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Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.
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Tejido Adiposo , Homeostasis , Resistencia a la Insulina , Linfocitos , Mitocondrias , Obesidad , Receptor de Muerte Celular Programada 1 , Proteínas Serina-Treonina Quinasas , Animales , Resistencia a la Insulina/inmunología , Receptor de Muerte Celular Programada 1/metabolismo , Ratones , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Mitocondrias/metabolismo , Humanos , Tejido Adiposo/metabolismo , Tejido Adiposo/inmunología , Obesidad/inmunología , Obesidad/metabolismo , Linfocitos/inmunología , Linfocitos/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Inmunidad Innata , Masculino , Mitofagia/inmunología , Quinasas de la Proteína-Quinasa Activada por el AMPRESUMEN
This article presents findings from a mixed-methods study exploring child welfare agency practices addressing children with prenatal substance exposure and their families. Data sources include: (a) interviews with 159 professionals in child welfare; (b) surveys with 271 professionals in child welfare; and (c) a systematic review of state and local child welfare documents guiding processes in the five states in the study sample. Findings from descriptive statistics of survey data, grounded theory analysis of interviews, and content analysis of documents suggest practices center on infants identified by hospitals as affected by prenatal substance exposure. Without practice guidance and access to treatment services, the needs of older children whose prenatal exposure to substances, including alcohol and other types of legal and illegal substances, is not recognized at birth may be overlooked.
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The stereoselective synthesis of complex targets requires the precise orchestration of chemical transformations that simultaneously establish the connectivity and spatial orientation of desired bonds. In this work, we describe a complementary paradigm for the synthesis of chiral molecules and their isomers, which tunes the three-dimensional structure of a molecule at a late stage. Key to the success of this strategy is the development of a mild and highly general photocatalytic method composed of decatungstate polyanion and disulfide cocatalysts, which enable the interconversion of unactivated tertiary stereogenic centers that were previously configurationally fixed. We showcase the versatility of this method-and the implementation of stereoediting logic-by the rapid construction of chiral scaffolds that would be challenging to access using existing tools and by the late-stage stereoediting of complex targets.
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OBJECTIVE: Peanut allergy has historically been difficult to manage, with most cases persisting into adulthood. Novel therapies for peanut allergy treatment are on the horizon, yet allergists must maintain a robust understanding of the risks and benefits of the current standard of therapy, avoidance diet. DATA SOURCES: A comprehensive literature search using PubMed of reviews and clinical articles was performed. STUDY SELECTIONS: Articles discussing peanut or other food-related allergic reactions, accidental exposures or anaphylaxis pertinent to avoidance diet or comparative to oral immunotherapy trials were selected. RESULTS: Peanut remains a leading allergen associated with accidental ingestions responsible for food-related reactions, both mild and severe. Fatal reactions, however, are rare and measures such as anaphylaxis plans can significantly decrease the risk of accidental anaphylaxis. Patients may over estimate situations thought to increase risk for reactions to peanut, such as inhalation or contact through skin. In oral immunotherapy trials, the rate of anaphylaxis secondary to treatment was significantly higher than avoidance practices. CONCLUSION: Clinicians should continue to discuss avoidance as a viable option for long-term peanut allergy management and empower patients to differentiate relevant situations in which accidental reactions might occur.
