Pharmacological fingerprint of antipsychotic drugs at the serotonin 5-HT2A receptor.

The intricate involvement of the serotonin 5-HT2A receptor (5-HT2AR) both in schizophrenia and in the activity of antipsychotic drugs is widely acknowledged. The currently marketed antipsychotic drugs, although effective in managing the symptoms of schizophrenia to a certain extent, are not without their repertoire of serious side effects. There is a need for better therapeutics to treat schizophrenia for which understanding the mechanism of action of the current antipsychotic drugs is imperative. With bioluminescence resonance energy transfer (BRET) assays, we trace the signaling signature of six antipsychotic drugs belonging to three generations at the 5-HT2AR for the entire spectrum of signaling pathways activated by serotonin (5-HT). The antipsychotic drugs display previously unidentified pathway preference at the level of the individual Gα subunits and ß-arrestins. In particular, risperidone, clozapine, olanzapine and haloperidol showed G protein-selective inverse agonist activity. In addition, G protein-selective partial agonism was found for aripiprazole and cariprazine. Pathway-specific apparent dissociation constants determined from functional analyses revealed distinct coupling-modulating capacities of the tested antipsychotics at the different 5-HT-activated pathways. Computational analyses of the pharmacological and structural fingerprints support a mechanistically based clustering that recapitulate the clinical classification (typical/first generation, atypical/second generation, third generation) of the antipsychotic drugs. The study provides a new framework to functionally classify antipsychotics that should represent a useful tool for the identification of better and safer neuropsychiatric drugs and allows formulating hypotheses on the links between specific signaling cascades and in the clinical outcomes of the existing drugs.

An analysis of the psychometric properties of the writing-specific cognitive strategies questionnaire for undergraduate students.

Writing strategies are needed to manage the complexity of writing tasks, especially at university, where writing tasks are for learning, professional, or scientific purposes and are highly demanding. The literature shows that many undergraduate students have defined, stable, writing strategies, although some lack proper strategic development and require explicit instruction in this regard. In both cases, adapting writing tasks to undergraduate students' preferences and instructing them effectively requires understanding their writing strategies, which will encourage optimal learning and writing proficiency. This is why valid, reliable, writing strategy assessment tools are essential. The present study focused on the validation of the Spanish Writing Strategies Questionnaire-Undergraduate Students (WSQ-SU), aimed at measuring undergraduate students' preferences for using different writing strategies. The sample comprised 978 Spanish undergraduates doing degrees in Infant, Primary or Social Education, Pedagogy and Psychology. The data from the questionnaire was explored by means of exploratory and confirmatory analysis, test-retest reliability to analyse temporal stability and convergent validity. Two factors, planning and revising, were identified through exploratory and confirmatory factor analysis, representing different writing strategies and supporting the original model. The results indicated adequate test-retest reliability and temporal stability. The results also showed the questionnaire's convergent validity; a direct, linear correlation between two factors and off-line planning and revising variables. Based on the results, the WSQ for undergraduate students-Spanish version has been shown to be a reliable and valid, scale that can be easily applied in the university context to explore undergraduate students' writing strategies.

Y-chromosome in the olfactory neuroepithelium as a potential biomarker of depression in women with male offspring: an exploratory study.

The persistence of fetal cells in the mother (fetal microchimerism (FMc)) has been described in maternal tissues essential to the newborn. FMc is associated with several diseases that start or worsen in pregnancy or postpartum. This exploratory study reports-for the first time-the presence of FMc in the olfactory neuroepithelium (ON) of both healthy and depressed women with male offspring. However, depressed women had fewer microchimeric cells (digital PCR). The existence of FMc in the ON could facilitate mother-child bonding. These findings open new pathways to study FMc in the ON, female depression, and mother-child bonding.

Role of cyclin-dependent kinase 5 in psychosis and the modulatory effects of cannabinoids.

