Tools for the assessment of business models around the exploitation of bidirectional electric vehicle chargers

Electric vehicles can be considered as important amounts of energy stored in batteries. The possibility of taking advantage of such energy to other ends out of transport is a great opportunity for the transition from combustion engine's vehicles to electric vehicles. To do this, it is necessary to use bidirectional chargers, so the energy can ow in both directions: from the vehicle to the electrical system it is connected to and vice versa. This project studies an optimization tool to assess the impact of exploiting the energy in electrical vehicles in buildings through bidirectional chargers and its application to two models representing two di erent kind of buildings: a medium o ce and a data center. Afterwards, business models around this idea are discussed

The Impact of the PI3K/Akt Signaling Pathway in Anxiety and Working Memory in Young and Middle-Aged PDK1 K465E Knock-In Mice

Dysfunction and dysregulation at the genetic, neural, and behavioral levels point at the fine-tuning of broadly spread networks as critical for a wide array of behaviors and mental processes through the life span. This brain-based evidence, from basic to behavioral neuroscience levels, is leading to a new conceptualization of mental health and disease. Thus, the Research Domain Criteria considers phenotypic differences observed among disorders as explained by variations in the nature and degree of neural circuitry disruptions, under the modulation of several developmental, compensatory, environmental, and epigenetic factors. In this context, we aimed to describe for the first time the in vivo behavioral impact of tweaking the PI3K/Akt signaling pathway known to play an essential role in the regulation of cellular processes, leading to diverse physiological responses. We explored the effects in young (YA, 3-4 months of age) and mature (MA, 11-14 months of age) male and female PDK1 K465E knock-in mice in a battery of tests under different anxiogenic conditions. The results evidenced that the double mutation of the PDK1 pleckstrin homology (PH) domain resulted in an enhancement of the negative valence system shown as an increase of responses of fear- and anxiety-like behaviors in anxiogenic situations. Interestingly, this seemed to be specific of YA and found regulated at middle age. In contrast, cognitive deficits, as measured in a spatial working memory task, were found in both YA and MA mutants and independently of the level of their anxious-like profiles. These distinct age- and function-dependent impacts would be in agreement with the distinct cortical and limbic deficits in the Akt signaling in the brain we have recently described in these same animals. The elicitation of age- and neuronal-dependent specific patterns suggests that fine-tuning the intensity of the PKB/Akt signal that enables diverse physiological response has also its in vivo translation into the negative valence system and age is a key regulatory factor

Sex-dependent signatures, time frames and longitudinal fine-tuning of the marble burying test in normal and ad-pathological aging mice

Altres ajuts: This work was funded by UAB-GE-260408 to L.G.-L.It also received financial support from Memorial Mercedes Llort Sender 2021/80/09241941.6.The marble burying (MB) test, a classical test based on the natural tendency of rodents to dig in diverse substrates and to bury small objects, is sensitive to some intrinsic and extrinsic factors. Here, under emerging neuroethological quantitative and qualitative analysis, the MB performance of 12-month-old male and female 3xTg-AD mice for Alzheimer's disease and age-matched counterparts of gold-standard C57BL6 strain with normal aging unveiled sex-dependent signatures. In addition, three temporal analyses, through the (1) time course of the performance, and (2) a repeated test schedule, identified the optimal time frames and schedules to detect sex-and genotype-dependent differences. Besides, a (3) longitudinal design from 12 to 16 months of age monitored the changes in the performance with aging, worsening in AD-mice, and modulation through the repeated test. In summary, the present results allow us to conclude that (1) the marble burying test is responsive to genotype, sex, aging, and its interactions; (2) the male sex was more sensitive to showing the AD-phenotype; (3) longitudinal assessment shows a reduction in females with AD pathology; (4) burying remains stable in repeated testing; (5) the time-course of marbles burying is useful; and (6) burying behavior most likely represents perseverative and/or stereotyped-like behavior rather than anxiety-like behavior in 3xTg-AD mice

Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism

SummaryIn cytotoxic T cells (CTL), Akt, also known as protein kinase B, is activated by the T cell antigen receptor (TCR) and the cytokine interleukin 2 (IL-2). Akt can control cell metabolism in many cell types but whether this role is important for CTL function has not been determined. Here we have shown that Akt does not mediate IL-2- or TCR-induced cell metabolic responses; rather, this role is assumed by other Akt-related kinases. There is, however, a nonredundant role for sustained and strong activation of Akt in CTL to coordinate the TCR- and IL-2-induced transcriptional programs that control expression of key cytolytic effector molecules, adhesion molecules, and cytokine and chemokine receptors that distinguish effector versus memory and naive T cells. Akt is thus dispensable for metabolism, but the strength and duration of Akt activity dictates the CTL transcriptional program and determines CTL fate

