bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ECONOMIST AS SCIENTIST, ENGINEER, OR PLUMBER?
Authors: Su Huei-Chun , Colander David
Published: June 2021

Some well-known economists suggest that a good economist should act like an engineer, a surgeon, a dentist, or even a plumber. These metaphors are useful in helping economists reflect the nature of economics and their role in society. But which is the most sensible one? This paper argues that economists should be playing all these roles and more, because economics is not a single entity, and each entity has separate goals, methods, and boundaries. To take this multiplicity of roles into account, this paper argues that in addition to the traditional boundary that delineates the disciplinary domain of economics against other sciences, an overarching boundary between economic science and applied policy needs to be recognized. It then examines Esther Duflo’s “economist as plumber” metaphor and suggests that a better metaphor for Duflo’s purpose would be “general contractor,” a metaphor that, if accepted, would suggest radical change in training applied policy economists.
Beyond adoption: the interaction between organic and inorganic fertilizer application, and vegetable productivity in Ghana
Authors: Amfo Bismark , Baba Ali Ernest
Published: June 2021

This study explores the causal association between organic and inorganic fertilizer application and vegetable productivity in Ghana. Primary data were obtained from 300 pepper, cabbage and lettuce producers. To correct for self-selection bias and endogeneity, Heckman selection and three-stage least-squares models were estimated. More producers used inorganic fertilizers for pepper, cabbage and lettuce production than those who used organic fertilizers. Vegetable producers applied higher quantities of organic fertilizers (2830 kg) per acre than inorganic fertilizers (880 kg). Organic cabbage and lettuce producers recorded higher productivity than inorganic producers, but inorganic pepper producers had higher productivity than organic producers. However, vegetable producers who applied either organic or inorganic fertilizers, or both, recorded higher productivity than those who did not apply fertilizer. Factors that enhance the application of organic and inorganic fertilizers and vegetable productivity are education, farm size and production for export, land ownership, farmer association membership and perception about fertilizer price. Organic and inorganic fertilizer application improves vegetable productivity, and productivity promotes fertilizer application. Private agencies and government should subsidize fertilizers, improve producers' access to agricultural information, and train producers on productivity-enhancing agronomic practices.
What is a firm? A reply to Jean-Philippe Robé
Authors: Deakin Simon , Gindis David , Hodgson Geoffrey M.
Published: June 2021

In his recent book onProperty, Power and Politics, Jean-Philippe Robé makes a strong case for the need to understand the legal foundations of modern capitalism. He also insists that it is important to distinguish between firms and corporations. We agree. But Robé criticizes our definition of firms in terms of legally recognized capacities on the grounds that it does not take the distinction seriously enough. He argues that firms are not legally recognized as such, as the law only knows corporations. This argument, which is capable of different interpretations, leads to the bizarre result that corporations are not firms. Using etymological and other evidence, we show that firms are treated as legally constituted business entities in both common parlance and legal discourse. The way the law defines firms and corporations, while the product of a discourse which is in many ways distinct from everyday language, has such profound implications for the way firms operate in practice that no institutional theory of the firm worthy of the name can afford to ignore it.
Entwicklung und Überprüfung von Erhebungsinstrumenten zur Erfassung der Fachkompetenz (angehender) frühpädagogischer Fachkräfte
Authors: Limberger Janina , Lorenzen Annika , Wirth Charlotta , Strohmer Janina , Fröhlich-Gildhoff Klaus
Published: June 2021

Zusammenfassung. Die Akademisierung des kindheitspädagogischen Sektors, die damit einhergehenden Professionalisierungsansprüche und die zunehmende Fokussierung auf die Kompetenzorientierung im Aus- und Weiterbildungsbereich bilden den Grundstein für das gestiegene Interesse an Möglichkeiten zur Erfassung von Fachkompetenzen im Bereich der Kindheitspädagogik. Nachfolgend werden die Entwicklung sowie die psychometrische Überprüfung dreier entsprechender Erhebungsinstrumente beschrieben. Von Mai 2017 bis April 2020 wurden hierfür sowohl das theoretische Wissen als auch das Handlungswissen im frühpädagogischen Bereich von 831 angehenden und geprüften pädagogischen Fachkräften (Fachschüler_innen in der Ausbildung zur/m Erzieher_in, Bachelor-Studierende der Kindheitspädagogik, pädagogische Fachkräfte in Kindertageseinrichtungen) erfasst. Eine explorative Faktorenanalyse ergab eine dreidimensionale Struktur der erfragten Kompetenzbereiche, wenngleich aufgrund schwacher Reliabilitäten beim Handlungswissen übergeordnete Faktoren gebildet wurden. Auf Basis der Ergebnisse einer Interkorrelationsanalyse konnte zusätzlich gezeigt werden, dass die Erhebungsinstrumente eine gute konvergente Validität aufweisen. Dies deutet darauf hin, dass die Erfassung von theoretischem Wissen und Handlungswissen zur Einschätzung der Fachkompetenz sinnvoll erscheint. Insgesamt können die Erhebungsinstrumente nach erster psychometrischer Überprüfung als akzeptable mögliche Herangehensweisen zur Kompetenzerfassung eingeschätzt werden.
Magma Decompression Rate Calculations With EMBER: A User‐Friendly Software to Model Diffusion of H2O, CO2, and S in Melt Embayments
Authors: Georgeais Guillaume , Koga Kenneth T. , Moussallam Yves , Rose‐Koga Estelle F.
Published: June 2021

