bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serial horizontal transfer of vitamin-biosynthetic genes enables the establishment of new nutritional symbionts in aphids’ di-symbiotic systems
Authors: Manzano-Marín Alejandro , d’acier Armelle Coeur , Clamens Anne-Laure , Orvain Céline , Cruaud Corinne , Barbe Valérie , Jousselin Emmanuelle 
Published: February 2019

ABSTRACTMany insects with a nutrient-restricted diet depend on obligate mutualistic bacteria for the provisioning of essential nutrients lacking from their food source, namely essential amino acids and B vitamins. Most aphids (Hemiptera: Aphididae), whose diet consists of phloem, rely on the bacterial endosymbiont Buchnera for the supply of the aforementioned compounds. However, in some aphid lineages Buchnera have lost the capability of producing these nutrients and thus the symbiotic consortium has accommodated an extra bacterial partner to supplement Buchnera’s deficiencies. In this work, we explore the di-symbiotic nutritional endosymbiosis of a group of Cinara aphids which has been found to harbour both Buchnera and an Erwinia-related symbiont. Using fluorescence in situ hybridisation, we have located this symbiont to the bacteriome where it inhabits its own bacteriocytes. Through whole-genome sequencing of the endosymbionts of 9 species of Erwinia-associated Cinara aphids, we have found that Ewrinia genomes are highly syntenic and all show significant genome reduction. Additionally, Erwinia symbionts display phylogenetic congruency with Buchnera, suggesting long-term co-divergence. Most significantly, we found that not only is Erwinia capable of complementing Buchnera’s auxotrophies, but that the genes involved in the biosynthesis of two B vitamins have actually been horizontally acquired from a Sodalis-related bacterium. Finally, this B-vitamin biosynthetic genes have been further transferred to a new Hamiltonella co-obligate symbiont in a specific Cinara lineage, thus displaying a tri-symbiotic system. These results highlight the important role horizontal gene transfer plays in the establishment of new obligate nutritional symbionts.
Early life DNA methylation profiles are indicative of age-related transcriptome changes
Authors: Hadad Niran , Masser Dustin R. , Blanco-Berdugo Laura , Stanford David R. , Freeman Willard M. 
Published: February 2019

AbstractAlterations to cellular and molecular programs with brain aging result in cognitive impairment and susceptibility to neurodegenerative disease. Changes in DNA methylation patterns, an epigenetic modification required for various CNS functions, are observed with aging and can be prevented by anti-aging interventions, but the functional outcomes of altered methylation on transcriptome profiles are poorly understood with brain aging. Integrated analysis of the hippocampal methylome and transcriptome with aging of male and female mice demonstrates that age-related differences in methylation and gene expression are anti-correlated within gene bodies and enhancers, but not promoters. Methylation levels at young age of genes altered with aging are positively associated with age-related expression changes even in the absence of significant changes to methylation with aging, a finding also observed in mouse Alzheimer’s models. DNA methylation patterns established in youth, in combination with other epigenetic marks, are able to predict changes in transcript trajectories with aging. These findings are consistent with the developmental origins of disease hypothesis and indicate that epigenetic variability in early life may explain differences in age-related disease.
ANP32A and ANP32B are key factors in the Rev dependent CRM1 pathway for nuclear export of HIV-1 unspliced mRNA
Authors: Wang Yujie , Zhang Haili , Na Lei , Du Cheng , Zhang Zhenyu , Zheng Yong-Hui , Wang Xiaojun 
Published: February 2019

