bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the malignancy and drug resistance of cancer cells from their membrane resealing response
Authors: Hui T. H. , Zhou Z. L. , Fong H. W. , Ngan Roger K. C. , Lee T. Y. , Au Joseph S. K. , Ngan A. H. W. , Yip Timothy T. C. , Lin Y. 
Published: May 2016

AbstractIn this report, we showed that two tumor cell characteristics, namely the malignancy and drug-resistance status can be evaluated by their membrane resealing response. Specifically, membrane pores in a number of pairs of cancer and normal cell lines originated from nasopharynx, lung and intestine were introduced by nano-mechanical puncturing. Interestingly, such nanometer-sized holes in tumor cells can reseal ~2–3 times faster than those in the corresponding normal cells. Furthermore, the membrane resealing time in cancer cell lines exhibiting resistance to several leading chemotherapeutic drugs was also found to be substantially shorter than that in their drug-sensitive counterparts, demonstrating the potential of using this quantity as a novel marker for future cancer diagnosis and drug resistance detection. Finally, a simple model was proposed to explain the observed resealing dynamics of cells which suggested that the distinct response exhibited by normal, tumor and drug resistant cells is likely due to the different tension levels in their lipid membranes, a conclusion that is also supported by direct cortical tension measurement.
Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials
Authors: Jeon Ok Hee , Panicker Leelamma M. , Lu Qiaozhi , Chae Jeremy J. , Feldman Ricardo A. , Elisseeff Jennifer H. 
Published: May 2016

AbstractBone substitutes can be designed to replicate physiological structure and function by creating a microenvironment that supports crosstalk between bone and immune cells found in the native tissue, specifically osteoblasts and osteoclasts. Human induced pluripotent stem cells (hiPSC) represent a powerful tool for bone regeneration because they are a source of patient-specific cells that can differentiate into all specialized cell types residing in bone. We show that osteoblasts and osteoclasts can be differentiated from hiPSC-mesenchymal stem cells and macrophages when co-cultured on hydroxyapatite-coated poly(lactic-co-glycolic acid)/poly(L-lactic acid) (HA–PLGA/PLLA) scaffolds. Both cell types seeded on the PLGA/PLLA especially with 5% w/v HA recapitulated the tissue remodeling process of human bone via coupling signals coordinating osteoblast and osteoclast activity and finely tuned expression of inflammatory molecules, resulting in accelerated in vitro bone formation. Following subcutaneous implantation in rodents, co-cultured hiPSC-MSC/-macrophage on such scaffolds showed mature bone-like tissue formation. These findings suggest the importance of coupling matrix remodeling through osteoblastic matrix deposition and osteoclastic tissue resorption and immunomodulation for tissue development.
Dynamic enhancement patterns of intrahepatic cholangiocarcinoma in cirrhosis on contrast-enhanced computed tomography: risk of misdiagnosis as hepatocellular carcinoma
Authors: Li Rui , Cai Ping , Ma Kuan-sheng , Ding Shi-Yi , Guo De-Yu , Yan Xiao-Chu 
Published: May 2016

AbstractThis study aimed to assess the features of intrahepatic cholangiocarcinoma (ICC) at computerized tomography (CT) and verify the risk of misdiagnosis of ICC as hepatocellular carcinoma (HCC) in cirrhosis. CT appearances of 98 histologically confirmed ICC nodules from 84 cirrhotic patients were retrospectively reviewed, taking into consideration the pattern and dynamic contrast uptake during the arterial, portal venous and delayed phases. During the arterial phase, 53 nodules (54.1%) showed peripheral rim-like enhancement, 35 (35.7%) hyperenhancement, 9 (9.2%) hypoenhancement and 1 (1.0%) isoenhancement. The ICC nodules showed heterogeneous dynamic contrast patterns, being progressive enhancement in 35 nodules (35.7%), stable enhancement in 28 nodules (28.6%), wash-in and wash-out pattern in 15 nodules (15.3%) and all other enhancement patterns in 20 nodules (20.4%). There were no significant differences in the dynamic vascular patterns of ICC according to nodule size (p > 0.05). ICC in cirrhosis has varied enhancement patterns at contrast-enhanced multiphase multidetector CT. Though the majority of ICC did not display typical radiological hallmarks of HCC, if dynamic CT scan was used as the sole modality for the non-invasive diagnosis of nodules in cirrhosis, the risk of misdiagnosis of ICC for HCC is not negligible.
Percolation Phase Transition of Surface Air Temperature Networks under Attacks of El Niño/La Niña
Authors: Lu Zhenghui , Yuan Naiming , Fu Zuntao 
Published: May 2016

