Fracture energy of wood and root burl wood of thuya (Tetraclinis articulata (Vahl) Masters)

International audienceThe fracture energy of wood and root burl wood of thuya, coming from the forest of Essaouira (Morocco), was measured using a single edge notched specimen bending (SENB) test method. The variations along the longitudinal and transverse directions were studied using specimens taken from one radial section of thuya wood and on radial section of thuya burl, originating from two different trees. Thuya burl was more resistant than thuya wood to crack propagation in RL system (in the tangential plane). This difference is explained by the presence of dark growths, composed of cells with thicker walls that make the burl wood usually denser than thuya wood. Thuya burl was more resistant to crack propagation in RL system (tangential plane) than in TL system (radial plane), which is consistent with the radial orientation of the dark growths. The observed decrease of fracture energy along the longitudinal direction was explained by the progressive reduction of dark growth concentration

Caractérisation physique du bois de la loupe de Thuya

International audienceCe travail constitue une contribution originale à l'étude de la densité et du retrait au séchage de la loupe de thuya provenant de la forêt de Khémisset (Maroc). La densité est souvent utilisée dans les étapes de prédiction des propriétés mécaniques du bois. Quant aux retraits linéaires, l'existence ou non d'une anisotropie entre les retraits radial, tangentiel et longitudinal préfigurent du comportement mécanique du bois. Les mesures de ces propriétés physiques sont réalisées sur 77 échantillons de 2×2×2cm3 découpés selon les directions radiale, tangentielle et longitudinale. L'analyse des résultats des mesures de densité permet de classer le bois de la loupe de thuya comme un bois dense. La densité de la loupe est plus élevée que celle du bois de thuya. Cette différence s'explique par la présence d'excroissances foncées composées de cellules aux parois plus épaisses que celles du bois de thuya. L'analyse des mesures de retraits montre une faible anisotropie de retraits, expliquée à l'échelle microscopique dans un plan de référence, par une orientation très variable des cellules. Ce résultat présuppose un comportement mécanique proche d'un comportement isotrope du bois de la loupe de thuya

DNA Double-Strand Break Repair Genes and Oxidative Damage in Brain Metastasis of Breast Cancer

Background Breast cancer frequently metastasizes to the brain, colonizing a neuro-inflammatory microenvironment. The molecular pathways facilitating this colonization remain poorly understood. Methods Expression profiling of 23 matched sets of human resected brain metastases and primary breast tumors by two-sided paired t test was performed to identify brain metastasis–specific genes. The implicated DNA repair genes BARD1 and RAD51 were modulated in human (MDA-MB-231-BR) and murine (4T1-BR) brain-tropic breast cancer cell lines by lentiviral transduction of cDNA or short hairpin RNA (shRNA) coding sequences. Their functional contribution to brain metastasis development was evaluated in mouse xenograft models (n = 10 mice per group). Results Human brain metastases overexpressed BARD1 and RAD51 compared with either matched primary tumors (1.74-fold, P < .001; 1.46-fold, P < .001, respectively) or unlinked systemic metastases (1.49-fold, P = .01; 1.44-fold, P = .008, respectively). Overexpression of either gene in MDA-MB-231-BR cells increased brain metastases by threefold to fourfold after intracardiac injections, but not lung metastases upon tail-vein injections. In 4T1-BR cells, shRNA-mediated RAD51 knockdown reduced brain metastases by 2.5-fold without affecting lung metastasis development. In vitro, BARD1- and RAD51-overexpressing cells showed reduced genomic instability but only exhibited growth and colonization phenotypes upon DNA damage induction. Reactive oxygen species were present in tumor cells and elevated in the metastatic neuro-inflammatory microenvironment and could provide an endogenous source of genotoxic stress. Tempol, a brain-permeable oxygen radical scavenger suppressed brain metastasis promotion induced by BARD1 and RAD51 overexpression. Conclusions BARD1 and RAD51 are frequently overexpressed in brain metastases from breast cancer and may constitute a mechanism to overcome reactive oxygen species–mediated genotoxic stress in the metastatic brain

Management of ErbB2-positive Breast Cancer: Insights from Preclinical and Clinical Studies with Lapatinib

The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer

Forest microclimates and climate change: importance, drivers and future research agenda

