bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional lability of RNA-dependent RNA polymerases in animals
Authors: Pinzón Natalia , Bertrand Stéphanie , Subirana Lucie , Busseau Isabelle , Escrivá Hector , Seitz Hervé
Published: June 2018

RNA interference (RNAi) requires RNA-dependent RNA polymerases (RdRPs) in many eukaryotes, and RNAi amplification constitutes the only known function for eukaryotic RdRPs. Yet in animals, classical model organisms can elicit RNAi without possessing RdRPs, and only nematode RNAi was shown to require RdRPs. Here we show that RdRP genes are much more common in animals than previously thought, even in insects, where they had been assumed not to exist. RdRP genes were present in the ancestors of numerous clades, and they were subsequently lost at a high frequency. In order to probe the function of RdRPs in a deuterostome (the cephalochordateBranchiostoma lanceolatum), we performed high-throughput analyses of small RNAs from variousBranchiostomadevelopmental stages. Our results show thatBranchiostomaRdRPs do not appear to participate in RNAi: we did not detect any candidate small RNA population exhibiting classical siRNA length or sequence features. Our results show that RdRPs have been independently lost in dozens of animal clades, and even in a clade where they have been conserved (cephalochordates) their function in RNAi amplification is not preserved. Such a dramatic functional variability reveals an unexpected plasticity in RNA silencing pathways.

Author summary

RNA interference (RNAi) is a conserved gene regulation system in eukaryotes. In non-animal eukaryotes, it necessitates RNA-dependent RNA polymerases (”RdRPs”). Among animals, only nematodes appear to require RdRPs for RNAi. Yet additional animal clades have RdRPs and it is assumed that they participate in RNAi. Here, we find that RdRPs are much more common in animals than previously thought, but their genes were independently lost in many lineages. Focusing on a species with RdRP genes (a cephalochordate), we found that it does not use them for RNAi. While RNAi is the only known function for eukaryotic RdRPs, our results suggest additional roles. Eukaryotic RdRPs thus have a complex evolutionary history in animals, with frequent independent losses and apparent functional diversification.
Identification and removal of sequencing artifacts produced by mispriming during reverse transcription in multiple RNA-seq technologies
Authors: Shivram Haridha , Iyer Vishwanath R.
Published: June 2018

The quality of RNA sequencing data relies on specific priming by the primer used for reverse transcription (RT-primer). Non-specific annealing of the RT-primer to the RNA template can generate reads with incorrect cDNA ends and can cause misinterpretation of data (RT mispriming). This kind of artifact in RNA-seq based technologies is underappreciated and currently no adequate tools exist to computationally remove them from published datasets. We show that mispriming can occur with as little as 2 bases of complementarity at the 3’ end of the primer followed by intermittent regions of complementarity. We also provide a computational pipeline that identifies cDNA reads produced from RT mispriming, allowing users to filter them out from any aligned dataset. Using this analysis pipeline, we identify thousands of mispriming events in a dozen published datasets from diverse technologies including short RNA-seq, total/mRNA-seq, HITS-CLIP and GRO-seq. We further show how RT-mispriming can lead to misinterpretation of data. In addition to providing a solution to computationally remove RT-misprimed reads, we also propose an experimental solution to avoid RT-mispriming by performing RNA-seq using thermostable group II intron derived reverse transcriptase (TGIRT-seq).
Transcribed microsatellite allele lengths are often correlated with gene expression levels in natural sunflower populations
Authors: Ranathunge Chathurani , Wheeler Gregory L. , Chimahusky Melody E. , Perkins Andy D. , Pramod Sreepriya , Welch Mark. E.
Published: June 2018

Microsatellites are common in most species. While an adaptive role for these highly mutable regions has been considered, little is known concerning their contribution towards phenotypic variation. We used populations of the common sunflower (Helianthus annuus) at two latitudes to quantify the effect of microsatellite allele length on phenotype at the level of gene expression. We conducted a common garden experiment with seed collected from sunflower populations in Kansas and Oklahoma followed by an RNA-Seq experiment on 95 individuals. The effect of microsatellite allele length on gene expression was assessed across 3325 microsatellites that could be consistently scored. Our study revealed 479 microsatellites at which allele length significantly correlates with gene expression (eSTRs). When irregular allele sizes not conforming to the motif length were removed, the number of eSTRs rose to 2379. The percentage of variation in gene expression explained by eSTRs ranged from 1–86% when controlling for population and allele-by-population interaction effects at the 479 eSTRs. Of these, 70.4% are in untranslated regions (UTRs). A Gene Ontology (GO) analysis revealed that eSTRs are significantly enriched for GO terms associated with cis- and trans-regulatory processes. These findings suggest that a substantial number of transcribed microsatellites can influence gene expression.
Whole genome sequencing,de novoassembly and phenotypic profiling for the new budding yeast speciesSaccharomyces jurei
Authors: Naseeb Samina , Alsammar Haya , Burgis Tim , Donaldson Ian , Knyazev Norman , Knight Christopher , Delneri Daniela
Published: June 2018

