Olfaction in the Anthropocene: NO3 negatively affects floral scent and nocturnal pollination.

There is growing concern about sensory pollutants affecting ecological communities. Anthropogenically enhanced oxidants [ozone (O3) and nitrate radicals (NO3)] rapidly degrade floral scents, potentially reducing pollinator attraction to flowers. However, the physiological and behavioral impacts on pollinators and plant fitness are unknown. Using a nocturnal flower-moth system, we found that atmospherically relevant concentrations of NO3 eliminate flower visitation by moths, and the reaction of NO3 with a subset of monoterpenes is what reduces the scent's attractiveness. Global atmospheric models of floral scent oxidation reveal that pollinators in certain urban areas may have a reduced ability to perceive and navigate to flowers. These results illustrate the impact of anthropogenic pollutants on an animal's olfactory ability and indicate that such pollutants may be critical regulators of global pollination.

An overview of the TROPICS NASA Earth Venture Mission.

The Time-Resolved Observations of Precipitation structure and storm Intensity with a Constellation of Smallsats (TROPICS) mission was selected by NASA as part of the Earth Venture-Instrument (EVI-3) program. The overarching goal for TROPICS is to provide nearly all-weather observations of 3D temperature and humidity, as well as cloud ice and precipitation horizontal structure, at high temporal resolution to conduct high-value science investigations of tropical cyclones. TROPICS will provide rapid-refresh microwave measurements (median refresh rate better than 60 min for the baseline mission) which can be used to observe the thermodynamics of the troposphere and precipitation structure for storm systems at the mesoscale and synoptic scale over the entire storm life cycle. TROPICS comprises six CubeSats in three low-Earth orbital planes. Each CubeSat will host a high-performance radiometer to provide temperature profiles using seven channels near the 118.75 GHz oxygen absorption line, water vapour profiles using three channels near the 183 GHz water vapour absorption line, imagery in a single channel near 90 GHz for precipitation measurements (when combined with higher-resolution water vapour channels), and a single channel near 205 GHz which is more sensitive to precipitation-sized ice particles. This observing system offers an unprecedented combination of horizontal and temporal resolution to measure environmental and inner-core conditions for tropical cyclones on a nearly global scale and is a major leap forward in the temporal resolution of several key parameters needed for assimilation into advanced data assimilation systems capable of utilizing rapid-update radiance or retrieval data. Launch readiness is currently projected for late 2019.

External validity of first-trimester algorithms in the prediction of pre-eclampsia disease severity.

OBJECTIVE: To compare disease features in women with pre-eclampsia between those who are correctly identified (true positive) and those who are missed (false negative) when applying first-trimester prediction algorithms for pre-eclampsia to a prospectively enrolled population. METHOD: Six first-trimester early (requiring delivery < 34 weeks' gestation) pre-eclampsia algorithms were applied to a prospective cohort of singleton pregnancies enrolled at first-trimester screening. Maternal outcomes, neonatal outcomes and severity parameters for pre-eclampsia were compared between true-positive and false-negative predictions. RESULTS: Twenty of 2446 (0.8%) women developed early pre-eclampsia, with 65% of these developing severe features and 20% HELLP syndrome. At enrollment, true-positive cases were more likely to be African-American and chronically hypertensive, while false-negative cases were more likely to be Caucasian. At delivery, true-positive cases were more likely to have pre-eclampsia superimposed on hypertension, severely elevated blood pressure and creatinine level > 1.1 mg/dL. False-negative cases were more likely to have HELLP syndrome (all P < 0.05). CONCLUSION: In an urban population with a high prevalence of chronic hypertension, patients who are correctly identified by first-trimester screening models are more likely to develop pre-eclampsia superimposed on chronic hypertension with severely elevated blood pressure and evidence of renal failure. In contrast, patients who are missed by these algorithms are more likely to have HELLP syndrome. Further research is needed to confirm these findings and the algorithm adjustments that may be necessary to better predict pre-eclampsia phenotypes.