AbstractThe nuclear export receptor CRM1 is an important regulator involved in the shuttling of various cellular and viral RNAs between the nucleus and the cytoplasm. HIV-1 Rev interacts with CRM1 in the late phase of HIV-1 replication to promote nuclear export of unspliced and single spliced HIV-1 transcripts. However, the knowledge of cellular factors that are involved in the CRM1-dependent viral RNA nuclear export remains inadequate. Here, we identified that ANP32A and ANP32B mediate the export of unspliced or partially spliced viral mRNA via interacting with Rev and CRM1. We found that double, but not single, knockout of ANP32A and ANP32B, significantly decreased the expression of gag protein. Reconstitution of either ANP32A or ANP32B restored the viral production equally. Disruption of both ANP32A and ANP32B expression led to a dramatic accumulation of unspliced viral mRNA in the nucleus. We further identified that ANP32A and ANP32B interact with both Rev and CRM1 to promote RNA transport and that this function is Rev/RRE-dependent, but not CTE-dependent. Together our data suggests that ANP32A and ANP32B are required for HIV-1 unspliced RNA export in the Rev-CRM1 pathway.Author summaryPosttranscriptional regulation of HIV-1 genome is very important for viral protein expression and viral replication. HIV-1 Rev protein bind to RRE structure of viral RNA and interacts with the mammalian nuclear export factor Chromosomal Maintenance 1 (CRM1) in the late phase of HIV-1 replication to promote nuclear export of unspliced and single spliced HIV-1 transcripts. The REV/RRE-CRM1 pathway has been investigated for years and many host factors have been reported to be involved, but the complicated complex and procedure remain largely unknown. Here the authors report that two host proteins, ANP32A and ANP32B, are novel key factors that support export of unspliced and partial spliced viral RNA from the nucleus to the cytosol. ANP32A/B can interact with both Rev and CRM1, and this interaction is necessary for Rev/RRE-CRM1 dependent viral RNA export. These results suggest that ANP32A and ANP32B are important in viral replication and could be potential targets for novel antiviral strategy.
Growth Phase Dependent Chromosome Condensation and H-NS Protein Redistribution in E. coli Under Osmotic Stress
Authors: Rafiei Nafiseh , Cordova Martha , Navarre William Wiley , Milstein Joshua N. 
Published: February 2019

AbstractThe heat-stable nucleoid-structuring (H-NS) protein is a global transcriptional regulator implicated in coordinating the expression of over 200 genes in E. coli bacteria. We have applied super-resolved microscopy to quantify the intracellular, spatial reorganization of H-NS in response to osmotic stress. We find that H-NS shows a growth phase dependent response to hyperosmotic shock. In stationary phase, H-NS detaches from a tightly compacted bacterial chromosome and is excluded from the nucleoid volume over an extended period of time. This behaviour is absent during rapid growth but may be induced by exposing the osmotically stressed culture to the DNA gyrase inhibitor, coumermycin. This compaction/H-NS exclusion phenomenon occurs in the presence of either potassium or sodium ions and is independent of the stress responsive sigma factor RpoS, or the H-NS paralog StpA.
Big root approximation of site-scale vegtation water uptake
Authors: Bouda Martin 
Published: February 2019

AbstractLand surface model (LSM) predictions of soil moisture and transpiration under water-limited conditions suffer from biases due to a lack of mechanistic process description of vegetation water uptake. Here, I derive a ‘big root’ approach from the porous pipe equation for root water uptake and compare its predictions of soil moistures during the 2010 summer drought at the Wind River Crane site to two previously used Ohm’s law analogue plant hydraulic models. Structural error due to inadequate representation of root system architecture (RSA) in both Ohm’s law analogue models yields significant and predictable moisture biases. The big root model greatly reduces these as it better represents RSA effects on pressure gradients and flows within the roots. It represents a major theoretical advance in understanding vegetation water limitation at site scale with potential to improve LSM predictions of soil moisture, temperature and surface heat, water, and carbon fluxes.
Cytoskeleton dynamics control early events of lateral root initiation in Arabidopsis
Authors: Barro Amaya Vilches , Stöckle Dorothee , Thellmann Martha , Ruiz-Duarte Paola , Bald Lotte , Louveaux Marion , Born Patrick von , Denninger Philipp , Goh Tatsuaki , Fukaki Hidehiro , Vermeer Joop EM , Maizel Alexis 
Published: February 2019

SUMMARYHow plant cells re-establish differential growth to initiate organs is poorly understood. Morphogenesis of lateral roots relies on the tightly controlled radial expansion and asymmetric division of founder cells. The cellular mechanisms that license and ensure these features are unknown. Here, we quantitatively analyse F-actin and microtubule dynamics during LR initiation. Using mutants, pharmacological and tissue-specific genetic perturbations, we show that dynamic reorganisation of both microtubule and F-actin networks is required for the asymmetric expansion of the founder cells. This cytoskeleton remodelling intertwine with auxin signalling in the pericycle and endodermis in order for founder cells to acquire a basic polarity required for initiating LR development. Our results reveal the conservation of cell remodelling and polarisation strategies between the Arabidopsis zygote and lateral root founder cells. We propose that coordinated, auxin-driven reorganisation of the cytoskeleton licenses asymmetric cell growth and divisions during embryonic and post-embryonic organogenesis.HIGHLIGHTSFailure for lateral root founder cells to undergo asymmetric radial expansion before division, leads to aberrant organ formation.Cortical microtubules arrays reorganise to facilitate this asymmetric expansion and F-actin the asymmetric division.Cytoskeletal reorganisation depends on auxin signalling.New genetic tools allow to perturb microtubules or actin in an inducible and cell-type specific manner.
SAXSDom: Modeling multi-domain protein structures using small-angle X-ray scattering data
Authors: Hou Jie , Adhikari Badri , Tanner John J. , Cheng Jianlin 
Published: February 2019

