Memorial University of Newfoundland

About: Memorial University of Newfoundland is a education organization based out in St. John's, Newfoundland and Labrador, Canada. It is known for research contribution in the topics: Population & Context (language use). The organization has 13818 authors who have published 27785 publications receiving 743594 citations. The organization is also known as: Memorial University & Memorial University of Newfoundland and Labrador.

Mass Spectrometry, Review of the Basics: Electrospray, MALDI, and Commonly Used Mass Analyzers

Abstract: Mass spectrometry (MS) has progressed to become a powerful analytical tool for both quantitative and qualitative applications. The first mass spectrometer was constructed in 1912 and since then it has developed from only analyzing small inorganic molecules to biological macromolecules, practically with no mass limitations. Proteomics research, in particular, increasingly depends on MS technologies. The ability of mass spectrometry analyzing proteins and other biological extracts is due to the advances gained through the development of soft ionization techniques such as electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) that can transform biomolecules into ions. ESI can efficiently be interfaced with separation techniques enhancing its role in the life and health sciences. MALDI, however, has the advantage of producing singly charges ions of peptides and proteins, minimizing spectral complexity. Regardless of the ionization source, the sensitivity of a mass spect...

Present Trends and the Future of Zircon in Geochronology: Laser Ablation ICPMS

Abstract: In situ U-Th-Pb geochronology was born some two decades ago with the introduction and development of high-resolution secondary ion mass spectrometry (SIMS or SHRIMP [Sensitive High Mass Resolution Ion MicroProbe]; Compston et al. 1984, Williams 1998, Compston 1999, Davis et al.; this volume, Ireland and Williams, this volume). This technique clearly demonstrated the existence of age heterogeneities within the single crystals of zircon and other accessory phases and therefore the need for high-spatial resolution (tens to hundreds of cubic micrometers) geochronological data. In situ dating by ion probe is capable of achieving an analytical precision that is only an order of magnitude worse than the conventional isotope dilution-thermal ionization mass spectrometry (ID-TIMS) dating technique. It has the advantage, however, of more readily identifying concordant portions of grains, does not require chemical treatment of samples prior to the analysis, is essentially nondestructive, and can achieve greater sample throughputs. A major obstacle to the wider use of ion probe dating has always been the high cost of instrumentation and hence relative scarcity of suitably equipped geologic laboratories. Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) emerged in 1985 and rapidly became an important analytical tool for trace element determinations in geological samples (Jackson et al. 1992). It was soon realized that the large variations in radiogenic Pb and Pb/ U isotopic ratios found in nature could be resolved by ICPMS techniques and, when coupled to a laser, ICPMS could be used as a dating tool similar to the ion probe. The pioneering work of Feng et al. (1993), Fryer et al. (1993), Hirata and Nesbitt (1995) and Jackson et al. (1996) illustrated the potential usefulness of laser sampling for in situ dating by ICPMS particularly well. However, these studies and others that followed also revealed the major …

Interorgan Amino Acid Transport and its Regulation

Abstract: Interorgan amino acid transport is a highly active and regulated process that provides amino acids to all tissues of the body, both for protein synthesis and to enable amino acids to be used for specific metabolic functions. It is also an important component of plasma amino acid homeostasis. Net movement of amino acids depends on the physiological and nutritional state. For example, in the fed state the dominant flux is from the intestine to the other tissues. In starvation the dominant flux is from muscle to the liver and kidney. A number of general principles underlie many amino acid fluxes: i) The body does not have a store for amino acids. This means that dietary amino acids, in excess of those required for protein synthesis, are rapidly catabolized; ii) Amino acid catabolism must occur in a manner that does not elevate blood ammonia. Thus, extrasplanchnic amino acid metabolism often involves an innocuous means of transporting nitrogen to the liver; iii) Because most amino acids are glucogenic, there will be a considerable flux of amino acids to the gluconeogenic organs when there is a need to produce glucose. In addition to these bulk flows, fluxes of many specific amino acids underlie specific organ function. These include intestinal oxidation of enteral amino acids, the intestinal/renal axis for arginine production, the brain uptake of neurotransmitter precursors and renal glutamine metabolism. There is no single means of regulating amino acid fluxes; rather, such varied mechanisms as substrate supply, enzyme activity, transporter activity and competitive inhibition of transport are all found.

Utility of whole-exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care.

Abstract: An accurate diagnosis is an integral component of patient care for children with rare genetic disease. Recent advances in sequencing, in particular whole-exome sequencing (WES), are identifying the genetic basis of disease for 25-40% of patients. The diagnostic rate is probably influenced by when in the diagnostic process WES is used. The Finding Of Rare Disease GEnes (FORGE) Canada project was a nation-wide effort to identify mutations for childhood-onset disorders using WES. Most children enrolled in the FORGE project were toward the end of the diagnostic odyssey. The two primary outcomes of FORGE were novel gene discovery and the identification of mutations in genes known to cause disease. In the latter instance, WES identified mutations in known disease genes for 105 of 362 families studied (29%), thereby informing the impact of WES in the setting of the diagnostic odyssey. Our analysis of this dataset showed that these known disease genes were not identified prior to WES enrollment for two key reasons: genetic heterogeneity associated with a clinical diagnosis and atypical presentation of known, clinically recognized diseases. What is becoming increasingly clear is that WES will be paradigm altering for patients and families with rare genetic diseases.