bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative Polyadenylation Regulates Patient-specific Tumor Growth by Individualizing the MicroRNA Target Site Landscape
Authors: Kim Soyeon , Bai Yulong , Fan Zhenjiang , Diergaarde Brenda , Tseng George C. , Park Hyun Jung 
Published: April 2019

AbstractBackgroundAlternative polyadenylation (APA) shortens or lengthens the 3’-untranslated region (3’-UTR) of hundreds of genes in cancer. While APA genes modify microRNA target sites in the 3’-UTRs to promote tumorigenesis, previous studies have focused on a subset of the modification landscape.MethodFor comprehensive understanding of the function of global APA events, we consider the total target site landscape of microRNAs that are significantly and collectively modified by global APA genes. To identify such microRNAs in spite of complex interactions between microRNAs and the APA genes, we developedProbabilisticInference ofMicroRNATarget Site Modification throughAPA(PRIMATA-APA).ResultsRunning PRIMATA-APA on TCGA breast cancer data, we identified that global APA events concentrate to modify target sites of particular microRNAs (target-site-modified-miRNAor tamoMiRNA). TamoMiRNAs are enriched for microRNAs known to regulate cancer etiology and treatments. Also, their target genes are enriched in cancer-associated pathways, suggesting that APA modifies target sites of tamoMiRNAs to progress tumors. Knockdown of NUDT21, a master 3’-UTR regulator in HeLa cells, confirmed the causal role of tamoMiRNAs for tumor growth.ConclusionsFurther, the expressions of tamoMiRNA target genes, enriched in cancer-associated pathways, vary across tumor samples as a function of patient-specific APA events, suggesting that APA is a novel regulatory axis for interpatient tumor heterogeneity.
3′-UTR shortening contributes to subtype-specific cancer growth by breaking stable ceRNA crosstalk of housekeeping genes
Authors: Fan Zhenjiang , Kim Soyeon , Bai Yulong , Diergaarde Brenda , Oesterreich Steffi , Park Hyun Jung 
Published: April 2019

ABSTRACTShortening of 3′UTRs (3′US) through alternative polyadenylation (APA) is a post-transcriptional mechanism that regulate expression of hundreds of genes in human cancers. In breast cancer, different subtypes of tumor samples, such as estrogen receptor positive and negative (ER+ and ER-), are characterized by distinct molecular mechanisms, suggesting possible differences in the post-transcriptional regulation between the subtype tumors. In this study, based on the profound tumorigenic role of 3′US interacting with competing-endogenous RNA (ceRNA) network (3′US-ceRNA effect), we hypothesize that the 3′US-ceRNA effect drives subtype-specific tumor growth. However, we found that the subtypes are available in different sample size, biasing the ceRNA network size and disabling the fair comparison of the 3′US-ceRNA effect. Using normalized Laplacian Matrix Eigenvalue Distribution, we addressed this bias and built the tumor ceRNA networks comparable between the subtypes. Based on the comparison, we identified a novel role of housekeeping (HK) genes as stable and strong miRNA sponges (sponge HK genes) that synchronize the ceRNA networks of normal samples (adjacent to ER+ and ER- tumor samples). We further found that distinct 3′US events in the ER- tumor break the stable sponge effect of HK genes in a subtype-specific fashion, especially in association with the aggressive and metastatic phenotypes. Knockdown of NUDT21, a master 3′-UTR regulator in HeLa cells, confirmed the causal role of 3′US-ceRNA effect repressing HK genes for tumor growth. In this study, we identified 3′US-ceRNA effect on the sponge HK genes for subtype-specific growth of ER- tumors.
Investigating Biomechanical Properties of A. tortilis as Related to their Habitat: A novel approach to characterize bending
Authors: Faris Ahmed , Altoum Rani , Salameh Iyad , Salameh Mohammed , Al-Mohannadi Saif , Mahmoud Abdulla 
Published: April 2019

ABSTRACTThe biomechanical properties of Acacia tortilis were investigated considering its habitat (wild vs. nursery). The plant materials were collected from partially urbanized area in Doha city and from Qatar Foundation Nursery. The results show that Acacia grown in field are more flexible than those grown in nursery. Young’s Modulus of Elasticity was found to be 191 MPa and 617 MPa and the Flexural Modulus was found to be 49 MPa and 575 MPa and the breaking force was found to be 210 and 550 N for nursery and field Acacia, respectively. The deflection angle was measured using sensitive flex sensors connected to Arduino boards and was found to be higher for field Acacia (50∘). Image processing techniques were used to mathematically describe the branch motion versus time diagrams.The plant part being investigated was covered with red tape and videotaped while subjected to a force causing it to bend. The stem was divided into 745 successive points and the change in their position with time taken frame by frame was converted into a change in position expressed through mathematical parameters. The bending movement of the branch was found to follow a power function H = (4001 − e0.06m).HighlightField grown Acacia have higher values of Young’s and Flexural Moduli than nursery grown ones thus conferring them more elasticity and flexibility.
Quantifying the contribution of sequence variants with regulatory and evolutionary significance to 34 bovine complex traits
Authors: Xiang Ruidong , Van Den Berg Irene , MacLeod Iona M. , Hayes Benjamin J. , Prowse-Wilkins Claire P. , Wang Min , Bolormaa Sunduimijid , Liu Zhiqian , Rochfort Simone J. , Reich Coralie M. , Mason Brett A. , Vander Jagt Christy J. , Daetwyler Hans D. , Lund Mogens S. , Chamberlain Amanda J. , Goddard Michael E. 
Published: April 2019

