bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of specific chromatin conformation affect ATRA-induced leukemia cell differentiation
Authors: Li Yanjian , He Yi , Liang Zhengyu , Wang Yang , Chen Fengling , Djekidel Mohamed Nadhir , Li Guipeng , Zhang Xu , Xiang Shuqin , Wang Zejun , Gao Juntao , Zhang Michael Q. , Chen Yang 
Published: February 2018

AbstractChromatin conformation plays a key role in regulating gene expression and controlling cell differentiation. However, the whole-genome chromatin conformation changes that occur during leukemia cell differentiation are poorly understood. Here, we characterized the changes in chromatin conformation, histone states, chromatin accessibility, and gene expression using an all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation model. The results showed that the boundaries of topological associated domains (TADs) were stable during differentiation; however, the chromatin conformations within several specific TADs were obviously changed. By combining H3K4me3, H3K27ac, and Hi-C signals, we annotated the differential gene-regulatory chromatin interactions upon ATRA induction. The gains and losses of the gene-regulatory chromatin interactions are significantly correlated with gene expression and chromatin accessibility. Finally, we found that the loss of GATA2 expression and DNA binding are crucial for the differentiation process, and changes in the chromatin structure around the GATA2 regulate its expression upon ATRA induction. This study provided both statistical insights and experimental details regarding the relationship between chromatin conformation changes and transcription regulation during leukemia cell differentiation, and the results suggested that the chromatin conformation is a new type of potential drug target for cancer therapy.
Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II
Authors: Ma Yiqiong , Yang Qian , Zhong Zhentong , Liang Wei , Zhang Lu , Yang Yingjie , Ding Guohua 
Published: February 2018

AbstractOur previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies showed that nephrin was required for cytoskeletal remodeling in glomerular podocytes. But its specific mechanisms remain incompletely understood. As a nonreceptor tyrosine kinase involved in cytoskeletal regulation, c-Abl may be a candidate of signaling proteins interacting with Src homology 2/3 (SH2/SH3) domains of nephrin. Therefore, it is proposed that c-Abl contributes to nephrin-dependent cytoskeletal remodeling of podocytes. Herein, we observed that nephrin-c-Abl colocalization were suppressed in glomeruli of patients with proteinuria. Next, CD16/7-nephrin and c-Abl vectors were constructed to investigate the nephrin-c-Abl signaling pathway in podocyte actin-cytoskeletal remodeling. The disorganized cytoskeleton stimulated by cytochalasin D in COS7 cells was dramatically restored by co-transfection with phosphorylated CD16/7-nephrin and c-Abl full-length constructs. Further, co-immunoprecipitation showed that phosphorylated CD16/7-nephrin interacted with wild-type c-Abl, but not with SH2/SH3-defective c-Abl. These findings suggest that phosphorylated nephrin is able to recruit c-Abl in a SH2/SH3-dependent manner and detached c-Abl from dephosphorylated nephrin contributes to cytoskeletal remodeling in podocytes.
Regenerative potential of tonsil mesenchymal stem cells on surgical cutaneous defect
Authors: Shin Sung-Chan , Seo Yoojin , Park Hee Young , Jung Da-Woon , Shin Tae-Hoon , Son Haejin , Kim Young Keum , Lee Jin-Choon , Sung Eui-Suk , Jang Jeon Yeob , Kim Hyung-Sik , Lee Byung-Joo 
Published: February 2018

