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Overexpression of the Runt-related transcription factor 2 ( RUNX2 ) has been reported in several cancer types, and the C-X-C motif chemokine receptor 4 ( CXCR4 ) has an important role in tumour progression. However, the interplay between CXCR4 and RUNX2 in melanoma cells remains poorly understood. In the present study, we used melanoma cells and a RUNX2 knockout ( RUNX2 -KO) in vitro model to assess the influence of RUNX2 on CXCR4 protein levels along with its effects on markers associated with cell invasion and autophagy. Osteotropism was assessed using a 3D microfluidic model. Moreover, we assessed the impact of CXCR4 on the cellular levels of key cellular signalling proteins involved in autophagy. We observed that melanoma cells express both RUNX2 and CXCR4 . Restored RUNX2 expression in RUNX2 KO cells increased the expression levels of CXCR4 and proteins associated with the metastatic process. The protein markers of autophagy LC3 and beclin were upregulated in response to increased CXCR4 levels. The CXCR4 inhibitor WZ811 reduced osteotropism and activated the mTOR and p70-S6 cell signalling proteins. Our data indicate that the RUNX2 transcription factor promotes the expression of the CXCR4 chemokine receptor on melanoma cells, which in turn promotes autophagy, cell invasiveness, and osteotropism, through the inhibition of the mTOR signalling pathway. Our data suggest that RUNX2 promotes melanoma progression by upregulating CXCR4 , and we identify the latter as a key player in melanoma-related osteotropism.

Functional electrical stimulation has been used in rehabilitation programs for patients with chronic spinal cord injury. When used correctly it is able to improve the well-being of patients. However, when the stimulus is not adequate it can accelerate the process of fatigue, reducing the time available for training the programmed motor activity. To optimize the configuration of the stimulatory parameters, we developed a tool capable of simulating the muscle strength performance in response to different stimulatory profiles. The tool was able to reproduce the behavior of motoneurons in chronic spinal cord injury and to estimate the muscular strength resulting from the application of different stimuli. We consider that this FES Simulator is a promising tool to design and simulate different profiles of electrical stimulation, optimizing the decision process of the stimulation parameters.

Background: For many decades, research on snake venom toxinology focused mainly on the venoms of Viperidae and Elapidae species, which were traditionally the only ones considered as venomous. However, much less interest has been given to the venom produced by opisthoglyphous colubrid snakes, since they were typically considered of no clinical relevance., Objective: The aim of this work is to perform a preliminary biochemical and venomic characterization of the venom of the colubrid snake Phalotris lemniscatus, a species that has been responsible for two relevant cases of envenomation in Uruguay., Methods: We extracted venom from collected specimens and performed different biochemical and proteomic assays to understand its toxin composition., Results: We found that the venom of P. lemniscatus is composed of protein families typically present in snake venoms, such as metallo and serine preoteases, L-amino acid oxidases, phospholipases A2s, Ctype lectines-like, Kunitz-type proteins and three-finger toxins. Activity assays demonstrated a highly active gelatinolytic component as well as a potent capability to induce blood coagulation., Conclusion: The results indicate that the venom of P. lemniscatus contains hemotoxic activities and components that resemble those found in Viperidae (Bothrops) snakes and that can induce a clinically relevant accident. Further studies are needed to better understand the venom composition of this colubrid snake and its most active compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: The objective of this study was to evaluate the airway volume of growing patients combining a morphological approach using cone beam computed tomography associated with functional data obtained by polysomnography examination after rapid maxillary expansion treatment., Study Design: 22 Caucasian patients (mean age 8.3±0.9 years) undergoing rapid maxillary expansion with Haas type expander banded on second deciduous upper molars were enrolled for this prospective study. Cone beam computed tomography scans and polysomnography exams were collected before placing the appliance (T0) and after 12 months (T1)., Methods: Image processing with airway volume computing and analyses of oxygen saturation and apnoea/hypopnoea index were performed., Results: Airway volume, oxygen saturation and apnea/hypopnea index underwent significant increase over time. However, no significant correlation was seen between their increases., Conclusion: The rapid maxillary expansion treatment induced significant increases in the total airway volume and respiratory performance. Functional respiratory parameters should be included in studies evaluating the RME treatment effects on the respiratory performance.

The Permo-Triassic archosauromorph record is crucial to understand the impact of the Permo-Triassic mass extinction on the early evolution of the group and its subsequent dominance in Mesozoic terrestrial ecosystems. However, the Permo-Triassic archosauromorph record is still very poor in most continents and hampers the identification of global macroevolutionary patterns. Here we describe cranial and postcranial bones from the Permo-Triassic Buena Vista Formation of northeastern Uruguay that contribute to increase the meagre early archosauromorph record from South America. A basioccipital fused to both partial exoccipitals and three cervical vertebrae are assigned to Archosauromorpha based on apomorphies or a unique combination of characters. The archosauromorph remains of the Buena Vista Formation probably represent a multi-taxonomic assemblage composed of non-archosauriform archosauromorphs and a 'proterosuchid-grade' animal. This assemblage does not contribute in the discussion of a Late Permian or Early Triassic age for the Buena Vista Formation, but reinforces the broad palaeobiogeographic distribution of 'proterosuchid grade' diapsids in Permo-Triassic beds worldwide.