bluuebunny/crossref_metadata_2025 huggingface dataset:
Change in Spatial Distribution Patterns and Regeneration of Populus euphratica under Different Surface Soil Salinity Conditions
Authors: Zhang Pei , Deng Xiaoya , Long Aihua , Xu Hailiang , Ye Mao , Li Junfeng
Published: June 2019

Ecological conservation and restoration have increasingly captured attention worldwide due to the degradation of ecosystems. As one of the most ecologically fragile areas, the Tarim River Basin, of Xinjiang, China, encountered serious decline of desert riparian forests. The Chinese government has implemented the “Ecological Water Conveyance Project” (EWCP) since 2000, protecting and restoring the dominant natural species of the desert riparian forests, i.e., Populus euphratica Oliv. The regenerative effect after the water conveyance was noteworthy. For the purpose of clarifying the mechanism of P. euphratica forest regeneration to find a better prescription for the ecological restoration works in the Tarim River Basin, we investigated the relationship between the distribution of P. euphratica and soil salinity. Experimentally evaluated the effects of surface soil salinity on P. euphratica seed germination and the influence of river flooding on the salinity of surface soils. The results showed that (1) P. euphratica trees mainly spread along the river channel within 2 km; with increasing vertical distance to the channel, the number of trees declined significantly; (2) where the salinity of the surface soil is high, there are less living P. euphratica trees; (3) the germination of P. euphratica seeds decreases with increased soil conductivity; when the soil conductivity was higher than 7 ms/cm, the germination of P. euphratica seeds was severely curtailed. (4) Flooding regimes were a pre-condition of P. euphratica restoration; they had profound effects on improving the germination of the seeds via ameliorating water conditions and reducing salinity. Our results point out that the most efficient ecological prescription for restoring and protecting desert riparian forests is to induce flooding twice yearly during June to August with 10- to 15-day durations each time. Such a plan (especially in the Tarim River Basin) should prioritize the protection of seedlings.
Identifying pre-disease signals before metabolic syndrome in mice by dynamical network biomarkers
Authors: Koizumi Keiichi , Oku Makito , Hayashi Shusaku , Inujima Akiko , Shibahara Naotoshi , Chen Luonan , Igarashi Yoshiko , Tobe Kazuyuki , Saito Shigeru , Kadowaki Makoto , Aihara Kazuyuki
Published: June 2019

The establishment of new therapeutic strategies for metabolic syndrome is urgently needed because metabolic syndrome, which is characterized by several disorders, such as hypertension, increases the risk of lifestyle-related diseases. One approach is to focus on the pre-disease state, a state with high susceptibility before the disease onset, which is considered as the best period for preventive treatment. In order to detect the pre-disease state, we recently proposed mathematical theory called the dynamical network biomarker (DNB) theory based on the critical transition paradigm. Here, we investigated time-course gene expression profiles of a mouse model of metabolic syndrome using 64 whole-genome microarrays based on the DNB theory, and showed the detection of a pre-disease state before metabolic syndrome defined by characteristic behavior of 147 DNB genes. The results of our study demonstrating the existence of a notable pre-disease state before metabolic syndrome may help to design novel and effective therapeutic strategies for preventing metabolic syndrome, enabling just-in-time preemptive interventions.
gH625-liposomes as tool for pituitary adenylate cyclase-activating polypeptide brain delivery
Authors: Iachetta Giuseppina , Falanga Annarita , Molino Yves , Masse Maxime , Jabès Francoise , Mechioukhi Yasmine , Laforgia Vincenza , Khrestchatisky Michel , Galdiero Stefania , Valiante Salvatore
Published: June 2019

The blood-brain barrier (BBB) regulates the traffic of molecules into the central nervous system (CNS) and also limits the drug delivery. Due to their flexible properties, liposomes are an attractive tool to deliver drugs across the BBB. We previously characterized gH625, a peptide derived from Herpes simplex virus 1. The present study investigates the efficiency of liposomes functionalized on their surface with gH625 to promote the brain uptake of neuroprotective peptide PACAP (pituitary adenylate cyclase-activating polypeptide). Using a rat in vitro BBB model, we showed that the liposomes preparations were non-toxic for the endothelial cells, as assessed by analysis of tight junction protein ZO1 organization and barrier integrity. Next, we found that gH625 improves the transfer of liposomes across endothelial cell monolayers, resulting in both low cellular uptake and increased transport of PACAP. Finally, in vivo results demonstrated that gH625 ameliorates the efficiency of liposomes to deliver PACAP to the mouse brain after intravenous administration. gH625-liposomes improve both PACAP reaching and crossing the BBB, as showed by the higher number of brain cells labelled with PACAP. gH625-liposomes represent a promising strategy to deliver therapeutic agents to CNS and to provide an effective imaging and diagnostic tool for the brain.
Optical logic operation via plasmon-exciton interconversion in 2D semiconductors
Authors: Kim Jung Ho , Lee Jubok , Kim Hyun , Yun Seok Joon , Kim Jeongyong , Lee Hyun Seok , Lee Young Hee
Published: June 2019

