Publications by authors named "Nathan Nelson"

126 Publications

Structure of plant photosystem I-plastocyanin complex reveals strong hydrophobic interactions.

Biochem J 2021 Jun;478(12):2371-2384

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

Photosystem I is defined as plastocyanin-ferredoxin oxidoreductase. Taking advantage of genetic engineering, kinetic analyses and cryo-EM, our data provide novel mechanistic insights into binding and electron transfer between PSI and Pc. Structural data at 2.74 Å resolution reveals strong hydrophobic interactions in the plant PSI-Pc ternary complex, leading to exclusion of water molecules from PsaA-PsaB/Pc interface once the PSI-Pc complex forms. Upon oxidation of Pc, a slight tilt of bound oxidized Pc allows water molecules to accommodate the space between Pc and PSI to drive Pc dissociation. Such a scenario is consistent with the six times larger dissociation constant of oxidized as compared with reduced Pc and mechanistically explains how this molecular machine optimized electron transfer for fast turnover.
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http://dx.doi.org/10.1042/BCJ20210267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238519PMC
June 2021

Agreement of Magnetic Resonance Imaging With Computed Tomography in the Assessment for Acute Skull Fractures in a Canine and Feline Cadaver Model.

Front Vet Sci 2021 22;8:603775. Epub 2021 Apr 22.

Office of Information Technology, University of Tennessee, Knoxville, TN, United States.

Computed tomography (CT) is the imaging modality of choice to evaluate patients with acute head trauma. However, magnetic resonance imaging (MRI) may be chosen in select cases. The objectives of this study were to evaluate the agreement of MRI with CT in the assessment for presence or absence of acute skull fractures in a canine and feline cadaver model, compare seven different MRI sequences (T1-W, T2-W, T2-FLAIR, PD-W, T2-W, "SPACE" and "VIBE"), and determine agreement of four different MRI readers with CT data. Pre- and post-trauma CT and MRI studies were performed on 10 canine and 10 feline cadaver heads. Agreement of MRI with CT as to presence or absence of a fracture was determined for 26 individual osseous structures and four anatomic regions (cranium, face, skull base, temporomandibular joint). Overall, there was 93.5% agreement in assessing a fracture as present or absent between MRI and CT, with a significant difference between the pre and post trauma studies (99.4 vs. 87.6%; < 0.0001; OR 0.042; 95% CI 0.034-0.052). There was no significant difference between dogs and cats. The agreement for the different MRI sequences with CT ranged from 92.6% (T2-W) to 94.4% (PD-W). There was higher agreement of MRI with CT in the evaluation for fractures of the face than other anatomic regions. Agreement with CT for individual MRI readers ranged from 92.6 to 94.7%. A PD-W sequence should be added to the MR protocol when evaluating the small animal head trauma patient.
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http://dx.doi.org/10.3389/fvets.2021.603775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100023PMC
April 2021

The Plasticity of Photosystem I.

Plant Cell Physiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.

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http://dx.doi.org/10.1093/pcp/pcab046DOI Listing
March 2021

Excitation energy transfer kinetics of trimeric, monomeric and subunit-depleted Photosystem I from Synechocystis PCC 6803.

Biochem J 2021 Apr;478(7):1333-1346

Biological Research Centre, University of Szeged, Temesvári krt. 62, Szeged 6726, Hungary.

Photosystem I is the most efficient photosynthetic enzyme with structure and composition highly conserved among all oxygenic phototrophs. Cyanobacterial Photosystem I is typically associated into trimers for reasons that are still debated. Almost universally, Photosystem I contains a number of long-wavelength-absorbing 'red' chlorophylls (Chls), that have a sizeable effect on the excitation energy transfer and trapping. Here we present spectroscopic comparison of trimeric Photosystem I from Synechocystis PCC 6803 with a monomeric complex from the ΔpsaL mutant and a 'minimal' monomeric complex ΔFIJL, containing only subunits A, B, C, D, E, K and M. The quantum yield of photochemistry at room temperature was the same in all complexes, demonstrating the functional robustness of this photosystem. The monomeric complexes had a reduced far-red absorption and emission equivalent to the loss of 1.5-2 red Chls emitting at 710-715 nm, whereas the longest-wavelength emission at 722 nm was not affected. The picosecond fluorescence kinetics at 77 K showed spectrally and kinetically distinct red Chls in all complexes and equilibration times of up to 50 ps. We found that the red Chls are not irreversible traps at 77 K but can still transfer excitations to the reaction centre, especially in the trimeric complexes. Structure-based Förster energy transfer calculations support the assignment of the lowest-energy state to the Chl pair B37/B38 and the trimer-specific red Chl emission to Chls A32/B7 located at the monomer-monomer interface. These intermediate-energy red Chls facilitate energy migration from the lowest-energy states to the reaction centre.
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http://dx.doi.org/10.1042/BCJ20210021DOI Listing
April 2021

ACVR President's Message.

Authors:
Nathan Nelson

Vet Radiol Ultrasound 2021 Jan;62(1):5-6

President, ACVR.

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http://dx.doi.org/10.1111/vru.12942DOI Listing
January 2021

Temperature Sensitive Photosynthesis: Point Mutated CEF-G, PRK, or PsbO Act as Temperature-Controlled Switches for Essential Photosynthetic Processes.

Front Plant Sci 2020 25;11:562985. Epub 2020 Sep 25.

