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1.
Pest Manag Sci ; 80(7): 3227-3237, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38357838

ABSTRACT

BACKGROUND: Wild pigs (Sus scrofa) are an invasive and destructive species throughout many regions of the world. A sodium nitrite (SN) toxic bait is currently used in Australia and being developed for use in the US and other countries to combat the increasing populations of wild pigs. In the US, efforts to modify the Australian SN-toxic bait and baiting strategy have focused on reducing issues with non-target animals accessing the SN-toxic bait spilled outside of bait stations by wild pigs. We tested and compared modifications for efficacy (with wild pigs) and hazards (with non-targets) in north-central Texas, US during summer (July 2021) and winter (March 2023) seasons. RESULTS: During both seasons we found that visitation to the bait sites declined 94-99% after deploying the SN-toxic bait, and we found a total of 106 dead wild pigs, indicating considerable lethality for the local population. Prior to deploying the SN-toxic bait, Global Positioning System (GPS)-collared wild pigs were more likely to cease visiting bait sites during summer when foraging resources were abundant. Farrowing decreased visitation to bait sites during the winter. We observed no dead non-targets during summer; winter results showed an average of 5.2 dead migrating birds per bait site (primarily Dark-eye juncos [Junco hyemalis]) from consuming SN-toxic bait spilled by wild pigs. The presence and winter-foraging behaviors of migrating birds appeared to increase hazards for those species. CONCLUSION: The current formulation of SN-toxic bait was effective at removing wild pigs during both seasons, however it is clear that different baiting strategies may be required in winter when migrating birds are present. Baiting wild pigs prior to farrowing during the winter, and during drier summers, may further improve efficacy of the bait. Reducing hazards to non-targets could be achieved by refining the SN-toxic bait or modifying bait stations to decrease the potential for spillage, decreasing environmental persistence if spilled, or decreasing attractiveness to migrating birds. © 2024 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.


Subject(s)
Seasons , Sodium Nitrite , Sus scrofa , Animals , Texas , Pest Control/methods , Birds , Introduced Species , Swine
2.
Pest Manag Sci ; 79(11): 4589-4598, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37431651

ABSTRACT

BACKGROUND: In 2018, a sodium nitrite (SN)-based toxic bait for invasive wild pigs (hereafter wild pigs; Sus scrofa), was evaluated to determine its effectiveness in reducing local wild pig populations in Texas. Localized population reductions of >70% were achieved, but spillage of bait outside wild pig-specific feeders (bait stations) caused by feeding wild pigs resulted in the deaths of non-target animals. To evaluate risks to non-target animals, we tested whether bait presentation influenced the total amount of bait spilled by wild pigs and estimated the associated risk to non-target species. RESULTS: We found that bait spilled outside bait stations could be reduced by >90% when compacted in trays, as opposed to being manually crumbled into pieces. We documented a mean spill rate of 0.913 g of bait per wild pig. Conservative risk assessments for nine non-target species for which SN toxicity data exist indicate that there is relatively low risk of lethal exposure, apart from zebra finches (Taeniopygia guttata) and white mice. Our results indicate that there may be enough spilled bait per feeding wild pig to kill 9.5 or 3.5 individuals of these species, respectively. Other species assessed range from 0.002 to 0.406 potential mortalities per wild pig. CONCLUSION: We demonstrated that the amount of bait spilled by wild pigs during feeding and the associated risk to non-target animals can be minimized by presenting the bait compacted in trays within bait stations. We recommend that baits be tightly compacted and secured in bait stations to minimize risks to non-target animals from spilled bait by wild pigs. © 2023 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

