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1.
Bioengineering (Basel). 2019 Jan 17;6(1). pii: E8. doi: 10.3390/bioengineering6010008.

Characterization of Plasma-Derived Extracellular Vesicles Isolated by Different Methods: A Comparison Study.

Author information

1
Department of Chemical and Enviromental Engineering, Faculty of Chemistry, University of Oviedo, 33006 Oviedo, Spain. eserranope@uoc.edu.
2
Department of Analytical and Physical Chemistry, Faculty of Chemistry, University of Oviedo, 33006 Oviedo, Spain. oliveiramyriam@outlook.es.
3
Department of Physics, Gijón Polytechnic School of Engineering, University of Oviedo, 33006 Oviedo, Spain. rivas@uniovi.es.
4
Neurology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain. simplementepon@gmail.com.
5
Neurology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain. jvillafani@yahoo.com.
6
Department of Morphology and Cellular Biology, Instituto de Neurociencias del Principado de Asturias (INEUROPA), University of Oviedo, 33006 Oviedo, Spain. anavarro@uniovi.es.
7
Department of Analytical and Physical Chemistry, Faculty of Chemistry, University of Oviedo, 33006 Oviedo, Spain. esther_sp84@yahoo.es.
8
Neurology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain. e.cernudamorollon@yahoo.es.

Abstract

Extracellular vesicles (EV) are small membrane structures released by cells that act as potent mediators of intercellular communication. The study of EV biology is important, not only to strengthen our knowledge of their physiological roles, but also to better understand their involvement in several diseases. In the field of biomedicine they have been studied as a novel source of biomarkers and drug delivery vehicles. The most commonly used method for EV enrichment in crude pellet involves serial centrifugation and ultracentrifugation. Recently, different protocols and techniques have been developed to isolate EV that imply less time and greater purification. Here we carry out a comparative analysis of three methods to enrich EV from plasma of healthy controls: ultracentrifugation, ExoQuickTM precipitation solution (System Biosciences), and Total Exosome Isolation kit (Invitrogen). Our results show that commercial precipitation reagents are more efficient and enable higher EV enrichment factors compared with traditional ultracentrifugation, although subsequent imaging analysis is not possible with some of them. We hope that this work will contribute to the current research on isolation techniques to assist the progress of clinical applications with diagnostic or therapeutic objectives.

KEYWORDS:

enrichment; extracellular vesicles; lateral flow immunoassay; nanoparticle tracking analysis; ultracentrifugation

PMID:
30658418
DOI:
10.3390/bioengineering6010008
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2.
Int J Mol Sci. 2019 Jan 17;20(2). pii: E379. doi: 10.3390/ijms20020379.

Analytical Methods for Detection of Plant Metabolomes Changes in Response to Biotic and Abiotic Stresses.

Author information

1
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland. apiasecka@ibch.poznan.pl.
2
Institute of Plant Genetics, Polish Academy of Sciences, Strzeszynska 34, 60-479 Poznań, Poland. apiasecka@ibch.poznan.pl.
3
Institute of Plant Genetics, Polish Academy of Sciences, Strzeszynska 34, 60-479 Poznań, Poland. pkac@igr.poznan.pl.
4
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland. mackis@ibch.poznan.pl.

Abstract

Abiotic and biotic stresses are the main reasons of substantial crop yield losses worldwide. Research devoted to reveal mechanisms of plant reactions during their interactions with the environment are conducted on the level of genome, transcriptome, proteome, and metabolome. Data obtained during these studies would permit to define biochemical and physiological mechanisms of plant resistance or susceptibility to affecting factors/stresses. Metabolomics based on mass spectrometric techniques is an important part of research conducted in the direction of breeding new varieties of crop plants tolerant to the affecting stresses and possessing good agronomical features. Studies of this kind are carried out on model, crop and resurrection plants. Metabolites profiling yields large sets of data and due to this fact numerous advanced statistical and bioinformatic methods permitting to obtain qualitative and quantitative evaluation of the results have been developed. Moreover, advanced integration of metabolomics data with these obtained on other omics levels: genome, transcriptome and proteome should be carried out. Such a holistic approach would bring us closer to understanding biochemical and physiological processes of the cell and whole plant interacting with the environment and further apply these observations in successful breeding of stress tolerant or resistant crop plants.

KEYWORDS:

abiotic stress; biotic stress; mass spectrometry; metabolome; metabolomics; secondary; specialized metabolites

PMID:
30658398
DOI:
10.3390/ijms20020379
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3.
Sci Rep. 2019 Jan 17;9(1):188. doi: 10.1038/s41598-018-37320-0.

Predictors of objective cognitive impairment and subjective cognitive complaints in patients with Fabry disease.

Author information

1
Department of Endocrinology and Metabolism, Amsterdam University Medical Centers location Academic Medical Center, Amsterdam, The Netherlands.
2
Department of Medical Psychology, Amsterdam University Medical Centers location Academic Medical Center, Amsterdam, The Netherlands.
3
Department of Neurology, Amsterdam University Medical Centers location Academic Medical Center, Amsterdam, The Netherlands.
4
Department of Radiology, Massachusetts General Hospital, Boston, United States.
5
Department of Radiology, Hospital Moinhos de Vento, Porto Alegre, Brazil.
6
Imaging Section, DASA, São Paulo, Brazil.
7
Clinical Research Unit/Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers location Academic Medical Center, Amsterdam, The Netherlands.
8
Department of Endocrinology and Metabolism, Amsterdam University Medical Centers location Academic Medical Center, Amsterdam, The Netherlands. m.langeveld@amc.uva.nl.

