bluuebunny/crossref_metadata_2025 huggingface dataset:
Ecoregions in the Mediterranean Sea Through the Reanalysis of Phytoplankton Functional Types and Carbon Fluxes
Authors: Ciavatta S. , Kay S. , Brewin R. J. W. , Cox R. , Di Cicco A. , Nencioli F. , Polimene L. , Sammartino M. , Santoleri R. , Skákala J. , Tsapakis M.
Published: September 2019

In this work we produced a long‐term reanalysis of the phytoplankton community structure in the Mediterranean Sea and used it to define ecoregions. These were based on the spatial variability of the phytoplankton type fractions and their influence on selected carbon fluxes. A regional ocean color product of four phytoplankton functional types (PFTs; diatoms, dinoflagellates, nanophytoplankton, and picophytoplankton) was assimilated into a coupled physical‐biogeochemical model of the Mediterranean Sea (Proudman Oceanographic Laboratory Coastal Ocean Modelling System‐European Regional Seas Ecosystem Model, POLCOMS–ERSEM) by using a 100‐member ensemble Kalman filter, in a reanalysis simulation for years 1998–2014. The reanalysis outperformed the reference simulation in representing the assimilated ocean color PFT fractions to total chlorophyll, although the skill for the ocean color PFT concentrations was not improved significantly. The reanalysis did not impact noticeably the reference simulation of not assimilated in situ observations, with the exception of a slight bias reduction for the situ PFT concentrations, and a deterioration of the phosphate simulation. We found that the Mediterranean Sea can be subdivided in three PFT‐based ecoregions, derived from the spatial variability of the PFT fraction dominance or relevance. Picophytoplankton dominates the largest part of open ocean waters; microphytoplankton dominates in a few, highly productive coastal spots near large‐river mouths; nanophytoplankton is relevant in intermediate‐productive coastal and Atlantic‐influenced waters. The trophic and carbon sedimentation efficiencies are highest in the microphytoplankton ecoregion and lowest in the picophytoplankton and nanophytoplankton ecoregions. The reanalysis and regionalization offer new perspectives on the variability of the structure and functioning of the phytoplankton community and related biogeochemical fluxes, with foreseeable applications in Blue Growth of the Mediterranean Sea.
Biogeochemical Anomalies at Two Southern California Current System Moorings During the 2014–2016 Warm Anomaly‐El Niño Sequence
Authors: Lilly Laura E. , Send Uwe , Lankhorst Matthias , Martz Todd R. , Feely Richard A. , Sutton Adrienne J. , Ohman Mark D.
Published: September 2019

We analyzed impacts of the 2014–2015 Pacific Warm Anomaly and 2015–2016 El Niño on physical and biogeochemical variables at two southern California Current System moorings (CCE2, nearshore upwelling off Point Conception; CCE1, offshore California Current). Nitrate and Chl‐a fluorescence were <1 μM and <1 Standardized Fluorescence Unit, respectively, at CCE2 for the entire durations of the Warm Anomaly and El Niño, the two longest periods of such low values in our time series. Negative nitrate and Chl‐a anomalies at CCE2 were interrupted briefly by upwelling conditions in spring 2015. Near‐surface temperature anomalies appeared simultaneously at both moorings in spring 2014, indicating region‐wide onset of Warm Anomaly temperatures, although sustained negative nitrate and Chl‐a anomalies only occurred offshore at CCE1 during El Niño (summer 2015 to spring 2016). Warm Anomaly temperature changes were expressed more strongly in near‐surface (<40 m) than subsurface (75 m) waters at both moorings, while El Niño produced comparable temperature anomalies at near‐surface and subsurface depths. Nearshore Ωaragonite at 76 m showed notably fewer undersaturation events during both warm periods, suggesting an environment more conducive to calcifying organisms. Planktonic calcifying molluscs (pteropods and heteropods) increased markedly in springs 2014 and 2016 and remained modestly elevated in spring 2015. Moorings provide high‐frequency measurements essential for resolving the onset timing of anomalous conditions and frequency and duration of short‐term (days‐to‐weeks) perturbations (reduced nitrate and aragonite undersaturation events) that can affect marine organisms.
Physical Mechanisms Controlling the Offshore Propagation of Convection in the Tropics: 2. Influence of Topography
Authors: Coppin David , Bellon Gilles
Published: September 2019

A set of idealized convection‐permitting simulations is performed to investigate the influence of topography on the physical mechanisms responsible for the nocturnal offshore propagation of convection around tropical islands. All simulations have an idealized island in the middle of a long channel oceanic domain, with constant sea surface temperature and without rotation. To diagnose the impact of topography, we compare a flat island simulation with two simulations with mountain ranges of different shapes. The topography over the island has a strong impact on the diurnal cycle of convection as clouds tend to remain all day over the highest topography. This weakens the diurnal cycle and the land breeze front and triggers a comparatively less frequent long‐distance offshore propagation of convection. As in the flat simulation, the distance of offshore propagation is particularly sensitive to humidity and temperature at the top of the boundary layer. A shallow circulation that is asymmetric with respect to the island influences the boundary layer top humidity and can favor propagation on one side of the island or the other. These results mimic cloud and precipitation patterns observed prior to the Madden‐Julian Oscillation propagation over the Maritime Continent. The shape of the topography does not seem to influence the offshore propagation of convection significantly except for mountain‐valley breezes that reinforce the land breeze and the establishment of the asymmetric shallow circulation.
Mechanisms and disease implications of sirtuin-mediated autophagic regulation
Authors: Lee In Hye
Published: September 2019

