Identification of genetic and biochemical mechanisms associated with heat shock and heat stress adaptation in grain amaranths.

Heat stress is poised to become a major factor negatively affecting plant performance worldwide. In terms of world food security, increased ambient temperatures are poised to reduce yields in cereals and other economically important crops. Grain amaranths are known to be productive under poor and/or unfavorable growing conditions that significantly affect cereals and other crops. Several physiological and biochemical attributes have been recognized to contribute to this favorable property, including a high water-use efficiency and the activation of a carbon starvation response. This study reports the behavior of the three grain amaranth species to two different stress conditions: short-term exposure to heat shock (HS) conditions using young plants kept in a conditioned growth chamber or long-term cultivation under severe heat stress in greenhouse conditions. The latter involved exposing grain amaranth plants to daylight temperatures that hovered around 50°C, or above, for at least 4 h during the day and to higher than normal nocturnal temperatures for a complete growth cycle in the summer of 2022 in central Mexico. All grain amaranth species showed a high tolerance to HS, demonstrated by a high percentage of recovery after their return to optimal growing conditions. The tolerance observed coincided with increased expression levels of unknown function genes previously shown to be induced by other (a)biotic stress conditions. Included among them were genes coding for RNA-binding and RNA-editing proteins, respectively. HS tolerance was also in accordance with favorable changes in several biochemical parameters usually induced in plants in response to abiotic stresses. Conversely, exposure to a prolonged severe heat stress seriously affected the vegetative and reproductive development of all three grain amaranth species, which yielded little or no seed. The latter data suggested that the usually stress-tolerant grain amaranths are unable to overcome severe heat stress-related damage leading to reproductive failure.

Habitat-adapted heterologous symbiont Salinispora arenicola promotes growth and alleviates salt stress in tomato crop plants.

To ensure food security given the current scenario of climate change and the accompanying ecological repercussions, it is essential to search for new technologies and tools for agricultural production. Microorganism-based biostimulants are recognized as sustainable alternatives to traditional agrochemicals to enhance and protect agricultural production. Marine actinobacteria are a well-known source of novel compounds for biotechnological uses. In addition, former studies have suggested that coral symbiont actinobacteria may support co-symbiotic photosynthetic growth and tolerance and increase the probability of corals surviving abiotic stress. We have previously shown that this activity may also hold in terrestrial plants, at least for the actinobacteria Salinispora arenicola during induced heterologous symbiosis with a wild Solanaceae plant Nicotiana attenuata under in vitro conditions. Here, we further explore the heterologous symbiotic association, germination, growth promotion, and stress relieving activity of S. arenicola in tomato plants under agricultural conditions and dig into the possible associated mechanisms. Tomato plants were grown under normal and saline conditions, and germination, bacteria-root system interactions, plant growth, photosynthetic performance, and the expression of salt stress response genes were analyzed. We found an endophytic interaction between S. arenicola and tomato plants, which promotes germination and shoot and root growth under saline or non-saline conditions. Accordingly, photosynthetic and respective photoprotective performance was enhanced in line with the induced increase in photosynthetic pigments. This was further supported by the overexpression of thermal energy dissipation, which fine-tunes energy use efficiency and may prevent the formation of reactive oxygen species in the chloroplast. Furthermore, gene expression analyses suggested that a selective transport channel gene, SlHKT1,2, induced by S. arenicola may assist in relieving salt stress in tomato plants. The fine regulation of photosynthetic and photoprotective responses, as well as the inhibition of the formation of ROS molecules, seems to be related to the induced down-regulation of other salt stress response genes, such as SlDR1A-related genes or SlAOX1b. Our results demonstrate that the marine microbial symbiont S. arenicola establishes heterologous symbiosis in crop plants, promotes growth, and confers saline stress tolerance. Thus, these results open opportunities to further explore the vast array of marine microbes to enhance crop tolerance and food production under the current climate change scenario.