Magma decompression rate is one of the most important parameters in controlling eruption dynamics. One way to determine decompression rate is by fitting a volatile elements diffusion profile to a concentration gradient in crystal‐hosted embayments. Previous studies have used a variety of diffusion models, limiting the possibility for inter‐study comparison. Here, we introduce EMBayment‐Estimated Rates (EMBER), a standalone versatile tool that models diffusion of volatile elements along melt embayments. Our model relies on the pdepe function of MATLAB to calculate diffusion profiles of H2O, CO2, and S through the finite difference method. EMBER uses a grid search seeking out the best fits for decompression rates, initial dissolved concentration of each studied volatile and initial exsolved gas content, while setting three constants: temperature along the ascent and pressure at the beginning and end of the ascent. Our model can compute the rate for basaltic, intermediate, and rhyolitic compositions. We applied EMBER to previous studies to evaluate and validate our model. We then reprocessed “homogeneously” the raw data from the literature for a comparison. In other words, the same protocol was used for each diffusion profiles removing the literature‐specific strategies used to constrain unknown parameters. With this comparison, we found a statistically significant positive correlation between maximum magma decompression rates and explosivity of the related eruption. EMBER is expected to help increase the number of volatile diffusion in embayments studies aiming at constraining magma decompression and ascent rates and to facilitate inter‐study comparisons.
A New Reference Model for the Evolution of Oceanic Lithosphere in a Cooling Earth
Authors: Korenaga Tomoko , Korenaga Jun , Kawakatsu Hitoshi , Yamano Makoto
Published: June 2021

We present a new reference model for the evolution of oceanic lithosphere, which incorporates the effects of incomplete viscous relaxation, radiogenic heating, and secular cooling. The new reference model is based solely on thermal conduction, that is, without involving the occurrence of small‐scale convection, and unlike the plate model, it does not contain unphysical boundary conditions. Yet, our model can explain both bathymetry and the heat flow data on the normal seafloor. The success of the new model owes to the use of realistic material properties in conduction modeling as well as the consideration of all of major processes that take place ubiquitously beneath seafloor. The effect of secular cooling on the bathymetry of old seafloor is particularly notable. Whereas secular cooling brings only weak temperature variations with an amplitude of ∼20 K, it can nonetheless affect global bathymetry substantially owing to the deep sensitivity of long‐wavelength topography kernels. We suggest that the well‐known fact that Earth has been cooling, which was not considered in any of previous reference models, may be the key to the long‐standing puzzle of seafloor flattening. The new reference model is expected to be useful to better quantify the impact of the emplacement of hotspot islands and oceanic plateaus, the effect of small‐scale convection, and the regional history of secular cooling in the convecting mantle.
Species of Feces Help Phytoplankton Feed Itself
Authors: Kornei Katherine
Published: June 2021

The unicellular plants more readily take up iron in the presence of salp feces than in krill feces, an experiment in Antarctica reveals.
An Ancient Meltwater Pulse Raised Sea Levels by 18 Meters
Authors: Hornyak Tim
Published: June 2021

Meltwater pulse 1A, a period of rapid sea level rise after the last deglaciation, was powered by melting ice from North America and Scandinavia, according to new research.
Chasing Cyclones from Space
Authors: Jackson Christopher , Ruff Tyler , Knaff John , Mouche Alexis , Sampson Charles
Published: June 2021

The pioneering use of satellite-based synthetic aperture radar to characterize tropical cyclones in near-real time has provided a crucial new tool with which to forecast powerful storms.
Robust Asymmetry of the Future Arctic Polar Vortex Is Driven by Tropical Pacific Warming
Authors: Matsumura Shinji , Yamazaki Koji , Horinouchi Takeshi
Published: June 2021

The future stratosphere is globally dominated by a strong radiative cooling due to the increase in greenhouse gases. However, we find that over North America, the Arctic stratospheric cooling is suppressed or rather warming occurs, whereas over Eurasia stratospheric cooling is most pronounced, leading to an asymmetric polar vortex, based on 21st century climate model simulations. There are many causes that drive polar vortex variability, which make future projections highly uncertain. Our model simulations demonstrate that tropical warming induces the asymmetric polar vortex. The eastern equatorial Pacific warming causes eastward‐shifted teleconnection with a deepened Aleutian low, which strengthens the polar vortex over Eurasia and weakens over North America by enhancing the vertical wave propagation into the stratosphere. The asymmetric polar vortex is projected to markedly develop in the 2030s, and so could affect winter surface climate over mid‐ to high‐latitudes of Eurasia in the near future.
Deep Learning for Geophysics: Current and Future Trends
Authors: Yu Siwei , Ma Jianwei
Published: June 2021

Recently deep learning (DL), as a new data‐driven technique compared to conventional approaches, has attracted increasing attention in geophysical community, resulting in many opportunities and challenges. DL was proven to have the potential to predict complex system states accurately and relieve the “curse of dimensionality” in large temporal and spatial geophysical applications. We address the basic concepts, state‐of‐the‐art literature, and future trends by reviewing DL approaches in various geosciences scenarios. Exploration geophysics, earthquakes, and remote sensing are the main focuses. More applications, including Earth structure, water resources, atmospheric science, and space science, are also reviewed. Additionally, the difficulties of applying DL in the geophysical community are discussed. The trends of DL in geophysics in recent years are analyzed. Several promising directions are provided for future research involving DL in geophysics, such as unsupervised learning, transfer learning, multimodal DL, federated learning, uncertainty estimation, and active learning. A coding tutorial and a summary of tips for rapidly exploring DL are presented for beginners and interested readers of geophysics.
A KDM4A-PAF1-mediated epigenomic network is essential for acute myeloid leukemia cell self-renewal and survival
Authors: Massett Matthew E. , Monaghan Laura , Patterson Shaun , Mannion Niamh , Bunschoten Roderick P. , Hoose Alex , Marmiroli Sandra , Liskamp Robert M. J. , Jørgensen Heather G. , Vetrie David , Michie Alison M. , Huang Xu
Published: June 2021