Accumulating evidence has indicated that sirtuins are key components of diverse physiological processes, including metabolism and aging. Sirtuins confer protection from a wide array of metabolic and age-related diseases, such as cancer, cardiovascular and neurodegenerative diseases. Recent studies have also suggested that sirtuins regulate autophagy, a protective cellular process for homeostatic maintenance in response to environmental stresses. Here, we describe various biological and pathophysiological processes regulated by sirtuin-mediated autophagy, focusing on cancer, heart, and liver diseases, as well as stem cell biology. This review also emphasizes key molecular mechanisms by which sirtuins regulate autophagy. Finally, we discuss novel insights into how new therapeutics targeting sirtuin and autophagy may potentially lead to effective strategies to combat aging and aging-related diseases.
Metaproteomics reveal that rapid perturbations in organic matter prioritize functional restructuring over taxonomy in western Arctic Ocean microbiomes
Authors: Mikan Molly P , Harvey H Rodger , Timmins-Schiffman Emma , Riffle Michael , May Damon H , Salter Ian , Noble William S , Nunn Brook L
Published: September 2019

We examined metaproteome profiles from two Arctic microbiomes during 10-day shipboard incubations to directly track early functional and taxonomic responses to a simulated algal bloom and an oligotrophic control. Using a novel peptide-based enrichment analysis, significant changes (p-value < 0.01) in biological and molecular functions associated with carbon and nitrogen recycling were observed. Within the first day under both organic matter conditions, Bering Strait surface microbiomes increased protein synthesis, carbohydrate degradation, and cellular redox processes while decreasing C1 metabolism. Taxonomic assignments revealed that the core microbiome collectively responded to algal substrates by assimilating carbon before select taxa utilize and metabolize nitrogen intracellularly. Incubations of Chukchi Sea bottom water microbiomes showed similar, but delayed functional responses to identical treatments. Although 24 functional terms were shared between experimental treatments, the timing, and degree of the remaining responses were highly variable, showing that organic matter perturbation directs community functionality prior to alterations to the taxonomic distribution at the microbiome class level. The dynamic responses of these two oceanic microbial communities have important implications for timing and magnitude of responses to organic perturbations within the Arctic Ocean and how community-level functions may forecast biogeochemical gradients in oceans.
Electrophysiological evaluation of extracellular spermine and alkaline pH on synaptic human GABAA receptors
Authors: Limon A. , Delbruck E. , Yassine A. , Pandya D. , Myers R. M. , Barchas J. D. , Lee F. , Schatzberg  , Watson S. J. , Akil H. , Bunney W. E. , Vawter M. P. , Sequeira A.
Published: September 2019

Polyamines have fundamental roles in brain homeostasis as key modulators of cellular excitability. Several studies have suggested alterations in polyamine metabolism in stress related disorders, suicide, depression, and neurodegeneration, making the pharmacological modulation of polyamines a highly appealing therapeutic strategy. Polyamines are small aliphatic molecules that can modulate cationic channels involved in neuronal excitability. Previous indirect evidence has suggested that polyamines can modulate anionic GABAA receptors (GABAARs), which mediate inhibitory signaling and provide a direct route to reduce hyperexcitability. Here, we attempted to characterize the effect that spermine, the polyamine with the strongest reported effect on GABAARs, has on human postmortem native GABAARs. We microtransplanted human synaptic membranes from the dorsolateral prefrontal cortex of four cases with no history of mental or neurological disorders, and directly recorded spermine effects on ionic GABAARs responses on microtransplanted oocytes. We show that in human synapses, inhibition of GABAARs by spermine was better explained by alkalization of the extracellular solution. Additionally, spermine had no effect on the potentiation of GABA-currents by diazepam, indicating that even if diazepam binding is enhanced by spermine, it does not translate to changes in functional activity. Our results clearly demonstrate that while extracellular spermine does not have direct effects on human native synaptic GABAARs, spermine-mediated shifts of pH inhibit GABAARs. Potential spermine-mediated increase of pH in synapses in vivo may therefore participate in increased neuronal activity observed during physiological and pathological states, and during metabolic alterations that increase the release of spermine to the extracellular milieu.
Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival
Authors: Cajuso Tatiana , Sulo Päivi , Tanskanen Tomas , Katainen Riku , Taira Aurora , Hänninen Ulrika A. , Kondelin Johanna , Forsström Linda , Välimäki Niko , Aavikko Mervi , Kaasinen Eevi , Ristimäki Ari , Koskensalo Selja , Lepistö Anna , Renkonen-Sinisalo Laura , Seppälä Toni , Kuopio Teijo , Böhm Jan , Mecklin Jukka-Pekka , Kilpivaara Outi , Pitkänen Esa , Palin Kimmo , Aaltonen Lauri A.
Published: September 2019

Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initiating events. Insertions are positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions is independently associated with poor disease-specific survival.
Caspase-11 signaling enhances graft-versus-host disease
Authors: Lu Yanyan , Meng Ran , Wang Xiangyu , Xu Yajing , Tang Yiting , Wu Jianfeng , Xue Qianqian , Yu Songlin , Duan Mingwu , Shan Dongyong , Wang Qingde , Wang Haichao , Billiar Timothy R. , Xiao Xianzhong , Chen Fangping , Lu Ben
Published: September 2019

Acute graft-versus-host disease (GVHD) remains a major obstacle for the wider usage of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an effective therapy for hematopoietic malignancy. Here we show that caspase-11, the cytosolic receptor for bacterial endotoxin (lipopolysaccharide: LPS), enhances GVHD severity. Allo-HSCT markedly increases the LPS-caspase-11 interaction, leading to the cleavage of gasdermin D (GSDMD). Caspase-11 and GSDMD mediate the release of interleukin-1α (IL-1α) in allo-HSCT. Deletion of Caspase-11 or Gsdmd, inhibition of LPS-caspase-11 interaction, or neutralizing IL-1α uniformly reduces intestinal inflammation, tissue damage, donor T cell expansion and mortality in allo-HSCT. Importantly, Caspase-11 deficiency does not decrease the graft-versus-leukemia (GVL) activity, which is essential to prevent cancer relapse. These findings have major implications for allo-HSCT, as pharmacological interference with the caspase-11 signaling might reduce GVHD while preserving GVL activity.
Rapid metabolic shifts occur during the transition between hunger and satiety in Drosophila melanogaster
Authors: Wilinski Daniel , Winzeler Jasmine , Duren William , Persons Jenna L. , Holme Kristina J. , Mosquera Johan , Khabiri Morteza , Kinchen Jason M. , Freddolino Peter L. , Karnovsky Alla , Dus Monica
Published: September 2019

Metabolites are active controllers of cellular physiology, but their role in complex behaviors is less clear. Here we report metabolic changes that occur during the transition between hunger and satiety in Drosophila melanogaster. To analyze these data in the context of fruit fly metabolic networks, we developed Flyscape, an open-access tool. We show that in response to eating, metabolic profiles change in quick, but distinct ways in the heads and bodies. Consumption of a high sugar diet dulls the metabolic and behavioral differences between the fasted and fed state, and reshapes the way nutrients are utilized upon eating. Specifically, we found that high dietary sugar increases TCA cycle activity, alters neurochemicals, and depletes 1-carbon metabolism and brain health metabolites N-acetyl-aspartate and kynurenine. Together, our work identifies the metabolic transitions that occur during hunger and satiation, and provides a platform to study the role of metabolites and diet in complex behavior.
Liquefaction of water on the surface of anisotropic two-dimensional atomic layered black phosphorus
Authors: Zhao Jinlai , Zhu Jiajie , Cao Rui , Wang Huide , Guo Zhinan , Sang David K. , Tang Jiaoning , Fan Dianyuan , Li Jianqing , Zhang Han
Published: September 2019

The growth and wetting of water on two-dimensional(2D) materials are important to understand the development of 2D material based electronic, optoelectronic, and nanomechanical devices. Here, we visualize the liquefaction processes of water on the surface of graphene, MoS2 and black phosphorus (BP) via optical microscopy. We show that the shape of the water droplets forming on the surface of BP, which is anisotropic, is elliptical. In contrast, droplets are rounded when they form on the surface of graphene or MoS2, which do not possess orthometric anisotropy. Molecular simulations show that the anisotropic liquefaction process of water on the surface of BP is attributed to the different binding energies of H2O molecules on BP along the armchair and zigzag directions. The results not only reveal the anisotropic nature of water liquefaction on the BP surface but also provide a way for fast and nondestructive determination of the crystalline orientation of BP.
Functional disease architectures reveal unique biological role of transposable elements
Authors: Hormozdiari Farhad , van de Geijn Bryce , Nasser Joseph , Weissbrod Omer , Gazal Steven , Ju Chelsea J. -T. , Connor Luke O’ , Hujoel Margaux L. A. , Engreitz Jesse , Hormozdiari Fereydoun , Price Alkes L.
Published: September 2019

Transposable elements (TE) comprise roughly half of the human genome. Though initially derided as junk DNA, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases remains unknown. Here, we analyze data from 41 independent diseases and complex traits to draw three conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39 ± 2% of heritability), TE explain substantially more heritability than expected based on their depletion for known functional annotations. This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring biological function. Third, Short Interspersed Nuclear Elements (SINE) are far more enriched for blood traits than for other traits. Our results can help elucidate the biological roles that TE play in the genetic architecture of diseases.
Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation
Authors: Huang Jian-Ping , Fang Chengli , Ma Xiaoyan , Wang Li , Yang Jing , Luo Jianying , Yan Yijun , Zhang Yu , Huang Sheng-Xiong
Published: September 2019

The skeleton of tropane alkaloids is derived from ornithine-derived N-methylpyrrolinium and two malonyl-CoA units. The enzymatic mechanism that connects N-methylpyrrolinium and malonyl-CoA units remains unknown. Here, we report the characterization of three pyrrolidine ketide synthases (PYKS), AaPYKS, DsPYKS, and AbPYKS, from three different hyoscyamine- and scopolamine-producing plants. By examining the crystal structure and biochemical activity of AaPYKS, we show that the reaction mechanism involves PYKS-mediated malonyl-CoA condensation to generate a 3-oxo-glutaric acid intermediate that can undergo non-enzymatic Mannich-like condensation with N-methylpyrrolinium to yield the racemic 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This study therefore provides a long sought-after biosynthetic mechanism to explain condensation between N-methylpyrrolinium and acetate units and, more importantly, identifies an unusual plant type III polyketide synthase that can only catalyze one round of malonyl-CoA condensation.
Auxin-sensitive Aux/IAA proteins mediate drought tolerance in Arabidopsis by regulating glucosinolate levels
Authors: Salehin Mohammad , Li Baohua , Tang Michelle , Katz Ella , Song Liang , Ecker Joseph R. , Kliebenstein Daniel J. , Estelle Mark
Published: September 2019