AbstractMany genome variants shaping mammalian phenotype are hypothesized to regulate gene transcription and/or to be under selection. However, most of the evidence to support this hypothesis comes from human studies. Systematic evidence for regulatory and evolutionary signals contributing to complex traits in a different mammalian model is needed. Sequence variants associated with gene expression (eQTLs) and concentration of metabolites (mQTLs), and under histone modification marks in several tissues were discovered from multi-omics data of over 400 cattle. Variants under selection and evolutionary constraint were identified using genome databases of multiple species. These analyses defined 30 sets of variants and for each set we estimated the genetic variance the set explained across 34 complex traits in 11,923 bulls and 32,347 cows with 17,669,372 imputed variants. The per-variant trait heritability of these sets across traits was highly consistent (r>0.94) between bulls and cows. Based on the per-variant heritability, conserved sites across 100 vertebrate species and mQTLs ranked the highest, followed by eQTLs, young variants, those under histone modification marks and selection signatures. From these results, we defined aFunctional-And-EvolutionaryTraitHeritability (FAETH) score indicating the functionality and predicted heritability of each variant. In 7,551 Danish cattle, the high FAETH-ranking variants had significantly increased genetic variances and genomic prediction accuracies in 3 production traits compared to the low FAETH-ranking variants. The FAETH framework combines the information of gene regulation, evolution and trait heritability to rank variants and the publicly available FAETH data provides a set of biological priors for cattle genomic selection worldwide.
The fungal gene cluster for biosynthesis of the antibacterial agent viriditoxin
Authors: Urquhart Andrew S. , Hu Jinyu , Chooi Yit-Heng , Idnurm Alexander 
Published: April 2019

AbstractBackgroundViriditoxin is one of the ‘classical’ secondary metabolites produced by fungi and that has antibacterial and other activities; however, the mechanism of its biosynthesis has remained unknown.ResultsHere, a gene cluster responsible for its synthesis was identified, using bioinformatic approaches from two species that produce viriditoxin and then through gene disruption and metabolite profiling. All eight genes in the cluster inPaecilomyces variotiiwere mutated, revealing their roles in the synthesis of this molecule and establishing its biosynthetic pathway which includes an interesting Baeyer-Villiger monooxygenase catalyzed reaction. Additionally, a candidate catalytically-inactive hydrolase was identified as being required for the stereoselective biosynthesis of (M)-viriditoxin. The localization of two proteins were assessed by fusing these proteins to green fluorescent protein, revealing that at least two intracellular structures are involved in the compartmentalization of the synthesis steps of this metabolite.ConclusionsThe full pathway for synthesis of viriditoxin was established by a combination of genomics, bioinformatics, gene disruption and chemical analysis processes. Hence, this work reveals the basis for the synthesis of an understudied class of fungal secondary metabolites and provides a new model species for understanding the synthesis of biaryl compounds with a chiral axis.
Pooled-parent exome sequencing to prioritise de novo variants in genetic disease
Authors: Dashnow Harriet , Bell Katrina M. , Stark Zornitza , Tan Tiong Y. , White Susan M. , Oshlack Alicia 
Published: April 2019