Semiactive Knee Orthotic Using a MR Damper and a Smart Insole to Control the Damping Force Sensing the Plantar Pressure.

This work presents the development of semiactive knee orthosis prototype that focus to absorb the forces and impacts in this joint during the human gait. This prototype consists of three subsystems: the first is a wireless and portable system capable of measuring the ground reaction forces in the stance phase of the gait cycle, by means of an instrumented insole with force sensing resistors strategically placed on the sole of the foot, an electronic device allows processing and transmit this information via Bluetooth to the control system. The second is a semiactive actuator, which has inside a magnetorheological fluid, highlighting its ability to modify its damping force depending on the intensity of the magnetic field that circulates through the MR fluid. It is regulated by a Proportional Derivative (PD) controller system according to the values of plantar pressure measured by the insole. The third component is a mechanical structure manufactured by 3D printing, which adapts to the morphology of the human leg. This exoskeleton is designed to support the forces on the knee controlling the action of the magnetorheological actuator by ground reaction forces. The purpose of this assistance system is to reduce the forces applied to the knee during the gait cycle, providing support and stability to this joint. The obtained experimental results indicate that the device fulfills the function by reducing 12 % of the impact forces on the user's knee.

Alzheimer's Disease in Bilingual Latinos: Clinical Decisions for Diagnosis and Treatment Planning.

Early and accurate identification of cognitive and functional decline in bilingual Latino/a older adults with Alzheimer's disease and related dementias continues to be a substantial public health concern. This paper highlights the heterogeneity in the clinical expression of Alzheimer's disease among bilingual Latino/as, the clinical decisions leading to a culturally and linguistically congruent neuropsychological assessment, and the interdisciplinary, multi-setting partnerships needed to ensure a healthy longevity post-diagnosis for the patient, the caregiver, and the family. Psychologists play an important role in advocating for the best standard of care, as the patients and families endure the long journey of care with dignity and respect.

Demographically adjusted norms for the Trail Making Test in native Spanish speakers: Results from the neuropsychological norms for the US-Mexico border region in Spanish (NP-NUMBRS) project.

OBJECTIVE: Despite the wide use of the Trail Making Test (TMT), there is a lack of normative data for Spanish speakers living in the USA. Here we describe the development of regional norms for the TMT for native Spanish speakers residing in the Southwest Mexico-Border Region of the USA. METHOD: Participants were 252 healthy native Spanish speakers, 58% women, from ages 19 to 60, and ranging in education from 0 to 20 years, recruited in San Diego, CA and Tucson, AZ. All completed the TMT in Spanish along with a comprehensive neuropsychological test battery as part of their participation in the Neuropsychological Norms for the US-Mexico Border Region in Spanish (NP-NUMBRS) project. Univariable and interactive effects of demographics on test performance were examined. T-scores were calculated using fractional polynomial equations to account for linear and any non-linear effects of age, education, and sex. RESULTS: Older age and lower education were associated with worse scores on both TMT A and B. No sex differences were found. The newly derived T-scores showed no association with demographic variables and displayed the expected 16% rates of impairment using a -1 SD cut point based on a normal distribution. By comparison, published norms for English-speaking non-Hispanic Whites applied to the current data yielded significantly higher impairment for both TMT A and B with more comparable rates using non-Hispanic African Americans norms. CONCLUSIONS: Population-specific, demographically adjusted regional norms improve the utility and diagnostic accuracy of the TMT for use with native Spanish speakers in the US-Mexico Border region.

Updated demographically adjusted norms for the Brief Visuospatial Memory Test-revised and Hopkins Verbal Learning Test-revised in Spanish-speakers from the U.S.-Mexico border region: The NP-NUMBRS project.

