26 results on '"Murray, Jason"'
Search Results
2. dATP elevation induces myocardial metabolic remodeling to support improved cardiac function.
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Mhatre, Ketaki N., Murray, Jason D., Flint, Galina, McMillen, Timothy S., Weber, Gerhard, Shakeri, Majid, Tu, An-Yue, Steczina, Sonette, Weiss, Robert, Marcinek, David J., Murry, Charles E., Raftery, Daniel, Tian, Rong, Moussavi-Harami, Farid, and Regnier, Michael
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OXYGEN consumption , *RIBONUCLEOSIDE diphosphate reductase , *TRANSGENIC mice , *HEART metabolism , *OXIDATIVE phosphorylation , *MYOSIN - Abstract
Hallmark features of systolic heart failure are reduced contractility and impaired metabolic flexibility of the myocardium. Cardiomyocytes (CMs) with elevated deoxy ATP (dATP) via overexpression of ribonucleotide reductase (RNR) enzyme robustly improve contractility. However, the effect of dATP elevation on cardiac metabolism is unknown. Here, we developed proteolysis-resistant versions of RNR and demonstrate that elevation of dATP/ATP to ∼1% in CMs in a transgenic mouse (TgRRB) resulted in robust improvement of cardiac function. Pharmacological approaches showed that CMs with elevated dATP have greater basal respiratory rates by shifting myosin states to more active forms, independent of its isoform, in relaxed CMs. Targeted metabolomic profiling revealed a significant reprogramming towards oxidative phosphorylation in TgRRB-CMs. Higher cristae density and activity in the mitochondria of TgRRB-CMs improved respiratory capacity. Our results revealed a critical property of dATP to modulate myosin states to enhance contractility and induce metabolic flexibility to support improved function in CMs. [Display omitted] • Ubiquitylation-resistant variant RRB in a transgenic mice model (TgRRB) elevates dATP in the heart and improves function. • TgRRB-CMs show greater basal oxygen consumption due to changes in myosin state by dATP. • TgRRB-CMs respond to elevated function with higher pools of oxidative metabolites, elevated OXPHOS, FAO, and energy reserve. • Long-term mitochondrial remodeling may occur to accommodate for the higher energy demands of the high functioning TgRRB-CMs. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Evaluation of bactericidal and anti-biofilm properties of a novel surface-active organosilane biocide against healthcare associated pathogens and Pseudomonas aeruginosa biolfilm.
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Murray, Jason, Muruko, Tendai, Gill, Chris I. R., Kearney, M. Patricia, Farren, David, Scott, Michael G., McMullan, Geoff, and Ternan, Nigel G.
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BACTERICIDES , *BIOFILMS , *PSEUDOMONAS aeruginosa , *NOSOCOMIAL infections , *ANTI-infective agents - Abstract
Healthcare acquired infections (HAI) pose a great threat in hospital settings and environmental contamination can be attributed to the spread of these. De-contamination and, significantly, prevention of re-contamination of the environment could help in preventing/reducing this threat. Goldshield (GS5) is a novel organosilane biocide marketed as a single application product with residual biocidal activity. We tested the hypothesis that GS5 could provide longer-term residual antimicrobial activity than existing disinfectants once applied to surfaces. Thus, the residual bactericidal properties of GS5, Actichlor and Distel against repeated challenge with Staphylococcus aureus ATCC43300 were tested, and showed that GS5 alone exhibited longer-term bactericidal activity for up to 6 days on 316I stainless steel surfaces. Having established efficacy against S. aureus, we tested GS5 against common healthcare acquired pathogens, and demonstrated that, on average, a 1 log10 bactericidal effect was exhibited by GS5 treated surfaces, although biocidal activity varied depending upon the surface type and the species of bacteria. The ability of GS5 to prevent Pseudomonas aeruginosa biofilm formation was measured in standard microtitre plate assays, where it had no significant effect on either biofilm formation or development. Taken together the data suggests that GS5 treatment of surfaces may be a useful means to reducing bacterial contamination in the context of infection control practices. [ABSTRACT FROM AUTHOR]
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- 2017
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4. Structural characterization of ribosome recruitment and translocation by type IV IRES.
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Murray, Jason, Savva, Christos G., Byung-Sik Shin, Dever, Thomas E., Ramakrishnan, V., and Fernández, Israel S.
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VIRAL ribosomes , *INITIATION factors (Biochemistry) , *CHROMOSOMAL translocation , *MESSENGER RNA , *GENETIC translation , *ELECTRON cryomicroscopy , *POST-translational modification , *VIRUSES - Abstract
Viral mRNA sequences with a type IV IRES are able to initiate translation without any host initiation factors. Initial recruitment of the small ribosomal subunit as well as two translocation steps before the first peptidyl transfer are essential for the initiation of translation by these mRNAs. Using electron cryomicroscopy (cryo-EM) we have structurally characterized at high resolution how the Cricket Paralysis Virus Internal Ribosomal Entry Site (CrPV-IRES) binds the small ribosomal subunit (40S) and the translocation intermediate stabilized by elongation factor 2 (eEF2). The CrPV-IRES restricts the otherwise flexible 40S head to a conformation compatible with binding the large ribosomal subunit (60S). Once the 60S is recruited, the binary CrPV-IRES/80S complex oscillates between canonical and rotated states (Fernández et al., 2014; Koh et al., 2014), as seen for pre-translocation complexes with tRNAs. Elongation factor eEF2 with a GTP analog stabilizes the ribosome-IRES complex in a rotated state with an extra ~3 degrees of rotation. Key residues in domain IV of eEF2 interact with pseudoknot I (PKI) of the CrPV-IRES stabilizing it in a conformation reminiscent of a hybrid tRNA state. The structure explains how diphthamide, a eukaryotic and archaeal specific post-translational modification of a histidine residue of eEF2, is involved in translocation. [ABSTRACT FROM AUTHOR]
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- 2016
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5. Franchising (& Distribution) Currents.