Department of Biochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Temperature sensitive mutants have been widely used to study structure, biogenesis and function of a large variety of essential proteins. However, this method has not yet been exploited for the study of photosynthesis. We used negative selection to isolate temperature-sensitive-photoautotrophic (TSP) mutants in . From a population of randomly mutagenized cells (n=12,000), a significant number of TSP mutants (n=157) were isolated. They were able to grow photoautotrophically at 25°C, but lacked this ability at 37°C. Further phenotypic characterization of these mutants enabled the identification of three unique and highly interesting mutant strains. Following, the selected strains were genetically characterized by extensive crossing and whole genome sequencing. Correspondingly, the single amino acid changes P628F in the Chloroplast-Elongation-Factor-G (CEF-G), P129L in Phosphoribulokinase (PRK), and P101H in an essential subunit of Photosystem II (PsbO) were identified. These key changes alter the proteins in such way that they were functional at the permissive temperature, however, defective at the restrictive temperature. These mutants are presented here as superb and novel tools for the study of a wide range of aspects relevant to photosynthesis research, tackling three distinct and crucial photosynthetic processes: Chloroplast translation, PET-chain, and CBB-cycle.
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http://dx.doi.org/10.3389/fpls.2020.562985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545824PMC
September 2020

The structure of a triple complex of plant photosystem I with ferredoxin and plastocyanin.

Nat Plants 2020 10 5;6(10):1300-1305. Epub 2020 Oct 5.

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

The ability of photosynthetic organisms to use sunlight as a sole source of energy is endowed by two large membrane complexes-photosystem I (PSI) and photosystem II (PSII). PSI and PSII are the fundamental components of oxygenic photosynthesis, providing oxygen, food and an energy source for most living organisms on Earth. Currently, high-resolution crystal structures of these complexes from various organisms are available. The crystal structures of megadalton complexes have revealed excitation transfer and electron-transport pathways within the various complexes. PSI is defined as plastocyanin-ferredoxin oxidoreductase but a high-resolution structure of the entire triple supercomplex is not available. Here, using a new cryo-electron microscopy technique, we solve the structure of native plant PSI in complex with its electron donor plastocyanin and the electron acceptor ferredoxin. We reveal all of the contact sites and the modes of interaction between the interacting electron carriers and PSI.
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http://dx.doi.org/10.1038/s41477-020-00779-9DOI Listing
October 2020

Species and termination method effects on phosphorus loss from plant tissue.

J Environ Qual 2020 Jan 20;49(1):97-105. Epub 2020 Jan 20.

Dep. of Agronomy, Kansas State Univ., 2004 Throckmorton Plant Sciences Center, 1712 Claflin Rd., Manhattan, KS, 66506, USA.

Cover crops are often recommended as a best management practice to reduce erosion, weed pressure, and nutrient loss. However, cover crops may be sources of phosphorus (P) to runoff water after termination. Two greenhouse trials were conducted to determine the effects of cover crop species, termination method, and time after termination on water-extractable P (WEP) release from crop biomass. Treatments were structured in a 3 × 3 × 3 factorial and arranged in a randomized complete block design with six replicates. Treatments included three cover crop species (triticale [× Triticosecale; Triticum × Secale 'Trical'], rapeseed [Brassica napus L. 'Winfred'], and crimson clover [Trifolium incarnatum L.]); three termination methods (clipping, freezing, and herbicide); and three WEP extraction times (1, 7, and 14 d after termination). Rapeseed consistently resulted in the least WEP when exposed to the same method of termination and at the same extraction time as the other species. For both trials, terminating crop tissue via freezing increased concentrations of WEP compared with other termination methods. The WEP release from cover crop tissue increased as the time after extraction increased, but the effect was greater for herbicide- and freeze-terminated cover crops and less for clipping-terminated cover crops. Future studies on WEP release from cover crops should pay close attention to the effects of extraction timing. Producers may be able to reduce P loss from cover crop tissue by selecting cover crop species with low WEP and minimizing the amount of biomass exposed to freezing conditions.
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http://dx.doi.org/10.1002/jeq2.20019DOI Listing
January 2020

Computed tomography in two recumbencies aides in the identification of pulmonary bullae in dogs with spontaneous pneumothorax.

Vet Radiol Ultrasound 2020 Nov 8;61(6):641-648. Epub 2020 Sep 8.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.

Spontaneous pneumothorax presents a unique diagnostic and therapeutic challenge in veterinary medicine, specifically with regard to accurate identification of bullous lesions. Positioning of dogs with spontaneous pneumothorax during CT has not previously been evaluated. This retrospective, diagnostic accuracy study was performed to evaluate the sensitivity, positive predictive value (PPV), and interobserver variability for detection of pulmonary bullae with dogs positioned in multiple recumbencies. Dogs underwent CT in sternal and dorsal recumbency followed by thoracic exploration via median sternotomy. Three American College of Veterinary Radiology-certified veterinary radiologists blinded to surgical findings reviewed dorsal and sternal images simultaneously. Severity of pneumothorax, degree of atelectasis, lesion location and size, and view in which lesions were most confidently identified were compared to surgical and histologic findings. Sensitivities and PPVs for bulla detection ranged from 57.7% to 69.2% and 62.1% to 78.9%, respectively. For two of the 3 radiologists, the location of bullae in the thorax was significantly associated with the recumbency in which the lesion was best identified. Degree of atelectasis was found to be associated with the ability to identify lesions (P ≤ .02). The interobserver variability for identification was good (κ = 0.670). The sensitivity of CT when performed in both sternal and dorsal recumbency is similar to that previously reported. Because the distribution of bullae is unknown prior to advanced imaging and bulla location affects which recumbency is most useful for identification, acquisition of CT images in both sternal and dorsal recumbency may improve detection of bullous lesions and aid surgical planning.
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http://dx.doi.org/10.1111/vru.12905DOI Listing
November 2020

Structure and energy transfer pathways of the Dunaliella Salina photosystem I supercomplex.

