bluuebunny/crossref_metadata_2025 huggingface dataset:
Uplift Evidences Related to the Recession of Groundwater Abstraction in a Pyroclastic-Alluvial Aquifer of Southern Italy
Authors: Coda Silvio , Confuorto Pierluigi , De Vita Pantaleone , Di Martire Diego , Allocca Vincenzo
Published: May 2019

Aquifer mismanagement is a common anthropogenic cause of subsidence and uplift phenomena in alluvial plains, representing one of the main natural hazards in urban areas due to related damage to urban structures and infrastructures. In this work, the groundwater rebound phenomenon that occurred in the last decades of the 20th century in the Lufrano area (Metropolitan area of Naples, Southern Italy) has been studied by integrating geological data, hydrogeological continuous monitoring and spaceborne SAR information derived from ERS-1/2 and ENVISAT satellites. In the period of 1989–2006, the Lufrano area, which hosts an important well field made up of 180 wells extracting groundwater for drinking use, suffered an initial over-exploitation of the aquifer which was followed by a sudden and severe decrease of the volume abstraction, resulting this last in a rapid ground uplift. The coupled analysis of hydrogeological and DInSAR data have shown a correspondence between piezometric level rise (up to 15 m) and ground uplift (up to 50 mm) trends in the period 1989–2006. In order to examine the spatio-temporal evolution of the phenomena and the cause-effect relationships, showing the link between the two phenomena and their rates, longitudinal cross-sections were carried out and comparisons between piezometric level rise and time-series of displacements were reconstructed. The obtained results represent an initial contribution to the definition of ground deformation related to groundwater level rise phenomena, providing a basis for future studies focused on the modelling of the hydro-mechanical properties of the aquifer.
Leveraging Patient/Community Partnerships to Disseminate Patient Centered Outcomes Research in Geriatrics
Authors: Lindquist Lee A. , Seltzer Anne , Forcucci Chris , Wong Norine , Ramirez-Zohfeld Vanessa
Published: May 2019

Background: With the growth of patient-centered outcomes research (PCOR), partnerships between researchers and patients have presented novel opportunities for disseminating results. A large gap exists in disseminating patient-centered research results to older adult patient end-users. We sought to examine the experiences of patient/community partners in disseminating PCOR results and characterize lessons learned that may facilitate future researcher-patient/community dissemination partnerships. Methods: Patient/community partners who participated in geriatrics-focused PCORI-funded research and were active in disseminating results, as part of their planned activities, were recruited for one-to-one qualitative interviews. Constant comparative and thematic analysis were used to identify and describe common themes that emerged in a survey of open-ended questions. Results: Ten individuals (four community partners, six patients) aged 55–87 years were interviewed. Analysis revealed that for successful dissemination, subjects felt it was vital to reach out to people affected by the results, leverage personal stories, and tap into pre-developed programming. Patient/Community partners identified potential audiences through word-of-mouth, community requests, and mapping a list of audiences—targeting those directly affected as well as those who worked with the audience (e.g., not specifically medical). Patient/community partners recommended that researchers engage patient/community partners for suggestions on audiences, show empathy, include diverse populations, and maintain a community-focus. One community partner stated, “Why wouldn’t we help disseminate results? It’s a no-brainer. We know people!” Conclusion: Patient/community partners provide effective ways to communicate results, new audiences to reach, improved communication with different audiences, and improved credibility of the findings. The lessons learned have implications for assisting future research-patient/community partnerships in the dissemination of their patient-centered research.
The Civic Scale: Strategies of Emplacement in Dambudzo Marechera and Ivan Vladislavić
Authors: Kruger Liam
Published: May 2019

This paper identifies and intervenes in the problems posed by reading postcolonial texts as representative, or encompassing of, the nation with which they are associated. Alternatively, it proposes that reading at the scale of the city offers a method for circumventing the elision of particularity which occurs when the nation, continent or globe are foregrounded in Western or Western-facing responses to these texts. The paper models what such a “scaled-down” reading might look like, attending to Dambudzo Marechera’s House of Hunger (1978) and Ivan Vladislavic’s Portrait With Keys: Joburg and What-What (2006), and their intricate relationships to the urban spaces of Harare and Johannesburg, respectively. At stake in these analyses are opportunities to identify what Jacques Rancière terms dissensus, or political contestation, rendered in spatial terms. This establishes a pliable counterdiscourse of the city which seeks and discerns meaning not through consensus or “sanctioned representation”; but through the complexities of affective attachments, the plurality of experiences, and the teeming heterogeneity of physical and literary spaces that have been previously flattened.
Recognizing the Values of Kashan Historic Urban Context for Achieving Appropriate Regeneration (Case Study: Sarpelleh Passageway)
Authors: Rezazadeh Ardebili Mojtaba , Rezazadeh Ardebili Romina , Moradi Mojgan
Published: May 2019