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Oates, Daniel J., Murray, Jason M., and Kilejian, Maral
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RETAIL franchises , *FRANCHISOR-franchisee relationships , *CONTRACTS , *DAMAGES (Law) , *INVOICES - Abstract
The article presents court cases related to international franchising as of October 1, 2015. The case Machado v. System4 LLC involves the franchise agreements that authorized plaintiffs to use the proprietary information of System4 LLC. The case Yumilicious Franchise LLC v. Barrie outlines the recovery of damages sought by the franchisor for unpaid invoices. Martin v. Bimbo Foods Bakeries Distribution LLC case cites the franchise agreement breach by failing to operate the route at a profit.
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- 2015
6. Prednisolone Attenuates Improvement of Cardiac and Skeletal Contractile Function and Histopathology by Lisinopril and Spironolactone in the mdx Mouse Model of Duchenne Muscular Dystrophy.
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Janssen, Paul M. L., Murray, Jason D., Schill, Kevin E., Rastogi, Neha, Schultz, Eric J., Tran, Tam, Raman, Subha V., and Rafael-Fortney, Jill A.
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DUCHENNE muscular dystrophy , *GENETIC disorders , *MUSCLE weakness , *ETIOLOGY of diseases , *ANGIOTENSIN converting enzyme , *LABORATORY mice , *SPIRONOLACTONE , *HISTOPATHOLOGY , *MUSCLE contraction - Abstract
Duchenne muscular dystrophy (DMD) is an inherited disease that causes striated muscle weakness. Recently, we showed therapeutic effects of the combination of lisinopril (L), an angiotensin converting enzyme (ACE) inhibitor, and spironolactone (S), an aldosterone antagonist, in mice lacking dystrophin and haploinsufficient for utrophin (utrn+/−;mdx, het mice); both cardiac and skeletal muscle function and histology were improved when these mice were treated early with LS. It was unknown to what extent LS treatment is effective in the most commonly used DMD murine model, the mdx mouse. In addition, current standard-of-care treatment for DMD is limited to corticosteroids. Therefore, potentially useful alternative or additive drugs need to be both compared directly to corticosteroids and tested in presence of corticosteroids. We evaluated the effectiveness of this LS combination in the mdx mouse model both compared with corticosteroid treatment (prednisolone, P) or in combination (LSP). We tested the additional combinatorial treatment containing the angiotensin II receptor blocker losartan (T), which is widely used to halt and treat the developing cardiac dysfunction in DMD patients as an alternative to an ACE inhibitor. Peak myocardial strain rate, assessed by magnetic resonance imaging, showed a negative impact of P, whereas in both diaphragm and extensor digitorum longus (EDL) muscle contractile function was not significantly impaired by P. Histologically, P generally increased cardiac damage, estimated by percentage area infiltrated by IgG as well as by collagen staining. In general, groups that only differed in the presence or absence of P (i.e. mdx vs. P, LS vs. LSP, and TS vs. TSP) demonstrated a significant detrimental impact of P on many assessed parameters, with the most profound impact on cardiac pathology. [ABSTRACT FROM AUTHOR]
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- 2014
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7. Trends in product recalls within the agri-food industry: Empirical evidence from the USA, UK and the Republic of Ireland
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Potter, Antony, Murray, Jason, Lawson, Benn, and Graham, Stephanie
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FOOD industry , *FOOD recall , *FOOD safety , *HAZARDOUS substances & health - Abstract
The increasing frequency of product recalls within the agri-food industry has led many to question food safety. Research studies also often focus on biological hazards without considering how past, present and emerging risks change over time. We undertake a systematic review of the different biological, operational and chemical hazards within the agri-food industry using a dataset of 2070 registered food recalls in the USA, UK and Republic of Ireland between 2004 and 2010. We show product recalls have become more frequent over time and operational hazards, rather than biological and chemical hazards, are the most frequent recall type within the agri-food industry. [ABSTRACT FROM AUTHOR]
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- 2012
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8. Myosin dynamics during relaxation in mouse soleus muscle and modulation by 2′‐deoxy‐ATP.
