Role of mTOR-regulated autophagy in spine pruning defects and memory impairments induced by binge-like ethanol treatment in adolescent mice

Adolescence is a brain maturation developmental period during which remodeling and changes in synaptic plasticity and neural connectivity take place in some brain regions. Different mechanism participates in adolescent brain maturation, including autophagy that plays a role in synaptic development and plasticity. Alcohol is a neurotoxic compound and its abuse in adolescence induces neuroinflammation, synaptic and myelin alterations, neural damage and behavioral impairments. Changes in synaptic plasticity and its regulation by mTOR have also been suggested to play a role in the behavioral dysfunction of binge ethanol drinking in adolescence. Therefore, by considering the critical role of mTOR in both autophagy and synaptic plasticity in the developing brain, the present study aims to evaluate whether binge ethanol treatment in adolescence would induce dysfunctions in synaptic plasticity and cognitive functions and if mTOR inhibition with rapamycin is capable of restoring both effects. Using C57BL/6 adolescent female and male mice (PND30) treated with ethanol (3 g/kg) on two consecutive days at 48-hour intervals over 2 weeks, we show that binge ethanol treatment alters the density and morphology of dendritic spines, effects that are associated with learning and memory impairments and changes in the levels of both transcription factor CREB phosphorylation and miRNAs. Rapamycin administration (3 mg/kg) prior to ethanol administration restores ethanol-induced changes in both plasticity and behavior dysfunctions in adolescent mice. These results support the critical role of mTOR/autophagy dysfunctions in the dendritic spines alterations and cognitive alterations induced by binge alcohol in adolescence

Numerical Investigations on the Fluid Behavior in the Near Wake of an Experimental Wind Turbine Model in the Presence of the Nacelle

Accurate predictions of the near wake of horizontal-axis wind turbines are critical in estimating and optimizing the energy production of wind farms. Consequently, accurate aerodynamic models of an isolated wind turbine are required. In this paper, the steady-state flow around an experimental horizontal-axis wind turbine (known as the MEXICO model) is investigated using full-geometry computational fluid dynamics (CFD) simulations. The simulations are performed using Reynolds-Averaged Navier-Stokes (RANS) equations in combination with the transitional k-kl-w turbulence model. The multiple reference frame (MRF) approach is used to allow the rotation of the blades. The impacts of the nacelle and blade rotation on the induction region and near wake are highlighted. Simulation cases under attached and detached flow conditions with and without the nacelle were compared to the detailed particle image velocimetry (PIV) measurements. The axial and radial flow behaviors at the induction region have been analyzed in detail. This study attempts to highlight the nacelle effects on the near wake flow and on numerical prediction accuracy under various conditions, as well as the possible reasons for these effects. According to simulation results, the rotation of blades dominates the near wake region, and including the nacelle geometry can improve both axial and radial flow prediction accuracy by up to 15% at high wind speeds. At low wind speeds, the nacelle effects can be ignored. The presence of the nacelle has also been shown to increase flow separation at the trailing edges of the blade airfoils, increasing both root and tip vorticities. Finally, small nacelle diameters are recommended to reduce flow separation on the blades and increase the average velocity downstream of the rotor, thereby optimizing wind farm output power

Effect of the FDT transmission frequency for an optimum content delivery using the FLUTE protocol

File Delivery over Unidirectional Transport (FLUTE) is the standard protocol used in unidirectional environments to provide reliability in the transmission of multimedia files. The key element of this protocol is the use of the File Delivery Table (FDT), which is the in-band mechanism used by FLUTE to inform clients about the files (and their characteristics) transmitted within a FLUTE session. Clients need to receive the FDT in order to start downloading files. Thus, the delivery of FDT packets and the proper configuration of their parameters have a great impact on the Quality of Experience perceived by the users of FLUTE content download services. This paper presents a complete analysis about how the FDT transmission frequency affects the download time of files. Moreover, results show which are the optimum values that minimize this download time. An appropriate configuration of the FDT transmission frequency as well as the use of AL-FEC mechanisms provides an optimum content delivery using the FLUTE protocol.This work is supported in part by the Ministerio de Economia y Competitividad of the Government of Spain under project COMINN (IPT-2012-0883-430000) and by the PAID-05-12 program of the Universitat Politecnica de Valencia.De Fez Lava, I.; Fraile Gil, F.; Guerri Cebollada, JC. (2013). Effect of the FDT transmission frequency for an optimum content delivery using the FLUTE protocol. Computer Communications. 36(12):1298-1309. https://doi.org/10.1016/j.comcom.2013.04.008S12981309361

