bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of interconnected vesicles in a liposomal cell model
Authors: Ali Doosti Baharan , Fjällborg Daniel , Kustanovich Kiryl , Jesorka Aldo , Cans Ann-Sofie , Lobovkina Tatsiana 
Published: August 2020

AbstractWe introduce an experimental method based upon a glass micropipette microinjection technique for generating a multitude of interconnected vesicles (IVs) in the interior of a single giant unilamellar phospholipid vesicle (GUV) serving as a cell model system. The GUV membrane, consisting of a mixture of soybean polar lipid extract and anionic phosphatidylserine, is adhered to a multilamellar lipid vesicle that functions as a lipid reservoir. Continuous IV formation was achieved by bringing a micropipette in direct contact with the outer GUV surface and subjecting it to a localized stream of a Ca2+ solution from the micropipette tip. IVs are rapidly and sequentially generated and inserted into the GUV interior and encapsulate portions of the micropipette fluid content. The IVs remain connected to the GUV membrane and are interlinked by short lipid nanotubes and resemble beads on a string. The vesicle chain-growth from the GUV membrane is maintained for as long as there is the supply of membrane material and Ca2+ solution, and the size of the individual IVs is controlled by the diameter of the micropipette tip. We also demonstrate that the IVs can be co-loaded with high concentrations of neurotransmitter and protein molecules and displaying a steep calcium ion concentration gradient across the membrane. These characteristics are analogous to native secretory vesicles and could, therefore, serve as a model system for studying secretory mechanisms in biological systems.
Peripheral serum metabolomic profiles inform central cognitive impairment
Authors: Wang Jingye , Wei Runmin , Xie Guoxiang , Arnold Matthias , Kueider-Paisley Alexandra , Louie Gregory , Mahmoudian Dehkordi Siamak , Blach Colette , Baillie Rebecca , Han Xianlin , De Jager Philip L. , Bennett David A. , Kaddurah-Daouk Rima , Jia Wei 
Published: August 2020

AbstractThe incidence of Alzheimer's disease (AD) increases with age and is becoming a significant cause of worldwide morbidity and mortality. However, the metabolic perturbation behind the onset of AD remains unclear. In this study, we performed metabolite profiling in both brain (n = 109) and matching serum samples (n = 566) to identify differentially expressed metabolites and metabolic pathways associated with neuropathology and cognitive performance and to identify individuals at high risk of developing cognitive impairment. The abundances of 6 metabolites, glycolithocholate (GLCA), petroselinic acid, linoleic acid, myristic acid, palmitic acid, palmitoleic acid and the deoxycholate/cholate (DCA/CA) ratio, along with the dysregulation scores of 3 metabolic pathways, primary bile acid biosynthesis, fatty acid biosynthesis, and biosynthesis of unsaturated fatty acids showed significant differences across both brain and serum diagnostic groups (P-value < 0.05). Significant associations were observed between the levels of differential metabolites/pathways and cognitive performance, neurofibrillary tangles, and neuritic plaque burden. Metabolites abundances and personalized metabolic pathways scores were used to derive machine learning models, respectively, that could be used to differentiate cognitively impaired persons from those without cognitive impairment (median area under the receiver operating characteristic curve (AUC) = 0.772 for the metabolite level model; median AUC = 0.731 for the pathway level model). Utilizing these two models on the entire baseline control group, we identified those who experienced cognitive decline in the later years (AUC = 0.804, sensitivity = 0.722, specificity = 0.749 for the metabolite level model; AUC = 0.778, sensitivity = 0.633, specificity = 0.825 for the pathway level model) and demonstrated their pre-AD onset prediction potentials. Our study provides a proof-of-concept that it is possible to discriminate antecedent cognitive impairment in older adults before the onset of overt clinical symptoms using metabolomics. Our findings, if validated in future studies, could enable the earlier detection and intervention of cognitive impairment that may halt its progression.
Effects of empagliflozin and target-organ damage in a novel rodent model of heart failure induced by combined hypertension and diabetes
Authors: Kräker Kristin , Herse Florian , Golic Michaela , Reichhart Nadine , Crespo-Garcia Sergio , Strauß Olaf , Grune Jana , Kintscher Ulrich , Ebrahim Manal , Bader Michael , Alenina Natalia , Heuser Arnd , Luft Friedrich C. , Müller Dominik N. , Dechend Ralf , Haase Nadine 
Published: August 2020

