Enzyme replacement therapy initiated in adulthood: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program.

Objective: To evaluate the impact of galsulfase enzyme replacement therapy (ERT) when initiated in adulthood for patients with mucopolysaccharidosis (MPS) VI.

Methods: In 2005, the multi-national, MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A sub-analysis was performed in patients who started ERT at ≥16 years of age and had received galsulfase for ≥6 months.

Enzyme replacement therapy outcomes across the disease spectrum: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program.

The impact of galsulfase enzyme replacement therapy in patients with mucopolysaccharidosis (MPS) VI with phenotypes at either end of the disease spectrum was evaluated. The MPS VI Clinical Surveillance Program (CSP) was established to collect long-term observational data from routine clinical and laboratory assessments. A subanalysis of the CSP was performed in patients with pretreatment urinary glycosaminoglycan (uGAG) levels <100 μg/mg and ≥200 μg/mg creatinine (low- and high-uGAG) who had received galsulfase for ≥6 months.

Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T.

Structures of a putative ζ-class glutathione S-transferase from the pathogenic fungus Coccidioides immitis.

Coccidioides immitis is a pathogenic fungus populating the southwestern United States and is a causative agent of coccidioidomycosis, sometimes referred to as Valley Fever. Although the genome of this fungus has been sequenced, many operons are not properly annotated. Crystal structures are presented for a putative uncharacterized protein that shares sequence similarity with ζ-class glutathione S-transferases (GSTs) in both apo and glutathione-bound forms.

Multiple levels of gene regulation mediate differentiation of the intracellular pathogen Leishmania.

For many years, mRNA abundance has been used as the surrogate measure of gene expression in biological systems. However, recent genome-scale analyses in both bacteria and eukaryotes have revealed that mRNA levels correlate with steady-state protein abundance for only 50-70% of genes, indicating that translation and post-translation processes also play important roles in determining gene expression. What is not yet clear is whether dynamic processes such as cell cycle progression, differentiation, or response to environmental changes change the relationship between mRNA and protein abundance.

TriTrypDB: a functional genomic resource for the Trypanosomatidae.

TriTrypDB (http://tritrypdb.org) is an integrated database providing access to genome-scale datasets for kinetoplastid parasites, and supporting a variety of complex queries driven by research and development needs. TriTrypDB is a collaborative project, utilizing the GUS/WDK computational infrastructure developed by the Eukaryotic Pathogen Bioinformatics Resource Center (EuPathDB.

Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei.

Background: Trypanosoma brucei, the causative agent of African sleeping sickness, undergoes a complex developmental cycle that takes place in mammalian and insect hosts and is accompanied by changes in metabolism and cellular morphology. While differences in mRNA expression have been described for many genes, genome-wide expression analyses have been largely lacking. Trypanosomatids represent a unique case in eukaryotes in that they transcribe protein-coding genes as large polycistronic units, and rarely regulate gene expression at the level of transcription initiation.

Implementation of microarrays for Methylobacterium extorquens AM1.

Microarrays are an important tool for understanding global gene expression changes, and the resulting data sets can be used to direct physiologic and metabolic studies. To take advantage of this technology, 60-mer oligonucleotide microarrays were designed for Methylobacterium extorquens AM1 to study gene expression changes that occur under differing physiological conditions. The carbon utilization pathways for methanol and succinate have been well characterized, and growth with these substrates was chosen as the condition used to validate the microarray data.

The genome of the kinetoplastid parasite, Leishmania major.

Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function.

The C.A.Ve. software tool for genome assembly.

Misassembly due to the presence of repetitive DNA sequences often complicates the contig assembly stage of genome sequencing. Accurate physical representations of chromosomes, such as restriction maps or contig maps, provide a means for validating the sequence assembly and clarifying alignment ambiguity. The Contig Assembly Verifier (CAVe) software tool allows the researcher to automatically reconcile a sequence assembly with a physical representation, and, if needed, to modify the assembly using an intuitive graphical user interface.

Identification of genes overexpressed in head and neck squamous cell carcinoma using a combination of complementary DNA subtraction and microarray analysis.

Objectives/hypothesis: To discover unique genes specific for squamous cell carcinoma of the head and neck for eventual development as tumor markers and vaccine candidates.

Study Design: Molecular biological analysis of fresh-frozen head and neck squamous cell cancer (HNSCC).

Methods: A subtractive library was made from two HNSCC and six normal tissues using a polymerase chain reaction (PCR)-based approach.