bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long noncoding RNA lncARSR confers resistance to Adriamycin and promotes osteosarcoma progression
Authors: Shen Peng , Cheng Yanfeng 
Published: May 2020

AbstractOne of the significant challenges for chemotherapy is the appearance of resistance to compounds. Although several signaling pathways have been implicated in the development of Adriamycin (ADM) resistance, mechanisms involved in ADM-resistant osteosarcoma progression remain unknown. The present study attempted to illustrate the role of long noncoding RNA ARSR (lncARSR) in the development of adapted ADM resistance. We found lncARSR overexpressed in the Adriamycin-resistant cell lines U2OS/ADM and MG63/ADM, accompanied with acquired multidrug resistance against to paclitaxel and cisplatin. Overexpression of lncARSR triggered rhodamine 123 efflux and survival, as well as the migration of Adriamycin-resistant cells. Inversely, the depletion of lncARSR promoted rhodamine 123 retention and apoptosis, while reducing the motility of ADM-resistant cells. Further investigation revealed that the upregulation of lncARSR enhanced multidrug resistance-associated protein-1 (MRP1), apoptosis inhibitor Survivin, and matrix metalloproteinase-2 (MMP2) through activating AKT. The reduction of lncARSR overcame the resistance to ADM in U2OS/ADM mouse model. The current study gained novel evidence for understanding the mechanisms underlying adaptive ADM resistance and provided rationales to improve clinical outcomes of refractory osteosarcoma.
Elevated microRNA-125b inhibits cytotrophoblast invasion and impairs endothelial cell function in preeclampsia
Authors: Li Qinghua , Han Yangyang , Xu Peng , Yin Lingxuan , Si Yanru , Zhang Cuijuan , Meng Yuhan , Feng Weiguo , Pan Zhifang , Gao Zhiqin , Li Jie , Yang Weiwei 
Published: May 2020

AbstractPreeclampsia (PE) is a life-threatening disorder of human pregnancy affecting 5–8% of all pregnancies. Currently, PE remains an elusive complicated and heterogenous medical condition with no early marker or symptoms is recognized for this serious pregnancy complications. Here, we profiled the plasma miRNA expression patterns associated with preeclampsia and found 16 miRNAs were deregulated (p < 0.01) in patients who later developed PE. Circulating hsa-miR-125b was aberrantly upregulated in early pregnancy and significantly reduced after delivery in preeclampsia. We then investigated the underlying molecular mechanisms between miR-125b and PE in vitro. We found that upregulated miR-125b can target KCNA1 to inhibit trophoblast invasion in human trophoblast cells. Moreover, overexpression of miR-125b in HUVECs impaired endothelial cell function through GPC1. The findings indicated that upregulated miR-125b leads to impaired placentation, and an increased risk of preeclampsia, Our studies provide novel insights into the underlying mechanisms on the association of miR-125b in early pregnancy and risk of PE, miR-125b might be a more specific predictive marker and a safe therapeutic target for treating patients with PE.
Community-level signatures of ecological succession in natural bacterial communities
Authors: Pascual-García Alberto , Bell Thomas 
Published: May 2020

AbstractA central goal in microbial ecology is to simplify the extraordinary biodiversity that inhabits natural environments into ecologically coherent units. We profiled (16S rRNA sequencing) > 700 semi-aquatic bacterial communities while measuring their functional capacity when grown in laboratory conditions. This approach allowed us to investigate the relationship between composition and function excluding confounding environmental factors. Simulated data allowed us to reject the hypothesis that stochastic processes were responsible for community assembly, suggesting that niche effects prevailed. Consistent with this idea we identified six distinct community classes that contained samples collected from distant locations. Structural equation models showed there was a functional signature associated with each community class. We obtained a more mechanistic understanding of the classes using metagenomic predictions (PiCRUST). This approach allowed us to show that the classes contained distinct genetic repertoires reflecting community-level ecological strategies. The ecological strategies resemble the classical distinction between r- and K-strategists, suggesting that bacterial community assembly may be explained by simple ecological mechanisms.
Deep brain stimulation-guided optogenetic rescue of parkinsonian symptoms
Authors: Valverde Sébastien , Vandecasteele Marie , Piette Charlotte , Derousseaux Willy , Gangarossa Giuseppe , Aristieta Arbelaiz Asier , Touboul Jonathan , Degos Bertrand , Venance Laurent 
Published: May 2020

AbstractDeep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson’s disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.
BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning
Authors: Liu Tongyu , Mi Lin , Xiong Jing , Orchard Peter , Yu Qi , Yu Lei , Zhao Xu-Yun , Meng Zhuo-Xian , Parker Stephen C. J. , Lin Jiandie D. , Li Siming 
Published: May 2020

