bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moving in complex environments: a biomechanical analysis of locomotion on inclined and narrow substrates
Authors: Clemente Christofer J. , Dick Taylor J.M. , Wheatley Rebecca , Gaschk Joshua , Abdul Nasir Ami Fadhillah Amir , Cameron Skye F. , Wilson Robbie S. 
Published: August 2018

AbstractCharacterisation of an organisms’ performance in different habitats provides insight into the conditions that allow it to survive and reproduce. In recent years, Northern quolls (Dasyurus hallucatus)—a medium-sized semi-arboreal marsupial native to northern Australia—have undergone significant population declines within open forest, woodland and riparian habitats, but less so in rocky areas. To explore this decline, we quantified the biomechanical performance of wild Northern quolls over inclined narrow (13 mm pole) and inclined wide (90 mm platform) substrates. We predicted that quolls may possess biomechanical adaptations to increase stability on narrow surfaces, which are more common in rocky habitats. Our results display that quolls have some biomechanical characteristics consistent with a stability advantage on narrow surfaces. This includes the coupled use of limb pairs and high grip torques (Max = 68.9 N.m, Min = −69.9 N.m), highlighting their ability to generate corrective forces to counteract the toppling moments commonly encountered during gait on narrow surfaces. However, unlike other arboreal specialists such as primates, speed was constrained on narrow surfaces, and quolls did not adopt diagonal sequence gaits. Quolls appear to adopt similar performance characteristics to cats and dogs which may limit their ability to outperform these key predators (invasive or otherwise) in particular habitats. This overlap may contribute to the declining population of Northern quolls on mainland Australia.
Diagnostic value of blood gene expression-based classifiers as exemplified for acute myeloid leukemia
Authors: Warnat-Herresthal Stefanie , Perrakis Konstantinos , Taschler Bernd , Becker Matthias , Seep Lea , Baßler Kevin , Günther Patrick , Schulte-Schrepping Jonas , Klee Kathrin , Ulas Thomas , Haferlach Torsten , Mukherjee Sach , Schultze Joachim L. 
Published: August 2018

ABSTRACTAcute Myeloid Leukemia (AML) is a severe, mostly fatal hematopoietic malignancy. Despite nearly two decades of promising results using gene expression profiling, international recommendations for diagnosis and differential diagnosis of AML remain based on classical approaches including assessment of morphology, immunophenotyping, cytochemistry, and cytogenetics. Concerns about the translation of whole transcriptome profiling include the robustness of derived predictors when taking into account factors such as study- and site-specific effects and whether achievable levels of accuracy are sufficient for practical use. In the present study, we sought to shed light on these issues via a large-scale analysis using machine learning methods applied to a total of 12,029 samples from 105 different studies. Taking advantage of the breadth of data and the now much improved understanding of high-dimensional modeling, we show that AML can be predicted with high accuracy. High-dimensional approaches - in which multivariate signatures are learned directly from genome-wide data with no prior biological knowledge - are highly effective and robust. We explore also the relationship between predictive signatures, differential expression and known AML-related genes. Taken together, our results support the notion that transcriptome assessment could be used as part of an integrated genomic approach in cancer diagnosis and treatment to be implemented early on for diagnosis and differential diagnosis of AML.One Sentence SummaryBlood gene expression data and machine learning were used to develop robust and accurate classifiers for diagnosis and differential diagnosis of acute myeloid leukemia based on analysis of more than 12,000 samples derived from more than 100 individual studies
Molecular and topological reorganizations in mitochondrial architecture interplay during Bax-mediated steps of apoptosis
Authors: Ader Nicholas R. , Hoffmann Patrick C. , Ganeva Iva , Borgeaud Alicia C. , Wang Chunxin , Youle Richard J. , Kukulski Wanda 
Published: August 2018

