bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct Impacts of Increased Aerosols on Cloud Droplet Number Concentration of Stratus/Stratocumulus and Cumulus
Authors: Jia H. , Ma X. , Yu F. , Liu Y. , Yin Y.
Published: November 2019

In situ aircraft measurements obtained during the RACORO field campaign are analyzed to study the aerosol effects on different cloud regimes. The results show that with increasing cloud condensation nuclei (CCN), cloud droplet number concentration (Nd) significantly increases in stratocumulus (Sc) while remains almost unchanged in cumulus (Cu). By using a new approach to strictly constrain the dynamics in Cu, we found that neither simultaneously changing cloud dynamics nor dilution of cloud water induced by entrainment‐mixing can explain the observed insensitivity of Nd. The different degree of reduction in cloud supersaturation caused by increasing aerosols might be responsible for the observed different aerosol indirect effect between Sc and Cu.
Eastward Propagating Second Harmonic Poloidal Waves Triggered by Temporary Outward Gradient of Proton Phase Space Density: Van Allen Probe A Observation
Authors: Yamamoto K. , Nosé M. , Keika K. , Hartley D. P. , Smith C. W. , MacDowall R. J. , Lanzerotti L. J. , Mitchell D. G. , Spence H. E. , Reeves G. D. , Wygant J. R. , Bonnell J. W. , Oimatsu S.
Published: November 2019

Two wave packets of second harmonic poloidal Pc 4 waves with a wave frequency of ~7 mHz were detected by Van Allen Probe A at a radial distance of ~5.8 RE and magnetic local time of 13 hr near the magnetic equator, where plasmaspheric refilling was in progress. Proton butterfly distributions with energy dispersions were also measured at the same time; the proton fluxes at 10–30 keV oscillated with the same frequency as the Pc 4 waves. Using the ion sounding technique, we find that the Pc 4 waves propagated eastward with an azimuthal wave number (m number) of ~220 and ~260 for each wave packet, respectively. Such eastward propagating high‐m (m > 100) waves were seldom reported in previous studies. The condition of drift‐bounce resonance is well satisfied for the estimated m numbers in both events. Proton phase space density was also examined to understand the wave excitation mechanism. We obtained temporal variations of the energy and radial gradient of the proton phase space density and find that temporal intensification of the radial gradient can generate the two wave packets. The cold electron density around the spacecraft apogee was >100 cm−3 in the present events, and hence the eigenfrequency of the Pc 4 waves became lower. This causes the increase of the m number which satisfies the resonance condition of drift‐bounce resonance for 10–30 keV protons and meets the condition for destabilization due to gyrokinetic effect.
Submesoscales Enhance Storm‐Driven Vertical Mixing of Nutrients: Insights From a Biogeochemical Large Eddy Simulation
Authors: Whitt D. B. , Lévy M. , Taylor J. R.
Published: November 2019

Storms deepen the mixed layer, entrain nutrients from the pycnocline, and fuel phytoplankton blooms in midlatitude oceans. However, the effects of oceanic submesoscale (0.1–10 km horizontal scale) physical heterogeneity on the physical‐biogeochemical response to a storm are not well understood. Here, we explore these effects numerically in a Biogeochemical Large Eddy Simulation (BLES), where a four‐component biogeochemical model is coupled with a physical model that resolves some submesoscales and some smaller turbulent scales (2 km to 2 m) in an idealized storm forcing scenario. Results are obtained via comparisons to BLES in smaller domains that do not resolve submesoscales and to one‐dimensional column simulations with the same biogeochemical model, initial conditions, and boundary conditions but parameterized turbulence and submesoscales. These comparisons show different behaviors during and shortly after the storm. During the storm, resolved submesoscales double the vertical nutrient flux. The vertical diffusivity is increased by a factor of 10 near the mixed layer base, and the mixing‐induced increase in potential energy is double. Resolved submesoscales also enhance horizontal nutrient and phytoplankton variance by a factor of 10. After the storm, resolved submesoscales maintain higher nutrient and phytoplankton variance within the mixed layer. However, submesoscales reduce net vertical nutrient fluxes by 50% and nearly shut off the turbulent diffusivity. Over the whole scenario, resolved submesoscales double storm‐driven biological production. Current parameterizations of submesoscales and turbulence fail to capture both the enhanced nutrient flux during the storm and the enhanced biological production.
Vertical Structure and Seasonal Variability of the Inflow to the Lofoten Basin Inferred From High‐Resolution Lagrangian Simulations
Authors: Dugstad Johannes S. , Koszalka Inga Monika , Isachsen Pål Erik , Dagestad Knut‐Frode , Fer Ilker
Published: November 2019

The Lofoten Basin in the eastern Nordic Seas plays a central role in modifying the warm Atlantic Water inflow toward the Arctic Ocean. Here, the Atlantic Water experiences increased residence times, cooling, and substantial transformation. In this study, we investigate the Atlantic Water inflow pathways to the Lofoten Basin and their vertical and seasonal variations using 2‐D and 3‐D Lagrangian simulations forced by a high‐resolution ocean model. Atlantic Water enters the basin from all directions, but we find two main inflow pathways at all vertical levels, one close to the Lofoten Escarpment in the southeast, associated with the Slope Current, and another close to the Helgeland Ridge in the southwest, associated with the Front Current. The surface inflow exhibits a stronger seasonal forcing than the inflow at depth as well as a stronger heat loss that is dominated by water masses entering the basin from the south. At deeper levels, the warm inflow from the east cools, while the relatively colder inflow from the west warms. The 2‐D and 3‐D synthetic trajectories show similar pathways. However, they are affected differently by the seasonal signal, giving different heat exchange patterns. Our results have implications for how results from Lagrangian observations in the region should be interpreted.
Bayesian Calibration of the Mg/Ca Paleothermometer in Planktic Foraminifera
Authors: Tierney Jessica E. , Malevich Steven B. , Gray William , Vetter Lael , Thirumalai Kaustubh
Published: November 2019

