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Managing scarce water resources has been central to the Murray–Darling Basin (MDB) regional development story. The article puts water into a broader context of key drivers in development in the MDB. In addition to water markets and water policy, key issues include climate change, the changing relative resilience and viability of urban centres, the role of government, the impact of technological change, underlying exogenously set commodity prices and exchange rates. All these factors have had a significant impact on development, some with little discussion but others, such as water, have been contested and bitterly fought over. The article also examines these drivers and how they might affect future development. [ABSTRACT FROM AUTHOR]

Australia experiences a wide range and increasing incidence of extreme hydrological events, including step changes in stream flows, extreme drought, bushfires followed by heavy rain, and storm events, which impact water availability and water quality. This article discusses the management of these events in the provision of water services in urban Australia. These events are being actively and effectively managed by large water service providers, covering around 80% of the population. But the experience for the remaining 20% is mixed, with smaller service providers often struggling to meet community expectations. This suggests a need for further governance reforms. [ABSTRACT FROM AUTHOR]

Sustainable Development Goal 6 seeks to address the increasing and unmet demand for water in many urban areas already struggling with inadequate water quality and supply. With climate change posing new threats, and both population growth and rural urban migration exacerbating existing issues, measures to reduce water demand sit alongside increasing water supply to address the problem. This article outlines Australia's experience in reducing water demand in urban areas, illustrating a range of measures that could contribute to meeting this goal. Key measures have a low fiscal cost, but require attention to governance. [ABSTRACT FROM AUTHOR]

Australia has husbanded its water resources to deliver laudable environmental and economic outcomes. But a close examination reveals some areas where decisions have resulted in poor outcomes and unsatisfactory use of public funds. This article examines some of these decisions through four case studies in which I suggest that current water infrastructure governance arrangements should be improved, through compelling politicians to place a greater focus on delivering value for money from infrastructure investments. Delivering higher-quality water services to remote indigenous communities should also be accorded a much higher priority. [ABSTRACT FROM AUTHOR]

A functional readout of the gut microbiome is necessary to enable precise control of the gut microbiome's functions, which support human health and prevent or minimize a wide range of chronic diseases. Stool metatranscriptomic analysis offers a comprehensive functional view of the gut microbiome, but despite its usefulness, it has rarely been used in clinical studies due to its complexity, cost, and bioinformatic challenges. This method has also received criticism due to potential intrasample variability, rapid changes, and RNA degradation. Here, we describe a robust and automated stool metatranscriptomic method, called Viomega, which was specifically developed for population-scale studies. Viomega includes sample collection, ambient temperature sample preservation, total RNA extraction, physical removal of ribosomal RNAs (rRNAs), preparation of directional Illumina libraries, Illumina sequencing, taxonomic classification based on a database of >110,000 microbial genomes, and quantitative microbial gene expression analysis using a database of ~100 million microbial genes. We applied this method to 10,000 human stool samples and performed several small-scale studies to demonstrate sample stability and consistency. In summary, Viomega is an inexpensive, high-throughput, automated, and accurate sample-to-result stool metatranscriptomic technology platform for large-scale studies and a wide range of applications. [ABSTRACT FROM AUTHOR]

This article discusses how key risks from extreme weather events might affect progress towards meeting Sustainable Development Goals 6 and 11 in cities in developing countries. It outlines the magnitude of the existing shortfall in safe water and sanitation services, and how climate change will exacerbate existing problems. It argues that the performance of many governments thus far has lacked urgency and purpose. Unless governments in particular become more committed, with redoubled effort, the goals are unlikely to be achieved. [ABSTRACT FROM AUTHOR]

The article examines the resilience of major Australian cities to extreme weather events. It reviews how and how well six of the largest Australian cities have responded to some recent water-related crises, covering droughts, floods and extreme storm events. It discusses examples of the preparedness for specific events, the immediate reaction to the event, the policy responses, and some of the more important challenges that remain. [ABSTRACT FROM AUTHOR]

This paper examines three actions by national and state governments – the role of the Cap, the Living Murray (TLM) and the National Action Plan for Water Security/Water for the Future, embodying the Murray–Darling Basin (MDB) Plan – in the Murray–Darling Basin over a 20-year period. The three actions sought to address declining environmental conditions through water policy reform. All were significant in their own way, but only the third offers the prospect of improving environmental outcomes. Taken together, the case studies illustrate that in real life and in complex, multilevelled policy-making, politics is central to water policy decision-making. [ABSTRACT FROM PUBLISHER]

