bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and characterization of recombinant Par j 1 and Par j 2 resembling the allergenic epitopes of Parietaria judaica pollen
Authors: Dorofeeva Yulia , Colombo Paolo , Blanca Miguel , Mari Adriano , Khanferyan Roman , Valenta Rudolf , Focke-Tejkl Margarete
Published: October 2019

The weed wall pellitory, Parietaria judaica, is one the most important pollen allergen sources in the Mediterranean area causing severe symptoms of hay fever and asthma in allergic patients. We report the expression of the major Parietaria allergens, Par j 1 and Par j 2 which belong to the family of lipid transfer proteins, in insect cells. According to circular dichroism analysis and gel filtration, the purified allergens represented folded and monomeric proteins. Insect cell-expressed, folded Par j 2 exhibited higher IgE binding capacity and more than 100-fold higher allergenic activity than unfolded Escherichia coli-expressed Par j 2 as demonstrated by IgE ELISA and basophil activation testing. IgE ELISA inhibition assays showed that Par j 1 and Par j 2, contain genuine and cross-reactive IgE epitopes. IgG antibodies induced by immunization with Par j 2 inhibited binding of allergic patients IgE to Par j 1 only partially. IgE inhibition experiments demonstrated that insect cell-expressed Par j 1 and Par j 2 together resembled the majority of allergenic epitopes of the Parietaria allergome and therefore both should be used for molecular diagnosis and the design of vaccines for allergen-specific immunotherapy of Parietaria allergy.
Human Adipose-derived Pericytes Display Steroidogenic Lineage Potential in Vitro and Influence Leydig Cell Regeneration in Vivo in Rats
Authors: Curley Michael , Gonzalez Zaniah N. , Milne Laura , Hadoke Patrick , Handel Ian , Péault Bruno , Smith Lee B.
Published: October 2019

Exogenous androgen replacement is used to treat symptoms associated with low testosterone in males. However, adverse cardiovascular risk and negative fertility impacts impel development of alternative approaches to restore/maintain Leydig cell (LC) androgen production. Stem Leydig cell (SLC) transplantation shows promise in this regard however, practicality of SLC isolation/transplantation impede clinical translation. Multipotent human adipose-derived perivascular stem cells (hAd-PSCs) represent an attractive extragonadal stem cell source for regenerative therapies in the testis but their therapeutic potential in this context is unexplored. We asked whether hAd-PSCs could be converted into Leydig-like cells and determined their capacity to promote regeneration in LC-ablated rat testes. Exposure of hAd-PSCs to differentiation-inducing factors in vitro upregulated steroidogenic genes but did not fully induce LC differentiation. In vivo, no difference in LC-regeneration was noted between Sham and hAd-PSC-transplanted rats. Interestingly, Cyp17a1 expression increased in hAd-PSC-transplanted testes compared to intact vehicle controls and the luteinising hormone/testosterone ratio returned to Vehicle control levels which was not the case in EDS + Sham animals. Notably, hAd-PSCs were undetectable one-month after transplantation suggesting this effect is likely mediated via paracrine mechanisms during the initial stages of regeneration; either directly by interacting with regenerating LCs, or through indirect interactions with trophic macrophages.
Coetaneous catalytic kinetic resolution of alkynes and azides through asymmetric triazole formation
Authors: Brittain William D. G. , Dalling Andrew G. , Sun Zhenquan , Duff Cécile S. Le , Male Louise , Buckley Benjamin R. , Fossey John S.
Published: October 2019

A non-enzymatic simultaneous (coined coetaneous) kinetic resolution of a racemic alkyne and racemic azide, utilising an asymmetric CuAAC reaction is reported. The use of a CuCl (R,R)-Ph-Pybox catalyst system effects a simultaneous kinetic resolution of two racemic starting materials to give one major triazolic diastereoisomer in the ratio 74:12:4:10 (dr 84:16, 90% ee maj). The corresponding control reaction using an achiral copper catalyst gives the four possible diastereoisomers in a 23:27:23:27 ratio, demonstrating minimal inherent substrate control.
Large scale and information effects on cooperation in public good games
Authors: Pereda María , Tamarit Ignacio , Antonioni Alberto , Cuesta Jose A. , Hernández Penélope , Sánchez Angel
Published: October 2019

The problem of public good provision is central in economics and touches upon many challenging societal issues, ranging from climate change mitigation to vaccination schemes. However, results which are supposed to be applied to a societal scale have only been obtained with small groups of people, with a maximum group size of 100 being reported in the literature. This work takes this research to a new level by carrying out and analysing experiments on public good games with up to 1000 simultaneous players. The experiments are carried out via an online protocol involving daily decisions for extended periods. Our results show that within those limits, participants’ behaviour and collective outcomes in very large groups are qualitatively like those in smaller ones. On the other hand, large groups imply the difficulty of conveying information on others’ choices to the participants. We thus consider different information conditions and show that they have a drastic effect on subjects’ contributions. We also classify the individual decisions and find that they can be described by a moderate number of types. Our findings allow to extend the conclusions of smaller experiments to larger settings and are therefore a relevant step forward towards the understanding of human behaviour and the organisation of our society.
Differentially Methylated Super-Enhancers Regulate Target Gene Expression in Human Cancer
Authors: Flam Emily L. , Danilova Ludmila , Kelley Dylan Z. , Stavrovskaya Elena , Guo Theresa , Considine Michael , Qian Jiang , Califano Joseph A. , Favorov Alexander , Fertig Elana J. , Gaykalova Daria A.
Published: October 2019

