bluuebunny/crossref_metadata_2025_split huggingface dataset:
A negative autoregulation network motif is required for synchronizedMyxococcus xanthusdevelopment
Authors: McLaughlin Maeve , Higgs Penelope I. 
Published: August 2019

AbstractTranscription factor autoregulation is a simple network motif (recurring circuit) built into genetic regulatory networks that direct cell behavior. Negative autoregulation (NAR) network motifs are particularly abundant in bacteria and provide specific functions, such as buffering against transcriptional noise. Here, we investigate the phenotypic consequence of perturbing NAR of a major transcription factor, MrpC, that controls the multicellular development program of the bacteriumMyxococcus xanthus. Launch of the developmental program directs certain cells in the population to first aggregate into haystack-shaped mounds, and then to differentiate into environmentally resistant spores to form mature fruiting bodies. Perturbation of MrpC NAR causes a striking phenotype in which cells lose synchronized transition from aggregation to sporulation. Instead, some cells abruptly exit aggregation centers and remain locked in a cohesive swarming state, while the remaining cells transition to spores inside residual fruiting bodies. As predicted, disruption of MrpC NAR led to an increased and broadened population distribution ofmrpCexpression. Examination of MrpC levels in developmental subpopulations duringin situdevelopment demonstrated cells locked in the swarms contained intermediate MrpC levels insufficient to promote sporulation. These results suggest an inherent property of NAR motifs that function in multicellular developmental programs is to facilitate synchronized responses.Significance StatementAll organisms use regulatory networks for cellular homeostasis, mediating appropriate responses to environmental changes, or to direct animal development. Understanding how the basic building blocks (motifs) of regulatory networks contribute to these processes is essential to mitigate the effects of mutations in regulatory networks (i.e.cancers) or to synthesize beneficial organisms. In this study, we demonstrate that a common regulatory motif, a transcription factor that represses its own expression, helps synchronize cells that engage in collective behaviors.
Assessing digital phenotyping to enhance genetic studies of human diseases
Authors: DeBoever Christopher , Tanigawa Yosuke , Aguirre Matthew , McInnes Greg , Lavertu Adam , Rivas Manuel A. 
Published: August 2019

AbstractPopulation-scale biobanks that combine genetic data and high-dimensional phenotyping for a large number of participants provide an exciting opportunity to perform genome-wide association studies (GWAS) to identify genetic variants associated with diverse quantitative traits and diseases. A major challenge for GWAS in population biobanks is ascertaining disease cases from heterogeneous data sources such as hospital records, digital questionnaire responses, or interviews. In this study, we use genetic parameters including genetic correlation to evaluate whether GWAS performed using cases in the UK Biobank ascertained from hospital records, questionnaire responses, and family history of diseases implicate similar disease genetics across a range of effect sizes. We find that hospital record and questionnaire GWAS largely identify similar genetic effects for many complex phenotypes and that combining together both phenotyping methods improves power to detect genetic associations. We also show that family GWAS using cases ascertained on family history of disease agrees with combined hospital record/questionnaire GWAS and that family history GWAS has better power to detect genetic associations for some phenotypes. Overall, this work demonstrates that digital phenotyping and unstructured phenotype data can be combined with structured data such as hospital records to identify cases for GWAS in biobanks and improve the ability of such studies to identify genetic associations.
Quantitative profiling of 1-Carbon Metabolites, Amino Acids and Precursors, and Plasmalogens in human plasma using Ultra-High-Pressure Liquid Chromatography coupled with Tandem Mass Spectrometry and robotic compound extraction
Authors: Andraos Stephanie , Goy Michael , Albert Ben , Kussmann Martin , Thorstensen Eric B. , O’Sullivan Justin M. 
Published: August 2019

AbstractAmino acids (AAs) and one-carbon (1-C) compounds are involved in a range of key metabolic pathways, and mediate numerous health and disease processes in the human body. Previous assays have quantified a limited selection of these compounds. Here, we describe an analytical method for the simultaneous quantification of 37 1-C metabolites, amino acids, precursors, and plasmalogens using reversed-phase ultra-high pressure liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Compound extraction from human plasma was tested manually before being robotically automated. The final analytical panel was validated on human plasma samples. Our automated and multiplexed method holds promise for application to large cohort studies.
Assessment of computational methods for the analysis of single-cell ATAC-seq data
Authors: Chen Huidong , Lareau Caleb , Andreani Tommaso , Vinyard Michael E. , Garcia Sara P. , Clement Kendell , Andrade-Navarro Miguel A , Buenrostro Jason D. , Pinello Luca 
Published: August 2019