Cyclin-dependent kinase 5 (CDK5) is a serine/threonine kinase that has emerged as a key regulator of neurotransmission in complex cognitive processes. Its expression is altered in treated schizophrenia patients, and cannabinoids modulate CDK5 levels in the brain of rodents. However, the role of this kinase, and its interaction with cannabis use in first-episode psychosis (FEP) patients is still not known. Hence, we studied the expression changes of CDK5 and its signaling partner, postsynaptic density protein 95 (PSD95) in olfactory neuroepithelial (ON) cells of FEP patients with (FEP/c) and without (FEP/nc) prior cannabis use, and in a dual-hit mouse model of psychosis. In this model, adolescent mice were exposed to the cannabinoid receptor 1 agonist (CB1R) WIN-55,212-2 (WIN: 1 mg/kg) during 21 days, and to the N-methyl-d-aspartate receptor (NMDAR) blocker phencyclidine (PCP: 10 mg/kg) during 10 days. FEP/c showed less social functioning deficits, lower CDK5 and higher PSD95 levels than FEP/nc. These changes correlated with social skills, but not cognitive deficits. Consistently, exposure of ON cells from FEP/nc patients to WIN in vitro reduced CDK5 levels. Convergent results were obtained in mice, where PCP by itself induced more sociability deficits, and PSD95/CDK5 alterations in the prefrontal cortex and hippocampus than exposure to PCP-WIN. In addition, central blockade of CDK5 activity with roscovitine in PCP-treated mice restored both sociability impairments and PSD95 levels. We provide translational evidence that increased CDK5 could be an early indicator of psychosis associated with social deficits, and that this biomarker is modulated by prior cannabis use.

Corrosion Resistance of Aluminum Alloy AA2024 with Hard Anodizing in Sulfuric Acid-Free Solution.

In the aeronautical industry, Al-Cu alloys are used as a structural material in the manufacturing of commercial aircraft due to their high mechanical properties and low density. One of the main issues with these Al-Cu alloy systems is their low corrosion resistance in aggressive substances; as a result, Al-Cu alloys are electrochemically treated by anodizing processes to increase their corrosion resistance. Hard anodizing realized on AA2024 was performed in citric and sulfuric acid solutions for 60 min with constant stirring using current densities 3 and 4.5 A/dm2. After anodizing, a 60 min sealing procedure in water at 95 °C was performed. Scanning electron microscopy (SEM) and Vickers microhardness (HV) measurements were used to characterize the microstructure and mechanical properties of the hard anodizing material. Electrochemical corrosion was carried out using cyclic potentiodynamic polarization curves (CPP) and electrochemical impedance spectroscopy (EIS) in a 3.5 wt. % NaCl solution. The results indicate that the corrosion resistance of Al-Cu alloys in citric acid solutions with a current density 4.5 A/dm2 was the best, with corrosion current densities of 2 × 10-8 and 2 × 10-9 A/cm2. Citric acid-anodized samples had a higher corrosion resistance than un-anodized materials, making citric acid a viable alternative for fabricating hard-anodized Al-Cu alloys.

First record of Tamarixiadahlsteni Zuparko (Hymenoptera, Eulophidae), a parasitoid of Triozaeugeniae Froggatt (Hemiptera, Triozidae) and current status of the Tamarixia species in Mexico.

Parasitic wasps of the genus Tamarixia represent important biological control agents of members of the true bug group, Psylloidea, and are host specific; therefore, they can be used to control insect pests. In this study we report, for the first time, the presence of the parasitoid Tamarixiadahlsteni in Mexico and its mitochondrial barcode region of the cytochrome oxidase I gene (COI). We also review the species diversity of the genus Tamarixia in Mexico.

Finite Element Modeling of Hot Rolling of 1075 Carbon Steel Process with Variable Cross Section.

Currently, it is common to use steel poles for applications in livestock and agriculture. In this work, finite element analysis of five hot rolling passes for the manufacture of farm poles using 1075 carbon steels from recycled railway material was developed. The steel industry in Mexico imports products from other countries or from companies specialized in metallurgy at an excessive cost. To be more competitive and save costs, companies seek the reutilization of existing resources such as the railway 1075 steel, which has good mechanical properties. SFTC DEFORM-3D software was used to model five hot rolling passes considering a variable cross section railway profile. The effect of rolling speed and temperature were considered to analyze flow behavior. Rolling loads were also determined.

Sex-Specific Effects of Synbiotic Exposure in Mice on Addictive-Like Behavioral Alterations Induced by Chronic Alcohol Intake Are Associated With Changes in Specific Gut Bacterial Taxa and Brain Tryptophan Metabolism.

