bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programming chain-growth copolymerization of DNA hairpin tiles for in-vitro hierarchical supramolecular organization
Authors: Zhang Honglu , Wang Yu , Zhang Huan , Liu Xiaoguo , Lee Antony , Huang Qiuling , Wang Fei , Chao Jie , Liu Huajie , Li Jiang , Shi Jiye , Zuo Xiaolei , Wang Lihua , Wang Lianhui , Cao Xiaoyu , Bustamante Carlos , Tian Zhongqun , Fan Chunhai 
Published: March 2019

AbstractFormation of biological filaments via intracellular supramolecular polymerization of proteins or protein/nucleic acid complexes is under programmable and spatiotemporal control to maintain cellular and genomic integrity. Here we devise a bioinspired, catassembly-like isothermal chain-growth approach to copolymerize DNA hairpin tiles (DHTs) into nanofilaments with desirable composition, chain length and function. By designing metastable DNA hairpins with shape-defining intramolecular hydrogen bonds, we generate two types of DHT monomers for copolymerization with high cooperativity and low dispersity indexes. Quantitative single-molecule dissection methods reveal that catalytic opening of a DHT motif harbouring a toehold triggers successive branch migration, which autonomously propagates to form copolymers with alternate tile units. We find that these shape-defined supramolecular nanostructures become substrates for efficient endocytosis by living mammalian cells in a stiffness-dependent manner. Hence, this catassembly-like in-vitro reconstruction approach provides clues for understanding structure-function relationship of biological filaments under physiological and pathological conditions.
Differential metabolic activity and discovery of therapeutic targets using summarized metabolic pathway models
Authors: Çubuk Cankut , Hidalgo Marta R. , Amadoz Alicia , Rian Kinza , Salavert Francisco , Pujana Miguel A. , Mateo Francesca , Herranz Carmen , Carbonell-Caballero Jose , Dopazo Joaquín 
Published: March 2019

AbstractIn spite of the increasing availability of genomic and transcriptomic data, there is still a gap between the detection of perturbations in gene expression and the understanding of their contribution to the molecular mechanisms that ultimately account for the phenotype studied. Alterations in the metabolism are behind the initiation and progression of many diseases, including cancer. The wealth of available knowledge on metabolic processes can therefore be used to derive mechanistic models that link gene expression perturbations to changes in metabolic activity that provide relevant clues on molecular mechanisms of disease and drug modes of action (MoA). In particular, pathway modules, which recapitulate the main aspects of metabolism, are especially suitable for this type of modeling. We present Metabolizer, a web-based application that offers an intuitive, easy-to-use interactive interface to analyze differences in pathway metabolic module activities that can also be used for class prediction and in silico prediction of knock-out (KO) effects. Moreover, Metabolizer can automatically predict the optimal KO intervention for restoring a diseased phenotype. We provide different types of validations of some of the predictions made by Metabolizer. Metabolizer is a web tool that allows understanding molecular mechanisms of disease or the MoA of drugs within the context of the metabolism by using gene expression measurements. In addition, this tool automatically suggests potential therapeutic targets for individualized therapeutic interventions.
Human causes of soil loss in rural karst environments: a case study of Guizhou, China
Authors: Zhao Longshan , Hou Rui 
Published: March 2019

AbstractRocky desertification induced by soil loss is a serious ecological problem in karst mountain areas. Lack of awareness in the local population of the need for soil conservation has led to intense human disturbance that has accelerated soil loss and in turn caused a high proportion of land in rural environments to undergo rocky desertification. In this review, we discuss five human-related causes that have accelerated soil loss in the rural karst mountainous areas of Guizhou Province, southwestern China. These causes include road erosion, house construction, steep slope cultivation, tourism development, and animal trampling. These activities destroy surface vegetation and increase the potential for soil loss through exposed swallow holes (karst fissures). In addition to the national development strategy of rural revitalization and countryside beautification already implemented in the western region, the human impacts on the rural environment must be addressed. We discuss some effective measures the government should adopt to control the various types of soil loss due to human activities. Our review and findings provide a better understanding of anthropogenic soil loss in karst rural environments and present information to raise people’s awareness of measures that are needed to protect the soil resources in this region.
Permanent dry soil layer a critical control on soil desiccation on China’s Loess Plateau
Authors: Zhao Chunlei , Jia Xiaoxu , Gongadze Kate , Shao Ming’an , Wu Lianhai , Zhu Yuanjun 
Published: March 2019

