bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding competing endogenous RNA networks for cancer biomarker discovery
Authors: Qi Xin , Lin Yuxin , Chen Jiajia , Shen Bairong 
Published: January 2019

Abstract
Crosstalk between competing endogenous RNAs (ceRNAs) is mediated by shared microRNAs (miRNAs) and plays important roles both in normal physiology and tumorigenesis; thus, it is attractive for systems-level decoding of gene regulation. As ceRNA networks link the function of miRNAs with that of transcripts sharing the same miRNA response elements (MREs), e.g. pseudogenes, competing mRNAs, long non-coding RNAs, and circular RNAs, the perturbation of crucial interactions in ceRNA networks may contribute to carcinogenesis by affecting the balance of cellular regulatory system. Therefore, discovering biomarkers that indicate cancer initiation, development, and/or therapeutic responses via reconstructing and analyzing ceRNA networks is of clinical significance. In this review, the regulatory function of ceRNAs in cancer and crucial determinants of ceRNA crosstalk are firstly discussed to gain a global understanding of ceRNA-mediated carcinogenesis. Then, computational and experimental approaches for ceRNA network reconstruction and ceRNA validation, respectively, are described from a systems biology perspective. We focus on strategies for biomarker identification based on analyzing ceRNA networks and highlight the translational applications of ceRNA biomarkers for cancer management. This article will shed light on the significance of miRNA-mediated ceRNA interactions and provide important clues for discovering ceRNA network-based biomarker in cancer biology, thereby accelerating the pace of precision medicine and healthcare for cancer patients.
The Adipokine Metrnl Ameliorates Chronic Colitis in Il-10–/– Mice by Attenuating Mesenteric Adipose Tissue Lesions During Spontaneous Colitis
Authors: Zuo Lugen , Ge Sitang , Ge Yuanyuan , Li Jingjing , Zhu Bing , Zhang Zongbing , Jiang Congqiao , Li Jing , Wang Suanhu , Liu Mulin , Li Shiqing , Wu Rong , Hu Jianguo 
Published: January 2019

Abstract

Background
Crosstalk between mesenteric adipose tissue [MAT] and the intestines affects the progression of Crohn’s disease [CD]. The adipokine metrnl regulates adipocyte function and has anti-inflammatory activity. We aimed to explore metrnl expression in CD MAT, investigate the influence of metrnl on the experimental colitis disease course and determine the mechanism underlying this effect.

Methods
Metrnl expression in MAT specimens obtained from patients with and without CD was tested by immunohistochemistry. Male Il-10–/– mice with spontaneous enteritis were divided into positive control and metrnl-treated [Metrnl-Fc, 10 mg/kg/d, intraperitoneally, 8 weeks] groups. Age-matched male wild-type [WT] mice were used as negative controls. The effects of metrnl on enteritis and mesenteric lesions and the potential controlling mechanisms were evaluated.

Results
Metrnl expression was higher in human CD MAT than in control MAT. Systemic delivery of metrnl significantly ameliorated chronic colitis in Il-10–/– mice, as demonstrated by decreases in the disease activity index, inflammatory score and proinflammatory mediators. The protective effects of metrnl on MAT included reduced mesenteric hypertrophy, increased adipocyte size, improved adipocyte intrinsic function and ameliorated inflammation. Metrnl treatment activated STAT5/PPAR-γ signaling and promoted adipocyte differentiation in the MAT.

Conclusions
Metrnl expression was increased in the MAT of CD patients. Metrnl administration attenuated mesenteric lesions by promoting adipocyte function and differentiation partly through STAT5/PPAR-γ signaling pathway activation, thereby ameliorating CD-like colitis in mice.
Role of non-active site residues in maintaining New Delhi metallo-β-lactamase-1(NDM-1) function: an approach of site-directed mutagenesis and docking
Authors: Ali Abid , Gupta Divya , Khan Asad U 
Published: January 2019

