“I shall read that you are my husband and you shall see me sign myself your wife”: Analyzing the Rhetorical Strategies of Heloise d’Argenteuil

This project strives to decouple the 12th century writer Heloise d’Argenteuil from her husband, the notorious Peter Abelard, establishing her as a significant thinker and writer, particularly in the tradition of women’s literature. Heloise, in fact, anticipated the querelle des femme of a later medieval scholar, Christine de Pizan, as she sought to combat stereotypical thinking about women within the circumscribed role of a devoted lover and wife to Abelard. Drawing on the work of Sally Livingston and others, I will examine various medieval discourses. In her letters, Heloise is revealed as a figure aspiring to be viewed not as a wife succumbing to a man, but rather as a woman devoting her mind, body, and future to her husband. Thus, this paper will examine her rhetorical strategies that engender a conversation between husband and wife and enable her to consciously retain an unbreakable connection with Abelard

NF-kB functions in synaptic signaling and behavior

Ca^(2+)-regulated gene transcription is essential to diverse physiological processes, including the adaptive plasticity associated with learning. We found that basal synaptic input activates the NF-kB transcription factor by a pathway requiring the Ca^(2+)/calmodulin-dependent kinase CaMKII and local submembranous Ca^(2+) elevation. The p65:p50 NF-kB form is selectively localized at synapses; p65-deficient mice have no detectable synaptic NF-kB. Activated NF-kB moves to the nucleus and could directly transmute synaptic signals into altered gene expression. Mice lacking p65 show a selective learning deficit in the spatial version of the radial arm maze. These observations suggest that long-term changes to adult neuronal function caused by synaptic stimulation can be regulated by NF-kB nuclear translocation and gene activation

The alpha1 subunit of the GABA(A) receptor modulates fear learning and plasticity in the lateral amygdala.

Synaptic plasticity in the amygdala is essential for emotional learning. Fear conditioning, for example, depends on changes in excitatory transmission that occur following NMDA receptor activation and AMPA receptor modification in this region. The role of these and other glutamatergic mechanisms have been studied extensively in this circuit while relatively little is known about the contribution of inhibitory transmission. The current experiments addressed this issue by examining the role of the GABA(A) receptor subunit alpha1 in fear learning and plasticity. We first confirmed previous findings that the alpha1 subunit is highly expressed in the lateral nucleus of the amygdala. Consistent with this observation, genetic deletion of this subunit selectively enhanced plasticity in the lateral amygdala and increased auditory fear conditioning. Mice with selective deletion of alpha1 in excitatory cells did not exhibit enhanced learning. Finally, infusion of a alpha1 receptor antagonist into the lateral amygdala selectively impaired auditory fear learning. Together, these results suggest that inhibitory transmission mediated by alpha1-containing GABA(A) receptors plays a critical role in amygdala plasticity and fear learning

The α1 Subunit of the GABA(A) Receptor Modulates Fear Learning and Plasticity in the Lateral Amygdala

Synaptic plasticity in the amygdala is essential for emotional learning. Fear conditioning, for example, depends on changes in excitatory transmission that occur following NMDA receptor activation and AMPA receptor modification in this region. The role of these and other glutamatergic mechanisms have been studied extensively in this circuit while relatively little is known about the contribution of inhibitory transmission. The current experiments addressed this issue by examining the role of the GABA(A) receptor subunit α1 in fear learning and plasticity. We first confirmed previous findings that the α1 subunit is highly expressed in the lateral nucleus of the amygdala. Consistent with this observation, genetic deletion of this subunit selectively enhanced plasticity in the lateral amygdala and increased auditory fear conditioning. Mice with selective deletion of α1 in excitatory cells did not exhibit enhanced learning. Finally, infusion of a α1 receptor antagonist into the lateral amygdala selectively impaired auditory fear learning. Together, these results suggest that inhibitory transmission mediated by α1-containing GABA(A) receptors plays a critical role in amygdala plasticity and fear learning

OligoArrayDb: pangenomic oligonucleotide microarray probe sets database

OligoArrayDb is a comprehensive database containing pangenomic oligonucleotide microarray probe sets designed for most of the sequenced genomes that are not covered by commercial catalog arrays. The availability of probe sequences, associated with custom microarray fabrication services offered by many companies and cores presents the unequalled possibility to perform microarray experiments on most of the sequenced organisms. OligoArrayDb contains more than 2.8 probes per gene in average for more than 600 organisms, mostly archaea and bacteria strains available from public database. On average, 98% of the annotated genes have at least one probe which is predicted to be specific to its intended target in >94% of the cases. OligoArrayDb is weekly updated as new sequenced genomes become available. Probe sequences, in addition to a comprehensive set of annotations can be downloaded from this database. OligoArrayDb is publicly accessible online at http://berry.engin.umich.edu/oligoarraydb

Genetic variants of the NOTCH3 gene in the elderly and magnetic resonance imaging correlates of age-related cerebral small vessel disease