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Anafilaxia/prevención & control , Desensibilización Inmunológica/métodos , Hipersensibilidad al Cacahuete/dietoterapia , Alérgenos/inmunología , Animales , Antígenos de Plantas/inmunología , Arachis/inmunología , Ensayos Clínicos como Asunto , Dietoterapia , Epinefrina/administración & dosificación , HumanosRESUMEN
BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy. Its relationship to the major atopic manifestations (atopic dermatitis [AD], IgE-mediated food allergy [IgE-FA], allergic rhinitis [AR], asthma) is not understood. OBJECTIVE: To determine the clinical characteristics, epidemiologic features, and natural history of FPIES in relation to the major atopic manifestations. METHODS: We examined our primary care birth cohort of 158,510 pediatric patients, of whom 214 patients met 2017 FPIES diagnostic criteria. We measured the influence of FPIES on developing subsequent atopic disease. RESULTS: Pediatric FPIES incidence was between 0.17% and 0.42% depending on birth year. As in prior reports, most patients had an acute presentation (78%), and milk, soy, oat, rice, potato, and egg were common triggers. The mean age of diagnosis was 6.8 months. Atopic comorbidity was higher in patients with FPIES compared with healthy children (AD, 20.6% vs 11.7%; IgE-FA, 23.8% vs 4.0%; asthma, 26.6% vs 18.4%; AR, 28.0% vs 16.7%; P < .001 χ2). However, longitudinal analyses indicated that prior FPIES did not influence the rate of atopy development. CONCLUSIONS: The incidence of FPIES in our cohort was initially low, but is increasing. Food allergen distribution, presentation, and age of onset are similar to prior reports. Patients with FPIES have high rates of atopic comorbidity. However, longitudinal analysis does not support direct causation as the etiology of these associations. Rather it suggests a shared predisposition to both types of allergy, or associative bias effects. This work refines our understanding of the natural history of FPIES by elucidating associations between FPIES and atopy.
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Enterocolitis , Hipersensibilidad a los Alimentos , Alérgenos , Animales , Niño , Comorbilidad , Enterocolitis/epidemiología , Hipersensibilidad a los Alimentos/epidemiología , Humanos , Lactante , SíndromeRESUMEN
Fragile X syndrome (FXS) is associated with deficits in various types of learning, including those that require the hippocampus. Relatedly, hippocampal long-term potentiation (LTP) is impaired in the Fmr1 knockout (KO) mouse model of FXS. Prior research found that infusion of brain-derived neurotrophic factor (BDNF) rescues LTP in the KOs. Here, we tested if, in Fmr1 KO mice, up-regulating BDNF production or treatment with an agonist for BDNF's TrkB receptor restores synaptic plasticity and improves learning. In hippocampal slices, bath infusion of the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) completely restored otherwise impaired hippocampal field CA1 LTP of Fmr1 KOs without effect in wild types (WTs). Similarly, acute, semi-chronic, or chronic treatments with 7,8-DHF rescued a simple hippocampus-dependent form of spatial learning (object location memory: OLM) in Fmr1 KOs without effect in WTs. The agonist also restored object recognition memory, which depends on cortical regions. Semi-chronic, but not acute, treatment with the ampakine CX929, which up-regulates BDNF expression, lowered the training threshold for OLM in WT mice and rescued learning in the KOs. Positive results were also obtained in a test for social recognition. An mGluR5 antagonist did not improve learning. Quantification of synaptic immunolabeling demonstrated that 7,8-DHF and CX929 increase levels of activated TrkB at excitatory synapses. Moreover, CX929 induced a robust synaptic activation of the TrkB effector ERK1/2. These results suggest that enhanced synaptic BDNF signaling constitutes a plausible strategy for treating certain aspects of the cognitive disabilities associated with FXS.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Síndrome del Cromosoma X Frágil , Discapacidad Intelectual , Glicoproteínas de Membrana/agonistas , Plasticidad Neuronal/fisiología , Animales , Modelos Animales de Enfermedad , Femenino , Flavanonas/farmacología , Masculino , Memoria , Ratones , Ratones Noqueados , Plasticidad Neuronal/efectos de los fármacos , Proteínas Tirosina QuinasasRESUMEN
The most clinically relevant food allergens are cow's milk, hen's egg, peanut, tree nuts, wheat, soy, fish, shellfish, and seeds. Heat-stable food allergens have molecular characteristics that enhance protein stability and gastrointestinal absorption and thus are more likely to cause systemic reactions on ingestion. In contrast, heat-labile food allergens lack these characteristics and do not typically elicit reactions if sufficiently altered by heat or acid. Immunologic cross-sensitization between food allergens is more common than clinical cross-reactivity. However, certain groups of food allergens, such as tree nuts, fish, and shellfish, are associated with high rates of clinical cross-reactivity. Knowing the rates of clinical cross-reactivity is important when providing guidance to patients with food allergy and families on what foods can be safely added to the diet and what foods should be avoided.
