Global Perturbation Research Articles

Changes in upper ocean hydrography and productivity across the Middle Eocene Climatic Optimum: Local insights and global implications from the Northwest Atlantic

Abstract The Middle Eocene Climatic Optimum (MECO; 40.5–40.0 Ma) was a pronounced climatic reversal during a long-term global cooling period. Despite conspicuous signals of warming and ocean acidification in global marine sedimentary records, changes in upper ocean thermal stratification and productivity have been less comprehensively understood across the MECO. Here we examined stratigraphic records of the middle Eocene succession (43.1–38.6 Ma) at Integrated Ocean Drilling Program Site U1408 in the Northwest Atlantic, to provide a detailed local environmental reconstruction and to bring new insights on spatiotemporal evolution of coupled hydrography and productivity across the MECO based on global comparison. The present temperature–oxygen isotope calibration inferred at least ~3 °C warming in the upper ocean during the MECO at the study site. Whereas further inter-proxy calibration is required, the present estimation supports expanded meridional surface temperature gradient in both hemispheres during the late middle Eocene. Vertical gradients in planktic foraminiferal oxygen isotope ratios revealed that relatively mixed upper water column prevailed during and immediately (~150 kyr) before the MECO. The observed ~102 kyr-scale local shifts in hydrography was possibly driven by the ~2.4-myr eccentricity modulation in the development of seasonal thermocline, rather than greenhouse gas forcing. Planktic and benthic foraminiferal accumulation rates at Site U1408 decreased and increased during the MECO and adjacent cooling episodes, respectively. The relationships between carbonate productivity and local hydrography varied through time in the Northwest Atlantic. Instead, we suggest that marine carbonate productivity and ocean chemistry was controlled by multiple eccentricity-scale changes in weathering intensity and nutrient supply, widely across the major ocean basins. Hypothesized prevailing decline in productivity agrees with a possible warming mechanism of the MECO, although it is challenged by several existing micropaleontological records suggesting increased bio-silica production and eutrophication at varying oceanographic settings. Further integration of different types of proxies and quantitative assessments will help understand complex biotic changes during significant global carbon cycle perturbations in a greenhouse world.

(-)-Epicatechin Modulates Mitochondrial Redox in Vascular Cell Models of Oxidative Stress.

Diabetes mellitus affects 451 million people worldwide, and people with diabetes are 3-5 times more likely to develop cardiovascular disease. In vascular tissue, mitochondrial function is important for vasoreactivity. Diabetes-mediated generation of excess reactive oxygen species (ROS) may contribute to vascular dysfunction via damage to mitochondria and regulation of endothelial nitric oxide synthase (eNOS). We have identified (–)-epicatechin (EPICAT), a plant compound and known vasodilator, as a potential therapy. We hypothesized that mitochondrial ROS in cells treated with antimycin A (AA, a compound targeting mitochondrial complex III) or high glucose (HG, global perturbation) could be normalized by EPICAT, and correlate with improved mitochondrial dynamics and cellular signaling. Human umbilical vein endothelial cells (HUVEC) were treated with HG, AA, and/or 0.1 or 1.0 μM of EPICAT. Mitochondrial and cellular superoxide, mitochondrial respiration, and cellular signaling upstream of mitochondrial function were assessed. EPICAT at 1.0 μM significantly attenuated mitochondrial superoxide in HG-treated cells. At 0.1 μM, EPICAT nonsignificantly increased mitochondrial respiration, agreeing with previous reports. EPICAT significantly increased complex I expression in AA-treated cells, and 1.0 μM EPICAT significantly decreased mitochondrial complex V expression in HG-treated cells. No significant effects were seen on either AMPK or eNOS expression. Our study suggests that EPICAT is useful in mitigating moderate ROS concentrations from a global perturbation and may modulate mitochondrial complex activity. Our data illustrate that EPICAT acts in the cell in a dose-dependent manner, demonstrating hormesis.

