bluuebunny/crossref_metadata_2025 huggingface dataset:
Involvement of patients and parents in research undertaken by the Australian and New Zealand Fontan Registry
Authors: d’Udekem Yves , Forsdick Victoria , du Plessis Karin
Published: August 2017

Research that is closely connected with the population it is studying and in which the translational value to healthcare is high is a laudable goal, but it is not often achieved. The Australian and New Zealand Fontan Registry has developed a model for involving patients and parents of children with a Fontan circulation in its research. The model involves consumer participation in the overarching Steering Committee, and has set in place multiple channels of communication allowing the early dissemination of research findings before peer-reviewing, and consumer feedback at all levels of the research. Our focus was not only to provide information but also to give a voice to this community and include them as researchers. These communication channels are a part of a larger network involving the practitioner community, support groups, funding agencies, and health authorities. This close connection with the target research population has multiple benefits: safeguarding the project; controlling and adjusting both the messages conveyed and the investigations; building a community; raising new ideas for research; increasing our research participation rate; increasing the weight of our endeavours; and, above all, increasing our own satisfaction in our research undertakings. In conclusion, the interactions with patients and their families within Australia and New Zealand provide one potential model for the involvement of patients and parents that may result in research that is more relevant, focussed, and practically applicable in a healthcare setting.
Acute toxicity of concomitant boost radiation therapy by volumetric-modulated arc therapy in head and neck cancers
Authors: Perisamy Kannan , Mukherji Ashutosh , Kandasamy Saravanan , Reddy K. Sathyanarayan
Published: August 2017

Introduction

Volumetric-modulated arc therapy (VMAT) is an advanced form of intensity-modulated radiation therapy that reduces treatment time without compromising plan quality. This study assessed acute toxicities in patients having carcinomas of oropharynx, larynx and hypopharynx treated with concomitant boost radiation therapy by VMAT.

Materials and methods

In this study, 30 patients of stages II–IVA disease were treated with concomitant boost radiation therapy using VMAT and those with stages III and IV also received concurrent chemotherapy with cisplatin 100 mg/m2 weekly thrice for two cycles. The total dose was 68·4 Gy/40 fractions/5.5 weeks (1·8 Gy/fraction/day to the large field for 28 fractions +1·5 Gy/fraction/day to boost field for the last 12 days of treatment). Radiation Therapy Oncology Group acute radiation morbidity scoring criteria was used to grade acute effects.

Results

All patients completed scheduled treatment with median duration of 44 days. No grade 4 skin and mucosal toxicities were observed; grade 3 skin and mucosal toxicities seen in six (20%) and eight (26·67%) patients, respectively; grade 3 dysphagia and laryngeal toxicity in eight (26·67%) and three (10%) patients, respectively; two patients had grade 4 laryngeal toxicity. No grade 3 or grade 4 haematological toxicities were seen.

Conclusion

VMAT-based concomitant boost radiation therapy allows for dose escalation with good patient tolerance by limiting acute toxicities.
Genetic variability in Indian populations of banana corm weevil [Cosmopolites sordidus (Coleoptera: Curculionidae)] assessed by RAPDs and AFLPs
Authors: Yadav Sweta Kumari U. , Singh Jyotsna , Padmanaban B. , Kumar Lalitha Sunil
Published: August 2017

Cosmopolites sordidus(Germar), commonly known as banana corm weevil, is an important economic pest in Asia that can cause severe yield loss depending upon the stage at which infestation occurs. In spite of its economic importance, little is known about the population structure of this pest in India. Random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP) were used to characterize the population genetic structure ofC. sordiduscollected from five hot spot locations in India. Nineteen RAPD primers and five selective AFLP primer combinations generated 147 and 304 amplification products, respectively. UPGMA dendrograms generated with both marker systems failed to reveal populations clustered based on geographic distance, which was confirmed by the Mantel test, which did not show a strong correlation between genetic distance and geographic distance. Values of indices of genetic identity showed that the populations were closely related. Though the gene flow estimate (Nm) between the populations was 0.469, suggesting restricted gene flow, the populations are not genetically distinct. These observations suggest that the range expansion of this banana pest in India has taken place through transport of infested corms and plant material, resulting in genetically close populations that are geographically distinct. These results provide important information on the population structure of this pest in India, which will aid in designing suitable strategies for its control and management, especially with respect to insecticide resistance.
Satellite Observations Could Help Forecast an Eruption’s End
Authors: Loomis Ilima
Published: August 2017

Researchers studying past volcanic activity found they could retrospectively predict when outflows of molten rock would cease for about 40% of effusive eruptions, the kind that produces flowing lava.
The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage
Authors: Yoo Seung-Jun , Cho Bongki , Lee Deokho , Son Gowoon , Lee Yeong-Bae , Soo Han Hyung , Kim Eunjoo , Moon Chanil , Moon Cheil
Published: August 2017

Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite the neuroprotective effect of EPO, clinical trials have shown its unexpected side effects, including undesirable proliferative effects such as erythropoiesis and tumor growth. Therefore, the development of EPO analogs that would confer neuroprotection without adverse effects has been attempted. In this study, we examined the potential of a novel EPO-based short peptide, MK-X, as a novel drug for stroke treatment in comparison with EPO. We found that MK-X administration with reperfusion dramatically reduced brain injury in an in vivo mouse model of ischemic stroke induced by middle cerebral artery occlusion, whereas EPO had little effect. Similar to EPO, MK-X efficiently ameliorated mitochondrial dysfunction followed by neuronal death caused by glutamate-induced oxidative stress in cultured neurons. Consistent with this effect, MK-X significantly decreased caspase-3 cleavage and nuclear translocation of apoptosis-inducing factor induced by glutamate. MK-X completely mimicked the effect of EPO on multiple activation of JAK2 and its downstream PI3K/AKT and ERK1/2 signaling pathways, and this signaling process was involved in the neuroprotective effect of MK-X. Furthermore, MK-X and EPO induced similar changes in the gene expression patterns under glutamate-induced excitotoxicity. Interestingly, the most significant difference between MK-X and EPO was that MK-X better penetrated into the brain across the brain–blood barrier than did EPO. In conclusion, we suggest that MK-X might be used as a novel drug for protection from brain injury caused by ischemic stroke, which penetrates into the brain faster in comparison with EPO, even though MK-X and EPO have similar protective effects against excitotoxicity.
Smac mimetics and oncolytic viruses synergize in driving anticancer T-cell responses through complementary mechanisms
Authors: Kim Dae-Sun , Dastidar Himika , Zhang Chunfen , Zemp Franz J. , Lau Keith , Ernst Matthias , Rakic Andrea , Sikdar Saif , Rajwani Jahanara , Naumenko Victor , Balce Dale R. , Ewanchuk Ben W. , Tailor Pankaj , Yates Robin M. , Jenne Craig , Gafuik Chris , Mahoney Douglas J.
Published: August 2017

Second mitochondrial activator of caspase (Smac)-mimetic compounds and oncolytic viruses were developed to kill cancer cells directly. However, Smac-mimetic compound and oncolytic virus therapies also modulate host immune responses in ways we hypothesized would complement one another in promoting anticancer T-cell immunity. We show that Smac-mimetic compound and oncolytic virus therapies synergize in driving CD8+ T-cell responses toward tumors through distinct activities. Smac-mimetic compound treatment with LCL161 reinvigorates exhausted CD8+ T cells within immunosuppressed tumors by targeting tumor-associated macrophages for M1-like polarization. Oncolytic virus treatment with vesicular stomatitis virus (VSVΔM51) promotes CD8+ T-cell accumulation within tumors and CD8+ T-cell activation within the tumor-draining lymph node. When combined, LCL161 and VSVΔM51 therapy engenders CD8+ T-cell-mediated tumor control in several aggressive mouse models of cancer. Smac-mimetic compound and oncolytic virus therapies are both in clinical development and their combination therapy represents a promising approach for promoting anticancer T-cell immunity.
Fast kinetics of magnesium monochloride cations in interlayer-expanded titanium disulfide for magnesium rechargeable batteries
Authors: Yoo Hyun Deog , Liang Yanliang , Dong Hui , Lin Junhao , Wang Hua , Liu Yisheng , Ma Lu , Wu Tianpin , Li Yifei , Ru Qiang , Jing Yan , An Qinyou , Zhou Wu , Guo Jinghua , Lu Jun , Pantelides Sokrates T. , Qian Xiaofeng , Yao Yan
Published: August 2017

Magnesium rechargeable batteries potentially offer high-energy density, safety, and low cost due to the ability to employ divalent, dendrite-free, and earth-abundant magnesium metal anode. Despite recent progress, further development remains stagnated mainly due to the sluggish scission of magnesium-chloride bond and slow diffusion of divalent magnesium cations in cathodes. Here we report a battery chemistry that utilizes magnesium monochloride cations in expanded titanium disulfide. Combined theoretical modeling, spectroscopic analysis, and electrochemical study reveal fast diffusion kinetics of magnesium monochloride cations without scission of magnesium-chloride bond. The battery demonstrates the reversible intercalation of 1 and 1.7 magnesium monochloride cations per titanium at 25 and 60 °C, respectively, corresponding to up to 400 mAh g−1 capacity based on the mass of titanium disulfide. The large capacity accompanies with excellent rate and cycling performances even at room temperature, opening up possibilities for a variety of effective intercalation hosts for multivalent-ion batteries.
Nanodiamonds suppress the growth of lithium dendrites
Authors: Cheng Xin-Bing , Zhao Meng-Qiang , Chen Chi , Pentecost Amanda , Maleski Kathleen , Mathis Tyler , Zhang Xue-Qiang , Zhang Qiang , Jiang Jianjun , Gogotsi Yury
Published: August 2017

Lithium metal has been regarded as the future anode material for high-energy-density rechargeable batteries due to its favorable combination of negative electrochemical potential and high theoretical capacity. However, uncontrolled lithium deposition during lithium plating/stripping results in low Coulombic efficiency and severe safety hazards. Herein, we report that nanodiamonds work as an electrolyte additive to co-deposit with lithium ions and produce dendrite-free lithium deposits. First-principles calculations indicate that lithium prefers to adsorb onto nanodiamond surfaces with a low diffusion energy barrier, leading to uniformly deposited lithium arrays. The uniform lithium deposition morphology renders enhanced electrochemical cycling performance. The nanodiamond-modified electrolyte can lead to a stable cycling of lithium | lithium symmetrical cells up to 150 and 200 h at 2.0 and 1.0 mA cm–2, respectively. The nanodiamond co-deposition can significantly alter the lithium plating behavior, affording a promising route to suppress lithium dendrite growth in lithium metal-based batteries.
Comparative Transcriptome Analysis Identified Candidate Genes Related to Bailinggu Mushroom Formation and Genetic Markers for Genetic Analyses and Breeding
Authors: Fu Yongping , Dai Yueting , Yang Chentao , Wei Peng , Song Bing , Yang Yang , Sun Lei , Zhang Zhi-Wu , Li Yu
Published: August 2017