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Beckwith-Wiedemann syndrome (BWS) is the most common epigenetic overgrowth and cancer predisposition disorder. Due to both varying molecular defects involving chromosome 11p15 and tissue mosaicism, patients can present with a variety of clinical features, leading to the newly defined Beckwith-Wiedemann spectrum (BWSp). The BWSp can be further divided into three subsets of patients: those presenting with classic features, those presenting with isolated lateralized overgrowth (ILO) and those not fitting into the previous two categories, termed atypical BWSp. Previous reports of patients with BWS have focused on those with the more recognizable, classic features, and limited information is available on those who fit into the atypical and ILO categories. Here, we present the first cohort of patients recruited across the entire BWSp, describe clinical features and molecular diagnostic characteristics, and provide insight into practical diagnosis and management recommendations that we have gained from this cohort.
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Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/terapia , Síndrome de Beckwith-Wiedemann/genética , Metilación de ADN , Femenino , Genotipo , Humanos , Lactante , Masculino , FenotipoRESUMEN
BACKGROUND: Human serum albumin (HSA) is a commonly used colloid for volume expansion and albumin replacement and during plasmapheresis. Colloids are an uncommon cause of anaphylaxis, and cases of hypersensitivity reactions to HSA are extremely rare. CASE REPORT: A 10-year-old boy with chronic inflammatory demyelinating polyneuropathy was treated with plasmapheresis, with albumin as the replacement fluid. He developed a severe reaction characterized by respiratory, gastrointestinal, and cutaneous symptoms. RESULTS: Skin testing to HSA was positive and resulted in objective systemic symptoms, suggesting an immediate hypersensitivity reaction to HSA. CONCLUSION: While colloids are an uncommon cause of immediate hypersensitivity reactions, they can lead to severe and potentially fatal reactions if not recognized and treated promptly.
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Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad Inmediata/diagnóstico , Plasmaféresis , Albúmina Sérica Humana/inmunología , Niño , Hipersensibilidad a las Drogas/etiología , Humanos , Hipersensibilidad Inmediata/etiología , Hipersensibilidad Inmediata/inmunología , Masculino , Plasmaféresis/efectos adversos , Plasmaféresis/métodos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy that is diagnosed based on clinical findings, but can be confirmed with oral food challenge (OFC). OFC is more often performed to assess the development of tolerance. Most studies describing OFCs in FPIES are limited in size. OBJECTIVE: We sought to describe our experience with OFCs using our FPIES protocol. Patients were given one-third of serving size with a 4-hour observation period, followed by home titration to full dose. METHODS: We conducted a retrospective chart review of patients who underwent OFC via the FPIES protocol from 2014 to 2017. Data regarding the history of reaction, age at the time of challenge, and reactions during challenge or with home introduction were collected. RESULTS: A total of 169 OFCs were completed under the FPIES protocol, in 119 patients to 19 different foods. Thirty challenges (18%) were positive, with 17 challenges (10%) during initial challenge and 13 (7.7%) during home dosing. Most reactions during initial challenge required intravenous fluids (IVF), but hypotension was uncommon. One hundred thirty-nine (82%) OFCs were negative with home introduction, indicating tolerance to the challenged foods. The mean age of passing a challenge to milk, soy, and grain was earlier than that of other solid foods. CONCLUSIONS: Our data suggest that our FPIES OFC protocol is safe. Early administration of IVF may prevent the development of hypotension. It is difficult to stratify the risk of severe or delayed reaction based on patient characteristics, and more data are needed to identify those appropriate for home introduction.