OBJECTIVE: We generated demographically adjusted norms for the Brief Visuospatial Memory Test-revised (BVMT-R) and the Hopkins Verbal Learning Test-revised (HVLT-R) for Spanish-speakers from the U.S.-Mexico border region as part of a larger normative project. Methods: Healthy native Spanish-speakers (n = 203; Age: 19-60 years; Education: 0-20 years, 59% women) living in Arizona (n = 63) and California (n = 140) completed the BVMT-R and the HVLT-R as part of the larger Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project. Raw scores were converted to T-scores utilizing fractional polynomial equations, which considered linear and non-linear effects of demographic variables (age, education, sex). To demonstrate the benefit of employing our population-specific norms, we computed the proportion of our participants whose test performance fell below one standard deviation (T-score < 40) when applying published norms from non-Hispanic English-speakers, compared to the base rate derived from the new normative sample. Results: The resulting demographically adjusted T-scores showed the expected psychometric properties and corrected the misclassification in rates of impairment that were obtained when applying norms based on the English-speaking sample. Unexpectedly, participants in Arizona obtained slightly lower HVLT-R T-scores than those in California. This site effect was not explained by available sociodemographic or language factors. Supplementary formulas were computed adjusting for site in addition to demographics. Conclusions: These updated norms improve accuracy in identification of learning and memory impairment among Spanish-speaking adults living in the U.S.-Mexico border region. It will be important to generate additional data for elders, as the present norms are only applicable to adults age 60 and younger.

Native Spanish-speaker's test performance and the effects of Spanish-English bilingualism: results from the neuropsychological norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) project.

Objective: We aimed to investigate whether or not demographically-corrected test scores derived from the Neuropsychological Norms for the U.S.-Mexico Border Region in Spanish (NP-NUMBRS) would be less accurate if applied to Spanish-speakers with various degrees of English fluency. Spanish-English Method: One hundred and seventy primarily Spanish-speaking adults from the NP-NUMBRS project completed a comprehensive neuropsychological test battery. T-scores adjusted for age, education, and sex (but not degree of bilingualism), were derived for each test utilizing population-specific normative data. English fluency was assessed via the Controlled Oral Word Association Test in English (F-A-S), and Spanish fluency with "P-M-R," and degree of relative English fluency was calculated as the ratio of English language words over total words produced in both languages. Effects of degree of bilingualism on the NUMBRS battery test scores (raw scores and T-scores) were examined via Pearson's product moment correlation coefficients, and language groups (Spanish dominant vs. relative bilingual) were compared on demographically adjusted T-scores via independent samples t-tests. Results: Higher Spanish-English bilingualism was associated with higher education and SES, and was significantly associated with higher raw scores on all tests, but only associated with higher T-scores on a limited number of tests (i.e., WAIS-III Digit Symbol, Symbol Search, Letter-Number Sequencing and Trails B). Conclusion: Degree of Spanish-English bilingualism generally did not account for significant variance in the normed tests beyond the standard demographic adjustments on most tests. Overall, the normative adjustments provided by the NP-NUMBRS project appear applicable to native Spanish speakers from the U.S.-Mexico border region with various degrees of Spanish-English bilingualism.

A Custom EOG-Based HMI Using Neural Network Modeling to Real-Time for the Trajectory Tracking of a Manipulator Robot.

Although different physiological signals, such as electrooculography (EOG) have been widely used in the control of assistance systems for people with disabilities, customizing the signal classification system remains a challenge. In most interfaces, the user must adapt to the classification parameters, although ideally the systems must adapt to the user parameters. Therefore, in this work the use of a multilayer neural network (MNN) to model the EOG signal as a mathematical function is presented, which is optimized using genetic algorithms, in order to obtain the maximum and minimum amplitude threshold of the EOG signal of each person to calibrate the designed interface. The problem of the variation of the voltage threshold of the physiological signals is addressed by means of an intelligent calibration performed every 3 min; if an assistance system is not calibrated, it loses functionality. Artificial intelligence techniques, such as machine learning and fuzzy logic are used for classification of the EOG signal, but they need calibration parameters that are obtained through databases generated through prior user training, depending on the effectiveness of the algorithm, the learning curve, and the response time of the system. In this work, by optimizing the parameters of the EOG signal, the classification is customized and the domain time of the system is reduced without the need for a database and the training time of the user is minimized, significantly reducing the time of the learning curve. The results are implemented in an HMI for the generation of points in a Cartesian space (X, Y, Z) in order to control a manipulator robot that follows a desired trajectory by means of the movement of the user's eyeball.

