bluuebunny/crossref_metadata_2025_split huggingface dataset:
Widespread localisation of lncRNA to ribosomes: Distinguishing features and evidence for regulatory roles
Authors: Carlevaro-Fita Juna , Rahim Anisa , Guigo Roderic , Vardy Leah A. , Johnson Rory 
Published: January 2015

AbstractThe function of long noncoding RNAs (lncRNAs) depends on their location within the cell. While most studies to date have concentrated on their nuclear roles in transcriptional regulation, evidence is mounting that lncRNA also have cytoplasmic roles. Here we comprehensively map the cytoplasmic and ribosomal lncRNA population in a human cell. Three-quarters (74%) of lncRNAs are detected in the cytoplasm, the majority of which (62%) preferentially cofractionate with polyribosomes. Ribosomal lncRNA are highly expressed across tissues, under purifying evolutionary selection, and have cytoplasmic-to-nuclear ratios comparable to mRNAs and consistent across cell types. LncRNAs may be classified into three groups by their ribosomal interaction: non-ribosomal cytoplasmic lncRNAs, and those associated with either heavy or light polysomes. A number of mRNA-like features destin lncRNA for light polysomes, including capping and 5’UTR length, but not cryptic open reading frames or polyadenylation. Surprisingly, exonic retroviral sequences antagonise recruitment. In contrast, it appears that lncRNAs are recruited to heavy polysomes through basepairing to mRNAs. Finally, we show that the translation machinery actively degrades lncRNA. We propose that light polysomal lncRNAs are translationally engaged, while heavy polysomal lncRNAs are recruited indirectly. These findings point to extensive and reciprocal regulatory interactions between lncRNA and the translation machinery.
SWS2 visual pigment evolution as a test of historically contingent patterns of plumage color evolution in Warblers
Authors: Bloch Natasha I. , Morrow James M. , Chang Belinda S.W. , Price Trevor D. 
Published: January 2015

ABSTRACTDistantly related clades that occupy similar environments may differ due to the lasting imprint of their ancestors – historical contingency. The New World warblers (Parulidae) and Old World warblers (Phylloscopidae) are ecologically similar clades that differ strikingly in plumage coloration. We studied genetic and functional evolution of the short-wavelength sensitive visual pigments (SWS2 and SWS1) to ask if altered color perception could contribute to the plumage color differences between clades. We show SWS2 is short-wavelength shifted in birds that occupy open environments, such as finches, compared to those in closed environments, including warblers. Sequencing of opsin genes and phylogenetic reconstructions indicate New World warblers were derived from a finch-like form that colonized from the Old World 15-20Ma. During this process the SWS2 gene accumulated 6 substitutions in branches leading to New World warblers, inviting the hypothesis that passage through a finch-like ancestor resulted in SWS2 evolution. In fact, we show spectral tuning remained similar across warblers as well as the finch ancestor. Results reject the hypothesis of historical contingency based on opsin spectral tuning, but point to evolution of other aspects of visual pigment function. Using the approach outlined here, historical contingency becomes a generally testable theory in systems where genotype and phenotype can be connected.
On The Organization Of Human T Cell Receptor Loci
Authors: Toor Amir A. , Toor Abdullah A. , Manjili Masoud H. 
Published: January 2015