AbstractType 2 diabetes mellitus and hypertension are two major risk factors leading to heart failure and cardiovascular damage. Lowering blood sugar by the sodium-glucose co-transporter 2 inhibitor empagliflozin provides cardiac protection. We established a new rat model that develops both inducible diabetes and genetic hypertension and investigated the effect of empagliflozin treatment to test the hypothesis if empagliflozin will be protective in a heart failure model which is not based on a primary vascular event. The transgenic Tet29 rat model for inducible diabetes was crossed with the mRen27 hypertensive rat to create a novel model for heart failure with two stressors. The diabetic, hypertensive heart failure rat (mRen27/tetO-shIR) were treated with empagliflozin (10 mg/kg/d) or vehicle for 4 weeks. Cardiovascular alterations were monitored by advanced speckle tracking echocardiography, gene expression analysis and immunohistological staining. The novel model with increased blood pressure und higher blood sugar levels had a reduced survival compared to controls. The rats develop heart failure with reduced ejection fraction. Empagliflozin lowered blood sugar levels compared to vehicle treated animals (182.3 ± 10.4 mg/dl vs. 359.4 ± 35.8 mg/dl) but not blood pressure (135.7 ± 10.3 mmHg vs. 128.2 ± 3.8 mmHg). The cardiac function was improved in all three global strains (global longitudinal strain − 8.5 ± 0.5% vs. − 5.5 ± 0.6%, global radial strain 20.4 ± 2.7% vs. 8.8 ± 1.1%, global circumferential strain − 11.0 ± 0.7% vs. − 7.6 ± 0.8%) and by increased ejection fraction (42.8 ± 4.0% vs. 28.2 ± 3.0%). In addition, infiltration of macrophages was decreased by treatment (22.4 ± 1.7 vs. 32.3 ± 2.3 per field of view), despite mortality was not improved. Empagliflozin showed beneficial effects on cardiovascular dysfunction. In this novel rat model of combined hypertension and diabetes, the improvement in systolic and diastolic function was not secondary to a reduction in left ventricular mass or through modulation of the afterload, since blood pressure was not changed. The mRen27/tetO-shIR strain should provide utility in separating blood sugar from blood pressure-related treatment effects.
Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide
Authors: Isabel Sandra , Graña-Miraglia Lucía , Gutierrez Jahir M. , Bundalovic-Torma Cedoljub , Groves Helen E. , Isabel Marc R. , Eshaghi AliReza , Patel Samir N. , Gubbay Jonathan B. , Poutanen Tomi , Guttman David S. , Poutanen Susan M. 
Published: August 2020

AbstractThe COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10–25 January) 2020. We also applied structural bioinformatics to assess the potential impact of D614G on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.
Interfacial rheology for the assessment of potential health effects of inhaled carbon nanomaterials at variable breathing conditions
Authors: Kondej Dorota , Sosnowski Tomasz R. 
Published: August 2020

AbstractLung surface is the first line of contact between inhaled carbon nanomaterials, CNMs, and the organism, so this is the place where pulmonary health effects begin. The paper analyzes the influence of several CNMs (single- and multi-walled nanotubes with various surface area: 90–1,280 m2/g and aspect ratio: 8–3,750) on the surface-active properties of the lung surfactant, LS, model (Survanta). Effects of CNM concentration (0.1–1 mg/ml) and surface oscillation rate were determined using the oscillating drop method at simulated breathing conditions (2–10 s per cycle, 37 °C). Based on the values of apparent elasticity and viscosity of the interfacial region, new parameters: Sε and Sμ were proposed to evaluate potential effect of particles on the LS at various breathing rates. Some of tested CNMs (e.g., COOH- functionalized short nanotubes) significantly influenced the surfactant dynamics, while the other had weaker effects even at high particle concentration. Analysis of changes in Sε and Sμ provides a new way to evaluate of a possible disturbance of the basic functions of LS. The results show that the expected pulmonary effects caused by inhaled CNMs at variable breathing rate depend not only on particle concentration (inhaled dose) but also on their size, structure and surface properties.
Autophagy regulates trophoblast invasion by targeting NF-κB activity
Authors: Oh Soo-young , Hwang Jae Ryoung , Choi Minji , Kim Yoo-Min , Kim Jung-Sun , Suh Yeon-Lim , Choi Suk-Joo , Roh Cheong-Rae 
Published: August 2020

