Chronic \u3b1-synuclein accumulation in rat hippocampus induces lewy bodies formation and specific cognitive impairments

Occurrence of Lewy bodies (LBs)/Lewy neurites (LNs) containing misfolded fibrillar a-synuclein (a-syn) is one of the pathologic hallmarks of memory impairment-linked synucleinopathies, such as Parkinson\u2019s disease (PD) and dementia with LBs (DLB). While it has been shown that brainstem LBs may contribute to motor symptoms, the neuropatho-logical substrates for cognitive symptoms are still elusive. Here, recombinant mouse a-syn fibrils were bilaterally injected in the hippocampus of female Sprague Dawley rats, which underwent behavioral testing for sensorimotor and spatial learning and memory abilities. No sensorimotor deficits affecting Morris water maze task performance were observed, nor was any reference memory disturbances detectable in injected animals. By contrast, significant impairments in working memory performance became evident at 12 months postinjection. These deficits were associated to a time-dependent increase in the levels of phosphorylated a-syn at Ser129 and in the stereologically esti-mated numbers of proteinase K (PK)-resistant a-syn aggregates within the hippocampus. Interestingly, pathologic a-syn aggregates were found in the entorhinal cortex and, by 12 months postinjection, also in the vertical limb of the diagonal band and the piriform cortices. No pathologic a-syn deposits were found within the substantia nigra (SN), the ventral tegmental area (VTA), or the striatum, nor was any loss of dopaminergic, noradrenergic, or cholinergic neurons detected in a-syn-injected animals, compared with controls. This would suggest that the behavioral impairmentsseeninthea-syn-injected animals might be determined by the long-term a-syn neuropathology, rather than by neurodegeneration per se, thus leading to the onset of working memory deficits

Aminoacid substitutions in the glycine zipper affect the conformational stability of amyloid beta fibrils

The aggregation of amyloid-beta peptides is associated with the pathogenesis of Alzheimer’s disease. The hydrophobic core of the amyloid beta sequence contains a GxxxG repeated motif, called glycine zipper, which involves crucial residues for assuring stability and promoting the process of fibril formation. Mutations in this motif lead to a completely different oligomerization pathway and rate of fibril formation. In this work, we have tested G33L and G37L residue substitutions by molecular dynamics simulations. We found that both protein mutations may lead to remarkable changes in the fibril conformational stability. Results suggest the disruption of the glycine zipper as a possible strategy to reduce the aggregation propensity of amyloid beta peptides. On the basis of our data, further investigations may consider this key region as a binding site to design/discover novel effective inhibitors. Communicated by Ramaswamy H. Sarma

Demographic Decline, Population Ageing and Modern Financial Approaches to Urban Policy

This article discusses the interaction between demographic aging, population decline, and various aspects of the local development challenges facing public authorities. In particular, this article examines some of the financial issues arising from population aging and decline and the ways in which new approaches to public finance are being used in support of European Union regional and urban policy. In this context, it is argued that a comprehensive portfolio investment approach has the potential to significantly improve policy effectiveness

AMYAND'S HERNIA, AN UNKNOWN ENTITY THAT MAY CAUSE SURGEONS DIFFICULTY: OUR EXPERIENCE AND LITERATURE REVIEW

Amyand's hernia is an inguinal hernia, containing the appendix within the hernial sac. Claudius Amyand described the first clinical case in 1735. Despite the high incidence of inguinal canal hernia disease in the population with approximately 20 milion patients that undergo hernia repair annually, Amyand's hernia is a rare clinical conditions. It is characterized by an incidence of 1 % (0,19-1.7) and in 0,13 % of all cases, the appendix is inflamed. In this article, we will present our experience related to the treatment of a complicated Amyand's hernia, occasionally found during an emergency surgery for the repair of an incarcerated inguinal hernia. In addition, we will conduct a medical review of this pathology that often represents an unpleasant surprise for the surgeon