The Mg/Ca ratio of planktic foraminifera is a widely used proxy for sea‐surface temperature but is also sensitive to other environmental factors. Previous work has relied on correcting Mg/Ca for nonthermal influences. Here, we develop a set of Bayesian models for Mg/Ca in four major planktic groups—Globigerinoides ruber (including both pink and white chromotypes), Trilobatus sacculifer, Globigerina bulloides, and Neogloboquadrina pachyderma (including N. incompta)—that account for the multivariate influences on this proxy in an integrated framework. We use a hierarchical model design that leverages information from both laboratory culture studies and globally distributed core top data, allowing us to include environmental sensitivities that are poorly constrained by core top observations alone. For applications over longer geological timescales, we develop a version of the model that incorporates changes in the Mg/Ca ratio of seawater. We test our models—collectively referred to as BAYMAG—on sediment trap data and on representative paleoclimate time series and demonstrate good agreement with observations and independent sea‐surface temperature proxies. BAYMAG provides probabilistic estimates of past temperatures that can accommodate uncertainties in other environmental influences, enhancing our ability to interpret signals encoded in Mg/Ca.
Satellite UV-Vis spectroscopy: implications for air quality trends and their driving forces in China during 2005–2017
Authors: Zhang Chengxin , Liu Cheng , Hu Qihou , Cai Zhaonan , Su Wenjing , Xia Congzi , Zhu Yizhi , Wang Siwen , Liu Jianguo
Published: November 2019

Abundances of a range of air pollutants can be inferred from satellite UV-Vis spectroscopy measurements by using the unique absorption signatures of gas species. Here, we implemented several spectral fitting methods to retrieve tropospheric NO2, SO2, and HCHO from the ozone monitoring instrument (OMI), with radiative simulations providing necessary information on the interactions of scattered solar light within the atmosphere. We analyzed the spatial distribution and temporal trends of satellite-observed air pollutants over eastern China during 2005–2017, especially in heavily polluted regions. We found significant decreasing trends in NO2 and SO2 since 2011 over most regions, despite varying temporal features and turning points. In contrast, an overall increasing trend was identified for tropospheric HCHO over these regions in recent years. Furthermore, generalized additive models were implemented to understand the driving forces of air quality trends in China and assess the effectiveness of emission controls. Our results indicated that although meteorological parameters, such as wind, water vapor, solar radiation and temperature, mainly dominated the day-to-day and seasonal fluctuations in air pollutants, anthropogenic emissions played a unique role in the long-term variation in the ambient concentrations of NO2, SO2, and HCHO in the past 13 years. Generally, recent declines in NO2 and SO2 could be attributed to emission reductions due to effective air quality policies, and the opposite trends in HCHO may urge the need to control anthropogenic volatile organic compound (VOC) emissions.
Coadministration of lithium and celecoxib reverses manic-like behavior and decreases oxidative stress in a dopaminergic model of mania induced in rats
Authors: Valvassori Samira S. , Tonin Paula T. , Dal-Pont Gustavo C. , Varela Roger B. , Cararo José Henrique , Garcia Abel Freitas , Gava Fernanda F. , Menegas Samira , Soares Jair C. , Quevedo João
Published: November 2019

The present study intends to investigate the effect of lithium (Li) and celecoxib (Cel) coadministration on the behavioral status and oxidative stress parameters in a rat model of mania induced by dextroamphetamine (d-AMPH). Male Wistar rats were treated with d-AMPH or saline (Sal) for 14 days; on the 8th day of treatment, rats received lithium (Li), celecoxib (Cel), Li plus Cel, or water until day 14. Levels of oxidative stress parameters were evaluated in the serum, frontal cortex, and hippocampus. d-AMPH administration induced hyperlocomotion in rats, which was significantly reversed by Li and Cel coadministration. In addition, d-AMPH administration induced damage to proteins and lipids in the frontal cortex and hippocampus of rats. All these impairments were reversed by treatment with Li and/or Cel, in a way dependent on cerebral area and biochemical analysis. Li and Cel coadministration reversed the d-AMPH-induced decrease in catalase activity in cerebral structures. The activity of glutathione peroxidase was decreased in the frontal cortex of animals receiving d-AMPH, and treatment with Li, Cel, or a combination thereof reversed this alteration in this structure. Overall, data indicate hyperlocomotion and alteration in oxidative stress biomarkers in the cerebral structures of rats receiving d-AMPH. Li and Cel coadministration can mitigate these modifications, comprising a potential novel approach for BD therapy.
POTEE drives colorectal cancer development via regulating SPHK1/p65 signaling
Authors: Shen Zhiyong , Feng Xiaochuang , Fang Yuan , Li Yongsheng , Li Zhenkang , Zhan Yizhi , Lin Mingdao , Li Guoxin , Ding Yi , Deng Haijun
Published: November 2019