3.
Nat Commun ; 13(1): 1604, 2022 03 25.
Article in English | MEDLINE | ID: mdl-35338144

ABSTRACT

The MERS coronavirus (MERS-CoV) is a highly pathogenic, emerging virus that produces accessory proteins to antagonize the host innate immune response. The MERS-CoV ORF4b protein has been shown to bind preferentially to the nuclear import adapter IMPα3 in infected cells, thereby inhibiting NF-κB-dependent innate immune responses. Here, we report high-resolution structures of ORF4b bound to two distinct IMPα family members. Each exhibit highly similar binding mechanisms that, in both cases, lack a prototypical Lys bound at their P2 site. Mutations within the NLS region dramatically alter the mechanism of binding, which reverts to the canonical P2 Lys binding mechanism. Mutational studies confirm that the novel binding mechanism is important for its nuclear import, IMPα interaction, and inhibition of innate immune signaling pathways. In parallel, we determined structures of the nuclear binding domain of NF-κB component p50 bound to both IMPα2 and α3, demonstrating that p50 overlaps with the ORF4b binding sites, suggesting a basis for inhibition. Our results provide a detailed structural basis that explains how a virus can target the IMPα nuclear import adapter to impair immunity, and illustrate how small mutations in ORF4b, like those found in closely related coronaviruses such as HKU5, change the IMPα binding mechanism.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Host-Pathogen Interactions , Humans , Immunity, Innate , NF-kappa B/metabolism
4.
Sci Rep ; 11(1): 19967, 2021 10 07.
Article in English | MEDLINE | ID: mdl-34620966

ABSTRACT

Toxic baiting of wild pigs (Sus scrofa) is a potential new tool for population control and damage reduction in the US. Field trials testing a prototype toxic bait (HOGGONE 2 containing 5% sodium nitrite [SN]), though, revealed that wild pigs spilled small particles of toxic bait outside of bait stations which subsequently created hazards for non-target species that consumed those particles, primarily passerine birds. To deter non-target birds from consuming particles of spilled bait, we tested four deterrents at mock bait sites (i.e., baited with bird seed) in north-central Colorado, USA during April-May 2020. We found a programable, inflatable deterrent device (scare dancer) reduced bird visitation by an average of 96%. Then, we evaluated the deterrent devices at SN-toxic bait sites in north-central Texas, USA during July 2020, where the devices were activated the morning following deployment of SN-toxic bait. Overall, we found 139 dead wild pigs at 10 bait sites following one night of toxic baiting, which represented an average of 91% reduction in wild pigs visiting bait sites. We found that deterrent devices were 100% effective at deterring birds from toxic bait sites. We found two dead non-target mice at bait sites without deterrent devices. We noted that deploying toxic bait in mid-summer rather than late-winter/early-spring reduced hazards to migrating birds because they were not present in our study area during July. We recommend using deterrent devices (i.e., novel, programmable, battery operated, continuous and erratic movement, and snapping sounds) to reduce hazards to non-target birds at SN-toxic bait sites. We further recommend deploying SN-toxic bait during seasons when migrating birds are not as abundant until further research demonstrates minimal risks to migrating birds.


Subject(s)
Animals, Wild , Birds , Pest Control/methods , Poisoning/prevention & control , Animals , Colorado , Sodium Nitrite/toxicity , Sus scrofa , Texas
5.
Int J Mol Sci ; 22(6)2021 Mar 23.
Article in English | MEDLINE | ID: mdl-33806862

ABSTRACT

Considering the widespread occurrence of oxalate in nature and its broad impact on a host of organisms, it is surprising that so little is known about the turnover of this important acid. In plants, oxalate oxidase is the most well-studied enzyme capable of degrading oxalate, but not all plants possess this activity. Recently, acyl-activating enzyme 3 (AAE3), encoding an oxalyl-CoA synthetase, was identified in Arabidopsis. This enzyme has been proposed to catalyze the first step in an alternative pathway of oxalate degradation. Since this initial discovery, this enzyme and proposed pathway have been found to be important to other plants and yeast as well. In this study, we identify, in Arabidopsis, an oxalyl-CoA decarboxylase (AtOXC) that is capable of catalyzing the second step in this proposed pathway of oxalate catabolism. This enzyme breaks down oxalyl-CoA, the product of AtAAE3, into formyl-CoA and CO2. AtOXC:GFP localization suggested that this enzyme functions within the cytosol of the cell. An Atoxc knock-down mutant showed a reduction in the ability to degrade oxalate into CO2. This reduction in AtOXC activity resulted in an increase in the accumulation of oxalate and the enzyme substrate, oxalyl-CoA. Size exclusion studies suggest that the enzyme functions as a dimer. Computer modeling of the AtOXC enzyme structure identified amino acids of predicted importance in co-factor binding and catalysis. Overall, these results suggest that AtOXC catalyzes the second step in this alternative pathway of oxalate catabolism.