Saccharomyces sensu strictocomplex consist of yeast species, which are not only important in the fermentation industry but are also model systems for genomic and ecological analysis. Here, we present the complete genome assemblies ofSaccharomyces jurei,a newly discoveredSaccharomyces sensu strictospecies from high altitude oaks. Phylogenetic and phenotypic analysis revealed thatS. jureiis a sister-species toS. mikatae,thanS. cerevisiae,andS. paradoxus.The karyotype ofS. jureipresents two reciprocal chromosomal translocations between chromosome VI/VII and I/XIII when compared toS. cerevisiaegenome. Interestingly, while the rearrangement I/XIII is unique toS. jurei,the other is in common withS. mikataestrain IFO1815, suggesting shared evolutionary history of this species after the split betweenS. cerevisiaeandS. mikatae.The number of Ty elements differed in the new species, with a higher number of Ty elements present inS. jureithan inS. cerevisiae.Phenotypically, theS. jureistrain NCYC 3962 has relatively higher fitness than the other strain NCYC 3947Tunder most of the environmental stress conditions tested and showed remarkably increased fitness in higher concentration of acetic acid compared to the othersensu strictospecies. Both strains were found to be better adapted to lower temperatures compared toS. cerevisiae.
Nucleus reuniens is required for encoding and retrieving precise, hippocampal-dependent contextual fear memories in rats
Authors: Ramanathan Karthik R. , Ressler Reed L. , Jin Jingji , Maren Stephen
Published: June 2018

The nucleus reuniens (RE) is a ventral midline thalamic nucleus that interconnects the medial prefrontal cortex (mPFC) and hippocampus (HPC). Considerable data indicate that HPC-mPFC circuits are involved in contextual and spatial memory; however, it is not clear whether the RE mediates the acquisition or retrieval of these memories. To examine this question, we inactivated the RE with muscimol before either the acquisition or retrieval of Pavlovian fear conditioning in rats; freezing served as the index of fear. We found that RE inactivation before conditioning impaired the acquisition of contextual freezing, whereas inactivation of the RE prior to retrieval testing increased the generalization of freezing to a novel context; inactivation of the RE did not affect either the acquisition or expression of auditory fear conditioning. Interestingly, contextual conditioning impairments were absent when retrieval testing was also conducted after RE inactivation. Contextual memories acquired under RE inactivation were hippocampal-independent, insofar as contextual freezing in rats conditioned under RE inactivation was insensitive to intra-hippocampal infusions of the NMDA receptor antagonist, D,L-amino-5-phosophonovaleric acid (APV). Together, these data reveal that the RE supports hippocampal-dependent encoding of precise contextual memories that allow discrimination of dangerous from safe contexts. When the RE is inactive, however, alternate neural systems acquire an impoverished contextual memory that is only expressed when the RE is offline.

SIGNIFICANCE STATEMENT

The midline thalamic nucleus reuniens (RE) coordinates communication between the hippocampus and medial prefrontal cortex, brain areas critical for contextual and spatial memory. Here we show that temporary pharmacological inactivation of RE impairs the acquisition and precision of contextual fear memories after Pavlovian fear conditioning in rats. However, inactivating the RE prior to retrieval testing restored contextual memory in rats conditioned after RE inactivation. Critically, we show that imprecise contextual memories acquired under RE inactivation are learned independently of the hippocampus. These data reveal that the RE is required for hippocampal-dependent encoding of precise contextual memories to support the discrimination of safe and dangerous contexts.
Site-directed mutagenesis of the 1,3-β glucan synthase catalytic subunit ofPneumocystis jiroveciiand susceptibility assays suggest its sensitivity to caspofungin
Authors: Luraschi A. , Richard S. , Hauser P. M.
Published: June 2018

The echinocandin caspofungin inhibits the catalytic subunit Gsc1 of the enzymatic complex synthetizing 1,3-β glucan, an essential compound of the fungal wall. Studies in rodents showed that caspofungin can treatPneumocystisinfections. However, its efficacy againstPneumocystis jirovecii, the species infecting exclusively humans, remains controversial. The aim of this study was to assess the sensitivity to caspofungin of theP. jiroveciiGsc1 subunit, as well as of those ofPneumocystis cariniiandPneumocystis murinainfecting respectively rats and mice. In absence of an establishedin vitroculture method forPneumocystisspecies, we used functional complementation of theSaccharomyces cerevisiae gsc1deletant. In the fungal pathogenCandida albicans, mutations leading to amino acid substitutions in Gsc1 confer resistance to caspofungin. We introduced the corresponding mutations into thePneumocystis gsc1genes using site-directed mutagenesis. In spot dilution tests, the sensitivity to caspofungin of the complemented strains decreased with the number of mutations introduced, suggesting that the wild-type enzymes are sensitive. The minimum inhibitory concentrations of caspofungin determined by E-test®and Yeastone®for strains complemented withPneumocystisenzymes (respectively 0.125 and 0.12 microg/ml) were identical to those upon complementation with the enzyme ofC. albicansthat is sensitive to caspofungin. However, they were lower than the MICs upon complementation with the enzyme of the resistant speciesCandida parapsilosis(0.19 and 0.25). Sensitivity levels of Gsc1 enzymes of the threePneumocystisspecies were similar. Our results suggest thatP. jiroveciiis sensitive to caspofungin during infections, asP. cariniiandP. murina.
Corilagin controls post-parasiticide schistosome egg-induced liver fibrosis by inhibiting Stat6 signalling pathway
Authors: Du Peng , Ma Qian , Xiong Jun , Wang Yao , Yang Fan , Jin Feng , Chen Yun-Fei , Shang Zhen-Zhong , Chen Zhi-Lin , Zhou Xuan , Li Hua-Rong , Zhao Lei
Published: June 2018