Aberrant gene expression plays critical roles in the development of colorectal cancer (CRC). Here we show that POTEE, which was identified as a member E of POTE ankyrin domain family, was significantly upregulated in colorectal tumors and predicted poor overall survival of CRC patients. In CRC cells, POTEE could act as an oncogene and could promote cell growth, cell-cycle progression, inhibit apoptosis, and elevates xenograft tumor growth. Mechanically, we used microarray analysis and identified a POTEE/SPHK1/p65 signaling axis, which affected the biological functions of CRC cells. Further evaluation showed that overexpression of POTEE could increase the protein expression of SPHK1, followed by promoting the phosphorylation and activation of p65 protein. Altogether, our findings suggested a POTEE/SPHK1/p65 signaling axis could promote colorectal tumorigenesis and POTEE might potentially serve as a novel biomarker for the diagnosis and an intervention of colorectal cancer.
Clustering knowledge and dispersing abilities enhances collective problem solving in a network
Authors: Gomez Charles J. , Lazer David M. J.
Published: November 2019

Diversity tends to generate more and better ideas in social settings, ranging in scale from small-deliberative groups to tech-clusters and cities. Implicit in this research is that there are knowledge-generating benefits from diversity that comes from mixing different individuals, ideas, and perspectives. Here, we utilize agent-based modeling to examine the emergent outcomes resulting from the manipulation of how diversity is distributed and how knowledge is generated within communicative social structures. In the context of problem solving, we focus on cognitive diversity and its two forms: ability and knowledge. For diversity of ability, we find that local diversity (intermixing of different agents) performs best at all time scales. However, for diversity of knowledge, we find that local homogeneity performs best in the long-run, because it maintains global diversity, and thus the knowledge-generating ability of the group, for a longer period.
Mapping the perturbome network of cellular perturbations
Authors: Caldera Michael , Müller Felix , Kaltenbrunner Isabel , Licciardello Marco P. , Lardeau Charles-Hugues , Kubicek Stefan , Menche Jörg
Published: November 2019

Drug combinations provide effective treatments for diverse diseases, but also represent a major cause of adverse reactions. Currently there is no systematic understanding of how the complex cellular perturbations induced by different drugs influence each other. Here, we introduce a mathematical framework for classifying any interaction between perturbations with high-dimensional effects into 12 interaction types. We apply our framework to a large-scale imaging screen of cell morphology changes induced by diverse drugs and their combination, resulting in a perturbome network of 242 drugs and 1832 interactions. Our analysis of the chemical and biological features of the drugs reveals distinct molecular fingerprints for each interaction type. We find a direct link between drug similarities on the cell morphology level and the distance of their respective protein targets within the cellular interactome of molecular interactions. The interactome distance is also predictive for different types of drug interactions.
Repurposing endogenous immune pathways to tailor and control chimeric antigen receptor T cell functionality
Authors: Sachdeva Mohit , Busser Brian W. , Temburni Sonal , Jahangiri Billal , Gautron Anne-Sophie , Maréchal Alan , Juillerat Alexandre , Williams Alan , Depil Stéphane , Duchateau Philippe , Poirot Laurent , Valton Julien
Published: November 2019

Endowing chimeric antigen receptor (CAR) T cells with additional potent functionalities holds strong potential for improving their antitumor activity. However, because potency could be deleterious without control, these additional features need to be tightly regulated. Immune pathways offer a wide array of tightly regulated genes that can be repurposed to express potent functionalities in a highly controlled manner. Here, we explore this concept by repurposing TCR, CD25 and PD1, three major players of the T cell activation pathway. We insert the CAR into the TCRα gene (TRACCAR), and IL-12P70 into either IL2Rα or PDCD1 genes. This process results in transient, antigen concentration-dependent IL-12P70 secretion, increases TRACCAR T cell cytotoxicity and extends survival of tumor-bearing mice. This gene network repurposing strategy can be extended to other cellular pathways, thus paving the way for generating smart CAR T cells able to integrate biological inputs and to translate them into therapeutic outputs in a highly regulated manner.
Picosecond to millisecond tracking of a photocatalytic decarboxylation reaction provides direct mechanistic insights
Authors: Bhattacherjee Aditi , Sneha Mahima , Lewis-Borrell Luke , Tau Omri , Clark Ian P. , Orr-Ewing Andrew J.
Published: November 2019

The photochemical decarboxylation of carboxylic acids is a versatile route to free radical intermediates for chemical synthesis. However, the sequential nature of this multi-step reaction renders the mechanism challenging to probe. Here, we employ a 100 kHz mid-infrared probe in a transient absorption spectroscopy experiment to track the decarboxylation of cyclohexanecarboxylic acid in acetonitrile-d3 over picosecond to millisecond timescales using a photooxidant pair (phenanthrene and 1,4-dicyanobenzene). Selective excitation of phenanthrene at 256 nm enables a diffusion-limited photoinduced electron transfer to 1,4-dicyanobenzene. A measured time offset in the rise of the CO2 byproduct reports on the lifetime (520 ± 120 ns) of a reactive carboxyl radical in solution, and spectroscopic observation of the carboxyl radical confirm its formation as a reaction intermediate. Precise clocking of the lifetimes of radicals generated in situ by an activated C-C bond fission will pave the way for improving the photocatalytic selectivity and turnover.
Room-temperature direct synthesis of semi-conductive PbS nanocrystal inks for optoelectronic applications
Authors: Wang Yongjie , Liu Zeke , Huo Nengjie , Li Fei , Gu Mengfan , Ling Xufeng , Zhang Yannan , Lu Kunyuan , Han Lu , Fang Honghua , Shulga Artem G. , Xue Ye , Zhou Sijie , Yang Fan , Tang Xun , Zheng Jiawei , Antonietta Loi Maria , Konstantatos Gerasimos , Ma Wanli
Published: November 2019