Placental growth factor in the first trimester: relationship with maternal factors and placental Doppler studies.

OBJECTIVE: Placental growth factor (PlGF) is a potent angiogenic factor that impacts on early placental vascular development. It was our aim to clarify relationships between PlGF and first-trimester maternal/placental factors that are related to placental development. METHODS: Prospectively enrolled patients at 11-14 weeks' gestation had serum PlGF measurement by enzyme-linked immunosorbent assay. Results were related to maternal age, parity, race, body mass index, mean arterial blood pressure (MAP), smoking/caffeine use and parameters of placental blood flow resistance. RESULTS: In 110 consecutive patients PlGF levels ranged between 1.0 and 176.1 pg/mL, showing a linear relationship with gestational age (GA) (PlGF = (1.4251 x GA) -74.951, r(2) = 0.0765, F = 8.941, P = 0.03). PlGF did not relate to maternal demographics but negatively correlated with MAP (Spearman rho = -0.191, P < 0.05). Bilateral uterine artery notching was associated with lower PlGF (40.7 (range, 1.01-131.6) vs. 51.1 (range, 6.4-176.1) pg/mL; Mann-Whitney P = 0.034.). A trend to lower levels was also observed when umbilical artery end-diastolic flow was absent (37.1 (range, 6.8-95) vs. 49.3 (range, 1.01-176.1) pg/mL; P = 0.05). CONCLUSION: PlGF in the first trimester is related to maternal cardiovascular factors and placental Doppler findings that are associated with subsequent placental dysfunction. The utility of this parameter as a first-trimester screening tool on a population basis requires further investigation.

Responding to the threat of bioterrorism: a microbial ecology perspective--the case of anthrax.

Anthrax is a disease of herbivores caused by the gram-positive bacterium Bacillus anthracis. It can affect cattle, sheep, swine, horses and various species of wildlife. The routes for the spread among wildlife are reviewed. There are three kinds of human anthrax--inhalation, cutaneous, and intestinal anthrax--which differ in their routes of infection and outcomes. In the United States, confirmation of cases is made by the isolation of B. anthracis and by biochemical tests. Vaccination is not recommended for the general public; civilians who should be vaccinated include those who, in their work places, come in contact with products potentially contaminated with B. anthracis spores, and people engaged in research or diagnostic activities. After September 11, 2001, there were bioterrorism anthrax attacks in the United States: anthrax-laced letters sent to multiple locations were the source of infectious B. anthracis. The US Postal Service issued recommendations to prevent the danger of hazardous exposure to the bacterium. B. anthracis spores can spread easily and persist for very long times, which makes decontamination of buildings very difficult. Early detection, rapid diagnosis, and well-coordinated public health response are the key to minimizing casualties. The US Government is seeking new ways to deter bioterrorism, including a tighter control of research on infectious agents, even though pathogens such as B. anthracis are widely spread in nature and easy to grow. It is necessary to define the boundary between defensive and offensive biological weapons research. Deterring bioterrorism should not restrict critical scientific research.

Preinduction cervical ripening. A randomized trial of intravaginal misoprostol alone vs. a combination of transcervical Foley balloon and intravaginal misoprostol.