Subject(s)
Arabidopsis/physiology , Carboxy-Lyases/metabolism , Oxalates/metabolism , Plant Physiological Phenomena , Amino Acid Sequence , Carboxy-Lyases/chemistry , Carboxy-Lyases/genetics , Chromatography, High Pressure Liquid , Cloning, Molecular , Enzyme Activation , Gene Expression Regulation, Plant , Metabolic Networks and Pathways , Models, Molecular , Oxidation-Reduction , Plant Development/genetics , Protein Conformation , Protein Transport
6.
J Patient Saf ; 17(8): e1585-e1588, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-32502115

ABSTRACT

OBJECTIVE: Opioids are high-risk medications in the inpatient setting because of their potential for significant patient harm. The primary objective was to identify risk factors that predispose inpatients to develop opioid-related adverse drug events (ORADE) requiring the use of naloxone. METHODS: In a retrospective case-control study, patients were included according to the following criteria: 18 years or older, 1 administered opioid doses or more, and admitted for 24 hours or more. Patients were excluded if they had a prehospital drug overdose, other indications for naloxone use, or were admitted to an intensive care unit, psychiatric medical unit, or in the emergency department. Patients were classified as cases if naloxone was administered and a selection of controls were frequency matched 2:1 based on medical or surgical status. A logistic regression model was used to evaluate for risk factors for ORADE. RESULTS: A total of 275 cases and 592 control patients were included into the final analysis. Variables that were associated with greater odds of naloxone administration included age of 65 years or older, female, length of stay, pulmonary diagnoses, use of gabapentinoids, and patient-controlled analgesia use. Antihistamines, continuous infusion, and intermittent nurse administered intravenous bolus routes had a negative association with naloxone use. CONCLUSIONS: Several risk factors were found to be associated with ORADE supporting many of the previously described risk factors, and the discovery of potential new ones, such as gabapentinoid use. Health care providers should consider the risk factors for hospitalized patients receiving opioids who may warrant lower doses, additional monitoring, or alternative agents.


Subject(s)
Analgesics, Opioid , Drug-Related Side Effects and Adverse Reactions , Aged , Analgesics, Opioid/adverse effects , Case-Control Studies , Female , Humans , Male , Middle Aged , Naloxone , Narcotic Antagonists , Retrospective Studies
8.
Pest Manag Sci ; 77(4): 1616-1625, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33200879

ABSTRACT

BACKGROUND: Wild pigs (Sus scrofa) are a destructive invasive species throughout many regions of the world. In 2018, a field evaluation of an early prototype of a sodium nitrite (SN) toxic bait in the United States revealed wild pigs dropped large amounts of the toxic bait outside the pig-specific bait stations while feeding, and thus subsequent hazards for non-target animals. We modified the SN-toxic bait formulation, the design of the bait station, and the baiting strategy to reduce dropped bait. We tested the modifications in Queensland, Australia (December 2018), Alabama, USA (August 2019), and Texas, USA (March 2020) under differing climatic and seasonal conditions for one night. RESULTS: Cumulatively we found 161 carcasses of all age classes of wild pigs using systematic transects. Remote camera indices indicated high lethality for wild pigs, achieving population reductions of 76.3 to 90.4%. Wild pigs dropped only small particles of SN-toxic bait (average = 55.5 g per bait site), which represented a 19-fold decrease from the previous trial. Despite this reduction, we found three Australian ravens (Corvus coronoides) in Queensland, two Virginia opossums (Didelphis virginiana) in Alabama, and 35 granivorous-passerine birds (mostly dark-eyed juncos [Junco hyemalis]) in Texas dead from consuming the dropped bait. We did not detect any population-level effects for those species. CONCLUSION: Our modifications were effective at reducing populations of wild pigs, but the deaths of non-target species require further steps to minimize these hazards. Next steps will include evaluating various deterrent devices for birds the morning after SN-toxic bait has been offered. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.


