scholarly journals Replication of Enterococcus faecalis Pheromone-Responding Plasmid pAD1: Location of the Minimal Replicon and oriV Site and RepA Involvement in Initiation of Replication

2004 ◽  
Vol 186 (15) ◽  
pp. 5003-5016 ◽  
Author(s):  
Maria Victoria Francia ◽  
Shuhei Fujimoto ◽  
Patricia Tille ◽  
Keith E. Weaver ◽  
Don B. Clewell
Keyword(s):  
Enterococcus Faecalis ◽  
Copy Number ◽  
Replication Origin ◽  
Plasmid Vector ◽  
Small Segment ◽  
Initiator Protein ◽  
Repeat Sequences ◽  
Initiation Of Replication ◽  
Relationship Of ◽  
The Relationship

ABSTRACT The hemolysin-determining plasmid pAD1 is a member of a widely disseminated family of highly conjugative elements commonly present in clinical isolates of Enterococcus faecalis. The determinants repA, repB, and repC, as well as adjacent iteron sequences, are believed to play important roles in pAD1 replication and maintenance. The repA gene encodes an initiator protein, whereas repB and repC encode proteins related to stability and copy number. The present study focuses specifically on repA and identifies a replication origin (oriV) within a central region of the repA determinant. A small segment of repA carrying oriV was able to support replication in cis of a plasmid vector otherwise unable to replicate, if an intact RepA was supplied in trans. We demonstrate that under conditions in which RepA is expressed from an artificial promoter, a segment of DNA carrying only repA is sufficient for stable replication in E. faecalis. We also show that RepA binds specifically to oriV DNA at several sites containing inverted repeat sequences (i.e., IR-1) and nonspecifically to single-stranded DNA, and related genetic analyses confirm that these sequences play an important role in replication. Finally, we reveal a relationship between the internal structure of RepA and its ability to recognize oriV. An in-frame deletion within repA resulting in loss of 105 nucleotides, including at least part of oriV, did not eliminate the ability of the altered RepA protein to initiate replication using an intact origin provided in trans. The relationship of RepA to other known initiator proteins is also discussed.

scholarly journals Copy number signatures predict chromothripsis and clinical outcomes in newly diagnosed multiple myeloma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kylee H. Maclachlan ◽  
Even H. Rustad ◽  
Andriy Derkach ◽  
Binbin Zheng-Lin ◽  
Venkata Yellapantula ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Copy Number ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Flexible Tool ◽  
Whole Exome ◽  
Hematological Cancers ◽  
Relationship Of ◽  
The Relationship ◽  
Validation Series

AbstractChromothripsis is detectable in 20–30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study we interrogate 752 NDMM patients using whole genome sequencing (WGS) to investigate the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC = 0.90) and can be used identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis is confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC = 0.97) and an independent series of 34 NDMM (AUC = 0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we are able to predict both the presence of chromothripsis (AUC = 0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data.

scholarly journals New pattern of EGFR amplification in glioblastoma and the relationship of gene copy number with gene expression profile

2010 ◽  
Vol 23 (6) ◽  
pp. 856-865 ◽  
Author(s):  
Concha Lopez-Gines ◽  
Rosario Gil-Benso ◽  
Ruben Ferrer-Luna ◽  
Rafael Benito ◽  
Eva Serna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Egfr Amplification ◽  
Relationship Of ◽  
The Relationship

scholarly journals The pfmdr1 Gene Is Associated with a Multidrug-Resistant Phenotype in Plasmodium falciparumfrom the Western Border of Thailand

1999 ◽  
Vol 43 (12) ◽  
pp. 2943-2949 ◽  
Author(s):  
R. N. Price ◽  
C. Cassar ◽  
A. Brockman ◽  
M. Duraisingh ◽  
M. van Vugt ◽  
...  
Keyword(s):  
Copy Number ◽  
Multidrug Resistant ◽  
Antimalarial Agents ◽  
Resistant Phenotype ◽  
Western Border ◽  
Almost All ◽  
Parasite Populations ◽  
Relationship Of ◽  
The Relationship

ABSTRACT On the western border of Thailand, Plasmodium falciparum has become resistant to almost all antimalarial agents. The molecular basis of resistance in these parasite populations has not been well characterized. This study assessed genetic polymorphisms in the pfmdr1 gene in 54 parasites collected from the western border of Thailand to determine the relationship ofpfmdr1 copy number and codon mutations with parasite sensitivities to mefloquine, chloroquine, halofantrine, quinine, and artesunate assessed in vitro. A point mutation at codon 86 (resulting in a change of Asn to Tyr) was associated with a significantly lower 50% inhibitory concentration (IC50) of mefloquine (median, 9 ng/ml versus 52.4 ng/ml; P = 0.003). Overall 35% of the isolates (19 of 54) had an increase in pfmdr1 copy number, and all 19 carried the wild-type allele at codon 86. Increasedpfmdr1 copy number was associated with higher IC50s of mefloquine (P = 0.04) and artesunate (P = 0.005), independent of polymorphism at codon 86. The relationship between pfmdr1 and resistance to structurally distinct antimalarial agents confirms the presence of a true multidrug-resistant phenotype.

scholarly journals Copy number signatures predict chromothripsis and associate with poor clinical outcomes in patients with newly diagnosed multiple myeloma

2020 ◽  
Author(s):  
Kylee H Maclachlan ◽  
Even H Rustad ◽  
Andriy Derkach ◽  
Binbin Zheng-Lin ◽  
Venkata Yellapantula ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Copy Number ◽  
Prognostic Impact ◽  
Newly Diagnosed ◽  
Flexible Tool ◽  
Whole Exome ◽  
Hematological Cancers ◽  
Relationship Of ◽  
The Relationship ◽  
Validation Series