Bailinggu (Pleurotus tuoliensis) is a major, commercially cultivated mushroom and widely used for nutritional, medicinal, and industrial applications. Yet, the mushroom’s genetic architecture and the molecular mechanisms underlying its formation are largely unknown. Here we performed comparative transcriptomic analysis during Bailinggu’s mycelia, primordia, and fruiting body stages to identify genes regulating fruiting body development and develop EST-SSR markers assessing the genetic value of breeding materials. The stage-specific and differentially expressed unigenes (DEGs) involved in morphogenesis, primary carbohydrate metabolism, cold stimulation and blue-light response were identified using GO and KEGG databases. These unigenes might help Bailinggu adapt to genetic and environmental factors that influence fructification. The most pronounced change in gene expression occurred during the vegetative-to-reproductive transition, suggesting that is most active and key for Bailinggu development. We then developed 26 polymorphic and informative EST-SSR markers to assess the genetic diversity in 82 strains of Bailinggu breeding materials. These EST-SSRs exhibited high transferability in closely related species P. eryngii var. ferulae and var. eryngii. Genetic population structure analysis indicated that China’s Bailinggu has low introgression with these two varieties and likely evolved independently. These findings provide new genes, SSR markers, and germplasm to enhance the breeding of commercially cultivated Bailinggu.
Neuroprotective Effects of CGP3466B on Apoptosis Are Modulated by Protein-L-isoaspartate (D-aspartate) O-methyltransferase/Mst1 Pathways after Traumatic Brain Injury in Rats
Authors: Liang Feng , Shi Ligen , Zheng Jingwei , Chen Sheng , Wang Yangxin , Zhang Jianmin
Published: August 2017

Neuronal apoptosis chiefly contributes to the cell loss following traumatic brain injury (TBI). CGP3466B is a compound related to the anti-Parkinsonism drug R-(−)-deprenyl. Previous studies have illuminated anti-apoptosis effects of CGP3466B in different cell lines, but the underlying mechanisms have not been fully elucidated. Mammalian sterile 20 (STE20)-like kinase1 (Mst1) is a core component of the Hippo signaling pathway. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is an enzyme that repairs damaged L-isoaspartyl residues in proteins. The present study was performed to investigate the neuroprotective effects of CGP3466B and to determine a potential PCMT1/Mst1 neuronal anti-apoptotic pathway after TBI. Double immunofluorescence staining demonstrated that PCMT1 and Mst1 are co-located in neurons. Administration of CGP3466B improved neurological function, downregulated the ROS level and alleviated brain edema at 24 h after TBI. CGP3466B alleviates neuronal apoptosis by increasing PCMT1 expression and subsequently inhibiting MST1 activation, resulting in changing the expression levels of Bax, Bcl-2 and active-caspase3. The TUNEL staining results also support the anti-apoptosis effects of CGP3466B. The anti-apoptotic effects of CGP3466B were abolished by chelerythrine, an Mst1 activator, without changing PCMT1 levels. In conclusion, our findings suggest CGP3466B may have a promising therapeutic potential by modulating PCMT1/Mst1 signaling pathway after TBI injury.
Dietary Fat Intake Modulates Effects of a Frequent ACE Gene Variant on Glucose Tolerance with association to Type 2 Diabetes
Authors: Schüler Rita , Osterhoff Martin A. , Frahnow Turid , Möhlig Matthias , Spranger Joachim , Stefanovski Darko , Bergman Richard N. , Xu Li , Seltmann Anne-Cathrin , Kabisch Stefan , Hornemann Silke , Kruse Michael , Pfeiffer Andreas F. H.
Published: August 2017

The frequent ACE insertion/deletion polymorphism (I/D) is, albeit inconsistently, associated with impaired glucose tolerance and insulin resistance. We recently observed an enhanced upregulation of ACE by elevated fat intake in GG-carriers of the I/D-surrogate rs4343 variant and therefore investigated its potential nutrigenetic role in glucose metabolism. In this nutritional intervention study 46 healthy and non-obese twin pairs consumed recommended low fat diets for 6 weeks before they received a 6-week high fat (HF) diet under isocaloric conditions. Intravenous glucose tolerance tests were performed before and after 1 and 6 weeks of HF diet. While glucose tolerance did not differ between genotypes at baseline it significantly declined in GG-carriers after 6 weeks HF diet (p = 0.001) with higher 2 h glucose and insulin concentrations compared to AA/AG-carriers (p = 0.003 and p = 0.042). Furthermore, the gene-diet interaction was confirmed in the cross-sectional Metabolic Syndrome Berlin Potsdam study (p = 0.012), with the GG-genotypes being significantly associated with prevalent type 2 diabetes for participants with high dietary fat intake ≥37% (GG vs. AA/AG, OR 2.36 [1.02–5.49], p = 0.045). In conclusion, the association between the rs4343 variant and glucose tolerance is modulated by dietary fat intake. The ACE rs4343 variant is a novel nutrient-sensitive type 2 diabetes risk marker potentially applicable for nutrigenetic dietary counseling.
The zero effect: voxel-based lesion symptom mapping of number transcoding errors following stroke
Authors: Haupt Marleen , Gillebert Céline R. , Demeyere Nele
Published: August 2017