Subject(s)
Animals, Wild , Sus scrofa , Animals , Australia , Queensland , Sodium Nitrite , Swine , Texas
9.
Am J Emerg Med ; 38(12): 2564-2569, 2020 12.
Article in English | MEDLINE | ID: mdl-31932132

ABSTRACT

PURPOSE: Evaluate opioid prescribing before and after emergency department (ED) renal colic guideline implementation focused on multi-modal pain management. METHODS: Retrospective study of ED patients who received analgesia for urolithiasis before and after guideline implementation. The guideline recommends oral acetaminophen, intravenous (IV) ketorolac, and a fluid bolus as first line, IV lidocaine as second line, and opioids as refractory therapy to control pain. Opioid exposure, adverse effects, length of stay (LOS), and ED representation were evaluated. Comparisons were made with univariate analyses. Backwards stepwise binomial multivariate logistic regression to identify factors related to opioid use was performed. RESULTS: Overall, 962 patients were included (451 pre- and 511 post-implementation). ED and discharge opioid use decreased; 65% vs. 58% and 71% vs. 63% in pre- and post-implementation groups, respectively. More post-implementation patients received non-opioid analgesia (65% vs. 56%) and non-opioid analgesia prior to opioids (50% vs. 38%). A longer ED LOS and higher initial pain score were associated with ED opioid administration. Guideline implementation, receiving non-opioid therapy first, and first renal colic episode were associated with decreased ED opioid administration. Seventeen adverse events (1.8%) were reported. There was no difference in change in ED pain score between groups, but patients in the post-implementation group were admitted more and had a higher 7-day ED representation (11% vs. 7%). CONCLUSIONS: A multimodal analgesia protocol for renal colic was associated with decreased opioid prescribing, higher rates of admission to the hospital, and a higher 7-day ED representation rate.


Subject(s)
Acetaminophen/therapeutic use , Analgesics, Non-Narcotic/therapeutic use , Analgesics, Opioid/therapeutic use , Anesthetics, Local/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Ketorolac/therapeutic use , Lidocaine/therapeutic use , Renal Colic/drug therapy , Administration, Intravenous , Administration, Oral , Adult , Female , Fluid Therapy , Humans , Male , Middle Aged , Practice Guidelines as Topic , Renal Colic/etiology , Urinary Calculi/complications
10.
Biochem Biophys Res Commun ; 505(1): 255-260, 2018 10 20.
Article in English | MEDLINE | ID: mdl-30245129

ABSTRACT

The Acyl-Activating Enzyme (AAE) 3 gene encodes an oxalyl-CoA synthetase that catalyzes the conversion of oxalate to oxalyl-CoA in a CoA and ATP-dependent manner. Although the biochemical activity of AAE3 has been established, its biological role in plant growth and development remains unclear. To advance our understanding of the role of AAE3 in plant growth and development, we report here the characterization of two Medicago truncatula AAE3 (Mtaae3) mutants. Characterization of a Mtaae3 RNAi mutant revealed an accumulation of calcium oxalate crystals and increased seed permeability. These phenotypes were also exhibited in the Arabidopsis aae3 (Ataae3) mutants. Unlike the Ataae3 mutants, the Mtaae3 RNAi mutant did not show a reduction in vegetative growth, decreased seed germination, or increased seed calcium concentration. In an effort to clarify these phenotypic differences, a Mtaae3 Tnt1 mutant was identified and characterized. This Mtaae3 Tnt1 mutant displayed reduced vegetative growth, decreased seed germination, and increased seed calcium concentration as well as an accumulation of calcium oxalate crystals and increased seed permeability as found in Ataae3. Overall, the results presented here show the importance of AAE3 in the growth and development of plants. In addition, this study highlights the ability to separate specific growth and development phenotypes based on the level of AAE3 gene expression.


