Differential consumption of malic acid and fructose in apple musts by Pichia kudriavzevii strains.

AIMS: To assess the capability of Pichia kudriavzevii strains isolated from wine, cider, and natural environments in North Patagonia to produce ciders with reduced malic acid levels. METHODS AND RESULTS: Fermentation kinetics and malic acid consumption were assessed in synthetic media and in regional acidic apple musts. All P. kudriavzevii strains degraded malic acid and grew in synthetic media with malic acid as the sole carbon source. Among these strains, those isolated from cider exhibited higher fermentative capacity, mainly due to increased fructose utilization; however, a low capacity to consume sucrose present in the must was also observed for all strains. The NPCC1651 cider strain stood out for its malic acid consumption ability in high-malic acid Granny Smith apple must. Additionally, this strain produced high levels of glycerol as well as acceptable levels of acetic acid. On the other hand, Saccharomyces cerevisiae ÑIF8 reference strain isolated from Patagonian wine completely consumed reducing sugars and sucrose and showed an important capacity for malic acid consumption in apple must fermentations. CONCLUSIONS: Pichia kudriavzevii NPCC1651 strain isolated from cider evidenced interesting features for the consumption of malic acid and fructose in ciders.

Loss of Depalmitoylation Disrupts Homeostatic Plasticity of AMPARs in a Mouse Model of Infantile Neuronal Ceroid Lipofuscinosis.

Protein palmitoylation is the only reversible post-translational lipid modification. Palmitoylation is held in delicate balance by depalmitoylation to precisely regulate protein turnover. While over 20 palmitoylation enzymes are known, depalmitoylation is conducted by fewer enzymes. Of particular interest is the lack of the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1) that causes the devastating pediatric neurodegenerative condition infantile neuronal ceroid lipofuscinosis (CLN1). While most of the research on Ppt1 function has centered on its role in the lysosome, recent findings demonstrated that many Ppt1 substrates are synaptic proteins, including the AMPA receptor (AMPAR) subunit GluA1. Still, the impact of Ppt1-mediated depalmitoylation on synaptic transmission and plasticity remains elusive. Thus, the goal of the present study was to use the Ppt1 -/- mouse model (both sexes) to determine whether Ppt1 regulates AMPAR-mediated synaptic transmission and plasticity, which are crucial for the maintenance of homeostatic adaptations in cortical circuits. Here, we found that basal excitatory transmission in the Ppt1 -/- visual cortex is developmentally regulated and that chemogenetic silencing of the Ppt1 -/- visual cortex excessively enhanced the synaptic expression of GluA1. Furthermore, triggering homeostatic plasticity in Ppt1 -/- primary neurons caused an exaggerated incorporation of GluA1-containing, calcium-permeable AMPARs, which correlated with increased GluA1 palmitoylation. Finally, Ca2+ imaging in awake Ppt1 -/- mice showed visual cortical neurons favor a state of synchronous firing. Collectively, our results elucidate a crucial role for Ppt1 in AMPAR trafficking and show that impeded proteostasis of palmitoylated synaptic proteins drives maladaptive homeostatic plasticity and abnormal recruitment of cortical activity in CLN1.SIGNIFICANCE STATEMENT Neuronal communication is orchestrated by the movement of receptors to and from the synaptic membrane. Protein palmitoylation is the only reversible post-translational lipid modification, a process that must be balanced precisely by depalmitoylation. The significance of depalmitoylation is evidenced by the discovery that mutation of the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (Ppt1) causes severe pediatric neurodegeneration. In this study, we found that the equilibrium provided by Ppt1-mediated depalmitoylation is critical for AMPA receptor (AMPAR)-mediated plasticity and associated homeostatic adaptations of synaptic transmission in cortical circuits. This finding complements the recent explosion of palmitoylation research by emphasizing the necessity of balanced depalmitoylation.

Association between CLOCK gene polymorphisms and ADHD in Mexican teenagers: A comprehensive assessment.

