bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanically Stretchable and Electrically Insulating Thermal Elastomer Composite by Liquid Alloy Droplet Embedment
Authors: Jeong Seung Hee , Chen Si , Huo Jinxing , Gamstedt Erik Kristofer , Liu Johan , Zhang Shi-Li , Zhang Zhi-Bin , Hjort Klas , Wu Zhigang 
Published: December 2015

AbstractStretchable electronics and soft robotics have shown unsurpassed features, inheriting remarkable functions from stretchable and soft materials. Electrically conductive and mechanically stretchable materials based on composites have been widely studied for stretchable electronics as electrical conductors using various combinations of materials. However, thermally tunable and stretchable materials, which have high potential in soft and stretchable thermal devices as interface or packaging materials, have not been sufficiently studied. Here, a mechanically stretchable and electrically insulating thermal elastomer composite is demonstrated, which can be easily processed for device fabrication. A liquid alloy is embedded as liquid droplet fillers in an elastomer matrix to achieve softness and stretchability. This new elastomer composite is expected useful to enhance thermal response or efficiency of soft and stretchable thermal devices or systems. The thermal elastomer composites demonstrate advantages such as thermal interface and packaging layers with thermal shrink films in transient and steady-state cases and a stretchable temperature sensor.
High glucose environment inhibits cranial neural crest survival by activating excessive autophagy in the chick embryo
Authors: Wang Xiao-Yu , Li Shuai , Wang Guang , Ma Zheng-Lai , Chuai Manli , Cao Liu , Yang Xuesong 
Published: December 2015

AbstractHigh glucose levels induced by maternal diabetes could lead to defects in neural crest development during embryogenesis, but the cellular mechanism is still not understood. In this study, we observed a defect in chick cranial skeleton, especially parietal bone development in the presence of high glucose levels, which is derived from cranial neural crest cells (CNCC). In early chick embryo, we found that inducing high glucose levels could inhibit the development of CNCC, however, cell proliferation was not significantly involved. Nevertheless, apoptotic CNCC increased in the presence of high levels of glucose. In addition, the expression of apoptosis and autophagy relevant genes were elevated by high glucose treatment. Next, the application of beads soaked in either an autophagy stimulator (Tunicamycin) or inhibitor (Hydroxychloroquine) functionally proved that autophagy was involved in regulating the production of CNCC in the presence of high glucose levels. Our observations suggest that the ERK pathway, rather than the mTOR pathway, most likely participates in mediating the autophagy induced by high glucose. Taken together, our observations indicated that exposure to high levels of glucose could inhibit the survival of CNCC by affecting cell apoptosis, which might result from the dysregulation of the autophagic process.
GFP-complementation assay to detect functional CPP and protein delivery into living cells
Authors: Milech Nadia , Longville Brooke AC , Cunningham Paula T , Scobie Marie N , Bogdawa Heique M , Winslow Scott , Anastasas Mark , Connor Theresa , Ong Ferrer , Stone Shane R , Kerfoot Maria , Heinrich Tatjana , Kroeger Karen M , Tan Yew-Foon , Hoffmann Katrin , Thomas Wayne R , Watt Paul M , Hopkins Richard M 
Published: December 2015

AbstractEfficient cargo uptake is essential for cell-penetrating peptide (CPP) therapeutics, which deliver widely diverse cargoes by exploiting natural cell processes to penetrate the cell’s membranes. Yet most current CPP activity assays are hampered by limitations in assessing uptake, including confounding effects of conjugated fluorophores or ligands, indirect read-outs requiring secondary processing and difficulty in discriminating internalization from endosomally trapped cargo. Split-complementation Endosomal Escape (SEE) provides the first direct assay visualizing true cytoplasmic-delivery of proteins at biologically relevant concentrations. The SEE assay has minimal background, is amenable to high-throughput processes and adaptable to different transient and stable cell lines. This split-GFP-based platform can be useful to study transduction mechanisms, cellular imaging and characterizing novel CPPs as pharmaceutical delivery agents in the treatment of disease.
Development of a pneumatically driven active cover lid for multi-well microplates for use in perfusion three-dimensional cell culture
Authors: Huang Song-Bin , Chou Dean , Chang Yu-Han , Li Ke-Cing , Chiu Tzu-Keng , Ventikos Yiannis , Wu Min-Hsien 
Published: December 2015

