Tim Wood

Bio: Tim Wood is an academic researcher from Anschutz Medical Campus. The author has contributed to research in topics: Newborn screening & Mucopolysaccharidosis. The author has an hindex of 23, co-authored 58 publications receiving 1703 citations. Previous affiliations of Tim Wood include Yale University.

X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome.

Abstract: Polyamines (putrescine, spermidine, spermine) are ubiquitous, simple molecules that interact with a variety of other molecules in the cell, including nucleic acids, phospholipids and proteins. Various studies indicate that polyamines are essential for normal cell growth and differentiation. Furthermore, these molecules, especially spermine, have been shown to modulate ion channel activities of certain cells. Nonetheless, little is known about the specific cellular functions of these compounds, and extensive laboratory investigations have failed to identify a heritable condition in humans in which polyamine synthesis is perturbed. We report the first polyamine deficiency syndrome caused by a defect in spermine synthase (SMS). The defect results from a splice mutation, and is associated with the Snyder–Robinson syndrome (SRS, OMIM_309583), an X-linked mental retardation disorder. The affected males have mild-to-moderate mental retardation (MR), hypotonia, cerebellar circuitry dysfunction, facial asymmetry, thin habitus, osteoporosis, kyphoscoliosis, decreased activity of SMS, correspondingly low levels of intracellular spermine in lymphocytes and fibroblasts, and elevated spermidine/spermine ratios. The clinical features observed in SRS are consistent with cerebellar dysfunction and a defective functioning of red nucleus neurons, which, at least in rats, contain high levels of spermine. Additionally, the presence of MR reflects a role for spermine in cognitive function, possibly by spermine's ability to function as an ‘intrinsic gateway’ molecule for inward rectifier K+ channels.

Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands

Abstract: Background Mucolipidoses II and III alpha/beta (ML II and ML III) are lysosomal disorders in which the essential mannose 6-phosphate recognition marker is not synthesised on to lysosomal hydrolases and other glycoproteins. The disorders are caused by mutations in GNPTAB, which encodes two of three subunits of the heterohexameric enzyme, N-acetylglucosamine-1phosphotransferase. Objectives Clinical, biochemical and molecular findings in 61 probands (63 patients) are presented to provide a broad perspective of these mucolipidoses. Methods GNPTAB was sequenced in all probands and/or parents. The activity of several lysosomal enzymes was measured in plasma, and GlcNAc-1-phosphotransferase was assayed in leucocytes. Thirty-six patients were studied in detail, allowing extensive clinical data to be

X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology

Abstract: Mutations in the creatine transporter gene, SLC6A8 (MIM 30036), located in Xq28, have been found in families with X-linked mental retardation (XLMR) as well as in males with idiopathic mental retardation (MR). In order to estimate the frequency of such mutations in the MR population, a screening of 478 males with MR of unknown cause was undertaken. All 13 exons of SLC6A8 were sequenced using genomic DNA. Six novel potentially pathogenic mutations were identified that were not encountered in at least 588 male control chromosomes: two deletions (p.Asn336del, p.Ile347del) and a splice site alteration (c.1016+2C>T) are considered pathogenic based on the nature of the variant. A mutation (p.Arg391Trp) should be considered pathogenic owing to its localization in a highly conserved region. Two other missense variants (p.Lys4Arg, p.Gly26Arg) are not conserved but were not observed in over 300 male control chromosomes. Their pathogenicity is uncertain. A missense variant (p.Val182Met), was classified as a polymorphism based on a normal creatine/creatinine (Cr:Crn) ratio and cerebral creatine signal in proton magnetic resonance spectroscopy (H-MRS) in the patient. Furthermore, we found 14 novel intronic and neutral variants that were not encountered in at least 280 male control chromosomes and should be considered as unclassified variants. Our findings of a minimum of four pathogenic mutations and two potentially pathogenic mutations indicate that about 1% of males with MR of unknown etiology might have a SLC6A8 mutation. Thus, DNA sequence analysis and/or a Cr:Crn urine screen is warranted in any male with MR of unknown cause.

Short-term effects of a simulated acid rain upon the growth and nutrient relations of Pinus strobus , L.

Abstract: Acidified precipitation may affect the productivity of forests by altering the availability of plant nutrients of by affecting the ability of trees to absorb and assimilate those nutrients. In this study, the short-term effects of simulated acid rain (pH range 5.6 - 2.3) upon the growth and nutrient relations of Eastern White Pine seedlings (Pinus strobus, L.) grown in a sandy loam soil were examined. Soil chemistry, soil leachate chemistry, seedling tissue chemistry, and seedling productivity were monitored. In spite of increased leaching of cations from the soil, resulting in near depletion of available K+1, Mg+2, and Ca+2 at pH 2.3, seedling productivity increased with acidity through the 20-week experimental period. Foliar nitrogen concentrations indicate that fertilization with NO3-1, added to the rain as HNO3, may have caused the growth increase. Implications of cation losses and NO3-1 fertilization are discussed.

Polyamines: essential factors for growth and survival.

Abstract: Polyamines are low molecular weight, aliphatic polycations found in the cells of all living organisms. Due to their positive charges, polyamines bind to macromolecules such as DNA, RNA, and proteins. They are involved in diverse processes, including regulation of gene expression, translation, cell proliferation, modulation of cell signalling, and membrane stabilization. They also modulate the activities of certain sets of ion channels. Because of these multifaceted functions, the homeostasis of polyamines is crucial and is ensured through regulation of biosynthesis, catabolism, and transport. Through isolation of the genes involved in plant polyamine biosynthesis and loss-of-function experiments on the corresponding genes, their essentiality for growth is reconfirmed. Polyamines are also involved in stress responses and diseases in plants, indicating their importance for plant survival. This review summarizes the recent advances in polyamine research in the field of plant science compared with the knowledge obtained in microorganisms and animal systems.

(Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms

Abstract: The serum- and glucocorticoid-inducible kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress (including cell shrinkage) and hormones (including gluco- and mineralocort...

Mammalian polyamine metabolism and function

Abstract: Polyamines are ubiquitous small basic molecules that play multiple essential roles in mammalian physiology. Their cellular content is highly regulated and there is convincing evidence that altered metabolism is involvement in many disease states. Drugs altering polyamine levels may therefore have a variety of important targets. This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism.

Acid Rain: A Serious Regional Environmental Problem

Abstract: At present, acid rain or snow is falling on most of the northeastern United States. The annual acidity value averages about pH 4, but values between pH 2.1 and 5 have been recorded for individual storms. The acidity of precipitation in this region apparently increased about 20 years ago, and the increase may have been associated with the augmented use of natural gas and with the installation of particle-removal devices in tall smokestacks. Only some of the ecological and economic effects of this widespread introduction of strong acids into natural systems are known at present, but clearly they must be considered in proposals for new energy sources and in the development of air quality emission standards.