CBP-mediated SMN acetylation modulates Cajal body biogenesis and the cytoplasmic targeting of SMN

The survival of motor neuron (SMN) protein plays an essential role in the biogenesis of spliceosomal snRNPs and the molecular assembly of Cajal bodies (CBs). Deletion of or mutations in the SMN1 gene cause spinal muscular atrophy (SMA) with degeneration and loss of motor neurons. Reduced SMN levels in SMA lead to deficient snRNP biogenesis with consequent splicing pathology. Here, we demonstrate that SMN is a novel and specific target of the acetyltransferase CBP (CREB-binding protein). Furthermore, we identify lysine (K) 119 as the main acetylation site in SMN. Importantly, SMN acetylation enhances its cytoplasmic localization, causes depletion of CBs, and reduces the accumulation of snRNPs in nuclear speckles. In contrast, the acetylation-deficient SMNK119R mutant promotes formation of CBs and a novel category of promyelocytic leukemia (PML) bodies enriched in this protein. Acetylation increases the half-life of SMN protein, reduces its cytoplasmic diffusion rate and modifies its interactome. Hence, SMN acetylation leads to its dysfunction, which explains the ineffectiveness of HDAC (histone deacetylases) inhibitors in SMA therapy despite their potential to increase SMN levels.     

Distribution of the meadow lizard in Europe and its realized ecological niche model

One of the most interesting but elusive members of the European herpetofauna is the meadow lizard (Darevskia praticola). It is a small, ground dwelling, predominantly forest living lacertid, for which many ecological and biological data are still missing. Moreover, at least for the western part of the species range (south-eastern Europe) its distribution and environmental associations are insufficiently known, likely due to difficulties in detection even with intensive field sampling. Here, we complemented the available literature records with our personal observations and explored the effects of environmental factors shaping the species ecological niche and distribution in Europe using the ecological niche modelling approach from Maxent software. The new records of the meadow lizard fill a gap in its known distribution. The most suitable habitats are in central and eastern Serbia, south-western Romania, and central, southern and south-western Bulgaria. Mean temperature of the coldest quarter, vegetation and slope had the strongest effect in defining the meadow lizard’s ecological niche. Niche suitability increased with the increase in forest cover and slope, while the temperature showed a bell-shaped response with a rather narrow tolerance range for temperature. Contrary to expectations, precipitation seemed to have no contribution to the species occurrence. Ecological niche model performance increased with a higher resolution of predictor variables despite the lower number of available occurrence records, although the slope variable had a greater predictive power when calculated at a lower resolution. Interestingly, high resolution vegetation variables (30 m) were able to show some level of habitat fragmentation, which likely resulted from deforestation. Overall, our results epitomize the effects of limited sampling on the biogeography inference of elusive species while having significant repercussions on conservation priorities and management of the species.     

Evaluation of the anti-angiogenic effect of aloe-emodin

The present study identified aloe-emodin (AE, a hydroxyanthraquinone from Aloe vera and other plants) as a new anti-angiogenic compound with inhibitory effects in an in vivo angiogenesis assay and evaluates its effects on specific key steps of the angiogenic process. AE inhibits endothelial cell proliferation, but this effect is not cell specific, since AE also inhibits tumor cell proliferation. Cell migration and invasion are not remarkably affected by AE. On the other hand, AE has different effects on endothelial and tumor cell gelatinases. Two main targets of the pharmacological action of AE as an anti-angiogenic compound seem to be urokinase secretion and tubule formation of endothelial cells. Finally, AE produces a remarkable photocytotoxic effect on tumor cells. Taken together, our data indicate that AE can behave both as an anti-tumor and an anti-angiogenic compound and suggest that AE could be a candidate drug for photodynamic therapy. Received 7 September 2006; received after revision 17 October 2006; accepted 31 October 2006     

Mesenchymal stem cells secretome: a new paradigm for central nervous system regeneration?

The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have been proposed as a possible therapeutic tool for CNS disorders. In addition to their differentiation potential, it is well accepted nowadays that their beneficial actions can also be mediated by their secretome. Indeed, it was already demonstrated, both in vitro and in vivo, that MSCs are able to secrete a broad range of neuroregulatory factors that promote an increase in neurogenesis, inhibition of apoptosis and glial scar formation, immunomodulation, angiogenesis, neuronal and glial cell survival, as well as relevant neuroprotective actions on different pathophysiological contexts. Considering their protective action in lesioned sites, MSCs’ secretome might also improve the integration of local progenitor cells in neuroregeneration processes, opening a door for their future use as therapeutical strategies in human clinical trials. Thus, in this review we analyze the current understanding of MSCs secretome as a new paradigm for the treatment of CNS neurodegenerative diseases.     

Anisakis simplex complex (Nematoda: Anisakidae) in zooplankton communities from temperate NE Atlantic waters

The euphausiid Nyctiphanes couchii and an unidentified mysid have been found, for the first time, with third-stage larvae (L₃) of the Anisakis simplex complex in the mesozooplanktonic community of the coastal upwelling system in Galicia (NW Spain). Parasite larvae were molecularly identified using the internal transcribed spacer (ITS) region. The prevalence of these parasites in the euphausiid population was 0.0019%. The existence of parasites in a variety of mesozooplankton organisms suggests that the transmission routes of A. simplex sensu stricto and A. pegrefii are wider than expected. The results suggest that these two Anisakis species are not specific to their intermediate hosts. Finally, the recruitment of A. simplex complex may be affected by oceanography, differing under upwelling or downwelling conditions.     