Background: Highly cross-linked polyethylene (XLPE) was developed to address the problem of wear and osteolysis associated with metal-on-conventional ultra-high molecular weight polyethylene (UHMWPE) bearing surfaces. The purpose of this study was to compare in vivo wear rates and clinical and radiographic outcomes between XLPE and UHMWPE in a prospective double-blinded randomized controlled trial with a minimum of 10 years of follow-up.Methods: We randomized 122 patients to receive either a conventional UHMWPE liner (Enduron; DePuy) or an XLPE liner (Marathon; DePuy). Ninety-one patients were assessed clinically and radiographically at a minimum of 10 years (range, 10.08 to 12.17 years). Oxford Hip Scores and Short Form-12 Health Survey scores were collected. The radiographs were analyzed for osteolysis and for 2-dimensional (2-D), 3-dimensional (3-D), and volumetric wear using validated software.Results: All 122 patients were accounted for at the 10-year follow-up evaluation. Twelve patients had undergone revision surgery, 21 patients had died (1 of whom had previously undergone revision surgery), and 2 patients were unable to return for follow-up, leaving 91 patients available for clinical and radiographic evaluation. At a minimum of 10 years, 3-D wear rates were significantly lower (p < 0.001) in the XLPE group (mean, 0.03 mm/yr) than in the conventional UHMWPE group (mean, 0.27 mm/yr). The prevalence of osteolysis was also significantly lower in the XLPE group (38% versus 8%, p < 0.005), as was the revision rate (14.6% versus 1.9%, p = 0.012), with 10 of the 12 revisions being in the Enduron group. There was no significant difference between the clinical scores of the 2 groups.Conclusions: XLPE liners have significantly reduced wear and are associated with a greater implant survival rate at 10 years compared with conventional UHMWPE liners.Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

The article discusses a meeting on innovation in water policy making organized at the Institute of Water Policy, National University of Singapore (NUS). Also includes approach of New Environmental Governance (NEG) towards environmental policy, and social conditions for technological change, engagement processes, or management paradigms.

Urban water security in Australia’s major cities is now very high, reflecting in part recent policy interventions. Important indirect potable water reuse projects were completed but no direct potable reuse project was undertaken and none seems likely in the near term. Governments have much to learn from decisions to build very large desalination and recycling plants, particularly around timing and scale. Future water reuse decisions are likely to have a much greater commercial focus. Policies and regulations giving more flexibility to decentralized provision of water-related services could result in further growth of climate-resilient water resources and non-potable reuse. [ABSTRACT FROM PUBLISHER]

Rapid eye movement (REM) sleep shares many underlying mechanisms with wakefulness, to a much greater extent than does non-REM, especially those relating to feeding behaviours, appetite, curiosity, exploratory (locomotor) activities, as well as aspects of emotions, particularly ‘fear extinction’. REM is most evident in infancy, thereafter declining in what seems to be a dispensable manner that largely reciprocates increasing wakefulness. However, human adults retain more REM than do other mammals, where for us it is most abundant during our usual final REM period (fREMP) of the night, nearing wakefulness. The case is made that our REM is unusual, and that (i) fREMP retains this ‘dispensability’, acting as a proxy for wakefulness, able to be forfeited (without REM rebound) and substituted by physical activity (locomotion) when pressures of wakefulness increase; (ii) REM's atonia (inhibited motor output) may be a proxy for this locomotion; (iii) our nocturnal sleep typically develops into a physiological fast, especially during fREMP, which is also an appetite suppressant; (iv) REM may have ‘anti-obesity’ properties, and that the loss of fREMP may well enhance appetite and contribute to weight gain (‘overeating’) in habitually short sleepers; (v) as we also select foods for their hedonic (emotional) values, REM may be integral to developing food preferences and dislikes; and (vii) REM seems to have wider influences in regulating energy balance in terms of exercise ‘substitution’ and energy (body heat) retention. Avenues for further research are proposed, linking REM with feeding behaviours, including eating disorders, and effects of REM-suppressant medications. [ABSTRACT FROM AUTHOR]

The NF-κB essential modulator (NEMO) is the master regulator of NF-κB signaling, controlling the immune and nervous systems. NEMO affects the activity of IκB kinase-β (IKKβ), which relieves the inhibition of the NF-κB transcriptional regulation machinery. Despite major effort, there is only a very sparse, phenomenological understanding of how NEMO regulates IKKβ and shows specificity in its large range of molecular interactions. We explore the key molecular interactions of NEMO using a molecular biophysics approach, incorporating rapid-mixing stopped-flow, high-pressure, and CD spectroscopies. Our study demonstrates that NEMO has a significant degree of native structural disorder and that molecular flexibility and ligand-induced conformational change are at the heart of the molecular interactions of NEMO. We found that long chain length, unanchored, linear polyubiquitin drives NEMO activity, enhancing the affinity of NEMO for IKKβ and the kinase substrate IκBα and promoting membrane association. We present evidence that unanchored polyubiquitin achieves this regulation by inducing NEMO conformational change by an allosteric mechanism. We combine our quantitative findings to give a detailed molecular mechanistic model for the activity of NEMO, providing insight into the molecular mechanism of NEMO activity with broad implications for the biological role of free polyubiquitin. [ABSTRACT FROM AUTHOR]

The Murray-Darling Basin Plan is now in place, marking a further significant step in water policy development and water reform in Australia's Murray-Darling Basin (MDB). While it is an important planning and regulatory framework in its own right, and one that should further enhance the efficiency and effectiveness of water markets in the MDB, implementation and enforcement of the plan and continued action by governments, communities and stakeholders on key reform commitments are required to ensure much-needed improvement in economic, social and environmental sustainability. This article outlines seven watch points that will affect whether the desired outcomes are achieved. [ABSTRACT FROM AUTHOR]

