Primer biases in the molecular assessment of diet in multiple insectivorous mammals

Our understanding of trophic interactions of small insectivorous mammals has been drastically improved with the advent of DNA metabarcoding. The technique has continued to be optimised over the years, with primer choice repeatedly being a vital factor for dietary inferences. However, the majority of dietary studies examining the effect of primer choice often rely on in silico analyses or comparing between species that occupy an identical niche type. Here, we apply DNA metabarcoding to empirically compare the prey detection capabilities of two widely used primer sets when assessing the diets of a flying (lesser horseshoe bat; Rhinolophus hipposideros) and two ground-dwelling insectivores (greater white-toothed shrew; Crocidura russula and pygmy shrew; Sorex minutus). Although R. hipposideros primarily rely on two prey orders (Lepidoptera and Diptera), the unique taxa detected by each primer shows that a combination of primers may be the best approach to fully describe bat trophic ecology. However, random forest classifier analysis suggests that one highly degenerate primer set detected the majority of both shrews’ diet despite higher levels of host amplification. The wide range of prey consumed by ground-dwelling insectivores can therefore be accurately documented from using a single broad-range primer set, which can decrease cost and labour. The results presented here show that dietary inferences will differ depending on the primer or primer combination used for insectivores occupying different niches (i.e., hunting in the air or ground) and demonstrate the importance of performing empirical pilot studies for novel study systems

Corneal ulcerative disease in dogs under primary veterinary care in England: epidemiology and clinical management

Abstract Background Corneal ulcerative disease (CUD) has the potential to adversely affect animal welfare by interfering with vision and causing pain. The study aimed to investigate for the first time the prevalence, breed-based risk factors and clinical management of CUD in the general population of dogs under primary veterinary care in England. Results Of 104,233 dogs attending 110 clinics participating within the VetCompass Programme from January 1st to December 31st 2013, there were 834 confirmed CUD cases (prevalence: 0.80%, 95% confidence interval (CI) 0.75–0.86). Breeds with the highest prevalence included Pug (5.42% of the breed affected), Boxer (4.98%), Shih Tzu (3.45%), Cavalier King Charles Spaniel (2.49%) and Bulldog (2.41%). Purebred dogs had 2.23 times the odds (95% CI 1.84–2.87, P < 0.001) of CUD compared with crossbreds. Brachycephalic types had 11.18 (95% CI 8.72–14.32, P < 0.001) and spaniel types had 3.13 (95% CI 2.38–4.12, P < 0.001) times the odds for CUD compared with crossbreds. Pain was recorded in 385 (46.2%) cases and analgesia was used in 455 (54.6%) of dogs. Overall, 62 (7.4%) cases were referred for advanced management and CUD contributed to the euthanasia decision for 10 dogs. Conclusions Breeds such as the Pug and Boxer, and conformational types such as brachycephalic and spaniels, demonstrated predisposition to CUD in the general canine population. These results suggest that breeding focus on periocular conformation in predisposed breeds should be considered in order to reduce corneal disease

Assessing the ecological impacts of invasive species based on their functional responses and abundances

Invasive species management requires allocation of limited resources towards the proactive mitigation of those species that could elicit the highest ecological impacts. However, we lack predictive capacity with respect to the identities and degree of ecological impacts of invasive species. Here, we combine the relative per capita effects and relative field abundances of invader as compared to native species into a new metric, “Relative Impact Potential” (RIP), and test whether this metric can reliably predict high impact invaders. This metric tests the impact of invaders relative to the baseline impacts of natives on the broader ecological community. We first derived the functional responses (i.e. per capita effects) of two ecologically damaging invasive fish species in Europe, the Ponto-Caspian round goby (Neogobius melanostomus) and Asian topmouth gudgeon (Pseudorasbora parva), and their native trophic analogues, the bullhead (Cottus gobio; also C. bairdi) and bitterling (Rhodeus amarus), towards several prey species. This establishes the existence and relative strengths of the predator-prey relationships. Then, we derived ecologically comparable field abundance estimates of the invader and native fish from surveys and literature. This establishes the multipliers for the above per capita effects. Despite both predators having known severe detrimental field impacts, their functional responses alone were of modest predictive power in this regard; however, incorporation of their abundances relative to natives into the RIP metric gave high predictive power. We present invader/native RIP biplots that provide an intuitive visualisation of comparisons among the invasive and native species, reflecting the known broad ecological impacts of the invaders. Thus, we provide a mechanistic understanding of invasive species impacts and a predictive tool for use by practitioners, for example, in risk assessments

