Effects of chlordiazepoxide on extinction and re-acquisition of operant behaviour in mice

Relatively little is known about the role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in extinction of appetitively motivated tasks. The benzodiazepine (BZ) chlordiazepoxide (CDP) was administered during extinction and re-acquisition of lever pressing by mice following food reinforced discrete-trial fixed-ratio 5 (FR-5) training. Typical FR behaviour was established during baseline training and persisted for several extinction sessions. There were 15 extinction sessions in all, followed by six re-acquisition sessions where food reinforcement was re-introduced. In a 2x2x2 between-group design, CDP (15 mg/kg) or vehicle injections were given prior to either the last two food reinforcement sessions and the first 10 extinction sessions, or the final five extinction sessions, or the six re-acquisition sessions. Initially CDP had no effect on the rate of extinction, but after several extinction sessions it significantly facilitated it. Surprisingly, if CDP was administered only after several sessions of extinction, it immediately produced facilitation. Thus the delayed effects of CDP are not due to drug accumulation. These data suggest that some neural change must occur before CDP can affect extinction processes. In re-acquisition sessions, CDP facilitated the reinstatement of food-reinforced lever pressing. Implications for neural and behavioural accounts of operant extinction are discussed.

Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour

Several recent studies have shown that reducing gamma-aminobutyric acid (GABA)-mediated neurotransmission retards extinction of aversive conditioning. However, relatively little is known about the effect of GABA on extinction of appetitively motivated tasks. We examined the effect of chlordiazepoxide (CDP), a classical benzodiazepine (BZ) and two novel subtype-selective BZs when administered to male C57Bl/6 mice during extinction following training on a discrete-trial fixed-ratio 5 (FR5) food reinforced lever-press procedure. Initially CDP had no effect, but after several extinction sessions CDP significantly facilitated extinction, i.e. slowed responding, compared with vehicle-treated mice. This effect was not due to drug accumulation because mice switched from vehicle treatment to CDP late in extinction showed facilitation immediately. Likewise, this effect could not be attributed to sedation because the dose of CDP used (15 mg/kg i.p.) did not suppress locomotor activity. The two novel subtype-selective BZ partial agonists, L-838417 and TP13, selectively facilitated extinction in similar fashion to CDP. The non-GABAergic anxiolytic buspirone was also tested and found to have similar effects when administered at a non-sedating dose. These studies demonstrate that GABA-mediated processes are important during extinction of an appetitively motivated task, but only after the animals have experienced several extinction sessions.

Biology as an agent of chemical and mineralogical change in soil

Earthworms have a significant impact on the functioning of soils and the processes that occur within them. Here we review our work on the impact of earthworms on soil mineralogy and chemistry, in particular focusing on the contribution of earthworms to mineral weathering and calcium carbonate in soils and the impact that earthworms have on metal mobility at contaminated sites.

Breeding biology of the White-headed Vulture Trigonoceps occipitalis in Kruger National Park, South Africa

Information on the breeding biology of the White-headed Vulture Trigonoceps occipitalis is limited and published data are few. Within the Kruger National Park in north-east South Africa there is a regionally important population of about 60 White-headed Vulture pairs, of which 22 pairs were monitored for five years between 2008 and 2012 to determine key aspects of their breeding biology. Across 73 pair/years the mean productivity of 55 breeding attempts was 0.69 chicks per pair. Median egg-laying date across all of the Kruger National Park was 27 June, but northern nests were approximately 30 d later than southern nests. Mean (SD) nearest-neighbour distance was 9 976  7 965 m and inter-nest distances ranged from 1 400 m to more than 20 km, but this did not differ significantly between habitat types. Breeding productivity did not differ significantly between habitat types. The results presented here are the first for this species in Kruger National Park and provide details against which future comparisons can be made.