Epigenomic dysregulation is a common pathological feature in human hematological malignancies. H3K9me3 emerges as an important epigenomic marker in acute myeloid leukemia (AML). Its associated methyltransferases, such as SETDB1, suppress AML leukemogenesis, whilst H3K9me3 demethylases KDM4C is required for mixed-lineage leukemia rearranged AML. However, the specific role and molecular mechanism of action of another member of the KDM4 family, KDM4A has not previously been clearly defined. In this study, we delineated and functionally validated the epigenomic network regulated by KDM4A. We show that selective loss of KDM4A is sufficient to induce apoptosis in a broad spectrum of human AML cells. This detrimental phenotype results from a global accumulation of H3K9me3 and H3K27me3 at KDM4A targeted genomic loci thereby causing downregulation of a KDM4A-PAF1 controlled transcriptional program essential for leukemogenesis, distinct from that of KDM4C. From this regulatory network, we further extracted a KDM4A-9 gene signature enriched with leukemia stem cell activity; the KDM4A-9 score alone or in combination with the known LSC17 score, effectively stratifies high-risk AML patients. Together, these results establish the essential and unique role of KDM4A for AML self-renewal and survival, supporting further investigation of KDM4A and its targets as a potential therapeutic vulnerability in AML.
Sgpl1 deletion elevates S1P levels, contributing to NPR2 inactivity and p21 expression that block germ cell development
Authors: Yuan Feifei , Wang Zhijuan , Sun Yanli , Wei Hongwei , Cui Yanying , Wu Zhanying , Zhang Chunyu , Xie Ke-Ping , Wang Fengchao , Zhang Meijia
Published: June 2021

Sphingosine phosphate lyase 1 (SGPL1) is a highly conserved enzyme that irreversibly degrades sphingosine-1-phosphate (S1P). Sgpl1-knockout mice fail to develop germ cells, resulting in infertility. However, the molecular mechanism remains unclear. The results of the present study showed that SGPL1 was expressed mainly in granulosa cells, Leydig cells, spermatocytes, and round spermatids. Sgpl1 deletion led to S1P accumulation in the gonads. In the ovary, S1P decreased natriuretic peptide receptor 2 (NPR2) activity in granulosa cells and inhibited early follicle growth. In the testis, S1P increased the levels of cyclin-dependent kinase inhibitor 1A (p21) and apoptosis in Leydig cells, thus resulting in spermatogenesis arrest. These results indicate that Sgpl1 deletion increases intracellular S1P levels, resulting in the arrest of female and male germ cell development via different signaling pathways.
Long-lasting renewable antibacterial porous polymeric coatings enable titanium biomaterials to prevent and treat peri-implant infection
Authors: Wu Shuyi , Xu Jianmeng , Zou Leiyan , Luo Shulu , Yao Run , Zheng Bingna , Liang Guobin , Wu Dingcai , Li Yan
Published: June 2021

Peri-implant infection is one of the biggest threats to the success of dental implant. Existing coatings on titanium surfaces exhibit rapid decrease in antibacterial efficacy, which is difficult to promisingly prevent peri-implant infection. Herein, we report an N-halamine polymeric coating on titanium surface that simultaneously has long-lasting renewable antibacterial efficacy with good stability and biocompatibility. Our coating is powerfully biocidal against both main pathogenic bacteria of peri-implant infection and complex bacteria from peri-implantitis patients. More importantly, its antibacterial efficacy can persist for a long term (e.g., 12~16 weeks) in vitro, in animal model, and even in human oral cavity, which generally covers the whole formation process of osseointegrated interface. Furthermore, after consumption, it can regain its antibacterial ability by facile rechlorination, highlighting a valuable concept of renewable antibacterial coating in dental implant. These findings indicate an appealing application prospect for prevention and treatment of peri-implant infection.
Drug repurposing screens identify chemical entities for the development of COVID-19 interventions
Authors: Bakowski Malina A. , Beutler Nathan , Wolff Karen C. , Kirkpatrick Melanie G. , Chen Emily , Nguyen Tu-Trinh H. , Riva Laura , Shaabani Namir , Parren Mara , Ricketts James , Gupta Anil K. , Pan Kastin , Kuo Peiting , Fuller MacKenzie , Garcia Elijah , Teijaro John R. , Yang Linlin , Sahoo Debashis , Chi Victor , Huang Edward , Vargas Natalia , Roberts Amanda J. , Das Soumita , Ghosh Pradipta , Woods Ashley K. , Joseph Sean B. , Hull Mitchell V. , Schultz Peter G. , Burton Dennis R. , Chatterjee Arnab K. , McNamara Case W. , Rogers Thomas F.
Published: June 2021

