The spatiotemporal context of individual specialization in resource use and environmental associations.

1. Individual niche specialization is widespread in natural populations and has key implications for higher levels of biological organization. This phenomenon, however, has been primarily quantified in resource niche axes, overlooking individual variation in environmental associations (i.e. abiotic conditions organisms experience). 2. Here, we explore what we can learn from a multidimensional perspective of individual niche specialization that integrates resource use and environmental associations into a common framework. 3. By combining predictions from theory and simple simulations, we illustrate how (i) multidimensional intraspecific niche variation and (ii) the spatiotemporal context of interactions between conspecifics scale up to shape emergent patterns of the population niche. 4. Contemplating individual specialization as a multidimensional, unifying concept across biotic and abiotic niche axes is a fundamental step towards bringing this concept closer to the n-dimensional niche envisioned by Hutchinson.

1. A especialização individual de nicho é prevalente em populações naturais e tem implicações importantes para níveis de organização biológica superiores. Esse fenômeno, entretanto, tem sido principalmente quantificado em eixos do nicho que representam o uso de recursos, negligenciando a variação individual em associações ambientais (i.e. as condições abióticas que organismos experimentam). 2. Aqui, exploramos o que podemos aprender a partir de uma perspectiva multidimensional da especialização individual que integra o uso de recursos e associações ambientais em uma abordagem única. 3. Ao combinar predições da teoria e simulações simples, ilustramos como (i) a variação intraespecífica multidimensional de nicho e (ii) o contexto espaço­temporal de interações entre conspecíficos podem moldar padrões emergentes do nicho de populações. 4. Encarar a especialização individual como um conceito multidimensional e unificador em eixos do nicho bióticos e abióticos é um passo fundamental na direção de aproximar esse conceito do nicho n­dimensional idealizado por Hutchinson.

Top-down effects of intraspeciflic predator behavioral variation.

Among-individual variation in predator traits is ubiquitous in nature. However, variation among populations in this trait variation has been seldom considered in trophic dynamics. This has left unexplored (a) to what degree does among-individual variation in predator traits regulate prey populations and (b) to what degree do these effects vary spatially. We address these questions by examining how predator among-individual variation in functional traits shapes communities across habitats of varying structural complexity, in field conditions. We manipulated Chinese mantis (Tenodera sinensis) density (six or twelve individuals) and behavioral trait variability (activity level by movement on an open field) in experimental patches of old fields with varying habitat complexity (density of plant material). Then, we quantified their impacts on lower trophic levels, specifically prey (arthropods > 4 mm) and plant biomass. Predator behavioral variability only altered prey biomass in structurally complex plots, and this effect depended on mantis density. In the plots with the highest habitat complexity and mantis density, behaviorally variable groups decreased prey biomass by 40.3%. In complex plots with low mantis densities, low levels of behavioral variability decreased prey biomass by 32.2%. Behavioral variability and low habitat complexity also changed prey community composition, namely by increasing ant biomass by 881%. Our results demonstrate that among-individual trait variation can shape species-rich prey communities. Moreover, these effects depend on both predator density and habitat complexity. Incorporating this important facet of ecological diversity revealed normally unnoticed effects of functional traits on the structure and function of food webs.

Guidelines-based therapeutic strategies for controlling hypertension in non-controlled hypertensive patients followed by family physicians in primary health care in Portugal: the GPHT-PT study.