Chronic alcohol intake has been shown to disrupt gut microbiota homeostasis, but whether microbiota modulation could prevent behavioral alterations associated with chronic alcohol intake remains unknown. We investigated the effects of synbiotic dietary supplementation on the development of alcohol-related addictive behavior in female and male mice and evaluated whether these effects were associated with changes in bacterial species abundance, short-chain fatty acids, tryptophan metabolism, and neurotransmitter levels in the prefrontal cortex and hippocampus. Chronic intermittent exposure to alcohol during 20 days induced escalation of intake in both female and male mice. Following alcohol deprivation, relapse-like behavior was observed in both sexes, but anxiogenic and cognitive deficits were present only in females. Synbiotic treatment reduced escalation and relapse to alcohol intake in females and males. In addition, the anxiogenic-like state and cognitive deficits observed in females following alcohol deprivation were abolished in mice exposed to synbiotic. Alcohol-induced differential alterations in microbial diversity and abundance in both sexes. In females, synbiotic exposure abrogated the alterations provoked by alcohol in Prevotellaceae UCG-001 and Ruminococcaceae UCG-014 abundance. In males, synbiotic exposure restored the changes induced by alcohol in Akkermansia and Muribaculum uncultured bacterium abundance. Following alcohol withdrawal, tryptophan metabolites, noradrenaline, dopamine, and γ-aminobutyric acid concentrations in the prefrontal cortex and the hippocampus were correlated with bacterial abundance and behavioral alterations in a sex-dependent manner. These results suggested that a dietary intervention with a synbiotic to reduce gut dysbiosis during chronic alcohol intake may impact differently the gut-brain-axis in females and males.

A Comparative Study of Corrosion AA6061 and AlSi10Mg Alloys Produced by Extruded and Additive Manufacturing.

The aim of this work was to evaluate the corrosion behavior of the AA6061 and AlSi10Mg alloys produced by extruded and additive manufacturing (selective laser melting, SLM). Alloys were immersed in two electrolytes in H2O and 3.5 wt. % NaCl solutions at room temperature and their corrosion behavior was studied by electrochemical noise technique (EN). Three different methods filtered EN signals, and the statistical analysis was employed to obtain Rn, the localization index (LI), Kurtosis, skew, and the potential spectral density analysis (PSD). The Energy Dispersion Plots (EDP) of wavelets method was employed to determine the type of corrosion and the Hilbert-Huang Transform (HHT), analyzing the Hilbert Spectra. The result indicated that the amplitude of the transients in the time series in potential and current is greater in the AlSi10Mg alloy manufactured by additive manufacturing. The amplitude of the transients decreases in both alloys (AA6061 and AlSi10Mg) as time increases.

Corrosion Resistance Measurement of 316L Stainless Steel Manufactured by Selective Laser Melting.

Selective laser melting (SLM) technology is ushering in a new era of advanced industrial production of metal components. It is of great importance to understand the relationship between the surface features and electrochemical properties of manufactured parts. This work studied the influence of surface orientation on the corrosion resistance of 316L stainless-steel (SS) components manufactured with SLM. The corrosion resistance of the samples was measured using linear polarization resistance (LPR) and electromechanical noise (EN) techniques under three different environments, H2O, 3.5 wt.% NaCl, and 20% H2SO4, analyzing the horizontal (XY) and vertical (XZ) planes. The microstructure and morphology of the samples were obtained by optical (OM) and scanning electron microscopy (SEM). The obtained microstructure showed the grains growing up from the fusion line to the melt pool center and, via SEM-EDS, the presence of irregular and spherical pores was observed. The highest corrosion rate was identified in the H2SO4 solution in the XZ plane with 2.4 × 10-2 mm/year and the XY plane with 1.31 × 10-3 mm/year. The EN technique along with the skewness factor were used to determine the type of corrosion that the material developed. Localized corrosion was observed in the NaCl electrolyte, for the XY and XZ planes (-1.65 and -0.012 skewness factors, respectively), attacking mainly the subgrains of the microstructure and, in some cases, the pores, caused by Cl ions. H2O and H2SO4 solutions presented a uniform corrosion mechanism for the two observed orientations. The morphology identified by SEM was correlated with the results obtained from the electrochemical techniques.

