Lateralization of the developing rat hippocampal formation

Differences between the left and right hemisphere of the brain have been observed in humans and rodents (Broca, 1861; Wernicke, 1881), including the hippocampal formation, a region of the brain that is necessary for some forms of learning and memory (Olton and Samuelson, 1976; deToledo-Morrell et al., 1988; Bernasconi-Guastalla et al., 1994; Tabibnia et al., 1994; Poe et al., 2000; Lister et al., 2006; Hanlon et al., 2005; Sommer et al., 2005; Moskal et al., 2006; Thompson et al., 2008; Klur et al., 2009). Although lateralization of the hippocampal formation has been studied in the adult, few have sought to directly examine the development of hippocampal lateralization (Moskal et al., 2006) and none have examined hippocampal lateralization in the embryo. The objective of the study outlined in this dissertation was to characterize the development of hippocampal lateralization in the rat. To achieve this objective, a rat CNS microarray with 1,178 genes representing the majority of ontological categories within the rat genome (Kroes et al., 2006) was used to examine lateralized gene expression in the embryonic rat hippocampal formation: 14 genes were all more highly expressed in the right hippocampus at E18 (Gross et al., 2008; Gross et al., 2010). Database for Annotation Visualization and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were also used to further investigate whether specific genes differentially expressed at E18 comprised pathways known to be important in the development of the hippocampal formation. Results demonstrated that genes related to structure, transcription and translation, cellular metabolism, glycolysis, and gap junction signaling were more highly expressed in the right hippocampus at E18. Expression of genes corresponding to proteins that comprise the gap junction signaling pathway were further examined using qRT-PCR. Results showed that alpha1a-tubulin, beta3-tubulin, and connexin43 were more highly expressed in the right hippocampus at E18. Using Western blot analysis, alpha1a-tubulin protein levels were also shown to be higher in the right hippocampus at E18. These results indicated that genes related to hippocampal growth and development were more highly expressed in the right hippocampus at E18, and furthermore they suggested that gap junctions may play a critical role in the development of hippocampal lateralization in the embryo. To further characterize the lateralized development of the rat hippocampal formation, the effect of N-methyl-D-aspartate glutamate receptor (NMDAR) mediated synaptic activity lateralized gene expression in the hippocampal formation during early postnatal development in the rat. During normal development, the pattern of lateralized gene expression displays a right-to-left shift in preferential expression between P6 and P9 (Moskal et al., 2006). A reduction in NMDA receptor (NMDAR) mediated synaptic activity using the selective NMDAR antagonist CPP, altered this pattern of lateralized gene expression at P9 (Rahimi et al., 2006, Gross et al., 2007; Claiborne et al., 2010). These data were then analyzed using Significance Analysis for Microarrays, DAVID, and GSEA analyses. The MAPK signaling pathway was enriched in the right hippocampal formation at P9 following CPP injections: these data were corroborated and extended using qRT-PCR. Expression of MAPK14 mRNA was not significantly different between the left and right hippocampal formation at postnatal day 6, nor was it greater in the right HF as compared to the left in saline treated rats at P9; however, MAPK14 mRNA was more highly expressed in the right hippocampal formation at P9 following a reduction in NMDAR activity between P6 and P9. c-Myc was more highly expressed in the right hippocampal formation at P6, and it was not differentially expressed during normal development or following saline control injections between P6 and P9. However, cMyc mRNA expression was significantly greater in the right hippocampal formation in CPP treated rats. These findings indicated that genes involved in the MAPK signaling pathway were upregulated in the right hippocampal formation during early postnatal development following a reduction in NMDAR-mediated synaptic activity. The findings presented in this dissertation are both novel and important: they are the first to demonstrate that lateralized gene expression is present in the embryonic rat hippocampal formation. Furthermore, these findings are the first to show the effect of early experience on the development of hippocampal lateralization in the first postnatal week. The results support the idea that differential gene expression patterns in the hippocampus are likely developmentally regulated and play a key role in the formation and function of that region and that the gene expression patterns can be significantly influenced by factors that modulate synapse plasticity

A Correlative Study of Gender and Social Style.

This study examines the concepts of social style and gender to determine if a relationship exists between the two constructs. The hypotheses suggested a direct relationship between the categories of the BSRI (masculine, feminine, androgynous, and undifferentiated) and the Social Style Analysis (driver, amiable, expressive, and analytical). Ninety-four participants completed two self-report surveys. Chi-square analysis performed on the data found a significant relationship between feminine and amiable as well as androgynous and expressive. While the analysis suggested that masculine/driver and undifferentiated/analytical were not independent, the relationship found was not significant

Blunt traumatic celiac artery avulsion managed with celiac artery ligation and open aorto-celiac bypass.

