bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repositioning septins within the core particle
Authors: Mendonça Deborah C. , Macedo Joci N. , Itri Rosangela , Guimaraes Samuel L. , Barroso da Silva Fernando L. , Cassago Alexandre , Garratt Richard C. , Portugal Rodrigo , Araujo Ana P. U. 
Published: March 2019

AbstractSeptins are GTP binding proteins considered to be a novel component of the cytoskeleton. They polymerize into filaments based on hetero-oligomeric core particles which, in humans, are either hexamers or octamers composed of two copies each of either three or four different septins from the 13 available. Not all combinations are possible as it is believed that these must obey substitution rules which determine that different septins must be derived from four distinct and well-established sub-groups. Here, we have purified and characterized one such combinations, SEPT5-SEPT6-SEPT7, and used TEM to derive the first structural information concerning its assembly. The full complex was purified using an affinity tag attached to only one of its components (SEPT7) and was able to bind to and perturb lipid bilayers. Although the complex assembled into elongated hexameric particles, the position of SEPT5 was incompatible with that predicted by the reported structure of SEPT2-SEPT6-SEPT7 based on the substitution rules. MBP-fusion constructs for SEPT5 and SEPT2 and immuno-staining clearly show that these septins occupy the terminal positions of the SEPT5-SEPT6-SEPT7 and SEPT2-SEPT6-SEPT7 hexamers, respectively. In so doing they expose a so-called NC interface which we show to be more susceptible to perturbation at high salt concentrations. Our results show that the true structure of the hexamer is inverted with respect to that described previously and, as such, is more compatible with that reported for yeast. Taken together, our results suggest that the mechanisms involved in spontaneous self-assembly of septin core particles and their filaments deserve further reflection.
Impact of pterygium on the ocular surface and meibomian glands
Authors: Wanzeler Ana Cláudia Viana , Barbosa Italo Antunes França , Duarte Bruna , Barbosa Eduardo Buzolin , Borges Daniel Almeida , Alves Monica 
Published: March 2019

AbstractPurposeTo analyze how ocular surface parameters correlate to pterygium and investigate the possible impact on tear film and meibomian glands.Methodswe investigated objective parameters of the ocular surface such as conjunctival hyperemia, tear film stability and volume, meibomian gland dysfunction, dry eye disease, corneal topography comparing healthy individuals and correlating with the pterygium clinical presentation.ResultsA total of 83 patients were included. Corneal astigmatism induction was 2.65 ± 2.52 D (0.4-11.8). The impact of pterygium on the ocular surface parameters compared to matched controls was seen in: conjunctival hyperemia (control 1.55±0.39/pterygium 2.14±0.69; p=0.0001), tear meniscus height (control 0.24±0.05 mm/pterygium 0.36±0.14mm; p 0.0002), meiboscore lower eyelid (control 0.29±0.64/pterygium 1.38±0.95; p 0.0001) and meiboscore upper eyelid (control 0.53±0.62/pterygium 0.98±0.75; p=0.0083). We found a high number of pterygium patients (88%) presented meibomian gland alterations. Interestingly, meibomian gland loss was coincident to the localization of the pterygium in 54% of the upper and 77% lower lids.ConclusionPterygium greatly impacts on ocular surface by inducing direct alterations in the pattern of meibomian glands besides corneal irregularities, conjunctival hyperemia and lacrimal film alterations, inducing significant symptoms and potential signs of dysfunction.
GCNA interacts with Spartan and Topoisomerase II to regulate genome stability
Authors: Davis Gregory M. , Dokshin Gregoriy A. , Sawle Ashley D. , Eldridge Matthew D. , Romer Katherine A. , Gourley Taylin E. , Molesworth Luke W. , Tatnell Hannah R. , Ozturk Ahmet R. , de Rooij Dirk G. , Hannon Gregory J. , Page David C. , Mello Craig C. , Carmell Michelle A. 
Published: March 2019