Using a novel metabolomics approach the current study aimed to further characterize the functional attributes of alpha-synuclein that mediate its involvement in neurodegeneration. The metabolic profiles of alpha-synuclein knockout and A53T mutant overexpressing mouse brains were studied using proton nuclear magnetic resonance (H NMR) and liquid chromatography mass spectrometry (LC/MS). Gene deletion and mutation were both associated with significant alterations in brain energy metabolism when compared with their respective wild-type controls. These changes indicated deficiencies in key metabolic pathways, including the tricarboxylic acid cycle, and significant differences in the concentrations of small molecules including adenine nucleotides, taurine, NAD and glutamine. Analysis of the metabolic pathways affected by both knockout and mutation further indicated involvement of alpha-synuclein in metabolic pathways of energy metabolism, cellular redox status and glycerophospholipid metabolism. As such, our data identify novel functions of alpha-synuclein, validate previous reports describing its contribution to energy metabolism and lipid synthesis and support the use of metabolomic analysis as a fundamental technique in defining the effect of protein expression and mutation in genetic models. [ABSTRACT FROM AUTHOR]

This paper focuses on the use of three economic approaches to water management in Australia that can increase the efficiency of water use and water security, thus providing a fillip to sustainability and economic growth: the establishment of water markets and water pricing; government spending; and the adoption of legislation and economic regulations promoting the development of water markets. Australia is well down the reform path, but needs to complete implementation. Australia's challenge is relevant to many countries struggling with demand and supply water imbalances, and the consequential declining environmental outcomes in rural areas and persistent water shortages in urban areas. [ABSTRACT FROM PUBLISHER]

This paper focuses on Australian water reform in a climate change context over the period between mid-2006 and end 2011, with a particular focus on the Murray Darling Basin (MDB). In Australia, during this period, the potential impacts from climate change became more central to the policy debate, and the implementation of what can be said to be a large-scale climate change adaptation programme commenced. The paper outlines the policy framework adopted by the government of the day and then draws out some of the key issues for water management against this background, and the attendant increased uncertainty. [ABSTRACT FROM PUBLISHER]

Summary: This study demonstrates a critical role for N-methylation in cyclosporin biosynthesis and maintenance of the biologically active cyclosporin conformation. The structural requirements for the AdoMet binding to CySyn were defined. N-methylation of specific amide positions in the cyclosporin backbone is critical for the complete assembly and cyclization of the cyclosporin peptide. A maximum of two desmethyl positions is tolerated before peptide assembly stalls. Subinhibitory concentrations of AdoMet analogs directed peptide assembly towards cyclosporins with less than seven N-methylated amide bonds. Molecular modeling and nuclear magnetic resonance analyses indicate that N-methylation of specific amide bond positions in the cyclosporin backbone is mandatory for the formation of a product-like conformation and recognition by the acceptor site of the downstream peptide bond forming C-domain. [Copyright &y& Elsevier]

Though extended night-time sleep mostly reduces the ‘afternoon dip’, little is known about evening benefits to alertness, or about comparisons with an afternoon nap or caffeine. Twenty healthy carefully screened adults, normal waking alertness levels, underwent four counterbalanced conditions: usual night sleep; night sleep extended<90 min (usual bed-time); up to 20 min afternoon nap; and 150 mg afternoon caffeine (versus decaffeinated coffee). Sleepiness was measured by afternoon and evening multiple sleep latency test (MSLTs), longer psychomotor vigilance test (PVT) sessions and a subjective sleepiness scale. Sleep was extended by average of 74 min, and all participants could nap 15–20 min. Sleep extension had little effect on PVT determined modest levels of morning sleepiness. Afternoon and evening MSLTs showed all active treatments significantly reduced the ‘dip’, with nap most effective until mid-evening; next effective was caffeine, then extension. Late evening sleepiness and subsequent sleep did not differ between conditions. Arguably, participants may have experienced some ‘sleep debt’, given they extended sleep and reflected some sleepiness within settings sensitive to sleepiness. Nevertheless, extended sleep seemed largely superfluous and inefficient in reducing modest levels of sleepiness when compared with a timely nap, and even caffeine. Sleep, such as food and fluid intakes, can be taken to excess of real biological needs, and for many healthy adults, there is a level of modest daytime sleepiness, only unmasked by very sensitive laboratory measures. It may reflect a requirement for more sleep or simply be within the bounds of normal acceptability. [ABSTRACT FROM AUTHOR]

Caffeine is the most widely used stimulant to counteract sleepiness. However, little is known about any placebo effect of caffeine in sleepy people and the effect of suggestibility. Over a 95 min test period, and in a counterbalanced design, 16 young healthy adults underwent 3 × 30 min sessions at the psychomotor vigilance test (PVT), during an early afternoon ‘dip’ enhanced by a prior night's sleep restriction (5 h). On both occasions they were given a cup of a decaffeinated coffee; once when the participant was verbally primed to suggest the coffee was caffeinated (Placebo) and on the other under neutral priming (Control). There were significantly fewer lapses and shorter reaction times following Placebo, for the initial two 30 min sessions, indicating that suggestion about consuming caffeine was effective in improving performance in moderately sleepy people. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The sleep literature increasingly points to an apparent chronic sleep debt in the general population. We investigated this by examining perceived shortfalls in daily sleep, using more indirect questioning methods. Methods: To determine perceived sleep deficits, 10,810 adults completed a simple questionnaire, which avoided leading questions and provided information on sleep length, daytime sleepiness, desired sleep length, a choice of attractive daytime activities in a “free hour”, and “stressful lifestyle”. From this we assessed whether deficits were reflected by increased daytime sleepiness or opting for more sleep when given attractive waking alternatives. Respondents were divided according to age and sex. Results: Half of men and women seemed to desire more sleep, but this apparent sleep deficit was not correlated with daytime sleepiness, for any age or sex group. Irrespective of deficit, few people opted for sleep when given waking alternatives. “Stressful lifestyle” was independently related to this sleep deficit. Conclusion: Desiring more sleep may also be synonymous with a need for more “time out”, as sleep deficit was unrelated to daytime sleepiness but rather related to “stressful lifestyle.” Extra sleep may not be the only anodyne for sleep deficit. [Copyright &y& Elsevier]