Lead sulphide (PbS) nanocrystals (NCs) are promising materials for low-cost, high-performance optoelectronic devices. So far, PbS NCs have to be first synthesized with long-alkyl chain organic surface ligands and then be ligand-exchanged with shorter ligands (two-steps) to enable charge transport. However, the initial synthesis of insulated PbS NCs show no necessity and the ligand-exchange process is tedious and extravagant. Herein, we have developed a direct one-step, scalable synthetic method for iodide capped PbS (PbS-I) NC inks. The estimated cost for PbS-I NC inks is decreased to less than 6 $·g−1, compared with 16 $·g−1 for conventional methods. Furthermore, based on these PbS-I NCs, photodetector devices show a high detectivity of 1.4 × 1011Jones and solar cells show an air-stable power conversion efficiency (PCE) up to 10%. This scalable and low-cost direct preparation of high-quality PbS-I NC inks may pave a path for the future commercialization of NC based optoelectronics.
Clonal selection confers distinct evolutionary trajectories in BRAF-driven cancers
Authors: Gopal Priyanka , Sarihan Elif Irem , Chie Eui Kyu , Kuzmishin Gwendolyn , Doken Semihcan , Pennell Nathan A. , Raymond Daniel P. , Murthy Sudish C. , Ahmad Usman , Raja Siva , Almeida Francisco , Sethi Sonali , Gildea Thomas R. , Peacock Craig D. , Adams Drew J. , Abazeed Mohamed E.
Published: November 2019

Molecular determinants governing the evolution of tumor subclones toward phylogenetic branches or fixation remain unknown. Using sequencing data, we model the propagation and selection of clones expressing distinct categories ofBRAFmutations to estimate their evolutionary trajectories. We show that strongly activatingBRAFmutations demonstrate hard sweep dynamics, whereas mutations with less pronounced activation of the BRAF signaling pathway confer soft sweeps or are subclonal. We use clonal reconstructions to estimate the strength of “driver” selection in individual tumors. Using tumors cells and human-derived murine xenografts, we show that tumor sweep dynamics can significantly affect responses to targeted inhibitors of BRAF/MEK or DNA damaging agents. Our study uncovers patterns of distinctBRAFclonal evolutionary dynamics and nominates therapeutic strategies based on the identity of theBRAFmutation and its clonal composition.
Band splitting with vanishing spin polarizations in noncentrosymmetric crystals
Authors: Liu Kai , Luo Wei , Ji Junyi , Barone Paolo , Picozzi Silvia , Xiang Hongjun
Published: November 2019

The Dresselhaus and Rashba effects are well-known phenomena in solid-state physics, in which spin–orbit coupling splits spin-up and spin-down energy bands of nonmagnetic non-centrosymmetric crystals. Here, we discuss a phenomenon we dub band splitting with vanishing spin polarizations (BSVSP), in which, as usual, spin-orbit coupling splits the energy bands in nonmagnetic non-centrosymmetric systems. Surprisingly, however, both split bands show no net spin polarization along certain high-symmetry lines in the Brillouin zone. In order to rationalize this phenomenon, we propose a classification of point groups into pseudo-polar and non-pseudo-polar groups. By means of first-principles simulations, we demonstrate that BSVSP can take place in both symmorphic (e.g., bulk GaAs) and non-symmorphic systems (e.g., two dimensional ferroelectric SnTe). Furthermore, we identify a linear magnetoelectric coupling in reciprocal space, which could be employed to tune the spin polarization with an external electric field. The BSVSP effect and its manipulation could therefore form the basis for future spintronic devices.
Publisher Correction: Seeded X-ray free-electron laser generating radiation with laser statistical properties
Authors: Gorobtsov Oleg Yu. , Mercurio Giuseppe , Capotondi Flavio , Skopintsev Petr , Lazarev Sergey , Zaluzhnyy Ivan A. , Danailov Miltcho B. , Dell’Angela Martina , Manfredda Michele , Pedersoli Emanuele , Giannessi Luca , Kiskinova Maya , Prince Kevin C. , Wurth Wilfried , Vartanyants Ivan A.
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives
Authors: Hamdan Ahmed Mohsen , Al-Gayyar Mohammed M. , Shams Mohamed E. E. , Alshaman Udai Salamh , Prabahar Kousalya , Bagalagel Alaa , Diri Reem , Noor Ahmad O. , Almasri Diena
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Floodplain land cover affects biomass distribution of fish functional diversity in the Amazon River
Authors: Arantes Caroline C. , Winemiller Kirk O. , Asher Alex , Castello Leandro , Hess Laura L. , Petrere Miguel , Freitas Carlos E. C.
Published: November 2019