ABSTRACTDuring apoptosis, Bcl-2 proteins such as Bax and Bak mediate the release of pro-apoptotic proteins from the mitochondria by clustering on the outer mitochondrial membrane and thereby permeabilizing it. However, it remains unclear how outer membrane openings form. Here, we combined different correlative microscopy and electron cryo-tomography approaches to visualize the effects of Bax activity on mitochondria in human cells. Our data show that Bax clusters localize near outer membrane ruptures of highly variable size. Bax clusters contain structural elements suggesting a higher-order organization of their components. Furthermore, unfolding of inner membrane cristae is coupled to changes in the supramolecular assembly of ATP synthases, particularly pronounced at membrane segments exposed to the cytosol by ruptures. Based on our results, we propose a comprehensive model in which molecular reorganizations of the inner membrane and sequestration of outer membrane components into Bax clusters interplay in the formation of outer membrane ruptures.
KLF4 binding is involved in the organization and regulation of 3D enhancer networks during acquisition and maintenance of pluripotency
Authors: Di Giammartino Dafne Campigli , Kloetgen Andreas , Polyzos Alexander , Liu Yiyuan , Kim Daleum , Murphy Dylan , Abuhashem Abderhman , Cavaliere Paola , Aronson Boaz , Shah Veevek , Dephoure Noah , Stadtfeld Matthias , Tsirigos Aristotelis , Apostolou Effie 
Published: August 2018

SUMMARYCell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors (TFs), as is strikingly exemplified by reprogramming somatic cells to pluripotent stem cells (PSCs) via expression of OCT4, KLF4, SOX2 and cMYC. How TFs orchestrate the complex molecular changes around their target gene loci in a temporal manner remains incompletely understood. Here, using KLF4 as a paradigm, we provide the first TF-centric view of chromatin reorganization and its association to 3D enhancer rewiring and transcriptional changes of linked genes during reprogramming of mouse embryonic fibroblasts (MEFs) to PSCs. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in the connectivity of enhancers, while disruption of individual KLF4 binding sites from PSC-specific enhancers was sufficient to impair enhancer-promoter contacts and reduce expression of associated genes. Our study provides an integrative view of the complex activities of a lineage-specifying TF during a controlled cell fate transition and offers novel insights into the order and nature of molecular events that follow TF binding.
Behavioral response to visual motion impacts population coding in the mouse visual thalamus
Authors: Socha Karolina , Whiteway Matt , Butts Daniel A. , Bonin Vincent 
Published: August 2018

SummaryVisual motion is a ubiquitous component of animals’ sensory experience and its encoding is critical for navigation and movement. Yet its impact on behavior and neural coding is not well understood. Combining pupillometry with cellular calcium imaging measurements of thalamocortical axons in awake behaving mice, we examined the impact of arousal and behavioral state on encoding of visual motion in the visual thalamus. We discovered that back-to-front visual motions elicits a robust behavioral response that shapes tunings of visual thalamic responses. Consistent with an arousal mechanism, the effects were pronounced during stillness and weak or absent during locomotor activity and under anesthesia. The impact on neuronal tuning was specific, biasing population response patterns in favor of back-to-front motion. The potent influence of visual motion on behavioral state dynamically affect sensory coding at early visual processing stages. Further research is required to reveal the circuitry and function of this novel mechanism.
Thylakoid-integrated recombinant Hcf106 participates in the chloroplast Twin Arginine Transport (cpTat) system
Authors: Ma Qianqian , Fite Kristen , Paul New Christopher , Dabney-Smith Carole 
Published: August 2018

