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1.  Poikilocytosis in Rabbits: Prevalence, Type, and Association with Disease 
PLoS ONE  2014;9(11):e112455.
Rabbits (Oryctolagus cuniculus) are a popular companion animal, food animal, and animal model of human disease. Abnormal red cell shapes (poikilocytes) have been observed in rabbits, but their significance is unknown. The objective of this study was to investigate the prevalence and type of poikilocytosis in pet rabbits and its association with physiologic factors, clinical disease, and laboratory abnormalities. We retrospectively analyzed blood smears from 482 rabbits presented to the University of California-Davis Veterinary Medical Teaching Hospital from 1990 to 2010. Number and type of poikilocytes per 2000 red blood cells (RBCs) were counted and expressed as a percentage. Acanthocytes (>3% of RBCs) were found in 150/482 (31%) rabbits and echinocytes (>3% of RBCs) were found in 127/482 (27%) of rabbits, both healthy and diseased. Thirty-three of 482 (7%) rabbits had >30% acanthocytes and echinocytes combined. Mild to moderate (>0.5% of RBCs) fragmented red cells (schistocytes, microcytes, keratocytes, spherocytes) were found in 25/403 (6%) diseased and 0/79 (0%) healthy rabbits (P = 0.0240). Fragmentation and acanthocytosis were more severe in rabbits with inflammatory disease and malignant neoplasia compared with healthy rabbits (P<0.01). The % fragmented cells correlated with % polychromasia, RDW, and heterophil, monocyte, globulins, and fibrinogen concentrations (P<0.05). Echinocytosis was significantly associated with renal failure, azotemia, and acid-base/electrolyte abnormalities (P<0.05). Serum cholesterol concentration correlated significantly with % acanthocytes (P<0.0001), % echinocytes (P = 0.0069), and % fragmented cells (P = 0.0109), but correlations were weak (Spearman ρ <0.02). These findings provide important insights into underlying pathophysiologic mechanisms that appear to affect the prevalence and type of naturally-occurring poikilocytosis in rabbits. Our findings support the need to carefully document poikilocytes in research investigations and in clinical diagnosis and to determine their diagnostic and prognostic value.
doi:10.1371/journal.pone.0112455
PMCID: PMC4234375  PMID: 25402479
2.  Trace Metals in Upland Headwater Lakes in Ireland 
Ambio  2013;42(6):702-714.
Trace elements (n = 23) in Irish headwater lakes (n = 126) were investigated to determine their ambient concentrations, fractionation (total, dissolved, and non-labile), and geochemical controls. Lakes were generally located in remote upland, acid-sensitive regions along the coastal margins of the country. Total trace metal concentrations were low, within the range of natural pristine surface waters; however, some lakes (~20 %) had inorganic labile aluminum and manganese at levels potentially harmful to aquatic organisms. Redundancy analysis indicated that geochemical weathering was the dominant controlling factor for total metals, compared with acidity for dissolved metals. In addition, many metals were positively correlated with dissolved organic carbon indicating their affinity (or complexation) with humic substances (e.g., aluminum, iron, mercury, lead). However, a number of trace metals (e.g., aluminum, mercury, zinc) were correlated with anthropogenic acidic deposition (i.e., non-marine sulfate), suggesting atmospheric sources or elevated leaching owing to acidic deposition. As transboundary air pollution continues to decline, significant changes in the cycling of trace metals is anticipated.
doi:10.1007/s13280-013-0381-y
PMCID: PMC3758813  PMID: 23436112
Water chemistry; Long-range atmospheric transport; Fractionation; Dissolved organic carbon; Geochemical weathering; Marine inputs
3.  Characterization of Genipin-Modified Dentin Collagen 
BioMed Research International  2014;2014:702821.
