The R-diastereomer of 6′-O-toluoyl-carba-LNA modification in the core region of siRNA leads to 24-times improved RNA silencing potency against the HIV-1 compared to its S-counterpart

MedChemComm ◽  
2011 ◽  
Vol 2 (11) ◽  
pp. 1110 ◽  
Author(s):  
Suman Dutta ◽  
Nipa Bhaduri ◽  
Ram Shankar Upadhayaya ◽  
Neha Rastogi ◽  
Sunita G. Chandel ◽  
...  
Keyword(s):  
Rna Silencing ◽  
Core Region ◽  
The Core ◽  
Hiv 1

scholarly journals Composition and Orientation of the Core Region of Novel HIV-1 Entry Inhibitors Influences Metabolic Stability

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1430
Author(s):  
Rama Karadsheh ◽  
Megan E. Meuser ◽  
Simon Cocklin
Keyword(s):  
Short Communication ◽  
Human Liver Microsome ◽  
Core Region ◽  
Metabolic Stability ◽  
Entry Inhibitor ◽  
Entry Inhibitors ◽  
The Core ◽  
The Stability ◽  
Hiv 1

Fostemsavir/temsavir is an investigational HIV-1 entry inhibitor currently in late-stage clinical trials. Although it holds promise to be a first-in-class Env-targeted entry inhibitor for the clinic, issues with bioavailability relegate its use to salvage therapies only. As such, the development of a small molecule HIV-1 entry inhibitor that can be used in standard combination antiretroviral therapy (cART) remains a longstanding goal for the field. We previously demonstrated the ability of extending the chemotypes available to this class of inhibitor as the first step towards this overarching goal. In addition to poor solubility, metabolic stability is a crucial determinant of bioavailability. Therefore, in this short communication, we assess the metabolic stabilities of five of our novel chemotype entry inhibitors. We found that changing the piperazine core region of temsavir alters the stability of the compound in human liver microsome assays. Moreover, we identified an entry inhibitor with more than twice the metabolic stability of temsavir and demonstrated that the orientation of the core replacement is critical for this increase. This work further demonstrates the feasibility of our long-term goal—to design an entry inhibitor with improved drug-like qualities—and warrants expanded studies to achieve this.

Intramitochondrial Viruses of Reptilian Cell Origin

1972 ◽  
Vol 30 ◽  
pp. 318-319
Author(s):  
Philip D. Lunger ◽  
H. Fred Clark
Keyword(s):  
Particle Production ◽  
Outer Zone ◽  
Density Variation ◽  
Core Region ◽  
Mitochondrial Membranes ◽  
Virus Particles ◽  
The Core ◽  
Vipera Russelli ◽  
Maturation Stages ◽  
Type Particle

In the course of fine structure studies of spontaneous “C-type” particle production in a viper (Vipera russelli) spleen cell line, designated VSW, virus particles were frequently observed within mitochondria. The latter were usually enlarged or swollen, compared to virus-free mitochondria, and displayed a considerable degree of cristae disorganization.Intramitochondrial viruses measure 90 to 100 mμ in diameter, and consist of a nucleoid or core region of varying density and measuring approximately 45 mμ in diameter. Nucleoid density variation is presumed to reflect varying degrees of condensation, and hence maturation stages. The core region is surrounded by a less-dense outer zone presumably representing viral capsid.Particles are usually situated in peripheral regions of the mitochondrion. In most instances they appear to be lodged between loosely apposed inner and outer mitochondrial membranes.

scholarly journals On the Nature of R 136, the Central Object of 30 Dor. A Comparison by the Galactic Cluster NGC 3603

1984 ◽  
Vol 108 ◽  
pp. 257-258
Author(s):  
Michael Rosa ◽  
Jorge Melnick ◽  
Preben Grosbol
Keyword(s):  
Core Region ◽  
H Ii Regions ◽  
Central Object ◽  
The Core ◽  
Dominant Component ◽  
Galactic Cluster ◽  
H Ii Region

The massive H II region NGC 3603 is the closest galactic counterpart to the giant LMC nebula 30 Dor. Walborn (1973) first compared the ionizing OB/WR clusters of the two H II regions and suggested that R 136, the unresolved luminous WR + 0 type central object of 30 Dor, might be a multiple system like the core region of NGC 3603. Suggestions that the dominant component of R 136, i.e. R 136A, might be either a single or a very few supermassive and superluminous stars (Schmidt-Kaler and Feitzinger 1982, Savage et al. 1983) have recently been disputed by Moffat and Seggewiss (1983) and Melnick (1983), who have presented spectroscopic and photometric evidence to support the hypothesis of an unresolved cluster of stars. We have extended Walborn's original comparison of the apparent morphology of the two clusters by digital treatment of the images to simulate how the galactic cluster would look like if it were located in the LMC

