bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fecal Fat Concentration and Excretion in the First 2 Years of Life
Authors: Wieczorek‐Filipiak Mirosława , Drzymała‐Czyż Sławomira , Szczepanik Mariusz , Szydłowski Jarosław , Walkowiak Dariusz , Nowak Jan K. , Moczko Jerzy A. , Walkowiak Jarosław 
Published: January 2019

ABSTRACTObjectives:Data on pancreatic exocrine secretion in the youngest children are scarce. The aim of the study was to determine the range of normal values for fecal fat concentration (FFC) and fecal fat excretion (FFE) in infants and toddlers up to 2 years of age.Methods:A total of 160 subjects aged 1 to 24 months (8 groups of 20: aged 1–3, 4–6 months, etc) were included in the study. In all children, FFC (%) and FFE (g/day) were assessed in 3‐day stool collection.Results:FFC correlated with age (r = −0.50, P < 0.0001). Of infants aged 1 to 3 months 65% had FFC higher than the <5% norm proposed for older children. The values of 90th/95th FFC percentile ranged from 9.7/13.0% at 1 month to 3.1/3.2% at 24 months. FFE did not differ between age groups. It was, however, higher than 4 and 3 g/day in 7.5% and 15.0% infants, respectively. The first detailed nomogram for the assessment of FFC and FFE in children aged 1 to 24 months was created.Conclusions:Healthy infants may have higher FFC and FFE than older children. We provide reference values, which should allow for both precise and facile FFC and FFE interpretation in clinical practice.
A sustained small increase in NOD1 expression promotes ligand-independent oncogenic activity
Authors: Rommereim Leah M. , Suresh Akhade Ajay , Dutta Bhaskar , Hutcheon Carolyn , Lounsbury Nicolas W. , Rostomily Clifford C. , Savan Ram , Fraser Iain D. C. , Germain Ronald N. , Subramanian Naeha 
Published: January 2019

AbstractSmall genetically-determined differences in transcription (eQTLs) are implicated in complex disease but the mechanisms by which small changes in gene expression impact complex disease are unknown. Here we show that a persistent small increase in expression of the innate sensor NOD1 precipitates large cancer-promoting changes in cell state. A ~1.2-1.4 fold increase in NOD1 protein concentration by loss of miR-15b/16 regulation sensitizes cells to ligand-induced inflammation, with an additional slight increase leading to ligand-independent NOD1 activation that is linked to poor prognosis in gastric cancer. Our data show that tight expression regulation of NOD1 prevents this sensor from exceeding a physiological switching checkpoint that promotes persistent inflammation and oncogene expression and reveal the impact of a single small quantitative change in cell state on cancer.One Sentence SummaryA small change in NOD1 expression has a large cancer-promoting impact on cell state.
Ends and middle: global force balance determines septum location in fission yeast
Authors: Goff Xavier Le , Comelles Jordi , Kervrann Charles , Riveline Daniel 
Published: January 2019

AbstractThe fission yeast cell is shaped as a very regular cylinder ending by hemi-spheres at both cell ends. Its conserved phenotypes are often used as read-outs for classifying interacting genes and protein networks. Using Pascal and Young-Laplace laws, we proposed a framework where scaling arguments predicted shapes. Here we probed quantitatively one of these relations which predicts that the division site would be located closer to the cell end with the larger radius of curvature. By combining genetics and quantitative imaging, we tested experimentally whether altered shapes of cell end correlate with a displaced division site, leading to asymmetric cell division. Our results show that the division site position depends on the radii of curvatures of both ends. This new geometrical mechanism for the proper division plane positioning could be essential to achieve even partitioning of cellular material at each cell division.
Registration for Image-Based Transcriptomics: Parametric Signal Features and Multivariate Information Measures
Authors: Chen Rebecca , Das Abhinav B. , Varshney Lav R. 
Published: January 2019

