bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAD2B acts as a negative regulatory partner of TCF4 on proliferation in human dermal papilla cells
Authors: Yu Nanlan , Song Zhiqiang , Zhang Kezhou , Yang Xichuan 
Published: September 2017

AbstractDermal papilla cells (DPCs) are important components of hair follicles and play a critical role in hair follicle development. However, the mechanisms by which DPCs induce hair follicle development remain unclear. In the present study, we identified the mitotic arrest deficient protein MAD2B as a modifier of DPCs. Overexpression of MAD2B inhibited DPC aggregative growth and proliferation induced by the Wnt signaling activator T cell factor 4 (TCF4), and decreased TCF4-induced expression and the release of hair growth-related cytokines, including hepatocyte growth factor, insulin-like growth factor-1, and vascular endothelial growth factor in DPCs. In contrast, knockdown of MAD2B promoted TCF4-induced DPC proliferation, but did not affect the expression and secretion of cytokines by TCF4-induced DPCs. These results suggest a functional antagonism between MAD2B and TCF4 in DPC-induced hair follicle development. Mechanistically, MAD2B physically interacted with TCF4 to repress TCF4 transcriptional activity via β-catenin mediation, leading to reduced β-catenin/TCF4-dependent transactivation and Wnt signaling activity. These results demonstrate, for the first time, that MAD2B plays a negative role in TCF4-induced DPC growth and proliferation.
Vδ2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure
Authors: Jagannathan Prasanna , Lutwama Fredrick , Boyle Michelle J. , Nankya Felistas , Farrington Lila A. , McIntyre Tara I. , Bowen Katherine , Naluwu Kate , Nalubega Mayimuna , Musinguzi Kenneth , Sikyomu Esther , Budker Rachel , Katureebe Agaba , Rek John , Greenhouse Bryan , Dorsey Grant , Kamya Moses R. , Feeney Margaret E. 
Published: September 2017

AbstractVδ2+γδ T cells are semi-innate T cells that expand markedly followingP. falciparum (Pf)infection in naïve adults, but are lost and become dysfunctional among children repeatedly exposed to malaria. The role of these cells in mediating clinical immunity (i.e. protection against symptoms) to malaria remains unclear. We measured Vδ2+T cell absolute counts at acute and convalescent malaria timepoints (n = 43), and Vδ2+counts, cellular phenotype, and cytokine production followingin vitrostimulation at asymptomatic visits (n = 377), among children aged 6 months to 10 years living in Uganda. Increasing age was associated with diminishedin vivoexpansion following malaria, and lower Vδ2 absolute counts overall, among children living in a high transmission setting. Microscopic parasitemia and expression of the immunoregulatory markers Tim-3 and CD57 were associated with diminished Vδ2+T cell pro-inflammatory cytokine production. Higher Vδ2 pro-inflammatory cytokine production was associated with protection from subsequentPfinfection, but also with an increased odds of symptoms once infected. Vδ2+T cells may play a role in preventing malaria infection in children living in endemic settings; progressive loss and dysfunction of these cells may represent a disease tolerance mechanism that contributes to the development of clinical immunity to malaria.
Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer
Authors: Ngô Huân M. , Zhou Ying , Lorenzi Hernan , Wang Kai , Kim Taek-Kyun , Zhou Yong , El Bissati Kamal , Mui Ernest , Fraczek Laura , Rajagopala Seesandra V. , Roberts Craig W. , Henriquez Fiona L. , Montpetit Alexandre , Blackwell Jenefer M. , Jamieson Sarra E. , Wheeler Kelsey , Begeman Ian J. , Naranjo-Galvis Carlos , Alliey-Rodriguez Ney , Davis Roderick G. , Soroceanu Liliana , Cobbs Charles , Steindler Dennis A. , Boyer Kenneth , Noble A. Gwendolyn , Swisher Charles N. , Heydemann Peter T. , Rabiah Peter , Withers Shawn , Soteropoulos Patricia , Hood Leroy , McLeod Rima 
Published: September 2017