AbstractBefore microfluidic-based cell culture models can be practically utilized for bioassays, there is a need for a transitional cell culture technique that can improve conventional cell culture models. To address this, a hybrid cell culture system integrating an active cover lid and a multi-well microplate was proposed to achieve perfusion 3-D cell culture. In this system, a microfluidic-based pneumatically-driven liquid transport mechanism was integrated into the active cover lid to realize 6-unit culture medium perfusion. Experimental results revealed that the flow of culture medium could be pneumatically driven in a flow-rate uniform manner. We used the system to successfully perform a perfusion 3-D cell culture of mesenchymal stem cells (MSCs) for up to 16 days. Moreover, we investigated the effects of various cell culture models on the physiology of MSCs. The physiological nature of MSCs can vary with respect to the cell culture model used. Using the perfusion 3-D cell culture format might affect the proliferation and osteogenic differentiation of MSCs. Overall, we have developed a cell culture system that can achieve multi-well microplate-based perfusion 3-D cell culture in an efficient, cost-effective and user-friendly manner. These features could facilitate the widespread application of perfusion cell culture models for cell-based assays.
Characterisation of radioiodinated flavonoid derivatives for SPECT imaging of cerebral prion deposits
Authors: Fuchigami Takeshi , Yamashita Yuki , Kawasaki Masao , Ogawa Ayaka , Haratake Mamoru , Atarashi Ryuichiro , Sano Kazunori , Nakagaki Takehiro , Ubagai Kaori , Ono Masahiro , Yoshida Sakura , Nishida Noriyuki , Nakayama Morio 
Published: December 2015

AbstractPrion diseases are fatal neurodegenerative diseases characterised by deposition of amyloid plaques containing abnormal prion protein aggregates (PrPSc). This study aimed to evaluate the potential of radioiodinated flavonoid derivatives for single photon emission computed tomography (SPECT) imaging of PrPSc. In vitro binding assays using recombinant mouse PrP (rMoPrP) aggregates revealed that the 4-dimethylamino-substituted styrylchromone derivative (SC-NMe2) had higher in vitro binding affinity (Kd = 24.5 nM) and capacity (Bmax = 36.3 pmol/nmol protein) than three other flavonoid derivatives (flavone, chalcone and aurone). Fluorescent imaging using brain sections from mouse-adapted bovine spongiform encephalopathy (mBSE)-infected mice demonstrated that SC-NMe2 clearly labelled PrPSc-positive prion deposits in the mice brain. Two methoxy SC derivatives, SC-OMe and SC-(OMe)2, also showed high binding affinity for rMoPrP aggregates with Ki values of 20.8 and 26.6 nM, respectively. In vitro fluorescence and autoradiography experiments demonstrated high accumulation of [125I]SC-OMe and [125I]SC-(OMe)2 in prion deposit-rich regions of the mBSE-infected mouse brain. SPECT/computed tomography (CT) imaging and ex vivo autoradiography demonstrated that [123I]SC-OMe showed consistent brain distribution with the presence of PrPSc deposits in the mBSE-infected mice brain. In conclusion, [123I]SC-OMe appears a promising SPECT radioligand for monitoring prion deposit levels in the living brain.
MCO Membranes: Enhanced Selectivity in High-Flux Class
Authors: Boschetti-de-Fierro Adriana , Voigt Manuel , Storr Markus , Krause Bernd 
Published: December 2015

