Hepatic effects of long‐term tamoxifen administration to cycling female rats

The metabolic implications of tamoxifen (TAM) used as preventive therapy of young premenopausal women with high risk of breast cancer is unknown. To unravel this problem, an animal model of long‐term TAM administration to cycling young adult female rats was used to evaluate its effects in the liver. Body weight and food consumption were monitored, and at the end of the study, both parameters were lower in TAM‐treated rats. Biochemical measurements showed that the TAM administration induced alterations in serum levels of liver enzymes when compared with control rats at different stages of the estrous cycle. In TAM‐treated rats, lower glycogen storage was observed in hepatocytes close to the portal areas and pericentrolobular cells had a higher concentration of glycogen. Liver sections of TAM‐treated rats presented mild steatosis—a high percentage of area occupied by lipid droplets in the hepatocytes. These results point to metabolic changes upon long‐term TAM therapy.     

Leaf wax n‐alkane patterns of six tropical montane tree species show species‐specific environmental response

It remains poorly understood how the composition of leaf wax n‐alkanes reflects the local environment. This knowledge gap inhibits the interpretation of plant responses to the environment at the community level and, by extension, inhibits the applicability of n‐alkane patterns as a proxy for past environments. Here, we studied the n‐alkane patterns of five Miconia species and one Guarea species, in the Ecuadorian Andes (653–3,507 m a.s.l.). We tested for species‐specific responses in the average chain length (ACL), the C₃₁/(C₃₁ + C₂₉) ratio (ratio), and individual odd n‐alkane chain lengths across an altitudinally driven environmental gradient (mean annual temperature, mean annual relative air humidity, and mean annual precipitation). We found significant correlations between the environmental gradients and species‐specific ACL and ratio, but with varying magnitude and direction. We found that the n‐alkane patterns are species‐specific at the individual chain length level, which could explain the high variance in metrics like ACL and ratio. Although we find species‐specific sensitivity and responses in leaf n‐alkanes, we also find a general decrease in “shorter” (<C₂₉) and an increase in “longer” (>C₃₁) chain lengths with the environmental gradients, most strongly with temperature, suggesting n‐alkanes are useful for reconstructing past environments.     

Variable actin dynamics requirement for the exit of different cargo from the trans-Golgi network

Efficient post-Golgi trafficking depends on microtubules, but actin filaments and actin-associated proteins are also postulated. Here we examined, by inverse fluorescence recovery after photobleaching, the role of actin dynamics in the exit from the TGN of fluorescent-tagged apical or basolateral and raft or non-raft-associated cargoes. Either the actin-stabilizing jasplakinolide or the actin-depolymerising latrunculin B variably but significantly inhibited post-Golgi traffic of non-raft associated apical p75NTR and basolateral VSV-G cargoes. The TGN-exit of the apical-destined VSV-G mutant was impaired only by latrunculin B. Strikingly, the raft-associated GPI-anchor protein was not affected by either actin toxin. Results indicate that actin dynamics participates in the TGN egress of both apical- and basolateral-targeted proteins but is not needed for apical raft-associated cargo.     

Constitutive traffic of melanocortin-4 receptor in Neuro2A cells and immortalized hypothalamic neurons

Melanocortin-4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that binds alpha-melanocyte-stimulating hormone (alpha-MSH) and has a central role in the regulation of appetite and energy expenditure. Most GPCRs are endocytosed following binding to the agonist and receptor desensitization. Other GPCRs are internalized and recycled back to the plasma membrane constitutively, in the absence of the agonist. In unstimulated neuroblastoma cells and immortalized hypothalamic neurons, epitopetagged MC4R was localized both at the plasma membrane and in an intracellular compartment. These two pools of receptors were in dynamic equilibrium, with MC4R being rapidly internalized and exocytosed. In the absence of alpha-MSH, a fraction of cell surface MC4R localized together with transferrin receptor and to clathrin-coated pits. Constitutive MC4R internalization was impaired by expression of a dominant negative dynamin mutant. Thus, MC4R is internalized together with transferrin receptor by clathrin-dependent endocytosis. Cell exposure toalpha-MSH reduced the amount of MC4R at the plasma membrane by blocking recycling of a fraction of internalized receptor, rather than by increasing its rate of endocytosis. The data indicate that, in neuronal cells, MC4R recycles constitutively and that alpha-MSH modulates MC4R residency at the plasma membrane by acting at an intracellular sorting step.     

Parameterization of the stomatal component of the DO3SE model for Mediterranean evergreen broadleaf species

An ozone (O3) deposition model (DO3SE) is currently used in Europe to define the areas where O3 concentrations lead to absorbed O3 doses that exceed the flux-based critical levels above which phytotoxic effects would be likely recorded. This mapping exercise relies mostly on the accurate estimation of O3 flux through plant stomata. However, the present parameterization of the modulation of stomatal conductance (g(s)) behavior by different environmental variables needs further adjustment if O3 phytotoxicity is to be assessed accurately at regional or continental scales. A new parameterization of the model is proposed for Holm oak (Quercus ilex), a tree species that has been selected as a surrogate for all Mediterranean evergreen broadleaf species. This parameterization was based on a literature review, and was calibrated and validated using experimentally measured data of g(s) and several atmospheric and soil parameters recorded at three sites of the Iberian Peninsula experiencing long summer drought, and very cold and dry winter air (El Pardo and Miraflores) or milder conditions (Tietar). A fairly good agreement was found between modeled and measured data (R2 = 0.64) at Tietar. However, a reasonable performance (R2 = 0.47-0.62) of the model was only achieved at the most continental sites when g(s) and soil moisture deficit relationships were considered. The influence of root depth on g(s) estimation is discussed and recommendations are made to build up separate parameterizations for continental and marine-influenced Holm oak sites in the future.     

Watch-ing out for chick limb development

Time control is a crucial issue during embryonic development.Nevertheless, little is known about how embryonic cells measuretime. Until recently, the only molecular clock known to operateduring vertebrate embryonic development was the somitogenesisclock, exclusively functioning in coordinating the precise timingof each new pair of somites formed from the presomitic mesoderm.We have recently evidenced that a similar molecular clock alsounderlies the timing at which autopod chondrogenic precursorsare laid down to form a skeletal limb element. In addition,we herein suggest that the molecular clock is not the only parallelismthat can be established between somitogenesis and limb-bud development.In an evolutionary perspective, we support the previously proposedidea that the molecular mechanisms involved in the segmentationof the body axis may have been partially reused in the mesodermof the lateral plate, thereby allowing the emergence of pairedappendages.     

Spatial scale,topography and thermoregulatory behaviour interact when modelling species’ thermal niches

The spatial scale at which climate and species’ occupancy data are gathered, and the resolution at which ecological models are run, can strongly influence predictions of species performance and distributions. Running model simulations at coarse rather than fine spatial resolutions, for example, can determine if a model accurately predicts the distribution of a species. The impacts of spatial scale on a model's accuracy are particularly pronounced across mountainous terrain. Understanding how these discrepancies arise requires a modelling approach in which the underlying processes that determine a species’ distribution are explicitly described. Here we use a process‐based model to explore how spatial resolution, topography and behaviour alter predictions of a species thermal niche, which in turn constrains its survival and geographic distribution. The model incorporates biophysical equations to predict the operative temperature (T_e), thermal‐dependent performance and survival of a typical insect, with a complex life‐cycle, in its microclimate. We run this model with geographic data from a mountainous terrain in South Africa using climate data at three spatial resolutions. We also explore how behavioural thermoregulation affects predictions of a species performance and survival by allowing the animal to select the optimum thermal location within each coarse‐grid cell. At the regional level, coarse‐resolution models predicted lower T_e at low elevations and higher T_e at high elevations than models run at fine‐resolutions. These differences were more prominent on steep, north‐facing slopes. The discrepancies in T_e in turn affected estimates of the species thermal niche. The modelling framework revealed how spatial resolution and topography influence predictions of species distribution models, including the potential impacts of climate change. These systematic biases must be accounted for when interpreting the outputs of future modelling studies, particularly when species distributions are predicted to shift from uniform to topographically heterogeneous landscapes.