α-Synuclein Drives Tau's Cytotoxic Aggregates Formation through Hydrophobic Interactions.

Tau and α-synuclein are proteins involved in pathologies known as tauopathies and synucleinopathies, respectively. Moreover, evidence shows that there is a crosstalk between them as is seen in the brains of individuals with sporadic neurodegenerative disorders. Based on that, we present data showing that the hydrophobic α-peptide 71 VTGVTAVAQKTV82 induces the aggregation of the full-length tau fragment in the absence of heparin assessed by ThT. Moreover, AFM images reveal the presence of straight filaments and amorphous aggregates of full-length tau in the presence of the α-peptide. Additionally, ITC experiments showed the interaction of the α-peptide with tau full-length (441 amino acids),4R (amino acids from 244 to 369), and both hexapeptides 275 VQIINK280 and 306 VQIVYK311 through hydrophobic interactions. The Raman spectroscopy spectra showed conformational changes in the Amide region in the aggregates formed with full-length tau and α-syn peptide. Furthermore, the incubation of extracellular aggregates with N2a cells showed morphological differences in the cellular body and the nucleus suggesting cell death. Moreover,, the incubation of different types of aggregates in cell culture provokes the release of Lactate dehydrogenase (LDH). Altogether, we found that α-synuclein peptide can drive the aggregation of full-length tau-provoking morphological and structural changes evoking cytotoxic effects.

Efectividad de la terapia robótica Armeo spring en la funcionalidad de extremidad superior de niños con parálisis cerebral unilateral espástica inyectados con toxina botulínica. Ensayo clínico aleatorio de grupos paralelos, simple ciego / Effectiveness of Armeo spring robotic therapy on upper limb functionality in children with spastic unilateral cerebral palsy injected with botulinum toxin. Randomized clinical trial of parallel groups, single blind

OBJETIVO: Comparar la efectividad de la terapia robótica Armeo spring (AS) con la Terapia Ocupacional (TO) para mejorar la funcionalidad de extremidad superior de niños/as entre 4-10 años con Parálisis cerebral (PC) unilateral e inyectados intramuscularmente con toxina botulínica tipo A en Instituto Teletón Concepción-Chile. PACIENTES Y MÉTODOS: Ensayo clínico controlado aleatorio de grupos paralelos AS y TO con una muestra de veinte niños clasificados con MACS I, II, III (10 paciente por grupo). Se realizaron 15 sesiones de tratamien­to, 3 veces/semana. Se aplicó escala QUEST y ABILHAND-kids, en tiempos basal, post intervención y seguimiento a 6 meses por Terapeuta Ocupacional que desconocía la asignación de los grupos. RESULTADOS: No hay diferencias significativas en subdimensiones y puntaje total QUEST en ambos grupos. En grupo TO se observan diferencias entre los tiempos T1 y T3 en las subdimen­siones movimiento disociado, agarre, carga de peso y puntaje total QUEST; y entre los tiempos T2 y T3 para movimiento disociado, carga de peso y puntaje total QUEST. En el grupo AS hubo diferencias entre T1 y T2 en movimiento disociado y puntaje total QUEST, y entre el T1 y T3 en puntaje disociado. En ABILHAND-kids no hay diferencias significativas entre ambos grupos y sólo en el grupo AS hay diferencias significativas entre los tiempos T1-T3 y T2-T3. DISCUSIÓN: La terapia robótica AS y la TO logran mejorar la funcionalidad de extremidad superior en niños con PC unilateral, no encontrándose diferencias entre ambos grupos.

OBJECTIVE: To evaluate the effectiveness of the robotic therapy Armeo spring (AS) in comparison with Occupational Therapy (OT) to improve the functio-nality of the upper limb of children between 4-10 years of age with unilateral cerebral palsy (CP) and injected with botulinum toxin type A in Instituto Teletón Concepción-Chile. PATIENTES AND METHODS: Randomised controlled clinical trial of parallel groups: conventional AS and OT. Twenty-three children classified with MACS I, II, III were randomised, twenty being analysed, corresponding to those who finished the intervention (10 from each group). Fifteen treatment sessions were carried out, three times per week. QUEST and ABILHAND-kids tests were applied at baseline (T1), post intervention (T2) and six-month follow-up (T3) by an Occupational Therapist who was unaware of the group assignment. RESULTS:In both groups there are no significant differences in their subdimensions and total QUEST score, however in the OT group differences are observed between T1-T3 in the subdimensions dissociated movement, grip, weight bearing and total QUEST score. There are also differences between T2-T3 for dissociated movement, weight bearing, and total QUEST score. In the AS group there were differences between T1 - T2 in dissociated movement and total QUEST score, and between T1-T3 only in dissociated movement. In ABILHAND-kids, there were no differences between both groups, only in AS group, there were only significant differences in evaluation in T1-T3 and T2 -T3. DISCUSSION: AS and OT robotic therapy can improve upper limb functionality in children with unilateral CP, not finding differences between both groups.

