bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNAknot: A new algorithm for RNA secondary structure prediction based on genetic algorithm and GRASP method
Authors: El Fatmi Abdelhakim , Bekri M. Ali , Benhlima Said 
Published: October 2019

The prediction of the optimal secondary structure for a given RNA sequence represents a challenging computational problem in bioinformatics. This challenge becomes harder especially with the discovery of different pseudoknot classes, which is a complex topology that plays diverse roles in biological processes. Many recent studies have been proposed to predict RNA secondary structure with some pseudoknot classes, but only a few of them have reached satisfying results in terms of both complexity and accuracy. Here we present RNAknot, a new method for predicting RNA secondary structure that contains the following components: stems, hairpin loops, multi-branched loops or multi-loops, bulge loops, and internal loops, in addition to two types of pseudoknots, H-type pseudoknot and Hairpin kissing. RNAknot is based on a genetic algorithm and Greedy Randomized Adaptive Search Procedure (GRASP), and it uses the free energy as fitness function to evaluate the obtained structures. In order to validate the performance of the presented method 131 tests have been performed using two datasets of 26 and 105 RNA sequences, which have been taken from the two data bases RNAstrand and Pseudobase respectively. The obtained results are compared with those of some RNA secondary structure prediction programs such as Vs_subopt, CyloFold, IPknot, Kinefold, RNAstructure, and Sfold. The results of this comparative study show that the prediction accuracy of our proposed approach is significantly improved compared to those obtained by the other programs. For the first dataset, RNAknot has the highest specificity (SP) (71.23%) and sensitivity (SN) (72.15%) averages compared to the other programs. Concerning the second dataset, the RNA secondary structure predictions obtained by the RNAknot correspond to the highest averages of SP (85.49%) and F-measure (79.97%) compared to the other programs. The program is available as a jar file in the link: www.bachmek.umi.ac.ma/wp-content/uploads/RNAknot.0.0.2.rar .
Linnaeus tercentenary and invertebrate taxonomy: an introduction*
Authors: ZHANG ZHI-QIANG , SHEAR WILLIAM A. 
Published: October 2019

Carl Linnaeus (1707–1778) is the founding father of modern taxonomy. The binominal nomenclatural system for species and the principles of biological classification that he developed in the 18th century provide the basis on which we name and group organisms today. The tenth edition of his monumental Systema Naturae (Linnaeus 1758) marks the beginning of zoological nomenclature (ICZN 1999) and zoology as a modern branch of the natural sciences. Linnaeus’ genius was to see and understand what others had not: the requirement for a simple, easily applied, and consistent system of classification. That the fundamental principles of his work have survived two and a half centuries of repeated challenges stands as a tribute to that genius.
Phylogeny and systematics of Diptera: Two decades of progress and prospects*
Authors: YEATES DAVID K. , WIEGMANN BRIAN M. , COURTNEY GREG W. , MEIER RUDOLF , LAMBKIN CHRISTINE , PAPE THOMAS 
Published: October 2019

The Diptera, or true flies (mosquitoes, gnats, and house flies) comprise 12-15% of animal species, and are the most ecologically diverse order of insects, spanning ecological roles from detritivory to vertebrate blood feeding and leaf mining. The earliest known fossil Diptera are from the early Triassic 240 mya, and the order probably arose in the late Permian. The earliest brachyceran fossils are found in the late Triassic and earliest Jurassic, but the diversification of the extremely diverse Calyptrata (ca. 30% of described species) began in the late Creataceous. The monophyly of the order is supported by numerous morphological and biological characters and molecular data sets. The major lineages within the order are well established, and we summarize major recent phylogenetic analyses in a supertree for the Diptera. Most studies concur that the traditional subordinal group Nematocera is paraphyletic, but relationships between the major lineages of these flies are not recovered consistently. There is particular instability around the placement of the tipulids and their relatives and the families of the Psychodomorpha as traditionally defined. The other major suborder, Brachycera, is clearly monophyletic, and the relationships between major brachyceran lineages have become clearer in recent decades. The Eremoneura, Cyclorrhapha, Schizophora and Calyptrata are monophyletic, however the “Orthorrhapha” and “Aschiza” are paraphyletic, and it is likely that the “Acalyptrata” are also. Ongoing phylogenetic analyses that span the diversity of the order shall establish a robust phylogeny of the group with increased quantitative rigor. This will enable a more precise understanding of the evolution of the morphology, biogeography, biology, and physiology of flies.
Phylum Echinodermata*
Authors: PAWSON DAVID L. 
Published: October 2019

