bluuebunny/crossref_metadata_2025_split huggingface dataset:
CrRLK1L receptor-like kinases HERCULES RECEPTOR KINASE 1 and ANJEA are female determinants of pollen tube reception
Authors: Galindo-Trigo Sergio , Blanco-Touriñán Noel , DeFalco Thomas A. , Wells Eloise S. , Gray Julie E , Zipfel Cyril , Smith Lisa M 
Published: September 2018

AbstractCommunication between the gametophytes is vital for angiosperm fertilisation. Multiple CrRLK1L-type receptor kinases prevent premature pollen tube burst, while another CrRLK1L protein, FERONIA (FER), is required for pollen tube burst in the female gametophyte. We report here the identification of two additional CrRLK1L homologues, HERCULES RECEPTOR KINASE 1 (HERK1) and ANJEA (ANJ), which act redundantly to promote pollen tube burst at the synergid cells. HERK1 and ANJ localise to the filiform apparatus of the synergid cells in unfertilised ovules, and in herk1 anj mutants a majority of ovules remain unfertilised due to pollen tube overgrowth, together indicating that HERK1 and ANJ act as female determinants for fertilisation. As in fer mutants, the synergid cell-specific, endomembrane protein NORTIA (NTA) is not relocalised after pollen tube reception; however, unlike fer mutants, reactive oxygen species levels are unaffected in herk1 anj double mutants. Both ANJ and HERK1 associate with FER and its proposed co-receptor LORELEI (LRE) in planta. Together, our data indicate that HERK1 and ANJ act with FER to mediate female-male gametophyte interactions during plant fertilisation.
MiR-146a-dependent regulation of CD24/AKT/β-catenin axis drives cancer stem cell phenotype in oral squamous cell carcinoma
Authors: Ghuwalewala Sangeeta , Ghatak Dishari , Das Sumit , Das Pijush , Butti Ramesh , Gorain Mahadeo , Kundu Gopal C , Roychoudhury Susanta 
Published: September 2018

AbstractCancer stem cells (CSCs) are known to potentiate tumor initiation and maintenance in Oral Squamous Cell Carcinoma (OSCC). Increasing evidences suggest that CD44highCD24low population in OSCC are potential CSCs. MicroRNAs (miRNAs) have emerged as crucial players in tumor development. However, their role in maintenance of OSCC stem cells remains unclear. Here we report that CD44highCD24low population within OSCC cells and primary HNSCC tumors have an elevated expression of miR-146a. Moreover, over-expression of miR-146a results in enhanced stemness phenotype by augmenting CD44highCD24low population. We demonstrate that miR-146a induces stemness by stabilizing β-catenin with concomitant loss of E-cadherin and CD24. Interestingly, CD24 is identified as a novel functional target of miR-146a and ectopic expression of CD24 abrogates miR-146a driven potential CSC phenotype. Mechanistic analysis reveals that higher CD24 levels inhibit AKT phosphorylation leading to β-catenin degradation. Using stably expressing miR-146a/CD24 OSCC cell lines, we also validate that the miR-146a/ CD24/AKT loop significantly alters tumorigenic ability in vivo. Furthermore, we confirmed that β-catenin trans-activates miR-146a, thereby forming a positive feedback loop contributing to stem cell maintenance. Collectively, our study demonstrates that miR-146a regulate CSCs in OSCC through CD24-AKT-β-catenin axis.HighlightsMiR-146a induces cancer stem cell characteristics in OSCC by targeting CD24CD24 abrogates miR-146a mediated stemness via β-catenin degradation in non-CSCsAkt/Wnt pathway is critical for sustenance of miR-146a driven potential CSCsThe miR-146a/CD24/AKT loop significantly alters tumorigenic ability in vivo
Movement Dynamics of Divisome and Penicillin-Binding Proteins (PBPs) in Cells of Streptococcus pneumoniae
Authors: Perez Amilcar J. , Cesbron Yann , Shaw Sidney L. , Villicana Jesus Bazan , Tsui Ho-Ching T. , Boersma Michael J , Ye Ziyun A. , Tovpeko Yanina , Dekker Cees , Holden Seamus , Winkler Malcolm E. 
Published: September 2018

ABSTRACTBacterial cell division and peptidoglycan (PG) synthesis are orchestrated by the coordinated dynamic movement of essential protein complexes. Recent studies show that bidirectional treadmilling of FtsZ filaments/bundles is tightly coupled to and limiting for both septal PG synthesis and septum closure in some bacteria, but not in others. Here we report the dynamics of FtsZ movement leading to septal and equatorial ring formation in the ovoid-shaped pathogen, Streptococcus pneumoniae (Spn). Conventional and single-molecule total internal reflection fluorescence microscopy (TIRFm) showed that nascent rings of FtsZ and its anchoring and stabilizing proteins FtsA and EzrA move out from mature septal rings coincident with MapZ rings early in cell division. This mode of continuous nascent ring movement contrasts with a failsafe streaming mechanism of FtsZ/FtsA/EzrA observed in a ΔmapZ mutant and another Streptococcus species. This analysis also provides several parameters of FtsZ treadmilling in nascent and mature rings, including treadmilling velocity in wild-type cells and ftsZ(GTPase) mutants, lifetimes of FtsZ subunits in filaments and of entire FtsZ filaments/bundles, and the processivity length of treadmilling of FtsZ filament/bundles. In addition, we delineated the motion of the septal PBP2x transpeptidase and its FtsW glycosyl transferase binding partner relative to FtsZ treadmilling in Spn cells. Five lines of evidence support the conclusion that movement of the bPBP2x:FtsW complex in septa depends on PG synthesis and not on FtsZ treadmilling. Together, these results support a model in which FtsZ dynamics and associations organize and distribute septal PG synthesis, but do not control its rate in Spn.SignificanceThis study answers two long-standing questions about FtsZ dynamics and its relationship to septal PG synthesis in Spn for the first time. In previous models, FtsZ concertedly moves from midcell septa to MapZ rings that have reached the equators of daughter cells. Instead, the results presented here show that FtsZ, FtsA, and EzrA filaments/bundles move continuously out from early septa as part of MapZ rings. In addition, this study establishes that the movement of bPBP2x:FtsW complexes in septal PG synthesis depends on and likely mirrors new PG synthesis and is not correlated with the treadmilling of FtsZ filaments/bundles. These findings are consistent with a mechanism where septal FtsZ rings organize directional movement of bPBP2x:FtsW complexes dependent on PG substrate availability.
GRID-seq assisted prediction of transcription factor binding motifs
Authors: Veldsman Werner Pieter 
Published: September 2018

AbstractExperimental validation of computationally predicted transcription factor binding motifs is desirable. Increased RNA levels in the vicinity of predicted protein-chromosomal binding motifs intuitively suggest regulatory activity. With this intuition in mind, the approach presented here juxtaposes publicly available experimentally derived GRID-seq data with binding motif predictions computationally determined by deep learning models. The aim is to demonstrate the feasibility of using RNA-sequencing data to improve binding motif prediction accuracy. Publicly available GRID-seq scores and computed DeepBind scores could be aggregated by chromosomal region and anomalies within the aggregated data could be detected using mahalanobis distance analysis. A mantel’s test of matrices containing pairwise hamming distances showed significant differences between 1) randomly ranked sequences, 2) sequences ranked by non-GRID-seq assisted scores, and 3) sequences ranked by GRID-seq assisted scores. Plots of mahalanobis ranked binding motifs revealed an inversely proportional relationship between GRID-seq scores and DeepBind scores. Data points with high DeepBind scores but low GRID-seq scores had no DNAse hypersensitivity clusters annotated to their respective sequences. However, DNase hypersensitivity was observed for high scoring DeepBind motifs with moderate GRID-seq scores. Binding motifs of interest were recognized by their deviance from the inversely proportional tendency, and the underlying context sequences of these predicted motifs were on occasion associated with DNAse hypersensitivity unlike the most highly ranked motif scores when DeepBind was used in isolation. This article presents a novel combinatory approach to predict functional protein-chromosomal binding motifs. The two underlying methods are based on recent developments in the fields of RNA sequencing and deep learning, respectively. They are shown to be suited for synergistic use, which broadens the scope of their respective applications.
The ecomorphology of southern African rodent incisors: Potential applications to the hominin fossil record
Authors: Paine Oliver C.C. , Leichliter Jennifer N. , Avenant Nico , Codron Daryl , Lawrence Austin , Sponheimer Matt 
Published: September 2018