Zero represents a special case in our numerical system because it is not represented on a semantic level. Former research has shown that this can lead to specific impairments when transcoding numerals from dictation to written digits. Even though, number processing is considered to be dominated by the left hemisphere, studies have indicated that both left as well as right hemispheric stroke patients commit errors when transcoding numerals including zeros. Here, for the first time, a large sample of subacute stroke patients (N = 667) was assessed without being preselected based on the location of their lesion, or a specific impairment in transcoding zero. The results show that specific errors in transcoding zeros were common (prevalence = 14.2%) and a voxel-based lesion symptom mapping analysis (n = 153) revealed these to be related to lesions in and around the right putamen. In line with former research, the present study argues that the widespread brain network for number processing also includes subcortical regions, like the putamen with connections to the insular cortex. These play a crucial role in auditory perception as well as attention. If these areas are lesioned, number processing tasks with higher attentional and working memory loads, like transcoding zeros, can be impaired.
The small GTPase, nucleolar GTP-binding protein 1 (NOG1), has a novel role in plant innate immunity
Authors: Lee Seonghee , Senthil-Kumar Muthappa , Kang Miyoung , Rojas Clemencia M. , Tang Yuhong , Oh Sunhee , Choudhury Swarup Roy , Lee Hee-Kyung , Ishiga Yasuhiro , Allen Randy D. , Pandey Sona , Mysore Kirankumar S.
Published: August 2017

Plant defense responses at stomata and apoplast are the most important early events during plant-bacteria interactions. The key components for the signaling of stomatal defense and nonhost resistance have not been fully characterized. Here we report the newly identified small GTPase, Nucleolar GTP-binding protein 1 (NOG1), functions for plant immunity against bacterial pathogens. Virus-induced gene silencing of NOG1 compromised nonhost resistance in N. benthamiana and tomato. Comparative genomic analysis showed that two NOG1 copies are present in all known plant species: NOG1-1 and NOG1-2. Gene downregulation and overexpression studies of NOG1-1 and NOG1-2 in Arabidopsis revealed the novel function of these genes in nonhost resistance and stomatal defense against bacterial pathogens, respectively. Specially, NOG1-2 regulates guard cell signaling in response to biotic and abiotic stimuli through jasmonic acid (JA)- and abscisic acid (ABA)-mediated pathways. The results here provide valuable information on the new functional role of small GTPase, NOG1, in guard cell signaling and early plant defense in response to bacterial pathogens.
Association between taste receptor (TAS) genes and the perception of wine characteristics
Authors: Carrai Maura , Campa Daniele , Vodicka Pavel , Flamini Riccardo , Martelli Irene , Slyskova Jana , Jiraskova Katerina , Rejhova Alexandra , Vodenkova Sona , Canzian Federico , Bertelli Alberto , Dalla Vedova Antonio , Bavaresco Luigi , Vodickova Ludmila , Barale Roberto
Published: August 2017

Several studies have suggested a possible relationship between polymorphic variants of the taste receptors genes and the acceptance, liking and intake of food and beverages. In the last decade investigators have attempted to link the individual ability to taste 6-n-propylthiouracil (PROP) and the sensations, such as astringency and bitterness, elicited by wine or its components, but with contradictory results. We have used the genotype instead of the phenotype (responsiveness to PROP or other tastants), to test the possible relation between genetic variability and the perception of wine characteristic in 528 subjects from Italy and the Czech Republic. We observed several interesting associations, among which the association between several TAS2R38 gene single nucleotide polymorphisms (P = 0.002) and the TAS2R16-rs6466849 polymorphism with wine sourness P = 0.0003). These associations were consistent in both populations, even though the country of origin was an important factor in the two models, thus indicating therefore that genetics alongside cultural factors also play a significant role in the individual liking of wine.
Litter chemistry explains contrasting feeding preferences of bacteria, fungi, and higher plants
Authors: Bonanomi Giuliano , Cesarano Gaspare , Lombardi Nadia , Motti Riccardo , Scala Felice , Mazzoleni Stefano , Incerti Guido
Published: August 2017

Litter decomposition provides a continuous flow of organic carbon and nutrients that affects plant development and the structure of decomposer communities. Aim of this study was to distinguish the feeding preferences of microbes and plants in relation to litter chemistry. We characterized 36 litter types by13C-CPMAS NMR spectroscopy and tested these materials on 6 bacteria, 6 fungi, and 14 target plants. Undecomposed litter acted as a carbon source for most of the saprophytic microbes, although with a large variability across litter types, severely inhibiting root growth. An opposite response was found for aged litter that largely inhibited microbial growth, but had neutral or stimulatory effects on root proliferation.13C-CPMAS NMR revealed that restricted resonance intervals within the alkyl C, methoxyl C,O-alkyl C and di-O-alkyl C spectral regions are crucial for understanding litter effects. Root growth, in contrast to microbes, was negatively affected by labile C sources but positively associated with signals related to plant tissue lignification. Our study showed that plant litter has specific and contrasting effects on bacteria, fungi and higher plants, highlighting that, in order to understand the effects of plant detritus on ecosystem structure and functionality, different microbial food web components should be simultaneously investigated.
Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection
Authors: Ali Mudassar , Pandey Rajan Kumar , Khatoon Nazia , Narula Aruna , Mishra Amit , Prajapati Vijay Kumar
Published: August 2017

