bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of Lateral Transport by Submesoscale Flows and Inertia‐Gravity Waves
Authors: Sinha Anirban , Balwada Dhruv , Tarshish Nathaniel , Abernathey Ryan
Published: March 2019

We investigate the role of small‐scale, high‐frequency motions on lateral transport in the ocean, by using velocity fields and particle trajectories from an ocean general circulation model (MITgcm‐llc4320) that permits submesoscale flows, inertia‐gravity waves, and tides. Temporal averaging/filtering removes most of the submesoscale turbulence, inertia‐gravity waves, and tides, resulting in a largely geostrophic flow, with a rapid drop‐off in energy at scales smaller than the mesoscales. We advect two types of Lagrangian particles: (a) 2‐D particles (surface restricted) and (b) 3‐D particles (advected in full three dimensions) with the filtered and unfiltered velocities and calculate Lagrangian diagnostics. At large length/time scales, Lagrangian diffusivity is comparable for filtered and unfiltered velocities, while at short scales, unfiltered velocities disperse particles much faster. We also calculate diagnostics of Lagrangian coherent structures:rotationally coherent Lagrangian vortices detected from closed contours of the Lagrangian‐averaged vorticity deviation and material transport barriers formed by ridges of maximum finite‐time Lyapunov exponent. For temporally filtered velocities, we observe strong material coherence, which breaks down when the level of temporal filtering is reduced/removed, due to vigorous small‐scale mixing. In addition, for the lowest temporal resolution, the 3‐D particles experience very little vertical motion, suggesting that degrading temporal resolution greatly reduces vertical advection by high‐frequency motions. Our study suggests that Lagrangian diagnostics based on satellite‐derived surface geostrophic velocity fields, even with higher spatial resolutions as in the upcoming Surface Water and Ocean Topography mission, may overestimate the presence of mesoscale coherent structures and underestimate dispersion.
The Single Column Atmosphere Model Version 6 (SCAM6): Not a Scam but a Tool for Model Evaluation and Development
Authors: Gettelman A. , Truesdale J. E. , Bacmeister J. T. , Caldwell P. M. , Neale R. B. , Bogenschutz P. A. , Simpson I. R.
Published: March 2019

The Single Column Atmosphere Model (SCAM) is a single column model version of the Community Atmosphere Model (CAM). Here we describe the functionality and features of SCAM6, available as part of CAM6 in the Community Earth System Model, version 2 (CESM2). SCAM6 features a wide selection of standard cases, as well as the ability to easily configure a case specified by the user based on a particular point in a CAM 3‐D simulation. This work illustrates how SCAM6 reproduces CAM6 results for physical parameterizations, mostly of moisture and clouds. We demonstrate how SCAM6 can be used for model development through different physics selections, as well as with parameter sweep experiments to highlight the sensitivity of cloud properties to the specification of the vapor deposition process in the cloud microphysics. Furthermore, we use SCAM6 to illustrate the sensitivity of CAM6 cloud radiative properties and precipitation to variable drop number (cloud microphysics properties). Finally, we illustrate how SCAM6 can be used to explore critical emergent processes such as cloud feedbacks and show that CAM6 cloud responses to surface warming in stratus and stratocumulus regimes are similar to those in CAM5. CAM6 has a larger response in the shallow cumulus regime than CAM5. CAM6 cloud feedbacks in the shallow cumulus regime are sensitive to turbulence parameters. SCAM6 is thus a valuable tool for model development, evaluation, and scientific analy sis and an important part of the model hierarchy in Community Earth System Model, version 2.
Crescent‐Shaped Electron Distributions at the Nonreconnecting Magnetopause: Magnetospheric Multiscale Observations
Authors: Tang B.‐B. , Li W. Y. , Graham D. B. , Rager A. C. , Wang C. , Khotyaintsev Yu. V. , Lavraud B. , Hasegawa H. , Zhang Y.‐C. , Dai L. , Giles B. L. , Dorelli J. C. , Russell C. T. , Lindqvist P.‐A. , Ergun R. E. , Burch J. L.
Published: March 2019

Crescent‐shaped electron distributions perpendicular to the magnetic field are an important indicator of the electron diffusion region in magnetic reconnection. They can be formed by the electron finite gyroradius effect at plasma boundaries or by demagnetized electron motion. In this study, we present Magnetospheric Multiscale mission observations of electron crescents at the flank magnetopause on 20 September 2017, where reconnection signatures are not observed. These agyrotropic electron distributions are generated by electron gyromotion at the thin electron‐scale magnetic boundaries of a magnetic minimum after magnetic curvature scattering. The variation of their angular range in the perpendicular plane is in good agreement with predictions. Upper hybrid waves are observed to accompany the electron crescents at all four Magnetospheric Multiscale spacecraft as a result of the beam‐plasma instability associated with these agyrotropic electron distributions. This study suggests electron crescents can be more frequently formed at the magnetopause.
Maternal hyperglycemia disturbs neocortical neurogenesis via epigenetic regulation in C57BL/6J mice
Authors: Ji Shufang , Zhou Wenjuan , Li Xian , Liu Shangming , Wang Fuwu , Li Xinyue , Zhao Tiantian , Ji Guangyu , Du Jingyi , Hao Aijun
Published: March 2019