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Ma, Weikang, Childers, Matthew, Murray, Jason, Moussavi‐Harami, Farid, Gong, Henry, Weiss, Robert, Daggett, Valerie, Irving, Thomas, and Regnier, Michael
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SOLEUS muscle , *MYOSIN , *MOLECULES , *MOLECULAR dynamics , *STRUCTURAL dynamics - Abstract
Key points: Skeletal muscle relaxation has been primarily studied by assessing the kinetics of force decay. Little is known about the resultant dynamics of structural changes in myosin heads during relaxation.The naturally occurring nucleotide 2‐deoxy‐ATP (dATP) is a myosin activator that enhances cross‐bridge binding and kinetics.X‐ray diffraction data indicate that with elevated dATP, myosin heads were extended closer to actin in relaxed muscle and myosin heads return to an ordered, resting state after contraction more quickly.Molecular dynamics simulations of post‐powerstroke myosin suggest that dATP induces structural changes in myosin heads that increase the surface area of the actin‐binding regions promoting myosin interaction with actin, which could explain the observed delays in the onset of relaxation.This study of the dATP‐induced changes in myosin may be instructive for determining the structural changes desired for other potential myosin‐targeted molecular compounds to treat muscle diseases. Here we used time‐resolved small‐angle X‐ray diffraction coupled with force measurements to study the structural changes in FVB mouse skeletal muscle sarcomeres during relaxation after tetanus contraction. To estimate the rate of myosin deactivation, we followed the rate of the intensity recovery of the first‐order myosin layer line (MLL1) and restoration of the resting spacing of the third and sixth order of meridional reflection (SM3 and SM6) following tetanic contraction. A transgenic mouse model with elevated skeletal muscle 2‐deoxy‐ATP (dATP) was used to study how myosin activators may affect soleus muscle relaxation. X‐ray diffraction evidence indicates that with elevated dATP, myosin heads were extended closer to actin in resting muscle. Following contraction, there is a slight but significant delay in the decay of force relative to WT muscle while the return of myosin heads to an ordered resting state was initially slower, then became more rapid than in WT muscle. Molecular dynamics simulations of post‐powerstroke myosin suggest that dATP induces structural changes in myosin that increase the surface area of the actin‐binding regions, promoting myosin interaction with actin. With dATP, myosin heads may remain in an activated state near the thin filaments following relaxation, accounting for the delay in force decay and the initial delay in recovery of resting head configuration, and this could facilitate subsequent contractions. Key points: Skeletal muscle relaxation has been primarily studied by assessing the kinetics of force decay. Little is known about the resultant dynamics of structural changes in myosin heads during relaxation.The naturally occurring nucleotide 2‐deoxy‐ATP (dATP) is a myosin activator that enhances cross‐bridge binding and kinetics.X‐ray diffraction data indicate that with elevated dATP, myosin heads were extended closer to actin in relaxed muscle and myosin heads return to an ordered, resting state after contraction more quickly.Molecular dynamics simulations of post‐powerstroke myosin suggest that dATP induces structural changes in myosin heads that increase the surface area of the actin‐binding regions promoting myosin interaction with actin, which could explain the observed delays in the onset of relaxation.This study of the dATP‐induced changes in myosin may be instructive for determining the structural changes desired for other potential myosin‐targeted molecular compounds to treat muscle diseases. [ABSTRACT FROM AUTHOR]
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- 2020
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9. Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes.
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Shao, Sichen, Murray, Jason, Brown, Alan, Taunton, Jack, Ramakrishnan, V., and Hegde, Ramanujan S.
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GUANOSINE triphosphatase , *RIBOSOMAL proteins , *MESSENGER RNA , *PEPTIDYLTRANSFERASE , *PROTEIN synthesis - Abstract
Summary In eukaryotes, accurate protein synthesis relies on a family of translational GTPases that pair with specific decoding factors to decipher the mRNA code on ribosomes. We present structures of the mammalian ribosome engaged with decoding factor⋅GTPase complexes representing intermediates of translation elongation (aminoacyl-tRNA⋅eEF1A), termination (eRF1⋅eRF3), and ribosome rescue (Pelota⋅Hbs1l). Comparative analyses reveal that each decoding factor exploits the plasticity of the ribosomal decoding center to differentially remodel ribosomal proteins and rRNA. This leads to varying degrees of large-scale ribosome movements and implies distinct mechanisms for communicating information from the decoding center to each GTPase. Additional structural snapshots of the translation termination pathway reveal the conformational changes that choreograph the accommodation of decoding factors into the peptidyl transferase center. Our results provide a structural framework for how different states of the mammalian ribosome are selectively recognized by the appropriate decoding factor⋅GTPase complex to ensure translational fidelity. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Fast and sensitive HPLC–MS/MS method for direct quantification of intracellular deoxyribonucleoside triphosphates from tissue and cells.
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Olafsson, Sigurast, Whittington, Dale, Murray, Jason, Regnier, Michael, and Moussavi-Harami, Farid
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DEOXYRIBONUCLEOSIDES , *TISSUE analysis , *DNA synthesis , *DNA repair , *HEART cells , *INTRACELLULAR tracking , *LIQUID chromatography-mass spectrometry - Abstract
Deoxyribonucleoside triphosphates (dNTPs) are used in DNA synthesis and repair. Even slight imbalances can have adverse biological effects. This study validates a fast and sensitive HPLC–MS/MS method for direct quantification of intracellular dNTPs from tissue. Equal volumes of methanol and water were used for nucleotide extraction from mouse heart and gastrocnemius muscle and isolated cardiomyocytes followed by centrifugation to remove particulates. The resulting supernatant was analyzed on a porous graphitic carbon chromatography column using an elution gradient of ammonium acetate in water and ammonium hydroxide in acetonitrile with a run time of just 10 min. Calibration curves of all dNTPs ranged from 62.5 to 2500 fmol injections and demonstrated excellent linearity (r 2 > 0.99). The within day and between day precision, as measured by the coefficient of variation (CV (%)), was < 25% for all points, including the lower limit of quantification (LLOQ). The inter-day accuracy was within 12% of expected concentration for the LLOQ and within 7% for all other points on the calibration curve. The intra-day accuracy was within 22% for the LLOQ and within 11% for all points on the curve. Compared to existing methods, this study presents a faster and more sensitive method for dNTP quantification. [ABSTRACT FROM AUTHOR]
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- 2017
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11. Extended stability of vasopressin 0.2 unit/mL in PVC containers.