Time of Flight based diagnostics for high energy laser driven ion beams

Nowadays the innovative high power laser-based ion acceleration technique is one of the most interesting challenges in particle acceleration field, showing attractive characteristics for future multidisciplinary applications, including medical ones. Nevertheless, peculiarities of optically accelerated ion beams make mandatory the development of proper transport, selection and diagnostics devices in order to deliver stable and controlled ion beams for multidisciplinary applications. This is the main purpose of the ELIMAIA (ELI Multidisciplinary Applications of laser-Ion Acceleration) beamline that will be realized and installed within 2018 at the ELI-Beamlines research center in the Czech Republic, where laser driven high energy ions, up to 60 MeV/n, will be available for users. In particular, a crucial role will be played by the on-line diagnostics system, recently developed in collaboration with INFN-LNS (Italy), consisting of TOF detectors, placed along the beamline (at different detection distances) to provide online monitoring of key characteristics of delivered beams, such as energy, fluence and ion species. In this contribution an overview on the ELIMAIA available ion diagnostics will be briefly given along with the preliminary results obtained during a test performed with high energy laser-driven proton beams accelerated at the VULCAN PW-laser available at RAL facility (U.K.)

Design of the ELIMAIA ion collection system

A system of permanent magnet quadrupoles (PMQs) is going to be realized byINFNLNS to be used as a collection system for the injection of laser driven ionbeams up to 60 AMeV in an energy selector based on four resistive dipoles. Thissystem is the first element of the ELIMED (ELI-Beamlines MEDical andMultidisciplinary applications) beam transport, dosimetry and irradiation linethat will be developed by INFN-LNS (It) and installed at the ELI-Beamlinesfacility in Prague (Cz). ELIMED will be the first users open transportbeam-line where a controlled laser-driven ion beam will be used formultidisciplinary researches. The definition of well specified characteristics,both in terms of performances and field quality, of the magnetic lenses iscrucial for the system realization, for the accurate study of the beam dynamicsand for the proper matching with the magnetic selection system which will bedesigned in the next months. Here, we report the design of the collection system and the adopted solutionsin order to realize a robust system form the magnetic point of view. Moreover,the first preliminary transport simulations are also described

Estratigrafía de alta resolución de depósitos de flujos gravitacionales de la Formación Los Molles (Grupo Cuyo - Jurásico) en la región de La Jardinera, cuenca Neuquina