AbstractNovel MCO high-flux membranes for hemodialysis have been developed with optimized permeability, allowing for filtration close to that of the natural kidney. A comprehensive in vitro characterization of the membrane properties by dextran filtration is presented. The sieving profile of pristine membranes, as well as that of membranes exposed to blood for 40 minutes, are described. The effective pore size (Stokes-Einstein radius) was estimated from filtration experiments before and after blood exposure and results were compared to hydrodynamic radii of middle and large uremic toxins and essential proteins. The results indicate that the tailored pore sizes of the MCO membranes promote removal of large toxins while ensuring the retention of albumin.
TALENs-mediated gene disruption of FLT3 in leukemia cells: Using genome-editing approach for exploring the molecular basis of gene abnormality
Authors: Wang Jue , Li Tongjuan , Zhou Mi , Hu Zheng , Zhou Xiaoxi , Zhou Shiqiu , Wang Na , Huang Liang , Zhao Lei , Cao Yang , Xiao Min , Ma Ding , Zhou Pengfei , Shang Zhen , Zhou Jianfeng 
Published: December 2015

AbstractNovel analytic tools are needed to elucidate the molecular basis of leukemia-relevant gene mutations in the post-genome era. We generated isogenic leukemia cell clones in which the FLT3 gene was disrupted in a single allele using TALENs. Isogenic clones with mono-allelic disrupted FLT3 were compared to an isogenic wild-type control clone and parental leukemia cells for transcriptional expression, downstream FLT3 signaling and proliferation capacity. The global gene expression profiles of mutant K562 clones and corresponding wild-type controls were compared using RNA-seq. The transcriptional levels and the ligand-dependent autophosphorylation of FLT3 were decreased in the mutant clones. TALENs-mediated FLT3 haplo-insufficiency impaired cell proliferation and colony formation in vitro. These inhibitory effects were maintained in vivo, improving the survival of NOD/SCID mice transplanted with mutant K562 clones. Cluster analysis revealed that the gene expression pattern of isogenic clones was determined by the FLT3 mutant status rather than the deviation among individual isogenic clones. Differentially expressed genes between the mutant and wild-type clones revealed an activation of nonsense-mediated decay pathway in mutant K562 clones as well as an inhibited FLT3 signaling. Our data support that this genome-editing approach is a robust and generally applicable platform to explore the molecular bases of gene mutations.
Influence of habitat quantity, quality and isolation on the distribution and abundance of two epiphytic lichens
Authors: Johansson Per , Ehrlén Johan 
Published: December 2015

SummaryWe assessed the relative importance of habitat quantity, quality and isolation for the distribution and local abundance of two epiphytic lichens,Parmelina tiliacea, which is red‐listed in Sweden, and the commonPleurosticta acetabulum. We predicted that habitat isolation should constrain the distribution of the mainly vegetatively dispersedP. tiliaceamore than the sexually dispersedP. acetabulum.All patches of habitat containing suitable host trees for the study species were mapped from aerial, infra‐red photographs. Presence and abundance of the lichens were recorded for a total of 3237 trees in 94 patches.Patch identity had strong influence on presence of both species on individual trees. Within patches, presence was positively correlated with tree size and was also influenced by tree species.At patch‐level, species presence was positively correlated with tree number and negatively correlated with the proportion of the boundary that bordered coniferous forest and with isolation. Abundance was mostly correlated with tree size or with the number of large trees at tree‐ and patch‐levels, respectively. ForP. acetabulum, within‐patch abundance was also influenced by isolation from other patches.Presence at patch‐level was affected by isolation for both species, but this effect differed between the three isolation measures used. There was no clear evidence that the distribution ofP. tiliaceawas more constrained by isolation than that ofP. acetabulum.Whilst this study emphasizes the importance of habitat quantity for species occupancy and local abundance, it shows that explanations of species occurrence in fragmented landscapes must also involve variables describing habitat quality and spatial configuration. Moreover it illustrates the difficulties in predicting species’ occupancy from general knowledge about their dispersal traits.
CD11b regulates obesity-induced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages
Authors: Zheng Chunxing , Yang Qian , Xu Chunliang , Shou Peishun , Cao Jianchang , Jiang Menghui , Chen Qing , Cao Gang , Han Yanyan , Li Fengying , Cao Wei , Zhang Liying , Zhang Li , Shi Yufang , Wang Ying 
Published: December 2015