This study aimed to evaluate markers of the CLOCK gene rs1801260 and rs4864548 in Mexican adolescents, addressing clinical and biological aspects previously associated with ADHD. 347 Mexican adolescents were assessed for mental disorders, metabolic disruption and related conditions, circadian preference, as well as genotyping for the CLOCK. We found a significant association between ADHD and the AA and AG genotypes of rs1801260. Also, we identified in the ADHD group that the total Triiodothyronine and total Thyroxine values were respectively 10 ng/dl units and 0.58 ug/dl units lower in females than in males. Previously reported common variations of the CLOCK gene have been associated with ADHD like the Rs1801260 polymorphism hereby we could consider it as risk factor, but genetic, biochemical and clinical studies in the Mexican population are entailed.

Synaptic Integration of Subquantal Neurotransmission by Colocalized G Protein-Coupled Receptors in Presynaptic Terminals.

In presynaptic terminals, membrane-delimited Gi/o-mediated presynaptic inhibition is ubiquitous and acts via Gßγ to inhibit Ca2+ entry, or directly at SNARE complexes to inhibit Ca2+-dependent synaptotagmin-SNARE complex interactions. At CA1-subicular presynaptic terminals, 5-HT1B and GABAB receptors colocalize. GABAB receptors inhibit Ca2+ entry, whereas 5-HT1B receptors target SNARE complexes. We demonstrate in male and female rats that GABAB receptors alter Pr, whereas 5-HT1B receptors reduce evoked cleft glutamate concentrations, allowing differential inhibition of AMPAR and NMDAR EPSCs. This reduction in cleft glutamate concentration was confirmed by imaging glutamate release using a genetic sensor (iGluSnFR). Simulations of glutamate release and postsynaptic glutamate receptor currents were made. We tested effects of changes in vesicle numbers undergoing fusion at single synapses, relative placement of fusing vesicles and postsynaptic receptors, and the rate of release of glutamate from a fusion pore. Experimental effects of Pr changes, consistent with GABAB receptor effects, were straightforwardly represented by changes in numbers of synapses. The effects of 5-HT1B receptor-mediated inhibition are well fit by simulated modulation of the release rate of glutamate into the cleft. Colocalization of different actions of GPCRs provides synaptic integration within presynaptic terminals. Train-dependent presynaptic Ca2+ accumulation forces frequency-dependent recovery of neurotransmission during 5-HT1B receptor activation. This is consistent with competition between Ca2+-synaptotagmin and Gßγ at SNARE complexes. Thus, stimulus trains in 5-HT1B receptor agonist unveil dynamic synaptic modulation and a sophisticated hippocampal output filter that itself is modulated by colocalized GABAB receptors, which alter presynaptic Ca2+ In combination, these pathways allow complex presynaptic integration.SIGNIFICANCE STATEMENT Two G protein-coupled receptors colocalize at presynaptic sites, to mediate presynaptic modulation by Gßγ, but one (a GABAB receptor) inhibits Ca2+ entry whereas another (a 5-HT1B receptor) competes with Ca2+-synaptotagmin binding to the synaptic vesicle machinery. We have investigated downstream effects of signaling and integrative properties of these receptors. Their effects are profoundly different. GABAB receptors alter Pr leaving synaptic properties unchanged, whereas 5-HT1B receptors fundamentally change properties of synaptic transmission, modifying AMPAR but sparing NMDAR responses. Coactivation of these receptors allows synaptic integration because of convergence of GABAB receptor alteration on Ca2+ and the effect of this altered Ca2+ signal on 5-HT1B receptor signaling. This presynaptic convergence provides a novel form of synaptic integration.

Munidopsis geyeri and M. exuta (Crustacea: Munidopsidae): A study of two deep-sea, amphi-Atlantic species that co-occur in the southern Gulf of Mexico.

The history of colonization and dispersal of fauna among deep-sea chemosynthetic ecosystems remains enigmatic and poorly understood. The distribution of squat lobsters of the genus Munidopsis Whiteaves, 1874 can be influenced by the rich organic matter and associated organism communities of chemosynthetic ecosystems. The present work analyzed the molecular relationships and morphology of individuals from different populations of Munidopsis exuta Macpherson & Segonzac, 2005 and M. geyeri Pequegnat & Pequegnat, 1970 in such ecosystems along the Atlantic Equatorial Belt, including the Chapopote Knoll, in the southern Gulf of Mexico. Munidopsis geyeri is re-described based on the present findings and reference to the literature. This analysis documented the genetic distances, as well as range of variation in the diagnostic characters that support the separation of M. exuta and M. geyeri. Our results confirm that the two species coexist in seep ecosystems and have an amphi-Atlantic distribution.

