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Global health initiatives are multistakeholder partnerships that mobilize and disburse resources to address global health challenges, often by supporting implementation of health programmes in low-and middle-income countries. (1) These initiatives [...]

Reducing the amount of plastic packaging being produced and disposed of is an urgent and significant challenge for regulators and for society more broadly. In recent years, the circular economy has emerged as a key paradigm for conceptualising solutions to plastic and other kinds of waste. While waste management is focused on dealing with materials once they are wasted, the circular economy paradigm calls for changes to the whole supply chain including how plastics are made and used. Australia, along with other nations, has incorporated the concept into waste laws and policies. This article addresses the challenge of using the reconceptualisation of waste offered by the circular economy paradigm in regulatory responses to plastic packaging. By developing principles that draw on the literature relating to the circular economy and regulatory studies, this article illustrates how to design regulatory interventions that support the creation of a circular economy for plastic packaging. Using these principles, the article evaluates Australia's regulatory framework for plastic packaging. Despite the political and media attention on reducing plastic packaging pollution, this article finds fundamental flaws and gaps in the regulation of plastic packaging and identifies options for improving the current approach consistent with the proposed regulatory design principles., I Introduction Plastic use and pollution is a pressing environmental and public health challenge linked to climate change and catastrophic biodiversity loss. (1) Plastic packaging is a particularly prominent form [...]

IntroductionThe heightened risk of COVID-19 infection and mortality in prisons is well documented, but COVID-19's impact on all-cause mortality in incarcerated populations has not yet been studied. This study analyzed mortality records from the Florida State Department of Corrections prison system population to evaluate the impact COVID-19 had on all-cause mortality and compare mortality rates and life expectancy with that of the overall state of Florida population.MethodsPopulation age and sex data for Florida State Department of Corrections were ascertained from the Florida State Department of Corrections Offender Based Information System. Death data by age, sex, and cause of death were acquired from medical records and Florida State Department of Corrections offender reports. The state of Florida demographic and death data were collected from the Census Bureau, Florida Department of Health, and Centers for Disease Control and Prevention. Age- and sex-standardized life table measures were calculated, and COVID-19 contributions to changes in life expectancy were assessed using Arriaga's decomposition.ResultsThe standardized mortality rate in the Florida State Department of Corrections population increased by 45% between 2019 and 2020, causing an overall 4.0-year decline in life expectancy. Over the same period, the state of Florida population's standardized mortality increased by 19%, resulting in an overall 2.7-year decline. Within the Florida State Department of Corrections population, life expectancy decline could be attributed exclusively to COVID-19 mortality.ConclusionsThe state of Florida prison population saw a substantial increase in mortality driven solely by COVID-19 mortality, leading to an overall 4-year decline in life expectancy. Given the findings and continued threat of COVID-19 outbreaks, Florida State Department of Corrections and other prison systems should strive to increase vaccination uptake, decrease prison populations, and commit to COVID-19 data transparency.

Our current knowledge of host-virus interactions in biofilms is limited to computational predictions based on laboratory experiments with a small number of cultured bacteria. However, natural biofilms are diverse and chiefly composed of uncultured bacteria and archaea with no viral infection patterns and lifestyle predictions described to date. Herein, we predict the first DNA sequence-based host-virus interactions in a natural biofilm. Using single-cell genomics and metagenomics applied to a hot spring mat of the Cone Pool in Mono County, California, we provide insights into virus-host range, lifestyle and distribution across different mat layers. Thirty-four out of 130 single cells contained at least one viral contig (26%), which, together with the metagenome-assembled genomes, resulted in detection of 59 viruses linked to 34 host species. Analysis of single-cell amplification kinetics revealed a lack of active viral replication on the single-cell level. These findings were further supported by mapping metagenomic reads from different mat layers to the obtained host-virus pairs, which indicated a low copy number of viral genomes compared to their hosts. Lastly, the metagenomic data revealed high layer specificity of viruses, suggesting limited diffusion to other mat layers. Taken together, these observations indicate that in low mobility environments with high microbial abundance, lysogeny is the predominant viral lifestyle, in line with the previously proposed "Piggyback-the-Winner" theory.

