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The number of psychology students at UK universities is at an all-time high (Higher Education Statistics Agency, 2022) and over half of psychology students who are interested in a career in mental health are specifically interested in becoming clinical psychologists (National Collaborating Centre for Mental Health, 2019) and from our experience (as a student, educator, and career consultant), aspiring to this career can result in high levels of anxiety. To explore the experiences of aspiring clinical psychologists, we conducted semi-structured interviews with thirteen undergraduate psychology students who hope to become clinical psychologists. From our thematic analysis (Braun & Clarke, 2006), we identified three themes: ‘Information: what, when, who?’, ‘The rocky road to clinical psychology training’ and ‘Choosing clinical psychology and its cost’. The study led to the development of an undergraduate ‘Clinical Psychology Club’ to support the career choices of aspiring undergraduate clinical psychologists.

We present a carboxylate-targeting reactive fragment screening platform using 2-aryl-5-carboxytetrazole (ACT) as the photoreactive functionality. This work will provide a simple accessible method to rapidly discover tool molecules to interrogate important biological targets.

Our subjective wellbeing is a mix of our personal and community wellbeing. One indication of their close relationship is the strong negative correlation between our own subjective wellbeing and the degree of subjective wellbeing inequality within our community. This negative relationship reflects our innate and socialized inequality aversion and holds regardless of whether the group is large as in the case of countries or small in the case of local neighbourhoods. While the country case has been well documented in the subjective wellbeing literature, the relationship between the local community distribution of subjective wellbeing and individual subjective wellbeing has received little attention. In this paper we demonstrate the sensitivity of individual life satisfaction to the distribution of life satisfaction within electoral wards in urban New Zealand and explore several possible behavioural drivers. We find that having social support and feeling a sense of community both reduce the negative effects of local subjective wellbeing inequality, while being less socially engaged exaggerates them. Our results highlight the potential that programmes aimed at reducing wellbeing inequalities within local communities might play in raising individual as well as average wellbeing.

Background The relationship between environmentally transmitted tick parasites, Ixodes spp., and their main reproductive host, deer, is generally thought to be positive. However, measuring host abundance and density directly can be challenging and indirect methods are often used. The observed relationship between the parasite and host may be affected by sampling scale and season, which could lead to different inferences being made. Here, we aimed to test the effect of sampling scale and season on the relationship between density of deer and the density of questing Ixodes ricinus nymphs. Methods The density of deer (primarily Dama dama) was estimated using line transect distance sampling of deer dung quantified in different seasons (winter and summer) and measured at three different nested scales (site, transect and observation level). Questing nymph density was measured using blanket drag methods and estimates were calculated at the same scales as deer density estimates. General linear models were used to evaluate the relationship between questing nymphs, deer density and other environmental variables at each sampling scale and each season deer density was measured at. Results While a positive relationship between deer density and questing nymph density was detected at the site and transect scale, no relationship was apparent at the observation level. This was likely due to increased variation and reduced precision of deer dung counts at the finest sampling scale. Seasonal changes in deer populations were observed likely reflecting seasonal shifts in habitat usage. The summer estimates of deer density explained questing nymph density whereas winter estimates did not. Conclusions Our results show that the scale of sampling can affect the detectability of the positive association between host and vector species. Furthermore, such associations can be obscured if hosts exhibit seasonal changes in habitat use. Thus, both sampling scale and season are important to consider when investigating the relationship between host and vector species.

Despite the vast array of different geochronological tools available, dating the Paleolithic remains one of the discipline’s greatest challenges. This review focuses on two different dating approaches: trapped charge and amino acid geochronology. While differing in their fundamental principles, both exploit time-dependent changes in signals found within crystals to generate a chronology for the material dated and hence, the associated deposits. Within each method, there is a diverse range of signals that can be analyzed, each covering different time ranges, applicable to different materials and suitable for different paleoenvironmental and archaeological contexts. This multiplicity of signals can at first sight appear confusing, but it is a fundamental strength of the techniques, allowing internal checks for consistency and providing more information than simply a chronology. For each technique, we present an overview of the basis for the time-dependent signals and the types of material that can be analyzed, with examples of their archaeological application, as well as their future potential.

The consequences of blast traumatic brain injury (blast-TBI) in humans are largely determined by the characteristics of the trauma insult and, within certain limits, the individual responses to the lesions inflicted [1]. In blast-TBI the mechanisms of brain vulnerability to the detonation of an explosive device are not entirely understood. They most likely result from a combination of the different physical aspects of the blast phenomenon, specifically extreme pressure oscillations (blast-overpressure wave – primary blast), projectile penetrating fragments (secondary blast) and acceleration-deceleration forces (tertiary blast), creating a spectrum of brain injury that ranges from mild to severe blast-TBI [2]. The pathophysiology of penetrating and inertially-driven blast-TBI has been extensively investigated for many years. However, the brain damage caused by blast-overpressure (primary blast) is much less understood and is unique to this type of TBI [3]. Indeed, there continues to be debate about how the pressure wave is transmitted and reflected through the brain and how it causes cellular damage [4]. No single model can mimic the clinical and mechanical complexity resulting from a real life blast-TBI [3]. The different models, non-biological (in silico or surrogate physical) and biological (ex vivo, in vitro or in vivo), tend to complement each other.

