A temperate super-Jupiter imaged with JWST in the mid-infrared.

Of the approximately 25 directly imaged planets to date, all are younger than 500 Myr, and all but six are younger than 100 Myr (ref. 1). Eps Ind A (HD209100, HIP108870) is a K5V star of roughly solar age (recently derived as 3.7-5.7 Gyr (ref. 2) and 3.5 - 1.3 + 0.8 Gyr (ref. 3)). A long-term radial-velocity trend4,5 and an astrometric acceleration6,7 led to claims of a giant planet2,8,9 orbiting the nearby star (3.6384 ± 0.0013 pc; ref. 10). Here we report JWST coronagraphic images which reveal a giant exoplanet that is consistent with these radial and astrometric measurements but inconsistent with the previously claimed planet properties. The new planet has a temperature of approximately 275 K and is remarkably bright at 10.65 and 15.50 µm. Non-detections between 3.5 and 5.0 µm indicate an unknown opacity source in the atmosphere, possibly suggesting a high-metallicity, high carbon-to-oxygen ratio planet. The best-fitting temperature of the planet is consistent with theoretical thermal evolution models, which were previously untested at this temperature range. The data indicate that this is probably the only giant planet in the system, and therefore we refer to it as b, despite it having significantly different orbital properties than the previously claimed planet b.

Meteorological factors and respiratory syncytial virus seasonality in subtropical Australia.

Evidence is emerging regarding the influence of meteorological factors on seasonal respiratory syncytial virus outbreaks. Data however, are limited for subtropical regions, especially in the southern hemisphere. We examined whether meteorological data (daily minimum and maximum temperatures, rainfall, relative humidity, dew point, daily global solar exposure) and tourist numbers were associated with the incidence of RSV in children aged <5 years for the Gold Coast region of South-East Queensland, Australia (latitude 28.0°S). RSV cases between 1 July 2007 and 30 June 2016 were identified from the Pathology Queensland Gold Coast Laboratory database. Time-series methods were used to identify seasonal patterns. RSV activity peaked in mid-to-late autumn (April-May), tapering in winter (June-August). While most meteorological variables measured were associated with RSV incidence, rainfall (ρ = 0.40, 95% confidence interval (CI) 0.32-0.48) and humidity (ρ = 0.38, 95% CI 0.29-0.46) 8 weeks earlier had the nearest temporal relationship. Tourist numbers were not correlated with RSV activity. Identifying meteorological conditions associated with seasonal RSV epidemics can improve understanding of virus transmission and assist planning for their impact upon the health sector, including timing of passive RSV immunoprophylaxis for high-risk infants and future public health interventions, such as maternal immunisation with RSV vaccines.

Access to HIV community services by vulnerable populations: evidence from an enhanced HIV/AIDS surveillance system.

HIV disproportionately affects vulnerable populations such as black and minority ethnic groups, men who have sex with men (MSM) and migrants, in many countries including those in the UK. Community organisations in the UK are charitable non-governmental organisations with a proportion of the workforce who volunteer, and provide invaluable additional support for people living with HIV (PLWHIV). Information on their contribution to HIV care in vulnerable groups is relatively sparse. Data generated from an enhanced HIV surveillance system in North West England, UK, was utilised for this study. We aimed to determine the characteristics of individuals who chose to access community services in addition to clinical services (1375 out of 4195 records of PLWHIV in clinical services). Demographic information, risk factors including residency status, uniquely gathered in this region, and deprivation scores were examined. Multivariate logistic regression modelling was conducted to predict the relative effect of patient characteristics on attendance at community services. Attendance at community services was highest in those living in the most, compared with least, deprived areas (p<0.001), and was most evident in MSM and heterosexuals. Compared to white UK nationals attendance was significantly higher in non-UK nationals of uncertain residency status (Adjusted odds ratio [AOR] = 21.91, 95% confidence interval [CI] 10.48-45.83; p<0.001), refugees (AOR = 5.75, 95% CI 3.3-10.03; p<0.001), migrant workers (AOR = 5.48, 95% CI 2.22-13.51; p<0.001) and temporary visitors (AOR = 3.44, 95% CI 1.68-7.05; p<0.001). Community services, initially established predominantly to support MSM, have responded to the changing demography of HIV and reach the most vulnerable members of society. Consequent to their support of migrant populations, community services are vital for the management of HIV in black and minority groups. Paradoxically, this coincides with increasing funding pressures on these services.