Offspring of mothers with hyperglycemia during pregnancy have a higher incidence of long-term neuropsychiatric disorders than offspring from a normal pregnancy, indicating that neocortical neurogenesis might be affected by maternal hyperglycemia. A paucity of study evaluating the effects of hyperglycemia on neocortical neurogenetic differentiation of neural stem cells, and the mechanism remains unclear. We sought to investigate the the roles and possible molecular mechanism of maternal hyperglycemia on neocortical neurogenetic differentiation of neural stem cells. We established a mouse model of a hyperglycemic pregnancy to study effects of intrauterine exposure to maternal hyperglycemia on neocortical neurogenesis. We observed morphological changes in the neocortex and detected the neurogenetic differentiation of neural stem cells in offspring affected by high glucose levels. We investigated the regulatory network between epigenetic modification and transcription factors in differentiated neural stem cells under hyperglycemic conditions. Maternal hyperglycemia disturbs neocortical lamination in some non-malformed offspring. Our results suggested that hyperglycemia altered the early-born neuron fate and the distribution of newborn neurons in deep layers by promoting the earlier differentiation of neural stem cells. Altered histone acetylation and its regulation on the transcription of proneural genes might be correlated to the disrupted differentiation of neural stem cells and altered distribution of newborn projection neurons in the neocortex. Our data raised the possibility that maternal hyperglycemia in pregnancy disturbs the laminar distribution of neocortical projection neurons in some non-malformed offspring via epigenetic regulation on neural stem cell differentiation and the birthdate of neocortical neurons.
Quantitative proteomic analyses of dynamic signalling events in cortical neurons undergoing excitotoxic cell death
Authors: Hoque Ashfaqul , Williamson Nicholas A. , Ameen S. Sadia , Ciccotosto Giuseppe D. , Hossain M. Iqbal , Oakhill Jonathan S. , Ng Dominic C. H. , Ang Ching-Seng , Cheng Heung-Chin
Published: March 2019

Excitotoxicity, caused by overstimulation or dysregulation of ionotropic glutamate receptors (iGluRs), is a pathological process directing neuronal death in many neurological disorders. The aberrantly stimulated iGluRs direct massive influx of calcium ions into the affected neurons, leading to changes in expression and phosphorylation of specific proteins to modulate their functions and direct their participation in the signalling pathways that induce excitotoxic neuronal death. To define these pathways, we used quantitative proteomic approaches to identify these neuronal proteins (referred to as the changed proteins) and determine how their expression and/or phosphorylation dynamically changed in association with excitotoxic cell death. Our data, available in ProteomeXchange with identifier PXD008353, identified over 100 changed proteins exhibiting significant alterations in abundance and/or phosphorylation levels at different time points (5–240 min) in neurons after glutamate overstimulation. Bioinformatic analyses predicted that many of them are components of signalling networks directing defective neuronal morphology and functions. Among them, the well-known neuronal survival regulators including mitogen-activated protein kinases Erk1/2, glycogen synthase kinase 3 (GSK3) and microtubule-associated protein (Tau), were selected for validation by biochemical approaches, which confirmed the findings of the proteomic analysis. Bioinformatic analysis predicted Protein Kinase B (Akt), c-Jun kinase (JNK), cyclin-dependent protein kinase 5 (Cdk5), MAP kinase kinase (MEK), Casein kinase 2 (CK2), Rho-activated protein kinase (Rock) and Serum/glucocorticoid-regulated kinase 1 (SGK1) as the potential upstream kinases phosphorylating some of the changed proteins. Further biochemical investigation confirmed the predictions of sustained changes of the activation states of neuronal Akt and CK2 in excitotoxicity. Thus, future investigation to define the signalling pathways directing the dynamic alterations in abundance and phosphorylation of the identified changed neuronal proteins will help elucidate the molecular mechanism of neuronal death in excitotoxicity.
Ultrafast energy relaxation dynamics of amide I vibrations coupled with protein-bound water molecules
Authors: Tan Junjun , Zhang Jiahui , Li Chuanzhao , Luo Yi , Ye Shuji
Published: March 2019

The influence of hydration water on the vibrational energy relaxation in a protein holds the key to understand ultrafast protein dynamics, but its detection is a major challenge. Here, we report measurements on the ultrafast vibrational dynamics of amide I vibrations of proteins at the lipid membrane/H2O interface using femtosecond time-resolved sum frequency generation vibrational spectroscopy. We find that the relaxation time of the amide I mode shows a very strong dependence on the H2O exposure, but not on the D2O exposure. This observation indicates that the exposure of amide I bond to H2O opens up a resonant relaxation channel and facilitates direct resonant vibrational energy transfer from the amide I mode to the H2O bending mode. The protein backbone motions can thus be energetically coupled with protein-bound water molecules. Our findings highlight the influence of H2O on the ultrafast structure dynamics of proteins.
Author Correction: Runx/Cbfβ complexes protect group 2 innate lymphoid cells from exhausted-like hyporesponsiveness during allergic airway inflammation
Authors: Miyamoto Chizuko , Kojo Satoshi , Yamashita Motoi , Moro Kazuyo , Lacaud Georges , Shiroguchi Katsuyuki , Taniuchi Ichiro , Ebihara Takashi
Published: March 2019