Integrated sedimentary, biotic, and paleoredox dynamics from multiple localities in southern Laurentia during the late Silurian (Ludfordian) extinction event

The Silurian was a time of major climatic transition punctuated by multiple biotic crises and global carbon cycle perturbations. The most severe of these biotic events was the late Silurian (Ludfordian) Lau/Kozlowskii extinction event (LKE) and the associated Lau carbon isotope excursion (CIE). Although the extinction event and Lau CIE are globally documented, the only records thus far of local and global marine paleoredox conditions through this interval are from a single region in Scandinavia. Here we examine four sections along a bathymetric transect of mixed carbonate-siliciclastic sediments from western Tennessee, USA. A novel approach using a multi-proxy dataset combining high-resolution geochemical data and microfacies analyses from multiple localities explores the possibilities of local/regional-scale redox heterogeneities during a time of widespread environmental upheaval on a global scale. Paired positive excursions recorded in carbonate carbon isotopes and carbonate-associated sulfate sulfur isotopes support recent work from carbonate and siliciclastic successions from Scandinavia, suggesting a global enhancement of organic carbon and pyrite burial driven by an expansion of euxinic (anoxic and sulfidic water column) conditions in the oceans during the mid-Ludfordian. Furthermore, positive excursions in organic carbon isotopes and pyrite sulfur isotopes reflect the global changes in redox. Stratigraphic trends in I/Ca ratios imply a local expansion of low-oxygen conditions, with low, but non-zero values during the rising limb and peak of the CIE. The fossil assemblages vary across the shelf and through the CIE interval. Stratigraphic changes in fossil assemblages and I/Ca are closely associated with local and global changes in oxygenation and sea level during the mid-Ludfordian. The collective data indicate significant biotic reorganization in response to changes in marine redox conditions and in conjunction with sea-level variation during the LKE interval, but detailed macroscopic biodiversity is currently unconstrained for this region.

Metabolomics Analysis Reveals Global Metabolic Changes in the Evolved E. coli Strain with Improved Growth and 1-Butanol Production in Minimal Medium.

Production of 1-butanol from microorganisms has garnered significant interest due to its prospect as a drop-in biofuel and precursor for a variety of commercially relevant chemicals. Previously, high 1-butanol titer has been reported in Escherichia coli strain JCL166, which contains a modified clostridial 1-butanol pathway. Although conventional and metabolomics-based strain improvement strategies of E. coli strain JCL166 have been successful in improving production in rich medium, 1-butanol titer was severely limited in minimal medium. To further improve growth and consequently 1-butanol production in minimal medium, adaptive laboratory evolution (ALE) using mutD5 mutator plasmid was done on JCL166. Comparative metabolomics analysis of JCL166 and BP1 revealed global perturbations in the evolved strain BP1 compared to JCL166 (44 out of 64 metabolites), encompassing major metabolic pathways such as glycolysis, nucleotide biosynthesis, and CoA-related processes. Collectively, these metabolic changes in BP1 result in improved growth and, consequently, 1-butanol production in minimal medium. Furthermore, we found that the mutation in ihfB caused by ALE had a significant effect on the metabolome profile of the evolved strain. This study demonstrates how metabolomics was utilized for characterization of ALE-developed strains to understand the overall effect of mutations acquired through evolution.

Marine redox variability from Baltica during extinction events in the latest Ordovician–early Silurian

It is well documented that Upper Ordovician and Silurian successions record multiple marine turnover events – including the second-largest mass extinction in the Phanerozoic – widespread glaciation, and multiple global carbon cycle perturbations. Whereas causal mechanisms for the Late Ordovician major mass extinction event involving climate, paleoceanographic variation, and δ13C records have been published, similar records remain poorly constrained for subsequent extinction events in the early Silurian. Here, we present new organic matter carbon isotope (δ13Corg) chemostratigraphy and corresponding paleoredox proxies (Fe speciation, [Mn, V, Mo], and pyrite sulfur isotopes) from two organic-rich drill core sections in Sweden and Latvia that span the upper Katian through lower Wenlock stages (446–431 Ma). Pyritized Fe and bulk sedimentary Mn concentrations from Upper Ordovician strata in southern Sweden suggest a local redox shift to more reducing conditions in the late Hirnantian, possibly including euxinic (anoxic and sulfidic water column) conditions that coincide with the second mass extinction pulse. The new high-resolution δ13Corg and δ34Spyr datasets from the late Aeronian (early Silurian) interval within both drill cores show positive excursions that are broadly coincident with the associated Sandvika and sedgwickii extinction events. Independently, Fe speciation and bulk sedimentary trace metal data from this late Aeronian interval record locally euxinic conditions in both the deep basinal (Sweden) and distal shelf (Latvia) settings before and during the late Aeronian positive δ13C excursion. This multiproxy paleoredox dataset provides the first direct evidence for local to regional expansion of reducing marine conditions coincident with this early Silurian (late Aeronian) biotic event and positive δ13C excursion. Additionally, new δ34Spyr values spanning the Llandovery/Wenlock boundary interval in the Latvia core show a positive excursion coincident with Fe speciation and trace metal enrichments that imply a local redox perturbation with intermittently euxinic bottom waters during the rising limb of the Ireviken positive δ13C excursion. The combination of these geochemical data for local- to regional-scale (more data required for global interpretations) changes in marine redox conditions with paleobiological records and evidence for eustatic sea-level rise indicate that environmental stresses related to an expansion of anoxic to euxinic conditions were a probable driver for several extinction events during the latest Ordovician–early Silurian.