(—)-Epigallocatechin-3-gallate interferes with mast cell adhesiveness, migration and its potential to recruit monocytes

Mast cells are multipotent effector cells of the immune system. They are able to induce and enhance angiogenesis via multiple pathways. (-)-Epigallocatechin-3-gallate (EGCG), a major component of green tea and a putative chemopreventive agent, was reported to inhibit tumor invasion and angiogenesis, processes that are essential for tumor growth and metastasis. Using the human mast cell line HMC-1 and commercial cDNA macroarrays, we evaluated the effect of EGCG on the expression of angiogenesis-related genes. Our data show that among other effects, EGCG treatment reduces expression of two integrins (alpha5 and beta3) and a chemokine (MCP1), resulting in a lower adhesion of mast cells associated with a decreased potential to produce signals eliciting monocyte recruitment. These effects on gene expression levels are functionally validated by showing inhibitory effects in adhesion, aggregation, migration and recruitment assays.     

Parthenogenetic Darevskia lizards mate frequently if they have the chance: a quantitative analysis of copulation marks in a sympatric zone

Several Caucasian rock lizards of the genus Darevskia of hybrid origin are known to reproduce parthenogenetically. Local communities can be composed exclusively of parthenogens, though syntopy with bisexual members of the genus may occur. In some localities, reproduction between bisexual and parthenogenetic Darevskia has been previously reported based on lizard intermediate morphology and karyology (3n, 4n). However, the frequency of such heterospecific matings remains unknown. We indirectly quantified the reproductive interactions through the inspection of copulation marks in females in a mixed Darevskia community from Kuchak (Armenia) composed of two hybrid parthenogens (D. armeniaca and D. unisexualis), one bisexual species (D. valentini) and their putative backcrosses. A total of 139 adults were randomly collected and photographed. Females were later measured (SVL), inspected for inguinal marks and ranked from 0 (no scars) to 3 (≥ 3 scars). The lizard species and ploidy determination was ensured by a parallel microsatellite analysis. Sex-ratio in the community was extremely biased due to the high abundance of parthenogenetic females. All female types displayed copulation marks with frequencies varying from 80% in D. valentini to 64% in D. armeniaca. Remarkably, 7 out of 11 (64%) backcross females also showed marks. In the most abundant D. armeniaca, the prevalence and intensity of copulation marks increased with body size, just as predicted for polygynous female lacertids. These results indicate that copulation between parthenogenetic and bisexual species in Darevskia mixed communities is common and driven by sexual selection, thus reinforcing previous suggestions of reproductive interaction in syntopy. Evolutionary implications of these findings are discussed.     

Discovery of a magma chamber and faults beneath a Mid-Atlantic Ridge hydrothermal field

Crust at slow-spreading ridges is formed by a combination of magmatic and tectonic processes, with magmatic accretion possibly involving short-lived crustal magma chambers. The reflections of seismic waves from crustal magma chambers have been observed beneath intermediate and fast-spreading centres, but it has been difficult to image such magma chambers beneath slow-spreading centres, owing to rough seafloor topography and associated seafloor scattering. In the absence of any images of magma chambers or of subsurface near-axis faults, it has been difficult to characterize the interplay of magmatic and tectonic processes in crustal accretion and hydrothermal circulation at slow-spreading ridges. Here we report the presence of a crustal magma chamber beneath the slow-spreading Lucky Strike segment of the Mid-Atlantic Ridge. The reflection from the top of the magma chamber, centred beneath the Lucky Strike volcano and hydrothermal field, is approximately 3 km beneath the sea floor, 3-4 km wide and extends up to 7 km along-axis. We suggest that this magma chamber provides the heat for the active hydrothermal vent field above it. We also observe axial valley bounding faults that seem to penetrate down to the magma chamber depth as well as a set of inward-dipping faults cutting through the volcanic edifice, suggesting continuous interactions between tectonic and magmatic processes.     

葡萄牙松材线虫与其媒介昆虫之间的互作

对松材线虫与其在葡萄牙和欧洲的媒介昆虫樟子松墨天牛(Monochamus galloprovincialis)进行了首次研究.在病死木中发现,松材线虫在天牛刚羽化时聚集在蛹室中,线虫主要集中在天牛的后胸部.天牛羽化后6周内,松材线虫主要在天牛成虫补充营养时进入新寄主树,其次在天牛产卵时也会进入寄主树.总的看来,松材线虫在欧洲与其携带天牛之间互作与其在亚洲与松墨天牛及在北美与卡来罗纳墨天牛之间的关系十分相似.经研究,影响线虫与天牛携带关系的因子有内源和外源两类因子,如化学气味和各种信号.但是,其他多数因子尚未了解.研究影响线虫与天牛携带关系的因子将有助于了解两种生物密切关系的内在机制,并有助于研发出新的防控方法.