Disparities in Access to Care Following Traumatic Digit Amputation.

Background: Care of digit amputations ranges from revision amputation to replantation. Many factors determine the treatment type. We looked at the epidemiology of amputation and factors associated with escalation of care after presenting to the emergency department (ED). We hypothesized that disparities in care following digit amputation exist. Methods: We queried the State ED Databases and State Inpatient Databases of the Healthcare Cost and Utilization Project and developed a cohort using the diagnosis codes for thumb and finger amputation. Escalation of care was defined as patients whose disposition from the ED was referral to a higher level hospital or inpatient admission. Bivariate and multivariable analyses were conducted to identify the characteristics associated with escalation of care. Results: Our cohort included 45 586 patients, of which 37 539 (82.4%) were men; 7130 (15.6%) and 38 456 (84.4%) suffered a thumb or finger amputation, respectively. The mean age was 39.3 ± 20.4 years, and 7487 (16.4%) received escalated care. Female sex (odds ratio [OR] = 0.7) was a negative independent predictor of escalation of care, while high income (OR = 1.1), machinery-related mechanism (OR = 1.8), self-harm (OR = 4.2), thumb amputation (OR = 1.7), Medicaid (OR = 1.3) or Medicare (OR = 1.1) insurance, trauma hospitals (OR = 1.3), and metropolitan teaching hospitals (OR = 1.2) were positive predictors. Conclusions: Male patients who suffered a thumb and/or self-inflicted amputation, are from a higher income zip code, have Medicaid or Medicare insurance, and present to a teaching trauma center are more likely to receive escalated care. This highlights differences in care that can serve as a starting point for work on barriers to access.

A machine learning approach for predictive models of adverse events following spine surgery.

BACKGROUND: Rates of adverse events following spine surgery vary widely by patient-, diagnosis-, and procedure-related factors. It is critical to understand the expected rates of complications and to be able to implement targeted efforts at limiting these events. PURPOSE: To develop and evaluate a set of predictive models for common adverse events after spine surgery. STUDY DESIGN: A retrospective cohort study. PATIENT SAMPLES: We extracted 345,510 patients from the Truven MarketScan (MKS) and MarketScan Medicaid Databases and 760,724 patients from the Centers for Medicare and Medicaid Services (CMS) Medicare database who underwent spine surgeries between 2009 and 2013. OUTCOME MEASURES: Overall adverse event (AE) occurrence and types of AE occurrence during the 30-day postoperative follow-up. METHODS: We applied a least absolute shrinkage and selection operator regularization method and a logistic regression approach for predicting the risks of an overall AE and the top six most commonly observed AEs. Predictors included patient demographics, location of the spine procedure, comorbidities, type of surgery performed, and preoperative diagnosis. RESULTS: The median ages of MKS and CMS patients were 49 years and 69, respectively. The most frequent individual AE was a cardiac dysfunction in CMS (10.6%) patients and a pulmonary complication (4.7%) in MKS. The area under the curve (AUC) of a prediction model for an overall AE was 0.7. Among the six individual prediction models, the model for predicting the risk of a pulmonary complication showed the greatest accuracy (AUC 0.76), and the range of AUC for these six models was 0.7 and 0.76. Medicaid status was one of the most important factors in predicting the occurrences of AEs; Medicaid recipients had increased odds of AEs by 20%-60% compared with non-Medicaid patients (odds ratios 1.28-1.6; p<10-10). Logistic regression showed higher AUCs than least absolute shrinkage and selection operator across these different models. CONCLUSIONS: We present a set of predictive models for AEs following spine surgery that account for patient-, diagnosis-, and procedure-related factors which can contribute to patient-counseling, accurate risk adjustment, and accurate quality metrics.