Microbial mats are found in a variety of modern environments, with evidence for their presence as old as the Archean. There is much debate about the rates and conditions of processes that eventually lithify and preserve mats as microbialites. Here, we apply novel tracer experiments to quantify both mat biomass addition and the formation of CaCO3. Microbial mats from Little Hot Creek (LHC), California, contain calcium carbonate that formed within multiple mat layers, and thus constitute a good test case to investigate the relationship between the rate of microbial mat growth and carbonate precipitation. The laminated LHC mats were divided into four layers via color and fabric, and waters within and above the mat were collected to determine their carbonate saturation states. Samples of the microbial mat were also collected for 16S rRNA analysis of microbial communities in each layer. Rates of carbonate precipitation and carbon fixation were measured in the laboratory by incubating homogenized samples from each mat layer with δ13C-labeled HCO3- for 24 h. Comparing these rates with those from experimental controls, poisoned with NaN3 and HgCl2, allowed for differences in biogenic and abiogenic precipitation to be determined. Carbon fixation rates were highest in the top layer of the mat (0.17% new organic carbon/day), which also contained the most phototrophs. Isotope-labeled carbonate was precipitated in all four layers of living and poisoned mat samples. In the top layer, the precipitation rate in living mat samples was negligible although abiotic precipitation occurred. In contrast, the bottom three layers exhibited biologically enhanced carbonate precipitation. The lack of correlation between rates of carbon fixation and biogenic carbonate precipitation suggests that processes other than autotrophy may play more significant roles in the preservation of mats as microbialites.

The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity.

KPN03535 (gi|152972051) is a putative lipoprotein of unknown function that is secreted by Klebsiella pneumoniae MGH 78578. The crystal structure reveals that despite a lack of any detectable sequence similarity to known structures, it is a novel variant of the OB-fold and structurally similar to the bacterial Cpx-pathway protein NlpE, single-stranded DNA-binding (SSB) proteins and toxins. K. pneumoniae MGH 78578 forms part of the normal human skin, mouth and gut flora and is an opportunistic pathogen that is linked to about 8% of all hospital-acquired infections in the USA. This structure provides the foundation for further investigations into this divergent member of the OB-fold family.

Proteins with the DUF2063 domain constitute a new Pfam family, PF09836. The crystal structure of a member of this family, NGO1945 from Neisseria gonorrhoeae, has been determined and reveals that the N-terminal DUF2063 domain is likely to be a DNA-binding domain. In conjunction with the rest of the protein, NGO1945 is likely to be involved in transcriptional regulation, which is consistent with genomic neighborhood analysis. Of the 216 currently known proteins that contain a DUF2063 domain, the most significant sequence homologs of NGO1945 (∼40-99% sequence identity) are from various Neisseria and Haemophilus species. As these are important human pathogens, NGO1945 represents an interesting candidate for further exploration via biochemical studies and possible therapeutic intervention.

The crystal structures of SPO0140 and Sbal_2486 were determined using the semiautomated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). The structures revealed a conserved core with domain duplication and a superficial similarity of the C-terminal domain to pleckstrin homology-like folds. The conservation of the domain interface indicates a potential binding site that is likely to involve a nucleotide-based ligand, with genome-context and gene-fusion analyses additionally supporting a role for this family in signal transduction, possibly during oxidative stress.

In many low- and middle-income countries, civil registration and vital statistics systems rely on passive reporting, with families expected to attend local registry offices to register vital events, such as [...]