AbstractThe wide spread of dry soil layers (DSL) in China’s Loess Plateau region has negative effects on the ecosystem, including soil degradation and vegetation failure. To understand the temporal persistence of DSL, a ca. 860 km south-north transect was established and soil water content of the 0–5 m depth soil layer repeatedly measured for a period of four years. The results indicated that DSL varied with time and had a distribution area over 21.5–47.0% in the 860 km transect during the study period. The DSL could be divided into temporary and permanent types based on the length of period for which the soil remains dry. While temporary DSL is recoverable, permanent DSL (which existed in 47 out of 86 sites) was apparently unrecoverable as it persisted throughout the observation period. Permanent DSL was characterized by high temporal persistence, severe soil desiccation and thick dry layers; all of which suggested severe negative effect on the ecosystem. Non-climatic factors, rather than climate factors, contributed more to the formation of permanent DSL in the study area. Thus, it was suggested that policies and measures should be enacted to control especially permanent DSL formation in the region.
Anti-VEGF injection frequency correlates with visual acuity outcomes in pro re nata neovascular AMD treatment
Authors: Wecker Thomas , Grundel Bastian , Reichl Sabine , Stech Milena , Lange Clemens , Agostini Hansjürgen , Böhringer Daniel , Stahl Andreas 
Published: March 2019

AbstractClinical trials report substantial gains in visual acuity (VA) for eyes treated with intravitreal anti-VEGF for neovascular AMD (nAMD). In clinical reality, VA outcomes are more variable. Here we investigate pro-re nata treatment frequencies and VA in a real-life cohort of 1382 eyes (1048 patients). Patients with nAMD and one year complete follow-up treated with pro-re nata anti-VEGF between 2009 and 2016 were included. Injection frequency and VA was analyzed clustered by year of first treatment. Baseline parameters were compared between years. Median injection frequency in the first year was 5 with an IQR (interquartile range) of 5 for patients treated in 2009 and 8 with an IQR of 3 for patients treated from 2012 onwards. Median VA outcomes at one year were −5 to ±0 letters for patients treated between 2009 and 2013 and ±0 to +2 letters for patients treated from 2013 onwards. This cohort comprises all severities and subtypes of nAMD. 39% of patients had baseline VA outside the range for the MARINA or ANCHOR clinical trials. Higher treatment frequency was associated with improved VA in our real-life nAMD cohort. With adequate injection frequency, almost 90% of eyes had stable or improved VA over one year. Median VA gains, however, were lower compared to clinical trials. This may be due to a wider range of baseline characteristics in real-life cohorts.
Alterations of Sphingolipid Metabolism in Different Types of Polycystic Ovary Syndrome
Authors: Li Juan , Xie Li-Min , Song Jin-Long , Yau Lee-Fong , Mi Jia-Ning , Zhang Chun-Ren , Wu Wan-Ting , Lai Mao-Hua , Jiang Zhi-Hong , Wang Jing-Rong , Ma Hong-Xia 
Published: March 2019

AbstractThe roles of sphingolipids in polycystic ovary syndrome (PCOS) are still unknown. This study aimed to investigate the sphingolipid characteristics for different types of PCOS using liquid chromatography-mass spectrometry (LC-MS). A total of 107 women with PCOS and 37 healthy women as normal controls were studied. PCOS patients were further classified into non-obesity with insulin resistance (IR) (NOIR), obesity with IR (OIR), and non-obesity and non-IR (NIR) subgroups. A total of 87 serum sphingolipids, including 9 sphingosines, 3 sphinganines, 1 sphingosine-1-phosphate (S1P), 19 ceramides (Cers), 1 ceramide-1-phosphate, 44 sphingomyelins (SMs), 4 hexosylceramides, and 6 lactosylceramides (LacCers) were analyzed using an improved sphingolipidomic approach based on LC-MS. Notable elevations in the levels of S1P, Cer, and SM were observed in PCOS patients when compared with healthy women, and SM species with long saturated acyl chains showed potential as novel biomarkers of PCOS. In addition, the level of LacCer was only elevated in NIR, and there was almost no change in NOIR and OIR. This study is the first to report the comprehensive sphingolipidomic profiling of different subgroups of PCOS with or without IR or obesity and suggests that serum sphingolipids might be useful as diagnostic biomarkers for different types of PCOS.
Designing a whole cell bioreporter to show antioxidant activities of agents that work by promotion of the KEAP1–NRF2 signaling pathway
Authors: Mozaheb Negar , Arefian Ehsan , Amoozegar Mohammad Ali 
Published: March 2019

