Fact, Fiction, or Evolution: Mechanism Hypothesis of Alzheimer’s Disease

The metabolism hypothesis of Alzheimer’s disease (AD) was first proposed in 1975. In normal aging and very mild AD, the cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) remained approximately constant, but the metabolism of glucose (CMRglu) declined markedly. This decline in CMRglu identified a specific and primary metabolic defect that triggered downstream cellular cascades evolving into AD and its characteristic neuropathological lesions. These findings led research about AD into the role of insulin resistance that foresaw modern trials of insulin for AD treatment. The metabolism hypothesis evolved over subsequent decades with improved in-vivo measurement of metabolic parameters and AD biomarkers in humans. A more recent model highlights the interrelationships between the default mode network (DMN) and biomarkers such as CMRglu, amyloid, and tau. In other words, metabolic conditions related to sustained cortical activity during aging throughout the lifetime are conducive to the deposition of amyloid. This activity is thought to underlie the “autobiographical self.” These ideas and findings motivate aging and AD-research focus on the biochemistry and cell biology of cerebral metabolism

Charge effects on the behavior of CTAB adsorbed on Au(111) electrodes in aqueous solutions

The behavior of adsorbed CTAB on Au(111) electrodes has been studied using electrochemical and FTIR experiments in different aqueous solutions. The results show that the adsorbed layer is stable in acidic solutions in the whole potential range of study. The observed electrochemical and FTIR behavior is compatible with the formation of a membrane of CTA+ on the electrode surface with the polar amino groups in contact with the surface. When the electrode charge is negative, the polar groups are attracted to the surface, so that the capacitance of the electrode is smaller than that recorded for the unmodified Au(111) electrode. As the charge becomes positive, the membrane detaches from the surface and water molecules permeate through it, changing the capacitance of the electrode and giving rise to characteristic peaks in the voltammetric profile. At potentials higher than these peaks, the behavior of the electrode is comparable to that observed for the unmodified electrode. The stability of the membrane is facilitated by the incorporation of anions of the supporting electrolyte. Those anions remain on the membrane even when the electrode is transferred to a different solution, as the electrochemical behavior shows.Financial support from Ministerio de Ciencia e Innovación (Project PID2019-105653GB-100 ) and Generalitat Valenciana (Project PROMETEO/2020/063 ) is acknowledged

On the behavior of CTAB/CTAOH adlayers on gold single crystal surfaces

The behavior of adsorbed CTAB and CTAOH on gold single crystal electrodes has been studied in solutions with different pH values. For the different single crystal electrodes, the adsorbed adlayer formed by CTA+ cations is in contact with the surface, when the electrode charge is negative. As the surface charge becomes positive, the adlayer detaches from the surface and water molecules permeate through it, giving rise to characteristic peaks in the voltammogram. Charge and laser induced jump temperature measurements show that the composition of the adlayer contains not only the CTA+ cations but also anions, which are required to stabilize the adlayer. In alkaline solutions, the higher solubility of CTAB/CTAOH in alkaline solutions leads to the partial desorption of the adlayer when these species are not present in the solution. When CTAB or CTAOH are dissolved in the alkaline cell solution, the adlayer is strongly bonded to the surface in the whole potential window due to the negative charge of the surface.Financial support from Ministerio de Ciencia e Innovación (Project PID2019-105653GB-I00) and Generalitat Valenciana (Project PROMETEO/2020/063) is acknowledged

Dynamic & Cyclic behaviour of ballast in the long term as determined in Cedex's track box