AbstractPreeclampsia is one of the most serious complications of pregnancy, affecting 5–10% of parturients worldwide. Recent studies have suggested that autophagy is involved in trophoblast invasion and may be associated with defective placentation underlying preeclampsia. We thus aimed to understand the mechanistic link between autophagy and trophoblast invasion. Using the two most commonly used trophoblast cell lines, JEG-3 and HTR-8/SVneo, we inhibited autophagy by ATG5 and beclin-1 shRNA. Conversion of LC3-II was evaluated in ATG5 and beclin-1 knock-down cells in the presence of the lysosomal protease inhibitors E-64d and pepstatin A, to detect the efficiency of autophagy inhibition. Upon autophagy inhibition, we measured cell invasion, activity of NF-κB and related signaling pathways, MMP-2, MMP-9, sFlt-1, and TNF-α levels. Autophagy inhibition increased the invasiveness of these trophoblastic cell lines and increased Akt and NF-κB activity as well as p65 expression. Of note, an NF-κB inhibitor significantly attenuated the trophoblast invasion induced by autophagy inhibition. Autophagy inhibition was also associated with increased MMP-2 and MMP-9 levels and decreased the production of sFlt-1 and TNF-α. Collectively, our results indicate that autophagy regulates trophoblast invasiveness in which the NF-κB pathway and MMP-2, MMP-9, sFlt-1 and TNF-α levels are affected.
Non-linear changes in modelled terrestrial ecosystems subjected to perturbations
Authors: Newbold Tim , Tittensor Derek P. , Harfoot Michael B. J. , Scharlemann Jörn P. W. , Purves Drew W. 
Published: August 2020

AbstractPerturbed ecosystems may undergo rapid and non-linear changes, resulting in ‘regime shifts’ to an entirely different ecological state. The need to understand the extent, nature, magnitude and reversibility of these changes is urgent given the profound effects that humans are having on the natural world. General ecosystem models, which simulate the dynamics of ecosystems based on a mechanistic representation of ecological processes, provide one novel way to project ecosystem changes across all scales and trophic levels, and to forecast impact thresholds beyond which irreversible changes may occur. We model ecosystem changes in four terrestrial biomes subjected to human removal of plant biomass, such as occurs through agricultural land-use change. We find that irreversible, non-linear responses commonly occur where removal of vegetation exceeds 80% (a level that occurs across nearly 10% of the Earth’s land surface), especially for organisms at higher trophic levels and in less productive ecosystems. Very large, irreversible changes to ecosystem structure are expected at levels of vegetation removal akin to those in the most intensively used real-world ecosystems. Our results suggest that the projected twenty-first century rapid increases in agricultural land conversion may lead to widespread trophic cascades and in some cases irreversible changes to ecosystem structure.
Impact of aerobic exercise type on blood flow, muscle energy metabolism, and mitochondrial biogenesis in experimental lower extremity artery disease
Authors: Pellegrin Maxime , Bouzourène Karima , Aubert Jean-François , Bielmann Christelle , Gruetter Rolf , Rosenblatt-Velin Nathalie , Poitry-Yamate Carole , Mazzolai Lucia 
Published: August 2020

AbstractExercise training (ET) is recommended for lower extremity artery disease (LEAD) management. However, there is still little information on the hemodynamic and metabolic adaptations by skeletal muscle with ET. We examined whether hindlimb perfusion/vascularization and muscle energy metabolism are altered differently by three types of aerobic ET. ApoE−/− mice with LEAD were assigned to one of four groups for 4 weeks: sedentary (SED), forced treadmill running (FTR), voluntary wheel running (VWR), or forced swimming (FS). Voluntary exercise capacity was improved and equally as efficient with FTR and VWR, but remained unchanged with FS. Neither ischemic hindlimb perfusion and oxygenation, nor arteriolar density and mRNA expression of arteriogenic-related genes differed between groups. 18FDG PET imaging revealed no difference in the steady-state levels of phosphorylated 18FDG in ischemic and non-ischemic hindlimb muscle between groups, nor was glycogen content or mRNA and protein expression of glucose metabolism-related genes in ischemic muscle modified. mRNA (but not protein) expression of lipid metabolism-related genes was upregulated across all exercise groups, particularly by non-ischemic muscle. Markers of mitochondrial content (mitochondrial DNA content and citrate synthase activity) as well as mRNA expression of mitochondrial biogenesis-related genes in muscle were not increased with ET. Contrary to FTR and VWR, swimming was ineffective in improving voluntary exercise capacity. The underlying hindlimb hemodynamics or muscle energy metabolism are unable to explain the benefits of running exercise.
Monitoring membrane viscosity in differentiating stem cells using BODIPY-based molecular rotors and FLIM
Authors: Kashirina Alena S. , López-Duarte Ismael , Kubánková Markéta , Gulin Alexander A. , Dudenkova Varvara V. , Rodimova Svetlana A. , Torgomyan Hayk G. , Zagaynova Elena V. , Meleshina Aleksandra V. , Kuimova Marina K. 
Published: August 2020