AbstractThe major signaling pathway in human cells is related to the antioxidant defense system. The main component of this system is a transcription factor, Nuclear Factor Erythroid 2-Related Factor 2 (NRF2). It regulates this system in different cellular situations under stimulation by oxidative stress or antioxidants. Thus, detecting the stimulation of NRF2 via a screening strategy may enable us to discover stimulating agents of NRF2-related signaling pathway. With this in mind, we designed a whole cell bioreporter containing the NRF2 response elements that are inserted in a luciferase vector, immediately upstream of a luciferase gene whose promoter has been removed. This bioreporter is activated by stimulators such as 3H-1,2-dithiole-3-thione (D3T), butyl hydroxyanisole (BHA) and ascorbic acid reacting as antioxidant agents. It was observed that the regulatory region of the NRF2 gene, which is identified by NRF2 protein, is located inside its coding region. This designed bioreporter can detect the presence of antioxidant agents. It also exhibits a significant linear correlation over different doses of these agents ranging from 0.8 to 80 μM for ascorbic acid, 0.1 to 100 μM for D3T, and 0.1 to 100 μM for BHA. This detection system is proven to be more sensitive than Real-time PCR, suggesting it to be a highly sensitive system among the available methods.
Adsorption of phosphate on iron oxide doped halloysite nanotubes
Authors: Almasri Dema A. , Saleh Navid B. , Atieh Muataz A. , McKay Gordon , Ahzi Said 
Published: March 2019

AbstractExcess phosphate in water is known to cause eutrophication, and its removal is imperative. Nanoclay minerals are widely used in environmental remediation due to their low-cost, adequate availability, environmental compatibility, and adsorption efficiency. However, the removal of anions with nanoclays is not very effective because of electrostatic repulsion from clay surfaces with a net negative charge. Among clay minerals, halloysite nanotubes (HNTs) possess a negatively charged exterior and a positively charged inner lumen. This provides an increased affinity for anion removal. In this study, HNTs are modified with nano-scale iron oxide (Fe2O3) to enhance the adsorption capacity of the nanosorbent. This modification allowed for effective distribution of these oxide surfaces, which are known to sorb phosphate via ligand exchange and by forming inner-sphere complexes. A detailed characterization of the raw and (Fe2O3) modified HNTs (Fe-HNT) is conducted. Influences of Fe2O3loading, adsorbent dosage, contact time, pH, initial phosphate concentration, and coexisting ions on the phosphate adsorption capacity are studied. Results demonstrate that adsorption on Fe-HNT is pH-dependent with fast initial adsorption kinetics. The underlying mechanism is identified as a combination of electrostatic attraction, ligand exchange, and Lewis acid-base interactions. The nanomaterial provides promising results for its application in water/wastewater treatment.
Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Patients with Cervical Cancer
Authors: Huang Huaping , Liu Qin , Zhu Lixia , Zhang Yan , Lu Xiaojuan , Wu Yawei , Liu Li 
Published: March 2019

AbstractThe systemic immune-inflammation index (SII) based on peripheral lymphocyte, neutrophil and platelet counts has been considered a good index that reflects the local immune response and systemic inflammation. However, the use of the SII has not been reported in cervical cancer. In this study, Kaplan-Meier survival analysis showed that a high SII was associated with poor prognosis in cervical cancer patients in the primary and validation cohorts. A higher SII had a significant correlation with larger tumours but had no correlation with other clinicopathological parameters. Among all systemic immune indexes, the SII is the only independent prognostic factor for cervical cancer patients. Compared with the area under the curve for the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR), the area for the SII was larger at 3 and 5 years. In addition, the SII still retains it prognostic values across all FIGO stages. The SII can independently predict the overall survival of patients with cervical cancer receiving radical resection and is thus superior to existing systemic inflammatory indexes. The prognostic nomogram based on the SII is a reliable model for predicting the postoperative survival of patients with cervical cancer.
Identification of key lncRNAs contributing to diabetic nephropathy by gene co-expression network analysis
Authors: Shang Jin , Wang Shuai , Jiang Yumin , Duan Yiqi , Cheng Genyang , Liu Dong , Xiao Jing , Zhao Zhanzheng 
Published: March 2019