This study aims to explore the effect of Corilagin (Cor) on post-parasiticide schistosome egg-induced hepatic fibrosis through the Stat6 signalling pathway in vitro and in vivo. Cellular and animal models were established and treated by Corilagin. The inhibitory effect of Corilagin was also confirmed in RAW264.7 cells in which Stat6 was overexpressed based on the GV367-Stat6-EGFP lentiviral vector system and in which Stat6 was knock-downed by gene specific siRNAs. As a result, Corilagin prevented increases in the protein level of Phospho-Stat6 (P-Stat6). Both the mRNA and protein levels of the downstream mediators SOCS1, KLF4, and PPARγ/δ were markedly suppressed after Corilagin treatment. Expression of ARG1 and FIZZ1/Retnla, Ym1, TGF-β and PDGF in serum were also inhibited by Corilagin. The pathological changes, area of granulomas of liver sections, and degree of hepatic fibrosis were significantly alleviated in the Corilagin group. The areas of CD68- and CD206-positive cells stained by immunofluorescence were significantly decreased by Corilagin. In conclusion, Corilagin can suppress post-parasiticide schistosome egg-induced hepatic fibrosis by inhibiting the Stat6 signalling pathway and provide a new therapeutic strategy for schistosomiasis liver fibrosis.
The demographic history of African Drosophila melanogaster
Authors: Kapopoulou Adamandia , Pfeifer Susanne P. , Jensen Jeffrey D. , Laurent Stefan
Published: June 2018

As one of the most commonly utilized organisms in the study of local adaptation, an accurate characterization of the demographic history of Drosophila melanogaster remains as an important research question. This owes both to the inherent interest in characterizing the population history of this model organism, as well as to the well-established importance of an accurate null demographic model for increasing power and decreasing false positive rates in genomic scans for positive selection. While considerable attention has been afforded to this issue in non-African populations, less is known about the demographic history of African populations, including from the ancestral range of the species. While qualitative predictions and hypotheses have previously been forwarded, we here present a quantitative model fitting of the population history characterizing both the ancestral Zambian population range as well as the subsequently colonized west African populations, which themselves served as the source of multiple non-African colonization events. These parameter estimates thus represent an important null model for future investigations in to African and non-African D. melanogaster populations alike.
Propofol inhibits endogenous formyl peptide-induced neutrophil activation and alleviates lung injury
Authors: Chen Chun-Yu , Tsai Yung-Fong , Huang Wei-Ju , Chang Shih-Hsin , Hwang Tsong-Long
Published: June 2018

Critically ill patients have a high risk of sepsis. Various studies have demonstrated that propofol has anti-inflammatory effects that may benefit critically ill patients who require anesthesia. However, the mechanism and therapeutic effect remain incompletely understood. Our previous data suggest that propofol can act as a formyl peptide receptor 1 (FPR1) antagonist. Here, we hypothesize that propofol mitigates sepsis-induced acute lung injury (ALI) by inhibiting mitochondria-derivedN-formyl peptide-mediated neutrophil activation. In human neutrophils, propofol competitively reduced the release of elastase, superoxide, and reactive oxygen species induced by fMMYALF, a human mitochondria-derivedN-formyl peptide. In addition, propofol significantly inhibited fMMYALF-induced chemotaxis, calcium mobilization, and phosphorylation of protein kinase B and mitogen-activated protein kinases. These results indicate that propofol suppresses neutrophil activation by blocking the interaction between endogenousN-formyl peptide and its receptor, FPR1, thus inhibiting downstream signaling. Furthermore, propofol alleviated alveolar wall disruption, edematous changes, and neutrophil infiltration in lipopolysaccharide-induced ALI in mice. Noticeably, propofol improved the survival of sepsis mice. This study indicates that the anti-neutrophil effects of propofol may benefit critically ill septic patients.
Long-term acclimation to different stress types: revealing tradeoffs between mesophyll and stomatal conductance
Authors: Zait Yotam , Shtein Ilana , Schwartz Amnon
Published: June 2018

Ziziphus spina-christi, a thermophilic tree, became more abundant in the Mediterranean, presumably due to increased winter temperatures. In order to predict the plant acclimation to future climate changes, we attempted to understand which factors underlie photosynthetic stress acclimation.

Stress acclimation to three major long-term abiotic stresses (drought, salinity and temperature) was investigated by measuring growth, gas exchange, chlorophyll fluorescence and leaf structure. We developed a stress index that allowed to precisely define stress level, enabling a comparison between stress types. For each stress, photosynthesis-limiting factors were compared: stomatal conductance (gs), mesophyll conductance (gm) and maximum capacity for Rubisco carboxylation (Vcmax).

Photosynthesis under all stresses was limited mostly bygsandgm(80-90%); whereas biochemistry (Vcmax) made a minor contribution (10-20%). The relative contribution ofgsandgmon photosynthetic limitation was influenced by stress type. During acclimation to drought or salinity, photosynthesis was limited by a decline ings, while intolerance to low temperatures was driven by decline ingm. Low mesophyll-imposed limitation was the best predictor of abiotic stress tolerance.

The results demonstrate how warming climate benefits thermophilic species. Moreover, current work gives methodology for stress studies, and defines the main factors underlying the plant response to climate change.

