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With bipartisan demand for reforming what the National Law Review has described as a 'lengthy, expensive, and perilous environmental review process,' is Congress set to break a logjam that has [...]

THE Environmental Protection Agency and the Federal Trade Commission are collecting public comments on proposals for voluntary efforts to cut waste in the environment from single-use bags, wraps, bottles, and [...]

Site-specific covalent conjugation offers a powerful tool to identify and understand protein–protein interactions. In this study, we discover that sulfur fluoride exchange (SuFEx) warheads effectively crosslink the Escherichia coliacyl carrier protein (AcpP) with its partner BioF, a key pyridoxal 5′-phosphate (PLP)-dependent enzyme in the early steps of biotin biosynthesis by targeting a tyrosine residue proximal to the active site. We identify the site of crosslink by MS/MS analysis of the peptide originating from both partners. We further evaluate the BioF–AcpP interface through protein crystallography and mutational studies. Among the AcpP-interacting BioF surface residues, three critical arginine residues appear to be involved in AcpP recognition so that pimeloyl-AcpP can serve as the acyl donor for PLP-mediated catalysis. These findings validate an evolutionary gain-of-function for BioF, allowing the organism to build biotin directly from fatty acid biosynthesis through surface modifications selective for salt bridge formation with acidic AcpP residues.

The gut microbiota is increasingly recognised as a key player in influencing human health and changes in the gut microbiota have been strongly linked with many non-communicable conditions in humans such as type 2 diabetes, obesity and cardiovascular disease. However, characterising the molecular mechanisms that underpin these associations remains an important challenge for researchers. The gut microbiota is a complex microbial community that acts as a metabolic interface to transform ingested food (and other xenobiotics) into metabolites that are detected in the host faeces, urine and blood. Many of these metabolites are only produced by microbes and there is accumulating evidence to suggest that these microbe-specific metabolites do act as effectors to influence human physiology. For example, the gut microbiota can digest dietary complex polysaccharides (such as fibre) into short-chain fatty acids (SCFA) such as acetate, propionate and butyrate that have a pervasive role in host physiology from nutrition to immune function. In this review we will outline our current understanding of the role of some key microbial metabolites, such as SCFA, indole and bile acids, in human health. Whilst many studies linking microbial metabolites with human health are correlative we will try to highlight examples where genetic evidence is available to support a specific role for a microbial metabolite in host health and well-being.

ABSTRACTThe Banister impulse-response (IR) model was designed to predict an athlete’s performance ability from their past training. Despite its long history, the model’s usefulness remains limited due to difficulties in obtaining precise parameter estimates and performance predictions. To help address these challenges, we developed a Bayesian implementation of the IR model, which formalises the combined use of prior knowledge and data. We report the following methodological contributions: 1) we reformulated the model to facilitate the specification of informative priors, 2) we derived the IR model in Bayesian terms, and 3) we developed a method that enabled the JAGS software to be used while enforcing parameter constraints. To demonstrate proof-of-principle, we applied the model to the data of a national-class middle-distance runner. We specified the priors from published values of IR model parameters, followed by estimating the posterior distributions from the priors and the athlete’s data. The Bayesian approach led to more precise and plausible parameter estimates than nonlinear least squares. We conclude that the Bayesian implementation of the IR model shows promise in addressing a primary challenge to its usefulness for athlete monitoring.

Background: Impaired driving is a public health issue, yet little is known concerning the prevalence of substance use in drivers involved in off-road vehicle crashes. The goal of the present study was to describe the demographics and prevalence of alcohol and drug use in drivers of off-road vehicle crashes. Methods: In this observational substudy, we collected clinical and toxicological data on all moderately or severely injured off-road vehicle drivers who had blood samples obtained within 6 h of the crash. Clinical data were extracted from patients’ medical charts and toxicology analyses were performed for blood alcohol, cannabinoids, recreational drugs, and impairing medications. Results: Thirty-three injured drivers met the inclusion criteria. The mean age was 37.6 ± 13.4 years and 79% were male. Blood alcohol was detected in 58% of drivers and 42% of these were above the legal limit. Tetrahydrocannabinol was positive in 12% of drivers, and 18% were positive for recreational drugs. Opiates were detected in 21% of drivers. Overall, 85% were positive for at least one substance and 39% tested positive for multiple substances. Conclusion: This study presents the first evidence of alcohol and drug use in off-road vehicle drivers after cannabis legalization in Canada. Our results show that over half of drivers in off-road vehicle crashes test positive for alcohol and 30% tested positive for THC, cocaine, or amphetamines. Opiates are also commonly detected in off-road vehicle drivers. Emergency department (ED) visits resulting from drug driving of off-road vehicles serve as an opportunity for screening, initiating treatment, and connecting patients to interventions for substance use disorders.

The article discusses the topic of bicycle lights and their effectiveness in ensuring visibility and safety for cyclists. Different perspectives are presented, including those of long-distance tandem cycle tourers and motorists. The cyclists argue that disruptive lights with irregular patterns and high brightness are the best, while motorists express concerns about the intensity and direction of the lights. The article also touches on the importance of reflective ankle bands and clothing for cyclists. The second part of the article briefly explains the science behind the loud noise produced when cracking knuckles. [Extracted from the article]

Will Lloyd's piece on Charles (Cover Story, 5 May) is an eye-opener--both the Transylvanian follies and the influence of the neo-Romantic writer Kathleen Raine, which explains much about the regressive [...]

FOR developers, farmers, and other interests, the Trump administration's 2020 rule defining 'waters of the United States' subject to federal permitting requirements was just fine. That's understandable. Under that regulation, [...]

DURING the Biden presidency, Congress has appropriated billions of dollars for EPA to award as grants supporting clean water, environmental justice, climate action, and other priorities. While many are elated [...]

3′-O-β-Glucosyl-4′,5′-didehydro-5′-deoxyadenosine 13is identified as a natural product of Streptomyces calvusand Streptomyces virens. It is also generated in vitroby direct β-glucosylation of 4′,5′-didehydro-5′-deoxyadenosine 12with the enzyme NucGT. The intact incorporation of oxygen-18 and deuterium isotopes from (±)[1-18O,1-2H2]-glycerol 14into C-5′ of nucleocidin 1and its related metabolites precludes 3′-O-β-glucosyl-4′,5′-didehydro-5′-deoxyadenosine 13as a biosynthetic precursor to nucleocidin 1.

ARE WE 'on a highway to climate hell with our foot on the accelerator,' as the UN secretary-general declared last November at COP27, the annual meeting of the parties to [...]

If the laser and tube were about 15 million km from the event horizon and the low-gravity observer were 200 million km away, the low-gravity observer would see it takes about 15 minutes for the laser to go around. High speed We know time slows down as gravity increases, so is the speed of light in high gravity different from its speed in low gravity? The low-gravity observer can calculate that the speed of light in that warped four-dimensional high-gravity space-time is the same as in their four-dimensional low-gravity space-time when correcting for that warping. [Extracted from the article]

IN signing the Inflation Reduction Act into law last August, President Biden said its $369 billion clean energy and climate provisions will fund 'the most aggressive action ever--ever, ever, ever--in [...]

As your Leader (23 September) points out, Liz Truss's pro-growth provisions do not stimulate growth, as the rich save while the poor spend disposable income. It also suggests raising Universal [...]