Restoration of the p53 tumor suppressor for personalised cancer therapy is a promising strategy. However, high-affinity MDM2 inhibitors have shown substantial side effects in clinical trials. Thus, elucidation of the molecular mechanisms of action of p53 reactivating molecules with alternative functional principle is of the utmost importance.Here, we report a discovery of a novel allosteric mechanism of p53 reactivation through targeting the p53 N-terminus which blocks both p53/MDM2 and p53/MDM4 interactions. Using biochemical assays and molecular docking, we identified the binding site of two p53 reactivating molecules, RITA and protoporphyrin IX (PpIX). Ion-mobility mass spectrometry revealed that the binding of RITA to serine 33 and serine 37 is responsible for inducing the allosteric shift in p53, which shields the MDM2 binding residues of p53 and prevents its interactions with MDM2 and MDM4. Our results point to an alternative mechanism of blocking p53 interaction with MDM2 and MDM4 and may pave the way for the development of novel allosteric inhibitors of p53/MDM2 and p53/MDM4 interactions.Contribution to the fieldGiven the immense importance of the p53 tumor suppressor for cancer, efforts have been made to identify p53 activators, which sterically inhibit MDM2. Because high-affinity MDM2 inhibitors are facing problems with considerable side effects, other approaches are needed to reactivate p53 for improved cancer therapy. The allosteric mechanism of action of p53 activator RITA, which we discovered, and its dependence on the oncogenic switch, is an unexpected turn in the p53 story. Our findings provide a basis for the development of p53 activators with a similar mode of functioning, either through the classical drug discovery route or through the drug repurposing approach. Allosteric modulators might have great potential as single agents, or in combination with the standard of care. Further, p53 modulators could serve as invaluable tools to better understand its biology.

Australian mango orchards, particularly of the 'Kensington Pride' cultivar, are often characterized by low yields and irregular bearing. Improved nutrition management techniques which increase total soil carbon sequestration and reduce nitrogen losses (nitrous oxide) may improve productivity and also reduce greenhouse gas emissions. A factorial trial was established in a 'Kensington Pride' mango orchard at Mareeba, Australia to assess the benefits of applying organic hay mulch to tree rows in combination with three nitrogen fertiliser treatments including two controlled-release fertiliser products. Three years after the initiation of treatments it was found that mango tree growth and fruit productivity was significantly improved when mulching was used to increase soil organic matter. Mulched soils had improved soil water holding capacity, less temperature variability, increased root biomass in the top soil, greater canopy leaf area and higher plant tissue potassium levels. Average fruit weights were increased by 10% and mango fruit yields per tree increased by 11%. Fruit quality was not affected when standard fungicide management treatments were used, although disease levels were higher with no post-harvest fungicide treatment. The nitrogen fertiliser products investigated did not have a significant influence on mango growth or final productivity. Trial results suggest that the adoption of mulching practices in mango orchards is a management practice which can increase orchard productivity and the sequestration of soil organic carbon, without detrimental effects on fruit quality.

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.

Woodrow Wilson's name remains forever entwined with the Paris Peace Conference and efforts to transform geopolitics after 1918. Despite recent emphases on the power of this so-called ‘Wilsonian Moment,’ initiatives by the American president remain controversial, and his principal global legacy has come to be defined as the rise of nationalism in the developing world. In the historiography of modern Japan, Wilson and the Paris Conference have long been identified less as opportunities than as challenges, embodied unmistakably in Prince Konoe Fumimaro's 1918 condemnation of the conference and the proposed League of Nations as beneficial only to the USA and Britain. Reading back from 1931, historians of modern Japan have located in the Versailles settlement seeds of an epic new expansionary effort from the Manchurian Incident to the destruction of Imperial Japan. This paper, by contrast, analyzes the interwar years on their own terms and, in so doing, locates the structural foundations of a dramatic Japanese national departure. Wilson is more than a ‘moment’ in interwar Japan. Embraced at the very moment that a largely agricultural and regional nineteenth-century Japan becomes a twentieth-century industrial state and world power, it is potent enough to withstand the illiberal tide of the 1930s and 40s to blossom again after the Second World War.