Traumatic celiac artery injuries are rare and highly lethal with reported mortality rates of 38-62%. The vast majority are caused by penetrating trauma with only 11 reported cases due to blunt trauma (Graham et al., 1978; Asensio et al., 2000, 2002). Only 3 of these cases were complete celiac artery avulsions. Management options described depend upon the type of injury and have included medical therapy with anti-platelet agents or anti-coagulants, endovascular stenting, and open ligation. We report a case of a survivor of complete celiac artery avulsion from blunt trauma managed by open bypass

An Exploratory Study Using Participation Plans for Inclusive Social Studies Instruction

Limited research exists on teaching social studies content, including intervention research, in inclusive settings for students with intellectual and developmental disabilities. The purpose of this exploratory project was to evaluate the use of participation plans for supporting students with intellectual and developmental disabilities in inclusive high school social studies classrooms. The study addressed two questions: (1) To what extent can students with IDD learn prioritized social studies content and skills in inclusive secondary settings? and (2) How do participation plans support students in learning prioritized social studies content and skills in inclusive general education settings? A university research team supported a public high school staff to employ a single-case, multiple baseline design across prioritized skills (knowledge of content, vocabulary, and summarization) and participants. Results showed students’ correct responses increased across prioritized skills after the team began using the participation plans. This discreet intervention exhibits promise for school staff (i.e., teachers, paraprofessionals) needing mediating tools for effective inclusive education. We discuss implications for future research and practice

Evidence for Prosody in Silent Reading

English speakers and expressive readers emphasize new content in an ongoing discourse. Do silent readers emphasize new content in their inner voice? Because the inner voice cannot be directly observed, we borrowed the cap-emphasis technique (e.g., “toMAYto”) from the pronunciation guides of dictionaries to elicit prosodic emphasis. Extrapolating from linguistic theories of focus prosody in spoken English, we predicted and found that silent readers in experiment 1 preferred cap-emphasized, newsworthy content (“James stole the BRACELET ) when the just-read story left them wondering what was stolen (compared with control trials). Readers preferred “JAMES stole the bracelet” when left wondering who the thief was. Experiment 2 generalized our findings to newsworthy function words and to a new behavioral measure, reaction time. As predicted, “He CAN” was judged more quickly and accurately following “Can he swim,” whereas “HE can” was judged more quickly and accurately following “Who can swim?” Our results suggest that readers engage focus prosody when they read silently

Bilateral Burkitt Lymphoma of the Ovaries: A Report of a Case in a Child with Williams Syndrome

A 10-year-old female with Williams Syndrome (WS) presented with a two-month history of fatigue, weight loss, and bilateral ovarian masses. Histologic, immunophenotypic, and cytogenetic studies confirmed the diagnosis of Burkitt lymphoma (BL). While there is no established association between the two disorders, this is the third case in the literature of Burkitt lymphoma in a patient with Williams Syndrome

NYX-2925 Is a Novel NMDA Receptor-Specific Spirocyclic-beta-Lactam That Modulates Synaptic Plasticity Processes Associated with Learning and Memory

Background: N-methyl-D-aspartate receptors are one member of a family of ionotropic glutamate receptors that play a pivotal role in synaptic plasticity processes associated with learning and have become attractive therapeutic targets for diseases such as depression, anxiety, schizophrenia, and neuropathic pain. NYX-2925 ((2S, 3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide) is one member of a spiro-beta-lactam-based chemical platform that mimics some of the dipyrrolidine structural features of rapastinel (formerly GLYX-13: threonine-proline-proline-threonine) and is distinct from known N-methyl-D-aspartate receptor agonists or antagonists such as D-cycloserine, ketamine, MK-801, kynurenic acid, or ifenprodil. Methods: The in vitro and in vivo pharmacological properties of NYX-2925 were examined. Results: NYX-2925 has a low potential for off-target activity, as it did not exhibit any significant affinity for a large panel of neuroactive receptors, including hERG receptors. NYX-2925 increased MK-801 binding to human N-methyl-D-aspartate receptor NR2A-D subtypes expressed in HEK cells and enhanced N-methyl-D-aspartate receptor current and long-term potentiation (LTP) in rat hippocampal slices (100-500 nM). Single dose ex vivo studies showed increased metaplasticity in a hippocampal LTP paradigm and structural plasticity 24 hours after administration (1 mg/kg p.o.). Significant learning enhancement in both novel object recognition and positive emotional learning paradigms were observed (0.01-1 mg/kg p.o.), and these effects were blocked by the N-methyl-D-aspartate receptor antagonist CPP. NYX-2925 does not show any addictive or sedative/ataxic side effects and has a therapeutic index of greater than 1000. NYX-2925 (1 mg/kg p.o.) has a cerebrospinal fluid half-life of 1.2 hours with a Cmax of 44 nM at 1 hour. Conclusions: NYX-2925, like rapastinel, activates an NMDA receptor-mediated synaptic plasticity process and may have therapeutic potential for a variety of NMDA receptor-mediated central nervous system disorders