Purpose: Behaviours occur across complex, dynamic timelines. Research methods to analyse these complex timelines have repeatedly used behaviour sequence analysis (BSA) as a primary method. Traditional BSA outputs, however, are limited in that they do not show how prevalent a behaviour sequence is throughout a sample or group. Until now, how many people in a sample showed the sequence was not analysed and reported. This paper aims to provide a new metric to calculate prevalence scores in BSA data sets. Design/methodology/approach: Open access recorded responses including nonverbal communication of deceptive and truthful individuals were analysed initially with a standard BSA approach and then the prevalence scores of transitions were calculated. Findings: Prevalence scores offered new insights into the distribution of sequences across groups. The prevalence score showed differences in which transitions were seen across the truthful and guilty samples. This offers new approaches to analysing nonverbal communication. Originality/value: This is the first paper to provide a prevalence score for BSA research and show how it can be used in applied research. The current prevalence score metric is provided and suggested for all future research into sequences.

Your Leader ('A planet on fire', 22 July) concludes, 'The world is already burning. It is not too late to change.' Yet it also refers to Andrew Marr's less optimistic [...]

FOR the numerous plant and animal species endangered by human activities, 2022 could be a crucial year. That's because this year three big international meetings are in play, potentially leading [...]

THE Securities and Exchange Commission's recent vote to propose a rule mandating that companies disclose their greenhouse gas emissions and climate change risks, if finalized, will be a big win [...]

CALL it a Glasgow half empty. During a press conference previewing the COP26 summit, President Biden's climate envoy, John Kerry, asserted, 'It's not inconsistent' for Biden to ask the 13-member [...]

ABSTRACT This study evaluates the effects of two types of asphalt emulsion, anionic and cationic emulsions, on the properties of two types of cement emulsified asphalt mortar (CEAM), low-modulus CEAM [...]

Helical structures are ubiquitous in nature and impart unique mechanical properties and multifunctionality1. So far, synthetic architectures that mimic these natural systems have been fabricated by winding, twisting and braiding of individual filaments1–7, microfluidics8,9, self-shaping1,10–13and printing methods14–17. However, those fabrication methods are unable to simultaneously create and pattern multimaterial, helically architected filaments with subvoxel control in arbitrary two-dimensional (2D) and three-dimensional (3D) motifs from a broad range of materials. Towards this goal, both multimaterial18–23and rotational243D printing of architected filaments have recently been reported; however, the integration of these two capabilities has yet to be realized. Here we report a rotational multimaterial 3D printing (RM-3DP) platform that enables subvoxel control over the local orientation of azimuthally heterogeneous architected filaments. By continuously rotating a multimaterial nozzle with a controlled ratio of angular-to-translational velocity, we have created helical filaments with programmable helix angle, layer thickness and interfacial area between several materials within a given cylindrical voxel. Using this integrated method, we have fabricated functional artificial muscles composed of helical dielectric elastomer actuators with high fidelity and individually addressable conductive helical channels embedded within a dielectric elastomer matrix. We have also fabricated hierarchical lattices comprising architected helical struts containing stiff springs within a compliant matrix. Our additive-manufacturing platform opens new avenues to generating multifunctional architected matter in bioinspired motifs.

The Regenerative Braking Energy (RBE) of metro trains plays an important role in metro energy saving. If the regenerative energy can be directly absorbed by the adjacent trains, the investment in other RBE usage equipments like super capacitors will be reduced. To increase the RBE usage, the overlaps of traction and braking processes of adjacent trains can be increased by timetable optimization or real-time train regulation. But if the overlaps cannot be realized, the RBE cannot be efficiently absorbed by the other trains. To solve this problem, this paper proposes an optimal train control method to absorb the RBE of the braking train by adjusting the speed profile of an adjacent train that runs at non-braking stage. A speed profile adjustment algorithm for the adjacent train is given considering the speed limits and gradients, in which a traction process is incorporated in the adjusted speed profile. Connected and unconnected DC power supply networks are both considered. In the connected DC power supply network, the RBE of the braking train can be absorbed by the adjacent adjusted train, which runs in the different power supply section. To test the robustness of the proposed algorithm, random train delays are considered in the simulations. The interstation running time will be regulated to reduce the train delay by a linear programming model, based on which, the speed profile of the cooperative train will be adjusted. Simulations are conducted based on a whole day data of Beijing Metro Line 4. The simulation results show that the proposed method improves the energy efficiency over 13% by improving RBE usage, and the proposed method also shows strong robustness in the train delay simulations, which makes it a promising method to be applied in real metro system.