Biology and reproductive behavior of Murgantia histrionica (Heteroptera: Pentatomidae)

Life history parameters and reproductive behaviors of the harlequin bug, Murgantia histrionica Hahn (Heteroptera: Pentatomidae), were determined. Total developmental time from egg to adult was ≈48 d. After a sexual maturation period of ≈7 d, both sexes mated repeatedly, with females laying multiple egg masses of 12 eggs at intervals of 3 d. Adult females lived an average of 41 d, whereas adult males lived an average of 25 d. Courtship and copulation activities peaked in the middle of the photophase. In mating experiments in which mixed sex pairs of virgin and previously mated bugs were combined in all possible combinations, the durations of courtship and copulation by virgin males were significantly longer with both virgin and previously mated females than the same behaviors for previously mated males. When given a choice between a virgin or previously mated female, previously mated males preferred to mate with virgin females, whereas virgin males showed no preference for virgin over previously mated females. Analyses of mating behaviors with ethograms and behavioral transition matrices suggested that a primary reason for failure to copulate by virgin males was the incorrect rotation of their pygophores to the copulation position, so that successful alignment of the genitalia could not occur.

Regulation of early steps of GPVI signal transduction by phosphatases: a systems biology approach

We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2), provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in controlling the rate, and therefore extent, of GPVI-stimulated platelet activation.

Which intrinsic traits predict vulnerability to extinction depends on the actual threatening processes

Understanding what makes some species more vulnerable to extinction than others is an important challenge for conservation. Many comparative analyses have addressed this issue exploring how intrinsic and extrinsic traits associate with general estimates of vulnerability. However, these general estimates do not consider the actual threats that drive species to extinction and hence, are more difficult to translate into effective management. We provide an updated description of the types and spatial distribution of threats that affect mammals globally using data from the IUCN for 5941 species of mammals. Using these data we explore the links between intrinsic species traits and specific threats in order to identify key intrinsic features associated with particular drivers of extinction. We find that families formed by small-size habitat specialists are more likely to be threatened by habitat-modifying processes; whereas, families formed by larger mammals with small litter sizes are more likely to be threatened by processes that directly affect survival. These results highlight the importance of considering the actual threatening process in comparative studies. We also discuss the need to standardize and rank threat importance in global assessments such as the IUCN Red List to improve our ability to understand what makes some species more vulnerable to extinction than others.

Variability in life-history and ecological traits is a buffer against extinction in mammals

Anthropogenic degradation of the world's ecosystems is leading to a widespread and accelerating loss of biodiversity. However, not all species respond equally to existing threats, raising the question: what makes a species more vulnerable to extinction? We propose that higher intraspecific variability may reduce the risk of extinction, as different individuals and populations within a species may respond differently to occurring threats. Supporting this prediction, our results show that mammalian species with more variable adult body masses, litter sizes, sexual maturity ages and population densities are less vulnerable to extinction. Our findings reveal the role of local variation among populations, particularly of large mammals, as a buffering mechanism against extinction, and emphasise the importance of considering trait variation in comparative analyses and conservation management.

Biases in comparative analyses of extinction risk: mind the gap

1. Comparative analyses are used to address the key question of what makes a species more prone to extinction by exploring the links between vulnerability and intrinsic species’ traits and/or extrinsic factors. This approach requires comprehensive species data but information is rarely available for all species of interest. As a result comparative analyses often rely on subsets of relatively few species that are assumed to be representative samples of the overall studied group. 2. Our study challenges this assumption and quantifies the taxonomic, spatial, and data type biases associated with the quantity of data available for 5415 mammalian species using the freely available life-history database PanTHERIA. 3. Moreover, we explore how existing biases influence results of comparative analyses of extinction risk by using subsets of data that attempt to correct for detected biases. In particular, we focus on links between four species’ traits commonly linked to vulnerability (distribution range area, adult body mass, population density and gestation length) and conduct univariate and multivariate analyses to understand how biases affect model predictions. 4. Our results show important biases in data availability with c.22% of mammals completely lacking data. Missing data, which appear to be not missing at random, occur frequently in all traits (14–99% of cases missing). Data availability is explained by intrinsic traits, with larger mammals occupying bigger range areas being the best studied. Importantly, we find that existing biases affect the results of comparative analyses by overestimating the risk of extinction and changing which traits are identified as important predictors. 5. Our results raise concerns over our ability to draw general conclusions regarding what makes a species more prone to extinction. Missing data represent a prevalent problem in comparative analyses, and unfortunately, because data are not missing at random, conventional approaches to fill data gaps, are not valid or present important challenges. These results show the importance of making appropriate inferences from comparative analyses by focusing on the subset of species for which data are available. Ultimately, addressing the data bias problem requires greater investment in data collection and dissemination, as well as the development of methodological approaches to effectively correct existing biases.