AbstractChromothripsis is detectable in 20-30% of newly diagnosed multiple myeloma (NDMM) patients and is emerging as a new independent adverse prognostic factor. In this study, we interrogate 752 NDMM patients using whole genome sequencing (WGS) to study the relationship of copy number (CN) signatures to chromothripsis and show they are highly associated. CN signatures are highly predictive of the presence of chromothripsis (AUC=0.90) and can be used to identify its adverse prognostic impact. The ability of CN signatures to predict the presence of chromothripsis was confirmed in a validation series of WGS comprised of 235 hematological cancers (AUC=0.97) and an independent series of 34 NDMM (AUC=0.87). We show that CN signatures can also be derived from whole exome data (WES) and using 677 cases from the same series of NDMM, we were able to predict both the presence of chromothripsis (AUC=0.82) and its adverse prognostic impact. CN signatures constitute a flexible tool to identify the presence of chromothripsis and is applicable to WES and WGS data.

The relationship of the scleractinian corals to the rugose corals

Paleobiology ◽  
1980 ◽  
Vol 6 (02) ◽  
pp. 146-160 ◽  
Author(s):  
William A. Oliver
Keyword(s):  
Critical Points ◽  
Scleractinian Corals ◽  
Convincing Evidence ◽  
Early Triassic ◽  
Rugose Corals ◽  
History Of ◽  
The Subject ◽  
Relationship Of ◽  
The Relationship ◽  
Biologic Factors

The Mesozoic-Cenozoic coral Order Scleractinia has been suggested to have originated or evolved (1) by direct descent from the Paleozoic Order Rugosa or (2) by the development of a skeleton in members of one of the anemone groups that probably have existed throughout Phanerozoic time. In spite of much work on the subject, advocates of the direct descent hypothesis have failed to find convincing evidence of this relationship. Critical points are:(1) Rugosan septal insertion is serial; Scleractinian insertion is cyclic; no intermediate stages have been demonstrated. Apparent intermediates are Scleractinia having bilateral cyclic insertion or teratological Rugosa.(2) There is convincing evidence that the skeletons of many Rugosa were calcitic and none are known to be or to have been aragonitic. In contrast, the skeletons of all living Scleractinia are aragonitic and there is evidence that fossil Scleractinia were aragonitic also. The mineralogic difference is almost certainly due to intrinsic biologic factors.(3) No early Triassic corals of either group are known. This fact is not compelling (by itself) but is important in connection with points 1 and 2, because, given direct descent, both changes took place during this only stage in the history of the two groups in which there are no known corals.

Skeletal elements of crinoid echinoderms: High-resolution structural and microanalytical results

1983 ◽  
Vol 41 ◽  
pp. 194-195
Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor
Keyword(s):  
High Resolution ◽  
Marine Invertebrates ◽  
Sea Urchins ◽  
Structural Features ◽  
Sea Stars ◽  
High Resolution Tem ◽  
Relationship Of ◽  
The Relationship ◽  
Insight Into

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.

Studies on Leukemogenic and Sarcomagenic Viruses

1970 ◽  
Vol 28 ◽  
pp. 156-157
Author(s):  
Leon Dmochowski
Keyword(s):  
Electron Microscopy ◽  
Electron Microscope ◽  
Morphological Properties ◽  
Mode Of Development ◽  
Relationship Of ◽  
The Relationship

Electron microscopy has proved to be an invaluable discipline in studies on the relationship of viruses to the origin of leukemia, sarcoma, and other types of tumors in animals and man. The successful cell-free transmission of leukemia and sarcoma in mice, rats, hamsters, and cats, interpreted as due to a virus or viruses, was proved to be due to a virus on the basis of electron microscope studies. These studies demonstrated that all the types of neoplasia in animals of the species examined are produced by a virus of certain characteristic morphological properties similar, if not identical, in the mode of development in all types of neoplasia in animals, as shown in Fig. 1.

The relationship of IGE receptor topography to signaling activity in RBL-2H3 mast cells

1991 ◽  
Vol 49 ◽  
pp. 236-237
Author(s):  
J.R. Pfeiffer ◽  
J.C. Seagrave ◽  
C. Wofsy ◽  
J.M. Oliver
Keyword(s):  
Mast Cells ◽  
Protein A ◽  
Scattered Electron ◽  
Ige Receptor ◽  
Receptor Complexes ◽  
Ige Binding ◽  
Electron Imaging ◽  
Small Clusters ◽  
Relationship Of ◽  
The Relationship

In RBL-2H3 rat leukemic mast cells, crosslinking IgE-receptor complexes with anti-IgE antibody leads to degranulation. Receptor crosslinking also stimulates the redistribution of receptors on the cell surface, a process that can be observed by labeling the anti-IgE with 15 nm protein A-gold particles as described in Stump et al. (1989), followed by back-scattered electron imaging (BEI) in the scanning electron microscope. We report that anti-IgE binding stimulates the redistribution of IgE-receptor complexes at 37“C from a dispersed topography (singlets and doublets; S/D) to distributions dominated sequentially by short chains, small clusters and large aggregates of crosslinked receptors. These patterns can be observed (Figure 1), quantified (Figure 2) and analyzed statistically. Cells incubated with 1 μg/ml anti-IgE, a concentration that stimulates maximum net secretion, redistribute receptors as far as chains and small clusters during a 15 min incubation period. At 3 and 10 μg/ml anti-IgE, net secretion is reduced and the majority of receptors redistribute rapidly into clusters and large aggregates.

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