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Proteínas en la Dieta/efectos adversos , Enterocolitis/diagnóstico , Enterocolitis/etiología , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/etiología , Alérgenos/administración & dosificación , Niño , Preescolar , Protocolos Clínicos , Proteínas en la Dieta/administración & dosificación , Femenino , Humanos , Lactante , Masculino , Derivación y Consulta , Estudios Retrospectivos , SíndromeRESUMEN
Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder that presents with a wide spectrum of clinical features including overgrowth, abdominal wall defects, macroglossia, neonatal hypoglycemia, and predisposition to embryonal tumors. It is associated with genetic and epigenetic changes on the chromosome 11p15 region, which includes two imprinting control regions. Here we review strategies for diagnosing and managing BWS and delineate commonly used genetic tests to establish a molecular diagnosis of BWS. Recommended first-line testing assesses DNA methylation and copy number variation of the BWS region. Tissue mosaicism can occur in patients with BWS, posing a challenge for genetic testing, and a negative test result does not exclude a diagnosis of BWS. Further testing should analyze additional tissue samples or employ techniques with higher diagnostic yield. Identifying the BWS molecular subtype is valuable for coordinating patient care because of the (epi)genotype-phenotype correlations, including different risks and types of embryonal tumors.
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Copy number variants (CNVs) are important in genome variation and genetic disease, with new mutations arising frequently in the germline and somatic cells. Replication stress caused by aphidicolin and hydroxyurea (HU) is a potent inducer of de novo CNVs in cultured mammalian cells. HU is used extensively for long-term management of sickle cell disease. Here, we examined the effects of HU treatment on germline CNVs in vivo in male mice to explore whether replication stress can act as a CNV mutagen in germline mitotic divisions as in cultured cells and whether this would support a concern for increased CNV mutations in offspring of men treated with HU. Several trials of HU administration were performed by oral gavage and subcutaneous pump, with CNVs characterized in C57BL/6 x C3H/HeJ hybrid mouse offspring by microarray and mate-pair sequencing. HU had a short half-life of ~14 min and a narrow dose window over which studies could be performed while maintaining fertility. Tissue histopathology and reticulocyte micronucleus assays verified that doses had a substantial tissue and genetic toxicity. CNVs were readily detected in offspring that originated in both paternal and maternal mouse strains, as de novo and inherited events. However, HU did not increase CNV formation above baseline levels. These results reveal a high rate of CNV mutagenesis in the mouse germline but do not support the hypothesis that HU would increase CNV formation during mammalian spermatogenesis, perhaps due to highly toxic effects on sperm development or experimental variables related to HU pharmacology in mice. Environ. Mol. Mutagen. 59:698-714, 2018. © 2018 Wiley Periodicals, Inc.
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Variaciones en el Número de Copia de ADN/genética , Replicación del ADN/genética , Células Germinativas/efectos de los fármacos , Hidroxiurea/toxicidad , Espermatogénesis/efectos de los fármacos , Espermatozoides/crecimiento & desarrollo , Animales , Variaciones en el Número de Copia de ADN/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Daño del ADN/genética , Replicación del ADN/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: The efficacy and safety of omalizumab has been demonstrated in children as young as 6 years of age. Omalizumab is currently approved for a range of immunoglobulin E (IgE) levels that differ by age. In patients with IgE levels higher than the indicated therapeutic window, only a few studies have demonstrated the efficacy and safety of its use. Specifically, no reported studies exist to describe the use of omalizumab in pediatric patients with asthma ages <12 years and with high IgE levels. OBJECTIVE: We reported a series of pediatric patients who were initiated on omalizumab despite an IgE level higher than the age-indicated therapeutic windows and aimed to describe whether omalizumab was safe and improved asthma outcomes. METHODS: Patients who initiated omalizumab in our pediatric allergy clinic between January 2008 and December 2015, with serum IgE levels higher than the age-indicated therapeutic ranges were included. Patient charts were reviewed to determine the number of asthma-related events in the 12 months before and after initiation of omalizumab and the Asthma Control Test™ scores at the time of initiation and at 12 months of therapy. RESULTS: Eleven patients were identified with pretreatment IgE levels higher than the age-approved thresholds. Five patients were ages <12 years, and six patients were ages >12 years. For all but one patient, the maximum recommended dose of 375 mg every 2 weeks was effective in reducing the need for corticosteroids, emergency department visits, or hospitalizations in the year after initiation of therapy. During the period of therapy, there were no reports of severe reactions. CONCLUSION: Despite a small study group, our results indicated that omalizumab may be safely used in pediatric patients with IgE levels higher than the indicated therapeutic windows.