AbstractMembrane fluidity plays an important role in many cell functions such as cell adhesion, and migration. In stem cell lines membrane fluidity may play a role in differentiation. Here we report the use of viscosity-sensitive fluorophores based on a BODIPY core, termed “molecular rotors”, in combination with Fluorescence Lifetime Imaging Microscopy, for monitoring of plasma membrane viscosity changes in mesenchymal stem cells (MSCs) during osteogenic and chondrogenic differentiation. In order to correlate the viscosity values with membrane lipid composition, the detailed analysis of the corresponding membrane lipid composition of differentiated cells was performed by time-of-flight secondary ion mass spectrometry. Our results directly demonstrate for the first time that differentiation of MSCs results in distinct membrane viscosities, that reflect the change in lipidome of the cells following differentiation.
Effects of HIV infection, antiretroviral therapy, and immune status on the speed of information processing and complex motor functions in adult Cameroonians
Authors: Kanmogne Georgette D. , Fonsah Julius Y. , Umlauf Anya , Moul Jacob , Doh Roland F. , Kengne Anne M. , Tang Bin , Tagny Claude T. , Nchindap Emilienne , Kenmogne Léopoldine , Franklin Donald , Njamnshi Dora M. , Kuate Callixte T. , Mbanya Dora , Njamnshi Alfred K. , Heaton Robert K. 
Published: August 2020

AbstractHIV-associated neurocognitive deficits include impaired speed-of-information processing (SIP) and motor functions. There is lack of Cameroonian adult norms for assessing SIP or motor functions. This study of 683 Cameroonians (320 HIV+, 363 HIV−) establishes demographically-adjusted norms for six SIP [Wechsler-Adult-Intelligence-Scale (WAIS)-III Digit Symbol (WAIS-IIIDS) and Symbol Search (WAIS-IIISS), Stroop Color-Naming, Stroop Word-Reading, Trail-Making Test-A (TMT-A), Color Trails-1 (CTT1)], and two motor function [Grooved Pegboard-dominant (GP-DH) and non-dominant (GP-NDH) hands] tests. We assessed viral effects on SIP and motor functions. HIV-infected persons had significantly lower (worse) T scores on GP-DH, WAIS-IIIDS, Stroop Word-Reading, TMT-A; lower motor and SIP summary T scores. Significantly higher proportion of cases (20.7%) than controls (10.3%) had impaired SIP. Male cases had better T scores than female cases on GP-NDH, WAIS-IIIDS, WAIS-IIISS, TMT-A, CTT1; better SIP summary T scores. Antiretroviral therapy (ART) was associated with significantly better T scores on GP-NDH, WAIS-IIIDS, Stroop Color-Naming; better motor and SIP summary T scores. Cases with higher CD4 had better T scores on WAIS-IIIDS, TMT-A, CTT1; better SIP summary T scores. Overall, we demonstrate that HIV infection in Cameroon is associated with deficits in SIP and motor functions; ART and higher CD4 are associated with better cognitive performance. We provide SIP and psychomotor functions normative standards, which will be useful for neurobehavioral studies in Cameroon of diseases affecting the brain.
Use of supercritical carbon dioxide technology for fabricating a tissue engineering scaffold for anterior cruciate ligament repair
Authors: Sherifi Ines , Bachy Manon , Laumonier Thomas , Petite Hervé , Hannouche Didier 
Published: August 2020