Current literature suggests that epigenetically regulated super-enhancers (SEs) are drivers of aberrant gene expression in cancers. Many tumor types are still missing chromatin data to define cancer-specific SEs and their role in carcinogenesis. In this work, we develop a simple pipeline, which can utilize chromatin data from etiologically similar tumors to discover tissue-specific SEs and their target genes using gene expression and DNA methylation data. As an example, we applied our pipeline to human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV + OPSCC). This tumor type is characterized by abundant gene expression changes, which cannot be explained by genetic alterations alone. Chromatin data are still limited for this disease, so we used 3627 SE elements from public domain data for closely related tissues, including normal and tumor lung, and cervical cancer cell lines. We integrated the available DNA methylation and gene expression data for HPV + OPSCC samples to filter the candidate SEs to identify functional SEs and their affected targets, which are essential for cancer development. Overall, we found 159 differentially methylated SEs, including 87 SEs that actively regulate expression of 150 nearby genes (211 SE-gene pairs) in HPV + OPSCC. Of these, 132 SE-gene pairs were validated in a related TCGA cohort. Pathway analysis revealed that the SE-regulated genes were associated with pathways known to regulate nasopharyngeal, breast, melanoma, and bladder carcinogenesis and are regulated by the epigenetic landscape in those cancers. Thus, we propose that gene expression in HPV + OPSCC may be controlled by epigenetic alterations in SE elements, which are common between related tissues. Our pipeline can utilize a diversity of data inputs and can be further adapted to SE analysis of diseased and non-diseased tissues from different organisms.
Osmotically Driven and Detected DNA Translocations
Authors: McMullen Angus , Araujo George , Winter Michele , Stein Derek
Published: October 2019

A salinity gradient propels a DNA molecule through a solid-state nanopore and generates an ionic current whose change allows for the detection of the translocation. Measurements and theoretical analyses reveal the role of diffusio-osmosis in driving these phenomena: After accounting for known salinity-dependent electrode effects, the measured current change caused by the presence of a DNA molecule inside the nanopore and the DNA translocation speed through it both increase with the magnitude of the applied salinity gradients. The effects are consistent with the theory of diffuisio-osmosis and strong enough to enable DNA translocations to overcome an applied retarding potential of tens of millivolts. This work illustrates how salinity gradients can be used to power and operate a nanopore sensor.
Marine heat wave and multiple stressors tip bull kelp forest to sea urchin barrens
Authors: Rogers-Bennett L. , Catton C. A.
Published: October 2019

Extreme climatic events have recently impacted marine ecosystems around the world, including foundation species such as corals and kelps. Here, we describe the rapid climate-driven catastrophic shift in 2014 from a previously robust kelp forest to unproductive large scale urchin barrens in northern California. Bull kelp canopy was reduced by >90% along more than 350 km of coastline. Twenty years of kelp ecosystem surveys reveal the timing and magnitude of events, including mass mortalities of sea stars (2013-), intense ocean warming (2014–2017), and sea urchin barrens (2015-). Multiple stressors led to the unprecedented and long-lasting decline of the kelp forest. Kelp deforestation triggered mass (80%) abalone mortality (2017) resulting in the closure in 2018 of the recreational abalone fishery worth an estimated $44 M and the collapse of the north coast commercial red sea urchin fishery (2015-) worth $3 M. Key questions remain such as the relative roles of ocean warming and sea star disease in the massive purple sea urchin population increase. Science and policy will need to partner to better understand drivers, build climate-resilient fisheries and kelp forest recovery strategies in order to restore essential kelp forest ecosystem services.
Computational/experimental evaluation of liver metastasis post hepatic injury: interactions with macrophages and transitional ECM
Authors: Hudson Shanice V. , Miller Hunter A. , Mahlbacher Grace E. , Saforo Douglas , Beverly Levi J. , Arteel Gavin E. , Frieboes Hermann B.
Published: October 2019

The complex interactions between subclinical changes to hepatic extracellular matrix (ECM) in response to injury and tumor-associated macrophage microenvironmental cues facilitating metastatic cell seeding remain poorly understood. This study implements a combined computational modeling and experimental approach to evaluate tumor growth following hepatic injury, focusing on ECM remodeling and interactions with local macrophages. Experiments were performed to determine ECM density and macrophage-associated cytokine levels. Effects of ECM remodeling along with macrophage polarization on tumor growth were evaluated via computational modeling. For primary or metastatic cells in co-culture with macrophages, TNF-α levels were 5× higher with M1 vs. M2 macrophages. Metastatic cell co-culture exhibited 10× higher TNF-α induction than with primary tumor cells. Although TGFβ1 induction was similar between both co-cultures, levels were slightly higher with primary cells in the presence of M1. Simulated metastatic tumors exhibited decreased growth compared to primary tumors, due to high local M1-induced cytotoxicity, even in a highly vascularized microenvironment. Experimental analysis combined with computational modeling may provide insight into interactions between ECM remodeling, macrophage polarization, and liver tumor growth.
Mechanism of Common-mode Noise Generation in Multi-conductor Transmission Lines
Authors: Jinno Souma , Kitora Shuji , Toki Hiroshi , Abe Masayuki
Published: October 2019

