bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene switching rate determines response to extrinsic perturbations in the self-activation transcriptional network motif
Authors: de Franciscis Sebastiano , Caravagna Giulio , Mauri Giancarlo , d’Onofrio Alberto 
Published: June 2016

AbstractGene switching dynamics is a major source of randomness in genetic networks, also in the case of large concentrations of the transcription factors. In this work, we consider a common network motif - the positive feedback of a transcription factor on its own synthesis - and assess its response to extrinsic noises perturbing gene deactivation in a variety of settings where the network might operate. These settings are representative of distinct cellular types, abundance of transcription factors and ratio between gene switching and protein synthesis rates. By investigating noise-induced transitions among the different network operative states, our results suggest that gene switching rates are key parameters to shape network response to external perturbations and that such response depends on the particular biological setting, i.e. the characteristic time scales and protein abundance. These results might have implications on our understanding of irreversible transitions for noise-related phenomena such as cellular differentiation. In addition these evidences suggest to adopt the appropriate mathematical model of the network in order to analyze the system consistently to the reference biological setting.
Mammalian metabolic rates in the hottest fish on earth
Authors: Wood Chris M. , Brix Kevin V. , De Boeck Gudrun , Bergman Harold L. , Bianchini Adalto , Bianchini Lucas F. , Maina John N. , Johannsson Ora E. , Kavembe Geraldine D. , Papah Michael B. , Letura Kisipan M. , Ojoo Rodi O. 
Published: June 2016

AbstractThe Magadi tilapia,Alcolapia grahami, a small cichlid fish of Lake Magadi, Kenya lives in one of the most challenging aquatic environments on earth, characterized by very high alkalinity, unusual water chemistry, and extreme O2, ROS, and temperature regimes. In contrast to most fishes which live at temperatures substantially lower than the 36–40 °C of mammals and birds, an isolated population (South West Hot Springs, SWHS) of Magadi tilapia thrives in fast-flowing hotsprings with daytime highs of 43 °C and night-time lows of 32 °C. Another population (Fish Springs Lagoon, FSL) lives in a lagoon with fairly stable daily temperatures (33–36 °C). The upper critical temperatures (Ctmax) of both populations are very high; moreover the SWHS tilapia exhibit the highest Ctmax(45.6 °C) ever recorded for a fish. Routine rates of O2consumption (MO2) measured on site, together with MO2and swimming performance at 25, 32, and 39 °C in the laboratory, showed that the SWHS tilapia exhibited the greatest metabolic performance ever recorded in a fish. These rates were in the basal range of a small mammal of comparable size, and were all far higher than in the FSL fish. The SWHS tilapia represents a bellwether organism for global warming.
Synergistic Effect of Compounds from a Chinese Herb: Compatibility and Dose Optimization of Compounds from N-Butanol Extract of Ipomoea stolonifera
Authors: Cai Congyi , Chen Yicun , Zhong Shuping , Zhang Yanmei , Jiang Jiyang , Xu Han , Shi Ganggang 
Published: June 2016

AbstractThe herbal medicine Ipomoea stolonifera (I. stolonifera) has previously been shown to have considerable anti-inflammatory potential in vivo and in vitro. To establish a method for exploring the synergistic effects of multiple compounds, we study the compatibility and dose optimization of compounds isolated from n-butanol extract of I. stolonifera (BE-IS). Raw264.7 cell was treated with lipopolysaccharide (LPS) in the presence of compounds from BE-IS, namely scopoletin, umbelliferone, esculetin, hesperetin and curcumin, using the orthogonal design, uniform design and median-effect method. To verify the best efficacy of principal constituents in vivo, the uniform design was used in the croton oil-induced mouse ear edema model. The results from LPS-induced the production of prostaglandin E2 (PGE2) show that, esculetin, curcumin and hesperetin were the principal constituents that had synergistic effects when used at the optimal ratio. Additionally, the principal constituents were found to work synergistically in the croton oil-induced mouse ear edema model at low doses. It turned out that the three experimental optimization and analysis methods (orthogonal design, uniform design and median-effect method) can be effectively used to solve both compatibility and dose optimization for combined use of multiple compounds.
Remarkable preservation of Ca2+ homeostasis and inhibition of apoptosis contribute to anti-muscle atrophy effect in hibernating Daurian ground squirrels
Authors: Fu Weiwei , Hu Huanxin , Dang Kai , Chang Hui , Du Bei , Wu Xue , Gao Yunfang 
Published: June 2016