Background: We report a case of an intraosseous cavernous hemangioma originating from the middle turbinate that expanded into the anterior skull base, without traversing the cribriform plate.Methods: The mass was found incidentally after a computed tomography head was ordered for unrelated reasons. On questioning, the patient denied any nasal symptoms. Magnetic resonance imaging showed an enhancing mass and the radiological imaging supported a broad differential.Results: The lesion was removed by endoscopic image-guided surgery, and the pathology was that of a benign intraosseous cavernous hemangioma. There was no residual hemangioma on postoperative imaging and the nasal mucosa healed well. This is the first report of an intraosseous cavernous hemangioma of the middle turbinate showing superior expansion to the anterior skull base.Conclusion: This case demonstrates the extent to which cavernous hemangiomas may expand into surrounding tissues. While these lesions are uncommon, they can be considered as part of a broad differential diagnosis of sinonasal tumors.

ABSTRACT The present study investigated the mechanical properties of cement emulsified asphalt mortar (CEAM) as a damping material for ballastless high-speed rail track bed. CEAM has unique properties that differ [...]

AbstractThey thought they felt something, perhaps. The wisp of an outline not distinct enough to trace. Good. They circled it, at times, and at other times found themselves within. As they walked (a sort of walking. Figurative but real. Digital, but here. Over months of events), it curled open and headed in several directions. Foldings in the backcloth that furrowed them along until, as they walked and talked, they felt that perhaps a territory was becoming simultaneously clearer and more obscure, that they might find a way to enquire, even as it meant becoming the folds themselves. As they coalesce, Scott, Jamie, and Dave each come to this project differently (of course). From their own situations, with their own problems and with different voices and ways of writing. We (for the first shift in voice) take post-qualitative inquiry to be infused with a question mark, wary of attempts to make it a ‘thing’. Yet here we are, drawn to potentials, to the opening of conditions, to the possibility of something still to come. We hope to make a shift, to realise (as in make manifest) ontology and its everyday performance as synonymous with environmental education. Environmental education as a life.

Aggregation of alpha-synuclein (α-Syn) drives Parkinson’s disease (PD), although the initial stages of self-assembly and structural conversion have not been directly observed inside neurons. In this study, we tracked the intracellular conformational states of α-Syn using a single-molecule Förster resonance energy transfer (smFRET) biosensor, and we show here that α-Syn converts from a monomeric state into two distinct oligomeric states in neurons in a concentration-dependent and sequence-specific manner. Three-dimensional FRET-correlative light and electron microscopy (FRET-CLEM) revealed that intracellular seeding events occur preferentially on membrane surfaces, especially at mitochondrial membranes. The mitochondrial lipid cardiolipin triggers rapid oligomerization of A53T α-Syn, and cardiolipin is sequestered within aggregating lipid–protein complexes. Mitochondrial aggregates impair complex I activity and increase mitochondrial reactive oxygen species (ROS) generation, which accelerates the oligomerization of A53T α-Syn and causes permeabilization of mitochondrial membranes and cell death. These processes were also observed in induced pluripotent stem cell (iPSC)–derived neurons harboring A53T mutations from patients with PD. Our study highlights a mechanism of de novo α-Syn oligomerization at mitochondrial membranes and subsequent neuronal toxicity.

The article explores the complexities and potential of regenerative agriculture as a solution to contemporary agricultural and environmental challenges. Topics discussed include the historical context and resurgence of regenerative agriculture, its differentiation from other farming practices, and the nuanced effectiveness of its applications in varying contexts and ecosystems.