Dengue is considered as a major health issue which causes a number of deaths worldwide each year; tropical countries are majorly affected by dengue outbreaks. It is considered as life threatening issue because, since many decades not a single effective approach for treatment and prevention of dengue has been developed. Therefore, to find new preventive measure, we used immunoinformatics approaches to develop a multi-epitope based subunit vaccine for dengue which can generate various immune responses inside the host. Different B-cell, TC cell, and TH cell binding epitopes were predicted for structural and non-structural proteins of dengue virus. Final vaccine constructs consisting of TC and TH cell epitopes and an adjuvant (β-defensin) at N-terminal of the construct. Presence of B-cell and IFN-γ inducing epitopes confirms the humoral and cell mediated immune response developed by designed vaccine. Designed vaccine was not found allergic and was potentially antigenic in nature. Modeling of tertiary structure and the refined model was used for molecular docking with TLR-3 (immune receptor). Molecular docking and dynamics simulation confirms the microscopic interactions between ligand and receptor. In silico cloning approach was used to ensure the expression and translation efficiency of vaccine within an expression vector.
BioFlow: a non-invasive, image-based method to measure speed, pressure and forces inside living cells
Authors: Boquet-Pujadas Aleix , Lecomte Timothée , Manich Maria , Thibeaux Roman , Labruyère Elisabeth , Guillén Nancy , Olivo-Marin Jean-Christophe , Dufour Alexandre C.
Published: August 2017

Cell motility is governed by a complex molecular machinery that converts physico-chemical cues into whole-cell movement. Understanding the underlying biophysical mechanisms requires the ability to measure physical quantities inside the cell in a simple, reproducible and preferably non-invasive manner. To this end, we developed BioFlow, a computational mechano-imaging method and associated software able to extract intracellular measurements including pressure, forces and velocity everywhere inside freely moving cells in two and three dimensions with high spatial resolution in a non-invasive manner. This is achieved by extracting the motion of intracellular material observed using fluorescence microscopy, while simultaneously inferring the parameters of a given theoretical model of the cell interior. We illustrate the power of BioFlow in the context of amoeboid cell migration, by modelling the intracellular actin bulk flow of the parasite Entamoeba histolytica using fluid dynamics, and report unique experimental measures that complement and extend both theoretical estimations and invasive experimental measures. Thanks to its flexibility, BioFlow is easily adaptable to other theoretical models of the cell, and alleviates the need for complex or invasive experimental conditions, thus constituting a powerful tool-kit for mechano-biology studies. BioFlow is open-source and freely available via the Icy software.
Amoeboid-mesenchymal migration plasticity promotes invasion only in complex heterogeneous microenvironments
Authors: Talkenberger Katrin , Cavalcanti-Adam Elisabetta Ada , Voss-Böhme Anja , Deutsch Andreas
Published: August 2017

During tissue invasion individual tumor cells exhibit two interconvertible migration modes, namely mesenchymal and amoeboid migration. The cellular microenvironment triggers the switch between both modes, thereby allowing adaptation to dynamic conditions. It is, however, unclear if this amoeboid-mesenchymal migration plasticity contributes to a more effective tumor invasion. We address this question with a mathematical model, where the amoeboid-mesenchymal migration plasticity is regulated in response to local extracellular matrix resistance. Our numerical analysis reveals that extracellular matrix structure and presence of a chemotactic gradient are key determinants of the model behavior. Only in complex microenvironments, if the extracellular matrix is highly heterogeneous and a chemotactic gradient directs migration, the amoeboid-mesenchymal migration plasticity allows a more widespread invasion compared to the non-switching amoeboid and mesenchymal modes. Importantly, these specific conditions are characteristic for in vivo tumor invasion. Thus, our study suggests that in vitro systems aiming at unraveling the underlying molecular mechanisms of tumor invasion should take into account the complexity of the microenvironment by considering the combined effects of structural heterogeneities and chemical gradients on cell migration.
Dynamic reverse phase transformation induced high-strain-rate superplasticity in low carbon low alloy steels with commercial potential
Authors: Cao Wenquan , Huang Chongxiang , Wang Chang , Dong Han , Weng Yuqing
Published: August 2017

Superplastic materials are capable of exhibiting large tensile elongation at elevated temperature, which is of great industrial significance because it forms the basis of a fabrication method to produce complex shapes. Superplasticity with elongation larger than 500% has been widely realized in many metals and alloys, but seldomly been succeeded in low carbon low alloy steel, even though it is commercially applied in the largest quantity. Here we report ultrahigh superplastic elongation of 900–1200% in the FeMnAl low carbon steels at high strain rate of 10−2–10−3 s−1. Such high-strain-rate superplasticity was attributed to dynamic austenite reverse phase transformation from a heavily cold rolled ferrite to fine-grained ferrite/austenite duplex microstructure and subsequent limited dynamic grain coarsening, under which a large fraction of high angle boundaries can be resulted for superplastic deformation. It is believed that this finding of the low carbon low alloy steel with ultrahigh superplasticity and relative low cost would remarkably promote the application of superplastic forming technique in automobile, aeronautical, astronautical and other fields.
Aspirin metabolite sodium salicylate selectively inhibits transcriptional activity of ATF6α and downstream target genes
Authors: Mügge Fernanda L. B. , Silva Aristóbolo M.
Published: August 2017

