Validation of the CAchexia SCOre (CASCO). Staging cancer patients: The use of miniCASCO as a simplified tool

The CAchexia SCOre (CASCO) was described as a tool for the staging of cachectic cancer patients. The aim of this study is to show the metric properties of CASCO in order to classify cachectic cancer patients into three different groups, which are associated with a numerical scoring. The final aim was to clinically validate CASCO for its use in the classification of cachectic cancer patients in clinical practice. We carried out a case -control study that enrolled prospectively 186 cancer patients and 95 age-matched controls. The score includes five components: (1) body weight loss and composition, (2) inflammation/metabolic disturbances/immunosuppression, (3) physical performance, (4) anorexia, and (5) quality of life. The present study provides clinical validation for the use of the score. In order to show the metric properties of CASCO, three different groups of cachectic cancer patients were established according to the results obtained with the statistical approach used: mild cachexia (15 â\u89¤ Ã\u97 â\u89¤ 28), moderate cachexia (29 â\u89¤ Ã\u97 â\u89¤ 46), and severe cachexia (47 â\u89¤ Ã\u97 â\u89¤ 100). In addition, a simplified version of CASCO, MiniCASCO (MCASCO), was also presented and it contributes as a valid and easy-to-use tool for cachexia staging. Significant statistically correlations were found between CASCO and other validated indexes such as Eastern Cooperative Oncology Group (ECOG) and the subjective diagnosis of cachexia by specialized oncologists. A very significant estimated correlation between CASCO and MCASCO was found that suggests that MCASCO might constitute an easy and valid tool for the staging of the cachectic cancer patients. CASCO and MCASCO provide a new tool for the quantitative staging of cachectic cancer patients with a clear advantage over previous classifications

Transthyretin Promotes Axon Growth via Regulation of Microtubule Dynamics and Tubulin Acetylation

Transthyretin (TTR), a plasma and cerebrospinal fluid protein, increases axon growth and organelle transport in sensory neurons. While neurons extend their axons, the microtubule (MT) cytoskeleton is crucial for the segregation of functional compartments and axonal outgrowth. Herein, we investigated whether TTR promotes axon elongation by modulating MT dynamics. We found that TTR KO mice have an intrinsic increase in dynamic MTs and reduced levels of acetylated α-tubulin in peripheral axons. In addition, they failed to modulate MT dynamics in response to sciatic nerve injury, leading to decreased regenerative capacity. Importantly, restoring acetylated α-tubulin levels of TTR KO dorsal root ganglia (DRG) neurons using an HDAC6 inhibitor is sufficient to completely revert defective MT dynamics and neurite outgrowth. In summary, our results reveal a new role for TTR in the modulation of MT dynamics by regulating α-tubulin acetylation via modulation of the acetylase ATAT1, and suggest that this activity underlies TTR neuritogenic function

Cambios en la cobertura vegetal y mapeo de un área protegida del NO argentino

Pero, Edgardo J. I.; José Busnelli; Juan P. Juliá. 2015. “Cambios en la cobertura vegetal y mapeo de un área protegida del NO argentino”. Lilloa 52 (1). La Reserva Experimental Horco Molle (REHM) es un área protegida perteneciente a la Facultad de Ciencias Naturales e Instituto Miguel Lillo (IML) de la Universidad Nacional de Tucumán. Su vegetación original corresponde a la parte sur del Distrito de Selvas de Transición de la Provincia Fitogeográfica de Las Yungas, también llamada Selva de “Tipa” y “Pacará”. Actualmente se encuentra en un estadio de sucesión secundaria luego de una extensa historia de deforestación y utilización para cultivo. Aceñolaza (1989) hizo un primer mapeo de la vegetación de la REHM. En este trabajo se realizó un nuevo mapeo, se superpusieron ambos mapas y se identificaron los cambios producidos en la vegetación entre 1989 y 2013. En 1989 un 70 % de la superficie estaba cubierta por pastizales y bosques de Guarán (Tecoma stans) y Afata blanca (Heliocarpus popayanensis). Actualmente el 51 % está ocupado por bosques de Ligustro o Siempre verde (Ligustrum lucidum), un árbol exótico invasor, común en las Sierras de San Javier. El 74 % de los bosques de Tecoma-Heliocarpus han sido desplazados por este invasor, lo cual demuestra que una comunidad pionera nativa puede ser ocupada por especies exóticas invasoras. Se considera que T. stans es un árbol que podría haber funcionado como percha para aves, facilitando la dispersión de L. lucidum. Aquellas áreas donde existían bosques nativos en estadios más avanzados de sucesión como los de Cebil colorado (Anadenanthera colubrina) y Laurel del cerro (Cinnamomum porphyria), aún mantienen su posición y han aumentado su superficie. Los resultados del trabajo detallan el proceso de recuperación del bosque que se viene dando en la zona. Por otra parte, el mapeo actualizado sirve de base para futuros planes de manejo de la zon

Integrins protect sensory neurons in models of paclitaxel-induced peripheral sensory neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known method for prevention or cure in clinics. CIPN often affects unmyelinated nociceptive sensory terminals. Despite the high prevalence, molecular and cellular mechanisms that lead to CIPN are still poorly understood. Here, we used a genetically tractable Drosophila model and primary sensory neurons isolated from adult mouse to examine the mechanisms underlying CIPN and identify protective pathways. We found that chronic treatment of Drosophila larvae with paclitaxel caused degeneration and altered the branching pattern of nociceptive neurons, and reduced thermal nociceptive responses. We further found that nociceptive neuron-specific overexpression of integrins, which are known to support neuronal maintenance in several systems, conferred protection from paclitaxel-induced cellular and behavioral phenotypes. Live imaging and superresolution approaches provide evidence that paclitaxel treatment causes cellular changes that are consistent with alterations in endosome-mediated trafficking of integrins. Paclitaxel-induced changes in recycling endosomes precede morphological degeneration of nociceptive neuron arbors, which could be prevented by integrin overexpression. We used primary dorsal root ganglia (DRG) neuron cultures to test conservation of integrin-mediated protection. We show that transduction of a human integrin β-subunit 1 also prevented degeneration following paclitaxel treatment. Furthermore, endogenous levels of surface integrins were decreased in paclitaxel-treated mouse DRG neurons, suggesting that paclitaxel disrupts recycling in vertebrate sensory neurons. Altogether, our study supports conserved mechanisms of paclitaxel-induced perturbation of integrin trafficking and a therapeutic potential of restoring neuronal interactions with the extracellular environment to antagonize paclitaxel-induced toxicity in sensory neurons