SummaryGCNA proteins are expressed across eukarya in pluripotent cells and have conserved functions in fertility. GCNA homologs Spartan/DVC-1 and Wss1 resolve DNA-protein crosslinks (DPCs), including Topoisomerase-DNA adducts, during DNA replication. We show that GCNA and Topoisomerase 2 (Top2) physically interact and colocalize on condensed chromosomes during mitosis, when Spartan is not present. We show thatC. elegans gcna-1mutants are sensitive to Top2 poison and accumulate mutations consistent with low fidelity repair of DNA damage, leading to loss of fitness and fertility over generations. We also demonstrate that mouse GCNA interacts with TOP2, andGcna-mutant mice exhibit abnormalities consistent with the inability to process DPCs, including chromatin condensation and crossover defects. Together, our findings provide evidence that GCNA maintains genomic integrity by processing Top2 DPCs in the germline and early embryo, where the genome is challenged with an increased DPC burden.
Extreme rainfall drives early onset cyanobacterial bloom
Authors: Larsen Megan L. , Baulch Helen M. , Schiff Sherry L. , Simon Dana F. , Sauvé Sébastien , Venkiteswaran Jason J. 
Published: March 2019

AbstractThe increasing prevalence of cyanobacteria-dominated harmful algal blooms is strongly associated with nutrient loading and changing climatic patterns. Changes to precipitation frequency and intensity, as predicted by current climate models, are likely to affect bloom development and composition through changes in nutrient fluxes and water column mixing. However, few studies have directly documented the effects of extreme precipitation events on cyanobacterial composition, biomass, and toxin production.We tracked changes in a eutrophic reservoir following an extreme precipitation event, describing an atypically early toxin-producing cyanobacterial bloom, successional progression of the phytoplankton community, toxins, and geochemistry.An increase in bioavailable phosphorus by more than 27-fold in surface waters preceded notable increases in Aphanizomenon flos-aquae throughout the reservoir approximately 2 weeks post flood and ~5 weeks before blooms typically occur. Anabaenopeptin-A and three microcystin congeners (microcystin-LR, -YR, and -RR) were detected at varying levels across sites during the bloom period, which lasted between 3 and 5 weeks.Synthesis and applications: These findings suggest extreme rainfall can trigger early cyanobacterial bloom initiation, effectively elongating the bloom season period of potential toxicity. However, effects will vary depending on factors including the timing of rainfall and reservoir physical structure. In contrast to the effects of early season extreme rainfall, a mid-summer runoff event appeared to help mitigate the bloom in some areas of the reservoir by increasing flushing.
Brain Age Prediction: Cortical and Subcortical Shape Covariation in the Developing Human Brain
Authors: Zhao Yihong , Klein Arno , Castellanos F. Xavier , Milham Michael P. 
Published: March 2019

AbstractCortical development is characterized by distinct spatial and temporal patterns of maturational changes across various cortical shape measures. There is a growing interest in summarizing complex developmental patterns into a single index, which can be used to characterize an individual’s brain age. We conducted this study with two primary aims. First, we sought to quantify covariation patterns for a variety of cortical shape measures, including cortical thickness, gray matter volume, surface area, mean curvature, and travel depth, as well as white matter volume, and subcortical gray matter volume. We examined these measures in a sample of 869 participants aged 5-18 from the Healthy Brain Network (HBN) neurodevelopmental cohort using the Joint and Individual Variation Explained (Lock et al., 2013) method. We validated our results in an independent dataset from the Nathan Kline Institute - Rockland Sample (NKI-RS; N=210) and found remarkable consistency for some covariation patterns. Second, we assessed whether covariation patterns in the brain can be used to accurately predict a person’s chronological age. Using ridge regression, we showed that covariation patterns can predict chronological age with high accuracy, reflected by our ability to cross-validate our model in an independent sample with a correlation coefficient of 0.84 between chronologic and predicted age. These covariation patterns also predicted sex with high accuracy (AUC=0.85), and explained a substantial portion of variation in full scale intelligence quotient (R2=0.10). In summary, we found significant covariation across different cortical shape measures and subcortical gray matter volumes. In addition, each shape measure exhibited distinct covariations that could not be accounted for by other shape measures. These covariation patterns accurately predicted chronological age, sex and general cognitive ability. In a subset of NKI-RS, test-retest (<1 month apart, N=120) and longitudinal scans (1.22 ± 0.29 years apart, N=77) were available, allowing us to demonstrate high reliability for the prediction models obtained and the ability to detect subtle differences in the longitudinal scan interval among participants (median and median absolute deviation of absolute differences between predicted age difference and real age difference = 0.53 ± 0.47 years, r=0.24, p-value=0.04).
Mapping Lung Cancer Epithelial-Mesenchymal Transition States and Trajectories with Single-Cell Resolution
Authors: Karacosta Loukia G. , Anchang Benedict , Ignatiadis Nikolaos , Kimmey Samuel C. , Benson Jalen A. , Shrager Joseph B. , Tibshirani Robert , Bendall Sean C. , Plevritis Sylvia K. 
Published: March 2019