A detailed understanding of abiotic stress tolerance in plants is essential to provide food security in the face of increasingly harsh climatic conditions. Glucosinolates (GLSs) are secondary metabolites found in the Brassicaceae that protect plants from herbivory and pathogen attack. Here we report that in Arabidopsis, aliphatic GLS levels are regulated by the auxin-sensitive Aux/IAA repressors IAA5, IAA6, and IAA19. These proteins act in a transcriptional cascade that maintains expression of GLS levels when plants are exposed to drought conditions. Loss of IAA5/6/19 results in reduced GLS levels and decreased drought tolerance. Further, we show that this phenotype is associated with a defect in stomatal regulation. Application of GLS to the iaa5,6,19 mutants restores stomatal regulation and normal drought tolerance. GLS action is dependent on the receptor kinase GHR1, suggesting that GLS may signal via reactive oxygen species. These results provide a novel connection between auxin signaling, GLS levels and drought response.
Central nicotine induces browning through hypothalamic κ opioid receptor
Authors: Seoane-Collazo Patricia , Liñares-Pose Laura , Rial-Pensado Eva , Romero-Picó Amparo , Moreno-Navarrete José María , Martínez-Sánchez Noelia , Garrido-Gil Pablo , Iglesias-Rey Ramón , Morgan Donald A. , Tomasini Naoki , Malone Samuel Andrew , Senra Ana , Folgueira Cintia , Medina-Gomez Gema , Sobrino Tomás , Labandeira-García José L. , Nogueiras Rubén , Domingos Ana I. , Fernández-Real José-Manuel , Rahmouni Kamal , Diéguez Carlos , López Miguel
Published: September 2019

Increased body weight is a major factor that interferes with smoking cessation. Nicotine, the main bioactive compound in tobacco, has been demonstrated to have an impact on energy balance, since it affects both feeding and energy expenditure at the central level. Among the central actions of nicotine on body weight, much attention has been focused on its effect on brown adipose tissue (BAT) thermogenesis, though its effect on browning of white adipose tissue (WAT) is unclear. Here, we show that nicotine induces the browning of WAT through a central mechanism and that this effect is dependent on the κ opioid receptor (KOR), specifically in the lateral hypothalamic area (LHA). Consistent with these findings, smokers show higher levels of uncoupling protein 1 (UCP1) expression in WAT, which correlates with smoking status. These data demonstrate that central nicotine-induced modulation of WAT browning may be a target against human obesity.
Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
Authors: Pan Dongqing , Walstein Kai , Take Annika , Bier David , Kaiser Nadine , Musacchio Andrea
Published: September 2019

Nucleosomes containing the histone H3 variant CENP-A are the epigenetic mark of centromeres, the kinetochore assembly sites required for chromosome segregation. HJURP is the CENP-A chaperone, which associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. How these proteins interact to promote CENP-A deposition remains poorly understood. Here we show that two repeats in human HJURP proposed to be functionally distinct are in fact interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it. HJURP binds CENP-A:H4 dimers, and therefore assembly of CENP-A:H4 tetramers must be performed by two Mis18αβ:M18BP1:HJURP complexes, or by the same complex in consecutive rounds. The Mis18α N-terminal tails blockade two identical HJURP-repeat binding sites near the Mis18αβ C-terminal helices. These were identified by photo-cross-linking experiments and mutated to separate Mis18 from HJURP centromere recruitment. Our results identify molecular underpinnings of eukaryotic chromosome inheritance and shed light on how centromeres license CENP-A deposition.
Gene networks that compensate for crosstalk with crosstalk
Authors: Müller Isaak E. , Rubens Jacob R. , Jun Tomi , Graham Daniel , Xavier Ramnik , Lu Timothy K.
Published: September 2019

Crosstalk is a major challenge to engineering sophisticated synthetic gene networks. A common approach is to insulate signal-transduction pathways by minimizing molecular-level crosstalk between endogenous and synthetic genetic components, but this strategy can be difficult to apply in the context of complex, natural gene networks and unknown interactions. Here, we show that synthetic gene networks can be engineered to compensate for crosstalk by integrating pathway signals, rather than by pathway insulation. We demonstrate this principle using reactive oxygen species (ROS)-responsive gene circuits in Escherichia coli that exhibit concentration-dependent crosstalk with non-cognate ROS. We quantitatively map the degree of crosstalk and design gene circuits that introduce compensatory crosstalk at the gene network level. The resulting gene network exhibits reduced crosstalk in the sensing of the two different ROS. Our results suggest that simple network motifs that compensate for pathway crosstalk can be used by biological networks to accurately interpret environmental signals.
Polyunsaturated fatty acid production by Yarrowia lipolytica employing designed myxobacterial PUFA synthases
Authors: Gemperlein Katja , Dietrich Demian , Kohlstedt Michael , Zipf Gregor , Bernauer Hubert S. , Wittmann Christoph , Wenzel Silke C. , Müller Rolf
Published: September 2019

Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly the omega-3 LC-PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), have been associated with beneficial health effects. Consequently, sustainable sources have to be developed to meet the increasing demand for these PUFAs. Here, we demonstrate the design and construction of artificial PUFA biosynthetic gene clusters (BGCs) encoding polyketide synthase-like PUFA synthases from myxobacteria adapted for the oleaginous yeast Yarrowia lipolytica. Genomic integration and heterologous expression of unmodified or hybrid PUFA BGCs yielded different yeast strains with specific LC-PUFA production profiles at promising yield and thus valuable for the biotechnological production of distinct PUFAs. Nutrient screening revealed a strong enhancement of PUFA production, when cells were phosphate limited. This represents, to the best of our knowledge, highest concentration of DHA (16.8 %) in total fatty acids among all published PUFA-producing Y. lipolytica strains.
ARID1A promotes genomic stability through protecting telomere cohesion
Authors: Zhao Bo , Lin Jianhuang , Rong Lijie , Wu Shuai , Deng Zhong , Fatkhutdinov Nail , Zundell Joseph , Fukumoto Takeshi , Liu Qin , Kossenkov Andrew , Jean Stephanie , Cadungog Mark G. , Borowsky Mark E. , Drapkin Ronny , Lieberman Paul M. , Abate-Shen Cory T. , Zhang Rugang
Published: September 2019

ARID1A inactivation causes mitotic defects. Paradoxically, cancers with high ARID1A mutation rates typically lack copy number alterations (CNAs). Here, we show that ARID1A inactivation causes defects in telomere cohesion, which selectively eliminates gross chromosome aberrations during mitosis. ARID1A promotes the expression of cohesin subunit STAG1 that is specifically required for telomere cohesion. ARID1A inactivation causes telomere damage that can be rescued by STAG1 expression. Colony formation capability of single cells in G2/M, but not G1 phase, is significantly reduced by ARID1A inactivation. This correlates with an increase in apoptosis and a reduction in tumor growth. Compared with ARID1A wild-type tumors, ARID1A-mutated tumors display significantly less CNAs across multiple cancer types. Together, these results show that ARID1A inactivation is selective against gross chromosome aberrations through causing defects in telomere cohesion, which reconciles the long-standing paradox between the role of ARID1A in maintaining mitotic integrity and the lack of genomic instability in ARID1A-mutated cancers.
Continuous artificial synthesis of glucose precursor using enzyme-immobilized microfluidic reactors
Authors: Zhu Yujiao , Huang Ziyu , Chen Qingming , Wu Qian , Huang Xiaowen , So Pui-Kin , Shao Liyang , Yao Zhongping , Jia Yanwei , Li Zhaohui , Yu Weixing , Yang Yi , Jian Aoqun , Sang Shengbo , Zhang Wendong , Zhang Xuming
Published: September 2019

Food production in green crops is severely limited by low activity and poor specificity of D-ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) in natural photosynthesis (NPS). This work presents a scientific solution to overcome this problem by immobilizing RuBisCO into a microfluidic reactor, which demonstrates a continuous production of glucose precursor at 13.8 μmol g−1 RuBisCO min−1 from CO2 and ribulose-1,5-bisphosphate. Experiments show that the RuBisCO immobilization significantly enhances enzyme stabilities (7.2 folds in storage stability, 6.7 folds in thermal stability), and also improves the reusability (90.4% activity retained after 5 cycles of reuse and 78.5% after 10 cycles). This work mimics the NPS pathway with scalable microreactors for continuous synthesis of glucose precursor using very small amount of RuBisCO. Although still far from industrial production, this work demonstrates artificial synthesis of basic food materials by replicating the light-independent reactions of NPS, which may hold the key to food crisis relief and future space colonization.
Deep brain stimulation and genetic variability in Parkinson’s disease: a review of the literature
Authors: Ligaard Johanne , Sannæs Julia , Pihlstrøm Lasse
Published: September 2019

Deep brain stimulation is offered as symptomatic treatment in advanced Parkinson’s disease, depending on a clinical assessment of the individual patient’s risk-benefit profile. Genetics contribute to phenotypic variability in Parkinson’s disease, suggesting that genetic testing could have clinical relevance for personalized therapy. Aiming to review current evidence linking genetic variation to deep brain stimulation treatment and outcomes in Parkinson’s disease we performed systematic searches in the Embase and PubMed databases to identify relevant publications and summarized the findings. We identified 39 publications of interest. Genetic screening studies indicate that monogenic forms of Parkinson’s disease and high-risk variants of GBA may be more common in cohorts treated with deep brain stimulation. Studies assessing deep brain stimulation outcomes in patients carrying mutations in specific genes are limited in size. There are reports suggesting that the phenotype associated with parkin mutations could be suitable for early surgery. In patients with LRRK2 mutations, outcomes of deep brain stimulation seem at least as good as in mutation-negative patients, whereas less favorable outcomes are seen in patients carrying mutations in GBA. Careful assessment of clinical symptoms remains the primary basis for clinical decisions associated with deep brain stimulation surgery in Parkinson’s disease, although genetic information could arguably be taken into account in special cases. Current evidence is scarce, but highlights a promising development where genetic profiling may be increasingly relevant for clinicians tailoring personalized medical or surgical therapy to Parkinson’s disease patients.
Quantum network routing and local complementation
Authors: Hahn F. , Pappa A. , Eisert J.
Published: September 2019