High-frequency ventilation with the Dräger Babylog 8000plus: measuring the delivered frequency.

BACKGROUND: Ventilator frequency is one of the determinants of tidal volume delivery during high-frequency ventilation. Clinicians increasingly use data on ventilator displays to inform their decisions. AIM: To measure the frequencies delivered by the Dräger Babylog 8000plus ventilator when used in high-frequency mode. METHODS: Ventilator waveforms using a test lung were recorded at the full range of settings 5-20 Hz using Spectra software at 1000 Hz. The changes in frequency produced by a 1-Hz change in set frequency were calculated. Actual and displayed frequencies were compared. RESULTS: For settings up to 12 Hz, median (range) difference between set and delivered frequencies was 0 (-0.4 to +0.1) Hz. Above 12 Hz, delivered frequency varied by -0.3 (-1.9 to +0.3) Hz. For 1-Hz changes in frequency settings, in the range 5-12 Hz, 1-Hz changes produced a change in delivered frequency of 1.0 (0.6-1.4) Hz. Above 12 Hz, the corresponding changes were 0.7 (0-2.9) Hz. The ventilator displays the set frequency during operation rather than the delivered frequency. CONCLUSION: At 12 Hz and below, the differences between set and delivered frequencies were relatively small compared with those at 13 Hz and higher. Above 13 Hz, the difference between set and delivered frequencies was up to 2.9 Hz. Some frequency setting changes did not result in a change in delivered frequency.

Major conservation policy issues for biodiversity in Oceania.

Oceania is a diverse region encompassing Australia, Melanesia, Micronesia, New Zealand, and Polynesia, and it contains six of the world's 39 hotspots of diversity. It has a poor record for extinctions, particularly for birds on islands and mammals. Major causes include habitat loss and degradation, invasive species, and overexploitation. We identified six major threatening processes (habitat loss and degradation, invasive species, climate change, overexploitation, pollution, and disease) based on a comprehensive review of the literature and for each developed a set of conservation policies. Many policies reflect the urgent need to deal with the effects of burgeoning human populations (expected to increase significantly in the region) on biodiversity. There is considerable difference in resources for conservation, including people and available scientific information, which are heavily biased toward more developed countries in Oceania. Most scientific publications analyzed for four threats (habitat loss, invasive species, overexploitation, and pollution) are from developed countries: 88.6% of Web of Science publications were from Australia (53.7%), New Zealand (24.3%), and Hawaiian Islands (10.5%). Many island states have limited resources or expertise. Even countries that do (e.g., Australia, New Zealand) have ongoing and emerging significant challenges, particularly with the interactive effects of climate change. Oceania will require the implementation of effective policies for conservation if the region's poor record on extinctions is not to continue.

One hundred questions of importance to the conservation of global biological diversity.

We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds.

Devices and pressure sources for administration of nasal continuous positive airway pressure (NCPAP) in preterm neonates.

BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is used to support preterm infants recently extubated, those experiencing significant apnoea of prematurity and those with respiratory distress soon after birth as an alternative to intubation and ventilation. This review focuses exclusively on identifying the most effective pressure source and interface for NCPAP delivery in preterm infants. OBJECTIVES: To determine which technique of pressure generation and which type of nasal interface for NCPAP delivery most effectively reduces the need for additional respiratory support in preterm infants extubated to NCPAP following intermittent positive pressure ventilation (IPPV) for respiratory distress syndrome (RDS) or in those treated with NCPAP soon after birth. SEARCH STRATEGY: The strategy included searches of MEDLINE (1966 - 2006), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006) CINAHL, abstracts from conference proceedings, cross-referencing of previous reviews and the use of expert informants. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing different techniques of NCPAP pressure generation and/or nasal interfaces in preterm infants extubated to NCPAP following IPPV for RDS or treated with NCPAP soon after birth. DATA COLLECTION AND ANALYSIS: Data was extracted and analysed by the first three authors. Dichotomous results were analysed using the relative risk (RR), risk difference (RD) and number needed to treat (NNT). MAIN RESULTS: 1. Preterm infants being extubated to NCPAP following a period of IPPV for RDS:Meta-analysis of the results from Davis 2001 and Roukema 1999a demonstrated that short binasal prongs are more effective at preventing re-intubation than single nasal or nasopharyngeal prongs [typical RR 0.59 (CI: 0.41, 0.85), typical RD -0.21 (CI: -0.35, -0.07), NNT 5 (CI: 3, 14)]. In one study comparing short binasal prong devices (Sun 1999), the re-intubation rate was significantly lower with the Infant Flow Driver than with the Medicorp prong [RR 0.33 (CI: 0.17, 0.67), RD -0.32 (CI: -0.49, -0.15), NNT 3 (CI: 2, 7)]. The other study comparing short binasal prong devices (Infant Flow Driver versus INCA prongs, Stefanescu 2003) demonstrated no significant difference in the re-intubation rate but did show a significant reduction in the total days in hospital in the Infant Flow Driver group [MD -12.60 (95% CI: -22.81, -2.39) days].2. Preterm infants primarily treated with NCPAP soon after birth:In the one trial identified, Mazzella 2001 found a significantly lower oxygen requirement and respiratory rate in those randomised to short binasal prongs when compared with CPAP delivered via nasopharyngeal prong. The requirement for intubation beyond 48 hours from randomisation was not assessed.3. Studies randomising preterm infants to different NCPAP systems using broad inclusion criteriaThe studies of Rego 2002 and Buettiker 2004 did not examine the primary outcomes of this review. Of the secondary outcomes, Rego 2002 demonstrated a significantly higher incidence of nasal hyperaemia with the use of the Argyle prong compared with Hudson prongs [RR 2.39 (95% CI: 1.27, 4.50), RD 0.28 (95% CI: 0.10, 0.46)]. One study comparing different techniques of pressure generation is awaiting further assessment as it is currently available in abstract form only. AUTHORS' CONCLUSIONS: Short binasal prong devices are more effective than single prongs in reducing the rate of re-intubation. Although the Infant Flow Driver appears more effective than Medicorp prongs the most effective short binasal prong device remains to be determined. The improvement in respiratory parameters with short binasal prongs suggests they are more effective than nasopharyngeal CPAP in the treatment of early RDS. Further studies incorporating longer-term outcomes are required. Studies are also needed to determine the optimal pressure source for the delivery of NCPAP.

Creating a framework for the prioritization of biosecurity risks to the New Zealand dairy industry.

The New Zealand dairy sector relies on robust biosecurity measures to control and mitigate a wide range of threats to the industry. To optimize the prioritization of organisms and manage the risk they pose to the sector in a transparent and credible way, the Dairy Biosecurity Risk Evaluation Framework (D-BRiEF) was developed. This comprehensive framework was specifically designed for decision support, using a standardized approach to address the full spectrum of biosecurity threats to the sector, including exotic and endemic animal disease organisms, pest plants and insects. D-BRiEF is underpinned by three main processes, namely (i) hazard identification; (ii) multicriteria risk assessment; and (iii) communication for risk management. Expert knowledge and empirical data, including associated uncertainty, are harnessed in a standardized format. Results feed into a probability-impact model that was developed in close collaboration with dairy sector economists to provide overall comparative 10-year quantitative economic impact estimates for each assessed risk organism. A description of the overarching framework, which applies to diverse organism groups, is presented with detailed methodology on both endemic and exotic animal disease risk organisms. Examples of visual outputs are included, although actual ranking results are not reported due to industry confidentiality. D-BRiEF can provide a decision advantage to DairyNZ biosecurity risk managers and sector stakeholders by creating a transparent process that can be interrogated and updated at multiple levels to fully understand the layers of risk posed by different organisms.

Prevalence of Cerebral Microhemorrhage following Chronic Blast-Related Mild Traumatic Brain Injury in Military Service Members Using Susceptibility-Weighted MRI.