AbstractIn this study, sea surface air temperature over the Pacific is constructed as a network, and the influences of sea surface temperature anomaly in the tropical central eastern Pacific (El Niño/La Niña) are regarded as a kind of natural attack on the network. The results show that El Niño/La Niña leads an abrupt percolation phase transition on the climate networks from stable to unstable or metastable phase state, corresponding to the fact that the climate condition changes from normal to abnormal significantly during El Niño/La Niña. By simulating three different forms of attacks on an idealized network, including Most connected Attack (MA), Localized Attack (LA) and Random Attack (RA), we found that both MA and LA lead to stepwise phase transitions, while RA leads to a second-order phase transition. It is found that most attacks due to El Niño/La Niña are close to the combination of MA and LA, and a percolation critical threshold Pc can be estimated to determine whether the percolation phase transition happens. Therefore, the findings in this study may renew our understandings of the influence of El Niño/La Niña on climate, and further help us in better predicting the subsequent events triggered by El Niño/La Niña.
First-in-class small molecule potentiators of cancer virotherapy
Authors: Dornan Mark H. , Krishnan Ramya , Macklin Andrew M. , Selman Mohammed , El Sayes Nader , Son Hwan Hee , Davis Colin , Chen Andrew , Keillor Kerkeslin , Le Penny J. , Moi Christina , Ou Paula , Pardin Christophe , Canez Carlos R. , Le Boeuf Fabrice , Bell John C. , Smith Jeffrey C. , Diallo Jean-Simon , Boddy Christopher N. 
Published: May 2016

AbstractThe use of engineered viral strains such as gene therapy vectors and oncolytic viruses (OV) to selectively destroy cancer cells is poised to make a major impact in the clinic and revolutionize cancer therapy. In particular, several studies have shown that OV therapy is safe and well tolerated in humans and can infect a broad range of cancers. Yet in clinical studies OV therapy has highly variable response rates. The heterogeneous nature of tumors is widely accepted to be a major obstacle for OV therapeutics and highlights a need for strategies to improve viral replication efficacy. Here, we describe the development of a new class of small molecules for selectively enhancing OV replication in cancer tissue. Medicinal chemistry studies led to the identification of compounds that enhance multiple OVs and gene therapy vectors. Lead compounds increase OV growth up to 2000-fold in vitro and demonstrate remarkable selectivity for cancer cells over normal tissue ex vivo and in vivo. These small molecules also demonstrate enhanced stability with reduced electrophilicity and are highly tolerated in animals. This pharmacoviral approach expands the scope of OVs to include resistant tumors, further potentiating this transformative therapy. It is easily foreseeable that this approach can be applied to therapeutically enhance other attenuated viral vectors.
Impaired Gut-Liver-Brain Axis in Patients with Cirrhosis
Authors: Ahluwalia Vishwadeep , Betrapally Naga S , Hylemon Phillip B , White Melanie B , Gillevet Patrick M , Unser Ariel B , Fagan Andrew , Daita Kalyani , Heuman Douglas M , Zhou Huiping , Sikaroodi Masoumeh , Bajaj Jasmohan S 
Published: May 2016

AbstractCirrhosis is associated with brain dysfunction known as hepatic encephalopathy (HE). The mechanisms behind HE are unclear although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. We aimed to define the individual contribution of specific gut bacterial taxa towards astrocytic and neuronal changes in brain function using multi-modal MRI in patients with cirrhosis. 187 subjects (40 controls, 147 cirrhotic; 87 with HE) underwent systemic inflammatory assessment, cognitive testing, stool microbiota analysis and brain MRI analysis. MR spectroscopy (MRS) changes of increased Glutamate/glutamine, reduced myo-inositol and choline are hyperammonemia-associated astrocytic changes, while diffusion tensor imaging (DTI) demonstrates changes in neuronal integrity and edema. Linkages between cognition, MRI parameters and gut microbiota were compared between groups. We found that HE patients had a significantly worse cognitive performance, systemic inflammation, dysbiosis and hyperammonemia compared to controls and cirrhotics without HE. Specific microbial families (autochthonous taxa negatively and Enterobacteriaceae positively) correlated with MR spectroscopy and hyperammonemia-associated astrocytic changes. On the other hand Porphyromonadaceae, were only correlated with neuronal changes on DTI without linkages with ammonia. We conclude that specific gut microbial taxa are related to neuronal and astrocytic consequences of cirrhosis-associated brain dysfunction.
RETRACTED ARTICLE: Alpha-ketoglutarate promotes skeletal muscle hypertrophy and protein synthesis through Akt/mTOR signaling pathways
Authors: Cai Xingcai , Zhu Canjun , Xu Yaqiong , Jing Yuanyuan , Yuan Yexian , Wang Lina , Wang Songbo , Zhu Xiaotong , Gao Ping , Zhang Yongliang , Jiang Qingyan , Shu Gang 
Published: May 2016