AbstractImage-based transcriptomics involves determining spatial patterns in gene expression across cells and tissues. Image registration is a necessary component of data analysis pipelines that study gene expression levels across different cells and intracellular structures. We consider images from multiplexed single molecule fluorescentin situhybridization (smFISH) and multiplexedin situsequencing (ISS) datasets from the Human Cell Atlas project and demonstrate a novel approach to groupwise image registration using a parametric representation of images based on finite rate of innovation sampling, together with practical optimization of empirical multivariate information measures.
Positively twisted: The complex evolutionary history of Reverse Gyrase suggests a non-hyperthermophilic Last Universal Common Ancestor
Authors: Catchpole Ryan , Forterre Patrick 
Published: January 2019

AbstractReverse gyrase (RG) is the only protein found ubiquitously in hyperthermophilic organisms, but absent from mesophiles. As such, its simple presence or absence allows us to deduce information about the optimal growth temperature of long-extinct organisms, even as far as the last universal common ancestor of extant life (LUCA). The growth environment and gene content of the LUCA has long been a source of debate in which RG often features. In an attempt to settle this debate, we carried out an exhaustive search for RG proteins, generating the largest RG dataset to date. Comprising 376 sequences, our dataset allows for phylogenetic reconstructions of RG with unprecedented size and detail. These RG phylogenies are strikingly different from those of known LUCA-encoded proteins, even when using the same set of species. Unlike LUCA-encoded proteins, RG does not form monophyletic archaeal and bacterial clades, suggesting RG emergence after the formation of these domains, and/or significant horizontal gene transfer. Even more strikingly, the branch lengths separating archaeal and bacterial groups are very short, inconsistent with the tempo of evolution from the time of the LUCA. Despite this, phylogenies limited to archaeal RG resolve most archaeal phyla, suggesting predominantly vertical evolution since the time of the last archaeal ancestor. In contrast, bacterial RG indicates emergence after the last bacterial ancestor followed by significant horizontal transfer. Taken together, these results suggest a non-hyperthermophilic LUCA and bacterial ancestor, with hyperthermophily emerging early in the evolution of the archaeal and bacterial domains.
Validity and internal consistency of EQ-5D-3L quality of life tool among pre-dialysis patients with chronic kidney disease in Sri Lanka, a lower middle-income country
Authors: Senanayake Sameera , Mahesh PKB , Gunawardena Nalika , Graves Nicholas , Kularatna Sanjeewa 
Published: January 2019

AbstractObjectiveEQ-5D-3L is a generic QOL tool used mainly in economic evaluations. Burden of Chronic Kidney Disease (CKD) is rising in Sri Lanka. Assessing the validity of generic QOL tools creates new opportunities of their utilization among patients with CKD.MethodsA cross-sectional study was conducted among 1036 CKD patients, selected using the simple random sampling technique. The validity was tested with six a-priori hypotheses. These included construct validity assessments, evaluating convergent validity and performing known group comparisons. EQ-5D-3L, Short Form-36 (SF-36), Center for Epidemiological Studies Depression Scale (CES-D-20) and General Health Questionnaire-12 (GHQ-12) were used to assess QOL, presence of depression and psychological distress respectively. Internal consistency of the whole tool and when each item is removed was assessed by Cronbach alpha.ResultsThe response rate was 99.2%. Majority of participants were males (n=646,62.4%) in the age category of 41-60 (n=530; 51.2%). Most were in either stage 4 or 5 of CKD (n=646,75.1%). The summary measures of SF-36, positively and significantly correlated with the EQ-5D-3L index and VAS scores (p<0.001). EQ-5D-3L QOL scores were significantly different between the group with depression and without as measured by CES-D-20 (p<0.001). Assessed using GHQ-12, similar significance was detected between the group with psychological distress and without (p<0.001). The Cronbach alpha was 0.834 and when each item was removed, ranged from 0.782 to 0.832.ConclusionEQ-5D-3L is a valid generic QOL tool with satisfactory internal consistency to be used among CKD patients in the pre-dialysis stage.
Fast estimation of genetic correlation for Biobank-scale data
Authors: Wu Yue , Burch Kathryn S. , Ganna Andrea , Pajukanta Päivi , Pasaniuc Bogdan , Sankararaman Sriram 
Published: January 2019