AhDGR2, an amaranth abiotic stress-induced DUF642 protein gene, modifies cell wall structure and composition and causes salt and ABA hyper-sensibility in transgenic Arabidopsis.

MAIN CONCLUSION: An amaranth DGR gene, induced under abiotic stress, modifies cell wall structure and causes hypersensitivity to ABA and salt when overexpressed in Arabidopsis. DUF642 is a highly conserved plant-specific family of unknown cell wall-associated proteins. The AhDGR2 gene, coding for a DUF642 protein, was significantly induced in grain amaranth (Amaranthus hypochondriacus) plants subjected to water-deficit and salinity stress, thereby suggesting its participation in abiotic stress tolerance in this plant. A role in development was also inferred from the higher AhDGR2 expression rates detected in young tissues. Subsequent overexpression of AhDGR2 in transgenic Arabidopsis plants (OE-AhDGR2) supported its possible role in development processes. Thus, OE-AhDGR2 plants generated significantly longer roots when grown in normal MS medium. However, they showed a hypersensitivity to increasing concentrations of abscisic acid or NaCl in the medium, as manifested by shorter root length, smaller and slightly chlorotic rosettes, as well as highly reduced germination rates. Contrary to expectations, OE-AhDGR2 plants were intolerant to abiotic stress. Moreover, cell walls in transgenic plants were thinner, in leaves, and more disorganized, in roots, and had significantly modified pectin levels. Lower pectin methylesterase activity detected in leaves of OE-AhDGR2 plants, but not in roots, was contrary to previous reports associating DUF642 proteins and decreased pectin esterification levels in cell walls. Nonetheless, microarray data identified candidate genes whose expression levels explained the phenotypes observed in leaves of OE-AhDGR2 plants, including several involved in cell wall integrity and extension, growth and development, and resistance to abiotic stress. These results support the role of DUF642 proteins in cell wall-related processes and offer novel insights into their possible role(s) in plants.

Overexpression of Grain Amaranth (Amaranthus hypochondriacus) AhERF or AhDOF Transcription Factors in Arabidopsis thaliana Increases Water Deficit- and Salt-Stress Tolerance, Respectively, via Contrasting Stress-Amelioration Mechanisms.

Two grain amaranth transcription factor (TF) genes were overexpressed in Arabidopsis plants. The first, coding for a group VII ethylene response factor TF (i.e., AhERF-VII) conferred tolerance to water-deficit stress (WS) in transgenic Arabidopsis without affecting vegetative or reproductive growth. A significantly lower water-loss rate in detached leaves coupled to a reduced stomatal opening in leaves of plants subjected to WS was associated with this trait. WS tolerance was also associated with an increased antioxidant enzyme activity and the accumulation of putative stress-related secondary metabolites. However, microarray and GO data did not indicate an obvious correlation between WS tolerance, stomatal closure, and abscisic acid (ABA)-related signaling. This scenario suggested that stomatal closure during WS in these plants involved ABA-independent mechanisms, possibly involving reactive oxygen species (ROS). WS tolerance may have also involved other protective processes, such as those employed for methyl glyoxal detoxification. The second, coding for a class A and cluster I DNA binding with one finger TF (i.e., AhDof-AI) provided salt-stress (SS) tolerance with no evident fitness penalties. The lack of an obvious development-related phenotype contrasted with microarray and GO data showing an enrichment of categories and genes related to developmental processes, particularly flowering. SS tolerance also correlated with increased superoxide dismutase activity but not with augmented stomatal closure. Additionally, microarray and GO data indicated that, contrary to AhERF-VII, SS tolerance conferred by AhDof-AI in Arabidopsis involved ABA-dependent and ABA-independent stress amelioration mechanisms.

