Repression of CIITA by the Epstein-Barr virus transcription factor Zta is independent of its dimerization and DNA binding

Repression of the cellular CIITA gene is part of the immune evasion strategy of the γherpes virus Epstein-Barr virus (EBV) during its lytic replication cycle in B-cells. In part this is mediated through down regulation of MHC class II gene expression via the targeted repression of CIITA, the cellular master regulator of MHC class II gene expression. The repression is achieved through a reduction in CIITA promoter activity initiated by the EBV transcription and replication factor Zta (BZLF1, EB1, ZEBRA). Zta is the earliest gene expressed during the lytic replication cycle. Zta interacts with sequence specific elements in promoters, enhancers and the replication origin (ZREs) and also modulates gene expression through interaction with cellular transcription factors and co-activators. Here we explore the requirements for Zta-mediated repression of the CIITA promoter. We find that repression by Zta is specific for the CIITA promoter and can be achieved in the absence of other EBV genes. Surprisingly, we find that the dimerization region of Zta is not required to mediate repression. This contrasts with an obligate requirement of this region to correctly orientate the DNA contact regions of Zta to mediate activation of gene expression through ZREs. Additional support for the model that Zta represses the CIITA promoter without direct DNA binding comes from promoter mapping that shows that repression does not require the presence of a ZRE in the CIITA promoter

16.3 Are Visual Motion Perception and Detection of Animacy Critical to Higher-Order Social Cognitive Function in Schizophrenia?

Background The observation that individuals with schizophrenia tend to misinterpret subtle social cues is often attributed to deficit in Theory of Mind (ToM). While ToM is commonly assessed using videos portraying interaction between actors, recent work in vision science shows that stimuli with no innate animate features can also convey similar social information through motion alone. These simplified stimuli are advantageous for experimental purposes and may provide further insights into perceptual mechanisms supporting social cognitive function. The Social Attribution Task-Multiple Choice (SAT-MC), based on the classic Hieder and Simmel (1944) stimuli, tells a story using three geometric shapes moving about a centrally fixed figure, followed by questions about what the viewer observed. Although there are no explicit social cues, viewers typically detect actions suggestive of relationships between objects, their intentions, and emotions. This talk will present findings from three studies examining psychometric, functional, and neurophysiological aspects on SAT -MC performance in schizophrenia. Methods Study 1 examined psychometric properties of two forms of the SAT-MC in comparison to video-based social cognitive tests using human actors in 32 schizophrenia (SZ) and 30 substance use disorder (SUD) participants. Study 2 examined functional relationships of the SAT-MC and affect recognition (BLERT) performance across neurocognitive, metacognitive, ToM, and symptom domains in 72 adults with SZ. Study 3 is an in-progress investigation of neurophysiological mechanisms of social cognition using test versions adapted for EEG recording. Chronic SZ, clinical high-risk (CHR), and healthy age-matched community samples are being collected. Results SZ scored significantly lower than SUD on two versions of the SAT-MC, each classifying ~60% of SZ as impaired, compared with ~30% of SUD. The two SAT-MC forms demonstrated good test-retest and parallel form reliability, minimal practice effect, high internal consistency, similar patterns of correlation with social cognitive test performance, and compared favorably to social cognitive tests across psychometric features. When examining functional correlates of SAT -MC performance, impairment is found to co-occur with deficits in affect recognition in the majority of cases but relates uniquely to reductions in verbal memory and emotional intelligence measures. Finally, a preliminary analysis (n=8 SZ, n=2 CHR) of EEG collected during SAT-MC video presentation finds significant correlations (r=.66-.72) between occipito-parietal gamma desynchronization and task performance. Additional analyses find task-related EEG during SAT to be predictive of affect recognition (BLERT) and ToM (TASIT) performance, with correlates including alpha desynchronization in frontal, occipital, and temporal regions, and synchronization of temporal theta and occipital gamma (all r > .5). Conclusions SAT-MC performance is found to be reliable using different stimuli, related to affect recognition and ToM in three independent samples, and shows high diagnostic specificity in classifying SZ against a SUD sample. Functional correlates also involve encoding and emotional intelligence abilities tested outside the visual modality. Analysis of neural oscillatory activity related SAT-MC performance to visual and attention processes, as well as engagement of a broader social cognitive network applied to affect recognition and ToM tasks. Impairment in visual motion processing appears integral to schizophrenia pathophysiology and a critical factor influencing social cognitive abilities attributed to higher-order ToM ability

Investors Prefer Entrepreneurial Ventures Pitched by Attractive Men

Entrepreneurship is a central path to job creation, economic growth, and prosperity. In the earliest stages of start-up business creation, the matching of entrepreneurial ventures to investors is critically important. The entrepreneur’s business proposition and previous experience are regarded as the main criteria for investment decisions. Our research, however, documents other critical criteria that investors use to make these decisions: the gender and physical attractiveness of the entrepreneurs themselves. Across a field setting (three entrepreneurial pitch competitions in the United States) and two experiments, we identify a profound and consistent gender gap in entrepreneur persuasiveness. Investors prefer pitches presented by male entrepreneurs compared with pitches made by female entrepreneurs, even when the content of the pitch is the same. This effect is moderated by male physical attractiveness: attractive males were particularly persuasive, whereas physical attractiveness did not matter among female entrepreneurs

Student Recital (April 27, 2012)