Laparoscopic Ovariectomy in Standing Mule Mares

Mules are hybrids bred from the mating of a jack donkey and a horse mare, known for their strength and resistance and still used to work in agriculture. Although they have been for long considered sterile, evidence of estrus cycle has been demonstrated together with abnormal behavior related to ovarian activity. In this study, a bilateral standing laparoscopic ovariectomy technique using the LigaSure technology was applied in 10 mare mules for treating unwanted behavioral patterns. The technique was effectively performed on these animals avoiding the risk of general anesthesia, and the use of the LigaSure technology allowed good hemostasis and reduced surgical time. Owners declared to be satisfied with the resolution of the behavior

The complete nucleotide sequence of a Spanish isolate of <i>Citrus psorosis</i> virus: comparative analysis with other ophioviruses

The complete genomic sequence (11278 nt) of Citrus psorosis virus (CPsV), isolate P-121 from Spain, was determined and compared with those from isolate CPV-4 and from other ophioviruses. The three RNAs of P-121 had similar size and identical organization as those of CPV-4. The 24K and the RdRp proteins were potentially encoded in the viral complementary (vc) strand of RNA 1, the 54K protein potentially encoded in vcRNA 2 and the coat protein encoded in vcRNA 3. These four proteins from P-121 and CPV-4 had 87, 92, 93 and 94% amino acid identity, respectively, but only 22, 38, 25 and 33% identity with their homologous proteins from Mirafiori lettuce big vein virus (MLBVV), the only other ophiovirus completely sequenced. Biological and genetic differences between CPsV and MLBVV (and the other ophioviruses), would support their future allocation in different genera within a tentative family Ophioviridae.Instituto de Biotecnología y Biología Molecula

Considerations for the optimal management of antibiotic therapy in elderly patients

Objectives: To maximise efficacy and minimise toxicity, special considerations are required for antibiotic prescription in elderly patients. This review aims to provide practical suggestions for the optimal management of antibiotic therapy in elderly patients. Methods: This was a narrative review. A literature search of published articles in the last 15 years on antibiotics and elderly patients was performed using the Cochrane Library and PubMed electronic databases. The three priority areas were identified: (i) pharmacokinetics/pharmacodynamics (PK/PD) for optimising dosage regimens and route of administration; (ii) antibiotic dosages in some special subpopulations; and (iii) treatment considerations relating to different antibiotic classes and their adverse events. Results: Clinicians should understand the altered PK/PD of drugs in this population owing to co-morbid conditions and normal physiological changes associated with ageing. The body of evidence justifies the need for individualised dose selection, especially in patients with impaired renal and liver function. Clinicians should be aware of the major drug–drug interactions commonly observed in the elderly as well as potential side effects. Conclusion: Antibiotic therapy in the elderly requires a comprehensive approach, including strategies to improve appropriate antibiotic prescribing, limit their use for uncomplicated infections and ensure the attainment of an optimal PK/PD target. To this purpose, further studies involving the elderly are needed to better understand the PK of antibiotics. Moreover, it is necessary to assess the role therapeutic drug monitoring in guiding antibiotic therapy in elderly patients in order to evaluate its impact on clinical outcome

Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I

Foscarnet (phosphonoformate trisodium salt), an antiviral used for the treatment of HIV and herpes virus infections, also acts as an activator or inhibitor of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Interaction of the drug with 11 CA isozymes has been investigated kinetically, and the X-ray structure of its adduct with isoform I (hCA I-foscarnet complex) has been resolved. The first CA inhibitor possessing a phosphonate zinc-binding group is thus evidenced, together with the factors governing recognition of such small molecules by a metalloenzyme active site. Foscarnet is also a clear-cut example of modulator of an enzyme activity which can act either as an activator or inhibitor of a CA isozyme