The Phylum Echinodermata, comprising approximately 7,000 living species, and 13,000 fossil species, is epitomized by the familiar sea star, a universal symbol of the marine realm. This distinctive group of animals may be briefly defined as possessing a skeleton of calcium carbonate in the form of calcite; a unique water-vascular system which mediates feeding, locomotion, and other functions; and a more or less conspicuous five-part radial symmetry. A closer look at some extant echinoderms will show that some taxa of sea cucumbers lack calcite in their body walls, some taxa of sea stars have “outgrown” five-part symmetry and may have 50 or more arms, and many echinoderms show a more or less conspicuous bilateral symmetry superimposed upon a radial pattern. Fossil echinoderms can be even more puzzling, for some are decidedly asymmetrical, and others may lack evidence of a water-vascular system. Perhaps the only truly reliable taxonomic character of the phylum is that its members today are restricted to the marine realm.
Cell-surface expression of RhD blood group polypeptide is posttranscriptionally regulated by the RhAG glycoprotein
Authors: Mouro-Chanteloup Isabelle , D'Ambrosio Anne Marie , Gane Pierre , Le Van Kim Caroline , Raynal Virginie , Dhermy Didier , Cartron Jean-Pierre , Colin Yves 
Published: October 2019

AbstractIn most cases, the lack of Rh in Rhnull red cells is associated with RHAG gene mutations. We explored the role of RhAG in the surface expression of Rh. Nonerythroid HEK293 cells, which lack Rh and RhAG, or erythroid K562 cells, which endogenously express RhAG but not Rh, were transfected with RhD and/or RhAG cDNAs using cytomegalovirus (CMV) promoter–based expression vectors. In HEK293 cells, a low but significant expression of RhD was obtained only when RhAG was expressed at a high level. In K562 cells, as expected from the opposite effects of the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) on erythroid and CMV promoters, the levels of endogenous RhAG and recombinant RhD transcripts were substantially decreased and enhanced upon TPA treatment of RhD-transfected cells (K562/RhD), respectively. However, flow cytometry and fluorescence microscopy analysis revealed a decreased cell-surface expression of both RhAG and RhD proteins. Conversely, TPA treatment of RhAG-transfected cells increased both the transcript and surface expression levels of RhAG. When K562/RhD cells were cotransfected by the RhAG cDNA, the TPA-mediated induction of recombinant RhAG and RhD transcription was associated with an increased membrane expression of both RhAG and RhD proteins. These results demonstrate the role of RhAG as a strictly required posttranscriptional factor regulating Rh membrane expression. In addition, because the postulated 2:2 stoichiometry between Rh and RhAG observed in the native red cell membrane could not be obtained in cotransfected K562 cells, our study also suggests that as yet unidentified protein(s) might be involved for optimal membrane expression of Rh.
Dose Intensity and Risk of Relapse for NHL after Allogeneic Transplant.
Authors: Rodriguez Roberto , Nademanee Auayporn , Carter Nora , Smith Eileen , Krishnan Amrita , Popplewell Leslie , Zain Jasmine , Kirschbaum Mark , Sano Allison , Patane Kathy , Nathwani Mudra , Spielberger Ricardo , Sarkodee-Adoo Clarence , Forman Stephen J. 
Published: October 2019