Quantum communication between distant parties is based on suitable instances of shared entanglement. For efficiency reasons, in an anticipated quantum network beyond point-to-point communication, it is preferable that many parties can communicate simultaneously over the underlying infrastructure; however, bottlenecks in the network may cause delays. Sharing of multi-partite entangled states between parties offers a solution, allowing for parallel quantum communication. Specifically for the two-pair problem, the butterfly network provides the first instance of such an advantage in a bottleneck scenario. In this paper, we propose a more general method for establishing EPR pairs in arbitrary networks. The main difference from standard repeater network approaches is that we use a graph state instead of maximally entangled pairs to achieve long-distance simultaneous communication. We demonstrate how graph-theoretic tools, and specifically local complementation, help decrease the number of required measurements compared to usual methods applied in repeater schemes. We examine other examples of network architectures, where deploying local complementation techniques provides an advantage. We finally consider the problem of extracting graph states for quantum communication via local Clifford operations and Pauli measurements, and discuss that while the general problem is known to be NP-complete, interestingly, for specific classes of structured resources, polynomial time algorithms can be identified.
Adhesive and non-adhesive internal hernia: clinical relevance and multi-detector CT images
Authors: Dou Lei , Yang Huiyuan , Wang Chao , Tang Hao , Li Dongjian
Published: September 2019

Internal hernia (IH)-related surgical acute abdomen is not well understood because of the rarity of cases and underdiagnosis. This study was performed to further understand the clinicopathological features and multi-detector computed tomography (MDCT) findings of IH in cases confirmed by surgery. In all, 51 patients with a definite diagnosis of IH confirmed during surgical exploration from Feb. 2012 to Feb. 2018 in our hospital were included in this research. Medical records, including MDCT images and intra-operative findings, were collected retrospectively. In all, 39 and 12 cases were categorized as adhesive IH (76.5%) and non-adhesive IH (23.5%), respectively. Among the patients with adhesive IH, 73% had a history of abdominal or pelvic surgery. Additionally, the mesentery was the most common component of adhesive bands (64.1%). Congenital peritoneal abnormalities and gastrointestinal reconstruction were the main causes of non-adhesive IH.As a specific sign, the fat notch sign was much more common in adhesive IH than in non-adhesive IH (P = 0.023). Bowel wall thickening (P = 0.041), abnormal bowel wall enhancement (P = 0.006) and twisted bowels with the vessel swirl sign (P = 0.004) were indicators of bowel necrosis. Among all of the cases of IH, 34 (66.7%) were complicated by bowel necrosis, and 1 patient died. In conclusion, non-adhesive IH has different clinicopathological features and MDCT findings from those of adhesive IH. MDCT is a useful tool with high sensitivity for confirming IH and may help to guide the early treatment of IH.
A New Hadrosaurine (Dinosauria: Hadrosauridae) from the Marine Deposits of the Late Cretaceous Hakobuchi Formation, Yezo Group, Japan
Authors: Kobayashi Yoshitsugu , Nishimura Tomohiro , Takasaki Ryuji , Chiba Kentaro , Fiorillo Anthony R. , Tanaka Kohei , Chinzorig Tsogtbaatar , Sato Tamaki , Sakurai Kazuhiko
Published: September 2019

A nearly complete skeleton of a new hadrosaurid, Kamuysaurus japonicus gen. et sp. nov., was discovered from the outer shelf deposits of the Upper Cretaceous Hakobuchi Formation of the Yezo Group in Hobetsu area of Mukawa town in Hokkaido, Japan. Kamuysaurus belongs to the sub-clade of Hadrosaurinae, Edmontosaurini, and forms a monophyly with Laiyangosaurus and Kerberosaurus from the northern Far East. Kamuysaurus has a long anterior platform for the nasofrontal sutural surface, which may indicate the presence of a small supracranial crest, similar to a sub-adult form of Brachylophosaurus based on the extension of the nasofrontal sutural surface. The Dispersal Extinction Cladogenesis analysis with the 50% Majority Rule consensus tree suggests that the clade of Kamuysaurus, Laiyangosaurus, and Kerberosaurus may have dispersed into Asia prior to the late Campanian and the potential endemism of this clade during the late Campanian and early Maastrichtian in the northern Far East. The results of both Dispersal Extinction Cladogenesis and Ancestral State Reconstruction analyses imply that the marine-influenced environment in North America during the Campanian may have played an important role for the hadrosaurid diversification in its early evolutionary history.
Closing the Nuclear Fuel Cycle with a Simplified Minor Actinide Lanthanide Separation Process (ALSEP) and Additive Manufacturing
Authors: Gelis Artem V. , Kozak Peter , Breshears Andrew T. , Brown M. Alex , Launiere Cari , Campbell Emily L. , Hall Gabriel B. , Levitskaia Tatiana G. , Holfeltz Vanessa E. , Lumetta Gregg J.
Published: September 2019

