Reply to: Shark mortality cannot be assessed by fishery overlap alone

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Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Characterization and Modeling of Spatial Variability in a Complex Alluvial Aquifer: Implications on Solute Transport

Field investigations of stratified alluvial deposits suggest that they can give rise to a hierarchy of permeability modes across scales, corresponding to a hierarchy of sedimentary unit types and thus may lead to enhanced plume spread in such media. In this work, we model the sedimentary architecture of the alluvium deposits in Fortymile Wash, Nevada, using a hierarchical transition probability geostatistical approach. The alluvial aquifer comprises a segment of the groundwater flow pathway from the potential high-level nuclear waste repository at Yucca Mountain, Nevada to the downstream accessible environment and may be a natural barrier to radionuclide migration. Thus our main goal is to quantify the impact of spatial variability in the alluvium on solute transport. The alluvial aquifer is a gravel-dominated braid-belt deposit, having lower-permeability paleosols interstratified with higher-permeability gravel-bar deposits. A three-dimensional hierarchical hydrofacies model is developed through fusion of multiple geologic data types and sources. Markov chain models of transition probabilities are employed to represent complex patterns of spatial variability at each hierarchical level in a geostatistical fashion and to impose realistic constraints to such variations through conditioning on existing data. The link between the alluvium spatial variability and solute dispersion at different spatiotemporal scales is demonstrated using the stochastic-Lagrangian transport theory. We show that the longitudinal macrodispersivity can be on the order of hundreds to thousands of meters, and it may not reach its asymptotic value until after 1,000 years of traveltime

Characterization and Modeling of Spatial Variability in a Complex Alluvial Aquifer: Implications on Solute Transport

Field investigations of stratified alluvial deposits suggest that they can give rise to a hierarchy of permeability modes across scales, corresponding to a hierarchy of sedimentary unit types and thus may lead to enhanced plume spread in such media. In this work, we model the sedimentary architecture of the alluvium deposits in Fortymile Wash, Nevada, using a hierarchical transition probability geostatistical approach. The alluvial aquifer comprises a segment of the groundwater flow pathway from the potential high-level nuclear waste repository at Yucca Mountain, Nevada to the downstream accessible environment and may be a natural barrier to radionuclide migration. Thus our main goal is to quantify the impact of spatial variability in the alluvium on solute transport. The alluvial aquifer is a gravel-dominated braid-belt deposit, having lower-permeability paleosols interstratified with higher-permeability gravel-bar deposits. A three-dimensional hierarchical hydrofacies model is developed through fusion of multiple geologic data types and sources. Markov chain models of transition probabilities are employed to represent complex patterns of spatial variability at each hierarchical level in a geostatistical fashion and to impose realistic constraints to such variations through conditioning on existing data. The link between the alluvium spatial variability and solute dispersion at different spatiotemporal scales is demonstrated using the stochastic-Lagrangian transport theory. We show that the longitudinal macrodispersivity can be on the order of hundreds to thousands of meters, and it may not reach its asymptotic value until after 1,000 years of traveltime

Geologic Controls on Interaction Between the Edwards and Trinity Aquifers, Balcones Fault System, Texas