Orally Active Peptide Vector Allows Using Cannabis to Fight Pain While Avoiding Side Effects.

The activation of cannabinoid CB1 receptors (CB1R) by Δ9-tetrahydrocannabinol (THC), the main component of Cannabis sativa, induces analgesia. CB1R activation, however, also causes cognitive impairment via the serotonin 5HT2A receptor (5HT2AR), a component of a CB1R-5HT2AR heteromer, posing a serious drawback for cannabinoid therapeutic use. We have shown that peptides reproducing CB1R transmembrane (TM) helices 5 and 6, fused to a cell-penetrating sequence (CPP), can alter the structure of the CB1R-5HT2AR heteromer and avert THC cognitive impairment while preserving analgesia. Here, we report the optimization of these prototypes into drug-like leads by (i) shortening the TM5, TM6, and CPP sequences, without losing the ability to disturb the CB1R-5HT2AR heteromer, and (ii) extensive sequence remodeling to achieve protease resistance and blood-brain barrier penetration. Our efforts have culminated in the identification of an ideal candidate for cannabis-based pain management, an orally active 16-residue peptide preserving THC-induced analgesia.

Cannabis Use Induces Distinctive Proteomic Alterations in Olfactory Neuroepithelial Cells of Schizophrenia Patients.

A close epidemiological link has been reported between cannabis use and schizophrenia (SCZ). However, biochemical markers in living humans related to the impact of cannabis in this disease are still missing. Olfactory neuroepithelium (ON) cells express neural features and offer a unique advantage to study biomarkers of psychiatric diseases. The aim of our study was to find exclusively deregulated proteins in ON cells of SCZ patients with and without a history of cannabis use. Thus, we compared the proteomic profiles of SCZ non-cannabis users (SCZ/nc) and SCZ cannabis users (SCZ/c) with control subjects non-cannabis users (C/nc) and control cannabis users (C/c). The results revealed that the main cascades affected in SCZ/nc were cell cycle, DNA replication, signal transduction and protein localization. Conversely, cannabis use in SCZ patients induced specific alterations in metabolism of RNA and metabolism of proteins. The levels of targeted proteins in each population were then correlated with cognitive performance and clinical scores. In SCZ/c, the expression levels of 2 proteins involved in the metabolism of RNA (MTREX and ZNF326) correlated with several cognitive markers and clinical signs. Moreover, use duration of cannabis negatively correlated with ZNF326 expression. These findings indicate that RNA-related proteins might be relevant to understand the influence of cannabis use on SCZ.

Olfactory Neuroepithelium Cells from Cannabis Users Display Alterations to the Cytoskeleton and to Markers of Adhesion, Proliferation and Apoptosis.

Cannabis is the third most commonly used psychoactive substance of abuse, yet it also receives considerable attention as a potential therapeutic drug. Therefore, it is essential to fully understand the actions of cannabis in the human brain. The olfactory neuroepithelium (ON) is a peripheral nervous tissue that represents an interesting surrogate model to study the effects of drugs in the brain, since it is closely related to the central nervous system, and sensory olfactory neurons are continually regenerated from populations of stem/progenitor cells that undergo neurogenesis throughout life. In this study, we used ON cells from chronic cannabis users and healthy control subjects to assess alterations in relevant cellular processes, and to identify changes in functional proteomic pathways due to cannabis consumption. The ON cells from cannabis users exhibited alterations in the expression of proteins that were related to the cytoskeleton, cell proliferation and cell death, as well as, changes in proteins implicated in cancer, gastrointestinal and neurodevelopmental pathologies. Subsequent studies showed cannabis provoked an increase in cell size and morphological alterations evident through ß-Tubulin III staining, as well as, enhanced beta-actin expression and a decrease in the ability of ON cells to undergo cell attachment, suggesting abnormalities of the cytoskeleton and cell adhesion system. Furthermore, these cells proliferated more and underwent less cell death. Our results indicate that cannabis may alter key processes of the developing brain, some of which are similar to those reported in mental disorders like DiGeorge syndrome, schizophrenia and bipolar disorder.

Parasitoids of Chrysopidae Eggs in Sinaloa Mexico.