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Bae, Hyunbeom, Weaver, Eric, Ellis, Steffani, and Murray, Jason
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SALT , *PHYSICAL & theoretical chemistry , *REFRIGERATION & refrigerating machinery , *VINYL chloride , *DRUG stability , *MASS spectrometry , *DRUG storage , *VASOPRESSIN - Abstract
Purpose Vasopressin is used to maintain blood pressure in vasodilatory shock. Vasopressin is diluted from concentrated vials prior to administration as a continuous infusion. This study evaluates the physical and chemical stability changes of vasopressin diluted to 0.2 units/mL with 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags stored under refrigeration. Methods Vasopressin Injection, USP, 20 unit/mL solution was diluted to 0.2 unit/mL with 0.9% sodium chloride injection, and stability changes were evaluated over 10 days via mass spectrometry on days 0, 7, and 10. Results Solutions of vasopressin 0.2 unit/mL in 0.9% sodium chloride injection in PVC bags were physically stable and showed less than 10% degradation over 10 days of refrigerated storage. Conclusion Vasopressin 0.2 unit/mL may be given a beyond-use date (BUD) of 10 days based on United States Pharmacopeia BUD recommendations, with this study showing less than 10% degradation over 10 days of refrigerated storage. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Predicting response of migratory fish populations to dam removal.
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Hayes, Daniel, Fricano, Gail, Turek, James, Jordaan, Adrian, Kulik, Brandon, Baker, Mary, and Murray, Jason
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DAM retirement , *MIGRATORY fishes , *NATURAL resources , *COST effectiveness , *PREDICTION models , *FISH populations , *HABITATS - Abstract
Dam removal is a potential habitat restoration alternative through which parties responsible for injuries to natural resources can provide compensation for reductions in fish populations. Predicting the potential response of migratory fish populations to candidate dam removal(s) is a critical step in the natural resource damage assessment process to evaluate whether the proposed action provides adequate compensation. There is currently no standard approach to making such predictions, particularly in cases where data on candidate streams with dams are limited. We considered six modeling approaches for addressing this problem and evaluated the features of each approach for this application. We judged that an approach based on habitat suitability indices and weighted usable area provides the best balance between predictive capacity and cost of model implementation. This balancing act evaluating the cost effectiveness of predictive models is worth consideration in a wide range of fisheries modeling applications. [ABSTRACT FROM AUTHOR]
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- 2023
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13. Structural basis for stop codon recognition in eukaryotes.
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Brown, Alan, Shao, Sichen, Murray, Jason, Hegde, Ramanujan S., and Ramakrishnan, V.
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EUKARYOTES , *PROTEIN synthesis , *PROTEIN binding , *STOP codons , *RIBOSOMES , *RIBOSOMAL RNA , *CRYOELECTRONICS - Abstract
Termination of protein synthesis occurs when a translating ribosome encounters one of three universally conserved stop codons: UAA, UAG or UGA. Release factors recognize stop codons in the ribosomal A-site to mediate release of the nascent chain and recycling of the ribosome. Bacteria decode stop codons using two separate release factors with differing specificities for the second and third bases. By contrast, eukaryotes rely on an evolutionarily unrelated omnipotent release factor (eRF1) to recognize all three stop codons. The molecular basis of eRF1 discrimination for stop codons over sense codons is not known. Here we present cryo-electron microscopy (cryo-EM) structures at 3.5-3.8 Å resolution of mammalian ribosomal complexes containing eRF1 interacting with each of the three stop codons in the A-site. Binding of eRF1 flips nucleotide A1825 of 18S ribosomal RNA so that it stacks on the second and third stop codon bases. This configuration pulls the fourth position base into the A-site, where it is stabilized by stacking against G626 of 18S rRNA. Thus, eRF1 exploits two rRNA nucleotides also used during transfer RNA selection to drive messenger RNA compaction. In this compacted mRNA conformation, stop codons are favoured by a hydrogen-bonding network formed between rRNA and essential eRF1 residues that constrains the identity of the bases. These results provide a molecular framework for eukaryotic stop codon recognition and have implications for future studies on the mechanisms of canonical and premature translation termination. [ABSTRACT FROM AUTHOR]
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- 2015
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14. Franchising (& Distribution) Currents.
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Batenhorst, Gary R., Oates, Daniel J., and Murray, Jason M.
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RETAIL franchise laws , *AUTOMOBILE dealer lawsuits , *PLAINTIFFS , *ECONOMIC competition - Abstract
The article discusses several court cases including Aston Martin Lagonda of N. Am. Inc. v. Lotus Motorsports Inc., Butler v. Lyons & Wolivar Inc., and Miller v. CareMinders Home Care Inc. It mentions the Aston case in which car manufacturer Aston Martin filed a case against Lotus citing competing dealership. It discusses the Miller's case in which plaintiff Donna Miller sued defendant CareMinders alleging misrepresentations regarding the purchase of CareMinders franchises.
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- 2014
15. Transnational Ecosystem Services: The Potential of Habitat Conservation for Waterfowl Through Recreational Hunting Activities.
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Rubio-Cisneros, Nadia T., Aburto-Oropeza, Octavio, Murray, Jason, Gonzalez-Abraham, Charlotte E., Jackson, Jeremy, and Ezcurra, Exequiel
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ENVIRONMENTAL management , *HABITAT conservation , *HUNTING , *WATERFOWL , *MANGROVE plants , *CONSUMERS' surplus , *INTERNATIONAL cooperation - Abstract
This article explores transnational ecosystem services in North America, provided by winter habitat for waterfowl in western Mexico coastal lagoons, and the hunting industry supported by these birds in the United States. This article shows that the number of waterfowl harvested in the United States is related to the abundance of waterfowl wintering in Mexico. On average, this flow of ecosystem services annually yields US$ 4.68 million in hunting stamp sales in the western United States. A demand curve, fitted to duck hunting licenses as a function of stamp price and previous-year waterfowl harvest, estimated US$3–6 million in consumer surplus produced in addition to governmental stamp sales revenue. This strongly suggests that waterfowl wintering habitat in western Mexico is economically valuable to U.S. hunters. Because hunters may benefit substantially from these habitats they may be willing to pay for conservation efforts in western Mexico that can result in transnational benefits received in the United States. [ABSTRACT FROM AUTHOR]
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- 2014
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16. Impact of etiology on force and kinetics of left ventricular end-stage failing human myocardium.
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Mashali, Mohammed A., Saad, Nancy S., Canan, Benjamin D., Elnakish, Mohammad T., Milani-Nejad, Nima, Chung, Jae-Hoon, Schultz, Eric J., Kiduko, Salome A., Huang, Amanda W., Hare, Austin N., Peczkowski, Kyra K., Fazlollahi, Farbod, Martin, Brit L., Murray, Jason D., Campbell, Courtney M., Kilic, Ahmet, Whitson, Bryan A., Mokadam, Nahush A., Mohler, Peter J., and Janssen, Paul M.L.
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MYOCARDIUM , *MEDICAL care costs , *TREATMENT effectiveness , *ETIOLOGY of diseases , *HEART beat - Abstract
Heart failure (HF) is associated with highly significant morbidity, mortality, and health care costs. Despite the significant advances in therapies and prevention, HF remains associated with poor clinical outcomes. Understanding the contractile force and kinetic changes at the level of cardiac muscle during end-stage HF in consideration of underlying etiology would be beneficial in developing targeted therapies that can help improve cardiac performance. Investigate the impact of the primary etiology of HF (ischemic or non-ischemic) on left ventricular (LV) human myocardium force and kinetics of contraction and relaxation under near-physiological conditions. Contractile and kinetic parameters were assessed in LV intact trabeculae isolated from control non-failing (NF; n = 58) and end-stage failing ischemic (FI; n = 16) and non-ischemic (FNI; n = 38) human myocardium under baseline conditions, length-dependent activation, frequency-dependent activation, and response to the β-adrenergic stimulation. At baseline, there were no significant differences in contractile force between the three groups; however, kinetics were impaired in failing myocardium with significant slowing down of relaxation kinetics in FNI compared to NF myocardium. Length-dependent activation was preserved and virtually identical in all groups. Frequency-dependent activation was clearly seen in NF myocardium (positive force frequency relationship [FFR]), while significantly impaired in both FI and FNI myocardium (negative FFR). Likewise, β-adrenergic regulation of contraction was significantly impaired in both HF groups. End-stage failing myocardium exhibited impaired kinetics under baseline conditions as well as with the three contractile regulatory mechanisms. The pattern of these kinetic impairments in relation to NF myocardium was mainly impacted by etiology with a marked slowing down of kinetics in FNI myocardium. These findings suggest that not only force development, but also kinetics should be considered as a therapeutic target for improving cardiac performance and thus treatment of HF. [Display omitted] • Impaired baseline contraction/relaxation kinetics is dependent on etiology of HF. • Length-dependent activation of force development is not impaired in HF myocardium. • Kinetics of HF myocardium do accelerate with heart rate similar to NF myocardium. • Isoproterenol has different inotropic action between NF and HF myocardium. • Improving impaired contractile kinetics may be key in combating human end-stage HF. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Cardiac myosin activation with 2-deoxy-ATP via increased electrostatic interactions with actin.