AbstractOne third of humans are infected lifelong with the brain-dwelling, protozoan parasite,Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage andT. gondiiinfection. These data were deconvoluted using three systems biology approaches: “Orbital-deconvolution” elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. “Cluster-deconvolution” revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, “disease-deconvolution” identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer’s disease, and cancer. This “reconstruction-deconvolution” logic provides templates of progenitor cells’ potentiating effects, and components affecting human brain parasitism and diseases.
Under-ice availability of phytoplankton lipids is key to freshwater zooplankton winter survival
Authors: Grosbois Guillaume , Mariash Heather , Schneider Tobias , Rautio Milla 
Published: September 2017

AbstractShortening winter ice-cover duration in lakes highlights an urgent need for research focused on under-ice ecosystem dynamics and their contributions to whole-ecosystem processes. Low temperature, reduced light and consequent changes in autotrophic and heterotrophic resources alter the diet for long-lived consumers, with consequences on their metabolism in winter. We show in a survival experiment that the copepod Leptodiaptomus minutus in a boreal lake does not survive five months under the ice without food. We then report seasonal changes in phytoplankton, terrestrial and bacterial fatty acid (FA) biomarkers in seston and in four zooplankton species for an entire year. Phytoplankton FA were highly available in seston (2.6 µg L−1) throughout the first month under the ice. Copepods accumulated them in high quantities (44.8 µg mg dry weight−1), building lipid reserves that comprised up to 76% of body mass. Terrestrial and bacterial FA were accumulated only in low quantities (<2.5 µg mg dry weight−1). The results highlight the importance of algal FA reserve accumulation for winter survival as a key ecological process in the annual life cycle of the freshwater plankton community with likely consequences to the overall annual production of aquatic FA for higher trophic levels and ultimately for human consumption.
Grip force when reaching with target uncertainty provides evidence for motor optimization over averaging
Authors: Nashed Joseph Y. , Diamond Jonathan S. , Gallivan Jason P. , Wolpert Daniel M. , Flanagan J. Randall 
Published: September 2017

AbstractWhen presented with competing potential reach targets and required to launch a movement before knowing which one will be cued as the target, people initially reach in the average target direction. Although this spatial averaging could arise from executing a weighted average of motor plans for the potential targets, it could also arise from planning a single, optimal movement. To test between these alternatives we used a task in which participants were required to reach to either a single target or towards two potential targets while grasping an object. A robotic device applied a lateral elastic load to the object requiring large grip forces for reaches to targets either side of midline and a minimal grip force for midline movements. As expected, in trials with two targets located either side of midline, participants initially reached straight ahead. Critically, on these trials the initial grip force was minimal, appropriate for the midline movement, and not the average of the large grip forces required for movements to the individual targets. These results indicate that under conditions of target uncertainty, people do not execute an average of planned actions but rather a single movement that optimizes motor costs.
Responses of LAI to rainfall explain contrasting sensitivities to carbon uptake between forest and non-forest ecosystems in Australia
Authors: Li Longhui , Wang Ying-Ping , Beringer Jason , Shi Hao , Cleverly James , Cheng Lei , Eamus Derek , Huete Alfredo , Hutley Lindsay , Lu Xingjie , Piao Shilong , Zhang Lu , Zhang Yongqiang , Yu Qiang 
Published: September 2017

AbstractNon-forest ecosystems (predominant in semi-arid and arid regions) contribute significantly to the increasing trend and interannual variation of land carbon uptake over the last three decades, yet the mechanisms are poorly understood. By analysing the flux measurements from 23 ecosystems in Australia, we found the the correlation between gross primary production (GPP) and ecosystem respiration (Re) was significant for non-forest ecosystems, but was not for forests. In non-forest ecosystems, both GPP and Re increased with rainfall, and, consequently net ecosystem production (NEP) increased with rainfall. In forest ecosystems, GPP and Re were insensitive to rainfall. Furthermore sensitivity of GPP to rainfall was dominated by the rainfall-driven variation of LAI rather GPP per unit LAI in non-forest ecosystems, which was not correctly reproduced by current land models, indicating that the mechanisms underlying the response of LAI to rainfall should be targeted for future model development.
Decoupled dynamic magnetic field measurements improves diffusion-weighted magnetic resonance images
Authors: Chu Ying-Hua , Hsu Yi-Cheng , Lin Fa-Hsuan 
Published: September 2017