AbstractBackgroundRecent innovations in single-cell Assay for Transposase Accessible Chromatin using sequencing (scATAC-seq) enable profiling of the epigenetic landscape of thousands of individual cells. scATAC-seq data analysis presents unique methodological challenges. scATAC-seq experiments sample DNA, which, due to low copy numbers (diploid in humans) lead to inherent data sparsity (1-10% of peaks detected per cell) compared to transcriptomic (scRNA-seq) data (20-50% of expressed genes detected per cell). Such challenges in data generation emphasize the need for informative features to assess cell heterogeneity at the chromatin level.ResultsWe present a benchmarking framework that was applied to 10 computational methods for scATAC-seq on 13 synthetic and real datasets from different assays, profiling cell types from diverse tissues and organisms. Methods for processing and featurizing scATAC-seq data were evaluated by their ability to discriminate cell types when combined with common unsupervised clustering approaches. We rank evaluated methods and discuss computational challenges associated with scATAC-seq analysis including inherently sparse data, determination of features, peak calling, the effects of sequencing coverage and noise, and clustering performance. Running times and memory requirements are also discussed.ConclusionsThis reference summary of scATAC-seq methods offers recommendations for best practices with consideration for both the non-expert user and the methods developer. Despite variation across methods and datasets, SnapATAC,Cusanovich2018, and cisTopic outperform other methods in separating cell populations of different coverages and noise levels in both synthetic and real datasets. Notably, SnapATAC was the only method able to analyze a large dataset (> 80,000 cells).
The differences between rewilding and restoring an ecologically degraded landscape
Authors: du Toit Johan T. , Pettorelli Nathalie 
Published: August 2019

Abstract

Rewilding is a developing concept in ecosystem stewardship that involves reorganizing and regenerating wildness in an ecologically degraded landscape, with present and future ecosystem function being of higher consideration than historical benchmark conditions. This approach differs from ecosystem restoration but the two concepts are often conflated because (a) they both rely on similar management actions (at least initially) and (b) it can be erroneously assumed that they both aim for similar states of wildness.

Rewilding and restoring both influence biodiversity, and common management actions such as species reintroductions (e.g. beavers or wolves) can be integral to a rewilding project. However, in contrast with restoration, rewilding has lower fidelity to taxonomic precedent and promotes taxonomic substitutions for extinct native species that once underpinned the delivery of key ecological functions.

We suggest the adaptive cycle as the appropriate conceptual framework in which to distinguish rewilding from ecosystem restoration. The focus of restoration ecology is to return an ecosystem to as close to its former state as is possible after a major disturbance, by directly reinstating it on the ‘foreloop’ of the adaptive cycle. In contrast, rewilding draws from the ‘backloop’ by promoting reorganization and redevelopment of the ecosystem under changing environmental conditions. If environmental conditions have changed so significantly that a regime shift is inevitable, then rewilding can facilitate the development of a novel ecosystem to sustain the provision of ecosystem services.

Synthesis and applications. Rewilding and restoring both have their places in biodiversity conservation. In each case, their respective merits should be weighed in relation to stakeholder priorities, prevailing and predicted environmental conditions, the level of biological organization targeted for management, and existing and future management capacity. We provide simple schematic decision‐pathways to assist in exploring whether an ecologically degraded landscape might be a candidate for restoration, active rewilding, or passive rewilding.
The relationship between adult height and diabetes in India: A countrywide cross‐sectional study
Authors: Al Ssabbagh Majd , Geldsetzer Pascal , Bärnighausen Till , Deckert Andreas 
Published: August 2019