The overexpression of an Amaranthus hypochondriacus NF-YC gene modifies growth and confers water deficit stress resistance in Arabidopsis.

Nuclear factor-Y (NF-Y), is a plant heterotrimeric transcription factor constituted by NF-YA, NF-YB and NF-YC subunits. The function of many NF-Y subunits, mostly of the A and B type, has been studied in plants, but knowledge regarding the C subunit remains fragmentary. Here, a water stress-induced NF-YC gene from Amaranthus hypochondriacus (AhNF-YC) was further characterized by its overexpression in transgenic Arabidospis thaliana plants. A role in development was inferred from modified growth rates in root, rosettes and inflorescences recorded in AhNF-YC overexpressing Arabidopsis plants, in addition to a delayed onset of flowering. Also, the overexpression of AhNF-YC caused increased seedling sensitivity to abscisic acid (ABA), and influenced the expression of several genes involved in secondary metabolism, development and ABA-related responses. An altered expression of the latter in water stressed and recovered transgenic plants, together with the observed increase in ABA sensitivity, suggested that their increased water stress resistance was partly ABA-dependent. An untargeted metabolomic analysis also revealed an altered metabolite pattern, both in normal and water stress/recovery conditions. These results suggest that AhNF-YC may play an important regulatory role in both development and stress, and represents a candidate gene for the engineering of abiotic stress resistance in commercial crops.

The novel and taxonomically restricted Ah24 gene from grain amaranth (Amaranthus hypochondriacus) has a dual role in development and defense.

Grain amaranths tolerate stress and produce highly nutritious seeds. We have identified several (a)biotic stress-responsive genes of unknown function in Amaranthus hypochondriacus, including the so-called Ah24 gene. Ah24 was expressed in young or developing tissues; it was also strongly induced by mechanical damage, insect herbivory and methyl jasmonate and in meristems and newly emerging leaves of severely defoliated plants. Interestingly, an in silico analysis of its 1304 bp promoter region showed a predominance of regulatory boxes involved in development, but not in defense. The Ah24 cDNA encodes a predicted cytosolic protein of 164 amino acids, the localization of which was confirmed by confocal microscopy. Additional in silico analysis identified several other Ah24 homologs, present almost exclusively in plants belonging to the Caryophyllales. The possible function of this gene in planta was examined in transgenic Ah24 overexpressing Arabidopsis thaliana and Nicotiana tabacum plants. Transformed Arabidopsis showed enhanced vegetative growth and increased leaf number with no penalty in one fitness component, such as seed yield, in experimental conditions. Transgenic tobacco plants, which grew and reproduced normally, had increased insect herbivory resistance. Modified vegetative growth in transgenic Arabidopsis coincided with significant changes in the expression of genes controlling phytohormone synthesis or signaling, whereas increased resistance to insect herbivory in transgenic tobacco coincided with higher jasmonic acid and proteinase inhibitor activity levels, plus the accumulation of nicotine and several other putative defense-related metabolites. It is proposed that the primary role of the Ah24 gene in A. hypochondriacus is to contribute to a rapid recovery post-wounding or defoliation, although its participation in defense against insect herbivory is also plausible.

Second-language fluency predicts native language stroop effects: evidence from Spanish-English bilinguals.

Studies have shown reduced Stroop interference in bilinguals compared to monolinguals defined dichotomously, but no study has explored how varying degrees of second language fluency, might affect linguistic inhibitory control in the first language. We examined effects of relative English fluency on the ability to inhibit the automatic reading response on the Golden version of the Stroop Test administered in Spanish. Participants were 141 (49% male) adult native Spanish speakers from the U.S.-Mexico border region (education range = 8-20 and age range = 20-63). A language dominance index was calculated as the ratio of English words to total words produced in both languages using the Controlled Oral Word Association Test with letters PMR in Spanish and FAS in English. Greater degree of English fluency as measured by the dominance index predicted better speed on the Stroop incongruent trial independent of education effects. On the other hand, neither the dominance index nor education predicted performance on the word reading and color-naming trials. These results suggest an advantage in inhibitory control among those with greater second-language ability.