AbstractBrown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.
LITESEC-T3SS - Light-controlled protein delivery into eukaryotic cells with high spatial and temporal resolution
Authors: Lindner Florian , Milne-Davies Bailey , Langenfeld Katja , Stiewe Thorsten , Diepold Andreas 
Published: May 2020

AbstractMany bacteria employ a type III secretion system (T3SS) injectisome to translocate proteins into eukaryotic host cells. Although the T3SS can efficiently export heterologous cargo proteins, a lack of target cell specificity currently limits its application in biotechnology and healthcare. In this study, we exploit the dynamic nature of the T3SS to govern its activity. Using optogenetic interaction switches to control the availability of the dynamic cytosolic T3SS component SctQ, T3SS-dependent effector secretion can be regulated by light. The resulting system, LITESEC-T3SS (Light-induced translocation of effectors through sequestration of endogenous components of the T3SS), allows rapid, specific, and reversible activation or deactivation of the T3SS upon illumination. We demonstrate the light-regulated translocation of heterologous reporter proteins, and induction of apoptosis in cultured eukaryotic cells. LITESEC-T3SS constitutes a new method to control protein secretion and translocation into eukaryotic host cells with unparalleled spatial and temporal resolution.
Efficient training of ANN potentials by including atomic forces via Taylor expansion and application to water and a transition-metal oxide
Authors: Cooper April M. , Kästner Johannes , Urban Alexander , Artrith Nongnuch 
Published: May 2020

AbstractArtificial neural network (ANN) potentials enable the efficient large-scale atomistic modeling of complex materials with near first-principles accuracy. For molecular dynamics simulations, accurate energies and interatomic forces are a prerequisite, but training ANN potentials simultaneously on energies and forces from electronic structure calculations is computationally demanding. Here, we introduce an efficient alternative method for the training of ANN potentials on energy and force information, based on an extrapolation of the total energy via a Taylor expansion. By translating the force information to approximate energies, the quadratic scaling with the number of atoms exhibited by conventional force-training methods can be avoided, which enables the training on reference datasets containing complex atomic structures. We demonstrate for different materials systems, clusters of water molecules, bulk liquid water, and a lithium transition-metal oxide that the proposed force-training approach provides substantial improvements over schemes that train on energies only. Including force information for training reduces the size of the reference datasets required for ANN potential construction, increases the transferability of the potential, and generally improves the force prediction accuracy. For a set of water clusters, the Taylor-expansion approach achieves around 50% of the force error improvement compared to the explicit training on all force components, at a much smaller computational cost. The alternative force-training approach thus simplifies the construction of general ANN potentials for the prediction of accurate energies and interatomic forces for diverse types of materials, as demonstrated here for water and a transition-metal oxide.
Biomimetic Coating-free Superomniphobicity
Authors: Das Ratul , Ahmad Zain , Nauruzbayeva Jamilya , Mishra Himanshu 
Published: May 2020

AbstractSuperomniphobic surfaces, which repel droplets of polar and apolar liquids, are used for reducing frictional drag, packaging electronics and foods, and separation processes, among other applications. These surfaces exploit perfluorocarbons that are expensive, vulnurable to physical damage, and have a long persistence in the environment. Thus, new approaches for achieving superomniphobicity from common materials are desirable. In this context, microtextures comprising “mushroom-shaped” doubly reentrant pillars (DRPs) have been shown to repel drops of polar and apolar liquids in air irrespective of the surface make-up. However, it was recently demonstrated that DRPs get instantaneously infiltrated by the same liquids on submersion because while they can robustly prevent liquid imbibition from the top, they are vulnerable to lateral imbibition. Here, we remedy this weakness through bio-inspiration derived from cuticles of Dicyrtomina ornata, soil-dwelling bugs, that contain cuboidal secondary granules with mushroom-shaped caps on each face. Towards a proof-of-concept demonstration, we created a perimeter of biomimicking pillars around arrays of DRPs using a two-photon polymerization technique; another variation of this design with a short wall passing below the side caps was investigated. The resulting gas-entrapping microtextured surfaces (GEMS) robustly entrap air on submersion in wetting liquids, while also exhibiting superomniphobicity in air. To our knowledge, this is the first-ever microtexture that confers upon intrinsically wetting materials the ability to simultaneously exhibit superomniphobicity in air and robust entrapment of air on submersion. These findings should advance the rational design of coating-free surfaces that exhibit ultra-repellence (or superomniphobicity) towards liquids.
Bone-like structure by modified freeze casting
Authors: Singh Gurdev , Soundarapandian S. 
Published: May 2020