Nanophotonic devices manipulating light for high-speed computing are a counterpart of speed-limited electronic circuits. Although plasmonic circuits are a promising platform for subwavelength miniaturization, the logic-operation principle is still limited to mimicking those of photonic waveguides using phase shifts, polarization, interference, and resonance. Meanwhile, reconfigurable interconversion between exciton and plasmon engender emerging applications like exciton transistors and multiplexers, exciton amplifiers, chiral valleytronics, and nonlinear excitonics. Here, we propose optical logic principles realized by exciton-plasmon interconversion in Ag-nanowires (NW) overlapped on transition metal dichalcogenides (TMDs) monolayers. Excitons generated from TMDs couple to the Ag-NW plasmons, eventually collected as output signals at the Ag-NW end. Using two lasers, we demonstrate AND gate by modulating single excitons in Ag-NW on MoS2 and a half-adder by modulating dual excitons in lateral WSe2 and WS2. Moreover, a 4-to-2 binary encoder is realized in partially overlapped MoSe2 and MoS2 using four-terminal laser inputs. Our results represent great advances in communication processing for optical photonics integrable with subwavelength architectures.
A comparison of a novel endoscopic “Su-Wang technique” with the open “Jaboulay’s procedure” for the surgical treatment of adult primary vaginal hydrocele
Authors: Lei Junhao , Luo Chunhua , Zhang Yangyang , Guo Yuming , Su Xinjun , Wang Xinghuan
Published: June 2019

This paper was aimed to introduce and compare outcomes of a novel “Su-Wang (S-W) technique” for endoscopic treatment of adult hydrocele with conventional open hydrocelectomy with “Jaboulay’s (JA) procedure” regarding adverse events (AEs) and patient satisfaction. In the randomized controlled trial, adult males with primary hydroceles were prospectively assigned into S-W or JA group. We recorded perioperative data and postoperative AEs (incision length, recurrence, hematoma, wound infection and edema vanished time). Finally, a total of 42 adult patients underwent the S-W (n = 22) or JA (n = 20) procedure. Procedures were successfully completed for all 42 patients. No significant differences were found between the two groups regarding age, symptom duration, body mass index, and size of the hydrocele. The incision length was significantly shorter in the S-W group (1.00 ± 0.24 cm) than in the JA group (6.10 ± 1.46 cm). After 6 months’ follow-up, complete data of 90.5% (38/42) were obtained. Severe AEs did not occur in any patient. Recurrence, hematoma, wound infection, edema vanished time values, and satisfaction in the S-W group were superior to those in the JA group. All patients in the S-W group were satisfied with this novel procedure, particularly due to the minimally invasive incision. In conclusion, the novel “S-W technique” for hydrocelectomy provided satisfactory cosmetic results with a 1-cm scrotal incision only. With the near-complete excision of the parietal TV, it resulted in no recurrence, fewer AEs, and rapid postoperative rehabilitation in comparison to the traditional “JA procedure.” The endoscopic “S-W technique” may be a viable alternative for the surgical treatment of adult primary vaginal hydrocele.
Functional Roles of Metabolic Intermediates in Regulating the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme
Authors: Hsieh Ju-Yi , Shih Wan-Ting , Kuo Yu-Hsuan , Liu Guang-Yaw , Hung Hui-Chih
Published: June 2019

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) has a dimer of dimers quaternary structure with two independent allosteric sites in each monomer. Here, we reveal the different effects of nucleotide ligands on the quaternary structure regulation and functional role of the human m-NAD(P)-ME exosite. In this study, size distribution analysis was utilized to investigate the monomer-dimer-tetramer equilibrium of m-NAD(P)-ME in the presence of different ligands, and the monomer-dimer (Kd,12) and dimer-tetramer (Kd,24) dissociation constants were determined with these ligands. With NAD+, the enzyme formed more tetramers, and its Kd,24 (0.06 µM) was 6-fold lower than the apoenzyme Kd,24 (0.34 µM). When ATP was present, the enzyme displayed more dimers, and its Kd,24 (2.74 µM) was 8-fold higher than the apoenzyme. Similar to the apoenzyme, the ADP-bound enzyme was present as a tetramer with a small amount of dimers and monomers. These results indicate that NAD+ promotes association of the dimeric enzyme into tetramers, whereas ATP stimulates dissociation of the tetrameric enzyme into dimers, and ADP has little effect on the tetrameric stability of the enzyme. A series of exosite mutants were created using site-directed mutagenesis. Size distribution analysis and kinetic studies of these mutants with NAD+ or ATP indicated that Arg197, Asn482 and Arg556 are essential for the ATP binding and ATP-induced dissociation of human m-NAD(P)-ME. In summary, the present results demonstrate that nucleotides perform discrete functions regulating the quaternary structure and catalysis of m-NAD(P)-ME. Such regulation by the binding of different nucleotides may be critically associated with the physiological concentrations of these ligands.
Dynamic adaptation of mesenchymal stem cell physiology upon exposure to surface micropatterns
Authors: Beijer Nick R. M. , Nauryzgaliyeva Zarina M. , Arteaga Estela M. , Pieuchot Laurent , Anselme Karine , van de Peppel Jeroen , Vasilevich Aliaksei S. , Groen Nathalie , Roumans Nadia , Hebels Dennie G. A. J. , Boer Jan de
Published: June 2019

