Informational efficiency and welfare

In a continuous-time market with a safe rate and a risky asset that pays a dividend stream depending on a latent state of the economy, several agents make consumption and investment decisions based on public information–prices and dividends–and private signals. If each investor has constant absolute risk aversion, equilibrium prices do not reveal all the private signals, but lead to the same estimate of the state of the economy that one would hypothetically obtain from the knowledge of all private signals. Accurate information leads to low volatility, ostensibly improving market efficiency, but also reduces each agent’s consumption through a decrease in the price of risk. Thus, informational efficiency is reached at the expense of agents’ welfare

Functional and molecular characterization of pendrin, the anion exchanger involved in Pendred syndrome, non-syndromic deafness and respiratory distresses.

Pendrin is an anion exchanger with affinity for several monovalent anions including iodide, chloride and bicarbonate. It is expressed in the inner ear, thyroid and kidney and more recently was also detected in the airways and in a number of other tissues. Pendrin was first identified as the protein that, if mutated, is responsible for the pathology referred to as Pendred syndrome, an autosomal recessive disorder characterized by bilateral sensorineural hearing loss associated to thyroid dysfunction with or without involvement of the vestibular system. Hypo- or non-functional mutations of pendrin are also responsible for the development of unilateral or bilateral hearing loss with enlargement of the vestibular aqueduct with no involvement of other organs (non-syndromic EVA). On the other hand, also the overexpression and hyper-function of pendrin have recently been associated with a number of other pathologies, such as hypertension, asthma and chronic obstructive pulmonary disease (COPD). In this work, we performed the functional characterization of 7 pendrin variants identified in a cohort of 58 deaf patients by our collaborators of the University of Campinas (Sao Paolo, Brazil), in order to define their role in the observed phenotype. The analysis of pendrin activity was performed by means of a fluorometric assay based on a halide-sensitive enhanced yellow fluorescence protein (EYFP) variant. Furthermore, the molecular defect of such mutants was analyzed, defining their subcellular localization and expression levels by means of confocal microscopy and western blot. We could assess the degree of functional impairment of the analyzed pendrin variants, contributing therefore to the genetic diagnosis of the screened patients. The genetic diagnosis of 5 out of 14 patients was definitively assessed as pendrin-related deafness, while for the remaining patients further genetic investigation is necessary, involving pendrin promoter and 3\u2019-UTR, as well as further deafness related genes. We could observe a clear correlation between measured functional impairment, sub-cellular localization and expression levels of these specific variants. In particular, loss of function variants (T193I and L445W) are retained in the ER and completely excluded from the plasma membrane, while reduction of function mutations (P142L, G149R, C282Y) show at least a partial trafficking to the PM. Based on these findings we hypothesized that pendrin mutant isoforms are targeted for proteasomal degradation. Starting from this hypothesis we could show that pharmacological inhibition of proteasomal degradation with 10\ub5M MG132 was capable to recover (i) total and (ii) plasma membrane expression levels of pendrin variants and, most importantly, (iii) transport activity of specific pendrin variants (P142L, T183I, Q413R, L445W) was improved upon treatment. Such result allows for further development of possible rescuing approaches of pendrin transport activity as a potential treatment of pendrin-related pathologies. A second part of the present study focuses on the search of a specific ligand of pendrin, with the aim of modulating the activity of the transporter, especially in those cases of pathological over-expression and hyperactivity, such as asthma, COPD and hypertension. No specific, non-toxic and potent inhibitor of pendrin could be identified so far and the screening of large compound libraries failed in identifying potential inhibitors. We therefore adopted a more targeted selection of candidates for the screening. We selected compounds among (i) established anion exchangers inhibitors, (ii) inhibitors of the pendrin homologue DRA, (iii) common diuretics and antihypertensive agents, and (iv) via two bioinformatic tools: meta-analysis and SHED alignments. Meta-analysis is an approach aimed to the mathematical definition of a protein topology based on its primary aminoacidic sequence, with no knowledge of its three-dimensional structure. SHED profile allows for the mathematical definition of small compounds according to the intra-molecular distribution of specific atomic features. The effect of the candidates ligands on pendrin activity was evaluated by means of the same fluorometric assay mentioned earlier. In the present study we could (i) confirm the inhibitory effect of previously assessed active compounds, Niflumic acid and NPPB, (ii) define for the first time the inhibitory effect of the anti-inflammatory, anti-rheumatic drug tenidap. In a second screening phase on further compounds suggested by the alignment of the so far identified active compounds niflumic acid and tenidap, according to the SHED profilng, we were able to identify two further active compounds, N-(2-chlorophenyl)-2-(2,4-dibromophenoxy)acetamide and flufenamic acid

Native and non-native egg parasitoids associated with brown marmorated stink bug (Halyomorpha halys [stål, 1855]; hemiptera: Pentatomidae) in western slovenia