AbstractThe human T cell repertoire is complex and is generated by the rearrangement of variable (V), diversity (D) and joining (J) segments on the T cell receptor (TCR) loci. The T cell repertoire demonstrates selfsimilarity in terms clonal frequencies when defined by V, D and J gene segment usage; therefore to determine whether the structural ordering of these gene segments on the TCR loci contributes to the observed clonal frequencies, the TCR loci were examined for self-similarity and periodicity in terms of gene segment organization. Logarithmic transformation of numeric sequence order demonstrated that the V and J gene segments for both T cell receptor α (TRA) and β (TRB) loci were arranged in a selfsimilar manner when the spacing between the adjacent segments was considered as a function of the size of the neighboring gene segment, with an average fractal dimension of ͠1.5. The ratio of genomic distance between either the J (in TRA) or D (in TRB) segments and successive V segments on these loci declined logarithmically with a slope of similar magnitude. Accounting for the gene segments occurring on helical DNA molecules in a logarithmic distribution, sine and cosine functions of the log transformed angular coordinates of the start and stop nucleotides of successive TCR gene segments showed an ordered progression from the 5’ to the 3’ end of the locus, supporting a log-periodic organization. T cell clonal frequencies, based on V and J segment usage, from three normal stem cell donors were plotted against the V and J segment on TRB locus and demonstrated a periodic distribution. We hypothesize that this quasi-periodic variation in gene-segment representation in the T cell clonal repertoire may be influenced by the location of the gene segments on the periodic-logarithmically scaled TCR loci. Interactions between the two strands of DNA in the double helix may influence the probability of gene segment usage by means of either constructive or destructive interference resulting from the superposition of the two helices.
Reprogramming LCLs to iPSCs Results in Recovery of Donor-Specific Gene Expression Signature
Authors: Thomas Samantha M. , Kagan Courtney , Pavlovic Bryan J. , Burnett Jonathan , Patterson Kristen , Pritchard Jonathan K. , Gilad Yoav 
Published: January 2015

AbstractRenewablein vitrocell cultures, such as lymphoblastoid cell lines (LCLs), have facilitated studies that contributed to our understanding of genetic influence on human traits. However, the degree to which cell lines faithfully maintain differences in donor-specific phenotypes is still debated. We have previously reported that standard cell line maintenance practice results in a loss of donor-specific gene expression signatures in LCLs. An alternative to the LCL model is the induced pluripotent stem cell (iPSC) system, which carries the potential to model tissue-specific physiology through the use of differentiation protocols. Still, existing LCL banks represent an important source of starting material for iPSC generation, and it is possible that the disruptions in gene regulation associated with long-term LCL maintenance could persist through the reprogramming process. To address this concern, we studied the effect of reprogramming mature LCLs to iPSCs on the ensuing gene expression patterns within and between six unrelated donor individuals. We show that the reprogramming process results in a recovery of donor-specific gene regulatory signatures. Since environmental contributions are unlikely to be a source of individual variation in our system of highly passaged cultured cell lines, our observations suggest that the effect of genotype on gene regulation is more pronounced in the iPSCs than in the LCL precursors. Our findings indicate that iPSCs can be a powerful model system for studies of phenotypic variation across individuals in general, and the genetic association with variation in gene regulation in particular. We further conclude that LCLs are an appropriate starting material for iPSC generation.
A pooling-based approach to mapping genetic variants associated with DNA methylation
Authors: Kaplow Irene M. , MacIsaac Julia L. , Mah Sarah M. , McEwen Lisa M. , Kobor Michael S. , Fraser Hunter B. 
Published: January 2015

ABSTRACTDNA methylation is an epigenetic modification that plays a key role in gene regulation. Previous studies have investigated its genetic basis by mapping genetic variants that are associated with DNA methylation at specific sites, but these have been limited to microarrays that cover less than 2% of the genome and cannot account for allele-specific methylation (ASM). Other studies have performed whole-genome bisulfite sequencing on a few individuals, but these lack statistical power to identify variants associated with DNA methylation. We present a novel approach in which bisulfite-treated DNA from many individuals is sequenced together in a single pool, resulting in a truly genome-wide map of DNA methylation. Compared to methods that do not account for ASM, our approach increases statistical power to detect associations while sharply reducing cost, effort, and experimental variability. As a proof of concept, we generated deep sequencing data from a pool of 60 human cell lines; we evaluated almost twice as many CpGs as the largest microarray studies and identified over 2,000 genetic variants associated with DNA methylation. We found that these variants are highly enriched for associations with chromatin accessibility and CTCF binding but are less likely to be associated with traits indirectly linked to DNA, such as gene expression and disease phenotypes. In summary, our approach allows genome-wide mapping of genetic variants associated with DNA methylation in any tissue of any species, without the need for individual-level genotype or methylation data.
Putative G-quadruplex forming sequence signatures in genes differentially transcribed upon loss of BLM or WRN helicases
Authors: Smestad John , James Maher L. 
Published: January 2015