Forest microclimates contrast strongly with the climate outside forests. To fully understand and better predict how forests' biodiversity and functions relate to climate and climate change, microclimates need to be integrated into ecological research. Despite the potentially broad impact of microclimates on the response of forest ecosystems to global change, our understanding of how microclimates within and below tree canopies modulate biotic responses to global change at the species, community and ecosystem level is still limited. Here, we review how spatial and temporal variation in forest microclimates result from an interplay of forest features, local water balance, topography and landscape composition. We first stress and exemplify the importance of considering forest microclimates to understand variation in biodiversity and ecosystem functions across forest landscapes. Next, we explain how macroclimate warming (of the free atmosphere) can affect microclimates, and vice versa, via interactions with land-use changes across different biomes. Finally, we perform a priority ranking of future research avenues at the interface of microclimate ecology and global change biology, with a specific focus on three key themes: (1) disentangling the abiotic and biotic drivers and feedbacks of forest microclimates; (2) global and regional mapping and predictions of forest microclimates; and (3) the impacts of microclimate on forest biodiversity and ecosystem functioning in the face of climate change. The availability of microclimatic data will significantly increase in the coming decades, characterizing climate variability at unprecedented spatial and temporal scales relevant to biological processes in forests. This will revolutionize our understanding of the dynamics, drivers and implications of forest microclimates on biodiversity and ecological functions, and the impacts of global changes. In order to support the sustainable use of forests and to secure their biodiversity and ecosystem services for future generations, microclimates cannot be ignored.Peer reviewe

Characterisation and categorisation of the diversity in viscoelastic vibrational properties between 98 wood types

International audienceContext Increased knowledge on diversity in wood properties would have implications both for fundamental research and for promoting a diversification of uses as material. *Aims The objective is to contribute to overcoming the critical lack of data on the diversity of wood dynamic mechanical/viscoelastic vibrational properties, by testing lesser-known species and categorizing sources of variability. *Methods Air-dry axial specific dynamic modulus of elasticity (E'/γ) and damping coefficient (tanδ) were measured on a wide sampling (1792 specimens) of 98 wood types from 79 species. An experimental device and protocol was designed for conducting systematic (i.e. rapid and reproducible) characterizations. *Results Diversity at the specimens' level corroborates the "standard" relationship between tanδ and E'/γ, which is discussed in terms of orientation of wood elements and of chemical composition. Diversity at the species level is expressed on the basis of results for normal heartwood, with specific gravity (γ) ranging from 0.2 to 1.3. Axial E'/γ ranges from 9 to 32 GPa and tanδ from 4×10-3 to 19×10-3. Properties distribution follows a continuum, but with group characteristics. The lowest values of tanδ are only found in certain tropical hardwoods. Results can also suggest alternative species for musical instruments making

Differential Impact of EGFR-Targeted Therapies on Hypoxia Responses: Implications for Treatment Sensitivity in Triple-Negative Metastatic Breast Cancer

In solid tumors, such as breast cancer, cells are exposed to hypoxia. Cancer cells adapt their metabolism by activating hypoxia-inducible factors (HIFs) that promote the transcription of genes involved in processes such as cell survival, drug resistance and metastasis. HIF-1 is also induced in an oxygen-independent manner through the activation of epidermal growth factor receptor tyrosine kinase (EGFR-TK). Triple-negative breast cancer (TNBC) is a subtype of invasive breast cancer characterized by negative expression of hormonal and HER2 receptors, and this subtype generally overexpresses EGFR. Sensitivity to three EGFR inhibitors (cetuximab, gefitinib and lapatinib, an HER2/EGFR-TK inhibitor) was evaluated in a metastatic TNBC cell model (MDA-MB-231), and the impact of these drugs on the activity and stability of HIF was assessed.MDA-MB-231 cells were genetically modified to stably express an enhanced green fluorescent protein (EGFP) induced by hypoxia; the Ca9-GFP cell model reports HIF activity, whereas GFP-P564 reports HIF stability. The reporter signal was monitored by flow cytometry. HIF-1 DNA-binding activity, cell migration and viability were also evaluated in response to EGFR inhibitors. Cell fluorescence signals strongly increased under hypoxic conditions (> 30-fold). Cetuximab and lapatinib did not affect the signal induced by hypoxia, whereas gefitinib sharply reduced its intensity in both cell models and also diminished HIF-1 alpha levels and HIF-1 DNA-binding activity in MDA-MB-231 cells. This gefitinib feature was associated with its ability to inhibit MDA-MB-231 cell migration and to induce cell mortality in a dose-dependent manner. Cetuximab and lapatinib had no effect on cell migration or cell viability.Resistance to cetuximab and lapatinib and sensitivity to gefitinib were associated with their ability to modulate HIF activity and stability. In conclusion, downregulation of HIF-1 through EGFR signaling seems to be required for the induction of a positive response to EGFR-targeted therapies in TNBC

Preclinical Models of Brain Metastasis

Research at the Brain Metastasis Group is supported by MINECO grants MINECO-Retos SAF2017-89643-R (M.V.), Bristol-Myers Squibb- Melanoma Research Alliance Young Investigator Award 2017 (498103) (M.V.), Beug Foundation’s Prize for Metastasis Research 2017 (M.V.), Fundación Ramón Areces (CIVP19S8163) (M.V.), Worldwide Cancer Research (19-0177) (M.V.), H2020-FETOPEN (828972)N