A catalytically active oscillator made from small organic molecules.

Oscillatory systems regulate many biological processes, including key cellular functions such as metabolism and cell division, as well as larger-scale processes such as circadian rhythm and heartbeat1-4. Abiotic chemical oscillations, discovered originally in inorganic systems5,6, inspired the development of various synthetic oscillators for application as autonomous time-keeping systems in analytical chemistry, materials chemistry and the biomedical field7-17. Expanding their role beyond that of a pacemaker by having synthetic chemical oscillators periodically drive a secondary function would turn them into significantly more powerful tools. However, this is not trivial because the participation of components of the oscillator in the secondary function might jeopardize its time-keeping ability. We now report a small molecule oscillator that can catalyse an independent chemical reaction in situ without impairing its oscillating properties. In a flow system, the concentration of the catalytically active product of the oscillator shows sustained oscillations and the catalysed reaction is accelerated only during concentration peaks. Augmentation of synthetic oscillators with periodic catalytic action allows the construction of complex systems that, in the future, may benefit applications in automated synthesis, systems and polymerization chemistry and periodic drug delivery.

Landscape-scale benefits of protected areas for tropical biodiversity.

The United Nations recently agreed to major expansions of global protected areas (PAs) to slow biodiversity declines1. However, although reserves often reduce habitat loss, their efficacy at preserving animal diversity and their influence on biodiversity in surrounding unprotected areas remain unclear2-5. Unregulated hunting can empty PAs of large animals6, illegal tree felling can degrade habitat quality7, and parks can simply displace disturbances such as logging and hunting to unprotected areas of the landscape8 (a phenomenon called leakage). Alternatively, well-functioning PAs could enhance animal diversity within reserves as well as in nearby unprotected sites9 (an effect called spillover). Here we test whether PAs across mega-diverse Southeast Asia contribute to vertebrate conservation inside and outside their boundaries. Reserves increased all facets of bird diversity. Large reserves were also associated with substantially enhanced mammal diversity in the adjacent unprotected landscape. Rather than PAs generating leakage that deteriorated ecological conditions elsewhere, our results are consistent with PAs inducing spillover that benefits biodiversity in surrounding areas. These findings support the United Nations goal of achieving 30% PA coverage by 2030 by demonstrating that PAs are associated with higher vertebrate diversity both inside their boundaries and in the broader landscape.

Logged tropical forests have amplified and diverse ecosystem energetics.

Old-growth tropical forests are widely recognized as being immensely important for their biodiversity and high biomass1. Conversely, logged tropical forests are usually characterized as degraded ecosystems2. However, whether logging results in a degradation in ecosystem functions is less clear: shifts in the strength and resilience of key ecosystem processes in large suites of species have rarely been assessed in an ecologically integrated and quantitative framework. Here we adopt an ecosystem energetics lens to gain new insight into the impacts of tropical forest disturbance on a key integrative aspect of ecological function: food pathways and community structure of birds and mammals. We focus on a gradient spanning old-growth and logged forests and oil palm plantations in Borneo. In logged forest there is a 2.5-fold increase in total resource consumption by both birds and mammals compared to that in old-growth forests, probably driven by greater resource accessibility and vegetation palatability. Most principal energetic pathways maintain high species diversity and redundancy, implying maintained resilience. Conversion of logged forest into oil palm plantation results in the collapse of most energetic pathways. Far from being degraded ecosystems, even heavily logged forests can be vibrant and diverse ecosystems with enhanced levels of ecological function.

Using global remote camera data of a solitary species complex to evaluate the drivers of group formation.