Terapia de reemplazo renal continua. Presentación de un caso / Continuous renal replacement therapy. Case report

RESUMEN La insuficiencia renal aguda es definida como la pérdida de función del riñón ocasionada por diversas causas, entre ellas infección e ingesta de fármacos. Esta entidad tiene alta morbilidad y mortalidad en las unidades de cuidados críticos. El tratamiento de la misma va desde la propia protección renal hasta la sustitución artificial de las funciones del riñón lesionado. En la actualidad la terapia de reemplazo renal continua se ha utilizado como soporte renal, y ofrece mayor estabilidad clínica a los pacientes más inestables. En esta revisión se comentan conceptos, indicaciones y los más recientes estudios que validan el uso de esta terapéutica, así como el método de programación que se utilizó en un paciente con diagnóstico de una leptospirosis icterohemorrágica (síndrome de Weil), que estuvo en shock séptico con disfunción multiorgánica, donde se empleó esta terapia con resultados satisfactorios (AU).

ABSTRACT Acute kidney failure is defined as the loss of kidney function caused by various causes, including infection and drug intake. This entity has high morbidity and mortality in critical care units. Treatment ranges from renal protection to artificial replacement of the functions of the injured kidney. Currently, continuous renal replacement therapy has been used as renal support, and offers greater clinical stability to the most unstable patients. In this review, authors discuss concepts, indications and the most recent studies that validate the use of this therapeutic, as well as the programming method that was used in a patient with diagnosis of icteric-hemorrhagic leptospirosis (Weil syndrome), who was in septic shock with multiorgan dysfunction, where this therapy was used with satisfactory results (AU).

Dolor abdominal crónico en un niño con Blastocystis hominis: a propósito de un caso / Chronic abdominal pain in a child with Blastocystis hominis: case report

RESUMEN El Blastocystis sp. es un parásito frecuente en el humano, identificado por el laboratorio en muestras de heces fecales. Se presentó el caso de un paciente de 5 años atendido en consulta de Gastroenterología en el Hospital Pediátrico Docente Provincial Eliseo Noel Caamaño, de Matanzas, por presentar dolor abdominal, heces pastosas, náuseas y vómitos desde hacía un año. Llevó tratamiento con ranitidina, omeprazol y domperidona, sin mejoría clínica. Se realizó estudio coproparasitológico en muestras de heces fecales seriadas, con la presencia del Blastocystis hominis. Se indicó tratamiento con metronidazol, sin mejoría clínica, y posteriormente se indicó como alternativa la nitazoxanida. Se evaluó a los 15 días, sin sintomatología y con negativización de las heces fecales seriadas. Resulta frecuente el desconocimiento y la poca importancia que los profesionales sanitarios muestran ante esta infestación, aunque cada vez más se confirma la participación del parásito en manifestaciones clínicas (AU).

ABSTRACT Blastocystis sp. is a frequent parasite in humans, identified in the laboratory in samples of fecal feces. The case of a 5-year-old patient is presented; he assisted the consultation of Gastroenterology in the Provincial Teaching Pediatric Hospital Eliseo Noel Caamaño in Matanzas, suffering abdominal pain, mash feces, nauseas and vomits for one year, and was treated with ranitidine, omeprazole and domperidone without clinical improvement. A coproparasitological study was carried out in serial fecal feces samples with the presence of Blastocystis hominis. Treatment with metronidazole was indicated without clinical improvement and them, as an alternative, nitazoxanide was indicated. He was evaluated at 15 days without symptoms and with negative serial fecal feces. The ignorance and the little importance that health professionals show towards this infestation are frequent, although more and more frequently it is confirmed the participation of the parasite in clinical manifestations (AU).

Developmental regulation of excitatory-inhibitory synaptic balance in the prefrontal cortex during adolescence.

The prefrontal cortex (PFC) is a cortical structure involved in a variety of complex functions in the cognitive and affective domains. The intrinsic function of the PFC is defined by the interaction of local glutamatergic and GABAergic neurons and their modulation by long-range inputs. The ensuing interactions generate a ratio of excitation and inhibition (E-I) in each output neuron, a balance which is refined during the adolescent to adult transition. In this short review, we aim to describe how an increase in GABAergic transmission during adolescence modifies the E-I ratio in adults. We further discuss how this new setpoint may change the dynamics of PFC networks observed during the transition to adulthood.

