Fifty years of capacity building in the search for new marine natural products.

The Convention on Biological Diversity, and the Nagoya Protocol in particular, provide a framework for the fair and equitable sharing of benefits arising from the utilization of biological resources and traditional knowledge, and ultimately aim to promote capacity-building in the developing world. However, measuring capacity-building is a challenging task due to its intangible nature. By compiling and analyzing a database of scientific peer-reviewed publications over a period of 50 y (1965 to 2015), we investigated capacity-building in global marine natural product discovery. We used publication and authorship metrics to assess how the capacity to become scientifically proficient, prolific, and independent has changed in bioprospecting countries. Our results show that marine bioprospecting is a dynamically growing field of research with continuously increasing numbers of participating countries, publications, and scientists. Yet despite longstanding efforts to promote equitability and scientific independence, not all countries have similarly increased their capacity to explore marine biodiversity within their national jurisdiction areas. Although developing countries show an increasing trend in the number of publications, a few developed countries still account for almost one-half of all publications in the field. Multiple lines of evidence suggest that economic capacity affects how well countries with species-rich marine ecosystems can scientifically explore those resources. Overall, the capacity-building data analyzed here provides a timely contribution to the ongoing international debate about access to and benefit-sharing of biological resources for countries exploring biodiversity within and outside their national jurisdiction areas.

Animal Models and Renal Biomarkers of Diabetic Nephropathy.

Diabetes mellitus (DM) is the first cause of end stage chronic kidney disease (CKD). Animal models of the disease can shed light on the pathogenesis of the diabetic nephropathy (DN) and novel and earlier biomarkers of the condition may help to improve diagnosis and prognosis. This review summarizes the most important features of animal models used in the study of DN and updates the most recent progress in biomarker research.

Detecting the macroevolutionary signal of species interactions.

Species interactions lie at the heart of many theories of macroevolution, from adaptive radiation to the Red Queen. Although some theories describe the imprint that interactions will have over long timescales, we are still missing a comprehensive understanding of the effects of interactions on macroevolution. Current research shows strong evidence for the impact of interactions on macroevolutionary patterns of trait evolution and diversification, yet many macroevolutionary studies have only a tenuous relationship to ecological studies of interactions over shorter timescales. We review current research in this area, highlighting approaches that explicitly model species interactions and connect them to broad-scale macroevolutionary patterns. We also suggest that progress has been made by taking an integrative interdisciplinary look at individual clades. We focus on African cichlids as a case study of how this approach can be fruitful. Overall, although the evidence for species interactions shaping macroevolution is strong, further work using integrative and model-based approaches is needed to spur progress towards understanding the complex dynamics that structure communities over time and space.

Eco-evolutionary feedbacks promote fluctuating selection and long-term stability of antagonistic networks.

Studies have shown the potential for rapid adaptation in coevolving populations and that the structure of species interaction networks can modulate the vulnerability of ecological systems to perturbations. Although the feedback loop between population dynamics and coevolution of traits is crucial for understanding long-term stability in ecological assemblages, modelling eco-evolutionary dynamics in species-rich assemblages is still a challenge. We explore how eco-evolutionary feedbacks influence trait evolution and species abundances in 23 empirical antagonistic networks. We show that, if selection due to antagonistic interactions is stronger than other selective pressures, eco-evolutionary feedbacks lead to higher mean species abundances and lower temporal variation in abundances. By contrast, strong selection of antagonistic interactions leads to higher temporal variation of traits and on interaction strengths. Our results present a theoretical link between the study of the species persistence and coevolution in networks of interacting species, pointing out the ways by which coevolution may decrease the vulnerability of species within antagonistic networks to demographic fluctuation.

Condition-dependent movement and dispersal in experimental metacommunities.

Dispersal and the underlying movement behaviour are processes of pivotal importance for understanding and predicting metapopulation and metacommunity dynamics. Generally, dispersal decisions are condition-dependent and rely on information in the broad sense, like the presence of conspecifics. However, studies on metacommunities that include interspecific interactions generally disregard condition-dependence. Therefore, it remains unclear whether and how dispersal in metacommunities is condition-dependent and whether rules derived from single-species contexts can be scaled up to (meta)communities. Using experimental protist metacommunities, we show how dispersal and movement depend on and are adjusted by the strength of interspecific interactions. We found that the predicting movement and dispersal in metacommunities requires knowledge on behavioural responses to intra- and interspecific interaction strengths. Consequently, metacommunity dynamics inferred directly from single-species metapopulations without taking interspecific interactions into account are likely flawed. Our work identifies the significance of condition-dependence for understanding metacommunity dynamics, stability and the coexistence and distribution of species.

