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Abstracts - Society for Developmental Biology

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neuronal signaling to smooth muscle. Our study demonstrates the importance of h-CaD on <strong>for</strong>ce development in smooth<br />

muscle and the need <strong>for</strong> further investigation of its potential role in intestinal motility disorders.<br />

Program/Abstract # 287<br />

The integrity of the hippocampus in SIV-infected infant Primates<br />

Burke, Mark; Curtis, Kimberly; Carryl, Heather; Haddad, Georges, College of Medicine, Howard University,<br />

Washington, United States; Abel, Kristina (School of Medicine, University of North Carolina, Chapel Hill, United States)<br />

Pediatric HIV infection remains a global health crisis with a worldwide infection rate of 2.5 million (WHO, Geneva<br />

Switzerland, 2009). Children are much more susceptible to HIV-1 neurological impairments than adults, which is<br />

exacerbated by co-infections. A main and obvious obstacle in pediatric HIV research is sample access. The proposed<br />

studies will take advantage of ongoing pediatric SIV pathogenesis and vaccine studies to maximize the use of nonhuman<br />

primate resources. This expands the original pediatric SIV-related immunology studies to include quantitative<br />

neuropathology studies. Newborn rhesus macaques (Macacca mulatta) that received oral inoculation with arepeatedexposure<br />

of SIVmac251 (n=3) or vehicle (control n=3) were recruited <strong>for</strong> this study. After a 6-18 week survival time, the<br />

animals were sacrificed and the brains prepared <strong>for</strong> quantitative histopathological analysis. Here we report the total<br />

neuronal population of CA1, CA2, and CA3 are significantly reduced after two months of SIV infection using designbased<br />

stereology. This project assesses the impact of early HIV infection on the brain towards the long-term goal of<br />

evaluating treatment paradigms designed to protect the integrity of the developing brain from combined viral and bacterial<br />

infections through an interdisciplinary approach.<br />

Program/Abstract # 288<br />

Temporal polar and anterior cingulate cortical thinning in psychopath offenders<br />

Calzado, Ana, Institute of Legal Medicine, Havana City, Cuba; Valdes-Sosa, Mitchell; Alvarez-Amador, Alfredo; Galán-<br />

García, Lídice; Melie-García, Lester; Alemán-Gómez, Yasser (Cuban Center of Neuroscience, Havana City, Cuba)<br />

Psychopathy is characterized by a lack of empathy and the <strong>for</strong>mation of transient and exploitive interpersonal relationships.<br />

The goal of this study was to determine whether brain regions implicated in emotional processing and behavioral<br />

regulation showed structural alterations in psychopath offenders. Using a surface-based whole brain analysis to detect<br />

associations between gray matter thickness and the Hare total score were identified in entire cortex analyses in 97 violent<br />

offenders (29 offenders with and 68 without psychopathy defined by the PCL-R scale. We found that psychopathy was<br />

associated with highly significant (FDR=0.01) thinning of the cortical surface within the left dorsal anterior cingulate and<br />

temporal pole cortices. Given recent evidences of gray matter changes during neurodevelopment, these findings may<br />

indicate impairment in cortical maturation in important brain areas implicated empathic and emotional processing in<br />

offenders with psychopathy. Keyword: psychopathy, MRI, thickness, offenders<br />

Program/Abstract # 289<br />

Identification of MPPED1 as a protein interacting with human FOXP2 R553H mutant protein associated with<br />

speech and language disorder<br />

Liu, Fu-chin; Chen, Yi-Chuan; Fong, Weng-Lam; Lu, Kuan-Ming, National Yang-Ming University, Taipei, Taiwan<br />

The genetic linkage study of the KE family shows that a missense R553H mutation of FOXP2 is the cause of a severe<br />

speech and language disorder in the affected members. Clinical neuroimaging studies indicate that the caudate nucleus of<br />

striatum and the inferior frontal gyrus are structurally and functionally abnormal in the patient's brain. FOXP2 is there<strong>for</strong>e<br />

the first gene identified to be involved in speech and language. Our study is aimed to study the biological function of<br />

FOXP2 in developmental and functional of the cortical basal ganglia circuits in the brain. FOXP2 was nuclear protein, but<br />

FOXP2R553H mutant protein was expressed in the cytosol. To identify the proteins that might interact with FOXP2R553H<br />

mutant protein, we pre<strong>for</strong>med the yeast two-hybrid system to screen <strong>for</strong> interacting proteins. We screened 1.31 x 109<br />

clones of human fetal brain cDNA library. One of the interacting proteins that we identified was Metallophosphoesterase<br />

Domain Containing Gene 1 (MPPED1), a cyclic nucleotide phosphodiesterase that was localized in cytosol. Coimmunoprecipitation<br />

assay confirmed that FOXP2R553H mutant protein, but not wild type FOXP2 protein interacted with<br />

MPPED1 in transfected HEK293T cells. Double immunostaining further demonstrated co-localization of FOXP2R553H<br />

mutant protein and MPPED1 in cytosol of transfected neural ST14A cells. These findings suggest that FOXP2R553H<br />

mutant protein may have gain-of-function by interacting with MPPED1 protein that can hydrolyze cAMP. The potential<br />

interference of MPPED1 activity by FOXP2R553H mutant protein may be involved in the pathophysiology of KE<br />

language disorder. Supported by National Science Council grant NSC97-2321-B-010-006, NSC98-2321-B-010-002,<br />

NSC99-2321-B-010-002, NSC100-2321-B-010-002.

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