OBJECTIVE: To determine if the addition of a mechanical ripening agent (transcervical Foley balloon) to a pharmacologic agent (intravaginal misoprostol) improves the efficiency of preinduction cervical ripening. STUDY DESIGN: Singleton patients with an indication for delivery, unfavorable cervix (Bishop score < or = 5) and no contraindication to labor were randomly assigned to two groups: misoprostol alone (25 micrograms intravaginally every 3 hours for no more than 12 hr) or combination therapy (25-French transcervical Foley balloon inflated to 50 mL of sterile water with identical intravaginal misoprostol dosing). All patients received a history and physical examination (including Bishop score), preripening ultrasound, electronic fetal heart rate and contraction monitoring (to rule out spontaneous labor and document fetal well-being). Multiple variables of perinatal outcome were analyzed, including the main outcome variables of ripening-to-delivery time and cesarean section rate. RESULTS: During August 1998 to August 1999, 81 patients were randomized, 40 to misoprostol alone and 41 to combination therapy. There were no differences between the groups with respect to maternal demographics, preripening Bishop score, maternal complications, intrapartum intervention or neonatal outcome. The misoprostol group spent longer periods of time in active labor, and there was a trend for the combination group to require oxytocin for longer intervals. These findings did not significantly affect the total ripening-to-delivery time or cesarean section rate which were similar for both groups. CONCLUSION: The addition of mechanical ripening with a transcervical Foley balloon to intravaginal misoprostol did not improve the efficiency of preinduction cervical ripening. Mechanical and pharmacologic cervical ripening agents appear to act independently rather than synergistically.

Revisiting the short cervix detected by transvaginal ultrasound in the second trimester: why cerclage therapy may not help.

OBJECTIVE: The purpose of this study was to identify the risk factors that are associated with increased neonatal morbidity in patients who were treated for sonographic evidence of internal os dilation and distal cervical shortening during the second trimester. STUDY DESIGN: From May 1998 to June 2000 patients between 16 and 24 weeks of gestation with the following sonographic criteria were randomly assigned to McDonald cerclage or no cerclage: internal os dilation and either membrane prolapse into the endocervical canal at least 25% of the total cervical length but not beyond the external os or a shortened distal cervix <2.5 cm. Before randomization, all patients were treated identically with an amniocentesis, multiple urogenital cultures, and therapy with indomethacin and clindamycin for 48 to 72 hours. Except for the cerclage, all patients were treated identically after randomization. Multiple variables of perinatal outcome were analyzed. A regression model with gestational age at delivery as the dependent variable was constructed and repeated with neonatal morbidity as the dependent variable. This model was applied to 3 populations: the cerclage group, the no cerclage group, and both groups combined. RESULTS: Of the 135 patients, 20 patients declined randomization, and 2 patients were diagnosed with acute chorioamnionitis. Of the 113 patients remaining, 55 patients were randomly assigned to the cerclage group, and 58 patients were randomly assigned to the no cerclage group. There were 8 rescue cerclage procedures (4 in each group). Regression analysis showed that readmission for preterm labor, chorioamnionitis, and abruption were consistently associated with early gestational age at delivery and increased morbidity. Cerclage did not affect perinatal outcome. CONCLUSION: The sonographic findings of second trimester internal os dilation, membrane prolapse, and distal cervical shortening likely represent a common pathway of several pathophysiologic processes. Use of cerclage does not alter any perinatal outcome variables. Increased neonatal morbidity in these patients appears to be associated with subclinical infection, preterm labor, and abruption.

Preinduction cervical ripening techniques compared.

OBJECTIVE: To assess the clinical efficacy of pharmacologic, mechanical and combination techniques of cervical ripening. STUDY DESIGN: From March 1997 to August 1998, all cervical-ripening patients at Lehigh Valley Hospital were randomly assigned to three groups: intravaginal misoprostol, intracervical Foley catheter, or combination prostaglandin E2 (PGE2) gel and Foley catheter. Inclusion criteria included Bishop score < or = 5 and no contraindication to labor. The remaining delivery process was actively managed according to established guidelines. Multiple variables in perinatal outcome were analyzed, with the cesarean section rate and time from ripening to delivery as the main outcome variables. RESULTS: Of the 205 patients, 65 were randomized to the misoprostol group, 71 to the Foley group and 69 to the catheter-and-gel group. There were no differences between groups in delivery indications, maternal demographics, ultrasound findings, labor interventions, intrapartum times, mode of delivery, postpartum complications or neonatal outcomes. The misoprostol group demonstrated a higher rate of uterine tachysystole and required oxytocin less when compared to the two catheter groups. CONCLUSION: The higher rate of uterine tachysystole with misoprostol did not increase the cesarean section rate. The higher rate of oxytocin required by the two catheter groups did not increase the delivery time intervals. There appears to be no benefit to adding intracervical or intravaginal PGE2 gel to the intracervical Foley balloon. The misoprostol and catheter ripening techniques have similar safety and efficacy.