AbstractMany proteins are composed of several domains that pack together into a complex tertiary structure. Some multidomain proteins can be challenging for protein structure modeling, particularly those for which templates can be found for the domains but not for the entire sequence. In such cases, homology modeling can generate high quality models of the domains but not for the assembled protein. Small-angle X-ray scattering (SAXS) reports on the solution structural properties of proteins and has the potential for guiding homology modeling of multidomain proteins. In this work, we describe a novel multi-domain protein assembly modeling method, SAXSDom, that integrates experimental knowledge from SAXS profiles with probabilistic Input-Output Hidden Markov model (IOHMM). Four scoring functions to account for the energetic contribution of SAXS restraints for domain assembly were developed and tested. The method was evaluated on multi-domain proteins from two public datasets. Based on the results, the accuracy of domain assembly was improved for 40 out of 46 CASP multi-domain proteins in terms of RMSD and TM-score when SAXS information was used. Our method also achieved higher accuracy for at least 45 out of 73 multi-domain proteins according to RMSD and TM-score metrics in the AIDA dataset. The results demonstrate that SAXS data can provide useful information to improve the accuracy of domain-domain assembly. The source code and tool packages are available athttp://github.com/multicom-toolbox/SAXSDom.
Cholesterol Myth and the Imperative Role of Functional Evaluation of Lipoproteins in Atherosclerotic Risk Prediction Strategies
Authors: Bhavani Ravi Divya , Ashokkumar Srinivasan , Prema Velusamy , Kishore Kumar S Narasimhan , Narasimhan Chakrapani Lakshmi , Singh Abhilasha , Thangarajeswari Mohan , Thiruvengadam Kannan , Arumugam Moongilpatti Angappa , Kalaiselvi Periandavan 
Published: February 2019

ABSTRACTObjectiveTo arrive at apposite risk prediction strategies in identifying markers that could delineate patients susceptible for atherosclerotic progression from other diabetic patient population thus circumventing undesirable drug exposure or conversely inadequate treatment.Research Design and MethodsThe study was designed to assess and compare the biochemical parameters along with lipoprotein ratios assessed in structural and functional aspects between the probable risk factor groups for CAD(diabetics with no symptoms for CAD) and untreated CAD patients (on admission for CAD) in a total of 593 participants. Anthropometric measurements were made and serum fasting glucose, lipid peroxide levels, lipid and lipoprotein ratio assessments were carried out. In addition to these basic parameters, oxidized LDL (Ox-LDL) and serum paraoxonase (PON) activity were also measured in this study. To ascertain the diagnostic accuracy of the individual markers, receiver operating characteristic curve analysis was carried out.ResultsSerum levels of blood lipids, lipid peroxides were higher in the diabetic and the cardiovascular patients with a concomitant decrease in the levels of HDL. Increased median levels of Ox-LDL and decreased PON activity was observed in the cardiovascular patients both with and without diabetes.ConclusionThis study proposes Ox-LDL/PON assessment would be more functional than the traditional LDL-c/HDL-c to categorize the risk group of patients into prospective atherosclerotic predisposed and non-predisposed population, thus enabling the former to get treated with appropriate medication.
Allometric Scaling of physiologically-relevant organoids
Authors: Magliaro Chiara , Rinaldo Andrea , Ahluwalia Arti 
Published: February 2019

