bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIK2 enhances synthesis of fatty acid and cholesterol in ovarian cancer cells and tumor growth through PI3K/Akt signaling pathway
Authors: Zhao Jing , Zhang Xiaohong , Gao Tian , Wang Shanci , Hou Yiran , Yuan Peng , Yang Yi , Yang Tao , Xing Jinliang , Li Jibin , Liu Shujuan 
Published: January 2020

AbstractSalt-inducible kinase 2 (SIK2) has been established as a regulator of diverse biological processes including cell metabolism. A recent study has reported that SIK2 is required for adipocyte-induced ovarian cancer (OC) survival through facilitating fatty acid oxidation. However, whether SIK2 also plays a role in the lipid synthesis in OC cells remains elusive. Here, we showed that SIK2 significantly promoted the lipid synthesis in OC cells. On the one hand, SIK2 enhanced fatty acid synthesis through upregulating the expression of sterol regulatory element binding protein 1c (SREBP1c) and thus the transcription of major lipogenic enzyme FASN. On the other hand, SIK2 promoted cholesterol synthesis through upregulating the expression of sterol regulatory element binding protein 2 (SREBP2) and thus the transcription of major cholesterol synthesis enzymes HMGCR. Moreover, PI3K/Akt signaling pathway was found to be involved in the upregulation of SREBP1c and SREBP2 in OC cells. Moreover, in vitro and in vivo assays indicated that the SIK2-regulated fatty acid and cholesterol synthesis played a critical role in the growth of OC cells. Our findings demonstrate that SIK2 is a critical regulator of lipid synthesis in OC cells and thus promotes OC growth, which provides a strong line of evidence for this molecule to be used as a therapeutic target in the treatment of this malignancy.
Sestrins are evolutionarily conserved mediators of exercise benefits
Authors: Kim Myungjin , Sujkowski Alyson , Namkoong Sim , Gu Bondong , Cobb Tyler , Kim Boyoung , Kowalsky Allison H. , Cho Chun-Seok , Semple Ian , Ro Seung-Hyun , Davis Carol , Brooks Susan V. , Karin Michael , Wessells Robert J. , Lee Jun Hee 
Published: January 2020

AbstractExercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance.
Nested helicoids in biological microstructures
Authors: Greenfeld Israel , Kellersztein Israel , Wagner H. Daniel 
Published: January 2020

AbstractHelicoidal formations often appear in natural microstructures such as bones and arthropods exoskeletons. Named Bouligands after their discoverer, these structures are angle-ply laminates that assemble from laminae of chitin or collagen fibers embedded in a proteinaceous matrix. High resolution electron microscope images of cross-sections through scorpion claws are presented here, uncovering structural features that are different than so-far assumed. These include in-plane twisting of laminae around their corners rather than through their centers, and a second orthogonal rotation angle which gradually tilts the laminae out-of-plane. The resulting Bouligand laminate unit (BLU) is highly warped, such that neighboring BLUs are intricately intertwined, tightly nested and mechanically interlocked. Using classical laminate analysis extended to laminae tilting, it is shown that tilting significantly enhances the laminate flexural stiffness and strength, and may improve toughness by diverting crack propagation. These observations may be extended to diverse biological species and potentially applied to synthetic structures.
Programming temporal morphing of self-actuated shells
Authors: Guseinov Ruslan , McMahan Connor , Pérez Jesús , Daraio Chiara , Bickel Bernd 
Published: January 2020

AbstractAdvances in shape-morphing materials, such as hydrogels, shape-memory polymers and light-responsive polymers have enabled prescribing self-directed deformations of initially flat geometries. However, most proposed solutions evolve towards a target geometry without considering time-dependent actuation paths. To achieve more complex geometries and avoid self-collisions, it is critical to encode a spatial and temporal shape evolution within the initially flat shell. Recent realizations of time-dependent morphing are limited to the actuation of few, discrete hinges and cannot form doubly curved surfaces. Here, we demonstrate a method for encoding temporal shape evolution in architected shells that assume complex shapes and doubly curved geometries. The shells are non-periodic tessellations of pre-stressed contractile unit cells that soften in water at rates prescribed locally by mesostructure geometry. The ensuing midplane contraction is coupled to the formation of encoded curvatures. We propose an inverse design tool based on a data-driven model for unit cells’ temporal responses.
Annexin-V stabilizes membrane defects by inducing lipid phase transition
Authors: Lin Yi-Chih , Chipot Christophe , Scheuring Simon 
Published: January 2020

