è stata riscontrata apertura della pleura mediastinica con parziale erniazione del polmone controlaterale e shift mediastinico. L’istologia ha mostrato dilatazione degli spazi aerei, rottura dei setti interalveolari, lieve infiammazione, assenza di fibrosi, stiramento radiale dei bronchi e riduzione del letto capillare. L’analisi di bulk RNA-sequencing ha identificato 553 geni espressi in modo differenziale (DEG)(P<0,001) tra pre e post-pneumonectomia. I primi 10 DEG up-regolati: Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; i primi 10 geni down-regolati: Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Tra i DEG è stata riscontrata una predominanza di geni specifici dei macrofagi. L’analisi di gene ontology basata su DAVID ha mostrato un significativo arricchimento della "via di segnalazione apoptotica estrinseca"(FDR q=7,60x10 -3), della via di “Risposta all’insulina”(FDR q=7,60x10 -3) ed un arricchimento di geni “Regolatori negativi del segnale DDX58/IFIH1”(FDR q=7.50x10 -4). Conclusioni Il presente studio conferma la presenza di variazioni macroscopiche e microscopiche fenotipiche dopo pneumonectomia. L’RNA sequencing e lo studio di genomica traslazionale hanno mostrato l’esistenza di geni singoli e di network di geni disregolati dopo pneumonectomia, prevalentemente in determinate popolazioni cellulari.

Percorsi di valorizzazione artistica di ambienti naturali per una nuova consapevolezza ecologica

L’idea di questa tesi nasce da due riflessioni maturate in parallelo nel corso del mio percorso di tirocinio e nate, più in generale, durante quello di studi. La prima è relativa ai tentativi di convergenza tra arte, scienza e cultura in linea con le strategie di pianificazione comunitarie del futuro, e la seconda sul tema del Service Design e in particolare dello Human Centered Design, considerato, nell’analisi di questo lavoro, insufficiente a inquadrare e cogliere interamente il sistema relazionale entro cui è contestualizzato l’utente-cittadino, o più in generale il soggetto per cui si progetta e si pianifica. Un primo passaggio concettuale e progettuale derivato da queste riflessioni è stato quindi quello dello spostamento del focus del servizio dall’esclusività dell’utente all’inclusività dell’utente inserito in un ambiente, in considerazione del bisogno latente e ultimo di ogni essere umano: una convivenza e una relazione sana e cosciente con ciò che lo circonda, sottolineando l’importanza della molteplicità di relazioni che legano ogni individuo al contesto in cui è inserito. Il progetto di tesi si pone infatti l’obiettivo di ribaltare la narrazione negativa e il graduale allontanamento degli abitanti di Ravenna dalle grandi aree naturali che circondano la città, attraverso un servizio di promozione che integri attività di produzione artistica e culturale con percorsi di ingaggio, sensibilizzazione e confronto dei cittadini e degli artisti stessi. Il servizio progettato è stato concretizzato in un sistema di valorizzazione artistica tramite residenze per ambienti naturali mirato alla diffusione di una nuova consapevolezza ecologica e territoriale nella popolazione. È stato sviluppato partendo da un evento di lancio site-specific per giungere alla definizione di un format idealmente replicabile ed espandibile per qualsiasi territorio in cui ve ne fosse bisogno.

Hypomorphic mutation in the site-1 protease Mbtps1 endows resistance to persistent viral infection in a cell-specific manner.

The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), which naturally persists in rodents, represents a model for HIV, HBV, and HCV. Cleavage of the viral glycoprotein precursor by membrane-bound transcription factor peptidase, site 1 (Mbtps1 or site-1 protease), is crucial for the life cycle of arenaviruses and therefore represents a potential target for therapy. Recently, we reported a viable hypomorphic allele of Mbtps1 (woodrat) encoding a protease with diminished enzymatic activity. Using the woodrat allele, we examine the role of Mbtps1 during persistent LCMV infection. Surprisingly, Mbtps1 inhibition limits persistent but not acute viral infection and is associated with an organ/cell type-specific decrease in viral titers. Analysis of bone marrow-derived dendritic cells from woodrat mice supports their specific role in resolving persistent viral infection. These results support in vivo targeting of Mbtps1 in the treatment of arenavirus infections and demonstrate a critical role for dendritic cells in persistent viral infections.