AbstractAs tissue engineering and regenerative medicine have evolved recently, stem cell therapy has been investigated in the field of impaired wound healing. Several studies have reported that mesenchymal stem cells derived from various tissues including bone marrow and adipose tissue can exert the regenerative efficacy in the wound healing. Previously, we have demonstrated the isolation and characterization of tonsil-derived mesenchymal stem cells (TMSCs) with excellent proliferative property. In the present study, we aimed to evaluate the regenerative efficacy of TMSCs in the wound healing process. Two distinct cutaneous surgical defects were generated in the dorsum of mice. Each wound was treated with TMSCs or phosphate-buffered saline (PBS), respectively. After sacrifice, the skin and subcutaneous tissues around the surgical defect were harvested and assessed for inflammation, re-epithelialization, dermal regeneration, and granulation tissue formation. The administration of TMSCs into wound beds significantly promoted the repair of surgical defects in mice. Especially, TMSCs efficiently contributed to the attenuation of excessive inflammation in the surgical lesion, as well as the augmentation of epidermal and dermal regeneration. To elucidate the underlying mechanisms, TMSCs were analyzed for their potency in immunomodulatory ability on immune cells, stimulatory effect on the proliferation of keratinocytes, and fibroblasts, as well as the regulation of fibroblast differentiation. TMSCs inhibited the non-specific or T-cell-specific proliferation of peripheral blood mononuclear cells, as well as the M1 polarization of macrophage-like cells. Moreover, TMSCs augmented the proliferation of skin-constituting fibroblasts and keratinocytes while they suppressed the differentiation of fibroblasts into myofibroblasts. Taken together, our findings demonstrate the regenerative potential of TMSCs in wound healing process through the regulation on inflammation, proliferation, and remodeling of various skin cells, implying that TMSCs can be a promising alternative for wound repair.
Dynamics of starvation and recovery predict extinction risk and both Damuth’s law and Cope’s rule
Authors: Yeakel Justin D. , Kempes Christopher P. , Redner Sidney 
Published: February 2018

AbstractThe eco-evolutionary dynamics of species are fundamentally linked to the energetic constraints of their constituent individuals. Of particular importance is the interplay between reproduction and the dynamics of starvation and recovery. To elucidate this interplay, here we introduce a nutritional state-structured model that incorporates two classes of consumers: nutritionally replete, reproducing consumers, and undernourished, nonreproducing consumers. We obtain strong constraints on starvation and recovery rates by deriving allometric scaling relationships and find that population dynamics are typically driven to a steady state. Moreover, these rates fall within a “refuge” in parameter space, where the probability of population extinction is minimized. We also show that our model provides a natural framework to predict steady state population abundances known as Damuth's law, and maximum mammalian body size. By determining the relative stability of an otherwise homogeneous population to a competing population with altered percent body fat, this framework provides a principled mechanism for a selective driver of Cope’s rule.
Nanobody-triggered lockdown of VSRs reveals ligand reloading in the Golgi
Authors: Früholz Simone , Fäßler Florian , Kolukisaoglu Üner , Pimpl Peter 
Published: February 2018

AbstractProtein degradation in lytic compartments is crucial for eukaryotic cells. At the heart of this process, vacuolar sorting receptors (VSRs) bind soluble hydrolases in the secretory pathway and release them into the vacuolar route. Sorting efficiency is suggested to result from receptor recycling. However, how and to where plant VSRs recycle remains controversial. Here we present a nanobody–epitope interaction-based protein labeling and tracking approach to dissect their anterograde and retrograde transport routes in vivo. We simultaneously employ two different nanobody–epitope pairs: one for the location-specific post-translational fluorescence labeling of receptors and the other pair to trigger their compartment-specific lockdown via an endocytosed dual-epitope linker protein. We demonstrate VSR recycling from the TGN/EE, thereby identifying the cis-Golgi as the recycling target and show that recycled VSRs reload ligands. This is evidence that bidirectional VSR-mediated sorting of vacuolar proteins exists and occurs between the Golgi and the TGN/EE.
3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection
Authors: Ortega-Prieto A. M. , Skelton J. K. , Wai S. N. , Large E. , Lussignol M. , Vizcay-Barrena G. , Hughes D. , Fleck R. A. , Thursz M. , Catanese M. T. , Dorner M. 
Published: February 2018

AbstractWith more than 240 million people infected, hepatitis B virus (HBV) is a major health concern. The inability to mimic the complexity of the liver using cell lines and regular primary human hepatocyte (PHH) cultures pose significant limitations for studying host/pathogen interactions. Here, we describe a 3D microfluidic PHH system permissive to HBV infection, which can be maintained for at least 40 days. This system enables the recapitulation of all steps of the HBV life cycle, including the replication of patient-derived HBV and the maintenance of HBV cccDNA. We show that innate immune and cytokine responses following infection with HBV mimic those observed in HBV-infected patients, thus allowing the dissection of pathways important for immune evasion and validation of biomarkers. Additionally, we demonstrate that the co-culture of PHH with other non-parenchymal cells enables the identification of the cellular origin of immune effectors, thus providing a valuable preclinical platform for HBV research.
High enthalpy storage thermoset network with giant stress and energy output in rubbery state
Authors: Fan Jizhou , Li Guoqiang 
Published: February 2018