AbstractIn the clinical setting, exome sequencing has become standard-of-care in diagnosing rare genetic disorders, however many patients remain unsolved. Trio sequencing has been demonstrated to produce a higher diagnostic yield than singleton (proband-only) sequencing. Parental sequencing is especially useful when a disease is suspected to be caused by a de novo variant in the proband, because parental data provide a strong filter for the majority of variants that are shared by the proband and their parents. However the additional cost of sequencing the parents makes the trio strategy uneconomical for many clinical situations. With two thirds of the sequencing budget being spent on parents, these are funds that could be used to sequence more probands. For this reason many clinics are reluctant to sequence parents.Here we propose a pooled-parent strategy for exome sequencing of individuals with likely de novo disease. In this strategy, DNA from all the parents of a cohort of unrelated probands is pooled together into a single exome capture and sequencing run. Variants called in the proband can then be filtered if they are also found in the parent pool, resulting in a shorter list of prioritised variants. To evaluate the pooled-parent strategy we performed a series of simulations by combining reads from individual exomes to imitate sample pooling. We assessed the recall and false positive rate and investigated the trade-off between pool size and recall rate. We compared the performance of GATK HaplotypeCaller individual and joint calling, and FreeBayes to genotype pooled samples. Finally, we applied a pooled-parent strategy to a set of real unsolved cases and showed that the parent pool is a powerful filter that is complementary to other commonly used variant filters such as population variant frequencies.
A field and video analysis guide for diver operated stereo‐video
Authors: Goetze Jordan S. , Bond Todd. , McLean Dianne L. , Saunders Benjamin J. , Langlois Tim J. , Lindfield Steve , Fullwood Laura. A. F. , Driessen Damon , Shedrawi George , Harvey Euan S. 
Published: April 2019

Abstract

There has been rapid uptake of stereo‐video‐based sampling techniques to collect species, abundance and body‐size information on fish assemblages and their associated habitats. Stereo‐video methods provide highly accurate estimates of body‐size, range and sampling area as well as a permanent record that can be cross‐checked or resampled for additional data. Due to these advantages, diver‐operated stereo‐video (stereo‐DOV) is becoming an increasingly popular alternative to underwater visual census.

We provide a comprehensive guide for researchers using stereo‐DOVs to survey fish assemblages and their associated habitat. Information on stereo‐DOV design, video camera settings, field operations and video analysis are outlined.

Stereo–DOV surveys permit rapid and simultaneous collection of data on fish diversity, abundance, length and behaviour as well as their associated habitat. However, biases associated with diver presence in the water and variation in detectability should be considered and are dependent on the location and focal species of the survey.

We recommend using stereo‐DOVs for diver‐based surveys of non‐cryptic fish assemblages, given the advantages described. An increased uptake of this methodology, following the standard procedures described herein, will reduce variation in methodology, assist in the synthesis of data on continental and global scales and provide accurate information to improve fisheries management and conservation.
Structural brain characteristics of anabolic–androgenic steroid dependence in men
Authors: Hauger Lisa E. , Westlye Lars T. , Fjell Anders M. , Walhovd Kristine B. , Bjørnebekk Astrid 
Published: April 2019

AbstractAimTo identify differences in brain morphology between dependent and non‐dependent male anabolic–androgenic steroid (AAS) users.DesignThis study used cross‐sectional data from a longitudinal study on male weightlifters.ParticipantsOslo University Hospital, Norway.SettingEighty‐one AAS users were divided into two groups; AAS‐dependent (n = 43) and AAS‐non‐dependent (n = 38).MeasurementsNeuroanatomical volumes and cerebral cortical thickness were estimated based on magnetic resonance imaging (MRI) using FreeSurfer. Background and health information were obtained using a semi‐structured interview. AAS‐dependence was evaluated in a standardized clinical interview using a version of the Structured Clinical Interview for DSM‐IV, adapted to apply to AAS‐dependence.FindingsCompared with non‐dependent users, dependent users had significantly thinner cortex in three clusters of the right hemisphere and in five clusters of the left hemisphere, including frontal, temporal, parietal and occipital regions. Profound differences were seen in frontal regions (left pars orbitalis, cluster‐wise P < 0.001, right superior frontal, cluster‐wise P < 0.001), as has been observed in other dependencies. Group differences were also seen when excluding participants with previous or current non‐AAS drug abuse (left pre‐central, cluster‐wise P < 0.001, left pars orbitalis, cluster‐wise P = 0.010).ConclusionMale dependent anabolic–androgenic steroid users appear to have thinner cortex in widespread regions, specifically in pre‐frontal areas involved in inhibitory control and emotional regulation, compared with non‐dependent anabolic–androgenic steroid users.
Composition and ecological drivers of the kwongan scrub and woodlands in the northern Swan Coastal Plain, Western Australia
Authors: Tsakalos James L. , Renton Michael , Dobrowolski Mark P. , Veneklaas Erik J. , Macintyre Paul D. , Broomfield Sarah J. , Mucina Ladislav 
Published: April 2019