BACKGROUND AND PURPOSE: Cerebral microhemorrhages are a known marker of mild traumatic brain injury. Blast-related mild traumatic brain injury relates to a propagating pressure wave, and there is evidence that the mechanism of injury in blast-related mild traumatic brain injury may be different from that in blunt head trauma. Two recent reports in mixed cohorts of blunt and blast-related traumatic brain injury in military personnel suggest that the prevalence of cerebral microhemorrhages is lower than in civilian head injury. In this study, we aimed to characterize the prevalence of cerebral microhemorrhages in military service members specifically with chronic blast-related mild traumatic brain injury. MATERIALS AND METHODS: Participants were prospectively recruited and underwent 3T MR imaging. Susceptibility-weighted images were assessed by 2 neuroradiologists independently for the presence of cerebral microhemorrhages. RESULTS: Our cohort included 146 veterans (132 men) who experienced remote blast-related mild traumatic brain injury (mean, 9.4 years; median, 9 years after injury). Twenty-one (14.4%) reported loss of consciousness for <30 minutes. Seventy-seven subjects (52.7%) had 1 episode of blast-related mild traumatic brain injury; 41 (28.1%) had 2 episodes; and 28 (19.2%) had >2 episodes. No cerebral microhemorrhages were identified in any subject, as opposed to the frequency of SWI-detectable cerebral microhemorrhages following blunt-related mild traumatic brain injury in the civilian population, which has been reported to be as high as 28% in the acute and subacute stages. CONCLUSIONS: Our results may reflect differences in pathophysiology and the mechanism of injury between blast- and blunt-related mild traumatic brain injury. Additionally, the chronicity of injury may play a role in the detection of cerebral microhemorrhages.

The role of the liver in glucagon metabolism.

Total plasma immunoreactive pancreatic glucagon (IRG) was measured in samples taken simultaneously from the proximal portal vein and superior vena cava of 26 healthy rats. The portal-peripheral ratio of IRG was 2.80+/-0.25, the portal-peripheral difference (Delta) 124+/-15 pg/ml, and percentage extraction 58+/-3. Gel filtration of paired portal and peripheral vein samples showed that reduction in the 3,500-dalton IRG component (glucagon) in peripheral samples accounted for almost all the differences, there being minimal and inconsistent changes in the high molecular weight (>40,000) fraction. The portal-peripheral ratio of the 3,500-dalton glucagon was 5.24+/-1.10, the portal-peripheral difference 130+/-33 pg/ml, and the percentage extraction 81+/-5. To study the transhepatic differences in the 9,000-dalton "proglucagon-like" material, the experiment was repeated in nine rats 24 h after bilateral nephrectomy, a procedure which increases plasma levels of this fraction. The portal-peripheral ratio for plasma IRG in these rats was 1.48+/-0.12, the portal-peripheral difference 140+/-29 pg/ml, and percentage extraction 28+/-5. Gel filtration revealed no consistent differences between portal and peripheral concentrations of the 9,000- and >40,000-dalton components, which comprised 40 and 13%, respectively, of the mean IRG level of 492+/-35 pg/ml. In contrast, there were marked differences between portal and peripheral levels of the 3,500-dalton component the ratio being 3.42+/-0.63, the portal-peripheral difference 182+/-32 pg/ml, and percentage extraction 64+/-5. Similar studies in a healthy dog, in which species there are significant circulating levels of the 9,000-dalton IRG component, confirmed the selective hepatic extraction of the 3,500-dalton fraction. We conclude that the various IRG fractions are metabolized differently by the liver, and that portal-peripheral ratios based on direct assay of plasma IRG will vary depending on the percentage glucagon immunoreactivity in each fraction; the greater the combined contribution of fractions other than the 3,500-dalton component to total plasma IRG, the lower will be the ratio. Because of the heterogeneity of circulating IRG and significant differences in the metabolism of its various components, gel filtration of plasma samples is necessary for precise quantitation of the hepatic uptake of each particular fraction.

Effects of open endotracheal suction on lung volume in infants receiving HFOV.

OBJECTIVE: To describe the pattern and magnitude of lung volume change during open endotracheal tube (ETT) suction in infants receiving high-frequency oscillatory ventilation (HFOV). DESIGN: Prospective observational clinical study. SETTING: Tertiary neonatal intensive care unit. PATIENTS AND PARTICIPANTS: Seven intubated and muscle-relaxed newborn infants receiving HFOV. INTERVENTIONS: Open ETT suction was performed for 6 s at -100 mmHg using a 6-F catheter passed to the ETT tip after disconnection from HFOV. The HFOV was then recommenced at the same settings as prior to ETT suction. MEASUREMENTS AND RESULTS: Change in lung volume (DeltaV (L)) referenced to baseline lung volume before suction was measured with a calibrated respiratory inductive plethysmography recording from 30 s before until 60 s after ETT suction. In all infants ETT suction resulted in significant loss of lung volume. The mean DeltaV (L) during suctioning was -13 ml/kg (SD 4 ml/kg) (p<0.0001 vs. baseline, repeated-measures ANOVA), with a mean 76.5% (SD 14.1%) of this volume loss being related to circuit disconnection. After recommencing HFOV lung volume was rapidly regained with mean DeltaV (L) at 60 s being 1 ml/kg (SD 4 ml/kg) below baseline (p>0.05, Tukey post-test). CONCLUSIONS: Open ETT suction caused a significant but transient loss of lung volume in muscle-relaxed newborn infants receiving HFOV.

Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

CRT improves the exercise capacity and functional reserve of the failing heart through enhancing the cardiac flow- and pressure-generating capacity.

BACKGROUND: While information on how cardiac resynchronisation therapy (CRT) affects cardiac performance at rest is readily available, the mechanisms whereby CRT alters cardiac function during maximal exercise are unclear. AIMS: We examined the medium-term effects of CRT on cardiac and physical functional reserve of patients with severe heart failure (CHF) and prolonged QRS duration. METHODS: Seventeen consecutive patients with severe CHF (NYHA III-IV) and widened QRS underwent maximal cardiopulmonary exercise testing with non-invasive central haemodynamic measurements before and 6-8 weeks after CRT pacemaker implantation. RESULTS: After CRT there were significant increases in exercise cardiac output by 19.3% (P=0.0048) from 9.5+/-3.4 l min(-1), peak mean arterial blood pressure by 14.1% (P=0.0001) from 91.3+/-13.6 mm Hg, and peak cardiac power output by 37.2% (P=0.0008) from 1.92+/-0.74 W. There were no significant changes in these variables at rest. Exercise duration (+42.3%, P=0.0002), NYHA functional class (P=0.0001) and SF-36 symptom score (P=0.0006) were also significantly improved. Powerful surrogate indicators of prognosis were also significantly improved with CRT: peak O(2) consumption (+20.9%, P=0.0007), VE/VCO(2) slope (-20.0%, P=0.005) and circulatory power (+42.0%, P=0.0012). CONCLUSION: In this cohort of patients, post-implant CRT significantly improved the flow-, pressure- and power-generating capacity of the failing hearts. This may be causally related to the improvements observed in exercise capacity, functional class and symptom scores.

Predicting successful extubation of very low birthweight infants.

OBJECTIVE: To determine the accuracy of three tests used to predict successful extubation of preterm infants. STUDY DESIGN: Mechanically ventilated infants with birth weight <1250 g and considered ready for extubation were changed to endotracheal continuous positive airway pressure (ET CPAP) for three minutes. Tidal volumes, minute ventilation (V e), heart rate, and oxygen saturation were recorded before and during ET CPAP. Three tests of extubation success were evaluated: (a) expired V e during ET CPAP; (b) ratio of V e during ET CPAP to V e during mechanical ventilation (V e ratio); (c) the spontaneous breathing test (SBT)-the infant passed this test if there was no hypoxia or bradycardia during ET CPAP. The clinical team were blinded to the results, and all infants were extubated. Extubation failure was defined as reintubation within 72 hours of extubation. RESULTS: Fifty infants were studied and extubated. Eleven (22%) were reintubated. The SBT was the most accurate of the three tests, with a sensitivity of 97% and specificity of 73% and a positive and negative predictive value for extubation success of 93% and 89% respectively. CONCLUSION: The SBT used just before extubation of infants <1250 g may reduce the number of extubation failures. Further studies are required to establish whether the SBT can be used as the primary determinant of an infant's readiness for extubation.

Nature and nurture: environmental influences on a genetic rat model of depression.

In this study, we sought to learn whether adverse events such as chronic restraint stress (CRS), or 'nurture' in the form of environmental enrichment (EE), could modify depression-like behavior and blood biomarker transcript levels in a genetic rat model of depression. The Wistar Kyoto More Immobile (WMI) is a genetic model of depression that aided in the identification of blood transcriptomic markers, which successfully distinguished adolescent and adult subjects with major depressive disorders from their matched no-disorder controls. Here, we followed the effects of CRS and EE in adult male WMIs and their genetically similar control strain, the Wistar Kyoto Less Immobile (WLI), that does not show depression-like behavior, by measuring the levels of these transcripts in the blood and hippocampus. In WLIs, increased depression-like behavior and transcriptomic changes were present in response to CRS, but in WMIs no behavioral or additive transcriptomic changes occurred. Environmental enrichment decreased both the inherent depression-like behavior in the WMIs and the behavioral difference between WMIs and WLIs, but did not reverse basal transcript level differences between the strains. The inverse behavioral change induced by CRS and EE in the WLIs did not result in parallel inverse expression changes of the transcriptomic markers, suggesting that these behavioral responses to the environment work via separate molecular pathways. In contrast, 'trait' transcriptomic markers with expression differences inherent and unchanging between the strains regardless of the environment suggest that in our model, environmental and genetic etiologies of depression work through independent molecular mechanisms.