The ongoing pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), necessitates strategies to identify prophylactic and therapeutic drug candidates for rapid clinical deployment. Here, we describe a screening pipeline for the discovery of efficacious SARS-CoV-2 inhibitors. We screen a best-in-class drug repurposing library, ReFRAME, against two high-throughput, high-content imaging infection assays: one using HeLa cells expressing SARS-CoV-2 receptor ACE2 and the other using lung epithelial Calu-3 cells. From nearly 12,000 compounds, we identify 49 (in HeLa-ACE2) and 41 (in Calu-3) compounds capable of selectively inhibiting SARS-CoV-2 replication. Notably, most screen hits are cell-line specific, likely due to different virus entry mechanisms or host cell-specific sensitivities to modulators. Among these promising hits, the antivirals nelfinavir and the parent of prodrug MK-4482 possess desirable in vitro activity, pharmacokinetic and human safety profiles, and both reduce SARS-CoV-2 replication in an orthogonal human differentiated primary cell model. Furthermore, MK-4482 effectively blocks SARS-CoV-2 infection in a hamster model. Overall, we identify direct-acting antivirals as the most promising compounds for drug repurposing, additional compounds that may have value in combination therapies, and tool compounds for identification of viral host cell targets.
Non-universal current flow near the metal-insulator transition in an oxide interface
Authors: Persky Eylon , Vardi Naor , Monteiro Ana Mafalda R. V. L. , van Thiel Thierry C. , Yoon Hyeok , Xie Yanwu , Fauqué Benoît , Caviglia Andrea D. , Hwang Harold Y. , Behnia Kamran , Ruhman Jonathan , Kalisky Beena
Published: June 2021

In systems near phase transitions, macroscopic properties often follow algebraic scaling laws, determined by the dimensionality and the underlying symmetries of the system. The emergence of such universal scaling implies that microscopic details are irrelevant. Here, we locally investigate the scaling properties of the metal-insulator transition at the LaAlO3/SrTiO3 interface. We show that, by changing the dimensionality and the symmetries of the electronic system, coupling between structural and electronic properties prevents the universal behavior near the transition. By imaging the current flow in the system, we reveal that structural domain boundaries modify the filamentary flow close to the transition point, preventing a fractal with the expected universal dimension from forming.
STAT1 potentiates oxidative stress revealing a targetable vulnerability that increases phenformin efficacy in breast cancer
Authors: Totten Stephanie P. , Im Young Kyuen , Cepeda Cañedo Eduardo , Najyb Ouafa , Nguyen Alice , Hébert Steven , Ahn Ryuhjin , Lewis Kyle , Lebeau Benjamin , La Selva Rachel , Sabourin Valérie , Martínez Constanza , Savage Paul , Kuasne Hellen , Avizonis Daina , Santos Martínez Nancy , Chabot Catherine , Aguilar-Mahecha Adriana , Goulet Marie-Line , Dankner Matthew , Witcher Michael , Petrecca Kevin , Basik Mark , Pollak Michael , Topisirovic Ivan , Lin Rongtuan , Siegel Peter M. , Kleinman Claudia L. , Park Morag , St-Pierre Julie , Ursini-Siegel Josie
Published: June 2021

Bioenergetic perturbations driving neoplastic growth increase the production of reactive oxygen species (ROS), requiring a compensatory increase in ROS scavengers to limit oxidative stress. Intervention strategies that simultaneously induce energetic and oxidative stress therefore have therapeutic potential. Phenformin is a mitochondrial complex I inhibitor that induces bioenergetic stress. We now demonstrate that inflammatory mediators, including IFNγ and polyIC, potentiate the cytotoxicity of phenformin by inducing a parallel increase in oxidative stress through STAT1-dependent mechanisms. Indeed, STAT1 signaling downregulates NQO1, a key ROS scavenger, in many breast cancer models. Moreover, genetic ablation or pharmacological inhibition of NQO1 using β-lapachone (an NQO1 bioactivatable drug) increases oxidative stress to selectively sensitize breast cancer models, including patient derived xenografts of HER2+ and triple negative disease, to the tumoricidal effects of phenformin. We provide evidence that therapies targeting ROS scavengers increase the anti-neoplastic efficacy of mitochondrial complex I inhibitors in breast cancer.
Bulk-surface coupling identifies the mechanistic connection between Min-protein patterns in vivo and in vitro
Authors: Brauns Fridtjof , Pawlik Grzegorz , Halatek Jacob , Kerssemakers Jacob , Frey Erwin , Dekker Cees
Published: June 2021

Self-organisation of Min proteins is responsible for the spatial control of cell division in Escherichia coli, and has been studied both in vivo and in vitro. Intriguingly, the protein patterns observed in these settings differ qualitatively and quantitatively. This puzzling dichotomy has not been resolved to date. Using reconstituted proteins in laterally wide microchambers with a well-controlled height, we experimentally show that the Min protein dynamics on the membrane crucially depend on the micro chamber height due to bulk concentration gradients orthogonal to the membrane. A theoretical analysis shows that in vitro patterns at low microchamber height are driven by the same lateral oscillation mode as pole-to-pole oscillations in vivo. At larger microchamber height, additional vertical oscillation modes set in, marking the transition to a qualitatively different in vitro regime. Our work reveals the qualitatively different mechanisms of mass transport that govern Min protein-patterns for different bulk heights and thus shows that Min patterns in cells are governed by a different mechanism than those in vitro.
Crystal structure of dopamine D1 receptor in complex with G protein and a non-catechol agonist
Authors: Sun Bingfa , Feng Dan , Chu Matthew Ling-Hon , Fish Inbar , Lovera Silvia , Sands Zara A. , Kelm Sebastian , Valade Anne , Wood Martyn , Ceska Tom , Kobilka Tong Sun , Lebon Florence , Kobilka Brian K.
Published: June 2021