Land-cover change often shifts the distribution of biomass in animal communities. However, the effects of land-cover changes on functional diversity remain poorly understood for many organisms and ecosystems, particularly, for floodplains. We hypothesize that the biomass distribution of fish functional diversity in floodplains is associated with land cover, which would imply that fish traits affect behavioral and/or demographic responses to gradients of land cover. Using data from surveys of 462 habitats covering a range of land-cover conditions in the Amazon River floodplain, we fitted statistical models to explain landscape-scale variation in functional diversity and biomass of all fish species as well as subsets of species possessing different functional traits. Forest cover was positively associated with fish biomass and the strength of this relationship varied according to functional groups defined by life history, trophic, migration, and swimming-performance/microhabitat-use traits. Forty-two percent of the functional groups, including those inferred to have enhanced feeding opportunities, growth, and/or reproductive success within forested habitats, had greater biomass where forest cover was greater. Conversely, the biomass of other functional groups, including habitat generalists and those that directly exploit autochthonous food resources, did not vary significantly in relation to forest cover. The niche space occupied by local assemblages (functional richness) and dispersion in trait abundances (functional dispersion) tended to increase with forest cover. Our study supports the expectation that deforestation in the Amazon River floodplain affects not only fish biomass but also functional diversity, with some functional groups being particularly vulnerable.
Quantitative PCR for leprosy diagnosis and monitoring in household contacts: A follow-up study, 2011–2018
Authors: Manta Fernanda S. N. , Barbieri Raquel R. , Moreira Suelen J. M. , Santos Paulo T. S. , Nery José A. C. , Duppre Nádia C. , Sales Anna M. , Pacheco Antônio G. , Hacker Mariana A. , Machado Alice M. , Sarno Euzenir N. , Moraes Milton O.
Published: November 2019

Household contacts (HHC) of leprosy patients exhibit high-risk of developing leprosy and contact tracing is helpful for early diagnosis. From 2011 to 2018,2,437 HHC were examined in a clinic in Rio de Janeiro, Brazil and 16S qPCR was used for diagnosis and monitoring of contacts. Fifty-four HHCs were clinically diagnosed with leprosy at intake. Another 25 exhibited leprosy-like skin lesions at intake, 8 of which were confirmed as having leprosy (50% of which were qPCR positive) and 17 of which were diagnosed with other skin diseases (6% qPCR positive). In skin biopsies, qPCR presented a sensitivity of 0.50 and specificity of 0.94. Furthermore, 955 healthy HHCs were followed-up for at least 3 years and skin scrapings were collected from earlobes for qPCR detection. Positive qPCR indicated a non-significant relative risk of 2.52 of developing the disease. During follow-up, those who progressed towards leprosy exhibited 20% qPCR positivity, compared to 9% of those who remained healthy. Disease-free survival rates indicated that age had a significant impact on disease progression, where patients over 60 had a greater chance of developing leprosy [HR = 32.4 (3.6–290.3)]. Contact tracing combined with qPCR may assist in early diagnosis and age is a risk factor for leprosy progression.
Differences in alveolo-capillary equilibration in healthy subjects on facing O2 demand
Authors: Beretta Egidio , Grasso Gabriele Simone , Forcaia Greta , Sancini Giulio , Miserocchi Giuseppe
Published: November 2019

Oxygen diffusion across the air-blood barrier in the lung is commensurate with metabolic needs and ideally allows full equilibration between alveolar and blood partial oxygen pressures. We estimated the alveolo-capillary O2 equilibration in 18 healthy subjects at sea level at rest and after exposure to increased O2 demand, including work at sea level and on hypobaric hypoxia exposure at 3840 m (PA ~ 50 mmHg). For each subject we estimated O2 diffusion capacity (DO2), pulmonary capillary blood volume (Vc) and cardiac output ($$\dot{Q}$$Q̇). We derived blood capillary transit time $${\boldsymbol{(}}{\boldsymbol{T}}{\boldsymbol{t}}{\boldsymbol{=}}\frac{{\boldsymbol{V}}{\boldsymbol{c}}}{\dot{{\boldsymbol{Q}}}}{\boldsymbol{)}}$$(Tt=VcQ̇) and the time constant of the equilibration process ($${\boldsymbol{\tau }}{\boldsymbol{=}}\frac{{\boldsymbol{\beta }}{\boldsymbol{V}}{\boldsymbol{c}}}{{\boldsymbol{D}}{{\boldsymbol{O}}}_{{\boldsymbol{2}}}}$$τ=βVcDO2, β being the slope of the hemoglobin dissociation curve). O2 equilibration at the arterial end of the pulmonary capillary was defined as $${{\bf{L}}}_{{\bf{e}}{\bf{q}}}{\boldsymbol{=}}{{\bf{e}}}^{{\boldsymbol{-}}\frac{{\bf{T}}t}{{\boldsymbol{\tau }}}}$$Leq=e−Ttτ. Leq greately differed among subjects in the most demanding O2 condition (work in hypoxia): lack of full equilibration was found to range from 5 to 42% of the alveolo-capillary PO2 gradient at the venous end. The present analysis proves to be sensible enough to highlight inter-individual differences in alveolo-capillary equilibration among healthy subjects.
Quantitative description and classification of protein structures by a novel robust amino acid network: interaction selective network (ISN)
Authors: Konno Shohei , Namiki Takao , Ishimori Koichiro
Published: November 2019