AbstractGenetic correlation is an important parameter in efforts to understand the relationships among complex traits. Current methods that analyze individual genotype data for estimating genetic correlation are challenging to scale to large datasets. Methods that analyze summary data, while being computationally efficient, tend to yield estimates of genetic correlation with reduced precision. We propose, SCORE, a randomized method of moments estimator of genetic correlation that is both scalable and accurate. SCORE obtains more precise estimates of genetic correlations relative to summary-statistic methods that can be applied at scale achieving a 50% reduction in standard error relative to LD-score regression (LDSC) and a 26% reduction relative to high-definition likelihood (HDL) (averaged over all simulations). The efficiency of SCORE enables computation of genetic correlations on the UK biobank dataset consisting of ≈ 300K individuals and ≈ 500K SNPs in a few hours (orders of magnitude faster than methods that analyze individual data such as GCTA). Across 780 pairs of traits in 291, 273 unrelated white British individuals in the UK Biobank, SCORE identifies significant genetic correlation between 200 additional pairs of traits over LDSC (beyond the 245 pairs identified by both).
The large loop-8 insert in Saccharomyces cerevisiae kinesin-5 Cin8 is necessary and sufficient to promote noncanonical microtubule interactions
Authors: Bell Kayla M. , Cochran Jared C. 
Published: January 2019

ABSTRACTSaccharomyces cerevisiae kinesin-5 Cin8 displays unconventional biochemical behavior including bidirectional motility and ability to bind multiple motor domains per αβ tubulin dimer in the microtubule lattice. Previous research suggested that a large loop-8 insert near the microtubule binding interface of Cin8 was critical for its noncanonical microtubule binding behavior. Here we utilized mutagenesis, thermodynamic, and kinetic assays to further understand the mechanism for how this loop-8 insert promotes super-stoichiometric microtubule binding in Cin8. This loop-8 insert that interrupts the conserved β5a/b hairpin was swapped between Cin8, Eg5 (KIF11, a human kinesin-5) and Kip1 (another S. cerevisiae kinesin-5). Cin8 with the loop-8 insert from Eg5 (Cin8-EL8) binds one motor per tubulin dimer, whereas Eg5 with the loop-8 insert from Cin8 (Eg5-CL8) binds approximately 2-4 motors per tubulin dimer. Eg5-CL8 bound the canonical and noncanonical sites on the microtubule lattice with weakened oligomerization between motors, while Cin8-EL8 showed only canonical site binding. These results demonstrate that the large loop-8 insert in Cin8 is necessary and sufficient to promote noncanonical microtubule binding behavior.
Fast and robust method for drug response biomarker identification and sample stratification
Authors: Bhattacharya Simanti , Das Amit 
Published: January 2019

AbstractWith unprecedented progress of cancer research, the world is now prepared with versatile arsenal of drugs to combat cancer. However, individual’s response to any drug or combination treatment stands as a major challenge and hence there exists the sheer need for personalized medication. Identification of drug response biomarkers from a wholistic tumor microenvironment analysis would guide researchers to develop custom-tailored treatment regimen.In this study, a fast and robust method has been developed to identify drug response biomarkers from entire transcriptomics data analysis in a data-driven manner. The biomarkers which were identified by the method, were able to stratify patients between responders vs non-responders population. Furthermore, bayesian network (BN) analysis, done on the data, brought forth a mechanistic insight into the role of identified biomarkers in regulating drug’s efficacy.The importance of this work lies with the protocol that is time saving and requires less computation power, yet analyzes a whole system data and helps the researchers to take a step forward towards the development of personalized care in effective cancer treatment.HighlightsSupervised machine learning approach to analyze gene expression data.Drug response biomarker identification.Categorization of samples for their drug response with the help of identified biomarkers.Functional enrichment to understand the biomarkers association with biological processes.Bayesian network analysis to develop causal structure among identified biomarkers and drug targets.Time and cost-effective pipeline for fast and robust prediction of drug response biomarkers.
Role of Era in Assembly and Homeostasis of the Ribosomal Small Subunit
Authors: Razi Aida , Davis Joseph H. , Hao Yumeng , Jahagirdar Dushyant , Thurlow Brett , Basu Kaustuv , Jain Nikhil , Gomez-Blanco Josue , Britton Robert A. , Vargas Javier , Guarné Alba , Woodson Sarah A. , Williamson James R. , Ortega Joaquin 
Published: January 2019