AbstractAnnexins are abundant cytoplasmic proteins, which bind to membranes that expose negatively charged phospholipids in a Ca2+-dependent manner. During cell injuries, the entry of extracellular Ca2+ activates the annexin membrane-binding ability, subsequently initiating membrane repair processes. However, the mechanistic action of annexins in membrane repair remains largely unknown. Here, we use high-speed atomic force microscopy (HS-AFM), fluorescence recovery after photobleaching (FRAP), confocal laser scanning microscopy (CLSM) and molecular dynamics simulations (MDSs) to analyze how annexin-V (A5) binds to phosphatidylserine (PS)-rich membranes leading to high Ca2+-concentrations at membrane, and then to changes in the dynamics and organization of lipids, eventually to a membrane phase transition. A5 self-assembly into lattices further stabilizes and likely structures the membrane into a gel phase. Our findings are compatible with the patch resealing through vesicle fusion mechanism in membrane repair and indicate that A5 retains negatively charged lipids in the inner leaflet in an injured cell.
Direction and symmetry transition of the vector order parameter in topological superconductors CuxBi2Se3
Authors: Kawai T. , Wang C. G. , Kandori Y. , Honoki Y. , Matano K. , Kambe T. , Zheng Guo-qing 
Published: January 2020

AbstractTopological superconductors have attracted wide-spreading interests for the bright application perspectives to quantum computing. Cu0.3Bi2Se3 is a rare bulk topological superconductor with an odd-parity wave function, but the details of the vector order parameter d and its pinning mechanism are still unclear. Here, we succeed in growing CuxBi2Se3 single crystals with unprecedented high doping levels. For samples with x = 0.28, 0.36 and 0.37 with similar carrier density as evidenced by the Knight shift, the in-plane upper critical field Hc2 shows a two-fold symmetry. However, the angle at which the Hc2 becomes minimal is different by 90° among them, which indicates that the d-vector direction is different for each crystal likely due to a different local environment. The carrier density for x = 0.46 and 0.54 increases substantially compared to x ≤ 0.37. Surprisingly, the in-plane Hc2 anisotropy disappears, indicating that the gap symmetry undergoes a transition from nematic to isotropic (possibly chiral) as carrier increases.
Continental degassing of helium in an active tectonic setting (northern Italy): the role of seismicity
Authors: Buttitta Dario , Caracausi Antonio , Chiaraluce Lauro , Favara Rocco , Gasparo Morticelli Maurizio , Sulli Attilio 
Published: January 2020

AbstractIn order to investigate the variability of helium degassing in continental regions, its release from rocks and emission into the atmosphere, here we studied the degassing of volatiles in a seismically active region of northern Italy (MwMAX = 6) at the Nirano-Regnano mud volcanic system. The emitted gases in the study area are CH4–dominated and it is the carrier for helium (He) transfer through the crust. Carbon and He isotopes unequivocally indicate that crustal-derived fluids dominate these systems. An high-resolution 3-dimensional reconstruction of the gas reservoirs feeding the observed gas emissions at the surface permits to estimate the amount of He stored in the natural reservoirs. Our study demonstrated that the in-situ production of 4He in the crust and a long-lasting diffusion through the crust are not the main processes that rule the He degassing in the region. Furthermore, we demonstrated that micro-fracturation due to the field of stress that generates the local seismicity increases the release of He from the rocks and can sustain the excess of He in the natural reservoirs respect to the steady-state diffusive degassing. These results prove that (1) the transport of volatiles through the crust can be episodic as function of rock deformation and seismicity and (2) He can be used to highlight changes in the stress field and related earthquakes.
The interaction of Multiple Sclerosis risk loci with Epstein-Barr virus phenotypes implicates the virus in pathogenesis
Authors: Afrasiabi Ali , Parnell Grant P. , Swaminathan Sanjay , Stewart Graeme J. , Booth David R. 
Published: January 2020