Subject(s)
Acetate-CoA Ligase/genetics , Gene Expression Regulation, Developmental , Gene Expression Regulation, Plant , Medicago truncatula/genetics , Plant Proteins/genetics , Acetate-CoA Ligase/metabolism , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis/metabolism , Calcium Oxalate/chemistry , Calcium Oxalate/metabolism , Crystallization , Medicago truncatula/enzymology , Medicago truncatula/growth & development , Mutation , Plant Proteins/metabolism , RNA Interference , Seeds/genetics , Seeds/growth & development , Seeds/metabolism
11.
Pest Manag Sci ; 74(1): 181-188, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28762643

ABSTRACT

BACKGROUND: An acute and orally delivered toxic bait containing micro-encapsulated sodium nitrite (MESN), is under development to provide a novel and humane technology to help curtail damage caused by invasive wild pigs (Sus scrofa). We evaluated potential secondary risks for non-target species by: testing whether four different types of micro-encapsulation coatings could reduce vomiting by invasive wild pigs, testing the levels of residual sodium nitrite (SN) in tissues of invasive wild pigs, testing the environmental persistence of SN in vomitus, and conducting a risk assessment for scavengers. RESULTS: Micro-encapsulation coatings did not affect the frequency of vomiting. We identified no risk of secondary poisoning for non-target scavengers that consume muscle, eyes, and livers of invasive wild pig carcasses because residual SN from the toxic bait was not detected in those tissues. The risk of secondary poisoning from consuming vomitus appeared low because ∼90% of the SN was metabolized or broken down prior to vomiting, and continued to degrade after being exposed to the environment. Secondary poisoning could occur for common scavengers that consume approximately ≥15% of their daily dietary requirements of digestive tract tissues or undigested bait from carcasses of invasive wild pigs in a rapid, single-feeding event. The likelihood of this occurring in a natural setting is unknown. The digestive tracts of poisoned invasive wild pigs contained an average of ∼4.35 mg/g of residual SN. CONCLUSION: Data from this study suggest no risks of secondary poisoning for non-target species (including humans) that consume muscle, liver, or eyes of invasive wild pigs poisoned with a MESN toxic bait. More species-specific testing for scavengers that consume digestive tract tissues and undigested bait is needed to reduce uncertainty about these potential risks. © 2017 Society of Chemical Industry.


Subject(s)
Animals, Wild , Pest Control/instrumentation , Poisoning/prevention & control , Sodium Nitrite/toxicity , Sus scrofa , Animals , Female , Male , Sodium Nitrite/metabolism , Vomiting/chemically induced , Vomiting/prevention & control
12.
Zebrafish ; 15(2): 202-205, 2018 04.
Article in English | MEDLINE | ID: mdl-29173090

ABSTRACT

The completion of the zebrafish genome sequence and advances in miniaturization and multiplexing were essential to the creation of techniques such as RNA-seq, ChIP-seq, and high-throughput behavioral and chemical screens. Multiplexing was also instrumental in the recent enhancement of the classic yeast one-hybrid interaction techniques to provide unprecedented discovery capabilities for protein-DNA interactions. Unfortunately its use for zebrafish research is currently hampered by the lack of an open reading frame (ORF) clone collection. As a first step toward a complete collection, we describe a small library of transcriptional regulatory proteins comprising 142 ORFs and its potential applications.


Subject(s)
Gene Regulatory Networks , Open Reading Frames , Transcription Factors/genetics , Zebrafish Proteins/genetics , Zebrafish/genetics , Animals , Cloning, Molecular , Computational Biology , Gene Expression Regulation , Gene Library , Transcription Factors/metabolism , Zebrafish/metabolism , Zebrafish Proteins/metabolism
13.
PLoS One ; 11(2): e0149850, 2016.
Article in English | MEDLINE | ID: mdl-26900946

ABSTRACT

Considering the widespread occurrence of oxalate in nature and its broad impact on a host of organisms, it is surprising that so little is known about the turnover of this important acid. In plants, oxalate oxidase is the most well studied enzyme capable of degrading oxalate, but not all plants possess this activity. Recently, an Acyl Activating Enzyme 3 (AAE3), encoding an oxalyl-CoA synthetase, was identified in Arabidopsis. AAE3 has been proposed to catalyze the first step in an alternative pathway of oxalate degradation. Whether this enzyme and proposed pathway is important to other plants is unknown. Here, we identify the Medicago truncatula AAE3 (MtAAE3) and show that it encodes an oxalyl-CoA synthetase activity exhibiting high activity against oxalate with a Km = 81 ± 9 µM and Vmax = 19 ± 0.9 µmoles min-1mg protein-1. GFP-MtAAE3 localization suggested that this enzyme functions within the cytosol of the cell. Mtaae3 knock-down line showed a reduction in its ability to degrade oxalate into CO2. This reduction in the capacity to degrade oxalate resulted in the accumulation of druse crystals of calcium oxalate in the Mtaae3 knock-down line and an increased susceptibility to oxalate-secreting phytopathogens such as Sclerotinia sclerotiorum. Taken together, these results suggest that AAE3 dependent turnover of oxalate is important to different plants and functions in the regulation of tissue calcium oxalate crystal accumulation and in defense against oxalate-secreting phytopathogens.


Subject(s)
Acyl Coenzyme A/metabolism , Ascomycota/physiology , Calcium Oxalate/metabolism , Medicago truncatula/metabolism , Medicago truncatula/microbiology , Plant Diseases/microbiology
14.
PLoS One ; 11(1): e0146712, 2016.
Article in English | MEDLINE | ID: mdl-26812148

ABSTRACT

Invasive feral swine (Sus scrofa) cause extensive damage to agricultural and wildlife resources throughout the United States. Development of sodium nitrite as a new, orally delivered toxicant is underway to provide an additional tool to curtail growth and expansion of feral swine populations. A micro-encapsulation coating around sodium nitrite is used to minimize detection by feral swine and maximize stability for the reactive molecule. To maximize uptake of this toxicant by feral swine, development a bait matrix is needed to 1) protect the micro-encapsulation coating so that sodium nitrite remains undetectable to feral swine, 2) achieve a high degree of acceptance by feral swine, and 3) be minimally appealing to non-target species. With these purposes, a field evaluation at 88 sites in south-central Texas was conducted using remote cameras to evaluate preferences by feral swine for several oil-based bait matrices including uncolored peanut paste, black-colored peanut paste, and peanut-based slurry mixed onto whole-kernel corn. These placebo baits were compared to a reference food, whole-kernel corn, known to be readily taken by feral swine (i.e., control). The amount of bait consumed by feral swine was also estimated using remote cameras and grid boards at 5 additional sites. On initial exposure, feral swine showed reduced visitations to the uncolored peanut paste and peanut slurry treatments. This reduced visitation subsided by the end of the treatment period, suggesting that feral swine needed time to accept these bait types. The black-colored peanut paste was visited equally to the control throughout the study, and enough of this matrix was consumed to deliver lethal doses of micro-encapsulated sodium nitrite to most feral swine during 1-2 feeding events. None of the treatment matrices reduced visitations by nontarget species, but feral swine dominated visitations for all matrices. It was concluded that black-colored peanut paste achieved satisfactory preference and consumption by feral swine, and no discernable preference by non-target species, compared to the other treatments.