Abstract
New Delhi metallo-β-lactamase-1 (NDM-1) has been known to hydrolyze nearly all β-lactam antibiotics, leading to a multidrug-resistant state. Hence, it is important to study its structure and function in relation to controlling infections caused by such resistant bacterial strains. Mutagenesis is one of the approaches used to explore it. No study has been performed to explore the role of non-active site residues in the enzyme activity. This study includes mutations of three non-active site residues to comprehend its structure and function simultaneously. Three non-active site laboratory mutants of NDM-1 were generated by site-directed mutagenesis. The minimum inhibitory concentrations of cefotaxime, cefoxitin, imipenem and meropenem were reduced by up to 4-fold for these mutants compared with wild-type. The hydrolytic activity of mutants was also found to be reduced. Mutants showed a significant change in secondary structure compared with wild-type, as determined by CD spectrophotometry. The catalytic properties and stability of these mutants were found to be reduced. Hence, it revealed an imperative role of non-active site residues in the enzymatic activity of NDM-1.
Eradicating Measles: A Call for an Exceptional Coordinated Global Effort
Authors: Durrheim David N , Andrus Jon K , Pfaff Günter , Tabassum Shahina , Bashour Hyam , Githanga David 
Published: January 2019

Abstract
There are compelling epidemiological, economic, and ethical arguments for setting a global measles eradication goal. The 6 chairpersons of Regional Verification Commissions for Measles and Rubella elimination advocate that the time for courageously accelerating efforts to ensure a world where no child dies of measles, is NOW!
Examining residual spatial correlation in variation partitioning of beta diversity in a subtropical forest
Authors: Cao Ke , Mi Xiangcheng , Zhang Liwen , Ren Haibao , Yu Mingjian , Chen Jianhua , Zhang Jintun , Ma Keping 
Published: January 2019

Abstract

Aims
The relative roles of ecological processes in structuring beta diversity are usually quantified by variation partitioning of beta diversity with respect to environmental and spatial variables or gamma diversity. However, if important environmental or spatial factors are omitted, or a scale mismatch occurs in the analysis, unaccounted spatial correlation will appear in the residual errors and lead to residual spatial correlation and problematic inferences.

Methods
Multi-scale ordination (MSO) partitions the canonical ordination results by distance into a set of empirical variograms which characterize the spatial structures of explanatory, conditional and residual variance against distance. Then these variance components can be used to diagnose residual spatial correlation by checking assumptions related to geostatistics or regression analysis. In this paper, we first illustrate the performance of MSO using a simulated data set with known properties, thus making statistical issues explicit. We then test for significant residual spatial correlation in beta diversity analyses of the Gutianshan (GTS) 24-ha subtropical forest plot in eastern China.

Important Findings
Even though we used up to 24 topographic and edaphic variables mapped at high resolution and spatial variables representing spatial structures at all scales, we still found significant residual spatial correlation at the 10 m × 10 m quadrat scale. This invalidated the analysis and inferences at this scale. We also show that MSO provides a complementary tool to test for significant residual spatial correlation in beta diversity analyses. Our results provided a strong argument supporting the need to test for significant residual spatial correlation before interpreting the results of beta diversity analyses.
The MHC class-II HLA-DR receptor mediates bat influenza A-like H17N10 virus entry into mammalian cells
Authors: Giotis Efstathios S , Carnell George , Young Erik F. , Ghanny Saleena , Soteropoulos Patricia , Barclay Wendy S , Skinner Michael A , Temperton Nigel 
Published: January 2019