To quantitatively categorize protein structures, we developed a quantitative coarse-grained model of protein structures with a novel amino acid network, the interaction selective network (ISN), characterized by the links based on interactions in both the main and side chains. We found that the ISN is a novel robust network model to show the higher classification probability in the plots of average vertex degree (k) versus average clustering coefficient (C), both of which are typical network parameters for protein structures, and successfully distinguished between “all-α” and “all-β” proteins. On the other hand, one of the typical conventional networks, the α-carbon network (CAN), was found to be less robust than the ISN, and another typical network, atomic distance network (ADN), failed to distinguish between these two protein structures. Considering that the links in the CAN and ADN are defined by the interactions only between the main chain atoms and by the distance of the closest atom pair between the two amino acid residues, respectively, we can conclude that reflecting structural information from both secondary and tertiary structures in the network parameters improves the quantitative evaluation and robustness in network models, resulting in a quantitative and more robust description of three-dimensional protein structures in the ISN.
Optimal efficiency of the Q-cycle mechanism around physiological temperatures from an open quantum systems approach
Authors: Tacchino Francesco , Succurro Antonella , Ebenhöh Oliver , Gerace Dario
Published: November 2019

The Q-cycle mechanism entering the electron and proton transport chain in oxygenic photosynthesis is an example of how biological processes can be efficiently investigated with elementary microscopic models. Here we address the problem of energy transport across the cellular membrane from an open quantum system theoretical perspective. We model the cytochrome $${b}_{6}\,f$$

b

6

f
protein complex under cyclic electron flow conditions starting from a simplified kinetic model, which is hereby revisited in terms of a Markovian quantum master equation formulation and spin-boson Hamiltonian treatment. We apply this model to theoretically demonstrate an optimal thermodynamic efficiency of the Q-cycle around ambient and physiologically relevant temperature conditions. Furthermore, we determine the quantum yield of this complex biochemical process after setting the electrochemical potentials to values well established in the literature. The present work suggests that the theory of quantum open systems can successfully push forward our theoretical understanding of complex biological systems working close to the quantum/classical boundary.
Multiplex analysis of 40 cytokines do not allow separation between endometriosis patients and controls
Authors: Knific Tamara , Fishman Dmytro , Vogler Andrej , Gstöttner Manuela , Wenzl René , Peterson Hedi , Rižner Tea Lanišnik
Published: November 2019

Endometriosis is a common gynaecological condition characterized by severe pelvic pain and/or infertility. The combination of nonspecific symptoms and invasive laparoscopic diagnostics have prompted researchers to evaluate potential biomarkers that would enable a non-invasive diagnosis of endometriosis. Endometriosis is an inflammatory disease thus different cytokines represent potential diagnostic biomarkers. As panels of biomarkers are expected to enable better separation between patients and controls we evaluated 40 different cytokines in plasma samples of 210 patients (116 patients with endometriosis; 94 controls) from two medical centres (Slovenian, Austrian). Results of the univariate statistical analysis showed no differences in concentrations of the measured cytokines between patients and controls, confirmed by principal component analysis showing no clear separation amongst these two groups. In order to validate the hypothesis of a more profound (non-linear) differentiating dependency between features, machine learning methods were used. We trained four common machine learning algorithms (decision tree, linear model, k-nearest neighbour, random forest) on data from plasma levels of proteins and patients’ clinical data. The constructed models, however, did not separate patients with endometriosis from the controls with sufficient sensitivity and specificity. This study thus indicates that plasma levels of the selected cytokines have limited potential for diagnosis of endometriosis.
Clinicopathological values of PD-L1 expression in HER2-positive breast cancer
Authors: Kurozumi Sasagu , Inoue Kenichi , Matsumoto Hiroshi , Fujii Takaaki , Horiguchi Jun , Oyama Tetsunari , Kurosumi Masafumi , Shirabe Ken
Published: November 2019

Several ongoing clinical trials are investigating the use of immuno-targeting therapy with programmed cell death protein-1 and programmed death-ligand 1 (PD-L1) inhibitors for triple-negative breast cancer. However, the role of PD-L1 expression in HER2-positive breast cancer remains unclear. We investigated the clinicopathological utility of PD-L1 expression in HER2-positive breast cancer. Cohort A included 248 patients with invasive breast cancer (all subtypes). Cohort B included 126 HER2-positive patients who received neoadjuvant chemotherapy (NAC) concomitant with trastuzumab. The relationship of PD-L1 expression on the cancer cells with clinicopathological factors including pathological complete response (pCR) and prognosis was investigated. In cohort A, 8.1% patients were PD-L1-positive; PD-L1 positivity showed a correlation with high degree of tumor-infiltrating lymphocytes (TILs), estrogen receptor negativity, progesterone receptor negativity, and high histological grade. In cohort B, 17.5% patients were PD-L1-positive; PD-L1 positivity showed a significant correlation with high degree of TILs and high abundance of CD8-positive TILs. The pCR rates were related to TILs and PD-L1 expression. Among PD-L1-negative patients, high CD8-positive TILs were associated with significantly better prognosis. In conclusion, 17.5% of HER2-positive type patients were PD-L1-positive. PD-L1 expression was associated with response to NAC with trastuzumab in patients with HER2-positive breast cancer.
Characterization of Matricellular Protein Expression Signatures in Mechanistically Diverse Mouse Models of Kidney Injury
Authors: Feng Daniel , Ngov Cindy , Henley Nathalie , Boufaied Nadia , Gerarduzzi Casimiro
Published: November 2019