AbstractTranslating the findings of genome wide association studies (GWAS) to new therapies requires identification of the relevant immunological contexts to interrogate for genetic effects. In one of the largest GWAS, more than 200 risk loci have been identified for Multiple Sclerosis (MS) susceptibility. Infection with Epstein-Barr virus (EBV) appears to be necessary for the development of Multiple Sclerosis (MS). Many MS risk loci are associated with altered gene expression in EBV infected B cells (LCLs). We have interrogated this immunological context to identify interaction between MS risk loci and EBV DNA copy number, intrinsic growth rate and EBV encoded miRNA expression. The EBV DNA copy number was associated with significantly more risk alleles for MS than for other diseases or traits. EBV miRNAs BART4-3p and BART3-5p were highly associated with EBV DNA copy number and MS risk loci. The poliovirus receptor (PVR) risk SNP was associated with EBV DNA copy number, PVR and miRNA expression. Targeting EBV miRNAs BART4-3p and BART3-5p, and the gene PVR, may provide therapeutic benefit in MS. This study also indicates how immunological context and risk loci interactions can be exploited to validate and develop novel therapeutic approaches.
Biomimetic cellular vectors for enhancing drug delivery to the lungs
Authors: Evangelopoulos Michael , Yazdi Iman K. , Acciardo Stefania , Palomba Roberto , Giordano Federica , Pasto Anna , Sushnitha Manuela , Martinez Jonathan O. , Basu Nupur , Torres Armando , Hmaidan Sarah , Parodi Alessandro , Tasciotti Ennio 
Published: January 2020

AbstractDespite recent advances in drug delivery, the targeted treatment of unhealthy cells or tissues continues to remain a priority. In cancer (much like other pathologies), delivery vectors are designed to exploit physical and biological features of unhealthy tissues that are not always homogenous across the disease. In some cases, shifting the target from unhealthy tissues to the whole organ can represent an advantage. Specifically, the natural organ-specific retention of nanotherapeutics following intravenous administration as seen in the lung, liver, and spleen can be strategically exploited to enhance drug delivery. Herein, we outline the development of a cell-based delivery system using macrophages as a delivery vehicle. When loaded with a chemotherapeutic payload (i.e., doxorubicin), these cellular vectors (CELVEC) were shown to provide continued release within the lung. This study provides proof-of-concept evidence of an alternative class of biomimetic delivery vectors that capitalize on cell size to provide therapeutic advantages for pulmonary treatments.
Quantum random number generators with entanglement for public randomness testing
Authors: Jacak Janusz E. , Jacak Witold A. , Donderowicz Wojciech A. , Jacak Lucjan 
Published: January 2020

AbstractWe discuss a simple idealistic quantum entanglement based protocol for quantum random number generation allowing a trusted third party to publicly perform arbitrarily complex tests of randomness without any violation of the secrecy of the generated bit sequences. The protocol diminishes also an average time of the randomness testing (thus enabling arbitrary shortening of this time with increasing number of entangled qubits).
Comparative Proteomic Analysis in Scar-Free Skin Regeneration in Acomys cahirinus and Scarring Mus musculus
Authors: Yoon Jung Hae , Cho Kun , Garrett Timothy J. , Finch Paul , Maden Malcolm 
Published: January 2020

AbstractThe spiny mouse,Acomys cahirinusdisplays a unique wound healing ability with regeneration of all skin components in a scar-free manner. To identify orchestrators of this regenerative response we have performed proteomic analyses of skin fromAcomysandMus musculusbefore and after wounding. Of the ~2000 proteins identified many are expressed at similar levels inAcomysandMus, but there are significant differences. Following wounding inMusthe complement and coagulation cascades, PPAR signaling pathway and ECM-receptor interactions predominate. InAcomys, other pathways predominate including the Wnt, MAPK, the ribosome, proteasome, endocytosis and tight junction pathways. Notable amongAcomysspecific proteins are several ubiquitin-associated enzymes and kinases, whereas inMusimmuno-modulation proteins characteristic of inflammatory response are unique or more prominent. ECM proteins such as collagens are more highly expressed inMus, but likely more important is the higher expression of matrix remodeling proteases inAcomys. Another distinctive difference betweenAcomysandMuslies in the macrophage-produced arginase 1 is found inMuswhereas arginase 2 is found inAcomys. Thus, we have identified several avenues for experimental approaches whose aim is to reduce the fibrotic response that the typical mammal displays in response to wounding.
A butanolic fraction from the standardized stem extract of Cassia occidentalis L delivered by a self-emulsifying drug delivery system protects rats from glucocorticoid-induced osteopenia and muscle atrophy
Authors: Pal Subhashis , Mittapelly Naresh , Husain Athar , Kushwaha Sapana , Chattopadhyay Sourav , Kumar Padam , Ramakrishna Eppalapally , Kumar Sudhir , Maurya Rakesh , Sanyal Sabyasachi , Gayen Jiaur R. , Mishra Prabhat R. , Chattopadhyay Naibedya 
Published: January 2020