Dispersal dynamics in food webs.

Studies of food webs suggest that limited nonrandom dispersal can play an important role in structuring food webs. It is not clear, however, whether density-dependent dispersal fits empirical patterns of food webs better than density-independent dispersal. Here, we study a spatially distributed food web, using a series of population-dispersal models that contrast density-independent and density-dependent dispersal in landscapes where sampled sites are either homogeneously or heterogeneously distributed. These models are fitted to empirical data, allowing us to infer mechanisms that are consistent with the data. Our results show that models with density-dependent dispersal fit the α, ß, and γ tritrophic richness observed in empirical data best. Our results also show that density-dependent dispersal leads to a critical distance threshold beyond which site similarity (i.e., ß tritrophic richness) starts to decrease much faster. Such a threshold can also be detected in the empirical data. In contrast, models with density-independent dispersal do not predict such a threshold. Moreover, preferential dispersal from more centrally located sites to peripheral sites does not provide a better fit to empirical data when compared with symmetric dispersal between sites. Our results suggest that nonrandom dispersal in heterogeneous landscapes is an important driver that shapes local and regional richness (i.e., α and γ tritrophic richness, respectively) as well as the distance-decay relationship (i.e., ß tritrophic richness) in food webs.

The contribution of intra- and interspecific tolerance variability to biodiversity changes along toxicity gradients.

The worldwide distribution of toxicants is an important yet understudied driver of biodiversity, and the mechanisms relating toxicity to diversity have not been adequately explored. Here, we present a community model integrating demography, dispersal and toxicant-induced effects on reproduction driven by intraspecific and interspecific variability in toxicity tolerance. We compare model predictions to 458 species abundance distributions (SADs) observed along concentration gradients of toxicants to show that the best predictions occur when intraspecific variability is five and ten times higher than interspecific variability. At high concentrations, lower settings of intraspecific variability resulted in predictions of community extinction that were not supported by the observed SADs. Subtle but significant species losses at low concentrations were predicted only when intraspecific variability dominated over interspecific variability. Our results propose intraspecific variability as a key driver for biodiversity sustenance in ecosystems challenged by environmental change.

Does sex speed up evolutionary rate and increase biodiversity?

Most empirical and theoretical studies have shown that sex increases the rate of evolution, although evidence of sex constraining genomic and epigenetic variation and slowing down evolution also exists. Faster rates with sex have been attributed to new gene combinations, removal of deleterious mutations, and adaptation to heterogeneous environments. Slower rates with sex have been attributed to removal of major genetic rearrangements, the cost of finding a mate, vulnerability to predation, and exposure to sexually transmitted diseases. Whether sex speeds or slows evolution, the connection between reproductive mode, the evolutionary rate, and species diversity remains largely unexplored. Here we present a spatially explicit model of ecological and evolutionary dynamics based on DNA sequence change to study the connection between mutation, speciation, and the resulting biodiversity in sexual and asexual populations. We show that faster speciation can decrease the abundance of newly formed species and thus decrease long-term biodiversity. In this way, sex can reduce diversity relative to asexual populations, because it leads to a higher rate of production of new species, but with lower abundances. Our results show that reproductive mode and the mechanisms underlying it can alter the link between mutation, evolutionary rate, speciation and biodiversity and we suggest that a high rate of evolution may not be required to yield high biodiversity.

Short-term evaluation of renal markers in overweight adult cats.