AbstractThe underlying mechanisms that hibernators deviated from muscle atrophy during prolonged hibernating inactivity remain elusive. This study tested the hypothesis that the maintenance of intracellular Ca2+ homeostasis and inhibition of apoptosis would be responsible for preventing muscle atrophy in hibernating Daurian ground squirrels. The results showed that intracellular Ca2+ homeostasis was maintained in soleus and extensor digitorum longus (EDL) in hibernation and post-hibernation, while cytosolic Ca2+ was overloaded in gastrocnemius (GAS) in hibernation with a recovery in post-hibernation. The Ca2+ overload was also observed in interbout arousals in all three type muscles. Besides, the Bax/Bcl-2 ratio was unchanged in transcriptional level among pre-hibernation, hibernation and interbout arousals and reduced to a minimum in post-hibernation. Furthermore, the Bax/Bcl-2 ratio in protein level was reduced in hibernation but recovered in interbout arousals. Although cytochrome C was increased in GAS and EDL in post-hibernation, no apoptosis was observed by TUNEL assay. These findings suggested that the intracellular Ca2+ homeostasis in hibernation might be regulated by the cytosolic Ca2+ overload during interbout arousals, which were likely responsible for preventing muscle atrophy via inhibition of apoptosis. Moreover, the muscle-specificity indicated that the different mechanisms against disuse-induced atrophy might be involved in different muscles in hibernation.
Defect engineering of the electronic transport through cuprous oxide interlayers
Authors: Fadlallah Mohamed M. , Eckern Ulrich , Schwingenschlögl Udo 
Published: June 2016

AbstractThe electronic transport through Au–(Cu2O)n–Au junctions is investigated using first-principles calculations and the nonequilibrium Green’s function method. The effect of varying the thickness (i.e., n) is studied as well as that of point defects and anion substitution. For all Cu2O thicknesses the conductance is more enhanced by bulk-like (in contrast to near-interface) defects, with the exception of O vacancies and Cl substitutional defects. A similar transmission behavior results from Cu deficiency and N substitution, as well as from Cl substitution and N interstitials for thick Cu2O junctions. In agreement with recent experimental observations, it is found that N and Cl doping enhances the conductance. A Frenkel defect, i.e., a superposition of an O interstitial and O substitutional defect, leads to a remarkably high conductance. From the analysis of the defect formation energies, Cu vacancies are found to be particularly stable, in agreement with earlier experimental and theoretical work.
There’s plenty of light at the bottom: statistics of photon penetration depth in random media
Authors: Martelli Fabrizio , Binzoni Tiziano , Pifferi Antonio , Spinelli Lorenzo , Farina Andrea , Torricelli Alessandro 
Published: June 2016

AbstractWe propose a comprehensive statistical approach describing the penetration depth of light in random media. The presented theory exploits the concept of probability density function f(z|ρ, t) for the maximum depth reached by the photons that are eventually re-emitted from the surface of the medium at distance ρ and time t. Analytical formulas for f, for the mean maximum depth 〈zmax〉 and for the mean average depth "Equation missing" reached by the detected photons at the surface of a diffusive slab are derived within the framework of the diffusion approximation to the radiative transfer equation, both in the time domain and the continuous wave domain. Validation of the theory by means of comparisons with Monte Carlo simulations is also presented. The results are of interest for many research fields such as biomedical optics, advanced microscopy and disordered photonics.
Unexpected involvement of staple leads to redesign of selective bicyclic peptide inhibitor of Grb7
Authors: Gunzburg Menachem J. , Kulkarni Ketav , Watson Gabrielle M. , Ambaye Nigus D. , Del Borgo Mark P. , Brandt Rebecca , Pero Stephanie C. , Perlmutter Patrick , Wilce Matthew C. J. , Wilce Jacqueline A. 
Published: June 2016