Dopamine D1 receptor (D1R) is an important drug target implicated in many psychiatric and neurological disorders. Selective agonism of D1R are sought to be the therapeutic strategy for these disorders. Most selective D1R agonists share a dopamine-like catechol moiety in their molecular structure, and their therapeutic potential is therefore limited by poor pharmacological properties in vivo. Recently, a class of non-catechol D1R selective agonists with a distinct scaffold and pharmacological properties were reported. Here, we report the crystal structure of D1R in complex with stimulatory G protein (Gs) and a non-catechol agonist Compound 1 at 3.8 Å resolution. The structure reveals the ligand bound to D1R in an extended conformation, spanning from the orthosteric site to extracellular loop 2 (ECL2). Structural analysis reveals that the unique features of D1R ligand binding pocket explains the remarkable selectivity of this scaffold for D1R over other aminergic receptors, and sheds light on the mechanism for D1R activation by the non-catechol agonist.
Establishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells
Authors: Freter Rasmus , Falletta Paola , Omrani Omid , Rasa Mahdi , Herbert Katharine , Annunziata Francesco , Minetti Alberto , Krepelova Anna , Adam Lisa , Käppel Sandra , Rüdiger Tina , Wang Zhao-Qi , Goding Colin R. , Neri Francesco
Published: June 2021

Dormancy, a reversible quiescent cellular state characterized by greatly reduced metabolic activity, protects from genetic damage, prolongs survival and is crucial for tissue homeostasis and cellular response to injury or transplantation. Dormant cells have been characterized in many tissues, but their identification, isolation and characterization irrespective of tissue of origin remains elusive. Here, we develop a live cell ratiometric fluorescent Optical Stem Cell Activity Reporter (OSCAR) based on the observation that phosphorylation of RNA Polymerase II (RNApII), a hallmark of active mRNA transcription elongation, is largely absent in dormant stem cells from multiple lineages. Using the small intestinal crypt as a model, OSCAR reveals in real time the dynamics of dormancy induction and cellular differentiation in vitro, and allows the identification and isolation of several populations of transcriptionally diverse OSCARhigh and OSCARlow intestinal epithelial cell states in vivo. In particular, this reporter is able to identify a dormant OSCARhigh cell population in the small intestine. OSCAR therefore provides a tool for a better understanding of dormant stem cell biology.
Changes in antibiotic prescription following an education strategy for acute respiratory infections
Authors: Delsors Eloisa , Monsó Francisco , López-Román Francisco Javier , Menárguez-Puche Juan Francisco , Gonzalez-Barberá María , Hukelova Hana , Martínez-Ros Maria Teresa , López-Santiago Asensio
Published: June 2021

The objective of this study was to assess the impact of an education intervention for primary health care physicians, based on the knowledge of clinical practice guidelines and availability of rapid antigen detection test for group A streptococci (GAS), on the improvement of antibiotic prescription for patients with acute respiratory tract infections. Before and after the intervention, physicians collected data from ten consecutive patients who attended during a 3-week period. This process was performed twice a year for 6 consecutive years (2012–2017). A total of 18,001 patients were visited by 391 primary care physicians during the study period, 55.6% before intervention and 44.4% after intervention. After intervention, the antibiotic prescription decreased significantly, from 33.0 to 23.4% (p < 0.01). However, there was a statistically significant increase (p < 0.01) in the use of penicillins. This study, carried out in daily practice conditions, confirms that the educational strategy was associated with an overall reduction in the use of antibiotics and an improvement in the antibiotic prescription profile in acute respiratory tract infections.
Integrating multiple chemical tracers to elucidate the diet and habitat of Cookiecutter Sharks
Authors: Carlisle Aaron B. , Allan Elizabeth Andruszkiewicz , Kim Sora L. , Meyer Lauren , Port Jesse , Scherrer Stephen , O’Sullivan John
Published: June 2021

The Cookiecutter shark (Isistius brasiliensis) is an ectoparasitic, mesopelagic shark that is known for removing plugs of tissue from larger prey, including teleosts, chondrichthyans, cephalopods, and marine mammals. Although this species is widely distributed throughout the world’s tropical and subtropical oceanic waters, like many deep-water species, it remains very poorly understood due to its mesopelagic distribution. We used a suite of biochemical tracers, including stable isotope analysis (SIA), fatty acid analysis (FAA), and environmental DNA (eDNA), to investigate the trophic ecology of this species in the Central Pacific around Hawaii. We found that large epipelagic prey constituted a relatively minor part of the overall diet. Surprisingly, small micronektonic and forage species (meso- and epipelagic) are the most important prey group for Cookiecutter sharks across the studied size range (17–43 cm total length), with larger mesopelagic species or species that exhibit diel vertical migration also being important prey. These results were consistent across all the tracer techniques employed. Our results indicate that Cookiecutter sharks play a unique role in pelagic food webs, feeding on prey ranging from the largest apex predators to small, low trophic level species, in particular those that overlap with the depth distribution of the sharks throughout the diel cycle. We also found evidence of a potential shift in diet and/or habitat with size and season. Environmental DNA metabarcoding revealed new prey items for Cookiecutter sharks while also demonstrating that eDNA can be used to identify recent prey in stomachs frozen for extended periods. Integrating across chemical tracers is a powerful tool for investigating the ecology of elusive and difficult to study species, such as meso- and bathypelagic chondrichthyans, and can increase the amount of information gained from small sample sizes. Better resolving the foraging ecology of these mesopelagic predators is critical for effective conservation and management of these taxa and ecosystems, which are intrinsically vulnerable to overfishing and exploitation.
Phase separation during blood spreading
Authors: Benabdelhalim Houssine , Brutin David
Published: June 2021