Fibrosis is the most common pathophysiological manifestation of Chronic Kidney Disease (CKD). It is defined as excessive deposition of extracellular matrix (ECM) proteins. Embedded within the ECM are a family of proteins called Matricellular Proteins (MCPs), which are typically expressed during chronic pathologies for ECM processing. As such, identifying potential MCPs in the pathological secretome of a damaged kidney could serve as diagnostic/therapeutic targets of fibrosis. Using published RNA-Seq data from two kidney injury mouse models of different etiologies, Folic Acid (FA) and Unilateral Ureteral Obstruction (UUO), we compared and contrasted the expression profile of various members from well-known MCP families during the Acute and Fibrotic injury phases. As a result, we identified common and distinct MCP expression signatures between both injury models. Bioinformatic analysis of their differentially expressed MCP genes revealed similar top annotation clusters from Molecular Function and Biological Process networks, which are those commonly involved in fibrosis. Using kidney lysates from FA- and UUO-injured mice, we selected MCP genes from our candidate list to confirm mRNA expression by Western Blot, which correlated with injury progression. Understanding the expressions of MCPs will provide important insight into the processes of kidney repair, and may validate MCPs as biomarkers and/or therapeutic targets of CKD.
A strategy for quality evaluation of salt-treated Apocyni Veneti Folium and discovery of efficacy-associated markers by fingerprint-activity relationship modeling
Authors: Chen Cuihua , Chen Jiali , Shi Jingjing , Chen Shuyu , Zhao Hui , Yan Ying , Jiang Yucui , Gu Ling , Chen Feiyan , Liu Xunhong
Published: November 2019

In this study, a fingerprint-activity relationship between chemical fingerprints and hepatoprotective activity was established to evaluate the quality of salt-treated Apocyni Veneti Folium (AVF). Characteristic fingerprints of AVF samples exposed to different concentrations of salt were generated by ultrafast liquid chromatography tandem triple time-of-flight mass/mass spectrometry (UFLC-Triple TOF-MS/MS), and a similarity analysis was performed based on common characteristic peaks by hierarchical clustering analysis (HCA). Then, the hepatoprotective activity of AVF against CCl4-induced acute liver damage in mice was investigated by assessing biochemical markers and histopathology, which showed that a high dose of AVF exposed to low levels of salt stress produced a marked amelioration of hepatic damage compared with the other salt-treated AVF. Finally, fingerprint-activity relationship modeling, which was capable of discovering the bioactive markers used in the quality evaluation, was investigated by the chemical fingerprints and the hepatoprotective activities utilizing multivariate statistical analysis, gray correlation analysis (GCA) and bivariate correlation analysis (BCA). The results showed that the accumulation of polyphenols, such as flavonoids and phenolic acids, in AVF subjected to low levels of salt stress could result in the effective scavenging of free radicals. Therefore, the present study may provide a powerful strategy to holistically evaluate the quality of salt-treated AVF in combination with chemical fingerprint and bioactivity evaluation.
Standardised Framework for Quantitative Analysis of Fibrillation Dynamics
Authors: Li Xinyang , Roney Caroline H. , Handa Balvinder S. , Chowdhury Rasheda A. , Niederer Steven A. , Peters Nicholas S. , Ng Fu Siong
Published: November 2019

The analysis of complex mechanisms underlying ventricular fibrillation (VF) and atrial fibrillation (AF) requires sophisticated tools for studying spatio-temporal action potential (AP) propagation dynamics. However, fibrillation analysis tools are often custom-made or proprietary, and vary between research groups. With no optimal standardised framework for analysis, results from different studies have led to disparate findings. Given the technical gap, here we present a comprehensive framework and set of principles for quantifying properties of wavefront dynamics in phase-processed data recorded during myocardial fibrillation with potentiometric dyes. Phase transformation of the fibrillatory data is particularly useful for identifying self-perpetuating spiral waves or rotational drivers (RDs) rotating around a phase singularity (PS). RDs have been implicated in sustaining fibrillation, and thus accurate localisation and quantification of RDs is crucial for understanding specific fibrillatory mechanisms. In this work, we assess how variation of analysis parameters and thresholds in the tracking of PSs and quantification of RDs could result in different interpretations of the underlying fibrillation mechanism. These techniques have been described and applied to experimental AF and VF data, and AF simulations, and examples are provided from each of these data sets to demonstrate the range of fibrillatory behaviours and adaptability of these tools. The presented methodologies are available as an open source software and offer an off-the-shelf research toolkit for quantifying and analysing fibrillatory mechanisms.
Development of a Staphylococcus aureus reporter strain with click beetle red luciferase for enhanced in vivo imaging of experimental bacteremia and mixed infections
Authors: Miller Robert J. , Crosby Heidi A. , Schilcher Katrin , Wang Yu , Ortines Roger V. , Mazhar Momina , Dikeman Dustin A. , Pinsker Bret L. , Brown Isabelle D. , Joyce Daniel P. , Zhang Jeffrey , Archer Nathan K. , Liu Haiyun , Alphonse Martin P. , Czupryna Julie , Anderson William R. , Bernthal Nicholas M. , Fortuno-Miranda Lea , Bulte Jeff W. M. , Francis Kevin P. , Horswill Alexander R. , Miller Lloyd S.
Published: November 2019

