Could a potential Anthropocene mass extinction define a new geological period?

A key aspect of the current debate about the Anthropocene focuses on defining a new geological epoch. Features of the Anthropocene include a biodiversity crisis with the potential to reach ‘mass extinction’ status alongside increasing global CO₂ and temperature. Previous geological boundaries associated with mass extinctions, rises in atmospheric CO₂ and rises in global temperature are more usually associated with transitions between geological periods. The current rapid increase in species extinctions suggest that a new mass extinction event is most likely imminent in the near-term future. Although CO₂ levels are currently low in comparison with the rest of the Phanerozoic, they are rising rapidly along with global temperatures. This suggests that defining the Anthropocene as a new geological period, rather than a new epoch, may be more consistent with previous geological boundaries in the Phanerozoic

A novel application of motion analysis for detecting stress responses in embryos at different stages of development.

Motion analysis is one of the tools available to biologists to extract biologically relevant information from image datasets and has been applied to a diverse range of organisms. The application of motion analysis during early development presents a challenge, as embryos often exhibit complex, subtle and diverse movement patterns. A method of motion analysis able to holistically quantify complex embryonic movements could be a powerful tool for fields such as toxicology and developmental biology to investigate whole organism stress responses. Here we assessed whether motion analysis could be used to distinguish the effects of stressors on three early developmental stages of each of three species: (i) the zebrafish Danio rerio (stages 19 h, 21.5 h and 33 h exposed to 1.5% ethanol and a salinity of 5); (ii) the African clawed toad Xenopus laevis (stages 24, 32 and 34 exposed to a salinity of 20); and iii) the pond snail Radix balthica (stages E3, E4, E6, E9 and E11 exposed to salinities of 5, 10 and 15). Image sequences were analysed using Sparse Optic Flow and the resultant frame-to-frame motion parameters were analysed using Discrete Fourier Transform to quantify the distribution of energy at different frequencies. This spectral frequency dataset was then used to construct a Bray-Curtis similarity matrix and differences in movement patterns between embryos in this matrix were tested for using ANOSIM

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Long-term and trans-life-cycle effects of exposure to ocean acidification in the green sea urchin Strongylocentrotus droebachiensis

Anthropogenic CO2 emissions are acidifying the world’s oceans. A growing body of evidence demonstrates that ocean acidification can impact survival, growth, development and physiology of marine invertebrates. Here, we tested the impact of long-term (up to 16 months) and trans-life-cycle (adult, embryo/larvae and juvenile) exposure to elevated pCO2 (1,200 μatm, compared to control 400 μatm) on the green sea urchin Strongylocentrotus droebachiensis. Female fecundity was decreased 4.5-fold when acclimated to elevated pCO2 for 4 months during reproductive conditioning, while no difference was observed in females acclimated for 16 months. Moreover, adult pre-exposure for 4 months to elevated pCO2 had a direct negative impact on subsequent larval settlement success. Five to nine times fewer offspring reached the juvenile stage in cultures using gametes collected from adults previously acclimated to high pCO2 for 4 months. However, no difference in larval survival was observed when adults were pre-exposed for 16 months to elevated pCO2. pCO2 had no direct negative impact on juvenile survival except when both larvae and juveniles were raised in elevated pCO2. These negative effects on settlement success and juvenile survival can be attributed to carry-over effects from adults to larvae and from larvae to juveniles. Our results support the contention that adult sea urchins can acclimate to moderately elevated pCO2 in a matter of a few months and that carry-over effects can exacerbate the negative impact of ocean acidification on larvae and juveniles

Ergothioneine Biosynthesis and Functionality in the Opportunistic Fungal Pathogen, Aspergillus fumigatus.

Ergothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation. Quantitative proteomic analysis revealed substantial proteomic remodelling in ΔegtA compared to wild-type under both basal and ROS conditions, whereby the abundance of 290 proteins was altered. Specifically, the reciprocal differential abundance of cystathionine γ-synthase and β-lyase, respectively, influenced cystathionine availability to effect EGT biosynthesis. A combined deficiency in EGT biosynthesis and the oxidative stress response regulator Yap1, which led to extreme oxidative stress susceptibility, decreased resistance to heavy metals and production of the extracellular siderophore triacetylfusarinine C and increased accumulation of the intracellular siderophore ferricrocin. EGT dissipated H2O2 in vitro, and elevated intracellular GSH levels accompanied abrogation of EGT biosynthesis. EGT deficiency only decreased resistance to high H2O2 levels which suggests functionality as an auxiliary antioxidant, required for growth at elevated oxidative stress conditions. Combined, these data reveal new interactions between cellular redox homeostasis, secondary metabolism and metal ion homeostasis

