Venous blood gas and lactate values in adult giraffe trained for voluntary jugular phlebotomy.

Blood gas analyses have previously been performed for giraffe under anesthesia and with physical restraint in a chute; however, reference values for giraffe that are trained to participate in venipuncture without chemical or physical restraint have not previously been described. Using a point-of-care blood gas and lactate analyzer and 20 giraffe trained for voluntary phlebotomy, values were determined for venous blood gasses and plasma lactate concentration. Ninety-five percent confidence in the mean values for venous pH (7.34-7.46), partial pressure of carbon dioxide (PCO2; 28.5-37.8 mmHg), partial pressure of oxygen (PO2; 56-102 mmHg), bicarbonate (HCO3 -; 18.9-21.0 mmol/L), base excess (BE; -6.0 to -3.6 mmol/L), total carbon dioxide (TCO2; 19.9-22.0 mmol/L), and lactate (0.32-0.56 mmol/L) were calculated. This is the first report on venous blood gas analysis values for giraffe without chemical or physical restraint. These data will provide a reference for clinical interpretation of venous blood gas and lactate values in giraffe and demonstrate some of the potential diagnostic benefits to training giraffe and other zoo species for voluntary medical procedures.

A 30 YEAR (1991-2020) RETROSPECTIVE MORTALITY REVIEW OF GIRAFFIDS (GIRAFFA SPP. AND OKAPIA JOHNSTONI) IN MANAGED CARE.

Identifying common causes of mortality in zoo giraffe (Giraffa spp.) and okapi (Okapia johnstoni) provides an opportunity to help improve welfare and population management for these endangered species. Mortality reports from 1,024 giraffe and 95 okapi in zoos were compiled from the Species 360 Zoological Information Management Software (ZIMS) utilizing the Morbidity & Mortality Analysis tool. Thirty years of mortality reports (1991-2020) were evaluated to help identify trends and evaluate the impacts, if any, of changes over time in husbandry and management practices. The most common causes of death for giraffe from 1991 to 2015 were neonatal issues (234/845, 27.7%), trauma (213/845, 25.2%), noninfectious disease (190/845, 22.5%), and infectious disease (188/845, 22.2%). In comparison, the most common causes of mortality for giraffe from 2016 to 2020, were noninfectious disease (78/179, 43.6%), trauma (39/179, 21.8%), neonatal issues (39/179, 21.8%), and infectious disease (17/179, 9.5%). The most common cause of death for okapi from 1991 to 2015 were neonatal issues (29/64, 45.3%), infectious disease (13/64, 20.3%), noninfectious disease (11/64, 17.2%), and trauma (10/64, 15.6%). In comparison, the most common cause of death for okapi from 2016 to 2020 was noninfectious disease (15/31, 48.4%), neonatal issues (8/31, 25.8%), and infectious disease (5/31, 16.1%). The results suggest that zoo giraffids have had a relative decrease in mortality from infectious diseases in recent years, whereas death from noninfectious causes has increased significantly. Trauma-related giraffe mortalities and neonatal mortality in both giraffe and okapi, although decreasing in prevalence between time periods, continue to be important causes of death in zoos. This is the first descriptive mortality review for the Giraffidae family and provides data on potential giraffe and okapi health issues that zoos could proactively address.

Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi-ascending dose study with a bioequivalence arm in healthy volunteers.

PF614, a trypsin-activated abuse protection oxycodone prodrug designed to reduce recreational drug abuse, was compared to OxyContin for safety and pharmacokinetics (PKs) of plasma oxycodone following oral administration. This study was a two-part design including a multi-ascending dose (part A) and a bioequivalence (BE) study (part B) in healthy volunteers. In part A, 24 subjects were randomized 3:1 to receive PF614 (50, 100, or 200 mg, n = 6/cohort) or OxyContin (20, 40, or 80 mg; n = 2/cohort) in ascending cohorts, delivered every 12 h for a total of nine doses. In part B, 60 subjects randomized in a four-way crossover to evaluate BE, received PF614 100 mg and OxyContin 40 mg in fasted and fed (high-fat diet) states. All subjects were naltrexone blocked prior to first study drug administration to protect against opioid-related adverse effects; repeat doses were provided on days 1-5. In part A, PF614 was well-tolerated following twice daily doses of up to 200 mg for 5 days. Plasma oxycodone maximal plasma concentration and area under the concentration time curve increased linearly with increasing doses. Part B showed that plasma oxycodone BE was achieved following 100 mg PF614 or 40 mg OxyContin under both fasted and fed conditions. Additionally, PF614 provided similar oxycodone exposures following both fasted and fed states. This study confirms findings from our single-ascending dose study, showing that PF614 100 mg releases oxycodone with a PK profile comparable to 40 mg OxyContin under both fasted and fed conditions and with a similar safety profile under naltrexone-blocked conditions.

