The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum

Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200–300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a “just-in-time” manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates

National Market Cow and Bull Beef Quality Audit - 1999

The National Non-Fed Beef Quality Audit – 1994 (NNFBQA-94) was conducted to benchmark the quality characteristics of market cows and bulls in the beef and dairy industries for purposes of encouraging implementation of quality management practices within the beef industry. From this audit, it was determined that producers were losing $69.90 for each market cow and bull harvested due to quality defects. As a means of recovering the lost value, producers were provided three means by which they could begin to recapture the lost value: 1) Manage market cows and bulls to minimize defects and quality deficiencies, 2) Monitor the health and condition of market cows and bulls, and 3) Market cows and bulls in a timely manner. The audit, now referred to as the National Market Cow and Bull Beef Quality Audit – 1999 (NMCBBQA-99), was conducted again in 1999 to determine the quality and consistency of market cows and bulls and to measure improvement in quality and consistency since 1994. Specifically, objectives of NMCBBQA-99 were to 1) identify and quantify, numerically and monetarily, the incidence of quality defects in U.S. market cows and bulls, their carcasses and offal items; 2) characterize as many as possible of the causes of quality defects in market cows and bulls; 3) compare the results of the NMCBBQA-99 to the NNFBQA-94; and 4) identify strategies and tactics to pursue and employ efforts to reduce/eliminate specific defects in the quality and consistency of market cow and bull beef

Hyaluronan: Pharmaceutical characterization and drug delivery

Hyaluronic acid ( HA), is a polyanionic polysaccharide that consists of N-acetyl-D-glucosamine and beta-glucoronic acid. It is most frequently referred to as hyaluronan because it exists in vivo as a polyanion and not in the protonated acid form. HA is distributed widely in vertebrates and presents as a component of the cell coat of many strains of bacteria. Initially the main functions of HA were believed to be mechanical as it has a protective, structure stabilizing and shock-absorbing role in the body. However, more recently the role of HA in the mediation of physiological functions via interaction with binding proteins and cell surface receptors including morphogenesis, regeneration, wound healing, and tumor invasion, as well as in the dynamic regulation of such interactions on cell signaling and behavior has been documented. The unique viscoelastic nature of hyaluronan along with its biocompatibility and nonimmunogenicity has led to its use in a number of cosmetic, medical, and pharmaceutical applications. More recently, HA has been investigated as a drug delivery agent for ophthalmic, nasal, pulmonary, parenteral, and dermal routes. The purpose of our review is to describe the physical, chemical, and biological properties of native HA together with how it can be produced and assayed along with a detailed analysis of its medical and pharmaceutical applications.Peer reviewe