Objective To estimate the economic impact likely to be achieved by efforts to vaccinate against 10 vaccine-preventable diseases between 2001 and 2020 in 73 low- and middle-income countries largely supported by Gavi, the Vaccine Alliance. Methods We used health impact models to estimate the economic impact of achieving forecasted coverages for vaccination against Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae and yellow fever. In comparison with no vaccination, we modelled the costs --expressed in 2010 United States dollars (US$)--of averted treatment, transportation costs, productivity losses of caregivers and productivity losses due to disability and death. We used the value-of-a-life-year method to estimate the broader economic and social value of living longer, in better health, as a result of immunization. Findings We estimated that, in the 73 countries, vaccinations given between 2001 and 2020 will avert over 20 million deaths and save US$ 350 billion in cost of illness. The deaths and disability prevented by vaccinations given during the two decades will result in estimated lifelong productivity gains totalling US$330 billion and US$9 billion, respectively. Over the lifetimes of the vaccinated cohorts, the same vaccinations will save an estimated US$ 5 billion in treatment costs. The broader economic and social value of these vaccinations is estimated at US$820 billion. Conclusion By preventing significant costs and potentially increasing economic productivity among some of the world's poorest countries, the impact of immunization goes well beyond health. Objectif Estimer l'impact economique qui pourrait decouler des efforts de vaccination contre 10 maladies a prevention vaccinale deployes entre 2001 et 2020 dans 73 pays a revenu faible et intermediaire, et largement soutenus par Gavi, I'Alliance du Vaccin. Methodes Nous avons utilise des modeles devaluation de l'impact sur la sante pour estimer l'impact economique qui decoulerait, si le taux de couverture prevu est atteint, des vaccinations contre Haemophilus influenzae type B, l'hepatite B, le papillomavirus humaln, l'encephalite japonaise, la rougeole, Neisseria meningitidis serogroupe A, le rotavirus, la rubeole, Streptococcus pneumoniae et la fievre jaune. Pour etablir une comparaison avec l'absence de vaccination, nous avons modelise les couts--exprimes en dollars des Etats-Unis 2010 (USD)--des traitements evites, les couts de transport, les pertes de productivite des soignants non professionnels et les pertes de productivite pour cause d'invalidite ou de deces. Nous avons utilise une methode permettant d'evaluer la valeur d'une annee de vie pour estimer la valeur economique et sociale au sens large d'une vie plus longue et en meilleure sante grace a la vaccination. Resultats D'apres nos estimations, les vaccinations pratiquees entre 2001 et 2020 dans les 73 pays permettront d'eviter plus de 20 millions de deces et d'economiser 350 milliards de dollars des Etats-Unis en couts sanitaires. Les cas de deces et d'invalidite evites grace a la vaccination pratiquee au cours de ees deux decennies entraineront des gains de productivite permanents respectivement estimes a 330 milliards de dollars des Etats-Unis et 9 milliards de dollars des Etats-Unis. On estime qu'au cours de la vie des cohortes vaccinees, les memes vaccinations permettront d'economiser 5 milliards de dollars des Etats-Unis en couts de traitement. La valeur economique et sociale au sens large de ees vaccinations est estimee a 820 milliards de dollars des Etats-Unis. Conclusion L'impact de la vaccination depasse le domaine de la sante, car il permet d'eviter d'importants couts et une augmentation potentielle de la productivite economique de certains des pays les plus pauvres du monde. Objetivo Estimarei impacto economico que probablemente se logaria con los esfuerzos de vacunar frente a 10 enfermedades evitables mediante la vacunacion entre 2001 y 2020 en 73 paises con ingresos bajos y medios ampliamente respaldados por la Gavi, la Vaccine Alliance. Metodos Se utilizaron modelos de impacto sanitario para estimar el impacto economico de lograr las coberturas previstas de vacunacion frente a Haemophilus influenzae tipo b, hepatitis B, virus del papiloma humano, encefalitis japonesa, sarampion, Neisseria meningitidis serogrupo A, rotavirus, rubeola, Streptococcus pneumoniae y fiebre amarilla. En comparacion con la no vacunacion, se modelaron los costes (expresados en dolares estadounidenses, USD, de 2010) de los tratamientos evitados, los costes de transporte, las perdidas de productividad de los proveedores de salud y las perdidas de productividad debido a la discapacidad y la muerte. Se utilizo el metodo de valor de vida anual para estimar de forma mas amplia el valor economico y social del hecho de vivir mas, con una mejor salud, como resultado de la inmunizacion. Resultados Se estimo que, en los 73 paises, las vacunas suministradas entre 2001 y 2020 evitaran mas de 20 millones de muertes y ahorraran 350 000 millones de USD en costes de enfermedades. Las muertes y las discapacidades evitadas gracias a las vacunas suministradas durante las dos decadas tendran como resultado unas ganancias permanentes estimadas en la productividad de un total de 330 000 millones de USD y 9 000 millones de USD, respectivamente. Durante la vida de las cohortes vacunadas, se estima que las mismas vacunaciones ahorraran 5 000 millones de USD en costes de tratamientos. El valor economico y social mas amplio de estas vacunas se estima en 820 000 millones de USD. Conclusion El impacto de las vacunas es positivo mas alla de la salud, ya que se evitan costes significativos y se aumenta potencialmente la productividad economica entre algunos de los paises mas pobres., Introduction While vaccination is generally regarded to be one of the most cost-effective interventions in public health, the introduction and sustained use of any new vaccine needs to be supported [...]

Objective To investigate disparities in full immunization coverage across and within 86 low- and middle-income countries. Methods In May 2015, using data from the most recent Demographic and Health Surveys [...]

