208 research outputs found
Identification of Annexin 2A as a fundamental mediator of glioblastoma cell dissemination and potential therapeutic target
No full textGlioblastoma multiforme (GBM) is the most devastating tumor of the brain, characterized by an almost inevitable tendency to recur after intensive treatments and a fatal prognosis. Indeed, despite recent technical improvements in GBM surgery, the complete eradication of cancer cell disseminated outside the tumor mass still remains a crucial issue for glioma patients management. In my PhD project, we identified Annexin 2A (ANXA2) as an important intracellular cytoskeletal protein expressed also on the surface of various types of cancer cells. Initially, we show that ANXA2 is over-expressed in IV grade GBM at various levels when compared to lower stage tumors. More importantly, we demonstrated that low/absent expression of ANXA2 identifies a subgroup of GBM patients endowed with better prognosis, suggesting that ANXA2 expression can be considered as an independent prognostic factor in glioma. We then analyzed the transcriptional changes associated to different levels of ANXA2 expression. In particular, we generated a series of ANXA2 dependent transcriptional signatures based on the comparison between ANXA2hi versus ANXA2lo expressing GBM patients from the TCGA and GSE13041 datasets (719 differentially expressed genes in common between the two cohorts), modulated transcripts after ANXA2 neutralization by specific antibody (855 differentially expressed genes) and the expression profiles of ANXA2 silenced cells respect to relative controls (3592 differentially expressed genes) in our primary GBM cell cultures. Interestingly, Gene Set Enrichment Analysis (GSEA) on the three different signatures obtained, revealed a negative enrichment of cell migration and mesenchymal transition related genes. These data strongly suggested the important role played by ANXA2 in GBM cell behavior and aggressiveness, allowing us to further setup strategies to specifically modulate its functions and dependent intracellular signaling. For this reason, we further analyzed ANXA2 functional activity in vitro in primary GBM cell cultures, demonstrating as ANXA2 is a major sustainer of GBM cell aggressiveness by regulating cellular invasion and motility together with cancer cell proliferation and differentiation status. Moreover, based on gene expression data of ANXA2 neutralized cells, we were able to test the prognostic potential of an ANXA2down signature in multiple cancer datasets, demonstrating that expression of genes regulated by ANXA2 fluctuations predict cancer patients outcome by themselves.
Finally, we then functionally mapped an ANXA2-dependent gene signature (TCGA and GSE13041 datasets analysis) by exploiting the Connectivity Map bioinformatic tool in order to identify compounds and approved drugs able to revert this signature of GBM aggressiveness. The compounds, significantly predicted to be able to counteract the ANXA2-dependent transcriptional signature, were analyzed for their ability to inhibit GBM cell invasion in vitro in primary GBM cultures. Finally, we applied ANXA2 dependent transcriptional signatures, previously generated from our primary GBM cells, to the QUADrATiC tool, which was allowed the exploration of a larger database of reference cell lines and perturbagens
Haptic working memory for grasping: the role of the parietal operculum
No full textWe investigated how haptic information on object geometry is encoded in the parietal operculum (OP) and is used for guiding object-directed motor acts in humans. We tested the effects of conditioning single-pulse transcranial magnetic stimulation (spTMS) applied to the left OP on corticospinal excitability assessed by a test spTMS applied to the ipsilateral motor cortex (M1) 5 ms after conditioning spTMS. Participants explored the size of a graspable object visually or haptically and waited for a go-signal to grasp it in the dark. They received TMS during the delay phase. In a separate group of participants performing the same task, conditioning spTMS was applied to the ventral premotor cortex (vPM) 7 ms before test spTMS. Results showed that conditioning TMS over OP modulated M1 output according to the information on object size that had been acquired haptically but not visually. Vice versa, conditioning TMS over vPM modulated M1 output according to information on object size acquired by vision but not haptically. Moreover spTMS over OP produced a significant modulation of the upcoming reaching behavior only when the object had been explored haptically. We show that OP contains a haptic memory of objects' macrogeometry and the appropriate motor plan for grasping them
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Online repetitive transcranial magnetic stimulation (TMS) to the parietal operculum disrupts haptic memory for grasping