Blood pools can spread on several types of substrates depending on the surrounding environment and conditions. Understanding the influence of these parameters on the spreading of blood pools can provide crime scene investigators with useful information. The focus of the present study is on phase separation, that is, when the serum spreads outside the main blood pool. For this purpose, blood pools with constant initial masses on wooden floors that were either varnished or not were created at ambient temperatures of $$21~^{\circ }\hbox {C}$$

21

∘

C

, $$29~^{\circ }\hbox {C}$$

29

∘

C

, and $$37~^{\circ }\hbox {C}$$

37

∘

C

with a relative humidity varying from 20 to 90%. The range $$21~^{\circ }\hbox {C}$$

21

∘

C

to $$37~^{\circ }\hbox {C}$$

37

∘

C

covers almost all worldwide indoor cases. The same whole blood from the same donor was used for all experiments. As a result, an increase in relative humidity was found to result in an increase in the final pool area. In addition, at the three different experimental temperatures, the serum spread outside the main pool at relative humidity levels above 50%. This phase separation is more significant on varnished substrates, and does not lead to any changes in the drying morphology. This phenomenon is explained by the competition between coagulation and evaporation.
Transformation of SOX9+ cells by Pten deletion synergizes with steatotic liver injury to drive development of hepatocellular and cholangiocarcinoma
Authors: Chen Jingyu , Debebe Anketse , Zeng Ni , Kopp Janel , He Lina , Sander Maike , Stiles Bangyan L.
Published: June 2021

SOX9 (Sex-determining region Y Box 9) is a well-characterized transcription factor that is a marker for progenitor cells in various tissues. In the liver, cells delineated by SOX9 are responsible for regenerating liver parenchyma when cell proliferation is impaired following chronic injury. However, whether these SOX9+ cells play a role in liver carcinogenesis has not been fully understood, although high SOX9 expression has been linked to poor survival outcome in liver cancer patients. To address this question, we developed a liver cancer mouse model (PtenloxP/loxP; Sox9-CreERT+; R26RYFP) where tumor suppressor Pten (phosphatase and tensin homolog deleted on chromosome ten) is deleted in SOX9+ cells following tamoxifen injection. In this paper, we employ lineage-tracing to demonstrate the tumorigenicity potential of the Pten-, SOX9+ cells. We show that these cells are capable of giving rise to mixed-lineage tumors that manifest features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA). Our results suggest that PTEN loss induces the transformation of SOX9+ cells. We further show that to activate these transformed SOX9+ cells, the presence of liver injury is crucial. Liver injury, induced by hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or high-fat diet (HFD), substantially increases tumor incidence and accelerates liver carcinogenesis from SOX9+ cells in Pten null mice but not in control mice. We further examine the mechanisms underlying tumor formation in this model to show that concurrent with the induction of niche signal (i.e., Wnt signaling), liver injury significantly stimulates the expansion of tumor-initiating cells (TICs). Together, these data show that (1) SOX9+ cells have the potential to become TICs following the primary transformation (i.e. Pten deletion) and that (2) liver injury is necessary for promoting the activation and proliferation of transformed SOX9+ cells, resulting in the genesis of mixed-lineage liver tumors.
Roughness of retinal layers in Alzheimer’s disease
Authors: Jáñez-García Lucía , Bachtoula Omar , Salobrar-García Elena , de Hoz Rosa , Ramirez Ana I. , Gil Pedro , Ramirez José M. , Jáñez-Escalada Luis
Published: June 2021

There is growing evidence that thinned retinal regions are interspersed with thickened regions in all retinal layers of patients with Alzheimer’s disease (AD), causing roughness to appear on layer thickness maps. The hypothesis is that roughness of retinal layers, assessed by the fractal dimension (FD) of their thickness maps, is an early biomarker of AD. Ten retinal layers have been studied in macular volumes of optical coherence tomography from 24 healthy volunteers and 19 patients with mild AD (Mini-Mental State Examination 23.42 ± 3.11). Results show that FD of retinal layers is greater in the AD group, the differences being statistically significant (p < 0.05). Correlation of layer FD with cognitive score, visual acuity and age reach statistical significance at 7 layers. Nearly all (44 out of 45) FD correlations among layers are positive and half of them reached statistical significance (p < 0.05). Factor analysis unveiled two independent factors identified as the dysregulation of the choroidal vascular network and the retinal inflammatory process. Conclusions: surface roughness is a holistic feature of retinal layers that can be assessed by the FD of their thickness maps and it is an early biomarker of AD.
Enhancement of astaxanthin accumulation using black light in Coelastrum and Monoraphidium isolated from Malaysia
Authors: Kaha Marshila , Iwamoto Koji , Yahya Nurul Ashyikin , Suhaimi Noraiza , Sugiura Norio , Hara Hirofumi , Othman Nor’Azizi , Zakaria Zuriati , Suzuki Kengo
Published: June 2021