The eggs parasitoids Myartsevaia chrysopae (Crawford) (Hymenoptera: Encyrtidae), Telenomus lobatus Johnson, Telenomus tridentatus Johnson (Hymenoptera: Scelionidae) and Trichogramma atopovirilia Oatman and Platner (Hymenoptera: Trichogrammatidae) are reported for the first time or in new localities in Mexico. Their occurrence was first discovered in 2018 during a survey of parasitism on chrysopid eggs, conducted on Sorghum bicolor L. Moench (Poales: Poaceae) and Zea mays L. (Poales: Poaceae) in different locations in Sinaloa, Mexico. The identity of the parasitoids was determined by morphology and for both species of Telenomus the barcode region of the cytochrome oxidase 1 gene (CO1) was generated to facilitate molecular diagnosis of these species in future studies.

Correction: Lara-Banda, M., et al. Alternative to Nitric Acid Passivation of 15-5 and 17-4PH Stainless Steel Using Electrochemical Techniques. Materials 2020, 13, 2836.

The author wishes to make the following correction to this paper [...].

Smelling the Dark Proteome: Functional Characterization of PITH Domain-Containing Protein 1 (C1orf128) in Olfactory Metabolism.

The Human Proteome Project (HPP) consortium aims to functionally characterize the dark proteome. On the basis of the relevance of olfaction in early neurodegeneration, we have analyzed the dark proteome using data mining in public resources and omics data sets derived from the human olfactory system. Multiple dark proteins localize at synaptic terminals and may be involved in amyloidopathies such as Alzheimer's disease (AD). We have characterized the dark PITH domain-containing protein 1 (PITHD1) in olfactory metabolism using bioinformatics, proteomics, in vitro and in vivo studies, and neuropathology. PITHD1-/- mice exhibit olfactory bulb (OB) proteome changes related to synaptic transmission, cognition, and memory. OB PITHD1 expression increases with age in wild-type (WT) mice and decreases in Tg2576 AD mice at late stages. The analysis across 6 neurological disorders reveals that olfactory tract (OT) PITHD1 is specifically upregulated in human AD. Stimulation of olfactory neuroepithelial (ON) cells with PITHD1 alters the ON phosphoproteome, modifies the proliferation rate, and induces a pro-inflammatory phenotype. This workflow applied by the Spanish C-HPP and Human Brain Proteome Project (HBPP) teams across the ON-OB-OT axis can be adapted as a guidance to decipher functional features of dark proteins. Data are available via ProteomeXchange with identifiers PXD018784 and PXD021634.

Electrochemical Behavior of Ti6Al4V Alloy Used in Dental Implants Immersed in Streptococcus gordonii and Fusobacterium nucleatum Solutions.

The titanium alloy, Ti6Al4V, is used in dentistry for dental implants because of its excellent resistance to corrosion and its high biocompatibility. However, periimplantitis is considered the main reason for treatment failure. The Ti6Al4V alloy was used to study the corrosion behavior for dental implant applications, using an experimental arrangement of three electrodes with the bacteria Streptococcus gordonii and Fusobacterium nucleatum, in addition to Ringer's lactate as electrolytes, at 37 °C and a pH of 5.6. Their electrochemical behavior was studied by open circuit potential (OCP) and cyclic potentiodynamic polarization (CPP) according to ASTM G3-14 and ASTM G61-11, respectively. Scanning electron microscopy (SEM) was employed to determine the morphology of the alloy studied. An experimental model, in situ, was established with the bacteria present in an oral environment to understand the electrochemical behavior of the alloy used in dental implants. The greatest corrosion in Ti6Al4V alloy was produced by the medium that contained the bacterium Streptococcus gordonii, which is considered a primary colonizer. In addition, the Ti6Al4V alloy presented uniform corrosion in the three solutions at the different exposure times showing a negative hysteresis in CPP.

Alternative to Nitric Acid Passivation of 15-5 and 17-4PH Stainless Steel Using Electrochemical Techniques.