The original version of this Article contained an error in the author affiliations. Affiliation 5 incorrectly read ‘Laboratory for Prediction of Cell Systems Dynamics, RIKEN Center for Biosystems Dynamics Research (BDR), Suite, Hyogo 565-0874, Japan.’ This has now been corrected in both the PDF and HTML versions of the Article.
Structural dynamics of a metal–organic framework induced by CO2 migration in its non-uniform porous structure
Authors: Zhao Pu , Fang Hong , Mukhopadhyay Sanghamitra , Li Aurelia , Rudić Svemir , McPherson Ian J. , Tang Chiu C. , Fairen-Jimenez David , Tsang S. C. Edman , Redfern Simon A. T.
Published: March 2019

Stimuli-responsive behaviors of flexible metal–organic frameworks (MOFs) make these materials promising in a wide variety of applications such as gas separation, drug delivery, and molecular sensing. Considerable efforts have been made over the last decade to understand the structural changes of flexible MOFs in response to external stimuli. Uniform pore deformation has been used as the general description. However, recent advances in synthesizing MOFs with non-uniform porous structures, i.e. with multiple types of pores which vary in size, shape, and environment, challenge the adequacy of this description. Here, we demonstrate that the CO2-adsorption-stimulated structural change of a flexible MOF, ZIF-7, is induced by CO2 migration in its non-uniform porous structure rather than by the proactive opening of one type of its guest-hosting pores. Structural dynamics induced by guest migration in non-uniform porous structures is rare among the enormous number of MOFs discovered and detailed characterization is very limited in the literature. The concept presented in this work provides new insights into MOF flexibility.
Purification of cross-linked RNA-protein complexes by phenol-toluol extraction
Authors: Urdaneta Erika C. , Vieira-Vieira Carlos H. , Hick Timon , Wessels Hans-Herrmann , Figini Davide , Moschall Rebecca , Medenbach Jan , Ohler Uwe , Granneman Sander , Selbach Matthias , Beckmann Benedikt M.
Published: March 2019

Recent methodological advances allowed the identification of an increasing number of RNA-binding proteins (RBPs) and their RNA-binding sites. Most of those methods rely, however, on capturing proteins associated to polyadenylated RNAs which neglects RBPs bound to non-adenylate RNA classes (tRNA, rRNA, pre-mRNA) as well as the vast majority of species that lack poly-A tails in their mRNAs (including all archea and bacteria). We have developed the Phenol Toluol extraction (PTex) protocol that does not rely on a specific RNA sequence or motif for isolation of cross-linked ribonucleoproteins (RNPs), but rather purifies them based entirely on their physicochemical properties. PTex captures RBPs that bind to RNA as short as 30 nt, RNPs directly from animal tissue and can be used to simplify complex workflows such as PAR-CLIP. Finally, we provide a global RNA-bound proteome of human HEK293 cells and the bacterium Salmonella Typhimurium.
Unveiling the operation mechanism of layered perovskite solar cells
Authors: Lin Yun , Fang Yanjun , Zhao Jingjing , Shao Yuchuan , Stuard Samuel J. , Nahid Masrur Morshed , Ade Harald , Wang Qi , Shield Jeffrey E. , Zhou Ninghao , Moran Andrew M. , Huang Jinsong
Published: March 2019

Layered perovskites have been shown to improve the stability of perovskite solar cells while its operation mechanism remains unclear. Here we investigate the process for the conversion of light to electrical current in high performance layered perovskite solar cells by examining its real morphology. The layered perovskite films in this study are found to be a mixture of layered and three dimensional (3D)-like phases with phase separations at micrometer and nanometer scale in both vertical and lateral directions. This phase separation is explained by the surface initiated crystallization process and the competition of the crystallization between 3D-like and layered perovskites. We further propose that the working mechanisms of the layered perovskite solar cells involve energy transfer from layered to 3D-like perovskite network. The impact of morphology on efficiency and stability of the hot-cast layered perovskite solar cells are also discussed to provide guidelines for the future improvement.
Loading ceftriaxone, vancomycin, and Bifidobacteria bifidum TMC3115 to neonatal mice could differently and consequently affect intestinal microbiota and immunity in adulthood
Authors: Cheng RuYue , Guo JiaWen , Pu FangFang , Wan ChaoMin , Shi Lei , Li HuaWen , Yang YuHong , Huang ChengYu , Li Ming , He Fang
Published: March 2019

Recent studies have demonstrated that antibiotics/or probiotics administration in early life play key roles on modulating intestinal microbiota and the alterations might cause long-lasting consequences both physiologically and immunologically. We investigated the effects of early life ceftriaxone, vancomycin and Bifidobacterium bifidum TMC3115 (TMC3115) treatment on intestinal microbiota and immunity both in neonates and adults even after termination of antibiotics exposure. We found that ceftriaxone and vancomycin, but not TMC3115, significantly altered the intestinal microbiota, serum total IgE level, and the morphology and function of the intestinal epithelium in the neonatal mice. In the adult stages, the diversity and composition of the intestinal microbiota were significantly different in the antibiotic-treated mice, and ceftriaxone-treated mice exhibited significantly higher serum total IgE and OVA-specific IgE levels. TMC3115 significantly mitigated the alteration of intestinal microbiota caused by ceftriaxone not vancomycin. Antibiotics and TMC3115 can differently modulate intestinal microbiota and SCFAs metabolism, affecting the development and function of the immunity and intestinal epithelium to different degrees in neonatal mice. Neonatal ceftriaxone-induced abnormal intestinal microbiota, immunity and epithelium could last to adulthood partly, which might be associated with the enhancement of host susceptibility to IgE-mediated allergies and related immune responses, TMC3115 may protect against the side effects of antibiotic treatment, at least partly.
64Cu and fluorescein labeled anti-miRNA peptide nucleic acids for the detection of miRNA expression in living cells
Authors: Croci Stefania , Manicardi Alex , Rubagotti Sara , Bonacini Martina , Iori Michele , Capponi Pier Cesare , Cicoria Gianfranco , Parmeggiani Maria , Salvarani Carlo , Versari Annibale , Corradini Roberto , Asti Mattia
Published: March 2019