Microalgae are important microorganisms which produce potentially valuable compounds. Astaxanthin, a group of xanthophyll carotenoids, is one of the most powerful antioxidants mainly found in microalgae, yeasts, and crustaceans. Environmental stresses such as intense light, drought, high salinity, nutrient depletion, and high temperature can induce the accumulation of astaxanthin. Thus, this research aims to investigate the effect of black light, also known as long-wave ultraviolet radiation or UV-A, as a stressor on the accumulation of astaxanthin as well as to screen the antioxidant property in two tropical green algal strains isolated from Malaysia, Coelastrum sp. and Monoraphidium sp. SP03. Monoraphidium sp. SP03 showed a higher growth rate (0.66 day−1) compared to that of Coelastrum sp. (0.22 day−1). Coelastrum sp. showed significantly higher accumulation of astaxanthin in black light (0.999 g mL culture−1) compared to that in control condition (0.185 g mL−1). Similarly, Monoraphidium sp. SP03 showed higher astaxanthin content in black light (0.476 g mL culture−1) compared to that in control condition (0.363 g mL culture−1). Coelastrum sp. showed higher scavenging activity (30.19%) when cultured in black light condition, indicating a correlation between the antioxidant activity and accumulation of astaxanthin. In this study, black light was shown to possess great potential to enhance the production of astaxanthin in microalgae.
Generation of tetracycline-controllable CYP3A4-expressing Caco-2 cells by the piggyBac transposon system
Authors: Ichikawa Moe , Akamine Hiroki , Murata Michika , Ito Sumito , Takayama Kazuo , Mizuguchi Hiroyuki
Published: June 2021

Caco-2 cells are widely used as an in vitro intestinal epithelial cell model because they can form a monolayer and predict drug absorption with high accuracy. However, Caco-2 cells hardly express cytochrome P450 (CYP), a drug-metabolizing enzyme. It is known that CYP3A4 is the dominant drug-metabolizing enzyme in human small intestine. In this study, we generated CYP3A4-expressing Caco-2 (CYP3A4-Caco-2) cells and attempted to establish a model that can simultaneously evaluate drug absorption and metabolism. CYP3A4-Caco-2 cells were generated by piggyBac transposon vectors. A tetracycline-controllable CYP3A4 expression cassette (tet-on system) was stably transduced into Caco-2 cells, thus regulating the levels of CYP3A4 expression depending on the doxycycline concentration. The CYP3A4 expression levels in CYP3A4-Caco-2 cells cultured in the presence of doxycycline were similar to or higher than those of adult small intestine. The CYP3A4-Caco-2 cells had enough ability to metabolize midazolam, a substrate of CYP3A4. CYP3A4 overexpression had no negative effects on cell proliferation, barrier function, and P-glycoprotein activity in Caco-2 cells. Thus, we succeeded in establishing Caco-2 cells with CYP3A4 metabolizing activity comparable to in vivo human intestinal tissue. This cell line would be useful in pharmaceutical studies as a model that can simultaneously evaluate drug absorption and metabolism.
Sex-specific impact of diabetes mellitus on left ventricular systolic function and prognosis in heart failure
Authors: Kwak Soongu , Hwang In-Chang , Park Jin Joo , Park Jae-Hyeong , Park Jun-Bean , Cho Goo-Yeong
Published: June 2021

We aimed to investigate the sex differences in associations of diabetes mellitus (DM) with echocardiographic phenotypes and clinical outcomes of heart failure (HF). We studied 4,180 patients admitted for acute HF between 2009 and 2016 (median follow-up, 31.7 months) whose left ventricular global longitudinal strain (LV-GLS) data were available. Patients were compared by sex and DM. Structural equation model (SEM) analysis was performed to evaluate the moderating effects of two causal paths, via ischemic heart disease (IHD) and LV-GLS, linking DM with mortality. Compared to non-diabetic women, diabetic women had significantly lower LV-GLS (11.3% versus 10.1%, p < 0.001), but the difference was attenuated within men (9.7% versus 9.2%, p = 0.014) (p-for-interaction by sex = 0.018). In Cox analyses, DM was an independent predictor for higher mortality in both sexes (women: adjusted hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.15–1.59 versus men: HR 1.24, 95% CI 1.07–1.44, p-for-interaction by sex = 0.699). Restricted cubic spline curves showed that LV-GLS consistently declined, and mortality increased in women with worsening hyperglycemia, but these trends were not evident in men. In SEM analysis, the main driver from DM to mortality differed by sex; men had a stronger effect via IHD than LV-GLS, whereas LV-GLS was the only predominant path in women.
Process optimization and enhancement of pesticide adsorption by porous adsorbents by regression analysis and parametric modelling
Authors: Dehghani Mohammad Hadi , Hassani Amir Hessam , Karri Rama Rao , Younesi Bahareh , Shayeghi Mansoureh , Salari Mehdi , Zarei Ahmad , Yousefi Mahmood , Heidarinejad Zoha
Published: June 2021

In the present study, the adsorptive removal of organophosphate diazinon pesticide using porous pumice adsorbent was experimentally investigated in a batch system, modelled and optimized upon response surface methodology (RSM) and artificial neural network-genetic algorithm (ANN-GA), fitted to isotherm, kinetic and thermodynamic models. The quantification of adsorbent elements was determined using EDX. XRD analysis was utilized to study the crystalline properties of adsorbent. The FT-IR spectra were taken from adsorbent before and after adsorption to study the presence and changes in functional groups. The constituted composition of the adsorbent was determined by XRF. Also, the ionic strength and adsorbent reusability were explored. The influences of operational parameters like pH, initial pesticide concentration, adsorbent dosage and contact time were investigated systematically. ANN-GA and RSM techniques were used to identify the optimal process variables that result in the highest removal. Based on the RSM approach, the optimization conditions for maximum removal efficiency is obtained at pH = 3, adsorbent dosage = 4 g/L, contact time = 30 min, and initial pesticide concentration = 6.2 mg/L. To accurately identify the parameters of nonlinear isotherm and kinetic models, a hybrid evolutionary differential evolution optimization (DEO) is applied. Results indicated that the equilibrium adsorption data were best fitted with Langmuir and Temkin isotherms and kinetic data were well described by pseudo-first and second-order kinetic models. The thermodynamic parameters such as entropy, enthalpy and Gibbs energy were evaluated to study the effect of temperature on pesticide adsorption.
Chronic liver disease not a significant comorbid condition for COVID-19
Authors: Lin Jiahao , Bao Bingting , Khurram Nigar Anjuman , Halsey Kasey , Choi Ji Whae , Wang Lesan , Tran Thi My Linh , Liao Wei-Hua , Feldman Michael D. , Zhang Paul J. , Wu Jing , Bai Harrison X.
Published: June 2021