This paper aims to identify the values of the historical context of Kashan city (Iran) and apply them in its regeneration process, and develop planning methods based on international perspectives and local experiences in Iran. The values and features should be carefully examined by evaluation methods, allowing for the transmission of urban context values to the future. This study will use an appropriate methodology to achieve a validated document based on values and their indicators, allowing for regeneration of the Sarpelleh historic neighborhood. We have divided the purposes of the current research into two levels: First, identification of the values of the historic context of Kashan and then providing an appropriate compatible pattern with contemporary contextual values in different dimensions; second, focusing on designing a cultural and historical axis to represent the values that are compatible with contemporary needs. The outcomes of this research are a clear indication of the values of the Sarpelleh historic neighborhood in three main categories: (1) historical and social values; (2) environmental and physical values; and (3) economic values—the regeneration plans of which are proposed in three alternatives. Note that the proposed regeneration plan balances all of the identified values, without neglecting any of them.
The Adductomics of Isolevuglandins: Oxidation of IsoLG Pyrrole Intermediates Generates Pyrrole–Pyrrole Crosslinks and Lactams
Authors: Bi Wenzhao , Jang Geeng-Fu , Zhang Lei , Crabb John W. , Laird James , Linetsky Mikhail , Salomon Robert G.
Published: May 2019

Isoprostane endoperoxides generated by free radical-induced oxidation of arachidonates, and prostaglandin endoperoxides generated through enzymatic cyclooxygenation of arachidonate, rearrange nonenzymatically to isoprostanes and a family of stereo and structurally isomeric γ-ketoaldehyde seco-isoprostanes, collectively known as isolevuglandins (isoLGs). IsoLGs are stealthy toxins, and free isoLGs are not detected in vivo. Rather, covalent adducts are found to incorporate lysyl ε-amino residues of proteins or ethanolamino residues of phospholipids. In vitro studies have revealed that adduction occurs within seconds and is uniquely prone to cause protein–protein crosslinks. IsoLGs accelerate the formation of the type of amyloid beta oligomers that have been associated with neurotoxicity. Under air, isoLG-derived pyrroles generated initially are readily oxidized to lactams and undergo rapid oxidative coupling to pyrrole–pyrrole crosslinked dimers, and to more highly oxygenated derivatives of those dimers. We have now found that pure isoLG-derived pyrroles, which can be generated under anoxic conditions, do not readily undergo oxidative coupling. Rather, dimer formation only occurs after an induction period by an autocatalytic oxidative coupling. The stable free-radical TEMPO abolishes the induction period, catalyzing rapid oxidative coupling. The amine N-oxide TMAO is similarly effective in catalyzing the oxidative coupling of isoLG pyrroles. N-acetylcysteine abolishes the generation of pyrrole–pyrrole crosslinks. Instead pyrrole-cysteine adducts are produced. Two unified single-electron transfer mechanisms are proposed for crosslink and pyrrole-cysteine adduct formation from isoLG-pyrroles, as well as for their oxidation to lactams and hydroxylactams.
Physical Education Pedagogies Built upon Theories of Movement Learning: How Can Environmental Constraints Be Manipulated to Improve Children’s Executive Function and Self-Regulation Skills?
Authors: Rudd James R. , O’Callaghan Laura , Williams Jacqueline
Published: May 2019

Physical education in schools has been marginalised across the globe, and as a result, children are missing out on opportunities to develop and acquire the foundation skills needed to lead a physically active life. The squeeze on physical education in schools, particularly in some western countries (United Kingdom, Australia and America), has been justified on the grounds that core subjects such as English and mathematics need more curriculum time, as this will lead to higher cognitive and academic performance. The aim of this paper is to highlight how physical education lessons in early childhood, underpinned by either of two major theories of motor learning, can support teachers in the creation of learning environments, as well as guide their pedagogical practice to facilitate children’s development of key cognitive skills, in particular executive function and self-regulation skills. These skills are crucial for learning and development and have been found to be a higher predictor of academic achievement than IQ. They also enable positive behaviour and allow us to make healthy choices for ourselves and others, therefore providing further evidence that the development of movement skills has the potential to secure positive attitudes and outcomes towards physical activity across the lifespan.
Quantifying Urban Spatial Variations of Anthropogenic VOC Concentrations and Source Contributions with a Mobile Sampling Platform
Authors: Gu Peishi , Dallmann Timothy R. , Li Hugh Z. , Tan Yi , Presto Albert A.
Published: May 2019

Volatile organic compounds (VOCs) are important atmospheric constituents because they contribute to formation of ozone and secondary aerosols, and because some VOCs are toxic air pollutants. We measured concentrations of a suite of anthropogenic VOCs during summer and winter at 70 locations representing different microenvironments around Pittsburgh, PA. The sampling sites were classified both by land use (e.g., high versus low traffic) and grouped based on geographic similarity and proximity. There was roughly a factor of two variation in both total VOC and single-ring aromatic VOC concentrations across the site groups. Concentrations were roughly 25% higher in winter than summer. Source apportionment with positive matrix factorization reveals that the major VOC sources are gasoline vehicles, solvent evaporation, diesel vehicles, and two factors attributed to industrial emissions. While we expected to observe significant spatial variability in the source impacts across the sampling domain, we instead found that source impacts were relatively homogeneous.
Effects of Different Types of Water and Nitrogen Fertilizer Management on Greenhouse Gas Emissions, Yield, and Water Consumption of Paddy Fields in Cold Region of China
Authors: Nie Tangzhe , Chen Peng , Zhang Zhongxue , Qi Zhijuan , Lin Yanyu , Xu Dan
Published: May 2019