ABSTRACTPutative G-quadruplex-forming sequences (PQS) have long been implicated in regulation of DNA replication and transcription, though their actual roles are unknown. To gain insight into potential PQS transcriptional function, we map and analyze PQS motifs in promoters of genes differentially-expressed in Bloom Syndrome (BS) and Werner Syndrome (WS), two human genetic disorders resulting in loss of PQS-interacting RecQ helicases. Non-B-DNA structures at PQS might be stabilized in these syndromes. For BS and WS we demonstrate that PQS promoter abundance is generally higher in down-regulated genes and lower in up-regulated genes, and show that these effects are position-dependent. To interpret these correlations we determined genome-wide PQS correlations with transcription using epigenetic information to predict gene expression. We report that 33% and 35% of analyzed PQS positions in promoter antisense and sense strands, respectively, displayed statistically-significant correlation with gene expression. Of these statistically-significant positions, 100% and 84% on antisense and sense strands, respectively, were correlated with reduced expression. This suggests that promoter PQS repress transcription. Finally, we report neural network clustering analysis of PQS motifs to demonstrate that genes differentially-expressed in BS and WS are significantly biased in their PQS motifs, suggesting an unappreciated biological relationship between PQS, RecQ helicases, and transcription.REVIEWER LINKS TO DEPOSITED DATAftp://www.jsmes.net/PQS_Genomics
Estimating stem cell fractions in hierarchically organized tumors
Authors: Werner Benjamin , Scott Jacob G. , Sottoriva Andrea , Anderson Alexander R.A. , Traulsen Arne , Altrock Philipp M. 
Published: January 2015

AbstractCancers arise as a result of genetic and epigenetic alterations. These accumulate in cells during the processes of tissue development, homeostasis and repair. Many tumor types are hierarchically organized and driven by a sub-population of cells often called cancer stem cells. Cancer stem cells are uniquely capable of recapitulating the tumor and can be highly resistant to radio-and chemotherapy treatment. We investigate tumor growth patterns from a theoretical standpoint and show how significant changes in pre-and post-therapy tumor dynamics are tied to the dynamics of cancer stem cells. We identify two characteristic growth regimes of a tumor population that can be leveraged to estimate cancer stem cell fractionsin vivousing simple linear regression. Our method is a mathematically exact result, parameter free and does not require any microscopic knowledge of the tumor properties. A more accurate quantification of the direct link between the sub-population driving tumor growth and treatment response promises new ways to individualize treatment strategies.Significance StatementUnder the cancer stem cell hypothesis a tumor population is driven by a fraction of self-renewing cancer stem cells. Absolute and relative size of this population in human cancers at any stage of the disease remains unknown. We formulate a mathematical model that describes the tumor cell population’s growth dynamics and response to therapy. This allows to estimate cancer stem cell fraction from longitudinal measurements of tumor size (often available from imaging). Such estimates are critical because treatment outcome and risk of relapse depend on the tumor’s capacity to self-renew. Ideally, by tailoring patient treatment strategies based on the relative abundance of cancer stem cells could lead to radically different therapeutic regime and to the successful eradication of the disease.
Evolutionary processes make invasion speed difficult to predict
Authors: Phillips Ben L. 
Published: January 2015

1AbstractA capacity to predict the spread rate of populations is critical for understanding the impacts of climate change and invasive species. Despite sophisticated theory describing how populations spread, the prediction of spread rate remains a formidable challenge. As well as the inherent stochasticity in the spread process, spreading populations are subject to strong evolutionary forces (operating on dispersal and reproductive rates) that can cause accelerating spread. Despite these strong evolutionary forces, serial founder events and drift on the expanding range edge mean that evolutionary trajectories in the invasion vanguard may be highly stochastic. Here I develop a model of spatial spread in continuous space that incorporates evolution of continuous traits under a quantitative genetic model of inheritance. I use this model to investigate the potential role of evolution on the variation in spread rate between replicate model realisations. Models incorporating evolution exhibited more than four times the variance in spread rate across replicate invasions compared with nonevolving scenarios. Results suggest that the majority of this increase in variation is driven by evolutionary stochasticity on the invasion front rather than initial founder events: in many cases evolutionary stochasticity on the invasion front contributed more than 90% of the variance in spread rate over 30 generations. Our uncertainty around predicted spread rates - whether for invasive species or those shifting under climate change - may be much larger than we expect when the spreading population contains heritable variation in rates of dispersal and reproduction.
Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness
Authors: Ren Yu-yu , Koch Lauren G. , Britton Steven L. , Qi Nathan R. , Treutelaar Mary K. , Burant Charles F. , Li Jun Z. 
Published: January 2015