AbstractFreeze casting has emerged as one of the most promising manufacturing methods to fabricate porous scaffolds in recent years. This is due to various reasons which include a wide range of materials which can be used in this process, easiness of the process, etc. One of the major objectives of this work was to fabricate bone-like structure by using a modified freeze casting process. In this work, Hydroxyapatite and Tricalcium phosphate scaffolds with bone-like structure were fabricated by understanding and utilizing the basic physics of freeze casting. Thermal conductivity of the base plate is a crucial factor for obtaining controlled pore and porosity distribution in a porous scaffold. It was found that designing the base plate with variable thermal conductivity has led to the formation of bone-like structure. Porous scaffolds were quantitatively analyzed for pore size and porosity distribution at center and circumference. Porosity at circumference was observed to be approximately dropped by 55%, a similar trend was seen for pore size. Therefore, it was significant evidence that modified freeze casting has capable in fabricating bone-like structures with ease and good control. This will open many new applications of porous scaffolds in biomedical, energy devices, chemical catalyst and many more.
Saturn’s near-equatorial ionospheric conductivities from in situ measurements
Authors: Shebanits O. , Hadid L. Z. , Cao H. , Morooka M. W. , Hunt G. J. , Dougherty M. K. , Wahlund J.-E. , Waite J. H. , Müller-Wodarg I. 
Published: May 2020

AbstractCassini’s Grand Finale orbits provided for the first time in-situ measurements of Saturn’s topside ionosphere. We present the Pedersen and Hall conductivities of the top near-equatorial dayside ionosphere, derived from the in-situ measurements by the Cassini Radio and Wave Plasma Science Langmuir Probe, the Ion and Neutral Mass Spectrometer and the fluxgate magnetometer. The Pedersen and Hall conductivities are constrained to at least 10−5–10−4 S/m at (or close to) the ionospheric peak, a factor 10–100 higher than estimated previously. We show that this is due to the presence of dusty plasma in the near-equatorial ionosphere. We also show the conductive ionospheric region to be extensive, with thickness of 300–800 km. Furthermore, our results suggest a temporal variation (decrease) of the plasma densities, mean ion masses and consequently the conductivities from orbit 288 to 292.
Optical Absorption Exhibits Pseudo-Direct Band Gap of Wurtzite Gallium Phosphide
Authors: da Silva Bruno C. , Couto Odilon D. D. , Obata Hélio T. , de Lima Mauricio M. , Bonani Fábio D. , de Oliveira Caio E. , Sipahi Guilherme M. , Iikawa Fernando , Cotta Mônica A. 
Published: May 2020

AbstractDefinitive evidence for the direct band gap predicted for Wurtzite Gallium Phosphide (WZ GaP) nanowires has remained elusive due to the lack of strong band-to-band luminescence in these materials. In order to circumvent this problem, we successfully obtained large volume WZ GaP structures grown by nanoparticle-crawling assisted Vapor-Liquid-Solid method. With these structures, we were able to observe bound exciton recombination at 2.14 eV with FHWM of approximately 1 meV. In addition, we have measured the optical absorption edges using photoluminescence excitation spectroscopy. Our results show a 10 K band gap at 2.19 eV and indicate a weak oscillator strength for the lowest energy band-to-band absorption edge, which is a characteristic feature of a pseudo-direct band gap semiconductor. Furthermore, the valence band splitting energies are estimated as 110 meV and 30 meV for the three highest bands. Electronic band structure calculations using the HSE06 hybrid density functional agree qualitatively with the valence band splitting energies.
Intermittent hypoxia modulates redox homeostasis, lipid metabolism associated inflammatory processes and redox post-translational modifications: Benefits at high altitude
Authors: Gangwar Anamika , Paul Subhojit , Ahmad Yasmin , Bhargava Kalpana 
Published: May 2020

AbstractIntermittent hypoxia, initially associated with adverse effects of sleep apnea, has now metamorphosed into a module for improved sports performance. The regimen followed for improved sports performance is milder intermittent hypoxic training (IHT) as compared to chronic and severe intermittent hypoxia observed in sleep apnea. Although several studies have indicated the mechanism and enough data on physiological parameters altered by IH is available, proteome perturbations remain largely unknown. Altitude induced hypobaric hypoxia is known to require acclimatization as it causes systemic redox stress and inflammation in humans. In the present study, a short IHT regimen consisting of previously reported physiologically beneficial FIO2 levels of 13.5% and 12% was administered to human subjects. These subjects were then airlifted to altitude of 3500 m and their plasma proteome along with associated redox parameters were analyzed on days 4 and 7 of high altitude stay. We observed that redox stress and associated post-translational modifications, perturbed lipid metabolism and inflammatory signaling were induced by IHT exposure at Baseline. However, this caused activation of antioxidants, energy homeostasis mechanisms and anti-inflammatory responses during subsequent high-altitude exposure. Thus, we propose IHT as a beneficial non-pharmacological intervention that benefits individuals venturing to high altitude areas.
Antecedent presentation of neurological phenotypes in the Collaborative Cross reveals four classes with complex sex-dependencies
Authors: Eldridge Raena , Osorio Daniel , Amstalden Katia , Edwards Caitlin , Young Colin R. , Cai James J. , Konganti Kranti , Hillhouse Andrew , Threadgill David W. , Welsh C. Jane , Brinkmeyer-Langford Candice 
Published: May 2020