AbstractBats are notorious reservoirs of diverse, potentially zoonotic viruses, exemplified by the evolutionarily distinct, influenza A-like viruses H17N10 and H18N11 (BatIVs). The surface glycoproteins [haemagglutinin (H) and neuraminidase (N)] of BatIVs neither bind nor cleave sialic acid receptors, which suggests that these viruses employ cell attachment and entry mechanisms that differ from those of classical influenza A viruses (IAVs). Identifying the cellular factors that mediate entry and determine susceptibility to infection will help assess the host range of BatIVs. Here, we investigated a range of cell lines from different species for their susceptibility to infection by pseudotyped viruses (PV) bearing bat H17 and/or N10 envelope glycoproteins. We show that a number of human haematopoietic cancer cell lines and the canine kidney MDCK II (but not MDCK I) cells are susceptible to H17-pseudotypes (H17-PV). We observed with microarrays and qRT-PCR that the dog leukocyte antigen DLA-DRA mRNA is over expressed in late passaged parental MDCK and commercial MDCK II cells, compared to early passaged parental MDCK and MDCK I cells, respectively. The human orthologue HLA-DRA encodes the alpha subunit of the MHC class II HLA-DR antigen-binding heterodimer. Small interfering RNA- or neutralizing antibody-targeting HLA-DRA, drastically reduced the susceptibility of Raji B cells to H17-PV. Conversely, over expression of HLA-DRA and its paralogue HLA-DRB1 on the surface of the unsusceptible HEK293T/17 cells conferred susceptibility to H17-PV. The identification of HLA-DR as an H17N10 entry mediator will contribute to a better understanding of the tropism of the virus and will elucidate its zoonotic transmission.
Management of family relationship information for a three-generation cohort study
Authors: Shimokawa Kazuro , Ishikuro Mami , Obara Taku , Metoki Hirohito , Mizuno Satoshi , Nagaie Satoshi , Nagai Masato , Yamanaka Chizuru , Matsubara Hiroko , Kato Mayumi , Sato Yuki , Ogishima Soichi , Takai-Igarashi Takako , Kikuya Masahiro , Hozawa Atsushi , Nagami Fuji , Kuriyama Shinichi , Kinoshita Kengo , Yamamoto Masayuki , Tanaka Hiroshi 
Published: January 2019

AbstractA system for inputting and storing family information, named “BirThree Enrollment,” was developed to promote a birth and three-generation cohort study (BirThree Cohort Study), and this system was operated successfully. In the study, it was necessary to satisfy many operational demands. Input information is overwritten and changed continuously. Complex kinship information must be quickly and accurately input and corrected, and information on those families not yet recruited must be retrieved. For these purposes, many devices are needed, from an input interface to the internal data structure. In the field of genetic statistics, a simple standard expressive form is used for describing family structure. This form has sufficient information for genetics; however, we developed this form further for our purposes in conducting the BirThree Cohort Study. To provide information about family roles as required in the BirThree Cohort Study, we expanded the data structure, and constructed the system that is able to be used for the daily operation. In our system, family pedigree information is stored along with initial clinical information, and enabled the input of all self-reported information to the data base. Operators are able to input this family information before the day is out. As a result, when recruitment is completed, family information will be completed concurrently. Therefore, it is possible to immediately know a certain person’s family structure. By using our system, data correction was improved dramatically, and the system was operated successfully. This study is the first report of the method for storing three generations of family data.
Systematic errors in connectivity inferred from activity in strongly coupled recurrent circuits
Authors: Das Abhranil , Fiete Ila R. 
Published: January 2019

AbstractUnderstanding the mechanisms of neural computation and learning will require knowledge of the underlying circuitry. Because it is slow, expensive, or often infeasible to directly measure the wiring diagrams of neural microcircuits, there has long been an interest in estimating them from neural recordings. We show that even sophisticated inference algorithms, applied to large volumes of data from every node in the circuit, are biased toward inferring connections between unconnected but strongly correlated neurons, a situation that is common in strongly recurrent circuits. This e ect, representing a failure to fully “explain away” non-existent connections when correlations are strong, occurs when there is a mismatch between the true network dynamics and the generative model assumed for inference, an inevitable situation when we model the real world. Thus, effective connectivity estimates should be treated with especial caution in strongly connected networks when attempting to infer the mechanistic basis of circuit activity. Finally, we show that activity states of networks injected with strong noise or grossly perturbed away from equilibrium may be a promising way to alleviate the problems of bias error.
Influenza A virus surface proteins are organized to help penetrate host mucus
Authors: Vahey Michael D. , Fletcher Daniel A. 
Published: January 2019