AbstractThe chloroplast Twin arginine transport (cpTat) system distinguishes itself as a protein transport pathway by translocating fully-folded proteins, using the proton-motive force (PMF) as the sole source of energy. The cpTat pathway is evolutionarily conserved with the Tat pathway found in the plasma membrane of many prokaryotes. The cpTat (E. coli) system uses three proteins, Tha4 (TatA), Hcf106 (TatB), and cpTatC (TatC), to form a transient translocase allowing the passage of precursor proteins. Briefly, cpTatC and Hcf106, with Tha4, form the initial receptor complex responsible for precursor protein recognition and binding in an energy-independent manner, while a separate pool of Tha4 assembles with the precursor-bound receptor complex in the presence the PMF. Analysis by blue-native polyacrylamide gel electrophoresis (BN-PAGE) shows that the receptor complex, in the absence of precursor, migrates near 700 kDa and contains cpTatC and Hcf106 with little Tha4 remaining after detergent solubilization. To investigate the role that Hcf106 may play in receptor complex oligomerization and/or stability, systematic cysteine substitutions were made in positions from the N-terminal transmembrane domain to the end of the predicted amphipathic helix of the protein. BN-PAGE analysis allowed us to identify the locations of amino acids in Hcf106 that were critical for interacting with cpTatC. Oxidative cross-linking allowed us to map interactions of the transmembrane domain and amphipathic helix region of Hcf106. In addition, we showed thatin vitroexpressed, integrated Hcf106 can interact with the precursor signal peptide domain and imported cpTatC, strongly suggesting that a subpopulation of the integrated Hcf106 is participating in competent cpTat complexes.
Insights from Comparison of the Renal and Skin Single Cell Transcriptomes in Lupus Nephritis
Authors: Der Evan , Suryawanshi Hemant , Morozov Pavel , Kustagi Manjunath , Goilav Beatrice , Ranabathou Saritha , Izmirly Peter , Clancy Robert , Belmont H. Michael , Koenigsberg Mordecai , Mokrzycki Michele , Rominieki Helen , Graham Jay A. , Rocca Juan P. , Bornkamp Nicole , Jordan Nicole , Schulte Emma , Wu Ming , Pullman James , Slowikowski Kamil , Raychaudhuri Soumya , Guthridge Joel , James Judith ,   Accelerating Medicines Partnership in RA/SLE network, Buyon Jill , Tuschl Thomas , Putterman Chaim 
Published: August 2018

AbstractLupus nephritis (LN) occurs in up to 50% of patients with systemic lupus erythematosus (SLE), and is a major contributor to mortality and morbidity. LN presents as a highly heterogeneous disease both in histopathology and response to therapy. The molecular and cellular processes leading to renal damage and to the heterogeneity of the disease are not well understood. To elucidate the processes underpinning the heterogeneity of LN, we applied singlecell RNA-sequencing (scRNA-seq) to renal biopsies from LN patients. Skin biopsies were evaluated as a source of biomarkers for monitoring kidney disease. Type-I interferon (IFN) response signatures were identified in tubular cells and keratinocytes, differentiating LN patients from healthy controls. Non-responders associated with higher IFN signatures in both tissue compartments. Moreover, non-response was also associated with a fibrotic signature in the tubular cells. Receptor-ligand interaction analysis indicated that the fibrotic process is likely mediated by FGF receptors with the initiating signal originating from infiltrating leukocytes. Differential expression analysis of tubular cells between proliferative and membranous LN pointed to several fibrosis-relevant pathways, which may offer insight into their histological differences. In summary, scRNA-seq was applied to LN to deconstruct its heterogeneity and provide novel targets for personalized approaches to therapy.
Identification of functional long non-coding RNAs in C. elegans
Authors: Akay Alper , Jordan David , Navarro Isabela C. , Wrzesinski Tomasz , Ponting Chris P. , Miska Eric A. , Haerty Wilfried 
Published: August 2018

AbstractBackgroundFunctional characterisation of the compact genome of the model organism Caenorhabditis elegans remains incomplete despite its sequencing twenty years ago. The last decade of research has seen a tremendous increase in the number of non-coding RNAs identified in various organisms. While we have mechanistic understandings of small non-coding RNA pathways, long non-coding RNAs represent a diverse class of active transcripts whose function remains less well characterised.ResultsBy analysing hundreds of published transcriptome datasets, we annotated 3,397 potential lncRNAs including 146 multi-exonic loci that showed increased nucleotide conservation and GC content relative to other non-coding regions. Using CRISPR / Cas9 genome editing we generated deletion mutants for ten long non-coding RNA loci. Using automated microscopy for in-depth phenotyping, we show that six of the long non-coding RNA loci are required for normal development and fertility. Using RNA interference mediated gene knock-down, we provide evidence that for two of the long non-coding RNA loci, the observed phenotypes are dependent on the corresponding RNA transcripts.ConclusionsOur results highlight that a large section of the non-coding regions of the C. elegans genome remain unexplored. Based on our in vivo analysis of a selection of high-confidence lncRNA loci, we expect that a significant proportion of these high-confidence regions is likely to have biological function at either the genomic or the transcript level.
Evaluating the quality of the 1000 Genomes Project data
Authors: Belsare Saurabh , Sakin-Levy Michal , Mostovoy Yulia , Durinck Steffen , Chaudhry Subhra , Xiao Ming , S. Peterson Andrew , Kwok Pui-Yan , Seshagiri Somasekar , Wall Jeffrey D. 
Published: August 2018