Highlight

We have compared the photosynthesis limitation resulting from long-term acclimation to three major a-biotic stresses (drought, salinity and temperature) to understand which limiting-factor are dominant under each type of stress.
FluoEM: Virtual labeling of axons in 3-dimensional electron microscopy data for long-range connectomics
Authors: Drawitsch Florian , Karimi Ali , Boergens Kevin M. , Helmstaedter Moritz
Published: June 2018

Volume electron microscopy (3D EM) has enabled the dense reconstruction of neuronal circuits in datasets that are so far about a few hundred micrometers in extent. In mammalian brains, most neuronal circuits are however highly non-local, such that a large fraction of the synapses in such a volume of neuropil originates from distant projection sources. The labeling and identification of such long-range axonal inputs from multiple sources within a densely reconstructed EM dataset has been notoriously difficult because of the limited color label space of EM. Here, we present FluoEM, a set of experimental and computational methods that allows the identification of multi-color fluorescently labeled axons in dense EM data without the need for artificially introduced fiducial marks or direct label conversion for EM. The approach is based on correlated imaging of the tissue and computational matching of neurite reconstructions, amounting to a virtual color labeling of axons in dense EM circuit data. We show that the identification of fluorescent light-microscopically (LM) imaged axons in 3D EM data from mouse cortex is faithfully possible as soon as the EM dataset is about 40-50 μm in extent, relying on the unique trajectories of axons in dense mammalian neuropil. The method is exemplified for the identification of longdistance axonal input into layer 1 of the mouse cerebral cortex.
Cell type-dependent differential activation of ERK by oncogenic KRAS in colon cancer and intestinal epithelium
Authors: Brandt Raphael , Sell Thomas , Lüthen Mareen , Uhlitz Florian , Klinger Bertram , Riemer Pamela , Giesecke-Thiel Claudia , Schulze Silvia , El-Shimy Ismail Amr , Kunkel Desiree , Fauler Beatrix , Mielke Thorsten , Mages Norbert , Herrmann Bernhard G , Sers Christine , Blüthgen Nils , Morkel Markus
Published: June 2018

Mutations activating the KRAS GTPase or the BRAF kinase are frequent in colorectal cancer and are thought to constitutively activate the terminal mitogen-activated protein kinase, ERK. Using mass cytometry, we found graded phosphorylation of ERK anti-correlated with cell differentiation in patient-derived colorectal cancer organoids, independent of KRAS mutational status. Reporter, single cell transcriptome and mass cytometry analyses showed that transgenic KRASG12V activated ERK in a cell type-specific pattern in mouse intestinal organoids. In contrast, transgenic BRAFV600E triggered high ERK activity and downstream gene expression in all intestinal cell types, followed by epithelial disorganisation. Quantitative network modelling from perturbation data revealed that activation of ERK is shaped by cell type-specific MEK to ERK feed forward and negative feedback signalling. We identified dual-specificity phosphatases as candidate modulators of ERK activity between intestinal cell types. Furthermore, we found that oncogenic KRAS, together with β-Catenin, favoured expansion of crypt cells with high ERK activity. Our experiments highlight key differences between ERK activity elicited by the BRAF or KRAS oncogenes in colorectal cancer and find unexpected heterogeneity in a signalling pathway with fundamental relevance for cancer therapy.
Identifying Mechanisms of Regulation to Model Carbon Flux During Heat Stress And Generate Testable Hypotheses
Authors: Hubbard Allen H. , Zhang Xiaoke , Jastrebski Sara , Lamont Susan J. , Singh Abhyudai , Schmidt Carl
Published: June 2018

Understanding biological response to stimuli requires identifying mechanisms that coordinate changes across pathways. One of the promises of multi-omics studies is achieving this level of insight by simultaneously identifying different levels of regulation. However, computational approaches to integrate multiple types of data are lacking. An effective systems biology approach would be one that uses statistical methods to detect signatures of relevant network motifs and then builds metabolic circuits from these components to model shifting regulatory dynamics. For example, transcriptome and metabolome data complement one another in terms of their ability to describe shifts in physiology. Here, we extend a previously described method used to identify single nucleotide polymorphism (SNP’s) associated with metabolic changes (Gieger et al., 2008). We apply this strategy to link changes in sulfur, amino acid and lipid production under heat stress by relating ratios of compounds to potential precursors and regulators. This approach provides integration of multi-omics data to link previously described, discrete units of regulation into functional pathways and hypothesizes novel biology relevant to the heat stress response.
Identification of Adomavirus Virion Proteins
Authors: Welch Nicole L. , Tisza Michael J. , Starrett Gabriel J. , Belford Anna K. , Pastrana Diana V. , Pang Yuk-Ying S. , Schiller John T. , An Ping , Cantalupo Paul G. , Pipas James M. , Koda Samantha , Subramaniam Kuttichantran , Waltzek Thomas B. , Bian Chao , Shi Qiong , Ruan Zhiqiang , Ng Terry Fei Fan , Buck Christopher B.
Published: June 2018

Adenoviruses, papillomaviruses, and polyomaviruses are collectively known as small DNA tumor viruses. Although it has long been recognized that small DNA tumor virus oncoproteins and capsid proteins show a variety of structural and functional similarities, it is unclear whether these similarities reflect descent from a common ancestor, convergent evolution, horizontal gene transfer among virus lineages, or acquisition of genes from host cells. Here, we report the discovery of a dozen new members of an emerging virus family, the Adomaviridae, that unite a papillomavirus/polyomavirus-like replicase gene with an adenovirus-like virion maturational protease. Adomaviruses were initially discovered in a lethal disease outbreak among endangered Japanese eels. New adomavirus genomes were found in additional commercially important fish species, such as tilapia, as well as in reptiles. The search for adomavirus sequences also revealed an additional candidate virus family, which we refer to as xenomaviruses, in mollusk datasets. Analysis of native adomavirus virions and expression of recombinant proteins showed that the virion structural proteins of adomaviruses are homologous to those of both adenoviruses and another emerging animal virus family called adintoviruses. The results pave the way toward development of vaccines against adomaviruses and suggest a framework that ties small DNA tumor viruses into a shared evolutionary history.