PURPOSE: In a prospective open study, with intervention, conducted in Primary Health Care Units by General Practitioners (GPs) in Portugal, the effectiveness of a single pill of candesartan/amlodipine (ARB/amlodipine), as the only anti-hypertension (anti-HTN) medication, in adult patients with uncontrolled HTN (BP > 140/or > 90 mm Hg), either previously being treated with anti-HTN monotherapies (Group I), or combinations with hydrochlorothiazide (HCTZ) (Group II), or not receiving medication at all (Group III), was evaluated across 12-weeks after implementation of the new therapeutic measure. MATERIALS AND METHODS: A total of 118 GPs recruited patients with uncontrolled HTN who met inclusion/exclusion criteria. Participants were assigned, according to severity, one of 3 (morning) fixed combination candesartan/amlodipine dosage (8/5 or 16/5 or 16/10 mg/day) and longitudinally evaluated in 3 visits (v0, v6 and v12 weeks). Office blood pressure was measured in each visit, and control of HTN was defined per guidelines (BP< 140/90 mmHg). RESULTS: Of the 1234 patients approached, 752 (age 61 ± 10 years, 52% women) participated in the study and were assigned to groups according to previous treatment conditions. The 3 groups exhibited a statistically significant increased control of blood pressure after receiving the fixed combination candesartan/amlodipine dosage. The overall proportion of controlled HTN participants increased from 0,8% at v0 to 82% at v12. The mean arterial blood pressure values decreased from SBP= 159.0 (± 13.0) and DBP= 91.1 (± 9.6) at baseline to SBP= 132,1 (± 11.3) and DBP= 77,5 (± 8.8) at 12 weeks (p < 0.01). Results remained consistent when controlling for age and sex. CONCLUSION: In patients with uncontrolled HTN, therapeutic measures in accordance with guidelines, with a fixed combination candesartan/amlodipine, allowed to overall achieve HTN control at 12 weeks in 82% of previously uncontrolled HTN patients, reinforcing the advantages of these strategies in primary clinical practice.

What is the context?Arterial hypertension (HTN) represents the main risk factor for cause of death from cardiovascular disease (CV). Adequate control of hypertension reduces CV risk and significantly prevents CV events and associated morbidity and mortality. This requires patients' adherence and persistence in implemented treatment and the achievement of tension targets that are related to the reduction of CV risk. The latest international recommendations indicate that hypertension control is insufficient in most countries. In Portugal, hypertension control is <43% and a significant number of patients treated do not comply with the recommendations.What is new?In a prospective, interventional, and multicentre study, carried out by General Practitioners (GPs) in Primary Health Care Units across Portugal, the objective was to determine (i) whether the presence of uncontrolled hypertension results from non-compliance with the provisions of the recommendations and the Integrated Care Process (PAI) of the Direção Geral de Saúde (DGS), i.e. inappropriate use of monotherapies or inadequate low doses of combinations of antihypertensives, and (ii) whether the adjustment of hypertension therapies, favouring the schemes provided in the recommendations, allows adequate control of arterial hypertension, in previously uncontrolled patients, when these are closely monitored in a 12-week time period.What is the impact?When the guidelines' therapeutic protocol is followed, as established for each identified group of patients (monotherapy, hydrochlorothiazide, and no medication), results indicate a marked and statistically significant improvements in both SBP and DBP values and hypertension control across time.

A prodrug strategy for the in vivo imaging of aldehyde dehydrogenase activity.

Therapy resistance is one of the biggest challenges facing clinical oncology. Despite a revolution in new anti-cancer drugs targeting multiple components of the tumour microenvironment, acquired or innate resistance frequently blunts the efficacy of these treatments. Non-invasive identification of drug-resistant tumours will enable modification of the patient treatment pathway through the selection of appropriate second-line treatments. Here, we have designed a prodrug radiotracer for the non-invasive imaging of aldehyde dehydrogenase 1A1 (ALDH1A1) activity. Elevated ALDH1A1 activity is a marker of drug-resistant cancer cells, modelled here with matched cisplatin-sensitive and -resistant human SKOV3 ovarian cancer cells. The aromatic aldehyde of our prodrug radiotracer was intracellularly liberated by esterase cleavage of the geminal diacetate and specifically trapped by ALDH through its conversion to the charged carboxylic acid. Through this mechanism of action, ALDH-specific retention of our prodrug radiotracer in the drug-resistant tumour cells was twice as high as the drug-sensitive cells. Acylal masking of the aldehyde afforded a modest protection from oxidation in the blood, which was substantially improved in carrier-added experiments. In vivo positron emission tomography imaging of tumour-bearing mice produced high tumour-to-background images and radiotracer uptake in high ALDH-expressing organs but was unable to differentiate between drug-sensitive and drug-resistant tumours. Alternative strategies to protect the labile aldehyde are currently under investigation.

Specific sequence of arrival promotes coexistence via spatial niche pre-emption by the weak competitor.