Towards abstraction of computational modelling of mammalian cell cycle: Model reduction pipeline incorporating multi-level hybrid petri nets

Cell cycle is a large biochemical network and it is crucial to simplify it to gain a clearer understanding and insights into the cell cycle. This is also true for other biochemical networks. In this study, we present a model abstraction scheme/pipeline to create a minimal abstract model of the whole mammalian cell cycle system from a large Ordinary Differential Equation model of cell cycle we published previously (Abroudi et al., 2017). The abstract model is developed in a way that it captures the main characteristics (dynamics of key controllers), responses (G1-S and G2-M transitions and DNA damage) and the signalling subsystems (Growth Factor, G1-S and G2-M checkpoints, and DNA damage) of the original model (benchmark). Further, our model exploits: (i) separation of time scales (slow and fast reactions), (ii) separation of levels of complexity (high-level and low-level interactions), (iii) cell-cycle stages (temporality), (iv) functional subsystems (as mentioned above), and (v) represents the whole cell cycle - within a Multi-Level Hybrid Petri Net (MLHPN) framework. Although hybrid Petri Nets is not new, the abstraction of interactions and timing we introduced here is new to cell cycle and Petri Nets. Importantly, our models builds on the significant elements, representing the core cell cycle system, found through a novel Global Sensitivity Analysis on the benchmark model, using Self Organising Maps and Correlation Analysis that we introduced in (Abroudi et al., 2017). Taken the two aspects together, our study proposes a 2-stage model reduction pipeline for large systems and the main focus of this paper is on stage 2, Petri Net model, put in the context of the pipeline. With the MLHPN model, the benchmark model with 61 continuous variables (ODEs) and 148 parameters were reduced to 14 variables (4 continuous (Cyc_Cdks - the main controllers of cell cycle) and 10 discrete (regulators of Cyc_Cdks)) and 31 parameters. Additional 9 discrete elements represented the temporal progression of cell cycle. Systems dynamics simulation results of the MLHPN model were in close agreement with the benchmark model with respect to the crucial metrics selected for comparison: order and pattern of Cyc_Cdk activation, timing of G1-S and G2-M transitions with or without DNA damage, efficiency of the two cell cycle checkpoints in arresting damaged cells and passing healthy cells, and response to two types of global parameter perturbations. The results show that the MLHPN provides a close approximation to the comprehensive benchmark model in robustly representing systems dynamics and emergent properties while presenting the core cell cycle controller in an intuitive, transparent and subsystems format.

Zero-site density matrix renormalization group and the optimal low-rank correction

A zero-site density matrix renormalization algorithm (DMRG0) is proposed to minimize the energy of matrix product states (MPS). Instead of the site tensors themselves, we propose to optimize sequentially the "message" tensors between neighbor sites, which contain the singular values of the bipartition. This leads to a local minimization step that is independent of the physical dimension of the site. Conceptually, it separates the optimization and decimation steps in DMRG. Furthermore, we introduce two new global perturbations based on the optimal low-rank correction to the current state, which are used to avoid local minima. They are determined variationally as the MPS closest to the one-step correction of the Lanczos or Jacobi-Davidson eigensolver, respectively. These perturbations mainly decrease the energy and are free of hand-tuned parameters. Compared to existing single-site enrichment proposals, our approach gives similar convergence ratios per sweep while the computations are cheaper by construction. Our methods may be useful in systems with many physical degrees of freedom per lattice site. We test our approach on the periodic Heisenberg spin chain for various spins, and on free electrons on the lattice.