SUMMARYTo reveal the role of the essential protein Era in the assembly of the 30S ribosomal subunit, we analyzed assembly intermediates that accumulated in Era-depletedEscherichia colicells using quantitative mass spectrometry, cryo-electron microscopy and in-cell footprinting. Our combined approach allowed for visualization of the small subunit as it assembled and revealed that with the exception of key helices in the platform domain, all other 16S rRNA domains were able to fold even in the absence of Era. Notably, the maturing particles did not stall while waiting for the platform domain to mature and instead re-routed their folding pathway to enable concerted maturation of other structural motifs spanning multiple rRNA domains. We also found that binding of Era to the mature 30S subunit destabilized helix 44 and the decoding center preventing binding of YjeQ, another assembly factor. This work establishes Era’s role in ribosome assembly and suggests new roles in maintaining ribosome homeostasis.
Multimodal cell type correspondence by intersectional mFISH in intact tissues
Authors: Nicovich Philip R. , Taormina Michael J. , Baker Christopher A. , Nguyen Thuc Nghi , Thomsen Elliot R. , Garren Emma , Long Brian , Gorham Melissa , Miller Jeremy A. , Hage Travis , Bosma-Moody Alice , Murphy Gabe J. , Levi Boaz P. , Close Jennie L. , Tasic Bosiljka , Lein Ed S. , Zeng Hongkui 
Published: January 2019

AbstractDefining a complete set of cell types within the cortex requires reconciling disparate results achieved through diverging methodologies. To address this correspondence problem, multiple methodologies must be applied to the same cells across multiple single-cell experiments. Here we present a new approach applying spatial transcriptomics using multiplexed fluorescencein situhybridization, (mFISH) to brain tissue previously interrogated through two photon optogenetic mapping of synaptic connectivity. This approach can resolve the anatomical, transcriptomic, connectomic, electrophysiological, and morphological characteristics of single cells within the mouse cortex.
Human DNA polymerase delta is a pentameric holoenzyme with dimeric p12 subunit: Implications in enzyme architecture and PCNA interaction
Authors: Khandagale Prashant , Peroumal Doureradjou , Manohar Kodavati , Acharya Narottam 
Published: January 2019

AbstractHuman DNA polymerase delta (Polδ), a holoenzyme consisting of p125, p50, p68 and p12 subunits, plays an essential role in all the three DNA transaction processes. Herein, using multiple physicochemical and cellular approaches we found that the p12 protein forms a dimer in solution.In vitroreconstitution and pull-down of cellular Polδ by tagged p12 authenticates pentameric nature of this critical holoenzyme. Further, a consensus PIP motif at the extreme carboxyl terminal tail and a homodimerization domain at the amino-terminus of the p12 subunit were identified. Our mutational analyses of p12 subunit suggest that3RKR5motif is critical for dimerization that facilitates p12 binding to IDCL of PCNA via its PIP motif98QCSLWHLY105. Additionally, we observed that oligomerization of the smallest subunit of Polδs is evolutionarily conserved as Cdm1 ofS. pombealso dimerzes. Thus, we suggest that human Polδ is a pentameric complex with a dimeric p12 subunit; and discuss implications of p12 dimerization in regulating enzyme architecture and PCNA interaction during DNA replication.
AGO1 in association with NEAT1 lncRNA contributes to nuclear and 3D chromatin architecture in human cells
Authors: Shuaib Muhammad , Parsi Krishna Mohan , Kawaji Hideya , Thimma Manjula , Adroub Sabir Abdu , Fort Alexandre , Ghosheh Yanal , Yamazaki Tomohiro , Mannen Taro , Seridi Loqmane , Fallatah Bodor , Albawardi Waad , Ravasi Timothy , Carninci Piero , Hirose Tetsuro , Orlando Valerio 
Published: January 2019