AbstractThe functional and structural resemblance of organoids to mammalian organs suggests that they might follow the same allometric scaling rules. However, despite their remarkable likeness to downscaled organs, non-luminal organoids are often reported to possess necrotic cores due to oxygen diffusion limits. To assess their potential as physiologically relevant in vitro models, we determined the range of organoid masses in which quarter power scaling as well as a minimum threshold oxygen concentration is maintained. Using data on brain organoids as a reference, computational models were developed to estimate oxygen consumption and diffusion at different stages of growth. The results show that mature brain (or other non-luminal) organoids generated using current protocols must lie within a narrow range of masses to maintain both quarter power scaling and viable cores. However, micro-fluidic oxygen delivery methods could be designed to widen this range, ensuring a minimum viable oxygen threshold throughout the constructs and mass dependent metabolic scaling. The results provide new insights into the significance of the allometric exponent in systems without a resource-supplying network and may be used to guide the design of more predictive and physiologically relevant in vitro models, providing an effective alternative to animals in research.
Grey matter volume changes and corresponding cellular metrics identified in a longitudinalin vivoimaging approach
Authors: Asan Livia , Falfan-Melgoza Claudia , Weber-Fahr Wolfgang , Beretta Carlo , Kuner Thomas , Knabbe Johannes 
Published: February 2019

AbstractMagnetic resonance imaging (MRI) of the brain combined with voxel-based morphometry (VBM) has revealed structural changes of grey and white matter in a range of neurological and psychiatric disorders. However, the cellular basis of volume changes observed with VBM has remained unclear. We devised an approach to systematically correlate changes in grey matter volume (GMV) with cellular composition. Mice were alternately examined with structural MRI and two-photonin vivomicroscopy at three time points, taking advantage of age-dependent changes in brain structure. We chose to image fluorescently labelled cell nuclei, because these can be readily imaged in large tissue volumes and allow inferences on several structural parameters: (1) the physical volume as determined from a subset of nuclei used to generate a geometrically defined space, (2) the number of cells, (3) the nearest neighbour distance measured between all nuclei as an indicator of cell clustering, and (4) the volume of the cell nuclei. Using this approach, we found that physical volume did not significantly correlate with GMV change, whereas mean nuclear volume was inversely correlated. When focusing on layers within the imaging volume, positive correlations of GMV were found with cell number near the cortical surface and nearest neighbour distance in deeper layers. Thus, the novel approach introduced here provided new insights into the factors underlying grey matter volume changes.
Orthogonal Drug Pooling Enhances Phenotype-based Discovery of Ocular Anti-angiogenic Drugs in Zebrafish Larvae
Authors: Ohnesorge Nils , Sasore Temitope , Hillary Daniel , Alvarez Yolanda , Carey Michelle , Kennedy Breandán N. 
Published: February 2019

AbstractUnbiased screening of large randomized chemical libraries in vivo is a powerful tool to find new drugs and targets. However, forward chemical screens in zebrafish can be time consuming and usually >99% of test compounds have no significant effect on the desired phenotype. Here, we sought to find bioactive drugs more efficiently and to comply with the 3R principles of replacement, reduction and refinement of animals in research. We investigated if pooling of drugs to simultaneously test 8-10 compounds in zebrafish larvae can increase the screening efficiency of an established assay that identifies drugs inhibiting developmental angiogenesis in the eye. In a phenotype-based screen, we tested 1760 small molecule compounds from the ChemBridge DIVERSet™ chemical library for their ability to inhibit the formation of distinct primary hyaloid vessels in the eye. Applying orthogonal pooling of the chemical library, we treated zebrafish embryos from 3 to 5 days post fertilization with pools of 8 or 10 compounds at 10 μM each. This reduced the number of tests from 1760 to 396. In 63% of cases, treatment showed sub-threshold effects of <40% reduction of primary hyaloid vessels. From 18 pool hits, we identified 8 compounds that reduce hyaloid vessels in the larval zebrafish eye by at least 40%. Compound 4-[4-(1H-benzimidazol-2-yl)phenoxy]aniline ranked as the most promising candidate with reproducible and dose-dependent effects. To our knowledge, this is the first report of a self-deconvoluting matrix strategy applied to drug screening in zebrafish. We conclude that the orthogonal drug pooling strategy is a cost-effective, time-saving and unbiased approach to discover novel inhibitors of developmental angiogenesis in the eye. Ultimately, this approach may identify new drugs or targets to mitigate disease caused by pathological angiogenesis in the eye e.g. diabetic retinopathy or age-related macular degeneration wherein blood vessel growth and leaky vessels lead to vision impairment or clinical blindness.
Interaction of NPC2 protein with Lysobisphosphatidic Acid is required for normal endolysosomal cholesterol trafficking
Authors: McCauliff Leslie A. , Langan Annette , Li Ran , Ilnytska Olga , Bose Debosreeta , Kahn Peter C. , Storch Judith 
Published: February 2019