Orbital pacing and secular evolution of the Early Jurassic carbon cycle

Global perturbations to the Early Jurassic environment (∼201 to ∼174 Ma), notably during the Triassic-Jurassic transition and Toarcian Oceanic Anoxic Event, are well studied and largely associated with volcanogenic greenhouse gas emissions released by large igneous provinces. The long-term secular evolution, timing, and pacing of changes in the Early Jurassic carbon cycle that provide context for these events are thus far poorly understood due to a lack of continuous high-resolution δ13C data. Here we present a δ13CTOC record for the uppermost Rhaetian (Triassic) to Pliensbachian (Lower Jurassic), derived from a calcareous mudstone succession of the exceptionally expanded Llanbedr (Mochras Farm) borehole, Cardigan Bay Basin, Wales, United Kingdom. Combined with existing δ13CTOC data from the Toarcian, the compilation covers the entire Lower Jurassic. The dataset reproduces large-amplitude δ13CTOC excursions (>3‰) recognized elsewhere, at the Sinemurian-Pliensbachian transition and in the lower Toarcian serpentinum zone, as well as several previously identified medium-amplitude (∼0.5 to 2‰) shifts in the Hettangian to Pliensbachian interval. In addition, multiple hitherto undiscovered isotope shifts of comparable amplitude and stratigraphic extent are recorded, demonstrating that those similar features described earlier from stratigraphically more limited sections are nonunique in a long-term context. These shifts are identified as long-eccentricity (∼405-ky) orbital cycles. Orbital tuning of the δ13CTOC record provides the basis for an astrochronological duration estimate for the Pliensbachian and Sinemurian, giving implications for the duration of the Hettangian Stage. Overall the chemostratigraphy illustrates particular sensitivity of the marine carbon cycle to long-eccentricity orbital forcing.

Stochastic turbulence modeling in RANS simulations via multilevel Monte Carlo

A multilevel Monte Carlo (MLMC) method for quantifying model-form uncertainties associated with the Reynolds-Averaged Navier-Stokes (RANS) simulations is presented. Two, high-dimensional, stochastic extensions of the RANS equations are considered to demonstrate the applicability of the MLMC method. The first approach is based on global perturbation of the baseline eddy viscosity field using a lognormal random field. A more general second extension is considered based on the work of [Xiao et al. (2017)], where the entire Reynolds Stress Tensor (RST) is perturbed while maintaining realizability. For two fundamental flows, we show that the MLMC method based on a hierarchy of meshes is asymptotically faster than plain Monte Carlo. Additionally, we demonstrate that for some flows an optimal multilevel estimator can be obtained for which the cost scales with the same order as a single CFD solve on the finest grid level.

Constraining oceanic oxygenation during the Shuram excursion in South China using thallium isotopes.

Ediacaran sediments record an unusual global carbon cycle perturbation that has been linked to widespread oceanic oxygenation, the Shuram negative C isotope excursion (NCIE). However, proxy-based estimates of global ocean redox conditions during this event have been limited largely due to proxy specificity (e.g., euxinic sediments for Mo and U isotopes). Modern global seawater documents a homogenous Tl isotope composition (ε205 Tl=-6.0) due to significant manganese oxide burial, which is recorded in modern euxinic sediments. Here, we provide new data documenting that sediments deposited beneath reducing but a non-sulfidic water column from the Santa Barbara Basin (ε205 Tl=-5.6±0.1) also faithfully capture global seawater Tl isotope values. Thus, the proxy utilization of Tl isotopes can extend beyond strictly euxinic settings. Second, to better constrain the global redox conditions during the Shuram NCIE, we measured Tl isotopes of locally euxinic and ferruginous shales of the upper Doushantuo Formation, South China. The ε205 Tl values of these shales exhibit a decreasing trend from ≈-3 to ≈-8, broadly coinciding with the onset of Shuram NCIE. There are ε205 Tl values (-5.1 to -7.8) during the main Shuram NCIE interval that approach values more negative than modern global seawater. These results suggest that manganese oxide burial was near or even greater than modern burial fluxes, which is likely linked to an expansion of oxic conditions. This ocean oxygenation may have been an important trigger for the Shuram NCIE and evolution of Ediacaran-type biota. Subsequently, Tl isotopes show an increasing trend from the modern ocean value to values near the modern global inputs or even heavier (ε205 Tl≈-2.5~0.4), occurring prior to recovery from the NCIE. These records may suggest that there was a decrease in the extent of oxygenated conditions in the global oceans during the late stage of the Shuram NCIE.

Globe-Trotting Aedes aegypti and Aedes albopictus: Risk Factors for Arbovirus Pandemics.