Author Summary

In contrast to cellular organisms, viruses do not encode any universally conserved genes. Even within a given family of viruses, the amino acid sequences encoded by homologous genes can diverge to the point of unrecognizability. Although members of an emerging virus family, the Adomaviridae, encode replicative DNA helicase proteins that are recognizably similar to those of polyomaviruses and papillomaviruses, the functions of other adomavirus genes have been difficult to identify. Using a combination of laboratory and bioinformatic approaches, we identify the adomavirus virion structural proteins. The results link adomavirus virion protein operons to those of other midsize non-enveloped DNA viruses, including adenoviruses and adintoviruses.
Comprehensive 2D and 3D phenotypic characterization of human invasive lobular carcinoma cell lines
Authors: Tasdemir Nilgun , Bossart Emily , Li Zheqi , Li Zhu , Levine Kevin M. , Jacobsen Britta M. , Tseng George C. , Davidson Nancy E. , Oesterreich Steffi
Published: June 2018

Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC) and characterized by the loss of E-cadherin-mediated adherens junctions. Despite displaying unique histological and clinical features, ILC still remains a chronically understudied disease with limited knowledge on the available laboratory research models. To this end, herein we report a comprehensive 2D and 3D phenotypic characterization of four Estrogen Receptor-positive human ILC cell lines - MDA-MB-134, SUM44, MDA-MB-330 and BCK4. Compared to the IDC cell lines MCF7, T47D and MDA-MB-231, ultra-low attachment culture conditions revealed a remarkable anchorage-independence ability that was unique to the ILC cells, a feature not evident in soft agar gels. 3D Collagen I and Matrigel culture indicated a generally loose morphology for the ILC cell lines, which exhibited differing preferences for adhesion to ECM proteins in 2D. Furthermore, ILC cells had limited migration and invasion ability in wound-scratch and transwell assays with the exception of haptotaxis to Collagen I. Transcriptional comparison of the cell lines confirmed the decreased cell proliferation and E-cadherin-mediated intercellular junctions in ILC, while uncovering the induction of novel pathways related to cyclic nucleotide phosphodiesterase activity, ion channels, drug metabolism and alternative cell adhesion molecules such as N-cadherin, some of which were also differentially regulated in ILC versus IDC tumors. Altogether, these studies will serve as an invaluable resource for the breast cancer research community and facilitate further functional discoveries towards understanding ILC, identifying novel drug targets and ultimately improving the outcome of patients with ILC.

Authors’ Contributions

Conception and design:N. Tasdemir, NE. Davidson, S. Oesterreich

Development of methodology:N. Tasdemir, L. Zhu, GC. Tseng, S. Oesterreich

Acquisition of data (performed experiments, processed data, etc.):N. Tasdemir, E. Bossart, Z. Li, Z. Li

Analysis and interpretation of data (e.g. biological interpretation, statistical analysis, computational analysis):N. Tasdemir, Z. Li, KM. Levine, NE. Davidson, S. Oesterreich

Writing, review and/or revision of the manuscript:N. Tasdemir, Z. Li, KM. Levine, BM. Jacobson, GC. Tseng, NE. Davidson, S. Oesterreich

Study supervision:NE. Davidson and S. Oesterreich
Identification of genes affecting saturated fat acid content in Elaeis guineensis by genome-wide association analysis
Authors: Xia Wei , Luo Tingting , Zhang Wei , Mason Annaliese S. , Huang Dongyi , Huang Xiaolong , Tang Wenqi , Dou Yajing , Zhang Chunyu , Xiao Yong
Published: June 2018

Oil palm is the highest yielding oil crop per unit area worldwide. Unfortunately, palm oil is often considered unhealthy. In particular, palmic acid (C16:0) is a major component of palm oil. In this study a total of 1 261 501 SNP markers were produced in a diversity panel of 200 oil palm individuals. Oil content in this population varied from 29.8% to 70.3%, palmic acid varied from 31.3% to 48.8%, and oleic acid varied from 31.3% to 50.1%. We identified 274 SNP markers significantly associated with fatty acid compositions; 44 candidate genes in the flanking regions of these SNPs were involved in fatty acid biosynthesis and metabolism. Among them, two acyl-ACP thioesterase B genes had differential expression patterns between the mesocarp and kernel, tissues which show different oil profiles in oil palm (high palmic acid and high lauric acid respectively). Overexpression of both genes caused a significant increase in palmic acid content, while overexpression of the EgFatB2 gene also caused an accumulation of lauric acid and myristic acid. Our research provides genome-wide SNPs, a set of markers significantly associated with fatty acid content, and validated candidate genes for future targeted breeding of lower saturated fat content in palm oil.
Epstein-Barr Virus May Contribute to Central Nervous System Involvement in HIV-positive Individuals
Authors: Lupia T , Milia MG , Atzori C , Audagnotto S , Imperiale D , Mighetto L , Pirriatore V , Gregori G , Lipani F , Ghisetti V , Bonora S , Di Perri G , Calcagno A
Published: June 2018