In response to ER stress, activating transcription factor 6 (ATF6) traffics from ER to Golgi apparatus where it is activated by cleavage before being translocated as transcription factor to the cell nucleus. In this work we describe ATF6α as a newly target of the aspirin metabolite sodium salicylate (NaSal). NaSal treatment of cells induces increases in ATF6α mRNA and protein levels, but these events are not accompanied by ATF6 activation. Conversely, NaSal inhibited ATF6 transactivating activity elicited by various ER stress-inducing stimuli in different cell types. This resulted in reduced expression of a subset of ATF6α target genes. Mechanistically, exposure of cells to NaSal results in ATF6α trapping at the Golgi apparatus, thus preventing nuclear translocation. This study provides evidence that NaSal compound restrains the activity of ATF6α, thereby preventing activation of a specific subset of ER-stress responsive genes implicated in different cellular responses.
Hypoxia imaging in cells and tumor tissues using a highly selective fluorescent nitroreductase probe
Authors: Yang Dan , Tian Hang Yu , Zang Tie Nan , Li Ming , Zhou Ying , Zhang Jun Feng
Published: August 2017

Hypoxia is a characteristic of locally advanced solid tumors, resulting from an imbalance between oxygen consumption and supply. In hypoxic solid tumors, an increased expression of nitroreductase (NTR) is detected, therefore, the development of NTR-targeted fluorescent probes to selectively and efficiently detect hypoxia in vivo is of utmost importance. In this study, a probe (1) has been designed and tested for effective optical detection of NTR in vitro and in vivo. The reduction of probe (1), catalyzed by NTR, resulted in changes of the electron-withdrawn nitrogen group into an electron-donation amino group. In addition, breakage of the O-C bond ensured selective fluorescence enhancement. The in vitro response towards exogenous NTR, from rat liver microsomes, resulted in the optical enhancement during the detection process. In vivo imaging of caerorhabditis elegans (C.elegan) further confirmed the detection of NTR by probe (1). Moreover, probe (1) was successfully used for the detection of hypoxia in both HI5 cells, and a murine tumor model, which demonstrates the potential of probe (1) for application in fluorescence bioimaging studies, and tumor hypoxia diagnosis.
Effect of Crystal Orientation on Femtosecond Laser-Induced Thermomechanical Responses and Spallation Behaviors of Copper Films
Authors: Xiong Qi-lin , Li Zhenhuan , Kitamura Takayuki
Published: August 2017

Ultrafast thermomechanical responses and spallation behaviours of monocrystal copper films irradiated by femtosecond laser pulse are investigated using molecular dynamics simulation (MDS). Films with 〈100〉, 〈110〉 and 〈111〉 crystal orientations along the thickness direction were studied. The results show that the crystal orientation has a significant effect on femtosecond laser-induced thermomechanical responses and spallation behaviors of monocrystal copper films. The discrepancy between normal stresses in copper films with different crystal orientation leads to distinct differences in lattice temperature. Moreover, the copper films with different crystal orientations present distinct spallation behaviors, including structural melting (atomic splashing) and fracture. The melting depth of 〈100〉 copper film is lower than that of 〈110〉 and 〈111〉 copper films for the same laser intensity. The dislocations and slip bands are formed and propagate from the solid-liquid interface of 〈110〉 and 〈111〉 copper films, while these phenomena do not appear in 〈100〉 copper film. Additionally, numerous slip bands are generated in the non-irradiated surface region of copper films due to reflection of mechanical stress. These slip bands can finally evolve into cracks (nanovoids) with time, which further result in the fracture of the entire films.
Coherent Raman Imaging of Live Muscle Sarcomeres Assisted by SFG Microscopy
Authors: Kim Hyunmin , Kim Do-Young , Joo Kyung-Il , Kim Jung-Hye , Jeong Soon Moon , Lee Eun Seong , Hahm Jeong-Hoon , Kim Kyuhyung , Moon Dae Woon
Published: August 2017

In this study, we used spectrally focused coherent anti-Stokes Raman scattering (spCARS) microscopy assisted by sum-frequency generation (SFG) to monitor the variations in the structural morphology and molecular vibrations of a live muscle of Caenorhabditis elegans. The subunits of the muscle sarcomeres, such as the M-line, myosin, dense body, and α-actinin, were alternatively observed using spCARS microscopy for different sample orientations, with the guidance of a myosin positional marker captured by SFG microscopy. Interestingly enough, the beam polarization dependence of the spCARS contrasts for two parallel subunits (dense body and myosin) showed a ~90° phase difference. The chemically sensitive spCARS spectra induced by the time-varying overlap of two pulses allowed (after a robust subtraction of the non-resonant background using a modified Kramers–Krönig transformation method) high-fidelity detection of various genetically modified muscle sarcomeres tuned to the C-H vibration (2800–3100 cm−1). Conversely, SFG image mapping assisted by phase-retrieved spCARS spectra also facilitated label-free monitoring of the changes in the muscle content of C. elegans that are associated with aging, based on the hypothesis that the C-H vibrational modes could serve as qualitative chemical markers sensitive to the amount and/or structural modulation of the muscle.
A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration
Authors: Yamashiro Kenji , Mori Keisuke , Honda Shigeru , Kano Mariko , Yanagi Yasuo , Obana Akira , Sakurada Yoichi , Sato Taku , Nagai Yoshimi , Hikichi Taiichi , Kataoka Yasushi , Hara Chikako , Koyama Yasurou , Koizumi Hideki , Yoshikawa Munemitsu , Miyake Masahiro , Nakata Isao , Tsuchihashi Takashi , Horie-Inoue Kuniko , Matsumiya Wataru , Ogasawara Masashi , Obata Ryo , Yoneyama Seigo , Matsumoto Hidetaka , Ohnaka Masayuki , Kitamei Hirokuni , Sayanagi Kaori , Ooto Sotaro , Tamura Hiroshi , Oishi Akio , Kabasawa Sho , Ueyama Kazuhiro , Miki Akiko , Kondo Naoshi , Bessho Hiroaki , Saito Masaaki , Takahashi Hidenori , Tan Xue , Azuma Keiko , Kikushima Wataru , Mukai Ryo , Ohira Akihiro , Gomi Fumi , Miyata Kazunori , Takahashi Kanji , Kishi Shoji , Iijima Hiroyuki , Sekiryu Tetsuju , Iida Tomohiro , Awata Takuya , Inoue Satoshi , Yamada Ryo , Matsuda Fumihiko , Tsujikawa Akitaka , Negi Akira , Yoneya Shin , Iwata Takeshi , Yoshimura Nagahisa
Published: August 2017