The social system of animals involves a complex interplay between physiology, natural history, and the environment. Long relied upon discrete categorizations of "social" and "solitary" inhibit our capacity to understand species and their interactions with the world around them. Here, we use a globally distributed camera trapping dataset to test the drivers of aggregating into groups in a species complex (martens and relatives, family Mustelidae, Order Carnivora) assumed to be obligately solitary. We use a simple quantification, the probability of being detected in a group, that was applied across our globally derived camera trap dataset. Using a series of binomial generalized mixed-effects models applied to a dataset of 16,483 independent detections across 17 countries on four continents we test explicit hypotheses about potential drivers of group formation. We observe a wide range of probabilities of being detected in groups within the solitary model system, with the probability of aggregating in groups varying by more than an order of magnitude. We demonstrate that a species' context-dependent proclivity toward aggregating in groups is underpinned by a range of resource-related factors, primarily the distribution of resources, with increasing patchiness of resources facilitating group formation, as well as interactions between environmental conditions (resource constancy/winter severity) and physiology (energy storage capabilities). The wide variation in propensities to aggregate with conspecifics observed here highlights how continued failure to recognize complexities in the social behaviors of apparently solitary species limits our understanding not only of the individual species but also the causes and consequences of group formation.

Heat-related changes in the velocity and kinetic energy of flowing blood influence the human heart's output during hyperthermia.

Passive whole-body hyperthermia increases limb blood flow and cardiac output ( Q ̇ $\dot Q$ ), but the interplay between peripheral and central thermo-haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia-induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and Q ̇ $\dot Q$ . Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3 h control (normothermic condition); (2) 3 h of single-leg heating; (3) 3 h of two-leg heating; and (4) 2.5 h of whole-body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, Q ̇ $\dot Q$ increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2 ≥ 0.803; P < 0.001), but not in the brain. LV systolic (end-systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole-body heating. These findings substantiate the idea that local hyperthermia-induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and Q ̇ $\dot Q$ through changes in blood velocity and kinetic energy. Localised heat-activated events in the peripheral circulation therefore affect the human heart's output. KEY POINTS: Local and whole-body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat-sensitive mechanisms are not fully established. Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: Q ̇ $\dot Q$ ) during passive single-leg, two-leg and whole-body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation. Single-leg, two-leg, and whole-body hyperthermia induced graded increases in leg blood flow and Q ̇ $\dot Q$ . Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole-body hyperthermia. The augmented Q ̇ $\dot Q$ with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy. The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia.

A Prebiotic Precursor to Life's Phosphate Transfer System with an ATP Analog and Histidyl Peptide Organocatalysts.

Biochemistry is dependent upon enzyme catalysts accelerating key reactions. At the origin of life, prebiotic chemistry must have incorporated catalytic reactions. While this would have yielded much needed amplification of certain reaction products, it would come at the possible cost of rapidly depleting the high energy molecules that acted as chemical fuels. Biochemistry solves this problem by combining kinetically stable and thermodynamically activated molecules (e.g., ATP) with enzyme catalysts. Here, we demonstrate a prebiotic phosphate transfer system involving an ATP analog (imidazole phosphate) and histidyl peptides, which function as organocatalytic enzyme analogs. We demonstrate that histidyl peptides catalyze phosphorylations via a phosphorylated histidyl intermediate. We integrate these histidyl-catalyzed phosphorylations into a complete prebiotic scenario whereby inorganic phosphate is incorporated into organic compounds though physicochemical wet-dry cycles. Our work demonstrates a plausible system for the catalyzed production of phosphorylated compounds on the early Earth and how organocatalytic peptides, as enzyme precursors, could have played an important role in this.

Formation of Peroxynitrite, [O-N-O-O]-, via a Cascade of Reactions between Ozonide and Ammonia.

We report on an unexpected reaction between ammonia and potassium ozonide dissolved in liq. NH3 resulting in the formation of peroxynitrite, [ONOO]-, which exclusively happens in the presence of a specific partially fluorinated aniline-based ammonium cation. High-resolution structural data of the peroxynitrite anion in cis-conformation have been obtained. We further studied this molecule anion by single crystal Raman spectroscopy. The cis and trans isomers of peroxynitrite were analysed computationally with respect to their relative energies, the cis-trans transition barrier and their decomposition pathways to the nitrate anion. By experimentally examining cations decorated with fluorine ligands to different degrees, we demonstrate that fluorine specific interactions play a crucial role in the unexpected formation of peroxynitrite and as a conspicuously structure directing factor for the underlying crystalline solid phases, exhibiting distinct micro-separations of fluorine and hydrogen enriched regions.