Epstein-Barr virus (EBV) often accesses the central nervous system (CNS) where it may lead to blood brain barrier (BBB) integrity disruption, facilitating the migration of immune cells into brain parenchyma. Our aim was to study the association between cerebrospinal fluid (CSF) EBV DNA and HIV-1 compartmental replication. 281 HIV-positive adults undergoing lumbar punctures for clinical reasons (excluding those with lymphoproliferative disorders) and CSF samples were examined. CSF virological, neurodamage (tau, p-tau, 1-42 beta amyloid) and immune activation (neopterin and S100beta) markers were measured by immune-enzymatic, ELISA and PCR validated methods. Two hundred eighty one patients were included; 111 (40.5 %) were naïve for antiretroviral treatment. CSF EBV DNA was detectable in 25 (21.9%) naïve and 26 (16%) treated patients at low levels (<100 and 146 copies/mL). Naïve EBV+ subjects presented higher CSF HIV RNA, biomarkers (t-tau, p-tau, neopterin) and higher rates of pleocytosis. Treated EBV+ individuals showed pleocytosis, higher CSF HIV RNA, CSF to serum albumin ratio, IgG index and neopterin. No association was observed between detectable CSF EBV DNA and the rate of CSF escape. In patients with plasma HIV RNA <20 copies/mL (n=97) CSF EBV DNA was detectable in 13 subjects (13.4%) and it was associated with pleocytosis, higher CSF HIV RNA and neopterin levels. EBV DNA was detectable in a considerable proportion of HIV-positive patients and it was associated with higher levels of CSF HIV RNA and neuronal damage/inflammation biomarkers. The role of EBV reactivation in HIV-associated CNS disorders warrant further studies.

Importance

EBV is a human gamma-herpesvirus with a seroprevalence in adults approaches 95% and the pattern of clinical manifestations is very heterogeneous and varies from asymptomatic or mild viral infection to a tightly linked with several malignancies as nasopharyngeal carcinoma, Hodgkin’s lymphoma and Burkitt’s lymphoma. HIV-infected and immunocompetent patients were both at risk of primary infection and complications linked to EBV.

Primary tropism of EBV is for lymphocytes (type B, T and NK), epithelial, endothelial and smooth muscle cells and establishes lifelong latent infection. Central nervous system could be affected by this herpesvirus in primary infection and reactivation and EBV-DNA is not an uncommon finding in CSF in HIV-infected population. The significance of our research is in identifying the presence of a link between HIV and EBV CNS replication.
A Fixed Moderate-dose Combination of Tiletamine+Zolazepam Outperforms Midazolam in Induction of Short-term Immobilization of Ball Pythons (Python regius)
Authors: Miller Lynn J. , Fetterer David P. , Lackemeyer Nicole L. , Lackemeyer Matthew G. , Donnelly Ginger C. , Steffens Jesse T. , Van Tongeren Sean A. , Fiallos Jimmy O. , Moore Joshua L. , Marko Shannon T. , Lugo-Roman Luis A. , Fedewa Greg , DeRisi Joseph L. , Kuhn Jens H. , Stahl Scott J.
Published: June 2018

Laboratory animals are commonly anesthetized to prevent pain and distress and to provide safe handling. Anesthesia procedures are well-developed for common laboratory mammals, but not as well established in reptiles. We assessed the performance of intramuscularly injected tiletamine (dissociative anesthetic) and zolazepam (benzodiazepine sedative) in fixed combination (2 mg/kg and 3 mg/kg) in comparison to 2 mg/kg of midazolam (benzodiazepine sedative) in ball pythons (Python regius). We measured heart and respiratory rates and quantified induction parameters (i.e., time to loss of righting reflex, time to loss of withdrawal reflex) and recovery parameters (i.e., time to regain righting reflex, withdrawal reflex, normal behavior). Mild decreases in heart and respiratory rates (median decrease of <10 beats per minute and <5 breaths per minute) were observed for most time points among all three anesthetic dose groups. No statistically significant difference between the median time to loss of righting reflex was observed among animals of any group (p = 0.783). However, the withdrawal reflex was lost in all snakes receiving 3mg/kg of tiletamine+zolazepam but not in all animals of the other two groups (p = 0.0004). In addition, the time for animals to regain the righting reflex and resume normal behavior was longer in the drug combination dose groups compared to the midazolam group (p = 0.0055). Our results indicate that midazolam is an adequate sedative for ball pythons but does not suffice to achieve reliable immobilization or anesthesia, whereas tiletamine+zolazepam achieves short-term anesthesia in a dose-dependent manner.
Seasonality controls the predictive skills of diatom based salinity transfer functions
Authors: Vilar Alejandra Goldenberg , Donders Timme , Cvetkoska Aleksandra , Wagner-Cremer Friederike
Published: June 2018