Lágrima / Francisco Tárrega Christpher Bosch, guitar Quando men vo (Musetta’s Waltz) / Giocomo Puccini from La Bohème Alison Kenney, soprano Three Irish Folk Songs / Padraic Colum arr. John Corigliano The Salley Gardens The Foggy Dew Jennifer Drake, flute Alison Kenney, soprano Flute Sonata / Paul Hindemith Sehr langsam Sehr lebhaft Jennifer Drake, flute Etude No. 10 / Heitor Villa-Lobos James Davidson, guitar Alleluja from Exultate Jubilate, K. 165 / Wolfgang Amadeus Mozart Mi Choe, soprano Sleep Now, Op. 10, No. 2 / Samuel Barber Meghan Foley, mezzo soprano Prelude No. 2 in C minor, BWV 847 / Johann Sebastian Bach Dan Maloney, marimbahttps://vc.bridgew.edu/student_concerts/1021/thumbnail.jp

Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression

Lytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an essential prerequisite for the spread of the virus. Differential regulation of a limited number of cellular genes has been reported in B-cells during the viral lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta (BZLF1, ZEBRA, EB1), drives some of these changes. Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome. Using sensitive transcriptome analyses we identified 2263 cellular genes whose expression is significantly changed during the EBV lytic replication cycle. Zta binds 278 of the regulated genes and the distribution of binding sites shows that Zta binds mostly to sites that are distal to transcription start sites. This differs from the prevailing view that Zta activates viral genes by binding exclusively at promoter elements. We show that a synthetic Zta binding element confers Zta regulation at a distance and that distal Zta binding sites from cellular genes can confer Zta-mediated regulation on a heterologous promoter. This leads us to propose that Zta directly reprograms the expression of cellular genes through distal elements

Student Recital (April 30, 2012)

Lute Suite No. 2, BWV 997 / Johann Sebastian Bach Fantasia James Davidson, guitar Cantabile et Presto / Geaorges Enesco Andante ma non troppo Presto Amethyst Lambert, flute Clarinet Concerto No. 3 in Bb / Karl Philipp Stamitz Romanze Rondo Sean Every, clarinet Let the Bright Seraphim / George Frideric Handel from Samson, HWV 57 Alison Kenney, soprano Etude in 6/8 / Morris Goldenberg Nicole Desmarais, marimba Nocturne, Op. 35 / Reinhold Glière David French, horn O’ Rest in the Lord from Elijah / Felix Mendelssohn Giotie Al Canto Mio from L’Euridice / Jacopi Peri Justine Smigel, soprano The Crucifixion, Op. 29, No. 5 / Samuel Barber Jordan Ennis, sopranohttps://vc.bridgew.edu/student_concerts/1022/thumbnail.jp

The DEEP2 Galaxy Redshift Survey: The Voronoi-Delaunay Method Catalog of Galaxy Groups

We present a public catalog of galaxy groups constructed from the spectroscopic sample of galaxies in the fourth data release from the Deep Extragalactic Evolutionary Probe 2 (DEEP2) Galaxy Redshift Survey, including the Extended Groth Strip (EGS). The catalog contains 1165 groups with two or more members in the EGS over the redshift range 0 0.6 in the rest of DEEP2. Twenty-five percent of EGS galaxies and fourteen percent of high-z DEEP2 galaxies are assigned to galaxy groups. The groups were detected using the Voronoi-Delaunay method (VDM) after it has been optimized on mock DEEP2 catalogs following similar methods to those employed in Gerke et al. In the optimization effort, we have taken particular care to ensure that the mock catalogs resemble the data as closely as possible, and we have fine-tuned our methods separately on mocks constructed for the EGS and the rest of DEEP2. We have also probed the effect of the assumed cosmology on our inferred group-finding efficiency by performing our optimization on three different mock catalogs with different background cosmologies, finding large differences in the group-finding success we can achieve for these different mocks. Using the mock catalog whose background cosmology is most consistent with current data, we estimate that the DEEP2 group catalog is 72% complete and 61% pure (74% and 67% for the EGS) and that the group finder correctly classifies 70% of galaxies that truly belong to groups, with an additional 46% of interloper galaxies contaminating the catalog (66% and 43% for the EGS). We also confirm that the VDM catalog reconstructs the abundance of galaxy groups with velocity dispersions above ~300 km s^(–1) to an accuracy better than the sample variance, and this successful reconstruction is not strongly dependent on cosmology. This makes the DEEP2 group catalog a promising probe of the growth of cosmic structure that can potentially be used for cosmological tests

Student Recital (April 23, 2012)

Londonderry Air / Joseph McCarthy arr. Domenico Savino Alison Kenney, soprano Zueignung, Op. 10, No. 1 / Richard Strauss Diane M. Card, alto from Dichterliebe, Op. 48 / Robert Schumann Im wunderschonen Monat Mai Ein Jungling liebt ein Madchen Allnachtlich im Traume Greg Fernandes, bass Prelude No. 4 / Heitor Villa-Lobos Nick Rice, guitar Kind of In Love / John Harbison Why / Jonathan Larson Samuel Lathrop, tenor Sonata for Saxophone in Eb and Piano / Bernard Heiden Chelsea Fisk, alto saxophone The Crucifixion, Op. 29, No. 5 / Samuel Barber Mary Sanker, soprano Sicilienne, Op. 78 / Gabriel Faure Charles Sherwin, trombone Sonata for Trumpet and Piano / Eric Ewazen II. James Sheehan, trumpethttps://vc.bridgew.edu/student_concerts/1035/thumbnail.jp

The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al