Knockdown of CXCL14 disrupts neurovascular patterning during ocular development.

The C-X-C motif ligand 14 (CXCL14) is a recently discovered chemokine that is highly conserved in vertebrates and expressed in various embryonic and adult tissues. CXCL14 signaling has been implicated to function as an antiangiogenic and anticancer agent in adults. However, its function during development is unknown. We previously identified novel expression of CXCL14 mRNA in various ocular tissues during development. Here, we show that CXCL14 protein is expressed in the anterior eye at a critical time during neurovascular development and in the retina during neurogenesis. We report that RCAS-mediated knockdown of CXCL14 causes severe neural defects in the eye including precocious and excessive innervation of the cornea and iris. Absence of CXCL14 results in the malformation of the neural retina and misprojection of the retinal ganglion neurons. The ocular neural defects may be due to loss of CXCL12 modulation since recombinant CXCL14 diminishes CXCL12-induced axon growth in vitro. Furthermore, we show that knockdown of CXCL14 causes neovascularization of the cornea. Altogether, our results show for the first time that CXCL14 plays a critical role in modulating neurogenesis and inhibiting ectopic vascularization of the cornea during ocular development.

Availability and costs of single cigarettes in Guatemala.

INTRODUCTION: Single-cigarette sales have been associated with increased cigarette accessibility to less educated, lower-income populations, and minors; lower immediate cost, and increased smoking cues. Since 1997, Guatemalan Law bans the sale of single cigarettes and packs with fewer than 20 cigarettes. In 2005, Guatemala ratified the World Health Organization Framework Convention on Tobacco Control (WHO FCTC); it is therefore obliged to "prohibit sale of cigarettes individually or in small packets." METHODS: Blocks were numbered and randomly selected in Guatemala City and 3 neighboring towns. All stores in each block were surveyed. Single-cigarette and fewer than 20-cigarette pack sales were assessed by observation and purchase attempts. Cigarette brands and manufacturers (Philip Morris, PM or British American Tobacco, BAT) were also recorded. Percentages and means were used to describe data. Analyses were done using STATA 11.0. RESULTS: Of 398 stores and street vendors surveyed, 75.6% (301) sold cigarettes. Of these, 91% (275) sold single cigarettes and none sold fewer than 20-cigarette packs. Only informal economic sectors sold singles. There was no difference on sales between Guatemala City and neighboring towns and by store type. Buying 20 single cigarettes was US$ 0.83 more expensive than buying a 20-cigarette pack. The most prevalent brands were Rubios (PM), Marlboro (PM), Payasos (BAT), and After Hours (BAT). CONCLUSIONS: Single-cigarettes sales are highly prevalent among informal economic sectors in Guatemala City and its neighboring towns. Our data should prove useful to advocate for FCTC Article 16 enforcement in Guatemala.

Vaccination with plasmid DNA encoding KMPII, TRYP, LACK and GP63 does not protect dogs against Leishmania infantum experimental challenge.

Vaccination of dogs, the domestic reservoir of Leishmania infantum, is the best method for controlling zoonotic visceral leishmaniasis. This strategy would reduce the incidence of disease in both the canine and, indirectly, the human population. Different vaccination approaches have been investigated against canine leishmaniasis (CaL) but to date there is only one licensed vaccine against this disease in dogs, in Brazil. DNA immunization is a promising method for inducing both humoral and cellular immune responses against this parasitic disease. Here, we report the results of a multiantigenic plasmid DNA vaccine encoding KMPII, TRYP, LACK and GP63 L. infantum antigens against experimentally induced CaL. Twelve dogs were randomly assigned to two groups receiving, at a 15 days interval, either four doses of plasmid DNA or similar injections of PBS. After vaccination, dogs were intravenously challenged with 5 x 10(7) promastigotes of L. infantum. The vaccine showed to be safe and well-tolerated. Neither cellular immune response nor antibodies directed against whole Leishmania antigen were detected after immunization in vaccinated dogs, although anti-LACK-specific antibodies were sporadically detected in two vaccinated dogs before challenge, thus suggesting that antigens were indeed expressed. A delay in the development of detectable specific immune response and parasite multiplication in vaccinated dogs was observed after challenge. Nevertheless, the multiantigenic Leishmania DNA vaccine was unable to induce protection against parasite dissemination or disease. This study emphasizes the need to strengthen DNA vaccines in order to obtain effective immune responses in models other than the murine.