AbstractWe recently reported that a butanol soluble fraction from the stem of Cassia occidentalis (CSE-Bu) consisting of osteogenic compounds mitigated methylprednisone (MP)-induced osteopenia in rats, albeit failed to afford complete protection thus leaving a substantial scope for further improvement. To this aim, we prepared an oral formulation that was a lipid-based self-nano emulsifying drug delivery system (CSE-BuF). The globule size of CSE-BuF was in the range of 100–180 nm of diluted emulsion and the zeta potential was −28 mV. CSE-BuF enhanced the circulating levels of five osteogenic compounds compared to CSE-Bu. CSE-BuF (50 mg/kg) promoted bone regeneration at the osteotomy site and completely prevented MP-induced loss of bone mass and strength by concomitant osteogenic and anti-resorptive mechanisms. The MP-induced downregulations of miR29a (the positive regulator of the osteoblast transcription factor, Runx2) and miR17 and miR20a (the negative regulators of the osteoclastogenic cytokine RANKL) in bone was prevented by CSE-BuF. In addition, CSE-BuF protected rats from the MP-induced sarcopenia and/or muscle atrophy by downregulating the skeletal muscle atrogenes, adverse changes in body weight and composition. CSE-BuF did not impact the anti-inflammatory effect of MP. Our preclinical study established CSE-BuF as a prophylactic agent against MP-induced osteopenia and muscle atrophy.
A special needs dentistry study of institutionalized individuals with intellectual disability in West Sumatra Indonesia
Authors: Ningrum Valendriyani , Wang Wen-Chen , Liao Hung-En , Bakar Abu , Shih Yin-Hwa 
Published: January 2020

AbstractPeople with intellectual disability have a higher risk of oral health problems. This study assessed the clinical oral health status and behaviors and treatment needs of people living in an institution in Padang, West Sumatra, Indonesia. We quantified oral health status of 65 individuals with intellectual disability using Oral Hygiene Index Simplified (OHIs), Angle’s classification of malocclusion, Community Periodontal Index and Treatment Need (CPITN), and decay index and also recorded their brushing behavior. We found that males had significantly lower OHIs (p < 0.001), more malocclusion (p < 0.001), greater caries number (p < 0.001), greater CPITN (p = 0.001) and higher need of dental treatment (p < 0.01) than females. Additionally, we found that high caries number was associated with poor OHIS, malocclusion, periodontal disease, and dependent brushing behavior (p < 0.001). The findings of this study imply that there is a gap in appropriate oral health care in individuals with intellectual disability. There should be a greater focus on providing appropriate oral health education to people with intellectual disability, improving the health literacy and quality of care of caregivers, and providing more dentists with specialized training in special needs dentistry.
Nucleus-specific linker histones Hho1 and Mlh1 form distinct protein interactions during growth, starvation and development in Tetrahymena thermophila
Authors: Nabeel-Shah Syed , Ashraf Kanwal , Saettone Alejandro , Garg Jyoti , Derynck Joanna , Lambert Jean-Philippe , Pearlman Ronald E. , Fillingham Jeffrey 
Published: January 2020