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Sea-ice-free Arctic during the Last Interglacial supports fast future loss

The Last Interglacial (LIG), a warmer period 130-116 ka before present, is a potential analog for future climate change. Stronger LIG summertime insolation at high northern latitudes drove Arctic land summer temperatures 4-5 °C higher than the preindustrial era. Climate model simulations have previously failed to capture these elevated temperatures, possibly because they were unable to correctly capture LIG sea-ice changes. Here, we show the latest version of the fully-coupled UK Hadley Center climate model (HadGEM3) simulates a more accurate Arctic LIG climate, including elevated temperatures. Improved model physics, including a sophisticated sea-ice melt-pond scheme, result in a complete simulated loss of Arctic sea ice in summer during the LIG, which has yet to be simulated in past generations of models. This ice-free Arctic yields a compelling solution to the longstanding puzzle of what drove LIG Arctic warmth and supports a fast retreat of future Arctic summer sea ice

Modeling complex ecological economic systems: toward an evolutionary, dynamic understanding of people and nature

Recent understanding about system dynamics and predictability that has emerged from the study of complex systems is creating new tools for modeling interactions between anthropogenic and natural systems. A range of techniques has become available through advances in computer speed and accessibility and by implementing a broad, interdisciplinary systems view

Manchester Clinical Placement Index (MCPI): Conditions for medical students’ learning in hospital and community placements

The drive to quality-manage medical education has created a need for valid measurement instruments. Validity evidence includes the theoretical and contextual origin of items, choice of response processes, internal structure, and interrelationship of a measure’s variables. This research set out to explore the validity and potential utility of an 11-item measurement instrument, whose theoretical and empirical origins were in an Experience Based Learning model of how medical students learn in communities of practice (COPs), and whose contextual origins were in a community-oriented, horizontally integrated, undergraduate medical programme. The objectives were to examine the psychometric properties of the scale in both hospital and community COPs and provide validity evidence to support using it to measure the quality of placements. The instrument was administered twice to students learning in both hospital and community placements and analysed using exploratory factor analysis and a generalizability analysis. 754 of a possible 902 questionnaires were returned (84% response rate), representing 168 placements. Eight items loaded onto two factors, which accounted for 78% of variance in the hospital data and 82% of variance in the community data. One factor was the placement learning environment, whose five constituent items were how learners were received at the start of the placement, people’s supportiveness, and the quality of organisation, leadership, and facilities. The other factor represented the quality of training—instruction in skills, observing students performing skills, and providing students with feedback. Alpha coefficients ranged between 0.89 and 0.93 and there were no redundant or ambiguous items. Generalisability analysis showed that between 7 and 11 raters would be needed to achieve acceptable reliability. There is validity evidence to support using the simple 8-item, mixed methods Manchester Clinical Placement Index to measure key conditions for undergraduate medical students’ experience based learning: the quality of the learning environment and the training provided within it. Its conceptual orientation is towards Communities of Practice, which is a dominant contemporary theory in undergraduate medical education

Framing Social Justice: The Ties That Bind a Multinational Occupational Community

The notion of a frame is central to the conceptualisation of social justice and the grounding of social justice claims. Influential theories of social justice are typically grounded in national or cosmopolitan framings. Those entitled to raise claims of injustice are identified as citizens of states or the globe, respectively. The re-visioning of understandings of space and belonging, incumbent in the processes of globalisation, problematises static geographical framings. We offer an alternative lens and argue for the inclusion of sociological data in accounts of social justice to identify the relevant framing of the community of entitlement. Drawing on secondary analysis of a qualitative dataset, we explore the case of multinational seafarers caught at the intersection of competing appeals to nationality and commonality as an exemplar of transnational workers. And, argue that there are compelling grounds to treat this group of multinational seafarers as a community of entitlement