AbstractSkeletal muscle weight loss is accompanied by small fiber size and low protein content. Alpha-ketoglutarate (AKG) participates in protein and nitrogen metabolism. The effect of AKG on skeletal muscle hypertrophy has not yet been tested, and its underlying mechanism is yet to be determined. In this study, we demonstrated that AKG (2%) increased the gastrocnemius muscle weight and fiber diameter in mice. Our in vitro study also confirmed that AKG dose increased protein synthesis in C2C12 myotubes, which could be effectively blocked by the antagonists of Akt and mTOR. The effects of AKG on skeletal muscle protein synthesis were independent of glutamate, its metabolite. We tested the expression of GPR91 and GPR99. The result demonstrated that C2C12 cells expressed GPR91, which could be upregulated by AKG. GPR91 knockdown abolished the effect of AKG on protein synthesis but failed to inhibit protein degradation. These findings demonstrated that AKG promoted skeletal muscle hypertrophy via Akt/mTOR signaling pathway. In addition, GPR91 might be partially attributed to AKG-induced skeletal muscle protein synthesis.
κ-Opioid Receptor Stimulation Improves Endothelial Function via Akt-stimulated NO Production in Hyperlipidemic Rats
Authors: Tian Fei , Zheng Xu-Yang , Li Juan , Zhang Shu-Miao , Feng Na , Guo Hai-Tao , Jia Min , Wang Yue-Min , Fan Rong , Pei Jian-Ming 
Published: May 2016

AbstractThis study was designed to investigate the effect of U50,488H (a selective κ-opioid receptor agonist) on endothelial function impaired by hyperlipidemia and to determine the role of Akt-stimulated NO production in it. Hyperlipidemic model was established by feeding rats with a high-fat diet for 14 weeks. U50,488H and nor-BNI (a selective κ-opioid receptor antagonist) were administered intraperitoneally. In vitro, the involvement of the PI3K/Akt/eNOS pathway in the effect of U50,488H was studied using cultured endothelial cells subjected to artificial hyperlipidemia. Serum total cholesterol and low-density lipoprotein cholesterol concentrations dramatically increased after high-fat diet feeding. Administration of U50,488H significantly alleviated endothelial ultrastructural destruction and endothelium-dependent vasorelaxation impairment caused by hyperlipidemia. U50,488H also increased Akt/eNOS phosphorylation and serum/medium NO level both in vivo and in vitro. U50,488H increased eNOS activity and suppressed iNOS activity in vivo. The effects of U50,488H were abolished in vitro by siRNAs targeting κ-opioid receptor and Akt or PI3K/Akt/eNOS inhibitors. All effects of U50,488H were blocked by nor-BNI. These results demonstrate that κ-opioid receptor stimulation normalizes endothelial ultrastructure and function under hyperlipidemic condition. Its mechanism is related to the preservation of eNOS phosphorylation through activation of the PI3K/Akt signaling pathway and downregulation of iNOS expression/activity.
Transcriptome analysis of Streptococcus pneumoniae treated with the designed antimicrobial peptides, DM3
Authors: Le Cheng-Foh , Gudimella Ranganath , Razali Rozaimi , Manikam Rishya , Sekaran Shamala Devi 
Published: May 2016