AbstractThe design of potent and specific peptide inhibitors to therapeutic targets is of enormous utility for both proof-of-concept studies and for the development of potential new therapeutics. Grb7 is a key signaling molecule in the progression of HER2 positive and triple negative breast cancers. Here we report the crystal structure of a stapled bicyclic peptide inhibitor G7-B1 in complex with the Grb7-SH2 domain. This revealed an unexpected binding mode of the peptide, in which the staple forms an alternative contact with the surface of the target protein. Based on this structural information, we designed a new series of bicyclic G7 peptides that progressively constrain the starting peptide, to arrive at the G7-B4 peptide that binds with an approximately 2-fold enhanced affinity to the Grb7-SH2 domain (KD = 0.83 μM) compared to G7-B1 and shows low affinity binding to Grb2-, Grb10- and Grb14-SH2 domains (KD > 100 μM). Furthermore, we determined the structure of the G7-B4 bicyclic peptide in complex with the Grb7-SH2 domain, both before and after ring closing metathesis to show that the closed staple is essential to the target interaction. The G7-B4 peptide represents an advance in the development of Grb7 inhibitors and is a classical example of structure aided inhibitor development.
The endothelial protein C receptor rs867186-GG genotype is associated with increased soluble EPCR and could mediate protection against severe malaria
Authors: Shabani Estela , Opoka Robert O. , Bangirana Paul , Park Gregory S. , Vercellotti Gregory M. , Guan Weihua , Hodges James S. , Lavstsen Thomas , John Chandy C. 
Published: June 2016

AbstractThe endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium falciparum endothelial cell binding in severe malaria (SM). Despite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies to date have provided conflicting data about the role of EPCR in SM. To better define this role, we performed genotyping for the rs867186-G variant, associated with increased sEPCR levels, and measured sEPCR levels in two prospective studies of Ugandan children designed to understand immunologic and genetic factors associated with neurocognitive deficits in SM including 551 SM children, 71 uncomplicated malaria (UM) and 172 healthy community children (CC). The rs867186-GG genotype was more frequent in CC (4.1%) than SM (0.6%, P = 0.002). The rs867186-G variant was associated with increased sEPCR levels and sEPCR was lower in children with SM than CC (P < 0.001). Among SM children, those who had a second SM episode showed a trend toward lower plasma sEPCR both at initial admission and at 6-month follow-up compared to those without repeated SM (P = 0.06 for both). The study findings support a role for sEPCR in severe malaria pathogenesis and emphasize a distinct role of sEPCR in malaria as compared to other infectious diseases.
Drosophila cells use nanotube-like structures to transfer dsRNA and RNAi machinery between cells
Authors: Karlikow Margot , Goic Bertsy , Mongelli Vanesa , Salles Audrey , Schmitt Christine , Bonne Isabelle , Zurzolo Chiara , Saleh Maria-Carla 
Published: June 2016

AbstractTunnelling nanotubes and cytonemes function as highways for the transport of organelles, cytosolic and membrane-bound molecules and pathogens between cells. During viral infection in the model organism Drosophila melanogaster, a systemic RNAi antiviral response is established presumably through the transport of a silencing signal from one cell to another via an unknown mechanism. Because of their role in cell-cell communication, we investigated whether nanotube-like structures could be a mediator of the silencing signal. Here, we describe for the first time in the context of a viral infection the presence of nanotube-like structures in different Drosophila cell types. These tubules, made of actin and tubulin, were associated with components of the RNAi machinery, including Argonaute 2, double-stranded RNA and CG4572. Moreover, they were more abundant during viral, but not bacterial, infection. Super resolution structured illumination microscopy showed that Argonaute 2 and tubulin reside inside the tubules. We propose that nanotube-like structures are one of the mechanisms by which Argonaute 2, as part of the antiviral RNAi machinery, is transported between infected and non-infected cells to trigger systemic antiviral immunity in Drosophila.
A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for β-catenin
Authors: Gallegos Lisa Leon , Ng Mei Rosa , Sowa Mathew E. , Selfors Laura M. , White Anne , Zervantonakis Ioannis K. , Singh Pragya , Dhakal Sabin , Harper J. Wade , Brugge Joan S. 
Published: June 2016