MiRNAs are single stranded RNAs of 18–22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 (64Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and 64Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and 64Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. 64Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases.
A quantitative analysis linking seabird mortality and marine debris ingestion
Authors: Roman Lauren , Hardesty Britta Denise , Hindell Mark A. , Wilcox Chris
Published: March 2019

Procellariiformes are the most threatened bird group globally, and the group with the highest frequency of marine debris ingestion. Marine debris ingestion is a globally recognized threat to marine biodiversity, yet the relationship between how much debris a bird ingests and mortality remains poorly understood. Using cause of death data from 1733 seabirds of 51 species, we demonstrate a significant relationship between ingested debris and a debris-ingestion cause of death (dose-response). There is a 20.4% chance of lifetime mortality from ingesting a single debris item, rising to 100% after consuming 93 items. Obstruction of the gastro-intestinal tract is the leading cause of death. Overall, balloons are the highest-risk debris item; 32 times more likely to result in death than ingesting hard plastic. These findings have significant implications for quantifying seabird mortality due to debris ingestion, and provide identifiable policy targets aimed to reduce mortality for threatened species worldwide.
Tightening Monogamy and Polygamy Inequalities of Multiqubit Entanglement
Authors: Farooq Ahmad , ur Rehman Junaid , Jeong Youngmin , Kim Jeong San , Shin Hyundong
Published: March 2019

Monogamy and polygamy relations of quantum entanglement characterize the sharing and distribution of entanglement in a multipartite system. Multiqubit entanglement can be characterized entirely with bipartite combinations by saturating the monogamy and polygamy inequalities. In this paper, we tighten monogamy and polygamy constraints for the squared convex-roof extended negativity and its dual measure by employing a genetic algorithm. This evolutionary algorithm optimizes inequality residual functions to improve the monogamy and polygamy relations of these entanglement measures.
Strong and recurring seasonality revealed within stream diatom assemblages
Authors: Snell M. A. , Barker P. A. , Surridge B. W. J. , Benskin C. McW. H. , Barber N. , Reaney S. M. , Tych W. , Mindham D. , Large A. R. G. , Burke S. , Haygarth P. M.
Published: March 2019

Improving stream water quality in agricultural landscapes is an ecological priority and a legislative duty for many governments. Ecosystem health can be effectively characterised by organisms sensitive to water quality changes such as diatoms, single-celled algae that are a ubiquitous component of stream benthos. Diatoms respond within daily timescales to variables including light, temperature, nutrient availability and flow conditions that result from weather and land use characteristics. However, little consideration has been given to the ecological dynamics of diatoms through repeated seasonal cycles when assessing trajectories of stream function, even in catchments actively managed to reduce human pressures. Here, six years of monthly diatom samples from three independent streams, each receiving differing levels of diffuse agricultural pollution, reveal robust and repeated seasonal variation. Predicted seasonal changes in climate-related variables and anticipated ecological impacts must be fully captured in future ecological and water quality assessments, if the apparent resistance of stream ecosystems to pollution mitigation measures is to be better understood.
Lifelong physical activity is associated with promoter hypomethylation of genes involved in metabolism, myogenesis, contractile properties and oxidative stress resistance in aged human skeletal muscle
Authors: Sailani M. Reza , Halling Jens Frey , Møller Henrik Devitt , Lee Hayan , Plomgaard Peter , Pilegaard Henriette , Snyder Michael P. , Regenberg Birgitte
Published: March 2019

Lifelong regular physical activity is associated with reduced risk of type 2 diabetes (T2D), maintenance of muscle mass and increased metabolic capacity. However, little is known about epigenetic mechanisms that might contribute to these beneficial effects in aged individuals. We investigated the effect of lifelong physical activity on global DNA methylation patterns in skeletal muscle of healthy aged men, who had either performed regular exercise or remained sedentary their entire lives (average age 62 years). DNA methylation was significantly lower in 714 promoters of the physically active than inactive men while methylation of introns, exons and CpG islands was similar in the two groups. Promoters for genes encoding critical insulin-responsive enzymes in glycogen metabolism, glycolysis and TCA cycle were hypomethylated in active relative to inactive men. Hypomethylation was also found in promoters of myosin light chain, dystrophin, actin polymerization, PAK regulatory genes and oxidative stress response genes. A cluster of genes regulated by GSK3β-TCF7L2 also displayed promoter hypomethylation. Together, our results suggest that lifelong physical activity is associated with DNA methylation patterns that potentially allow for increased insulin sensitivity and a higher expression of genes in energy metabolism, myogenesis, contractile properties and oxidative stress resistance in skeletal muscle of aged individuals.
Time-resolved decoding of metabolic signatures of in vitro growth of the hemibiotrophic pathogen Colletotrichum sublineolum
Authors: Tugizimana Fidele , Djami-Tchatchou Arnaud T. , Fahrmann Johannes F. , Steenkamp Paul A. , Piater Lizelle A. , Dubery Ian A.
Published: March 2019