PHARMACOKINETICS AND EFFICACY OF A SINGLE TOPICAL DOSE OF EPRINOMECTIN IN GIRAFFE (GIRAFFA SPP.).

Growing resistance to current antiparasitic medications, both in livestock and in zoological species under human care, makes it imperative to evaluate available drugs on the market, such as eprinomectin. In this prospective study, five males and one female of reticulated (Giraffa reticulata; n = 2), Masai (Giraffa tippelskirchii; n = 1), Nubian (Giraffa camelopardalis; n = 2), and hybrid subspecies (n = 1) of giraffe, received 1.5 mg/kg eprinomectin topically along the dorsum. Using high-performance liquid chromatography, concentrations of eprinomectin in plasma samples collected at 0, 4, 24, and 48 h, and 7, 14, 21, and 28 d were evaluated following drug administration. Complete blood cell counts and biochemistry panels were performed before (n = 6) and after (n = 3) eprinomectin administration. Samples for modified double centrifugal fecal flotation (n = 6) were evaluated prior to eprinomectin administration to evaluate for endoparasites and were repeated after the study (n = 5). Noncompartmental pharmacokinetic analysis was applied to the data. The observed maximum plasma concentration was 11.45 ng/ml and the time of observed maximum concentration was 2.67 d. The mean terminal half-life was 5.16 d. No adverse effects were observed related to eprinomectin administration and no blood work changes were observed. Parasite loads decreased (n = 3) or did not change (n = 2) after eprinomectin administration. The mean peak plasma concentration of eprinomectin in giraffe was similar to that achieved in cattle, despite using three times the dose.

"We must be mentally strong": exploring barriers to mental health in correctional services.

Introduction: The inherent nature of work in correctional services can have negative effects on correctional worker mental health and well-being. Methods: The current study, a replication, analyzes survey data collected from provincial and territorial correctional workers staffed in six regions across Canada (n = 192). Specifically, participants were asked at the end of an extensive mental health and well-being survey an open-ended question requesting any additional feedback or information. Results: Four predominant themes were identified in the data: (1) stigma pertaining to a need to recognize mental health concerns within correctional services; (2) the idea that correctional services wear on the mind and body; (3) a need for better relationships with and support from correctional supervisors, upper management, and ministerial leadership; and (4) suggestions to improve correctional services to help the sector realize its full potential and maximize workplace health. Discussion: We discuss the implications of these findings, with an emphasis on finding ways to promote positive organizational and cultural change in correctional services.

Assaying Effector Cell-to-Cell Mobility in Plant Tissues Identifies Hypermobility and Indirect Manipulation of Plasmodesmata.

In plants, plasmodesmata establish cytoplasmic continuity between cells to allow for communication and resource exchange across the cell wall. While plant pathogens use plasmodesmata as a pathway for both molecular and physical invasion, the benefits of molecular invasion (cell-to-cell movement of pathogen effectors) are poorly understood. To establish a methodology for identification and characterization of the cell-to-cell mobility of effectors, we performed a quantitative live imaging-based screen of candidate effectors of the fungal pathogen Colletotrichum higginsianum. We predicted C. higginsianum effectors by their expression profiles, the presence of a secretion signal, and their predicted and in planta localization when fused to green fluorescent protein. We assayed for cell-to-cell mobility of nucleocytosolic effectors and identified 14 that are cell-to-cell mobile. We identified that three of these effectors are "hypermobile," showing cell-to-cell mobility greater than expected for a protein of that size. To explore the mechanism of hypermobility, we chose two hypermobile effectors and measured their impact on plasmodesmata function and found that even though they show no direct association with plasmodesmata, each increases the transport capacity of plasmodesmata. Thus, our methods for quantitative analysis of cell-to-cell mobility of candidate microbe-derived effectors, or any suite of host proteins, can identify cell-to-cell hypermobility and offer greater understanding of how proteins affect plasmodesmal function and intercellular connectivity. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Do both anticipated relief and anticipated regret predict decisions about influenza vaccination?