The role of circadian rhythms in individuals with attention deficit hyperactivity disorder and obesity: A narrative review / El papel de los ritmos circadianos en personas con trastorno por déficit de atención con hiperactividad y obesidad: Una revisión narrativa

Abstract Background A relationship between attention deficit hyperactivity disorder (ADHD) and obesity has been consistently documented. Obesity and metabolic syndrome have been associated with misalignment between daily activities and circadian rhythm. ADHD patients have a high prevalence of delayed sleep phase syndrome, which is a circadian rhythm disorder. Understanding this relationship is important for the evaluation of obese population at risk. Objective The aim of this narrative review was to summarize the information updated until 2019 about the role of circadian rhythms in obese ADHD individuals. Method A search was performed in MEDLINE, EMBASE, and Google Scholar database. The terms ADHD, obesity, circadian rhythm, sleep disorders, adolescent, adult, Adolesc, circadian, attention deficit hyperactivity disorder, and child were combined with logical functions. Results A total of 132 articles were reviewed. Evidence showed that ADHD subjects have an increased risk to present obesity and circadian rhythms disorders. Some possible pathways for this relationship have been hypothesized including obesity as a risk factor, an underpinned common biological dysfunction, and behavioral and cognitive features of individuals with ADHD. As most of the articles are methodologically cross-sectional, it is not possible to establish causative associations. Discussion and conclusion This review points out the importance of early recognizing and treating circadian rhythms disorders and obesity in ADHD patients. Future studies must be carried out with a longitudinal design to establish the effect of each comorbidity in the treatment of individuals with ADHD.

Resumen Antecedentes La relación entre el trastorno por déficit de atención con hiperactividad (TDAH) y la obesidad se ha documentado consistentemente. Por otro lado, el síndrome metabólico y la obesidad se han asociado con un desfase del ritmo circadiano. En poblaciones clínicas con TDAH se han encontrado una alta prevalencia del trastorno de fase de sueño retrasada, el cual es un trastorno del ritmo circadiano. Entender la relación entre estos padecimientos es importante para evaluar la población en riesgo de obesidad. Objetivo Resumir la información actualizada hasta 2019 sobre el rol del ritmo circadiano en individuos obesos con TDAH. Método Se realizó una búsqueda de artículos en las bases de datos MEDLINE, EMBASE y Google Scholar. Los términos TDAH, obesidad, ritmos circadianos, trastornos del sueño, adolescentes, adultos y niños se combinaron con operadores lógicos. Resultados Se revisaron un total de 132 artículos. La evidencia demostró que los sujetos con TDAH tienen un alto riesgo de sufrir obesidad y ritmos circadianos alterados. Existen algunas hipótesis para establecer esta relación, incluyendo la obesidad como factor de riesgo para TDAH, la disfunción biológica común entre estos trastornos y las características conductuales y cognitivas de los individuos con TDAH. Sin embargo, como la mayoría de los artículos son transversales, no es posible establecer una asociación causal. Discusión y conclusión Esta revisión señala la importancia del reconocimiento temprano y tratamiento de los trastornos del ritmo circadiano y obesidad en pacientes con TDAH. Estudios futuros deben realizarse de manera longitudinal para establecer el efecto de estas comorbilidades en el tratamiento de los individuos con TDAH.

Caracterización clínica, endoscópica e histológica de los pólipos colorrectales en pacientes de edades pediátricas. Matanzas / Clinical, endoscopic and pathological characterization of colorectal polyps in pediatric patients, Matanzas