The mechanism of common-mode noise generation in multi-conductor transmission lines is presented. Telegraphic equations, wave equations, and reflection coefficients in the normal and common modes are derived, which provide the mechanism of common-mode noise generation. In addition to coupling among transmission lines, the origin of the common-mode noise generation is elucidated by deriving the reflection coefficients in the normal and common modes.
NMR-based metabolomics in pediatric drug resistant epilepsy – preliminary results
Authors: Boguszewicz Łukasz , Jamroz Ewa , Ciszek Mateusz , Emich-Widera Ewa , Kijonka Marek , Banasik Tomasz , Skorupa Agnieszka , Sokół Maria
Published: October 2019

Epilepsy in children is the most frequent, heterogeneous and difficult to classify chronic neurologic condition with the etiology found in 35–40% of patients. Our aim is to detect the metabolic differences between the epileptic children and the children with no neurological abnormalities in order to define the metabolic background for therapy monitoring. The studied group included 28 epilepsy patients (median age 12 months) examined with a diagnostic protocol including EEG, videoEEG, 24-hour-EEG, tests for inborn errors of metabolism, chromosomal analysis and molecular study. The reference group consisted of 20 patients (median age 20 months) with no neurological symptoms, no development delay nor chronic diseases. 1H-NMR serum spectra were acquired on 400 MHz spectrometer and analyzed using multivariate and univariate approach with the application of correction for age variation. The epilepsy group was characterized by increased levels of serum N-acetyl-glycoproteins, lactate, creatine, glycine and lipids, whereas the levels of citrate were decreased as compared to the reference group. Choline, lactate, formate and dimethylsulfone were significantly correlated with age. NMR-based metabolomics could provide information on the dynamic metabolic processes in drug-resistant epilepsy yielding not only disease-specific biomarkers but also profound insights into the disease course, treatment effects or drug toxicity.
The effect of anxiety on brain activation patterns in response to inspiratory occlusions: an fMRI study
Authors: Chan Pei-Ying S. , Wu Yu-Ting , Hsu Ai-Ling , Li Chia-Wei , Wu Changwei W. , von Leupoldt Andreas , Hsu Shih-Chieh
Published: October 2019

Respiratory sensations such as breathlessness are prevalent in many diseases and are amplified by increased levels of anxiety. Cortical activation in response to inspiratory occlusions in high- and low-anxious individuals was found different in previous studies using the respiratory-related evoked potential method. However, specific brain areas showed different activation patterns remained unknown in these studies. Therefore, the purpose of this study was to compare cortical and subcortical neural substrates of respiratory sensation in response to inspiratory mechanical occlusion stimuli between high- and low-anxious individuals using functional magnetic resonance imaging (fMRI). In addition, associations between brain activation patterns and levels of anxiety, and breathlessness were examined. Thirty-four (17 high- and 17 low-anxious) healthy non-smoking adults with normal lung function completed questionnaires on anxiety (State Trait Anxiety Inventory - State), and participated in a transient inspiratory occlusion fMRI experiment. The participants breathed with a customized face-mask while respiration was repeatedly interrupted by a transient inspiratory occlusion of 150-msec, delivered every 2 to 4 breaths. Breathlessness was assessed by self-report. At least 32 occluded breaths were collected for data analysis. The results showed that compared to the low-anxious group, the high-anxious individuals demonstrated significantly greater neural activations in the hippocampus, insula, and middle cingulate gyrus in response to inspiratory occlusions. Moreover, a significant relationship was found between anxiety levels and activations of the right inferior parietal gyrus, and the right precuneus. Additionally, breathlessness levels were significantly associated with activations of the bilateral thalamus, bilateral insula and bilateral cingulate gyrus. The above evidences support stronger recruitment of emotion-related cortical and subcortical brain areas in higher anxious individuals, and thus these areas play an important role in respiratory mechanosensation mediated by anxiety.
Rigorous sampling of docking poses unveils binding hypothesis for the halogenated ligands of L-type Amino acid Transporter 1 (LAT1)
Authors: Singh Natesh , Villoutreix Bruno O. , Ecker Gerhard F.
Published: October 2019

L-type Amino acid Transporter 1 (LAT1) plays a significant role in the growth and propagation of cancer cells by facilitating the cross-membrane transport of essential nutrients, and is an attractive drug target. Several halogen-containing L-phenylalanine-based ligands display high affinity and high selectivity for LAT1; nonetheless, their molecular mechanism of binding remains unclear. In this study, a combined in silico strategy consisting of homology modeling, molecular docking, and Quantum Mechanics-Molecular Mechanics (QM-MM) simulation was applied to elucidate the molecular basis of ligand binding in LAT1. First, a homology model of LAT1 based on the atomic structure of a prokaryotic homolog was constructed. Docking studies using a set of halogenated ligands allowed for deriving a binding hypothesis. Selected docking poses were subjected to QM-MM calculations to investigate the halogen interactions. Collectively, the results highlight the dual nature of the ligand-protein binding mode characterized by backbone hydrogen bond interactions of the amino acid moiety of the ligands and residues I63, S66, G67, F252, G255, as well as hydrophobic interactions of the ligand’s side chains with residues I139, I140, F252, G255, F402, W405. QM-MM optimizations indicated that the electrostatic interactions involving halogens contribute to the binding free energy. Importantly, our results are in good agreement with the recently unraveled cryo-Electron Microscopy structures of LAT1.
DNA methylation-based biological age, genome-wide average DNA methylation, and conventional breast cancer risk factors
Authors: Chen Minyuan , Wong Ee Ming , Nguyen Tuong L. , Dite Gillian S. , Stone Jennifer , Dugué Pierre-Antoine , Giles Graham G. , Southey Melissa C. , Milne Roger L. , Hopper John L. , Li Shuai
Published: October 2019