AbstractBackgroundOne major aspect of the epidemiological transition happening in India is the increased diabetes prevalence. Poor environmental conditions in early childhood potentially can increase the risk of developing diabetes in adulthood. Adults' height as an indirect indicator might reflect such conditions. In this paper, we investigate the relationship between adult height as a proxy for early childhood conditions and the risk of developing diabetes in India.MethodsThis cross‐sectional study used national representative data of the latest National Family Health Survey (2015‐2016), comprising 512 616 women aged 20 to 49 and 87 281 men aged 20 to 54. We applied the multivariable fractional polynomials approach in logistic regression models to allow for nonlinear relationships between height and diabetes, separated by sex. Additionally, we fitted logistic regression models with height categories. Fixed effects linear probability models were used to control for potential confounding.ResultsThe study revealed a linear relationship between increasing height and increasing diabetes risk among men. Among women, the shortest were at the highest risk (not significant).ConclusionsAmong Indian men, being taller increases the risk of developing diabetes, which contradicts findings from other countries. In contrast, the shortest women seem to be at the greatest risk. Hence, public health interventions in India might be well advised to focus more on the nutrition status of young girls.
Intrauterine inhibition of chemokine receptor 4 signaling modulates local and systemic inflammation in ovine pregnancy
Authors: McIntosh Stacia Z. , Maxam Clara J. , Maestas Marlie M. , Quinn Kelsey E. , Ashley Ryan L. 
Published: August 2019

AbstractProblemChemokines help coordinate inflammation within the fetal‐maternal microenvironment during gestation. The chemokine CXCL12 signaling through its receptor CXCR4 regulates inflammatory activity, but this phenomenon is not well understood during pregnancy, and there are no reports exploring the role of this pair in peripheral immune tolerance during gestation. Herein, we hypothesize that intrauterine CXCL12‐CXCR4 signaling governs local and systemic immunomodulatory dynamics during early gestation in ewes.Method of studyOsmotic pumps were surgically installed for intrauterine infusion of a CXCR4 inhibitor, AMD3100, beginning on day 12 post‐breeding in sheep. Endometrial tissues were collected on day 35 of gestation and evaluated for inflammatory potential, Akt pathway activation, and autophagy induction. Demonstrative of peripheral immune activity, levels of select cytokines were assessed in daily blood samples collected throughout the study, as well as in corpus luteum and spleen on day 35.ResultsAnti‐inflammatory IL10 was primarily localized to endometrial glandular epithelium with lower abundance when CXCR4 was antagonized. Inhibition of CXCR4 at the fetal‐maternal interface resulted in less activation of Akt in endometrium, while evidence of autophagy induction was greater. Corpora lutea from ewes receiving intrauterine AMD3100 exhibited lower interferon‐gamma (IFNG) expression. Blood inflammatory potential was differentially altered in a temporal fashion throughout infusion. IL10 abundance in spleen was greater following CXCR4 inhibition at the fetal‐maternal interface, while IFNG was less.ConclusionIntrauterine CXCL12‐CXCR4 signaling governs endometrial and systemic inflammation; disruption of this axis may have detrimental impacts on offspring and maternal health.
Peripapillary border tissue of the choroid and peripapillary scleral flange in human eyes
Authors: Jonas Rahul A. , Holbach Leonard 
Published: August 2019

AbstractPurposeTo assess dimensions and associations of the peripapillary border tissue of the choroid (PBT‐C) and peripapillary scleral flange (PBT‐S).MethodsThe histomorphometric investigation included histological sections of enucleated eyes of Caucasian patients. Using light microscopy, the PBT dimensions were measured.ResultsThe study included 85 eyes (85 patients) with an age of 62.0 years (14.1 years) (mean (SD)) (range:37–87 years) and mean axial length of 26.7 mm (3.5 mm) (range:21.0–37.0 mm). Thicker PBT‐C thickness (mean: 68.8 μm (35.7 μm)) was associated with shorter axial length (p < 0.001; standardized regression coefficient beta: −0.50), and longer PBT‐C length (mean: 531 μm (802 μm)) was correlated with longer axial length (p < 0.001;beta:0.66). PBT‐C cross‐sectional area (mean 17 050 μm2 (10 420 μm2)) was not significantly associated with axial length (p = 0.37). Decreasing with longer axial length (p < 0.001;beta:0.64), the angle between PBT‐C and Bruch's membrane was approximately 90° in non‐highly myopic eyes without overhanging Bruch's membrane (BM), it ranged between 100° and 180° in eyes with BM overhanging into the intrapapillary region, and it was close to 0° in eyes with parapapillary gamma zone. Thicker thickness of PBT‐S (mean:83 μm (21 μm)) was correlated with presence of glaucoma (p = 0.02). Optic nerve pia mater thickness (mean:109 μm (44 μm)) increased with glaucoma presence (p = 0.046;beta:0.31) but not with axial length (p = 0.34).ConclusionsPeripapillary border tissue of the choroid (PBT‐C) and PBT‐S as continuation of the optic nerve pia mater are distinct structures, with PBT‐C remodelling during myopic axial elongation and PBT‐S being mostly independent of axial elongation. PBT‐C and PBT‐S may be of importance for the optic nerve head biomechanics and PBT‐C for separation of the choroidal space from the intrapapillary compartment.
MMPs, TIMPs and BMP‐4 in medial rectus muscle obtained from intermittent exotropia patients and their clinical correlations
Authors: Lee Yoon Pyo , Choi Dong Gyu 
Published: August 2019