ABSTRACTElucidating a continuum of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in clinical samples promises new insights in cancer progression and drug response. Using mass cytometry time-course analysis, we resolve lung cancer EMT states through TGFβ-treatment and identify through TGFβ-withdrawal, an MET state previously unrealized. We demonstrate significant differences between EMT and MET trajectories using a novel computational tool (TRACER) for reconstructing trajectories between cell states. Additionally, we construct a lung cancer reference map of EMT and MET states referred to as the EMT-MET STAte MaP (STAMP). Using a neural net algorithm, we project clinical samples onto the EMT-MET STAMP to characterize their phenotypic profile with single-cell resolution in terms of ourin vitroEMT-MET analysis. In summary, we provide a framework that can be extended to phenotypically characterize clinical samples in the context ofin vitrostudies showing differential EMT-MET traits related to metastasis and drug sensitivity.
Identification of bacteria involved in the decomposition of lignocellulosic biomass treated with cow rumen fluid by metagenomic analysis
Authors: Lee Chol Gyu , Baba Yasunori , Asano Ryoki , Fukuda Yasuhiro , Tada Chika , Nakai Yutaka 
Published: March 2019

AbstractPreviously, pretreatment of plant biomass using rumen fluid systems was developed to decompose cell wall. However, microbes which involved in plant cell wall decomposition in this system have not been identified, because the conditions of this system are different from the in situ rumen environment. We investigated the bacteria involved in the decomposition of cellulose and hemicellulose in a waste paper with the rumen pretreatment system using shotgun metagenomic analysis with next generation sequencing. After pretreatment of waste paper, about a half of the cellulose and hemicellulose content was decomposed. Genes encoding for cellulase and hemicellulase were mainly found to belonging to Ruminococcus, Clostridium, and Exiguobacterium. This study shows that Clostridium and Exiguobacterium, which have not been identified as predominant genus involved in cellulose and hemicellulose decomposition, might be categorized as the main fibrolytic bacteria in this system.
Interkinetic nuclear migration in the zebra1sh retina as a diffusive process
Authors: Azizi Afnan , Herrmann Anne , Wan Yinan , Buse Salvador J. R. P. , Keller Philipp J. , Goldstein Raymond E. , Harris William A. 
Published: March 2019

AbstractA major hallmark of neural development is the oscillatory movement of nuclei between the apical and basal surfaces of the neuroepithelium during the process of interkinetic nuclear migration (IKNM). Here, we employ long-term, rapid lightsheet and two-photon imaging of Zebrafish retinas in vivo during early development to uncover the physical processes that govern the behavior of nuclei during IKNM. These images allow the capture of reliable tracks of nuclear movements and division during early retinogenesis for many tightly packed nuclei. These tracks are then used to create and test a theory of retinal IKNM as a diffusive process across a nuclear concentration gradient generated by the addition of new nuclei at the apical surface. The analysis reveals the role of nuclear packing at the apical surface on the migration dynamics of nuclei, provides a robust quantitative explanation for the distribution of nuclei across the retina, and may have implications for stochastic fate choice in this system.
A weak Foxp3 hypomorph enhances spontaneous and therapeutic immune surveillance of cancer in mice
Authors: Almeida-Santos José , Bergman Marie-Louise , Cabral Inês Amendoeira , Correia Vasco , Caramalho Íris , Demengeot Jocelyne 
Published: March 2019