In vivo bioluminescence imaging has been used to monitor Staphylococcus aureus infections in preclinical models by employing bacterial reporter strains possessing a modified lux operon from Photorhabdus luminescens. However, the relatively short emission wavelength of lux (peak 490 nm) has limited tissue penetration. To overcome this limitation, the gene for the click beetle (Pyrophorus plagiophtalamus) red luciferase (luc) (with a longer >600 emission wavelength), was introduced singly and in combination with the lux operon into a methicillin-resistant S. aureus strain. After administration of the substrate D-luciferin, the luc bioluminescent signal was substantially greater than the lux signal in vitro. The luc signal had enhanced tissue penetration and improved anatomical co-registration with infected internal organs compared with the lux signal in a mouse model of S. aureus bacteremia with a sensitivity of approximately 3 × 104 CFU from the kidneys. Finally, in an in vivo mixed bacterial wound infection mouse model, S. aureus luc signals could be spectrally unmixed from Pseudomonas aeruginosa lux signals to noninvasively monitor the bacterial burden of both strains. Therefore, the S. aureus luc reporter may provide a technological advance for monitoring invasive organ dissemination during S. aureus bacteremia and for studying bacterial dynamics during mixed infections.
Social defeat stress-specific increase in c-Fos expression in the extended amygdala in mice: Involvement of dopamine D1 receptor in the medial prefrontal cortex
Authors: Numa Chisato , Nagai Hirotaka , Taniguchi Masayuki , Nagai Midori , Shinohara Ryota , Furuyashiki Tomoyuki
Published: November 2019

We recently reported that dopamine D1 receptor in the medial prefrontal cortex (mPFC) is activated by subthreshold social defeat stress and suppresses the induction of depressive-like behavior in mice. However, which mPFC projection(s) mediates this antidepressant-like effect remains poorly understood. Here we show that social defeat stress specifically increased c-Fos expression, a marker for neuronal activity, in distinct brain regions involved in emotional regulation, relative to novelty-induced exploration. Among these brain areas, D1 knockdown in the mPFC decreased social defeat stress-induced c-Fos expression in the interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a subregion of the extended amygdala. Using retrograde adeno-associated virus vectors and transgenic mice expressing Cre recombinase under the D1 promoter, we also found that D1-expressing deep-layer pyramidal neurons in the mPFC send direct projections to the IPAC. These findings indicate that social defeat stress specifically activates neurons in distinct brain areas, among which the IPAC is regulated by dopamine D1 receptor in the mPFC perhaps through direct projections. Thus, this study provides hints toward identifying neural circuits that underlie antidepressant-like effects of stress-induced dopamine D1 receptor signaling in the mPFC.
Insect larvae, Hermetia illucens in poultry by-product meal for barramundi, Lates calcarifer modulates histomorphology, immunity and resistance to Vibrio harveyi
Authors: Chaklader Md Reaz , Siddik Muhammad A. B. , Fotedar Ravi , Howieson Janet
Published: November 2019

This study investigated the effects of replacement of fishmeal (FM) with poultry by-product (PBM) protein, supplemented with black soldier fly, Hermetia illucens (HI) larvae on growth, histomormhology, immunity and resistance to Vibrio harveyi in juvenile barramundi. Two hundred and twenty five barramundi averaging 3.51 ± 0.03 g were randomly allocated into three groups and fed isonitrogenous and isocalorific diets containing different levels of PBM supplemented with HI as follows: Control (FM based diet), 45PBM + HI (45% PBM supplemented with 10% HI), and 90PBM + HI (90% PBM supplemented with 10% HI) for 6 weeks. Results showed that dietary inclusion of 45PBM + HI significantly improved the growth performance than control whereas growth inhibition occurred in the 90PBM + HI. The 45PBM + HI groups demonstrated significant increases in histometric measurements (villus and enterocyte width, and microvilli height) and acidic mucins. The impaired growth in 90PBM + HI groups was further associated with multifocal necrosis in the liver, an upregulation of the stress related genes (HSP70 and HSP90) and increase in the levels of liver enzymes. When 45PBM + HI was fed, survival against V. harveyi increased significantly and also an increase in serum immunity and immune-related genes in the head kidney was observed after infection.
Spatial distribution of decadal ice-thickness change and glacier stored water loss in the Upper Ganga basin, India during 2000–2014
Authors: Bandyopadhyay Debmita , Singh Gulab , Kulkarni Anil V.
Published: November 2019

Himalayan glaciers have long been the focus of glaciologists across the world while trying to understand the contrasting patterns of elevation and mass changes. However, with limited number of ground observations, a comprehensive assessment of mass balance on a regional scale still remains elusive. Using the synoptic coverage of remote sensing data, we estimate a detailed spatial variation of glacier ice thickness change in the Central Himalaya of Uttarakhand using geodetic method, on a catchment scale. High resolution TerraSAR-X/TanDEM-X (12 m) and SRTM (30 m) digital elevation models (DEMs) have been utilized. The mean elevation change in the catchments is found to be −9.56 ± 0.2 m (mean annual elevation change rate is −0.68 ± 0.01 m a−1). To highlight the water potential of this region, the total ice mass loss has been estimated to be 16.0 ± 1.2 Gigatonne (Gt) from 2000–2014 from eight identified catchments namely Yamunotri, Bhagirathi, Mandakini, Alaknanda, Dhauliganga, Pindar, Goriganga and Kali/Sarda. The estimated mass balance has been validated using reported observations on five selective glaciers and the coefficient of determination is 0.93. This spatial variation of ice thickness estimated in the eight catchments is critical, as the melt-water from these glaciers contribute to the upper Ganga basin.