Introduction: Two species of Aedes (Ae.) mosquitoes (Ae. aegypti and Ae. albopictus) are primary vectors for emerging arboviruses that are a significant threat to public health and economic burden worldwide. Distribution of these vectors and the associated arboviruses, such as dengue virus, chikungunya virus, yellow fever virus, and Zika virus, was for a long time restricted by geographical, ecological, and biological factors. Presently, arbovirus emergence and dispersion are more rapid and geographically widespread, largely due to expansion of the range for these two mosquitoes that have exploited the global transportation network, land perturbation, and failure to contain the mosquito population coupled with enhanced vector competence. Ae. aegypti and Ae. albopictus may also sustain transmission between humans without having to depend on their natural reservoir forest cycles due to arthropod adaptation to urbanization. Currently, there is no single strategy that is adequate to control these vectors, especially when managing arbovirus outbreaks.Objective: This review aimed at presenting the characteristics and abilities of Ae. aegypti and Ae. albopictus, which can drive a global public health risk, and suggests strategies for prevention and control.Methods: This review presents the geographic range, reproduction and ecology, vector competence, genetic evolution, and biological and chemical control of these two mosquito species and how they have changed and developed over time combined with factors that may drive pandemics and mitigation measures.Conclusion: We suggest that more efforts should be geared toward the development of a concerted multidisciplinary approach.

Two distinct episodes of marine anoxia during the Permian-Triassic crisis evidenced by uranium isotopes in marine dolostones

The end-Permian mass extinction (EPME; ca. 251.94 Ma) is the most severe mass extinction in the geological record. Detailed paleobiological investigations show a very rapid EPME event, and recently published δ238U data show a large negative excursion and thus a massive shift to globally expanded anoxia at the main extinction phase in the latest Permian. The negative shift in δ238U is in correlation with a globally characterized negative δ13C excursion near the Permian-Triassic boundary (PTB). In some highly expanded PTB carbonate sections, however, there are two distinct negative δ13C excursions whereas uranium isotopes (δ238U) from such sections have not yet been examined, leaving a gap in the understanding of the global perturbations of marine redox conditions immediately following the EPME. Here, we present a new δ238U study of syn-depositional dolostones from a well-characterized and highly expanded drill core, which recorded two pronounced negative δ13C excursions across the PTB, from the Carnic Alps, Austria. This drill core extends 331-meters across the PTB and provides a unique opportunity to explore the detailed timing, duration, and extent of marine redox chemistry changes before, during, and immediately after the EPME. Our new δ238U record shows two negative shifts, which are correlated with the two negative δ13C excursions. The first negative δ238U excursion preceding the EPME confirms the recently published δ238U records from across the EPME and support that syndepositional marine dolostones can record δ238U trends of seawater similar to that of limestones. Modeling of uranium isotope cycling in the latest Permian and earliest Triassic oceans suggests two distinct stages of expanded marine anoxia separated by a brief interval (∼100 kyr) of reoxygenation across the PTB. The first anoxic episode lasted for ∼ 60 kyr while anoxic seafloor area expanded to cover >18% of the entire seafloor, coeval with the main EPME horizon, agreeing with marine anoxia as a proximate kill mechanism for the EPME. The second anoxic event was less intense compared to the first anoxic pulse but sustained for a longer duration. A global modeling of coupled C, P, and U cycles show that two pulses of volcanic carbon injection that drives global warming and increased phosphorus weathering rate can reasonably reproduce our data to match two phases of anoxia. The model also demonstrates that the loss of terrestrial vegetation in the EPME is crucial to generating an intervening interval of oxygenated ocean. Our new study adds to a growing body of evidence that the global marine redox conditions underwent rapid oscillations during the EPME event and continued afterward, which may have played a central role in delaying the marine ecosystem recovery in the Early Triassic.

Unraveling short- and long-term carbon cycle variations during the Oceanic Anoxic Event 2 from the Paris Basin Chalk