AbstractIt is well established that therapeutic impairment of Foxp3+regulatory T cells (Treg) in mice and humans favors immune rejection of solid tumors. Less explored are the genetic associations between Foxp3 allelic variants and tumor incidence, only sporadically reported in human studies. In this work, we tested and demonstrate that Foxp3fGFP, an allele classified as hypomorphic in Th1 inflammatory contexts but not affecting health at steady state, confers increased anti-tumor immunity. Our conclusions stem out of the analysis of three tumor models of different tissue origin, in two murine genetic backgrounds. When compared to wild type animals, mice carrying the Foxp3fGFPallele spontaneously delay, reduce or prevent primary tumor growth, decrease metastasis growth and potentiate the response to anti-CTLA4 monotherapy. These findings suggest that allelic variance at the Foxp3 locus may have significant impact on cancer incidence and/or the success of cancer-immunotherapies in humans.
Effect of Saudi and Egyptian pomegranate polyphenols in regulating the activity of PON1, PON2 and lipid profile for preventing coronary heart disease
Authors: BinMowyna Mona Nasser , Binobead Manal Abdulaziz , Al Badr Nawal Abdullah , AlSedairy Sahar Abdulaziz , Rahim Elredh Islam Abdul , Al-Qahtani Wedad Saeed 
Published: March 2019

AbstractSaudi and Egyptian pomegranate juice (APJ and EPJ) contains potent polyphenols antioxidants which were found to reduce serum and macrophage oxidative stress. The protective effects of APJ and EPJ against atherogenicity were evaluated by feeding mice with hypercholesterolemic diet supplemented with PJ. PJ consumption reduced mice serum Triglycerides (TG), Total cholesterol (TC) and (low density lipoprotein (LDL-c) and increase in the High-density lipoprotein (HDL-c) compared with mouse with control diet or atherogenic diet. The risk ratio and atherogenic index were significantly lower in either APJ or EPJ supplemented group. Paraoxonase 1 (PON1) which remains associated with HDL showed significant increase in the activity in mice supplemented with PJ compared to mice with atherogenic diet (AD). PJ consumption significantly reduced lipid peroxidation and increased glutathione levels. The reduction in lipid peroxidation varied from 57 to 76%. PJ supplementation reduced peritoneal macrophages (MPM) mediated oxidation of LDL by 68 to 82% and decreased mouse peritoneal macrophages (MPM) Ox-LDL uptake by 31 to 48%. A significant up regulation of macrophage PON2 activity was induced by PJ reducing the macrophage oxidative stress. In conclusion, PJ consumption resulted in anti-oxidative and antiatherogenic effects on serum and macrophages which could prevent atherosclerosis and coronary heart diseases.
Generation of a white-albino phenotype from cobalt blue and yellow-albino trouts: inheritance pattern and chromatophores analysis
Authors: Hattori Ricardo Shohei , Yoshinaga Tulio Teruo , Butzge Arno Juliano , Hattori-Ihara Shoko , Tsukamoto Ricardo Yasuichi , Takahashi Neuza Sumico , Tabata Yara Aiko 
Published: March 2019