Accumulation of human immunodeficiency virus-specific cytotoxic T lymphocytes away from the predominant site of virus replication during primary infection.

Down-regulation of the initial burst of viremia during primary human immunodeficiency virus (HIV) infection is thought to be mediated predominantly by HIV-specific CD8+ cytotoxic T lymphocytes (CTL). This response is associated with major perturbations in the T cell receptor (TCR) repertoire. To investigate the failure of the cellular immune response to adequately control viral spread and replication and to prevent establishment of HIV infection, changes in the TCR repertoire and in the distribution of virus-specific CTL between blood and lymph node were analyzed in three patients with primary infection. By the combined use of clonotype-specific polymerase chain reaction and analysis of the frequency of in vivo activated HIV-specific CTL, it was shown that HIV-specific CTL clones preferentially accumulated in blood as opposed to lymph node. Accumulation of HIV-specific CTL in blood occurred prior to effective down-regulation of virus replication in both blood and lymph node. These findings should provide new insights into how HIV, and possibly other viruses, elude the immune response of the host during primary infection.

New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site.

Although increasing evidence suggests that CTL are important to fight the development of some cancers, the frequency of detectable tumor-specific T cells is low in cancer patients, and these cells have generally poor functional capacities, compared with virus-specific CD8(+) T cells. The generation with a vaccine of potent CTL responses against tumor Ags therefore remains a major challenge. In the present study, ex vivo analyses of Melan-A-specific CD8(+) T cells following vaccination with Melan-A peptide and CpG oligodeoxynucleotides revealed the successful induction in the circulation of effective melanoma-specific T cells, i.e., with phenotypic and functional characteristics similar to those of CTL specific for immunodominant viral Ags. Nonetheless, the eventual impact on tumor development in vaccinated melanoma donors remained limited. The comprehensive study of vaccinated patient metastasis shows that vaccine-driven tumor-infiltrating lymphocytes, although activated, still differed in functional capacities compared with blood counterparts. This coincided with a significant increase of FoxP3(+) regulatory T cell activity within the tumor. The consistent induction of effective tumor-specific CD8(+) T cells in the circulation with a vaccine represents a major achievement; however, clinical benefit may not be achieved unless the tumor environment can be altered to enable CD8(+) T cell efficacy.

Homing phenotypes of tumor-specific CD8 T cells are predetermined at the tumor site by crosspresenting APCs.

Expression of tissue-specific homing molecules directs antigen-experienced T cells to particular peripheral tissues. In studies using soluble antigens that focused on skin and gut, antigen-presenting cells (APCs) within regional lymphoid tissues were proposed to be responsible for imprinting homing phenotypes. Whether this occurs in other sites and after physiologic antigen processing and presentation is unknown. We define in vivo imprinting of distinct homing phenotypes on monospecific T cells responding to antigens expressed by tumors in intracerebral, subcutaneous, and intraperitoneal sites with efficient brain-tropism of CD8 T cells crossprimed in the cervical lymph nodes (LNs). Multiple imprinting programs could occur simultaneously in the same LN when tumors were present in more than one site. Thus, the identity of the LN is not paramount in determining the homing phenotype; this critical functional parameter is dictated upstream at the site of antigen capture by crosspresenting APCs.