Resumen Introducción: los pólipos del colon son los tumores más comunes del tracto gastrointestinal. Se presentan relativamente frecuentes en niños. El método eficaz para su diagnóstico es la colonoscopia que permite su tratamiento mediante la polipectomía. Objetivo: determinar las características clínicas, endoscópicas e histológicas de los pólipos colorrectales, diagnosticados en niños atendidos en el Hospital Pediátrico Provincial "Eliseo Noel Caamaño", de la ciudad de Matanzas. Materiales y métodos: se realizó un estudio descriptivo, retrospectivo en niños diagnosticados con pólipos colorrectales y atendidos en el hospital. En el período comprendido del 2010 al 2018. Se estudiaron 141 pacientes menores de 18 años, con diagnóstico de pólipos por colonoscopia confirmado en el estudio histológico. Se excluyeron los pacientes con diagnósticos diferentes a pólipos y aquellos que no se pudieron estudiar histológicamente. Resultados: se observó mayor frecuencia de pacientes con pólipos en las edades entre 1 y 10 años (37,6 %), del sexo masculino (57,4 %). Los síntomas más frecuentes fueron el sangramiento digestivo bajo, (96,3 %) y prolapso de masa T por el recto, (27 %). Los pólipos estudiados se localizaron con mayor frecuencia en rectosigmoide (73, 4 %), predominando los pólipos únicos (78 %), pediculados (56,2 %), de 1-2 cm de tamaño (53,2 %). Histológicamente predominaron los pólipos juveniles, (62,1 %) seguidos de los inflamatorios (33 %). Conclusiones: los pólipos fueron más frecuentes en las edades de 1 y 10 años y en el sexo masculino. Se demostró la importancia de la colonoscopia en el diagnóstico precoz de estas lesiones (AU).

ABSTRACT Introduction: colon polyps are the most common tumors of the gastrointestinal tract. They are found relatively frequently in children. The efficacious method for their treatment is the colonoscopy, allowing their treatment through polypectomy. Objective: to determine the histological, endoscopic and clinical characteristics of colorectal polyps diagnosed in children who attended the Pediatric Provincial Hospital "Eliseo Noel Caamaño", of Matanzas. Materials and methods: a retrospective, descriptive study was carried out in children diagnosed with colorectal polyps in the hospital in the period from 2010 to 2018. 141 patients under 18 years-old were studied, all with diagnosis of polyps by colonoscopy confirmed in the histological study. The patients with different diagnosis but polyps were excluded, and also those who could not be histologically studied. Results: the highest frequency of patients with polyps was found in ages between 1 and 10 years (37,6 %), and the male sex (57.4 %). The most frequent symptoms were low digestive bleeding (96.3 %) and Mass T prolapse through the rectum (27 %). The studied polyps were more frequently located in the rectosigmoid (73.4 %). The single polyps predominated (78 %)m and the pedunculated ones (56.2 %) of 1-2 cm size (53.2 %). Histologically predominated young polyps (62.1 %), followed by the inflammatory ones (33 %). Conclusions: polyps were more frequent at the ages from 1 to 10 years and in the male sex. The authors showed the importance of colonoscopy in the precocious diagnosis of these lesions (AU).

Diferencias de género ante el horror moral manifiesto de un parricidio / Gender differences facing the manifest moral horror of a parricide

RESUMEN Fundamento: Las diferencias emocionales de género han sido poco estudiadas desde el enfoque del juicio moral. En particular, se desconoce la incidencia de las emociones morales primarias en el juicio moral, y si los hombres y las mujeres frente al horror moral, a través del orgullo y la culpa, razonan de manera diferente sobre lo correcto y lo incorrecto. Objetivo: identificar las diferencias de género frente al horror moral manifiesto de un parricidio. Métodos: estudio descriptivo explicativo, que se aplicó el Cuestionario Moral Emocional a 170 participantes (118 mujeres y 52 hombres). Se realizó la prueba de confiabilidad de los subíndices de culpa y orgullo, cuya consistencia interna resultó buena. La prueba t de Student se realizó para demostrar las hipótesis sobre las diferencias entre hombres y mujeres. Resultados: el valor medio del subíndice de horror moral obtenido por las mujeres fue mayor que el de los hombres. Sin embargo, no hubo diferencias importantes en el juicio moral emocional, ni con respecto a los índices de culpa u orgullo. Conclusión: las mujeres expresan mayor horror ante un estímulo moral violento. Se observó cierto comportamiento inverso entre culpa y orgullo en los participantes. Las diferencias de género, significativas o no, pueden deberse a la regulación emocional.

ABSTRACT Background: Emotional gender differences have been little studied from the perspective of moral judgment. In particular, the incidence of primary moral emotions on moral judgment is unknown, and whether men and women in the face of moral horror, through pride and guilt, think differently about right and wrong. Objective: to identify gender differences facing the manifest moral horror of a parricide. Methods: descriptive explanatory study, which applied the Emotional Moral Questionnaire to 170 participants (118 women and 52 men). The reliability test of the guilt and pride subscripts was performed, whose internal consistency was good. Student's t-test was performed to demonstrate the hypotheses about the differences between men and women. Results: the average value of the moral horror subscript obtained by women was higher than that of men. However, there were no significant differences in emotional moral judgment, nor with respect to rates of guilt or pride. Conclusion: women express greater horror at a violent moral stimulus. A certain reverse behavior between guilt and pride was observed in the participants. Gender differences, significant or not, may be due to emotional regulation.

