High affinity binding of amyloid β-peptide to calmodulin: Structural and functional implications.

Amyloid β-peptides (Aβ) are a major hallmark of Alzheimer's disease (AD) and their neurotoxicity develop with cytosolic calcium dysregulation. On the other hand, calmodulin (CaM), a protein which plays a major multifunctional role in neuronal calcium signaling, has been shown to be involved in the regulation of non-amyloidogenic processing of amyloid β precursor protein (APP). Using fluorescent 6-bromoacetyl-2-dimethylaminonaphthalene derivatives of CaM, Badan-CaM, and human amyloid β(1-42) HiLyte™-Fluor555, we show in this work that Aβ binds with high affinity to CaM through the neurotoxic Aβ25-35 domain. In addition, the affinity of Aβ for calcium-saturated CaM conformation is approximately 20-fold higher than for CaM conformation in the absence of calcium (apo-CaM). Moreover, the value of Kd of 0.98 ± 0.11 nM obtained for Aβ1-42 dissociation from CaM saturated by calcium point out that CaM is one of the cellular targets with highest affinity for neurotoxic Aβ peptides. A major functional consequence of Aβ-CaM interaction is that it slowdowns Aβ fibrillation. The novel and high affinity interaction between calmodulin and Aβ shown in this work opens a yet-unexplored gateway to further understand the neurotoxic effect of Aβ in different neural cells and also to address the potential of calmodulin and calmodulin-derived peptides as therapeutic agents in AD

Healthy Sitting Behaviour Enhancement using a Smart Chair System

The aim of this paper is to present a smart chair prototype to monitor the sitting behaviour of people in wheelchair to re-educate them about long periods of time standing still and in the same position and giving them a feedback about this. The project is mainly focused on those who have been in a wheelchair for a short time. The sitting posture monitoring in the developed smart chair system can help or promote people to achieve and maintain healthy sitting behaviour, and prevent or reduce diseases caused by poor sitting behaviour, like bedsores (pressure ulcers)

Gold compounds inhibit the Ca2+-ATPase activity of brain PMCA and human neuroblastoma SH-SY5Y cells and decrease cell viability

Plasma membrane calcium ATPases (PMCA) are key proteins in the maintenance of calcium (Ca2+) homeostasis. Dysregulation of PMCA function is associated with several human pathologies, including neurodegenerative diseases, and, therefore, these proteins are potential drug targets to counteract those diseases. Gold compounds, namely of Au(I), are well-known for their therapeutic use in rheumatoid arthritis and other diseases for centuries. Herein, we report the ability of dichloro(2-pyridinecarboxylate)gold(III) (1), chlorotrimethylphosphinegold(I) (2), 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidenegold(I) chloride (3), and chlorotriphenylphosphinegold(I) (4) compounds to interfere with the Ca2+-ATPase activity of pig brain purified PMCA and with membranes from SH-SY5Y neuroblastoma cell cultures. The Au(III) compound (1) inhibits PMCA activity with the IC50 value of 4.9 µM, while Au(I) compounds (2, 3, and 4) inhibit the protein activity with IC50 values of 2.8, 21, and 0.9 µM, respectively. Regarding the native substrate MgATP, gold compounds 1 and 4 showed a non-competitive type of inhibition, whereas compounds 2 and 3 showed a mixed type of inhibition. All gold complexes showed cytotoxic effects on human neuroblastoma SH-SY5Y cells, although compounds 1 and 3 were more cytotoxic than compounds 2 and 4. In summary, this work shows that both Au (I and III) compounds are high-affinity inhibitors of the Ca2+-ATPase activity in purified PMCA fractions and in membranes from SH-SY5Y human neuroblastoma cells. Additionally, they exert strong cytotoxic effects.Projects BFU2017-85723-P (to A.M.M. and C.G.-M.), and PID2020-115512GB-I00 (to A.M.M.) funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”. We acknowledge Fundação para a Ciência e a Tecnologia (FCT) project UIDB/04326/2020, Associate Laboratory for Green Chemistry–LAQV, financed by national funds from FCT/MCTES (UIDB/50006/2020 and UIDP/50006/2020) and Scientific Employment Stimulus-Institutional Call (CEECINST/00102/2018).info:eu-repo/semantics/publishedVersio