Words or code first? Is the legacy document or a code statement the better starting point for complexity-reducing legal automation?

Law is a critical tool that humans have created to assist them in managing complex social interactions. Computational Law holds the potential to significantly enhance our capacity to express and manage legal complexity, and a number of advantages can result from restating public and private legal rules in computable form. Capturing that potential depends in part on the approaches taken to automation. One set of choices involves whether to translate directly into code from existing natural language statements of laws, regulations and contracts or whether to step back, envision the basic structure underlying those statements and build a software approach that reflects that structure in a code-native manner. We argue that many advantages can flow from the second approach, and we present a specific use case of a simplified insurance policy as an example of this approach. Large language models may assist in this process, but are not yet a replacement for a code-native utility. This article is part of the theme issue 'A complexity science approach to law and governance'.

Exercise Dependency and Overuse Injuries in Attention Deficit Hyperactivity Disorder.

ABSTRACT: Attention deficit hyperactivity disorder (ADHD) is a common condition, but current medications have limitations, pushing a drive for alternative approaches. Different exercise-focused approaches have shown promise, but concern has also been raised about individuals with ADHD showing greater risk of addiction, including exercise dependency. Using an online survey, we examined current exercise practices, including exercise dependency and the presence of overuse injury, which could result from overexercising, in 114 adults with ADHD. We found that most were regularly exercising. None were classified as exercise dependent, but 38.9% were deemed symptomatic nondependent. Hyperactive-impulsive symptoms were a predictor of the level of exercise withdrawal experienced, and the co-occurrence of autism spectrum disorder was associated with greater risk of overuse injuries. The data indicate that ADHD may confer some greater risk of exercise dependency, aligning with previous studies investigating other addictions and suggesting further research is critical.

Examining the importance of local and global patterns for familiarity detection in soccer action sequences.

Pattern recognition is a defining characteristic of expertise across multiple domains. Given the dynamic interactions at local and global levels, team sports can provide a vehicle for investigating skilled pattern recognition. The aims of this study were to investigate whether global patterns could be recognised on the basis of localised relational information and if relations between certain display features were more important than others for successful pattern recognition. Elite (n = 20), skilled (n = 34) and less-skilled (n = 37) soccer players completed three recognition paradigms of stimuli presented in point-light format across three counterbalanced conditions: 'whole-part'; 'part-whole'; and 'whole-whole'. 'Whole' clips represented a 11 vs. 11 soccer match and 'part' clips presented the same passages of play with only two central attacking players or two peripheral players shown. Elite players recognised significantly more accurately than the skilled and less-skilled groups. Participants were significantly more accurate in the 'whole-whole' condition compared to others, and recognised stimuli featuring the two central attacking players significantly more accurately than those featuring peripheral players. Findings provide evidence that elite players can encode localised relations and then extrapolate this information to recognise more global macro patterns.

The effects of internal representations on performance and fluidity in a motor task.

Individuals can differ in the mode in which they experience conscious thought. These differences in visualisation and verbalisation can also be evident during motor control. The Internal Representation Questionnaire (IRQ) was developed to measure propensity to engage certain types of representations, but its ability to predict motor control and links to reinvestment and motor imagery have not been tested. 159 included participants completed the IRQ, movement specific reinvestment scale (MSRS), and a novel online motor task before and after a period of practice. Results showed that the IRQ Verbal and Orthographic factors were significant predictors of scores on the MSRS. The IRQ factor of Manipulational Representations predicted motor performance both before and after practice. The fluidity of executed movements were predicted by the IRQ verbalisation factor where higher propensity to verbalise was associated with higher levels of jitter, but only after a period of practice. Results suggest there may be some informative conceptual overlap between internal verbalisations and reinvestment and that the propensity to manipulate internal representations may be predictive of motor performance in new tasks. The IRQ has potential to be a valuable tool for predicting motor performance.