AbstractCell-cell adhesion is central to morphogenesis and maintenance of epithelial cell state. We previously identified 27 candidate cell-cell adhesion regulatory proteins (CCARPs) whose down-regulation disrupts epithelial cell-cell adhesion during collective migration. Using a protein interaction mapping strategy, we found that 18 CCARPs link to core components of adherens junctions or desmosomes. We further mapped linkages between the CCARPs and other known cell-cell adhesion proteins, including hits from recent screens uncovering novel components of E-cadherin adhesions. Mechanistic studies of one novel CCARP which links to multiple cell-cell adhesion proteins, the phosphatase DUSP23, revealed that it promotes dephosphorylation of β-catenin at Tyr 142 and enhances the interaction between α- and β-catenin. DUSP23 knockdown specifically diminished adhesion to E-cadherin without altering adhesion to fibronectin matrix proteins. Furthermore, DUSP23 knockdown produced “zipper-like” cell-cell adhesions, caused defects in transmission of polarization cues, and reduced coordination during collective migration. Thus, this study identifies multiple novel connections between proteins that regulate cell-cell interactions and provides evidence for a previously unrecognized role for DUSP23 in regulating E-cadherin adherens junctions through promoting the dephosphorylation of β-catenin.
Phase-Transformation-Induced Extra Thermal Expansion Behavior of (SrxBa1–x)TiO3/Cu Composite
Authors: Sheng Jie , Wang Lidong , Li Shouwei , Yin Benke , Liu Xiangli , Fei Wei-Dong 
Published: June 2016

AbstractThe properties of metal matrix composites (MMCs) can be optimized effectively through adjusting the type or the volume fraction of reinforcement. Generally, the coefficient of thermal expansion (CTE) of MMCs can be reduced by increasing the volume fraction of the reinforcement with lower CTE than metal matrix. However, it is great challenge to fabricate low CTE MMCs with low reinforcement volume fraction because of the limitation of reinforcement CTEs. SrxBa1−xTiO3 (SBT) powder presents negative thermal expansion behavior during the phase transformation from tetragonal to cubic phase. Here, we demonstrate that the phase transformation of SBT can be utilized to reduce and design the thermal expansion properties of SBT particle-reinforced Cu (SBT/Cu) composite, and ultralow CTE can be obtained in SBT/Cu composite. The X-ray diffraction analysis on heating indicates that the temperature range of phase transformation is extended greatly, therefore, the low CTE can be achieved within wide temperature range. Landau-Devonshire theory study on the phase transformation behaviors of SBT particles in the composite indicates that thermal mismatch stress significantly affects the Curie temperature of SBT particles and the CTE of the composite. The results given in the present study provide a new approach to design the MMCs with low CTE.
Cryo-thermal therapy elicits potent anti-tumor immunity by inducing extracellular Hsp70-dependent MDSC differentiation
Authors: Zhu Jun , Zhang Yan , Zhang Aili , He Kun , Liu Ping , Xu Lisa X. 
Published: June 2016

AbstractAchieving control of metastatic disease is a long-sought goal in cancer therapy. Treatments that encourage a patient’s own immune system are bringing new hopes in reaching such a goal. In clinic, local hyperthermia and cryoablation have been explored to induce anti-tumor immune responses against tumors. We have also developed a novel therapeutic modality of cryo-thermal treatment by alternating liquid nitrogen (LN2) cooling and radio frequency (RF) heating, and better therapeutic effect was achieved in treating metastatic cancer in animal model. In this study, we investigated the mechanism of systemic immune response elicited by cryo-thermal therapy. In the 4T1 murine mammary carcinoma model, we found that local cryo-thermal therapy resulted in a considerable reduction of distant lung metastases, and improved long-term survival. Moreover, results of tumor re-challenge experiments indicated generation of a strong tumor-specific immune memory after the local treatment of primary tumors. Our further study indicated that cryo-thermal therapy caused an elevated extracellular release of Hsp70. Subsequently, Hsp70 induced differentiation of MDSCs into mature DCs, contributing to the relief of MDSCs-mediated immunosuppression and ultimately the activation of strong anti-tumor immune response. Our findings reveal new insight into the mechanism of robust therapeutic effects of cryo-thermal therapy against metastatic cancers.
Orexin 2 Receptor Antagonism is Sufficient to Promote NREM and REM Sleep from Mouse to Man
Authors: Gotter Anthony L. , Forman Mark S. , Harrell Charles M. , Stevens Joanne , Svetnik Vladimir , Yee Ka Lai , Li Xiaodong , Roecker Anthony J. , Fox Steven V. , Tannenbaum Pamela L. , Garson Susan L. , Lepeleire Inge De , Calder Nicole , Rosen Laura , Struyk Arie , Coleman Paul J. , Herring W. Joseph , Renger John J. , Winrow Christopher J. 
Published: June 2016