Application of biomodification techniques to dentin can improve its biochemical and biomechanical properties. Several collagen cross-linking agents have been reported to strengthen the mechanical properties of dentin. However, the characteristics of collagen that has undergone agent-induced biomodification are not well understood. The objective of this study was to analyze the effects of a natural cross-linking agent, genipin (GE), on dentin discoloration, collagen stability, and changes in amino acid composition and lysyl oxidase mediated natural collagen cross-links. Dentin collagen obtained from extracted bovine teeth was treated with three different concentrations of GE (0.01%, 0.1%, and 0.5%) for several treatment times (0–24 h). Changes in biochemical properties of NaB3H4-reduced collagen were characterized by amino acid and cross-link analyses. The treatment of dentin collagen with GE resulted in a concentration- and time-dependent pigmentation and stability against bacterial collagenase. The lysyl oxidase-mediated trivalent mature cross-link, pyridinoline, showed no difference among all groups while the major divalent immature cross-link, dehydro-dihydroxylysinonorleucine/its ketoamine in collagen treated with 0.5% GE for 24 h, significantly decreased compared to control (P < 0.05). The newly formed GE-induced cross-links most likely involve lysine and hydroxylysine residues of collagen in a concentration-dependent manner. Some of these cross-links appear to be reducible and stabilized with NaB3H4.
doi:10.1155/2014/702821
PMCID: PMC3984863  PMID: 24795891
4.  Outcome after redo-mitral valve replacement in adult patients: a 10-year single-centre experience 
The aim of this study was to investigate the overall outcome of adult patients undergoing redo-mitral valve replacement (redo-MVR) at our institution. Forty-nine patients (24 males) underwent redo-MVR with either bioprosthetic (n = 24) or mechanical valves (n = 25) between January 2000 and 2010. Median age of patients was 63 years (range 21–80 years), and the mean additive EuroSCORE was 12 ± 4. Median time to re-operation was 8.2 ± 6.6 years for first time redo-MVR and 6.4 ± 5.6 years for second-time redo-MVR. Indications included prosthetic endocarditis (n = 22), para-prosthetic leak (n = 12), structural valve degeneration (n = 8), prosthetic valve thrombosis (n = 6) and malignancy (n = 1). The mean follow-up was 47.5 ± 37.0 months (range 0.1–112.3 months). In-hospital mortality was 12% (n = 6). Mean hospital stay was 17 ± 11 days (range 8–50 days). Actuarial survival at 1 and 5 years was 81 ± 5% and 72 ± 6%, respectively. Three patients required re-intervention: two for prosthetic valve endocarditis and one for para-prosthetic leak. Multivariate analysis showed that overall survival was associated with the LVEF < 50% (P < 0.001), concomitant AVR (P < 0.001) and urgent surgery (P = 0.03).
doi:10.1093/icvts/ivs005
PMCID: PMC3735849  PMID: 22294560
Mitral; Redo; Outcome
5.  Changes in the Chemistry of Small Irish lakes 
Ambio  2011;41(2):170-179.
A re-survey of acid-sensitive lakes in Ireland (initial survey 1997) was carried out during spring 2007 (n = 60). Since 1997, atmospheric emissions of sulfur dioxide and deposition of non-marine sulfate (SO42−) in Ireland have decreased by ~63 and 36%, respectively. Comparison of water chemistry between surveys showed significant decreases in the concentration of SO42−, non-marine SO42−, and non-marine base cations. In concert, alkalinity increased significantly; however, no change was observed in surface water pH and total aluminum. High inter-annual variability in sea salt inputs and increasing (albeit non-significant) dissolved organic carbon may have influenced the response of pH and total aluminum (as ~70% is organic aluminum). Despite their location on the western periphery of Europe, and dominant influence from Atlantic air masses, the repeat survey suggests that the chemistry of small Irish lakes has shown a significant response to reductions in air pollution driven primarily by the implementation of the Gothenburg Protocol under the UNECE Convention on Long-Range Transboundary Air Pollution.
doi:10.1007/s13280-011-0177-x
PMCID: PMC3357841  PMID: 22396096
Lake chemistry; Sulfate; Emissions; Sea salts; Dissolved organic carbon
6.  Congenital coronary artery disease 
BMJ : British Medical Journal  2008;336(7644):605.
