bluuebunny/crossref_metadata_2025_split huggingface dataset:
FHL2 mediates podocyte Rac1 activation and foot process effacement in hypertensive nephropathy
Authors: Li Szu-Yuan , Chu Pao-Hsien , Huang Po-Hsun , Hsieh Tsung-Han , Susztak Katalin , Tarng Der-Cherng 
Published: April 2019

AbstractRAAS inhibition has been the standard treatment for CKD for years because it can reduce proteinuria and hence retard renal function decline, but the proteinuria reduction effect is still insufficient in many patients. Podocyte foot process and slit diaphragm are the final barrier to prevent serum proteins leak into urine, and podocyte foot process effacement is the common pathway of all proteinruic diseases. Cell structure are regulated by three evolutionarily conserved Rho GTPases, notably, Rac1 activation is sufficient and necessary for podocyte foot process effacement, however, Rac1 inhibition is not an option for kidney disease treatment because of its systemic side effects. Four-and-a-half LIM domains protein 2 (FHL2) is highly expressed in podocytes and has been implicated in regulating diverse biological functions. Here, we used micro-dissected human kidney samples, in vitro podocyte culture experiments, and a hypertension animal model to determine the possible role of FHL2 in hypertensive nephropathy. FHL2 was abundantly upregulated in hypertensive human glomeruli and animal kidney samples. Genetic deletion of the FHL2 did not alter normal renal structure or function but mitigated hypertension-induced podocyte foot process effacement and albuminuria. Mechanistically, angiotensin II-induced podocyte cytoskeleton reorganization via FAK-Rac1 axis, FHL2 binds with FAK and is an important mediator of Ang II induced Rac1 activation, thus, FHL2 inhibition can selectively block FAK-Rac1 axis in podocyte and prevent proteinuria. These results provide important insights into the mechanisms of podocyte foot process effacement and points out a promising strategy to treat kidney disease.
Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane
Authors: Barrett David W. , John Rebecca K. , Thrasivoulou Christopher , Mata Alvaro , Deprest Jan A. , Becker David L. , David Anna L. , Chowdhury Tina T. 
Published: April 2019

AbstractMechanical and inflammatory signals in the fetal membrane play an important role in extracellular matrix (ECM) remodelling in order to dictate the timing of birth. We developed a mechanical model that mimics repetitive stretching of the amniotic membrane (AM) isolated from regions over the placenta (PAM) or cervix (CAM) and examined the effect of cyclic tensile strain (CTS) on mediators involved in mechanotransduction (Cx43, AKT), tissue remodelling (GAGs, elastin, collagen) and inflammation (PGE2, MMPs). In CAM and PAM specimens, the application of CTS increased GAG synthesis, PGE2 release and MMP activity, with concomitant reduction in collagen and elastin content. Co-stimulation with CTS and pharmacological agents that inhibit either Cx43 or AKT, differentially influenced collagen, GAG and elastin in a tissue-dependent manner. SHG confocal imaging of collagen fibres revealed a reduction in SHG intensity after CTS, with regions of disorganisation dependent on tissue location. CTS increased Cx43 and AKT protein and gene expression and the response could be reversed with either CTS, the Cx43 antisense or AKT inhibitor. We demonstrate that targeting Cx43 and AKT prevents strain-induced ECM damage and promotes tissue remodelling mechanisms in the AM. We speculate that a combination of inflammatory and mechanical factors could perturb typical mechanotransduction processes mediated by Cx43 signalling. Cx43 could therefore be a potential therapeutic target to prevent inflammation and preterm premature rupture of the fetal membranes.
Slow Down of the Gulf Stream during 1993–2016
Authors: Dong Shenfu , Baringer Molly O. , Goni Gustavo J. 
Published: April 2019

AbstractThe Gulf Stream, the main heat-carrier from low to high latitudes in the North Atlantic Ocean, influences the climate and weather in the northern hemisphere. In this study we determine and analyze the position, speed, and width of the Gulf Stream (GS) from 80°W–50°W using satellite altimeter sea surface height (SSH) measurements to examine the possible link between changes in the strength of the GS and coastal sea levels along the U.S. East Coast. During our 24-year study period (1993–2016), the GS experienced a southward shift east of 65°W after passing the New England Seamount chain. This southward shift was accompanied by a weakening of the GS, associated with an increase in SSH to the north of the GS. West of 70°W, however, we found no statistically significant trends in the GS properties, consistent with results based on in situ measurements. This lack of a trend to the west fails to support a direct link between a long-term slowdown of the GS west of 70°W and sea level rise acceleration along the U.S. East Coast, though a slowdown of the GS east of 65°W may contribute to sea level rise. It is also possible that heat carried to the region by the GS may be responsible for these observed sea level changes.
The emergence of synchrony in networks of mutually inferring neurons
Authors: Palacios Ensor Rafael , Isomura Takuya , Parr Thomas , Friston Karl 
Published: April 2019