BACKGROUND: Obesity has been proposed as an independently risk factor for chronic kidney disease (CKD) in people, but its role in feline kidney function is unknown. OBJECTIVE: Obesity has been proposed as an independent risk factor for chronic kidney disease (CKD) in people, but its role in feline kidney function is unknown. This study prospectively evaluated the effect of overweight on the concentration of symmetric dimethylarginine (SDMA) and creatinine in a cohort of healthy cats. METHODS: Forty healthy adult cats were included, 14 with a body condition score (BCS) = 5 and 26 with a BCS > 5. Cats were examined every 6 months, for up to 12 months. SDMA and creatinine were measured at baseline and follow-up. RESULTS: No effect was found for time of follow-up (p = 0.072), overweight (p = 0.9442) or their interaction (p = 0.902) on SDMA, though a significant effect was found for age (p < 0.001) [older cats showing higher SDMA] and sex (p = 0.007) [male cats showing higher SDMA]. Regarding creatinine, no effect for time (p = 0.671), age (p = 0.061), overweight (p = 0.319) or the latter's interaction (p = 0.386) were found. CONCLUSIONS: In the short term, markers of renal function did not show an association with overweight. The role of obesity in feline kidney function still warrants further evaluation.

SOCS2 protects against chemical-induced hepatocellular carcinoma progression by modulating inflammation and cell proliferation in the liver.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, but the precise intracellular mechanisms underlying the progression of this inflammation associated cancer are not well established. SOCS2 protein plays an important role in the carcinogenesis of different tumors by regulating cytokine signalling through the JAK/STAT axis. However, its role in HCC is unclear. Here, we investigate the role of SOCS2 in HCC progression and its potential as HCC biomarker. The effects of SOCS2 in HCC progression were evaluated in an experimental model of diethylnitrosamine (DEN)-induced HCC in C57BL/6 and SOCS2 deficient mice, in cultured hepatic cells, and in liver samples from HCC patients. Mice lacking SOCS2 showed higher liver tumor burden with increased malignancy grade, inflammation, fibrosis, and proliferation than their controls. Protein and gene expression analysis reported higher pSTAT5 and pSTAT3 activation, upregulation of different proteins involved in survival and proliferation, and increased levels of proinflammatory and pro-tumoral mediators in the absence of SOCS2. Clinically relevant, downregulated expression of SOCS2 was found in neoplasia from HCC patients compared to healthy liver tissue, correlating with the malignancy grade. In summary, our data show that lack of SOCS2 increases susceptibility to chemical-induced HCC and suggest the tumor suppressor role of this protein by regulating the oncogenic and inflammatory responses mediated by STAT5 and STAT3 in the liver. Hence, SOCS2 emerges as an attractive target molecule and potential biomarker to deepen in the study of HCC treatment.

Evaluation of the ACTH stimulation test using a low dose of a depot formulation in healthy dogs and in dogs with untreated Cushing's syndrome.

The sensitivity of the adrenocorticotropic hormone (ACTH) stimulation test to detect Cushing's Syndrome (CS) using a depot formulation needs to be evaluated. The aims of this study were to propose a reference interval (RI) for cortisol values 1-hour after administration of a low-dose of depot ACTH in healthy dogs, and to evaluate the sensitivity of this test to detect CS, differentiating among types of CS based on ultrasound findings. Forty-one healthy dogs (20 males, 21 females) were prospectively included. Additionally, 90 dogs with CS (31 males, 59 females) were retrospectively included. Dogs with CS were ultrasonographically classified as follows: 44 dogs with symmetrical adrenomegaly consistent with pituitary-dependent hypercortisolism (PDH), 8 dogs with unilateral adrenomegaly and atrophy of the contralateral adrenal gland or unilateral or bilateral adrenomegaly with malignancy features consistent with adrenal-dependent hypercortisolism (ADH), 34 dogs with equivocal adrenal asymmetry (EAA) and 4 dogs with normal adrenal thickness. In healthy dogs, lower and upper limit of the 95% RI for 1-hour post-ACTH cortisol concentration and their 90% confidence intervals, were 4.4 (2.7-5.8) µg/dl and 18.4 (16.5-20.0) µg/dl, respectively. Post-ACTH cortisol concentration was above the RI in 90.0% (ci95%, 76.1-100) of dogs with CS. An elevated post-ACTH cortisol concentration was detected in 95.5% (ci95%, 76.1-100) of dogs with PDH, 62.5% (ci95%, 46.1-78.9) of dogs with ADH and 88.2% (ci95%, 69.1-100) of dogs with EAA. The sensitivity of the ACTH stimulation test using a low-dose of depot ACTH in high in dogs with CS.