Cerebral small vessel disease-related brain lesions such as white matter lesions and lacunes are common findings of magnetic resonance imaging in the elderly. These lesions are thought to be major contributors to disability in old age, and risk factors that include age and hypertension have been established. The radiological, histopathologic and clinical phenotypes of age-related cerebral small vessel disease remarkably resemble autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, which is caused by mutations in NOTCH3. We hypothesized that genetic variations in NOTCH3 also play a role in age-related cerebral small vessel disease. We directly sequenced all 33 exons, the promoter and 3′-untranslated region of NOTCH3 in 195 participants with either coalescent white matter lesions or lacunes and compared the results to 82 randomly selected participants with no focal changes on magnetic resonance images in the Austrian Stroke Prevention Study. We detected nine common and 33 rare single nucleotide polymorphisms, of which 20 were novel. All common single nucleotide polymorphisms were genotyped in the entire cohort (n = 888), and four of them, rs1043994, rs10404382, rs10423702 and rs1043997, were associated significantly with both the presence and progression of white matter lesions. The association was confined to hypertensives, a result which we replicated in the Cohorts for Heart and Ageing Research in Genomic Epidemiology Consortium on an independent sample of 4773 stroke-free hypertensive elderly individuals of European descent (P = 0.04). The 33 rare single nucleotide polymorphisms were scattered over the NOTCH3 gene with three being located in the promoter region, 24 in exons (18 non-synonymous), three in introns and three in the 3′-untranslated region. None of the single nucleotide polymorphisms affected a cysteine residue. Sorting Intolerant From Tolerant, PolyPhen2 analyses and protein structure simulation consistently predicted six of the non-synonymous single nucleotide polymorphisms (H170R, P496L, V1183M, L1518M, D1823N and V1952M) to be functional, with four being exclusively or mainly detected in subjects with severe white matter lesions. In four individuals with rare non-synonymous single nucleotide polymorphisms, we noted anterior temporal lobe hyperintensity, hyperintensity in the external capsule, lacunar infarcts or subcortical lacunar lesions. None of the observed abnormalities were specific to cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. This is the first comprehensive study investigating (i) the frequency of NOTCH3 variations in community-dwelling elderly and (ii) their effect on cerebral small vessel disease related magnetic resonance imaging phenotypes. We show that the NOTCH3 gene is highly variable with both common and rare single nucleotide polymorphisms spreading across the gene, and that common variants at the NOTCH3 gene increase the risk of age-related white matter lesions in hypertensives. Additional investigations are required to explore the biological mechanisms underlying the observed association

New Episodic Learning Interferes with the Reconsolidation of Autobiographical Memories

It is commonly assumed that, with time, an initially labile memory is transformed into a permanent one via a process of consolidation. Yet, recent evidence indicates that memories can return to a fragile state again when reactivated, requiring a period of reconsolidation. In the study described here, we found that participants who memorized a story immediately after they had recalled neutral and emotional experiences from their past were impaired in their memory for the neutral (but not for the emotional) experiences one week later. The effect of learning the story depended critically on the preceding reactivation of the autobiographical memories since learning without reactivation had no effect. These results suggest that new learning impedes the reconsolidation of neutral autobiographical memories

A High Through-Put Reverse Genetic Screen Identifies Two Genes Involved in Remote Memory in Mice

Previous studies have revealed that the initial stages of memory formation require several genes involved in synaptic, transcriptional and translational mechanisms. In contrast, very little is known about the molecular and cellular mechanisms underlying later stages of memory, including remote memory (i.e. 7-day memory). To identify genes required for remote memory, we screened randomly selected mouse strains harboring known mutations. In our primary reverse genetic screen, we identified 4 putative remote memory mutant strains out of a total of 54 lines analyzed. Additionally, we found 11 other mutant strains with other abnormal profiles. Secondary screens confirmed that mutations of integrin β2 (Itgβ2) and steryl-O-acyl transferase 1 (Soat1) specifically disrupted remote memory. This study identifies some of the first genes required for remote memory, and suggests that screens of targeted mutants may be an efficient strategy to identify molecular requirements for this process

Coupled Analysis of In Vitro and Histology Tissue Samples to Quantify Structure-Function Relationship

The structure/function relationship is fundamental to our understanding of biological systems at all levels, and drives most, if not all, techniques for detecting, diagnosing, and treating disease. However, at the tissue level of biological complexity we encounter a gap in the structure/function relationship: having accumulated an extraordinary amount of detailed information about biological tissues at the cellular and subcellular level, we cannot assemble it in a way that explains the correspondingly complex biological functions these structures perform. To help close this information gap we define here several quantitative temperospatial features that link tissue structure to its corresponding biological function. Both histological images of human tissue samples and fluorescence images of three-dimensional cultures of human cells are used to compare the accuracy of in vitro culture models with their corresponding human tissues. To the best of our knowledge, there is no prior work on a quantitative comparison of histology and in vitro samples. Features are calculated from graph theoretical representations of tissue structures and the data are analyzed in the form of matrices and higher-order tensors using matrix and tensor factorization methods, with a goal of differentiating between cancerous and healthy states of brain, breast, and bone tissues. We also show that our techniques can differentiate between the structural organization of native tissues and their corresponding in vitro engineered cell culture models