Selective Role of the Catalytic PI3K Subunit p110β in Impaired Higher Order Cognition in Fragile X Syndrome

SummaryDistinct isoforms of the PI3K catalytic subunit have specialized functions in the brain, but their role in cognition is unknown. Here, we show that the catalytic subunit p110β plays an important role in prefrontal cortex (PFC)-dependent cognitive defects in mouse models of Fragile X syndrome (FXS), an inherited intellectual disability. FXS is caused by loss of function of the fragile X mental retardation protein (FMRP), which binds and translationally represses mRNAs. PFC-selective knockdown of p110β, an FMRP target that is translationally upregulated in FXS, reverses deficits in higher cognition in Fmr1 knockout mice. Genetic full-body reduction of p110β in Fmr1 knockout mice normalizes excessive PI3K activity, restores stimulus-induced protein synthesis, and corrects increased dendritic spine density and behavior. Notably, adult-onset PFC-selective Fmr1 knockdown mice show impaired cognition, which is rescued by simultaneous p110β knockdown. Our results suggest that FMRP-mediated control of p110β is crucial for neuronal protein synthesis and cognition

Paraganglioma de corpo carotídeo com abaulamento de orofaringe – Relato de caso

Introdução: Os paragangliomas são tumores altamente vascularizados frequentemente benignos e unilaterais. Sua localização é no corpo carotídeo sendo rara sua expressão com predominância no espaço parafaríngeo. Os tumores parafaríngeos dividem-se em  pré ou pós estilóides,  sendo o adenoma pleomórfico e o schwanoma do vago respectivamente as principais patologias que acometem a região. Objetivo: relatar um caso de paraganglioma de corpo carotídeo unilateral com extensão ao espaço parafaríngeo. Relato: CLH, 66 anos,feminino, observou a presença de assimetria na região amigdalina à direita há aproximadamente 1 ano sem outros sintomas sintomas. A oroscopia e videotelelaringoscopia evidenciou assimetria da loja amigalina direita com suspeita de massa expansiva que projetava a amígdala e pilar posterior para a linha média extendendo-se inferiormente até a vertente externa do seio piriforme .No exame do pescoco apresentava à direita extensão da massa para a região jugulo-carotídea (nível II)de consistência aumentada. A suspeita clínica de glômus foi confirmada por estudo tomográfico computadorizado contrastado do pescoço, ressonância nuclear magnética e angiorressonância de vasos cervicais que definiram uma lesão ovalada com 5X4x6cm, na topografia do espaço carotídeo direito  deslocando a artéria carótida externa e interna  na região do bulbo carotídeo, hipervascularizada, com extensão ao espaço parafaríngeo e sugestiva de paraganglioma carotídeo.O tratamento indicado foi a ressecção cirúrgica sem a realização de embolização prévia. Conclusão: O Paraganglioma carotídeo é um tumor raro e de crescimento lento que acomete a região jugulo-carotídea. A extensão parafaríngea é rara e deve estar no diagnóstico diferencial das patologias do espaço parafaríngeo

The ion seeps tonight: Assessing ionic transport in multilayered nanocomposites

Figure 6 – Schematic of cation (M+) transport through an organized multilayered composite. Controlling ion transport across membranes and interfaces is one of the central themes challenging technological pursuits ranging from corrosion to energy storage and chemical separations. Here, we present several examples in which we have studied the application of multilayer nanocomposites to regulate ion transport. These composites comprise organized layers of functional or structural elements, integrated within composites such that the specific nanostructure and composition of the materials play important roles in defining ionic interactions and mobility. In cases such as corrosion inhibition, thin film composite coatings are intended to block ionic transport, retarding deleterious corrosion reactions. We show that by manipulating the materials chemistry of highly organized polymer clay nanocomposite thin film barriers, it is possible to significantly increase corrosion resistance of steel samples in a simulated sea water environment. In contrast, for energy storage applications such as batteries, composite separators capable of rapid ionic diffusion are desired for high current performance. We explore how layered composite structures may provide effective ion diffusion planes, leading to promising ionic conductivity in new solid state separators. Finally, in chemical separations, the selective transport of ions becomes important. We examine how manipulating the chemical and electrostatic composition of layered polyelectrolyte materials leads to preferential cation transport through these composite structures, a key property for an effective separations membrane. These different technologies exemplify how the principles governing ion transport through multilayered materials can be adapted for widely varied applications, and they illustrate the potential for this materials development strategy to enable new classes of functional composite materials. Please click Additional Files below to see the full abstract