Post-translational add-ons mark the path in exosomal protein sorting

Extracellular vesicles (EVs) are released by cells to the extracellular environment to mediate inter-cellular communication. Proteins, lipids, nucleic acids and metabolites shuttled in these vesicles modulate specific functions in recipient cells. The enrichment of selected sets of proteins in EVs compared with global cellular levels suggests the existence of specific sorting mechanisms to specify EV loading. Diverse post-translational modifications (PTMs) of proteins participate in the loading of specific elements into EVs. In this review, we offer a perspective on PTMs found in EVs and discuss the specific role of some PTMs, specifically Ubiquitin and Ubiquitin-like modifiers, in exosomal sorting of protein components. The understanding of these mechanisms will provide new strategies for biomedical applications. Examples include the presence of defined PTM marks on EVs as novel biomarkers for the diagnosis and prognosis of certain diseases, or the specific import of immunogenic components into EVs for vaccine generation.     

Human endoglin as a potential new partner involved in platelet–endothelium interactions

Complex interactions between platelets and activated endothelium occur during the thrombo-inflammatory reaction at sites of vascular injuries and during vascular hemostasis. The endothelial receptor endoglin is involved in inflammation through integrin-mediated leukocyte adhesion and transmigration; and heterozygous mutations in the endoglin gene cause hereditary hemorrhagic telangiectasia type 1. This vascular disease is characterized by a bleeding tendency that is postulated to be a consequence of telangiectasia fragility rather than a platelet defect, since platelets display normal functions in vitro in this condition. Here, we hypothesize that endoglin may act as an adhesion molecule involved in the interaction between endothelial cells and platelets through integrin recognition. We find that the extracellular domain of human endoglin promotes specific platelet adhesion under static conditions and confers resistance of adherent platelets to detachment upon exposure to flow. Also, platelets adhere to confluent endothelial cells in an endoglin-mediated process. Remarkably, Chinese hamster ovary cells ectopically expressing the human αIIbβ3 integrin acquire the capacity to adhere to myoblast transfectants expressing human endoglin, whereas platelets from Glanzmann’s thrombasthenia patients lacking the αIIbβ3 integrin are defective for endoglin-dependent adhesion to endothelial cells. Furthermore, the bleeding time, but not the prothrombin time, is significantly prolonged in endoglin-haplodeficient (Eng ^+/?) mice compared to Eng ^+/+ animals. These results suggest a new role for endoglin in αIIbβ3 integrin-mediated adhesion of platelets to the endothelium, and may provide a better understanding on the basic cellular mechanisms involved in hemostasis and thrombo-inflammatory events.     

Mutations in the cyclin family member FAM58A cause an X-linked dominant disorder characterized by syndactyly, telecanthus and anogenital and renal malformations

We identified four girls with a consistent constellation of facial dysmorphism and malformations previously reported in a single mother-daughter pair. Toe syndactyly, telecanthus and anogenital and renal malformations were present in all affected individuals; thus, we propose the name 'STAR syndrome' for this disorder. Using array CGH, qPCR and sequence analysis, we found causative mutations in FAM58A on Xq28 in all affected individuals, suggesting an X-linked dominant inheritance pattern for this recognizable syndrome.     

Comparison of distribution and habitat characteristics between an endemic and a wide-ranging cryptic species of Peromyscus on the Baja California Peninsula

Peromyscus eva and Peromyscus fraterculus are 2 morphologically similar species of the Peromyscus eremicus group occurring on the Baja California Peninsula. Due to the similarity between these 2 species, their ranges have been greatly confused; consequently, the specific habitat characteristics for each group are not well known. The goal of this study was to assess distribution ranges and characteristics of preferred habitats for P. eva and P. fraterculus in more detail. We identified taxonomy of individuals by evaluating genetic patterns produced by restriction fragment length polymorphisms (RFLPs). We evaluated the banding pattern generated by Alu I and Bam HI restriction enzymes in an 850-bp cytochrome b fragment. Consistent differences in number and size of fragments allowed for discrimination of individuals to species. The heterogeneity and evenness indexes showed that the microhabitat of P. fraterculus contained less-diverse soil types and is more homogeneous than the microhabitat of P. eva. In the state of Baja California Sur, P. eva occurs exclusively in the flat areas along the Pacific coast from the Vizcaino Desert to the south, including Margarita Island, with one small population in the Loreto area adjacent to Carmen Island. The habitats occupied by P. eva were heterogeneous (areas with friable, soft sandy soil and a low percentage of small stones). Peromyscus fraterculus occurs mostly in Baja California Norte, with some populations distributed in Baja California Sur, particularly in the western areas of the Vizcaino Desert along the mountain range, in the gulf side of the peninsula south of the city of La Paz, and in a small area on the eastern side of Sierra de Las Cruces. This species was mostly found on hard soil with high medium-size stone content.     