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Powers, Joseph D., Chen-Ching Yuan, McCabe, Kimberly J., Murray, Jason D., Childers, Matthew Carter, Flint, Galina V., Moussavi-Harami, Farid, Mohran, Saffie, Castillo, Romi, Zuzek, Carla, Weikang Ma, Daggett, Valerie, McCulloch, Andrew D., Irving, Thomas C., and Regnier, Michael
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MYOSIN , *ADENOSINE triphosphate , *SARCOMERES , *MYOCARDIUM , *X-ray diffraction - Abstract
The naturally occurring nucleotide 2-deoxy-adenosine 5Œ-triphosphate (dATP) can be used by cardiac muscle as an alternative energy substrate for myosin chemomechanical activity. We and others have previously shown that dATP increases contractile force in normal hearts and models of depressed systolic function, but the structural basis of these effects has remained unresolved. In this work, we combine multiple techniques to provide structural and functional information at the angstrom-nanometer and millisecond time scales, demonstrating the ability to make both structural measurements and quantitative kinetic estimates of weak actin. myosin interactions that underpin sarcomere dynamics. Exploiting dATP as a molecular probe, we assess how small changes in myosin structure translate to electrostatic-based changes in sarcomere function to augment contractility in cardiac muscle. Through Brownian dynamics simulation and computational structural analysis, we found that deoxy-hydrolysis products [2-deoxy-adenosine 5Œ-diphosphate (dADP) and inorganic phosphate (Pi)] bound to prepowerstroke myosin induce an allosteric restructuring of the actin-binding surface on myosin to increase the rate of crossbridge formation. We then show experimentally that this predicted effect translates into increased electrostatic interactions between actin and cardiac myosin in vitro. Finally, using small-angle X-ray diffraction analysis of sarcomere structure, we demonstrate that the proposed increased electrostatic affinity of myosin for actin causes a disruption of the resting conformation of myosin motors, resulting in their repositioning toward the thin filament before activation. The dATP-mediated structural alterations in myosin reported here may provide insight into an improved criterion for the design or selection of small molecules to be developed as therapeutic agents to treat systolic dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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18. Etiology-dependent impairment of relaxation kinetics in right ventricular end-stage failing human myocardium.
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Chung, Jae-Hoon, Martin, Brit L., Canan, Benjamin D., Elnakish, Mohammad T., Milani-Nejad, Nima, Saad, Nancy S., Repas, Steven J., Schultz, J. Eric J., Murray, Jason D., Slabaugh, Jessica L., Gearinger, Rachel L., Conkle, Jennifer, Karaze, Tallib, Rastogi, Neha, Chen, Mei-Pian, Crecelius, Will, Peczkowski, Kyra K., Ziolo, Mark T., Fedorov, Vadim V., and Kilic, Ahmet
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MYOCARDIUM physiology , *RIGHT heart ventricle diseases , *LEFT heart ventricle diseases , *HEART failure patients , *BETA adrenoceptors - Abstract
Background In patients with end-stage heart failure, the primary etiology often originates in the left ventricle, and eventually the contractile function of the right ventricle (RV) also becomes compromised. RV tissue-level deficits in contractile force and/or kinetics need quantification to understand involvement in ischemic and non-ischemic failing human myocardium. Methods and results The human population suffering from heart failure is diverse, requiring many subjects to be studied in order to perform an adequately powered statistical analysis. From 2009-present we assessed live tissue-level contractile force and kinetics in isolated myocardial RV trabeculae from 44 non-failing and 41 failing human hearts. At 1 Hz stimulation rate (in vivo resting state) the developed active force was not different in non-failing compared to failing ischemic nor non-ischemic failing trabeculae. In sharp contrast, the kinetics of relaxation were significantly impacted by disease, with 50% relaxation time being significantly shorter in non-failing vs. non-ischemic failing, while the latter was still significantly shorter than ischemic failing. Gender did not significantly impact kinetics. Length-dependent activation was not impacted. Although baseline force was not impacted, contractile reserve was critically blunted. The force-frequency relation was positive in non-failing myocardium, but negative in both ischemic and non-ischemic myocardium, while the β-adrenergic response to isoproterenol was depressed in both pathologies. Conclusions Force development at resting heart rate is not impacted by cardiac pathology, but kinetics are impaired and the magnitude of the impairment depends on the underlying etiology. Focusing on restoration of myocardial kinetics will likely have greater therapeutic potential than targeting force of contraction. [ABSTRACT FROM AUTHOR]
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- 2018
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19. Transforming growth factor β-activated kinase 1 signaling pathway critically regulates myocardial survival and remodeling.
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Li, Lei, Chen, Yi, Doan, Jessica, Murray, Jason, Molkentin, Jeffery D, and Liu, Qinghang
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Background: Programmed necrosis (necroptosis) plays an important role in development, tissue homeostasis, and disease pathogenesis. The molecular mechanisms that regulate necroptosis in the heart and its physiological relevance in myocardial remodeling and heart failure remain largely unknown.Methods and Results: Here, we identified an obligate function for TAK1 (transforming growth factor β-activated kinase 1, gene name Map3k7) in regulating necroptotic myocyte death, myocardial remodeling, and heart failure propensity. Cardiac-specific ablation of Map3k7 in mice induced spontaneous apoptosis and necroptosis that led to adverse remodeling and heart failure, and these effects were abolished by ablation of tumor necrosis factor receptor-1. Mechanistically, TAK1 functions as a molecular switch in tumor necrosis factor receptor-1 signaling by regulating the formation of 2 cell death complexes, RIP 1 (receptor-interacting protein 1)-FADD (Fas-associated protein with death domain)-caspase 8 and RIP1-RIP3, a process that is dependent on FADD and caspase 8 as scaffolding molecules. Importantly, inhibition of RIP1 or RIP3 largely blocked necroptotic cell death, adverse remodeling, and heart failure in TAK1-deficient mice.Conclusions: These results indicate that TAK1 functions as a key survival factor in the heart by directly antagonizing necroptosis, which is critical for the maintenance of myocardial homeostasis and the prevention of adverse myocardial remodeling. [ABSTRACT FROM AUTHOR]- Published
- 2014
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20. Transforming Growth Factor β-Activated Kinase 1 Signaling Pathway Critically Regulates Myocardial Survival and Remodeling.