OBJECTIVE: Anticipated regret has been found to predict vaccination intentions and behaviours. We examined whether anticipated relief also predicts seasonal influenza vaccination intentions and behaviour. Given claims about differences in their antecedents and function, we distinguished between counterfactual relief (relief that a worse outcome did not obtain) and temporal relief (relief that an unpleasant experience is over). DESIGN: Cross-sectional. METHODS: Unvaccinated participants (N = 295) were recruited online in November 2020. Participants completed measures of anticipated regret, anticipated counterfactual relief, and anticipated temporal relief and measures of theory of planned behaviour constructs (attitudes, norms, perceived control, and intentions). One month later, the same participants were re-surveyed and asked to report their vaccination status. RESULTS: Although all anticipated emotion measures were associated with intentions and behaviour, only anticipated counterfactual relief and regret independently predicted vaccination intentions in regression analyses. Mediation analysis showed both anticipated counterfactual relief and regret were indirectly, via intentions, associated with behaviour. CONCLUSIONS: Results suggest that, regardless of valence, counterfactual emotions predict vaccination intention and, indirectly, behaviour. Furthermore, participants may differ in their sensitivity to the anticipation of positive versus negative counterfactual emotions. These findings may permit more precise targeting of interventions to increase vaccine uptake.

A two-strain model of infectious disease spread with asymmetric temporary immunity periods and partial cross-immunity.

We introduce a two-strain model with asymmetric temporary immunity periods and partial cross-immunity. We derive explicit conditions for competitive exclusion and coexistence of the strains depending on the strain-specific basic reproduction numbers, temporary immunity periods, and degree of cross-immunity. The results of our bifurcation analysis suggest that, even when two strains share similar basic reproduction numbers and other epidemiological parameters, a disparity in temporary immunity periods and partial or complete cross-immunity can provide a significant competitive advantage. To analyze the dynamics, we introduce a quasi-steady state reduced model which assumes the original strain remains at its endemic steady state. We completely analyze the resulting reduced planar hybrid switching system using linear stability analysis, planar phase-plane analysis, and the Bendixson-Dulac criterion. We validate both the full and reduced models with COVID-19 incidence data, focusing on the Delta (B.1.617.2), Omicron (B.1.1.529), and Kraken (XBB.1.5) variants. These numerical studies suggest that, while early novel strains of COVID-19 had a tendency toward dramatic takeovers and extinction of ancestral strains, more recent strains have the capacity for co-existence.

Pharmacokinetics, safety, and tolerability of inhaled remdesivir in healthy participants.

Intravenous remdesivir (RDV) is US Food and Drug Administration-approved for hospitalized and nonhospitalized individuals with coronavirus disease 2019. RDV undergoes intracellular metabolic activation to form the active triphosphate, GS-443902, and other metabolites. Alternative administration routes, including localized pulmonary delivery, can lower systemic exposure and maximize exposure at the site of action. This study evaluated the pharmacokinetics (PK) and safety of inhaled RDV in healthy adults. This phase Ia, randomized, placebo-controlled study evaluated inhaled RDV in healthy participants randomized 4:1 to receive RDV or placebo as single doses (4 cohorts) or multiple once-daily doses (3 cohorts). Doses in cohorts 1-6 were administered as an aerosolized solution for inhalation through a sealed facemask; doses in cohort 7 were administered as an aerosolized solution for inhalation through a mouthpiece. Safety was assessed throughout the study. Seventy-two participants were enrolled (inhaled RDV, n = 58 and placebo, n = 14). Following single RDV doses, RDV, GS-704277, and GS-441524 plasma PK parameters indicated dose-proportional increases in area under the concentration-time curve (AUC) extrapolated to infinite time, AUC from time zero to last quantifiable concentration, and maximum observed concentration. Analyte plasma concentrations after multiple RDV doses were consistent with those for single-dose RDV. Analyte plasma exposures were lower when RDV was administered with a mouthpiece versus a sealed facemask. The most common adverse events included nausea, dizziness, and cough. Single- and multiple-dose inhaled RDV exhibited linear and dose-proportional plasma PK. Administration of RDV via inhalation was generally safe and well-tolerated.