Biochim Biophys Acta Bioenerg 2020 10 20;1861(10):148253. Epub 2020 Jun 20.

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address:

Oxygenic photosynthesis evolved more than 3 billion years ago in cyanobacteria. The increased complexity of photosystem I (PSI) became apparent from the high-resolution structures that were obtained for the complexes that were isolated from various organisms, ranging from cyanobacteria to plants. These complexes are all evolutionarily linked. In this paper, the researchers have uncovered the increased complexity of PSI in a single organism demonstrated by the coexistance of two distinct PSI compositions. The Large Dunaliella PSI contains eight additional subunits, six in PSI core and two light harvesting complexes. Two additional chlorophyll a molecules pertinent for efficient excitation energy transfer in state II transition were identified in PsaL and PsaO. Short distances between these newly identified chlorophylls correspond with fast excitation transfer rates previously reported during state II transition. The apparent PSI conformations could be a coping mechanism for the high salinity.
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http://dx.doi.org/10.1016/j.bbabio.2020.148253DOI Listing
October 2020

Structure of a minimal photosystem I from the green alga Dunaliella salina.

Nat Plants 2020 03 2;6(3):321-327. Epub 2020 Mar 2.

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Solar energy harnessed by oxygenic photosynthesis supports most of the life forms on Earth. In eukaryotes, photosynthesis occurs in chloroplasts and is achieved by membrane-embedded macromolecular complexes that contain core and peripheral antennae with multiple pigments. The structure of photosystem I (PSI) comprises the core and light-harvesting (LHCI) complexes, which together form PSI-LHCI. Here we determined the structure of PSI-LHCI from the salt-tolerant green alga Dunaliella salina using X-ray crystallography and electron cryo-microscopy. Our results reveal a previously undescribed configuration of the PSI core. It is composed of only 7 subunits, compared with 14-16 subunits in plants and the alga Chlamydomonas reinhardtii, and forms the smallest known PSI. The LHCI is poorly conserved at the sequence level and binds to pigments that form new energy pathways, and the interactions between the individual Lhca1-4 proteins are weakened. Overall, the data indicate the PSI of D. salina represents a different type of the molecular organization that provides important information for reconstructing the plasticity and evolution of PSI.
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http://dx.doi.org/10.1038/s41477-020-0611-9DOI Listing
March 2020

Endemic North American Plants as Potentially Suitable Agents for Wound Cleaning Under Resource Scarce Conditions.

Wilderness Environ Med 2019 Dec 17;30(4):401-406. Epub 2019 Oct 17.

Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, OK.

Introduction: Skin and subcutaneous infections are dangerous sequelae of soft tissue injuries, especially in austere situations where medical technology is not available. Numerous plant species endemic to North America have been described as having antibacterial properties. Of these, St. John's wort (Hypericum perforatum), chamomile (Matricaria chamomilla), and white oak (Quercus alba) were selected for testing against Staphylococcus aureus. Our objective was to assess the suitability of all 3 plants as potential antiseptic agents using methods easily replicated in a resource-scarce environment.

Methods: Water-soluble natural products were extracted from different concentrations of each plant part using either mechanical agitation at ambient temperature or boiling in unsterilized tap water. Antibacterial activity of each extract against S aureus was assessed using a conventional agar well diffusion bioassay. Zones of inhibition were measured using electronic calipers and were compared to tap water as the negative control.

Results: Aqueous extracts of St. John's wort and white oak bark displayed antibacterial effects against S aureus, with St. John's wort being more potent. Chamomile displayed no inhibitory properties at the concentrations examined.

Conclusions: These data suggest that both St. John's wort and white oak are potential candidates for infection prophylaxis and therapy in austere wilderness scenarios, with St. John's wort being the more potent agent. White oak may be more logistically feasible because the larger surface area of a white oak tree allows for harvesting a larger quantity of bark compared to the smaller surface area of the St. John's wort plant.
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http://dx.doi.org/10.1016/j.wem.2019.06.002DOI Listing
December 2019

Optical imaging provides rapid verification of static small beams, radiosurgery, and VMAT plans with millimeter resolution.

Med Phys 2019 Nov 4;46(11):5227-5237. Epub 2019 Oct 4.

Thayer School of Engineering, Dartmouth College Hanover, Hanover, NH, 03755, USA.

Purpose: We demonstrate the feasibility of optical imaging as a quality assurance tool for static small beamlets, and pretreatment verification tool for radiosurgery and volumetric-modulated arc therapy (VMAT) plans.

Methods: Small static beams and clinical VMAT plans were simulated in a treatment planning system (TPS) and delivered to a cylindrical tank filled with water-based liquid scintillator. Emission was imaged using a blue-sensitive, intensified CMOS camera time-gated to the linac pulses. For static beams, percentage depth and cross beam profiles of projected intensity distribution were compared to TPS data. Two-dimensional (2D) gamma analysis was performed on all clinical plans, and the technique was tested for sensitivity against common errors (multileaf collimator position, gantry angle) by inducing deliberate errors in the VMAT plans control points. The technique's detection limits for spatial resolution and the smallest number of control points that could be imaged reliably were also tested. The sensitivity to common delivery errors was also compared against a commercial 2.5D diode array dosimeter.