The value of diatoms as bioindicators of contemporary and palaeolimnological studies through transfer function development has increased in the last decades. While they represent a tremendous advance in (palaeo) ecology, these models also leave behind important sources of uncertainties that are often ignored. In the present study we tackle two of the most important sources of uncertainty in the development of diatom salinity inference models: the effect of secondary variables associated to seasonality and the comparison of conventional cross-validation methods with a validation based on independent datasets. Samples (diatoms and environmental variables) were taken in spring, summer and autumn in the freshwater and brackish ditches of the province of North Holland in 1993 and sampled again different locations of the same province in 2008-2010 to validate the models. We found that the abundance of the dominant species significantly changed between the seasons, leading to inconsistent estimates of species optima and tolerances. A model covering intra-annual variability (all seasons combined) provides averages of species optima and tolerances, reduces the effect of secondary variables due to the seasonality effects, thus providing the strongest relationship between salinity and diatom species. In addition, the ‘all-season’ model also reduces the edge effects usually found in all unimodal-based calibration methods. While based on cross-validation all four models seem to perform relatively well, a validation with an independent dataset emphasizes the importance of using models covering intra-annual variability to perform realistic reconstructions.
Retinoblastoma 1 (RB1) modulates the proliferation of chicken preadipocytes
Authors: Wang Yu-Xiang , Wang Hai-Xia , Na Wei , Qin Fei-Yue , Zhang Zhi-Wei , Dong Jia-Qiang , Li Hui , Zhang Hui
Published: June 2018

Retinoblastoma 1 (RB1) has been extensively studied in mammalian species, but its function in avian species is unclear. The objective of this study was to reveal the role of chicken RB1 (Gallus gallus RB1, gRB1) in the proliferation of preadipocytes. In the current study, quantitative real-time PCR analysis showed that the expression levels of gRB1 transiently increased during the proliferation of preadipocytes. The MTT assay showed that gRB1 overexpression suppressed preadipocyte proliferation, and gRB1 interference promoted preadipocyte proliferation. Additionally, cell-cycle analysis indicated that gRB1 may play a crucial role in the G1/S transition. Consistently, gene expression analysis showed that gRB1 knockdown promoted marker of proliferation Ki-67 (MKi67) expression at 96 h (P < 0.05), and that overexpression of gRB1 reduced MKi67 expression at 72 h (P < 0.05). Together, our study demonstrated that gRB1 inhibited preadipocyte proliferation at least in part by inhibiting the G1 to S phase transition.
Restoring striatal WAVE-1 improves maze exploration performance of GluN1 knockdown mice
Authors: Chen Yuxiao , Milenkovic Marija , Salahpour Ali , Soderling Scott H. , Ramsey Amy J.
Published: June 2018

NMDA receptors are important for cognition and are implicated in neuropsychiatric disorders. GluN1 knockdown (GluN1KD) mice have reduced NMDA receptor levels, striatal spine density deficits, and cognitive impairments. However, how NMDA depletion leads to these effects is unclear. Since Rho GTPases are known to regulate spine density and cognition, we examined the levels of RhoA, Rac1, and Cdc42 signaling proteins. Striatal Rac1-pathway components are reduced in GluN1KD mice, with Rac1 and WAVE-1 deficits at 6 and 12 weeks of age. Concurrently, medium spiny neuron (MSN) spine density deficits are present in mice at these ages. To determine whether WAVE-1 deficits were causal or compensatory in relation to these phenotypes, we intercrossed GluN1KD mice with WAVE-1 overexpressing (WAVE-Tg) mice to restore WAVE-1 levels. GluN1KD-WAVE-Tg hybrids showed rescue of striatal WAVE-1 protein levels and MSN spine density, as well as selective behavioral rescue in the Y-maze and 8-arm radial maze tests. GluN1KD-WAVE-Tg mice expressed normalized WAVE-1 protein levels in the hippocampus, yet spine density of hippocampal CA1 pyramidal neurons was not significantly altered. Our data suggest a nuanced role for WAVE-1 effects on cognition and a delineation of specific cognitive domains served by the striatum. Rescue of striatal WAVE-1 and MSN spine density may be significant for goal-directed exploration and associated long-term memory in mice.
Kernel machine tests of association between brain networks and phenotypes
Authors: Jensen Alexandria M , Tregellas Jason R , Sutton Brianne , Xing Fuyong , Ghosh Debashis
Published: June 2018

Applications of quantitative network analysis to functional brain connectivity have become popular in the last decade due to their ability to describe the general topological principles of brain networks. However, many issues arise when standard statistical analysis techniques are applied to functional magnetic resonance imaging (fMRI) connectivity maps. Frequently, summary measures of these maps, such as global efficiency and clustering coefficients, collapse the changing structures of graph topology from many scales to one. This can result in a loss of whole-brain spatio-temporal pattern information that may be significant in association and prediction analyses. Drawing from the electrical engineering field, the resistance perturbation distance is a quantification of similarity between graphs on the same vertex set that has been shown to identify changes in dynamic graphs, such as those from fMRI, while not being computationally expensive or result in a loss of information. This work proposes a novel kernel-based regression scheme that incorporates the resistance perturbation distance to better understand the association with biological phenotypes from fMRI using both simulated and real datasets.
Cooperative Non-bonded Forces Control Membrane Binding of the pH-Low Insertion Peptide pHLIP
Authors: Gupta C. , Ren Y. , Mertz B.
Published: June 2018