ABSTRACTData from the 1000 Genomes project is quite often used as a reference for human genomic analysis. However, its accuracy needs to be assessed to understand the quality of predictions made using this reference. We present here an assessment of the genotype, phasing, and imputation accuracy data in the 1000 Genomes project. We compare the phased haplotype calls from the 1000 Genomes project to experimentally phased haplotypes for 28 of the same individuals sequenced using the 10X Genomics platform. We observe that phasing and imputation for rare variants are unreliable, which likely reflects the limited sample size of the 1000 Genomes project data. Further, it appears that using a population specific reference panel does not improve the accuracy of imputation over using the entire 1000 Genomes data set as a reference panel. We also note that the error rates and trends depend on the choice of definition of error, and hence any error reporting needs to take these definitions into account.
Transcriptomic and functional analysis of the oosome, a unique form of germ plasm in the waspNasonia vitripennis
Authors: Quan Honghu , Lynch Jeremy 
Published: August 2018

AbstractBackgroundThe oosome is the germline determinant in the waspNasonia vitripennisand is homologous to the polar granules ofDrosophila. Despite a common evolutionary origin and developmental role, the oosome is morphologically quite distinct from polar granules. It is a solid sphere that migrates within the cytoplasm before budding out and forming pole cells.ResultsTo gain an understanding of both the molecular basis of the novel form of the oosome, and the conserved essential features of germ plasm, we quantified and compared transcript levels between embryo fragments that contained the oosome, and those that did not. The identity of the localized transcripts indicated thatNasoniauses different molecules to carry out conserved germ plasm functions. In addition, functional testing of a sample of localized transcripts revealed potentially novel mechanisms of ribonucleoprotein assembly and pole cell cellularization in the wasp.ConclusionsOur results demonstrate that numerous novel and unexpected molecules have been recruited in order produce the unique characteristics of the oosome and pole cell formation inNasonia. This work will serve as the basis for further investigation into the patterns of germline determinant evolution among insects, the molecular basis of extreme morphology of ribonucleoproteins, and the incorporation of novel components into developmental networks.
A New Phylogenetic Framework for the Animal-adaptedMycobacterium tuberculosisComplex
Authors: Brites Daniela , Loiseau Chloe , Menardo Fabrizio , Borrell Sonia , Boniotti Maria Beatrice , Warren Robin , Dippenaar Anzaan , Charles Parsons Sven David , Beisel Christian , Behr Marcel A. , Fyfe Janet A , Coscolla Mireia , Gagneux Sebastien 
Published: August 2018

AbstractTuberculosis (TB) affects humans and other animals and is caused by bacteria from theMycobacterium tuberculosiscomplex (MTBC). Previous studies have shown that there are at least nine members of the MTBC infecting animals other than humans; these have also been referred to as ecotypes. However, the ecology and the evolution of these animal-adapted MTBC ecotypes are poorly understood. Here we screened 12,886 publicly available MTBC genomes and newly sequenced 17 animal-adapted MTBC strains, gathering a total of 529 genomes of animal-adapted MTBC strains. Phylogenomic and comparative analyses confirm that the animal-adapted MTBC members are paraphyletic with some members more closely related to the human-adaptedMycobacterium africanumLineage 6 than to other animal-adapted strains. Furthermore, we identified four main animal-adapted MTBC clades that might correspond to four main host shifts; two of these clades are proposed to reflect independent cattle domestication events. Contrary to what would be expected from an obligate pathogen, MTBC nucleotide diversity was not positively correlated with host phylogenetic distances, suggesting that host tropism in the animal-adapted MTBC seems to be driven more by contact rates and demographic aspects of the host population rather than host relatedness. By combining phylogenomics with ecological data, we propose an evolutionary scenario in which the ancestor of Lineage 6 and all animal-adapted MTBC ecotypes was a generalist pathogen that subsequently adapted to different host species. This study provides a new phylogenetic framework to better understand the evolution of the different ecotypes of the MTBC and guide future work aimed at elucidating the molecular mechanisms underlying host specificity.
GenoDup Pipeline: a tool to detect genome duplication using the dS-based method
Authors: Mao Yafei , Satoh Noriyuki 
Published: August 2018