AbstractLow output in stress and energy in rubbery state has been a bottleneck for wide-spread applications of thermoset shape memory polymers (SMPs). Traditionally, stress or energy storage in thermoset network is through entropy reduction by mechanical deformation or programming. We here report another mechanism for energy storage, which stores energy primarily through enthalpy increase by stretched bonds during programming. As compared to entropy-driven counterparts, which usually have a stable recovery stress from tenths to several MPa and energy output of several tenths MJ/m3, our rubbery network achieved a recovery stress of 17.0 MPa and energy output of 2.12 MJ/m3 in bulk form. The giant stress and energy release in the rubbery state will enhance applications of thermoset SMPs in engineering structures and devices.
Interventions to enhance the adoption of asthma self-management behaviour in the South Asian and African American population: a systematic review
Authors: Ahmed Salina , Steed Liz , Harris Katherine , Taylor Stephanie J. C. , Pinnock Hilary 
Published: February 2018

AbstractSouth Asian and other minority communities suffer poorer asthma outcomes, have a higher rate of unscheduled care and benefit less from most existing self-management interventions when compared to the majority population. Possible reasons for these differences include failure to implement asthma self-management strategies, or that strategies implemented were inappropriate for their needs; alternatively, they may relate to the minority and/or lower socioeconomic status of these populations. We aimed to synthesise evidence from randomised controlled trials for asthma self-management in South Asian and Black populations from different sociocultural contexts, and identify barriers and facilitators to implementing self-management. We systematically searched eight electronic databases, and research registers, and manually searched relevant journals and reference lists of reviews. Seventeen trials met the inclusion criteria and were analysed narratively. We found two culturally targeted interventions compared to fifteen culturally modified interventions. Interventions used diverse self-management strategies; education formed a central component. Interventions in South Asian and African-American minority communities were less effective than interventions delivered in indigenous populations in South Asia, though the latter trials were at higher risk of bias. Education, with continuous professional support, was common to most interventions. Facilitators to asthma self-management included: ensuring culturally/linguistically appropriate education, adapting to learning styles, addressing daily stressors/social support and generic self-management strategies. In conclusion, when developing and evaluating self-management interventions aimed at different cultures, the influence of sociocultural contexts (including whether patients are from a minority or indigenous population) can be important for the conceptualisation of culture and customisation of self-management strategies.
Expression, Purification and Characterization of the Human Cannabinoid 1 Receptor
Authors: Mallipeddi Srikrishnan , Zvonok Nikolai , Makriyannis Alexandros 
Published: February 2018

AbstractThe human cannabinoid 1 receptor (hCB1) is involved in numerous physiological processes and therefore provides a wide scope of potential therapeutic opportunities to treat maladies such as obesity, cardio-metabolic disorders, substance abuse, neuropathic pain, and multiple sclerosis. Structure-based drug design using the current knowledge of the hCB1 receptor binding site is limited and requires purified active protein. Heterologous expression and purification of functional hCB1 has been the bottleneck for ligand binding structural studies using biophysical methods such as mass spectrometry, x-ray crystallography and NMR. We constructed several plasmids for in-cell or in vitro Escherichia coli (E. coli) based expression of truncated and stabilized hCB1 receptor (hΔCB1 and hΔCB1T4L) variants and evaluated their competency to bind the CP-55,940 ligand. MALDI-TOF MS analysis of in vitro expressed and purified hΔCB1T4Lhis6 variants, following trypsin digestion, generated ~80% of the receptor sequence coverage. Our data demonstrate the feasibility of a cell-free expression system as a promising part of the strategy for the elucidation of ligand binding sites of the hCB1 receptor using a “Ligand Assisted Protein Structure” (LAPS) approach.
Being slightly overweight is associated with a better quality of life in breast cancer survivors
Authors: Xia Juan , Tang Zheng , Deng Qinglong , Wang Jiwei , Yu Jinming 
Published: February 2018