Human mesenchymal stem (hMSCs) are defined as multi-potent colony-forming cells expressing a specific subset of plasma membrane markers when grown on flat tissue culture polystyrene. However, as soon as hMSCs are used for transplantation, they are exposed to a 3D environment, which can strongly impact cell physiology and influence proliferation, differentiation and metabolism. Strategies to control in vivo hMSC behavior, for instance in stem cell transplantation or cancer treatment, are skewed by the un-physiological flatness of the standard well plates. Even though it is common knowledge that cells behave differently in vitro compared to in vivo, only little is known about the underlying adaptation processes. Here, we used micrometer-scale defined surface topographies as a model to describe the phenotype of hMSCs during this adaptation to their new environment. We used well established techniques to compare hMSCs cultured on flat and topographically enhanced polystyreneand observed dramatically changed cell morphologies accompanied by shrinkage of cytoplasm and nucleus, a decreased overall cellular metabolism, and slower cell cycle progression resulting in a lower proliferation rate in cells exposed to surface topographies. We hypothesized that this reduction in proliferation rate effects their sensitivity to certain cancer drugs, which was confirmed by higher survival rate of hMSCs cultured on topographies exposed to paclitaxel. Thus, micro-topographies can be used as a model system to mimic the natural cell micro-environment, and be a powerful tool to optimize cell treatment in vitro.
Towards understanding partial adaptation to the subterranean habitat in the European cave spider, Meta menardi: An ecocytological approach
Authors: Lipovšek Saška , Leitinger Gerd , Janžekovič Franc , Kozel Peter , Dariš Barbara , Perc Matjaž , Devetak Dušan , Weiland Nina , Novak Tone
Published: June 2019

The European cave spider, Meta menardi, is a representative of the troglophiles, i.e. non-strictly subterranean organisms. Our aim was to interpret the cytological results from an ecological perspective, and provide a synthesis of the hitherto knowledge about M. menardi into a theory of key features marking it a troglophile. We studied ultrastructural changes of the midgut epithelial cells in individuals spending winter under natural conditions in caves, using light microscopy and TEM. The midgut diverticula epithelium consisted of secretory cells, digestive cells and adipocytes. During winter, gradual vacuolization of some digestive cells appeared, and some necrotic digestive cells and necrotic adipocytes appeared. This cytological information completes previous studies on M. menardi starved under controlled conditions in the laboratory. In experimental starvation and natural winter conditions, M. menardi gradually exploit reserve compounds from spherites, protein granules and through autophagy, and energy-supplying lipids and glycogen, as do many overwintering arthropods. We found no special cellular response to living in the habitat. Features that make it partly adapted to the subterranean habitat include starvation hardiness as a possible preadaptation, an extremely opportunistic diet, a partly reduced orb, tracking and capturing prey on bare walls and partly reduced tolerance to below-zero temperatures.
Genome-wide identification of glutathione S-transferase gene family in pepper, its classification, and expression profiling under different anatomical and environmental conditions
Authors: Islam Shiful , Sajib Saikat Das , Jui Zakya Sultana , Arabia Shatil , Islam Tahmina , Ghosh Ajit
Published: June 2019

Glutathione S-transferases (GSTs) compose a family of multifunctional enzymes involved in the numerous aspects of regulating plant growth, development, and stress response. An in silico genome-wide analysis of pepper (Capsicum annuum L.) was performed to identify eighty-five GST genes that were annotated according to their chromosomal location. Segmental duplication contributed more than tandem duplication for the expansion of GST gene family in pepper. All the identified members belong to ten different classes which are highly conserved among Arabidopsis, rice, tomato and potato counterparts indicating the pre-dicot-monocot split diversification of GST classes. Gene structure, protein domain, and motif organization were found to be notably conserved over the distinct phylogenetic groups, which demonstrated the evolutionary significant role of each class. Expression of most of the CaGST transcripts as well as the total pepper GST activity was found to be significantly up-regulated in response to cold, heat, drought, salinity and osmotic stress conditions. Presence of various hormone and stress-responsive cis-elements on most of the putative CaGST promoter regions could be directly correlated with the alteration of their transcripts. All these findings might provide opportunities for future functional validation of this important gene family in pepper.
An Improved Method for Fabrication of Ag-GO Nanocomposite with Controlled Anti-Cancer and Anti-bacterial Behavior; A Comparative Study
Authors: Khorrami Sadegh , Abdollahi Zahra , Eshaghi Ghazaleh , Khosravi Arezoo , Bidram Elham , Zarrabi Ali
Published: June 2019

In this study, two green procedures for Silver-Graphene Oxide (Ag-GO) nanocomposite synthesis were investigated. As a common method, AgNO3 was first loaded on the GO surface and then was reduced and stabilized by walnut green husk extract, producing Ag-GO-І. As an innovative approach, GO was first exposed to the extract and then the AgNO3 was added as the second step, producing Ag-GO-П. Physicochemical properties, antibacterial and cytotoxicity activity of both nanocomposites were subsequently studied comparing with free silver nanoparticles (AgNPs) and pure GO. Based on the results, exposure of GO to the extract, as a reducing agent, at the first/last step of the synthesis process resulted in the fundamental differences in the final products. So that, high amounts of agglomerated silver nanoparticles were formed between the GO sheets, when using the common method, whereas in Ag-GO-П, small AgNPs were formed on the GO sheets without aggregation, entirely covering the sheets. Antibacterial and cytotoxic behavior of these nanomaterials could be compared as AgNPs > Ag-GO-П > Ag-GO-І. It is assumed that these differences are due to control of unwanted nucleation in the synthesis process that Ag nanoparticles are smaller with less agglomeration when the GO surfaces are pre-treated with reducing agent.
Soft culture substrates favor stem-like cellular phenotype and facilitate reprogramming of human mesenchymal stem/stromal cells (hMSCs) through mechanotransduction
Authors: Gerardo Heloísa , Lima Ana , Carvalho João , Ramos João R. D. , Couceiro Sofia , Travasso Rui D. M. , Pires das Neves Ricardo , Grãos Mário
Published: June 2019