AbstractBackgroundTo measure the amounts of matrix metalloproteinase (MMP)‐2, MMP‐9, tissue inhibitor of metalloproteinase (TIMP)‐1, TIMP‐2 and bone morphogenetic protein (BMP)‐4 in medial rectus muscle (MR) tissue obtained from intermittent exotropia (IXT) patients and to investigate the correlation between each protein amount and the clinical features of IXT including angles of deviation, age at surgery, duration of IXT and postoperative recurrence.MethodsThe protein amounts were measured by enzyme‐linked immunosorbent assay (ELISA) in MR collected during surgery for 78 IXT patients.ResultsThe mean amount of MMP‐2 per mm of resected MR was 0.86 ng, of MMP‐9, 2.72 ng, of TIMP‐1, 1.99 ng, of TIMP‐2, 0.92 ng and of BMP‐4, 0.82 pg. MMP‐2 showed a positive correlation with angle of deviation at distance and at near, age at surgery and duration of IXT (p = 0.000, p = 0.000, p = 0.000, p = 0.022, respectively, Spearman's rank correlation analysis). MMP‐9 showed a positive correlation with angle of deviation at distance and at near (p = 0.001, p = 0.024) and BMP‐4 showed a positive correlation with angle of deviation at distance (p = 0.012). TIMP‐1 showed a negative correlation with angle of deviation at distance and at near (p = 0.003, p = 0.000).ConclusionIn IXT patients, MMPs and BMP‐4 tended to increase and TIMPs to decrease with increasing angle of deviation, greater age at surgery and longer duration of IXT.
Tumour size criteria for Group D and E eyes in the International Classification System for Retinoblastoma: effects on rates of globe salvage and high‐risk histopathologic features
Authors: Kim Jonathan W. , Shah Sona N. , Green Sarah , O'Fee John , Tamrazi Benita , Berry Jesse L. 
Published: August 2019

AbstractPurposeTo determine the significance of large tumour size as a criteria for classifying advanced intraocular retinoblastoma, analysing rates of globe survival and high‐risk (HE) histopathologic features.MethodsRetrospective chart review of 212 eyes diagnosed with Group D (111 eyes) or Group E (101 eyes) retinoblastoma in at least one eye from January 1, 2006 to December 31, 2016 using the Los Angeles (LA) Classification System (no tumour size criteria for Group E). The 111 Group D tumours were then reclassified to Group E using 10, 12, 14, 16, 18 mm tumour size criteria, as determined by ultrasound or magnetic resonance imaging dimensions.ResultsFor eyes in the original LA classification, 66.7% of Group D and 10.5% of Group E eyes undergoing globe preservation therapy avoided enucleation or radiotherapy (p < 0.0001; median follow‐up of 33.0 months). In the LA classification, 8.5% of Group D and 26.3% of Group E enucleated globes had HE histopathologic features (p = 0.0065). When Group D eyes with tumours meeting the size criteria were reclassified to Group E, 65.7–74.4% of Group D and 16.1–36.7% of Group E eyes avoided enucleation or radiotherapy. Applying the tumour size criteria, 0–10.9% of Group D and 20.7–23.8% of Group E eyes had HE histopathologic features.ConclusionOur retrospective analysis suggests that a large tumour size criteria for Group E retinoblastoma have no clinical basis, given that the LA classification system provided the greatest separation in globe salvage rates between Group D and E eyes. The LA classification system was also able to show a statistically significant difference in the rates of HE histopathologic features between Group D and E eyes. To avoid discrepancies in the literature, we recommend that centres use one uniform system for classifying advanced intraocular retinoblastoma.
Prediction of late displacement of the globe in orbital blowout fractures
Authors: Ji Yongrong , Zhou Yixiong , Shen Qin , Xu Wei , Ge Shengfang , Gu Lixu , Fan Xianqun 
Published: August 2019