AbstractThe taxonomic identification of mammalian fauna within fossil assemblages is a well-established component of paleoenvironmental reconstructions. However, many fragmentary specimens recovered from fossil sites are often disregarded as they can be difficult to identify with the precision required for taxonomic methods. For this reason, the large numbers of isolated rodent incisors that are often recovered from hominin fossil bearing sites have generally been seen as offering little interpretive value. Ecomorphological analysis, often referred to as a “taxon-free” method, can potentially circumvent this problem by focusing on the adaptive, rather than the taxonomic significance of rodent incisor morphology. Here, we determine if the morphology of the upper incisors of modern southern African rodents reflects dietary behavior using discriminant function analysis. Our model suggests that a strong ecomorphological signal exists in our modern sample and we apply these results to two samples of isolated incisors from the hominin fossil bearing sites, Sterkfontein and Swartkrans.
Dipeptidyl dipeptidase-4 inhibitor, MK-0626, promotes bone marrow-derived endothelial progenitor cell bioactivities for vascular regeneration in diet-induced obese mice
Authors: Salybekov Amankeldi A. , Masuda Haruchika , Miyazaki Kozo , Sheng Yin , Sato Atsuko , Shizuno Tomoko , Iida Yumi , Okada Yoshinori , Asahara Takayuki 
Published: September 2018

AbstractMetabolic syndrome (MS), overlapping type 2 diabetes, hyperlipidemia, and/or hypertension, based on high-fat diet, poses risk for cardiovascular disease. A critical feature associated with such risk is the functional impairment of endothelial progenitor cells (EPCs). Dipeptidyl dipeptidase-4 inhibitors are known not only to inhibit degradation of incretins to control blood glucose levels, but also to improve EPC bioactivity and induce anti-inflammatory effects in tissues. In the present study, we investigated the effects of such an inhibitor, MK-06266, in ischemia model of MS using diet-induced obese (DIO) mice. EPC bioactivity was examined in MK-0626-administered DIO mice and non-treated control group, using an EPC colony-forming assay and bone marrow cKit+ Sca-1+ lineage-cells, and peripheral blood-mononuclear cells. Our results showed that, in vitro, the effect of MK-0626 treatment on EPC bioactivities and differentiation was superior in comparison with non-treatment. Further, in vivo hindlimb ischemia model experiment indicated that microvascular density and pericyte-recruited arteriole number were increased in MK-0626-administered group, but not control group. Lineage profiling of isolated cells from ischemic tissues disclosed that MK-0626 administration has an inhibitory effect on unproductive inflammation. This occurred via a decrease in the influx of total blood cells and pro-inflammatory cells such as neutrophils, total macrophages, M1, total T-cells, cytotoxic T-cells, and B-cells, with a concomitant increase in number of regeneration-associated cells, such as M2/M ratio and Treg/T-helper. Laser Doppler analysis revealed that at day 14 after ischemic injury, blood perfusion in hindlimb was grater in DIO mice treated with MK-0626, but not in control. In conclusion, the dipeptidyl dipeptidase-4 inhibitor has a positive effect on EPC differentiation in MS model of DIO mice. Following ischemic injury, DPP-4 i sharply reduces recruitment of pro-inflammatory cells into ischemic tissue, and triggers regeneration and reparation process. Thus, DPP-4 i is a promising therapeutic agent for MS treatment.
Robust nomenclature and software for enhanced reproducibility in molecular modeling of small molecules
Authors: Dashti Hesam , Wedell Jonathan R. , Cornilescu Gabriel , Schwieters Charles D. , Westler William M. , Markley John L. , Eghbalnia Hamid R. 
Published: September 2018