Subject(s)
Poisons/administration & dosage , Sodium Nitrite/administration & dosage , Sus scrofa , Animals , Animals, Wild , Food Preferences , Introduced Species , Population Control , Texas
15.
J Neural Eng ; 12(1): 016009, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25504690

ABSTRACT

OBJECTIVE: For intracortical brain-machine interfaces (BMIs), action potential voltage waveforms are often sorted to separate out individual neurons. If these neurons contain independent tuning information, this process could increase BMI performance. However, the sorting of action potentials ('spikes') requires high sampling rates and is computationally expensive. To explicitly define the difference between spike sorting and alternative methods, we quantified BMI decoder performance when using threshold-crossing events versus sorted action potentials. APPROACH: We used data sets from 58 experimental sessions from two rhesus macaques implanted with Utah arrays. Data were recorded while the animals performed a center-out reaching task with seven different angles. For spike sorting, neural signals were sorted into individual units by using a mixture of Gaussians to cluster the first four principal components of the waveforms. For thresholding events, spikes that simply crossed a set threshold were retained. We decoded the data offline using both a Naïve Bayes classifier for reaching direction and a linear regression to evaluate hand position. MAIN RESULTS: We found the highest performance for thresholding when placing a threshold between -3 and -4.5 × Vrms. Spike sorted data outperformed thresholded data for one animal but not the other. The mean Naïve Bayes classification accuracy for sorted data was 88.5% and changed by 5% on average when data were thresholded. The mean correlation coefficient for sorted data was 0.92, and changed by 0.015 on average when thresholded. SIGNIFICANCE: For prosthetics applications, these results imply that when thresholding is used instead of spike sorting, only a small amount of performance may be lost. The utilization of threshold-crossing events may significantly extend the lifetime of a device because these events are often still detectable once single neurons are no longer isolated.


Subject(s)
Action Potentials/physiology , Brain Mapping/methods , Brain-Computer Interfaces , Motor Cortex/physiology , Neurons/physiology , Pattern Recognition, Automated/methods , Algorithms , Animals , Data Interpretation, Statistical , Macaca mulatta , Nerve Net/physiology , Reproducibility of Results , Sensitivity and Specificity
16.
J Neural Eng ; 11(4): 046020, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24995476

ABSTRACT

OBJECTIVE: Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. APPROACH: We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the flexibility and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. MAIN RESULTS: Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average firing rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. SIGNIFICANCE: Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic motor neuroscience and for the successful translation of BMIs to people with paralysis.


Subject(s)
Brain-Computer Interfaces , Movement/physiology , Animals , Behavior, Animal/physiology , Biomechanical Phenomena , Electrodes, Implanted , Electrophysiological Phenomena/physiology , Macaca mulatta , Microelectrodes , Models, Neurological , Motor Cortex/physiology , Rotation , Visual Prosthesis , Walking/physiology
17.
J Exp Bot ; 65(18): 5193-204, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25005136

ABSTRACT

Plants acquire nitrogen in the form of amino acids from the soil, and transport proteins located in the plasma membrane of root cells are required for this process. It was found that the Arabidopsis lysine-histidine-like transporter LHT6 is expressed in root cells important for amino acid uptake, including the epidermis, root hairs, and cortex. Transport studies with lht6 mutants using high levels of amino acids demonstrated that LHT6 is in fact involved in amino acid uptake. To determine if LHT6 plays a role in nitrogen acquisition at soil amino acid concentrations, growth and uptake studies were performed with low levels of toxic amino acid analogues and radiolabelled amino acids, respectively. In addition, mutants of AAP1, another root amino acid transporter, and lht6/aap1 double mutants were examined. The results showed that LHT6 is involved in uptake of acidic amino acids, glutamine and alanine, and probably phenylalanine. LHT6 seems not to transport basic or other neutral amino acids, or, alternatively, other transporters might compensate for eliminated LHT6 function. Previous studies suggested that AAP1 only takes up amino acids at high concentrations; however, here it is demonstrated that the transporter functions in acquisition of glutamate and neutral amino acids when present at soil concentrations. When comparing the characterized root uptake systems, it appears that transporters both with overlapping substrate specificity and with preference for specific substrates are required to access the soil amino acid pool.