Abstract

This study investigates the relationship between objective cognitive impairment (OCI), subjective cognitive complaints and depressive symptoms in men and women with classical and non-classical Fabry disease (FD). Cognitive functioning was assessed using a neuropsychological test battery, subjective cognitive complaints using a structured interview and depressive symptoms using a depression scale (CESD). Eighty-one patients were included (mean age 44.5 ± 14.3, 35% men, 74% classical). Subjective cognitive complaints were reported by 64% of all patients. OCI was present in thirteen patients (16%), predominantly in men with classical FD. Thirty-one patients (38%) had a high score (≥16) on the CESD scale. Male sex (OR, 6.8; 95%CI, 1.6-39.8; p = 1.6 * 10-2) and stroke (OR, 6.4; 95% CI, 1.1-41.0; p = 3.7 * 10-2) were independently positively associated with OCI, and premorbid IQ (one IQ point increase: OR, 0.91; 95%CI, 0.82-0.98; p = 3.8 * 10-2) was independently negatively associated with OCI. The CESD-score (one point increase: OR, 1.07; 95% CI, 1.02-1.13; p = 3.3 * 10-3) and a history of depression (OR, 2.7; 95% CI, 1.1-7.3; p = 3.9 * 10-2) were independently positively associated with subjective cognitive complaints. OCI is present in 16% of FD patients, warranting referral for neuropsychological assessment. Nevertheless, subjective cognitive complaints are related to depressive symptoms, emphasizing the importance of recognition and treatment of the latter.

PMID:
30655570
DOI:
10.1038/s41598-018-37320-0
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4.
J Synchrotron Radiat. 2019 Jan 1;26(Pt 1):184-193. doi: 10.1107/S1600577518015370. Epub 2019 Jan 1.

Quantification of propagating and standing surface acoustic waves by stroboscopic X-ray photoemission electron microscopy.

Author information

1
Experiments Divison, ALBA Synchrotron, Carrer de la Llum 2-26, Cerdanyola del Valles, 08290 Barcelona, Spain.
2
Department of Condensed Matter Physics, University of Barcelona, 08028 Barcelona, Spain.
3
Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, 08193 Bellaterra, Spain.
4
Paul-Drude-Institut für Festkörperelektronik, Leibniz-Institut im Forschungsverbund Berlin eV, Germany.
5
Institut für Physik, Johannes Gutenberg Universität, Staudingerweg 7, D-55128 Mainz, Germany.

Abstract

The quantification of surface acoustic waves (SAWs) in LiNbO3 piezoelectric crystals by stroboscopic X-ray photoemission electron microscopy (XPEEM), with a temporal smearing below 80 ps and a spatial resolution below 100 nm, is reported. The contrast mechanism is the varying piezoelectric surface potential associated with the SAW phase. Thus, kinetic energy spectra of photoemitted secondary electrons measure directly the SAW electrical amplitude and allow for the quantification of the associated strain. The stroboscopic imaging combined with a deliberate detuning allows resolving and quantifying the respective standing and propagating components of SAWs from a superposition of waves. Furthermore, standing-wave components can also be imaged by low-energy electron microscopy (LEEM). Our method opens the door to studies that quantitatively correlate SAWs excitation with a variety of sample electronic, magnetic and chemical properties.

KEYWORDS:

LEEM; LiNbO3; standing and propagating SAW; stroboscopic XPEEM; surface acoustic waves (SAWs)

5.
Neurotox Res. 2019 Jan 15. doi: 10.1007/s12640-018-9993-0. [Epub ahead of print]

Differential Expression of Striatal ΔFosB mRNA and FosB mRNA After Different Levodopa Treatment Regimens in a Rat Model of Parkinson's Disease.

Author information

1
Laboratory of Neuropharmacology, Faculty of Chemistry Sciences, Benemerita Universidad Autonoma de Puebla, Puebla, Mexico.
2
Institut de Neurociències, Departamento de Bioquímica y de Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Edifici M, Campus de la UAB, C.P. 08193, Barcelona, Spain.
3
Movement Disorders Unit, Deparment of Neurology, Hospital de la Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.
4
Laboratory of Neuropsychopharmacology of Movement Disorders, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
5
Biomedical Research Institute Sant Pau (IIB-Sant Pau), Barcelona, Spain.
6
Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
7
Unidad Periférica de Neurociencias Inst. Nacional de Neurología y Neurocirugía Manuel Velasco S, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico.
8
Institut de Neurociències, Departamento de Bioquímica y de Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Edifici M, Campus de la UAB, C.P. 08193, Barcelona, Spain. jose.aguilera@uab.cat.
9
Centro Investigación Biomedica en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain. jose.aguilera@uab.cat.
10
Laboratory of Neuropharmacology, Faculty of Chemistry Sciences, Benemerita Universidad Autonoma de Puebla, Puebla, Mexico. ilhlimon@yahoo.com.mx.
11
Laboratory of Neuropharmacology, FCQ-Benemérita Universidad Autónoma de Puebla, 14 Sur y Av. San Claudio C.U. Edificio 105C, A.P. 72570, Puebla de Zaragoza, Puebla, Mexico. ilhlimon@yahoo.com.mx.