Downregulation of parvalbumin expression in the prefrontal cortex during adolescence causes enduring prefrontal disinhibition in adulthood.

The expression of the calcium binding protein parvalbumin (PV) has been observed in several cortical regions during development in a temporal pattern consistent with increased afferent-dependent activity. In the prefrontal cortex (PFC), PV expression appears last and continues to substantially increase throughout adolescence, yet the significance of this increase remains unclear. Because of the expression of PV in fast-spiking GABAergic interneurons, we hypothesized that PV upregulation during adolescence is necessary to sustain the increase in GABAergic activity observed in the PFC during this period. To test this hypothesis, we utilized an RNAi strategy to directly downregulate PV levels in the PFC during adolescence and examined its impact on prefrontal GABAergic function, plasticity, and associated behaviors during adulthood. The data indicate that a mere 25% reduction of adult PV levels in the PFC was sufficient to reduce local GABAergic transmission onto pyramidal neurons, disrupt prefrontal excitatory-inhibitory balance, and alter processing of afferent information from the ventral hippocampus. Accordingly, these animals displayed an impairment in the level of extinction learning of a trace fear conditioning response, a behavioral paradigm that requires intact PFC-ventral hippocampus connectivity. These results indicate the PV upregulation observed in the PFC during adolescence is necessary for refinement of prefrontal GABAergic function, the absence of which results in immature afferent processing and a hypofunctional state. Importantly, these results suggest there is a critical window of plasticity during which PV upregulation supports the acquisition of mature GABAergic phenotype necessary to sustain adult PFC functions.

Algunas consideraciones sobre el reflujo gastroesofágico en infantes / Several view about gastroesophageal reflux in children

RESUMEN El reflujo gastroesofágico presenta variaciones en cuanto a su definición, pero continúa causando una elevada morbilidad y mortalidad, a pesar que las estadísticas no recogen cifras exactas, su manejo sigue siendo controversial. En la práctica médica, se podría decir que el reflujo gastroesofágico fisiológico, no patológico, usualmente se acompaña de regurgitación, y que en esta enfermedad el síntoma principal de presentación en los niños, es el vómito. Cuando el reflujo gastroesofágico es mantenido, persistente, a pesar de la medidas posturales y dietéticas indicadas, provocando sintomatología digestiva y extradigestiva, se considera patológico, capaz de provocar una enfermedad por reflujo gastroesofágico. En neumología, no todo niño que tiene sibilancias es un asmático, en gastroenterología no todo niño que vomita o regurgita tiene un reflujo gastroesofágico. Actualmente, se conocen ciertas patologías y condiciones de tórpida evolución que por su historia natural y morbimortalidad, se catalogan como reflujo gastroesofágico refractario, cuyo pronóstico implica una diferente orientación terapéutica. El niño con reflujo gastroesofágico incluye las medidas antirreflujo, tratamiento medicamentoso y quirúrgico (AU).

ABSTRACT The Gastroesophageal Reflux presents variations as for its definition, but it continues causing a high morbility and mortality, to weigh that the statistics don't pick up exact report, its handling continues being controversial. In the medical practice, one could say that the reflux physiologic gastroesophageal, not pathological, usually accompanies of regurgitation, and that in this illness the main symptom of presentation in the children, is the vomit. When RGE is maintained, persistent, in spite of the measures posturales and dietary suitable, provoking digestive symptoms and extradigestive, it is considered pathological, able to provoke an illness for reflux gastroesophageal . In Neumology, not all boy that has lung sonority is an asthmatic one, in Gastroenterology not all boy that vomits or it regurgitation he has a reflux gastroesophageal. At the moment, certain pathologies and conditions of torpid evolution are known that for their natural history and morbimortality, they are classified as reflux refractory gastroesophageal whose presage implies a therapeutic different orientation. The boy with reflux gastroesophageal includes the measures antirreflux, treatment prescribes and surgical (AU).