AbstractUnesterified cholesterol accumulation in the late endosomal/lysosomal (LE/LY) compartment is the cellular hallmark of Niemann-Pick C (NPC) disease, caused by defects in the genes encoding NPC1 or NPC2. We previously reported the dramatic stimulation of NPC2 cholesterol transport rates by the LE/LY phospholipid lysobisphosphatidic acid (LBPA) and in these studies sought to determine their functional relationship in normal LE/LY cholesterol egress. Here we demonstrate that NPC2 interacts directly with LBPA and identify the NPC2 hydrophobic knob domain as the site of interaction. Using its precursor phosphatidylglycerol (PG), we show that PG-induced LBPA enrichment results in clearance of accumulated cholesterol from NPC1-deficient cells but is ineffective in cells lacking functional NPC2. Together these studies reveal a heretofore unknown aspect of intracellular cholesterol trafficking, in which NPC2 and LBPA function together in an obligate step of sterol egress from the LE/LY compartment, which appears to be independent of NPC1.
Phylogenetic relationships among the clownfish-hosting sea anemones
Authors: Titus Benjamin M. , Benedict Charlotte , Laroche Robert , Gusmão Luciana C. , Deusen Vanessa Van , Chiodo Tommaso , Meyer Christopher P. , Berumen Michael L. , Bartholomew Aaron , Yanagi Kensuke , Reimer James D. , Fujii Takuma , Daly Marymegan , Rodríguez Estefanía 
Published: February 2019

AbstractThe clownfish-sea anemone symbiosis has been a model system for understanding fundamental evolutionary and ecological processes. However, our evolutionary understanding of this symbiosis comes entirely from studies of clownfishes. A holistic understanding of a model mutualism requires systematic, biogeographic, and phylogenetic insight into both partners. Here, we conduct the largest phylogenetic analysis of sea anemones (Order Actiniaria) to date, with a focus on expanding the biogeographic and taxonomic sampling of the 10 nominal clownfish-hosting species. Using a combination of mtDNA and nuDNA loci we test 1) the monophyly of each clownfish-hosting family and genus, 2) the current anemone taxonomy that suggests symbioses with clownfishes evolved multiple times within Actiniaria, and 3) whether, like the clownfishes, there is evidence that host anemones have a Coral Triangle biogeographic origin. Our phylogenetic reconstruction demonstrates widespread poly-and para-phyly at the family and genus level, particularly within the family Stichodactylidae and genus Sticodactyla, and suggests that symbioses with clownfishes evolved minimally three times within sea anemones. We further recover evidence for a Tethyan biogeographic origin for some clades. Our data provide the first evidence that clownfish and some sea anemone hosts have different biogeographic origins, and that there may be cryptic species of host anemones. Finally, our findings reflect the need for a major taxonomic revision of the clownfish-hosting sea anemones.
The impact of pro-inflammatory cytokines on the β-cell regulatory landscape provides new insights into the genetics of type 1 diabetes
Authors: Ramos-Rodríguez M. , Raurell-Vila H. , Colli ML. , Alvelos MI. , Subirana M. , Juan-Mateu J. , Norris R. , Turatsinze JV. , Nakayasu ES. , Webb-Robertson BJ. , Inshaw JRJ. , Marchetti P. , Piemonti L. , Esteller M. , Todd JA. , Metz TO. , Eizirik DL. , Pasquali L. 
Published: February 2019

AbstractEarly stages of type 1 diabetes (T1D) are characterized by local autoimmune inflammation and progressive loss of insulin-producing pancreatic β cells. We show here that exposure to pro-inflammatory cytokines unmasks a marked plasticity of the β-cell regulatory landscape. We expand the repertoire of human islet regulatory elements by mapping stimulus-responsive enhancers linked to changes in the β-cell transcriptome, proteome and 3D chromatin structure. Our data indicates that the β cell response to cytokines is mediated by the induction of novel regulatory regions as well as the activation of primed regulatory elements pre-bound by islet-specific transcription factors. We found that T1D-associated loci are enriched of the newly mapped cis-regulatory regions and identify T1D-associated variants disrupting cytokine-responsive enhancer activity in human β cells. Our study illustrates how β cells respond to a pro-inflammatory environment and implicate a role for stimulus-response islet enhancers in T1D.