SignificanceObesity is associated with long-term low-grade inflammation characterized by the accumulation of adipose tissue macrophages (ATMs). One important molecule that regulates the migration of monocytes/macrophages is CD11b (integrin αM). Here we show an unexpected role of CD11b in modulating the IL-4/STAT6 signaling in macrophages, thereby limiting IL-4/STAT6–mediated proliferation and alternative activation of ATMs. In the absence of CD11b, there is an increase in ATM in situ proliferation and an enhancement of alternatively polarized phenotypes. Importantly, the alternatively activated ATMs attenuate obesity-related insulin resistance in CD11b-deficient mice. These results reveal a previously unidentified physiological function of CD11b, which could be a therapeutic target for insulin resistance.
Effects of DNA replication on mRNA noise
Authors: Peterson Joseph R. , Cole John A. , Fei Jingyi , Ha Taekjip , Luthey-Schulten Zaida A. 
Published: December 2015

Significance
Gene expression noise affects a cell’s biological state and contributes to such phenomena as phenotype switching and cell fate determination. By examining chromosome replication—which is tightly controlled and thus exhibits little noise—we show that variability in mRNA levels across a population is less than previously expected. This noise is due to the transient relaxation of the mRNA from a low- to a high-copy steady state after a gene replication event. Gene location, mRNA degradation rate, and cell doubling time all contribute to observed noise. Our results demonstrate that it is essential to account for gene replication when modelling gene expression or when interpreting experimental results.
Updated Maturity Estimates for Flatfishes (Pleuronectidae) in the Eastern Bering Sea, with Implications for Fisheries Management
Authors: TenBrink Todd T. , Wilderbuer Thomas K. 
Published: December 2015

Abstract
Female Yellowfin Sole Limanda aspera, Alaska Plaice Pleuronectes quadrituberculatus, and Flathead Sole Hippoglossoides elassodon were collected from the eastern Bering Sea during known prespawning, spawning, and postspawning periods in 2012 and 2013, and their ovaries and otoliths were sampled for use in histological analysis to update historical maturity estimates. For fisheries management, new information on maturity at age can lead to possible changes in estimated reproduction potential (measured as female spawning stock biomass [SSB]) and values of fishing mortality reference points. Our analysis indicated that Yellowfin Sole currently mature at an age similar to that estimated in a study conducted 20 years ago. An evaluation of impacts on the stock assessment indicated that updated estimates of Yellowfin Sole SSB were over 7% higher, but the reference points only changed slightly. The first histologically derived maturity estimates for Alaska Plaice were close to the anatomically derived estimates (visual assessments from 1987), resulting in a marginal decrease (5%) in SSB, but changes in reference points were near 10%. Based on the new maturity estimates for Flathead Sole, SSB estimates increased by 7% compared with estimates currently used in the stock assessment, which relied on maturity data collected in 1999 and 2000. The change in Flathead Sole SSB was concomitant with changes of 16–18% in fishing mortality reference points. Our results indicated minimal differences from historical maturity estimates after re-examination, but in some cases those differences led to relatively large changes in the respective reference points, underscoring the reference points' sensitivity to changes in maturity. Incorporation of these new maturity estimates into the stock assessment process provides valuable updated information for fisheries managers. However, a more comprehensive sampling program is needed to investigate the spatial and temporal aspects of reproduction for each species.
Received November 13, 2014; accepted September 3, 2015
JM25-1, a Lidocaine Analog Combining Airway Relaxant and Antiinflammatory Properties
Authors: Serra Magda F. , Neves Josiane S. , Couto Gina C. , Cotias Amanda C. , Pão Camila R. , Olsen Priscilla C. , de Carvalho Katharinne I. Moraes , Anjos-Valotta Edna A. , Faria Robson X. , Costa Jorge C. S. , Cordeiro Renato S. B. , Silva Patricia M. R. , Martins Marco A. 
Published: December 2015

AbstractAbstract
In comparison to lidocaine, JM25-1 was more effective in reducing bronchial smooth muscle constriction, airway hyperreactivity, lung inflammation, and peribronchial fibrosis. These data lend support for further investigation of the therapeutic potential of JM25-1 for the treatment of bronchospasm.