Results: A spatial resolution of 1 mm was achieved with our imaging setup. The optical projected percentage depth intensity profiles agreed to within 2% relative to the TPS data for small static square beams (5, 10, and 50 mm ). For projected cross beam profiles, a gamma pass rate >99% was achieved for a 3%/1 mm criteria. All clinical plans passed the 3%/3 mm criteria with >95% passing rate. A static 5 mm beam with 20 Monitor Units could be measured with an average percent difference of 5.5 ± 3% relative to the TPS. The technique was sensitive to multileaf collimator errors down to 1 mm and gantry angle errors of 1°.

Conclusions: Optical imaging provides ample spatial resolution for imaging small beams. The ability to faithfully image down to 20 MU of 5 mm, 6 MV beamlets prove the ability to perform quality assurance for each control point within dynamic plans. The technique is sensitive to small offset errors in gantry angles and multileaf collimator (MLC) leaf positions, and at certain scenario, it exhibits higher sensitivity than a commercial 2.5D diode array.
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http://dx.doi.org/10.1002/mp.13797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082501PMC
November 2019

The impact of tongue dimension on air volume in brachycephalic dogs.

Vet Surg 2020 Apr 30;49(3):512-520. Epub 2019 Jul 30.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina.

Objective: To compare the dimensions and density of the tongue in brachycephalic and mesaticephalic dog breeds and to document the relative extents of the nasopharyngeal and oropharyngeal airways occupied by the tongue and palatal tissues.

Study Design: Case control study.

Animals: Sixteen brachycephalic dogs and 12 mesaticephalic dogs.

Methods: The volume of the tongue was measured with computed tomography in all dogs. Cross-sectional areas of tongue, oropharynx, nasopharynx, and palatal soft tissue were evaluated at two levels, the caudal aspect of the hard palate and the level of the hamulae of the pterygoid. Density of the tongue and soft palate were measured. All variables were compared between brachycephalic and mesaticephalic dogs (P ≤ .05).

Results: Absolute tongue volumes did not differ between groups, the volume of the tongue was greater in brachycephalic dogs than in mesaticephalic dogs when expressed relative to (a) body weight (median 5650, interquartile range [IQR] 4833-6522 vs median 4454, IQR 4309-4743, respectively), (b) ratio between skull length/width (70 833, IQR 62490-126 209 vs 48 064, IQR 22984-64 279, respectively), and (c) skull length (689.93, IQR 618.55-970.61 vs 460.04, IQR 288.77-561.69, respectively). The proportion of air (oropharyngeal and nasopharyngeal)/soft tissue (tongue and palatal tissue) in brachycephalic dogs was decreased by approximately 60%, and the tongue was approximately 10 times denser in brachycephalic dogs than in mesaticephalic dogs.

Conclusion: A relative macroglossia was detected in brachycephalic dogs along with reduced air volume in the upper airway. Tongues of brachycephalic dogs were denser than those of mesaticephalic dogs.

Clinical Significance: The relative macroglossia in brachycephalic breeds may contribute to upper airway obstruction.
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http://dx.doi.org/10.1111/vsu.13302DOI Listing
April 2020

Evaluation of ultrasonographically determined ratios of kidney length to aorta diameter for assessment of kidney size in healthy young dogs.

Am J Vet Res 2019 Aug;80(8):764-770

Objective: To determine whether previously described cutoffs for ultrasonographically determined kidney length-to-aorta diameter ratio (KL:Ao) for evaluation of kidney size in adult dogs are applicable to healthy dogs 1 to 18 months of age and to assess interobserver and intraobserver variability for ultrasonographic kidney and aorta measurements in these dogs grouped according to age.

Animals: 82 dogs.

Procedures: 41 university-owned dogs and 41 client- or staff-owned dogs of 3 age groups (approx 1, 6, and 12 to 18 months of age) underwent ultrasonographic examination by 3 observers. Kidney length, kidney width, and diameter of the aorta were measured by each observer 3 times, and KL:Ao and kidney length-to-body weight ratio were calculated for each dog. Measurements and calculated ratios for the 3 age groups were compared by statistical methods; interobserver and intraobserver variability were calculated.

Results: Mean kidney length, kidney width, and aorta diameter were smaller, and calculated KL:Ao and kidney length-to-body weight ratio were larger, for dogs of the 1-month age group than for dogs of the 6-month and 12 to 18-month age groups. There were significant interobserver differences for ultrasonographic measurements in all age groups; these were most frequent in the youngest group of dogs and affected KL:Ao for that group only.

Conclusions And Clinical Relevance: Results revealed that 1-month-old dogs have larger kidneys relative to body weight and aorta diameter than do older dogs. Interobserver variability for the youngest group of dogs indicated limited usefulness of these measurements and related ratios for neonatal dogs in clinical practice. The KL:Ao values for dogs ≥ 6 months of age in this study were similar to values previously described for dogs > 12 months of age.
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http://dx.doi.org/10.2460/ajvr.80.8.764DOI Listing
August 2019

Development of PLEAD: A Database Containing Event-based Runoff Phosphorus Loadings from Agricultural Fields.