AbstractAntecedent viral infection may contribute to increased susceptibility to several neurological diseases, such as multiple sclerosis and Parkinson’s disease. Variation in clinical presentations of these diseases is often associated with gender, genetic background, or a combination of these and other factors. The complicated etiologies of these virally influenced diseases are difficult to study in conventional laboratory mouse models, which display a very limited number of phenotypes. We have used the genetically and phenotypically diverse Collaborative Cross mouse panel to examine complex neurological phenotypes after viral infection. Female and male mice from 18 CC strains were evaluated using a multifaceted phenotyping pipeline to define their unique disease profiles following infection with Theiler’s Murine Encephalomyelitis Virus, a neurotropic virus. We identified 4 distinct disease progression profiles based on limb-specific paresis and paralysis, tremors and seizures, and other clinical signs, along with separate gait profiles. We found that mice of the same strain had more similar profiles compared to those of different strains, and also identified strains and phenotypic parameters in which sex played a significant role in profile differences. These results demonstrate the value of using CC mice for studying complex disease subtypes influenced by sex and genetic background. Our findings will be useful for developing novel mouse models of virally induced neurological diseases with heterogenous presentation, an important step for designing personalized, precise treatments.
The role of Staphylococcus aureus lipoproteins in hematogenous septic arthritis
Authors: Mohammad Majd , Hu Zhicheng , Ali Abukar , Kopparapu Pradeep Kumar , Na Manli , Jarneborn Anders , Stroparo Mariana do Nascimento , Nguyen Minh-Thu , Karlsson Anna , Götz Friedrich , Pullerits Rille , Jin Tao 
Published: May 2020

AbstractPermanent joint dysfunction is a devastating complication in patients with septic arthritis. Staphylococcus aureus (S. aureus) lipoproteins (Lpp), the predominant ligands for TLR2, are known to be arthritogenic and induce bone destruction when introduced directly into the joint. Here, we aim to investigate the importance of S. aureus Lpp and TLR2 in a hematogenous septic arthritis model, which is the most common route of infection in humans. C57BL/6 wild-type and TLR2 deficient mice were intravenously inoculated with S. aureus Newman parental strain or its lipoprotein-deficient Δlgt mutant strain. The clinical course of septic arthritis, radiological changes, and serum levels of cytokines and chemokines, were assessed. Newman strain induced more severe and frequent clinical septic polyarthritis compared to its Δlgt mutant in TLR2 deficient mice, but not in wild-type controls. Bone destruction, however, did not differ between groups. Lpp expression was associated with higher mortality, weight loss as well as impaired bacterial clearance in mouse kidneys independent of TLR2. Furthermore, Lpp expression induced increased systemic pro-inflammatory cytokine and neutrophil chemokine release. Staphylococcal Lpp are potent virulence factors in S. aureus systemic infection independent of host TLR2 signalling. However, they have a limited impact on bone erosion in hematogenous staphylococcal septic arthritis.
First-In-Human Phase 1 Clinical Trials – A Single-Center Experience In The Era Of Modern Oncotherapeutics
Authors: Paluri Ravi K. , Li Peng , Anderson Ashley , Nandagopal Lakshminarayana , McArdle Traci , Young Matthew , Robert Franscisco , Naik Gurudatta , Saleh Mansoor 
Published: May 2020

AbstractIn the era of precision medicine the treatment options for cancer patients and subsequent outcomes are expected to improve. We present a review of patients enrolled in first-in-human Phase1 trials at University of Alabama at Birmingham. Between 1/2015–6/2017, 162 cancer patients (whole cohort, WC) were enrolled on phase1 studies receiving either targeted therapy (TT) or immuno-therapy (IOT). We assessed 90 day mortality (90DM) and time to treatment failure (TTF) to determine the predictors. Of the WC (122 (TT), 40 (IOT)), 90 (56%) received ≥ 2 prior therapies and 38 (24%) ⩾ 5 prior therapies. Overall, Grade 3 or 4 events were observed in 33% (WC) vs 31% (TT) vs 38% (IOT). The 90DM was 9.3% (WC) vs 7.4% (TT) vs 15% (IOT). The median TTF was 4.2 months vs 4.5 m vs 3.6 m. The number of lines of prior therapy and performance status were identified as outcome predictors. Our data reflects the new trend in precision oncology where majority received non-cytotoxic therapeutic interventions. The observation that number of lines of prior therapy and performance status predictive of PFS and 90DM emphasizes the need to consider phase1 trials earlier, preferably upon progression following definitive therapy.