Background Animal-attached devices can be used on cryptic species to measure their movement and behaviour, enabling unprecedented insights into fundamental aspects of animal ecology and behaviour. However, direct observations of subjects are often still necessary to translate biologging data accurately into meaningful behaviours. As many elusive species cannot easily be observed in the wild, captive or domestic surrogates are typically used to calibrate data from devices. However, the utility of this approach remains equivocal. Methods Here, we assess the validity of using captive conspecifics, and phylogenetically-similar domesticated counterparts (surrogate species) for calibrating behaviour classification. Tri-axial accelerometers and tri-axial magnetometers were used with behavioural observations to build random forest models to predict the behaviours. We applied these methods using captive Alpine ibex (Capra ibex) and a domestic counterpart, pygmy goats (Capra aegagrus hircus), to predict the behaviour including terrain slope for locomotion behaviours of captive Alpine ibex. Results Behavioural classification of captive Alpine ibex and domestic pygmy goats was highly accurate (> 98%). Model performance was reduced when using data split per individual, i.e., classifying behaviour of individuals not used to train models (mean ± sd = 56.1 ± 11%). Behavioural classifications using domestic counterparts, i.e., pygmy goat observations to predict ibex behaviour, however, were not sufficient to predict all behaviours of a phylogenetically similar species accurately (> 55%). Conclusions We demonstrate methods to refine the use of random forest models to classify behaviours of both captive and free-living animal species. We suggest there are two main reasons for reduced accuracy when using a domestic counterpart to predict the behaviour of a wild species in captivity; domestication leading to morphological differences and the terrain of the environment in which the animals were observed. We also identify limitations when behaviour is predicted in individuals that are not used to train models. Our results demonstrate that biologging device calibration needs to be conducted using: (i) with similar conspecifics, and (ii) in an area where they can perform behaviours on terrain that reflects that of species in the wild.

CysE and CysK, the last two enzymes of the cysteine biosynthetic pathway, engage in a bienzyme complex, cysteine synthase, with yet incompletely characterized three-dimensional structure and regulatory function. Being absent in mammals, the two enzymes and their complex are attractive targets for antibacterial drugs. We have used hydrogen/deuterium exchange MS to unveil how complex formation affects the conformational dynamics of CysK and CysE. Our results support a model where CysE is present in solution as a dimer of trimers, and each trimer can bind one CysK homodimer. When CysK binds to one CysE monomer, intratrimer allosteric communication ensures conformational and dynamic symmetry within the trimer. Furthermore, a long-range allosteric signal propagates through CysE to induce stabilization of the interface between the two CysE trimers, preparing the second trimer for binding the second CysK with a nonrandom orientation. These results provide new molecular insights into the allosteric formation of the cysteine synthase complex and could help guide antibacterial drug design., Graphical Abstract, Highlights • HDX-MS reveals complex formation impact on conformational dynamics of CysK and CysE. • CysK binding ensures conformational symmetry within the CysE trimer. • Long-range allostery propagates through CysE stabilizing the inter-trimer interface. • Insights into the allostery of CS complex could help guide antibacterial drug design., In Brief We have used hydrogen/deuterium exchange MS to unveil the allosteric changes occurring during complex formation of CysE and CysK, the last two enzymes of cysteine biosynthetic pathway in bacteria. Significant changes in conformation and dynamics occur in each protein upon complex formation, including long distance intraprotein and interprotein communication. Being absent in mammals, both CysE and CysK represent potential targets for new antibacterial drugs, and our results on the formation and allostery of the complex could help guide drug development.

Background Traumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats. Methods Young adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure. Results Xenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation. Conclusions Our findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.

Summary Evolution on islands, together with the often extreme phenotypic changes associated with it, has attracted much interest from evolutionary biologists. However, measuring the rate of change of phenotypic traits of extinct animals can be challenging, in part due to the incompleteness of the fossil record. Here, we use combined molecular and fossil evidence to define the minimum and maximum rate of dwarfing in an extinct Mediterranean dwarf elephant from Puntali Cave (Sicily). 1 Despite the challenges associated with recovering ancient DNA from warm climates, 2 we successfully retrieved a mitogenome from a sample with an estimated age between 175,500 and 50,000 years. Our results suggest that this specific Sicilian elephant lineage evolved from one of the largest terrestrial mammals that ever lived 3 to an island species weighing less than 20% of its original mass with an estimated mass reduction between 0.74 and 200.95 kg and height reduction between 0.15 and 41.49 mm per generation. We show that combining ancient DNA with paleontological and geochronological evidence can constrain the timing of phenotypic changes with greater accuracy than could be achieved using any source of evidence in isolation.