Metabolomics has emerged as a powerful approach to comprehensively interrogate cellular biochemistry. As such, we applied an untargeted liquid chromatography-mass spectrometry metabolomic strategy to elucidate metabolome changes in the anthracnose-causing hemibiotrophic sorghum pathogen, Colletotrichum sublineolum. An in vitro batch culture study model with different carbon sources, glucose, arabinose and rhamnose, were used to support fungal growth over a period of twelve days. Metabolites representing the intracellular and extracellular (secreted) metabolomes were extracted with methanol and subjected to LC-MS analyses. Chemometric modelling revealed a metabolic variation trajectory, comprising three distinct stages that metabolically describe the adaptation of the fungus to diminishing nutrients. Selected marker gene expression indicated stage one (0–3 d.p.i) as corresponding to the early logarithmic phase. Stage two can be interpreted as an intermediate transitionary stage with stage three corresponding to the stationary phase (9–12 d.p.i). Stage one was characterised by up-regulation of endo-metabolites such as ferricrocin, fatty acids and flavone-conjugates, while stage three was characterised by the secretion of phytotoxins, including colletotrichin and colletotric acid. Ultimately, results from our in vitro model reveal previously unknown insights into the dynamic aspects of metabolome reprogramming in the growth phases of Colletotrichum spp as determined by nutrients obtainable from plant cell walls.
Identification and expression of candidate chemosensory receptors in the white-spotted flower chafer, Protaetia brevitarsis
Authors: Liu Hongmin , Zhang Xiaofang , Liu Chunqin , Liu Yongqiang , Mei Xiangdong , Zhang Tao
Published: March 2019

Accurate detection and recognition of chemical signals play extremely important roles for insects in their survival and reproduction. Chemosensory receptors, including odorant receptors (ORs), ionotropic receptors (IRs) and gustatory receptors (GRs), are involved in detection of volatile signals. In the present study, we aimed to identify candidate chemosensory receptors, and RNA-seq technology was employed to sequence the antennal transcriptome of Protaetia brevitarsis (Coleoptera: Scarabaeidae: Cetoniinae), a native agricultural and horticultural pest in East-Asia. According to the sequence similarity analysis, we identified 72 PbreORs, 11 PbreGRs and eight PbreIRs. Among PbreORs, PbreOR2, PbreOR33 and PbreOR53 were preliminarily classified into pheromone receptors. Further qRT-PCR analysis indicated that 11 PbreORs were specifically expressed in the antennae of male P. brevitarsis, whereas 23 PbreORs were specifically expressed in the female antennae. Our results laid a solid foundation for further functional elucidations of insect chemoreceptors, which could be used as the potential targets of pest management.
Dynamic Imaging of Glucose and Lactate Metabolism by 13C-MRS without Hyperpolarization
Authors: Brender Jeffrey R. , Kishimoto Shun , Merkle Hellmut , Reed Galen , Hurd Ralph E. , Chen Albert P. , Ardenkjaer-Larsen Jan Henrik , Munasinghe Jeeva , Saito Keita , Seki Tomohiro , Oshima Nobu , Yamamoto Kazutoshi , Choyke Peter L. , Mitchell James , Krishna Murali C.
Published: March 2019

Metabolic reprogramming is one of the defining features of cancer and abnormal metabolism is associated with many other pathologies. Molecular imaging techniques capable of detecting such changes have become essential for cancer diagnosis, treatment planning, and surveillance. In particular, 18F-FDG (fluorodeoxyglucose) PET has emerged as an essential imaging modality for cancer because of its unique ability to detect a disturbed molecular pathway through measurements of glucose uptake. However, FDG-PET has limitations that restrict its usefulness in certain situations and the information gained is limited to glucose uptake only.13C magnetic resonance spectroscopy theoretically has certain advantages over FDG-PET, but its inherent low sensitivity has restricted its use mostly to single voxel measurements unless dissolution dynamic nuclear polarization (dDNP) is used to increase the signal, which brings additional complications for clinical use. We show here a new method of imaging glucose metabolism in vivo by MRI chemical shift imaging (CSI) experiments that relies on a simple, but robust and efficient, post-processing procedure by the higher dimensional analog of singular value decomposition, tensor decomposition. Using this procedure, we achieve an order of magnitude increase in signal to noise in both dDNP and non-hyperpolarized non-localized experiments without sacrificing accuracy. In CSI experiments an approximately 30-fold increase was observed, enough that the glucose to lactate conversion indicative of the Warburg effect can be imaged without hyper-polarization with a time resolution of 12s and an overall spatial resolution that compares favorably to 18F-FDG PET.
Cationic Intrinsically Disordered Antimicrobial Peptides (CIDAMPs) Represent a New Paradigm of Innate Defense with a Potential for Novel Anti-Infectives
Authors: Latendorf Ties , Gerstel Ulrich , Wu Zhihong , Bartels Joachim , Becker Alexander , Tholey Andreas , Schröder Jens-Michael
Published: March 2019