AbstractField probes are miniature receiver coils with localized NMR-active samples inside. They are useful in monitoring magnetic field. This information can be used to improve magnetic resonance image quality. While field probes are coupled to each other marginally in most applications, this coupling can cause incorrect resonance frequency estimates and image reconstruction errors. Here, we propose a method to reduce the coupling between field probes in order to improve the accuracy of magnetic field estimation. An asymmetric sensitivity matrix describing the coupling between channels of field probes and NMR active droplets within field probes was empirically measured. Localized signal originating from each probe was derived from the product of the inverse of the sensitivity matrix and the coupled probe measurements. This method was used to estimate maps of dynamic magnetic fields in diffusion weighted MRI. The estimated fields using decoupled probe measurement led to images more robust to eddy currents caused by diffusion sensitivity gradients along different directions.
Oscillatory dynamics of p38 activity with transcriptional and translational time delays
Authors: Zhang Yuan , Liu Haihong , Yan Fang , Zhou Jin 
Published: September 2017

AbstractRecent experimental evidence reports that oscillations of p38 MAPK (p38) activity would efficiently induce pro-inflammatory gene expression, which might be deleterious to immune systems and may even cause cellular damage and apoptosis. It is widely accepted now that transcriptional and translational delays are ubiquitous in gene expression, which can typically result in oscillatory responses of gene regulations. Consequently, delay-driven sustained oscillations in p38 activity (p38*) could in principle be commonplace. Nevertheless, so far the studies of the impact of such delays on p38* have been lacking both experimentally and theoretically. Here, we use experimental data to develop a delayed mathematical model, with the aim of understanding how such delays affect oscillatory behaviour on p38*. We analyze the stability and oscillation of the model with and without explicit time delays. We show that a sufficiently input stimulation strength is prerequisite for generating p38* oscillations, and that an optimal rate of model parameters is also essential to these oscillations. Moreover, we find that the time delays required for transcription and translation in mitogen-activated protein kinase phosphatase-1 (MKP-1) gene expression can drive p38* to be oscillatory even when the concentration of p38* level is at a stable state. Furthermore, the length of these delays can determine the amplitude and period of the oscillations and can enormously extend the oscillatory ranges of model parameters. These results indicate that time delays in MKP-1 synthesis are required, albeit not sufficient, for p38* oscillations, which may lead to new insights related to p38 oscillations.
Rhus coriaria increases protein ubiquitination, proteasomal degradation and triggers non-canonical Beclin-1-independent autophagy and apoptotic cell death in colon cancer cells
Authors: Athamneh Khawlah , Hasasna Hussain El , Samri Halima Al , Attoub Samir , Arafat Kholoud , Benhalilou Nehla , Rashedi Asma Al , Dhaheri Yusra Al , AbuQamar Synan , Eid Ali , Iratni Rabah 
Published: September 2017

AbstractColorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Here, we investigated the anticancer effect ofRhus coriariaextract (RCE) on HT-29 and Caco-2 human colorectal cancer cells. We found that RCE significantly inhibited the viability and colony growth of colon cancer cells. Moreover, RCE induced Beclin-1-independent autophagy and subsequent caspase-7-dependent apoptosis. Blocking of autophagy by chloroquine significantly reduced RCE-induced cell death, while blocking of apoptosis had no effect on RCE-induced cell death. Mechanistically, RCE inactivated the AKT/mTOR pathway by promoting the proteasome-dependent degradation of both proteins. Strikingly, we also found that RCE targeted Beclin-1, p53 and procaspase-3 to degradation. Proteasome inhibition by MG-132 not only restored these proteins to level comparable to control cells, but also reduced RCE-induced cell death and blocked the activation of autophagy and apoptosis. The proteasomal degradation of mTOR, which occurred only 3 hours post-RCE treatment was concomitant with an overall increase in the level of ubiquitinated proteins and translated stimulation of proteolysis by the proteasome. Our findings demonstrate thatRhus coriariapossesses strong anti-colon cancer activity through stimulation of proteolysis as well as induction of autophagic and apoptotic cell death, making it a potential and valuable source of novel therapeutic cancer drug.
STIM1-dependent Ca2+ signaling regulates podosome formation to facilitate cancer cell invasion
Authors: Chen Yun-Wen , Lai Chieh-Shan , Chen Yih-Fung , Chiu Wen-Tai , Chen Hong-Chen , Shen Meng-Ru 
Published: September 2017