AbstractOrexin neuropeptides regulate sleep/wake through orexin receptors (OX1R, OX2R); OX2R is the predominant mediator of arousal promotion. The potential for single OX2R antagonism to effectively promote sleep has yet to be demonstrated in humans. MK-1064 is an OX2R-single antagonist. Preclinically, MK-1064 promotes sleep and increases both rapid eye movement (REM) and non-REM (NREM) sleep in rats at OX2R occupancies higher than the range observed for dual orexin receptor antagonists. Similar to dual antagonists, MK-1064 increases NREM and REM sleep in dogs without inducing cataplexy. Two Phase I studies in healthy human subjects evaluated safety, tolerability, pharmacokinetics and sleep-promoting effects of MK-1064, and demonstrated dose-dependent increases in subjective somnolence (via Karolinska Sleepiness Scale and Visual Analogue Scale measures) and sleep (via polysomnography), including increased REM and NREM sleep. Thus, selective OX2R antagonism is sufficient to promote REM and NREM sleep across species, similarly to that seen with dual orexin receptor antagonism.
The roles of RelA/(p)ppGpp in glucose-starvation induced adaptive response in the zoonotic Streptococcus suis
Authors: Zhang Tengfei , Zhu Jiawen , Wei Shun , Luo Qingping , Li Lu , Li Shengqing , Tucker Alexander , Shao Huabin , Zhou Rui 
Published: June 2016

AbstractThe (p)ppGpp signal molecules play a central role in the stringent response (SR) to adapt to nutrient starvation in bacteria, yet the carbohydrate starvation induced adaptive response and the roles of SR in this response is not well characterized, especially in Gram-positives. Here, two (p)ppGpp synthetases RelA and RelQ are identified in Streptococcus suis, an important emerging zoonotic Gram-positive bacterium, while only RelA is functional under glucose starvation. To characterize the roles of RelA/(p)ppGpp in glucose starvation response in S. suis, the growth curves and transcriptional profiles were compared between the mutant strain ΔrelA [a (p)ppGpp0 strain under glucose starvation] and its parental strain SC-19 [(p)ppGpp+]. The results showed great difference between SC-19 and ΔrelA on adaptive responses when suffering glucose starvation and demonstrated that RelA/(p)ppGpp plays important roles in adaptation to glucose starvation. Besides the classic SR including inhibition of growth and related macromolecular synthesis, the extended adaptive response also includes inhibited glycolysis and carbon catabolite repression (CCR)-mediated carbohydrate-dependent metabolic switches. Collectively, the pheno- and genotypic characterization of the glucose starvation induced adaptive response in S. suis makes a great contribution to understanding better the mechanism of SR.
Resolving Fine-Scale Heterogeneity of Co-seismic Slip and the Relation to Fault Structure
Authors: Milliner C. W. D. , Sammis C. , Allam A. A. , Dolan J. F. , Hollingsworth J. , Leprince S. , Ayoub F. 
Published: June 2016

AbstractFault slip distributions provide important insight into the earthquake process. We analyze high-resolution along-strike co-seismic slip profiles of the 1992 Mw = 7.3 Landers and 1999 Mw = 7.1 Hector Mine earthquakes, finding a spatial correlation between fluctuations of the slip distribution and geometrical fault structure. Using a spectral analysis, we demonstrate that the observed variation of co-seismic slip is neither random nor artificial, but self-affine fractal and rougher for Landers. We show that the wavelength and amplitude of slip variability correlates to the spatial distribution of fault geometrical complexity, explaining why Hector Mine has a smoother slip distribution as it occurred on a geometrically simpler fault system. We propose as a physical explanation that fault complexity induces a heterogeneous stress state that in turn controls co-seismic slip. Our observations detail the fundamental relationship between fault structure and earthquake rupture behavior, allowing for modeling of realistic slip profiles for use in seismic hazard assessment and paleoseismology studies.