J Environ Qual 2019 Mar;48(2):510-517

Computer models are commonly used for predicting risks of runoff P loss from agricultural fields by enabling simulation of various management practices and climatic scenarios. For P loss models to be useful tools, however, they must accurately predict P loss for a wide range of climatic, physiographic, and land management conditions. A complicating factor in developing and evaluating P loss models is the relative scarcity of available measured field data that adequately capture P losses before and after implementing management practices in a variety of physiographic settings. Here, we describe the development of the P Loss in runoff Events from Agricultural fields Database (PLEAD)-a compilation of event-based, field-scale dissolved and/or total P loss runoff loadings from agricultural fields collected at various research sites located in the US Heartland and southern United States. The database also includes runoff and erosion rates; soil-test P; tillage practices; planting and harvesting rates and practices; fertilizer application rate, method, and timing; manure application rate, method, and timing; and livestock grazing density and timing. In total, >1800 individual runoff events-ranging in duration from 0.4 to 97 h-have been included in the database. Event runoff P losses ranged from <0.05 to 1.3 and 3.0 kg P ha for dissolved and total P, respectively. The data contained in this database have been used in multiple research studies to address important modeling questions relevant to P management planning. We provide these data to encourage additional studies by other researchers. The PLEAD database is available at .
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http://dx.doi.org/10.2134/jeq2018.09.0337DOI Listing
March 2019

Ammonium tetrathiomolybdate treatment of copper-associated hepatopathy in dogs.

J Vet Intern Med 2019 May 18;33(3):1336-1343. Epub 2019 Mar 18.

Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan.

Background: Copper-associated hepatopathy (CAH) is a common cause of liver disease in dogs. Although d-penicillamine can be an effective treatment, some dogs fail treatment or develop adverse effects. Ammonium tetrathiomolybdate (TTM) has been used to treat pathologic copper accumulation in other species, but its therapeutic potential for CAH is unknown.

Objectives: To investigate short-term safety and efficacy of TTM for treatment of CAH.

Animals: Ten dogs with CAH.

Methods: Prospective study. All dogs were treated with TTM PO for 6 weeks, and hepatic biopsies were performed after the treatment course. Dog experiencing initial decreases in hepatic copper concentrations ([Cu] ) received 6 additional weeks of TTM treatment and underwent 1 additional biopsy. Physical and laboratory examinations were performed every 2 weeks for study duration.

Results: Eight of 10 dogs had decreases in [Cu] . Compared to baseline (median, 1606 μg/g; range, 572-5158 μg/g), [Cu] were decreased at 6 weeks (1033 μg/g, 450-2975 μg/g; P = .04) and 12 weeks (931 μg/g, 218-1677 μg/g; P = .02). Hepatic molybdenum concentrations increased >50-fold (P < 0.001). Changes in histologic scores and hematologic and biochemical test results were variable and not significantly different from baseline. One dog developed presumed immune-mediated anemia and thrombocytopenia, but it was unclear if this was related to TTM administration.

Conclusions And Clinical Importance: Results suggest that TTM can effectively decrease [Cu] in some dogs with CAH. Larger studies are needed to determine the overall safety and efficacy of TTM for treating CAH and how it compares with current treatments.
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http://dx.doi.org/10.1111/jvim.15474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524386PMC
May 2019

Crystal Structure of Photosystem I Monomer From PCC 6803.

Front Plant Sci 2018 4;9:1865. Epub 2019 Jan 4.

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

A single histidine addition to the C-terminus of PsaL of sp. PCC 6803 was previously reported by our lab to shift the trimer-to-monomer ratio of PSI in favor of the monomeric form. P700 re-reduction and NADP photo-reduction measurements of the PsaL strain show no effect on PSI activity in comparison to the WT trimeric PSI. Crystal structure of the PsaL monomeric PSI reveals several alterations that occurred in the trimerisation site of PSI, primarily a deformation of the C-terminus of PsaL and loss of chlorophyll a and β-carotene molecules.
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http://dx.doi.org/10.3389/fpls.2018.01865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328476PMC
January 2019

Constrictive Bronchiolitis Obliterans in a Dog.

J Am Anim Hosp Assoc 2019 Mar/Apr;55(2):e55201. Epub 2019 Jan 17.

From NorthStar VETS, Robbinsville, New Jersey (S.L.W.); Department of Small Animal Clinical Sciences (D.L., S.C.), and Department of Pathobiology and Diagnostic Investigation (K.J.W.), College of Veterinary Medicine, Michigan State University, East Lansing, Michigan; and College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina (N.C.N.).

A 2 yr old, neutered male rottweiler was evaluated for a chronic cough that had acutely worsened. Computed tomographic examination revealed a diffuse alveolar pattern in the right, middle, and left cranial lung lobes. Aerated parenchymal tissue was not observed in the left cranial lung lobe, and both lobes were markedly decreased in volume. Lobectomy of the right middle and left cranial lung lobes was performed. Histopathologic examination of both lungs identified alveolar collapse associated with marked chronic bronchial and bronchiolar luminal concentric fibrosis leading to reduced airway lumen diameter and bronchiolar destruction. The clinical signs and airway pathology were consistent with constrictive bronchiolitis obliterans. The dog remained stable for over 2 yr with glucocorticoid therapy and intermittent antimicrobics. Although the polypoid form of bronchiolitis obliterans has been described in cattle and occasionally in dogs, constrictive bronchiolitis obliterans has not been reported previously in veterinary species.
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http://dx.doi.org/10.5326/JAAHA-MS-6821DOI Listing
August 2019

Clinical features of canine pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

J Vet Intern Med 2019 Jan 29;33(1):114-123. Epub 2018 Nov 29.

Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan.

Background: Histologic features of pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) have been described in dogs but without a thorough clinical description.

Objectives: To report the clinical features, diagnostics, treatment, and outcome of dogs with histologic evidence of PVOD and PCH.

Animals: Fifteen pet dogs meeting histopathologic criteria of PVOD (occlusive remodeling of small-sized to medium-sized pulmonary veins) or PCH (alveolar capillary proliferation and congestion), or both.

Methods: Medical records of dogs with PVOD and PCH identified based on histopathologic features between 2003 and 2017 were retrospectively reviewed.

Results: Fifteen dogs met inclusion criteria of a histologic diagnosis of PVOD or PCH or both. Dogs were older (median 11 years) with no apparent breed or sex predisposition. Dogs presented with acute clinical signs (median 3 days), usually respiratory distress. Thoracic radiography (available in 10 dogs) revealed right cardiomegaly and patchy or diffuse interstitial to alveolar patterns, with 9 dogs having a normal left cardiac silhouette. In 5 dogs tested, pulmonary arterial hypertension (PAH) was documented. In all 3 dogs, thoracic computed tomography scans showed pulmonary arterial enlargement and perivascular diffuse nodular ground-glass opacities. Ten of 15 dogs died within 1 day; median survival was 3 days.

Conclusions And Clinical Importance: In dogs with PAH, the inability to document left-sided congestive heart failure and failure to identify another cause of signs of respiratory disease should increase suspicion for PVOD and PCH. With increased awareness of PVOD and PCH by clinicians and pathologists, dogs with compatible clinicopathologic features should be evaluated for these pulmonary vascular disorders.
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http://dx.doi.org/10.1111/jvim.15351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335444PMC
January 2019

Radioactive iodine uptake in hyperthyroid cats after administration of recombinant human thyroid stimulating hormone.

J Vet Intern Med 2018 Nov 13;32(6):1891-1896. Epub 2018 Oct 13.

Departments of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, 48824.

Background: Radioactive iodine therapy is considered the treatment of choice for hyperthyroidism in cats, but the availability of this modality is limited by costs and hospitalization requirements. Administration of recombinant human thyroid stimulating hormone (rh-TSH) to humans with thyroid neoplasia or nodular goiter can increase thyroidal iodine uptake, thereby allowing the use of lower radioactive iodine doses for treatment. Veterinary studies of this subject are limited, and results are conflicting.

Objective: To investigate the effects of rh-TSH administration on thyroidal iodine uptake in hyperthyroid cats.

Animals: Ten client-owned hyperthyroid cats.

Methods: In this prospective clinical study, cats were administered saline (placebo), 50 μg rh-TSH (low-dose), and 100 μg rh-TSH (high-dose) in randomized crossover design with treatments separated by 7-10 days. After each treatment, thyroid scintigraphy was performed by administering 300 μCi I and assessing radionuclide uptake 8 and 24 hours later. Serum thyroid hormone concentrations were measured at each visit.

Results: Thyroidal percent iodine uptakes (mean ± SD at 8 and 24 hours) in cats treated with placebo (25.2 ± 13.4%, 30.0 ± 12.8%), low-dose (24.1 ± 12.5%, 29.4 ± 13.7%), and high-dose rh-TSH (24.2 ± 16.3%, 30.8 ± 15.3%) were not different (P = .76). Independent of rh-TSH administration, percent iodine uptakes were positively correlated with serum thyroid hormone concentrations.

Conclusions And Clinical Importance: One-time administration of rh-TSH, even at high doses, would not be expected to lower radioactive iodine doses needed for treatment of hyperthyroidism in cats. Investigations of alternate strategies to increase thyroidal uptake of radioactive iodine are warranted.
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http://dx.doi.org/10.1111/jvim.15295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271304PMC
November 2018

Publication rates of podium and poster abstract presentations at the 2010 and 2011 society of gynecologic oncology conferences.

Gynecol Oncol Rep 2018 May 3;24:6-9. Epub 2018 Feb 3.

Oklahoma State University Center for Health Sciences, Tulsa, OK, United States.

Objective: This study aimed to determine the publication rate of oral and poster abstracts presented at the 2010 and 2011 Society of Gynecologic Oncology (SGO) conferences as well as the journals that most commonly published these studies, their 5-year impact factor, the time to publication, and the reasons for nonpublication.

Methods: Abstracts presented at the 2010-2011 SGO conferences were included in this study. We searched Google, Google Scholar, and PubMed to locate published reports of these abstracts. If an abstract's full-text manuscript could not be located, an author of the conference abstract was contacted via email to inquire whether the research was published. If the research was unpublished, the authors were asked to provide the reason for nonpublication. The time to publication, journal, and journal impact factor were noted for abstracts that reached full-text publication.

Results: A total of 725 abstracts were identified, of which 386 (53%) reached publication in a peer-reviewed journal. Oral presentations were published at a higher rate than poster presentations. Most (70%) reached publication within 2 years of abstract presentation. Abstracts were published in 89 journals, but most (39%) were published in Gynecologic Oncology. The mean time to publication was 15.7 months, with a mean 5-year impact factor of 4.956.

Conclusions: A 53% publication rate indicates that the SGO conference selection process favors research likely to be published and, thus, presumably of high quality. The overall publication rate is higher than that reported for many other biomedical conferences.
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http://dx.doi.org/10.1016/j.gore.2018.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993534PMC
May 2018

Influence of immune-mediated hemolytic anemia on flow velocities in the portal vein and caudal vena cava measured by use of pulsed-wave Doppler ultrasonography in dogs.