Abstract
Reduced intensity regimens (RIR) have largely replaced conventional myeloablative regimens (CMR) for patients with NHL undergoing allogeneic transplant. However, the impact of dose reduction on relapse has not been extensively studied. We performed a retrospective analysis of 88 patients conditioned with CMR (n=48) and a RIR (n=40) of fludarabine 125mg/m2 and melphalan 140mg/m2. GVHD prophylaxis was with cyclosporine + MTX +/− prednisone for CMR and cyclosporine + MMF +/− MTX for the RIR.
CMR RIR P Value N 48 40 Low grade B-cell 18 16 NS Intermediate grade B-cell 16 12 NS Mantle cell 10 5 NS T cell 4 7 NS Age (years, median, range) 44 (18–54) 51 (20–67) 0.0002 No of prior regimens (median) 3 2 0.02 Previous autologous transplant 5 16 0.002 Chemosensitivity at transplant 24 31 0.007 FTBI regimen 41 0 <0.0001 MUD 8 17 0.009 PBSC 16 36 0.0001 Median follow-up (months,range) 65 (33-95) 20 (6-42)
CMR were significantly associated with a lower rate of relapse (RR) of 15% versus 38% after RIR (p=0.017). The 1-year TRM was 38% for CMR and 24% for RIR (p=NS). Kaplan-Meier 2-year OS/PFS for CMR is 52%/48% versus 57%/48% for RIR (p=NS). When analyzed by diagnosis, CMR were significantly associated with decreased RR (10% vs 60%, p=0.004) for intermediate grade B-cell (figure 1). Univariate analysis of patient and treatment-related prognostic factors showed improved survival with chemosensitive disease; treatment intensity was the single predictor of relapse for the entire group, but, when stratified by diagnosis, for intermediate grade B-cell only. In conclusion, CMR provide better disease control for intermediate grade B-cell NHL.
Figure Figure
SDF-1-CXCR4 and HGF-c-met Axes Regulate Mobilization/Recruitment to Injured Tissue of Human Mesenchymal Stem Cells.
Authors: Son Bo-Ra , Zhao Dongling , Marquez-Curtis Leah A. , Shirvaikar Neeta , Ratajczak Mariusz Z. , Janowska-Wieczorek Anna 
Published: October 2019

Abstract
Human mesenchymal stem cells (MSC) have been shown to egress from the bone marrow (BM), circulate in peripheral blood (PB) and differentiate into many cell types, making them attractive as a potential therapeutic tool for organ/tissue regeneration. However the signals required for their mobilization into PB and their recruitment into injured sites are not fully understood. We previously reported that stromal-derived factor (SDF)-1 and hepatocyte growth factor (HGF) are upregulated at sites of tissue damage (Cancer Research2003; 63:7926; Leukemia2004; 18:29) and in this study we examined whether these factors mediate the migration of MSC. We investigated (i) the expression in MSC of CXCR4 and c-met, the cognate receptors of SDF-1 and HGF, (ii) whether they are functional after early and late passages (using a chemotaxis assay across fibronectin and the reconstituted basement membrane Matrigel), and (iii) whether MSC express matrix metalloproteinases (MMPs) known to facilitate mobilization and homing of stem cells. MSC were derived from human bone marrow (BM) or cord blood (CB) and maintained for up to 18 passages (in IMDM and 10–20% FCS) with monitoring of markers for cardiac (Nkx2.5/Csx, GATA-4 and MEF2-C), skeletal muscle (Myo-D and myogenin) and endothelial cells (VE-cadherin and VEGFR-2). We found that (i) CB and BM MSC strongly express CXCR4 and c-met transcripts for up to 15 passages, (ii) these receptors are functional as the MSC cells were chemotactic and chemoinvasive (across Matrigel) towards gradients of SDF-1 (100 ng/mL) or HGF (40 ng/mL), and (iii) CB and BM MSC express MMP-2 mRNA and secrete both latent and active forms of MMP-2. Moreover, we found that CB and BM MSC expressed mRNA for all three cardiac markers and the endothelial marker VE-cadherin, indicating their potential for heart regeneration. In conclusion, these results indicate that the SDF-1-CXCR4 and HGF-c-met axes are important signaling pathways in MSC mobilization and their trafficking in PB, and could be involved in recruitment of MSC to damaged tissues (e.g., myocardium).
Impaired In Vitro Osteogenesis in Multiple Myeloma Bone Marrow Osteoprogenitor Cells.
Authors: Bose Nandita , Kahler Rachel A. , Li Xiaodong , Bergemann Hope , Rajkumar Vincent , Westendorf Jennifer , Anna Masellis 
Published: October 2019

Abstract
In individuals with the plasma cell malignancy multiple myeloma, there is evidence that bone formation rates are reduced and that increased ostoeclastic bone resorption is associated with impaired osteoblast function. We investigated the osteogenic differentiation capacity of myeloma bone marrow mesenchymal progenitor cells (MPCs). We also examined the expression levels and activity of Runx2, the transcription factor required for osteogenesis.
Bone marrow MPCs were cultured in osteogenic induction medium and assessed for bone alkaline phosphatase (bALP) expression (Sigma kit), induction of osteoblast specific genes like osteocalcin (RT-PCR) and mineralization by von Kossa staining. Immunoblot analysis and electrophoretic mobility shift assays (EMSA) were used to determine Runx2 expression and DNA-binding activity respectively. RT-PCR was used to sequence Runx2 and detect any mutations or deletions present within its domains. Transactivation ability of Runx2 was measured by its ability to activate osteocalcin promoter in transient transfection assays.
Myeloma -derived MPCs showed reduced levels of bALP and osteocalcin transcript and a lower degree of mineralization, in osteogenic induction medium, as compared to that of the healthy donors. Immunoblot analysis and EMSA indicated equivalent Runx2 expression and DNA-binding capacity, respectively, in both healthy donor and myeloma-derived MPCs. Sequence analysis of Runx2 indentified a splice variant of Runx2 lacking exon 8 (Runx2D8) in myeloma patients with reduced transactivation ability. Co-transfection of the splice variant led to reduced transcriptional activity of the full-length Runx2. The reduced transactivation ability of spliced Runx2, as well as its suppressive action on the transactivation function of full-length Runx2, likely contributes to the defective osteogenesis clinically observed in myeloma pateints.
Ceramide-1-Phosphate a Novel Mediator for Phagocytosis.
Authors: Hinkovska-Galcheva Vania Tz , Shayman Jmes A. , Kindzelskii Andrei L. , Hiraoka Miki , Abe Akira , Petty Howard R. , Boxer Laurence A. 
Published: October 2019

Abstract
We identified the generation of ceramide-1-phosphate (C1P) through activation of a ceramide kinase in neutrophils. Our previous studies indicated that C1P enhanced calcium-dependent fusion of liposomes. We hypothesized that human ceramide kinase (hCERK) activity and C1P synthesis leads to enhanced phagocytosis through a mechanism involving modulating membrane fluidity and Ca2+ generation. hCERK was stably transfected into COS-1 cells bearing FcγRIIA. hCERK activity was 2.3 times higher in cells transfected with hCERK than in the FcγRIIA cells or cells transfected with pc-vector. Stably transfected cells showed a 3-fold increase in phagocytosis. Besides increasing phagocytosis, the percentage of ingesting COS-1 cells increased from 43+ 11 in control cells and 50 + 11 in pc-vector control to 70 + 9 (p<0.0001, n=6) in pc-hCERK transfected cells. Cells labeled with [3H]-D-erythro-sphingosine and challenged with particles increased both phagocytosis by three fold and C1P levels by two times compared to resting controls. FcγRIIA, pc-vector and pc-hCERK transfected cells were subjected to cellular fractionation. Utilizing an antibody to c-Myc we confirmed that c-Myc tagged pc-hCERK was localized in the raft fraction, which was identified by a caveolin-1 marker. To assess plasma membrane fluidity we labeled COS–1 cells with 2-dimethylamino-6-lauroylnaphthalene (Laurdan). Cells transfected with pc-hCERK showed higher liquid crystalline order than control and vector transfected cells, a condition favorable to promote membrane fusion. Such ordered structures are reported to be the site of Ca2+ waves ignition. High speed imaging revealed that cells bearing pc-hCERK showed two Ca2+ waves beginning at the leading edge of the cell that propagated in both directions. When the two waves reached the vicinity of the phagosome, a secondary waves split off from each of them, then propagated about the perimeter of the phagosome. That was inhibitable by employing a store-operated Ca2+ channel (SOC) inhibitor. This behavior is unique to the FcγRIIA/pc-hCERK transfected cells. In conclusion transfected COS-1 cells were able to increase their C1P levels during phagocytosis. This changed the structural order parameter of the lipid rafts where hCERK is localized and likely contributed to phagocytosis by promoting phagosome development. Lipid rafts were enriched in Ca2+ signaling machinery and in turn pc-hCERK transfection resulted in a novel means to markedly enhance phagocytosis by generating Ca2+ movement from SOC.
Loss of Heterozygosity on Chromosome 9p24 Is the Most Frequent Chromosomal Aberration in Polycythemia Vera and Idiopathic Myelofibrosis.
Authors: Kralovics Robert , Passamonti Francesco , Liu Kun , Teo Soon-Siong , Bench Anthony , Tichelli Andre , Lazzarino Mario , Green Anthony R. , Cazzola Mario , Skoda Radek C. 
Published: October 2019