Abstract The Oceanic Anoxic Event 2 (OAE2, ca. 94.6 Ma) is one of the major perturbations in the global carbon cycle during the Phanerozoic. Stable carbon isotopes (δ13C) from marine and continental sedimentary environments document this carbon cycle perturbation with a pronounced (> 2‰) positive carbon isotope excursion (CIE). Although the OAE2 stratigraphic interval has been intensively studied in terms of paleoceanography and paleoclimatology, several climatic and carbon cycle aspects are not yet well-understood. In particular, cyclic short-term Milankovitch-scale δ13C variations within the OAE2 and their potential implications for the global carbon cycle have been rarely addressed. Here, we present high-resolution (5 cm, ~2 kyr) δ13C data spanning the OAE2 from the Paris Basin Chalk (Poigny Craie-701 drill-core) to show high amplitude short-term δ13C oscillations, superimposed on the major CIE. Time-series analysis indicates that short-term oscillations are astronomically paced, with eccentricity cycles being the most prominent. Orbital forcing of δ13C variations is further supported by time-series analysis of the English Chalk (Eastbourne section). We suggest that orbitally paced carbon cycle oscillations were amplified by considerable emission of greenhouse gases from volcanism that caused the overall CIE. Astronomical calibration of the whole OAE2 (the perturbation and recovery phases) from the Poigny record provides a duration equivalent to eight to eight and a half short eccentricity cycles. Cyclostratigraphic correlations among several OAE2 key records indicate the same duration of the whole CIE. However, duration of the interval from the onset of CIE till the Cenomanian-Turonian boundary (CTB) is significantly different from one basin to another. In particular, a difference of almost two short eccentricity cycles is highlighted between the Anglo-Paris and Western Interior basins. According to cyclostratigraphic approach and correlations, the entry of W. devonense was at least 200 kyr later in the Western Interior Basin (WIB, USA) than in Europe. Key calcareous nannofossil biohorizons (e.g., Quadrum gartneri) are also stratigraphically upshifted in the WIB with respect to the European sections, hence concurring with the hypothesis of a younger CTB in the WIB. We ascribe such significant temporal offset to diachroneity of the CTB, which is likely the result of different, regional biotic responses to the global OAE2 paleoenvironmental perturbation.

Formation of microbial organic carbonates during the Late Jurassic from the Northern Tethys (Amu Darya Basin, Uzbekistan): Implications for Jurassic anoxic events

Abstract The Late Jurassic was a period of major global carbon cycle perturbations with episodes of anoxia leading to regional accumulation of organic matter in sediments worldwide. The Tubiegatan section (SW Gissar Mountains, Uzbekistan) located in the Northern Tethys, shows atypical organic-rich limestone and marl deposits (up to 6% of total organic carbon) marked by pronounced negative excursions of δ13Ccarb (amplitude of ca. 12‰) and δ13Corg (amplitude of ca. 4‰) recorded during the Middle Oxfordian (Transversarium Zone). A transdisciplinary approach including sedimentology, palynofacies characterization, mineralogy, organic and inorganic geochemistry was carried out to elucidate the origin of these organic-rich deposits. Highest TOC are measured in nodular limestones, and lowest δ13Ccarb values in thinly laminated facies consisting in alternances of infra-millimeter-thick organic and carbonate laminae. In the latter, the presence of organic-carbonate peloids and of possible remnants of exopolymeric substances associated with clay indicate that these structures are probably mineralized laminated benthic microbial mats (i.e., stromatolites). Rock-Eval pyrolysis coupled to palynofacies analyses point to a dominant altered marine organic matter of probable algal/microbial origin, with subordinate continental phytoclasts inputs in the upper part of the organic-rich interval. Trace elements (U/Th, V/Cr and Mo/Al ratios) indicate two anoxic episodes coinciding with the highest TOC, punctuated by dysoxic periods. Such O2-depleted conditions have allowed the preservation and probably the development of anaerobic microbial communities in the microbial mats. In these latter, sulfate reduction probably had a significant contribution to the production of carbonates, which would explain the precipitation of pyrite and the relatively low δ13Ccarb values. The progressive decrease then disappearance of kaolinite from the base of the organic-rich interval, is interpreted as a progressive aridification of the Amu Darya Basin during the Transversarium Zone, culminating with the progradation of a large-scale gypsum sabkha overlying the organic deposits. Overall, the organic-rich deposits could record the onset of the disconnection of the Amu Darya Basin from the open sea to the south, induced by compression and subsequent uplifts in the Afghan and Central Iranian blocks. The elevated evaporation, coupled with the presence of hydrological barriers (such as coral reefs) could have led to the formation of local to regional anoxic conditions in the Amu Darya Basin. Similar microbial organic accumulations are recently known throughout the Tethys (e.g., Arabian Plate, Western Europe) and from other oceans (e.g., Central Atlantic, Pacific) during the Late Jurassic, suggesting common controlling factors. The increase of organic matter storage worldwide coupled with potential methane release could have in turn induced major perturbations of the carbon cycle during the Oxfordian-Kimmeridgian interval. The relatively shallow anoxia model proposed in this study contrasts with the well-known organic carbon-rich pelagic models proposed for the Jurassic anoxia (e.g., Toarcian, Kimmeridgian) and Cretaceous OAEs.

20% of US electricity from wind will have limited impacts on system efficiency and regional climate

Impacts from current and future wind turbine (WT) deployments necessary to achieve 20% electricity from wind are analyzed using high resolution numerical simulations over the eastern USA. Theoretical scenarios for future deployments are based on repowering (i.e. replacing with higher capacity WTs) thus avoiding competition for land. Simulations for the contemporary climate and current WT deployments exhibit good agreement with observed electricity generation efficiency (gross capacity factors (CF) from simulations = 45–48%, while net CF for WT installed in 2016 = 42.5%). Under the scenario of quadrupled installed capacity there is a small decrease in system-wide efficiency as indicated by annual mean CF. This difference is approximately equal to that from the two simulation years and may reflect saturation of the wind resource in some areas. WT modify the local near-surface climate in the grid cells where they are deployed. The simulated impact on near-surface climate properties at both the regional and local scales does not increase with increasing WT installed capacity. Climate impacts from WT are modest compared to regional changes induced by historical changes in land cover and to the global temperature perturbation induced by use of coal to generate an equivalent amount of electricity.

CGLFold: a contact-assisted de novo protein structure prediction using global exploration and loop perturbation sampling algorithm.

Regions that connect secondary structure elements in a protein are known as loops, whose slight change will produce dramatic effect on the entire topology. This study investigates whether the accuracy of protein structure prediction can be improved using a loop-specific sampling strategy. A novel de novo protein structure prediction method that combines global exploration and loop perturbation is proposed in this study. In the global exploration phase, the fragment recombination and assembly are used to explore the massive conformational space and generate native-like topology. In the loop perturbation phase, a loop-specific local perturbation model is designed to improve the accuracy of the conformation and is solved by differential evolution algorithm. These two phases enable a cooperation between global exploration and local exploitation. The filtered contact information is used to construct the conformation selection model for guiding the sampling. The proposed CGLFold is tested on 145 benchmark proteins, 14 free modeling (FM) targets of CASP13 and 29 FM targets of CASP12. The experimental results show that the loop-specific local perturbation can increase the structure diversity and success rate of conformational update and gradually improve conformation accuracy. CGLFold obtains template modeling score ≥ 0.5 models on 95 standard test proteins, 7 FM targets of CASP13 and 9 FM targets of CASP12. The source code and executable versions are freely available at https://github.com/iobio-zjut/CGLFold. Supplementary data are available at Bioinformatics online.

A Prospective Observational Feasibility Study of Jugular Bulb Microdialysis in Subarachnoid Hemorrhage

Cerebral metabolic perturbations are common in aneurysmal subarachnoid hemorrhage (aSAH). Monitoring cerebral metabolism with intracerebral microdialysis (CMD) allows early detection of secondary injury and may guide decisions on neurocritical care interventions, affecting outcome. However, CMD is a regional measuring technique that is influenced by proximity to focal lesions. Continuous microdialysis of the cerebral venous drainage may provide information on global cerebral metabolism relevant for the care of aSAH patients. This observational study aimed to explore the feasibility of jugular bulb microdialysis (JBMD) in aSAH and describe the output characteristics in relation to conventional multimodal monitoring. Patients with severe aSAH were included at admission or after in-house deterioration when local clinical guidelines prompted extended multimodal monitoring. Non-dominant frontal CMD, intracranial pressure (ICP), partial brain tissue oxygenation pressure (PbtO2), and cerebral perfusion pressure (CPP) were recorded every hour. The dominant jugular vein was accessed by retrograde insertion of a microdialysis catheter with the tip placed in the jugular bulb under ultrasound guidance. Glucose, lactate, pyruvate, lactate/pyruvate ratio, glycerol, and glutamate were studied for correlation to intracranial measurements. Modified Rankin scale was assessed at 6months. Twelve adult aSAH patients were monitored during a mean 4.2 ± 2.6days yielding 22,041 data points for analysis. No complications related to JBMD were observed. Moderate or strong significant monotonic CMD-to-JBMD correlations were observed most often for glucose (7 patients), followed by lactate (5 patients), and pyruvate, glycerol, and glutamate (3 patients). Moderate correlation for lactate/pyruvate ratio was only seen in one patient. Analysis of critical periods defined by ICP > 20, CPP < 65, or PbtO2 < 15 revealed a tendency toward stronger CMD-to-JBMD associations in patients with many or long critical periods. Possible time lags between CMD and JBMD measurements were only identified in 6 out of 60 patient variables. With the exception of pyruvate, a dichotomized outcome was associated with similar metabolite patterns in JBMD and CMD. A nonsignificant tendency toward greater differences between outcome groups was seen in JBMD. Continuous microdialysis monitoring of the cerebral drainage in the jugular bulb is feasible and safe. JBMD-to-CMD correlation is influenced by the type of metabolite measured, with glucose and lactate displaying the strongest associations. JBMD lactate correlated more often than CMD lactate to CPP, implying utility for detection of global cerebral metabolic perturbations. Studies comparing JBMD to other global measures of cerebral metabolism, e.g., PET CT or Xenon CT, are warranted.