Background Tri-axial accelerometers are frequently deployed on terrestrial quadrupedal mammals using collars, because they are easy to fit and are thought to have minimal impact on the subject. Collar-attached devices are not fixed to the body and can move independently of the body. This may result in inaccurate measures of acceleration, reducing the accuracy of measured body movement. We determined the effect of collar size and collar weight on acceleration measured by a collar-mounted accelerometer on a quadruped mammal. The aim was to suggest best practice for sizes and weights of collars on which to deploy tri-axial accelerometers. Using pygmy goats, Capra aegagrus hircus, which were trained to walk at different speeds (0.8–3.0 km/h) on a treadmill, we measured body acceleration using a collar-mounted tri-axial accelerometer, with different collar sizes (individual neck circumference + 1 cm to + 9 cm) and collar weight (0.4% to 1.2% of individual weight). Results There was a significant effect of collar size, collar weight and walking speed on measured acceleration. Measured acceleration was less accurate and more variable when collars were looser and heavier. To measure body acceleration more accurately, we found that collar size should be within 5 cm or 16% of an individual’s neck circumference when it was heavy (up to 1.2% of animal’s body weight) or within 7 cm (33%) of neck circumference if the collar was light (up to 0.6% of animal body weight). Conclusion We suggest that not only reporting collar size and weight for welfare purposes, but it is also important to consider these aspects for scientific rigour, to ensure data are collected as accurately as possible. We provide guidelines for researchers fitting collar-attached devices to ensure a higher degree of accuracy of recorded body acceleration.

Evolution on islands, and the often extreme phenotypic changes associated with it, has attracted much interest from evolutionary biologists. However, measuring the rate of change of a particular phenotypic trait of extinct animals can be challenging, due to the incompleteness of the fossil record. Here, we use combined molecular and fossil evidence to define the minimum and maximum rate of dwarfing in an extinct Mediterranean dwarf elephant from Puntali Cave (Sicily). Despite the challenges associated with recovering ancient DNA from warm climates, we successfully retrieved a mitogenome from a sample with an estimated age between 147,000 and 50,000 years. Our results suggest that this specific Sicilian elephant lineage evolved from one of the largest terrestrial mammals in the Pleistocene to a comparatively small-bodied island species, with an estimated average mass reduction of 0.79 - 18.45 kg and height reduction of 0.15 - 3.41 mm per generation. We show that combining ancient DNA, palaeontological and geochronological evidence can constrain the timing of phenotypic changes within narrower age boundaries than could be achieved using any source of evidence in isolation.

From the “Japan bashing” era of the 1980s, we have entered another era of “Japan passing,” this time even more serious than during the Clinton administration. Selling Japan was easy when the Japanese economy was the envy of the world. In 2018, however, academics and pundits need an extra incentive to talk about Japan. How might we restore international attention to Japan? We might do so by looking at Japan through a global prism. The history of Meiji and modern Japan have limited relevance for those outside Japan unless we change the fundamental focus of our examination. Investigations should aspire not simply to explain the when, where, what, and how of modern Japan. Rather, a history of Meiji and modern Japan should, most fundamentally, be fashioned as a history of the modern world. A global history of modern Japan recognizes the power of Edo era Japan; talks about Meiji as critical to the rise of modern economics, politics and empire; and understands Japan’s vital contribution to an internationalist and integrated twentieth- and twenty-first century. A global history of modern Japan is, in essence, a history of the modern world through the prism of Japan, and it indicates that continued Japanese leadership in the twenty-first century may help sustain a world political and economic order that lacks full American support.

Banana production in the north Queensland region of Australia represents 90% of the total production in Australia. However, in this region banana plantations are constrained by the need to protect environmentally sensitive areas such as the Great Barrier Reef, climatic impacts such as cyclones, high labour costs and soil-borne diseases. To overcome the constraints and improve the resilience of banana production systems, innovations are required, particularly regarding the management of the soil. Field experiments were established comparing vegetative groundcover, primarily pinto peanut (Arachis pintoi), to bare soil, and three nitrogen application treatments: 350 kg N ha-1 crop-1, 180 kg N ha-1 crop-1 applied as urea and 180 kg N ha-1 crop-1 applied as urea treated with 3,4-dimethyl pyrazole phosphate (Entec), a nitrification inhibitor. The agronomic aspects of banana production systems were determined by measurements of plant height, leaf emergence, bunch generation intervals and bunch characteristics. Additionally, measurements of leaf chlorophyll and nutrients were used to determine if management was restricting nutrient uptake. The first banana crop had reduced vegetative growth and an increased generation interval with the vegetative groundcover treatment compared to bare soil. Similarly, reduced N application reduced vegetative production of bananas and the Entec N treatment reduced bunch weight. However, fertiliser use efficiency was doubled in the lower N treatments relative to application of 350 kg N ha-1 crop-1. In the second crop, a reduction in the vegetative growth of bananas was again observed with lower N treatments, no significant differences in bunch weight was recorded. For banana producers to adopt agro-ecological production practices, penalties in vegetative plant growth need to be overcome, or benefits other than production need to be revealed, such as increased disease suppression.