127 research outputs found
The effectiveness of motor activity on psychomotor development in school-aged children
In continuity with research on learning through mirror neurons (Rizzolatti G., Sinigaglia C. 2005), with a constructivist conviction (Bellantonio, 2014) it is stated that sports practice, as an instrument that exposes the person to multiple and different motor stimuli and perceptive is an effective medium for psychomotor development. In addition to promoting physical growth and organic development, motor skills also promote the growth of learning. It is no coincidence that psychomotor activity educates and realizes the whole of the person and constitutes an important means of interacting with it through movement. (Lapierre, A., 2001) The research group from Salerno conducted a field research involving a sample of 281 children between 6 and 8 years old, who were given the APCM-2 protocol (Sabbadini, 2005) and who were divided into three categories thanks to a survey completed through questionnaires: children who practice motor activity, children who do not practice motor activity, children who have not returned the questionnaire (group that is supposed to be mixed). It has emerged that participation in a motor activity produces positive effects on the development of the motor pattern and therefore of the person as a whole, achieving homogeneously higher scores on average than the other groups. Therefore, motor activities in school age represent a facilitator in psychomotor development as the stimulation of fundamental motor skills helps children in recreational activities by allowing them to manipulate their environmental conditions and control their own bodies. (Goodway, 2003)
Risk factors for visceral leishmaniasis in a new epidemic site in Amhara Region, Ethiopia
We conducted a case-control study to evaluate risk factors for visceral leishmaniasis during an epidemic in a previously unaffected district of Ethiopia. We also collected blood and bone marrow specimens from dogs in the outbreak villages. In multivariable analyses of 171 matched case-control pairs, dog ownership, sleeping under an acacia tree during the day, and habitually sleeping outside at night were associated with significantly increased risk. Specimens from 7 (3.8%) dogs were positive by immunofluorescent antibody test (IFAT) and both enzyme-linked immunosorbent assays (ELISAs), whereas Leishmania DNA was detected in 5 (2.8%) bone marrow aspirates (from 3 seropositive and 2 seronegative dogs). Insecticide-treated nets may only protect a portion of those at risk. Further research on the vectors, the role of the dog in the transmission cycle, and the effect of candidate interventions are needed to design the best strategy for control
Sigma-2 receptor agonist derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) induce cell death via mitochondrial superoxide production and caspase activation in pancreatic cancer
Abstract
Background
Despite considerable efforts by scientific research, pancreatic cancer is the fourth leading cause of cancer related mortalities. Sigma-2 receptors, which are overexpressed in several tumors, represent promising targets for triggering selective pancreatic cancer cells death.
Methods
We selected five differently structured high-affinity sigma-2 ligands (PB28, PB183, PB221, F281 and PB282) to study how they affect the viability of diverse pancreatic cancer cells (human cell lines BxPC3, AsPC1, Mia PaCa-2, and Panc1 and mouse Panc-02, KCKO and KP-02) and how this is reflected in vivo in a tumor model.
Results
Important cytotoxicity was shown by the compounds in the aggressive Panc02 cells, where cytotoxic activity was caspase-3 independent for four of the five compounds. However, both cytotoxicity and caspase-3 activation involved generation of Reactive Oxygen Species (ROS), which could be partially reverted by the lipid antioxidant \u3b1-tocopherol, but not by the hydrophilic N-acetylcysteine (NAC) indicating crucial differences in the intracellular sites exposed to oxidative stress induced by sigma-2 receptor ligands. Importantly, all the compounds strongly increased the production of mitochondrial superoxide radicals except for PB282. Despite a poor match between in vitro and the in vivo efficacy, daily treatment of C57BL/6 mice bearing Panc02 tumors resulted in promising effects with PB28 and PB282 which were similar compared to the current standard-of-care chemotherapeutic gemcitabine without showing signs of systemic toxicities.