DNA methylation-based biological age (DNAm age), as well as genome-wide average DNA methylation, have been reported to predict breast cancer risk. We aimed to investigate the associations between these DNA methylation-based risk factors and 18 conventional breast cancer risk factors for disease-free women. A sample of 479 individuals from the Australian Mammographic Density Twins and Sisters was used for discovery, a sample of 3354 individuals from the Melbourne Collaborative Cohort Study was used for replication, and meta-analyses pooling results from the two studies were conducted. DNAm age based on three epigenetic clocks (Hannum, Horvath and Levine) and genome-wide average DNA methylation were calculated using the HumanMethylation 450 K BeadChip assay data. The DNAm age measures were positively associated with body mass index (BMI), smoking, alcohol drinking and age at menarche (all nominal P < 0.05). Genome-wide average DNA methylation was negatively associated with smoking and number of live births, and positively associated with age at first live birth (all nominal P < 0.05). The association of DNAm age with BMI was also evident in within-twin-pair analyses that control for familial factors. This study suggests that some lifestyle and hormonal risk factors are associated with these DNA methylation-based breast cancer risk factors, and the observed associations are unlikely to be due to familial confounding but are likely causal. DNA methylation-based risk factors could interplay with conventional risk factors in modifying breast cancer risk.
Selection of suitable reference genes for gene expression studies in myxosporean (Myxozoa, Cnidaria) parasites
Authors: Kosakyan Anush , Alama-Bermejo Gema , Bartošová-Sojková Pavla , Born-Torrijos Ana , Šíma Radek , Nenarokova Anna , Eszterbauer Edit , Bartholomew Jerri , Holzer Astrid S.
Published: October 2019

Myxozoans (Cnidaria: Myxozoa) are an extremely diversified group of endoparasites some of which are causative agents of serious diseases in fish. New methods involving gene expression studies have emerged over the last years to better understand and control myxozoan diseases. Quantitative RT-PCR is the most extensively used approach for gene expression studies. However, the accuracy of the results depends on the normalization of the data to reference genes. We studied the expression of eight commonly used reference genes, adenosylhomocysteinase (AHC1), beta actin (ACTB), eukaryotic translation elongation factor 2 (EF2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1), DNA-directed RNA polymerase II (RPB2), 18S ribosomal RNA (18S), 28S ribosomal RNA (28S) across different developmental stages of three myxozoan species, Sphaerospora molnari, Myxobolus cerebralis and Ceratonova shasta, representing the three major myxozoan linages from the largest class Myxosporea. The stable reference genes were identified using four algorithms: geNorm, NormFinder, Bestkeeper and ΔCq method. Additionally, we analyzed transcriptomic data from S. molnari proliferative and spore-forming stages to compare the relative amount of expressed transcripts with the most stable reference genes suggested by RT-qPCR. Our results revealed that GAPDH and EF2 are the most uniformly expressed genes across the different developmental stages of the studied myxozoan species.
Heart Rate Correction of the J-to-Tpeak Interval
Authors: Hnatkova Katerina , Vicente Jose , Johannesen Lars , Garnett Christine , Strauss David G. , Stockbridge Norman , Malik Marek
Published: October 2019

Drug-induced changes of the J to T peak (JTp) and J to the median of area under the T wave (JT50) were reported to differentiate QT prolonging drugs that are predominant blockers of the delayed potassium rectifier current from those with multiple ion channel effects. Studies of drug-induced JTp/JT50 interval changes might therefore facilitate cardiac safety evaluation of new pharmaceuticals. It is not known whether formulas for QT heart rate correction are applicable to JTp and JT50 intervals. QT/RR, JTp/RR, and JT50/RR profiles were studied in 523 healthy subjects aged 33.5 ± 8.4 years (254 females). In individual subjects, 1,256 ± 220 electrocardiographic measurements of QT, JTp, and JT50 intervals were available including a 5-minute history of RR intervals preceding each measurement. Curvilinear, linear and log-linear regression models were used to characterize individual QT/RR, JTp/RR, and JT50/RR profiles both without and with correction for heart rate hysteresis. JTp/RR and JT50/RR hysteresis correction needs to be included but the generic universal correction for QT/RR hysteresis is also applicable to JTp/RR and JT50/RR profiles. Once this is incorporated, median regression coefficients of the investigated population suggest linear correction formulas JTpc = JTp + 0.150(1-RR) and JT50c = JT50 + 0.117(1-RR) where RR intervals of the underlying heart rate are hysteresis-corrected, and all measurements expressed in seconds. The established correction formulas can be proposed for future clinical pharmacology studies that show drug-induced heart rate changes of up to approximately 10 beats per minute.
Metabolomic profiling identifies novel associations with Electrolyte and Acid-Base Homeostatic patterns
Authors: Menni Cristina , McCallum Linsay , Pietzner Maik , Zierer Jonas , Aman Alisha , Suhre Karsten , Mohney Robert P. , Mangino Massimo , Friedrich Nele , Spector Tim D. , Padmanabhan Sandosh
Published: October 2019