Abstract: We have determined the structure of the reduced form of the DsbA oxidoreductase from Vibrio cholerae. The reduced structure shows a high level of similarity to the crystal structure of the oxidized form and is typical of this class of enzyme containing a thioredoxin domain with an inserted α-helical domain. Proteolytic and thermal stability measurements show that the reduced form of DsbA is considerably more stable than the oxidized form. NMR relaxation data have been collected and analyzed using a model-free approach to probe the dynamics of the reduced and oxidized states of DsbA. Akaike''s information criteria have been applied both in the selection of the model-free models and the diffusion tensors that describe the global motions of each redox form. Analysis of the dynamics reveals that the oxidized protein shows increased disorder on the pico- to nanosecond and micro- to millisecond timescale. Many significant changes in dynamics are located either close to the active site or at the insertion points between the domains. In addition, analysis of the diffusion data shows there is a clear difference in the degree of interdomain movement between oxidized and reduced DsbA with the oxidized form being the more rigid. Principal components analysis has been employed to indicate possible concerted movements in the DsbA structure, which suggests that the modeled interdomain motions affect the catalytic cleft of the enzyme. Taken together, these data provide compelling evidence of a role for dynamics in the catalytic cycle of DsbA. [Copyright &y& Elsevier]

Summary: Transcellular diffusion across the absorptive epithelial cells (enterocytes) of the small intestine is the main route of absorption for most orally administered drugs. The process by which lipophilic compounds transverse the aqueous environment of the cytoplasm, however, remains poorly defined. In the present study, we have identified a structurally diverse group of lipophilic drugs that display low micromolar binding affinities for a cytosolic lipid-binding protein—intestinal fatty acid-binding protein (I-FABP). Binding to I-FABP significantly enhanced the transport of lipophilic drug molecules across a model membrane, and the degree of transport enhancement was related to both drug lipophilicity and I-FABP binding affinity. These data suggest that intracellular lipid-binding proteins such as I-FABP may enhance the membrane transport of lipophilic xenobiotics and facilitate drug access to the enterocyte cytoplasm and cytoplasmic organelles. [Copyright &y& Elsevier]

Following night-time sleep restriction, afternoon driving performance during the bi-circadian surge in afternoon sleepiness is markedly worsened by blood alcohol concentrations (BACs) well under most national driving limits. This study assessed how driving with this same sleep restriction and BACs (av 40 mg and 28 mg alcohol/100 ml blood at the beginning and end of drive, respectively) respond during the evening circadian rise in alertness. In a 2 × 2 (alcohol versus control drink [double blind] × normal night sleep versus sleep restricted), repeated-measures design, eight healthy young men drove for 2 h from 18:00 h, in a real-car simulator, on a monotonous, simulated highway. Driving impairment (lane drifting), subjective sleepiness and EEG measures of sleepiness were recorded. While sleep restriction alone produced significant impairments to evening driving and subjective sleepiness, alcohol alone did not. However, alcohol combined with sleep restriction significantly worsened all indices, although, this was less than that found for afternoon driving with identical interventions. Whereas low BACs may not affect driving in normally alert drivers in the early evening, the addition of moderate sleep restriction still produces a dangerous combination. Probably, there is no ‘safe’ level of alcohol intake for otherwise sleepy drivers, at any time of the day. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Others have shown that frontally dominant EEG activity of around 7–8 Hz is linked to ongoing cognitive performance. Interestingly, we have found that this EEG activity is particularly evident during the relatively artefact-free period following “lights out” at bedtime when people report “thinking” when lying relaxed in their own beds prior to the appearance of EEG-determined sleepiness. Here, we explore the extent to which this localised activity is indicative of ‘trait’ performance on left frontal neuropsychological tasks, as well as with less localised, more general tasks. Twelve right-handed young adults (mean age: 21.3 years) and 12 right-handed older adults (mean age: 67.2 years) underwent (i) morning, laboratory-based, waking EEGs comprising (eyes closed) contrived thinking tasks, and (ii) a home-based wake EEG at bedtime. EEGs divided the cortex into the four comparable quadrants: Fp1–F3; Fp2–F4; O1–P3; and O2–P4. From a wide frequency band of 3–10 Hz analysed in 1-Hz bins, only 7–8 Hz was associated with the neuropsychological performance (nonverbal planning, verbal fluency) for both younger and older participants. This was most evident during relaxed waking after ‘lights out,’ and from the left frontal EEG. Such associations were not apparent for the other EEG channels or for the nonspecific tasks. Laboratory-based daytime, frontal EEG recordings are problematic because of eye movement artefact and when participants are not fully relaxed. In contrast, the nighttime data are almost artefact-free and from fully relaxed participants. This particular EEG is useful for assessing cortically localised behaviour and indicates that a more traditional approach of using large bandwidths (e.g., the whole of “alpha” or “theta” ranges) may mask subfrequencies of functional importance. [Copyright &y& Elsevier]