AbstractComputational molecular dynamics, energy minimization, and modeling of molecular interactions are widely used in studies involving natural products, metabolites, and drugs. Manually directed computational steps commonly utilize an evolving collection of experimental and computational data, to which new data sources are added or modified as needed. Several software packages capable of incorporating sources of data are available, but the process remains error prone owing to the complexities of preparing and maintaining a consistent set of input files and the proper post-processing of derived data. We have devised a methodology and implemented it using an extensible software pipeline called RUNER (for Robust and Unique Nomenclature for Enhanced Reproducibility) that creates a robust and standardized computational process. The pipeline combines a web service and a graphical user interface (GUI) to enable seamless modifications and verified maintenance of atom force field parameters. The GUI provides an implementation for the widely used molecular modeling software package Xplor-NIH. We describe the RUNER software and demonstrate the rationale for the pipeline through examples of structural studies of small molecules and natural products. The software, pipeline, force field parameters, and file verification data for more than 4,100 compounds (including FDA-approved drugs and natural products) are freely accessible from [http://runer.nmrfam.wisc.edu].Author SummaryWe describe an automated and verifiable computational pipeline for calculating the force field parameters of small molecules. The pipeline integrates several software tools and guarantees reproducibility of the parameters by utilizing a standard nomenclature across multiple computational steps and by maintaining file verification identifiers. We demonstrate the application of this pipeline to (a) processing of more than 4,100 compounds in high-throughput mode, and (b) structural studies of natural products. The graphical user interface (GUI) associated with the pipeline facilitates the manually tedious steps of force field parameters adjustments and supports visualization of the process.
A cellular automaton for modeling non-trivial biomembrane ruptures
Authors: Gupta Abhay , Reint Ganna , Gözen Irep , Taylor Michael 
Published: September 2018

AbstractA novel cellular automaton (CA) for simulating biological membrane rupture is proposed. Constructed via simple rules governing deformation, tension, and fracture, the CA incorporates ideas from standard percolation models and bond-based fracture methods. The model is demonstrated by comparing simulations with experimental results of a double bilayer lipid membrane expanding on a solid substrate. Results indicate that the CA can capture non-trivial rupture morphologies such as floral patterns and the saltatory dynamics of fractal avalanches observed in experiments. Moreover, the CA provides insight into the poorly understood role of inter-layer adhesion, supporting the hypothesis that the density of adhesion sites governs rupture morphology.
Evolution of embryo implantation was enabled by the origin of decidual cells in eutherian mammals
Authors: Chavan Arun R. , Griffith Oliver W. , Stadtmauer Daniel , Maziarz Jamie , Pavlicev Mihaela , Fishman Ruth , Koren Lee , Romero Roberto , Wagner Günter P. 
Published: September 2018

AbstractEmbryo implantation is the first step in the establishment of pregnancy in eutherian (Placental) mammals. Although viviparity evolved prior to the common ancestor of marsupials and eutherian mammals (therian ancestor), implantation is unique to eutherians. The ancestral therian pregnancy likely involved a short phase of attachment between the fetal and maternal tissues followed by parturition rather than implantation, similar to the mode of pregnancy found in marsupials such as the opossum. Embryo implantation in eutherian mammals as well as embryo attachment in opossum, induce a homologous inflammatory response in the uterus. Here, we elucidate the evolutionary mechanism by which the ancestral inflammatory fetal-maternal attachment was transformed into the process of implantation. We performed a comparative transcriptomic and immunohistochemical study of the gravid and non-gravid uteri of two eutherian mammals, armadillo (Dasypus novemcinctus) and hyrax (Procavia capensis); a marsupial outgroup, opossum (Monodelphis domestica); and compared it to previously published data on rabbit (Oryctolagus cuniculus). This taxon sampling allows inference of the eutherian ancestral state. Our results show that in the eutherian lineage, the ancestral inflammatory response was domesticated by suppressing a detrimental componentviz. signaling by the cytokine IL17A, while retaining components that are beneficial to placentation,viz. angiogenesis, vascular permeability, remodeling of extracellular matrix. IL17A mediates recruitment of neutrophils to inflamed mucosal tissues, which, if unchecked, can damage the uterus as well as the embryo and lead to expulsion of the fetus. We hypothesized that the uterine decidual stromal cells, which evolved coincidentally with embryo implantation, evolved, in part, to prevent IL17A-mediated neutrophil infiltration. We tested a prediction of this hypothesisin vitro, and showed that decidual stromal cells can suppress differentiation of human naïve T cells into IL17A-producing Th17 cells. Together, these results provide a mechanistic understanding of early stages of the evolution of the eutherian mode of pregnancy, and also identify a potentially ancestral function of an evolutionary novelty, the decidual stromal cell-type.
Truncating Variant Burden in High Functioning Autism and Pleiotropic Effects ofLRP1Across Psychiatric Phenotypes
Authors: Torrico Bàrbara , Shaw Alex D , Mosca Roberto , Vivó-Luque Norma , Hervás Amaia , Fernàndez-Castillo Noèlia , Aloy Patrick , Bayés Monica , Fullerton Janice M. , Cormand Bru , Toma Claudio 
Published: September 2018