Faults of the Balcones fault system exert important controls on the groundwater hydrology of the Edwards and Trinity Aquifers, including the following: (i) faults juxtapose permeable and relatively impermeable hydrogeologic units, (ii) the normal fault system causes structural thinning of the Edwards and Trinity Aquifer strata, and (iii) faults provide potential pathways for infiltration of water into the groundwater systems and for lateral and vertical movement of groundwater. We present examples of these structural geologic controls on aquifer properties using data and observations from the Helotes 7.5-minute quadrangle and the Hidden Valley fault exposed in Canyon Lake Gorge. Geologic framework modeling of the Helotes quadrangle illustrates the strong potential for direct communication between the Edwards Group and Glen Rose Formation in this area. The 100+ m displacement of the Haby Crossing fault is responsible for dropping the Edwards Aquifer from hilltop exposures north of the fault to mostly buried (confined) on the south side of the fault. Consequently, the area designated as Edwards Aquifer recharge zone is at its narrowest in this part of the Balcones Fault Zone. The Hidden Valley fault has an estimated 60-70 m of throw (vertical component of displacement) along the approximately 800 m of Upper Glen Rose Limestone exposure at Canyon Lake Gorge. Water ponds on the fault zone in some places, sinks into the fault along other stretches, and discharges laterally from the fault zone in yet another. These examples of locally high permeability of an exhumed fault show the importance of map-scale faults for groundwater flow. They also cast doubt on interpretations that such faults would act as barriers to across-fault flow in cases where such faults juxtapose Glen Rose Limestone with Glen Rose Limestone or the more permeable Edwards Limestone with Glen Rose Limestone. High permeability zones under and near stream channels may serve as fast pathways of communication from the Trinity to Edwards Aquifers. Direct

Geologic Controls on Interaction Between the Edwards and Trinity Aquifers, Balcones Fault System, Texas

Faults of the Balcones fault system exert important controls on the groundwater hydrology of the Edwards and Trinity Aquifers, including the following: (i) faults juxtapose permeable and relatively impermeable hydrogeologic units, (ii) the normal fault system causes structural thinning of the Edwards and Trinity Aquifer strata, and (iii) faults provide potential pathways for infiltration of water into the groundwater systems and for lateral and vertical movement of groundwater. We present examples of these structural geologic controls on aquifer properties using data and observations from the Helotes 7.5-minute quadrangle and the Hidden Valley fault exposed in Canyon Lake Gorge. Geologic framework modeling of the Helotes quadrangle illustrates the strong potential for direct communication between the Edwards Group and Glen Rose Formation in this area. The 100+ m displacement of the Haby Crossing fault is responsible for dropping the Edwards Aquifer from hilltop exposures north of the fault to mostly buried (confined) on the south side of the fault. Consequently, the area designated as Edwards Aquifer recharge zone is at its narrowest in this part of the Balcones Fault Zone. The Hidden Valley fault has an estimated 60-70 m of throw (vertical component of displacement) along the approximately 800 m of Upper Glen Rose Limestone exposure at Canyon Lake Gorge. Water ponds on the fault zone in some places, sinks into the fault along other stretches, and discharges laterally from the fault zone in yet another. These examples of locally high permeability of an exhumed fault show the importance of map-scale faults for groundwater flow. They also cast doubt on interpretations that such faults would act as barriers to across-fault flow in cases where such faults juxtapose Glen Rose Limestone with Glen Rose Limestone or the more permeable Edwards Limestone with Glen Rose Limestone. High permeability zones under and near stream channels may serve as fast pathways of communication from the Trinity to Edwards Aquifers. Direct

Structural framework of the Edwards Aquifer recharge zone in south-central Texas

The Edwards Aquifer, the major source of water for many communities in central Texas, is threatened by population growth and development over its recharge zone. The location of the recharge and confined zones and the flow paths of the aquifer are controlled by the structure of and deformation processes within the Balcones fault system, a major system of predominantly down-to-the-southeast normal faults. We investigate the geologic structure of the Edwards Aquifer to assess the large-scale aquifer architecture, analyze fault offset and stratigraphic juxtaposition relationships, evaluate fault-zone deformation and dissolution and fault-system architecture, and investigate fault-block deformation and scaling of small-scale (intrablock) normal faults. Characterization of fault displacement shows a pattern of aquifer thinning that is likely to influence fault-block communication and flow paths. Flow-path constriction may be exacerbated by increased fault-segment connectivity associated with large fault displacements. Also, increased fault-zone deformation associated with larger-displacement faults is likely to further influence hydrologic properties. Overall, faulting is expected to produce strong permeability anisotropy such that maximum permeability is subhorizontal and parallel to fault-bedding intersections. At all scales, aquifer permeability is either unchanged or enhanced parallel to faults and in many cases decreased perpendicular to faults