Wireless, Multi-Sensor System-on-Chip for pH and Amperometry Powered by Body Heat.

This article presents a body-heat-powered, multi-sensor SoC for measurement of chemical and biological sensors. Our approach combines analog front-end sensor interfaces for voltage- (V-to-I) and current-mode (potentiostat) sensors with a relaxation oscillator (RxO) readout scheme targeting << 10 µW power consumption. The design was implemented as a complete sensor readout system-on-chip, including a low-voltage energy harvester compatible with thermoelectric generation and a near-field wireless transmitter. A prototype IC was fabricated in a 0.18 µm CMOS process as a proof-of-concept. As measured, full-range pH measurement consumes 2.2 µW at maximum, where the RxO consumes 0.7 µW and measured linearity of the readout circuit demonstrates R 2 0.999. Glucose measurement is also demonstrated using an on-chip potentiostat circuit as the input of the RxO, with a readout power consumption as low as 1.4 µ W. As a final proof-of-principle, both pH and glucose measurement are demonstrated while powering from body heat using a centimeter-scale thermoelectric generator on the skin surface, and pH measurement is further demonstrated with an on-chip transmitter for wireless data transmission. Long-term, the presented approach may enable a variety of biological, electrochemical, and physical sensor readout schemes with microwatt operation for batteryless and power autonomous sensor systems.

A Reconfigurable Tri-Mode Frequency-Locked Loop Readout Circuit for Biosensor Interfaces.

In this article, a frequency-locked loop (FLL) based multimodal readout integrated circuit (IC) for interfacing with off-chip temperature, electrochemical, and pH sensors is presented. By reconfiguring its switched-capacitor feedback network, the readout circuit is able to measure resistance, current, and voltage without additional active analog front-end circuits. A prototype IC was fabricated in a 0.18 µm CMOS process. Measured results show that when measuring resistance, the input-referred resistance resolution is 10.5 Ω for 100 Hz integration bandwidth. Using an off-chip thermistor, the readout circuit covers a temperature range of 0-75 °C and achieves an equivalent temperature resolution of 16.4 mKrms. In current mode, the readout circuit has an input range of 0.5µA and an input-referred current noise as low as 40.6 pArms for 100 Hz bandwidth. Interfacing with an on-chip potentiostat, glucose chronoamperometry is demonstrated. In voltage mode, a minimum input-referred voltage noise of 31.7 µVrms is achieved, and the IC can measure a pH range from 1.6 to 12 using a commercial pH probe. At a 1.2 V supply, power consumption of the readout circuit is below 10 µW for all three measurement modes. Additionally, the prototype IC includes an integrated wireless transmitter that implements on-off keying modulation, and a wireless multimodal sensing system utilizing the FLL-based readout circuit is demonstrated.

A PDLP-NHL3 complex integrates plasmodesmal immune signaling cascades.

The plant immune system relies on the perception of molecules that signal the presence of a microbe threat. This triggers signal transduction that mediates a range of cellular responses via a collection of molecular machinery including receptors, small molecules, and enzymes. One response to pathogen perception is the restriction of cell-to-cell communication by plasmodesmal closure. We previously found that while chitin and flg22 trigger specialized immune signaling cascades in the plasmodesmal plasma membrane, both execute plasmodesmal closure via callose synthesis at the plasmodesmata. Therefore, the signaling pathways ultimately converge at or upstream of callose synthesis. To establish the hierarchy of signaling at plasmodesmata and characterize points of convergence in microbe elicitor-triggered signaling, we profiled the dependence of plasmodesmal responses triggered by different elicitors on a range of plasmodesmal signaling machinery. We identified that, like chitin, flg22 signals via RESPIRATORY BURST OXIDASE HOMOLOGUE D (RBOHD) to induce plasmodesmal closure. Further, we found that PLASMODESMATA-LOCATED PROTEIN 1 (PDLP1), PDLP5, and CALLOSE SYNTHASE 1 (CALS1) are common to microbe- and salicylic acid (SA)-triggered responses, identifying PDLPs as a candidate signaling nexus. To understand how PDLPs relay a signal to CALS1, we screened for PDLP5 interactors and found NON-RACE SPECIFIC DISEASE RESISTANCE/HIN1 HAIRPIN-INDUCED-LIKE protein 3 (NHL3), which is also required for chitin-, flg22- and SA-triggered plasmodesmal responses and PDLP-mediated activation of callose synthesis. We conclude that a PDLP-NHL3 complex acts as an integrating node of plasmodesmal signaling cascades, transmitting multiple immune signals to activate CALS1 and plasmodesmata closure.

Eye Drop Adherence With an Eye Drop Bottle Cap Monitor.

PRCIS: An eye drop bottle cap monitor with audio and visual alarms measured eye drop adherence in 50 subjects with glaucoma. Baseline adherence rates were too high to test if the alarms could improve adherence. PURPOSE: To determine if an eye drop bottle cap monitor can measure and improve adherence. MATERIALS AND METHODS: The Devers Drop Device (D3, Universal Adherence LLC) was designed to measure eye drop adherence by detecting bottle cap removal and replacement, and it can provide text, visual and audio alerts when a medication is due. In Stage 1, we determined baseline adherence for 50 subjects using a nightly eye drop over a 25-day period. Subjects with less than 90% baseline adherence were eligible for Stage 2. In Stage 2, we randomized subjects to receive either no reminder or automated D3 alerts for their nightly eye drop over a subsequent 25-day period. We defined adherence as the proportion of drops administered within 3 hours of the subjects' scheduled dosing time. Subjects completed 3 questions regarding satisfaction with the device and willingness to pay. RESULTS: The D3 monitor remained attached to the eye drop bottle cap for the duration of the study and collected adherence data in all 50 patients. In Stage 1, the mean adherence rate was 90 ± 18% (range 32-100%). Forty (80%) subjects had an adherence rate greater than 90%. Adherence rates were too high in Stage 1 to adequately test the effects of reminders in Stage 2. Ninety-eight percent (49/50) and 96% (48/50) of subjects agreed "the device always stayed attached to the bottle cap" and "I was able to use the device to take the drops", respectively. Patients would pay $61±83 (range $0-400) for a similar device to improve adherence. CONCLUSIONS: The D3 can measure eye drop adherence. Research subjects reported high satisfaction and willingness to pay for an eye drop bottle cap monitor. Glaucoma patients have high adherence when they are being monitored, and future studies with research subjects screened for poor adherence may further determine the benefit of electronic monitoring of adherence with and without electronic reminders.

A framework for deriving analytic steady states of biochemical reaction networks.

The long-term behaviors of biochemical systems are often described by their steady states. Deriving these states directly for complex networks arising from real-world applications, however, is often challenging. Recent work has consequently focused on network-based approaches. Specifically, biochemical reaction networks are transformed into weakly reversible and deficiency zero generalized networks, which allows the derivation of their analytic steady states. Identifying this transformation, however, can be challenging for large and complex networks. In this paper, we address this difficulty by breaking the complex network into smaller independent subnetworks and then transforming the subnetworks to derive the analytic steady states of each subnetwork. We show that stitching these solutions together leads to the analytic steady states of the original network. To facilitate this process, we develop a user-friendly and publicly available package, COMPILES (COMPutIng anaLytic stEady States). With COMPILES, we can easily test the presence of bistability of a CRISPRi toggle switch model, which was previously investigated via tremendous number of numerical simulations and within a limited range of parameters. Furthermore, COMPILES can be used to identify absolute concentration robustness (ACR), the property of a system that maintains the concentration of particular species at a steady state regardless of any initial concentrations. Specifically, our approach completely identifies all the species with and without ACR in a complex insulin model. Our method provides an effective approach to analyzing and understanding complex biochemical systems.

Assessing Road to Mental Readiness (R2MR) training among correctional workers in Canada.

BACKGROUND: Mental health frameworks, best practices, and the well-being of public safety personnel in Canada are topics of increasing interest to both researchers and organizations. To protect and improve worker mental health, different training programs have been implemented to serve this population. The Road to Mental Readiness (R2MR) training regimen is one such program specialized to build cultural awareness of mental health, reduce stigma, and mitigate the cumulative impacts of exposures to potentially psychologically traumatic events among public safety personnel. However, limited research has been conducted to evaluate the effectiveness of R2MR, especially among correctional workers. METHODS: The current study analyzed 307 open-ended survey responses to four (4) questions about R2MR garnered from 124 Canadian provincial and territorial correctional workers between 2018-2020 to reveal their understandings and perceptions of R2MR training, and to identify what learned skills they found challenging or easy to implement. RESULTS: The results suggest that R2MR training plays a significant role in decreasing stigma and increasing mental health awareness. Across jurisdictions, R2MR creates a supportive space for open dialogue around mental health meant to shift cultural and individual barriers that often hinder treatment-seeking. Some respondents also indicated that R2MR was a starting point for intervention. CONCLUSIONS: Further research is necessary to understand how R2MR and other programs could support the mental health and well-being of correctional workers.