Water management and nitrogen (N) fertilizers are the two main driving factors of greenhouse gas emissions. In this paper, two irrigation modes, controlled irrigation (CI) and flood irrigation (FI), and four nitrogen fertilizer levels (N0: 0, N1: 85, N2: 110, and N3: 135 kg·hm−2) were set to study the effect of different irrigation modes and N fertilizer amount on greenhouse-gas emissions of paddy fields in cold region by using the static chamber-gas chromatograph method; yield and water consumption were also analyzed. The results showed that, compared with FI, CI significantly reduced CH4 emissions by 19.42~46.94%, but increased N2O emissions by 5.66~11.85%. Under the two irrigation modes, N fertilizers could significantly increase N2O emissions, but the CH4 emissions of each N treatment showed few differences. Compared with FI, appropriate N application under CI could significantly increase grain number per spike, seed-setting rate, and 1000-grain weight, thus increasing yield. Under the two irrigation modes, water consumption increased with the increase of N application rate, and the total water consumption of CI was significantly lower than that of FI. The global warming potential (GWP) of CI was significantly smaller than that of FI. The trend of GWP in each treatment was similar to that of CH4. Through comprehensive comparison and analysis of water productivity (WP), gas emission intensity (GHGI), and the yield of each treatment, we found that CI+N2 treatment had the highest WP (2.05 kg·m−3) and lowest GHGI (0.37 kg CO2-eq·kg−1), while maintaining high yield (10,224.4 kg·hm−2). The results of this study provide an important basis for guiding high yield, water-savings, and emission reduction of paddy fields in cold regions.
Implementation of 3D Printing Technology in the Field of Prosthetics: Past, Present, and Future
Authors: Manero Albert , Smith Peter , Sparkman John , Dombrowski Matt , Courbin Dominique , Kester Anna , Womack Isaac , Chi Albert
Published: May 2019

There is an interesting and long history of prostheses designed for those with upper-limb difference, and yet issues still persist that have not yet been solved. Prosthesis needs for children are particularly complex, due in part to their growth rates. Access to a device can have a significant impact on a child’s psychosocial development. Often, devices supporting both cosmetic form and user function are not accessible to children due to high costs, insurance policies, medical availability, and their perceived durability and complexity of control. These challenges have encouraged a grassroots effort globally to offer a viable solution for the millions of people living with limb difference around the world. The innovative application of 3D printing for customizable and user-specific hardware has led to open-source Do It Yourself “DIY” production of assistive devices, having an incredible impact globally for families with little recourse. This paper examines new research and development of prostheses by the maker community and nonprofit organizations, as well as a novel case study exploring the development of technology and the training methods available. These design efforts are discussed further in the context of the medical regulatory framework in the United States and highlight new associated clinical studies designed to measure the quality of life impact of such devices.
Synergetic Relationship between Urban and Rural Water Poverty: Evidence from Northwest China
Authors: Liu Wenxin , Zhao Minjuan , Cai Yu , Wang Rui , Lu Weinan
Published: May 2019

Combining the measurement of urban and rural areas to link water and poverty provides a new insight into the fields of water resources management and poverty alleviation. Owing to rapid urban development, water resource conflicts between urban and rural areas are gettingbecoming more intensified and more complex. This study details the application of a water poverty index (WPI) using 26 indicators to evaluate urban and rural water poverty in northwest China during the period 2000–2017. This study also analyzes temporal variations of urban and rural water poverty by the kernel density estimation (KDE). We found that the level of water poverty is gradually declining over time and the improvements in urban and rural areas are not harmonious. Additionally, it applies the synergic theory to analyze the relationships between urban and rural water poverty. The correspondence analysis between urban and rural water poverty is significant because of the synergic level results. The results show that there are four primary types in northwest China: synchronous areas, urban-priority areas, rural-priority areas, and conflict areas, and their evolution stages. The results suggest the need for location-specific policy interventions. Furthermore, we put forward corresponding countermeasures. The research findings also provide a theoretical foundation for the evaluation of urban and rural water poverty, and a regional strategy to relieve conflict between urban and rural water poverty.
Management of STEC Gastroenteritis: Is There a Role for Probiotics?
Authors: Giordano Mario , Baldassarre Maria Elisabetta , Palmieri Viviana , Torres Diletta D. , Carbone Vincenza , Santangelo Luisa , Gentile Federico , Panza Raffaella , Di Mauro Federica , Capozza Manuela , Di Mauro Antonio , Laforgia Nicola
Published: May 2019

Shiga toxin-producing Escherichia Coli (STEC) infections routinely run as a common gastroenteritis, but in many cases they may evolve towards hemolytic uremic syndrome (HUS). HUS is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Gut microorganisms have a fundamental impact on human physiology, because they modulate normal intestinal functions and play a pivotal role in influencing the local and systemic immune responses. Despite surveillance established in many countries and major progresses in the understanding of STEC-HUS mechanisms, no specific treatment is currently available. Targeting the gut microbiota could represent a new potential therapeutic strategy in STEC infection. In this paper, we reviewed the current knowledge about microbiota characteristics of patients with STEC infections, as well as in vitro and in vivo evidence of probiotic supplementation in managing STEC gastroenteritis and in HUS onset prevention.
Pricing Strategies in Dual-Channel Reverse Supply Chains Considering Fairness Concern
Authors: Wu Di , Chen Juhong , Yan Ruyu , Zhang Ruijun
Published: May 2019