Am J Vet Res 2018 May;79(5):518-524

OBJECTIVE To compare blood flow velocities of the portal vein (PV) and caudal vena cava (CVC) measured by use of pulsed-wave Doppler ultrasonography in clinically normal dogs and dogs with primary immune-mediated hemolytic anemia (IMHA). ANIMALS 11 client-owned dogs admitted to a veterinary teaching hospital for management of primary IMHA and 21 staff- or student-owned clinically normal dogs. PROCEDURES Flow velocities in the PV and CVC at the porta hepatis were evaluated in conscious unsedated dogs with concurrent ECG monitoring; evaluations were performed before dogs with IMHA received heparin or blood transfusions. Three measurements of peak velocity at end expiration were obtained for each vessel, and the mean was calculated. Results were compared between IMHA and control groups. RESULTS Mean ± SD blood flow velocity in the CVC differed between control (63.0 ± 18.6 cm/s) and IMHA (104 ± 36.9 cm/s) groups. Variance in dogs with IMHA was significantly greater than that for the clinically normal dogs. No significant difference in blood flow velocity in the PV was detected between IMHA and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Higher blood flow velocities were detected by use of pulsed-wave Doppler ultrasonography in the CVC of dogs with naturally occurring IMHA and may be used to predict anemia in patients suspected of having IMHA.
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http://dx.doi.org/10.2460/ajvr.79.5.518DOI Listing
May 2018

Structure and function of photosystem I in Cyanidioschyzon merolae.

Photosynth Res 2019 Mar 26;139(1-3):499-508. Epub 2018 Mar 26.

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978, Tel Aviv, Israel.

The evolution of photosynthesis from primitive photosynthetic bacteria to higher plants has been driven by the need to adapt to a wide range of environmental conditions. The red alga Cyanidioschyzon merolae is a primitive organism, which is capable of performing photosynthesis in extreme acidic and hot environments. The study of its photosynthetic machinery may provide new insight on the evolutionary path of photosynthesis and on light harvesting and its regulation in eukaryotes. With that aim, the structural and functional properties of the PSI complex were investigated by biochemical characterization, mass spectrometry, and X-ray crystallography. PSI was purified from cells grown at 25 and 42 °C, crystallized and its crystal structure was solved at 4 Å resolution. The structure of C. merolae reveals a core complex with a crescent-shaped structure, formed by antenna proteins. In addition, the structural model shows the position of PsaO and PsaM. PsaG and PsaH are present in plant complex and are missing from the C. merolae model as expected. This paper sheds new light onto the evolution of photosynthesis, which gives a strong indication for the chimerical properties of red algae PSI. The subunit composition of the PSI core from C. merolae and its associated light-harvesting antennae suggests that it is an evolutionary and functional intermediate between cyanobacteria and plants.
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http://dx.doi.org/10.1007/s11120-018-0501-4DOI Listing
March 2019

Structure of the plant photosystem I.

Biochem Soc Trans 2018 04 27;46(2):285-294. Epub 2018 Feb 27.

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel

Plant photosystem I (PSI) is one of the most intricate membrane complexes in nature. It comprises two complexes, a reaction center and light-harvesting complex (LHC), which together form the PSI-LHC supercomplex. The crystal structure of plant PSI was solved with two distinct crystal forms. The first, crystallized at pH 6.5, exhibited 21 symmetry; the second, crystallized at pH 8.5, exhibited 212121 symmetry. The surfaces involved in binding plastocyanin and ferredoxin are identical in both forms. The crystal structure at 2.6 Å resolution revealed 16 subunits, 45 transmembrane helices, and 232 prosthetic groups, including 143 chlorophyll , 13 chlorophyll , 27 β-carotene, 7 lutein, 2 xanthophyll, 1 zeaxanthin, 20 monogalactosyl diglyceride, 7 phosphatidyl diglyceride, 5 digalactosyl diglyceride, 2 calcium ions, 2 phylloquinone, and 3 iron sulfur clusters. The model reveals detailed interactions, providing mechanisms for excitation energy transfer and its modulation in one of nature's most efficient photochemical machine.
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http://dx.doi.org/10.1042/BST20170299DOI Listing
April 2018

Structure and function of wild-type and subunit-depleted photosystem I in Synechocystis.

Biochim Biophys Acta Bioenerg 2018 09 4;1859(9):645-654. Epub 2018 Feb 4.

Department of Biochemistry and Molecular Biology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address:

The ability of photosynthetic organisms to use the sun's light as a sole source of energy sustains life on our planet. Photosystems I (PSI) and II (PSII) are large, multi-subunit, pigment-protein complexes that enable photosynthesis, but this intriguing process remains to be explained fully. Currently, crystal structures of these complexes are available for thermophilic prokaryotic cyanobacteria. The mega-Dalton trimeric PSI complex from thermophilic cyanobacterium, Thermosynechococcus elongatus, was solved at 2.5 Å resolution with X-ray crystallography. That structure revealed the positions of 12 protein subunits (PsaA-F, PsaI-M, and PsaX) and 127 cofactors. Although mesophilic organisms perform most of the world's photosynthesis, no well-resolved trimeric structure of a mesophilic organism exists. Our research model for a mesophilic cyanobacterium was Synechocystis sp. PCC6803. This study aimed to obtain well-resolved crystal structures of [1] a monomeric PSI with all subunits, [2] a trimeric PSI with a reduced number of subunits, and [3] the full, trimeric wild-type PSI complex. We only partially succeeded with the first two structures, but we successfully produced the trimeric PSI structure at 2.5 Å resolution. This structure was comparable to that of the thermophilic species, but we provided more detail. The PSI trimeric supercomplex consisted of 33 protein subunits, 72 carotenoids, 285 chlorophyll a molecules, 51 lipids, 9 iron-sulfur clusters, 6 plastoquinones, 6 putative calcium ions, and over 870 water molecules. This study showed that the structure of the PSI in Synechocystis sp. PCC6803 differed from previously described PSI structures. These findings have broadened our understanding of PSI structure.
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http://dx.doi.org/10.1016/j.bbabio.2018.02.002DOI Listing
September 2018