AbstractLncRNA is reported to have important role in diabetic nephropathy (DN). Here, we aim to identify key lncRNAs of DN using bioinformatics and systems biological methods. Method: Five microarray data sets from Gene Expression Omnibus (GEO) database were included. Probe sets were re-annotated. In the training set, differential expressed genes (DEGs) were identified. Weighted gene co-expression network analysis (WGCNA) was constructed to screen diabetic-related hub genes and reveal their potential biological function. Two more human data sets and mouse data sets were used as validation sets. Results: A total of 424 DEGs, including 10 lncRNAs, were filtered in the training data set. WGCNA and enrichment analysis of hub genes showed that inflammation and metabolic disorders are prominent in DN. Three key lncRNAs (NR_130134.1, NR_029395.1 and NR_038335.1) were identified. These lncRNAs are also differently expressed in another two human data sets. Functional enrichment of the mouse data sets showed consistent changes with that in human, indicating similar changes in gene expression pattern of DN and confirmed confidence of our analysis. Human podocytes and mesangial cells were culture in vitro. QPCR and fluorescence in situ hybridization were taken out to validate the expression and relationship of key lncRNAs and their related mRNAs. Results were also consistent with our analysis. Conclusions: Inflammation and metabolic disorders are prominent in DN. We identify three lncRNAs that are involved in these processes possibly by interacting with co-expressed mRNAs.
Modelling environmentally suitable areas for the potential introduction and cultivation of the emerging oil crop Paeonia ostii in China
Authors: Peng Li-Ping , Cheng Fang-Yun , Hu Xian-Ge , Mao Jian-Feng , Xu Xing-Xing , Zhong Yuan , Li San-Yuan , Xian Hong-Li 
Published: March 2019

AbstractPaeonia ostii is a traditional ornamental and medicinal species that has attracted considerable interest for its high oil value. To facilitate the effective and rational cultivation and application of P. ostii in China, it is necessary to determine its potential spatial habitat distribution and environmental requirements. Using high-resolution environmental data for current and future climate scenarios, the potential suitable area and climatic requirements of P. ostii were modelled. Among the 11 environmental variables investigated, growing degree days, precipitation of the wettest month, mean temperature of the coldest quarter, global UV-B radiation, annual precipitation, and soil pH played major roles in determining the suitability of a habitat for the cultivation of P. ostii. Under the current environmental conditions in China, a total area of 20.31 × 105 km2 is suitable for growing P. ostii, accounting for 21.16% of the country’s total land area. Under the two future climate scenario/year combinations (i.e., representative concentration pathways [RCPs], RCP2.6 and RCP8.5 in 2050), this species would increase its suitable area at high latitudes while decrease at low latitudes. These results present valuable information and a theoretical reference point for identifying the suitable cultivation areas of P. ostii.
Infants’ advances in speech perception shape their earliest links between language and cognition
Authors: Perszyk Danielle R. , Waxman Sandra R. 
Published: March 2019

AbstractThe power of human language derives not only from the precision of its signal or the complexity of its grammar, but also from its links to cognition. Infants as young as 3 months have begun to link language and core cognitive capacities. At 3 and 4 months, this link is not exclusive to human language: listening to vocalizations of nonhuman primates also supports infant cognition. By 6 months, infants have tuned this link to human speech alone. Here we provide evidence that infants’ increasing precision in speech perception shapes which signals they will link to cognition. Infants listening to German, a nonnative language that shares key rhythmic and prosodic properties with their own native language (English), successfully formed object categories. In contrast, those listening to Cantonese, a language that differs considerably in these suprasegmental properties, failed. This provides the first evidence that infants’ increasingly precise perceptual tuning to the sounds of their native language sets constraints on the range of human languages they will link to cognition: infants begin to specify which human languages they will link to core cognitive capacities even before they sever the link between nonhuman primate vocalizations and cognition.
Activation of the PERK-ATF4 pathway promotes chemo-resistance in colon cancer cells
Authors: Shi Zhong , Yu Xiaofu , Yuan Meiqin , Lv Wangxia , Feng Tingting , Bai Rui , Zhong Haijun 
Published: March 2019