The fierce competition in the recycling industry and the rapid development of internet technology has prompted recycling centers to develop a dual-channel reverse supply chain with both offline and online recycling channels. After the introduction of online channels, recycling centers and third-party recyclers (TPR) have paid attention to the division of profits in supply chain systems and the behavior of fairness concerns. Therefore, it is necessary to help recycling enterprises make pricing decisions in consideration of fairness concerns. This paper is aimed at answering the following two main questions: (1) When the recycling center or TPR have fairness concerns, how does the optimal pricing and revenue of supply chain members change when both sides are neutral? (2) When the fairness concern coefficient changes, how does the overall revenue of the supply chain system change? How should supply chain members adjust their pricing decisions to maximize their own profits? In order to solve the above problems, Stackelberg game models were made from three aspects: both sides are neutral, only the TPR has fairness concerns, and only the recycling center has fairness concerns. Based on the results of the example analyses for the model, we found that when only the TPR has fairness concerns, the profit of the recycling center and the transfer price of offline channels will decrease, while the profit of TPR is the opposite. Furthermore, when only a recycling center has fairness concerns, it will lead to the reduction of not only the recycling price and transfer price of offline channels, but also the profits of the entire supply chain system. Specially, whether it is for a recycling center or TPR, a lower level of fairness concern coefficient has a stronger impact on pricing and revenue than at high levels.
Examining the Features of Parks That Children Visit During Three Stages of Childhood
Authors: Flowers Elliott P. , Timperio Anna , Hesketh Kylie D. , Veitch Jenny
Published: May 2019

Parks provide an opportunity for children to be physically active, but are rarely fully utilised. A better understanding of which park features attract children of varying ages is needed. This study examined which features are present at parks that children visit most often at different stages throughout childhood. Parents reported the park their child visited most often at three timepoints: T1 = 3–5 years, T2 = 6–8 years, and T3 = 9–11 years. These parks were then audited (using a purposely created audit tool) to capture information relating to access, activity areas and quality. Online mapping tools were also used to determine walking distance to parks and park size. Parks visited at T2 were further from home, larger, and had more road crossings, full courts, other facilities and comfort amenities such as toilets and lights than T1 parks. Parks visited at T3 were larger and had more sports ovals compared to T1 parks, and were significantly less likely to have barbeque facilities than T2 parks. Our findings suggest that as children transition from pre-school (T1), to primary school age (T2 and T3), they visit parks that have more facilities to support sport and active recreation.
Socio-Ecological Natural Experiment with Randomized Controlled Trial to Promote Active Commuting to Work: Process Evaluation, Behavioral Impacts, and Changes in the Use and Quality of Walking and Cycling Paths
Authors: Aittasalo Minna , Tiilikainen Johanna , Tokola Kari , Suni Jaana , Sievänen Harri , Vähä-Ypyä Henri , Vasankari Tommi , Seimelä Timo , Metsäpuro Pasi , Foster Charlie , Titze Sylvia
Published: May 2019

Active commuting to work (ACW) has beneficial effects on health, traffic, and climate. However, more robust evidence is needed on how to promote ACW. This paper reports the findings of a multilevel natural experiment with a randomized controlled trial in 16 Finnish workplaces. In Phase 1, 11 workplaces (1823 employees) from Area 1 were exposed to environmental improvements in walking and cycling paths. In Phase 2, five more workplaces (826 employees) were recruited from Area 2 and all workplaces were randomized into experimental group (EXP) promoting ACW with social and behavioral strategies and comparison group (COM) participating only in data collection. Process and impact evaluation with questionnaires, travel diaries, accelerometers, traffic calculations, and auditing were conducted. Statistics included Wilcoxon Signed Ranks Test, Mann-Whitney U-test, and after-before differences with 95% confidence intervals (95% CI). After Phase 1, positive change was seen in the self-reported number of days, which the employees intended to cycle part of their journey to work in the following week (p = 0.001). After Phase 2, intervention effect was observed in the proportion of employees, who reported willingness to increase walking (8.7%; 95% CI 1.8 to 15.6) and cycling (5.5%; 2.2 to 8.8) and opportunity to cycle part of their journey to work (5.9%; 2.1 to 9.7). To conclude, the intervention facilitated employees’ motivation for ACW, which is the first step towards behavior change.
Effects of Simulated Herbivory on the Vegetative Reproduction and Compensatory Growth of Hordeum brevisubulatum at Different Ontogenic Stages
Authors: Yuan Jihong , Wang Ping , Yang Yunfei
Published: May 2019