Who are the women and men in Veterans Health Administration's current spinal cord injury population?

Spinal cord injury (SCI) care is a high priority for the Veterans Health Administration (VHA). Aging Veterans, new cases of SCI from recent conflicts, and increasing numbers of women Veterans have likely changed the profile of the VHA SCI population. This study characterizes the current Veteran population with SCI with emphasis on healthcare utilization and women Veterans. We analyzed VHA administrative data from 2002-2003 and 2007-2008, analyzing composition, demographics, and healthcare use. The population is mostly male (>97%) and largely between 45 and 64 years old. Over 30% are over the age of 65. They are frequent users of healthcare, with an average of 21 visits per year. Women Veterans with SCI form a small but distinct subpopulation, being younger and less likely to be married and having a higher burden of disease. We must understand how the VHA population with SCI is changing to anticipate and provide the best care for these complex patients.

Isolation of three new naturally occurring compounds from the culture of Micromonospora sp. P1068.

Bioassay guided isolation of an antibacterial extract prepared from the fermentation broth of a Micromonospora sp. P1068 led to the isolation of eight compounds identified as (3R) 3,4',7-trihydroxy-isoflavanone (1), 3-hydroxydehydrodaidzein, daidzein (2), 3-methyl-1H-indole-2-carboxylic acid (3), 1H-indole-3-carboxaldehyde (4), 3-(p-hydroxyphenyl)-N-methylpropionamide, N-methylphloretamide (5), phenyl acetic acid (6), 2-hydroxy phenyl acetic acid (7) and 4-hydroxy-5-methoxy-benzoic acid (8). Compounds 1 and 5 were found to be novel chemical entities while 3 was isolated from a natural source for the first time. All compounds were evaluated for their antimicrobial activities against a panel of clinically significant microorganisms. Compound 4 was active against Staphylococcus aureus (MIC, 32 microg/ml), Enterococcus faecium (MIC, 32 microg/ml) and Escherichia coli (MIC, 64 microg/ml).

Novel alpha-pyrones produced by a marine Pseudomonas sp. F92S91: taxonomy and biological activities.

Inhibitors of the enzymes involved in fatty acid biosynthesis (FAB) have been reported as antibacterial agents. These include thiolactomycin, cerulenin, triclosan, diazoborine, naphthyridinones, aminopyridines and pyridoindoles. Our search for new FAB inhibitors, using a lacZ reporter cell-based screen, led to several confirmed hits. Culture F92S91, later identified as a Pseudomonas sp. based on 16S profiling, was found to produce two alpha-pyrones (I and II) and three high molecular weight peptides. The pyrones were unstable under acidic conditions, and they were rearranged into a furanone derivative (III). Of these compounds, pyrone I was the most active with MICs (microg/ml) against B. subtilis (1 to approximately 2), MRSA (2 to approximately 4), M. catarrhalis (4) and VRE (2 to approximately 64). Effects on macromolecular synthesis and membrane functions were tested in B. subtilis. Pyrone I nonspecifically inhibited incorporation of radiolabeled precursors into DNA, RNA and protein within 5 minutes of drug exposure, similar to that of triclosan. Both compounds also inhibited the cellular uptake of these precursors. Cerulenin did not have an effect until 30 minutes of drug treatment. Pyrone I and triclosan were membrane-active (BacLight test); however, pyrone I (at < or = 128 microg/ml concentration) was not hemolytic to human RBCs in contrast to triclosan, which was hemolytic at 16 microg/ml. These data suggest that pyrone-I, unlike triclosan, selectively affects bacterial membrane function.