Expanded low-carbon baseload power production through the use of nuclear fission can be enabled by recycling long-lived actinide isotopes within the nuclear fuel cycle. This approach provides the benefits of (a) more completely utilizing the energy potential of mined uranium, (b) reducing the footprint of nuclear geological repositories, and (c) reducing the time required for the radiotoxicity of the disposed waste to decrease to the level of uranium ore from one hundred thousand years to a few hundred years. A key step in achieving this goal is the separation of long-lived isotopes of americium (Am) and curium (Cm) for recycle into fast reactors. To achieve this goal, a novel process was successfully demonstrated on a laboratory scale using a bank of 1.25-cm centrifugal contactors, fabricated by additive manufacturing, and a simulant containing the major fission product elements. Americium and Cm were separated from the lanthanides with over 99.9% completion. The sum of the impurities of the Am/Cm product stream using the simulated raffinate was found to be 3.2 × 10−3 g/L. The process performance was validated using a genuine high burnup used nuclear fuel raffinate in a batch regime. Separation factors of nearly 100 for 154Eu over 241Am were achieved. All these results indicate the process scalability to an engineering scale.
Experimentally-driven mathematical modeling to improve combination targeted and cytotoxic therapy for HER2+ breast cancer
Authors: Jarrett Angela M. , Shah Alay , Bloom Meghan J. , McKenna Matthew T. , Hormuth David A. , Yankeelov Thomas E. , Sorace Anna G.
Published: September 2019

The goal of this study is to experimentally and computationally investigate combination trastuzumab-paclitaxel therapies and identify potential synergistic effects due to sequencing of the therapies with in vitro imaging and mathematical modeling. Longitudinal alterations in cell confluence are reported for an in vitro model of BT474 HER2+ breast cancer cells following various dosages and timings of paclitaxel and trastuzumab combination regimens. Results of combination drug regimens are evaluated for drug interaction relationships based on order, timing, and quantity of dose of the drugs. Altering the order of treatments, with the same total therapeutic dose, provided significant changes in overall cell confluence (p < 0.001). Two mathematical models are introduced that are constrained by the in vitro data to simulate the tumor cell response to the individual therapies. A collective model merging the two individual drug response models was designed to investigate the potential mechanisms of synergy for paclitaxel-trastuzumab combinations. This collective model shows increased synergy for regimens where trastuzumab is administered prior to paclitaxel and suggests trastuzumab accelerates the cytotoxic effects of paclitaxel. The synergy derived from the model is found to be in agreement with the combination index, where both indicate a spectrum of additive and synergistic interactions between the two drugs dependent on their dose order. The combined in vitro results and development of a mathematical model of drug synergy has potential to evaluate and improve standard-of-care combination therapies in cancer.
Effect of diluent type, cryoprotectant concentration, storage method and freeze/thaw rates on the post-thaw quality and fertility of cryopreserved alpaca spermatozoa
Authors: Stuart C. C. , Vaughan J. L. , Kershaw C. M. , de Graaf S. P. , Bathgate R.
Published: September 2019

This study compared protocols for cryopreservation of ejaculated, papain-treated alpaca spermatozoa. This included different concentrations of egg yolk (EY; 5, 10 or 15%) and glycerol (2, 5 or 10%), diluent types (SHOTOR, lactose, skim milk or INRA-96™), freeze rates (2, 4 or 8 cm above liquid nitrogen; LN), thaw rates (37 °C for 1 min or 42 °C for 20 sec) and storage vessels (pellets, 0.25 mL straws or 0.5 mL straws). Spermatozoa were assessed pre-freeze and 0, 30, 60 and 90 min post-thaw. Forty-one hembras were inseminated with either fresh, papain-treated or frozen-thawed spermatozoa. Motility was affected by EY concentration (P < 0.001), diluent type (P < 0.001), freeze rate (P = 0.003) and storage vessel (P = 0.001). Viability was affected by EY concentration (P < 0.001), diluent type (P < 0.001), storage vessel (P = 0.002) and thaw rate (P = 0.03). For artificial insemination (AI), semen was diluted 1:3 in a lactose-based diluent, with 5% EY and glycerol. Freezing was in 0.5 mL straws, 2 cm above LN for 4 min then thawing at 37 °C for 1 min. Pregnancy rates of those ovulated (n = 26) were not different (1/5 fresh, 1/4 papain-treated, 0/17 frozen-thawed; P = 0.10). Pregnancy can be achieved after AI with papain-treated spermatozoa. Further work is needed to determine the optimal dose, timing and location for insemination.
Hepatitis C virus (HCV) genotype 1b displays higher genetic variability of hypervariable region 1 (HVR1) than genotype 3
Authors: Janiak Maciej , Perlejewski Karol , Grabarczyk Piotr , Kubicka-Russel Dorota , Zagordi Osvaldo , Berak Hanna , Osuch Sylwia , Pawełczyk Agnieszka , Bukowska-Ośko Iwona , Płoski Rafał , Laskus Tomasz , Caraballo Cortés Kamila
Published: September 2019

Hepatitis C virus (HCV) is characterized by high genetic variability, which is manifested both at the inter-host and intra-host levels. However, its role in the clinical course of infection is less obvious. The aim of the present study was to determine the genetic variability of HCV HVR1 (hypervariable region 1) of genotype 1b and 3 in plasma of blood donors in the early seronegative stage of infection (HCV-RNA+, anti-HCV−) and in samples from chronically infected patients using next-generation sequencing. Sequencing errors were corrected, and haplotypes inferred using the ShoRAH software. Genetic diversity parameters (intra-host number of variants, number of nucleotide substitutions and diversity per site) were assessed by DNA SP and MEGA. During the early infection, the number of variants were significantly lower in subjects infected with genotype 3 than with genotype 1b (p < 0.02). Similarly, intra-host number of variants, number of nucleotide substitutions and diversity per site were lower in genotype 3 chronic infection (p < 0.0005). In addition, early infection was characterized by significantly lower HVR1 variability values (p < 0.04) when compared to chronic infection for both genotypes. It seems that the observed differences in HVR1 variability represent an inherent property of particular viral genotypes.
Phase-change like process through bond switching in distorted and resonantly bonded crystal
Authors: Yang Won Jun , Park Hanjin , Kim Da Sol , Ha Taewoo , Park Seung Jong , Ahn Min , Kim Jae Hoon , Kwon Young-Kyun , Cho Mann-Ho
Published: September 2019