Calibration of the APEX Model to Simulate Management Practice Effects on Runoff, Sediment, and Phosphorus Loss.

J Environ Qual 2017 Nov;46(6):1332-1340

Process-based computer models have been proposed as a tool to generate data for Phosphorus (P) Index assessment and development. Although models are commonly used to simulate P loss from agriculture using managements that are different from the calibration data, this use of models has not been fully tested. The objective of this study is to determine if the Agricultural Policy Environmental eXtender (APEX) model can accurately simulate runoff, sediment, total P, and dissolved P loss from 0.4 to 1.5 ha of agricultural fields with managements that are different from the calibration data. The APEX model was calibrated with field-scale data from eight different managements at two locations (management-specific models). The calibrated models were then validated, either with the same management used for calibration or with different managements. Location models were also developed by calibrating APEX with data from all managements. The management-specific models resulted in satisfactory performance when used to simulate runoff, total P, and dissolved P within their respective systems, with > 0.50, Nash-Sutcliffe efficiency > 0.30, and percent bias within ±35% for runoff and ±70% for total and dissolved P. When applied outside the calibration management, the management-specific models only met the minimum performance criteria in one-third of the tests. The location models had better model performance when applied across all managements compared with management-specific models. Our results suggest that models only be applied within the managements used for calibration and that data be included from multiple management systems for calibration when using models to assess management effects on P loss or evaluate P Indices.
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http://dx.doi.org/10.2134/jeq2016.07.0272DOI Listing
November 2017

Multisite Evaluation of APEX for Water Quality: II. Regional Parameterization.

J Environ Qual 2017 Nov;46(6):1349-1356

Phosphorus (P) Index assessment requires independent estimates of long-term average annual P loss from fields, representing multiple climatic scenarios, management practices, and landscape positions. Because currently available measured data are insufficient to evaluate P Index performance, calibrated and validated process-based models have been proposed as tools to generate the required data. The objectives of this research were to develop a regional parameterization for the Agricultural Policy Environmental eXtender (APEX) model to estimate edge-of-field runoff, sediment, and P losses in restricted-layer soils of Missouri and Kansas and to assess the performance of this parameterization using monitoring data from multiple sites in this region. Five site-specific calibrated models (SSCM) from within the region were used to develop a regionally calibrated model (RCM), which was further calibrated and validated with measured data. Performance of the RCM was similar to that of the SSCMs for runoff simulation and had Nash-Sutcliffe efficiency (NSE) > 0.72 and absolute percent bias (|PBIAS|) < 18% for both calibration and validation. The RCM could not simulate sediment loss (NSE < 0, |PBIAS| > 90%) and was particularly ineffective at simulating sediment loss from locations with small sediment loads. The RCM had acceptable performance for simulation of total P loss (NSE > 0.74, |PBIAS| < 30%) but underperformed the SSCMs. Total P-loss estimates should be used with caution due to poor simulation of sediment loss. Although we did not attain our goal of a robust regional parameterization of APEX for estimating sediment and total P losses, runoff estimates with the RCM were acceptable for P Index evaluation.
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http://dx.doi.org/10.2134/jeq2016.07.0254DOI Listing
November 2017

Multisite Evaluation of APEX for Water Quality: I. Best Professional Judgment Parameterization.

J Environ Qual 2017 Nov;46(6):1323-1331

The Agricultural Policy Environmental eXtender (APEX) model is capable of estimating edge-of-field water, nutrient, and sediment transport and is used to assess the environmental impacts of management practices. The current practice is to fully calibrate the model for each site simulation, a task that requires resources and data not always available. The objective of this study was to compare model performance for flow, sediment, and phosphorus transport under two parameterization schemes: a best professional judgment (BPJ) parameterization based on readily available data and a fully calibrated parameterization based on site-specific soil, weather, event flow, and water quality data. The analysis was conducted using 12 datasets at four locations representing poorly drained soils and row-crop production under different tillage systems. Model performance was based on the Nash-Sutcliffe efficiency (NSE), the coefficient of determination () and the regression slope between simulated and measured annualized loads across all site years. Although the BPJ model performance for flow was acceptable (NSE = 0.7) at the annual time step, calibration improved it (NSE = 0.9). Acceptable simulation of sediment and total phosphorus transport (NSE = 0.5 and 0.9, respectively) was obtained only after full calibration at each site. Given the unacceptable performance of the BPJ approach, uncalibrated use of APEX for planning or management purposes may be misleading. Model calibration with water quality data prior to using APEX for simulating sediment and total phosphorus loss is essential.
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http://dx.doi.org/10.2134/jeq2016.06.0226DOI Listing
November 2017