The extent to which sleepy drivers are aware of sleepiness has implications for the prevention of sleep-related crashes, especially for drivers younger than 30 years old who are most at risk. Using a real car interactive simulator, we report on EEG, subjective sleepiness, and lane drifting (sleepiness-related driving impairment) from 38 sleep-restricted, healthy young adults undergoing nontreatment control conditions from three (unpublished) investigations using the same experimental protocols for assessing various drinks intended to alleviate sleepiness. Participants drove 2 h during midafternoon under monotonous conditions. For all studies, subjective sleepiness and EEG activity indicative of sleepiness were highly correlated, with both changing concomitantly, along with lane drifting. Drivers had knowledge of their physiological sleepiness. There were indications that sugar content of these drinks may additionally affect sleepiness. [ABSTRACT FROM AUTHOR]

Abstract Low frequency (<1 Hz) delta EEG in sleep is of increasing interest as it indicates cortical reorganization, especially in the prefrontal cortex (PFC). Other research shows that delta power in sleep is positively linked to waking cerebral metabolic rate. Such findings suggest that<1 Hz activity may reflect waking performance at neuropsychological tests specific to the PFC. We investigated this unexplored area. Sleep EEGs (Fp1 –F3 , Fp2 –F4 , O1 –P3 , O2 –P4 ) were recorded in 24 healthy 61–75-year-olds. We found significant associations between 0.5–1.0 Hz power from the left frontal EEG channel, in the first non-REM period, and performance at tasks more specific to the left PFC (e.g., nonverbal planning and verbal fluency). This association was absent from the posterior channels. Neither age nor response times were confounding factors. This potential sleep EEG marker for PFC neuropsychological function in healthy, older people also points to further uses of the sleep EEG in understanding the role of sleep. [ABSTRACT FROM AUTHOR]

Investigates the effectiveness of 200 milligrams of caffeine in preventing early morning driver sleepiness. Prevalence of sleep-related vehicle accidents in the early morning; Reduction in driving incidents in the first 30 minutes and subjective sleepiness in the first hour after caffeine intake.

Historical evidence suggests that sleep deprivation affects temporal memory, but this has not been studied systematically. We explored the effects of 36 hr of sleep deprivation on a neuropsychological test of temporal memory. To promote optimal performance, the test was short, novel, and interesting, and caffeine was used to reduce ''sleepiness''. A total of 40 young adults were randomized into four groups: control + caffeine (Cc), control + placebo (Cp), sleep deprived + caffeine (SDc), and sleep deprived + placebo (SDp). Controls slept normally. Caffeine (350 mg) or placebo were given just prior to testing. The task comprised colour photographs of unknown faces and had two components: recognition memory (distinction between previously presented and novel faces), and recency discrimination (temporal memory), when a previously shown face was presented. An interpolated task, self-ordered pointing, acted as a distraction. Caffeine had no effects within control conditions, but significantly reduced subjective sleepiness in SDc. Recognition was unaffected by sleep deprivation, whereas for recency, sleep deprivation groups scored significantly lower than controls. There was no significant improvement of recency with caffeine in the SDc group. Both sleep deprivation groups had poorer insight into their performance with recency. Self-ordered pointing remained unchanged. In conclusion, sleep deprivation impairs temporal memory (i.e. recency) despite other conditions promoting optimal performance. [ABSTRACT FROM AUTHOR]

Presents high-resolution nuclear magnetic resonance (NMR) spectral data for neuropeptide K in trifluoroethanol-d3. Estimation of distance and dihedral constraints; Spectral assignment; Secondary structural analysis; Generation of three-dimensional structures.

Previous research has shown that caffeine and a<15-min nap effectively and separately reduce sleepiness in drivers for 1 hr. in the present study, we examined in 12 sleepy individuals the treatments combined, taken during a 30-min break, prior to a longer (2 hr) continuous monotonous afternoon drive in a car simulator. Nonnap comparisons were 200 mg caffeine only and placebo. For placebo, driving incidents, subjective and electroencephalographic measures of sleepiness all reflected a mid-afternoon peak. This peek was significantly reduced by caffeine and eliminated by the combined treatment, which reduced incidents to 9% of placebo levels versus 34% of placebo levels for caffeine alone. Naps comprising "nonsleep dozing" were still effective. [ABSTRACT FROM AUTHOR]