We conducted a genome-wide association study (GWAS) on the outcome of anti-VEGF treatment for exudative age-related macular degeneration (AMD) in a prospective cohort. Four hundred and sixty-one treatment-naïve AMD patients were recruited at 13 clinical centers and all patients were treated with 3 monthly injections of ranibizumab followed by pro re nata regimen treatment for one year. Genomic DNA was collected from all patients for a 2-stage GWAS on achieving dry macula after the initial treatment, the requirement for an additional treatment, and visual acuity changes during the 12-month observation period. In addition, we evaluated 9 single-nucleotide polymorphisms (SNPs) in 8 previously reported AMD-related genes for their associations with treatment outcome. The discovery stage with 256 patients evaluated 8,480,849 SNPs, but no SNPs showed genome-wide level significance in association with treatment outcomes. Although SNPs with P-values of <5 × 10−6 were evaluated in replication samples of 205 patients, no SNP was significantly associated with treatment outcomes. Among AMD-susceptibility genes, rs10490924 in ARMS2/HTRA1 was significantly associated with additional treatment requirement in the discovery stage (P = 0.0023), and pooled analysis with the replication stage further confirmed this association (P = 0.0013). ARMS2/HTRA1 polymorphism might be able to predict the frequency of injection after initial ranibizumab treatment.
Pancreatic islet macroencapsulation using microwell porous membranes
Authors: Skrzypek Katarzyna , Groot Nibbelink Milou , van Lente Jéré , Buitinga Mijke , Engelse Marten A. , de Koning Eelco J. P. , Karperien Marcel , van Apeldoorn Aart , Stamatialis Dimitrios
Published: August 2017

Allogeneic islet transplantation into the liver in combination with immune suppressive drug therapy is widely regarded as a potential cure for type 1 diabetes. However, the intrahepatic system is suboptimal as the concentration of drugs and nutrients there is higher compared to pancreas, which negatively affects islet function. Islet encapsulation within semipermeable membranes is a promising strategy that allows for the islet transplantation outside the suboptimal liver portal system and provides environment, where islets can perform their endocrine function. In this study, we develop a macroencapsulation device based on thin microwell membranes. The islets are seeded in separate microwells to avoid aggregation, whereas the membrane porosity is tailored to achieve sufficient transport of nutrients, glucose and insulin. The non-degradable, microwell membranes are composed of poly (ether sulfone)/polyvinylpyrrolidone and manufactured via phase separation micro molding. Our results show that the device prevents aggregation and preserves the islet’s native morphology. Moreover, the encapsulated islets maintain their glucose responsiveness and function after 7 days of culture (stimulation index above 2 for high glucose stimulation), demonstrating the potential of this novel device for islet transplantation.
Choroid Plexitis and Ependymitis by Magnetic Resonance Imaging are Biomarkers of Neuronal Damage and Inflammation in HIV-negative Cryptococcal Meningoencephalitis
Authors: Hammoud Dima A. , Mahdi Eman , Panackal Anil A. , Wakim Paul , Sheikh Virginia , Sereti Irini , Bielakova Bibi , Bennett John E. , Williamson Peter R.
Published: August 2017

CNS cryptococcal meningoencephalitis in both HIV positive (HIV+) and HIV negative (HIV−) subjects is associated with high morbidity and mortality despite optimal antifungal therapy. We thus conducted a detailed analysis of the MR imaging findings in 45 HIV− and 11 HIV+ patients to identify imaging findings associated with refractory disease. Ventricular abnormalities, namely ependymitis and choroid plexitis were seen in HIV− but not in HIV+ subjects. We then correlated the imaging findings in a subset of HIV− subjects (n = 17) to CSF levels of neurofilament light chain (NFL), reflective of axonal damage and sCD27, known to best predict the presence of intrathecal T-cell mediated inflammation. We found that ependymitis on brain MRI was the best predictor of higher log(sCD27) levels and choroid plexitis was the best predictor of higher log(NFL) levels. The availability of predictive imaging biomarkers of inflammation and neurological damage in HIV− subjects with CNS cryptococcosis may help gauge disease severity and guide the therapeutic approach in those patients.
A novel prognostic index—neutrophil times γ-glutamyl transpeptidase to lymphocyte ratio (NγLR) predicts outcome for patients with hepatocellular carcinoma
Authors: Li Jun , Liao Yan , Suo Liya , Zhu Pengpeng , Chen Xinhuang , Dang Wei , Liao Minjun , Qin Liling , Liao Weijia
Published: August 2017