Background
Inhaled lidocaine antagonized bronchospasm in animal models and patients, but adverse effects limited its efficacy. This study evaluated the antibronchospasm potential of the analog JM25-1, exploring in vitro mechanisms and translation to an animal model.

Methods
The effectiveness of JM25-1 was assessed in GH3 cells, rat tracheal rings, mouse lymphocytes, and human eosinophil systems in vitro, assessing changes in Na+ current, contraction, proliferation, and survival, respectively. Lung function and inflammatory changes were studied in ovalbumin-sensitized mice.

Results
The efficacy of JM25-1 was higher than lidocaine in inhibiting carbachol-induced and calcium-induced tracheal contractions (maximum effect inhibition at 1 mM [%]: 67 ± 10 [JM25-1] vs. 41 ± 11 [lidocaine] [P < 0.001] for carbachol; 100 ± 3 [JM25-1] vs. 36 ± 26 [lidocaine] [P < 0.001] for Ca2+; mean ± SD; n = 9 each) but lower in Na+ current (50% inhibitory concentration = 151.5, n = 8 vs. 0.2 mM; n = 5; P < 0.001). JM25-1 also inhibited eosinophil survival (dead cells [%]: 65 ± 6; n = 4; P < 0.001 at 1 mM) and lymphocyte proliferation (cells in phase S + G2 [%]: 94 ± 10; n = 6; P < 0.001) at 0.6 mM. Aerosolized JM25-1 (1%) decreased lung eosinophil numbers from 13.2 ± 2.4 to 1.7 ± 0.7 × 104/μm2 (n = 6; P < 0.001) and neutrophils from 1.9 ± 0.4 to 0.2 ± 0.1 × 104/μm2 (n = 7; P < 0.001). Other parameters, including airway hyperreactivity, cytokines, mucus, and extracellular matrix deposition, were also sensitive to aerosolized JM25-1.

Conclusion
These findings highlight the potential of JM25-1, emphasizing its putative value in drug development for clinical conditions where there is bronchospasm.
Disambiguating Pharmacodynamic Efficacy from Behavior with Neuroimaging
Authors: Wanigasekera Vishvarani , Mezue Melvin , Andersson Jesper , Kong Yazhuo , Tracey Irene 
Published: December 2015

AbstractAbstract
After development of experimental central sensitization, gabapentin reduces the activation of pain-related brain areas as well as functional connectivity between the thalamus and secondary somatosensory cortex, whereas ibuprofen does not when compared with placebo. Functional imaging may be a viable tool for evaluating analgesic efficacy during early stages of drug development.

Background
Attrition rates of new analgesics during drug development are high; poor assay sensitivity with reliance on subjective outcome measures being a crucial factor.

Methods
The authors assessed the utility of functional magnetic resonance imaging with capsaicin-induced central sensitization, a mechanism relevant in neuropathic pain, for obtaining mechanism-based objective outcome measures that can differentiate an effective analgesic (gabapentin) from an ineffective analgesic (ibuprofen) and both from placebo. The authors used a double-blind, randomized phase I study design (N = 24) with single oral doses.

Results
Only gabapentin suppressed the secondary mechanical hyperalgesia–evoked neural response in a region of the brainstem’s descending pain modulatory system (right nucleus cuneiformis) and left (contralateral) posterior insular cortex and secondary somatosensory cortex. Similarly, only gabapentin suppressed the resting-state functional connectivity during central sensitization between the thalamus and secondary somatosensory cortex, which was plasma gabapentin level dependent. A power analysis showed that with 12 data sets, when using neural activity from the left posterior insula and right nucleus cuneiformis, a statistically significant difference between placebo and gabapentin was detected with probability ≥ 0.8. When using subjective pain ratings, this reduced to less than or equal to 0.6.

Conclusions
Functional imaging with central sensitization can be used as a sensitive mechanism–based assay to guide go/no-go decisions on selecting analgesics effective in neuropathic pain in early human drug development. We also show analgesic modulation of neural activity by using resting-state functional connectivity, a less challenging paradigm that is ideally suited for patient studies because it requires no task or pain provocation.