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Hipergammaglobulinemia/sangre , Hipergammaglobulinemia/tratamiento farmacológico , Inmunoglobulina E/sangre , Omalizumab/uso terapéutico , Adolescente , Niño , Femenino , Humanos , Hipergammaglobulinemia/diagnóstico , Masculino , Omalizumab/administración & dosificación , Omalizumab/efectos adversos , Resultado del TratamientoRESUMEN
Knowledge of nanoparticle (NP)-membrane interactions is important to advances in nanomedicine as well as for determining the safety of NPs to humans and the ecosystem. This study focuses on a unique mechanism of cytotoxicity, cell membrane destabilization, which is principally dependent on the nanoparticle nature of the material rather than on its molecular properties. We investigated the interactions of 2, 5, 10, and 40nm gold NPs with supported lipid bilayer (SLB) of L-α-phosphatidylcholine using quartz crystal microbalance with dissipation monitoring (QCM-D). Gold NPs were tested both in the absence of and in the presence of polymethacrylic acid (PMAA), used to simulate the natural organic matter (NOM) in the environment. In the absence of PMAA, for all NP sizes, we observed only small mass losses (1 to 6ng) from the membrane. This small lipid removal may be a free energy lowering mechanism to relieve stresses induced by the adsorption of NPs, with the changes too small to affect the membrane integrity. In the presence of PMAA, we observed a net mass increase in the case of smaller NPs. We suggest that the increased adhesion between the NP and the bilayer, promoted by PMAA, causes sufficient NP adsorption on the bilayer to overcompensate for any loss of lipid. The most remarkable observation is the significant mass loss (60ng) for the case of 40nm NPs. We attribute this to the lipid bilayer engulfing the NP and leaving the crystal surface. We propose a simple phenomenological model to describe the competition between the particle-bilayer adhesion energy, the bilayer bending energy, and the interfacial energy at bilayer defect edges. The model shows that the larger NPs, which become more adhesive because of the polymer adsorption, are engulfed by the bilayer and leave the crystal surface, causing large mass loss and membrane disruption. The QCM-D measurements thus offer direct evidence that even if NPs are intrinsically not cytotoxic, they can become cytotoxic in the presence of environmental organic matter which modulates the adhesive interactions between the nanoparticle and the membrane.
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Oro/química , Membrana Dobles de Lípidos/química , Nanopartículas del Metal/química , Fosfatidilcolinas/química , Tecnicas de Microbalanza del Cristal de Cuarzo , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Since food allergy knowledge and perceptions may influence prevention and management of school-based reactions, we evaluated them among nurses in an urban school district. All District of Columbia public school nurses were asked to anonymously complete a food allergy knowledge and attitude questionnaire. Knowledge scores were calculated as percentage of correct responses. Attitude responses were tabulated across five-point Likert scales, ranging from strongly disagree to strongly agree. The knowledge questionnaire was completed by 87% of eligible nurses and the attitude questionnaire by 83%. The mean total knowledge score was 76 ± 13 with domain score highest for symptom recognition and lowest for treatment. Regarding attitudes, most (94%) felt food allergy is a serious health problem, for which schools should have guidelines (94%). Fewer believed that nut-free schools (82%) and allergen-free tables (44%) should be implemented. Negative perceptions of parents were identified as: parents of food-allergic children are overprotective (55%) and make unreasonable requests of schools (15%). Food allergy knowledge deficits and mixed attitudes exist among this sample of urban school nurses, particularly related to management of reactions and perceptions of parents. Food allergy education of school nurses should be targeted to improve their knowledge and attitudes.
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Many antimicrobial peptides (AMPs) kill bacteria by disrupting the lipid bilayer structure of their inner membrane. However, there is only limited quantitative information in the literature to differentiate between AMPs of differing molecular properties, in terms of how they interact with the membrane. In this study, we have used quartz crystal microbalance with dissipation monitoring (QCM-D) to probe the interactions between a supported bilayer membrane of egg phosphatidylcholine (egg PC) and four structurally different AMPs: alamethicin, chrysophsin-3, indolicidin, and sheep myeloid antimicrobial peptide (SMAP-29). Multiple signatures from the QCM-D measurements were extracted, differentiating the AMPs, that provide information on peptide addition to and lipid removal from the membrane, the dynamics of peptide-membrane interactions and the rates at which the peptide actions are initiated. The mechanistic variations in peptide action were related to the fundamental structural properties of the peptides including the hydrophobicity, hydrophobic moment, and the probability of α-helical secondary structures.