AbstractThe clinical significance of STIM proteins and Orai Ca2+ channels in tumor progression has been demonstrated in different types of cancers. Podosomes are dynamic actin-rich cellular protrusions that facilitate cancer cell invasiveness by degrading extracellular matrix. Whether STIM1-dependent Ca2+ signaling facilitates cancer cell invasion through affecting podosome formation remains unclear. Here we show that the invasive fronts of cancer tissues overexpress STIM1, accompanied by active store-operated Ca2+ entry (SOCE). Interfering SOCE activity by SOCE inhibitors and STIM1 or Orai1 knockdown remarkably affects podosome rosettes formation. Mechanistically, STIM1-silencing significantly alters the podosome rosettes dynamics, shortens the maintenance phase of podosome rosettes and reduces cell invasiveness. The subsequently transient expression of STIM1 cDNA in STIM1-null (STIM1−/−) mouse embryo fibroblasts rescues the suppression of podosome formation, suggesting that STIM1-mediated SOCE activation directly regulates podosome formation. This study uncovers SOCE-mediated Ca2+ microdomain that is the molecular basis for Ca2+ sensitivity controlling podosome formation.
IL-37 is associated with osteoarthritis disease activity and suppresses proinflammatory cytokines production in synovial cells
Authors: Ding Liping , Hong Xiaoping , Sun Baodong , Huang Qin , Wang Xiaoqi , Liu Xiaokai , Li Lingyun , Huang Zhong , Liu Dongzhou 
Published: September 2017

AbstractThe objective of this study is to investigate the correlation between IL-37 level and osteoarthritis activity and to determine the anti-inflammatory effects of IL-37 in peripheral blood mononuclear cells (PBMCs) and synovial cells (SCs) from osteoarthritis (OA) patients, which including 32 patients with erosive inflammatory OA (EIOA) and 40 patients with primary generalized OA (PGOA), 40 age and sex matched healthy volunteers were recruited as healthy controls (HCs). The protein and relative mRNA levels of IL-37 were significant increased in the blood of EIOA patients compared with those of PGOA patients and HCs. Serum IL-37 levels of OA patients were positively correlated with VAS score, as well as with CRP, ESR in blood. Positive correlations were also observed among IL-37 with IL-1β, TNF-α and IL-6 in synovial cells. Furthermore, the expression of IL-1β, TNF-α and IL-6 in PBMCs and SCs from EIOA patients was suppressed by IL-37 in vitro. In conclusion, our results indicated that IL-37 increased in EIOA patients and was positively correlated with disease activity, the pro-inflammatory cytokines such as IL-1β, TNF-α and IL-6 in PBMCs and synovial cells from EIOA patients were restrained by recombinant IL-37. Thus, IL-37 may serve as a novel therapeutic target for the treatment of OA inflammation.
Two-dimensional Dirac particles in a Pöschl-Teller waveguide
Authors: Hartmann R. R. , Portnoi M. E. 
Published: September 2017

AbstractWe obtain exact solutions to the two-dimensional (2D) Dirac equation for the one-dimensional Pöschl-Teller potential which contains an asymmetry term. The eigenfunctions are expressed in terms of Heun confluent functions, while the eigenvalues are determined via the solutions of a simple transcendental equation. For the symmetric case, the eigenfunctions of the supercritical states are expressed as spheroidal wave functions, and approximate analytical expressions are obtained for the corresponding eigenvalues. A universal condition for any square integrable symmetric potential is obtained for the minimum strength of the potential required to hold a bound state of zero energy. Applications for smooth electron waveguides in 2D Dirac-Weyl systems are discussed.
Polycystin-1 inhibits eIF2α phosphorylation and cell apoptosis through a PKR-eIF2α pathway
Authors: Tang Yan , Wang Zuocheng , Yang JungWoo , Zheng Wang , Chen Di , Wu Guanqing , Sandford Richard , Tang Jingfeng , Chen Xing-Zhen 
Published: September 2017