AbstractPurposeTo establish a linear measuring method in computed tomographic (CT) images to predict the displacement of the globe late after orbital blowout fracture.MethodsSubjects were retrospectively included. Inclusion criteria were as follows: (1) adult subjects (≥18 years old at the time of trauma); (2) unilateral orbital medial‐wall and/or floor fractures; (3) CT examination at least 30 days after trauma. Exclusion criteria were as follows: (1) facial or orbital fracture extending to other parts of the orbit than medial‐wall and/or floor; (2) history of orbital or ocular abnormality other than the orbital trauma; (3) severe ocular trauma accompanied by the orbital trauma; (4) orbital fracture treated surgically before the CT examination. A co‐ordinate system was built based on the orbital CT scans. Displacements of orbital walls, displacement of the globe and relative location of the fracture site were measured. Correlations between the variables were investigated.ResultsNinety‐nine per cent of fracture sites of the medial wall and 100% of fracture sites of the floor were posterior to the centre of the unaffected globe. The affected globe moved significantly medially (p < 0.001) and backwards (p < 0.001) in pure medial‐wall fracture; backwards (p < 0.001) and downwards (p = 0.017) in pure floor fracture; and medially (p < 0.001), backwards (p < 0.001) and downwards (p < 0.001) in medial‐wall and floor fractures. Displacement of the globe was correlated with displacements of the orbital walls, and the regression formulae were therefore fitted. Application of the formulae revealed that the same extent of orbital wall displacement caused more displacement of the globe in female patients than in male patients.ConclusionsA linear measuring method in a three‐dimensional co‐ordinate system was established to identify the displacements of orbital walls and the displacement of the globe in orbital blowout fractures. The regression formulae generated in this study might be used in clinical practice to predict late displacement of the globe by measuring the displacements of orbital walls.
A cross‐sectional study of vitreous and serum high mobility group box‐1 levels in proliferative diabetic retinopathy
Authors: Shen Yinchen , Cao Hui , Chen Feng'e , Suo Yan , Wang Ning , Xu Xun 
Published: August 2019

AbstractPurposeWe determined vitreous and serum levels of high mobility group box‐1 (HMGB‐1) in patients with proliferative diabetic retinopathy (PDR) and elucidate their relationship with receptor for advanced glycation end products (RAGE), vascular endothelial growth factor (VEGF) and interleukin‐1β (IL‐1β).MethodsIn this cross‐sectional study, patients with PDR who underwent vitrectomy were enrolled, and the control group included non‐diabetic eyes. Vitreous and serum samples were analysed for HMGB‐1, RAGE, VEGF and IL‐1β by ELISA. We investigated the correlation between serum and vitreous levels of each cytokine, and we analysed the influence of intravitreal anti‐VEGF treatment prior to vitrectomy on the cytokine levels in PDR.ResultsOf 78 eyes of 78 patients enrolled consecutively, there were 32 PDR eyes and 46 control eyes. The serum levels were higher in diabetic than in non‐diabetic subjects for HMGB‐1, RAGE, VEGF and IL‐1β (all p < 0.001), respectively. Similarly, the vitreous levels were higher in diabetic than in non‐diabetic subjects for HMGB‐1 (p < 0.001), RAGE (p = 0.001), VEGF (p < 0.001) and IL‐1β (p < 0.001), respectively. We found a positive correlation between serum and vitreous levels of HMGB‐1 in patient with PDR (p = 0.047, R = 0.353). There was a negative correlation between serum and vitreous levels of VEGF in patient with PDR (p = 0.001, R = −0.546). For the subgroup analysis, we detected that the vitreous levels of RAGE were significantly lower in patients who underwent anti‐VEGF injection prior to vitrectomy than those who did not (p < 0.001).ConclusionsOur findings suggest that HMGB‐1 is involved in PDR disorders, and it may be a novel therapeutic target to inhibit progression of PDR.