Stimulation of hepatocellular proliferation by a serum factor from thioacetamide-treated rats.

Rats treated with thioacetamide undergo hepatocellular proliferation reminscent of liver regeneration following partial hepatectomy. 36 h after administration of 50 mg thioacetamide/kg body weight to rats, [3H]thymidine incorporation into hepatic DNA reaches a peak of 78-10(3) dpm/mg DNA compared to a control of 3.2-10(3) dpm/mg DNA. Serum obtained from 6 to 48 h after administration of thioacetamide to rats stimulated hepatic but not kidney DNA synthesis in mice and rats. Autoradiography revealed an increase in the incorporation of labelled thymidine into the nuclei of mouse hepatocytes. The mitotic index of the liver was also increased. The serum factor stimulating these changes in the liver was non-dialyzable and heat stable. These results indicate that thioacetamide induced liver injury results in a humoral factor which stimulates DNA synthesis in rat and mouse identified in the serum from partially hepatectomized rats.

The regulation of mouse liver ornithine decarboxylase by metabolites.

The enzyme ornithine decarboxylase (L-Ornithine carboxy-lyase, EC 4.1.1.17), has been partially purified from the livers of mice subjected to partial hepatectomy (6-8 h previously). Mouse liver ornithine decarboxylase requires pyridoxal phosphate, and dithiothreitol for maximal activity. The enzyme has a pH optimum of 7.3, it is inhibited in the presence of 0.3 M phosphate, glycine, Tricine and Tris. It shows no dependence on metal ions and is inhibited by high salt concentrations, particularly ammonium salts. The kinetics of the enzyme have been studied with putrescine (and analogs), spermidine and spermine, in the presence of both high and low levels of pyridoxal phosphate. High concentrations of pyridoxal phosphate inhibit the enzyme. The enzyme is also inhibited by low concentrations of putrescine (1 mM). As the concentration of putrescine increased to 10 mM, non-competitive inhibition was observed, this could be reversed by addition of higher levels of pyridoxal phosphate. Spermidine and spermine inhibit (noncompetitively) only at high concentrations (10 mM). Ornithine inhibits at high concentrations (2 mM). Spectral studies have shown that the observed kinetics of competitive inhibition at low concentrations of polyamine changing to noncompetitive inhibition at high polyamine concentrations are due to competition between enzyme and substrate (or inhibitor) for free (non-enzyme bound) pyridoxal phosphate. Noncompetitive inhibition arises through the formation of transient Schiff base complexes between amines and free pyridoxal phosphate. It also appears that the binding of substrate to the active site takes place through Schiff base formation with enzyme bound pyridoxal phosphate.

The behaviour of lung surfactant in electrolyte solutions.

Surface and electrokinetic properties of purified calf lung surfactant in various electrolyte solutions were determined. Surface properties were pH dependent in distilled water and the surfactant performed as a good lung surfactant only below pH 4. In more physiological media it was pH insensitive over the range 2-8.5. In distilled water at pH 6 its surface properties improved when NaCl was added up to 20 mM; above this concentration it had the surface properties required to stabilise alveoli. The surface properties of surfactant in distilled water were also restored by certain cations (Ca2+, Mg2+, Mn2+, Cd2+ and Ni2+) but not others (Na+, K+, La3+ and Fe3+) when added to an ionic strength of 5.6 mM. Cations that restored its surface activity also reduced the surface charge density on the surfactant particles. Aggregation of surfactant by various metal chlorides was studied by light scattering measurements and bore no relation to surface activity or the charge on the particles. Aggregation of surfactant particles by Ca2+, Cd2+ and Mn2+ was instantly reversed by addition of excess EGTA. The influence of electrolytes on the surface properties of lung surfactant is explained in terms of the electrostatic forces operating in the system.