Inhibition of SERCA and PMCA Ca2+-ATPase activities by polyoxotungstates

Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phospho-tungstate anions [P2W18O62]6-(intact, {P2W18}), [P2W17O61]10-(monolacunary, {P2W17}), [P2W15O56]12-(trilacunary, {P2W15}), [H2P2W12O48]12-(hexalacunary, {P2W12}), [H3P2W15V3O62]6- (trivanadium-substituted, {P2W15V3}) and by Preyssler-type anion [NaP5W30O110]14-({P5W30}). The speciation in the solu-tions of tested POTs was investigated by 31P and 51V NMR spectroscopy. The tested POTs inhibited SERCA Ca2+- ATPase activity, whereby the Preyssler POT showed the strongest effect, with an IC50 value of 0.37 mu M. For {P2W17} and {P2W15V3} higher IC50 values were determined: 0.72 and 0.95 mu M, respectively. The studied POTs showed to be more potent inhibitors of PMCA Ca2+-ATPase activity, with lower IC50 values for {P2W17}, {P5W30} and {P2W15V3}.info:eu-repo/semantics/publishedVersio

Recent Overview of Solar Photocatalysis and Solar Photo-Fenton Processes for Wastewater Treatment

This literature research, although not exhaustive, gives perspective to solar-driven photocatalysis, such as solar photo-Fenton and TiO2 solar photocatalysis, reported in the literature for the degradation of aqueous organic pollutants. Parameters that influence the degradation and mineralization of organics like catalyst preparation, type and load of catalyst, catalyst phase, pH, applied potential, and type of organic pollutant are addressed. Such parameters may also affect the photoactivity of the catalysts used in the studied solar processes. Solar irradiation is a renewable, abundant, and pollution-free energy source for low-cost commercial applications. Therefore, these solar processes represent an environmentally friendly alternative mainly because the use of electricity can be decreased/avoided

Proteína total en suero sanguíneo de vaquillonas braford recriadas en un sistema pastoril y silvopastoril de la Llanura Deprimida Salina de Tucumán

En estudios de nutrición, el suero sanguíneo es ampliamente utilizado para determinar niveles de metabolitos en los animales. La determinación de proteínas totales en plasma de sangre bovina se utiliza como un parámetro en el control de la salud y nutrición animal. El objetivo del presente trabajo es determinar si el sistema de producción silvopastoril (S) vs pastoril (P) y los meses de activo crecimiento de la pastura (Dic, Ene, Feb, Mar) de la pastura tiene un efecto sobre la concentración de proteína total en suero (g L-1) en vaquillonas en recría. Se utilizaron 24 vaquillonas de raza Braford del IIACS-INTA, ubicado en el dpto Leales, Tucumán, Argentina (27º11´10.60´´S y 65º14´32.45´´O). El clima es de tipo subtropical sub-húmedo con estación seca. El diseño experimental es Bloques y el arreglo factorial 2x2, donde el modelo es y=s.m.mxs.e. La unidad experimental es la vaquillona. El área experimental es de 9 has de S y 9 has de P. No se encontraron diferencias significativas entre los sistemas, con valor promedio para P de 61,0 g L-1 y para S de 60,2 g L-1. Entre el mes de febr. y marzo no se encontraron diferencia con valores de 64,3 g L-1y 62,4 g L-1respetivamente a su vez Marzo no difirió de Ene. con un valor de 60,3 g L-1presentándose el menor valor en el mes de Dic. 55,4g L-1. No se encontró efectos entre los sistemas pero si entre los meses evaluados, con una diferencia muy marcada entre dic. y feb. Manteniéndose estos valores dentro de los parámetros normalesFil: Gutierrez, Esteban O.. Universidad Nacional de TucumánFil: Torres, Juan Carlos. Universidad Nacional de TucumánFil: Lara, Javier. Universidad Nacional de TucumánFil: Mata, Alejandro. Universidad Nacional de TucumánFil: Llobril Ayala, Ana Luz. Universidad Nacional de TucumánFil: Torres, Tirso. Universidad Nacional de Tucumá

Death in the sun: the bioarchaeology of an early post-medieval hospital in Gibraltar

In 2014, during construction work at the ex-Civil Hospital in Gibraltar, excavations led by the Gibraltar Museum revealed a major, previously unknown burial ground containing more than 200 skeletons. We present the historical, archaeological and radiometric dating evidence from the site alongside the results of initial osteological analyses. The data indicate that the burials pertain to an earlier 16th-century Spanish hospice, and therefore stand to offer new insights into the functioning of this early modern hospital and the health and movements of people at a time of incipient globalization

Analytical modeling of hot behavior of Ti-6Al-4V alloy at large strain

Hot deformation behavior of the Ti-6Al-4V alloy is studied through hot torsion tests. Cylindrical samples are twisted at different strain rates and temperatures in the β phase domain. The recorded torque vs twisting angle data are converted to strain vs stress data using the appropriate methods. All the flow curves obtained are characteristic of continuous dynamic recrystallization. The flow stresses exhibit rapid growth to reach a single maximum followed by a decrease and a steady-state regime. The influence of strain rate and temperature is taken into account. An analytical model is proposed, which gives accurate flow curves for the Ti-6Al-4V alloy for processing temperatures between 1000°C and 1100°C and strain rates between 0.01/s and 1/s. The model is validated by further experimental tests