AbstractChromatin organization influences most aspects of gene expression regulation. The linker histone H1, along with the core histones, is a key component of eukaryotic chromatin. Despite its critical roles in chromatin structure and function and gene regulation, studies regarding the H1 protein-protein interaction networks, particularly outside of Opisthokonts, are limited. The nuclear dimorphic ciliate protozoan Tetrahymena thermophila encodes two distinct nucleus-specific linker histones, macronuclear Hho1 and micronuclear Mlh1. We used a comparative proteomics approach to identify the Hho1 and Mlh1 protein-protein interaction networks in Tetrahymena during growth, starvation, and sexual development. Affinity purification followed by mass spectrometry analysis of the Hho1 and Mlh1 proteins revealed a non-overlapping set of co-purifying proteins suggesting that Tetrahymena nucleus-specific linker histones are subject to distinct regulatory pathways. Furthermore, we found that linker histones interact with distinct proteins under the different stages of the Tetrahymena life cycle. Hho1 and Mlh1 co-purified with several Tetrahymena-specific as well as conserved interacting partners involved in chromatin structure and function and other important cellular pathways. Our results suggest that nucleus-specific linker histones might be subject to nucleus-specific regulatory pathways and are dynamically regulated under different stages of the Tetrahymena life cycle.
Rolipram Protects Mice from Gram-negative Bacterium Escherichia coli-induced Inflammation and Septic Shock
Authors: Lu Xiaying , Wang Juan , Chen Xiaohuan , Jiang Yong , Pan Zhixing K. 
Published: January 2020

AbstractSepsis is typically triggered by an overwhelming systemic inflammatory response to pathogens, and may lead to severe organ dysfunction and/or death. Sepsis consequently has a high mortality rate and a high rate of complications for survivors, despite modern medical advances. Therefore, drug identification and validation for the treatment of sepsis is of the utmost importance. As a selective phosphodiesterase-4 inhibitor, rolipram also exhibits the abilities of inhibiting multiple pro-inflammatory cytokines production in macrophages and toxin-induced inflammation in mice. However, this drug has never been studied as a sepsis treatment method. We found that rolipram significantly improves survival in mice challenged with gram-negative bacterium E. coli, CLP, or E. coli derived lipopolysaccharide. We have also found that rolipram inhibits organ damage, pro-inflammatory cytokine production, and intracellular migration of early-stage inflammatory elements. Our results also show that rolipram increases anti-inflammatory cytokine production. The protective effects of rolipram on septic mice may result from inhibition of the MAP kinase and NF-κB signaling pathways. Rolipram may therefore be a potential novel sepsis treatment, one that would bypass the time-consuming and costly drug-discovery process.
Bio-organic fertilizer with reduced rates of chemical fertilization improves soil fertility and enhances tomato yield and quality
Authors: Ye Lin , Zhao Xia , Bao Encai , Li Jianshe , Zou Zhirong , Cao Kai 
Published: January 2020

AbstractThe extensive use of chemical fertilizers poses serious collateral problems such as environmental pollution, pest resistance development and food safety decline. Researches focused on applying plant-beneficial microorganisms to partially replace chemical fertilizer use is increasing due to the requirement of sustainable agriculture development. Thus to investigate the possibility of a plant-beneficial Trichoderma strain and its bio-organic fertilizer product in saving chemical fertilizer application and in improving crop quality, a field trial and continuous pot experiments were carried out with tomato. Four treatments were set up: a reduced application of chemical fertilizer (75% of the conventional application) plus Trichoderma-enriched bio-organic fertilizer (BF), organic fertilizer (OF) or Trichoderma spore suspension (SS), with using the 100% rate of the conventional chemical fertilizer as the control (CF). The results showed that the total soluble sugar, Vitamin C and nitrate accumulations were, respectively, +up to 24%, +up to 57% and –up to 62% in the tomatoes of the BF treatment compared to those of the control (CF). And both of the pot and field trials revealed that reduced rates of chemical fertilizer plus bio-organic fertilizer produced tomato yields equivalent to those obtained using the 100% of the chemical fertilizer. However, application with the inoculant alone (SS) or combined with the organic fertilizer alone (OF) would lead to a yield decreases of 6–38% and 9–35% over the control. Since the increased abundance of soil microflora and the enhanced soil fertility frequently showed positive linear correlations especially in the BF-treated soils, we conclude that the efficacy of this bio-organic fertilizer for maintaining a stable tomato yield and improving tomato quality may be due to the improved soil microbial activity. Thus, the results suggest that the Trichoderma bio-organic fertilizer could be employed in combination with the appropriate rates of chemical fertilizers to get maximum benefits regarding yield, quality and fertilizer savings.