Abstract
Myeloproliferative disorders (MPD) represent a heterogeneous group of diseases characterized by excessive myeloid cell production and clonal hematopoiesis. The appearance of the MPD stem cell clone is believed to be a consequence of an as yet unknown somatic mutation. The genetic basis for clonal hematopoiesis in MPD has been extensively studied using cytogenetic analysis, but no invariant chromosomal aberration has been found. Recently, we identified loss of heterozygosity of chromosome 9p (9pLOH) as a clonal defect in a small cohort of polycythemia vera (PV) patients. Here we extended this study to a total of 295 patients with MPD; 171 with PV, 91 with essential thrombocythemia (ET), and 33 with idiopathic myelofibrosis (IMF). The 9pLOH was detected in 62/171 patients with PV (36%) and in 10/33 patients with IMF (30%). Thus, 9pLOH is the most frequent chromosomal aberration in PV and IMF described to date. Interestingly, only 2/91 patients with the diagnosis of ET had 9pLOH. The reason for this difference is currently unknown and may be related to the presence of polyclonal hematopoiesis in a proportion of ET. By increasing the microsatellite marker density used for the LOH mapping in all 68 patients with 9pLOH, we identified a 6.2 Mbp minimal common LOH region. Copy number analysis performed by quantitative PCR revealed that all patients with 9pLOH had two copies of the chromosomal region involved in LOH. This finding excludes deletions as the genetic mechanism underlying 9pLOH and indicates that mitotic recombination is involved. This explains why this chromosomal defect remained hidden to cytogenetic analysis, FISH, or comparative genomic hybridization. 9pLOH results in partial uniparental disomy (UDP) of chromosome 9p. The phenotypic consequences of UPD are often associated with genes undergoing genomic imprinting. However, in two of our patients with 9pLOH, we were able to determine the parental origin of the lost chromosome by analyzing their parents. In one patient, the maternal chromosome was lost, whereas in the other patient, the paternal chromosome was missing. This variability of parental origin of UDP makes the involvement of imprinted genes in the expansion of the 9pLOH clone unlikely and favors a tumor suppressor mechanism. CDKN2A and CDKN2B genes (INK4A, INK4B), localized on 9p21, are among the most frequently mutated tumor suppressors in human malignancies. However, the CDKN2A/B locus is not part of the minimal 9pLOH region in MPD. The 6.2 Mbp common 9pLOH region contains 40 genes and ESTs. We determined which of these genes are expressed in hematopoietic cells and are currently sequencing the cDNAs of these genes to search for mutations.
Increased and Pathological Emperipolesis of Neutrophils within Megakaryocytes Associated with Myelofibrosis in GATA-1LowMice.
Authors: Migliaccio Anna Rita , Centurione Lucia , Di Baldassarre Angela , Zingariello Maria , Bosco Domenico , Gatta Valentina , Rana Rosa Alba , Di Virgilio Antonio , Vannucchi Alessandro M. 
Published: October 2019

Abstract
GATA-1 is a transcription factor involved in the intrinsic control of erythroid, megakaryocytic and mast cell differentiation. Experimentally-induced deletion of the megakaryocytic (Mk)-specific regulatory sequences of GATA-1 (Gata1tm2Sho or GATA-1low mutation) results in severe thrombocytopenia, because of defective thrombocytopoiesis, and myelofibrosis. The relationship, if any, between defective megakaryocytopoiesis and development of the disease is still poorly understood. Electron microscopy studies, coupled with immuno-electron microscopy, have allowed us to determine that the GATA-1low mutation blocks Mk maturation between stage I and II, resulting in accumulation of defective Mk in the tissues of GATA-1low mice. The block in maturation includes failure to properly organize α-granules, since von Willebrand factor is barely detectable in mutant Mk while P-selectin, although expressed at normal level, is found mainly associated with the Demarcation Membrane System (DMS) rather than with granules. Conversely, both von Willebrand factor and P-selectin are barely detectable in the megathrombocytes in the blood from GATA-1low mice. Both in marrow and spleen, mutant Mk are surrounded by numerous myeloperoxidase-positive neutrophils, some of which appear in the process of establishing contact with the Mk by fusing their membrane with those of the DMS. As a result, 16 (in spleen) - 34 (in marrow) percent of GATA-1low Mk contain 1-3 neutrophils embedded in a vacuolated cytoplasm. The neutrophil-embedded GATA-1low Mk have morphological features (high electron density and negativity to TUNEL staining) compatible with those of cells dying from para-apoptosis. We suggest that such an increased and pathological neutrophil emperipolesis represents one of the mechanisms leading to myelofibrosis by releasing Mk cytokines (TGF-β) and neutrophil proteases (myeloperoxidase) in the microenvironment which result, respectively, in marrow fibrosis and abnormal stem/progenitor cell trafficking.