The 6 cylinder servo-hydraulic loading system of CEDEX's track box (250 kN, 50 Hz) has been recently implemented with a new piezoelectric loading system (±20 kN, 300 Hz) allowing the incorporation of low amplitude high frequency dynamic load time histories to the high amplitude low frequency quasi-static load time histories used so far in the CEDEX's track box to assess the inelastic long term behavior of ballast under mixed traffic in conventional and high- speed lines. This presentation will discuss the results obtained in the first long-duration test performed at CEDEX's track box using simultaneously both loading systems, to simulate the pass-by of 6000 freight vehicles (1M of 225 kN axle loads) travelling at a speed of 120 km/h over a line with vertical irregularities corresponding to a medium quality lin3e level. The superstructure of the track tested at full scale consisted of E 60 rails, stiff rail pads (mayor que 450 kN/mm), B90.2 sleepers with USP 0.10 N/mm and a 0.35 m thick ballast layer of ADIF first class. A shear wave velocity of 250 m/s can be assumed for the different layers of the track sub-base. The ballast long-term settlements will be compared with those obtained in a previous long-duration quasi- static test performed in the same track, for the RIVAS [EU co-funded] project, in which no dynamic loads where considered. Also, the results provided by a high diameter cyclic triaxial cell with ballast tested in full size will be commented. Finally, the progress made at CEDEX's Geotechnical Laboratory to reproduce numerically the long term behavior of ballast will be discussed

Lower Devonian faunistic succession from the Obejo-Valsequillo-Puebla la Reina Domain (Ossa-Morena Zone, Spain); a preliminary multidisciplinary approach

Lack of adequately palaeontological studies, complex tectonics and discontinuous outcrops difficult the knowledge of the Devonian litho –and biostratigraphic sequence from the Obejo-Valsequillo-Puebla de la Reina Domain and prompted us to start a multidisciplinary study (conodonts, brachiopods, corals, stromatoporids, ostracods, dacryoconarids, fish remains, biofacies) of the region. Herein we present data from four sections (Peñón Cortado –PCR, Pozo del Rincón -PZR, Guadámez 2 –GUA 2 and Zújar –ZUJ) that allow the establishment of a preliminary time framework for further studies

La práctica médico-quirúrgica en la primera generación del movimiento "novator" a través de las obras de Juan Bautista Juanini (Milán, 1632 - Madrid, 1691) : imagen historiográfica, saberes médicos y prácticas quirúrgicas

El objetivo principal de este trabajo es realizar un nuevo acercamiento a la figura histórica, la obra y, en concreto, la práctica médico-quirúrgica de un autor hispanoitaliano de finales del siglo XVII. Nos referimos concretamente al cirujano cortesano Juan Bautista Juanini (Milán, 1632 - Madrid, 1691). Como objetivo secundario se trataría de intentar realizar una nueva presentación biográfica del autor dentro de una recapitulación más general del papel que representó en el contexto de la revolución científica y médica de los países del sur de Europa, y en concreto entre los miembros de la primera generación de "novatores" hispánicos.L'objectiu principal d'aquest treball és realitzar un nou apropament a la figura històrica, a l'obra i, en concret, a la pràctica medicoquirúrgica d'un autor hispanoitalià de final del segle XVII. Ens referim concretament al cirurgià cortesà Juan Bautista Juanini (Milà, 1632 - Madrid, 1691). Com a objectiu secundari, es tracta d'intentar fer una nova presentació biogràfica de l'autor dins d'una recapitulació més general del papel que va representar en el context de la revolució cientifica i mèdica dels països del sud d'Europa i, més concretament, entre els membres de la primera generació de "novatores" hispànics

A combined strategy involving Sanger and 454 pyrosequencing increases genomic resources to aid in the management of reproduction, disease control and genetic selection in the turbot (Scophthalmus maximus)