An overview of the genome of Nostoc punctiforme, a multicellular, symbiotic cyanobacterium.

Nostoc punctiforme is a filamentous cyanobacterium with extensive phenotypic characteristics and a relatively large genome, approaching 10 Mb. The phenotypic characteristics include a photoautotrophic, diazotrophic mode of growth, but N. punctiforme is also facultatively heterotrophic; its vegetative cells have multiple developmental alternatives, including terminal differentiation into nitrogen-fixing heterocysts and transient differentiation into spore-like akinetes or motile filaments called hormogonia; and N. punctiforme has broad symbiotic competence with fungi and terrestrial plants, including bryophytes, gymnosperms and an angiosperm. The shotgun-sequencing phase of the N. punctiforme strain ATCC 29133 genome has been completed by the Joint Genome Institute. Annotation of an 8.9 Mb database yielded 7432 open reading frames, 45% of which encode proteins with known or probable known function and 29% of which are unique to N. punctiforme. Comparative analysis of the sequence indicates a genome that is highly plastic and in a state of flux, with numerous insertion sequences and multilocus repeats, as well as genes encoding transposases and DNA modification enzymes. The sequence also reveals the presence of genes encoding putative proteins that collectively define almost all characteristics of cyanobacteria as a group. N. punctiforme has an extensive potential to sense and respond to environmental signals as reflected by the presence of more than 400 genes encoding sensor protein kinases, response regulators and other transcriptional factors. The signal transduction systems and any of the large number of unique genes may play essential roles in the cell differentiation and symbiotic interaction properties of N. punctiforme.

A randomized trial of cerclage versus no cerclage among patients with ultrasonographically detected second-trimester preterm dilatation of the internal os.

OBJECTIVE: The aim of this study was to compare perinatal outcomes of patients with second-trimester ultrasonographic evidence of preterm dilatation of the internal os treated with cerclage versus those of patients not treated with cerclage. STUDY DESIGN: From May 1998 through June 1999 patients with ultrasonographic evidence of preterm dilatation of the internal os between 16 and 24 weeks' gestation were randomly assigned to receive a McDonald cerclage or no cerclage. Before random assignment all patients underwent amniocentesis and urogenital cultures and then received 48 hours of therapy with indomethacin and antibiotics. After treatment each patient was followed up as an outpatient with bed rest and weekly ultrasonographic evaluation. RESULTS: Of the 61 patients 31 were randomly assigned to cerclage and 30 were randomly assigned to no cerclage. There were no differences between groups with respect to maternal demographic characteristics, risk factors for preterm birth, cervical measurements, rescue procedures, readmission, chorioamnionitis, and abruptio placentae. The mean gestational age at delivery (33.5 +/- 6.3 weeks) and the perinatal death rate (12. 9%) in the cerclage group were similar to the mean gestational age at delivery (34.7 +/- 4.7 weeks; P =.4) and the perinatal death rate (10.0%; P =.9) in the no-cerclage group. CONCLUSION: Treatment with McDonald cerclage of preterm dilatation of the cervix detected ultrasonographically during the second trimester did not improve perinatal outcomes.

Interaction between LIS1 and doublecortin, two lissencephaly gene products.