In the search for potential mechanisms underlying the remarkable resistance of healthy skin against infection by soil bacteria likePseudomonas(P.)aeruginosawe identified fragments of the intrinsically disordered protein hornerin as potent microbicidal agents in the stratum corneum. We found that, independent of the amino acid (AA)-sequence, any tested linear cationic peptide containing a high percentage of disorder-promoting AA and a low percentage of order-promoting AA is a potent microbicidal antimicrobial. We further show that the antimicrobial activity of these cationic intrinsically disordered antimicrobial peptides (CIDAMPs) depends on the peptide chain length, its net charge, lipidation and environmental conditions. The ubiquitous presence of latent CIDAMP sources in nature suggests a common and yet overlooked adapted innate disinfection system of body surfaces. The simple structure and virtually any imaginable sequence or composition of disorder-promoting AA allow the generation of a plethora of CIDAMPs. These are potential novel microbicidal anti-infectives for various bacterial pathogens, includingP. aeruginosa, methicillin-resistantStaphylococcus aureus(MRSA) and fungal pathogens likeCandida albicansandCryptococcus neoformans.
Reduced habit-driven errors in Parkinson’s Disease
Authors: Bannard Colin , Leriche Mariana , Bandmann Oliver , Brown Christopher H. , Ferracane Elisa , Sánchez-Ferro Álvaro , Obeso José , Redgrave Peter , Stafford Tom
Published: March 2019

Parkinson’s Disease can be understood as a disorder of motor habits. A prediction of this theory is that early stage Parkinson’s patients will display fewer errors caused by interference from previously over-learned behaviours. We test this prediction in the domain of skilled typing, where actions are easy to record and errors easy to identify. We describe a method for categorizing errors as simple motor errors or habit-driven errors. We test Spanish and English participants with and without Parkinson’s, and show that indeed patients make fewer habit errors than healthy controls, and, further, that classification of error type increases the accuracy of discriminating between patients and healthy controls. As well as being a validation of a theory-led prediction, these results offer promise for automated, enhanced and early diagnosis of Parkinson’s Disease.
Variation in genome size, cell and nucleus volume, chromosome number and rDNA loci among duckweeds
Authors: Hoang Phuong T. N. , Schubert Veit , Meister Armin , Fuchs Jörg , Schubert Ingo
Published: March 2019

Duckweeds are small, free-floating, largely asexual and highly neotenous organisms. They display the most rapid growth among flowering plants and are of growing interest in aquaculture and genome biology. Genomic and chromosomal data are still rare. Applying flow-cytometric genome size measurement, microscopic determination of frond, cell and nucleus morphology, as well as fluorescence in situ hybridization (FISH) for localization of ribosomal DNA (rDNA), we compared eleven species, representative for the five duckweed genera to search for potential correlations between genome size, cell and nuclei volume, simplified body architecture (neoteny), chromosome numbers and rDNA loci. We found a ~14-fold genome size variation (from 160 to 2203 Mbp), considerable differences in frond size and shape, highly variable guard cell and nucleus size, chromosome number (from 2n = 36 to 82) and number of 5S and 45S rDNA loci. In general, genome size is positively correlated with guard cell and nucleus volume (p < 0.001) and with the neoteny level and inversely with the frond size. In individual cases these correlations could be blurred for instance by particular body and cell structures which seem to be linked to specific floating styles. Chromosome number and rDNA loci variation between the tested species was independent of the genome size. We could not confirm previously reported intraspecific variation of chromosome numbers between individual clones of the genera Spirodela and Landoltia.
Women’s preferences for men’s facial masculinity are strongest under favorable ecological conditions
Authors: Marcinkowska Urszula M. , Rantala Markus J. , Lee Anthony J. , Kozlov Mikhail V. , Aavik Toivo , Cai Huajian , Contreras-Garduño Jorge , David Oana A. , Kaminski Gwenaël , Li Norman P. , Onyishi Ike E. , Prasai Keshav , Pazhoohi Farid , Prokop Pavol , Cardozo Sandra L. Rosales , Sydney Nicolle , Taniguchi Hirokazu , Krams Indrikis , Dixson Barnaby J. W.
Published: March 2019

The strength of sexual selection on secondary sexual traits varies depending on prevailing economic and ecological conditions. In humans, cross-cultural evidence suggests women’s preferences for men’s testosterone dependent masculine facial traits are stronger under conditions where health is compromised, male mortality rates are higher and economic development is higher. Here we use a sample of 4483 exclusively heterosexual women from 34 countries and employ mixed effects modelling to test how social, ecological and economic variables predict women’s facial masculinity preferences. We report women’s preferences for more masculine looking men are stronger in countries with higher sociosexuality and where national health indices and human development indices are higher, while no associations were found between preferences and indices of intra-sexual competition. Our results show that women’s preferences for masculine faces are stronger under conditions where offspring survival is higher and economic conditions are more favorable.
Enriched environment alleviates stress-induced dry-eye through the BDNF axis
Authors: Sano Kokoro , Kawashima Motoko , Imada Toshihiro , Suzuki Toru , Nakamura Shigeru , Mimura Masaru , Tanaka Kenji F. , Tsubota Kazuo
Published: March 2019