The developmental activities of women's professional pathway cricketers.

The growth of investment in women's cricket has led to the development of new professional pathways. However, there is lack of specific evidence to support the development of these athletes. This study aimed to take a first step in understanding the participation histories of female cricketers selected into English women's professional academies. 84 players completed the Participation History Questionnaire (PHQ) to capture details of activities engaged in across development, including milestones, cricket activity, and engagement in other sport activities. There were relative age effects where players' birthdate distributions differed from national norms (X2 = 8.451, p = .003, V = 0.227), and more players than expected attended independent schools (X2 = 7.980, p = .005, V = 0.232). Participants engaged in cricket informally before coach led training, have siblings (particularly brothers) interested in cricket and often played boy's cricket before engaging in the girl's or women's game. Developmental activities were characterised by early engagement, high levels of diversification, and very low levels of play compared to high levels of formal practice and match play. These findings have implications for the advancement of talent identification and development policies and processes in women's cricket.

Sex Differences in Hydration Biomarkers and Test-Retest Reliability Following Passive Dehydration.

This study investigated (a) differences between males and females for changes in serum, tear, and urine osmolality, hematocrit, and urine specific gravity following acute passive dehydration and (b) assessed the reliability of these biomarkers separately for each sex. Fifteen males (age: 26.3 ± 3.5 years, body mass: 76 ± 7 kg) and 15 females (age: 28.8 ± 6.4 years, body mass: 63 ± 7 kg) completed a sauna protocol twice (5-28 days apart), aiming for 4% body mass loss (BML). Urine, blood, and tear markers were collected pre- and postdehydration, and change scores were calculated. Male BML was significantly greater than that of females in Trial 1 (3.53% ± 0.55% vs. 2.53% ± 0.43%, p < .001) and Trial 2 (3.36% ± 0.66% vs. 2.53% ± 0.44%, p = .01). Despite significant differences in BML, change in hematocrit was the only change marker that displayed a significant difference in Trial 1 (males: 3% ± 1%, females: 2% ± 1%, p = .004) and Trial 2 (males: 3% ± 1%, females: 1% ± 1%, p = .008). Regression analysis showed a significant effect for sex (male) predicting change in hematocrit (ß = 0.8, p = .032) and change in serum osmolality (ß = -3.3, p = .005) when controlling for BML but not for urinary or tear measures. The intraclass correlation coefficients for females (ICC 2, 1) were highest for change in urine specific gravity (ICC = .62, p = .006) and lowest for change in tear osmolarity (ICC = -.14, p = .689), whereas for males, it was posthematocrit (ICC = .65, p = .003) and post tear osmolarity (ICC = .18, p = .256). Generally, biomarkers showed lower test-retest reliability in males compared with females but, overall, were classified as poor-moderate in both sexes. These findings suggest that the response and reliability of hydration biomarkers are sex specific and highlight the importance of accounting for BML differences.

Cross-adaptation from heat stress to hypoxia: A systematic review and exploratory meta-analysis.

Cross-adaptation (CA) refers to the successful induction of physiological adaptation under one environmental stressor (e.g., heat), to enable subsequent benefit in another (e.g., hypoxia). This systematic review and exploratory meta-analysis investigated the effect of heat acclimation (HA) on physiological, perceptual and physical performance outcome measures during rest, and submaximal and maximal intensity exercise in hypoxia. Database searches in Scopus and MEDLINE were performed. Studies were included when they met the Population, Intervention, Comparison, and Outcome criteria, were of English-language, peer-reviewed, full-text original articles, using human participants. Risk of bias and study quality were assessed using the COnsensus based Standards for the selection of health status Measurement INstruments checklist. Nine studies were included, totalling 79 participants (100 % recreationally trained males). The most common method of HA included fixed-intensity exercise comprising 9 ± 3 sessions, 89 ± 24-min in duration and occurred within 39 ± 2 °C and 32 ± 13 % relative humidity. CA induced a moderate, beneficial effect on physiological measures at rest (oxygen saturation: g = 0.60) and during submaximal exercise (heart rate: g = -0.65, core temperature: g = -0.68 and skin temperature: g = -0.72). A small effect was found for ventilation (g = 0.24) and performance measures (peak power: g = 0.32 and time trial time: g = -0.43) during maximal intensity exercise. No effect was observed for perceptual outcome measures. CA may be appropriate for individuals, such as occupational or military workers, whose access to altitude exposure prior to undertaking submaximal activity in hypoxic conditions is restricted. Methodological variances exist within the current literature, and females and well-trained individuals have yet to be investigated. Future research should focus on these cohorts and explore the mechanistic underpinnings of CA.