AbstractPrevious research has implicatedde novo(DN) and inherited truncating mutations in autism spectrum disorder (ASD). We aim to investigate whether the load of inherited truncating mutations contribute similarly to high functioning autism (HFA), and to characterise genes harbouring DN variants in HFA.We performed whole-exome sequencing (WES) in 20 HFA families (average IQ = 100). No difference was observed in the number of transmitted versus non-transmitted truncating alleles to HFA (117 vs 130,P= 0.32). Transmitted truncating and DN variants in HFA were not enriched in GO or KEGG categories, nor autism-related gene sets. However, in a HFA patient we identified a DN variant in a canonical splice site ofLRP1, a post-synaptic density gene that is a target for the FMRP. This DN leads to in-frame skipping of exon-29, removing 2 of 6 blades of the β-propeller domain-4 of LRP1, with putative functional consequences. Results using large datasets implicateLRP1across psychiatric diseases: i) DN are associated with ASD (P= 0.039) and schizophrenia (P= 0.008) from combined sequencing projects; ii) Common variants using Psychiatric Genomics Consortium GWAS datasets show gene-based association in schizophrenia (P= 6.6E-07) and across six psychiatric diseases (meta-analysisP= 8.1E-05); and iii) burden of ultra-rare pathogenic variants is higher in ASD (P= 1.2E-05), using WES from 6,135 schizophrenia patients, 1,778 ASD patients and 6,245 controls. Previous and current studies suggest an impact of truncating mutations restricted to severe ASD phenotypes associated with intellectual disability. We provide evidence for pleiotropic effects of common and rare variants in theLRP1gene across psychiatric phenotypes.
Temperature preference biases parental genome retention during hybrid evolution
Authors: Heil Caiti Smukowski , Large Christopher R. L. , Patterson Kira , Dunham Maitreya J. 
Published: September 2018

AbstractInterspecific hybridization can introduce genetic variation that aids in adaptation to new or changing environments. Here we investigate how the environment, and more specifically temperature, interacts with hybrid genomes to alter parental genome representation over time. We evolvedSaccharomyces cerevisiaexSaccharomyces uvarumhybrids in nutrient-limited continuous culture at 15°C for 200 generations. In comparison to previous evolution experiments at 30°C, we identified a number of temperature specific responses, including the loss of theS. cerevisiaeallele in favor of the cryotolerantS. uvarumallele for several portions of the hybrid genome. In particular, we discovered a genotype by environment interaction in the form of a reciprocal loss of heterozygosity event on chromosome XIII. Which species haplotype is lost or maintained is dependent on the parental species temperature preference and the temperature at which the hybrid was evolved. We show that a large contribution to this directionality is due to temperature sensitivity at a single locus, the high affinity phosphate transporterPHO84. This work helps shape our understanding of what forces impact genome evolution after hybridization, and how environmental conditions may favor or disfavor hybrids over time.
Study on electrochemical behavior of 690 alloy with corrosion products in simulated PWR primary water environment
Authors: Cheng Xuequn , Zuo Xiao Mei 
Published: September 2018

Purpose
The purpose of this paper is to study the electrochemical behavior of 690 alloy with corrosion products in simulated pressurized water reactor (PWR) primary water environment.

Design/methodology/approach
This paper opted for a laboratory study using simulation of high temperature and high pressure environment immersion testing. The electrochemical behavior was studied by potentiodynamic polarization, electrochemical impedance spectroscopy, scanning Kelvin probe microscopy (SKP). Moreover, the corrosion products were analyzed by X-ray photoelectron spectroscopy.

Findings
The results demonstrated that the particle majority in the 690 alloy corrosion products subsequent to high temperature and high pressure immersion testing were mainly oxides of Fe and Ni, which protected the matrix. As the immersion testing duration increased, the corrosion potential of the 690 alloy apparently increased, and the corrosion current density de'creased, while the corrosion resistance Rf increased gradually along with the density. The SKP demonstrated that the EKP increased by nearly 400 mV from −0.42 to −0.03 V following the immersion testing, indicating that the corrosion product film played an apparent protective role on the substrate.

Originality/value
This paper provides a theoretical basis for the corrosion behavior and inhibition mechanism of 690 alloy in PWR primary water environment.