Nova descoberta sobre la formació de neurones

Investigadors del Institut de Neurociències i del Departament de Bioquímica i Biologia Molecular de la UAB han definit una via de senyalització intracel·lular clau per a la correcta formació de les neurones. La recerca, liderada pel doctor Jose R. Bayascas, ha estat publicada a Molecular and Cellular Biology, i pot permetre en el futur desenvolupar fàrmacs d'interès terapèutic, especialment en el camp de la psiquiatria.Investigadores del Instituto de Neurociencias y del Departamento de Bioquímica y Biología Molecular de la UAB han definido una vía de señalización intracelular clave para la correcta formación de las neuronas. La investigación, liderada por el doctor Jose R. Bayascas, ha sido publicada en Molecular and Cellular Biology y puede permitir desarrollar fármacos de interés terapéutico en el futuro, especialmente en el campo de la psiquiatría

Molecular Insights into the Regulation of 3-Phosphoinositide-Dependent Protein Kinase 1 : Modeling the Interaction between the Kinase and the Pleckstrin Homology Domains

The 3-phosphoinositide-dependent protein kinase 1 (PDK1) K465E mutant kinase can still activate protein kinase B (PKB) at the membrane in a phosphatidylinositol-3,4,5-trisphosphate (PIP3, PtdIns(3,4,5)P3) independent manner. To understand this new PDK1 regulatory mechanism, docking and molecular dynamics calculations were performed for the first time to simulate the wild-type kinase domain-pleckstrin homology (PH) domain complex with PH-in and PH-out conformations. These simulations were then compared to the PH-in model of the KD-PH(mutant K465E) PDK1 complex. Additionally, three KD-PH complexes were simulated, including a substrate analogue bound to a hydrophobic pocket (denominated the PIF-pocket) substrate-docking site. We find that only the PH-out conformation, with the PH domain well-oriented to interact with the cellular membrane, is active for wild-type PDK1. In contrast, the active conformation of the PDK1 K465E mutant is PH-in, being ATP-stable at the active site while the PIF-pocket is more accessible to the peptide substrate. We corroborate that both the docking-site binding and the catalytic activity are in fact enhanced in knock-in mouse samples expressing the PDK1 K465E protein, enabling the phosphorylation of PKB in the absence of PIP3binding

The death receptor antagonist FAIM promotes neurite outgrowth by a mechanism that depends on ERK and NF-κB signaling

Fas apoptosis inhibitory molecule (FAIM) is a protein identified as an antagonist of Fas-induced cell death. We show that FAIM overexpression fails to rescue neurons from trophic factor deprivation, but exerts a marked neurite growth–promoting action in different neuronal systems. Whereas FAIM overexpression greatly enhanced neurite outgrowth from PC12 cells and sympathetic neurons grown with nerve growth factor (NGF), reduction of endogenous FAIM levels by RNAi decreased neurite outgrowth in these cells. FAIM overexpression promoted NF-κB activation, and blocking this activation by using a super-repressor IκBα or by carrying out experiments using cortical neurons from mice that lack the p65 NF-κB subunit prevented FAIM-induced neurite outgrowth. The effect of FAIM on neurite outgrowth was also blocked by inhibition of the Ras–ERK pathway. Finally, we show that FAIM interacts with both Trk and p75 neurotrophin receptor NGF receptors in a ligand-dependent manner. These results reveal a new function of FAIM in promoting neurite outgrowth by a mechanism involving activation of the Ras–ERK pathway and NF-κB

Phosphoinositide-dependent kinase 1 controls migration and malignant transformation but not cell growth and proliferation in PTEN-null lymphocytes

In normal T cell progenitors, phosphoinositide-dependent kinase l (PDK1)–mediated phosphorylation and activation of protein kinase B (PKB) is essential for the phosphorylation and inactivation of Foxo family transcription factors, and also controls T cell growth and proliferation. The current study has characterized the role of PDK1 in the pathology caused by deletion of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN). PDK1 is shown to be essential for lymphomagenesis caused by deletion of PTEN in T cell progenitors. However, PTEN deletion bypasses the normal PDK1-controlled signaling pathways that determine thymocyte growth and proliferation. PDK1 does have important functions in PTEN-null thymocytes, notably to control the PKB–Foxo signaling axis and to direct the repertoire of adhesion and chemokine receptors expressed by PTEN-null T cells. The results thus provide two novel insights concerning pathological signaling caused by PTEN loss in lymphocytes. First, PTEN deletion bypasses the normal PDK1-controlled metabolic checkpoints that determine cell growth and proliferation. Second, PDK1 determines the cohort of chemokine and adhesion receptors expressed by PTEN-null cells, thereby controlling their migratory capacity