Clinical outcomes of patients with hepatocellular carcinoma (HCC) are highly variable. This study aims to identify and validate a simple, readily available, and objective prognostic index for the management of HCC. Data from 724 HCC patients undergoing curative resection were evaluated and randomly divided into two cohorts for building and validating the prognostic index. A best model, NγLR = (neutrophil count [109/L] × γ-glutamyl transpeptidase [U/L]) /(lymphocyte count [109/L] × U/L), was selected. An optimal cut-off value of 103.6 for NγLR stratified patients into high NγLR (>103.6) and low NγLR (≤103.6) groups. NγLR > 103.6 was closely associated with HCC malignant characteristics. Elevated NγLR predicted a worse overall survival (OS) and progression-free survival (PFS) for HCC patients and remained an independent predictor for both types of survival. Moreover, early recurrence rates in patients with NγLR > 103.6 were higher than that in patients with NγLR ≤ 103.6 (P < 0.0001). NγLR was an important independent predictor of survival for HCC patients and might be a new promising method to identify patients at different risks of early recurrence and survival after curative resection.
RIPK1 protects hepatocytes from death in Fas-induced hepatitis
Authors: Filliol Aveline , Farooq Muhammad , Piquet-Pellorce Claire , Genet Valentine , Dimanche-Boitrel Marie-Thérèse , Vandenabeele Peter , Bertrand Mathieu J. M. , Samson Michel , Le Seyec Jacques
Published: August 2017

Hepatocyte death is a central event during liver disease progression, in which immune cells play key roles by activating members of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF), including TNFR1 (TNFRSF1A), Fas (TNFRSF6) and TRAIL-R2 (TNFRSF10B). Receptor Interacting Protein Kinase 1 (RIPK1) emerged as a signaling node downstream of these receptors. In the case of TNFR1, RIPK1 has been demonstrated to paradoxically serve as a scaffold to promote the survival of hepatocytes and as a kinase to kill them. To evaluate whether RIPK1 also protects hepatocytes from death in response to FasL or TRAIL, we took advantage of liver parenchymal cell-specificRipk1knockout mice (Ripk1LPC-KO). We found thatRipk1LPC-KOmice, as well as primary hepatocytes derived from them, were more susceptible to Fas-mediated apoptosis than their respective WT counterparts. Fas-induced hepatocyte death was independent of TNF-α signaling. Interestingly, while TRAIL administration did not induce hepatitis inRipk1LPC-KOmice or in their WT counterparts, its combination with IFN-γ only induced TNF-α dependent apoptosis in theRipk1LPC-KOmice. Together, our data demonstrate the protective role of RIPK1 downstream of Fas and highlight the general protective function of RIPK1 in hepatocytes exposed to inflammatory conditions, where TNF-α, FasL and/or TRAIL are present.
Unraveling the correlation between microbiota succession and metabolite changes in traditional Shanxi aged vinegar
Authors: Nie Zhiqiang , Zheng Yu , Xie Sankuan , Zhang Xianglong , Song Jia , Xia Menglei , Wang Min
Published: August 2017

Shanxi aged vinegar (SAV) is a well-known vinegar produced by traditional solid-state fermentation and has been used in China for thousands of years. However, how microorganisms and their metabolites change along with fermentation is unclear. Here, 454 high-throughput sequencing and denaturing gradient gel electrophoresis were used to investigate the composition of microbial community. Metabolites were further analyzed by gas chromatography–mass spectrometry and high–performance liquid chromatography. Results showed that the composition of bacterial community changed dramatically at different stages of fermentation. The bacterial genera (relative abundance > 0.1%) decreased from 17 in daqu (starter used in starch saccharification) to 2 at the 12th day of alcohol fernemtation (AF). 15 bacterial genera at the 1st day of acetic acid fermentation (AAF) decreased to 4 genera, involving Acetobacter (50.9%), Lactobacillus (47.9%), Komagataeibacter (formerly Gluconacetobacter, 0.7%) and Propionibacterium (0.1%) at the 7th day of AAF. The structure of fungal community was more homogeneous. Saccharomyces and Saccharomycopsis were predominant in AF and AAF. A total of 87 kinds of nonvolatile metabolites were detected. Canonical correspondence analysis showed a significant correlation between the microbiota succession and the formation of metabolites during the fermentation of SAV. This study provides detailed information for the fermentation mechanism of traditional SAV.
Shade Inhibits Leaf Size by Controlling Cell Proliferation and Enlargement in Soybean
Authors: Wu Yushan , Gong Wanzhuo , Yang Wenyu
Published: August 2017

To gain more insight into the physiological function of shade and how shade affects leaf size, we investigated the growth, leaf anatomical structure, hormones and genes expressions in soybean. Soybean seeds were sown in plastic pots and were allowed to germinate and grow for 30 days under shade or full sunlight conditions. Shade treated plants showed significantly increase on stem length and petiole length, and decrease on stem diameters, shoot biomass and its partition to leaf also were significantly lower than that in full sunlight. Smaller and thinner on shade treated leaves than corresponding leaves on full sunlight plants. The decreased leaf size caused by shade was largely attributable to cell proliferation in young leaves and both cell proliferation and enlargement in old leaves. Shade induced the expression of a set of genes related to cell proliferation and/or enlargement, but depended on the developmental stage of leaf. Shade significantly increased the auxin and gibberellin content, and significantly decreased the cytokinin content in young, middle and old leaves. Taken together, these results indicated that shade inhibited leaf size by controlling cell proliferation and enlargement, auxin, gibberellin and cytokinin may play important roles in this process.