AbstractThis paper considers the emergence of a generalised synchrony in ensembles of coupled self-organising systems, such as neurons. We start from the premise that any self-organising system complies with the free energy principle, in virtue of placing an upper bound on its entropy. Crucially, the free energy principle allows one to interpret biological systems as inferring the state of their environment or external milieu. An emergent property of this inference is synchronisation among an ensemble of systems that infer each other. Here, we investigate the implications of neuronal dynamics by simulating neuronal networks, where each neuron minimises its free energy. We cast the ensuing ensemble dynamics in terms of inference and show that cardinal behaviours of neuronal networks – both in vivo and in vitro – can be explained by this framework. In particular, we test the hypotheses that (i) generalised synchrony is an emergent property of free energy minimisation; thereby explaining synchronisation in the resting brain: (ii) desynchronisation is induced by exogenous input; thereby explaining event-related desynchronisation and (iii) structure learning emerges in response to causal structure in exogenous input; thereby explaining functional segregation in real neuronal systems.
Effect of co-infection with a small intestine-restricted helminth pathogen on oral prion disease pathogenesis in mice
Authors: Sánchez-Quintero Alejandra , Bradford Barry M. , Maizels Rick , Donaldson David S. , Mabbott Neil A. 
Published: April 2019

AbstractThe early replication of some orally-acquired prion strains upon stromal-derived follicular dendritic cells (FDC) within the small intestinal Peyer’s patches is essential to establish host infection, and for the disease to efficiently spread to the brain. Factors that influence the early accumulation of prions in Peyer’s patches can directly influence disease pathogenesis. The host’s immune response to a gastrointestinal helminth infection can alter susceptibility to co-infection with certain pathogenic bacteria and viruses. Here we used the natural mouse small intestine-restricted helminth pathogen Heligmosomoides polygyrus to test the hypothesis that pathology specifically within the small intestine caused by a helminth co-infection would influence oral prion disease pathogenesis. When mice were co-infected with prions on d 8 after H. polygyrus infection the early accumulation of prions within Peyer’s patches was reduced and survival times significantly extended. Natural prion susceptible hosts such as sheep, deer and cattle are regularly exposed to gastrointestinal helminth parasites. Our data suggest that co-infections with small intestine-restricted helminth pathogens may be important factors that influence oral prion disease pathogenesis.
Preventing nasal airway collapse with irradiated homologous costal cartilage versus expanded polytetrafluoroethylene: a novel animal model for nasal airway reconstruction
Authors: Yen Cheng-I , Zelken Jonathan A. , Chang Chun-Shin , Chen Hung-Chang , Yang Shih-Yi , Chang Shu-Yin , Yang Jui-Yung , Chuang Shiow-Shuh , Hsiao Yen-Chang 
Published: April 2019

AbstractAirway collapse can occur when the forces of inhalation overpower the strength of the nasal lining flap. The authors established an animal model of the reconstructed nasal airway, and examined mechanical properties of tissue composites based on various materials. Twenty-three Sprague-Dawley rats were divided into three experimental groups: control (n = 5), irradiated homologous costal cartilage (IHCC, n = 10), and expanded polytetrafluoroethylene (ePTFE, n = 8). Two dorsal skin flaps represented nasal lining and skin envelope. No framework, an IHCC or ePTFE rim graft was used as framework. At three weeks, changes in the cross-sectional area of the lining flap were measured when negative pressure was applied. En-bloc specimens containing the graft and soft tissue were examined for histological change and tissue ingrowth. Reduction of cross-sectional area with simulated inhalation was 87.74% in the control group, 82.76% (IHCC), and 67.29% (ePTFE). Cross-sectional reduction was significantly less in ePTFE group than control group (p = 0.004) and IHCC group (p = 0.001). The difference was not significant in the control and IHCC groups. There was histologic evidence of tissue ingrowth in the ePTFE group. This novel animal model of nasal airway reconstruction supports the use and potential benefit of using ePTFE for prevention of airway collapse.
Phytoplankton gross primary production increases along cascading impoundments in a temperate, low-discharge river: Insights from high frequency water quality monitoring
Authors: Engel Fabian , Attermeyer Katrin , Ayala Ana I. , Fischer Helmut , Kirchesch Volker , Pierson Don C. , Weyhenmeyer Gesa A. 
Published: April 2019

AbstractDamming alters carbon processing along river continua. Estimating carbon transport along rivers intersected by multiple dams requires an understanding of the effects of cascading impoundments on the riverine metabolism. We analyzed patterns of riverine metabolism and phytoplankton biomass (chlorophylla; Chla) along a 74.4-km river reach intersected by six low-head navigation dams. Calculating gross primary production (GPP) from continuous measurements of dissolved oxygen concentration, we found a maximum increase in the mean GPP by a factor of 3.5 (absolute difference of 0.45 g C m−3d−1) along the first 26.5 km of the study reach, while Chlaincreased over the entire reach by a factor of 2.9 (8.7 µg l−1). In the intermittently stratified section of the deepest impoundment the mean GPP between the 1 and 4 m water layer differed by a factor of 1.4 (0.31 g C m−3d−1). Due to the strong increase in GPP, the river featured a wide range of conditions characteristic of low- to medium-production rivers. We suggest that cascading impoundments have the potential to stimulate riverine GPP, and conclude that phytoplankton CO2uptake is an important carbon flux in the river Saar, where a considerable amount of organic matter is of autochthonous origin.
A new role for RU486 (mifepristone): it protects sperm from premature capacitation during cryopreservation in buffalo
Authors: Dalal Jasmer , Kumar Pradeep , Chandolia R. K. , Pawaria Shikha , Rajendran Rasika , Sheoran Suman , Andonissamy Jerome , Kumar Dharmendra 
Published: April 2019

AbstractThe objective of this study was to determine the mechanism by which RU 486 (mifepristone) protects sperm to undergo premature capacitation during cryopreservation. For this, semen ejaculate (n = 20) was divided into four equal fractions and diluted using egg yolk-based extender supplemented with different concentrations of RU 486 (0, 5, 10 and 20 µM) and cryopreserved. We found that RU 486 did not impair the post-thaw sperm kinetics and motility but prevented cholesterol efflux, calcium influx, and protected CatSper channels during cryopreservation. The RU 486 protected sperm from premature capacitation which was confirmed by intracellular calcium level, expression of tyrosine phosphorylated proteins (75 and 80 kDa) and CTC (chlortetracycline) assay. Furthermore, antioxidant ability of RU 486 was reflected by the ferric reducing ability, lower production of sperm malondialdehyde and intracellular reactive oxygen species. Also, we demonstrated that RU 486 treated sperm underwent normal capacitation, zona pellucida binding and zygote cleavage indicating normal fertilizing ability of sperm. In conclusion, we report a new role of RU 486 in protecting buffalo sperm from premature capacitation during cryopreservation.
Fabrication of multifunctional titanium surfaces by producing hierarchical surface patterns using laser based ablation methods
Authors: Zwahr Christoph , Helbig Ralf , Werner Carsten , Lasagni Andrés Fabián 
Published: April 2019

AbstractTextured implant surfaces with micrometer and sub-micrometer features can improve contact properties like cell adhesion and bacteria repellency. A critical point of these surfaces is their mechanical stability during implantation. Therefore, strategies capable to provide both biocompatibility for an improved implant healing and resistance to wear for protecting the functional surface are required. In this work, laser-based fabrication methods have been used to produce hierarchical patterns on titanium surfaces. Using Direct Laser Writing with a nanosecond pulsed laser, crater-like structures with a separation distance of 50 µm are produced on unpolished titanium surfaces. Directly on this texture, a hole-like pattern with 5 µm spatial period is generated using Direct Laser Interference Patterning with picosecond pulses. While the smaller features should reduce the bacterial adhesion, the larger geometry was designed to protect the smaller features from wear. On the multifunctional surface, the adherence of E. Coli bacteria is reduced by 30% compared to the untreated reference. In addition, wear test performed on the multiple-scale patterns demonstrated the possibility to protect the smaller features by the larger craters. Also, the influence of the laser treatment on the growth of a titanium oxide layer was evaluated using Energy Dispersive X-Ray Spectroscopy analysis.
Passive microinjection within high-throughput microfluidics for controlled actuation of droplets and cells
Authors: Azarmanesh Milad , Dejam Morteza , Azizian Pooya , Yesiloz Gurkan , Mohamad Abdulmajeed A. , Sanati-Nezhad Amir 
Published: April 2019

AbstractMicroinjection is an effective actuation technique used for precise delivery of molecules and cells into droplets or controlled delivery of genes, molecules, proteins, and viruses into single cells. Several microinjection techniques have been developed for actuating droplets and cells. However, they are still time-consuming, have shown limited success, and are not compatible with the needs of high-throughput (HT) serial microinjection. We present a new passive microinjection technique relying on pressure-driven fluid flow and pulsative flow patterns within an HT droplet microfluidic system to produce serial droplets and manage rapid and highly controlled microinjection into droplets. A microneedle is secured within the injection station to confine droplets during the microinjection. The confinement of droplets on the injection station prevents their movement or deformation during the injection process. Three-dimensional (3D) computational analysis is developed and validated to model the dynamics of multiphase flows during the emulsion generation. We investigate the influence of pulsative flows, microneedle parameters and synchronization on the efficacy of microinjection. Finally, the feasibility of implementing our microinjection model is examined experimentally. This technique can be used for tissue engineering, cells actuation and drug discovery as well as developing new strategies for drug delivery.
Toxicity and cytopathology mediated by Bacillus thuringiensis in the midgut of Anticarsia gemmatalis (Lepidoptera: Noctuidae)
Authors: Castro Bárbara Monteiro de Castro e , Martinez Luis Carlos , Barbosa Sergio Guedes , Serrão José Eduardo , Wilcken Carlos Frederico , Soares Marcus Alvarenga , da Silva Antonio Alberto , de Carvalho Amélia Guimarães , Zanuncio José Cola 
Published: April 2019

AbstractBioinsecticides and transgenic plants, based on Bacillus thuringiensis (Bt) toxins are important when managing Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae), a soybean defoliator pest. The interaction of these toxins with the caterpillar’s midgut cells determines their efficacy as an insecticide. The objective was to evaluate the toxicity of B. thuringiensis, subsp. kurstaki strain HD-1 and cytopathological changes mediated by these bacterial toxins in the midgut of A. gemmatalis caterpillars. Insecticidal efficacy was determined by calculating lethal concentration values (LC25, LC50, LC75, LC90 and LC99) in the laboratory. Midgut fragments from A. gemmatalis were extracted after bacterial ingestion and evaluated by light, transmission electron and confocal microscopy. The Bt median lethal concentrations showed toxicity [LC50 = 0.46 (0.43–0.49) mg mL−1] to fourth instar A. gemmatalis caterpillars after 108 hours. Bt induces severe cytotoxicity to A. gemmatalis midgut epithelial cells with increasing exposure over time, causing cellular disorganization, microvillus degeneration, cell fragmentation and protrusion, peritrophic membrane rupture, and cell vacuolization. The cell nuclei presented condensed chromatin and an increase in lysosome numbers. Apoptosis occurred in the midgut cells of caterpillars exposed to Bt. A regenerative response in A. gemmatalis caterpillars was observed 8 hours after exposure to Bt, however this response was not continuous. Toxins produced by Bt are harmful to A. gemmatalis at median concentration with structural damage and death of the midgut epithelial cells of this insect.
Structural analogues of roscovitine rescue the intracellular traffic and the function of ER-retained ABCB4 variants in cell models
Authors: Vauthier Virginie , Ben Saad Amel , Elie Jonathan , Oumata Nassima , Durand-Schneider Anne-Marie , Bruneau Alix , Delaunay Jean-Louis , Housset Chantal , Aït-Slimane Tounsia , Meijer Laurent , Falguières Thomas 
Published: April 2019

AbstractAdenosine triphosphate binding cassette transporter, subfamily B member 4 (ABCB4) is the transporter of phosphatidylcholine at the canalicular membrane of hepatocytes. ABCB4 deficiency, due to genetic variations, is responsible for progressive familial intrahepatic cholestasis type 3 (PFIC3) and other rare biliary diseases. Roscovitine is a molecule in clinical trial that was shown to correct the F508del variant of cystic fibrosis transmembrane conductance regulator (CFTR), another ABC transporter. In the present study, we hypothesized that roscovitine could act as a corrector of ABCB4 traffic-defective variants. Using HEK and HepG2 cells, we showed that roscovitine corrected the traffic and localisation at the plasma membrane of ABCB4-I541F, a prototypical intracellularly retained variant. However, roscovitine caused cytotoxicity, which urged us to synthesize non-toxic structural analogues. Roscovitine analogues were able to correct the intracellular traffic of ABCB4-I541F in HepG2 cells. Importantly, the phospholipid secretion activity of this variant was substantially rescued by three analogues (MRT2-235, MRT2-237 and MRT2-243) in HEK cells. We showed that these analogues also triggered the rescue of intracellular traffic and function of two other intracellularly retained ABCB4 variants, i.e. I490T and L556R. Our results indicate that structural analogues of roscovitine can rescue genetic variations altering the intracellular traffic of ABCB4 and should be considered as therapeutic means for severe biliary diseases caused by this class of variations.
Efficacy and safety assessment of two enterococci phages in an in vitro biofilm wound model
Authors: Melo Luís D. R. , Ferreira R. , Costa Ana R. , Oliveira H. , Azeredo J. 
Published: April 2019

AbstractChronic wounds affect thousands of people worldwide, causing pain and discomfort to patients and represent significant economical burdens to health care systems. The treatment of chronic wounds is very difficult and complex, particularly when wounds are colonized by bacterial biofilms which are highly tolerant to antibiotics. Enterococcus faecium and Enterococcus faecalis are within the most frequent bacteria present in chronic wounds. Bacteriophages (phages) have been proposed as an efficient and alternative against antibiotic-resistant infections, as those found in chronic wounds. We have isolated and characterized two novel enterococci phages, the siphovirus vB_EfaS-Zip (Zip) and the podovirus vB_EfaP-Max (Max) to be applied during wound treatment. Both phages demonstrated lytic behavior against E. faecalis and E. faecium. Genome analysis of both phages suggests the absence of genes associated with lysogeny. A phage cocktail containing both phages was tested against biofilms formed in wound simulated conditions at a multiplicity of infection of 1.0 and a 2.5 log CFU.mL−1 reduction in the bacterial load after at 3 h of treatment was observed. Phages were also tested in epithelial cells colonized by these bacterial species and a 3 log CFU.mL−1 reduction was observed using both phages. The high efficacy of these new isolated phages against multi-species biofilms, their stability at different temperatures and pH ranges, short latent periods and non-cytotoxicity to epithelial cells suggest their therapeutic use to control infectious biofilms present in chronic wounds.
3D analysis of the whole subcutaneous adipose tissue reveals a complex spatial network of interconnected lobules with heterogeneous browning ability
Authors: Dichamp Jules , Barreau Corinne , Guissard Christophe , Carrière Audrey , Martinez Yves , Descombes Xavier , Pénicaud Luc , Rouquette Jacques , Casteilla Louis , Plouraboué Franck , Lorsignol Anne 
Published: April 2019

AbstractAdipose tissue, as the main energy storage organ and through its endocrine activity, is interconnected with all physiological functions. It plays a fundamental role in energy homeostasis and in the development of metabolic disorders. Up to now, this tissue has been analysed as a pool of different cell types with very little attention paid to the organization and putative partitioning of cells. Considering the absence of a complete picture of the intimate architecture of this large soft tissue, we developed a method that combines tissue clearing, acquisition of autofluorescence or lectin signals by confocal microscopy, segmentation procedures based on contrast enhancement, and a new semi-automatic image analysis process, allowing accurate and quantitative characterization of the whole 3D fat pad organization. This approach revealed the unexpected anatomic complexity of the murine subcutaneous fat pad. Although the classical picture of adipose tissue corresponds to a superposition of simple and small ellipsoidal lobules of adipose cells separated by mesenchymal spans, our results show that segmented lobules display complex 3D poly-lobular shapes. Despite differences in shape and size, the number of these poly-lobular subunits is similar from one fat pad to another. Finally, investigation of the relationships of these subunits between each other revealed a never-described organization in two clusters with distinct molecular signatures and specific vascular and sympathetic nerve densities correlating with different browning abilities. This innovative procedure reveals that subcutaneous adipose tissue exhibits a subtle functional heterogeneity with partitioned areas, and opens new perspectives towards understanding its functioning and plasticity.