The response of plant vegetative reproduction and compensatory growth to herbivory has been widely discussed in biological and ecological research. Most previous research has supported the idea that both vegetative reproduction and compensatory growth are affected by their ontogenic stage. However, in many studies, the effects of foraging at different ontogenic stages was often confounded with the effects of foraging at different phenological periods for perennials. Our experiment was conducted in a natural meadow with a perennial grass, Hordeum brevisubulatum, and four ontogenic stages were chosen as our experimental objects. Three different clipping intensities during three phenological periods were implemented to explore the effects of simulating animal foraging on vegetative reproduction and compensatory plant growth. The results indicated that there were significant effects of ontogenic stage, phenological period, and clipping intensity on vegetative reproduction and compensatory growth. Moderate clipping intensities significantly increased the number of vegetative tillers, the total number of juvenile tillers and buds, and the aboveground biomass at early phenological periods for individuals at early ontogenic stages. Our results suggested that moderate clipping intensities could induce only an over-compensation response in perennial grasses at both the early ontogenic stage and phenological period, and the ability of compensatory growth gradually decreased with the progression of the ontogenic stage. This is of great significance to the primary production of grasslands subjected to herbivory.
Mutational and Combinatorial Control of Self-Assembling and Disassembling of Human Proteasome α Subunits
Authors: Sekiguchi Taichiro , Satoh Tadashi , Kurimoto Eiji , Song Chihong , Kozai Toshiya , Watanabe Hiroki , Ishii Kentaro , Yagi Hirokazu , Yanaka Saeko , Uchiyama Susumu , Uchihashi Takayuki , Murata Kazuyoshi , Kato Koichi
Published: May 2019

Eukaryotic proteasomes harbor heteroheptameric α-rings, each composed of seven different but homologous subunits α1–α7, which are correctly assembled via interactions with assembly chaperones. The human proteasome α7 subunit is reportedly spontaneously assembled into a homotetradecameric double ring, which can be disassembled into single rings via interaction with monomeric α6. We comprehensively characterized the oligomeric state of human proteasome α subunits and demonstrated that only the α7 subunit exhibits this unique, self-assembling property and that not only α6 but also α4 can disrupt the α7 double ring. We also demonstrated that mutationally monomerized α7 subunits can interact with the intrinsically monomeric α4 and α6 subunits, thereby forming heterotetradecameric complexes with a double-ring structure. The results of this study provide additional insights into the mechanisms underlying the assembly and disassembly of proteasomal subunits, thereby offering clues for the design and creation of circularly assembled hetero-oligomers based on homo-oligomeric structural frameworks.
Oncogenic Effect of the Novel Fusion Gene VAPA-Rab31 in Lung Adenocarcinoma
Authors: Yoon Daseul , Bae Kieun , Kim Jin-Hee , Choi Yang-Kyu , Yoon Kyong-Ah
Published: May 2019

Fusion genes have been identified as oncogenes in several solid tumors including lung, colorectal, and stomach cancers. Here, we characterized the fusion gene, VAPA-Rab31, discovered from RNA-sequencing data of a patient with lung adenocarcinoma who did not harbor activating mutations in EGFR, KRAS and ALK. This fusion gene encodes a protein comprising the N-terminal region of vesicle-associated membrane protein (VAMP)-associated protein A (VAPA) fused to the C-terminal region of Ras-related protein 31 (Rab31). Exogenous expression of VAPA-Rab31 in immortalized normal bronchial epithelial cells demonstrated the potential transforming effects of this fusion gene, including increased colony formation and cell proliferation in vitro. Also, enhanced tumorigenicity upon VAPA-Rab31 was confirmed in vivo using a mouse xenograft model. Metastatic tumors were also detected in the liver and lungs of xenografted mice. Overexpression of VAPA-Rab31 upregulated anti-apoptotic protein Bcl-2 and phosphorylated CREB both in cells and xenograft tumors. Reduced apoptosis and increased phosphorylation of CREB and Erk were observed in VAPA-Rab31-overexpressing cells after bortezomib treatment. Elevated Bcl-2 level via activated CREB contributed to the resistance to the bortezomib-induced apoptosis. Our data suggest the oncogenic function of the novel fusion gene VAPA-Rab31 via upregulated Bcl-2 and activated CREB in lung cancer.
Quantitative Imaging of Gd Nanoparticles in Mice Using Benchtop Cone-Beam X-ray Fluorescence Computed Tomography System
Authors: Zhang Siyuan , Li Liang , Chen Jiayou , Chen Zhiqiang , Zhang Wenli , Lu Hongbing
Published: May 2019

Nanoparticles (NPs) are currently under intensive research for their application in tumor diagnosis and therapy. X-ray fluorescence computed tomography (XFCT) is considered a promising non-invasive imaging technique to obtain the bio-distribution of nanoparticles which include high-Z elements (e.g., gadolinium (Gd) or gold (Au)). In the present work, a set of experiments with quantitative imaging of GdNPs in mice were performed using our benchtop XFCT device. GdNPs solution which consists of 20 mg/mL NaGdF4 was injected into a nude mouse and two tumor-bearing mice. Each mouse was then irradiated by a cone-beam X-ray source produced by a conventional X-ray tube and a linear-array photon counting detector with a single pinhole collimator was placed on one side of the beamline to record the intensity and spatial information of the X-ray fluorescent photons. The maximum likelihood iterative algorithm with scatter correction and attenuation correction method was applied for quantitative reconstruction of the XFCT images. The results show that the distribution of GdNPs in each target slice (containing liver, kidney or tumor) was well reconstructed and the concentration of GdNPs deposited in each organ was quantitatively estimated, which indicates that this benchtop XFCT system provides convenient tools for obtaining accurate concentration distribution of NPs injected into animals and has potential for imaging of nanoparticles in vivo.
Nogo-B Receptor Directs Mitochondria-Associated Membranes to Regulate Vascular Smooth Muscle Cell Proliferation
Authors: Yang Yi-Dong , Li Man-Man , Xu Gang , Feng Lan , Zhang Er-Long , Chen Jian , Chen De-Wei , Gao Yu-Qi
Published: May 2019