Peptides with the ability to bind and insert into the cell membrane have immense potential in biomedical applications. pH (Low) Insertion Peptide (pHLIP), a water-soluble polypeptide derived from helix C of bacteriorhodopsin, can insert into a membrane at acidic pH to form a stable transmembrane α-helix. The insertion process takes place in three stages: pHLIP is unstructured and soluble in water at neutral pH (state I), unstructured and bound to the surface of a membrane at neutral pH (state II), and inserted into the membrane as an α-helix at low pH (state III). Using molecular dynamics (MD) simulations, we have modeled state II of pHLIP and a fast-folding variant of pHLIP, in which each peptide is bound to a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer surface. Our results provide strong support for recently published spectroscopic studies, namely that pHLIP preferentially binds to the bilayer surface as a function of location of anionic amino acids and that backbone dehydration occurs upon binding. Unexpectedly, we also observed several instances of segments of pHLIP folding into a stable helical turn. Our results provide a molecular level of detail that is essential to providing new insights into pHLIP function and to facilitate design of variants with improved cell-penetrating capabilities.
The IICR and the non-stationary structured coalescent: demographic inference with arbitrary changes in population structure
Authors: Rodríguez Willy , Mazet Olivier , Grusea Simona , Boitard Simon , Chikhi Lounès
Published: June 2018

In the last years, a wide range of methods allowing to reconstruct past population size changes from genome-wide data have been developed. At the same time, there has been an increasing recognition that population structure can generate genetic data similar to those produced under models of population size change. Recently, Mazet et al. (2016) showed that, for any model of population structure, it is always possible to find a panmictic model with a particular function of population size changes, having exactly the same distribution ofT2(the coalescence time for a sample of size two) to that of the structured model. They called this function IICR (Inverse Instantaneous Coalescence Rate) and showed that it does not necessarily correspond to population size changes under non panmictic models. Besides, most of the methods used to analyse data under models of population structure tend to arbitrarily fix that structure and to minimise or neglect population size changes. Here we extend the seminal work of Herbots (1994) on the structured coalescent and propose a new framework, the Non-Stationary Structured Coalescent (NSSC) that incorporates demographic events (changes in gene flow and/or deme sizes) to models of nearly any complexity. We show how to compute the IICR under a wide family of stationary and non-stationary models. As an example we address the question of human and Neanderthal evolution and discuss how the NSSC framework allows to interpret genomic data under this new perspective.

Author summary

Genomic data are becoming available for a rapidly increasing number of species, and contain information about their recent evolutionary history. If we wish to understand how they expanded, contracted or admixed as a consequence of recent and ancient environmental changes, we need to develop general inferential methods. Currently, demographic inference is either done assuming that a species is a single panmictic population or using arbitrary structured models. We use the concept of IICR (Inverse of the Instantaneous Coalescence Rate) together with Markov chains theory to develop a general inferential framework which we call the Non-Stationary Structured Coalescent and apply it to explain human and Neanderthal genomic data in a single structured model.
Effect of Heterogeneity in Recombination Rate on Variation in Realised Relationship
Authors: White Ian M.S. , Hill William G.
Published: June 2018

Individuals of specified pedigree relationship vary in the proportion of the genome they share identical by descent, i.e. in their realised or actual relationship. Basing predictions of the variance in realised relationship solely on the proportion of the map length shared implicitly assumes that both recombination rate and genetic information are uniformly distributed along the genome, ignoring the possible existence of recombination hotspots, and failing to distinguish between coding and non-coding sequences. In this paper we quantify the effects of heterogeneity in recombination rate at broad and fine scale levels on the variation in realised relationship. A chromosome with variable recombination rate usually shows more variance in realised relationship than does one having the same map length with constant recombination rate, especially if recombination rates are higher towards chromosome ends. Reductions in variance can also be found, and the overall pattern of change is quite complex. In general, local (fine-scale) variation in recombination rate, e.g. hotspots, has a small influence on the variance in realised relationship. Differences in rates across longer regions and between chromosome ends can increase or decrease the variance in realised relationship, depending on the genomic architecture.
Fatigue life prediction of ceramic-matrix composites
Authors: Li Longbiao
Published: June 2018

Purpose

This paper aims to predict fatigue life and fatigue limit of fiber-reinforced ceramic-matrix composites (CMCs) with different fiber preforms, i.e. unidirectional, cross-ply, 2D-, 2.5D- and 3D-woven, at room and elevated temperatures.

Design/methodology/approach

Under cyclic loading, matrix multicracking and interface debonding occur upon first loading to fatigue peak stress, and the interface wear appears with increasing cycle number, leading to degradation of the interface shear stress and fibers strength. The relationships between fibers fracture, cycle number, fatigue peak stress and interface wear damage mechanism have been established based on the global load sharing (GLS) criterion. The evolution of fibers broken fraction versus cycle number curves of fiber-reinforced CMCs at room and elevated temperatures have been obtained.

Findings

The predicted fatigue life S–N curve can be divided into two regions, i.e. the Region I controlled by the degradation of interface shear stress and fibers strength and the Region II controlled by the degradation of fibers strength.

Practical/implications

The proposed approach can be used to predict the fatigue life and fatigue limit of unidirectional, cross-ply, 2D-, 2.5D- and 3D-woven CMCs under cyclic loading.

Originality/value

The fatigue damage mechanisms and fibers failure model were combined together to predict the fatigue life and fatigue limit of fiber-reinforced CMCs with different fiber preforms.