"I Found Comfort in Exercising": Exploring Experiences With Exercise for Adults With Attention-Deficit/Hyperactivity Disorder.

Little is known about how adults with attention-deficit/hyperactivity disorder (ADHD) experience exercise, resulting in a lack of recommendations for supporting this population. We aimed to explore how adults with ADHD experience exercise as a management tool before and after diagnosis and how and why individuals experience issues related to exercise dependence. Fifteen active adults with a diagnosis of ADHD participated in semistructured interviews. Three overarching themes were identified: (a) exercise as a necessity for ADHD, reflecting the need to exercise before a formal ADHD diagnosis, and use of exercise as a management tool postdiagnosis; (b) goals and achievements to live by, reflecting how exercise patterns revolved around a need to make progress toward targets; and (c) activity or exercise: a roller coaster journey, covering the ups and downs of exercise journeys. This article highlights the importance of exercise for adults to manage ADHD and how this can be encouraged and supported.

Pattern visual evoked potentials show an inferior-superior topographic shift through maturation in childhood.

The pattern-reversal visual evoked potential (prVEP) is an established routine clinical test. Its objectivity is particularly valuable for assessing visual pathway function in children. International standards specify at a minimum that an active electrode is placed on the occiput at Oz, but we find an additional inferior electrode at the inion (Iz) provides larger and more sensitive prVEPs in young persons. This study assesses the significance and age-dependence of these observations. PrVEPs were recorded from 1487 patients considered ophthalmologically normal aged <20 years old, to a range of check widths including International Society for Clinical Electrophysiology of Vision (ISCEV) standard large (50') and small (12.5') check widths. P100 peak-time and amplitude from both electrode sites were analysed. A subset of 256 children were studied longitudinally by fitting logistic regression models including a random effect on subjects. PrVEPs were largest over the Iz electrode for the majority of infants and children. This transitioned with age to become equal or smaller at Oz as a function of check width. For ISCEV standard large and small check widths, transition periods were ∼8 and ∼12 years of age, respectively. We estimated abnormal result classifications of 3.7% with use of an Oz electrode alone, which decreases to 0.0-0.5% when adding or using an Iz electrode. The inferior dominance of prVEP topography in children may be explained by age-related anatomical changes altering the cortical dipole, combined with physiological maturation of the neural generators of the prVEP. We recommend the Iz electrode is used routinely in recording of prVEPs in children. KEY POINTS: Pattern visual evoked potentials (PVEPs) are an established clinical test which provide objective assessment of visual pathway function. These are particularly valuable in providing objective information of vision in children. International standards specify the active recording electrode should be placed at the mid-occiput (Oz), but we find that pattern-reversal visual evoked potential amplitudes are larger for a lower placed electrode (Iz) in young persons. This was assessed in 1487 patients who had simultaneous PVEP recording at both electrode positions, and it was found that the majority of PVEPs in children were larger over the Iz electrode. The developmental differences in PVEP distribution transitioned to be equal between Iz and Oz with increasing age as a function of check width, at ∼8 and ∼12 years old for large and small check widths, respectively. These differences will improve diagnostic accuracy of paediatric PVEPs. We hypothesise these changes reflect developmental anatomical and neurophysiological changes altering the PVEP dipole.