Abstract

Levodopa-induced dyskinesia (LID) is the main side effect associated with levodopa treatment and represents the biggest challenge for Parkinson's disease therapy. While the overexpression of ΔFosB transcription factor is related to the development of LID, few studies have been undertaken on fosB gene transcriptional regulation induced by levodopa in vivo. The aim of this study is to evaluate the expression of ΔFosB mRNA and FosB mRNA in the striatum after acute, chronic, and subchronic levodopa treatment in rats with unilateral 6-OHDA-lesion in the medial forebrain bundle. qRT-PCR was used to compare the levels of ΔFosB and FosB mRNA expression in the dopamine-denervated striatum following levodopa treatment. While the results obtained after a single levodopa dose indicate a significant increase of ∆FosB mRNA expression in the striatum 1 h post-injection, the levels returned to baseline values after 24 h. After subchronic levodopa treatment, the levels of ∆FosB and FosB mRNA expression were lower 1 h post-administration of levodopa in comparison with acute effect. However, after chronic levodopa treatment, ∆FosB mRNA expression in the striatum persisted in dyskinetic rats only, and positive correlation was found between the levels of ∆FosB mRNA expression 1 h after levodopa administration and the level of dyskinetic severity. In summary, acute levodopa treatment led to highly increased levels of ∆FosB mRNA expression in the striatum. While repeated administration induced a partial desensitization of the fosB gene in the striatum, it did not suppress its activity completely, which could explain why dyskinesia appears after chronic levodopa treatment.

KEYWORDS:

Dyskinesia; Levodopa; Striatum; fosB gene; ΔFosB mRNA

6.
Adv Mater. 2019 Jan 15:e1806817. doi: 10.1002/adma.201806817. [Epub ahead of print]

Enhancing Light Emission in Interface Engineered Spin-OLEDs through Spin-Polarized Injection at High Voltages.

Author information

1
Instituto de Ciencia Molecular (ICMol), Universidad de Valencia. Catedrático José Beltrán 2, 46890, Paterna, Spain.
2
Instituto per lo Studio dei Materiali Nanostrutturati ISMN - CNR, Via Gobetti, 101, Bologna, 40129, Italy.
3
Department of Physics and Research Center OPTIMAS, University of Kaiserslautern, Erwin-Schroedinger-Strasse 46, 67663, Kaiserslautern, Germany.
4
Experimentelle Physik VI, Technische Universität Dortmund, 44221, Dortmund, Germany.

Abstract

The quest for a spin-polarized organic light-emitting diode (spin-OLED) is a common goal in the emerging fields of molecular electronics and spintronics. In this device, two ferromagnetic (FM) electrodes are used to enhance the electroluminescence intensity of the OLED through a magnetic control of the spin polarization of the injected carriers. The major difficulty is that the driving voltage of an OLED device exceeds a few volts, while spin injection in organic materials is only efficient at low voltages. The fabrication of a spin-OLED that uses a conjugated polymer as bipolar spin collector layer and ferromagnetic electrodes is reported here. Through a careful engineering of the organic/inorganic interfaces, it is succeeded in obtaining a light-emitting device showing spin-valve effects at high voltages (up to 14 V). This allows the detection of a magneto-electroluminescence (MEL) enhancement on the order of a 2.4% at 9 V for the antiparallel (AP) configuration of the magnetic electrodes. This observation provides evidence for the long-standing fundamental issue of injecting spins from magnetic electrodes into the frontier levels of a molecular semiconductor. The finding opens the way for the design of multifunctional devices coupling the light and the spin degrees of freedom.

KEYWORDS:

molecular spintronics; multifunctional spintronic devices; spin-OLED; spin-injection

7.
Am J Bot. 2019 Jan;106(1):123-136. doi: 10.1002/ajb2.1223. Epub 2019 Jan 15.

Variation in the transcriptome of different ecotypes of Arabidopsis thaliana reveals signatures of oxidative stress in plant responses to spaceflight.

Author information

1
Department of Biochemistry and Molecular Biology, University of Nevada-Reno, 1664 N. Virginia Street, Reno, NV, 89557, USA.
2
Department of Botany, University of Wisconsin-Madison, Birge Hall, 430 Lincoln Drive, Madison, WI, 53706, USA.

Abstract

PREMISE OF THE STUDY:

Spaceflight provides a unique environment in which to dissect plant stress response behaviors and to reveal potentially novel pathways triggered in space. We therefore analyzed the transcriptomes of Arabidopsis thaliana plants grown on board the International Space Station to find the molecular fingerprints of these space-related response networks.

METHODS:

Four ecotypes (Col-0, Ws-2, Ler-0 and Cvi-0) were grown on orbit and then their patterns of transcript abundance compared to ground-based controls using RNA sequencing.

KEY RESULTS:

Transcripts from heat-shock proteins were upregulated in all ecotypes in spaceflight, whereas peroxidase transcripts were downregulated. Among the shared and ecotype-specific changes, gene classes related to oxidative stress and hypoxia were detected. These spaceflight transcriptional response signatures could be partly mimicked on Earth by a low oxygen environment and more fully by oxidative stress (H2 O2 ) treatments.

CONCLUSIONS:

These results suggest that the spaceflight environment is associated with oxidative stress potentially triggered, in part, by hypoxic response. Further, a shared spaceflight response may be through the induction of molecular chaperones (such as heat shock proteins) that help protect cellular machinery from the effects of oxidative damage. In addition, this research emphasizes the importance of considering the effects of natural variation when designing and interpreting changes associated with spaceflight experiments.

KEYWORDS:

Arabidopsis thaliana ; BRIC ; ecotype; heat shock protein; hypoxia; peroxidase; reactive oxygen species; spaceflight

PMID:
30644539
DOI:
10.1002/ajb2.1223
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8.
Sci Rep. 2019 Jan 15;9(1):136. doi: 10.1038/s41598-018-36907-x.

Plant microbiome-dependent immune enhancing action of Echinacea purpurea is enhanced by soil organic matter content.

Author information

1
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, P.O. Box 1848, University, MS, USA.
2
Department of Biology, The University of Mississippi, University, MS, USA.
3
Crop Production Systems Research Unit, USDA Agricultural Research Service, P.O. Box 350, Stoneville, MS, USA.
4
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, P.O. Box 1848, University, MS, USA. ndpugh@olemiss.edu.
5
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, P.O. Box 1848, University, MS, USA. dpasco@olemiss.edu.
6
Department of BioMolecular Sciences, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, P.O. Box 1848, University, MS, USA. dpasco@olemiss.edu.

Abstract

We previously demonstrated that extracts from Echinacea purpurea material varied substantially in their ability to activate macrophages in vitro and that this variation was due to differences in their content of bacterial components. The purpose of the current study was to identify soil conditions (organic matter, nitrogen, and moisture content) that alter the macrophage activation potential of E. purpurea and determine whether these changes in activity correspond to shifts in the plant-associated microbiome. Increased levels of soil organic matter significantly enhanced macrophage activation exhibited by the root extracts of E. purpurea (p < 0.0001). A change in soil organic matter content from 5.6% to 67.4% led to a 4.2-fold increase in the macrophage activation potential of extracts from E. purpurea. Bacterial communities also differed significantly between root materials cultivated in soils with different levels of organic matter (p < 0.001). These results indicate that the level of soil organic matter is an agricultural factor that can alter the bacterial microbiome, and thereby the activity, of E. purpurea roots. Since ingestion of bacterial preparation (e.g., probiotics) is reported to impact human health, it is likely that the medicinal value of Echinacea is influenced by cultivation conditions that alter its associated bacterial community.

9.
Clin Rheumatol. 2019 Jan 14. doi: 10.1007/s10067-019-04436-1. [Epub ahead of print]

Mindfulness is associated with psychological health and moderates the impact of fibromyalgia.

Author information

1
Center for Complementary and Integrative Medicine & Division of Rheumatology, Tufts Medical Center, Tufts University School of Medicine, 800 Washington Street, Box 406, Boston, MA, 02111, USA.
2
The Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, USA.
3
Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA, USA.
4
Center for Treatment Comparison and Integrative Analysis, Tufts Medical Center, Boston, MA, USA.
5
Center for Complementary and Integrative Medicine & Division of Rheumatology, Tufts Medical Center, Tufts University School of Medicine, 800 Washington Street, Box 406, Boston, MA, 02111, USA. cwang2@tuftsmedicalcenter.org.

Abstract

OBJECTIVE:

Previous studies suggest mindfulness is associated with pain and depression. However, its impact in individuals with fibromyalgia remains unclear. We examined associations between mindfulness and physical and psychological symptoms, pain interference, and quality of life in fibromyalgia patients.

METHODS:

We performed a cross-sectional analysis on baseline data from a fibromyalgia clinical trial. Mindfulness was assessed using the Five Facet Mindfulness Questionnaire (FFMQ). Pearson's correlations and multivariable linear regression models were used to evaluate associations between mindfulness and fibromyalgia impact, pain interference, physical function, depression, anxiety, stress, self-efficacy, and health-related quality of life. We also examined whether mindfulness moderated associations between fibromyalgia impact and psychological outcomes.

RESULTS:

A total of 177 participants (age 52.0 ± 12.2 (SD) years; 93.2% women; 58.8% white; body mass index 30.1 ± 6.7 kg/m2; FFMQ score 131.3 ± 20.7; Revised Fibromyalgia Impact Questionnaire score 57.0 ± 19.4) were included. Higher total mindfulness was significantly associated with lower fibromyalgia impact (r = - 0.25), pain interference (r = - 0.31), stress (r = - 0.56), anxiety (r = - 0.58), depression (r = - 0.54), and better mental health-related quality of life (r = 0.57). Describing, Acting-with-awareness, and Non-judging facets of mindfulness were also associated with these outcomes. Mindfulness moderated the effect of fibromyalgia impact on anxiety (interaction P = 0.01).

CONCLUSION:

Higher mindfulness is associated with less pain interference, lower impact of fibromyalgia, and better psychological health and quality of life in people with fibromyalgia. Mindfulness moderates the influence of fibromyalgia impact on anxiety, suggesting mindfulness may alter how patients cope with fibromyalgia. Future studies should assess how mind-body therapies aiming to cultivate mindfulness may impact the well-being of patients with fibromyalgia.

KEY POINTS:

• Higher mindfulness was associated with better psychological health and lower overall impact of fibromyalgia. • Mindfulness moderated the relationship between overall fibromyalgia impact and anxiety.

KEYWORDS:

Anxiety; Depression; Fibromyalgia; Mindfulness; Pain; Quality of life; Stress

10.
Curr Opin Psychol. 2018 Dec 13;28:120-125. doi: 10.1016/j.copsyc.2018.12.004. [Epub ahead of print]

Mindfulness, acceptance, and emotion regulation: perspectives from Monitor and Acceptance Theory (MAT).

Author information

1
University of Pittsburgh, United States. Electronic address: ekl24@pitt.edu.
2
Carnegie Mellon University, United States.

Abstract

Experiential acceptance-an orientation of receptivity and noninterference with present-moment experiences-is described as central to mindfulness interventions, yet little experimental work has tested acceptance as a mechanism for mindfulness intervention effects. Guided by Monitor and Acceptance Theory (MAT), this review situates acceptance as an emotion regulation mechanism and reviews self-report mindfulness literature showing that attention monitoring skills are only associated with beneficial mental and physical health outcomes when accompanied by acceptance skills. New experimental dismantling work shows that removing acceptance training from mindfulness interventions reduces their efficacy for improving stress, positive emotion, and social relationship outcomes. Overall, converging evidence demonstrates that acceptance is a critical emotion regulation mechanism of mindfulness interventions. This work advances basic research, has translational value, and offers opportunities for future research.

11.
Int J Bipolar Disord. 2019 Jan 12;7(1):3. doi: 10.1186/s40345-018-0137-5.

Rumination related activity in brain networks mediating attentional switching in euthymic bipolar patients.

Author information

1
Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Kalliopi.Apazoglou@unige.ch.
2
Department of Mental Health and Psychiatry, University Hospital of Geneva, Geneva, Switzerland.
3
Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
4
Department of Neuroscience, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

Abstract

INTRODUCTION:

Mood disorder patients have a tendency to be more internally oriented, with difficulties in switching attentional focus, which might result in the generation of negative thoughts, such as rumination. The present study explored self-referential neural activity correlating with rumination tendency and attentional switching capacity in bipolar disorder.

METHODS:

Twenty euthymic bipolar patients and twenty matched healthy controls underwent a novel introspection task of switching between internally and externally focused attention during a word processing task, while their brain activity was assessed using functional MRI.

RESULTS:

During internal focus, higher activity in self-related regions (mPFC, PCC) was found in euthymic bipolar patients as compared to controls, verifying the hypothesis of exaggerated recruitment of self-referential processes in bipolar subjects. Switching from internal to external focus revealed higher parahippocampal activity in patients as compared to controls, additionally more pronounced when switching away from negative as compared to positive self-referential information. Furthermore, rumination traits correlated with activity in PCC, subgenual and pregenual ACC, and bilateral anterior insula during repetition of internal focus, specifically when evaluating negative words. Finally, we used ACC subregions that correlated with tendency to ruminate as seeds for a whole brain connectivity analysis. Patients showed stronger connectivity between sgACC (seed), pgACC, dPFC, and anterior insula during internal focus, whereas pgACC (seed) was more strongly connected to parahippocampal gyrus when switching from internal to external focus.

CONCLUSIONS:

These findings reveal an overactive rumination-related network whose activity is enhanced by negative information in euthymic bipolar patients, which could possibly contribute to impaired switching of thoughts away from internal attention.

KEYWORDS:

Attentional switch; Bipolar disorder; RRS; Rumination; Self-reference; sgACC

12.
Bull Math Biol. 2019 Jan 11. doi: 10.1007/s11538-018-00566-w. [Epub ahead of print]

From Fixation Probabilities to d-player Games: An Inverse Problem in Evolutionary Dynamics.

Author information

1
Departamento de Matemática and Centro de Matemática e Apliçoes, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829-516, Caparica, Portugal.
2
Instituto de Matemática e Estatística, Universidade Federal Fluminense, R. Prof. Marcos Waldemar de Freitas Reis, s/n, Niterói, RJ, 24210-201, Brasil. maxsouza@id.uff.br.

Abstract

The probability that the frequency of a particular trait will eventually become unity, the so-called fixation probability, is a central issue in the study of population evolution. Its computation, once we are given a stochastic finite population model without mutations and a (possibly frequency dependent) fitness function, is straightforward and it can be done in several ways. Nevertheless, despite the fact that the fixation probability is an important macroscopic property of the population, its precise knowledge does not give any clear information about the interaction patterns among individuals in the population. Here we address the inverse problem: from a given fixation pattern and population size, we want to infer what is the game being played by the population. This is done by first exploiting the framework developed in Chalub and Souza (J Math Biol 75:1735-1774, 2017), which yields a fitness function that realises this fixation pattern in the Wright-Fisher model. This fitness function always exists, but it is not necessarily unique. Subsequently, we show that any such fitness function can be approximated, with arbitrary precision, using d-player game theory, provided d is large enough. The pay-off matrix that emerges naturally from the approximating game will provide useful information about the individual interaction structure that is not itself apparent in the fixation pattern. We present extensive numerical support for our conclusions.

KEYWORDS:

Fixation probability; Game theory; Inverse problems; Wright–Fisher process

13.
Virol J. 2019 Jan 11;16(1):7. doi: 10.1186/s12985-018-1106-4.

Identification and localization of Tospovirus genus-wide conserved residues in 3D models of the nucleocapsid and the silencing suppressor proteins.

Author information

1
Department of Plant Pathology, Washington State University, Pullman, WA, 99164, USA.
2
Department of Mathematics and Computer Science, University of Missouri, St. Louis, MO, 63121, USA.
3
Department of Microbiology and Immunology, Louisiana State University, Shreverport, LA, 71101, USA.
4
Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO, 65211, USA.
5
Department of Plant Pathology, Washington State University, Pullman, WA, 99164, USA. hrp@wsu.edu.

Abstract

BACKGROUND:

Tospoviruses (genus Tospovirus, family Peribunyaviridae, order Bunyavirales) cause significant losses to a wide range of agronomic and horticultural crops worldwide. Identification and characterization of specific sequences and motifs that are critical for virus infection and pathogenicity could provide useful insights and targets for engineering virus resistance that is potentially both broad spectrum and durable. Tomato spotted wilt virus (TSWV), the most prolific member of the group, was used to better understand the structure-function relationships of the nucleocapsid gene (N), and the silencing suppressor gene (NSs), coded by the TSWV small RNA.

METHODS:

Using a global collection of orthotospoviral sequences, several amino acids that were conserved across the genus and the potential location of these conserved amino acid motifs in these proteins was determined. We used state of the art 3D modeling algorithms, MULTICOM-CLUSTER, MULTICOM-CONSTRUCT, MULTICOM-NOVEL, I-TASSER, ROSETTA and CONFOLD to predict the secondary and tertiary structures of the N and the NSs proteins.

RESULTS:

We identified nine amino acid residues in the N protein among 31 known tospoviral species, and ten amino acid residues in NSs protein among 27 tospoviral species that were conserved across the genus. For the N protein, all three algorithms gave nearly identical tertiary models. While the conserved residues were distributed throughout the protein on a linear scale, at the tertiary level, three residues were consistently located in the coil in all the models. For NSs protein models, there was no agreement among the three algorithms. However, with respect to the localization of the conserved motifs, G18 was consistently located in coil, while H115 was localized in the coil in three models.

CONCLUSIONS:

This is the first report of predicting the 3D structure of any tospoviral NSs protein and revealed a consistent location for two of the ten conserved residues. The modelers used gave accurate prediction for N protein allowing the localization of the conserved residues. Results form the basis for further work on the structure-function relationships of tospoviral proteins and could be useful in developing novel virus control strategies targeting the conserved residues.

KEYWORDS:

Conserved amino acids; Nucleoprotein; Silencing suppressor; Three-dimensional protein structure; Tospovirus

14.
Int J Mol Sci. 2019 Jan 9;20(2). pii: E237. doi: 10.3390/ijms20020237.

Transcriptome Analysis Reveals the Mechanism of Fluoride Treatment Affecting Biochemical Components in Camellia sinensis.

Author information

1
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. 2016104092@njau.edu.cn.
2
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. panjunting@ibcas.ac.cn.
3
Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China. panjunting@ibcas.ac.cn.
4
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. 2017804197@njau.edu.cn.
5
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. myc@njau.edu.cn.
6
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. 2017104087@njau.edu.cn.
7
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. zhuxujun@njau.edu.cn.
8
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. njauwb@njau.edu.cn.
9
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. fangwp@njau.edu.cn.
10
College of Horticulture, Nanjing Agricultural University, Nanjing 210095, China. wangyuhua@njau.edu.cn.

Abstract

Tea (Camellia sinensis (L.) O. Kuntze), one of the main crops in China, is high in various bioactive compounds including flavonoids, catechins, caffeine, theanine, and other amino acids. C. sinensis is also known as an accumulator of fluoride (F), and the bioactive compounds are affected by F, however, the mechanism remains unclear. Here, the effects of F treatment on the accumulation of F and major bioactive compounds and gene expression were investigated, revealing the molecular mechanisms affecting the accumulation of bioactive compounds by F treatment. The results showed that F accumulation in tea leaves gradually increased under exogenous F treatments. Similarly, the flavonoid content also increased in the F treatment. In contrast, the polyphenol content, free amino acids, and the total catechins decreased significantly. Special amino acids, such as sulfur-containing amino acids and proline, had the opposite trend of free amino acids. Caffeine was obviously induced by exogenous F, while the theanine content peaked after two day-treatment. These results suggest that the F accumulation and content of bioactive compounds were dramatically affected by F treatment. Furthermore, differentially expressed genes (DEGs) related to the metabolism of main bioactive compounds and amino acids, especially the pivotal regulatory genes of catechins, caffeine, and theanine biosynthesis pathways, were identified and analyzed using high-throughput Illumina RNA-Seq technology and qRT-PCR. The expression of pivotal regulatory genes is consistent with the changes of the main bioactive compounds in C. sinensis leaves, indicating a complicated molecular mechanism for the above findings. Overall, these data provide a reference for exploring the possible molecular mechanism of the accumulation of major bioactive components such as flavonoid, catechins, caffeine, theanine and other amino acids in tea leaves in response to fluoride treatment.

KEYWORDS:

Camellia sinensis; RNA-Seq; bioactive compounds; fluoride; transcriptome

PMID:
30634430
DOI:
10.3390/ijms20020237
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15.
Mol Nutr Food Res. 2019 Jan 11:e1800813. doi: 10.1002/mnfr.201800813. [Epub ahead of print]

Fish Oil Protects Wild Type and Uncoupling Protein 1-Deficient Mice from Obesity and Glucose Intolerance by Increasing Energy Expenditure.

Author information

1
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-000, Brazil.
2
Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, 05508-000, Brazil.
3
Department of Nutritional Sciences and Obesity Research Cluster, Texas Tech University, Lubbock, 79409, TX, USA.

Abstract

SCOPE:

The mechanisms and involvement of uncoupling protein 1 (UCP1) in the protection from obesity and insulin resistance induced by intake of a high-fat diet rich in omega-3 (n-3) fatty acids are investigated.

METHODS AND RESULTS:

C57BL/6J mice are fed either a low-fat (control group) or one of two isocaloric high-fat diets containing either lard (HFD) or fish oil (HFN3) as fat source and evaluated for body weight, adiposity, energy expenditure, glucose homeostasis, and inguinal white and interscapular brown adipose tissue (iWAT and iBAT, respectively) gene expression, lipidome, and mitochondrial bioenergetics. HFN3 intake protected from obesity, glucose and insulin intolerances, and hyperinsulinemia. This is associated with increased energy expenditure, iWAT UCP1 expression, and incorporation of n-3 eicosapentaenoic and docosahexaenoic fatty acids in iWAT and iBAT triacylglycerol. Importantly, HFN3 is equally effective in reducing body weight gain, adiposity, and glucose intolerance and increasing energy expenditure in wild-type and UCP1-deficient mice without recruiting other thermogenic processes in iWAT and iBAT, such as mitochondrial uncoupling and SERCA-mediated calcium and creatine-driven substrate cyclings.

CONCLUSION:

Intake of a high-fat diet rich in omega-3 fatty acids protects both wild-type and UCP1-deficient mice from obesity and insulin resistance by increasing energy expenditure through unknown mechanisms.

KEYWORDS:

energy expenditure; fish oil; nonshivering thermogenesis; omega-3 fatty acids; uncoupling protein 1; white and brown adipose tissues

16.
Stat Med. 2019 Jan 10. doi: 10.1002/sim.8090. [Epub ahead of print]

Extreme learning machine Cox model for high-dimensional survival analysis.

Author information

1
School of Mathematics and Statistics, Central South University, Changsha, China.
2
Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, California.

Abstract

Some interesting recent studies have shown that neural network models are useful alternatives in modeling survival data when the assumptions of a classical parametric or semiparametric survival model such as the Cox (1972) model are seriously violated. However, to the best of our knowledge, the plausibility of adapting the emerging extreme learning machine (ELM) algorithm for single-hidden-layer feedforward neural networks to survival analysis has not been explored. In this paper, we present a kernel ELM Cox model regularized by an L0 -based broken adaptive ridge (BAR) penalization method. Then, we demonstrate that the resulting method, referred to as ELMCoxBAR, can outperform some other state-of-art survival prediction methods such as L1 - or L2 -regularized Cox regression, random survival forest with various splitting rules, and boosted Cox model, in terms of its predictive performance using both simulated and real world datasets. In addition to its good predictive performance, we illustrate that the proposed method has a key computational advantage over the above competing methods in terms of computation time efficiency using an a real-world ultra-high-dimensional survival data.

KEYWORDS:

censored data; extreme learning machine; machine learning; regularized Cox model; survival analysis

17.
Curr Genet. 2019 Jan 10. doi: 10.1007/s00294-019-00931-9. [Epub ahead of print]

Fusarium oxysporum f. sp. lycopersici C2H2 transcription factor FolCzf1 is required for conidiation, fusaric acid production, and early host infection.

Author information

1
State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, China. yingziyun@fafu.edu.cn.
2
State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, China.
3
Fujian Institute for Food and Drug Quality Control, Fuzhou, China.
4
State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, China. wbshim@tamu.edu.
5
Department of Plant Pathology and Microbiology, Texas A&M University, College Station, TX, USA. wbshim@tamu.edu.
6
State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, China. wangzh@fafu.edu.cn.
7
Institute of Oceanography, Minjiang University, Fuzhou, China. wangzh@fafu.edu.cn.

Abstract

The soil-borne, asexual fungus Fusarium oxysporum f.sp. lycopersici (Fol) is a causal agent of tomato wilt disease. The infection process of Fol comprises root recognition, adhesion, penetration, colonization of the root cortex and hyphal proliferation within the xylem vessels, which are under the regulation of virulence-involved transcription factors (TFs). In this study, we identified a gene, designated FolCZF1, which encodes a C2H2 TF in Fol. The homologs of FolCzf1 are also known to affect pathogenicity in F. graminearum and Magnaporthe oryzae on wheat and rice, respectively. We learned that FolCZF1 transcript level is upregulated in conidia and early host infection stage, which led us to hypothesize that FolCzf1 is associated with early host infection in Fol. The FolCZF1 deletion mutant (ΔFolCZF1) exhibited defects in growth rate, conidiation, conidia morphology and a complete loss of virulence on tomato root. Further microscopic observation showed that ΔFolCZF1 can penetrate the root but the primary infection hypha cannot extend its colonization inside the host tissue, suggesting that FolCzf1 TF plays an important role in early infection. Fusaric acid, a secondary metabolite produced by Fusarium species, is suggested as a virulence factor in many crop diseases. We found that FolCzf1 plays a critical role in fusaric acid production by regulating the expression of fusaric acid biosynthesis genes. In summary, FolCzf1 is required for conidiation, secondary metabolism, and early host infection in Fol, and we propose that homologs of FolCzf1 are required for early parasitic growth in other plant pathogenic filamentous fungi.

KEYWORDS:

FolCzf1; Fusaric acid; Fusarium oxysporum; Transcription factor; Virulence

18.
Materials (Basel). 2019 Jan 6;12(1). pii: E157. doi: 10.3390/ma12010157.

Laser Cutting: A Review on the Influence of Assist Gas.

Author information

1
Department of Applied Physics, University of Vigo, EEI, Lagoas-Marcosende 9. Vigo 36310, Spain. ariveiro@uvigo.es.
2
Department of Applied Physics, University of Vigo, EEI, Lagoas-Marcosende 9. Vigo 36310, Spain. fquintero@uvigo.es.
3
Department of Applied Physics, University of Vigo, EEI, Lagoas-Marcosende 9. Vigo 36310, Spain. mohamed@uvigo.es.
4
Department of Applied Physics, University of Vigo, EEI, Lagoas-Marcosende 9. Vigo 36310, Spain. jesusdv@uvigo.es.
5
Department of Materials Engineering, Applied Mechanics and Construction, University of Vigo, EEI, Lagoas-Marcosende, Vigo 36310, Spain. flusqui@uvigo.es.
6
Department of Applied Physics, University of Vigo, EEI, Lagoas-Marcosende 9. Vigo 36310, Spain. jpou@uvigo.es.
7
Department of Applied Physics, University of Vigo, EEI, Lagoas-Marcosende 9. Vigo 36310, Spain. racomesana@uvigo.es.

Abstract

Assist gas plays a central role in laser fusion cutting. In this work, the aerodynamic interactions between the assist gas and the workpiece are reviewed. An insight into those phenomena that hinder the cutting quality and performance is provided. These phenomena include shock waves, choking, boundary layer separation, etc. The most relevant and promising attempts to overcome these common problems related to the gas dynamics are surveyed. The review of the current scientific literature has revealed some gaps in the current knowledge of the role of the assist gas dynamics in laser cutting. The assist gas interactions have been investigated only under static conditions; and the dynamic interaction with the molten material on the cutting front has not been addressed. New nozzle designs with improved efficiency of molten material removal are required to improve cut quality; and cutting speed in current industrial laser cutting machines; especially in those assisted by new high-brightness laser sources.

KEYWORDS:

assist gas; laser cutting; nozzles; shock waves

PMID:
30621346
DOI:
10.3390/ma12010157
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19.
Pharmaceutics. 2019 Jan 5;11(1). pii: E20. doi: 10.3390/pharmaceutics11010020.

Chitosan-Based Mucoadhesive Vaginal Tablets for Controlled Release of the Anti-HIV Drug Tenofovir.

Author information

1
Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. racazorl@ucm.es.
2
Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. fnotar01@ucm.es.
3
Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. aracelimartin@ucm.es.
4
Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. rruizcar@ucm.es.
5
Instituto de Cerámica y Vidrio, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain. aitanath@icv.csic.es.
6
Instituto de Cerámica y Vidrio, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain. jrubio@icv.csic.es.
7
Departamento de Farmacia Galénica y Tecnología Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. mdveiga@ucm.es.

Abstract

Vaginal microbicides have the potential to give women at high risk of contracting HIV the option of self-protection by preventing the sexual transmission of the virus. In this paper, mucoadhesive vaginal tablets based on chitosan, alone and in combination with pectin and locust bean gum, were developed for the sustained release of tenofovir (an antiretroviral drug). The formulations were placed in simulant vaginal fluid (SVF) to swell, and Hg porosity and SEM microscopy were used for the microstructural characterization of the swelling witnesses. The results show that the association of pectin and chitosan generated polyelectrolyte complexes and produced a robust system able to maintain its structure during the swelling process, when small pores are formed. Drug release and bovine vaginal mucoadhesion studies were performed in SVF showing that tenofovir-controlled dissolution profiles and adhesion to the mucosa were conditioned by the swelling processes of the polymer/s in each formulation. Tablets based on chitosan/pectin have the most homogeneous tenofovir dissolution profiles and last up to 96 h, remaining attached to the vaginal mucosa for the same period. These formulations can therefore be considered a good option for the self-protection of women from the sexual transmission of HIV.

KEYWORDS:

chitosan; locust bean gum; mucoadhesive vaginal tablets; natural polymers combination; pectin; tenofovir controlled release; vaginal preexposure prophylaxis of HIV

PMID:
30621307
DOI:
10.3390/pharmaceutics11010020
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20.
Pharmaceutics. 2019 Jan 4;11(1). pii: E14. doi: 10.3390/pharmaceutics11010014.

Development of A New Delivery System Based on Drug-Loadable Electrospun Nanofibers for Psoriasis Treatment.

Author information

1
Institute of Research, Development and Innovation in Biotechnology of Elche (IDiBE) and Molecular and Cellular Biology Institute (IBMC), Miguel Hernández University (UMH), 03202 Elche, Spain. leticia.martinez@goumh.umh.es.
2
Institute of Research, Development and Innovation in Biotechnology of Elche (IDiBE) and Molecular and Cellular Biology Institute (IBMC), Miguel Hernández University (UMH), 03202 Elche, Spain. a.mira@umh.es.
3
Institute of Research, Development and Innovation in Biotechnology of Elche (IDiBE) and Molecular and Cellular Biology Institute (IBMC), Miguel Hernández University (UMH), 03202 Elche, Spain. asia.fernandez@umh.es.
4
Institute of Research, Development and Innovation in Biotechnology of Elche (IDiBE) and Molecular and Cellular Biology Institute (IBMC), Miguel Hernández University (UMH), 03202 Elche, Spain. rmateo@umh.es.
5
Institute of Research, Development and Innovation in Biotechnology of Elche (IDiBE) and Molecular and Cellular Biology Institute (IBMC), Miguel Hernández University (UMH), 03202 Elche, Spain. r.mallavia@umh.es.
6
Institute of Research, Development and Innovation in Biotechnology of Elche (IDiBE) and Molecular and Cellular Biology Institute (IBMC), Miguel Hernández University (UMH), 03202 Elche, Spain. alber.falco@umh.es.

Abstract

Psoriasis is a chronic autoimmune systemic disease with an approximate incidence of 2% worldwide; it is commonly characterized by squamous lesions on the skin that present the typical pain, stinging, and bleeding associated with an inflammatory response. In this work, poly(methyl vinyl ether-alt-maleic ethyl monoester) (PMVEMA-ES) nanofibers have been designed as a delivery vehicle for three therapeutic agents with palliative properties for the symptoms of this disease (salicylic acid, methyl salicylate, and capsaicin). For such a task, the production of these nanofibers by means of the electrospinning technique has been optimized. Their morphology and size have been characterized by optical microscopy and scanning electron microscopy (SEM). By selecting the optimal conditions to achieve the smallest and most uniform nanofibers, approximate diameters of up to 800⁻900 nm were obtained. It was also determined that the therapeutic agents that were used were encapsulated with high efficiency. The analysis of their stability over time by GC-MS showed no significant losses of the encapsulated compounds 15 days after their preparation, except in the case of methyl salicylate. Likewise, it was demonstrated that the therapeutic compounds that were encapsulated conserved, and even improved, their capacity to activate the transient receptor potential cation channel 1 (TRPV1) channel, which has been associated with the formation of psoriatic lesions.

KEYWORDS:

PMVE/MA; TRPV1; capsaicin; electrospinning; nanofibers; psoriasis

PMID:
30621136
DOI:
10.3390/pharmaceutics11010014
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