Biophysical cues influence many aspects of cell behavior. Stiffness of the extracellular matrix is probed by cells and transduced into biochemical signals through mechanotransduction protein networks, strongly influencing stem cell behavior. Cellular stemness is intimately related with mechanical properties of the cell, like intracellular contractility and stiffness, which in turn are influenced by the microenvironment. Pluripotency is associated with soft and low-contractility cells. Hence, we postulated that soft cell culture substrates, presumably inducing low cellular contractility and stiffness, increase the reprogramming efficiency of mesenchymal stem/stromal cells (MSCs) into induced pluripotent stem cells (iPSCs). We demonstrate that soft substrates (1.5 or 15 kPa polydimethylsiloxane – PDMS) caused modulation of several cellular features of MSCs into a phenotype closer to pluripotent stem cells (PSCs). MSCs cultured on soft substrates presented more relaxed nuclei, lower maturation of focal adhesions and F-actin assembling, more euchromatic and less heterochromatic nuclear DNA regions, and increased expression of pluripotency-related genes. These changes correlate with the reprogramming of MSCs, with a positive impact on the kinetics, robustness of colony formation and reprogramming efficiency. Additionally, substrate stiffness influences several phenotypic features of iPS cells and colonies, and data indicates that soft substrates favor full iPSC reprogramming.
A model of ganglion axon pathways accounts for percepts elicited by retinal implants
Authors: Beyeler Michael , Nanduri Devyani , Weiland James D. , Rokem Ariel , Boynton Geoffrey M. , Fine Ione
Published: June 2019

Degenerative retinal diseases such as retinitis pigmentosa and macular degeneration cause irreversible vision loss in more than 10 million people worldwide. Retinal prostheses, now implanted in over 250 patients worldwide, electrically stimulate surviving cells in order to evoke neuronal responses that are interpreted by the brain as visual percepts (‘phosphenes’). However, instead of seeing focal spots of light, current implant users perceive highly distorted phosphenes that vary in shape both across subjects and electrodes. We characterized these distortions by asking users of the Argus retinal prosthesis system (Second Sight Medical Products Inc.) to draw electrically elicited percepts on a touchscreen. Using ophthalmic fundus imaging and computational modeling, we show that elicited percepts can be accurately predicted by the topographic organization of optic nerve fiber bundles in each subject’s retina, successfully replicating visual percepts ranging from ‘blobs’ to oriented ‘streaks’ and ‘wedges’ depending on the retinal location of the stimulating electrode. This provides the first evidence that activation of passing axon fibers accounts for the rich repertoire of phosphene shape commonly reported in psychophysical experiments, which can severely distort the quality of the generated visual experience. Overall our findings argue for more detailed modeling of biological detail across neural engineering applications.
Paired Box-1 (PAX1) Activates Multiple Phosphatases and Inhibits Kinase Cascades in Cervical Cancer
Authors: Su Po-Hsuan , Lai Hung-Cheng , Huang Rui-Lan , Chen Lin-Yu , Wang Yu-Chi , Wu Tzu-I , Chan Michael W. Y. , Liao Chi-Chun , Chen Chien‐Wen , Lin Wei-Yu , Chang Cheng-Chang
Published: June 2019

DNA methylation alteration, such as global hypomethylation and localized hypermethylation, within the promoters of tumor suppressor genes, is an important risk factor in cervical cancer. The potential use of DNA methylation detection, in cervical cancer screening or triage of mildly abnormal cytology, has recently been demonstrated. In particular, PAX1 DNA methylation testing was approved as an adjunct to cytology, in Taiwan, and is now undergoing registration trials in China. However, the function of PAX1 in cancer biology remains largely unknown. Here, we show that PAX1 inhibits malignant phenotypes upon oncogenic stress. Specifically, PAX1 expression inhibited the phosphorylation of multiple kinases, after challenges with oncogenic growth factors such as EGF and IL-6. Analogously, PAX1 activated a panel of phosphatases, including DUSP1, 5, and 6, and inhibited EGF/MAPK signaling. PAX1 also interacted with SET1B, increasing histone H3K4 methylation and DNA demethylation of numerous phosphatase-encoding genes. Furthermore, hypermethylated PAX1 associated with poor prognosis in cervical cancer. Taken together, this study reveals, for the first time, the functional relevance of PAX1 in cancer biology, and further supports the prospect of targeting multifold oncogenic kinase cascades, which jointly contribute to multiresistance, via epigenetic reactivation of PAX1.
Early pregnancy serum levels of perfluoroalkyl substances and risk of preeclampsia in Swedish women
Authors: Wikström Sverre , Lindh Christian H. , Shu Huan , Bornehag Carl-Gustaf
Published: June 2019

Preeclampsia is a major cause of maternal and fetal morbidity. Emerging research shows an association with environmental exposures. The present aim was to investigate associations between early pregnancy serum levels of perfluoroalkyl substances (PFAS) and preeclampsia. Within the Swedish SELMA study, eight PFAS were measured at median 10 gestational weeks and cases of preeclampsia were postnatally identified from registers. Associations between individual PFAS and preeclampsia were assessed, adjusting for parity, age, weight and smoking. Out of 1,773 women in the study group, 64 (3.6%), developed preeclampsia. A doubling of PFOS and PFNA exposure, corresponding to an inter-quartile increase, was associated with an increased risk for preeclampsia of about 38–53% respectively. Serum PFOS within the highest quartile was associated with an odds ratio of 2.68 (CI 95%: 1.17–6.12), equal to the increased risk associated with nulliparity, when compared to exposure in the first quartile. The same associations were identified, although with higher risk estimates, in analyses restricted to nulliparous women. For other PFAS, there were no associations. In conclusion and consistent with limited previous research only on PFOS, increasing serum levels of PFOS and PFNA during early pregnancy were associated with a clinically relevant risk of preeclampsia, adjusting for established confounders.
Simultaneous gains in grain yield and nitrogen efficiency over 70 years of maize genetic improvement
Authors: Mueller Sarah M. , Messina Carlos D. , Vyn Tony J.
Published: June 2019

The competing demands of increasing grain yields to feed a growing population and decreasing nitrogen (N) fertilizer use and loss to the environment poses a grand challenge to farmers and society, and necessitates achieving improved N use efficiency (NUE) in cereal crops. Although selection for increased yield in maize has improved NUE over time, the present understanding of the physiological determinants of NUE and its key components hampers the design of more effective breeding strategies conducive to accelerating genetic gain for this trait. We show that maize NUE gains have been supported by more efficient allocation of N among plant organs during the grain filling period. Comparing seven maize hybrids commercialized between 1946 and 2015 from a single seed company in multiple N fertilizer treatments, we demonstrate that modern hybrids produced more grain per unit of accumulated N by more efficiently remobilizing N stored in stems than in leaves to support kernel growth. Increases in N fertilizer recovery and N harvest index at maturity were mirrored by a steady decrease in stem N allocation in this era study. These insights can inform future breeding strategies for continued NUE gains through improved conversion efficiency of accumulated plant N into grain yield.
Oral administration of EPA-rich oil impairs collagen reorganization due to elevated production of IL-10 during skin wound healing in mice
Authors: Burger Beatriz , Kühl Carolina M. C. , Candreva Thamiris , Cardoso Renato da S. , Silva Jéssica R. , Castelucci Bianca G. , Consonni Sílvio R. , Fisk Helena L. , Calder Philip C. , Vinolo Marco Aurélio R. , Rodrigues Hosana G.
Published: June 2019

Wound healing is an essential process for organism survival. Some fatty acids have been described as modulators of wound healing. However, the role of omega-3 fatty acids is unclear. In the present work, we investigate the effects of oral administration of eicosapentaenoic acid (EPA)-rich oil on wound healing in mice. After 4 weeks of EPA-rich oil supplementation (2 g/kg of body weight), mice had increased serum concentrations of EPA (20:5ω-3) (6-fold) and docosahexaenoic acid (DHA; 22:6ω-3) (33%) in relation to control mice. Omega-3 fatty acids were also incorporated into skin in the EPA fed mice. The wound healing process was delayed at the 3rd and 7th days after wounding in mice that received EPA-rich oil when compared to control mice but there was no effect on the total time required for wound closure. Collagen reorganization, that impacts the quality of the wound tissue, was impaired after EPA-rich oil supplementation. These effects were associated with an increase of M2 macrophages (twice in relation to control animals) and interleukin-10 (IL-10) concentrations in tissue in the initial stages of wound healing. In the absence of IL-10 (IL-10−/− mice), wound closure and organization of collagen were normalized even when EPA was fed, supporting that the deleterious effects of EPA-rich oil supplementation were due to the excessive production of IL-10. In conclusion, oral administration of EPA-rich oil impairs the quality of wound healing without affecting the wound closure time likely due to an elevation of the anti-inflammatory cytokine IL-10.
In vivo measurements reveal a single 5′-intron is sufficient to increase protein expression level in Caenorhabditis elegans
Authors: Crane Matthew M. , Sands Bryan , Battaglia Christian , Johnson Brock , Yun Soo , Kaeberlein Matt , Brent Roger , Mendenhall Alex
Published: June 2019

Introns can increase gene expression levels using a variety of mechanisms collectively referred to as Intron Mediated Enhancement (IME). IME has been measured in cell culture and plant models by quantifying expression of intronless and intron-bearing reporter genes in vitro. We developed hardware and software to implement microfluidic chip-based gene expression quantification in vivo. We altered position, number and sequence of introns in reporter genes controlled by the hsp-90 promoter. Consistent with plant and mammalian studies, we determined a single, natural or synthetic, 5′-intron is sufficient for the full IME effect conferred by three synthetic introns, while a 3′-intron is not. We found coding sequence can affect IME; the same three synthetic introns that increase mcherry protein concentration by approximately 50%, increase mEGFP by 80%. We determined IME effect size is not greatly affected by the stronger vit-2 promoter. Our microfluidic imaging approach should facilitate screens for factors affecting IME and other intron-dependent processes.
Discovery and characterization of functional modules associated with body weight in broilers
Authors: Tarsani Eirini , Kranis Andreas , Maniatis Gerasimos , Avendano Santiago , Hager-Theodorides Ariadne L. , Kominakis Antonios
Published: June 2019

Aim of the present study was to investigate whether body weight (BW) in broilers is associated with functional modular genes. To this end, first a GWAS for BW was conducted using 6,598 broilers and the high density SNP array. The next step was to search for positional candidate genes and QTLs within strong LD genomic regions around the significant SNPs. Using all positional candidate genes, a network was then constructed and community structure analysis was performed. Finally, functional enrichment analysis was applied to infer the functional relevance of modular genes. A total number of 645 positional candidate genes were identified in strong LD genomic regions around 11 genome-wide significant markers. 428 of the positional candidate genes were located within growth related QTLs. Community structure analysis detected 5 modules while functional enrichment analysis showed that 52 modular genes participated in developmental processes such as skeletal system development. An additional number of 14 modular genes (GABRG1, NGF, APOBEC2, STAT5B, STAT3, SMAD4, MED1, CACNB1, SLAIN2, LEMD2, ZC3H18, TMEM132D, FRYL and SGCB) were also identified as related to body weight. Taken together, current results suggested a total number of 66 genes as most plausible functional candidates for the trait examined.
Investigating the properties of TBA variants with twin thrombin binding domains
Authors: Amato Teresa , Virgilio Antonella , Pirone Luciano , Vellecco Valentina , Bucci Mariarosaria , Pedone Emilia , Esposito Veronica , Galeone Aldo
Published: June 2019

In this paper, we report studies concerning thrombin binding aptamer (TBA) dimeric derivatives in which the 3′-ends of two TBA sequences have been joined by means of linkers containing adenosine or thymidine residues and/or a glycerol moiety. CD and electrophoretic investigations indicate that all modified aptamers are able to form G-quadruplex domains resembling that of the parent TBA structure. However, isothermal titration calorimetry measurements of the aptamer/thrombin interaction point to different affinities to the target protein, depending on the type of linker. Consistently, the best ligands for thrombin show anticoagulant activities higher than TBA. Interestingly, two dimeric aptamers with the most promising properties also show far higher resistances in biological environment than TBA.
Century-long Taylor-Quinney interpretation of plasticity-induced heating reexamined
Authors: Zubelewicz Aleksander
Published: June 2019

In thermomechanics, the Taylor–Quinney coefficient specifies fraction of plastic work converted to heat. We challenge the nearly century-long interpretation. We postulate that some fraction of energy delivered to the plastically deformed material is responsible for readjustments of deformation pathways making the plastic flow a kinematically admissible process. The rerouting triggers mesoscale dynamic excitations and activates plasticity-induced heat. Another part of the energy is stored in lattice, while the rest of it contributes to the development of dislocation structures. According to this interpretation, plastic work is not converted to heat, but increases probability of the microstructural adaptiveness and, in this manner, contributes to configurational entropy of the system.
Impact of carbon inputs on soil carbon fractionation, sequestration and biological responses under major nutrient management practices for rice-wheat cropping systems
Authors: Bhardwaj Ajay Kumar , Rajwar Deepika , Mandal Uttam Kumar , Ahamad Sharif , Kaphaliya Bhumija , Minhas Paramjit Singh , Prabhakar Mathyam , Banyal Rakesh , Singh Ranbir , Chaudhari Suresh Kumar , Sharma Parbodh Chander
Published: June 2019

Major nutrient management systems for rice-wheat cropping were compared for their potential to credit organic carbon (C) to the soil, its fractionation into active (very labile, VLc; labile, Lc) and passive (less labile, LLc; non-labile, NLc) pools, and crop yield responses. A ten-year long experiment was used to study effects of: (i) no inputs (Control, O), (ii) 100% inorganic fertilizers (F) compared to reduced fertilizers inputs (55%) supplemented with biomass incorporation from (iii) opportunity legume crop (Vigna radiata) (LE), (iv) green manure (Sesbania aculeata) (GM), (v) farmyard manure (FYM), (vi) wheat stubble (WS), and (vii) rice stubble (RS). Maximum C input to soil (as the percentage of C assimilated in the system) was in GM (36%) followed by RS (34%), WS (33%), LE (24%), and FYM (21%) compared to O (15%) and F (15%). Total C input to soil had a direct effect on soil C stock, soil C fractions (maximum in VLc and LLc), yet the responses in terms of biological yield were controlled by the quality of the biomass (C:N ratio, decomposition, etc.) incorporated. Legume-based biomass inputs accrued most benefits for soil C sequestration and biological productivity.
Circulating pro- and anti-angiogenic factors in multi-stage liver disease and hepatocellular carcinoma progression
Authors: Joo Yu Young , Jang Jeong Won , Lee Sung Won , Yoo Sun Hong , Kwon Jung Hyun , Nam Soon Woo , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew
Published: June 2019

To date, few studies have carried out a simultaneous determination of multiple pro- and anti-angiogenic factors during liver diseases progression. This study investigated the dynamic change in circulating angiogenic factors in multi-step carcinogenesis and hepatocellular carcinoma (HCC) progression. Serum levels of major pro-angiogenic [Vascular endothelial growth factor (VEGF), Basic fibroblast growth factor (b-FGF)] and anti-angiogenic [Thrombospondin-1 (TSP-1), Endostatin] factors were identified by enzyme-linked immunosorbent assay and correlated with liver diseases progression and outcomes of HCC patients undergoing transarterial chemo-embolization. A total of 240 patients (156 HCC, 37 cirrhosis and 47 chronic hepatitis) were enrolled in this study. While progressing from chronic hepatitis, cirrhosis to HCC, VEGF and b-FGF levels showed a significant change. Particularly, b-FGF yielded the highest AUROC value for a diagnosis of HCC and its distinction from other disease groups. A trend towards increasing VEGF levels was observed from Child-Pugh class A, B to C. VEGF and TSP-1 levels increased with the advance of cancer stage, with a remarkable increase in TSP-1 at an intermediate stage. Pretreatment levels of VEGF, TSP-1, and endostatin independently predicted the overall survival of patients. VEGF and TSP-1 levels correlated with progression-free survival. Our study demonstrated the dynamic angiogenic switch and the roles that individual pro- and anti-angiogenic factors contribute to carcinogenesis and HCC progression during the course of multi-step liver diseases. These imply the future possibility of testing pro- and anti-angiogenic panels as a diagnostic marker and a guide in decision-making about upcoming targeted therapies.
Caffeine exposure induces browning features in adipose tissue in vitro and in vivo
Authors: Velickovic Ksenija , Wayne Declan , Leija Hilda Anaid Lugo , Bloor Ian , Morris David E. , Law James , Budge Helen , Sacks Harold , Symonds Michael E. , Sottile Virginie
Published: June 2019

Brown adipose tissue (BAT) is able to rapidly generate heat and metabolise macronutrients, such as glucose and lipids, through activation of mitochondrial uncoupling protein 1 (UCP1). Diet can modulate UCP1 function but the capacity of individual nutrients to promote the abundance and activity of UCP1 is not well established. Caffeine consumption has been associated with loss of body weight and increased energy expenditure, but whether it can activate UCP1 is unknown. This study examined the effect of caffeine on BAT thermogenesis in vitro and in vivo. Stem cell-derived adipocytes exposed to caffeine (1 mM) showed increased UCP1 protein abundance and cell metabolism with enhanced oxygen consumption and proton leak. These functional responses were associated with browning-like structural changes in mitochondrial and lipid droplet content. Caffeine also increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression and mitochondrial biogenesis, together with a number of BAT selective and beige gene markers. In vivo, drinking coffee (but not water) stimulated the temperature of the supraclavicular region, which co-locates to the main region of BAT in adult humans, and is indicative of thermogenesis. Taken together, these results demonstrate that caffeine can promote BAT function at thermoneutrality and may have the potential to be used therapeutically in adult humans.
Tau is required for the function of extrasynaptic NMDA receptors
Authors: Pallas-Bazarra Noemí , Draffin Jonathan , Cuadros Raquel , Antonio Esteban José , Avila Jesús
Published: June 2019

Tau is a microtubule-associated neuronal protein found mainly in axons. However, increasing evidence indicates that it is also present in dendrites, where it serves as an essential mediator of synaptic NMDA (N-methyl-D-aspartate) receptor-dependent excitotoxicity. Of note, NMDA receptors can also be found outside synapses in the plasma membrane, and activation of extrasynaptic NMDA receptors has been shown to be more linked to excitotoxicity than the activation of synaptic ones. Little is known about the role of Tau in the activity of extrasynaptic NMDA receptors. Thus, we have used a Tau knockout mouse model (Tau−/− mice) to analyze the consequences of Tau absence in extrasynaptic NMDA receptor activity. We demonstrate that absence of Tau leads to a decrease in functional extrasynaptic NMDA receptors in the hippocampus. We propose that this impairment in extrasynaptic NMDA receptor activity may contribute to the well-known neuroprotective effect associated with Tau deficiency under pathological conditions.
Identification of small molecule enzyme inhibitors as broad-spectrum anthelmintics
Authors: Tyagi Rahul , Elfawal Mostafa A. , Wildman Scott A. , Helander Jon , Bulman Christina A. , Sakanari Judy , Rosa Bruce A. , Brindley Paul J. , Janetka James W. , Aroian Raffi V. , Mitreva Makedonka
Published: June 2019

Targeting chokepoint enzymes in metabolic pathways has led to new drugs for cancers, autoimmune disorders and infectious diseases. This is also a cornerstone approach for discovery and development of anthelmintics against nematode and flatworm parasites. Here, we performed omics-driven knowledge-based identification of chokepoint enzymes as anthelmintic targets. We prioritized 10 of 186 phylogenetically conserved chokepoint enzymes and undertook a target class repurposing approach to test and identify new small molecules with broad spectrum anthelmintic activity. First, we identified and tested 94 commercially available compounds using an in vitro phenotypic assay, and discovered 11 hits that inhibited nematode motility. Based on these findings, we performed chemogenomic screening and tested 32 additional compounds, identifying 6 more active hits. Overall, 6 intestinal (single-species), 5 potential pan-intestinal (whipworm and hookworm) and 6 pan-Phylum Nematoda (intestinal and filarial species) small molecule inhibitors were identified, including multiple azoles, Tadalafil and Torin-1. The active hit compounds targeted three different target classes in humans, which are involved in various pathways, including carbohydrate, amino acid and nucleotide metabolism. Last, using representative inhibitors from each target class, we demonstrated in vivo efficacy characterized by negative effects on parasite fecundity in hamsters infected with hookworms.
Unraveling the role of the CbrA histidine kinase in the signal transduction of the CbrAB two-component system in Pseudomonas putida
Authors: Monteagudo-Cascales Elizabet , García-Mauriño Sofía M. , Santero Eduardo , Canosa Inés
Published: June 2019

The histidine kinase CbrA of the CbrAB two-component system of Pseudomonas putida is a key element to recognise the activating signal and mediate auto- and trans-phosphorylation of the response element CbrB. CbrA is encoded by the gene cbrA which is located downstream of a putative open reading frame we have named cbrX. We describe the role of the CbrX product in the expression of CbrA and show there is translational coupling of the genes. We also explore the role of the transmembrane (TM) and PAS domains of CbrA in the signal recognition. A ΔcbrXA mutant lacking its TM domains is uncoupled in its growth in histidine and citrate as carbon sources, but its overexpression restores the ability to grow in such carbon sources. In these conditions ΔTM-CbrA is able to respond to carbon availability, thus suggesting an intracellular nature for the signal sensed.
Self-assembled Cube-like Copper Oxide Derived from a Metal-Organic Framework as a High-Performance Electrochemical Supercapacitive Electrode Material
Authors: Aljaafari Abdullah , Parveen Nazish , Ahmad Faheem , Alam Mir Waqas , Ansari Sajid Ali
Published: June 2019

Interest in pseudocapacitive materials, especially cuprous oxide, has grown owing to its various advantageous properties and application as electrode materials in the energy storage devices. The work presented here, a cubic Cu2O framework was synthesized using a simple and one-step modified polyol-assisted (metal-organic framework) solvothermal method. The structural configuration was rationalized by systematically studying the effect of the reaction time on the morphology and growth of the Cu2O. In addition, a range of microscopic and spectroscopic techniques was employed to further characterize the obtained cubic Cu2O. The morphological effect on the electrochemical supercapacitive performance of the obtained cubic Cu2O was also examined by cyclic-voltammetry (CV) and galvanostatic-charge-discharge (G-C-D) method. The obtained outcome shows that the cubic Cu2O synthesized using a reaction time of 12 h (Cu2O-12h; Csp~365 Fg−1) exhibited superior capacitive performance as compared to the cubic Cu2O synthesized at 8 h (Cu2O-8h; Csp~151 Fg−1) and 10 h (Cu2O-10h; Csp~195 Fg−1) at the current density of 0.75 Ag−1. Furthermore, the Cu2O-12h electrode exhibits energy density of 16.95 Wh/Kg at a power density of 235.4 W/Kg and higher power density of 2678.5 W/Kg at low current density. In particular, the cube-like Cu2O-12h exhibited excellent capacitive performance and rate capability as compared to Cu2O-8h and Cu2O-10h, owing to its unique three-dimensional morphology, which facilitates the formation of various active sites for intercalation of the electrolyte during the electrochemical process. These results show the as-obtained Cu2O could be a promising supercapacaitive electrode material for various applications.
CDK inhibitors reduce cell proliferation and reverse hypoxia-induced metastasis of neuroblastoma tumours in a chick embryo model
Authors: Swadi Rasha R. , Sampat Keerthika , Herrmann Anne , Losty Paul D. , See Violaine , Moss Diana J.
Published: June 2019

Neuroblastoma is a paediatric cancer with a poor prognosis. This is in part due to widespread metastasis at time of presentation, which is refractory to current treatment modalities. New therapeutic agents that can control not only tumour growth but also metastasis are urgently needed. The differentiation therapy, retinoic acid, is currently used in clinic, leading to terminal differentiation of neuroblastoma cells thus reducing tumour growth in the primary tumour as well as at metastatic sites. However, retinoic acid only works in a subset of patients. We investigated the potential of CDK inhibitors, Palbociclib and RO-3306, on neuroblastoma cell differentiation, tumour progression and metastasis by utilising a 3R compliant cost effective preclinical chick embryo model. In both SK-N-AS and BE(2)C cell lines, when engrafted on the chorioallantoic membrane of chick embryos, we observed a reduction of tumour cell proliferation as well as a reduction in hypoxia preconditioning-driven metastasis by 60%. In addition, the expression of a panel of genes with known roles in metastasis, which increased upon hypoxia-preconditioning, was largely reduced by a CDK1 inhibitor. These results provide a promising alternative to currently existing therapies and might aid the development of new treatment protocols for retinoic acid-resistant patients.
Low-diluted Phenacetinum disrupted the melanoma cancer cell migration
Authors: Fuselier Camille , Terryn Christine , Berquand Alexandre , Crowet Jean-Marc , Bonnomet Arnaud , Molinari Michael , Dauchez Manuel , Martiny Laurent , Schneider Christophe
Published: June 2019

Dynamic and reciprocal interactions generated by the communication between tumor cells and their matrix microenvironment, play a major role in the progression of a tumor. Indeed, the adhesion of specific sites to matrix components, associated with the repeated and coordinated formation of membrane protrusions, allow tumor cells to move along a determined pathway. Our study analyzed the mechanism of action of low-dilutedPhenacetinumon murine cutaneous melanoma process in a fibronectin matrix environment. We demonstrated a reduction of dispersed cell migration, early and for as long as 24 h, by altering the formation of cell protrusions. Moreover, low-dilutedPhenacetinumdecreased cell stiffness highly on peripheral areas, due to a disruption of actin filaments located just under the plasma membrane. Finally, it modified the structure of the plasma membrane by accumulating large ordered lipid domains and disrupted B16 cell migration by a likely shift in the balance between ordered and disordered lipid phases. Whereas the correlation between the excess of lipid raft and cytoskeleton disrupting is not as yet established, it is clear that low-dilutedPhenacetinumacts on the actin cytoskeleton organization, as confirmed by a decrease of cell stiffness affecting ultimately the establishment of an effective migration process.