Metabolic responses to high pCO2 conditions at a CO2 vent site in juveniles of a marine isopod species assemblage

We are starting to understand the relationship between metabolic rate responses and species' ability to respond to exposure to high pCO2. However, most of our knowledge has come from investigations of single species. The examination of metabolic responses of closely related species with differing distributions around natural elevated CO2 areas may be useful to inform our understanding of their adaptive significance. Furthermore, little is known about the physiological responses of marine invertebrate juveniles to high pCO2, despite the fact they are known to be sensitive to other stressors, often acting as bottlenecks for future species success. We conducted an in situ transplant experiment using juveniles of isopods found living inside and around a high pCO2 vent (Ischia, Italy): the CO2 'tolerant' Dynamene bifida and 'sensitive' Cymodoce truncata and Dynamene torelliae. This allowed us to test for any generality of the hypothesis that pCO2 sensitive marine invertebrates may be those that experience trade-offs between energy metabolism and cellular homoeostasis under high pCO2 conditions. Both sensitive species were able to maintain their energy metabolism under high pCO2 conditions, but in C. truncata this may occur at the expense of [carbonic anhydrase], confirming our hypothesis. By comparison, the tolerant D. bifida appeared metabolically well adapted to high pCO2, being able to upregulate ATP production without recourse to anaerobiosis. These isopods are important keystone species; however, given they differ in their metabolic responses to future pCO2, shifts in the structure of the marine ecosystems they inhabit may be expected under future ocean acidification conditions

Two spatiotemporally distinct value systems shape reward-based learning in the human brain

Avoiding repeated mistakes and learning to reinforce rewarding decisions is critical for human survival and adaptive actions. Yet, the neural underpinnings of the value systems that encode different decision-outcomes remain elusive. Here coupling single-trial electroencephalography with simultaneously acquired functional magnetic resonance imaging, we uncover the spatiotemporal dynamics of two separate but interacting value systems encoding decision-outcomes. Consistent with a role in regulating alertness and switching behaviours, an early system is activated only by negative outcomes and engages arousal-related and motor-preparatory brain structures. Consistent with a role in reward-based learning, a later system differentially suppresses or activates regions of the human reward network in response to negative and positive outcomes, respectively. Following negative outcomes, the early system interacts and downregulates the late system, through a thalamic interaction with the ventral striatum. Critically, the strength of this coupling predicts participants’ switching behaviour and avoidance learning, directly implicating the thalamostriatal pathway in reward-based learning

Survival and long-term maintenance of tertiary trees in the Iberian Peninsula during the Pleistocene. First record of Aesculus L.

The Italian and Balkan peninsulas have been places traditionally highlighted as Pleistocene glacial refuges. The Iberian Peninsula, however, has been a focus of controversy between geobotanists and palaeobotanists as a result of its exclusion from this category on different occasions. In the current paper, we synthesise geological, molecular, palaeobotanical and geobotanical data that show the importance of the Iberian Peninsula in the Western Mediterranean as a refugium area. The presence of Aesculus aff. hippocastanum L. at the Iberian site at Cal Guardiola (Tarrasa, Barcelona, NE Spain) in the Lower– Middle Pleistocene transition helps to consolidate the remarkable role of the Iberian Peninsula in the survival of tertiary species during the Pleistocene. The palaeodistribution of the genus in Europe highlights a model of area abandonment for a widely-distributed species in the Miocene and Pliocene, leading to a diminished and fragmentary presence in the Pleistocene and Holocene on the southern Mediterranean peninsulas. Aesculus fossils are not uncommon within the series of Tertiary taxa. Many appear in the Pliocene and suffer a radical impoverishment in the Lower–Middle Pleistocene transition. Nonetheless some of these tertiary taxa persisted throughout the Pleistocene and Holocene up to the present in the Iberian Peninsula. Locating these refuge areas on the Peninsula is not an easy task, although areas characterised by a sustained level of humidity must have played an predominant role

Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer

\ua92019 American Association for Cancer Research.PURPOSE: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623). PATIENTS AND METHODS: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity. RESULTS: Of the 55 patients, 51% had received ≥2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab + doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%-37%]. Median duration of response (DOR) was 4.2 months (range: 1.0+-9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%-43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%-35%), median DOR of 6.0 months (range: 1.0+-9.7), and 6-month PFS rate of 40% (95% CI: 24%-55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed. CONCLUSIONS: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer