bluuebunny/crossref_metadata_2025 huggingface dataset:
Turbulent Scales Observed in a River Plume Entering a Fjord
Authors: McPherson R. A. , Stevens C. L. , O'Callaghan J. M.
Published: November 2019

Observations of turbulent mixing are quantified in the near‐field region (first several kilometers) of a controlled river flow entering Doubtful Sound, New Zealand. Measurement techniques include direct turbulence measurements using microstructure profilers in both Eulerian and quasi‐Lagrangian perspectives and turbulent overturn analysis. Over 500 profiles of vertical microstructure were collected within the inner fjord. With high flow speeds of the surface plume over 2 m/s and some of the strongest stratification (N2∼10−1 s−2) recorded in the coastal ocean, turbulent overturning (Thorpe, LT) scales are used to indirectly infer turbulence dissipation rates (ϵ) and compared with direct measurements in a quasi‐idealized laboratory setting. There exists an inverse relationship between directly measured estimates of ϵ and distance from the plume discharge point. Peak values of ϵ>10−2 W/kg are observed within 500 m from the discharge point, among the highest turbulence dissipation rates recorded in oceanic shear flows. Thorpe scales range from below 1 cm in the pycnocline to a few meters in the weakly stratified ambient water below the plume. Stratification within the surface layer constrains the vertical dimension, limiting LT. Therefore, LT is an unreliable estimator of L0, where LO is the Ozmidov scale and is used to infer ϵ. Care must thus be taken when applying this method of overturn analysis in an environment where stratification or physical boundaries limit the vertical extent of overturns.
Multidecadal Changes in Meteorological Drought Severity and Their Drivers in Mainland China
Authors: Apurv Tushar , Xu Yue‐Ping , Wang Zhuo , Cai Ximing
Published: November 2019

This study analyzes the multidecadal changes in the severity of extreme meteorological droughts at the regional scale in China during 1951–2017. Dominance analysis is applied to multiple linear regression models to quantify the relative influence of global warming and internal variability on the meteorological drought severity in nine climate regions of China to understand which drivers are the most significant for each region and how they are likely to influence the severity of droughts in the near future (10–20 years). The influence of internal variability is represented by the Pacific Decadal Oscillation (PDO) and the Atlantic Multidecadal Oscillation (AMO). The PDO and global warming are found to have a stronger influence on the multidecadal variability of drought severity in China than the AMO. Global warming is found to be the more dominant driver of multidecadal variability of drought severity in the western parts of China, whereas the PDO is found to have a more dominant influence in the eastern parts of China. In the near future, global warming and the PDO are both likely to contribute to reduction of drought severity in Xinjiang, Northwest, and Tibet regions. The positive phase of the PDO is also expected to reduce the severity of droughts in Inner Mongolia and South China. On the other hand, both the PDO and global warming are expected to contribute to increase in drought severity in North and Southwest China in the near future.
Pre-clinical activity of combined LSD1 and mTORC1 inhibition in MLL-translocated acute myeloid leukaemia
Authors: Deb Gauri , Wingelhofer Bettina , Amaral Fabio M. R. , Maiques-Diaz Alba , Chadwick John A. , Spencer Gary J. , Williams Emma L. , Leong Hui-Sun , Maes Tamara , Somervaille Tim C. P.
Published: November 2019

The histone demethylase lysine-specific demethylase 1 (LSD1 or KDM1A) has emerged as a candidate therapeutic target in acute myeloid leukaemia (AML); tranylcypromine-derivative inhibitors induce loss of clonogenic activity and promote differentiation, in particular in the MLL-translocated molecular subtype of AML. In AML, the use of drugs in combination often delivers superior clinical activity. To identify genes and cellular pathways that collaborate with LSD1 to maintain the leukaemic phenotype, and which could be targeted by combination therapies, we performed a genome-wide CRISPR-Cas9 dropout screen. We identified multiple components of the amino acid sensing arm of mTORC1 signalling—RRAGA, MLST8, WDR24 and LAMTOR2—as cellular sensitizers to LSD1 inhibition. Knockdown of mTORC1 components, or mTORC1 pharmacologic inhibition, in combination with LSD1 inhibition enhanced differentiation in both cell line and primary cell settings, in vitro and in vivo, and substantially reduced the frequency of clonogenic primary human AML cells in a modelled minimal residual disease setting. Synergistic upregulation of a set of transcription factor genes associated with terminal monocytic lineage differentiation was observed. Thus, dual mTORC1 and LSD1 inhibition represents a candidate combination approach for enhanced differentiation in MLL-translocated AML which could be evaluated in early phase clinical trials.
Childhood intelligence attenuates the association between biological ageing and health outcomes in later life
Authors: Stevenson Anna J. , McCartney Daniel L. , Hillary Robert F. , Redmond Paul , Taylor Adele M. , Zhang Qian , McRae Allan F. , Spires-Jones Tara L. , McIntosh Andrew M. , Deary Ian J. , Marioni Riccardo E.
Published: November 2019

The identification of biomarkers that discriminate individual ageing trajectories is a principal target of ageing research. Some of the most promising predictors of biological ageing have been developed using DNA methylation. One recent candidate, which tracks age-related phenotypes in addition to chronological age, is ‘DNAm PhenoAge’. Here, we performed a phenome-wide association analysis of this biomarker in a cohort of older adults to assess its relationship with a comprehensive set of both historical, and contemporaneously-measured, phenotypes. Higher than expected DNAm PhenoAge compared with chronological age, known as epigenetic age acceleration, was found to associate with a number of blood, cognitive, physical fitness and lifestyle variables, and with mortality. Notably, DNAm PhenoAge, assessed at age 70, was associated with cognitive ability at age 11, and with educational attainment. Adjusting for age 11 cognitive ability attenuated the majority of the cross-sectional later-life associations between DNAm PhenoAge and health outcomes. These results highlight the importance of early life factors on healthy older ageing.
Sleep EEG slow-wave activity in medicated and unmedicated children and adolescents with attention-deficit/hyperactivity disorder
Authors: Furrer Melanie , Jaramillo Valeria , Volk Carina , Ringli Maya , Aellen Robert , Wehrle Flavia M. , Pugin Fiona , Kurth Salome , Brandeis Daniel , Schmid Markus , Jenni Oskar G. , Huber Reto
Published: November 2019

Slow waves (1–4.5 Hz) are the most characteristic oscillations of deep non-rapid eye movement sleep. The EEG power in this frequency range (slow-wave activity, SWA) parallels changes in cortical connectivity (i.e., synaptic density) during development. In patients with attention-deficit/hyperactivity disorder (ADHD), prefrontal cortical development was shown to be delayed and global gray matter volumes to be smaller compared to healthy controls. Using data of all-night recordings assessed with high-density sleep EEG of 50 children and adolescents with ADHD (mean age: 12.2 years, range: 8–16 years, 13 female) and 86 age- and sex-matched healthy controls (mean age: 12.2 years, range: 8–16 years, 23 female), we investigated if ADHD patients differ in the level of SWA. Furthermore, we examined the effect of stimulant medication. ADHD patients showed a reduction in SWA across the whole brain (−20.5%) compared to healthy controls. A subgroup analysis revealed that this decrease was not significant in patients who were taking stimulant medication on a regular basis at the time of their participation in the study. Assuming that SWA directly reflects synaptic density, the present findings are in line with previous data of neuroimaging studies showing smaller gray matter volumes in ADHD patients and its normalization with stimulant medication.
The Penrose Effect and its acceleration by the war on drugs: a crisis of untranslated neuroscience and untreated addiction and mental illness
Authors: Grecco Gregory G. , Andrew Chambers R.
Published: November 2019

In 1939, British psychiatrist Lionel Penrose described an inverse relationship between mental health treatment infrastructure and criminal incarcerations. This relationship, later termed the ‘Penrose Effect’, has proven remarkably predictive of modern trends which have manifested as reciprocal components, referred to as ‘deinstitutionalization’ and ‘mass incarceration’. In this review, we consider how a third dynamic—the criminalization of addiction via the ‘War on Drugs’, although unanticipated by Penrose, has likely amplified the Penrose Effect over the last 30 years, with devastating social, economic, and healthcare consequences. We discuss how synergy been the Penrose Effect and the War on Drugs has been mediated by, and reflects, a fundamental neurobiological connection between the brain diseases of mental illness and addiction. This neuroscience of dual diagnosis, also not anticipated by Penrose, is still not being adequately translated into improving clinical training, practice, or research, to treat patients across the mental illness-addictions comorbidity spectrum. This failure in translation, and the ongoing fragmentation and collapse of behavioral healthcare, has worsened the epidemic of untreated mental illness and addictions, while driving unsustainable government investment into mass incarceration and high-cost medical care that profits too exclusively on injuries and multi-organ diseases resulting from untreated addictions. Reversing the fragmentation and decline of behavioral healthcare with decisive action to co-integrate mental health and addiction training, care, and research—may be key to ending criminalization of mental illness and addiction, and refocusing the healthcare system on keeping the population healthy at the lowest possible cost.
In vivo delivery of VEGF RNA and protein to increase osteogenesis and intraosseous angiogenesis
Authors: Rumney Robin M. H. , Lanham Stuart A. , Kanczler Janos M. , Kao Alexander P. , Thiagarajan Lalitha , Dixon James E. , Tozzi Gianluca , Oreffo Richard O. C.
Published: November 2019

Deficient bone vasculature is a key component in pathological conditions ranging from developmental skeletal abnormalities to impaired bone repair. Vascularisation is dependent upon vascular endothelial growth factor (VEGF), which drives both angiogenesis and osteogenesis. The aim of this study was to examine the efficacy of blood vessel and bone formation following transfection with VEGF RNA or delivery of recombinant human VEGF165 protein (rhVEGF165) across in vitro and in vivo model systems. To quantify blood vessels within bone, an innovative approach was developed using high-resolution X-ray computed tomography (XCT) to generate quantifiable three-dimensional reconstructions. Application of rhVEGF165 enhanced osteogenesis, as evidenced by increased human osteoblast-like MG-63 cell proliferation in vitro and calvarial bone thickness following in vivo administration. In contrast, transfection with VEGF RNA triggered angiogenic effects by promoting VEGF protein secretion from MG-63VEGF165 cells in vitro, which resulted in significantly increased angiogenesis in the chorioallantoic (CAM) assay in ovo. Furthermore, direct transfection of bone with VEGF RNA in vivo increased intraosseous vascular branching. This study demonstrates the importance of continuous supply as opposed to a single high dose of VEGF on angiogenesis and osteogenesis and, illustrates the potential of XCT in delineating in 3D, blood vessel connectivity in bone.
Insights into the 400 million-year-old eyes of giant sea scorpions (Eurypterida) suggest the structure of Palaeozoic compound eyes
Authors: Schoenemann Brigitte , Poschmann Markus , Clarkson Euan N. K.
Published: November 2019

Sea scorpions (Eurypterida, Chelicerata) of the Lower Devonian (~400 Mya) lived as large, aquatic predators. The structure of modern chelicerate eyes is very different from that of mandibulate compound eyes [Mandibulata: Crustacea and Tracheata (Hexapoda, such as insects, and Myriapoda)]. Here we show that the visual system of Lower Devonian (~400 Mya) eurypterids closely matches that of xiphosurans (Xiphosura, Chelicerata). Modern representatives of this group, the horseshoe crabs (Limulidae), have cuticular lens cylinders and usually also an eccentric cell in their sensory apparatus. This strongly suggests that the xiphosuran/eurypterid compound eye is a plesiomorphic structure with respect to the Chelicerata, and probably ancestral to that of Euchelicerata, including Eurypterida, Arachnida and Xiphosura. This is supported by the fact that some Palaeozoic scorpions also possessed compound eyes similar to those of eurypterids. Accordingly, edge enhancement (lateral inhibition), organised by the eccentric cell, most useful in scattered light-conditions, may be a very old mechanism, while the single-lens system of arachnids is possibly an adaptation to a terrestrial life-style.
Reassessment of a juvenile Daspletosaurus from the Late Cretaceous of Alberta, Canada with implications for the identification of immature tyrannosaurids
Authors: Voris Jared T. , Zelenitsky Darla K. , Therrien François , Currie Philip J.
Published: November 2019

Daspletosaurus is a large tyrannosaurine found in upper Campanian deposits of Alberta and Montana. Although several large subadult and adult individuals of this taxon are known, only one juvenile individual, TMP 1994.143.1, has been identified. This specimen has played a key role in the idea that juvenile tyrannosaurid individuals are difficult to differentiate among species. Here the taxonomic affinity of TMP 1994.143.1 is reassessed in light of a juvenile tyrannosaurine postorbital recently discovered in the Dinosaur Park Formation of Alberta. Anatomical comparisons and phylogenetic analyses reveal that TMP 1994.143.1 is referable to the albertosaurine Gorgosaurus libratus, whereas the new postorbital belongs to a small juvenile Daspletosaurus. This taxonomic reassignment of TMP 1994.143.1 results in the juvenile ontogenetic stage of Daspletosaurus being known only from two isolated cranial elements. The new postorbital provides insights into early Daspletosaurus ontogeny, revealing that the cornual process developed earlier or faster than in other tyrannosaurids. Although some ontogenetic changes in the postorbital are found to be unique to Daspletosaurus, overall changes are most consistent with those of other large tyrannosaurines. Our results also show that diagnostic features develop early in ontogeny, such that juveniles of different tyrannosaurid species are easier to differentiate than previously thought.
The influence of urban form on the grid integration of renewable energy technologies and distributed energy systems
Authors: Perera A. T. D. , Coccolo Silvia , Scartezzini Jean-Louis
Published: November 2019

Standard and newly designed building blocks for complex urban sites– also designated by urban archetypes - are used in this study to quantify the influence of urban forms on their energy demand and energy systems design. An energy hub, which consists on a multi-carrier energy system involving multiple energy conversion, storage and/or network technologies, is employed to quantify the impact of the urban morphology on the energy system requirements. This study reveals that urban archetypes have a notable influence on the heating and cooling energy demands of city districts that can be characterized using form factors and floor area ratio. However, the influence on demand profiles cannot be assessed based on the aforementioned indicators. The cost of energy systems can increase up to 50% due to the impact of urban forms that are well beyond the increase of peak and/or annual energy demands. In addition, renewable energy integration to the grid as well its utilization in districts is influenced by urban forms. This makes it essential to consider energy system design as a part of the urban planning process moving even beyond building simulation.
Engineering of chimeric peptides as antagonists for the G protein-coupled receptor, RXFP4
Authors: Praveen Praveen , Bathgate Ross A. D. , Hossain Mohammed Akhter
Published: November 2019

Insulin-like peptide 5 (INSL5) is a very important pharma target for treating human conditions such as anorexia and diabetes. However, INSL5 with two chains and three disulfide bridges is an extremely difficult peptide to assemble by chemical or recombinant means. In a recent study, we were able to engineer a simplified INSL5 analogue 13 which is a relaxin family peptide receptor 4 (RXFP4)-specific agonist. To date, however, no RXFP4-specific antagonist (peptide or small molecule) has been reported in the literature. The focus of this study was to utilize the non-specific RXFP3/RXFP4 antagonist ΔR3/I5 as a template to rationally design an RXFP4 specific antagonist. Unexpectedly, we demonstrated that ΔR3/I5 exhibited partial agonism at RXFP4 when expressed in CHO cells which is associated with only partial antagonism of INSL5 analogue activation. In an attempt to improve RXFP4 specificity and antagonist activity we designed and chemically synthesized a series of analogues of ΔR3/I5. While all the chimeric analogues still demonstrated partial agonism at RXFP4, one peptide (Analogue 17) exhibited significantly improved RXFP4 specificity. Importantly, analogue 17 has a simplified structure which is more amenable to chemical synthesis. Therefore, analogue 17 is an ideal template for further development into a specific high affinity RXFP4 antagonist which will be an important tool to probe the physiological role of RXFP4/INSL5 axis.
Cu(II) and magnetite nanoparticles decorated melamine-functionalized chitosan: A synergistic multifunctional catalyst for sustainable cascade oxidation of benzyl alcohols/Knoevenagel condensation
Authors: Alirezvani Zahra , Dekamin Mohammad G. , Valiey Ehsan
Published: November 2019

The uniform decoration of Cu(II) species and magnetic nanoparticles on the melamine-functionalized chitosan afforded a new supramolecular biopolymeric nanocomposite (Cs-Pr-Me-Cu(II)-Fe3O4). The morphology, structure, and catalytic activity of the Cs-Pr-Me-Cu(II)-Fe3O4 nanocomposite have been systematically investigated. It was found that Cs-Pr-Me-Cu(II)-Fe3O4 nanocomposite can smoothly promote environmentally benign oxidation of different benzyl alcohol derivatives by tert-butyl hydroperoxide (TBHP) to their corresponding benzaldehydes and subsequent Knoevenagel condensation with malononitrile, as a multifunctional catalyst. Interestingly, Fe3O4 nanoparticles enhance the catalytic activity of Cu(II) species. The corresponding benzylidenemalononitriles were formed in high to excellent yields at ambient pressure and temperature. The heterogeneous Cs-Pr-Me-Cu(II)-Fe3O4 catalyst was also very stable with almost no leaching of the Cu(II) species into the reaction medium and could be easily recovered by an external magnet. The recycled Cs-Pr-Me-Cu(II)-Fe3O4 was reused at least four times with slight loss of its activity. This is a successful example of the combination of chemo- and bio-drived materials catalysis for mimicing biocatalysis as well as sustainable and one pot multistep synthesis.
The α1-adrenoceptor inhibitor ρ-TIA facilitates net hunting in piscivorous Conus tulipa
Authors: Dutt Mriga , Giacomotto Jean , Ragnarsson Lotten , Andersson Åsa , Brust Andreas , Dekan Zoltan , Alewood Paul F. , Lewis Richard J.
Published: November 2019

Cone snails use separately evolved venoms for prey capture and defence. While most use a harpoon for prey capture, the Gastridium clade that includes the well-studied Conus geographus and Conus tulipa, have developed a net hunting strategy to catch fish. This unique feeding behaviour requires secretion of “nirvana cabal” peptides to dampen the escape response of targeted fish allowing for their capture directly by mouth. However, the active components of the nirvana cabal remain poorly defined. In this study, we evaluated the behavioural effects of likely nirvana cabal peptides on the teleost model, Danio rerio (zebrafish). Surprisingly, the conantokins (NMDA receptor antagonists) and/or conopressins (vasopressin receptor agonists and antagonists) found in C. geographus and C. tulipa venom failed to produce a nirvana cabal-like effect in zebrafish. In contrast, low concentrations of the non-competitive adrenoceptor antagonist ρ-TIA found in C. tulipa venom (EC50 = 190 nM) dramatically reduced the escape response of zebrafish larvae when added directly to aquarium water. ρ-TIA inhibited the zebrafish α1-adrenoceptor, confirming ρ-TIA has the potential to reverse the known stimulating effects of norepinephrine on fish behaviour. ρ-TIA may act alone and not as part of a cabal, since it did not synergise with conopressins and/or conantokins. This study highlights the importance of using ecologically relevant animal behaviour models to decipher the complex neurobiology underlying the prey capture and defensive strategies of cone snails.
1H NMR study of the interaction of trans-resveratrol with soybean phosphatidylcholine liposomes
Authors: Cardia Maria Cristina , Caddeo Carla , Lai Francesco , Fadda Anna Maria , Sinico Chiara , Luhmer Michel
Published: November 2019

Resveratrol (RSV) is a well-known natural derivative with a wide range of biological and pharmacological activities. Despite of these demonstrated properties, it exhibits low both aqueous solubility and chemical stability and therefore low bioavailability. Consequently, the major concern of the technological research is to exploit delivery systems able to overcome bioavailability problems. In the recent past liposomes have been successfully studied for these purposes. In this paper, 1H-NMR spectroscopy, Nuclear Overhauser Spectroscopy (NOESY) as well as Paramagnetic Relaxation Enhancements (PRE) experiments have been carried out to quantitatively investigate the incorporation of resveratrol, at both the liposome preparation stage and by preformed liposomes, also with the aim to characterize resveratrol- soybean phosphatidylcholine (P90G) lipid bilayer interactions. Overall results of 1H NMR spectroscopy analysis suggest that RSV is located nearby the phosphocholine headgroups and also provide quantitative data on the incorporation of RSV (5% w/w), which corresponds to a 150-fold increase with respect to the solubility of RSV in water. Beside, considering that the same level of RSV incorporation was obtained via spontaneous uptake by preformed P90G liposomes, it can be concluded that RSV easily diffuses through the lipid bilayer.
Amplicon deep sequencing improves Plasmodium falciparum genotyping in clinical trials of antimalarial drugs
Authors: Gruenberg Maria , Lerch Anita , Beck Hans-Peter , Felger Ingrid
Published: November 2019

Clinical trials monitoring malaria drug resistance require genotyping of recurrent Plasmodium falciparum parasites to distinguish between treatment failure and new infection occurring during the trial follow up period. Because trial participants usually harbour multi-clonal P. falciparum infections, deep amplicon sequencing (AmpSeq) was employed to improve sensitivity and reliability of minority clone detection. Paired samples from 32 drug trial participants were Illumina deep-sequenced for five molecular markers. Reads were analysed by custom-made software HaplotypR and trial outcomes compared to results from the previous standard genotyping method based on length-polymorphic markers. Diversity of AmpSeq markers in pre-treatment samples was comparable or higher than length-polymorphic markers. AmpSeq was highly reproducible with consistent quantification of co-infecting parasite clones within a host. Outcomes of the three best-performing markers, cpmp, cpp and ama1-D3, agreed in 26/32 (81%) of patients. Discordance between the three markers performed per sample was much lower by AmpSeq (six patients) compared to length-polymorphic markers (eleven patients). Using AmpSeq for discrimination of recrudescence and new infection in antimalarial drug trials provides highly reproducible and robust characterization of clone dynamics during trial follow-up. AmpSeq overcomes limitations inherent to length-polymorphic markers. Regulatory clinical trials of antimalarial drugs will greatly benefit from this unbiased typing method.
Ecological networks: Pursuing the shortest path, however narrow and crooked
Authors: Costa Andrea , Martín González Ana M. , Guizien Katell , Doglioli Andrea M. , Gómez José María , Petrenko Anne A. , Allesina Stefano
Published: November 2019

Representing data as networks cuts across all sub-disciplines in ecology and evolutionary biology. Besides providing a compact representation of the interconnections between agents, network analysis allows the identification of especially important nodes, according to various metrics that often rely on the calculation of the shortest paths connecting any two nodes. While the interpretation of a shortest paths is straightforward in binary, unweighted networks, whenever weights are reported, the calculation could yield unexpected results. We analyzed 129 studies of ecological networks published in the last decade that use shortest paths, and discovered a methodological inaccuracy related to the edge weights used to calculate shortest paths (and related centrality measures), particularly in interaction networks. Specifically, 49% of the studies do not report sufficient information on the calculation to allow their replication, and 61% of the studies on weighted networks may contain errors in how shortest paths are calculated. Using toy models and empirical ecological data, we show how to transform the data prior to calculation and illustrate the pitfalls that need to be avoided. We conclude by proposing a five-point check-list to foster best-practices in the calculation and reporting of centrality measures in ecology and evolution studies.
The landscape of tiered regulation of breast cancer cell metabolism
Authors: Katzir Rotem , Polat Ibrahim H. , Harel Michal , Katz Shir , Foguet Carles , Selivanov Vitaly A. , Sabatier Philippe , Cascante Marta , Geiger Tamar , Ruppin Eytan
Published: November 2019

Altered metabolism is a hallmark of cancer, but little is still known about its regulation. In this study, we measure transcriptomic, proteomic, phospho-proteomic and fluxomics data in a breast cancer cell-line (MCF7) across three different growth conditions. Integrating these multiomics data within a genome scale human metabolic model in combination with machine learning, we systematically chart the different layers of metabolic regulation in breast cancer cells, predicting which enzymes and pathways are regulated at which level. We distinguish between two types of reactions, directly and indirectly regulated.Directly-regulatedreactions include those whose flux is regulated by transcriptomic alterations (~890) or via proteomic or phospho-proteomics alterations (~140) in the enzymes catalyzing them. We term the reactions that currently lack evidence for direct regulation as (putative)indirectly regulated(~930). Many metabolic pathways are predicted to be regulated at different levels, and those may change at different media conditions. Remarkably, we find that the flux of predicted indirectly regulated reactions is strongly coupled to the flux of the predicted directly regulated ones, uncovering a tiered hierarchical organization of breast cancer cell metabolism. Furthermore, the predicted indirectly regulated reactions are predominantly reversible. Taken together, this architecture may facilitate rapid and efficient metabolic reprogramming in response to the varying environmental conditions incurred by the tumor cells. The approach presented lays a conceptual and computational basis for mapping metabolic regulation in additional cancers.
Climate change could overturn bird migration: Transarctic flights and high-latitude residency in a sea ice free Arctic
Authors: Clairbaux Manon , Fort Jérôme , Mathewson Paul , Porter Warren , Strøm Hallvard , Grémillet David
Published: November 2019

Climate models predict that by 2050 the Arctic Ocean will be sea ice free each summer. Removing this barrier between the Atlantic and the Pacific will modify a wide range of ecological processes, including bird migration. Using published information, we identified 29 arctic-breeding seabird species, which currently migrate in the North Atlantic and could shift to a transarctic migration towards the North Pacific. We also identified 24 arctic-breeding seabird species which may shift from a migratory strategy to high-arctic year-round residency. To illustrate the biogeographical consequences of such drastic migratory shifts, we performed an in-depth study of little auks (Alle alle), the most numerous artic seabird. Coupling species distribution models and climatic models, we assessed the adequacy of future wintering and breeding areas for transarctic migrants and high-arctic year-round residents. Further, we used a mechanistic bioenergetics model (Niche Mapper), to compare the energetic costs of current little auk migration in the North Atlantic with potential transarctic and high-arctic residency strategies. Surprisingly, our results indicate that transarctic little auk migration, from the North Atlantic towards the North Pacific, may only be half as costly, energetically, than high-arctic residency or migration to the North Atlantic. Our study illustrates how global warming may radically modify the biogeography of migratory species, and provides a general methodological framework linking migratory energetics and spatial ecology.
Tracking capsule activation and crack healing in a microcapsule-based self-healing polymer
Authors: McDonald S. A. , Coban S. B. , Sottos N. R. , Withers P. J.
Published: November 2019

Structural polymeric materials incorporating a microencapsulated liquid healing agent demonstrate the ability to autonomously heal cracks. Understanding how an advancing crack interacts with the microcapsules is critical to optimizing performance through tailoring the size, distribution and density of these capsules. For the first time, time-lapse synchrotron X-ray phase contrast computed tomography (CT) has been used to observe in three-dimensions (3D) the dynamic process of crack growth, microcapsule rupture and progressive release of solvent into a crack as it propagates and widens, providing unique insights into the activation and repair process. In this epoxy self-healing material, 150 µm diameter microcapsules within 400 µm of the crack plane are found to rupture and contribute to the healing process, their discharge quantified as a function of crack propagation and distance from the crack plane. Significantly, continued release of solvent takes place to repair the crack as it grows and progressively widens.
Long-term stability of marine dissolved organic carbon emerges from a neutral network of compounds and microbes
Authors: Mentges A. , Feenders C. , Deutsch C. , Blasius B. , Dittmar T.
Published: November 2019

Dissolved organic carbon (DOC) is the main energy source for marine heterotrophic microorganisms, but a small fraction of DOC resists microbial degradation and accumulates in the ocean. The reason behind this recalcitrance is unknown. We test whether the long-term stability of DOC requires the existence of structurally refractory molecules, using a mechanistic model comprising a diverse network of microbe-substrate interactions. Model experiments reproduce three salient observations, even when all DOC compounds are equally degradable: (i) >15% of an initial DOC pulse resists degradation, but is consumed by microbes if concentrated, (ii) the modelled deep-sea DOC reaches stable concentrations of 30–40 mmolC/m3, and (iii) the mean age of deep-sea DOC is several times the age of deep water with a wide range from <100 to >10,000 years. We conclude that while structurally-recalcitrant molecules exist, they are not required in the model to explain either the amount or longevity of DOC.
Full title: High glucose protects mesenchymal stem cells from metformin-induced apoptosis through the AMPK-mediated mTOR pathway
Authors: He Xiao , Yang Yi , Yao Meng-Wei , Ren Ting-ting , Guo Wei , Li Ling , Xu Xiang
Published: November 2019

Micro- and macro-vascular events are directly associated with hyperglycemia in patients with type 2 diabetes mellitus (T2DM), but whether intensive glucose control decreases the risk of diabetic cardiovascular complications remains uncertain. Many studies have confirmed that impaired quality and quantity of mesenchymal stem cells (MSCs) plays a pathogenic role in diabetes. Our previous study found that the abundance of circulating MSCs was significantly decreased in patients with T2DM, which was correlated with the progression of diabetic complications. In addition, metformin-induced MSC apoptosis is one of the reasons for the decreased quantity of endogenous or exogenous MSCs during intensive glucose control. However, the role of glucose in metformin-induced MSC apoptosis during intensive glucose control in T2DM remains unknown. In this study, we found that metformin induces MSC apoptosis during intensive glucose control, while high glucose (standard glucose control) could significantly reverse its adverse effect in an AMPK-mTOR pathway dependent manner. Thus, our results indicate that the poorer clinical benefit of the intensive glucose control strategy may be related to an adverse effect due to metformin-induced MSC apoptosis during intensive glucose control therapy in patients with T2DM.
Spatial and temporal patterns of a pulsed resource dynamically drive the distribution of specialist herbivores
Authors: Doublet Violette , Gidoin Cindy , Lefèvre François , Boivin Thomas
Published: November 2019

Patterns and drivers of the spatio-temporal distribution of herbivores are key elements of their ecological and evolutionary impacts on plant populations. Herbivore spatial distributions may be influenced by increased (RCH: resource concentration hypothesis) or decreased (RDH: resource dilution hypothesis) resource densities, but the effect of temporal variations in resource densities on such distributions remains poorly documented. We used a survey of a masting tree species and its seed predators in Southeastern France to address the effect of a host’s pulsed resource on the spatio-temporal distributions of highly specialized insect herbivores feeding on seeds. Variations in both resource and seed predator densities were assessed by estimating seed production and seed infestation rates in focus trees during 10 consecutive years. We found increasing seed infestation rates with decreasing host tree densities in years of low seed production, indicating a RDH pattern of seed predators. However, such pattern was not persistent in years of high seed production during which seed infestation rates did not depend on host tree densities. We showed that temporal variations in resource density can lead to transience of seed predator spatial distribution. This study highlights how predictions of plant-herbivore interactions in natural ecosystems may rely on temporal components underlying RCH and RDH hypotheses.
Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis
Authors: Takenaka Kazuhiro , Tominaga Keiichi , Kanazawa Mimari , Fukushi Koh , Tanaka Takanao , Kanamori Akira , Sugaya Takeshi , Tsuchida Kouhei , Iijima Makoto , Goda Kenichi , Irisawa Atsushi
Published: November 2019

While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.
Respiratory tract infections among French Hajj pilgrims from 2014 to 2017
Authors: Hoang Van-Thuan , Ali-Salem Saliha , Belhouchat Khadidja , Meftah Mohammed , Sow Doudou , Dao Thi-Loi , Ly Tran Duc Anh , Drali Tassadit , Ninove Laetitia , Yezli Saber , Alotaibi Badriah , Raoult Didier , Parola Philippe , Pommier de Santi Vincent , Gautret Philippe
Published: November 2019

Respiratory tract infections (RTIs) are common among Hajj pilgrims, but risk factors for RTIs and respiratory pathogen acquisition during the Hajj are not clearly identified. Based on previous studies, most frequent pathogens acquired by Hajj pilgrims were investigated: rhinovirus, human coronaviruses, influenza viruses, Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Haemophilus influenzae. 485 pilgrims were included. 82.1% presented with RTIs. Respiratory chronic diseases were associated with cough, Influenza-like illness (ILI) and the acquisition of H. influenzae. Vaccination against invasive pneumococcal diseases (IPD) and influenza was associated with a decrease in the acquisition of S. pneumoniae and prevalence of ILI (aRR = 0.53, 95%CI [0.39–0.73] and aRR = 0.69, 95%CI [0.52–0.92] respectively). Individuals carrying rhinovirus and H. influenzae-S. pneumoniae together were respectively twice and five times more likely to have respiratory symptoms. Individual with H. influenzae-K. pneumoniae carriage were twice (p = 0.04) as likely to develop a cough. The use of disposable handkerchiefs was associated with a decrease in the acquisition of S. aureus (aRR = 0.75, 95%CI [0.57–0.97]). Results could be used to identify pilgrims at increased risk of RTIs and acquisition of respiratory pathogens. Results also confirm the effectiveness of influenza and IPD vaccinations in reducing ILI symptoms and acquisition of S. pneumoniae carriage respectively.
Pharmacogenetics of amfepramone in healthy Mexican subjects reveals potential markers for tailoring pharmacotherapy of obesity: results of a randomised trial
Authors: Gómez-Silva Magdalena , Piñeyro-Garza Everardo , Vargas-Zapata Rigoberto , Gamino-Peña María Elena , León-García Armando , de León Mario Bermúdez , Llerena Adrián , León-Cachón Rafael B. R.
Published: November 2019

Amfepramone (AFP) is an appetite-suppressant drug used in the treatment of obesity. Nonetheless, studies on interindividual pharmacokinetic variability and its association with genetic variants are limited. We employed a pharmacokinetic and pharmacogenetic approach to determine possible metabolic phenotypes of AFP and identify genetic markers that could affect the pharmacokinetic variability in a Mexican population. A controlled, randomized, crossover, single-blind, two-treatment, two-period, and two sequence clinical study of AFP (a single 75 mg dose) was conducted in 36 healthy Mexican volunteers who fulfilled the study requirements. Amfepramone plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed using real-time PCR with TaqMan probes. Four AFP metabolizer phenotypes were found in our population: slow, normal, intermediate, and fast. Additionally, two gene polymorphisms, ABCB1-rs1045642 and CYP3A4-rs2242480, had a significant effect on AFP pharmacokinetics (P < 0.05) and were the predictor factors in a log-linear regression model. The ABCB1 and CYP3A4 gene polymorphisms were associated with a fast metabolizer phenotype. These results suggest that metabolism of AFP in the Mexican population is variable. In addition, the genetic variants ABCB1-rs1045642 and CYP3A4-rs2242480 may partially explain the AFP pharmacokinetic variability.
PedMap: a pediatric diseases map generated from clinical big data from Hangzhou, China
Authors: Li Haomin , Yu Gang , Dong Cong , Jia Zheng , An Jiye , Duan Huilong , Shu Qiang
Published: November 2019

Epidemiological knowledge of pediatric diseases may improve professionals’ understanding of the pathophysiology of and risk factors for diseases and is also crucial for decision making related to workforce and resource planning in pediatric departments. In this study, a pediatric disease epidemiology knowledgebase called PedMap (http://pedmap.nbscn.org) was constructed from the clinical data from 5 447 202 outpatient visits of 2 189 868 unique patients at a children’s hospital (Hangzhou, China) from 2013 to 2016. The top 100 most-reported pediatric diseases were identified and visualized. These common pediatric diseases were clustered into 4 age groups and 4 seasons. The prevalence, age distribution and co-occurrence diseases for each disease were also visualized. Furthermore, an online prediction tool based on Gaussian regression models was developed to predict pediatric disease incidence based on weather information. PedMap is the first comprehensive epidemiological resource to show the full view of age-related, seasonal, climate-related variations in and co-occurrence patterns of pediatric diseases.
Maritime Aerosol Optical and Microphysical Properties in the South China Sea Under Multi-source Influence
Authors: Zhang Chi , Xu Hua , Li Zhengqiang , Xie Yisong , Li Donghui
Published: November 2019

The South China Sea hosts a wide range of aerosol pollutants with the uneven development of socio-economic and complicated meteorology system. To fill the gap of the maritime aerosol characteristics over the sea, we selected the multi-year ground-based measurements of Taiping Site and Dongsha Site to investigate the optical and microphysical properties. In Taiping, the vast majority of aerosol optical depths (AODs) are less than 0.2, but that of Dongsha shows the wider distribution of AODs from 0 to 0.6. Angstrom Exponent frequency distribution in Taiping peaks at the range of 0.75–1.25 but that has the left-skewed distribution in Taiping Island. Moreover, there is a variation in the coarse-mode volume concentration in Taiping Island but less variation in the fine mode. The seasonal maritime aerosol properties of Taiping and Dongsha have been analyzed that can be employed as a maritime look up table (LUT) kernel in coupled atmospheric retrieval and correction algorithms.
Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile
Authors: Cruite Justin T. , Kovacikova Gabriela , Clark Kenzie A. , Woodbrey Anne K. , Skorupski Karen , Kull F. Jon
Published: November 2019

The AraC/XylS-family transcriptional regulator ToxT is the master virulence activator ofVibrio cholerae, the gram-negative bacterial pathogen that causes the diarrheal disease cholera. Unsaturated fatty acids (UFAs) found in bile inhibit the activity of ToxT. Crystal structures of inhibited ToxT bound to UFA or synthetic inhibitors have been reported, but no structure of ToxT in an active conformation had been determined. Here we present the 2.5 Å structure of ToxT without an inhibitor. The structure suggests release of UFA or inhibitor leads to an increase in flexibility, allowing ToxT to adopt an active conformation that is able to dimerize and bind DNA. Small-angle X-ray scattering was used to validate a structural model of an open ToxT dimer bound to the cholera toxin promoter. The results presented here provide a detailed structural mechanism for virulence gene regulation inV. choleraeby the UFA components of bile and other synthetic ToxT inhibitors.
Single-atom nickel confined nanotube superstructure as support for catalytic wet air oxidation of acetic acid
Authors: Jin Chengyu , Ma Lei , Sun Wenjing , Han Peiwei , Tan Xiangdong , Wu Huiling , Liu Mengyang , Jin Haibo , Wu Zhongshuai , Wei Huangzhao , Sun Chenglin
Published: November 2019

Single-atom confined materials (SACMs) have been widely researched as catalysts in many fields within recent years. However, this class of materials may not only serve as a catalyst but also as a support material for certain reactions. Here we propose a general strategy to use SACMs as supports for tuning loaded noble metal (e.g., Ru) nanoparticles with enhanced catalytic activity. As a proof of concept, a nickel single-atom confined nitrogen-doped carbon nanotube (NCNT) superstructure is prepared as a support to load noble metal Ru for catalytic wet air oxidation of acetic acid. Improved catalytic activity with a mineralization rate of ~97.5% is achieved. Further, adsorption configurations based on DFT calculations also confirm our deduction that the introduction of single-atom Ni changes the intrinsic property of NCNTs and affects the loaded active Ru nanoparticles.
A rapid, multiplexed kinase activity assay using 8-plex iTRAQ labeling, SPE, and MALDI-TOF/TOF MS
Authors: Liu Yu-Ching , Tsai Fuu-Jen , Chen Chao-Jung
Published: November 2019

Synthesized peptide substrates with iTRAQ labeling has been used for in vitro kinase assay using cell lysates and detected by MALDI TOF/TOF MS.
Progress in the isolation of aptamers to light-up the dyes and the applications
Authors: Gao Tian , Luo Yu , Li Wenjing , Cao Yanwei , Pei Renjun
Published: November 2019

The progress in the selection of aptamers to light-up the dyes and the related applications are reviewed.
A method for recording the two phases of dopamine release in mammalian brain striatum slices
Authors: Jiao Ruiying , Liu Wei , Yin Lili , Qiao Zhongjun , Li Jie , Zhou Li , Younus Muhammad , Wang Li , Xu Huadong , Zhou Zhuan
Published: November 2019

Striatal dopamine (DA) release plays an essential role in many physiological functions including motor and non-motor behaviors (such as reward, motivation, and cognition).
Raman spectroscopy as a potential diagnostic tool to analyse biochemical alterations in lung cancer
Authors: Zheng Qingfeng , Li Junyi , Yang Lin , Zheng Bo , Wang Jiangcai , Lv Ning , Luo Jianbin , Martin Francis L. , Liu Dameng , He Jie
Published: November 2019

Raman spectroscopy can be used as a rapid diagnosis tool in lung cancer to help us understand cancer progression at molecular level and improve clinical practices.
Pd–NiO-Y/CNT nanofoam: a zeolite-carbon nanotube conjugate exhibiting high durability in methanol oxidation
Authors: Sharma Mukesh , Das Biraj , Baruah Manash J. , Bhattacharyya Pradip K. , Saikia Lakshi , Bania Kusum K
Published: November 2019

Pd–NiO hybridized with zeolite and multiwalled carbon nanotube appeared as highly effective electrocatalyst in methanol oxidation reaction.