The gene for the Thermotoga maritima Trk potassium transporter component TrkA was originally thought to be a frameshift mutation and not to encode a functional protein. However, expression from this gene yielded a complex consisting of two distinct proteins designated TM1088A and -B. Genetic complementation of Escherichia coli mutants unable to transport potassium suggests that TM1088A/B is part of a functional Trk potassium transporter complex with the membrane protein TM1089. The protein structure for TM1088A shows a characteristic Rossmann fold indicating an [NAD.sup.+] binding site and has structural similarity to potassium channel-related proteins. Ligand binding studies indicated that ATP, ADP, and AMP stabilized TM1088A to a much greater degree than NADH and NAD, consistent with the crystal structure of TM1088A, which contains a bound AMP natural ligand at the characteristic GXGXXG nucleotide binding site. Mutation of single and all glycines at this nucleotide binding site eliminated in vitro protein stabilization by the ligand, yet these mutated proteins could still functionally complement the E. coli potassium uptake mutants. We predict that this new two-subunit class of TrkA proteins is present in a number of organisms. A further subclass of the predicted two-subunit TrkA proteins lack an identifiable membrane-spanning subunit of the Trk [K.sup.+] transporter. This class, as exemplified by Mycobacterium tuberculosis, did not complement E. coli potassium transport with the native E. coil TrkH; thus, it may require a novel TrkH-like protein for activity or provide an alternate function in vivo.

Objective To document the use of active management of the third stage of labour for preventing postpartum haemorrhage and to explore factors associated with such use in seven developing countries. [...]

Abstract Background Meningococcal meningitis is a major cause of disease worldwide, with frequent epidemics particularly affecting an area of sub-Saharan Africa known as the “meningitis belt”. Neisseria meningitidis group A (MenA) is responsible for major epidemics in Africa. Recently W-135 has emerged as an important pathogen. Currently, the strategy for control of such outbreaks is emergency use of meningococcal (MC) polysaccharide vaccines, but these have a limited ability to induce herd immunity and elicit an adequate immune response in infant and young children. In recent times initiatives have been taken to introduce meningococcal conjugate vaccine in these African countries. Currently there are two different types of MC conjugate vaccines at late stages of development covering serogroup A and W-135: a multivalent MC conjugate vaccine against serogroup A,C,Y and W-135; and a monovalent conjugate vaccine against serogroup A. We aimed to perform a structured assessment of these emerging meningococcal vaccines as a means of reducing global meningococal disease burden among children under 5 years of age. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In the first stage we systematically reviewed the literature related to emerging MC vaccines relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results For MenA conjugate vaccine the experts showed very high level of optimism (~ 90% or more) for 7 out of the 12 criteria. The experts felt that the likelihood of efficacy on meningitis was very high (~ 90%). Deliverability, acceptability to health workers, end users and the effect on equity were all seen as highly likely (~ 90%). In terms of the maximum potential impact on meningitis disease burden, the median potential effectiveness of the vaccines in reduction of overall meningitis mortality was estimated to be 20%; (interquartile range 20-40% and min. 8%, max 50 %). For the multivalent meningococcal vaccines the experts had similar optimism for most of the 12 CHNRI criteria with slightly lower optimism in answerability and low development cost criteria. The main concern was expressed over the cost of product, its affordability and cost of implementation. Conclusions With increasing recognition of the burden of meningococcal meningitis, especially during epidemics in Africa, it is vitally important that strategies are taken to reduce the morbidity and mortality attributable to this disease. Improved MC vaccines are a promising investment that could substantially contribute to reduction of child meningitis mortality world-wide.

Abstract Background Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP) or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA) vaccine offering protection for all serotypes. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results The experts expressed very high level of optimism (over 80%) that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9 relevant CHNRI criteria. The median potential effectiveness of conjugate SP vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 25% (interquartile range 20-38%, min. 15%, max 45%). For low cost, cross-protective common protein vaccines for SP the experts expressed concerns over answerability (72%) and the level of development costs (50%), while the scores for all other criteria were over 80%. The median potential effectiveness of common protein vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 30% (interquartile range 26-40%, min. 20%, max 45%). Conclusions Improved SP vaccines are a very promising investment that could substantially contribute to reduction of child mortality world-wide.