Conclusions
Overall, this study identified differential sensitivities of pancreatic cancer cells to structurally diverse sigma-2 receptor ligands. Of note, we identified the mitochondrial superoxide pathway as a previously unrecognized sigma-2 receptor-activated process, which encourages further studies on sigma-2 ligand-mediated cancer cell death for the targeted treatment of pancreatic tumors
Lysosomal membrane permeabilization is an early event in sigma-2 receptor ligand mediated cell death in pancreatic cancer
BACKGROUND: Sigma-2 receptor ligands have been studied for treatment of pancreatic cancer because they are preferentially internalized by proliferating cells and induce apoptosis. This mechanism of apoptosis is poorly understood, with varying reports of caspase-3 dependence. We evaluated multiple sigma-2 receptor ligands in this study, each shown to decrease tumor burden in preclinical models of human pancreatic cancer. RESULTS: Fluorescently labeled sigma-2 receptor ligands of two classes (derivatives of SW43 and PB282) localize to cell membrane components in Bxpc3 and Aspc1 pancreatic cancer cells and accumulate in lysosomes. We found that interactions in the lysosome are critical for cell death following sigma-2 ligand treatment because selective inhibition of a protective lysosomal membrane glycoprotein, LAMP1, with shRNA greatly reduced the viability of cells following treatment. Sigma-2 ligands induced lysosomal membrane permeabilization (LMP) and protease translocation triggering downstream effectors of apoptosis. Subsequently, cellular oxidative stress was greatly increased following treatment with SW43, and the hydrophilic antioxidant N-acetylcysteine (NAC) gave greater protection against this than a lipophilic antioxidant, α-tocopherol (α-toco). Conversely, PB282-mediated cytotoxicity relied less on cellular oxidation, even though α-toco did provide protection from this ligand. In addition, we found that caspase-3 induction was not as significantly inhibited by cathepsin inhibitors as by antioxidants. Both NAC and α-toco protected against caspase-3 induction following PB282 treatment, while only NAC offered protection following SW43 treatment. The caspase-3 inhibitor DEVD-FMK offered significant protection from PB282, but not SW43. CONCLUSIONS: Sigma-2 ligand SW43 commits pancreatic cancer cells to death by a caspase-independent process involving LMP and oxidative stress which is protected from by NAC. PB282 however undergoes a caspase-dependent death following LMP protected by DEVD-FMK and α-toco, which is also known to stabilize the mitochondrial membrane during apoptotic stimuli. These differences in mechanism are likely dependent on the structural class of the compounds versus the inherent sigma-2 binding affinity. As resistance of pancreatic cancers to specific apoptotic stimuli from chemotherapy is better appreciated, and patient-tailored treatments become more available, ligands with high sigma-2 receptor affinity should be chosen based on sensitivities to apoptotic pathways
Velocity Distributions in a Gas-Gun Microparticle Accelerator
Here, we build and characterize a single-stage gas-gun microparticle accelerator, where a pressurized gas expands and launches particles on a target. The microparticles in the range of 60-250 ÎŒm are accelerated by the expansion of pressurized nitrogen. By using a high-speed camera, we study how the velocity distribution of accelerated particles is modified by particle size, pressure in the gas reservoir, valve's opening time, and diaphragm's thickness and composition. We employ this microparticle accelerator to study the impact of glass particles with diameters of (69 ± 6) ÎŒm accelerated at moderate velocities âŒ(10-25) m/s, using films of poly-dimethylsiloxane as targets.Fil: Barrios Borregales, Siria Karely del Carmen. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de FĂsica del Sur. Universidad Nacional del Sur. Departamento de FĂsica. Instituto de FĂsica del Sur; Argentina. Universidad Nacional del Sur. Departamento de FĂsica; ArgentinaFil: Lance, Pedro Santiago. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de FĂsica del Sur. Universidad Nacional del Sur. Departamento de FĂsica. Instituto de FĂsica del Sur; Argentina. Universidad Nacional del Sur. Departamento de FĂsica; ArgentinaFil: Abate, Anabella Angela. Universidad Nacional del Sur. Departamento de FĂsica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de FĂsica del Sur. Universidad Nacional del Sur. Departamento de FĂsica. Instituto de FĂsica del Sur; ArgentinaFil: Prieto, GermĂĄn. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de FĂsica del Sur. Universidad Nacional del Sur. Departamento de FĂsica. Instituto de FĂsica del Sur; Argentina. Universidad Nacional del Sur. Departamento de IngenierĂa; ArgentinaFil: GarcĂa, NicolĂĄs. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de FĂsica del Sur. Universidad Nacional del Sur. Departamento de FĂsica. Instituto de FĂsica del Sur; Argentina. Universidad Nacional del Sur. Departamento de FĂsica; ArgentinaFil: Piqueras, Cristian Martin. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Planta Piloto de IngenierĂa QuĂmica. Universidad Nacional del Sur. Planta Piloto de IngenierĂa QuĂmica; ArgentinaFil: Vega, Daniel Alberto. Universidad Nacional del Sur. Departamento de FĂsica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de FĂsica del Sur. Universidad Nacional del Sur. Departamento de FĂsica. Instituto de FĂsica del Sur; ArgentinaFil: Satti, Angel Jose. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de QuĂmica del Sur. Universidad Nacional del Sur. Departamento de QuĂmica. Instituto de QuĂmica del Sur; ArgentinaFil: Gomez, Leopoldo Raimundo. Universidad Nacional del Sur. Departamento de FĂsica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Conicet - BahĂa Blanca. Instituto de FĂsica del Sur. Universidad Nacional del Sur. Departamento de FĂsica. Instituto de FĂsica del Sur; Argentin
Proceedings from the Fourth International Symposium on sigma-2 receptors: Role in health and disease
The sigma-2 receptor (S2R) complex has been implicated in central nervous system disorders ranging from anxiety and depression to neurodegenerative disorders such as Alzheimer\u27s disease (AD). The proteins comprising the S2R complex impact processes including autophagy, cholesterol synthesis, progesterone signaling, lipid membrane-bound protein trafficking, and receptor stabilization at the cell surface. While there has been much progress in understanding the role of S2R in cellular processes and its potential therapeutic value, a great deal remains unknown. Th
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