Most cognitive tests administered during sleep loss are well rehearsed to remove practice effects. This can introduce tedium and a loss of novelty, which may be the key to the test's subsequent sensitivity to sleep loss, and why it may need only a few minutes administration before sleep loss effects are apparent. There is little evidence to show that any of these tests are actually affected by sleep loss if given de novo, without practice, but using a non-sleep deprived control group. Although the sleep deprivation literature advocates that short, novel and stimulating tests would not be expected to be sensitive to sleep loss, recent sleep loss findings using neuropsychological tests focussing on the prefrontal cortex, indicate that such tests may challenge this maxim. Twenty healthy young adults were randomly assigned to two groups: nil sleep deprivation (control), and 36h continuous sleep deprivation (SD). Two, novel, interesting and short (6 min) language tests, known (by brain imaging) to have predominantly a PFC focus, were given, once, towards the end of SD: (i) the Haylings test – which measures the capacity to inhibit strong associations in favour of novel responses, and (ii) a variant of the word fluency test – innovation in a verb-to-noun association. Subjects were exhorted to do their best. Compared with control subjects both tasks were significantly impaired by SD. As a check on the effects on the Haylings test, a repeat study was undertaken with 30 more subjects randomly divided as before. The outcome was similar. Linguistically, sleep loss appears to interfere with novel responses and the ability to suppress routine answers. [ABSTRACT FROM AUTHOR]

This study explored the effects of soil acidity on vegetative growth and germination of wheat. Five wheat cultivars, two American ('Triumph 64,' 'Wakefield') and three Russian ('Mironovskaya 808,' 'Bezostaya,' and 'Inna'), were investigated for germination, growth, and dry matter accumulation under controlled conditions to eliminate the effect of environmental factors such as temperature, light, and precipitation. Soils with similar texture and various pH values were chosen for experiments. Soil was sampled from pastures where future wheat production may occur. Dry Matter Accumulation (DMA), percentage of seed germination, and height of seedlings were strongly reduced by acidic soils. The percent of wheat seeds germination (pH 4.99) for American cultivars Wakefield and Triumph 64 was 80.7 and 71.3 respectively. The percent of germination for Russian varieties was 74.0 (Mironovskaya 808), 75.6 (Bezostaya), and 77.3 (Inna) at pH 4.99. The height of seedlings for tested cultivars was always less on acidic soil (pH 4.99). Developing a wider range of wheat cultivars tested for acidic soils of southeastern Oklahoma would make a significant contribution to agriculture. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: Laboratory-based studies show that drowsiness increases the propensity to become distracted. As this phenomenon has not been investigated in drowsy drivers, we underwent a pilot study under realistic monotonous driving conditions to see if distraction was more apparent when drowsy; if so, how does it affect driving performance? Methods: A repeated measures counterbalanced design whereby participants drove for two hours in a fully interactive car simulator during the bi circadian afternoon drive, after a night of either normal (baseline) or restricted sleep to five hours (sleep restriction). Videos of drivers’ faces were analysed blind for short (<3s) and long (>3s) distractions, in which drivers took their eyes off the road ahead. These results were compared with the likelihood of simultaneous lane-drifting incidents, when at least two wheels left the driving lane. Results: More distractions occurred after restricted sleep (p <0.005) for both short and long distractions (p <0.05). There was an overall significant (p <0.02) positive correlation between distractions and driving incidents for both conditions but with significantly more distraction-related incidents after sleep restriction (p <0.03). Conclusions: Following restricted sleep, drivers had an increased propensity to become distracted, which was associated with an increased likelihood of poor driving performance as evidenced by the car leaving the driving lane. [Copyright &y& Elsevier]

The article focuses on reduced false positives in autism screening via digital biomarkers inferred from deep comorbidity patterns. Topics include the develop digital biomarkers for autism spectrum disorder (ASD) has computed from patterns of past medical encounters, and the leverage uncharted ASD comorbidities, with no requirement of additional blood work, or procedures, to estimate the autism comorbid risk score.

The preparation of polymer thin films or surface coatings that display a static water contact angle >95° often requires hierarchical roughness features or surface functionalization steps. In addition, inherently hydrophobic polymers such as fluoropolymers often possess low glass transition temperatures, reducing their application where thermal stability is required. Herein, the first reported synthesis of 2,3,4,5,6-pentafluorostyrene (PFS) and N-phenylmaleimide (NMI) via reversible addition-fragmentation chain-transfer (RAFT)-mediated free radical polymerization is presented, with a view towards the preparation of inherently hydrophobic polymers with a high glass transition temperature. A suite of copolymers were prepared and characterized, and owing to the inherent rigidity of the maleimide group in the polymer backbone and π-π interactions between adjacent PFS and NMI groups, very high glass transition temperatures were achieved (up to 1808C). The copolymerization of N-pentafluorophenylmaleimide was also performed, also resulting in extremely high glass transition temperature copolymers; however, these polymers did not exhibit characteristics of being under RAFT control. Thin films of PFS-NMI copolymers exhibited a static contact angle >100°, essentially independent of the amount of NMI incorporated into the polymer. [ABSTRACT FROM AUTHOR]

Focuses on an economic and trade analysis perspective of the impact of governments use of risk-benefit analysis in making decisions about the regulatory approval and labeling policies for food products produced with the use of agricultural biotechnology. Change in consumer demand for labeling of genetically modified food; Approval of a measure requiring companies to label genetically modified food by European Union.