AbstractIn our previous studies, we generated a short 13 amino acid antimicrobial peptide (AMP), DM3, showing potent antipneumococcal activity in vitro and in vivo. Here we analyse the underlying mechanisms of action using Next-Generation transcriptome sequencing of penicillin (PEN)-resistant and PEN-susceptible pneumococci treated with DM3, PEN and combination of DM3 and PEN (DM3PEN). DM3 induced differential expression in cell wall and cell membrane structural and transmembrane processes. Notably, DM3 altered the expression of competence-induction pathways by upregulating CelA, CelB and CglA while downregulating Ccs16, ComF and Ccs4 proteins. Capsular polysaccharide subunits were downregulated in DM3-treated cells, however, it was upregulated in PEN- and DM3PEN-treated groups. Additionally, DM3 altered the amino acids biosynthesis pathways, particularly targeting ribosomal rRNA subunits. Downregulation of cationic AMPs resistance pathway suggests that DM3 treatment could autoenhance pneumococci susceptibility to DM3. Gene enrichment analysis showed that unlike PEN and DM3PEN, DM3 treatment exerted no effect on DNA-binding RNA polymerase activity but observed downregulation of RpoD and RNA polymerase sigma factor. In contrast to DM3, DM3PEN altered the regulation of multiple purine/pyrimidine biosynthesis and metabolic pathways. Future studies based on in vitro experiments are proposed to investigate the key pathways leading to pneumococcal cell death caused by DM3.
Soil Water Balance and Water Use Efficiency of Dryland Wheat in Different Precipitation Years in Response to Green Manure Approach
Authors: Zhang Dabin , Yao Pengwei , Na Zhao , Cao Weidong , Zhang Suiqi , Li Yangyang , Gao Yajun 
Published: May 2016

AbstractWinter wheat (Triticum aestivum L.) monoculture is conventionally cultivated followed by two to three months of summer fallow in the Loess Plateau. To develop a sustainable cropping system, we conducted a six-year field experiment to investigate the effect of leguminous green manure (LGM) instead of bare fallow on the yield and water use efficiency (WUE) of winter wheat and the soil water balance (SWB) in different precipitation years in a semi-arid region of northwest China. Results confirmed that planting LGM crop consumes soil water in the fallow season can bring varied effects to the subsequent wheat. The effect is positive or neutral when the annual precipitation is adequate, so that there is no significant reduction in the soil water supplied to wheat. If this is not the case, the effect is negative. On average, the LGM crop increased wheat yield and WUE by 13% and 28%, respectively, and had considerable potential for maintaining the SWB (0–200 cm) compared with fallow management. In conclusion, cultivation of the LGM crop is a better option than fallow to improve the productivity and WUE of the next crop and maintain the soil water balance in the normal and wet years in the Loess Plateau.
Prenatal ketamine exposure causes abnormal development of prefrontal cortex in rat
Authors: Zhao Tianyun , Li Chuanxiang , Wei Wei , Zhang Haixing , Ma Daqing , Song Xingrong , Zhou Libing 
Published: May 2016

AbstractKetamine is commonly used for anesthesia and as a recreational drug. In pregnant users, a potential neurotoxicity in offspring has been noted. Our previous work demonstrated that ketamine exposure of pregnant rats induces affective disorders and cognitive impairments in offspring. As the prefrontal cortex (PFC) is critically involved in emotional and cognitive processes, here we studied whether maternal ketamine exposure influences the development of the PFC in offspring. Pregnant rats on gestational day 14 were treated with ketamine at a sedative dose for 2 hrs, and pups were studied at postnatal day 0 (P0) or P30. We found that maternal ketamine exposure resulted in cell apoptosis and neuronal loss in fetal brain. Upon ketamine exposure in utero, PFC neurons at P30 showed more dendritic branching, while cultured neurons from P0 PFC extended shorter neurites than controls. In addition, maternal ketamine exposure postponed the switch of NR2B/2A expression, and perturbed pre- and postsynaptic protein expression in the PFC. These data suggest that prenatal ketamine exposure impairs neuronal development of the PFC, which may be associated with abnormal behavior in offsprings.
Broadband diffuse terahertz wave scattering by flexible metasurface with randomized phase distribution
Authors: Zhang Yin , Liang Lanju , Yang Jing , Feng Yijun , Zhu Bo , Zhao Junming , Jiang Tian , Jin Biaobing , Liu Weiwei 
Published: May 2016