AbstractInfluenza A virus (IAV) enters cells by binding to sialic acid on the cell surface. To accomplish this while avoiding immobilization by sialic acid in host mucus, viruses rely on a balance between the receptor-binding protein hemagglutinin (HA) and the receptor-cleaving protein neuraminidase (NA). Although genetic aspects of this balance are well-characterized, little is known about how the spatial organization of these proteins in the viral envelope may contribute. Using site-specific fluorescent labeling and super-resolution microscopy, we show that HA and NA are asymmetrically distributed on the surface of filamentous viruses, creating an organization of binding and cleaving activities that causes viruses to step consistently away from their NA-rich pole. This Brownian ratchet-like diffusion produces persistent directional mobility that resolves the virus’s conflicting needs to both penetrate mucus and stably attach to the underlying cells, and could contribute to the prevalence of the filamentous phenotype in clinical isolates of IAV.
Comparative analysis of epigenetic aging clocks from CpG characteristics to functional associations
Authors: Liu Zuyun , Leung Diana , Levine Morgan 
Published: January 2019

AbstractTo date, a number of epigenetic clocks have been developed using DNA methylation data, aimed at approximating biological aging in multiple tissues/cells. However, despite the assumption that these clocks are meant to capture the same phenomenon-aging, their correlations with each other are weak, and there is a lack of consistency in their associations with outcomes of aging. Therefore, the goal of this study was to compare and contrast the molecular characteristics and functional associations of 11 existing epigenetic clocks, using data from diverse human tissue and cell types. Results suggest that the CpGs comprised in the various clocks differ in regards to the consistency of their age correlations across tissues/cells. Using microarray expression data from purified CD14+ monocytes, we found that six clocks—Yang, Hannum, Lin, Levine, Horvath1, and Horvath2—has relatively similar transcriptional profiles. Network analysis revealed nine co-expression modules, most of which display robust correlations across various clocks. One significant module—turquoise is involved in mitochondrial translation, gene expression, respiratory chain complex assembly, and oxidative phosphorylation. Finally, using data from 143B cells with chronically depleted mtDNA (rho0) and 143B controls, we found that rho0 cells have more than a three-standard deviation increase in epigenetic age for Levine (p=0.006), Lin (p=0.012), and Yang (p=0.013). In summary, these results demonstrate the shared and contrasting features of existing epigenetic clocks, in regards to the CpG characteristic, tissue specificity, and co-regulatory gene network signatures, and suggesting a link between two hallmarks of aging—epigenetic alterations and mitochondrial dysfunction.
Concurrent Duties
Authors: Taylor Aaron 
Published: January 2019

AbstractThis paper offers an account of concurrent liability, and in particular the existence of, and interaction between, concurrent contractual and non‐contractual duties. It argues for five essential propositions: (1) a defendant can owe simultaneous private law duties towards a claimant, the content of which overlaps in whole or in part; (2) cases of concurrent liability in contract and negligence involve independent duties, which are concurrent but not coextensive; (3) the doctrine of concurrent liability is conceptually distinct from the rule that the claimant must elect between inconsistent remedies; (4) if the defendant commits a wrong in breach of more than one duty, the claimant has a prima facie choice to sue for any of those breaches; and (5) the content of one any duty might affect the content of the other. The last of these principles, it is argued, provide an explanation for the recent decisions in Wellesley Partners v Withers and AIB v Mark Redler.
Reducing Homelessness or Re‐ordering the Deckchairs?
Authors: Cowan Dave 
Published: January 2019

The Homelessness Reduction Act 2017 has come into force trumpeting nothing less than the need for a ‘culture change’ among local housing authorities implementing it. Although it aims to reduce homelessness, it is more likely to hide long‐term systemic issues in the housing system. It is argued that the 2017 Act's significant alterations are likely to result in a re‐ordering of the deckchairs on the Titanic of housing policy. Following a biography and critique of the homelessness legislation as being out of time and place, as well as a discussion of the 2017 Act itself, three central points are made: the 2017 Act has ushered in a form of neo‐liberal government of the homeless; the understanding of the household seeking assistance has fundamentally altered, from passive applicant to active citizen; the private rented market provides the sole mechanism for performing the duties but remains problematic.
895. PEREZIA RECURVATA SUBSP. RECURVATA
Authors: Hind Nicholas , Babel Katarzyna 
Published: January 2019