The number of patients with dry eye disease (DED) is increasing, and DED has become an urgent public health problem. A comorbidity of mental disorders has been reported in DED patients. We hypothesized that physical and psychological stressors impair tear secretion. To examine the relationship between stress loading and decreased tear secretion, we established a stress-induced DED mouse model, which permitted us to address the underlying mechanism of pathogenesis and resilience. Enriched environment (EE) was an effective intervention to prevent and alleviate stress-induced decreased tear secretion. Because stress loading resulted in decreased brain-derived neurotrophic factor (BDNF) expression while EE resulted in increased expression, we focused on the role of BDNF in tear secretion. Using two distinct Bdnf gene knockdown mice, we evaluated whether BDNF was a deterministic factor in regulating tear secretion in healthy and stressed conditions. Bdnf knockdown mice showed decreased basal tear secretion and loss of stress tolerance by EE for tear secretion. These results suggest that BDNF expression is related to tear secretion and to the pathology of DED.
PARP1 rs1805407 Increases Sensitivity to PARP1 Inhibitors in Cancer Cells Suggesting an Improved Therapeutic Strategy
Authors: Abecassis Irina , Sedgewick Andrew J. , Romkes Marjorie , Buch Shama , Nukui Tomoko , Kapetanaki Maria G. , Vogt Andreas , Kirkwood John M. , Benos Panayiotis V. , Tawbi Hussein
Published: March 2019

Personalized cancer therapy relies on identifying patient subsets that benefit from a therapeutic intervention and suggest alternative regimens for those who don’t. A new data integrative approach, based on graphical models, was applied on our multi-modal –omics, and clinical data cohort of metastatic melanoma patients. We found that response to chemotherapy is directly linked to ten gene expression, four methylation variables and PARP1 SNP rs1805407. PARP1 is a DNA repair gene critical for chemotherapy response and for which FDA-approved inhibitors are clinically available (olaparib). We demonstrated that two PARP inhibitors (ABT-888 and olaparib) make SNP carrier cancer cells of various histologic subtypes more sensitive to alkylating agents, but they have no effect in wild-type cells. Furthermore, PARP1 inhibitors act synergistically with chemotherapy in SNP carrier cells (especially in ovarian cancer for which olaparib is FDA-approved), but they are additive at best in wild-type cancer cells. Taken together, our results suggest that the combination of chemotherapy and PARP1 inhibition may benefit the carriers of rs1805407 in the future and may be used in personalized therapy strategies to select patients that are more likely to respond to PARP inhibitors.
Terahertz emission from gold nanorods irradiated by ultrashort laser pulses of different wavelengths
Authors: Takano Keisuke , Asai Motoki , Kato Kosaku , Komiyama Hideaki , Yamaguchi Akihisa , Iyoda Tomokazu , Tadokoro Yuzuru , Nakajima Makoto , Bakunov Michael I.
Published: March 2019

Electron photoemission and ponderomotive acceleration by surface enhanced optical fields is considered as a plausible mechanism of terahertz radiation from metallic nanostructures under ultrafast laser excitation. To verify this mechanism, we studied experimentally terahertz emission from an array of gold nanorods illuminated by intense (~10–100 GW/cm2) femtosecond pulses of different central wavelengths (600, 720, 800, and 1500 nm). We found for the first time that the order of the dependence of the terahertz fluence on the laser intensity is, unexpectedly, almost the same (~4.5–4.8) for 720, 800, and 1500 nm and somewhat higher (~6.6) for 600 nm. The results are explained by tunneling currents driven by plasmonically enhanced laser field. In particular, the pump-intensity dependence of the terahertz fluence is more consistent with terahertz emission from the sub-cycle bursts of the tunneling current rather than with the ponderomotive mechanism.
Functional analysis of ZmMADS1a reveals its role in regulating starch biosynthesis in maize endosperm
Authors: Dong Qing , Wang Fang , Kong Jingjing , Xu Qianqian , Li Tingchun , Chen Long , Chen Hongjian , Jiang Haiyang , Li Cheng , Cheng Beijiu
Published: March 2019

MADS-box family proteins play an important role in grain formation and flower development; however, the molecular mechanisms by which transcription factors regulate the starch metabolism pathway are unclear in maize. Here, we report a transcription factor, ZmMADS1a, that controls starch biosynthesis in maize (Zea mays L.). We demonstrate the expression of ZmMADS1a in tassel, silk, and endosperm, and show that the protein is localized to the cell nucleus. Compared with the control, seeds of overexpressing ZmMADS1a increased starch content (especially amylose content), had smaller starch granules and altered chemical structure. Meanwhile, overexpression of ZmMADS1a resulted in increases in the contents of soluble sugars and reducing sugars in maize. ZmMADS1a plays a positive regulatory role in the starch biosynthesis pathway by up-regulating several starch biosynthesis related genes. We also show that ZmMADS1a has a similar adjustment mechanism of starch biosynthesis in rice. Collectively, our study suggests that ZmMADS1a functions as a positive regulator of starch biosynthesis by regulating the expression of key starch metabolism genes during seed development.
The uremic toxin p-cresyl sulfate induces proliferation and migration of clear cell renal cell carcinoma via microRNA-21/ HIF-1α axis signals
Authors: Wu Tsai-Kun , Wei Chyou-Wei , Pan Ying-Ru , Hsu Ren-Jun , Wu Chung-Yi , Yu Yung-Luen
Published: March 2019