Methodologies for the Participant Construction of Knowledge

Over the last few decades there have been increasingly rapid changes in all fields (economic, political, etc. ...) leading to new forms of education and research. During the 1990s we have been working on innovative forms of education and participant research. In this context, this article includes some reflections on specific experiences of the construction of collective knowledge carried out in several cities, mainly in Spain and Latin America. It focuses on concrete postgraduate course experiences and it shows some innovative ways of collaborative relations between University, Public Administrations, and Social Organizations. The main theoretical and methodological principles of these experiences are also developed. On the other hand, we have been developing a network with some Latin partners on both sides of the ocean and we have recently made contacts with partners from English-speaking countries. We hope this article will contribute to building new bridges and communications on participant and instituent forms of knowledge construction.     

Simulating FAS-induced apoptosis by using P systems

In contrast to differential equations, P systems are an unconventional model of computation which takes into consideration the discrete character of the quantity of components and the inherent randomness that exists in biological phenomena. The key feature of P systems is their compartmentalised structure which represents the heterogeneity of the structural organisation of the cells, and where one can take into account the role played by membranes in the functioning of the system, for example signalling at the cell surface, selective uptake of substances from the media, diffusion across different compartments, etc. We show here that P systems can be a reliable tool for Systems Biology and could even outperform in some cases the current simulation techniques based on differential equations. We will also use a strategy based on the well known Gillespie algorithm but running on more than one compartment called Multi-compartmental Gillespie Algorithm.     

Cellular modelling using P systems and process algebra

In this paper various molecular chemical interactions are modelled under different computational paradigms. P systems andπ-calculus are used to describe intra-cellular reactions like protein-protein interactions and gene regulation control.     

澳门建筑遗产之移植特征

澳门历史城区被新增为世界历史文化遗产,澳门历史建筑的价值也正逐步被发掘,它是我国最古老的西式建筑遗产,也是东西方建筑艺术的综合体现,是中国历史城市中极具特色的组合.其中,"移植性"是澳门建筑遗产一个重要的文化特征,并体现在其城市格局、建筑风格、建筑构造与细部装饰中,反映出澳门建筑对来自世界各地不同文化的移植与包容.     

Stage-specific sensitivity to p53 restoration during lung cancer progression

Tumorigenesis is a multistep process that results from the sequential accumulation of mutations in key oncogene and tumour suppressor pathways. Personalized cancer therapy that is based on targeting these underlying genetic abnormalities presupposes that sustained inactivation of tumour suppressors and activation of oncogenes is essential in advanced cancers. Mutations in the p53 tumour-suppressor pathway are common in human cancer and significant efforts towards pharmaceutical reactivation of defective p53 pathways are underway. Here we show that restoration of p53 in established murine lung tumours leads to significant but incomplete tumour cell loss specifically in malignant adenocarcinomas, but not in adenomas. We define amplification of MAPK signalling as a critical determinant of malignant progression and also a stimulator of Arf tumour-suppressor expression. The response to p53 restoration in this context is critically dependent on the expression of Arf. We propose that p53 not only limits malignant progression by suppressing the acquisition of alterations that lead to tumour progression, but also, in the context of p53 restoration, responds to increased oncogenic signalling to mediate tumour regression. Our observations also underscore that the p53 pathway is not engaged by low levels of oncogene activity that are sufficient for early stages of lung tumour development. These data suggest that restoration of pathways important in tumour progression, as opposed to initiation, may lead to incomplete tumour regression due to the stage-heterogeneity of tumour cell populations.