Subject(s)
Amino Acid Transport Systems, Neutral/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Nitrogen/metabolism , Plant Roots/metabolism , Amino Acid Transport Systems, Neutral/genetics , Amino Acids/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Models, Biological , Plant Roots/genetics
18.
J Neural Eng ; 11(2): 026001, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24503597

ABSTRACT

OBJECTIVE: Intracortical brain-computer interface (BCI) decoders are typically retrained daily to maintain stable performance. Self-recalibrating decoders aim to remove the burden this may present in the clinic by training themselves autonomously during normal use but have only been developed for continuous control. Here we address the problem for discrete decoding (classifiers). APPROACH: We recorded threshold crossings from 96-electrode arrays implanted in the motor cortex of two rhesus macaques performing center-out reaches in 7 directions over 41 and 36 separate days spanning 48 and 58 days in total for offline analysis. MAIN RESULTS: We show that for the purposes of developing a self-recalibrating classifier, tuning parameters can be considered as fixed within days and that parameters on the same electrode move up and down together between days. Further, drift is constrained across time, which is reflected in the performance of a standard classifier which does not progressively worsen if it is not retrained daily, though overall performance is reduced by more than 10% compared to a daily retrained classifier. Two novel self-recalibrating classifiers produce a ~15% increase in classification accuracy over that achieved by the non-retrained classifier to nearly recover the performance of the daily retrained classifier. SIGNIFICANCE: We believe that the development of classifiers that require no daily retraining will accelerate the clinical translation of BCI systems. Future work should test these results in a closed-loop setting.


Subject(s)
Action Potentials/physiology , Brain-Computer Interfaces/classification , Electrodes, Implanted , Motor Cortex/physiology , Photic Stimulation/methods , Psychomotor Performance/physiology , Animals , Calibration , Macaca mulatta , Male , Microelectrodes
19.
FEBS Lett ; 588(1): 160-6, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24291261

ABSTRACT

Although oxalic acid is common in nature our understanding of the mechanism(s) regulating its turnover remains incomplete. In this study we identify Saccharomyces cerevisiae acyl-activating enzyme 3 (ScAAE3) as an enzyme capable of catalyzing the conversion of oxalate to oxalyl-CoA. Based on our findings we propose that ScAAE3 catalyzes the first step in a novel pathway of oxalate degradation to protect the cell against the harmful effects of oxalate derived from an endogenous process or an environmental source.


Subject(s)
Acyl Coenzyme A/metabolism , Coenzyme A Ligases/metabolism , Oxalates/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Carbon Dioxide/metabolism , Coenzyme A Ligases/genetics , Gene Expression Regulation, Developmental , Gene Expression Regulation, Fungal , Hydrogen-Ion Concentration , Kinetics , Models, Biological , Mutation , Reverse Transcriptase Polymerase Chain Reaction , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/growth & development , Saccharomyces cerevisiae Proteins/genetics
20.
Nature ; 487(7405): 51-6, 2012 Jul 05.
Article in English | MEDLINE | ID: mdl-22722855

ABSTRACT

Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from what is known about primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well the analogy between motor and visual cortex holds. Single-neuron responses in motor cortex are complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. Here we find that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behaviour. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate an unexpected yet surprisingly simple structure in the population response. This underlying structure explains many of the confusing features of individual neural responses.


Subject(s)
Macaca mulatta/physiology , Models, Neurological , Motor Cortex/cytology , Motor Cortex/physiology , Movement/physiology , Neurons/cytology , Animals , Biomechanical Phenomena , Electromyography , Leeches , Male , Rotation , Swimming , Walking
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