Electrolytes have a crucial role in maintaining health and their serum levels are homeostatically maintained within a narrow range by multiple pathways involving the kidneys. Here we use metabolomics profiling (592 fasting serum metabolites) to identify molecular markers and pathways associated with serum electrolyte levels in two independent population-based cohorts. We included 1523 adults from TwinsUK not on blood pressure-lowering therapy and without renal impairment to look for metabolites associated with chloride, sodium, potassium and bicarbonate by running linear mixed models adjusting for covariates and multiple comparisons. For each electrolyte, we further performed pathway enrichment analysis (PAGE algorithm). Results were replicated in an independent cohort. Chloride, potassium, bicarbonate and sodium associated with 10, 58, 36 and 17 metabolites respectively (each P < 2.1 × 10−5), mainly lipids. Of all the electrolytes, serum potassium showed the most significant associations with individual fatty acid metabolites and specific enrichment of fatty acid pathways. In contrast, serum sodium and bicarbonate showed associations predominantly with amino-acid related species. In the first study to examine systematically associations between serum electrolytes and small circulating molecules, we identified novel metabolites and metabolic pathways associated with serum electrolyte levels. The role of these metabolic pathways on electrolyte homeostasis merits further studies.
Subtle Cr isotope signals track the variably anoxic Cryogenian interglacial period with voluminous manganese accumulation and decrease in biodiversity
Authors: Xu Lingang , Frank Anja B. , Lehmann Bernd , Zhu Jianming , Mao Jingwen , Ju Yongze , Frei Robert
Published: October 2019

Earth’s atmosphere experienced a step of profound oxygenation during the Neoproterozoic era, accompanied by diversification of animals. However, during the Cryogenian period (720–635 million years ago) Earth experienced its most severe glaciations which likely impacted marine ecosystems and multicellular life in the oceans. In particular, large volumes of Mn and Fe accumulated during the interglacial intervals of the Cryogenian glaciations, indicating large anoxic marine metal reservoirs. Here we present chromium isotope-, rare earth element-, and redox-sensitive trace element data of sedimentary rocks from the interglacial Datangpo Formation deposited between the Sturtian and Marinoan glaciations in South China, in an attempt to investigate the oxidation state of the oceans and atmosphere. Both the Cr isotope and trace element data indicate mainly anoxic water conditions with cryptic oxic surface water incursions after the Sturtian glaciation. Glacial-fed manganese precipitated as manganese carbonate in anoxic basins, and the non-fractionated δ53Cr record of −0.10 ± 0.06‰ identifies anoxic conditions with a cryptic component of slightly fractionated Cr isotope composition in manganese ore, in line with distinctly fractionated Mo isotope composition. Both the manganese carbonate ore and the black shales exhibit very low redox-sensitive element concentrations. Our study demonstrates that the oxygenation of the seawater, and inferably of the atmosphere, at the beginning of the Cryogenian interglacial interval was much subdued. The post-glacial rebound then allowed the Ediacaran biological diversity.
Ultrasound-derived changes in thickness of human ankle plantar flexor muscles during walking and running are not homogeneous along the muscle mid-belly region
Authors: Hodson-Tole E. F. , Lai A. K. M.
Published: October 2019

Skeletal muscle thickness is a valuable indicator of several aspects of a muscle’s functional capabilities. We used computational analysis of ultrasound images, recorded from 10 humans walking and running at a range of speeds (0.7–5.0 m s−1), to quantify interactions in thickness change between three ankle plantar flexor muscles (soleus, medial and lateral gastrocnemius) and quantify thickness changes at multiple muscle sites within each image. Statistical analysis of thickness change as a function of stride cycle (1d statistical parametric mapping) revealed significant differences between soleus and both gastrocnemii across the whole stride cycle as they bulged within the shared anatomical space. Within each muscle, changes in thickness differed between measurement sites but not locomotor condition. For some of the stride, thickness measures taken from the distal-mid image region represented the mean muscle thickness, which may therefore be a reliable region for these measures. Assumptions that muscle thickness is constant during a task, often made in musculoskeletal models, do not hold for the muscles and locomotor conditions studied here and researchers should not assume that a single thickness measure, from one point of the stride cycle or a static image, represents muscle thickness during dynamic movements.
Identification of Molecular Fluorophore as a Component of Carbon Dots able to Induce Gelation in a Fluorescent Multivalent-Metal-Ion-Free Alginate Hydrogel
Authors: Kasak Peter , Danko Martin , Zavahir Sifani , Mrlik Miroslav , Xiong Yuan , Yousaf Ammar Bin , Lai Wing-Fu , Krupa Igor , Tkac Jan , Rogach Andrey L.
Published: October 2019