Halyomorpha halys (Hemiptera: Pentatomidae), native to East Asia, has become a globally invasive pest, as a serious threat to agricultural production and a notorious nuisance pest in urban areas. Considerable efforts have been made so far to develop effective pest control measures to prevent crop damage. Biological control of this invasive stink bug by egg parasitoids has proven to be the most environmentally sustainable long-term solution. Knowledge of the native egg parasitoid fauna is of key importance when implementing a biological control program. Therefore, the main objective of our study was to detect egg parasitoid species associated with H. halys in the Goriška region (Western Slovenia) and to evaluate their impact on the pest population under field conditions. In the years 2019 and 2020, around 4600 H. halys eggs were collected in the wild and more than 3400 sentinel eggs were exposed to detect parasitoids in the field. Five egg-parasitoid species emerged from H. halys eggs: Anastatus bifasciatus (Hymenoptera: Eupelmidae), Telenomus sp., Trissolcus basalis, Trissolcus mitsukurii (Hymenoptera: Scelionidae) and Ooencyrtus telenomicida (Hymenoptera: Encyrtidae), all of them are new records for Slovenia. The native species, An. bifasciatus, dominated in urban and suburban areas, while non-native Tr. mitsukurii prevailed in agricultural areas. Overall parasitism rates of naturally laid eggs by the parasitoid species complex in 2019 and 2020 was 3.0 and 14.4%, respectively. Rapid recruitment of native parasitoids, early detection of an effective alien parasitoid species and increasing overall parasitism rates are very encouraging results, which need to be followed and verified in future research

Adaptação transcultural e validação da Hamilton Early Warning Score para o Brasil

Objetivo: Adaptar transculturalmente e validar, para a língua portuguesa, a Hamilton Early Warning Score para detectar a deterioração clínica em serviços de emergência.Método: Estudo metodológico compreendendo as etapas de tradução, síntese, retrotradução, comitê de especialistas (n=13), pré-teste, envio e análise das propriedades de medidas em uma amostra composta por 188 pacientes. Comparou-se a Canadian Acute Scale Triage com a Hamilton Early Warning Score. Foram utilizados o Coeficiente Kappa Ponderado, Coeficiente de Correlação Intraclasse e de Pearson, Regressão Logística Binária e a Área Sob a Curva Receiver Operating Characteristic para a análise dos dados.Resultados: A Hamilton Early Warning Score apresentou confiabilidade excelente, ou seja, α=0,924 (p<0,001). A validade de construto identificou correlação forte e negativa r=-0,75 e a preditiva apresentou um odds ratio de 1,63, IC 95% (1,358-1,918) (p<0,001).Conclusão: A Hamilton Early Warning Score em português é válida e confiável para reconhecer pacientes em condição de deterioração clínica em serviços de emergência. Palavras-chave: Estudo de validação. Alerta rápido. Deterioração clínica. Serviços médicos de emergência. Comparação transcultural. Segurança do paciente

Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability

Excitatory synapses in the CNS are highly dynamic structures that can show activity- dependent remodeling and stabilization in response to learning and memory. Synapses are enveloped with intricate processes of astrocytes known as perisynaptic astrocytic processes (PAPs). PAPs are motile structures displaying rapid actin-dependent movements and are characterized by Ca²⁺ elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca²⁺ events in astrocytes and PAP morphological dynamics remain unclear.Results In the hippocampus, we found that PAPs show extensive structural plasticity that is regulated by synaptic activity through astrocytic metabotropic glutamate receptors and intracellular calcium signaling. Synaptic activation that induces long-term potentiation caused a transient PAP motility increase leading to an enhanced astrocytic coverage of the synapse. Selective activation of calcium signals in individual PAPs using exogenous metabotropic receptor expression and two-photon uncaging reproduced these effects and enhanced spine stability. In vivo imaging in the somatosensory cortex of adult mice revealed that increased neuronal activity through whisker stimulation similarly elevates PAP movement. This in vivo PAP motility correlated with spine coverage and was predictive of spine stability.Conclusions This study identifies a novel bidirectional interaction between synapses and astrocytes, in which synaptic activity and synaptic potentiation regulate PAP structural plasticity, which in turn determines the fate of the synapse. This mechanism may represent an important contribution of astrocytes to learning and memory processes

Multifactorial analysis of the stochastic epigenetic variability in cord blood confirmed an impact of common behavioral and environmental factors but not of in vitro conception.