Dinosaurs in decline tens of millions of years before their final extinction

Whether dinosaurs were in a long-term decline or whether they were reigning strong right up to their final disappearance at the Cretaceous–Paleogene (K-Pg) mass extinction event 66 Mya has been debated for decades with no clear resolution. The dispute has continued unresolved because of a lack of statistical rigor and appropriate evolutionary framework. Here, for the first time to our knowledge, we apply a Bayesian phylogenetic approach to model the evolutionary dynamics of speciation and extinction through time in Mesozoic dinosaurs, properly taking account of previously ignored statistical violations. We find overwhelming support for a long-term decline across all dinosaurs and within all three dinosaurian subclades (Ornithischia, Sauropodomorpha, and Theropoda), where speciation rate slowed down through time and was ultimately exceeded by extinction rate tens of millions of years before the K-Pg boundary. The only exceptions to this general pattern are the morphologically specialized herbivores, the Hadrosauriformes and Ceratopsidae, which show rapid species proliferations throughout the Late Cretaceous instead. Our results highlight that, despite some heterogeneity in speciation dynamics, dinosaurs showed a marked reduction in their ability to replace extinct species with new ones, making them vulnerable to extinction and unable to respond quickly to and recover from the final catastrophic event.

Nothing is safe: intolerance of uncertainty is associated with compromised fear extinction learning

Extinction-resistant fear is considered to be a central feature of pathological anxiety. Here we sought to determine if individual differences in Intolerance of Uncertainty (IU), a potential risk factor for anxiety disorders, underlies compromised fear extinction. We tested this hypothesis by recording electrodermal activity in 38 healthy participants during fear acquisition and extinction. We assessed the temporality of fear extinction, by examining early and late extinction learning. During early extinction, low IU was associated with larger skin conductance responses to learned threat vs. safety cues, whereas high IU was associated with skin conductance responding to both threat and safety cues, but no cue discrimination. During late extinction, low IU showed no difference in skin conductance between learned threat and safety cues, whilst high IU predicted continued fear expression to learned threat, indexed by larger skin conductance to threat vs. safety cues. These findings suggest a critical role of uncertainty-based mechanisms in the maintenance of learned fear.

Larger brain size indirectly increases vulnerability to extinction in mammals

Although previous studies have addressed the question of why large brains evolved, we have limited understanding of potential beneficial or detrimental effects of enlarged brain size in the face of current threats. Using novel phylogenetic path analysis, we evaluated how brain size directly and indirectly, via its effects on life-history and ecology, influences vulnerability to extinction across 474 mammalian species. We found that larger brains, controlling for body size, indirectly increase vulnerability to extinction by extending the gestation period, increasing weaning age, and limiting litter sizes. However, we found no evidence of direct, beneficial or detrimental, effects of brain size on vulnerability to extinction, even when we explicitly considered the different types of threats that lead to vulnerability. Order-specific analyses revealed qualitatively similar patterns for Carnivora and Artiodactyla. Interestingly, for Primates, we found that larger brain size was directly (and indirectly) associated with increased vulnerability to extinction. Our results indicate that under current conditions the constraints on life-history imposed by large brains outweigh the potential benefits, undermining the resilience of the studied mammals. Contrary to the selective forces that have favoured increased brain size throughout evolutionary history, at present, larger brains have become a burden for mammals.