We introduce a simple approach to fabricate fluorescent multivalent metal ion-free alginate hydrogels, which can be produced using carbon dots accessible from natural sources (citric acid and L-cysteine). Molecular fluorophore 5-oxo-2,3-dihydro-5H-[1,3]-thiazolo[3,2-a] pyridine-3,7-dicarboxylic acid (TPDCA), which is formed during the synthesis of carbon dots, is identified as a key segment for the crosslinking of hydrogels. The crosslinking happens through dynamic complexation of carboxylic acid groups of TPDCA and alginate cages along with sodium ions. The TPDCA derived hydrogels are investigated regarding to their thermal, rheological and optical properties, and found to exhibit characteristic fluorescence of this aggregated molecular fluorophore. Moreover, gradient hydrogels with tunable mechanical and optical properties and controlled release are obtained upon immersion of the hydrogel reactors in solutions of divalent metal ions (Ca2+, Cu2+, and Ni2+) with a higher affinity to alginate.
Underlying structure in the dynamics of chase and escape interactions
Authors: Tsutsui Kazushi , Shinya Masahiro , Kudo Kazutoshi
Published: October 2019

Chase and escape behaviors are important skills in many sports. Previous studies have described the behaviors of the attacker (escaper) and defender (chaser) by focusing on their positional relationship and have presented several key parameters that affect the outcome (successful attack or defense). However, it remains unclear how each individual agent moves, and how the outcome is determined in this type of interaction. To address these questions, we constructed a chase and escape task in a virtual space that allowed us to manipulate agents’ kinematic parameters. We identified the basic strategies of each agent and their robustness to changes in their parameters. Moreover, we identified the determinants of the outcome and a geometrical explanation of their importance. Our results revealed the underlying structure of a simplified human chase and escape interaction and provided the insight that, although each agent apparently moves freely, their strategies in two-agent interactions are in fact rather constrained.
A PQ-loop protein Ypq2 is involved in the exchange of arginine and histidine across the vacuolar membrane of Saccharomyces cerevisiae
Authors: Kawano-Kawada Miyuki , Manabe Kunio , Ichimura Haruka , Kimura Takumi , Harada Yuki , Ikeda Koichi , Tanaka Shiho , Kakinuma Yoshimi , Sekito Takayuki
Published: October 2019

In nutrient-rich conditions, basic amino acids are actively accumulated into the vacuoles by H+-coupled transporters in Saccharomyces cerevisiae. In addition to the H+-coupled systems, the existence of an exchanger for arginine and histidine was indicated by kinetic analysis using isolated vacuolar membrane vesicles; however, the gene(s) involved in the activity has not been identified. Here, we show that the uptake activity of arginine driven by an artificially imposed histidine gradient decreased significantly by the disruption of the gene encoding vacuolar PQ-loop protein Ypq2, but not by those of Ypq1 and Ypq3. The exchange activity was restored by the expression of YPQ2. Furthermore, the substitution of a conserved proline residue, Pro29, in Ypq2 greatly decreased the exchange activity. These results suggest that Ypq2 is responsible for the exchange activity of arginine and histidine across the vacuolar membrane, and the conserved proline residue in the PQ-loop motif is required for the activity.
Seasonal distribution and population dynamics of limnic microalgae and their association with physico-chemical parameters of river Noyyal through multivariate statistical analysis
Authors: Kumar Pandian Suresh , Thomas Jibu
Published: October 2019

The present investigation embarks on understanding the relationship between microalgal species assemblages and their associated physico-chemical parameter dynamics of the catchment region of river Noyyal. Totally, 142 microalgae cultures belonging to 10 different families were isolated from five different sites during four seasons and relative percentage distribution showed that Scenedesmaceae (36.6%) and site S1 (26.4%) with predominant microalgae population. Diversity indices revealed that microalgae communities were characterized by high Hʹ index, lower Simpson dominance, and Margalef index value with indefinite patterns of annual variations. Results showed that variation in the physico-chemical parameters in each sampling site has its impact on the microalgae population during each season. Multivariate statistical analysis viz., Karl Pearson’s correlation coefficient, principal component analysis, and canonical correspondence analysis were applied on microalgae species data, to evaluate the seasonal relationship between microalgae and physico-chemical parameters. The findings of our study concluded that the physico- chemical parameters influenced the dominant taxa of microalgae Chlorellaceae, Scenedesmaceae and Chlorococcaceae in river Noyyal and gives a base data for the seasonal and dynamic relationship between environmental parameters and microalgae population.
Highly Tough, Biocompatible, and Magneto-Responsive Fe3O4/Laponite/PDMAAm Nanocomposite Hydrogels
Authors: Lee Jin Hyun , Han Wen Jiao , Jang Hyo Seon , Choi Hyoung Jin
Published: October 2019

Magneto-responsive hydrogels (MRHs) have attracted considerable attention in various applications owing to their smart response to an externally applied magnetic field. However, their practical uses in biomedical fields are limited by their weak mechanical properties and possible toxicity to the human body. In this study, tough, biocompatible, and magneto-responsive nanocomposite hydrogels (MR_NCHs) were developed by the in-situ free-radical polymerization of N, N-dimethylacrylamide (DMAAm) and laponite and Fe3O4 nanoparticles. The effects of the concentrations of DMAAm, water, and laponite and Fe3O4 nanoparticles in the pre-gel solutions or mixtures on the viscoelastic and mechanical properties of the corresponding hydrogels were examined by performing rheological and tensile tests, through which the mixture composition producing the best MR_NCH system was optimized. The effects were also explained by the possible network structures of the MR_NCHs. Moreover, the morphology, chemical structure, and thermal and mechanical properties of the MR_NCHs were analyzed, while comparing with those of the poly(DMAAm) (PDMAAm) hydrogels and laponite/PDMAAm NCHs. The obtained optimal MR_NCH exhibited noticeable magnetorheological (MR) behavior, excellent mechanical properties, and good biocompatibility. This study demonstrates how to optimize the best Fe3O4/laponite/PDMAAm MR_NCH system and its potential as a soft actuator for the pharmaceutical and biomedical applications.
Changes in the consumption of antiepileptics and psychotropic medicines after starting low dose naltrexone: A nation-wide register-based controlled before-after study
Authors: Raknes Guttorm , Småbrekke Lars
Published: October 2019

In this controlled before-after study based on data from the Norwegian Prescription Database, we examine whether starting off-label use of Low Dose Naltrexone (LDN) is followed by changes in the consumption of psychotropic medicines including antiepileptics. Patients that collected LDN for the first time in 2013 (N = 11247) were included and stratified into three groups based on LDN exposure. We compared differences in means of cumulative number of defined daily doses (DDD) as well as changes in the number of users one year before and one year after starting LDN. There was a dose-response association between increasing LDN exposure and reductions in the number of users of antiepileptics, antipsychotics and antidepressants. There were significant difference-in-differences in DDDs between the groups with the lowest and highest LDN exposure of antipsychotics (1.4 DDD, 95% CI 0.4 to 2.3, p = 0.007), and in number of users of antiepileptics (3.1% points, 95% CI 1.6% to 4.6%, p < 0.001), antipsychotics (2.1% points, 95% CI 1.2% to 3%, p < 0.001), and antidepressants (2.8% points, 95% CI 1.1% to 4.4%, p = 0.001). The findings show an association between the initiation of persistent LDN use and reduced consumption of several psychotropic medicines and antiepileptics. Beneficial effects of LDN in the treatment of psychiatric diseases cannot be ruled out.
EV-associated miRNAs from pleural lavage as potential diagnostic biomarkers in lung cancer
Authors: Roman-Canal Berta , Moiola Cristian Pablo , Gatius Sònia , Bonnin Sarah , Ruiz-Miró Maria , González Esperanza , Ojanguren Amaia , Recuero José Luis , Gil-Moreno Antonio , Falcón-Pérez Juan M. , Ponomarenko Julia , Porcel José M. , Matias-Guiu Xavier , Colas Eva
Published: October 2019

Lung cancer is the leading cause of cancer-related deaths among men and women in the world, accounting for the 25% of cancer mortality. Early diagnosis is an unmet clinical issue. In this work, we focused to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the pleural lavage, a proximal fluid in lung cancer patients, as a source of potential biomarkers. We isolated EVs by ultracentrifuge method from 25 control pleural fluids and 21 pleural lavages from lung cancer patients. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 288 out of the 754 miRNAs that were contained in the OpenArray. The differential expression analysis yielded a list of 14 miRNAs that were significantly dysregulated (adj. p-value < 0.05 and logFC lower or higher than 3). Using Machine Learning approach we discovered the lung cancer diagnostic biomarkers; miRNA-1-3p, miRNA-144-5p and miRNA-150-5p were found to be the best by accuracy. Accordance with our finding, these miRNAs have been related to cancer processes in previous studies. This results opens the avenue to the use of EV-associated miRNA of pleural fluids and lavages as an untapped source of biomarkers, and specifically, identifies miRNA-1-3p, miRNA-144-5p and miRNA 150-5p as promising biomarkers of lung cancer diagnosis.
Habitat availability explains variation in climate-driven range shifts across multiple taxonomic groups
Authors: Platts Philip J. , Mason Suzanna C. , Palmer Georgina , Hill Jane K. , Oliver Tom H. , Powney Gary D. , Fox Richard , Thomas Chris D.
Published: October 2019

Range shifting is vital for species persistence, but there is little consensus on why individual species vary so greatly in the rates at which their ranges have shifted in response to recent climate warming. Here, using 40 years of distribution data for 291 species from 13 invertebrate taxa in Britain, we show that interactions between habitat availability and exposure to climate change at the range margins explain up to half of the variation in rates of range shift. Habitat generalists expanded faster than more specialised species, but this intrinsic trait explains less of the variation in range shifts than habitat availability, which additionally depends on extrinsic factors that may be rare or widespread at the range margin. Similarly, while climate change likely underlies polewards expansions, we find that more of the between-species variation is explained by differences in habitat availability than by changes in climatic suitability. A model that includes both habitat and climate, and their statistical interaction, explains the most variation in range shifts. We conclude that climate-change vulnerability assessments should focus as much on future habitat availability as on climate sensitivity and exposure, with the expectation that habitat restoration and protection will substantially improve species’ abilities to respond to uncertain future climates.
Spatiotemporal dynamics of different CO2 fixation strategies used by prokaryotes in a dimictic lake
Authors: Alfreider Albin , Tartarotti Barbara
Published: October 2019

The Calvin-Benson-Bassham (CBB) cycle and the 3-hydroxypropionate/4-hydroxybutyrate (HP/HB) cycle are two inorganic carbon assimilation pathways widely used by prokaryotic autotrophs in lakes. We investigated the effect of mixing periods and stable water stratification patterns on the trajectories of both CO2 fixation strategies in a dimictic lake (Piburger See), because information on the spatiotemporal dynamics of prokaryotes using these pathways in freshwater ecosystems is far from complete. Based on a quantitative approach (droplet digital PCR) of genes coding for key enzymes in different CO2 assimilation pathways, nine depths covering the entire water column were investigated on a monthly basis for one year. Our data show that the abundance of photoautotrophs and obligate chemolithoautotrophs preferentially using form IA RubisCO was determined by seasonal variations. Highest numbers were observed in summer, while a strong decline of prokrayotes using RubisCO form IA was measured between December and May, the period where the lake was mostly covered by ice. The spatiotemporal distribution patterns of genes coding for RubisCO form IC genes, an enzyme usually used by facultative autotrophs for CO2 assimilation, were less pronounced. Bacteria harboring RubisCO form II were dominating the oxygen limited hypolimnion, while nitrifying Thaumarchaeota using the HP/HB cycle were of minor importance in the lake. Our data reveal that the seasonal heterogeneity, which is determined by the dimictic thermal regime of the lake, results in pronounced spatiotemporal changes of different CO2 assimilation pathways with depth-dependent environmental parameters as key factors for their distribution.
Characterizing ecosystem phenological diversity and its macroecology with snow cover phenology
Authors: Lin Yi , Hyyppä Juha
Published: October 2019

One critical challenge of exploring flora phenology is on characterizing ecosystem phenological diversity (EPD), and thus how EPD’s performance is influenced by climate changes has also been an open macro-ecological question. To fill these two gaps, we proposed an innovative method for reflecting EPD, by taking the advantage of the often-classified inverse factor of spatial resolution discrepancy between the used remote sensing datasets of vegetation phenological dates (green-up and brown-up) and snow cover phenological dates (SPDs) (onset and end) around the Arctic, and further, we examined the cross response/feedbacks of the two kinds of EPDs to the two categories of SPDs. We found that the circumpolar green-up and brown-up EPDs both were shrinking, driven more by the delaying of the onset SPDs than the advancing of the end SPDs; North America and North Eurasia performed with inconsistent EPD response/feedbacks to the related SPD anomalies; and further, the EPD-SPD response/feedbacks in some locations exhibited the time-lag effect, e.g., the green-up EPDs made the strongest response to the onset SPDs of two years earlier. Overall, the validated method and the new findings are of implications for improving the phenology modules in Earth system models, and the contributions of the present study have enlightening significance for kicking off the new EPD branch in macrosystem phenological ecology.
Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells
Authors: Han Shan , Gao Hongwei , Chen Shaoru , Wang Qinqin , Li Xinxing , Du Li-Jun , Li Jun , Luo Ying-Ying , Li Jun-Xiu , Zhao Li-Chun , Feng Jianfang , Yang Shilin
Published: October 2019

Inflammation is a complex physiological process that poses a serious threat to people’s health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-α in RAW264.7 cells administrated with LPS. PCA1 blocked IκB-α degradation, inhibited IKKα/β and IκBα phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.
Mitochondria- and nucleolus-targeted copper(i) complexes with pyrazole-linked triphenylphosphine moieties for live cell imaging
Authors: Mayank Mayank , Rani Richa , Singh Ashutosh , Garg Neha , Kaur Navneet , Singh Narinder
Published: October 2019

We developed C1 and C2 metallo-complexes as highly efficient cell imaging tools. These complexes enabled us to visualize mitochondria and nucleolus in a single experiment via live cell imaging techniques.
Optimizing a simple procedure to determine organochlorine compounds in sediment samples: practical considerations
Authors: García-Alonso Susana , Gómez-López Luis Vicente , Pérez-Pastor Rosa María
Published: October 2019

Small sizes of sediment samples (0.25 g) and solvent (1 mL) were used to determine 18 organochlorine compounds in contaminated areas.
Chemical derivatization coupled with matrix assisted laser desorption ionization time-of-flight mass spectrometry for convenient and efficient N-glycan detection in human plasma
Authors: Bai H. H. , Liu J. , Cheng X. Q. , Wang X. H.
Published: October 2019

A chemical derivatization coupled with matrix assisted laser desorption ionization time-of-flight mass spectrometry based method was used for convenient and efficient N-glycan detection.
A mechano-colloidal approach for the controlled synthesis of metal nanoparticles
Authors: de Oliveira Paulo F. M. , Quiroz Jhon , de Oliveira Daniela C. , Camargo Pedro H. C.
Published: October 2019

We propose a mechano-colloidal approach marrying the attractive features of both mechanochemical and colloidal syntheses to produce well-defined Au nanoparticles.
Process-tracing study on the post-assembly modification of poly-NHC-based metallosupramolecular cylinders with tunable aggregation-induced emission
Authors: Wang Yi-Shou , Bai Sha , Wang Yao-Yu , Han Ying-Feng
Published: October 2019

A process-tracing and aggregation-induced emission (AIE) study of a covalent post-assembly modification (PAM) process of the AuI–CNHC cylinders was presented.