Heterologous regulation of CXCR4 lysosomal trafficking.

G protein-coupled receptor (GPCR) signaling is regulated by members of the protein kinase C (PKC) and GPCR kinase (GRK) families, although the relative contribution of each to GPCR function varies among specific GPCRs. The CXC motif receptor 4 (CXCR4) is a member of the GPCR superfamily that binds the CXC motif chemokine ligand 12 (CXCL12), initiating signaling that is subsequently terminated in part by internalization and lysosomal degradation of CXCR4. The purpose of this study is to define the relative contribution of PKC and GRK to CXCR4 signaling attenuation by studying their effects on CXCR4 lysosomal trafficking and degradation. Our results demonstrate that direct activation of PKC via the phorbol ester phorbol 12-myristate 13-acetate (PMA) mimics CXCL12-mediated desensitization, internalization, ubiquitination, and lysosomal trafficking of CXCR4. In agreement, heterologous activation of PKC by stimulating the chemokine receptor CXCR5 with its ligand, CXCL13, also mimics CXCL12-mediated desensitization, internalization, ubiquitination, and lysosomal degradation of CXCR4. Similar to CXCL12, PMA promotes PKC-dependent phosphorylation of serine residues within CXCR4 C-tail that are required for binding and ubiquitination by the E3 ubiquitin ligase AIP4 (atrophin-interacting protein 4). However, inhibition of PKC activity does not alter CXCL12-mediated ubiquitination and degradation of CXCR4, suggesting that other kinases are also required. Accordingly, siRNA-mediated depletion of GRK6 results in decreased degradation and ubiquitination of CXCR4. Overall, these results suggest that PKC and GRK6 contribute to unique aspects of CXCR4 phosphorylation and lysosomal degradation to ensure proper signal propagation and termination.

Genome Sequence of Oenococcus oeni UNQOe19, the First Fully Assembled Genome Sequence of a Patagonian Psychrotrophic Oenological Strain.

Oenococcus oeni UNQOe19 is a native strain isolated from a Patagonian pinot noir wine undergoing spontaneous malolactic fermentation. Here, we present the 1.83-Mb genome sequence of O. oeni UNQOe19, the first fully assembled genome sequence of a psychrotrophic strain from an Argentinean wine.

Advantages of Using Blend Cultures of Native L. plantarum and O. oeni Strains to Induce Malolactic Fermentation of Patagonian Malbec Wine.

The malolactic fermentation (MLF) of Patagonian Malbec wine inoculated with blend cultures of selected native strains of Lactobacillus plantarum and Oenococcus oeni was monitored during 14 days, analyzing the strains ability to modify the content of some organic acids and to change the volatile compounds profile. The performance of the LAB strains was tested as single and blends cultures of both species. An implantation control by RAPD PCR was also carried out to differentiate among indigenous and inoculated strains. The L. plantarum strains UNQLp11 and UNQLp155 and the O. oeni strain UNQOe73.2 were able to remain viable during the monitoring time of MLF, whereas the O. oeni strain UNQOe31b showed a decrease of five log CFU at day 14. The four strains assayed showed a similar behavior in wine whether they were inoculated individually or as blend cultures. All strains were able to consume L-malic acid, particularly the L. plantarum strains, which showed the highest consumption values at day 14, both as single or blend cultures. The changes in the volatile compounds profile of Malbec wine samples, before and after MLF, were determined by HS-SPME and GC-MS technique. Wines inoculated with blend cultures containing strain UNQLp155 showed a decrease in the total alcohols content and an increase in the total esters content. On the other hand, wines inoculated with single cultures of strains UNQLp155, UNQOe31b or UNQOe73.2 showed no significant decrease in the total alcohols concentration but a significant increase in the total esters content. When strain UNQLp11 was inoculated as single or as blend culture with strain UNQOe31b, wines exhibited an increase in the total alcohols content, and a decrease in the total esters content. The content of diethyl succinate showed the greatest increase at final of MLF, and a particular synergistic effect in its synthesis was observed with a blend culture of strains UNQLp155 and UNQOe73.2. These results suggest that the use of blend cultures formulated with strains belonging to L. plantarum and O. oeni species could offer an interesting advantage to induce MLF in Malbec wines, contributing to diversify their aromatic profiles.