AbstractTissue-engineered grafts may be useful in Anterior Cruciate Ligament (ACL) repair and provide a novel, alternative treatment to clinical complications of rupture, harvest site morbidity and biocompatibility associated with autografts, allografts and synthetic grafts. We successfully used supercritical carbon dioxide (Sc-CO2) technology for manufacturing a “smart” biomaterial scaffold, which retains the native protein conformation and tensile strength of the natural ACL but is decellularized for a decreased immunogenic response. We designed and fabricated a new scaffold exhibiting (1) high tensile strength and biomechanical properties comparable to those of the native tissue, (2) thermodynamically-stable extra-cellular matrix (ECM), (3) preserved collagen composition and crosslinking, (4) a decellularized material milieu with potential for future engineering applications and (5) proven feasibility and biocompatibility in an animal model of ligament reconstruction. Because of the “smart” material ECM, this scaffold may have the potential for providing a niche and for directing stem cell growth, differentiations and function pertinent to new tissue formation. Sc-CO2-related technology is advanced and has the capability to provide scaffolds of high strength and durability, which sustain a lifetime of wear and tear under mechanical loading in vivo.
How memory effects, check dams, and channel geometry control erosion and deposition by debris flows
Authors: de Haas T. , Nijland W. , de Jong S. M. , McArdell B. W. 
Published: August 2020

AbstractDebris flows can grow greatly in size and hazardous potential by eroding bed and bank material, but effective hazard assessment and mitigation is currently hampered by limited understanding of erosion and deposition dynamics. We have collected high-resolution pre- and post-flow topography for 6 debris flows over a 3 km long unconsolidated reach of the Illgraben channel in the Swiss Alps with drone-based photogrammetry. We show that the spatio-temporal patterns of erosion and deposition in debris-flow torrents are highly variable and dynamic. Check dams strongly control the spatial patterns of erosion and deposition. We identify a memory effect where erosion is strong at locations of strong deposition during previous flows and vice versa. Large sediment inputs from subcatchments initially result in new channel erosion through the subcatchment deposits and simultaneous upstream deposition, likely as a result of backwater effects. It is generally believed that erosion increases with debris-flow magnitude, but we show that there is a limit to debris-flow bulking set by channel geometry. These findings provide key guidelines for flow volume forecasting, emphasizing the importance of memory effects and the need to resolve both erosion and deposition in predictive models.
Performance demonstration of a hybrid Compton camera with an active pinhole for wide-band X-ray and gamma-ray imaging
Authors: Omata Akihisa , Kataoka Jun , Fujieda Kazuya , Sato Shogo , Kuriyama Eri , Kato Hiroki , Toyoshima Atsushi , Teramoto Takahiro , Ooe Kazuhiro , Liu Yuwei , Matsunaga Keiko , Kamiya Takashi , Watabe Tadashi , Shimosegawa Eku , Hatazawa Jun 
Published: August 2020

AbstractX-ray and gamma-ray imaging are technologies with several applications in nuclear medicine, homeland security, and high-energy astrophysics. However, it is generally difficult to realize simultaneous wide-band imaging ranging from a few tens of keV to MeV because different interactions between photons and the detector material occur, depending on the photon energies. For instance, photoabsorption occurs below 100 keV, whereas Compton scattering dominates above a few hundreds of keV. Moreover, radioactive sources generally emit both X-ray and gamma-ray photons. In this study, we develop a “hybrid” Compton camera that can simultaneously achieve X-ray and gamma-ray imaging by combining features of “Compton” and “pinhole” cameras in a single detector system. Similar to conventional Compton cameras, the detector consists of two layers of scintillator arrays with the forward layer acting as a scatterer for high-energy photons (> 200 keV) and an active pinhole for low-energy photons (< 200 keV). The experimental results on the performance of the hybrid camera were consistent with those from the Geant4 simulation. We simultaneously imaged $$^{241}$$

241

Am (60 keV) and $$^{137}$$

137

Cs (662 keV) in the same field of view, achieving an angular resolution of 10$$^\circ $$

∘

(FWHM) for both sources. In addition, imaging of $$^{211}$$

211

At was conducted for the application in future nuclear medicine, particularly radionuclide therapy. The initial demonstrative images of the $$^{211}$$

211

At phantom were reconstructed using the pinhole mode (using 79 keV) and Compton mode (using 570 keV), exhibiting significant similarities in source-position localization. We also verified that a mouse injected with 1 MBq of $$^{211}$$

211

At can be imaged via pinhole-mode measurement in an hour.