AbstractTo examine the association between BMI and QOL in breast cancer survivors in China, we conducted a cross-sectional survey and recruited 10708 breast cancer survivors. Survivors self-reported QOL was measured using the EORTC QLQ-C30 and the QLQ-BR23. The impact of BMI on QOL was examined through standard least squares regression. Normal weight and overweight survivors were more likely to have a better QOL than underweight and obese survivors and the results were similar to survivors diagnosed as having chronic diseases. After adjustment for clinical and sociodemographic factors, the QOL increased with increasing BMI in breast cancer survivors ranged from underweight to overweight with no chronic diseases, especially in the scales of emotional function and fatigue. Obese breast cancer survivors reported a significantly worse QOL compared to normal weight and overweight breast cancer survivors. Within breast cancer survivors with one or more chronic diseases, it was more obvious that overweight ones had a significantly better QOL with clear evidence of a dose relationship across underweight to overweight in almost all scales. Unlike obese breast cancer survivors without chronic diseases, the ones with chronic disease(s) had a similar QOL compared to normal weight breast cancer survivors in all scales except in the domain of fatigue.
Daily circadian misalignment impairs human cognitive performance task-dependently
Authors: Chellappa Sarah L. , Morris Christopher J. , Scheer Frank A. J. L. 
Published: February 2018

AbstractShift work increases the risk for human errors, such that drowsiness due to shift work has contributed to major industrial disasters, including Space Shuttle Challenger, Chernobyl and Alaska Oil Spill disasters, with extraordinary socio-economical costs. Overnight operations pose a challenge because our circadian biology inhibits cognitive performance at night. Yet how the circadian system modulates cognition over multiple days under realistic shift work conditions remains to be established. Importantly, because task-specific cognitive brain regions show different 24-h circadian dynamics, we hypothesize that circadian misalignment impacts cognition task-dependently. Using a biologically-driven paradigm mimicking night shift work, with a randomized, cross-over design, we show that misalignment between the circadian pacemaker and behavioral/environmental cycles increases cognitive vulnerability on sustained attention, cognitive throughput, information processing and visual-motor performance over multiple days, compared to circadian alignment (day shifts). Circadian misalignment effects are task-dependent: while they acutely impair sustained attention with recovery after 3-days, they progressively hinder daily learning. Individuals felt sleepier during circadian misalignment, but they did not rate their performance as worse. Furthermore, circadian misalignment effects on sustained attention depended on prior sleep history. Collectively, daily circadian misalignment may provide an important biological framework for developing countermeasures against adverse cognitive effects in shift workers.
Molecular determinants of Guanylate Cyclase Activating Protein subcellular distribution in photoreceptor cells of the retina
Authors: López-Begines Santiago , Plana-Bonamaisó Anna , Méndez Ana 
Published: February 2018

AbstractRetinal guanylate cyclase (RetGC) and guanylate cyclase activating proteins (GCAPs) play an important role during the light response in photoreceptor cells. Mutations in these proteins are linked to distinct forms of blindness. RetGC and GCAPs exert their role at the ciliary outer segment where phototransduction takes place. We investigated the mechanisms governing GCAP1 and GCAP2 distribution to rod outer segments by expressing selected GCAP1 and GCAP2 mutants as transient transgenes in the rods of GCAP1/2 double knockout mice. We show that precluding GCAP1 direct binding to RetGC (K23D/GCAP1) prevented its distribution to rod outer segments, while preventing GCAP1 activation of RetGC post-binding (W94A/GCAP1) did not. We infer that GCAP1 translocation to the outer segment strongly depends on GCAP1 binding affinity for RetGC, which points to GCAP1 requirement to bind to RetGC to be transported. We gain further insight into the distinctive regulatory steps of GCAP2 distribution, by showing that a phosphomimic at position 201 is sufficient to retain GCAP2 at proximal compartments; and that the bovine equivalent to blindness-causative mutation G157R/GCAP2 results in enhanced phosphorylation in vitro and significant retention at the inner segment in vivo, as likely contributing factors to the pathophysiology.
An allogeneic ‘off the shelf’ therapeutic strategy for peripheral nerve tissue engineering using clinical grade human neural stem cells
Authors: O’Rourke C. , Day A. G. E. , Murray-Dunning C. , Thanabalasundaram L. , Cowan J. , Stevanato L. , Grace N. , Cameron G. , Drake R. A. L. , Sinden J. , Phillips J. B. 
Published: February 2018