Large-scale human genetic data1–3have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient samples, we demonstrate that the lineage transcription factor paired box 8 (PAX8) is required for oncogenic signalling by two common genetic alterations that cause clear cell renal cell carcinoma (ccRCC) in humans: the germline variant rs7948643 at 11q13.3 and somatic inactivation of the von Hippel-Lindau tumour suppressor (VHL)4–6. VHLloss, which is observed in about 90% of ccRCCs, can lead to hypoxia-inducible factor 2α (HIF2A) stabilization6,7. We show that HIF2A is preferentially recruited to PAX8-bound transcriptional enhancers, including a pro-tumorigenic cyclin D1 (CCND1) enhancer that is controlled by PAX8 and HIF2A. The ccRCC-protective allele C at rs7948643 inhibits PAX8 binding at this enhancer and downstream activation of CCND1expression. Co-option of a PAX8-dependent physiological programme that supports the proliferation of normal renal epithelial cells is also required for MYCexpression from the ccRCC metastasis-associated amplicons at 8q21.3-q24.3 (ref. 8). These results demonstrate that transcriptional lineage factors are essential for oncogenic signalling and that they mediate tissue-specific cancer risk associated with somatic and inherited genetic variants.

Hip fractures represent a significant workload of both emergency and orthopaedic departments within the National Health Service (NHS). Pain relief is key in treating hip fractures as highlighted by both National Institute of Clinical Excellence (NICE) and British Orthopaedic Association Standards for Trauma (BOAST) guidelines. However, the literature shows that patients with cognitive impairment tend to have inconsistent pain management, leading to worse outcomes. We conducted a case–control study looking at 296 patients who presented with hip fractures to a major trauma centre between 1 December 2019 and 30 May 2020. Cognition was assessed using pre-recorded Abbreviated Mental Test Scores (AMTS). There was no significant difference between pain relief provided to patients with or without cognitive impairment in both the pre-hospital (p = 0.208) and Accident & Emergency (A&E) (p = 0.154) setting. A larger proportion of patients in A&E did not receive any pain relief (18.6% versus 42.2%). Pre-hospital, the higher the pain score, the stronger the analgesia given (R = 0.435, p = 0.000). This relationship was present in both the cognitively impaired (R = 0.572, p = 0.000) and cognitively intact groups (R = 0.390 p = 0.000). Strength of analgesia and pain scores did not correlate in A&E (R = 0.014, p = 0.826). Cognition did not impact the time to analgesia both pre-hospital (p = 0.291) and in A&E (p = 0.332); however, patients waited significantly longer to receive pain relief in A&E (29.61 minutes versus 150.28 minutes). Fascia-iliaca blocks were administered to 58.4% of the cohort, with no significant difference noted between cognition status. Overall, cognition does not impact pain management both pre-hospital and in A&E. There is still room for improvement, particularly in the assessment of pain in the cognitively impaired. A possible solution is the utilisation of the Bolton Pain Assessment Tool, a validated pain assessment tool for the cognitively impaired that has been utilised in the trauma setting with good effect.

A statement by the chief executive of Unilever, quoted in your Leader ('The message to the planet', 18 September), encapsulates current fears: 'there will be no jobs or prosperity on [...]

The provisions and recommendations of the 2009 fiscal budget presented by the U.S. President George W. Bush are discussed. The possibility that the Democrats may choose to leave major spending decisions to the newly elected president is not ruled out.

The fiscal 2008 Labor, Health and Human Services appropriations bill cleared by Congress, and expected to face a presidential veto, is presented.

A combined fiscal 2008 Labor, Health and Human Services, Education and Military Construction and Veterans Affairs spending bill approved by the House-Senate conference is discussed.

The dispute over a small amount in the budget that both parties are using to symbolize all their fiscal policy disagreements is discussed.

A married couple came in to see me for the first time: mid-30s, two kids, Christians, active church members. I'll call them Bob and Susie. Susie, in tears, told me [...]