AbstractAside from their roles in the cytoplasm, RNA-interference components have been reported to localize also in the nucleus of human cells. In particular, AGO1 associates with active chromatin and appears to influence global gene expression. However, the mechanistic aspects remain elusive. Here, we identify AGO1 as a paraspeckle component that in combination with the NEAT1 lncRNA maintains 3D genome architecture. We demonstrate that AGO1 interacts with NEAT1 lncRNA and its depletion affects NEAT1 expression and the formation of paraspeckles. By Hi-C analysis in AGO1 knockdown cells, we observed global changes in chromatin organization, including TADs configuration, and A/B compartment mixing. Consistently, distinct groups of genes located within the differential interacting loci showed altered expression upon AGO1 depletion. NEAT1 knockout cells displayed similar changes in TADs and higher-order A/B compartmentalization. We propose that AGO1 in association with NEAT1 lncRNA can act as a scaffold that bridges chromatin and nuclear bodies to regulate genome organization and gene expression in human cells.
Tandem Directional CTCF Sites Balance Protocadherin Promoter Usage
Authors: Wu Qiang , Guo Ya , Lu Yujia , Li Jingwei , Wu Yonghu , Jia Zhilian 
Published: January 2019

ABSTRACTCTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the Pcdhα and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter usage. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.
A High-Throughput Physiological Functional Phenotyping System for Time- and Cost-Effective Screening of Potential Biostimulants
Authors: Dalal Ahan , Bourstein Ronny , Haish Nadav , Shenhar Itamar , Wallach Rony , Moshelion Menachem 
Published: January 2019

ABSTRACTThe improvement of crop productivity under abiotic stress is one of the biggest challenges faced by the agricultural scientific community. Despite extensive research, the research-to-commercial transfer rate of abiotic stress-resistant crops remains very low. This is mainly due to the complexity of genotype◻×◻environment interactions and in particular, the ability to quantify the dynamic plant physiological response profile to a dynamic environment.Most existing phenotyping facilities collect information using robotics and automated image acquisition and analysis. However, their ability to directly measure the physiological properties of the whole plant is limited. We demonstrate a high-throughput functional phenotyping system (HFPS) that enables comparing plants’ dynamic responses to different ambient conditions in dynamic environments due to its direct and simultaneous measurement of yield-related physiological traits of plants under several treatments. The system is designed as one-to-one (1:1) plant–[sensors+controller] units, i.e., each individual plant has its own personalized sensor, controller and irrigation valves that enable (i) monitoring water-relation kinetics of each plant–environment response throughout the plant’s life cycle with high spatiotemporal resolution, (ii) a truly randomized experimental design due to multiple independent treatment scenarios for every plant, and (iii) reduction of artificial ambient perturbations due to the immobility of the plants or other objects. In addition, we propose two new resilience-quantifying-related traits that can also be phenotyped using the HFPS: transpiration recovery rate and night water reabsorption.We use the HFPS to screen the effects of two commercial biostimulants (a seaweed extract—ICL-SW, and a metabolite formula—ICL-NewFo1) on Capsicum annuum under different irrigation regimes. Biostimulants are considered an alternative approach to improving crop productivity. However, their complex mode of action necessitates cost-effective pre-field phenotyping. The combination of two types of treatment (biostimulants and drought) enabled us to evaluate the precision and resolution of the system in investigating the effect of biostimulants on drought tolerance. We analyze and discuss plant behavior at different stages, and assess the penalty and trade-off between productivity and survivability. In this test case, we suggest a protocol for the screening of biostimulants’ physiological mechanisms of action.