AbstractAerobic exercise capacity can influence many complex traits including obesity and type 2 diabetes. We established two rat lines by divergent selection of intrinsic aerobic capacity. The high capacity runners (HCR) and low capacity runners (LCR) differed by ~9-fold in aerobic capacity after 32 generations, and diverged in body fat, blood glucose, and other health indicators. To study the interplay among genetic differentiation, age, and strenuous exercise, we performed microarray-based gene expression analyses in skeletal muscle with a 2×2×2 design to compare HCR and LCR, old and young animals, and between rest and exhaustion, for a total of eight groups (n=6 each). Transcripts for mitochondrial function are expressed higher in HCR than LCR at both rest and exhaustion, for both age groups. Extracellular matrix components decrease with age in both lines and both rest and exhaustion. Interestingly, age-effects in many pathways are more pronounced in LCR, suggesting that HCR’s higher innate aerobic capacity underlies both increased lifespan and heathspan.
The P-element strikes again: the recent invasion of naturalDrosophila simulanspopulations
Authors: Kofler Robert , Hill Tom , Nolte Viola , Betancourt Andrea , Schlötterer Christian 
Published: January 2015

AbstractThe P-element is one of the best understood eukaryotic transposable elements. It invadedDrosophila melanogasterpopulations within a few decades, but was thought to be absent from close relatives, includingD. simulans. Five decades after the spread inD. melanogaster, we provide evidence that the P-element has also invadedD. simulans. P-elements inD. simulansappears to have been acquired recently fromD. melanogasterprobably via a single horizontal transfer event. Expression data indicate that the P-element is processed in the germline ofD. simulans, and genomic data show an enrichment of P-element insertions in putative origins of replication, similar to that seen inD. melanogaster. This ongoing spread of the P-element in natural populations provides an unique opportunity to understand the dynamics of transposable element spreads and the associated piRNA defense mechanisms.
Strong spurious transcription likely a cause of DNA insert bias in typical metagenomic clone libraries
Authors: Lam Kathy N. , Charles Trevor C. 
Published: January 2015

ABSTRACTBackgroundClone libraries provide researchers with a powerful resource with which to study nucleic acid from diverse sources. Metagenomic clone libraries in particular have aided in studies of microbial biodiversity and function, as well as allowed the mining of novel enzymes for specific functions of interest. These libraries are often constructed by cloning large-inserts (∼30 kb) into a cosmid or fosmid vector. Recently, there have been reports of GC bias in fosmid metagenomic clone libraries, and it was speculated that the bias may be a result of fragmentation and loss of AT-rich sequences during the cloning process. However, evidence in the literature suggests that transcriptional activity or gene product toxicity may play a role in library bias.ResultsTo explore the possible mechanisms responsible for sequence bias in clone libraries, and in particular whether fragmentation is involved, we constructed a cosmid clone library from a human microbiome sample, and sequenced DNA from three different steps of the library construction process: crude extract DNA, size-selected DNA, and cosmid library DNA. We confirmed a GC bias in the final constructed cosmid library, and we provide strong evidence that the sequence bias is not due to fragmentation and loss of AT-rich sequences but is likely occurring after the DNA is introduced intoE. coli. To investigate the influence of strong constitutive transcription, we searched the sequence data for consensus promoters and found thatrpoD/σ70promoter sequences were underrepresented in the cosmid library. Furthermore, when we examined the reference genomes of taxa that were differentially abundant in the cosmid library relative to the original sample, we found that the bias appears to be more closely correlated with the number ofrpoD/σ70consensus sequences in the genome than with simple GC content.ConclusionsThe GC bias of metagenomic clone libraries does not appear to be due to DNA fragmentation. Rather, analysis of promoter consensus sequences provides support for the hypothesis that strong constitutive transcription from sequences recognized asrpoD/σ70consensus-like inE. colimay lead to plasmid instability or loss of insert DNA. Our results suggest that despite widespread use ofE. colito propagate foreign DNA, the effects ofin vivotranscriptional activity may be under-appreciated. Further work is required to tease apart the effects of transcription from those of gene product toxicity.
ControllingE. coligene expression noise
Authors: Kim Kyung Hyuk , Choi Kiri , Bartley Bryan , Sauro Herbert M. 
Published: January 2015