SummaryPerezia recurvata (Vahl) Less. subsp. recurvata (Compositae: Mutisieae: Nassuaviinae) is described and illustrated. Comments are provided on its cultivation, propagation and availability, although currently only available from one supplier in the United Kingdom. The problematic taxonomy of this genus is discussed. A brief comment is made on the history of the type collections of two synonyms of Perezia recurvata, and of Perdicium L. within which Vahl originally described the basionym of Perezia recurvata. The adaptive anatomy of the leaves of Perezia recurvata are commented on and likened to those found in Nassauvia falklandica, and the presence of the unique group of phytochemical compounds, the recurvatianes, is mentioned.
Agricultural Use of Reclaimed Water in Florida: Food for Thought
Authors: Parsons Lawrence R. 
Published: January 2019

AbstractFlorida has successfully irrigated agricultural crops with reclaimed water (RW) for more than 50 years. Florida and California are the two largest producers and users of RW in the U.S. To allay early fears about RW, Florida regulatory agencies established rules in the 1980s that prohibited direct contact of RW with crops that are not processed but eaten raw. This means that RW cannot be used for direct contact irrigation or frost protection of crops such as strawberries or blueberries. Other states do not have such limitations on RW use. Reclaimed water has an excellent safety record, and no health problems have occurred from its use. The main edible crop that uses RW in Florida is citrus. Reclaimed water contains some macro‐ and micronutrients, but can provide only a small amount of nitrogen (N) to citrus. Some RW sources can provide adequate N to turf grass. Reclaimed water production has increased dramatically in the past 20 years, and much of the increased flow has gone to public access irrigation. While still important, agricultural use of RW as a percentage of total flow may continue to decrease, but the supply of RW continues to grow as Florida’s population increases.
Water Chemistry During Baseflow Helps Inform Watershed Management: A Case Study of the Lake Wister Watershed, Oklahoma
Authors: Austin Bradley J. , Patterson Steve , Haggard Brian E. 
Published: January 2019

AbstractNonpoint source (NPS) pollution from agricultural and urban development is a primary source of nutrients and decreased water quality in aquatic systems. Installation of best management practices (BMPs) within critical source areas of the watershed can be helpful at reducing the transport of nutrients to waterbodies; however, prioritizing these areas may be difficult. The objective of this study was to develop several potential frameworks for prioritizing subwatersheds using baseflow water chemistry data in relation to a simple human development index (HDI; total percent agriculture and urban development). At a monthly interval, samples were collected at 26 sites throughout the Oklahoma portion of the Lake Wister Watershed (LWW) and analyzed for total nitrogen, total phosphorus, total suspended solids, and chlorophyll a. Changepoint analysis for each parameter found significant thresholds for each of the parameters ranging from 20 to 30% HDI. Changepoint analysis summary statistics were used to develop prioritization frameworks for the LWW that could be used to target subwatersheds where BMP installation would have the greatest effect at improving water quality. Additionally, regression models developed from the relationships between water quality parameters and HDI values serve as realistic targets for improving water quality, with the modeled line representing the target concentration for a given HDI value. After BMPs have been implemented, baseflow monitoring should continue at the subwatershed scale to track changes in water quality. Focusing monitoring efforts at the subwatershed scale will provide an earlier indication of the effectiveness of BMPs, as it may take several decades to detect improvements in water quality at the larger watershed scale.
Food Security as a Water Grand Challenge
Authors: Bangira Courage 
Published: January 2019

AbstractPerhaps the biggest challenge the world faces is providing sufficient, nutritious, and safe food at the right time for its ever‐increasing population. Considering current world population growth trends, it is estimated that the global population will be about 10 billion by the year 2050. Therefore, food production should at least double in the same period if food security is to be satisfied. Water and land resources play a pivotal role in agriculture and directly connect to food security. At the same time, the capacity to produce food is constrained by global climate changes and increased pressure on land resources. These challenges are more severe in Southern Asia, Sub‐Saharan Africa, and East Asia, where conflict and lack of capacity to fund agricultural research and food production are common. Strategies that simultaneously increase food production and reduce threats to food security are therefore needed. The objectives of this paper are to review the grand challenges of global food security and to propose strategies for mitigating food insecurity, with an emphasis on the link between water resources and food production.