Mitochondria-associated membranes (MAM) are a well-recognized contact link between the mitochondria and endoplasmic reticulum that affects mitochondrial biology and vascular smooth muscle cells (VSMCs) proliferation via the regulation of mitochondrial Ca2+(Ca2+m) influx. Nogo-B receptor (NgBR) plays a vital role in proliferation, epithelial-mesenchymal transition, and chemoresistance of some tumors. Recent studies have revealed that downregulation of NgBR, which stimulates the proliferation of VSMCs, but the underlying mechanism remains unclear. Here, we investigated the role of NgBR in MAM and VSMC proliferation. We analyzed the expression of NgBR in pulmonary arteries using a rat model of hypoxic pulmonary hypertension (HPH), in which rats were subjected to normoxic recovery after hypoxia. VSMCs exposed to hypoxia and renormoxia were used to assess the alterations in NgBR expression in vitro. The effect of NgBR downregulation and overexpression on VSMC proliferation was explored. The results revealed that NgBR expression was negatively related with VSMCs proliferation. Then, MAM formation and the phosphorylation of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) was detected. We found that knockdown of NgBR resulted in MAM disruption and augmented the phosphorylation of IP3R3 through pAkt, accompanied by mitochondrial dysfunction including decreased Ca2+m, respiration and mitochondrial superoxide, increased mitochondrial membrane potential and HIF-1α nuclear localization, which were determined by confocal microscopy and Seahorse XF-96 analyzer. By contrast, NgBR overexpression attenuated IP3R3 phosphorylation and HIF-1α nuclear localization under hypoxia. These results reveal that dysregulation of NgBR promotes VSMC proliferation via MAM disruption and increased IP3R3 phosphorylation, which contribute to the decrease of Ca2+m and mitochondrial impairment.
Synthesis and Applications of Biopolymer Composites
Authors: Díez-Pascual Ana María
Published: May 2019

In recent years, there has been a growing demand for a clean and pollution-free environment and an evident target to minimizing fossil fuel [...]
Inflammatory and Molecular Pathways in Heart Failure—Ischemia, HFpEF and Transthyretin Cardiac Amyloidosis
Authors: Michels da Silva Diana , Langer Harald , Graf Tobias
Published: May 2019

Elevated pro-inflammatory biomarkers and cytokines are associated with morbidity and mortality in heart failure (HF). Preclinical and clinical studies have shown multiple inflammatory mechanisms causing cardiac remodeling, dysfunction and chronic failure. Therapeutics in trials targeting the immune response in heart failure and its effects did not result in evident benefits regarding clinical endpoints and mortality. This review elaborates pathways of immune cytokines in pathogenesis and worsening of heart failure in clinical and cellular settings. Besides the well-known mechanisms of immune activation and inflammation in atherosclerosis causing ischemic cardiomyopathy or myocarditis, attention is focused on other mechanisms leading to heart failure such as transthyretin (TTR) amyloidosis or heart failure with preserved ejection fraction. The knowledge of the pathogenesis in heart failure and amyloidosis on a molecular and cellular level might help to highlight new disease defining biomarkers and to lead the way to new therapeutic targets.
Human Liver Regeneration: An Etiology Dependent Process
Authors: Van Haele Matthias , Snoeck Janne , Roskams Tania
Published: May 2019

Regeneration of the liver has been an interesting and well-investigated topic for many decades. This etiology and time-dependent mechanism has proven to be extremely challenging to investigate, certainly in human diseases. A reason for this challenge is found in the numerous interactions of different cell components, of which some are even only temporarily present (e.g., inflammatory cells). To orchestrate regeneration of the epithelial cells, their interaction with the non-epithelial components is of utmost importance. Hepatocytes, cholangiocytes, liver progenitor cells, and peribiliary glands have proven to be compartments of regeneration. The ductular reaction is a common denominator in virtually all liver diseases; however, it is predominantly found in late-stage hepatic and biliary diseases. Ductular reaction is an intriguing example of interplay between epithelial and non-epithelial cells and encompasses bipotential liver progenitor cells which are able to compensate for the loss of the exhausted hepatocytes and cholangiocytes in biliary and hepatocytic liver diseases. In this manuscript, we focus on the etiology-specific damage that is observed in different human diseases and how the liver regulates the regenerative response in an acute and chronic setting. Furthermore, we describe the importance of morphological keynotes in different etiologies and how spatial information is of relevance for every basic and translational research of liver regeneration.
Connecting West and East
Authors: Zhang Ming , Moalin Mohamed , Haenen Guido R.M.M.
Published: May 2019

Despite their similarities, Western medicine and Eastern medicine are very different because they are built on different fundamentals. The general idea has arisen that we will benefit by connecting Western and Eastern medicine. First, both the merits as well as the limitations of both types of medicine are discussed. It was concluded that to create a bridge, we should focus on similarities that inspire the further unravelling of the molecular mechanism of the mode of action and toxicity of Traditional Chinese Medicine. It is suggested that the energy perspective provides a basis to integrate Eastern and Western medicine.
The Physics of Entropic Pulling: A Novel Model for the Hsp70 Motor Mechanism
Authors: Sousa Rui , Lafer Eileen M.
Published: May 2019

Hsp70s use ATP to generate forces that disassemble protein complexes and aggregates, and that translocate proteins into organelles. Entropic pulling has been proposed as a novel mechanism, distinct from the more familiar power-stroke and Brownian ratchet models, for how Hsp70s generate these forces. Experimental evidence supports entropic pulling, but this model may not be well understood among scientists studying these systems. In this review we address persistent misconceptions regarding the dynamics of proteins in solution that contribute to this lack of understanding, and we clarify the basic physics of entropic pulling with some simple analogies. We hope that increased understanding of the entropic pulling mechanism will inform future efforts to characterize how Hsp70s function as motors, and how they coordinate with their regulatory cochaperones in mechanochemical cycles that transduce the energy of ATP hydrolysis into physical changes in their protein substrates.
Computational Aminoacyl-tRNA Synthetase Library Design for Photocaged Tyrosine
Authors: Baumann Tobias , Hauf Matthias , Richter Florian , Albers Suki , Möglich Andreas , Ignatova Zoya , Budisa Nediljko
Published: May 2019

Engineering aminoacyl-tRNA synthetases (aaRSs) provides access to the ribosomal incorporation of noncanonical amino acids via genetic code expansion. Conventional targeted mutagenesis libraries with 5–7 positions randomized cover only marginal fractions of the vast sequence space formed by up to 30 active site residues. This frequently results in selection of weakly active enzymes. To overcome this limitation, we use computational enzyme design to generate a focused library of aaRS variants. For aaRS enzyme redesign, photocaged ortho-nitrobenzyl tyrosine (ONBY) was chosen as substrate due to commercial availability and its diverse applications. Diversifying 17 first- and second-shell sites and performing conventional aaRS positive and negative selection resulted in a high-activity aaRS. This MjTyrRS variant carries ten mutations and outperforms previously reported ONBY-specific aaRS variants isolated from traditional libraries. In response to a single in-frame amber stop codon, it mediates the in vivo incorporation of ONBY with an efficiency matching that of the wild type MjTyrRS enzyme acylating cognate tyrosine. These results exemplify an improved general strategy for aaRS library design and engineering.
Interaction of Mycotoxin Alternariol with Serum Albumin
Authors: Fliszár-Nyúl Eszter , Lemli Beáta , Kunsági-Máté Sándor , Dellafiora Luca , Dall’Asta Chiara , Cruciani Gabriele , Pethő Gábor , Poór Miklós
Published: May 2019

Alternariol (AOH) is a mycotoxin produced by Alternaria species. In vitro studies suggest the genotoxic, mutagenic, and endocrine disruptor effects of AOH, and an increased incidence of esophageal cancer has been reported related to higher AOH exposure. Human serum albumin (HSA) is the most abundant plasma protein in the circulation, it is able to affect toxicokinetic properties of numerous xenobiotics. HSA forms stable complexes with several mycotoxins, however, the interaction of AOH with albumin has not been examined. In this study, the complex formation of AOH with HSA was tested, employing fluorescence spectroscopy, ultrafiltration, and molecular modeling. Each spectroscopic measurement shows the formation of stable AOH-HSA complexes (K = 4 × 105 L/mol). Investigations with site markers (in spectroscopic and ultrafiltration models) as well as modeling studies suggest that AOH occupies Sudlow’s site I as a high-affinity binding site in HSA. The binding affinity of AOH towards bovine, porcine, and rat albumins was also tested, suggesting that AOH binds to rat albumin with considerably higher affinity than other albumins tested. Our results demonstrate the strong interaction of AOH with serum albumins, suggesting the potential in vivo importance of these interactions.
Role of Cyclin-Dependent Kinase Inhibitors in Endometrial Cancer
Authors: Giannone Gaia , Tuninetti Valentina , Ghisoni Eleonora , Genta Sofia , Scotto Giulia , Mittica Gloria , Valabrega Giorgio
Published: May 2019

Endometrial Cancer (EC) is an important cause of death in women worldwide. Despite early diagnosis and optimal treatment of localized disease, relapsed patients have few therapeutic options because after first line therapy, currently no standard of care exists. On the basis of endocrine positivity of most endometrioid ECs, Endocrine Therapy (ET) is a reasonable and widely accepted option. Better knowledge of molecular mechanisms involved in cancer highlighted the deregulated activity of Cyclin-Dependent Kinases (CDKs) in the cell cycle as a hallmark of carcinogenesis supporting the development of a new class of drugs: CDK inhibitors (CDKis). The aim of this review is to give an overview on CDKis preclinical, early clinical activity and future development in EC. Use of CDKis has a strong preclinical rationale but we have poor clinical data. Similar to breast cancer, most ongoing trials are investigating synergistic associations between CDKis and ET. These trials will probably help in defining the best clinical setting of CDKis in ECs, which are the best partner drugs, and how to manage CDKis toxicities with a focus on potential biomarkers of response.
Transcriptomic Analysis Reveals a Comprehensive Calcium- and Phytohormone-Dominated Signaling Response in Leymus chinensis Self-Incompatibility
Authors: Chen Shuangyan , Jia Junting , Cheng Liqin , Zhao Pincang , Qi Dongmei , Yang Weiguang , Liu Hui , Dong Xiaobing , Li Xiaoxia , Liu Gongshe
Published: May 2019