Background: Enoxaparin, a low-molecular-weight heparin, is known to possess anti-inflammatory properties. However, its clinical exploitation as an anti-inflammatory agent is hampered by its anticoagulant effect and the associated risk of bleeding. Objective: The aim of the current study was to examine the ability of non-anticoagulant fractions of enoxaparin to inhibit the release of key inflammatory cytokines in primed peripheral blood mononuclear cells derived from allergic mild asthmatics. Methods: Peripheral blood mononuclear cells from allergic asthmatics were activated with phytohaemag glutinin (PHA), concanavalin-A (ConA) or phorbol 12-myristate 13-acetate (PMA) in the presence or absence of enoxaparin fractions before cytokine levels were quantified using specific cytokine bead arrays. Together with nuclear magnetic resonance analysis,time-dependent and target-specific effects of enoxaparin fractions were used to elucidate structural determinants for their anti-inflammatory effect and gain mechanistic insights into their anti-inflammatory activity. Results: Two non-anticoagulant fractions of enoxaparin were identified that significantly inhibited T-cell activation. A disaccharide fraction of enoxaparin inhibited the release of IL-4, IL-5, IL-13 and TNF-α by more than 57% while a tetrasaccharide fraction was found to inhibit the release of tested cytokines by more than 68%. Our data suggest that the observed response is likely to be due to an interaction of 6-O-sulfated tetrasaccharide with cellular receptor(s). Conclusion and Clinical Relevance: The two identified anti-inflammatory fractions lacked anticoagulant activity and are therefore not associated with risk of bleeding. The findings highlight the potential therapeutic use of enoxaparin-derived fractions, in particular tetrasaccharide, in patients with chronic inflammatory disorders. [ABSTRACT FROM AUTHOR]

Background: Enoxaparin, a mixture of anticoagulant and non-anticoagulant fractions, is widely used as an anticoagulant agent. However, it is also reported to possess anti-inflammatory properties. Our study indicated that enoxaparin inhibits the release of IL-6 and IL-8 from A549 pulmonary epithelial cells. Their release causes extensive lung tissue damage. The use of enoxaparin as an anti-inflammatory agent is hampered due to the risk of bleeding associated with its anticoagulant fractions. Therefore, we aimed to identify the fraction responsible for the observed anti-inflammatory effect of enoxaparin and to determine the relationship between its structure and biological activities. Methods: A549 pulmonary epithelial cells were pre-treated in the presence of enoxaparin and its fractions. The levels of IL-6 and IL-8 released from the trypsin-stimulated cells were measured by ELISA. The anticoagulant activity of the fraction responsible for the effect of enoxaparin was determined using an anti-factor-Xa assay. The fraction was structurally characterised using nuclear magnetic resonance. The fraction was 2-O, 6-O or N-desulfated to determine the position of sulfate groups required for the inhibition of interleukins. High-performance size-exclusion chromatography was performed to rule out that the observed effect was due to the interaction between the fraction and trypsin or interleukins. Results: Enoxaparin (60μg/mL) inhibited the release of IL-6 and IL-8 by >30%. The fraction responsible for this effect of enoxaparin was found to be a disaccharide composed of α-L-iduronic-acid and α-D-glucosamine-6-sulfate. It (15μg/mL) inhibited the release of interleukins by >70%. The 6-O sulphate groups were responsible for its anti-inflammatory effect. The fraction did not bind to trypsin or interleukins, suggesting the effect was not due to an artefact of the experimental model. Conclusion: The identified disaccharide has no anticoagulant activity and therefore eliminates the risk of bleeding associated with enoxaparin. Future in-vivo studies should be designed to validate findings of the current study. [ABSTRACT FROM AUTHOR]

Indole-3-pyruvic acid (IPyA) isanimportant naturally occurring biosynthetic intermediate whose quantitation by standard analytic techniques can be complicated as it can exist as either the keto or enol tautomer. Here, we present a detailed analysis of the tautomerism of IPyA and provide further evidence that the two tautomers of IPyA may be readily separated by ultra high-performance liquid chromatography and that the relative proportions of each form may be controlled using temperature and pH. [ABSTRACT FROM AUTHOR]

Abstract: Young men figure prominently in sleep-related road crashes. Non-driving studies show them to be particularly vulnerable to sleep loss, compared with older men. We assessed the effect of a normal night''s sleep vs. prior sleep restricted to 5h, in a counterbalanced design, on prolonged (2h) afternoon simulated driving in 20 younger (av. 23y) and 19 older (av. 67y) healthy men. Driving was monitored for sleepiness related lane deviations, EEGs were recorded continuously and subjective ratings of sleepiness taken every 200s. Following normal sleep there were no differences between groups for any measure. After sleep restriction younger drivers showed significantly more sleepiness-related deviations and greater 4–11Hz EEG power, indicative of sleepiness. There was a near significant increase in subjective sleepiness. Correlations between the EEG and subjective measures were highly significant for both groups, indicating good self-insight into increasing sleepiness. We confirm the greater vulnerability of younger drivers to sleep loss under prolonged afternoon driving. [Copyright &y& Elsevier]