Although some methods to improve phase-change memory efficiency have been proposed, an effective experimental approach to induce a phase-change like process without external heat energy has not yet been reported. Herein we have shown that GeTe is a prototype phase-change material, which can exhibit a non-thermal phase-change-like process under uniaxial stress. Due to its structural characteristics like directional structural instability and resonance bonding under 1% uniaxial stress, we observed that bond switching in the GeTe film between short and long bonds is possible. Due to this phase change, GeTe displays the same phase-change as crystal layer rotation. Crystal layer rotation has not been observed in the conventional phase change process using intermediate states, but it is related to the structural characteristics required for maintaining local coordination. Moreover, since the resonance bonding characteristics are effectively turned off upon applying uniaxial stress, the high-frequency dielectric constant can be significantly decreased. Our results also show that the most significant process in the non-thermal phase transition of phase-change materials is the modulation of the lattice relaxation process after the initial perturbation, rather than the method inducing the perturbation itself. Finally, these consequences suggest that a new type of phase-change memory is possible through changes in the optical properties under stress.
Epidemiological and clinical characteristics of children hospitalized due to influenza A and B in the south of Europe, 2010–2016
Authors: Jané Mireia , Vidal Maria José , Soldevila Nuria , Romero Arancha , Martínez Ana , Torner Nuria , Godoy Pere , Launes Cristian , Rius Cristina , Marcos Maria Angeles , Dominguez Angela
Published: September 2019

Influenza produces annual epidemics that affect 5–15% of the world population. Complications and hospitalizations are more frequent in childhood. This study describes and analyses the epidemiological and clinical characteristics of children hospitalized due to confirmed influenza in influenza surveillance sentinel hospitals in Catalonia. Retrospective descriptive study conducted in six influenza seasons (2010–2011 to 2015–2016) in persons aged 0–17 years diagnosed with laboratory-confirmed influenza requiring hospitalization. 291 cases were notified to the health authorities: 79.4% were due to the influenza A virus and 20.6% to the B virus. The most common subtype was H1N1 with 57.6% of cases: 52.6% were male, 56.7% were aged <2 years, and 24.4% were aged <1 year. 62.2% of cases had pneumonia, 26.8% acute respiratory distress syndrome and 11.7% bacterial pneumonia. 5.8% of cases were vaccinated and 21.3% required intensive care unit admission, of whom 54.8% were aged <2 years. There were 3 deaths, all with influenza A infection. Influenza A cases were younger than influenza B cases (OR 3.22; 95% CI: 1.73–6.00). Conclusion: Children aged <2 years are especially vulnerable to the A H1N1 virus, including those without pre-existing chronic disease. These results are relevant for the planning of vaccination programs to improve maternal and child health.
A Granger causality analysis of groundwater patterns over a half-century
Authors: Singh Nitin K. , Borrok David M.
Published: September 2019

Groundwater depletion in many areas of the world has been broadly attributed to irrigation. However, more formal, data-driven, causal mechanisms of long-term groundwater patterns have not been assessed. Here, we conducted the first Granger causality analysis to identify the “causes” of groundwater patterns using the rice-producing parishes of Louisiana, USA, as an example. Trend analysis showed a decline of up to 6 m in groundwater level over 51 years. We found that no single cause explained groundwater patterns for all parishes. Causal linkages were noted between groundwater and area harvested, number of irrigation wells, summer precipitation totals, and drought. Bi-directional linkages were noted between groundwater and rice yield, suggesting feedback between both time series. Causal linkages were absent between groundwater and many drivers where significant correlations were noted, highlighting the importance of using robust causal relationships over illusive correlations to detect the cause. These results advance our understanding of groundwater dynamics and can reveal a key connection between food and groundwater.
Costs and benefits of social connectivity in juvenile Greylag geese
Authors: Szipl Georgine , Depenau Marie , Kotrschal Kurt , Hemetsberger Josef , Frigerio Didone
Published: September 2019

Living in groups has various advantages and disadvantages for group members. We investigated the fitness consequences of early social connectivity (normalized Freeman degrees based on nearest neighbour data), physiology (levels of excreted corticosterone metabolites assayed from droppings), and agonistic interactions in a group of free-ranging greylag geese (Anseranser). Forty-four greylag geese below 3 years of age were observed in three different seasonal phases: during the re-aggregation of the flock in autumn, at the end of the winter and during the forthcoming breeding season. We show that corticosterone metabolite levels and initiated and received aggression increased with increasing social connectivity. Individuals had higher connectivity scores in the winter flock than during the mating and breeding seasons. One-year old juveniles were more connected than 2- and 3-year old individuals. In addition, we examined the link between social connectivity during early development and reproductive success several years later. We found that birds with greater connectivity early in life attempted to breed at a younger age. Furthermore, successful breeders with higher early connectivity scores had higher numbers of fledged goslings. Our results show that social context in early life stages may have long-term effects on individual fitness.