Efficacy of Climate Forcings in PDRMIP Models.

Quantifying the efficacy of different climate forcings is important for understanding the real‐world climate sensitivity. This study presents a systematic multimodel analysis of different climate driver efficacies using simulations from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP). Efficacies calculated from instantaneous radiative forcing deviate considerably from unity across forcing agents and models. Effective radiative forcing (ERF) is a better predictor of global mean near‐surface air temperature (GSAT) change. Efficacies are closest to one when ERF is computed using fixed sea surface temperature experiments and adjusted for land surface temperature changes using radiative kernels. Multimodel mean efficacies based on ERF are close to one for global perturbations of methane, sulfate, black carbon, and insolation, but there is notable intermodel spread. We do not find robust evidence that the geographic location of sulfate aerosol affects its efficacy. GSAT is found to respond more slowly to aerosol forcing than CO2 in the early stages of simulations. Despite these differences, we find that there is no evidence for an efficacy effect on historical GSAT trend estimates based on simulations with an impulse response model, nor on the resulting estimates of climate sensitivity derived from the historical period. However, the considerable intermodel spread in the computed efficacies means that we cannot rule out an efficacy‐induced bias of ±0.4 K in equilibrium climate sensitivity to CO2 doubling when estimated using the historical GSAT trend.

Blocks in Tricarboxylic Acid Cycle of Salmonella enterica Cause Global Perturbation of Carbon Storage, Motility, and Host-Pathogen Interaction.

The tricarboxylic acid (TCA) cycle is a central metabolic hub in most cells. Virulence functions of bacterial pathogens such as facultative intracellular Salmonella enterica serovar Typhimurium (S Typhimurium) are closely connected to cellular metabolism. During systematic analyses of mutant strains with defects in the TCA cycle, a strain deficient in all fumarase isoforms (ΔfumABC) elicited a unique metabolic profile. Alongside fumarate, S Typhimurium ΔfumABC accumulates intermediates of the glycolysis and pentose phosphate pathway. Analyses by metabolomics and proteomics revealed that fumarate accumulation redirects carbon fluxes toward glycogen synthesis due to high (p)ppGpp levels. In addition, we observed reduced abundance of CheY, leading to altered motility and increased phagocytosis of S Typhimurium by macrophages. Deletion of glycogen synthase restored normal carbon fluxes and phagocytosis and partially restored levels of CheY. We propose that utilization of accumulated fumarate as carbon source induces a status similar to exponential- to stationary-growth-phase transition by switching from preferred carbon sources to fumarate, which increases (p)ppGpp levels and thereby glycogen synthesis. Thus, we observed a new form of interplay between metabolism of S Typhimurium and cellular functions and virulence.IMPORTANCE We performed perturbation analyses of the tricarboxylic acid cycle of the gastrointestinal pathogen Salmonella enterica serovar Typhimurium. The defect of fumarase activity led to accumulation of fumarate but also resulted in a global alteration of carbon fluxes, leading to increased storage of glycogen. Gross alterations were observed in proteome and metabolome compositions of fumarase-deficient Salmonella In turn, these changes were linked to aberrant motility patterns of the mutant strain and resulted in highly increased phagocytic uptake by macrophages. Our findings indicate that basic cellular functions and specific virulence functions in Salmonella critically depend on the proper function of the primary metabolism.

Multiscale dynamics of tight junction remodeling.

Epithelial cells form tissues that generate biological barriers in the body. Tight junctions (TJs) are responsible for maintaining a selectively permeable seal between epithelial cells, but little is known about how TJs dynamically remodel in response to physiological forces that challenge epithelial barrier function, such as cell shape changes (e.g. during cell division) or tissue stretching (e.g. during developmental morphogenesis). In this Review, we first introduce a framework to think about TJ remodeling across multiple scales: from molecular dynamics, to strand dynamics, to cell- and tissue-scale dynamics. We then relate knowledge gained from global perturbations of TJs to emerging information about local TJ remodeling events, where transient localized Rho activation and actomyosin-mediated contraction promote TJ remodeling to repair local leaks in barrier function. We conclude by identifying emerging areas in the field and propose ideas for future studies that address unanswered questions about the mechanisms that drive TJ remodeling.