To explore the role of chronic liver disease (CLD) in COVID-19. A total of 1439 consecutively hospitalized patients with COVID-19 from one large medical center in the United States from March 16, 2020 to April 23, 2020 were retrospectively identified. Clinical characteristics and outcomes were compared between patients with and without CLD. Postmortem examination of liver in 8 critically ill COVID-19 patients was performed. There was no significant difference in the incidence of CLD between critical and non-critical groups (4.1% vs 2.9%, p = 0.259), or COVID-19 related liver injury between patients with and without CLD (65.7% vs 49.7%, p = 0.065). Postmortem examination of liver demonstrated mild liver injury associated central vein outflow obstruction and minimal to moderate portal lymphocytic infiltrate without evidence of CLD. Patients with CLD were not associated with a higher risk of liver injury or critical/fatal outcomes. CLD was not a significant comorbid condition for COVID-19.
Evolutionary history expands the range of signaling interactions in hybrid multikinase networks
Authors: Ortet Philippe , Fochesato Sylvain , Bitbol Anne-Florence , Whitworth David E. , Lalaouna David , Santaella Catherine , Heulin Thierry , Achouak Wafa , Barakat Mohamed
Published: June 2021

Two-component systems (TCSs) are ubiquitous signaling pathways, typically comprising a sensory histidine kinase (HK) and a response regulator, which communicate via intermolecular kinase-to-receiver domain phosphotransfer. Hybrid HKs constitute non-canonical TCS signaling pathways, with transmitter and receiver domains within a single protein communicating via intramolecular phosphotransfer. Here, we report how evolutionary relationships between hybrid HKs can be used as predictors of potential intermolecular and intramolecular interactions (‘phylogenetic promiscuity’). We used domain-swap genes chimeras to investigate the specificity of phosphotransfer within hybrid HKs of the GacS–GacA multikinase network of Pseudomonas brassicacearum. The receiver domain of GacS was replaced with those from nine donor hybrid HKs. Three chimeras with receivers from other hybrid HKs demonstrated correct functioning through complementation of a gacS mutant, which was dependent on strains having a functional gacA. Formation of functional chimeras was predictable on the basis of evolutionary heritage, and raises the possibility that HKs sharing a common ancestor with GacS might remain components of the contemporary GacS network. The results also demonstrate that understanding the evolutionary heritage of signaling domains in sophisticated networks allows their rational rewiring by simple domain transplantation, with implications for the creation of designer networks and inference of functional interactions.
Sleep duration and napping in relation to colorectal and gastric cancer in the MCC-Spain study
Authors: Papantoniou Kyriaki , Castaño-Vinyals Gemma , Espinosa Ana , Turner Michelle C. , Martín-Sánchez Vicente , Casabonne Delphine , Aragonés Nuria , Gómez-Acebo Inés , Ardanaz Eva , Jimenez-Moleon Jose-Juan , Amiano Pilar , Molina-Barceló Ana , Alguacil Juan , Fernández-Tardón Guillermo , Huerta José María , Hernández-Segura Natalia , Perez-Gomez Beatriz , Llorca Javier , Vidán-Alli Juana , Olmedo-Requena Rocıo , Gil Leire , Castañon-López Carmen , Pollan Marina , Kogevinas Manolis , Moreno Victor
Published: June 2021

Sleep duration is a novel and potentially modifiable risk factor for cancer. We evaluated the association of self-reported sleep duration and daytime napping with odds of colorectal and gastric cancer. We included 2008 incident colorectal cancer cases, 542 gastric cancer cases and 3622 frequency-matched population controls, recruited in the MCC-Spain case–control study (2008–2013). Sleep information, socio-demographic and lifestyle characteristics were obtained through personal interviews. Multivariable adjusted logistic regression models were used to estimate odds ratios (OR) with 95% confidence intervals (CI) for cancer, across categories of sleep duration (≤ 5, 6, 7, 8, ≥ 9 hours/day), daytime napping frequency (naps/week) and duration (minutes/nap). Compared to 7 hours of sleep, long sleep was associated with increased odds of colorectal (OR≥9 hours: 1.59; 95%CI 1.30–1.94) and gastric cancer (OR≥9 hours: 1.95; 1.37–2.76); short sleep was associated with increased odds of gastric cancer (OR≤5 hours: 1.32; 0.93–1.88). Frequent and long daytime naps increased the odds of colorectal (OR6–7 naps/week, ≥30 min: 1.32; 1.14–1.54) and gastric cancer (OR6–7 naps/week, ≥30 min: 1.56; 1.21–2.02). Effects of short sleep and frequent long naps were stronger among participants with night shift-work history. Sleep and circadian disruption may jointly play a role in the etiology of colorectal and gastric cancer.