Frequency-dependent selection predicts patterns of radiations and biodiversity.

Most empirical studies support a decline in speciation rates through time, although evidence for constant speciation rates also exists. Declining rates have been explained by invoking pre-existing niches, whereas constant rates have been attributed to non-adaptive processes such as sexual selection and mutation. Trends in speciation rate and the processes underlying it remain unclear, representing a critical information gap in understanding patterns of global diversity. Here we show that the temporal trend in the speciation rate can also be explained by frequency-dependent selection. We construct a frequency-dependent and DNA sequence-based model of speciation. We compare our model to empirical diversity patterns observed for cichlid fish and Darwin's finches, two classic systems for which speciation rates and richness data exist. Negative frequency-dependent selection predicts well both the declining speciation rate found in cichlid fish and explains their species richness. For groups like the Darwin's finches, in which speciation rates are constant and diversity is lower, speciation rate is better explained by a model without frequency-dependent selection. Our analysis shows that differences in diversity may be driven by incipient species abundance with frequency-dependent selection. Our results demonstrate that genetic-distance-based speciation and frequency-dependent selection are sufficient to explain the high diversity observed in natural systems and, importantly, predict decay through time in speciation rate in the absence of pre-existing niches.

Ultrasonographic evaluation of adrenal gland size in two body weight categories of healthy adult cats.

OBJECTIVES: Adrenal gland size and its association with body weight have been rarely evaluated in cats. This study was undertaken to assess the association between feline body weight and adrenal gland thickness, and to propose reference intervals (RIs) for adrenal gland thickness in healthy cats. METHODS: This was a cross-sectional study in which 39 healthy cats were included. The cats were divided into two weight categories, classified as ⩽4.0 kg and >4-8 kg of ideal body weight (with 13 and 26 cats in each group, respectively), which took into consideration the body condition score of the cats. All cats underwent an ultrasound examination that was taken from a subcostal position. Maximum dorsoventral thicknesses of the left (MTL) and right (MTR) adrenal glands were measured in a sagittal plane. RIs were obtained for the maximum thickness (MT), which included the MTLs and MTRs of each cat. RIs with the 90% confidence intervals were calculated according to American Society for Veterinary Clinical Pathology guidelines on RIs. RESULTS: No statistical differences for adrenal gland thickness were observed between the left and right (P = 0.543) adrenal glands or between male and female cats (P = 0.943). Mean MT was significantly greater in the group of cats weighing >4-8 kg compared with the group of cats weighing ⩽4 kg (3.7 ± 0.6 vs 3.2 ± 0.4 mm; P <0.005). The lower limit of the RI for MT was 2.4 mm (range 2.2-2.6 mm) in the group weighing ⩽4 kg and 2.6 mm (range 2.4-2.8 mm) in the group weighing >4-8 kg. The upper limit of the RI for MT was 3.9 mm (range 3.7-4.1 mm) in the group of cats weighing ⩽4 kg and 4.8 mm (range 4.6-5.1 mm) in the group of cats weighing >4-8 kg. CONCLUSIONS AND RELEVANCE: The use of RIs based on two group sizes allows for a more accurate ultrasonographic evaluation of adrenal gland thickness in cats. The maximum normal adrenal gland thickness is lower in smaller cats (3.9 mm for those weighing ⩽4 kg and 4.8 mm for those weighing >4-8 kg).

Ultrasound evaluation of adrenal gland size in clinically healthy dogs and in dogs with hyperadrenocorticism.