doi:10.1136/bmj.39449.573356.DE
PMCID: PMC2267947
7.  Trypanosoma brucei UDP-galactose-4′-epimerase in ternary complex with NAD+ and the substrate analogue UDP-4-deoxy-4-fluoro-α-d-galactose 
The structure of recombinant T. brucei UDP-galactose-4′-epimerase cocrystallized with NAD+ and the substrate analogue UDP-4-deoxy-4-fluoro-α-d-galactose has been determined at medium resolution. Comparisons with structures of human and E. coli UDP-galactose-4′-epimerase–ligand complexes reveal that the hexose moieties are able to adopt different orientations in the active site.
The structure of the NAD-dependent oxidoreductase UDP-galactose-4′-epimerase from Trypanosoma brucei in complex with cofactor and the substrate analogue UDP-4-deoxy-4-fluoro-α-d-galactose has been determined using diffraction data to 2.7 Å resolution. Despite the high level of sequence and structure conservation between the trypanosomatid enzyme and those from humans, yeast and bacteria, the binding of the 4-fluoro-α-d-galactose moiety is distinct from previously reported structures. Of particular note is the observation that when bound to the T. brucei enzyme, the galactose moiety of this fluoro-derivative is rotated approximately 180° with respect to the orientation of the hexose component of UDP-glucose when in complex with the human enzyme. The architecture of the catalytic centre is designed to effectively bind different orientations of the hexose, a finding that is consistent with a mechanism that requires the sugar to maintain a degree of flexibility within the active site.
doi:10.1107/S1744309106028740
PMCID: PMC2242870  PMID: 16946458
short-chain dehydrogenase/reductases; Trypanosoma brucei; UDP-galactose-4′-epimerase; UDP-4-deoxy-4-fluoro-α-d-galactose
8.  Elevated carbon dioxide and ozone alter productivity and ecosystem carbon content in northern temperate forests 
Global Change Biology  2014;20(8):2492-2504.
Three young northern temperate forest communities in the north-central United States were exposed to factorial combinations of elevated carbon dioxide (CO2) and tropospheric ozone (O3) for 11 years. Here, we report results from an extensive sampling of plant biomass and soil conducted at the conclusion of the experiment that enabled us to estimate ecosystem carbon (C) content and cumulative net primary productivity (NPP). Elevated CO2 enhanced ecosystem C content by 11%, whereas elevated O3 decreased ecosystem C content by 9%. There was little variation in treatment effects on C content across communities and no meaningful interactions between CO2 and O3. Treatment effects on ecosystem C content resulted primarily from changes in the near-surface mineral soil and tree C, particularly differences in woody tissues. Excluding the mineral soil, cumulative NPP was a strong predictor of ecosystem C content (r2 = 0.96). Elevated CO2 enhanced cumulative NPP by 39%, a consequence of a 28% increase in canopy nitrogen (N) content (g N m−2) and a 28% increase in N productivity (NPP/canopy N). In contrast, elevated O3 lowered NPP by 10% because of a 21% decrease in canopy N, but did not impact N productivity. Consequently, as the marginal impact of canopy N on NPP (ΔNPP/ΔN) decreased through time with further canopy development, the O3 effect on NPP dissipated. Within the mineral soil, there was less C in the top 0.1 m of soil under elevated O3 and less soil C from 0.1 to 0.2 m in depth under elevated CO2. Overall, these results suggest that elevated CO2 may create a sustained increase in NPP, whereas the long-term effect of elevated O3 on NPP will be smaller than expected. However, changes in soil C are not well-understood and limit our ability to predict changes in ecosystem C content.
doi:10.1111/gcb.12564
PMCID: PMC4261895  PMID: 24604779
air pollution; carbon sequestration; carbon storage; elevated carbon dioxide (CO2); free-air CO2 enrichment (FACE); net primary productivity (NPP); nitrogen; soil carbon
9.  Protein Therapy 
PMCID: PMC2616368  PMID: 18118670

Results 1-9 (9)