bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbiota and metabolome responses in the cecum and serum of broiler chickens fed with plant essential oils or virginiamycin
Authors: Chen Yan , Wang Jun , Yu Longfei , Xu Tianyue , Zhu Nianhua
Published: March 2020

This study investigated the cecal microbiota and serum metabolite profile of chickens fed with plant essential oils (PEO) or virginiamycin (VIRG) using high-throughput 16S rRNA gene sequencing and untargeted metabolomics approach. The main aim of this work was to explore the biochemical mechanisms involved in the improved growth performance of antibiotics and their alternatives in animal production. The results showed that both PEO and VIRG treatment significantly increased the relative abundance of phyla Bacteroidetes and decreased the abundance of phyla Firmicutes and genus of Lactobacillus in cecal microbiota of chickens. Compared to the control group (CT group), the relative abundance of genus of Alistipes, unclassified Rikenellaceae, Roseburia, and Anaeroplasma was enriched in the PEO group; that of genus Bacteroides, Lachnospiraceae, and unclassified Enterobacteriaceae was enriched in the cecal microbiota of the VIRG group. Untargeted metabolomics analyses revealed that the PEO treatment modified 102 metabolites and 3 KEGG pathways (primary bile acid biosynthesis and phenylalanine metabolism) in the cecal microbiota, and 81 metabolites and relevant KEGG pathways (fructose and mannose metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid.) in the serum of the chicken. Compared to the CT group, VIRG treatment group differed 217 metabolites and 10 KEGG pathways in cecal contents and 142 metabolites and 7 KEGG pathways in serum of chickens. Pearson’s correlation analysis showed that phyla Bacteroidetes and genus of Bacteroides, Alistipes, and unclassified Rikenellaceae (in the VIRG and PE group) were positively correlated with many lipid metabolites. However, phyla Firmicutes and genera Lactobacillus (higher in the CT group) were negatively correlated with the lipid and thymine metabolism, and positively correlated with hydroxyisocaproic acid, cytosine, and taurine. This study shows that dietary supplementation with PEO and VIRG altered the composition and metabolism profile of the cecal microbiota, modified the serum metabolism profile.
Robot-Driven Locomotor Perturbations Reveal Synergy-Mediated, Context-Dependent Feedforward and Feedback Mechanisms of Adaptation
Authors: Severini Giacomo , Koenig Alexander , Adans-Dester Catherine , Cajigas Iahn , Cheung Vincent C. K. , Bonato Paolo
Published: March 2020

Humans respond to mechanical perturbations that affect their gait by changing their motor control strategy. Previous work indicates that adaptation during gait is context dependent, and perturbations altering long-term stability are compensated for even at the cost of higher energy expenditure. However, it is unclear if gait adaptation is driven by unilateral or bilateral mechanisms, and what the roles of feedback and feedforward control are in the generation of compensatory responses. Here, we used a robot-based adaptation paradigm to investigate if feedback/feedforward and unilateral/bilateral contributions to locomotor adaptation are also context dependent in healthy adults. A robot was used to induce two opposite unilateral mechanical perturbations affecting the step length over multiple gait cycles. Electromyographic signals were collected and analyzed to determine how muscle synergies change in response to perturbations. The results unraveled different unilateral modulation dynamics of the muscle-synergy activations during adaptation, characterized by the combination of a slow-progressive feedforward process and a fast-reactive feedback-driven process. The relative unilateral contributions of the two processes to motor-output adjustments, however, depended on which perturbation was delivered. Overall, these observations provide evidence that, in humans, both descending and afferent drives project onto the same spinal interneuronal networks that encode locomotor muscle synergies.
Preparation and antimicrobial activity of ZnO-NPs coated cotton/starch and their functionalized ZnO-Ag/cotton and Zn(II) curcumin/cotton materials
Authors: El-Nahhal Issa M. , Salem Jamil , Anbar Rawan , Kodeh Fawzi S. , Elmanama Abdelraouf
Published: March 2020

ZnO-NPs coated cotton or starched cotton fibers were successfully prepared via ultrasound irradiation. Different concentrations of soluble corn starch (1–3 starch wt.%) were used to stabilize ZnO-NPs onto the surface of cotton fabrics as entrapped species. The use of none-toxic biocompatible starch has improved the adhesion properties of the cotton fibers towards ZnO-NPs. This also enhanced the durability of ZnO-NPs onto the cotton fabrics and decreased their leaching from the surface of cotton fabrics. When 3 starch wt.% solution was used, deposition of ZnO-NP increased by 53% after 10 washing cycles. The antibacterial activity against Staphylococcus aureus and Escherichia coli increased by 50 and 21.5%, respectively. Functionalization of ZnO coated cotton with silver nanoparticles (Ag-NPs) and curcumin results in formation of ZnO-Ag/cotton and Zn(II) curcumin/cotton composites. The functionalized nanocomposites ZnO-Ag coated cotton material showed a synergistic antimicrobial behavior than that of individual ZnO/cotton material. The Zn(II) curcumin complex coated cotton showed higher antibacterial activities against both Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacteria than that of the ZnO/cotton material.
The Role of the Subthalamic Nucleus in Inhibitory Control of Oculomotor Behavior in Parkinson’s Disease
Authors: Bakhtiari Shahab , Altinkaya Ayca , Pack Christopher C. , Sadikot Abbas F.
Published: March 2020