Skeletal muscle angiogenic, regulatory, and heat shock protein responses to prolonged passive hyperthermia of the human lower limb.

Passive hyperthermia induces a range of physiological responses including augmenting skeletal muscle mRNA expression. This experiment aimed to examine gene and protein responses to prolonged passive leg hyperthermia. Seven young participants underwent 3 h of resting unilateral leg heating (HEAT) followed by a further 3 h of rest, with the contralateral leg serving as an unheated control (CONT). Muscle biopsies were taken at baseline (0 h), and at 1.5, 3, 4, and 6 h in HEAT and 0 and 6 h in CONT to assess changes in selected mRNA expression via qRT-PCR, and HSP72 and VEGFα concentration via ELISA. Muscle temperature (Tm) increased in HEAT plateauing from 1.5 to 3 h (+3.5 ± 1.5°C from 34.2 ± 1.2°C baseline value; P < 0.001), returning to baseline at 6 h. No change occurred in CONT. Endothelial nitric oxide synthase (eNOS), Forkhead box O1 (FOXO-1), Hsp72, and VEGFα mRNA increased in HEAT (P < 0.05); however, post hoc analysis identified that only Hsp72 mRNA statistically increased (at 4 h vs. baseline). When peak change during HEAT was calculated angiopoietin 2 (ANGPT-2) decreased (-0.4 ± 0.2-fold), and C-C motif chemokine ligand 2 (CCL2) (+2.9 ± 1.6-fold), FOXO-1 (+6.2 ± 4.4-fold), Hsp27 (+2.9 ± 1.7-fold), Hsp72 (+8.5 ± 3.5-fold), Hsp90α (+4.6 ± 3.7-fold), and VEGFα (+5.9 ± 3.1-fold) increased from baseline (all P < 0.05). At 6 h Tm were not different between limbs (P = 0.582; CONT = 32.5 ± 1.6°C, HEAT = 34.3 ± 1.2°C), and only ANGPT-2 (P = 0.031; -1.3 ± 1.4-fold) and VEGFα (P = 0.030; 1.1 ± 1.2-fold) differed between HEAT and CONT. No change in VEGFα or HSP72 protein concentration were observed over time; however, peak change in VEGFα did increase (P < 0.05) in HEAT (+140 ± 184 pg·mL-1) versus CONT (+7 ± 86 pg·mL-1). Passive hyperthermia transiently augmented ANGPT-2, CCL2, eNOS, FOXO-1, Hsp27, Hsp72, Hsp90α and VEGFα mRNA, and VEGFα protein.

Two pathogen loci determine Blumeria graminis f. sp. tritici virulence to wheat resistance gene Pm1a.

Blumeria graminis f. sp. tritici (Bgt) is a globally important fungal pathogen of wheat that can rapidly evolve to defeat wheat powdery mildew (Pm) resistance genes. Despite periodic regional deployment of the Pm1a resistance gene in US wheat production, Bgt strains that overcome Pm1a have been notably nonpersistent in the United States, while on other continents, they are more widely established. A genome-wide association study (GWAS) was conducted to map sequence variants associated with Pm1a virulence in 216 Bgt isolates from six countries, including the United States. A virulence variant apparently unique to Bgt isolates from the United States was detected in the previously mapped gene AvrPm1a (BgtE-5612) on Bgt chromosome 6; an in vitro growth assay suggested no fitness reduction associated with this variant. A gene on Bgt chromosome 8, Bgt-51526, was shown to function as a second determinant of Pm1a virulence, and despite < 30% amino acid identity, BGT-51526 and BGTE-5612 were predicted to share > 85% of their secondary structure. A co-expression study in Nicotiana benthamiana showed that BGTE-5612 and BGT-51526 each produce a PM1A-dependent hypersensitive response. More than one member of a B. graminis effector family can be recognized by a single wheat immune receptor, and a two-gene model is necessary to explain virulence to Pm1a.