The Tennessee Center for AIDS Research HIV Research Training Program for Minority High School and Undergraduate Students: Development, Implementation, and Early Outcomes.

Background: The Southern region of the United States has the highest HIV incidence, and new infections disproportionately affect Black Americans. The Tennessee Center for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI) program supports the training of individuals from groups underrepresented in medicine and science in multiple areas of research to increase the pool of HIV-focused investigators at early educational and career stages.

Setting: The Tennessee CFAR is a partnership between Vanderbilt University Medical Center, Meharry Medical College (one of the oldest historically Black medical colleges), Tennessee Department of Health, and Nashville Community AIDS Resources, Education and Services (a sophisticated community service organization, which emphasizes research training responsive to regional and national priorities).

Sox10-cre BAC transgenes reveal temporal restriction of mesenchymal cranial neural crest and identify glandular Sox10 expression.

Diversity of neural crest derivatives has been studied with a variety of approaches during embryonic development. In mammals Cre-LoxP lineage tracing is a robust means to fate map neural crest relying on cre driven from regulatory elements of early neural crest genes. Sox10 is an essential transcription factor for normal neural crest development.

The School for Science and Math at Vanderbilt: An Innovative Research-Based Program for High School Students.

The School for Science and Math at Vanderbilt (SSMV) is an innovative partnership program between a Research I private university and a large urban public school system. The SSMV was started in 2007 and currently has 101 students enrolled in the program, with a total of 60 students who have completed the 4-yr sequential program. Students attend the SSMV for one full day per week during the school year and 3-6 wk in the summers following their ninth- to 11th-grade years, with each grade of 26 students coming to the Vanderbilt campus on a separate day.

Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations.

Deficiency of carbamoyl phosphate synthetase I (CPSI) results in hyperammonemia ranging from neonatally lethal to environmentally induced adult-onset disease. Over 24 years, analysis of tissue and DNA samples from 205 unrelated individuals diagnosed with CPSI deficiency (CPSID) detected 192 unique CPS1 gene changes, of which 130 are reported here for the first time. Pooled with the already reported mutations, they constitute a total of 222 changes, including 136 missense, 15 nonsense, 50 changes of other types resulting in enzyme truncation, and 21 other changes causing in-frame alterations.

Assessing the functional characteristics of synonymous and nonsynonymous mutation candidates by use of large DNA constructs.

As we identify more and more genetic changes, either through mutation studies or population screens, we need powerful tools to study their potential molecular effects. With these tools, we can begin to understand the contributions of genetic variations to the wide range of human phenotypes. We used our catalogue of molecular changes in patients with carbamyl phosphate synthetase I (CPSI) deficiency to develop such a system for use in eukaryotic cells.

The frequent observation of evidence for nonsense-mediated decay in RNA from patients with carbamyl phosphate synthetase I deficiency.

CPSI deficiency is an inborn error of metabolism caused by mutations in the first, rate-determining enzyme of the urea cycle. Our mutation detection data from this disorder suggest that a significant number of mutant alleles cause RNA instability, most likely through the nonsense-mediated decay pathway. We identified 26 non-consanguinous CPSID patients with an available RNA source (liver tissue or cell line) and screened both genomic DNA and RNA for the identification and classification of mutations.

Environmentally determined genetic expression: clinical correlates with molecular variants of carbamyl phosphate synthetase I.

Carbamyl phosphate synthetase I (CPSI) determines the rate-limiting entry of free ammonia into the urea cycle. Disruption of CPSI affects the liver's ability to remove waste nitrogen and produce arginine, citrulline, and urea. Arginine is the necessary precursor for the critical biomolecule, nitric oxide (NO).

Characterization of genomic structure and polymorphisms in the human carbamyl phosphate synthetase I gene.

Human carbamyl phosphate synthetase I (CPSI) is an essential hepatic enzyme that initiates the urea cycle. Deficiency of this enzyme usually results in lethal hyperammonemia. CPSI is encoded by the CPSI gene located on chromosome 2q35.

Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations.

The mitochondrial trifunctional protein (TFP) is an enzyme complex of the fatty acid beta-oxidation cycle composed of an alpha- and a beta-subunit. The two encoding genes are located in the same region on chromosome 2 (2p23). TFP deficiency due to either alpha- or beta-subunit mutations is characterized by mutational and phenotypic heterogeneity with severe, early-onset, cardiac forms and milder, later-onset, myopathic phenotypes.

Hepatocyte nuclear factor-4 alpha mediates the stimulatory effect of peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) on glucose-6-phosphatase catalytic subunit gene transcription in H4IIE cells.

It has recently been shown that adenoviral-mediated expression of peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) in hepatocytes stimulates glucose-6-phosphatase catalytic subunit (G6Pase) gene expression. A combination of fusion gene, gel retardation and chromatin immunoprecipitation assays revealed that, in H4IIE cells, PGC-1 alpha mediates this stimulation through an evolutionarily conserved region of the G6Pase promoter that binds hepatocyte nuclear factor-4 alpha.