Comparative phyloproteomics identifies conserved plasmodesmal proteins.

Plasmodesmata are cytosolic bridges, lined by the plasma membrane and traversed by endoplasmic reticulum; plasmodesmata connect cells and tissues, and are critical for many aspects of plant biology. While plasmodesmata are notoriously difficult to extract, tissue fractionation and proteomic analyses can yield valuable knowledge of their composition. Here we have generated two novel proteomes to expand tissue and taxonomic representation of plasmodesmata: one from mature Arabidopsis leaves and one from the moss Physcomitrium patens, and leveraged these and existing data to perform a comparative analysis to identify evolutionarily conserved protein families that are associated with plasmodesmata. Thus, we identified ß-1,3-glucanases, C2 lipid-binding proteins, and tetraspanins as core plasmodesmal components that probably serve as essential structural or functional components. Our approach has not only identified elements of a conserved plasmodesmal proteome, but also demonstrated the added power offered by comparative analysis for recalcitrant samples. Conserved plasmodesmal proteins establish a basis upon which ancient plasmodesmal function can be further investigated to determine the essential roles these structures play in multicellular organism physiology in the green lineages.

Development of a robot-assisted thoracic surgery (RATS) program. Lessons learned after 2500 cases.

Robotic surgery provides significant advantages in terms of an optimal three-dimensional and magnified view of the surgical field, superior maneuverability of surgical instruments, removal of surgeon's tremor and excellent ergonomics. Nonetheless, the adoption of this technology in thoracic surgery has been slower than in other specialties such as urology, gynecology or digestive surgery. In this article we describe our institution's experience in robotic-assisted thoracic surgery (RATS) in the span from 2012 to 2020. During this time the average annual growth of the program has been 55%. Among the most frequently procedures performed were lobectomies, wedge resection and segmentectomies. Surgical time and length of stay decreased as the number of procedures performed increased, relative to the learning curve. Additional important elements considered relevant to the success of the program are the resources available, leadership, motivation of the surgical team, adequate and stepwise training, as well as the collection of data for periodic analysis of results. All those initiatives have led to a relevant improvement of financial variables reflecting a cost reduction.

Relief in everyday life.

Despite being implicated in a wide range of psychological and behavioral phenomena, relief remains poorly understood from the perspective of psychological science. What complicates the study of relief is that people seem to use the term to describe an emotion that occurs in two distinct situations: when an unpleasant episode is over, or upon realizing that an outcome could have been worse. This study constitutes a detailed empirical investigation of people's reports of everyday episodes of relief. A set of four studies collected a large corpus (N = 1,835) of first-person reports of real-life episodes of relief and examined people's judgments about the antecedents of relief, its relation to counterfactual thoughts, and its subsequent effects on decision making. Some participants described relief experiences that had either purely temporal or purely counterfactual precursors. Nevertheless, the findings indicated that the prototypical instance of relief appears to be one in which both these elements are present. The results also suggest that, although relief is frequently experienced in situations in which people are not responsible for the relief-inducing event, nevertheless they typically report that the experience had a positive impact on subsequent decision making. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Diffusion and bulk flow of amino acids mediate calcium waves in plants.

In plants, a variety of stimuli trigger long-range calcium signals that travel rapidly along the vasculature to distal tissues via poorly understood mechanisms. Here, we use quantitative imaging and analysis to demonstrate that traveling calcium waves are mediated by diffusion and bulk flow of amino acid chemical messengers. We propose that wounding triggers release of amino acids that diffuse locally through the apoplast, activating the calcium-permeable channel GLUTAMATE RECEPTOR-LIKE 3.3 as they pass. Over long distances through the vasculature, the wound-triggered dynamics of a fluorescent tracer show that calcium waves are likely driven by bulk flow of a channel-activating chemical. We observed that multiple stimuli trigger calcium waves with similar dynamics, but calcium waves alone cannot initiate all systemic defense responses, suggesting that mobile chemical messengers are a core component of complex systemic signaling in plants.