Mutations in either LIS1 or DCX are the most common cause for type I lissencephaly. Here we report that LIS1 and DCX interact physically both in vitro and in vivo. Epitope-tagged DCX transiently expressed in COS cells can be co-immunoprecipitated with endogenous LIS1. Furthermore, endogenous DCX could be co-immunoprecipitated with endogenous LIS1 in embryonic brain extracts, demonstrating an in vivo association. The two protein products also co-localize in transfected cells and in primary neuronal cells. In addition, we demonstrate homodimerization of DCX in vitro. Using fragments of both LIS1 and DCX, the domains of interaction were mapped. LIS1 and DCX interact with tubulin and microtubules. Our results suggest that addition of DCX and LIS1 to tubulin enhances polymerization in an additive fashion. In in vitro competition assays, when LIS1 is added first, DCX competes with LIS1 in its binding to microtubules, but when DCX is added prior to the addition of LIS1 it enhances the binding of LIS1 to microtubules. We conclude that LIS1 and DCX cross-talk is important to microtubule function in the developing cerebral cortex.

Doublecortin mutations cluster in evolutionarily conserved functional domains.

Mutations in the X-linked gene doublecortin ( DCX ) result in lissencephaly in males or subcortical laminar heterotopia ('double cortex') in females. Various types of mutation were identified and the sequence differences included nonsense, splice site and missense mutations throughout the gene. Recently, we and others have demonstrated that DCX interacts and stabilizes microtubules. Here, we performed a detailed sequence analysis of DCX and DCX-like proteins from various organisms and defined an evolutionarily conserved Doublecortin (DC) domain. The domain typically appears in the N-terminus of proteins and consists of two tandemly repeated 80 amino acid regions. In the large majority of patients, missense mutations in DCX fall within the conserved regions. We hypothesized that these repeats may be important for microtubule binding. We expressed DCX or DCLK (KIAA0369) repeats in vitro and in vivo. Our results suggest that the first repeat binds tubulin but not microtubules and enhances microtubule polymerization. To study the functional consequences of DCX mutations, we overexpressed seven of the reported mutations in COS7 cells and examined their effect on the microtubule cytoskeleton. The results demonstrate that some of the mutations disrupt microtubules. The most severe effect was observed with a tyrosine to histidine mutation at amino acid 125 (Y125H). Produced as a recombinant protein, this mutation disrupts microtubules in vitro at high molar concentration. The positions of the different mutations are discussed according to the evolutionarily defined DC-repeat motif. The results from this study emphasize the importance of DCX-microtubule interaction during normal and abnormal brain development.

A femtomolar-acting neuroprotective peptide induces increased levels of heat shock protein 60 in rat cortical neurons: a potential neuroprotective mechanism.

Activity-dependent neurotrophic factor (ADNF) was recently isolated from conditioned media of astrocytes stimulated with vasoactive intestinal peptide (VIP). ADNF provided neuroprotection at femtomolar concentration against a wide variety of toxic insults. A nine amino acid peptide (ADNF-9) captured with even greater potency the neuroprotective activity exhibited by the parent protein. Utilizing Northern and Western blot analyses, it was now shown that ADNF-9 increased the expression of heat shock protein 60 (hsp60) in rat cerebral cortical cultures. In contrast, treatment with the Alzheimer's toxin, the beta-amyloid peptide, reduced the amount of intracellular hsp60. Treatment with ADNF-9 prevented the reduction in hsp60 produced by the beta-amyloid peptide. The protection against the beta-amyloid peptide-associated cell death provided by ADNF-9 may be mediated in part by intracellular increases in hsp60.

Power of univariate and multivariate analyses of repeated measurements in controlled clinical trials.

The power of univariate and multivariate tests of significance is compared in relation to linear and nonlinear patterns of treatment effects in a repeated measurement design. Bonferroni correction was used to control the experiment-wise error rate in combining results from univariate tests of significance accomplished separately on average level, linear, quadratic, and cubic trend components. Multivariate tests on these same components of the overall treatment effect, as well as a multivariate test for between-groups difference on the original repeated measurements, were also evaluated for power against the same representative patterns of treatment effects. Results emphasize the advantage of parsimony that is achieved by transforming multiple repeated measurements into a reduced set of mean ngful composite variables representing average levels and rates of change. The Bonferroni correction applied to the separate univariate tests provided experiment-wise protection against Type I error, produced slightly greater experiment-wise power than a multivariate test applied to the same components of the data patterns, and provided substantially greater power than a multivariate test on the complete set of original repeated measurements. The separate univariate tests provide interpretive advantage regarding locus of the treatment effects.