AbstractArtificial tissues constructed from therapeutic cells offer a promising approach for improving the treatment of severe peripheral nerve injuries. In this study the effectiveness of using CTX0E03, a conditionally immortalised human neural stem cell line, as a source of allogeneic cells for constructing living artificial nerve repair tissue was tested. CTX0E03 cells were differentiated then combined with collagen to form engineered neural tissue (EngNT-CTX), stable aligned sheets of cellular hydrogel. EngNT-CTX sheets were delivered within collagen tubes to repair a 12 mm sciatic nerve injury model in athymic nude rats. Autologous nerve grafts (autografts) and empty tubes were used for comparison. After 8 weeks functional repair was assessed using electrophysiology. Further, detailed histological and electron microscopic analysis of the repaired nerves was performed. Results indicated that EngNT-CTX supported growth of neurites and vasculature through the injury site and facilitated reinnervation of the target muscle. These findings indicate for the first time that a clinically validated allogeneic neural stem cell line can be used to construct EngNT. This provides a potential ‘off the shelf’ tissue engineering solution for the treatment of nerve injury, overcoming the limitations associated with nerve autografts or the reliance on autologous cells for populating repair constructs.
Softening due to Grain Boundary Cavity Formation and its Competition with Hardening in Helium Implanted Nanocrystalline Tungsten
Authors: Cunningham W. Streit , Gentile Jonathan M. , El-Atwani Osman , Taylor Chase N. , Efe Mert , Maloy Stuart A. , Trelewicz Jason R. 
Published: February 2018

AbstractThe unique ability of grain boundaries to act as effective sinks for radiation damage plays a significant role in nanocrystalline materials due to their large interfacial area per unit volume. Leveraging this mechanism in the design of tungsten as a plasma-facing material provides a potential pathway for enhancing its radiation tolerance under fusion-relevant conditions. In this study, we explore the impact of defect microstructures on the mechanical behavior of helium ion implanted nanocrystalline tungsten through nanoindentation. Softening was apparent across all implantation temperatures and attributed to bubble/cavity loaded grain boundaries suppressing the activation barrier for the onset of plasticity via grain boundary mediated dislocation nucleation. An increase in fluence placed cavity induced grain boundary softening in competition with hardening from intragranular defect loop damage, thus signaling a new transition in the mechanical behavior of helium implanted nanocrystalline tungsten.
Thermally-Conductive and Mechanically-Robust Graphene Nanoplatelet Reinforced UO2 Composite Nuclear Fuels
Authors: Yao Tiankai , Xin Guoqing , Scott Spencer Michael , Gong Bowen , Lian Jie 
Published: February 2018

AbstractLow thermal transport behavior along the radial direction of nuclear fuel pellets and pellet-cladding mechanical interaction significantly impact fuel performance and the safety of current nuclear energy systems. Here we report a new strategy of advanced fuel design in which highly thermally-conductive and mechanically-robust graphene nanoplatelets are incorporated into UO2 fuel matrix to improve fuel thermal-mechanical properties. The 2D geometry of the graphene nanoplatelets enables a unique lamellar structure upon fuel consolidation by spark plasma sintering. The thermal conductivity along the radial direction of the sintered fuel pellets at room temperature reaches 12.7 and 19.1 wm−1K−1 at 1 wt.% and 5 wt.% loadings of the graphene nanoplatelets, respectively, representing at least 74% and 162% enhancements as compared to pure UO2 fuel pellets. Indentation testing suggests great capability of the 2D graphene nanoplatelets to deflect and pin crack propagation, drastically improving the crack propagation resistance of fuel matrix. The estimated indentation fracture toughness reaches 3.5 MPa·m1/2 by 1 wt.% loading of graphene nano-platelets, representing a 150% improvement over 1.4 MPa·m1/2 for pure UO2 fuel pellets. Isothermal annealing of the composite fuel indicates that the graphene nano-platelet is able to retain its structure and properties against reaction with UO2 matrix up to 1150 °C.