AbstractIntracellular protein copy numbers show significant cell-to-cell variability within an isogenic population due to the random nature of biological reactions. Here we show how the variability in copy number can be controlled by perturbing gene expression. Depending on the genetic network and host, different perturbations can be applied to control variability. To understand more fully how noise propagates and behaves in biochemical networks we developed stochastic control analysis (SCA) which is a sensitivity-based analysis framework for the study of noise control. Here we apply SCA to synthetic gene expression systems encoded on plasmids that are transformed intoEscherichia coli. We show that (1) dual control of transcription and translation efficiencies provides the most efficient way of noise-vs.-mean control. (2) The expressed proteins follow the gamma distribution function as found in chromosomal proteins. (3) One of the major sources of noise, leading to the cell-to-cell variability in protein copy numbers, is related to bursty translation. (4) By taking into account stochastic fluctuations in autofluorescence, the correct scaling relationship between the noise and mean levels of the protein copy numbers was recovered for the case of weak fluorescence signals.
SW#db: GPU-accelerated exact sequence similarity database search
Authors: Korpar Matija , Šošić Martin , Blažeka Dino , Šikić Mile 
Published: January 2015

AbstractThe deluge of next-generation sequencing (NGS) data and expanding database poses higher requirements for protein similarity search. State-of-the-art tools such as BLAST are not fast enough to cope with these requirements. Because of that it is necessary to create new algorithms that will be faster while keeping similar sensitivity levels. The majority of protein similarity search methods are based on a seed-and-extend approach which uses standard dynamic programming algorithms in the extend phase. In this paper we present a SW#db tool and library for exact similarity search. Although its running times, as standalone tool, are comparable to running times of BLAST it is primarily designed for the extend phase where there are reduced number of candidates in the database. It uses both GPU and CPU parallelization and when we measured multiple queries on Swiss-prot and Uniref90 databases SW#db was 4 time faster than SSEARCH, 6-10 times faster than CUDASW++ and more than 20 times faster than SSW.
Non-cyanobacterial diazotrophs mediate dinitrogen fixation in biological soil crusts during early crust formation
Authors: Pepe-Ranney Charles , Koechli Chantal , Potrafka Ruth , Andam Cheryl , Eggleston Erin , Garcia-Pichel Ferran , Buckley Daniel H 
Published: January 2015

1ABSTRACTBiological soil crusts (BSC) are key components of ecosystem productivity in arid lands and they cover a substantial fraction of the terrestrial surface. In particular, BSC N2-fixation contributes significantly to the nitrogen (N) budget of arid land ecosystems. In mature crusts, N2-fixation is largely attributed to heterocystous cyanobacteria, however, early successional crusts possess few N2-fixing cyanobacteria and this suggests that microorganisms other than cyanobacteria mediate N2-fixation during the critical early stages of BSC development. DNA stable isotope probing (DNA-SIP) with15N2revealed thatClostridiaceaeandProteobacteriaare the most common microorganisms that assimilate15N2in early successional crusts. TheClostridiaceaeidentified are divergent from previously characterized isolates, though N2fixation has previously been observed in this family. The Proteobacteria identified share >98.5 %SSU rRNA gene sequence identity with isolates from genera known to possess diazotrophs (e.g.Pseudomonas,Klebsiella,Shigella, andIdeonella). The low abundance of these heterotrophic diazotrophs in BSC may explain why they have not been characterized previously. Diazotrophs play a critical role in BSC formation and characterization of these organisms represents a crucial step towards understanding how anthropogenic change will affect the formation and ecological function of BSC in arid ecosystems.