Legionella: from environmental habitats to disease pathology, detection and control.

Studies on Legionella show a continuum from environment to human disease. Legionellosis is caused by Legionella species acquired from environmental sources, principally water sources such as cooling towers, where Legionella grows intracellularly in protozoa within biofilms. Aquatic biofilms, which are widespread not only in nature, but also in medical and dental devices, are ecological niches in which Legionella survives and proliferates and the ultimate sources to which outbreaks of legionellosis can be traced. Invasion and intracellular replication of L. pneumophila within protozoa in the environment play a major role in the transmission of Legionnaires' disease. Protozoa provide the habitats for the environmental survival and reproduction of Legionella species. L. pneumophila proliferates intracellularly in various species of protozoa within vacuoles studded with ribosomes, as it also does within macrophages. Growth within protozoa enhances the environmental survival capability and the pathogenicity (virulence) of Legionella. The growth requirements of Legionella, the ability of Legionella to enter a viable non-culturable state, the association of Legionella with protozoa and the occurrence of Legionella within biofilms complicates the detection of Legionella and epidemiological investigations of legionellosis. Polymerase chain reaction (PCR) methods have been developed for the molecular detection of Legionella and used in environmental and epidemiological studies. Various physical and chemical disinfection methods have been developed to eliminate Legionella from environmental sources, but gaining control of Legionella in environmental waters, where they are protected from disinfection by growing within protozoa and biofilms, remains a challenge, and one that must be overcome in order to eliminate sporadic outbreaks of legionellosis.

The medical threat of biological weapons.

There is a heightened threat of biological weapons being used for biological warfare or bioterrorism. Many of the microorganisms and toxins that may be used as such biological weapons can easily be acquired and mass produced. Dissemination of aerosols of these biological agents can produce mass casualties. If used by a terrorist they may overwhelm our current public health system. Some biological agents, such as Bacillus anthracis (anthrax) and botulinum toxin, are considered far more likely than others to be used as biological weapons; smallpox virus was apparently produced in mass quantities by the former Soviet Union and may also be a serious threat. The release of such agents could go undetected for several hours or days and would be followed by mass illnesses and a first line of response by the public health community. Rapid epidemiological investigation to identify the nature of the disease outbreak would be critical for limiting casualties. For many, but not all, biological agents there are medical treatments that can greatly lower the mortality rate. There currently are, however, insufficient supplies of medicinals and trained personnel to cope with a massive bioterrorist or biological warfare use of biological weapons. Increasing our preparedness is critical.

Preventing the misuse of microorganisms: the role of the American Society for Microbiology in protecting against biological weapons.

The American Society for Microbiology's (ASM) involvement with issues surrounding biological weapons began during World War II and continues to the present time. The Public and Scientific Affairs Board (PSAB) of the ASM has played an important role in monitoring and responding to legislative and regulatory issues involving biological weapons. As this review makes apparent, there is no consensus of opinion among scientists on their role in biological defense research, or is it likely that there will ever be complete agreement. There is consensus that steps should be taken to prevent biological warfare and that openness of scientific research and global surveillance of disease outbreaks can significantly increase transparency for detecting development of biological weapons. The ASM recommends increased attention to and efforts directed toward global surveillance of disease outbreaks, not only to aid public health organizations in improving human health, but also to establish baseline data against which unusual disease outbreaks can be assessed. Issues of how best to increase global security and to achieve a scientifically based verification protocol of the Biological Weapons Convention are important and continue to be addressed by the ASM.