Historical contingency, such as the order of species arrival, can modify competitive outcomes via niche modification or pre-emption. However, how these mechanisms ultimately modify stabilising niche and average fitness differences remains largely unknown. By experimentally assembling two congeneric spider mite species feeding on tomato plants during two generations, we show that order of arrival affects species' competitive ability and changes the outcome of competition. Contrary to expectations, order of arrival did not cause positive frequency dependent priority effects. Instead, coexistence was predicted when the inferior competitor (Tetranychus urticae) arrived first. In that case, T. urticae colonised the preferred feeding stratum (leaves) of T. evansi leading to spatial niche pre-emption, which equalised fitness and reduced niche differences, driving community assembly to a close-to-neutrality scenario. Our study demonstrates how the order of species arrival and the spatial context of competitive interactions may jointly determine whether species can coexist.

Animal tracking moves community ecology: Opportunities and challenges.

Individual decisions regarding how, why and when organisms interact with one another and with their environment scale up to shape patterns and processes in communities. Recent evidence has firmly established the prevalence of intraspecific variation in nature and its relevance in community ecology, yet challenges associated with collecting data on large numbers of individual conspecifics and heterospecifics have hampered integration of individual variation into community ecology. Nevertheless, recent technological and statistical advances in GPS-tracking, remote sensing and behavioural ecology offer a toolbox for integrating intraspecific variation into community processes. More than simply describing where organisms go, movement data provide unique information about interactions and environmental associations from which a true individual-to-community framework can be built. By linking the movement paths of both conspecifics and heterospecifics with environmental data, ecologists can now simultaneously quantify intraspecific and interspecific variation regarding the Eltonian (biotic interactions) and Grinnellian (environmental conditions) factors underpinning community assemblage and dynamics, yet substantial logistical and analytical challenges must be addressed for these approaches to realize their full potential. Across communities, empirical integration of Eltonian and Grinnellian factors can support conservation applications and reveal metacommunity dynamics via tracking-based dispersal data. As the logistical and analytical challenges associated with multi-species tracking are surmounted, we envision a future where individual movements and their ecological and environmental signatures will bring resolution to many enduring issues in community ecology.

Polymorphism promotes edge utilization by marsh crabs.

Understanding how habitat edges affect ecological processes is crucial given widespread and increasing modifications to natural landscapes. Resource specialization is a key factor affecting among-species edge responses, but we know little about how intraspecific resource use variation mediates edge utilization. Here, we integrate stomach content analysis, geometric morphometrics and feeding experiments to explore the role of resource polymorphism in mediating marsh crab (Panopeus obesus) foraging within the marsh-oyster reef boundary. Stomachs of edge individuals contained a greater proportion of morphologically defended edge prey (bivalves) compared to core marsh individuals, and edge individuals possessed relatively tall and robust claw morphology for manipulating such prey. We further show experimentally that phenotypic changes of edge P. obesus are associated with enhanced feeding efficiency on small, but not large edge prey. Morphological and ecological traits of edge P. obesus overlapped with the edge-occurring congener, P. herbstii, suggesting some degree of functional convergence despite the potential for interspecific competition within edges. Though this polymorphism is likely plastic, the success of P. obesus along edges could subsidize predator production within marshes and alter top-down pressure across mosaic estuarine landscapes. More generally, our study reveals polymorphism as a driver of edge utilization, while yielding new insight into the processes that maintain or erode spatial niche differentiation within predator guilds.

Prevalence and Characteristics of Chronic Pain Among Patients in Portuguese Primary Care Units.

INTRODUCTION: Chronic pain (CP) negatively impacts the lives of almost 2 billion people worldwide, including approximately 37% of adults in Portugal. As most of these patients are followed by a general practitioner, identifying the prevalence and characterizing the pain of patients who visit primary care units will provide valuable insights into the CP landscape in Portugal. METHODS: To achieve this goal, an observational, cross-sectional study was conducted in 58 primary care units of mainland Portugal between June 2017 and March 2018. Interviews were conducted with 8445 patients, and 578 CP patients were characterized. RESULTS: We observed that one third of patients suffered from CP, and of these, approximately one third felt that their pain management was insufficient. Most of the population was 55 years old or older, retired, and had more than three comorbidities. However, age and the number and type of comorbidities were not predictors of pain intensity. Additionally, most of the population had pain or discomfort that hindered their mobility and the performance of their everyday activities. This decrease in the quality of life led to feelings of anxiety and depression, which were associated with pain intensity. CONCLUSION: Given the high prevalence of CP, strategies to improve the quality of life of these patients and decrease the negative impacts, as well as awareness campaigns to increase the populations' knowledge of this condition, are essential for the suitable and timely treatment of CP.