p-Cresyl sulfate (pCS), a uremic toxin, can cause renal damage and dysfunction. Studies suggest that renal dysfunction increases the prevalence of renal cancer. However, the effect of pCS on the proliferation and migration of renal cancer is unclear. Clear cell renal cell carcinoma (ccRCC) expresses mutant von Hippel-Lindau gene and is difficult to treat. Hypoxia-inducible factor-1α and 2-α (HIF-1α and HIF-2α) as well as microRNA-21 (miR-21) can regulate the proliferation and migration of ccRCC cells. However, the association between HIF-α and miR-21 in ccRCC remains unclear. Therefore, the effects of pCS on ccRCC cells were investigated for HIF-α and miR-21 signals. Our results showed that pCS induced overexpression of HIF-1α and promoted the proliferation and regulated epithelial-mesenchymal transition-related proteins, including E-cadherin, fibronectin, twist and vimentin in ccRCC cells. pCS treatment increased miR-21 expression. Specifically, inhibition of miR-21 blocked pCS-induced proliferation and migration. Taken together, the present results demonstrate that pCS directly induced the proliferation and migration of ccRCC cells through mechanisms involving miR-21/HIF-1α signaling pathways.
Parallel colonization of subalpine habitats in the central European mountains by Primula elatior
Authors: Konečná Veronika , Nowak Michael D. , Kolář Filip
Published: March 2019

The island-like distribution of subalpine habitats across mountain ranges can trigger the parallel evolution of locally adapted ecotypes. Such naturally replicated scenarios allow testing hypotheses on how elevational differentiation structures genetic diversity within species. Nevertheless, the parallel colonization of subalpine habitats across different mountain ranges has only rarely been documented with molecular data. We chose Primula elatior (Primulaceae), naturally spanning entire elevation range in multiple mountain regions of central Europe, to test for the origin of its scattered subalpine populations. Nuclear microsatellite variation revealed three genetic groups corresponding with the distinct study regions. We found that genetic differentiation between foothill and subalpine populations within each region was relatively low, suggesting that the colonization of subalpine habitats occurred independently within each mountain range. Furthermore, the strongest differentiation was usually found between the subalpine populations suggesting that mountain ridges may act as migration barriers that can reduce gene flow more strongly than elevational differences between foothill and subalpine populations. Finally, we found that subalpine colonization did not result in a loss of genetic diversity relative to foothill populations in agreement with the high migration rates that we document here between the subalpine and the foothill populations. In summary, our study shows subalpine Primula elatior populations are genetically diverse and distinct results of parallel colonization events from multiple foothill gene pools.
Frequent pattern mining in multidimensional organizational networks
Authors: Gadár László , Abonyi János
Published: March 2019

Network analysis can be applied to understand organizations based on patterns of communication, knowledge flows, trust, and the proximity of employees. A multidimensional organizational network was designed, and association rule mining of the edge labels applied to reveal how relationships, motivations, and perceptions determine each other in different scopes of activities and types of organizations. Frequent itemset-based similarity analysis of the nodes provides the opportunity to characterize typical roles in organizations and clusters of co-workers. A survey was designed to define 15 layers of the organizational network and demonstrate the applicability of the method in three companies. The novelty of our approach resides in the evaluation of people in organizations as frequent multidimensional patterns of multilayer networks. The results illustrate that the overlapping edges of the proposed multilayer network can be used to highlight the motivation and managerial capabilities of the leaders and to find similarly perceived key persons.
HER2 and p95HER2 differentially regulate miRNA expression in MCF-7 breast cancer cells and downregulate MYB proteins through miR-221/222 and miR-503
Authors: Gorbatenko Andrej , Søkilde Rolf , Sorensen Ester E. , Newie Inga , Persson Helena , Morancho Beatriz , Arribas Joaquin , Litman Thomas , Rovira Carlos , Pedersen Stine Falsig
Published: March 2019

The HER2 oncogene and its truncated form p95HER2 play central roles in breast cancer. Here, we show that although HER2 and p95HER2 generally elicit qualitatively similar changes in miRNA profile in MCF-7 breast cancer cells, a subset of changes are distinct and p95HER2 shifts the miRNA profile towards the basal breast cancer subtype. High-throughput miRNA profiling was carried out 15, 36 and 60 h after HER2 or p95HER2 expression and central hits validated by RT-qPCR. miRNAs strongly regulated by p95HER2 yet not by HER2, included miR-221, miR-222, miR-503, miR-29a, miR-149, miR-196 and miR-361. Estrogen receptor-α (ESR1) expression was essentially ablated by p95HER2 expression, in a manner recapitulated by miR-221/-222 mimics. c-Myb family transcription factors MYB and MYBL1, but not MYBL2, were downregulated by p95HER2 and by miR-503 or miR-221/-222 mimics. MYBL1 3′UTR inhibition by miR-221/222 was lost by deletion of a single putative miR-221/222 binding sites. p95HER2 expression, or knockdown of either MYB protein, elicited upregulation of tissue inhibitor of matrix metalloprotease-2 (TIMP2). miR-221/222 and -503 mimics increased, and TIMP2 knockdown decreased, cell migration and invasion. A similar pathway was operational in T47D- and SKBr-3 cells. This work reveals important differences between HER2- and p95HER2- mediated miRNA changes in breast cancer cells, provides novel mechanistic insight into regulation of MYB family transcription factors by p95HER2, and points to a role for a miR-221/222– MYB family–TIMP2 axis in regulation of motility in breast cancer cells.