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Lei Li, Yi Chen, Doan, Jessica, Murray, Jason, Molkentin, Jeffery D., and Qinghang Liu
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TRANSFORMING growth factors-beta , *HEART cells , *NECROSIS , *HOMEOSTASIS , *MOLECULAR cardiology - Abstract
Background--Programmed necrosis (necroptosis) plays an important role in development, tissue homeostasis, and disease pathogenesis. The molecular mechanisms that regulate necroptosis in the heart and its physiological relevance in myocardial remodeling and heart failure remain largely unknown. Methods and Results--Here, we identified an obligate function for TAK1 (transforming growth factor β-activated kinase 1, gene name Map3k7) in regulating necroptotic myocyte death, myocardial remodeling, and heart failure propensity. Cardiac-specific ablation of Map3k7 in mice induced spontaneous apoptosis and necroptosis that led to adverse remodeling and heart failure, and these effects were abolished by ablation of tumor necrosis factor receptor-1. Mechanistically, TAK1 functions as a molecular switch in tumor necrosis factor receptor-1 signaling by regulating the formation of 2 cell death complexes, RIP 1 (receptor-interacting protein 1)-FADD (Fas-associated protein with death domain)-caspase 8 and RIP1-RIP3, a process that is dependent on FADD and caspase 8 as scaffolding molecules. Importantly, inhibition of RIP 1 or RIP3 largely blocked necroptotic cell death, adverse remodeling, and heart failure in TAK1-deficient mice. Conclusions--These results indicate that TAK1 functions as a key survival factor in the heart by directly antagonizing necroptosis, which is critical for the maintenance of myocardial homeostasis and the prevention of adverse myocardial remodeling. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
21. Herbaceous plant community composition in created wetlands over seven years in northern New York, USA.
- Author
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ANDREW COLE, CHARLES, URBAN, CHRISTOPHER A., RUSSO, PAUL, MURRAY, JASON, HOYT, DAVE, and BROOKS, ROBERT P.
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CONSTRUCTED wetlands , *WETLAND planting , *WETLAND plants , *WETLAND soils , *PLANT diversity ,POPULATION regeneration ,FORT Drum (N.Y.) - Abstract
The results of a seven-year study of the herbaceous plant communities of five created wetlands constructed at Fort Drum, New York is presented. It details the methods used in constructing the wetlands such as an analysis of hydrology and soils; the use of cover plants including redtop (Agrostis gigantea), creeping foxtail (Alopecurus arundinaceus), and perennial ryegrass (Lolium perenne); and the use of a wetland seed bank which included 23 species of wetland plants. The evolution of plant diversity in the constructed wetlands is detailed.
- Published
- 2013
- Full Text
- View/download PDF
22. A General Business Model for Marine Reserves.
- Author
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Sala, Enric, Costello, Christopher, Dougherty, Dawn, Heal, Geoffrey, Kelleher, Kieran, Murray, Jason H., Rosenberg, Andrew A., and Sumaila, Rashid
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MARINE parks & reserves , *BIODIVERSITY , *ECOSYSTEM services , *FISHERIES , *EMPIRICAL research , *BUSINESS models , *STAKEHOLDERS , *ENVIRONMENTAL protection - Abstract
Marine reserves are an effective tool for protecting biodiversity locally, with potential economic benefits including enhancement of local fisheries, increased tourism, and maintenance of ecosystem services. However, fishing communities often fear short-term income losses associated with closures, and thus may oppose marine reserves. Here we review empirical data and develop bioeconomic models to show that the value of marine reserves (enhanced adjacent fishing + tourism) may often exceed the pre-reserve value, and that economic benefits can offset the costs in as little as five years. These results suggest the need for a new business model for creating and managing reserves, which could pay for themselves and turn a profit for stakeholder groups. Our model could be expanded to include ecosystem services and other benefits, and it provides a general framework to estimate costs and benefits of reserves and to develop such business models. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
23. The illusion of plenty: hyperstability masks collapses in two recreational fisheries that target fish spawning aggregations.
- Author
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Erisman, Brad E., Allen, Larry G., Claisse, Jeremy T., Pondella, Daniel J., Miller, Eric F., Murray, Jason H., and Walters, Carl
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SPAWNING , *FISH reproduction , *SEA basses , *FISHERY management - Abstract
Fisheries that target fish spawning aggregations can exhibit hyperstability, in which catch per unit effort (CPUE) remains elevated as stock abundance declines, but empirical support is limited. We compiled several fishery-dependent and fishery-independent data sets to assess stock trends in the barred sand bass () and the kelp bass () in southern California, USA, evaluate the interaction between spawning aggregations and fishing activities, and test for hyperstability. Annual and seasonal trends from fisheries and population data indicate that regional stocks of both species have collapsed in response to overfishing of spawning aggregations and changes in environmental conditions. The aggregating behavior of fish and persistent targeting of spawning aggregations by recreational fisheries combined to produce a hyperstable relationship between CPUE and stock abundance in both species, which created the illusion that population levels were stable and masked fishery collapses. Differences in the rate of decline between the two species may be related to the size, duration, and spatial distribution of their spawning aggregations. Results of this study provide empirical evidence of hyperstability in aggregation-based fisheries and demonstrate that CPUE data be used with caution and given low weight when fishery-independent data are available. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
24. Early Treatment With Lisinopril and Spironolactone Preserves Cardiac and Skeletal Muscle in Duchenne Muscular Dystrophy Mice.