Background: Genomic resources for plant and animal species that are under exploitation primarily for human consumption are increasingly important, among other things, for understanding physiological processes and for establishing adequate genetic selection programs. Current available techniques for high-throughput sequencing have been implemented in a number of species, including fish, to obtain a proper description of the transcriptome. The objective of this study was to generate a comprehensive transcriptomic database in turbot, a highly priced farmed fish species in Europe, with potential expansion to other areas of the world, for which there are unsolved production bottlenecks, to understand better reproductive- and immune-related functions. This information is essential to implement marker assisted selection programs useful for the turbot industry. Results: Expressed sequence tags were generated by Sanger sequencing of cDNA libraries from different immunerelated tissues after several parasitic challenges. The resulting database (“Turbot 2 database”) was enlarged with sequences generated from a 454 sequencing run of brain-hypophysis-gonadal axis-derived RNA obtained from turbot at different development stages. The assembly of Sanger and 454 sequences generated 52,427 consensus sequences (“Turbot 3 database”), of which 23,661 were successfully annotated. A total of 1,410 sequences were confirmed to be related to reproduction and key genes involved in sex differentiation and maturation were identified for the first time in turbot (AR, AMH, SRY-related genes, CYP19A, ZPGs, STAR FSHR, etc.). Similarly, 2,241 sequences were related to the immune system and several novel key immune genes were identified (BCL, TRAF, NCK, CD28 and TOLLIP, among others). The number of genes of many relevant reproduction- and immune-related pathways present in the database was 50–90% of the total gene count of each pathway. In addition, 1,237 microsatellites and 7,362 single nucleotide polymorphisms (SNPs) were also compiled. Further, 2,976 putative natural antisense transcripts (NATs) including microRNAs were also identified Conclusions: The combined sequencing strategies employed here significantly increased the turbot genomic resources available, including 34,400 novel sequences. The generated database contains a larger number of genes relevant for reproduction- and immune-associated studies, with an excellent coverage of most genes present in many relevant physiological pathways. This database also allowed the identification of many microsatellites and SNP markers that will be very useful for population and genome screening and a valuable aid in marker assisted selection programs.The current work was granted by the Spanish Government thanks to a Consolider Project (Project Aquagenomics, ref. CDS2007-0002) and to projects AGL2006-13158-C03 and AGL2009-13282-C01 and C02. LR was supported by an Aquagenomics postdoctoral contract and BGP was supported by an Isidro Parga Pondal research fellowship from the Xunta de Galicia (Spain).S

AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B-chronic lymphocytic leukemia cells. Interference with the Akt/NF-kB survival pathway

8 páginas, 5 figuras -- PAGS nros. 572-579Clinical treatment of B-cell chronic lymphocytic leukemia (B-CLL) is limited by the progressive drug resistance and nonselectivity of most drugs towards malignant cells. Depsipeptides are present in certain bacteria and display potent antitumor activity. We have studied the effect of the novel cyclodepsipeptide AT514 (serratamolide) from Serratia marcescens on B-CLL cell viability. AT514 induced apoptosis of B-CLL cells from the 21 patients studied, as confirmed by Annexin-V binding and nuclei condensation, with an average IC50 of 13 M. AT514 was effective in those B-CLL cases resistant to fludarabine, but had no effect on normal PBL. AT514 preferentially activated the intrinsic apoptotic pathway, as evidenced by loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9 and -3, but not of caspase-8. Importantly, AT514 interfered with phosphatidylinositol-3 kinase and protein kinase C survival signals since it increased the apoptotic effect of LY294002 and BisI inhibitors, and induced Akt dephosphorylation at Ser 473. AT514 also decreased NF-B activity by dramatically reducing the levels of p65 in B-CLL. This was confirmed on functional assays using NF-B-luc-transfected Raji cells and transgenic mice. Our results establish that AT514 induces apoptosis of primary B-CLL cells and could be useful for clinical treatment of this malignancyThis work was supported by grants 08.3/0030.1/2003 from the Comunidad Autónoma de Madrid, SAF2003-00824 from the Ministerio de Ciencia y Tecnología (MCyT), and 01/1183 from Fondo de Investigación Sanitaria (to AGP); and CIDEM Grant 301888 (Generalitat de Catalunya)/Fundació Bosch i Gimpera, to RPT). E Escobar and E López-Martín were supported by fellowships from MCyTPeer reviewe