AbstractColon cancer is a major health problem worldwide. While chemotherapy remains a main approach for treating late-stage colon cancer patients, most, if not all, of them will develop drug resistance and die of uncontrollable disease progression eventually. Therefore, identification of mechanism of drug resistance and development of overcoming strategy hold great significance in management of colon cancer. In this study, we discovered that activation of the PERK branch of the unfolded protein response (UPR) pathways is required for colon cancer cells to survive treatment of 5-Fluorouracil (5-FU), one of the first-line chemotherapeutics for late-stage colon cancer patients. Genetic and pharmacological inhibition of PERK or its downstream factors greatly sensitize colon cancer cells to 5-FU. Most importantly, in vivo use of PERK inhibitor synergizes with 5-FU in suppressing the growth of colon cancer cells in mouse models. In summary, our findings established a promising way to overcome resistance to chemotherapy in colon cancer.
Mutations in DNA repair genes are associated with increased neoantigen burden and a distinct immunophenotype in lung squamous cell carcinoma
Authors: Chae Young Kwang , Anker Jonathan F. , Oh Michael S. , Bais Preeti , Namburi Sandeep , Agte Sarita , Giles Francis J. , Chuang Jeffrey H. 
Published: March 2019

AbstractDeficiencies in DNA repair pathways, including mismatch repair (MMR), have been linked to higher tumor mutation burden and improved response to immune checkpoint inhibitors. However, the significance of MMR mutations in lung cancer has not been well characterized, and the relevance of other processes, including homologous recombination (HR) and polymerase epsilon (POLE) activity, remains unclear. Here, we analyzed a dataset of lung squamous cell carcinoma samples from The Cancer Genome Atlas. Variants in DNA repair genes were associated with increased tumor mutation and neoantigen burden, which in turn were linked with greater tumor infiltration by activated T cells. The subset of tumors with DNA repair gene variants but without T cell infiltration exhibited upregulation of TGF-β and Wnt pathway genes, and a combined score incorporating these genes and DNA repair status accurately predicted immune cell infiltration. Finally, high neoantigen burden was positively associated with genes related to cytolytic activity and immune checkpoints. These findings provide evidence that DNA repair pathway defects and immunomodulatory genes together lead to specific immunophenotypes in lung squamous cell carcinoma and could potentially serve as biomarkers for immunotherapy.
3-Dimensional characterization of cortical bone microdamage following placement of orthodontic microimplants using Optical Coherence Tomography
Authors: Lakshmikantha Hemanth Tumkur , Ravichandran Naresh Kumar , Jeon Mansik , Kim Jeehyun , Park Hyo-Sang 
Published: March 2019

AbstractMicroimplants are being used extensively in clinical practice to achieve absolute anchorage. Success of microimplant mainly depend on its primary stability onto the cortical bone surface and the associated Microdamage of the cortical bone during insertion procedure leads to many a microimplants to fail and dislodge from the cortical bone leading to its failure. Even though, previous studies showed occurrence of microdamage in the cortical bone, they were mainly 2-dimension studies or studies that were invasive to the host. In the present study, we used a non-invasive, non-ionizing imaging technique- Optical Coherence Tomography (OCT), to image and analyze the presence of microdamage along the cortical bone surrounding the microimplant. We inserted 80 microimplants in two different methods (drill and drill free method) and in two different angulations onto the cortical bone surface. Images were obtained in both 2D and 3D imaging modes. In the images, microdamage in form of microcracks on the cortical bone surface around the bone-microimplant interface and micro-elevations of the cortical bone in angulated microimplant insertions and the presence of bone debris due to screwing motion of the microimplant on insertion can be appreciated visually and quantitatively through the depth intensity profile analysis of the images.