H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis

Aberrant methylation of seven potential binding sites of the CTCF factor in the differentially methylated region upstream of the H19 gene (H19-DMR) has been suggested as critical for the regulation of IGF2 and H19 imprinted genes. In this study, we analyzed the allele-specific methylation pattern of CTCF binding sites 5 and 6 using methylationsensitive restriction enzyme PCR followed by RFLP analysis in matched tumoral and lymphocyte DNA from head-and-neck squamous cell carcinoma (HNSCC) patients, as well as in lymphocyte DNA from control individuals who were cancer-free. The monoallelic methylation pattern was maintained in CTCF binding site 5 in 22 heterozygous out of 91 samples analyzed. Nevertheless, a biallelic methylation pattern was detected in CTCF binding site 6 in a subgroup of HNSCC patients as a somatic acquired feature of tumor cells. An atypical biallelic methylation was also observed in both tumor and lymphocyte DNA from two patients, and at a high frequency in the control group (29 out of 64 informative controls). Additionally, we found that the C/T transition detected by HhaI RFLP suppressed one dinucleotide CpG in critical CTCF binding site 6, of a mutation showing polymorphic frequencies. Although a heterogeneous methylation pattern was observed after DNA sequencing modified by sodium bisulfite, the biallelic methylation pattern was confirmed in 9 out of 10 HNSCCs. These findings are likely to be relevant in the epigenetic regulation of the DMR, especially in pathological conditions in which the imprinting of IGF2 and H19 genes is disrupted.

Relationship between B-Cell-specific moloney murine leukemia virus integration site 1 (BMI-1) and homologous recombination regulatory genes in invasive ductal breast carcinomas

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is a Polycomb group protein that is able to induce telomerase activity, enabling the immortalization of epithelial cells. Immortalized cells are more susceptible to double-strand breaks (DSB), which are subsequently repaired by homologous recombination (HR). BRCA1 is among the HR regulatory genes involved in the response to DNA damage associated with the RAD51 protein, which accumulates in DNA damage foci after signaling H2AX, another important marker of DNA damage. Topoisomerase III beta (topoIII beta) removes HR intermediates before chromosomal segregation, preventing damage to cellular DNA structure. In breast carcinomas positive for BMI-1 the role of proteins involved in HR remains to be investigated. The aim of this study was to evaluate the association between BMI-1 and homologous recombination proteins. Using tissue microarrays containing 239 cases of primary breast tumors, the expression of Bmi-1, BRCA-1, H2AX, Rad51, p53, Ki-67, topoIII beta, estrogen receptors (ER), progesterone receptors (PR), and HER-2 was analyzed by immunohistochemistry. We observed high Bmi-1 expression in 66 cases (27.6%). Immunohistochemical overexpression of BMI-1 was related to ER (p=0.004), PR (p<0.001), Ki-67 (p<0.001), p53 (p=0.003), BRCA1 (p=0.003), H2AX (p=0.024) and topoIII beta (p<0,001). Our results show a relationship between the expression of BMI-1 and HR regulatory genes, suggesting that Bmi-1 overexpression might be an important event in HR regulation. However, further studies are necessary to understand the mechanisms in which Bmi-1 could regulate HR pathways in invasive ductal breast carcinomas.

Site- and species-specific responses of forest growth to climate across the European continent

Aim To evaluate the climate sensitivity of model-based forest productivity estimates using a continental-scale tree-ring network. Location Europe and North Africa (30–70° N, 10° W–40° E). Methods We compiled close to 1000 annually resolved records of radial tree growth for all major European tree species and quantified changes in growth as a function of historical climatic variation. Sites were grouped using a neural network clustering technique to isolate spatiotemporal and species-specific climate response patterns. The resulting empirical climate sensitivities were compared with the sensitivities of net primary production (NPP) estimates derived from the ORCHIDEE-FM and LPJ-wsl dynamic global vegetation models (DGVMs). Results We found coherent biogeographic patterns in climate response that depend upon (1) phylogenetic controls and (2) ambient environmental conditions delineated by latitudinal/elevational location. Temperature controls dominate forest productivity in high-elevation and high-latitude areas whereas moisture sensitive sites are widespread at low elevation in central and southern Europe. DGVM simulations broadly reproduce the empirical patterns, but show less temperature sensitivity in the boreal zone and stronger precipitation sensitivity towards the mid-latitudes. Main conclusions Large-scale forest productivity is driven by monthly to seasonal climate controls, but our results emphasize species-specific growth patterns under comparable environmental conditions. Furthermore, we demonstrate that carry-over effects from the previous growing season can significantly influence tree growth, particularly in areas with harsh climatic conditions – an element not considered in most current-state DGVMs. Model–data discrepancies suggest that the simulated climate sensitivity of NPP will need refinement before carbon-cycle climate feedbacks can be accurately quantified.