INTRODUCTION An important goal of ergonomics design is ensuring that workers have sufficient physical strength to perform the required tasks. It is usually of additional interest that tasks be performed […], Acceptable limits derived from psychophysical methodologies have been proposed, measured, and employed in a range of applications. There is little existing work, however, on such limits for single-digit exertions and relatively limited evidence on several fundamental issues related to data collection and processing of a sequence of self-regulated exertion levels. An experimental study was conducted using 14 male and 10 female participants (age range 18-31 years) from whom maximal voluntary exertions and maximal acceptable limits (MALs) were obtained using the index finger and thumb. Moderate to high levels of consistency were found for both measures between sessions separated by one day. Single MAL values, determined from a time series of exertions, were equivalent across three divergent processing methods and between values obtained from 5- and 25-mm samples. A critical interpretation of these and earlier results supports continued use of acceptable limits but also suggests that they should be used with some caution and not equated with safe limits. This research can be applied toward future development of exertion limits based on perceived acceptability.

The anaerobic ethylbenzene dehydrogenase is a heterodimer and oxidizes 4-fluro-ethylbenzene and the non-aromatic hydrocarbons. Gene sequence data reveal that ebdA, ebdb, and ebdC encode the alpha-, beta-, and gamma-subunits, respectively. The alpha and beta subunits bind molybdopterin and 4Fe-4S whereas the gamma subunit functions as a membrane anchor domain.

Research is conducted on the in vitro characterization of anaerobic ethylbenzene mineralization enzymes ethylbenzene dehydrogenase and 1-phenylethanol dehydrogenase in bacterium Azoarcus sp.strain EB1. The presence of both enzymes in cells grown on 1-phenylethanol and acetophenone substrate is described.

Background: One important way to transform food systems for human and planetary health would be to reduce the production and consumption of animals for food. The over-production and over-consumption of meat and dairy products is resource-intensive, energy-dense and creates public health and food equity risks, including the creation of superbugs and antimicrobial resistance, contamination and pollution of land and waterways, and injustice to animals and humans who work in the sector. Yet the continuing and expanding use of animals is entrenched in food systems. One policy response frequently suggested by parties from all sectors (industry, government and civil society) is voluntary or mandatory labelling reforms to educate consumers about the healthiness and sustainability of food products, and thus reduce demand. This paper evaluates the pitfalls and potentials of labelling as an incremental regulatory governance stepping-stone to transformative food system change. Methods: We use empirical data from a study of the regulatory politics of animal welfare and environmental claims on Australian products together with an ecological regulation conceptual approach to critically evaluate the potential of labelling as a regulatory mechanism. Results: We show that labelling is generally ineffective as a pathway to transformative food system change for three reasons: it does not do enough to redistribute power away from dominant actors to those harmed by the food system; it is vulnerable to greenwashing and reductionism; and it leads to market segmentation rather than collective political action. Conclusion: We suggest the need for regulatory governance that is ecological by design. Labelling can only be effective when connected to a broader suite of measures to reduce overall production and consumption of meat. We conclude with some recommendations as to how public health advocates and policy entrepreneurs might strategically use and contest labelling and certification schemes to build support for transformative food system change and to avoid the regressive consequences of labelling. [ABSTRACT FROM AUTHOR]

NADPH oxidase 2 (NOX2) produces the superoxide anion radical (O2-), which has functions in both cell signaling and immune defense. NOX2 is a multimeric-protein complex consisting of several protein subunits including the GTPase Rac. NOX2 uniquely facilitates an oxidative burst, which is described by initially slow O2- production, which increases over time. The NOX2 oxidative burst is considered critical to immune defense because it enables expedited O2- production in response to infections. However, the mechanism of the initiation and progression of this oxidative burst and its implications for regulation of NOX2 have not been clarified. In this study, we show that the NOX2 oxidative burst is a result of autoactivation of NOX2 coupled with the redox function of Rac. NOX2 autoactivation begins when active Rac triggers NOX2 activation and the subsequent production of O2-, which in turn activates redox-sensitive Rac. This activated Rac further activates NOX2, amplifying the feedforward cycle and resulting in a NOX2-mediated oxidative burst. Using mutagenesis-based kinetic and cell analyses, we show that enzymatic activation of Rac is exclusively responsible for production of the active Rac trigger that initiates NOX2 autoactivation, whereas redox-mediated Rac activation is the main driving force of NOX2 autoactivation and contributes to generation of ~98% of the active NOX2 in cells. The results of this study provide insight into the regulation of NOX2 function, which could be used to develop therapeutics to control immune responses associated with dysregulated NOX2 oxidative bursts. [ABSTRACT FROM AUTHOR]