Sheepgrass (Leymus chinensis (Trin.) Tzvel.) is an economically and ecologically important forage in the grass family. Self-incompatibility (SI) limits its seed production due to the low seed-setting rate after self-pollination. However, investigations into the molecular mechanisms of sheepgrass SI are lacking. Therefore, microscopic observation of pollen germination and pollen tube growth, as well as transcriptomic analyses of pistils after self- and cross-pollination, were performed. The results indicated that pollen tube growth was rapidly inhibited from 10 to 30 min after self-pollination and subsequently stopped but preceded normally after cross-pollination. Time course comparative transcriptomics revealed different transcriptome dynamics between self- and cross-pollination. A pool of SI-related signaling genes and pathways was generated, including genes related to calcium (Ca2+) signaling, protein phosphorylation, plant hormone, reactive oxygen species (ROS), nitric oxide (NO), cytoskeleton, and programmed cell death (PCD). A putative SI response molecular model in sheepgrass was presented. The model shows that SI may trigger a comprehensive calcium- and phytohormone-dominated signaling cascade and activate PCD, which may explain the rapid inhibition of self-pollen tube growth as observed by cytological analyses. These results provided new insight into the molecular mechanisms of sheepgrass (grass family) SI.
Plasticity and Potency of Mammary Stem Cell Subsets During Mammary Gland Development
Authors: Lee Eunmi , Piranlioglu Raziye , Wicha Max S. , Korkaya Hasan
Published: May 2019

It is now widely believed that mammary epithelial cell plasticity, an important physiological process during the stages of mammary gland development, is exploited by the malignant cells for their successful disease progression. Normal mammary epithelial cells are heterogeneous and organized in hierarchical fashion, in which the mammary stem cells (MaSC) lie at the apex with regenerative capacity as well as plasticity. Despite the fact that the majority of studies supported the existence of multipotent MaSCs giving rise to both basal and luminal lineages, others proposed lineage restricted unipotent MaSCs. Consistent with the notion, the latest research has suggested that although normal MaSC subsets mainly stay in a quiescent state, they differ in their reconstituting ability, spatial localization, and molecular and epigenetic signatures in response to physiological stimuli within the respective microenvironment during the stages of mammary gland development. In this review, we will focus on current research on the biology of normal mammary stem cells with an emphasis on properties of cellular plasticity, self-renewal and quiescence, as well as the role of the microenvironment in regulating these processes. This will include a discussion of normal breast stem cell heterogeneity, stem cell markers, and lineage tracing studies.
A Computation-Efficient Group Key Distribution Protocol Based on a New Secret Sharing Scheme
Authors: Jiao Runhai , Ouyang Hong , Lin Yukun , Luo Yaoming , Li Gang , Jiang Zaiyu , Zheng Qian
Published: May 2019

With the development of 5G and the Internet of Things (IoT), mobile terminals are widely used in various applications under multicast scenarios. However, due to the limited computation resources of mobile terminals, reducing the computation cost of members in group key distribution processes of dynamic groups has become an important issue. In this paper, we propose a computation-efficient group key distribution (CEGKD) protocol. First, an improved secret sharing scheme is proposed to construct faster encryption and decryption algorithms. Second, the tree structure of logical key hierarchy (LKH) is employed to implement a simple and effective key-numbering method. Theoretical analysis is given to prove that the proposed protocol meets forward security and backward security. In addition, the experiment results show that the computation cost of CEGKD on the member side is reduced by more than 85% compared with that of the LKH scheme.
Raspberry as a Source for the Development of Drosophila suzukii Attractants: Laboratory and Commercial Polytunnel Trials
Authors: Lasa Rodrigo , Toledo-Hernández Ricardo A. , Rodríguez Douglas , Williams Trevor
Published: May 2019

Several commercial products and home-made attractants have been developed for monitoring and mass-trapping of the spotted wing drosophila, Drosophila suzukii. Growers in Mexico have adopted an attractant based on a fermenting mixture of raspberry pulp and sucrose, with anecdotally promising results. We compared the capture rates of traps baited with raspberry pulp + sucrose with captures from a range of alternative attractants. Raspberry pulp alone or with sucrose was more attractive than apple cider vinegar (ACV) or SuzukiiTrap and similar to baker’s yeast + sucrose in laboratory cage studies. Synthetic raspberry aroma (0.1–10% concentration), in water or mixed with ACV, did not improve capture rates in the laboratory. Traps baited with raspberry + sucrose or ACV had similar captures of D. suzukii in raspberry or blackberry polytunnels in Michoacán, Mexico. Raspberry + sucrose baited traps captured significantly higher numbers of other drosophilid species, leading to higher total numbers of captured flies (all species), which may explain why Mexican growers favor the raspberry-based attractant. The commercial products SuzukiiTrap and Z-Kinol had lower captures than ACV in polytunnels, although SuzukiiTrap had the highest selectivity in captures of D. suzukii (81% of flies captured). A two-component trap (2C trap) baited with ACV + ethanol as the drowning solution and raspberry pulp + sucrose or baker’s yeast + sucrose in a ventilated tube device was markedly more effective than the trap currently used by growers. We conclude that raspberry pulp + sucrose is as effective for the attraction of D. suzukii as ACV under commercial polytunnel conditions. The 2C trap performed better than the transparent cup trap currently used by berry producers in Mexico.