El Grupo Cuyo en el área del arroyo La Jardinera (Pliensbachiano a Caloviano Temprano) refleja una fisiografía de cuenca de plataforma y talud. Una discordancia de orden mayor define la culminación de una espesa sucesión de turbiditas y representa un límite de secuencia de 2do orden. La más antigua secuencia de 2do orden comprende el tramo basal de la Formación Los Molles e incluye un ciclo transgresivo-regresivo asignado a estratos de base de talud y fondo de cuenca. La secuencia más joven, que incluye el resto del Grupo Cuyo, consiste de una sucesión regresiva puntuada por varios desplazamientos abruptos de elementos fisiográficos (límites de secuencia de 3er orden). Las secuencias depositacionales de 3er orden incluyen depósitos de talud y de base de talud del Aaleniano de la Formación Los Molles, facies de plataforma del Bajociano Temprano en la transición entre las formaciones Los Molles y Lajas, y sedimentitas de plataforma interna a nearshore del Bajociano medio a tardío de la Formación Lajas, que es a su vez cubierta por depósitos del Bathoniano aluvial de la Formación Challacó. Ciclos de más alta frecuencia alternan en la sucesión y han controlado el origen, depositación y abandono de los elementos arquitecturales. Análisis de facies y de elementos arquitecturales indican que los depósitos gravitatorios densos de la Formación Los Molles encuadran en un modelo de rampa submarina. Los tres tipos de flujos gravitacionales (GF) han sido relacionados a caídas del nivel del mar de 4to orden. Los GF1 fueron asignados a flujos hiperpícnicos producidos durante un cortejo temprano de mar bajo de 4to orden, coevo con incisión fluvial en la plataforma, que evolucionaran a flujos turbidíticos en el talud, produciendo cargas de pulsos depositacionales cuya signatura composicional es fluvial. El sistema de GF1 incluye canales relativamente pequeños sobre el talud, lóbulos bien desarrollados en la base del talud y la planicie de fondo de cuenca proximales, así como lóbulos adventicios en la planicie del fondo de cuenca. Los estratos GF2 fueron asignados a flujos hiperpícnicos influenciados por un componente oscilatorio y relacionados a cortejos tardíos de mar bajo de 4to orden, que también incluyen relleno de canales incididos. Ellos están caracterizados en el talud por areniscas onduladas y laminadas ampliamente distribuidas y facies heterolíticas, que incluyen scours de bajo relieve en sus porciones centrales. Ellos representan flujos densos más diluidos y de grano más fino con respecto a los GF1. Los GF3, también asociados con cuñas de mar bajo de 4to orden, comprenden depósitos de flujos en masa y debris de talud y de base de talud, que representan clásicos surges de corta duración causados por debilidades en taludes relativamente abruptos. Los cortejos transgresivos y de mar alto de 4to orden llevaron al abandono de la etapa turbidítica y extensiva depositación de fango.The Pliensbachian to Early Callovian Cuyo Group in the Arroyo La Jardinera area reflects a shelf-slope-basin plain physiography. A major unconformity defines the onset of a thick turbidite succession and represents a 2nd order sequence boundary. The older 2nd order depositional sequence comprises the base of Los Molles Formation and includes a transgressive-regressive cycle ascribed to basin plain and slope rise strata. The younger one, which includes the rest of the Cuyo Group, consists of a regressive succession punctuated by several abrupt shifts of physiographic elements (3rd order sequence boundaries). The 3rd order depositional sequences include Aalenian slope rise and slope deposits in the Los Molles Formation, Early Bajocian shelfal facies at the transition of the Los Molles and Lajas formations, and Middle to Late Bajocian inner shelf to nearshore strata in the Lajas Formation that are overlain by Bathonian alluvial deposits of the Challacó Formation. Higher frequency cycles punctuate the succession and have controlled the origin, deposition and abandonment of the architectural elements. Facies and architectural elements analyses indicate that gravity flow deposits in the Los Molles Formation fit in a submarine ramp model. The three identified gravity flow (GF) types have been related to 4th order relative sea-level falls. The GF1 was ascribed to hyperpycnal flows produced during 4th order early lowstand, coeval to fluvial incision on the shelf, which were ignited in the slope and produced depletive depositional pulses with a fluvial compositional signature. The GF1 system includes relatively small channels in the slope, well-developed lobes in the slope rise and proximal basin plain, and lobe fringes in the basin plain. The GF2 strata were ascribed to hyperpycnal flows influenced by an oscillatory component and related to the 4th order late lowstand systems tract that also includes the incised channels fill. They are characterized in the slope by widespread, undulating and laminated sandstone and heterolithic facies, which include low relief scours at their central portions. They represent more diluted and finer-grained density flows relative to the GF1. The GF3, also associated with the 4th order lowstand wedge, comprises mass and debris flow deposits in the slope and slope rise that represent classical, short-lived surges caused by slope failures on relatively steep slopes. The 4th order transgressive and highstand systems tracts led to the abandonment of the turbidite stages and widespread mud deposition.Fil: Paim, Paulo S. G.. Universidad de Vale do Rio dos Sinos; BrasilFil: Silveira, Ariane. Universidad de Vale do Rio dos Sinos; BrasilFil: Lavina, Ernesto L. C.. Universidad de Vale do Rio dos Sinos; BrasilFil: Faccini, Ubiratan F.. Universidad de Vale do Rio dos Sinos; BrasilFil: Leanza, Hector Armando. Secretaría de Industria y Minería. Servicio Geológico Minero Argentino; Argentina. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Teixeira de Oliveira, J. M. M.. Universidad de Vale do Rio dos Sinos; BrasilFil: D'Avila, Roberto S. F.. Universidad de Vale do Rio dos Sinos; Brasil. Petrobras Argentina S.a; Argentin

Porous covalent organic nanotubes and their assembly in loops and toroids

Carbon nanotubes, and synthetic organic nanotubes more generally, have in recent decades been widely explored for application in electronic devices, energy storage, catalysis and biosensors. Despite noteworthy progress made in the synthesis of nanotubular architectures with well-defined lengths and diameters, purely covalently bonded organic nanotubes have remained somewhat challenging to prepare. Here we report the synthesis of covalently bonded porous organic nanotubes (CONTs) by Schiff base reaction between a tetratopic amine-functionalized triptycene and a linear dialdehyde. The spatial orientation of the functional groups promotes the growth of the framework in one dimension, and the strong covalent bonds between carbon, nitrogen and oxygen impart the resulting CONTs with high thermal and chemical stability. Upon ultrasonication, the CONTs form intertwined structures that go on to coil and form toroidal superstructures. Computational studies give some insight into the effect of the solvent in this assembly process