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2 which encodes polycystin-1 (PC1) and polycystin-2, respectively. PC1 was previously shown to slow cell proliferation and inhibit apoptosis but the underlying mechanisms remain elusive or controversial. Here we showed in cultured mammalian cells and Pkd1 knockout mouse kidney epithelial cells that PC1 and its truncation mutant comprising the last five transmembrane segments and the intracellular C-terminus (PC1-5TMC) down-regulate the phosphorylation of protein kinase R (PKR) and its substrate eukaryotic translation initiation factor 2 alpha (eIF2α). PKR is known to be activated by interferons and dsRNAs, inhibits protein synthesis and induces apoptosis. By co-immunoprecipitation experiments we found that PC1 truncation mutants associate with PKR, or with PKR and its activator PACT. Further experiments showed that PC1 and PC1-5TMC reduce phosphorylation of eIF2α through inhibiting PKR phosphorylation. Our TUNEL experiments using tunicamycin, an apoptosis inducer, and GADD34, an inhibitor of eIF2α phosphorylation, demonstrated that PC1-5TMC inhibits apoptosis of HEK293T cells in a PKR-eIF2α-dependent manner, with concurrent up- and down-regulation of Bcl-2 and Bax, respectively, revealed by Western blotting. Involvement of PC1-regulated eIF2α phosphorylation and a PKR-eIF2α pathway in cell apoptosis may be an important part of the mechanism underlying ADPKD pathogenesis.
Production and Characteristics of a Novel Xylose- and Alkali-tolerant GH 43 β-xylosidase from Penicillium oxalicum for Promoting Hemicellulose Degradation
Authors: Ye Yanxin , Li Xuezhi , Zhao Jian 
Published: September 2017

Abstractβ-xylosidase is a pivotal enzyme for complete degradation of xylan in hemicelluloses of lignocelluloses, and the xylose- and alkali-tolerant β-xylosidase with high catalytic activity is very attractive for promoting enzymatic hydrolysis of alkaline-pretreated lignocellulose. In this study, a novel intracellular glycoside hydrolase family 43 β-xylosidase gene (xyl43) from Penicillium oxalicum 114-2 was successfully high-level overexpressed in Pichia pastoris, and the secreted enzyme was characterized. The β-xylosidase Xyl43 exhibited great pH stability and high catalytic activity in the range of pH 6.0 to 8.0, and high tolerance to xylose with the Ki value of 28.09 mM. The Xyl43 could effectively promote enzymatic degradation of different source of xylan and hemicellulose contained in alkaline-pretreated corn stover, and high conversion of xylan to xylose could be obtained.
Phosphoenolpyruvate Carboxykinase Maintains Glycolysis-driven Growth in Drosophila Tumors
Authors: Hussain Rashid , Shaukat Zeeshan , Khan Mahwish , Saint Robert , Gregory Stephen L. 
Published: September 2017

AbstractTumors frequently fail to pass on all their chromosomes correctly during cell division, and this chromosomal instability (CIN) causes irregular aneuploidy and oxidative stress in cancer cells. Our objective was to test knockdowns of metabolic enzymes in Drosophila to find interventions that could exploit the differences between normal and CIN cells to block CIN tumor growth without harming the host animal. We found that depleting by RNAi or feeding the host inhibitors against phosphoenolpyruvate carboxykinase (PEPCK) was able to block the growth of CIN tissue in a brat tumor explant model. Increasing NAD+ or oxidising cytoplasmic NADH was able to rescue the growth of PEPCK depleted tumors, suggesting a problem in clearing cytoplasmic NADH. Consistent with this, blocking the glycerol-3-phosphate shuttle blocked tumor growth, as well as lowering ROS levels. This work suggests that proliferating CIN cells are particularly vulnerable to inhibition of PEPCK, or its metabolic network, because of their compromised redox status.