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Péptidos Catiónicos Antimicrobianos/metabolismo , Membrana Dobles de Lípidos/metabolismo , Tecnicas de Microbalanza del Cristal de Cuarzo , Alameticina/química , Alameticina/metabolismo , Secuencia de Aminoácidos , Animales , Péptidos Catiónicos Antimicrobianos/química , Proteínas Sanguíneas/química , Proteínas Sanguíneas/metabolismo , Catelicidinas/química , Catelicidinas/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Membrana Dobles de Lípidos/química , Datos de Secuencia Molecular , Fosfatidilcolinas/química , Estructura Secundaria de Proteína , OvinosRESUMEN
Recent studies have shown that short, spaced trains of afferent stimulation produce much greater long-term potentiation (LTP) than that obtained with a single, prolonged stimulation episode. The present studies demonstrate that spaced training regimens, based on these LTP timing rules, facilitate learning in wild-type (WT) mice and can offset learning and synaptic signaling impairments in the fragile X mental retardation 1 (Fmr1) knockout (KO) model of fragile X syndrome. We determined that 5 min of continuous training supports object location memory (OLM) in WT but not Fmr1 KO mice. However, the same amount of training distributed across three short trials, spaced by one hour, produced robust long-term memory in the KOs. At least three training trials were needed to realize the benefit of spacing, and intertrial intervals shorter or longer than 60 min were ineffective. Multiple short training trials also rescued novel object recognition in Fmr1 KOs. The spacing effect was surprisingly potent: just 1 min of OLM training, distributed across three trials, supported robust memory in both genotypes. Spacing also rescued training-induced activation of synaptic ERK1/2 in dorsal hippocampus of Fmr1 KO mice. These results show that a spaced training regimen designed to maximize synaptic potentiation facilitates recognition memory in WT mice and can offset synaptic signaling and memory impairments in a model of congenital intellectual disability.
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Modelos Animales de Enfermedad , Síndrome del Cromosoma X Frágil/psicología , Sistema de Señalización de MAP Quinasas , Memoria , Transducción de Señal , Animales , Síndrome del Cromosoma X Frágil/enzimología , Ratones , Ratones NoqueadosRESUMEN
Alamethicin is a 20-amino-acid, α-helical antimicrobial peptide that is believed to kill bacteria through pore formation in the inner membranes. We used quartz crystal microbalance with dissipation monitoring (QCM-D) to explore the interactions of alamethicin with a supported lipid bilayer. Changes in frequency (Δf) and dissipation (ΔD) measured at different overtones as a function of peptide concentration were used to infer peptide-induced changes in the mass and rigidity of the membrane as well as the orientation of the peptide in the bilayer. The measured Δf were positive, corresponding to a net mass loss from the bilayer, with substantial mass losses at 5 µM and 10 µM alamethicin. The measured Δf at various overtones were equal, indicating that the mass change in the membrane was homogeneous at all depths consistent with a vertical peptide insertion. Such an orientation coupled to the net mass loss was in agreement with cylindrical pore formation and the negligibly small ΔD suggested that the peptide walls of the pores stabilized the surrounding lipid organization. Dynamics of the interactions examined through Δf vs. ΔD plots suggested that the peptides initially inserted into the membrane and caused disordering of the lipids. Subsequently, lipids were removed from the bilayer to create pores and alamethicin caused the remaining lipids to reorder and stabilize within the membrane. Based on model calculations, we concluded that the QCM-D data cannot confirm or rule out whether peptide clusters coexist with pores in the bilayer. We have also proposed a way to calculate the peptide-to-lipid ratio (P/L) in the bilayer from QCM-D data and found the calculated P/L as a function of the peptide concentration to be similar to the literature data for vesicle membranes.