The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to ischemia.

Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC-induced neuroprotection both in cultured neurons (in vitro) and rat brain (in vivo). Our results show that PC increased neuronal MDM2 protein levels, which prevented ischemiainduced p53 stabilization and neuronal death. Indeed, PC attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2-p53 pathway was confirmed in rat brain using a PC model in vivo. These findings demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection against a subsequent ischemic insult and poses MDM2 as an essential target in ischemic tolerance

Ambient light modulation of exogenous attention to threat

Planet Earth’s motion yields a 50 % day–50 % night yearly balance in every latitude or longitude, so survival must be guaranteed in very different light conditions in many species, including human. Cone- and rod-dominant vision, respectively specialized in light and darkness, present several processing differences, which are—at least partially—reflected in event-related potentials (ERPs). The present experiment aimed at characterizing exogenous attention to threatening (spiders) and neutral (wheels) distractors in two environmental light conditions, low mesopic (L, 0.03 lx) and high mesopic (H, 6.5 lx), yielding a differential photoreceptor activity balance: rod > cone and rod < cone, respectively. These distractors were presented in the lower visual hemifield while the 40 participants were involved in a digit categorization task. Stimuli, both targets (digits) and distractors, were exactly the same in L and H. Both ERPs and behavioral performance in the task were recorded. Enhanced attentional capture by salient distractors was observed regardless of ambient light level. However, ERPs showed a differential pattern as a function of ambient light. Thus, significantly enhanced amplitude to salient distractors was observed in posterior P1 and early anterior P2 (P2a) only during the H context, in late P2a during the L context, and in occipital P3 during both H and L contexts. In other words, while exogenous attention to threat was equally efficient in light and darkness, cone-dominant exogenous attention was faster than rod-dominant, in line with previous data indicating slower processing times for rod- than for cone-dominant visionThis research was supported by the Grants PSI2014-54853-P and PSI2012-37090 from the Ministerio de Economía y Competitividad of Spain (MINECO

Measurement of W-pair production in e+e−e^+ e^- collisions at 189 GeV

The production of W-pairs is analysed in a data samplecollected by ALEPH at a mean centre-of-mass energy of 188.6 GeV,corresponding to an integrated luminosity of 174.2 pb^-1. Crosssections are given for different topologies of W decays intoleptons or hadrons. Combining all final states and assumingStandard Model branching fractions, the total W-pair cross sectionis measured to be 15.71 +- 0.34 (stat) +- 0.18 (syst) pb.Using also the W-pair data samples collected by ALEPH at lowercentre-of-mass energies, the decay branching fraction of the W bosoninto hadrons is measured to be BR (W hadrons) = 66.97+- 0.65 (stat) +- 0.32 (syst) %, allowing a determination of theCKM matrix element |V(cs)|= 0.951 +- 0.030 (stat) +- 0.015 (syst)

Sexual Relationships in Hispanic Countries: a Literature Review

This is a pre-print of an article published in Current Sexual Health Reports. The final authenticated version is available online at: https://doi.org/10.1007/s11930-020-00272-6Purpose of Review: Sexuality is a complex dimension for which culture seems to play an important role, particularly in countries that are more traditional. This review summarizes the knowledge about sexual relationships in Hispanic countries, considering sexual debut, attitudes, behaviors, and satisfaction. Recent Findings: In line with the literature reviewed, the sexual double standard seems to be continuing to influence sexual relationships. Some countries show more open expressions of sexuality based on the level of gender inequality or sexualized context, and within countries, variables such as religious commitment, family characteristics, and access to resources may play important roles in sexuality. Summary: Future research, policies, and interventions should consider these specific characteristics, including these forms of expression of sexuality, in the adjustment of cross-cultural and cross-national strategies

Searches for neutral Higgs bosons in e+e−e^{+}e^{-} collisions at centre-of-mass energies from 192 to 202 GeV

Searches for neutral Higgs bosons are performed with the 237 pb^-1 of data collected in 1999 by the ALEPH detector at LEP, for centre-of-mass energies between 191.6 and 201.6 GeV. These searches apply to Higgs bosons within the context of the Standard Model and its minimal supersymmetric extension (MSSM) as well as to invisibly decaying Higgs bosons. No evidence of a signal is seen. A lower limit on the mass of the Standard Model Higgs boson of 107.7 GeV/c^2 at 95% confidence level is set. In the MSSM, lower limits of 91.2 and 91.6 GeV/c^2 are derived for the masses of the neutral Higgs bosons h and A, respectively. For a Higgs boson decaying invisibly and produced with the Standard Model cross section, masses below 106.4 GeV/c^2 are excluded

Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes. However, the specific location and properties of these heteromers have remained largely unknown. Here, by using techniques that allowed a precise visualization of the heteromers in situ in combination with sophisticated genetically-modified animal models, together with biochemical and pharmacological approaches, we provide a high resolution expression map and a detailed functional characterization of A2AR-CB1R heteromers in the dorsal striatum. Specifically, our data unveil that the A2AR-CB1R heteromer (i) is essentially absent from corticostriatal projections and striatonigral neurons, and, instead, is largely present in striatopallidal neurons, (ii) displays a striking G protein-coupled signaling profile, where co-stimulation of both receptors leads to strongly reduced downstream signaling, and (iii) undergoes an unprecedented dysfunction in Huntington’s disease, an archetypal disease that affects striatal neurons. Altogether, our findings may open a new conceptual framework to understand the role of coordinated adenosine-endocannabinoid signaling in the indirect striatal pathway, which may be relevant in motor function and neurodegenerative diseases

Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics

The assessment of oocyte quality in human in vitro fertilization (IVF) is getting increasing attention from embryologists. Oocyte selection and the identification of the best oocytes, in fact, would help to limit embryo overproduction and to improve the results of oocyte cryostorage programs. Follicular fluid (FF) is easily available during oocyte pick-up and theorically represents an optimal source on non-invasive biochemical predictors of oocyte quality. Unfortunately, however, the studies aiming to find a good molecular predictor of oocyte quality in FF were not able to identify substances that could be used as reliable markers of oocyte competence to fertilization, embryo development and pregnancy. In the last years, a well definite trend toward passing from the research of single molecular markers to more complex techniques that study all metabolites of FF has been observed. The metabolomic approach is a powerful tool to study biochemical predictors of oocyte quality in FF, but its application in this area is still at the beginning. This review provides an overview of the current knowledge about the biochemical predictors of oocyte quality in FF, describing both the results coming from studies on single biochemical markers and those deriving from the most recent studies of metabolomic

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk