bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fenestral diaphragms and PLVAP associations in liver sinusoidal endothelial cells are developmentally regulated
Authors: Auvinen Kaisa , Lokka Emmi , Mokkala Elias , Jäppinen Norma , Tyystjärvi Sofia , Saine Heikki , Peurla Markus , Shetty Shishir , Elima Kati , Rantakari Pia , Salmi Marko 
Published: October 2019

AbstractEndothelial cells contain several nanoscale domains such as caveolae, fenestrations and transendothelial channels, which regulate signaling and transendothelial permeability. These structures can be covered by filter-like diaphragms. A transmembrane PLVAP (plasmalemma vesicle associated protein) protein has been shown to be necessary for the formation of diaphragms. The expression, subcellular localization and fenestra-forming role of PLVAP in liver sinusoidal endothelial cells (LSEC) have remained controversial. Here we show that fenestrations in LSEC contain PLVAP-diaphragms during the fetal angiogenesis, but they lose the diaphragms at birth. Although it is thought that PLVAP only localizes to diaphragms, we found luminal localization of PLVAP in adult LSEC using several imaging techniques. Plvap-deficient mice revealed that the absence of PLVAP and diaphragms did not affect the morphology, the number of fenestrations or the overall vascular architecture in the liver sinusoids. Nevertheless, PLVAP in fetal LSEC (fenestrations with diaphragms) associated with LYVE-1 (lymphatic vessel endothelial hyaluronan receptor 1), neuropilin-1 and VEGFR2 (vascular endothelial growth factor receptor 2), whereas in the adult LSEC (fenestrations without diaphragms) these complexes disappeared. Collectively, our data show that PLVAP can be expressed on endothelial cells without diaphragms, contradict the prevailing concept that biogenesis of fenestrae would be PLVAP-dependent, and reveal previously unknown PLVAP-dependent molecular complexes in LSEC during angiogenesis.
Ultrasound-assisted gatifloxacin delivery in mouse cornea, in vivo
Authors: Jegal Uk , Lee Jun Ho , Lee Jungbin , Jeong Hyerin , Kim Myoung Joon , Kim Ki Hean 
Published: October 2019

AbstractGatifloxacin is a 4th generation fluoroquinolone antibiotic used in the clinic to treat ocular infection. One limitation of gatifloxacin is its relatively poor corneal penetration, and the increase of its trans-corneal delivery would be beneficial to reduce the amount or frequency of daily dose. In this study, ultrasound treatment was applied to enhance the trans-corneal delivery of gatifloxacin without damage. Experiments were conducted on mouse eyes in ex vivo and in vivo conditions. Ultrasound waves with 1 MHz in frequency, 1.3 W/cm2 in intensity were applied onto the mouse cornea for 5 minutes, and then gatifloxacin ophthalmic solution was instilled and left there for 10 minutes. 3D gatifloxacin distribution in the cornea was measured by two-photon microscopy (TPM) imaging based on its intrinsic fluorescence. Longitudinal TPM imaging of ultrasound treated mouse corneas showed the increase of initial gatifloxacin intensities on the corneal surface compared to untreated mouse corneas by 67%, and then the increased gatifloxacin delivery into the cornea from the surface at later time. The delivered gatifloxacin in the corneal epithelium stayed longer in the ultrasound treated corneas than in the untreated corneas. The enhanced trans-corneal delivery and extended stay of gatifloxacin in the mouse cornea by ultrasound treatment could be beneficial for therapeutic effects. This study demonstrated the detail process of enhanced trans-corneal gatifloxacin delivery by ultrasound treatment.
Differential interleukin-1β induction by uropathogenic Escherichia coli correlates with its phylotype and serum C-reactive protein levels in Korean infants
Authors: Jung Jong-Hyeok , Hong Hyun Jung , Gharderpour Aziz , Cho Jae Young , Baek Bum-Seo , Hur Yong , Kim Byoung Choul , Kim Donghyun , Seong Seung-Yong , Lim Jae-Young , Seo Sang-Uk 
Published: October 2019

AbstractUrinary tract infection (UTI) is one of the most common bacterial infections in infants less than age 1 year. UTIs frequently recur and result in long-term effects include sepsis and renal scarring. Uropathogenic Escherichia coli (UPEC), the most prevalent organism found in UTIs, can cause host inflammation via various virulence factors including hemolysin and cytotoxic necrotizing factors by inducing inflammatory cytokines such as interleukin (IL)-1β. However, the ability of each UPEC organism to induce IL-1β production may differ by strain. Furthermore, the correlation between differential IL-1β induction and its relevance in pathology has not been well studied. In this study, we isolated UPEC from children under age 24 months and infected bone-marrow derived macrophages with the isolates to investigate secretion of IL-1β. We found that children with higher concentrations of C-reactive protein (CRP) were more likely to harbor phylotype B2 UPEC strains that induced more IL-1β production than phylotype D. We also observed a significant correlation between serum CRP level and in vitro IL-1β induction by phylotype B2 UPEC bacteria. Our results highlight the diversity of UPEC in terms of IL-1β induction capacity in macrophages and suggest a potential pathogenic role in UTIs by inducing inflammation in infants.
Between-subject variability in the influence of mental imagery on conscious perception
Authors: Dijkstra N. , Hinne M. , Bosch S. E. , van Gerven M. A. J. 
Published: October 2019

AbstractMental imagery and visual perception rely on similar neural mechanisms, but the function of this overlap remains unclear. One idea is that imagery can influence perception. Previous research has shown that imagining a stimulus prior to binocular presentation of rivalling stimuli increases the chance of perceiving the imagined stimulus. In this study we investigated how this effect interacts with bottom-up sensory input by comparing psychometric response curves for congruent and incongruent imagery in humans. A Bayesian hierarchical model was used, allowing us to simultaneously study group-level effects as well as effects for individual participants. We found strong effects of both imagery as well as its interaction with sensory evidence within individual participants. However, the direction of these effects were highly variable between individuals, leading to weak effects at the group level. This highlights the heterogeneity of conscious perception and emphasizes the need for individualized investigation of such complex cognitive processes.
Decadal acidification in Atlantic and Mediterranean water masses exchanging at the Strait of Gibraltar
Authors: Flecha Susana , Pérez Fiz F. , Murata Akihiko , Makaoui Ahmed , Huertas I. Emma 
Published: October 2019

AbstractSeawater pH is undergoing a decreasing trend due to the absorption of atmospheric CO2, a phenomenon known as ocean acidification (OA). Biogeochemical processes occurring naturally in the ocean also change pH and hence, for an accurate assessment of OA, the contribution of the natural component to the total pH variation must be quantified. In this work, we used 11 years (2005–2015) of biogeochemical measurements collected at the Strait of Gibraltar to estimate decadal trends of pH in two major Mediterranean water masses, the Western Mediterranean Deep Water (WMDW) and the Levantine Intermediate Water (LIW) and assess the magnitude of natural and anthropogenic components on the total pH change. The assessment was also performed in the North Atlantic Central Water (NACW) feeding the Mediterranean Sea. Our analysis revealed a significant human impact on all water masses in terms of accumulation of anthropogenic CO2. However, the decadal pH decline found in the WMDW and the NACW was markedly affected by natural processes, which accounted for by nearly 60% and 40% of the total pH decrease, respectively. The LIW did not exhibit a significant pH temporal trend although data indicated natural and anthropogenic perturbations on its biogeochemical signatures.
Natural phenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidase IV
Authors: Huang Po-Kai , Lin Shian-Ren , Chang Chia-Hsiang , Tsai May-Jwan , Lee Der-Nan , Weng Ching-Feng 
Published: October 2019

AbstractDipeptidyl peptidase IV (DPP IV) is a surface glycoprotein that can degrade glucagon like pepetide-1 (GLP-1) by decreasing blood sugar. Herbal medicines for diabetic therapy are widely used with acceptable efficacy but unsatisfied in advances. DPP IV was chosen as a template to employ molecular docking via Discovery Studio to search for natural phenolic compounds whether they have the inhibitory function of DPP IV. Then, docking candidates were validated and further performed signal pathway via Caco-2, C2C12, and AR42J cells. Lastly, a diet-induced diabetes in mice were applied to examine the efficacy and toxicity of hit natural phenolic products in long-term use (in vivo). After screening, curcumin, syringic acid, and resveratrol were found in high affinity with DPP IV enzymes. In enzymatic tests, curcumin and resveratrol showed potential inhibition of DPP IV. In vitro assays, curcumin inhibited of DPP IV activity in Caco-2 cells and ERK phosphorylation in C2C12 cells. Additionally, curcumin attenuated blood sugar in S961-treated C57BL/6 mice and in diet-induced diabetic ICR mice and long-term regulate HbA1c in diabetic mice. Curcumin targeted to DPP IV for reducing blood glucose, it possesses potential and alternative substitution of synthetic clinical drugs for the medication of diabetes.
Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice
Authors: Madsen Mette Simone Aae , Holm Jacob Bak , Pallejà Albert , Wismann Pernille , Fabricius Katrine , Rigbolt Kristoffer , Mikkelsen Martin , Sommer Morten , Jelsing Jacob , Nielsen Henrik Bjørn , Vrang Niels , Hansen Henrik H. 
Published: October 2019

AbstractEnteroendocrine L-cell derived peptide hormones, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), have become important targets in the treatment of type 2 diabetes, obesity and intestinal diseases. As gut microbial imbalances and maladaptive host responses have been implicated in the pathology of obesity and diabetes, this study aimed to determine the effects of pharmacologically stimulated GLP-1 and GLP-2 receptor function on the gut microbiome composition in diet-induced obese (DIO) mice. DIO mice received treatment with a selective GLP-1 receptor agonist (liraglutide, 0.2 mg/kg, BID) or dual GLP-1/GLP-2 receptor agonist (GUB09–145, 0.04 mg/kg, BID) for 4 weeks. Both compounds suppressed caloric intake, promoted a marked weight loss, improved glucose tolerance and reduced plasma cholesterol levels. 16S rDNA sequencing and deep-sequencing shotgun metagenomics was applied for comprehensive within-subject profiling of changes in gut microbiome signatures. Compared to baseline, DIO mice assumed phylogenetically similar gut bacterial compositional changes following liraglutide and GUB09-145 treatment, characterized by discrete shifts in low-abundant species and related bacterial metabolic pathways. The microbiome alterations may potentially associate to the converging biological actions of GLP-1 and GLP-2 receptor signaling on caloric intake, glucose metabolism and lipid handling.
Metallic edge states in zig-zag vertically-oriented MoS2 nanowalls
Authors: Tinoco Miguel , Maduro Louis , Conesa-Boj Sonia 
Published: October 2019

AbstractThe remarkable properties of layered materials such as MoS2 strongly depend on their dimensionality. Beyond manipulating their dimensions, it has been predicted that the electronic properties of MoS2 can also be tailored by carefully selecting the type of edge sites exposed. However, achieving full control over the type of exposed edge sites while simultaneously modifying the dimensionality of the nanostructures is highly challenging. Here we adopt a top-down approach based on focus ion beam in order to selectively pattern the exposed edge sites. This strategy allows us to select either the armchair (AC) or the zig-zag (ZZ) edges in the MoS2 nanostructures, as confirmed by high-resolution transmission electron microscopy measurements. The edge-type dependence of the local electronic properties in these MoS2 nanostructures is studied by means of electron energy-loss spectroscopy measurements. This way, we demonstrate that the ZZ-MoS2 nanostructures exhibit clear fingerprints of their predicted metallic character. Our results pave the way towards novel approaches for the design and fabrication of more complex nanostructures based on MoS2 and related layered materials for applications in fields such as electronics, optoelectronics, photovoltaics, and photocatalysts.
Roles of monocarboxylate transporter subtypes in promotion and suppression of osteoclast differentiation and survival on bone
Authors: Imai Hiroko , Yoshimura Kentaro , Miyamoto Yoichi , Sasa Kiyohito , Sugano Marika , Chatani Masahiro , Takami Masamichi , Yamamoto Matsuo , Kamijo Ryutaro 
Published: October 2019

AbstractMonocarboxylate transporters (MCTs) provide transmembrane transport of monocarboxylates such as lactate and pyruvate. The present results showed that α-cyano-4-hydroxycinnamic acid (CHC), an inhibitor of MCTs, promoted osteoclast differentiation from macrophages at lower concentrations (0.1–0.3 mM) and suppressed that at a higher concentration (1.0 mM). On the other hand, CHC reduced the number of mature osteoclasts on the surface of dentin in a concentration-dependent manner. Additionally, macrophages and osteoclasts were found to express the Mct1, Mct2, and Mct4 genes, with Mct1 and Mct4 expression higher in macrophages, and that of Mct2 higher in osteoclasts. Although Mct1 gene knockdown in macrophages enhanced osteoclast formation induced by RANKL, Mct2 gene knockdown suppressed that. Finally, Mct2 gene silencing in mature osteoclasts decreased their number and, thereby, bone resorption. These results suggest that MCT1 is a negative regulator and MCT2 a positive regulator of osteoclast differentiation, while MCT2 is required for bone resorption by osteoclasts.
An Automated, Quantitative, and Multiplexed Assay Suitable for Point-of-Care Hepatitis B Virus Diagnostics
Authors: Gani Adi Wijaya , Wei Wei , Shi Run-Zhang , Ng Elaine , Nguyen Mindie , Chua Mei-Sze , So Samuel , Wang Shan X. 
Published: October 2019

AbstractHepatitis B virus (HBV) infection has a global reach with high prevalence in resource-limited areas like China and Africa. HBV patients in these areas have limited access to the currently used, costly HBV assays, which are performed in centralized clinical laboratories using single-plexed assays with bulky and expensive instruments. We aim to overcome these limitations by developing a simple and affordable HBV diagnostic platform to allow for timelier diagnosis and intervention of HBV infection. Using giant magnetoresistive (GMR) biosensor chips, we developed an automated and multiplexed quantitative platform for the measurement of a panel of HBV serology markers, including HBV “e” antigen (HBeAg), HBV surface antigen (HBsAg), and the antibody against HBsAg (anti-HBs). Our assay platform was able to detect each HBV marker with high specificity and sensitivity (with three orders of magnitude in dynamic range for each marker). Blinded analysis of HBV patient sera showed excellent correlation between our multiplexed quantitative HBsAg results and the qualitative results obtained using FDA-approved immunoassays, as well as those obtained using quantitative, single-plexed, enzyme-linked immunosorbent assays (ELISAs). The portable, automated, multiplexed, quantitative HBV serology assay platform we designed shows great promise as a more accessible alternative for HBV screening, diagnosis, and treatment monitoring.
Impacts of Maize Domestication and Breeding on Rhizosphere Microbial Community Recruitment from a Nutrient Depleted Agricultural Soil
Authors: Brisson Vanessa L. , Schmidt Jennifer E. , Northen Trent R. , Vogel John P. , Gaudin Amélie C. M. 
Published: October 2019

AbstractMaize domestication and breeding have resulted in drastic and well documented changes in aboveground traits, but belowground effects on root system functioning and rhizosphere microbial communities remain poorly understood, despite their critical importance for nutrient and water acquisition. We investigated the rhizosphere microbial community composition and structure of ten Zea mays accessions along an evolutionary transect (two teosinte, three inbred maize lines, and five modern maize hybrids) grown in nutrient depleted soil from a low input agricultural system. Microbial community analysis revealed significant differences in community composition between soil compartments (proximal vs. distal rhizosphere) and between plant genetic groups (teosinte, inbred, and modern hybrid). Only a small portion of the microbial community was differentially selected across plant genetic groups: 3.7% of prokaryotic community members and 4.9% of fungal community members were significantly associated with a specific plant genetic group. Indicator species analysis showed the greatest differentiation between modern hybrids and the other two plant genetic groups. Co-occurrence network analysis revealed that microbial co-occurrence patterns of the inbred maize lines’ rhizosphere were significantly more similar to those of the teosintes than to the modern hybrids. Our results suggest that advances in hybrid development significantly impacted rhizosphere microbial communities and network assembly.
Allogeneic dendritic cells induce potent antitumor immunity by activating KLRG1+CD8 T cells
Authors: Wang Chao , Li Zhengyuan , Zhu Zhongli , Chai Yijie , Wu Yiqing , Yuan Zhenglong , Chang Zhijie , Wang Zhao , Zhang Minghui 
Published: October 2019

AbstractThe graft-versus-leukemia effect reminds us to observe the allogeneic cell elicited anti-tumor immune responses. Here we immunized recipient B6 mice with different types of allogenic leukocytes and found that vaccination with allogenic dendritic cells (alloDC) elicited the most efficient protection against broad-spectrum tumors. The recipient lymphocytes were analyzed and the data showed that CD8 T cells increased significantly after immunization and expressed effector memory T cell marker KLRG1. Functional evaluation demonstrated that these KLRG1+CD8 T cells could kill tumor cells in vitro and in vivo in Granzyme B- and Fas/FasL-dependent manners with no tumor antigen specificity, and tend to migrate into tumor sites by high expression of heparanase. Adoptive transfer of these cells could provide antitumor protection against tumors. AlloDC could also treat mice with residual tumors and combination of anti-PD1 antibody could enhance this effects. Together, our study showed that alloDC-immunization could induce potent antitumor effect through the expansion of KLRG1+CD8 T cells, which can work as both preventive and therapeutic tumor vaccines.
Bispectrum and Recurrent Neural Networks: Improved Classification of Interictal and Preictal States
Authors: Gagliano Laura , Bou Assi Elie , Nguyen Dang K. , Sawan Mohamad 
Published: October 2019

AbstractThis work proposes a novel approach for the classification of interictal and preictal brain states based on bispectrum analysis and recurrent Long Short-Term Memory (LSTM) neural networks. Two features were first extracted from bilateral intracranial electroencephalography (iEEG) recordings of dogs with naturally occurring focal epilepsy. Single-layer LSTM networks were trained to classify 5-min long feature vectors as preictal or interictal. Classification performances were compared to previous work involving multilayer perceptron networks and higher-order spectral (HOS) features on the same dataset. The proposed LSTM network proved superior to the multilayer perceptron network and achieved an average classification accuracy of 86.29% on held-out data. Results imply the possibility of forecasting epileptic seizures using recurrent neural networks, with minimal feature extraction.
Existence of multiple scales in uncertainty of numerical weather prediction
Authors: Song Hyo-Jong 
Published: October 2019

AbstractNumerical weather prediction provides essential information of societal influence. Advances in the initial condition estimation have led to the improvement of the prediction skill. The process to produce the better initial condition (analysis) with the combination of short-range forecast and observation over the globe requires information about uncertainty of the forecast results to decide how much observation is reflected to the analysis and how far the observation information should be propagated. Forecast ensemble represents the error of the short-range forecast at the instance. The influence of observation propagating along with forecast ensemble correlation needs to be restricted by localized correlation function because of less reliability of sample correlation. So far, solitary radius of influence is usually used since there has not been an understanding about the realism of multiple scales in the forecast uncertainty. In this study, it is explicitly shown that multiple scales exist in short-range forecast error and any single-scale localization approach could not resolve this situation. A combination of Gaussian correlation functions of various scales is designed, which more weighs observation itself near the data point and makes ensemble perturbation, far from the observation position, more participate in decision of the analysis. Its outstanding performance supports the existence of multi-scale correlation in forecast uncertainty.
Diaminoquinazoline MMV675968 from Pathogen Box inhibits Acinetobacter baumannii growth through targeting of dihydrofolate reductase
Authors: Songsungthong Warangkhana , Yongkiettrakul Suganya , Bohan Louise E. , Nicholson Eric S. , Prasopporn Sunisa , Chaiyen Pimchai , Leartsakulpanich Ubolsree 
Published: October 2019

AbstractAntibiotic resistance in Acinetobacter baumannii is a major global health threat. New drugs with novel chemical structures are needed to overcome a myriad of resistance mechanisms in A. baumannii. In this study, we screened an open-source Pathogen Box library for anti-A. baumannii compounds. Compound MMV675968 (a diaminoquinazoline analog) was the only non-reference compound found to inhibit the growth of all four A. baumannii test strains with IC50 of 0.6–2.7 μM, IC90 of 0.7–3.9 μM, and MIC of 1.6–10 μM. We showed that MMV675968 targeted A. baumannii dihydrofolate reductase (AbDHFR) as determined by an E. coli surrogate whose growth was dependent on AbDHFR function and by an in vitro DHFR activity assay. Additionally, chemical scaffolds of DHFR inhibitors that are effective as antibiotics against A. baumannii were identified using an in vitro DHFR activity assay and A. baumannii growth inhibition. MMV675968 was the most potent among DHFR inhibitors tested in inhibiting A. baumannii growth. This study shows for the first time that MMV675968 inhibits A. baumannii growth via selective inhibition of AbDHFR and is therefore a promising scaffold for further antibiotic development against A. baumannii.