Mirtazapine attenuates cocaine seeking in rats.

BACKGROUND: Relapse to cocaine use is a major problem in the clinical treatment of cocaine addiction. Antidepressants have been studied for their therapeutic potential to treat cocaine use disorder. Research has suggested that antidepressants attenuate both drug craving and the re-acquisition of drug-seeking and drug-taking behaviors. This study examined the efficacy of mirtazapine, an antidepressant/anxiolytic, in decreasing cocaine seeking in rats. METHODS: We used the cocaine self-administration paradigm to assess the effects of mirtazapine on rats trained to self-administer cocaine or food under a fixed-ratio schedule. Mirtazapine (30 mg/kg, i.p.) was administered during extinction. RESULTS: Mirtazapine significantly attenuated non-reinforced lever-press responses during extinction. Moreover, the mirtazapine dosed for 30 days during extinction produced sustained attenuation of lever-press responses during re-acquisition of cocaine self-administration, without changing food-seeking behavior. Our results showed that mirtazapine attenuated the re-acquisition of cocaine-seeking responses. CONCLUSION: Our study pointed to the efficacy of mirtazapine in reducing the risk of drug relapse during abstinence, suggesting for its potential use as a novel pharmacological agent to treat drug abuse.

GABAergic Function as a Limiting Factor for Prefrontal Maturation during Adolescence.

Adolescence is a vulnerable period for the onset of mental illnesses including schizophrenia and affective disorders, yet the neurodevelopmental processes underlying this vulnerability remain poorly understood. The prefrontal cortex (PFC) and its local GABAergic system are thought to contribute to the core of cognitive deficits associated with such disorders. However, clinical and preclinical end-point analyses performed in adults are likely to give limited insight into the cellular mechanisms that are altered during adolescence but are only manifested in adulthood. This perspective summarizes work regarding the developmental trajectories of the GABAergic system in the PFC during adolescence to provide an insight into the increased susceptibility to psychiatric disorders during this critical developmental period.

Mechanisms contributing to prefrontal cortex maturation during adolescence.

Adolescence is defined as a transitional period between childhood and adulthood characterized by changes in social interaction and acquisition of mature cognitive abilities. These changes have been associated with the maturation of brain regions involved in the control of motivation, emotion, and cognition. Among these regions, the protracted development of the human prefrontal cortex during adolescence has been proposed to underlie the maturation of cognitive functions and the regulation of affective responses. Studies in animal models allow us to test the causal contribution of specific neural processes in the development of the prefrontal cortex and the acquisition of adult behavior. This review summarizes the cellular and synaptic mechanisms occurring in the rodent prefrontal cortex during adolescence as a model for understanding the changes underlying human prefrontal development.

Early adolescent MK-801 exposure impairs the maturation of ventral hippocampal control of basolateral amygdala drive in the adult prefrontal cortex.

The adolescent susceptibility to the onset of psychiatric disorders is only beginning to be understood when factoring in the development of the prefrontal cortex (PFC). The functional maturation of the PFC is dependent upon proper integration of glutamatergic inputs from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA). Here we assessed how transient NMDAR blockade during adolescence alters the functional interaction of vHipp-BLA inputs in regulating PFC plasticity. Local field potential recordings were used to determine changes in long-term depression (LTD) and long-term potentiation (LTP) of PFC responses resulting from vHipp and BLA high-frequency stimulation in adult rats that received repeated injections of saline or the NMDAR antagonist MK-801 from postnatal day 35 (P35) to P40. We found that early adolescent MK-801 exposure elicited an age- and input-specific dysregulation of vHipp-PFC plasticity, characterized by a shift from LTD to LTP without altering the BLA-induced LTP. Data also showed that the vHipp normally resets the LTP state of BLA transmission; however, this inhibitory regulation is absent following early adolescent MK-801 treatment. This deficit was reminiscent of PFC responses seen in drug-naive juveniles. Notably, local prefrontal upregulation of GABAAα1 function completely restored vHipp functionality and its regulation of BLA plasticity in MK-801-treated rats. Thus, NMDAR signaling is critical for the periadolescent acquisition of a GABA-dependent hippocampal control of PFC plasticity, which enables the inhibitory control of the prefrontal output by the vHipp. A dysregulation of this pathway can alter PFC processing of other converging afferents such as those from the BLA.