Assessing the repeatability, robustness to disturbance, and parent-offspring colony resemblance of collective behavior.

Groups of animals possess phenotypes such as collective behaviour, which may determine the fitness of group members. However, the stability and robustness to perturbations of collective phenotypes in natural conditions is not established. Furthermore, whether group phenotypes are transmitted from parent to offspring groups with fidelity is required for understanding how selection on group phenotypes contributes to evolution, but parent-offspring resemblance at the group level is rarely estimated. We evaluated the repeatability, robustness to perturbation and parent-offspring resemblance of collective foraging aggressiveness in colonies of the social spider Anelosimus eximius. Among-colony differences in foraging aggressiveness were consistent over time but changed if the colony was perturbed through the removal of individuals or via individuals' removal and subsequent return. Offspring and parent colony behaviour were correlated at the phenotypic level, but only once the offspring colony had settled after being translocated, and the correlation overlapped with zero at the among-colony level. The parent-offspring resemblance was not driven by a shared elevation but could be due to other environmental factors. The behaviour of offspring colonies in a common garden laboratory setting was not correlated with the behaviour of the parent colony nor with the same colony's behaviour once it was returned to the field. The phenotypes of groups represent a potentially important tier of biological organization, and assessing the stability and heritability of such phenotypes helps us better understand their role in evolution.

Iron(II)/Persulfate Mediated Newman-Kwart Rearrangement.

Herein, we report that iron(II)/ammonium persulfate in aqueous acetonitrile mediates the Newman-Kwart rearrangement of O-aryl carbamothioates. Electron-rich substrates react rapidly under moderate heating to afford the rearranged products in excellent yields. The mild conditions, rapid reaction rates, and suitability for scale up offers immediate practical benefits to access functionalized thiophenols.

Behaviour, morphology and microhabitat use: what drives individual niche variation?

Generalist populations are often composed of individuals each specialized on only a subset of the resources exploited by the entire population. However, the traits underlying such niche variation remain underexplored. Classically, ecologists have focused on understanding why populations vary in their degree of intraspecific niche variation, with less attention paid to how individual-level traits lead to intraspecific differences in niches. We investigated how differences in behaviour, morphology and microhabitat affect niche variation between and within individuals in two species of spider Anelosimus studiosus and Theridion murarium. Our results convey that behaviour (i.e. individual aggressiveness) was a key driver of intraspecific trophic variation in both species. More aggressive individuals capture more prey, but particularly more Coleoptera, Hymenoptera and Diptera. These findings suggest that behavioural traits play a critical role in determining individuals' diet and that behaviour can be a powerful force in driving intraspecific niche variation.

Competition and resource breadth shape niche variation and overlap in multiple trophic dimensions.

Competition plays a central role in the maintenance of biodiversity. A backbone of classic niche theory is that local coexistence of competitors is favoured by the contraction or divergence of species' niches. However, this effect should depend on the diversity of resources available in the local environment, particularly when resources vary in multiple ecological dimensions. Here, we investigated how available resource breadth (i.e. prey diversity) and competition together shape multidimensional niche variation (between and within individuals) and interspecific niche overlap in 42 populations of congeneric tropical frog species. We modelled realized niches in two key trophic dimensions (prey size and carbon stable isotopes) and sampled available food resources to quantify two-dimensional resource breadth. We found a 14-fold variation in multidimensional population niche width across populations, most of which was accounted for by within-individual diet variation. This striking variation was predicted by an interaction whereby individual niche breadth increased with resource breadth and decreased with the number of congeneric competitors. These ecological gradients also interact to influence the degree of niche overlap between species, which surprisingly decreased with population total niche width, providing novel insights on how similar species can coexist in local communities. Together, our results emphasize that patterns of exploitation of resources in multiple dimensions are driven by both competitive interactions and extrinsic factors such as local resource breadth.

Habitat structure changes the relationships between predator behavior, prey behavior, and prey survival rates.

The individual behavioral traits of predators and prey sometimes determine the outcome of their interactions. Here, we examine whether changes to habitat complexity alter the effects of predator and prey behavior on their survival rates. Specifically, we test whether behavioral traits (activity level, boldness, and perch height) measured in predators and prey or multivariate behavioral volumes best predict the survival rates of both trophic levels in staged mesocosms with contrasting structural complexity. Behavioral volumes and hypervolumes are a composite group-level behavioral diversity metric built from the individual-level behavioral traits we measured in predators and prey. We stocked mesocosms with a host plant and groups of cannibalistic predators (n = 5 mantises/mesocosm) and their prey (n = 15 katydids/mesocosm), and mesocosms varied in the presence/absence of additional non-living climbing structures. We found that mantis survival rates were unrelated to any behavioral metric considered here, but were higher in structurally complex mesocosms. Unexpectedly, katydids were more likely to survive when mantis groups occupied larger behavioral volumes, indicating that more behaviorally diverse predator groups are less lethal. Katydid mortality was also increased when both predators and prey exhibited higher average perch heights, but this effect was increased by the addition of supplemental structure. This is consistent with the expectation that structural complexity increases the effect of intraspecific behavioral variation on prey survival rates. Collectively, these results convey that the effects of predator and prey behavior on prey survival could depend highly on the environment in which they are evaluated.

Measurement of Tumor Antioxidant Capacity and Prediction of Chemotherapy Resistance in Preclinical Models of Ovarian Cancer by Positron Emission Tomography.

PURPOSE: Drug resistance is a major obstacle for the effective treatment of patients with high-grade serous ovarian cancer (HGSOC). Currently, there is no satisfactory way to identify patients with HGSOC that are refractive to the standard of care. Here, we propose the system xc - radiotracer (4S)-4-(3-[18F]fluoropropyl)-l-glutamate ([18F]FSPG) as a non-invasive method to measure upregulated antioxidant pathways present in drug-resistant HGSOC. EXPERIMENTAL DESIGN: Using matched chemotherapy sensitive and resistant ovarian cancer cell lines, we assessed their antioxidant capacity and its relation to [18F]FSPG uptake, both in cells and in animal models of human ovarian cancer. We identified the mechanisms driving differential [18F]FSPG cell accumulation and evaluated [18F]FSPG tumor uptake as predictive marker of treatment response in drug-resistant tumors. RESULTS: High intracellular glutathione (GSH) and low reactive oxygen species corresponded to decreased [18F]FSPG cell accumulation in drug-resistant versus drug-sensitive cells. Decreased [18F]FSPG uptake in drug-resistant cells was a consequence of changes in intracellular cystine, a key precursor in GSH biosynthesis. In vivo, [18F]FSPG uptake was decreased nearly 80% in chemotherapy-resistant A2780 tumors compared with parental drug-sensitive tumors, with nonresponding tumors displaying high levels of oxidized-to-reduced GSH. Treatment of drug-resistant A2780 tumors with doxorubicin resulted in no detectable change in tumor volume, GSH, or [18F]FSPG uptake. CONCLUSIONS: This study demonstrates the ability of [18F]FSPG to detect upregulated antioxidant pathways present in drug-resistant cancer. [18F]FSPG may therefore enable the identification of patients with HGSOC that are refractory to standard of care, allowing the transferal of drug-resistant patients to alternative therapies, thereby improving outcomes in this disease.

Mapping Aldehyde Dehydrogenase 1A1 Activity using an [18 F]Substrate-Based Approach.

Aldehyde dehydrogenases (ALDHs) catalyze the oxidation of aldehydes to carboxylic acids. Elevated ALDH expression in human cancers is linked to metastases and poor overall survival. Despite ALDH being a poor prognostic factor, the non-invasive assessment of ALDH activity in vivo has not been possible due to a lack of sensitive and translational imaging agents. Presented in this report are the synthesis and biological evaluation of ALDH1A1-selective chemical probes composed of an aromatic aldehyde derived from N,N-diethylamino benzaldehyde (DEAB) linked to a fluorinated pyridine ring either via an amide or amine linkage. Of the focused library of compounds evaluated, N-ethyl-6-(fluoro)-N-(4-formylbenzyl)nicotinamide 4 b was found to have excellent affinity and isozyme selectivity for ALDH1A1 in vitro. Following 18 F-fluorination, [18 F]4 b was taken up by colorectal tumor cells and trapped through the conversion to its 18 F-labeled carboxylate product under the action of ALDH. In vivo positron emission tomography revealed high uptake of [18 F]4 b in the lungs and liver, with radioactivity cleared through the urinary tract. Oxidation of [18 F]4 b, however, was observed in vivo, which may limit the tissue penetration of this first-in-class radiotracer.