No full textThe parietal operculum (OP) contains haptic memory on the geometry of objects that is readily transferrable to the motor cortex but a causal role of OP in memory-guided grasping is only speculative. We explored this issue by using online high-frequency repetitive transcranial magnetic stimulation (rTMS). The experimental task was performed by blindfolded participants acting on objects of variable size. Trials consisted in three phases: haptic exploration of an object, delay, and reach-grasp movement onto the explored object. Motor performance was evaluated by the kinematics of finger aperture. Online rTMS was applied to the left OP region separately in each of the three phases of the task. The results showed that rTMS altered grip aperture only when applied in the delay phase to the OP. In a second experiment a haptic discriminative (match-to-sample) task was carried out on objects similar to those used in the first experiment. Online rTMS was applied to the left OP. No psychophysical effects were induced by rTMS on the detection of explicit haptic object size. We conclude that neural activity in the OP region is necessary for proficient memory-guided haptic grasping. The function of OP seems to be critical while maintaining the haptic memory trace and less so while encoding it or retrieving it
Comment on: Onset of eosinophilic granulomatosis with polyangiitis in a patient treated with an IL-5 pathway inhibitor for severe asthma: reply
No full textComment on: Onset of eosinophilic granulomatosis with polyangiitis in a patient treated with an IL-5 pathway inhibitor for severe asthma: repl
Onset of eosinophilic granulomatosis with polyangiitis in a patient treated with an IL-5 pathway inhibitor for severe asthma
No full textOnset of eosinophilic granulomatosis with polyangiitis in a patient treated with an IL-5 pathway inhibitor for severe asthm
Análisis de la congruencia de los objetivos curriculares del actual programa de formación de profesores de educación física, de la Universidad Católica del Maule, desde la perspectiva de los programas de curso
No full textThis work corresponds to a summary of the thesis presented by the author in order to get the Master Degree, where it is analyzed the existent congruencies between the curricular objectives of the current initial formation program of Physical Education Teachers, from the Catholic University of Maule, and the different course programs that conform its curricular structure.El presente trabajo, es una síntesis de la Tesis presentada por el autor para optar al grado de Magíster, donde se analizan las congruencias existentes entre los objetivos curriculares del actual programa de formación inicial de profesores de Educación Física de la Universidad Católica del Maule y los planteados por los distintos programas de cursos que componen su estructura curricular
The motor system resonates to the distal goal of observed actions: Testing the inverse pliers paradigm in an ecological setting
No full textDoes motor mirroring in humans reflect the observed movements or the goal of the observed motor acts? Tools that dissociate the agent/object dynamics from the movements of the body parts used to operate them provide a model for testing resonance to both movements and goals. Here, we describe the temporal relationship of the observer's motor excitability, assessed with transcranial magnetic stimulation (TMS), with the observed goal-directed tool actions, in an ecological setting. Motor-evoked potentials (MEPs) to TMS were recorded from the opponens pollicis (OP, thumb flexor) and the extensor indicis proprius (EIP, index extensor) muscles of participants while they observed a person moving several small objects with a pair of normal pliers (closed by finger flexion) or reverse pliers (opened by finger flexion). The MEPs were a significant predictor of the pliers' kinematics that occurred in a variable time interval between -400 and +300 ms from TMS. Whatever pliers' type was being observed, OP MEPs correlated positively and EIP MEPs correlated negatively with the velocity of pliers' tips closure. This datum was confirmed both at individual and at a group level. Motor simulation can be demonstrated in single observers in a "real-life" ecological setting. The relation of motor resonance to the tool type shows that the observer's motor system codes the distal goal of the observed acts (i.e., grasping and releasing objects) in terms of its own motor vocabulary, irrespective of the actual finger movements that were performed by the observed actor
Influence of Environmental Factors on the Surface Feeding Behaviour of Immature Male Whale Sharks in the Gulf of Tadjoura (Djibouti)
No full textThe East African country of Djibouti is known to host an important seasonal feeding aggregation of whale sharks that allows the frequent observation of their surface feeding behaviour. The influence of environmental factors on the different whale shark feeding strategies (passive, active, and vertical) was studied over a four-year period (2017, 2020, 2022, 2024) in the Gulf of Tadjoura. Across 81 immature male whale sharks identified and 1082 surface feeding behaviours recorded in this period, the chlorophyll-a concentration was the main parameter predicting the choice of the filter-feeding technique. Active and vertical feeding behaviours were associated with rainfall, lower sea surface temperature, worse sea conditions, and low wind speed during the morning, all factors positively correlated to chlorophyll-a concentration. On the contrary, passive feeding behaviour was favoured in the inverse environmental conditions. Both passive and vertical feeding behaviours occurred during El Niño events, whereas active feeding was more common during La Niña events. Since it is known that whale shark abundance and distribution are associated with food availability at coastal locations, it is fundamental to understand environmental drivers of filter-feeding strategies when managing conservation efforts for this endangered species. Recommendations for future research work at this site are presented
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