Inhibiting inappropriate actions in a context is an important part of the human cognitive repertoire, and deficiencies in this ability are common in neurological and psychiatric disorders. An anti-saccade is a simple oculomotor task that tests this ability by requiring inhibition of saccades to peripheral targets (pro-saccade) and producing voluntary eye movements toward the mirror position (anti-saccades). Previous studies provide evidence for a possible contribution from the basal ganglia in anti-saccade behavior, but the precise role of different components is still unclear. Parkinson’s disease patients with implanted deep brain stimulators (DBS) in subthalamic nucleus (STN) provide a unique opportunity to investigate the role of the STN in anti-saccade behavior. Previous attempts to show the effect of STN DBS on anti-saccades have produced conflicting observations. For example, the effect of STN DBS on anti-saccade error rate is not yet clear. Part of this inconsistency may be related to differences in dopaminergic states in different studies. Here, we tested Parkinson’s disease patients on anti- and pro-saccade tasks ON and OFF STN DBS, in ON and OFF dopaminergic medication states. First, STN DBS increases anti-saccade error rate while patients are OFF dopamine replacement therapy. Second, dopamine replacement therapy and STN DBS interact: L-dopa reduces the effect of STN DBS on anti-saccade error rate. Third, STN DBS induces different effects on pro- and anti-saccades in different patients. These observations provide evidence for an important role for the STN in the circuitry underlying context-dependent modulation of visuomotor action selection.
Comparison of tuning properties of gamma and high-gamma power in local field potential (LFP) versus electrocorticogram (ECoG) in visual cortex
Authors: Dubey Agrita , Ray Supratim
Published: March 2020

Electrocorticogram (ECoG), obtained from macroelectrodes placed on the cortex, is typically used in drug-resistant epilepsy patients, and is increasingly being used to study cognition in humans. These studies often use power in gamma (30–70 Hz) or high-gamma (>80 Hz) ranges to make inferences about neural processing. However, while the stimulus tuning properties of gamma/high-gamma power have been well characterized in local field potential (LFP; obtained from microelectrodes), analogous characterization has not been done for ECoG. Using a hybrid array containing both micro and ECoG electrodes implanted in the primary visual cortex of two female macaques (for some stimulus conditions, separate ECoG and microelectrode arrays in two additional male macaques were also used), we compared the stimulus tuning preferences of gamma/high-gamma power in LFP versus ECoG in up to four monkeys, and found them to be surprisingly similar. High-gamma power, thought to index the average firing rate around the electrode, was highest for the smallest stimulus (0.3° radius), and decreased with increasing size in both LFP and ECoG, suggesting local origins of both signals. Further, gamma oscillations were similarly tuned in LFP and ECoG to stimulus orientation, contrast and spatial frequency. This tuning was significantly weaker in electroencephalogram (EEG), suggesting that ECoG is more like LFP than EEG. Overall, our results validate the use of ECoG in clinical and basic cognitive research.
Variation in prostaglandin metabolism during growth of the diatom Thalassiosira rotula
Authors: Di Dato Valeria , Barbarinaldi Roberta , Amato Alberto , Di Costanzo Federica , Fontanarosa Carolina , Perna Anna , Amoresano Angela , Esposito Francesco , Cutignano Adele , Ianora Adrianna , Romano Giovanna
Published: March 2020

Prostaglandins (PGs) are hormone-like mediators in many physiological and pathological processes that are present in all vertebrates, in some terrestrial and aquatic invertebrates, and have also been identified in some macroalgae. They have recently been reported also in marine microalgae but their role as chemical mediators is largely unknown. Here we studied the expression pattern of the PG biosynthetic pathway during different growth phases of the centric diatom Thalassiosira rotula and assessed the release of PGs in the surrounding environment for the first time. We show that enzymes responsible for PGs formation such as cyclooxygenase, prostaglandin E synthase 2-like and prostaglandin F synthase are mainly expressed at the end of the exponential phase and that PGs are released especially during the stationary and senescent phases, suggesting a possible signaling function for these compounds. Phylogenetic analysis of the limiting enzyme, COX, indicate the presence in diatoms of more than one enzyme related to the oxidative metabolism of fatty acids belonging to the peroxidase-cyclooxygenase superfamily. These findings suggest a more complex evolution and diversity of metabolic pathways leading to the synthesis of lipid mediators in diatoms.
Lymph node metastasis around the entrance point to recurrent laryngeal nerve in papillary thyroid carcinoma
Authors: Lv Tian , Liu Zhuoran , Yan Jiqi
Published: March 2020

There are few reports on the lymph nodes of entrance point to recurrent laryngeal nerve (LN-epRLN) in patients with papillary thyroid carcinoma (PTC). Thus, we investigated the clinical significance of LN-epRLN and implications it may have. An observational analysis of 878 consecutive patients with PTC who underwent thyroidectomy from April 2016 to March 2017 was conducted. We explored the surrounding tissue of laryngeal entry point, during routine central lymph node dissection (CLND). The lymph node specimens were sent separately for routine histopathological examination. Thereafter, complications and follow-ups were recorded. LN-epRLNs were found in 73 of the 878 patients, with the metastatic rate of 3.76%. Univariate and multivariate analysis showed central lymph node metastases can serve as independent predictors for LN-epRLN metastasis. In summary, we confirmed the significance of LN-epRLN in metastasis and recurrence, which required precise anatomy and thorough CLND. In PTC patients, especially in suspicious presence of central cervical lymph node metastasis, attention should be given to excising the nodal tissue at the laryngeal entry point.
Transcriptome analysis uncovers the gene expression profile of salt-stressed potato (Solanum tuberosum L.)
Authors: Li Qing , Qin Yuzhi , Hu Xinxi , Li Guangcun , Ding Hongying , Xiong Xingyao , Wang Wanxing
Published: March 2020

Potato (Solanum tuberosum L.) is an important staple food worldwide. However, its growth has been heavily suppressed by salt stress. The molecular mechanisms of salt tolerance in potato remain unclear. It has been shown that the tetraploid potato Longshu No. 5 is a salt-tolerant genotype. Therefore, in this study we conducted research to identify salt stress response genes in Longshu No. 5 using a NaCl treatment and time-course RNA sequencing. The total number of differentially expressed genes (DEGs) in response to salt stress was 5508. Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, it was found that DEGs were significantly enriched in the categories of nucleic acid binding, transporter activity, ion or molecule transport, ion binding, kinase activity and oxidative phosphorylation. Particularly, the significant differential expression of encoding ion transport signaling genes suggests that this signaling pathway plays a vital role in salt stress response in potato. Finally, the DEGs in the salt response pathway were verified by Quantitative real-time PCR (qRT-PCR). These results provide valuable information on the salt tolerance of molecular mechanisms in potatoes, and establish a basis for breeding salt-tolerant cultivars.
Downregulation of HLA-ABC expression through promoter hypermethylation and downmodulation of MIC-A/B surface expression in LMP2A-positive epithelial carcinoma cell lines
Authors: Singh Shweta , Banerjee Subrata
Published: March 2020

Epstein Barr Virus (EBV) is a human herpesvirus, and has been reported to be associated with nasopharyngeal carcinoma, gastric carcinoma, Burkitt’s lymphoma and Hodgkin’s lymphoma. In most of the associated tumors, the virus remains in a latently infected state. During latency, EBV expresses Latent Membrane Protein 2A (LMP2A) along with few other genes. We previously showed that LMP2A causes downregulation of HLA-ABC surface expression in EBV associated gastric carcinomas. However, the mechanism that leads to this downregulation remain unclear. We therefore analyzed methylation-mediated regulation of HLA-ABC expression by LMP2A. Interestingly, according to the ‘missing self’ hypothesis, when there is a decrease in HLA-ABC surface expression, expression of NKG2D ligands’ must be upregulated to facilitate killing by Natural Killer (NK) cells. Analysis of NKG2D ligands’ expression, revealed downregulation of MIC-A/B surface expression in response to LMP2A. Furthermore, the role of Unfolded Protein Response (UPR) in the regulation of MIC-A/B surface expression in cells expressing LMP2A was also investigated. Protein Disulfide Isomerase (PDI) mediated inhibition of MIC-A/B surface expression was observed in LMP2A expressing cells. Our current findings provide new insights in LMP2A arbitrated dysregulation of host immune response in epithelial cell carcinomas.
Molecular origin of the Raman signal from Aspergillus nidulans conidia and observation of fluorescence vibrational structure at room temperature
Authors: Han Zehua , Strycker Benjamin D. , Commer Blake , Wang Kai , Shaw Brian D. , Scully Marlan O. , Sokolov Alexei V.
Published: March 2020

Successful approaches to identification and/or biological characterization of fungal specimens through Raman spectroscopy may require the determination of the molecular origin of the Raman response as well as its separation from the background fluorescence. The presence of fluorescence can interfere with Raman detection and is virtually impossible to avoid. Fluorescence leads to a multiplicity of problems: one is noise, while another is “fake” spectral structure that can easily be confused for spontaneous Raman peaks. One solution for these problems is Shifted Excitation Raman Difference Spectroscopy (SERDS), in which a tunable light source generates two spectra with different excitation frequencies in order to eliminate fluorescence from the measured signal. We combine a SERDS technique with genetic breeding of mutant populations and demonstrate that the Raman signal from Aspergillus nidulans conidia originates in pigment molecules within the cell wall. In addition, we observe unambiguous vibrational fine-structure in the fluorescence response at room temperature. We hypothesize that the vibrational fine-structure in the fluorescence results from the formation of flexible, long-lived molecular cages in the bio-polymer matrix of the cell wall that partially shield target molecules from the immediate environment and also constrain their degrees of freedom.
Linear systems analysis for laminar fMRI: Evaluating BOLD amplitude scaling for luminance contrast manipulations
Authors: van Dijk Jelle A. , Fracasso Alessio , Petridou Natalia , Dumoulin Serge O.
Published: March 2020

A fundamental assumption of nearly all functional magnetic resonance imaging (fMRI) analyses is that the relationship between local neuronal activity and the blood oxygenation level dependent (BOLD) signal can be described as following linear systems theory. With the advent of ultra-high field (7T and higher) MRI scanners, it has become possible to perform sub-millimeter resolution fMRI in humans. A novel and promising application of sub-millimeter fMRI is measuring responses across cortical depth, i.e. laminar imaging. However, the cortical vasculature and associated directional blood pooling towards the pial surface strongly influence the cortical depth-dependent BOLD signal, particularly for gradient-echo BOLD. This directional pooling may potentially affect BOLD linearity across cortical depth. Here we assess whether the amplitude scaling assumption for linear systems theory holds across cortical depth. For this, we use stimuli with different luminance contrasts to elicit different BOLD response amplitudes. We find that BOLD amplitude across cortical depth scales with luminance contrast, and that this scaling is identical across cortical depth. Although nonlinearities may be present for different stimulus configurations and acquisition protocols, our results suggest that the amplitude scaling assumption for linear systems theory across cortical depth holds for luminance contrast manipulations in sub-millimeter laminar BOLD fMRI.
SLAM-MS: Mutation scanning of stem-loop amplicons with TaqMan probes by quantitative DNA melting analysis
Authors: Kondratova V. N. , Botezatu I. V. , Shelepov V. P. , Lichtenstein A. V.
Published: March 2020

DNA Melting Analysis (DMA) with a TaqMan probe covering the mutation “hot spot” is a simple, sensitive, and “closed tube” method of mutation detection. However, DMA requires asymmetric PCR to produce single-stranded amplicons capable of interacting with TaqMan probes. This makes quantitative analysis impossible owing to low amplification efficiency. Moreover, bi-strand mutation detection necessitates two independent PCRs. The SLAM-MS (Stem-Loop AMplicon Mutation Scanning) assay, in which symmetric PCR is performed using primers with 5'-universal primer sequence (UPS), has been developed to detect KRAS mutations. Some of the resulting amplicons, sense and antisense, adopt single-stranded stem-loop conformation and become unable to renature, but able to hybridize with TaqMan probes. Hybrids of stem-loops and complementary TaqMan probes are suitable for melting analysis and simultaneous bi-strand mutation scanning. In addition, the areas under the melting peaks are determined by the PeakFit software, a non-linear iterative curve fitting program, to evaluate the wild-type/mutant allele ratio. Thus, the SLAM-MS assay permits quantification of both the number of copies of the target sequence and the percentage of mutant alleles. For mutant enrichment, the SLAM-MS assay uses TaqMan probes as PCR blocking agents allowing an ~10 times higher mutation detection sensitivity than High Resolution Melting (HRM) assay.
Parturitions, menopause and other physiological stressors are recorded in dental cementum microstructure
Authors: Cerrito Paola , Bailey Shara E. , Hu Bin , Bromage Timothy G.
Published: March 2020

The life history pattern of recent humans is uniquely derived in many of its aspects including an extended post-reproductive lifespan combined with short interbirth intervals. A number of theories have been proposed to explain the evolution of this unusual pattern. However most have been difficult to test due to the fragmentary nature of the hominin fossil record and the lack of methods capable of inferring such later life history events. In search of a method we tested the hypothesis that the physiologically impactful events of parturition and menopause are recorded in dental cementum microstructure. We performed histomorphological analyses of 47 teeth from 15 individuals with known life history events and were able to detect reproductive events and menopause in all females. Furthermore, we found that other stressful events such as systemic illnesses and incarceration are also detectable. Finally, through the development of a novel analytical method we were able to time all such events with high accuracy (R-squared = 0.92).
Assessing Autonomic Function from Electrodermal Activity and Heart Rate Variability During Cold-Pressor Test and Emotional Challenge
Authors: Ghiasi Shadi , Greco Alberto , Barbieri Riccardo , Scilingo Enzo Pasquale , Valenza Gaetano
Published: March 2020

Standard functional assessment of autonomic nervous system (ANS) activity on cardiovascular control relies on spectral analysis of heart rate variability (HRV) series. However, difficulties in obtaining a reliable measure of sympathetic activity from HRV spectra limits the exploitation of sympatho-vagal metrics. On the other hand, measures of electrodermal activity (EDA) have been demonstrated to provide a reliable quantifier of sympathetic dynamics. In this study we propose novel indices of phasic autonomic regulation mechanisms by combining HRV and EDA correlates and thoroughly investigating their time-varying dynamics. HRV and EDA series were gathered from 26 healthy subjects during a cold-pressor test and emotional stimuli. Instantaneous linear and nonlinear (bispectral) estimates of vagal dynamics were obtained from HRV through inhomogeneous point-process models, and combined with a sensitive maker of sympathetic tone from EDA spectral power. A wavelet decomposition analysis was applied to estimate phasic components of the proposed sympatho-vagal indices. Results show significant statistical differences for the proposed indices between the cold-pressor elicitation and previous resting state. Furthermore, an accuracy of 73.08% was achieved for the automatic emotional valence recognition. The proposed nonlinear processing of phasic ANS markers brings novel insights on autonomic functioning that can be exploited in the field of affective computing and psychophysiology.
Iodine and bromine in fish consumed by indigenous peoples of the Russian Arctic
Authors: Sobolev Nikita , Aksenov Andrey , Sorokina Tatiana , Chashchin Valery , Ellingsen Dag G. , Nieboer Evert , Varakina Yulia , Plakhina Elena , Onuchina Alexandra , Thomassen Magny Skinlo , Thomassen Yngvar
Published: March 2020

Fish muscle may constitute one of the main sources of iodine (I) for the indigenous peoples of the Russian Arctic, although limited information is available about its content in commonly consumed fish species. In the current study, bromine (Br), I, the essential elements (copper, selenium and zinc) and other non-essential elements — specifically mercury, arsenic (As), cadmium, lead and nickel — have been quantified in 10 fish species consumed by people living in the Nenets and Chukotka Regions. Fish muscle was analysed by ICP-MS after nitric acid or tetramethylammonium hydroxide digestion. Certified reference materials were employed and concentrations are reported as geometric means (GMs). Atlantic cod (6.32 mg/kg) and navaga (0.934 mg/kg) contained substantially higher amounts of I than all other fish species, while broad whitefish had the lowest (0.033 mg/kg). By comparison, navaga contained more Br (14.5 mg/kg) than the other fish species, ranging 7.45 mg/kg in Atlantic cod to 2.39 mg/kg in northern pike. A significant inter-fish association between As and I in freshwater and marine fish was observed, suggesting common sources and perhaps parallel absorption patterns. Only Atlantic cod and, to lesser extent, navaga constituted significant dietary sources of I.
Stability of copper acetate at high P-T and the role of organic acids and CO2 in metallic mineralization
Authors: Ni Zhiyong , Chen Yanjing , Zheng Haifei , Li Nuo , Li Heping
Published: March 2020

Many metal deposits were formed by carbonic fluids (rich in CO2) as indicated by fluid inclusions in minerals, but the precise role of CO2 in metal mineralization remains unclear. The main components in fluid inclusions, i.e. H2O and CO2, correspond to the decomposed products of organic acids, which lead us to consider that in the mineralization process the organic acids transport and then discharge metals when they are stable and unstable, respectively. Here we show that the thermal stability of copper acetate solution at 15–350 °C (0.1–830 MPa) provides insight as to the role of organic acids in metal transport. Results show that the copper acetate solution is stable at high P-T conditions under low geothermal gradient of <19 °C/km, with an isochore of P = 1.89 T + 128.58, verifying the possibility of copper transportation as acetate solution. Increasing geothermal gradient leads to thermal dissociation of copper acetate in the way of 4Cu(CH3 COO)2 + 2H2O = 4Cu + 2CO2 + 7CH3COOH. The experimental results and inferences in this contribution agree well with the frequently observed fluid inclusions and wall-rock alterations of carbonate, sericite and quartz in hydrothermal deposits, and provide a new dimension in the understanding of the role of CO2 during mineralization.
First principles study of oxygen vacancy activation energy barrier in zirconia-based resistive memory
Authors: Hur Ji-Hyun
Published: March 2020

Unlike experimental measurements that appeared to be quite large activation barriers, oxygen vacancies in zirconia-based resistive random access memory (ReRAM) are believed to migrate with a fairly low energy barrier, and this discrepancy has not been noticed nor seriously questioned up to date. In this paper, we work on this problem by means of first-principles calculations categorizing all the possible migration pathways by crystallographic directions. From the results, it is found that the low activation energy of oxygen vacancy that is expected from the switching characteristic of the device is originated from +2q charged oxygen vacancies in a nanometer-sized filament migrating into a particular crystallographic direction of monoclinic zirconia.
Neural magnetic field dependent fMRI toward direct functional connectivity measurements: A phantom study
Authors: Ito Yosuke , Ueno Masahito , Kobayashi Tetsuo
Published: March 2020

Recently, the main issue in neuroscience has been the imaging of the functional connectivity in the brain. No modality that can measure functional connectivity directly, however, has been developed yet. Here, we show the novel MRI sequence, called the partial spinlock sequence toward direct measurements of functional connectivity. This study investigates a probable measurement of phase differences directly associated with functional connectivity. By employing partial spinlock imaging, the neural magnetic field might influence the magnetic resonance signals. Using simulation and phantom studies to model the neural magnetic fields, we showed that magnetic resonance signals vary depending on the phase of an externally applied oscillating magnetic field with non-right flip angles. These results suggest that the partial spinlock sequence is a promising modality for functional connectivity measurements.
Resveratrol and its Related Polyphenols Contribute to the Maintenance of Genome Stability
Authors: Matsuno Yusuke , Atsumi Yuko , Alauddin Md. , Rana Md. Masud , Fujimori Haruka , Hyodo Mai , Shimizu Atsuhiro , Ikuta Tomoki , Tani Hiroko , Torigoe Hidetaka , Nakatsu Yoshimichi , Tsuzuki Teruhisa , Komai Michio , Shirakawa Hitoshi , Yoshioka Ken-ichi
Published: March 2020

Genomic destabilisation is associated with the induction of mutations, including those in cancer-driver genes, and subsequent clonal evolution of cells with abrogated defence systems. Such mutations are not induced when genome stability is maintained; however, the mechanisms involved in genome stability maintenance remain elusive. Here, resveratrol (and related polyphenols) is shown to enhance genome stability in mouse embryonic fibroblasts, ultimately protecting the cells against the induction of mutations in the ARF/p53 pathway. Replication stress-associated DNA double-strand breaks (DSBs) that accumulated with genomic destabilisation were effectively reduced by resveratrol treatment. In addition, resveratrol transiently stabilised the expression of histone H2AX, which is involved in DSB repair. Similar effects on the maintenance of genome stability were observed for related polyphenols. Accordingly, we propose that polyphenol consumption can contribute to the suppression of cancers that develop with genomic instability, as well as lifespan extension.
Near-future ocean warming and acidification alter foraging behaviour, locomotion, and metabolic rate in a keystone marine mollusc
Authors: Horwitz Rael , Norin Tommy , Watson Sue-Ann , Pistevos Jennifer C. A. , Beldade Ricardo , Hacquart Simon , Gattuso Jean-Pierre , Rodolfo-Metalpa Riccardo , Vidal-Dupiol Jeremie , Killen Shaun S. , Mills Suzanne C.
Published: March 2020

Environmentally-induced changes in fitness are mediated by direct effects on physiology and behaviour, which are tightly linked. We investigated how predicted ocean warming (OW) and acidification (OA) affect key ecological behaviours (locomotion speed and foraging success) and metabolic rate of a keystone marine mollusc, the sea hareStylocheilus striatus, a specialist grazer of the toxic cyanobacteriumLyngbya majuscula. We acclimated sea hares to OW and/or OA across three developmental stages (metamorphic, juvenile, and adult) or as adults only, and compare these to sea hares maintained under current-day conditions. Generally, locomotion speed and time to locate food were reduced ~1.5- to 2-fold when the stressors (OW or OA) were experienced in isolation, but reduced ~3-fold when combined. Decision-making was also severely altered, with correct foraging choice nearly 40% lower under combined stressors. Metabolic rate appeared to acclimate to the stressors in isolation, but was significantly elevated under combined stressors. Overall, sea hares that developed under OW and/or OA exhibited a less severe impact, indicating beneficial phenotypic plasticity. Reduced foraging success coupled with increased metabolic demands may impact fitness in this species and highlight potentially large ecological consequences under unabated OW and OA, namely in regulating toxic cyanobacteria blooms on coral reefs.
Accuracy of Two Point-of-Care Tests for Rapid Diagnosis of Bovine Tuberculosis at Animal Level using Non-Invasive Specimens
Authors: Kelley Holden V. , Waibel Sarah M. , Sidiki Sabeen , Tomatis-Souverbielle Cristina , Scordo Julia M. , Hunt W. Garret , Barr N. , Smith R. , Silwani Sayeed N. , Averill James J. , Baer Susan , Hengesbach Janet , Yildiz Vedat O. , Pan Xueliang , Gebreyes Wondwossen A. , Balada-Llasat Joan-Miquel , Wang Shu-Hua , Torrelles Jordi B.
Published: March 2020

Bovine tuberculosis (BTB) testing in cattle requires a significant investment of time, equipment, and labor. Novel, rapid, cheaper and accurate methods are needed. The Alere Determine TB lipoarabinomannan antigen (LAM-test) is a World Health Organization-endorsed point-of-care urine test designed to detect active TB disease in humans. The Lionex Animal TB Rapid Test (Lionex-test) is a novel animal specific TB diagnostic blood test. An animal level analysis was performed using urine (n = 141) and milk (n = 63) samples from depopulated BTB-suspected cattle to test the accuracy of the LAM-test when compared to results of positive TB detection by any routine BTB tests (BOVIGAM, necropsy, histology, culture, PCR) that are regularly performed by the United States Department of Agriculture (USDA). The agreement between the urine LAM-test and USDA standard tests were poor at varying testing time points. The same milk samples did not elicit statistically significant agreement with the Lionex-test, although positive trends were present. Hence, we cannot recommend the LAM-test as a valid BTB diagnostic test in cattle using either urine or milk. The Lionex-test’s production of positive trends using milk samples suggests larger sample sizes may validate the Lionex-test in accurately diagnosing BTB in cattle using milk samples, potentially providing a quick and reliable field test for BTB.
Organomineral Fertilizer as Source of P and K for Sugarcane
Authors: Crusciol Carlos Alexandre Costa , Campos Murilo de , Martello Jorge Martinelli , Alves Cleiton José , Nascimento Carlos Antonio Costa , Pereira Júlio Cesar dos Reis , Cantarella Heitor
Published: March 2020

Sugarcane (Saccharum spp) crop has high social, economic and environmental importance for several regions throughout the world. However, the increasing demand for efficiency and optimization of agricultural resources generates uncertainties regarding high mineral fertilizer consumption. Thereby, organomineral fertilizers are to reduce the conventional sources consumption. Thus, this study was carried out to evaluate the agronomic and economic sugarcane performancies and the residual effect of P and K under mineral and organomineral fertilization. Growth and technological parameters, leaf and soil nutrients concentration in surface and subsurface layers were analyzed from sugarcane planting (plant cane) until the first ratoon. Agronomic and economic sugarcane efficiency were evaluated. At the first ratoon, resin-extractable P provided by mineral and organomineral fertilizers were, respectively, 15 and 11 mg kg−1 in the 0.0–0.2 m, and 28 and 31 mg kg−1 in 0.2–0.4 m layer. However, exchangeable K in the 0.0–0.2 m layer was 1.88 and 1.58 mmolc kg−1 for mineral and organomineral fertilizers, respectively. The yield gains over the control reached with mineral and organomineral fertilizers were, respectively, 10.99 and 17 Mg ha−1 at the lowest fertilizer rate; and 29.25 and 61.3 Mg ha−1 at the highest fertilizer rate. Agronomic and economic organomineral fertilizer efficiencies are more pronounced in plant cane. Summing two harvests, the organomineral is 7% more profitable than mineral fertilizer.
Viruses with different genome types adopt a similar strategy to pack nucleic acids based on positively charged protein domains
Authors: Requião Rodrigo D. , Carneiro Rodolfo L. , Moreira Mariana Hoyer , Ribeiro-Alves Marcelo , Rossetto Silvana , Palhano Fernando L. , Domitrovic Tatiana
Published: March 2020

Capsid proteins often present a positively charged arginine-rich sequence at their terminal regions, which has a fundamental role in genome packaging and particle stability for some icosahedral viruses. These sequences show little to no conservation and are structurally dynamic such that they cannot be easily detected by common sequence or structure comparisons. As a result, the occurrence and distribution of positively charged domains across the viral universe are unknown. Based on the net charge calculation of discrete protein segments, we identified proteins containing amino acid stretches with a notably high net charge (Q > + 17), which are enriched in icosahedral viruses with a distinctive bias towards arginine over lysine. We used viral particle structural data to calculate the total electrostatic charge derived from the most positively charged protein segment of capsid proteins and correlated these values with genome charges arising from the phosphates of each nucleotide. We obtained a positive correlation (r = 0.91, p-value <0001) for a group of 17 viral families, corresponding to 40% of all families with icosahedral structures described to date. These data indicated that unrelated viruses with diverse genome types adopt a common underlying mechanism for capsid assembly based on R-arms.
Increase in environmental temperature affects exploratory behaviour, anxiety and social preference in Danio rerio
Authors: Angiulli E. , Pagliara V.  , Cioni C. , Frabetti F. , Pizzetti F. , Alleva E. , Toni M.
Published: March 2020

The aim of this work is to investigate the effect of a temperature increase on the behaviour of adult zebrafish (Danio rerio) maintained for 21 days at 34 °C (treatment) and 26 °C (control). The temperatures chosen are within the vital range of zebrafish and correspond to temperatures that this species encounters in the natural environment. Previous results showed that the same treatment affects the brain proteome and the behaviour of adult zebrafish by producing alterations in the proteins involved in neurotransmitter release and synaptic function and impairing fish exploratory behaviour. In this study, we have investigated the performance of treated and control zebrafish during environmental exploration by using four behavioural tests (novel tank diving, light and dark preference, social preference and mirror biting) that are paradigms for assessing the state of anxiety, boldness, social preference and aggressive behaviour, respectively. The results showed that heat treatment reduces anxiety and increases the boldness of zebrafish, which spent more time in potentially dangerous areas of the tank such as the top and the uncovered bright area and at a distance from the social group, thus decreasing protection for the zebrafish. These data suggest that the increase in ambient temperature may compromise zebrafish survival rate in the natural environment.
From thoughtless awareness to effortful cognition: alpha - theta cross-frequency dynamics in experienced meditators during meditation, rest and arithmetic
Authors: Rodriguez-Larios Julio , Faber Pascal , Achermann Peter , Tei Shisei , Alaerts Kaat
Published: March 2020

Neural activity is known to oscillate within discrete frequency bands and the synchronization between these rhythms is hypothesized to underlie information integration in the brain. Since strict synchronization is only possible for harmonic frequencies, a recent theory proposes that the interaction between different brain rhythms is facilitated by transient harmonic frequency arrangements. In this line, it has been recently shown that the transient occurrence of 2:1 harmonic cross-frequency relationships between alpha and theta rhythms (i.e. falpha ≈ 12 Hz; ftheta ≈ 6 Hz) is enhanced during effortful cognition. In this study, we tested whether achieving a state of ‘mental emptiness’ during meditation is accompanied by a relative decrease in the occurrence of 2:1 harmonic cross-frequency relationships between alpha and theta rhythms. Continuous EEG recordings (19 electrodes) were obtained from 43 highly experienced meditators during meditation practice, rest and an arithmetic task. We show that the occurrence of transient alpha:theta 2:1 harmonic relationships increased linearly from a meditative to an active cognitive processing state (i.e. meditation < rest < arithmetic task). It is argued that transient EEG cross-frequency arrangements that prevent alpha:theta cross-frequency coupling could facilitate the experience of ‘mental emptiness’ by avoiding the interaction between the memory and executive components of cognition.
Horizontal and Vertical Distance Perception in Altered Gravity
Authors: Clément Gilles , Bukley Angie , Loureiro Nuno , Lindblad Louise , Sousa Duarte , Zandvilet André
Published: March 2020

The perception of the horizontal and vertical distances of a visual target to an observer was investigated in parabolic flight during alternating short periods of normal gravity (1 g). microgravity (0 g), and hypergravity (1.8 g). The methods used for obtaining absolute judgments of egocentric distance included verbal reports and visually directed motion toward a memorized visual target by pulling on a rope with the arms (blind pulling). The results showed that, for all gravity levels, the verbal reports of distance judgments were accurate for targets located between 0.6 and 6.0 m. During blind pulling, subjects underestimated horizontal distances as distances increased, and this underestimation decreased in 0 g. Vertical distances for up targets were overestimated and vertical distances for down targets were underestimated in both 1 g and 1.8 g. This vertical asymmetry was absent in 0 g. The results of the present study confirm that blind pulling and verbal reports are independently influenced by gravity. The changes in distance judgments during blind pulling in 0 g compared to 1 g support the view that, during an action-based task, subjects base their perception of distance on the estimated motor effort of navigating to the perceived object.
Metabolomic study of soft corals from the Colombian Caribbean: PSYCHE and 1H-NMR comparative analysis
Authors: Santacruz Liliana , Hurtado Diana X. , Doohan Roisin , Thomas Olivier P. , Puyana Mónica , Tello Edisson
Published: March 2020

Marine organisms have evolved to survive against predators in complex marine ecosystems via the production of chemical compounds. Soft corals (Cnidaria, Anthozoa, Octocorallia) are an important source of chemically diverse metabolites with a broad spectrum of biological activities. Herein, we perform a comparative study between high-resolution proton nuclear magnetic resonance (1H-NMR) and pure shift yielded by chirp excitation (PSYCHE) experiments to analyze the metabolic profile of 24 soft corals from the Colombian Caribbean to correlate chemical fingerprints with their cytotoxic activity against three cancer cell lines (human cervical carcinoma (SiHa), human prostatic carcinoma (PC3) and human lung adenocarcinoma (A549)). All data obtained were explored using multivariate analysis using principal components analysis (PCA) and orthogonal partial least squares (OPLS) analysis. The results did not show a significant correlation between clusters using 1H-NMR data in the PCA and OPLS-DA models and therefore did not provide conclusive evidence; on the other hand, a metabolomic analysis of PSYCHE data obtained under the same parameters revealed that when a decoupled experiment is performed, it was possible to establish a statistically valid correlation between the chemical composition of soft corals and their cytotoxic activity against the PC3 cancer cell line, where the asperdiol and plexaurolone markers were putatively identified and related to the cytotoxic activity presented by extracts of Plexaurella sp. and Plexaura kukenthali, respectively. These results increase the speed, effectiveness and reliability of analyses for the study of this type of complex matrices.
Metastasis-associated fibroblasts promote angiogenesis in metastasized pancreatic cancer via the CXCL8 and the CCL2 axes
Authors: Pausch Thomas M. , Aue Elisa , Wirsik Naita M. , Freire Valls Aida , Shen Ying , Radhakrishnan Praveen , Hackert Thilo , Schneider Martin , Schmidt Thomas
Published: March 2020

The characteristic desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) is a key contributor to its lethality. This stromal microenvironment is populated by cancer-associated fibroblasts (CAFs) that interact with cancer cells to drive progression and chemo-resistance. Research has focused on CAFs in the primary tumour but not in metastases, calling into question the role of analogous metastasis-associated fibroblasts (MAFs). We infer a role of MAFs in murine hepatic metastases following untargeted treatment with the anti-angiogenic drug sunitinib in vivo. Treated metastases were smaller and had fewer stromal cells, but were able to maintain angiogenesis and metastasis formation in the liver. Furthermore, sunitinib was ineffective at reducing MAFs alongside other stromal cells. We speculate that cancer cells interact with MAFs to maintain angiogenesis and tumour progression. Thus, we tested interactions between metastatic pancreatic cancer cells and fibroblasts using in vitro co-culture systems. Co-cultures enhanced fibroblast proliferation and induced angiogenesis. We identify carcinoma-educated fibroblasts as the source of angiogenesis via secretions of CXCL8 (aka IL-8) and CCL2 (aka MCP-1). Overall, we demonstrate that metastasis-associated fibroblasts have potential as a therapeutic target and highlight the CXCL8 and CCL2 axes for further investigation.
Author Correction: Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
Authors: Smolarczyk Ryszard , Cichoń Tomasz , Pilny Ewelina , Jarosz-Biej Magdalena , Poczkaj Aleksandra , Kułach Natalia , Szala Stanisław
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The First 3D Model of the Full-Length KIT Cytoplasmic Domain Reveals a New Look for an Old Receptor
Authors: Inizan François , Hanna Myriam , Stolyarchuk Maxim , Chauvot de Beauchêne Isaure , Tchertanov Luba
Published: March 2020

Receptor tyrosine kinases (RTKs) are key regulators of normal cellular processes and have a critical role in the development and progression of many diseases. RTK ligand-induced stimulation leads to activation of the cytoplasmic kinase domain that controls the intracellular signalling. Although the kinase domain of RTKs has been extensively studied using X-ray analysis, the kinase insert domain (KID) and the C-terminal are partially or fully missing in all reported structures. We communicate the first structural model of the full-length RTK KIT cytoplasmic domain, a crucial target for cancer therapy. This model was achieved by integration of ab initio KID and C-terminal probe models into an X-ray structure, and by their further exploration through molecular dynamics (MD) simulation. An extended (2-µs) MD simulation of the proper model provided insight into the structure and conformational dynamics of the full-length cytoplasmic domain of KIT, which can be exploited in the description of the KIT transduction processes.
Hypoxia-inducible factor-1 alpha maintains mouse articular cartilage through suppression of NF-κB signaling
Authors: Okada Keita , Mori Daisuke , Makii Yuma , Nakamoto Hideki , Murahashi Yasutaka , Yano Fumiko , Chang Song Ho , Taniguchi Yuki , Kobayashi Hiroshi , Semba Hiroaki , Takeda Norihiko , Piao Wen , Hanaoka Kenjiro , Nagano Tetsuo , Tanaka Sakae , Saito Taku
Published: March 2020

HIF-1α, an essential transcription factor under hypoxic condition, is indispensable for chondrocytes during skeletal development but its expression and roles in articular chondrocytes are yet to be revealed. We examined HIF-1α protein expression and the hypoxic condition during mouse osteoarthritis (OA) development using state of the art hypoxic probes and found that its expression decreased as OA progressed, coinciding with the change in hypoxic conditions in articular cartilage. Gain- and loss-of-function of HIF-1α in cell culture experiments showed that HIF-1α suppressed catabolic genes such as Mmp13 and Hif2a. We confirmed these anticatabolic effects by measuring glycosaminoglycan release from wild type and conditional knock-out mice femoral heads cultured ex vivo. We went on to surgically induce OA in mice with chondrocyte-specific deletion of Hif1a and found that the development of OA was exacerbated. Increased expression of catabolic factors and activation of NF-κB signalling was clearly evident in the knock-out mice. By microarray analysis, C1qtnf3 was identified as a downstream molecule of HIF-1α, and experiments showed it exerted anti-catabolic effects through suppression of NF-κB. We conclude that HIF-1α has an anti-catabolic function in the maintenance of articular cartilage through suppression of NF-κB signalling.