AbstractAlbinism is the most common color variation described in fish and is characterized by a white or yellow phenotype according to the species. In rainbow troutOncorhynchus mykiss, aside from yellow-albino phenotypes, cobalt blue variants with autosomal, recessive inheritance have also been reported. In this study, we investigated the inheritance pattern and chromatophores distribution/abundance of cobalt blue trouts obtained from a local fish farm. Based on crosses with wild-type and dominant yellow-albino lines, we could infer that cobalt blue are dominant over wild-type and co-dominant in relation to yellow-albino phenotype, resulting in a fourth phenotype: the white-albino. Analysis of chromatophores revealed that cobalt blue trouts present melanophores, as the wild-type, and a reduced number of xanthophores. As regards to the white-albino phenotype, they were not only devoid of melanophores but also presented a reduced number of xanthophores. Cobalt blue and white-albino trouts also presented a more elongated body shape and, most remarkably, a smaller pituitary gland compared to wild-type and yellow-albino, suggesting that the allele for blue color is somehow linked with this abnormal pituitary phenotype. These phenotypes represent interesting models for research on body pigmentation in salmonids and on the mechanisms behind endocrine control of color patterning.
Reduced chromatin accessibility underlies gene expression differences in homologous chromosome arms of hexaploid wheat and diploidAegilops tauschii
Authors: Lu Fu-Hao , McKenzie Neil , Gardiner Laura-Jayne , Luo Ming-Cheng , Hall Anthony , Bevan Michael W 
Published: March 2019

AbstractPolyploidy has been centrally important in driving the evolution of plants, and leads to alterations in gene expression that are thought to underlie the emergence of new traits. Despite the common occurrence of these global patterns of altered gene expression in polyploids, the mechanisms involved are not well understood. Using a precise framework of highly conserved syntenic genes on hexaploid wheat chromosome 3DL and its progenitor 3L chromosome arm of diploidAegilops tauschii, we show that 70% of these genes exhibited proportionally reduced gene expression, in which expression in the hexaploid context of the 3DL genes was approximately 40% of the levels observed in diploidAe. tauschii.Many genes showing elevated expression during later stages of grain development in wheat compared toAe. tauschii.Gene sequence and methylation differences accounted for only a few cases of differences in gene expression. In contrast, large scale patterns of reduced chromatin accessibility of genes in the hexaploid chromosome arm compared to its diploid progenitor were correlated with observed overall reduction in gene expression and differential gene expression. Therefore, that an overall reduction in accessible chromatin underlies the major differences in gene expression that results from polyploidization.
Leishmania majordegrades murine CXCL1 – an immune evasion strategy
Authors: Yorek Matthew S. , Poudel Barun , Mazgaeen Lalita , Pope R. Marshall , Wilson Mary E. , Gurung Prajwal 
Published: March 2019

AbstractLeishmaniasis is a global health problem with an estimated report of 2 million new cases every year and more than 1 billion people at risk of contracting this disease in endemic areas. The innate immune system plays a central role in controllingL. majorinfection by initiating a signaling cascade that results in production of pro-inflammatory cytokines and recruitment of both innate and adaptive immune cells. Upon infection withL. major, CXCL1 is produced locally and plays an important role in the recruitment of neutrophils to the site of infection. Herein, we report thatL. majorspecifically targets murine CXCL1 for degradation. The degradation of CXCL1 is not dependent on host factors asL. majorcan directly degrade recombinant CXCL1 in a cell-free system. Using mass spectrometry, we discovered that theL. majorprotease cleaves at the C-terminal end of murine CXCL1. Finally, our data suggest thatL. majormetalloproteases are involved in the direct cleavage and degradation of CXCL1, and a synthetic peptide spanning the CXCL1 cleavage site can be used to inhibitL. majormetalloprotease activity. In conclusion, our study has identified an immune evasion strategy employed byL. majorto evade innate immune responses in mice, likely reservoirs in the endemic areas, and further highlights that targeting theseL. majormetalloproteases may be important in controlling infection within the reservoir population and transmittance of the disease.Authors’ summaryOur study discovered a highly specific role forL. majormetalloprotease in cleaving and degrading murine CXCL1. Indeed,L. majormetalloprotease did not cleave murine CXCL2 or human CXCL1, CXCL2 and CXCL8. CXCL1 is a critical chemokine required for neutrophil recruitment to the site of infection; thus, we propose that this metalloprotease may have evolved to evade immune responses specifically in the murine host. We have further identified that the C-terminal end on CXCL1 is targeted for cleavage by theL. majormetalloprotease. Finally, this cleavage site information was used to design peptides that are able to inhibit CXCL1 degradation byL. major. Our study highlights an immune evasion strategy utilized byL. majorto establish infection within a murine host.