AbstractThe nature of community patterns and environmental drivers in kwongan mediterranean‐type shrubland on nutrient‐poor soils occurring in Western Australia remain poorly examined. We aimed to determine whether (i) classification of the kwongan vegetation of the northern Swan Coastal Plain would be ecologically informative and (ii) which environmental drivers underpin the plant community patterns. The study area was positioned on the northern Swan Coastal Plain, locality of Cooljarloo (30°39′ S, 115°22′ E), situated 170 km north of Perth, Western Australia. Compositional (518 species × 337 relevés) and environmental data set (29 variables × 87 relevés) describing time since last fire, soil chemical and physical properties, and terrain characteristics were analysed using classification and ordination techniques. OptimClass assisted in the selection of a robust data transformation, resemblance function and clustering algorithm to identify the vegetation patterns. Major ecological drivers of the vegetation patterns were detected using distance‐based redundancy analysis (db‐RDA). Classification revealed major groupings of Wet Heath and Banksia Woodland distinguishable by the high prevalence of myrtyoid and proteoid taxa, respectively. On floristic‐sociological grounds, we recognised four Wet Heath and two Banksia Woodland communities. The Wet Heath was constrained to areas of higher litter depth (db‐RDA axis 1: 9%). Soil chemical and physical properties explained the highest proportion (17%) of the compositional variance, while the terrain‐ and fire‐related variables explained 2% and <0.001%, respectively. While fire explained little compositional variance overall, a separate db‐RDA analysis found that it may play an important pattern‐structuring role within Banksia Woodlands. Fine‐scale compositional patterns correspond only to a small extent to environmental data; the substantial unexplained variance may be due to slow‐acting neutral and stochastic processes.
Umbilical artery pH and base excess at birth are poor predictors of neurodevelopmental morbidity in early childhood
Authors: Leinonen Elina , Gissler Mika , Haataja Leena , Andersson Sture , Rahkonen Petri , Rahkonen Leena , Metsäranta Marjo 
Published: April 2019

AbstractAimWe sought to evaluate the associations between umbilical artery pH and base excess and neurodevelopmental outcome at four years of age.MethodsThis study comprised 84 588 singleton children born alive at term in 2005–2011 in the hospital district of Helsinki and Uusimaa in Finland. Data from the maternity hospital information system were linked to the data from the Medical Birth Register and the Hospital Discharge Register. Neurodevelopmental morbidity included cerebral palsy, epilepsy, intellectual or sensorineural impairment.ResultsAfter adjustment for maternal and perinatal factors, a combination of pH <7.00 and base excess <−16.00 was associated with infant death (adjusted odds ratio 19.97; 95% confidence interval 5.38–74.17). Values of pH 7.00–7.10 were associated with cerebral palsy (adjusted odds ratio 2.40; 95% confidence interval 1.05–5.47). A combination of low five‐minute Apgar score and umbilical artery base excess <−16.00 showed the highest positive predictive value (9.1%) for neurodevelopmental impairments. When umbilical artery pH <7.00 was included, a positive predictive value of 25.0% was observed for infant mortality.ConclusionLow umbilical artery pH and base excess at birth were the poor predictors of long‐term neurodevelopmental morbidity in an unselected population. However, these parameters might be useful in assessing the risk of infant mortality.
Trajectories of pain predict disabilities affecting daily living in arthritis
Authors: James Richard J. E. , Walsh David A. , Ferguson Eamonn 
Published: April 2019

PurposeTo examine the interplay between pain and disability in arthritis when adjusting for patient heterogeneity in pain progression. There is consistent evidence to suggest that people experience osteoarthritis heterogeneously, with subgroups of people having different trajectories of pain. However, at present it is unclear how these pain trajectories are related to functional disability. We ask the question: Do levels of disability track changes in pain across different pain trajectories?MethodsSecondary analysis of a subset (n = 889) from a cohort of older English adults, representative of the general population (the English Longitudinal Study of Ageing). The relationship between pain and functional disability was compared in three domains of disability: mobility, activities of daily living (ADL) and instrumental ADL. These represent increasingly complex forms of self‐care required for independent living. Data analysis compared the heterogeneous analysis of pain (different trajectories) and disability compared to treating pain as a simpler homogenous construct.ResultsOn a population level, pain was significantly positively correlated with increased disability in all three domains, and the relationship remained stable over time. However, when heterogeneity was examined respondents whose pain improved did not show a corresponding improvement in disability in two domains (ADL and mobility).ConclusionsThese findings highlight how, for some people, alleviating pain, the main symptom of arthritis, might not prevent the persistence or progression of disability. Even when pain improves, further interventions that improve disability are likely to be required.
Statement of contribution

What is already known on this subject?

Pain and functional limitation in daily living are common symptoms of arthritis.

Arthritis pain is heterogeneous – there are trajectories of people whose pain gets better or worse.

However, to date no study has looked at the relationship between trajectories of arthritis pain and functional disability outside of the minority of people with rheumatoid arthritis.

What does this study add?

Treating pain as heterogeneous explained disability better than treating pain as a single entity.

Respondents in a trajectory of worsening pain reported functional disability in two domains (mobility and activities of daily living) also got worse over time.

People in a trajectory of decreasing pain over time did not experience a reduction in disability, despite pain being the most common reason for why people limit their daily functioning.

This suggests further intervention is required for people with arthritis, even when the most visible symptoms have been alleviated.