Abstract: Objectives: To examine the effects on monotonous driving of normal sleep versus one night of sleep restriction in continuous positive airway pressure (CPAP) treated obstructive sleep apnoea (OSA) patients compared with age matched healthy controls. Methods: Nineteen CPAP treated compliant male OSA patients (OSA-treated patients (OPs)), aged 50–75years, and 20 healthy age-matched controls underwent both a normal night’s sleep and sleep restriction to 5h (OPs remained on CPAP) in a counterbalanced design. All participants completed a 2h afternoon monotonous drive in a realistic car simulator. Driving was monitored for sleepiness-related minor and major lane deviations, with ‘safe’ driving time being total time driven prior to first major lane deviation. EEGs were recorded continuously, and subjective sleepiness ratings were taken at regular intervals throughout the drive. Results: After a normal night’s sleep, OPs and controls did not differ in terms of driving performance or in their ability to assess the levels of their own sleepiness, with both groups driving ‘safely’ for approximately 90min. However, after sleep restriction, OPs had a significantly shorter (65min) safe driving time and had to apply more compensatory effort to maintain their alertness compared with controls. They also underestimated the enhanced sleepiness. Nevertheless, apart from this caveat, there were generally close associations between subjective sleepiness, likelihood of a major lane deviation and EEG changes indicative of sleepiness. Conclusions: With a normal night’s sleep, effectively treated older men with OSA drive as safely as healthy men of the same age. However, after restricted sleep, driving impairment is worse than that of controls. This suggests that, although successful CPAP treatment can alleviate potential detrimental effects of OSA on monotonous driving following normal sleep, these patients remain more vulnerable to sleep restriction. [Copyright &y& Elsevier]

Protective effects of estrogen against experimental stroke and neuronal ischemic insult are well-documented, but it is not known whether estrogen prevents ischemic injury to brain endothelium, a key component of the neurovascular unit. Increasing evidence indicates that estrogen exerts protective effects through mitochondrial mechanisms. We previously found 17β-estradiol (E2) to improve mitochondrial efficiency and reduce mitochondrial superoxide in brain blood vessels and endothelial cells. Thus we hypothesized E2 will preserve mitochondrial function and protect brain endothelial cells against ischemic damage. To test this, an in vitro ischemic model, oxygen-glucose deprivation (OGD)/reperfusion, was applied to immortalized mouse brain endothelial cells (bEnd.3). OGD/reperfusion-induced cell death was prevented by long-term (24, 48 h), but not short-term (0.5, 12 h), pretreatment with 10 nmol/L E2. Protective effects of E2 on endothelial cell viability were mimicked by an estrogen-receptor (ER) agonist selective for ERα (PPT), but not by one selective for ERβ (DPN). In addition, E2 significantly decreased mitochondrial superoxide and preserved mitochondrial membrane potential and ATP levels in early stages of OGD/reperfusion. All of the E2 effects were blocked by the ER antagonist, ICI-182,780. These findings indicate that E2 can preserve endothelial mitochondrial function and provide protection against ischemic injury through ER-mediated mechanisms. [ABSTRACT FROM AUTHOR]

Oxidative protein folding in Gram-negative bacteria results in the formation of disulfide bonds between pairs of cysteine residues. This is a multistep process in which the dithiol-disulfide oxidoreductase enzyme, DsbA, plays a central role. The structure of DsbA comprises an all helical domain of unknown function and a thioredoxin domain, where active site cysteines shuttle between an oxidized, substrate-bound, reduced form and a DsbB-bound form, where DsbB is a membrane protein that reoxidizes DsbA. Most DsbA enzymes interact with a wide variety of reduced substrates and show little specificity. However, a number of DsbA enzymes have now been identified that have narrow substrate repertoires and appear to interact specifically with a smaller number of substrates. The transient nature of the DsbA-substrate complex has hampered our understanding of the factors that govern the interaction of DsbA enzymes with their substrates. Here we report the crystal structure of a complex between Escherichia coli DsbA and a peptide with a sequence derived from a substrate. The binding site identified in the DsbA-peptide complex was distinct from that observed for DsbB in the DsbA-DsbB complex. The structure revealed details of the DsbA-peptide interaction and suggested a mechanism by which DsbA can simultaneously show broad specificity for substrates yet exhibit specificity for DsbB. This mode of binding was supported by solution nuclear magnetic resonance data as well as functional data, which demonstrated that the substrate specificity of DsbA could be modified via changes at the binding interface identified in the structure of the complex. [ABSTRACT FROM AUTHOR]

Abstract: Seemingly, many healthy adults have accrued a sleep debt, as determined by findings based on the multiple sleep latency test (MSLT). However, our recent, extensive survey found self-reported sleep deficit was not linked to daytime sleepiness determined by the Epworth sleepiness scale (ESS). Here, we report on the link between self-reported sleep deficit and gold standard measures of sleepiness: MSLT, Psychomotor vigilance test (PVT) and Karolinska Sleepiness Scale (KSS). Habitual sleep time in forty-three participants, from using a week long sleep diary and actiwatch data, compared with self-ratings of how much sleep they needed, provided estimates of apparent sleep deficit or otherwise. They were split into categories: ‘sleep deficit’ (Av. −47 min), ‘sleep plus’ (Av. 47 min) or ‘neutral’ (Av. 0±15 min), depicting perceived shortfall (or excess) sleep. Although the deficit group desired to sleep longer than the other groups, they actually obtained similar habitual nightly sleep as the neutral group, but less than the sleep plus group. ‘Survival curves’ based on those falling asleep during the MSLT showed no difference between the groups. Neither was there any difference between the groups for the PVT, KSS, or ESS. Here, factors other than sleepiness seem to influence self-perceived sleep deficits. [Copyright &y& Elsevier]