AbstractSuppressing specular electromagnetic wave reflection or backward radar cross section is important and of broad interests in practical electromagnetic engineering. Here, we present a scheme to achieve broadband backward scattering reduction through diffuse terahertz wave reflection by a flexible metasurface. The diffuse scattering of terahertz wave is caused by the randomized reflection phase distribution on the metasurface, which consists of meta-particles of differently sized metallic patches arranged on top of a grounded polyimide substrate simply through a certain computer generated pseudorandom sequence. Both numerical simulations and experimental results demonstrate the ultralow specular reflection over a broad frequency band and wide angle of incidence due to the re-distribution of the incident energy into various directions. The diffuse scattering property is also polarization insensitive and can be well preserved when the flexible metasurface is conformably wrapped on a curved reflective object. The proposed design opens up a new route for specular reflection suppression and may be applicable in stealth and other technology in the terahertz spectrum.
New paradigm to assess brain cell morphology by diffusion-weighted MR spectroscopy in vivo
Authors: Palombo Marco , Ligneul Clémence , Najac Chloé , Le Douce Juliette , Flament Julien , Escartin Carole , Hantraye Philippe , Brouillet Emmanuel , Bonvento Gilles , Valette Julien 
Published: May 2016

Significance
Characterizing the microstructure of an organ noninvasively using molecular diffusion measurements represents a major challenge in medical imaging and life science. In this work, we propose concepts in diffusion magnetic resonance to noninvasively extract morphological properties of brain cells that are out of reach of existing neuroimaging techniques, such as diffusion-weighted MRI. We show how long-range morphology of neurons and astrocytes can affect the diffusion of cell-specific metabolites at ultra-long diffusion times and that adequate modeling strategy seems to allow extracting morphological parameters such as astrocytic and neuronal process length and complexity, opening the way to noninvasive histology of the brain. We believe that the concepts and methods introduced here may represent a significant breakthrough in neuroimaging and neurosciences.
Networks of highly branched stigmarian rootlets developed on the first giant trees
Authors: Hetherington Alexander J. , Berry Christopher M. , Dolan Liam 
Published: May 2016

Significance
Coal swamps were the carbon burial factories of the Carboniferous period, forming huge coal deposits and driving climate cooling. The Carboniferous forests were also home to the first giant (>50 m) trees to grow on the planet. These trees were anchored by a unique structure termed a stigmarian system, which is hypothesized to represent a leafy shoot modified to function as a root. Here, we report the discovery of the complex, highly branched rootlet structure of these trees. Our findings demonstrate that rootlet architecture is conserved from the giant extinct trees of the Carboniferous to the small extant herbs of today’s flora.
nArgBP2 regulates excitatory synapse formation by controlling dendritic spine morphology
Authors: Lee Sang-Eun , Kim Yoonju , Han Jeong-Kyu , Park Hoyong , Lee Unghwi , Na Myeongsu , Jeong Soomin , Chung ChiHye , Cestra Gianluca , Chang Sunghoe 
Published: May 2016

Significance
Recent studies have implicated postsynaptic scaffolding protein synapse-associated protein 90/postsynaptic density protein 95-associated protein 3 (SAPAP3) or Shank3 in mood disorders such as bipolar disorder, autism, and obsessive-compulsive disorders. Neural Abelson-related gene-binding protein 2 (nArgBP2) is a binding partner of both SAPAP3 and Shank3, and its genetic deletion in mice leads to manic/bipolar-like behavior resembling symptoms of bipolar disorder. Remarkably, nothing is known about the synaptic function of nArgBP2 or its connection with the synaptic alterations associated with bipolar disorder. Here, we provide compelling evidence that nArgBP2 regulates spine morphogenesis and that its ablation causes a robust and selective inhibition of excitatory synapse formation by controlling actin dynamics. Our results revealed the underlying mechanism for the synaptic dysfunction caused by nArgBP2 down-regulation that may be associated with human bipolar disorder.
Antifreeze proteins govern the precipitation of trehalose in a freezing-avoiding insect at low temperature
Authors: Wen Xin , Wang Sen , Duman John G. , Arifin Josh Fnu , Juwita Vonny , Goddard William A. , Rios Alejandra , Liu Fan , Kim Soo-Kyung , Abrol Ravinder , DeVries Arthur L. , Henling Lawrence M. 
Published: May 2016

Significance
Survival strategies for overwintering insects rely on the biochemical components in body fluids, where trehalose and antifreeze proteins (AFPs) are sometimes the best-known and extensively studied carbohydrate and protein components occurring in winters in both freeze-tolerant (they can survive if frozen) and freeze-avoiding species (they die if frozen). AFPs are known to lower the freezing temperature and defer the growth of ice, whereas their roles in freeze-tolerant species have long been speculated. By examining the larval blood of a freeze-avoiding beetle, we reveal a new role for AFPs by demonstrating that AFPs effectively inhibit trehalose crystallization. This finding provides a novel approach for cold protection and for inhibiting trehalose crystallization in medical and industrial applications.