ABSTRACTUnderstanding whole genome duplication (WGD), or polyploidy, is fundamental to investigating the origin and diversification of organisms in evolutionary biology. The wealth of genomic data generated by next generation sequencing (NGS) has resulted in an urgent need for robust and accurate tools to detect WGD. Here, we present a useful and user-friendly pipeline called GenoDup for inferring WGD using the dS-based method. We have successfully applied GenoDup to identify WGD in empirical data from both plants and animals. The GenoDup Pipeline provides a reliable and useful tool to infer WGD from NGS data.
Comparative analysis of the effect of genomic isolators flanking transgenes to avoid positional effects in Arabidopsis
Authors: Pérez-González Ana , Caro Elena 
Published: August 2018

HighlightWe have studied the effect of different insulator sequences over transgene expression levels and variability, and over transgene integration, using NGS. Our results compare the benefits obtained by their use.AbstractFor more than 20 years, plant biologists have tried to achieve complete control of transgene expression, but until gene targeting techniques become routine, flanking transgenes with genetic insulators can help avoid positional effects. Insulators are DNA sequences with barrier activity that protect transgenes from interferences with the host genome. We have, for the first time, compared the effect of three insulator sequences previously described in the literature and of a matrix attachment region from Arabidopsis never tested before. Our results indicate that the use of all sequences increases transgene expression, but only the last one reduces variability between lines and between individuals to a minimum. We have analyzed the integration of insulator-flanked T-DNAs using whole genome re-sequencing (to our knowledge, also the first time) and found chiMAR lines with insertions located within heterochromatic regions of the genome, characterized by DNA methylation that did not spread into the T-DNA, suggesting that chiMAR can shelter transgene insertions from neighboring repressive epigenetic states. Finally, we could also observe a loss of accuracy of the RB insertion in the lines harboring insulators, evidenced by a high frequency of truncation of T-DNAs and of insertion of vector backbone that, however, did not affect transgene expression.
Developing a newborn rat model of meningitis without concomitant bacteremia by intraventricular injection of K1 (-) Escherichia coli
Authors: Chang Yun Sil , Ahn So Yoon , Sung Dong Kyung , Kim Young Eun , Sung Se In , Joo So Yoon , Park Won Soon 
Published: August 2018

AbstractNeonatal meningitis caused by Escherichia coli results in high mortality and neurological disabilities, and the concomitant systemic bacteremia confounds its mortality and brain injury. This study developed an experimental model of neonatal meningitis without concomitant systemic bacteremia by determining the bacterial inoculum of K1 capsule-negative E. coli by intraventricular injection in newborn rats. Meningitis was induced by intraventricular intraventricular injection of 1 × 102 (low dose), 5 × 102 (medium dose), or 1 × 103 (high dose) colony forming units (CFU) of K1 (-) E. coli (EC5ME) in Sprague-Dawley rats at postnatal day 11. Ampicillin was started at postnatal day 12. Blood and cerebrospinal fluid (CSF) cultures were performed at 6 h, 1 day, and 6 days after inoculation. Brain magnetic resonance imaging (MRI) was performed at postnatal days 12 and 17. Survival was monitored, and brain tissues were obtained for histological and biochemical analyses at P12 and P17. Survival was inoculum dose-dependent, with lowest survival in high dose group (20&#0x0025;) compared with medium (80%) or low (70%) dose group. CSF bacterial counts in low and medium dose group were significantly lower than that in high dose group at 6 h, but not at 24 h after inoculation. No bacteria were isolated from the blood throughout the experiment, or from the CSF at postnatal day 17. Brain MRI showed an inoculum dose-dependent increase in the extent of ventriculomegaly, cerebral infarct, extent of brain injury, and inflammatory responses. We developed a newborn rat model of bacterial meningitis without concomitant systemic bacteremia by intraventricular injection of K1 (-) E.coli.