Background: An increased incidence of imprint-associated disorders has been reported in babies born from assisted reproductive technology (ART). However, previous studies supporting an association between ART and an altered DNA methylation status of the conceived babies have been often conducted on a limited number of methylation sites and without correction for critical potential confounders. Moreover, all the previous studies focused on the identification of methylation changes shared among subjects while an evaluation of stochastic differences has never been conducted. This study aims to evaluate the effect of ART and other common behavioral or environmental factors associated with pregnancy on stochastic epigenetic variability using a multivariate approach. Results: DNA methylation levels of cord blood from 23 in vitro and 41 naturally conceived children were analyzed using the Infinium HumanMethylation450 BeadChips. After multiple testing correction, no statistically significant difference emerged in the number of cord blood stochastic epigenetic variations or in the methylation levels between in vitro- and in vivo-conceived babies. Conversely, four multiple factor analysis dimensions summarizing common phenotypic, behavioral, or environmental factors (cord blood cell composition, pre or post conception supplementation of folates, birth percentiles, gestational age, cesarean section, pre-gestational mother's weight, parents' BMI and obesity status, presence of adverse pregnancy outcomes, mother's smoking status, and season of birth) were significantly associated with stochastic epigenetic variability. The stochastic epigenetic variation analysis allowed the identification of a rare imprinting defect in the locus GNAS in one of the babies belonging to the control population, which would not have emerged using a classical case-control association analysis. Conclusions: We confirmed the effect of several common behavioral or environmental factors on the epigenome of newborns and described for the first time an epigenetic effect related to season of birth. Children born after ART did not appear to have an increased risk of genome-wide changes in DNA methylation either at specific loci or randomly scattered throughout the genome. The inability to identify differences between cases and controls suggests that the number of stochastic epigenetic variations potentially induced by ART was not greater than that naturally produced in response to maternal behavior or other common environmental factors

Dynamical classification of Trans-Neptunian Objects detected by the Dark Energy Survey

FINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQThe outer solar system contains a large number of small bodies (known as trans-Neptunian objects or TNOs) that exhibit diverse types of dynamical behavior. The classification of bodies in this distant region into dynamical classes-subpopulations that expe1594113FINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQSem informaçãoSem informação465376/2014-2Funding for the DES Projects has been provided by the U.S. Department of Energy, the U.S. National Science Foundation, the Ministry of Science and Education of Spain, the Science and Technology Facilities Council of the United Kingdom, the Higher Educati

Testing the isotropy of the dark energy Survey's extreme trans-neptunian objects

We test whether the population of "extreme"trans-Neptunian objects (eTNOs) detected in the first four years of the Dark Energy Survey (DES Y4) data exhibit azimuthal asymmetries that might be evidence of gravitational perturbations from an unseen super-Earth in a distant orbit. By rotating the orbits of the detected eTNOs, we construct a synthetic population that, when subject to the DES selection function, reproduces the detected distribution of eTNOs in the orbital elements a, e, and i as well as absolute magnitude H, but has uniform distributions in mean anomaly M, longitude of ascending node Ω, and argument of perihelion ω. We then compare the detected distributions in each of Ω, ω, and the longitude of perihelion {equation presented} to those expected from the isotropic population, using Kuiper's variant of the Kolmogorov-Smirnov test. The three angles are tested for each of four definitions of the eTNO population, choosing among a > (150, 250) au and perihelion q > (30, 37) au. These choices yield 3-7 eTNOs in the DES Y4 sample. Among the 12 total tests, two have the likelihood of drawing the observed angles from the isotropic population at p 250 and q > 37 au and the four detections at a > 250 and q > 30 au have a Ω distribution with p ≈ 0.03 coming from the isotropic construction, but this is not strong evidence of anisotropy given the 12 different tests. The DES data taken on their own are thus consistent with azimuthal isotropy and do not require a "Planet 9"hypothesis. The limited sky coverage and object count mean, however, that the DES data by no means falsify this hypothesis

Testing the isotropy of the Dark Energy Survey's extreme trans-Neptunian objects

We test whether the population of "extreme" trans-Neptunian objects (eTNOs) detected in the Y4 Dark Energy Survey (DES) data exhibit azimuthal asymmetries which might be evidence of gravitational perturbations from an unseen super-Earth in a distant orbit. By rotating the orbits of the detected eTNOs, we construct a synthetic population which, when subject to the DES selection function, reproduces the detected distribution of eTNOs in the orbital elements $a,e,$ and $i$ as well as absolute magnitude $H$, but has uniform distributions in mean anomaly $M$, longitude of ascending node $\Omega,$ and argument of perihelion $\omega.$ We then compare the detected distributions in each of $\Omega, \omega,$ and $\varpi\equiv\Omega+\omega$ to those expected from the isotropic population, using Kuiper's variant of the Kolmogorov-Smirnov test. The three angles are tested for each of 4 definitions of the eTNO population, choosing among $a>(150,250)$ AU and perihelion $q>(30,37)$ AU. These choices yield 3--7 eTNOs in the DES Y4 sample. Among the twelve total tests, two have the likelihood of drawing the observed angles from the isotropic population at $p250, q>37$ AU, and the 4 detections at $a>250, q>30$ AU, have $\Omega$ distribution with $p=0.03$ of coming from the isotropic construction, but this is not strong evidence of anisotropy given the 12 different tests. The DES data taken on their own are thus consistent with azimuthal isotropy and do not require a "Planet 9" hypothesis. The limited sky coverage and object count mean, however, that the DES data by no means falsify this hypothesis.Comment: Accepted on PS