Involvement of a plasmid in Escherichia coli envelope alterations.

A plasmid-containing wild-type Escherichia coli strain was treated with two plasmid-curing agents, sodium dodecyl sulfate and ethidium bromide. Plasmid elimination was accompanied by drastic changes in the morphology of the colonies. Analysis of the cured strain by scanning and transmission electron microscopy showed important alterations in size and morphology of the cells. Metabolic differences were also found between the wild-type and cured cells.     

EphA2-Induced Angiogenesis in Ewing Sarcoma Cells Works through bFGF Production and Is Dependent on Caveolin-1

Angiogenesis is the result of the combined activity of the tumor microenvironment and signaling molecules. The angiogenic switch is represented as an imbalance between pro- and anti-angiogenic factors and is a rate-limiting step in the development of tumors. Eph receptor tyrosine kinases and their membrane-anchored ligands, known as ephrins, constitute the largest receptor tyrosine kinase (RTK) subfamily and are considered a major family of pro-angiogenic RTKs. Ewing sarcoma (EWS) is a highly aggressive bone and soft tissue tumor affecting children and young adults. As other solid tumors, EWS are reliant on a functional vascular network for the delivery of nutrients and oxygen and for the removal of waste. Based on the biological roles of EphA2 in promoting angiogenesis, we explored the functional role of this receptor and its relationship with caveolin-1 (CAV1) in EWS angiogenesis. We demonstrated that lack of CAV1 results in a significant reduction in micro vascular density (MVD) on 3 different in vivo models. In vitro, this phenomenon correlated with inactivation of EphA2 receptor, lack of AKT response and downregulation of bFGF. We also demonstrated that secreted bFGF from EWS cells acted as chemoattractant for endothelial cells. Furthermore, interaction between EphA2 and CAV1 was necessary for the right localization and signaling of the receptor to produce bFGF through AKT and promote migration of endothelial cells. Finally, introduction of a dominant-negative form of EphA2 into EWS cells mostly reproduced the effects occurred by CAV1 silencing, strongly suggesting that the axis EphA2-CAV1 participates in the promotion of endothelial cell migration toward the tumors favoring EWS angiogenesis.     

Human Survivin and Trypanosoma cruzi Calreticulin Act in Synergy against a Murine Melanoma In Vivo

Immune-based anti-tumor or anti-angiogenic therapies hold considerable promise for the treatment of cancer. The first approach seeks to activate tumor antigen-specific T lymphocytes while, the second, delays tumor growth by interfering with blood supply. Tumor Associated Antigens are often employed to target tumors with therapeutic drugs, but some are also essential for tumor viability. Survivin (Surv) is a member of the inhibitor of apoptosis protein family that is considered a Tumor Associated Antigen important for cancer cell viability and proliferation. On the other hand, Trypanosoma cruzi (the agent of Chagas’ disease) calreticulin (TcCRT) displays remarkable anti-angiogenic properties. Because these molecules are associated with different tumor targets, we reasoned that immunization with a Surv-encoding plasmid (pSurv) and concomitant TcCRT administration should generate a stronger anti-tumor response than application of either treatment separately. To evaluate this possibility, C57BL/6 mice were immunized with pSurv and challenged with an isogenic melanoma cell line that had been pre-incubated with recombinant TcCRT (rTcCRT). Following tumor cell inoculation, mice were injected with additional doses of rTcCRT. For the combined regimen we observed in mice that: i). Tumor growth was impaired, ii). Humoral anti-rTcCRT immunity was induced and, iii). In vitro rTcCRT bound to melanocytes, thereby promoting the incorporation of human C1q and subsequent macrophage phagocytosis of tumor cells. These observations are interpreted to reflect the consequence of the following sequence of events: rTcCRT anti-angiogenic activity leads to stress in tumor cells. Murine CRT is then translocated to the external membrane where, together with rTcCRT, complement C1 is captured, thus promoting tumor phagocytosis. Presentation of the Tumor Associated Antigen Surv induces the adaptive anti-tumor immunity and, independently, mediates anti-endothelial cell immunity leading to an important delay in tumor growth.     

Skull morphology of bottlenose dolphins from different ocean populations with emphasis on South America

The bottlenose dolphin, genus Tursiops, is cosmopolitan occurring in tropical and temperate regions, with morphological variation between and within different oceans. Since the genus' taxonomy has been under discussion for a long time, this work aimed at analyzing the cranial variability of T. truncatus from different regions of the world. Geometric Morphometrics analyses were performed in 201 skulls of adult specimens, on dorsal, ventral, and lateral views, from the Eastern North Pacific, Eastern North Atlantic, Eastern South Atlantic, and Western South Atlantic oceans. The results indicate differences between individuals that inhabit the Atlantic and Pacific oceans. Within the Atlantic Ocean, there is an evident longitudinal differentiation of specimens from the eastern and western regions. A latitudinal separation was also observed, considering specimens from the North and South Atlantic Ocean. In the Western South Atlantic statistical differences were found between two morphological groups, identified as T. gephyreus (sensu Lahille, 1908) and T. truncatus, and the cross-validation presented 98% as minimum confidence for correct classification of these two groups. The present study provides strong morphological support to consider these two lineages as separate species.     

Connectotyping: Model Based Fingerprinting of the Functional Connectome

A better characterization of how an individual’s brain is functionally organized will likely bring dramatic advances to many fields of study. Here we show a model-based approach toward characterizing resting state functional connectivity MRI (rs-fcMRI) that is capable of identifying a so-called “connectotype”, or functional fingerprint in individual participants. The approach rests on a simple linear model that proposes the activity of a given brain region can be described by the weighted sum of its functional neighboring regions. The resulting coefficients correspond to a personalized model-based connectivity matrix that is capable of predicting the timeseries of each subject. Importantly, the model itself is subject specific and has the ability to predict an individual at a later date using a limited number of non-sequential frames. While we show that there is a significant amount of shared variance between models across subjects, the model’s ability to discriminate an individual is driven by unique connections in higher order control regions in frontal and parietal cortices. Furthermore, we show that the connectotype is present in non-human primates as well, highlighting the translational potential of the approach.