BACKGROUND: Precise reference intervals of adrenal gland thickness are required for detection of adrenomegaly in dogs with hyperadrenocorticism (HAC). METHODS: Eighty-six clinically healthy dogs were prospectively included, and 91 dogs with untreated HAC were retrospectively evaluated. Dorso-ventral adrenal gland thickness was ultrasonographically measured on the sagittal plane. Dogs were classified into four body weight categories, and those with HAC were also ultrasonographically classified as consistent with pituitary-dependent HAC (PDH), adrenal-dependent HAC (FAT), equivocal adrenal asymmetry (EAA), or normal adrenal thickness. RESULTS: The upper limits for left adrenal gland in clinically healthy dogs were 5.1 mm (≥2.5-5 kg), 5.5 mm (>5-10 kg), 6.4 mm (>10-20 kg), and 7.3 mm (>20-40 kg), and for right adrenal gland the upper limits were 5.3 mm (≥2.5-5 kg), 6.8 mm (>5-10 kg), 7.5 mm (>10-20 kg), and 8.7 mm (>20-40 kg). The sensitivity of ultrasound to detect adrenomegaly in dogs with HAC was 95.6%. Most dogs with HAC (56.0%) had ultrasound findings consistent with either PDH or FAT; however, EAA was commonly occurring in 39.6% of dogs with HAC. CONCLUSIONS: The sensitivity of ultrasonography to detect adrenomegaly in dogs with HAC is high when using four weight categories. EAA is common in dogs with HAC.

Cranial Structure of Varanus komodoensis as Revealed by Computed-Tomographic Imaging.

This study aimed to describe the anatomic features of the normal head of the Komodo dragon (Varanus komodoensis) identified by computed tomography. CT images were obtained in two dragons using a helical CT scanner. All sections were displayed with a bone and soft tissue windows setting. Head reconstructed, and maximum intensity projection images were obtained to enhance bony structures. After CT imaging, the images were compared with other studies and reptile anatomy textbooks to facilitate the interpretation of the CT images. Anatomic details of the head of the Komodo dragon were identified according to the CT density characteristics of the different organic tissues. This information is intended to be a useful initial anatomic reference in interpreting clinical CT imaging studies of the head and associated structures in live Komodo dragons.

Studying the heterogeneous pathogenesis of canine diabetes: Observational characterization of an island population.

BACKGROUND: Canine diabetes mellitus has mostly been studied in northern European, Australian and American populations, whereas other regions have received less attention. OBJECTIVES: We evaluated the epidemiological, clinical and histopathological features of diabetic dogs in Gran Canaria, Spain. METHODS: Prevalence and incidence were estimated. Clinical features were analysed, and serum and genomic DNA were obtained. Dogs with presumed idiopathic or immune-mediated diabetes, were DLA-typed and antibodies against GAD65 and IA-2 were assessed. Pancreases from ten diabetic dogs were examined and compared with pancreases from non-diabetic dogs. RESULTS AND CONCLUSIONS: Twenty-nine diabetic dogs were identified in a population of 5,213 (prevalence: 0.56%; incidence: 0.37%). Most were female (79%) and sexually intact (87% of females, 83% of males). Diabetes secondary to dioestrus (55.2%) and insulin-deficient diabetes (20.7%) were the most frequent types. Antibodies against GAD65 and IA-2 were identified in two out of five cases and DLA-genotyping revealed novel haplotypes. Breed distribution differed between diabetic and non-diabetic dogs. Reduced number of pancreatic islets and ß-cell mass were observed, with vacuolation of islet cells and ductal epithelium. In this population, where neutering is not standard practice, diabetes secondary to dioestrus is the most frequent diabetes subtype. Genetic susceptibility also differed from previous studies. These results support the heterogeneous pathogenesis of canine diabetes.

Risk of Secondary Infection Waves of COVID-19 in an Insular Region: The Case of the Balearic Islands, Spain.

The Spanish government declared the lockdown on March 14th, 2020 to tackle the fast-spreading of COVID-19. As a consequence, the Balearic Islands remained almost fully isolated due to the closing of airports and ports, these isolation measures and the home-based confinement have led to a low prevalence of COVID-19 in this region. We propose a compartmental model for the spread of COVID-19 including five compartments (Susceptible, Exposed, Presymptomatic Infective, Diseased, and Recovered), and the mobility between municipalities. The model parameters are calibrated with the temporal series of confirmed cases provided by the Spanish Ministry of Health. After calibration, the proposed model captures the trend of the official confirmed cases before and after the lockdown. We show that the estimated number of cases depends strongly on the initial dates of the local outbreak onset and the number of imported cases before the lockdown. Our estimations indicate that the population has not reached the level of herd immunization necessary to prevent future outbreaks. While the low prevalence, in comparison to mainland Spain, has prevented the saturation of the health system, this low prevalence translates into low immunization rates, therefore facilitating the propagation of new outbreaks that could lead to secondary waves of COVID-19 in the region. These findings warn about scenarios regarding after-lockdown-policies and the risk of second outbreaks, emphasize the need for widespread testing, and could potentially be extrapolated to other insular and continental regions.

Laboratory assessment of trilostane treatment in dogs with pituitary-dependent hyperadrenocorticism.

BACKGROUND: Results of ACTH stimulation test (ACTHst), pre- and post-trilostane serum cortisol concentrations (SCCs), urine concentration (urine-specific gravity [USG]), and urine cortisol : creatinine ratios (UCCRs) are common variables used to monitor trilostane treatment of dogs with pituitary-dependent hyperadrenocorticism (PDH). However, none has consistently discriminated dogs receiving an adequate dose (A) from those overdosed (O) or underdosed (U). OBJECTIVES: To assess and compare recommended monitoring variables, including serial SCCs in a cohort of dogs with PDH treated with trilostane. ANIMALS: Privately owned dogs with PDH (n = 22) and 3 healthy dogs (controls). METHODS: Prospective, multicenter, 2-day study. On day "a" (randomized): ACTHst was completed. Day "b" (>2 to <7 days later): SCCs were assessed -0.5 hours, immediately before, and 1, 2, 2.5, 3, 3.5, 4, 6, 8, and 12 hours after trilostane administration. On the first study day, urine collected at home was assessed for USG, UCCR and owner opinions regarding PDH were categorized as: A (clinical signs resolved), U (remains symptomatic), or ill (possible O). RESULTS: At 27 pairs of evaluations, 7 dogs were categorized as A, 19 U, and 1 possible O (excluded from the study). There was overlap in SCC results from the A and U dogs at every time point. Results of USG, UCCR, and ACTHst did not discriminate A from U dogs. Trilostane suppresses SCC within 1 hour of administration and its duration of action in most PDH dogs is <8 hours. CONCLUSIONS AND CLINICAL IMPORTANCE: No single variable or group of variables reliably discriminated A dogs from U dogs during trilostane treatment for PDH.

Positive associations among rare species and their persistence in ecological assemblages.

According to the competitive exclusion principle, species with low competitive abilities should be excluded by more efficient competitors; yet, they generally remain as rare species. Here, we describe the positive and negative spatial association networks of 326 disparate assemblages, showing a general organization pattern that simultaneously supports the primacy of competition and the persistence of rare species. Abundant species monopolize negative associations in about 90% of the assemblages. On the other hand, rare species are mostly involved in positive associations, forming small network modules. Simulations suggest that positive interactions among rare species and microhabitat preferences are the most probable mechanisms underpinning this pattern and rare species persistence. The consistent results across taxa and geography suggest a general explanation for the maintenance of biodiversity in competitive environments.

The temporal dynamics of resource use by frugivorous birds: a network approach.

Ecological network patterns are influenced by diverse processes that operate at different temporal rates. Here we analyzed whether the coupled effect of local abundance variation, seasonally phenotypic plastic responses, and species evolutionary adaptations might act in concert to shape network patterns. We studied the temporal variation in three interaction properties of bird species (number of interactions per species, interaction strength, and interaction asymmetry) in a temporal sequence of 28 plant-frugivore interaction networks spanning two years in a Mediterranean shrubland community. Three main hypotheses dealing with the temporal variation of network properties were tested, examining the effects of abundance, switching behavior between alternative food resources, and morphological traits in determining consumer interaction patterns. Our results demonstrate that temporal variation in consumer interaction patterns is explained by short-term variation in resource and bird abundances and seasonal dietary switches between alternative resources (fleshy fruits and insects). Moreover, differences in beak morphology are associated with differences in switching behavior between resources, suggesting an important role of foraging adaptations in determining network patterns. We argue that beak shape adaptations might determine generalist and specialist feeding behaviors and thus the positions of consumer species within the network. Finally, we provide a preliminary framework to interpret phylogenetic signal in plant-animal networks. Indeed, we show that the strength of the phylogenetic signal in networks depends on the relative importance of abundance, behavioral, and morphological variables. We show that these variables strongly differ in their phylogenetic signal. Consequently, we suggest that moderate and significant phylogenetic effects should be commonly observed in networks of species interactions.