Increasingly stringent environmental regulations in different sectors of industry, especially the aeronautical sector, suggest the need for more investigations regarding the effect of environmentally friendly corrosion protective processes. Passivation is a finishing process that makes stainless steels more rust resistant, removing free iron from the steel surface resulting from machining operations. This results in the formation of a protective oxide layer that is less likely to react with the environment and cause corrosion. The most commonly used passivating agent is nitric acid. However, it is know that high levels of toxicity can be generated by using this agent. In this work, a study has been carried out into the electrochemical behavior of 15-5PH (precipitation hardening) and 17-4PH stainless steels passivated with (a) citric and (b) nitric acid solutions for 60 and 90 min at 49 °C, and subsequently exposed to an environment with chlorides. Two electrochemical techniques were used: electrochemical noise (EN) and potentiodynamic polarization curves (PPC) according to ASTM G199-09 and ASTM G5-13, respectively. The results obtained indicated that, for both types of steel, the passive layer formed in citric acid as passivating solution had very similar characteristics to that formed with nitric acid. Furthermore, after exposure to the chloride-containing solution and according with the localization index (LI) values obtained, the stainless steels passivated in citric acid showed a mixed type of corrosion, whereas the steels passivated in nitric acid showed localized corrosion. Overall, the results of the R n values derived show very low and similar corrosion rates for the stainless steels passivated with both citric and nitric acid solutions.

Corrosion Behavior of AISI 1018 Carbon Steel in Localized Repairs of Mortars with Alkaline Cements and Engineered Cementitious Composites.

The selection of materials for repairs of reinforced concrete structures is a serious concern. They are chosen for the mechanical capacity that the repair mortar achieves. However, several important characteristics have been left aside, such as the adhesion of the repair mortar with the concrete substrate, the electrical resistivity and-hugely important-the protection against corrosion that the repair material can provide to the reinforcing steel. The aim of this work was to study the corrosion behavior of AISI 1018 carbon steel (CS) in mortars manufactured with alkaline cements, engineered cementitious composites (ECC), and supplementary cementitious materials (SCM). Two types of ordinary Portland cement (OPC) 30R and 40R were used. The constituent materials for the mortars with ECC mixture mortars they use OPC 40R, class F fly ash (FA), silica fume (SF) and polypropylene (PP) fibers. The sodium hydroxide (NaOH) and sodium silicate (Na2SiO3) were used as activating agents in alkali activated cements. The reinforced specimens were immersed in two different electrolytes, exposed to a 3.5 wt % of NaCl and Na2SO4 solutions, for 12 months and their electrochemical behavior was studied by half-cell potential (Ecorr) and linear polarization resistance (LPR) according to ASTM C876-15 and ASTM G59-97, respectively. The results obtained indicated that, the mortar they have the best performance and durability, is the conventional MCXF mortar, with OPC 30R and addition of 1% polypropylene PP fiber improves the behavior against the attack of chlorides and sulfates.

Altered Signaling in CB1R-5-HT2AR Heteromers in Olfactory Neuroepithelium Cells of Schizophrenia Patients is Modulated by Cannabis Use.

Schizophrenia (SCZ) has been associated with serotonergic and endocannabinoid systems dysregulation, but difficulty in obtaining in vivo neurological tissue has limited its exploration. We investigated CB1R-5-HT2AR heteromer expression and functionality via intracellular pERK and cAMP quantification in olfactory neuroepithelium (ON) cells of SCZ patients non-cannabis users (SCZ/nc), and evaluated whether cannabis modulated these parameters in patients using cannabis (SCZ/c). Results were compared vs healthy controls non-cannabis users (HC/nc) and healthy controls cannabis users (HC/c). Further, antipsychotic effects on heteromer signaling were tested in vitro in HC/nc and HC/c. Results indicated that heteromer expression was enhanced in both SCZ groups vs HC/nc. Additionally, pooling all 4 groups together, heteromer expression correlated with worse attentional performance and more neurological soft signs (NSS), indicating that these changes may be useful markers for neurocognitive impairment. Remarkably, the previously reported signaling properties of CB1R-5-HT2AR heteromers in ON cells were absent, specifically in SCZ/nc treated with clozapine. These findings were mimicked in cells from HC/nc exposed to clozapine, suggesting a major role of this antipsychotic in altering the quaternary structure of the CB1R-5-HT2AR heteromer in SCZ/nc patients. In contrast, cells from SCZ/c showed enhanced heteromer functionality similar to HC/c. Our data highlight a molecular marker of the interaction between antipsychotic medication and cannabis use in SCZ with relevance for future studies evaluating its association with specific neuropsychiatric alterations.