- Author
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Rafael-Fortney, Jill A., Chimanji, Neeraj S., Schill, Kevin E., Martin, Christopher D., Murray, Jason D., Ganguly, Ranjit, Stangland, Jenna E., Tran, Tam, Ying Xu, Canan, Benjamin D., Mays, Tessily A., Delfín, Dawn A., Janssen, Paul M. L., and Raman, Subha V.
- Subjects
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TREATMENT of Duchenne muscular dystrophy , *MEDICAL research , *CARDIOMYOPATHIES , *ALDOSTERONE antagonists , *HEART failure , *DYSTROPHIN , *METALLOPROTEINASES - Abstract
Background-Nearly universal cardiomyopathy in Duchenne muscular dystrophy (DMD) contributes to heart failure and death. Because DMD patients show myocardial fibrosis well before functional impairment, we postulated that earlier treatment using drugs with antifibrotic effect may be beneficial. Methods and Results-Three groups of 10 utrn+/-;mdx, or "het" mice, deficient for dystrophin and haploinsufficient for utrophin with skeletal myopathy and cardiomyopathy that closely mimics clinical DMD were studied. One het group received spironolactone and lisinopril starting at 8 weeks of life (het-treated-8); a second received the same starting at 4 weeks of life (het-treated-4), and the third het group was untreated. At 20 weeks, all mice had normal ejection fractions though circumferential strain rate was abnormal (-0.21±0.08) in untreated hets. This improved to -0.40±0.07 in het-treated-8 mice (P=0.003) and further improved to -0.56±0.10 in het-treated-4 mice (P=0.014 for het-treated-4 versus het-treated-8). Treated mice showed less cardiomyocyte damage, with a 44% reduction in intracardiomyocyte serum immunoglobulin G localization in het-treated-8 mice (P<0.0001) and a further 53% reduction in het-treated-4 mice (P=0.0003 versus het-treated-8); matrix metalloproteinases were similarly reduced. Cardiac, limb, and diaphragm function by ex vivo muscle testing remained at 80% of normal with early treatment compared to a decline to 40% of normal skeletal muscle function without treatment. Conclusions-These findings offer clinically available medications with proven antifibrotic effect as a new therapeutic strategy in DMD. Early initiation greatly attenuated myocardial disease and, for the first time with these drugs, improved skeletal myopathy. Thus, early initiation of such agents warrants further clinical evaluation to maintain ambulatory, respiratory, and cardiac function for patients with DMD and related myopathies. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
25. Mangroves in the Gulf of California increase fishery yields.
- Author
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Aburto-Oropeza, Octavio, Ezcurra, Exequiel, Danemann, Gustavo, Valdez, Victor, Murray, Jason, and Sala, Enric
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MANGROVE plants , *ENVIRONMENTAL degradation , *FISHERIES & the environment , *BIODIVERSITY , *MARINE biodiversity - Abstract
Mangroves are disappearing rapidly worldwide despite their well documented biodiversity and the ecosystem services they provide. Failure to link ecological processes and their societal benefits has favored highly destructive aquaculture and tourism developments that threaten mangroves and result in costly "externalities." Specifically, the potentially irreparable damage to fisheries because of mangrove loss has been belittled and is greatly underestimated. Here, we show that, in the Gulf of California, fisheries landings are positively related to the local abundance of mangroves and, in particular, to the productive area in the mangrove-water fringe that is used as nursery and/or feeding grounds by many commercial species. Mangrove-related fish and crab species account for 32% of the small-scale fisheries landings in the region. The annual economic median value of these fisheries is US $37,500 per hectare of mangrove fringe, falling within the higher end of values previously calculated worldwide for all mangrove services together. The ten-year discounted value of one hectare of fringe is >300 times the official cost set by the Mexican government. The destruction of mangroves has a strong economic impact on local fishing communities and on food production in the region. Our valuation of the services provided by mangroves may prove useful in making appropriate decisions for a more efficient and sustainable use of wetlands. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
26. Comparison of the long-term water levels of created and natural reference wetlands in northern New York, USA
- Author
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Cole, Charles Andrew, Urban, Christopher A., Russo, Paul, Murray, Jason, Hoyt, Dave, and Brooks, Robert P.
- Subjects
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WETLANDS , *HYDROLOGY , *AQUATIC sciences , *AQUATIC resources - Abstract
Abstract: Long-term evaluation of hydrology on created wetlands in the United States is rare, as most such assessments are short-term and driven by regulatory and permit requirements. Long-term studies are critical to the understanding of the development of function in created wetlands. We measured water levels at 12-h intervals at five created wetlands at Fort Drum, northern New York, from 1994 to 2003 and compared that data with information from three reference wetlands, collected at the beginning and the end of that 10-year period. During that time span, the created wetlands were wetter than the reference wetlands as measured by median depth to water and the percentage of time water was within 30cm of the surface. The two groups also differed in the duration of dry, saturated, and inundated periods. The mitigation wetlands were wetter than the reference wetlands likely as a result of the practice of excavating down to water table depths to generate site hydrology. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
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