Reconstruction of the last three millennia South American Monsoon variability over the Amazon basin using speleothem isotope records 

2021 ◽  
Author(s):  
Marcela Eduarda Della Libera de Godoy ◽  
Valdir F. Novello ◽  
Francisco William Cruz
Keyword(s):  
High Resolution ◽  
Amazon Basin ◽  
Rainfall Variability ◽  
Isotope Analysis ◽  
Core Region ◽  
South American ◽  
The South ◽  
Continuous Increase ◽  
South American Monsoon ◽  
The Core

<p>South American Monsoon System (SAMS) and its main feature, the South American Convergence Zone (SACZ) are responsible for the major distribution of moisture in South America. The current work presents a novel high-resolution oxygen isotope record (δ<sup>18</sup>O) based on speleothems from southwest Amazon basin (Brazil), right at SAMS' core region and SACZ onset, where there is still a gap of high resolution paleoclimate records. The novel δ<sup>18</sup>O record presents an average of 3 year-resolution, composed by 1344 stable isotope analysis performed in two speleothems with a well-resolved chronology (37 U/Th ages) with average errors <1%. This work aims to describe the rainfall variability of the core region of the South American monsoon for the last 3k years and to take a broader look at precipitation patterns over Amazon basin. The Rondônia δ18O record shows three main stages throughout this time period. The first is from -1000 to ~400 CE, where it’s in accordance with most of other paleorecords from the Amazon basin. the second segment  is from ~400 to 1200 CE, when there is a continuous increase in the δ18O record until it reaches its highest values around 850 CE during the MCA (800-1200 CE), which is in accordance with western Amazon records, whilst the record in eastern Amazon presents an opposite trend. Thus, a precipitation dipole over Amazon emerges from ~400 CE onwards, majorly triggered by anomalous climate changes such as MCA, where western (eastern) Amazon is drier (wetter). During LIA (1450-1800 CE), on the other hand, Rondônia record presents its lowest values, also agreeing with western records and with records under the influence of SACZ whilst on eastern Amazon a drier period is established. Therefore, with this novel paleoclimate record located at the core region of SAMS, it's possible to evidence the dynamics of the precipitation dipole over the Amazon region, as well as understand the SACZ intensity variations.</p>

BAF is required for emerin assembly into the reforming nuclear envelope

2001 ◽  
Vol 114 (24) ◽  
pp. 4575-4585 ◽  
Author(s):  
Tokuko Haraguchi ◽  
Takako Koujin ◽  
Miriam Segura-Totten ◽  
Kenneth K. Lee ◽  
Yosuke Matsuoka ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Hela Cells ◽  
Core Region ◽  
Lamin B ◽  
The Core ◽  
Double Stranded Dna ◽  
Recessive Form ◽  
Nuclear Envelope Assembly

Mutations in emerin cause the X-linked recessive form of Emery-Dreifuss muscular dystrophy (EDMD). Emerin localizes at the inner membrane of the nuclear envelope (NE) during interphase, and diffuses into the ER when the NE disassembles during mitosis. We analyzed the recruitment of wildtype and mutant GFP-tagged emerin proteins during nuclear envelope assembly in living HeLa cells. During telophase, emerin accumulates briefly at the ‘core’ region of telophase chromosomes, and later distributes over the entire nuclear rim. Barrier-to-autointegration factor (BAF), a protein that binds nonspecifically to double-stranded DNA in vitro, co-localized with emerin at the ‘core’ region of chromosomes during telophase. An emerin mutant defective for binding to BAF in vitro failed to localize at the ‘core’ in vivo, and subsequently failed to localize at the reformed NE. In HeLa cells that expressed BAF mutant G25E, which did not show ‘core’ localization, the endogenous emerin proteins failed to localize at the ‘core’ region during telophase, and did not assemble into the NE during the subsequent interphase. BAF mutant G25E also dominantly dislocalized LAP2β and lamin A from the NE, but had no effect on the localization of lamin B. We conclude that BAF is required for the assembly of emerin and A-type lamins at the reforming NE during telophase, and may mediate their stability in the subsequent interphase.

Expression of hepatitis B viral core region in mammalian cells

1986 ◽  
Vol 6 (5) ◽  
pp. 1393-1400
Author(s):  
M J Roossinck ◽  
S Jameel ◽  
S H Loukin ◽  
A Siddiqui
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mammalian Cells ◽  
Expression System ◽  
Core Region ◽  
Core Antigen ◽  
Northern Blot Hybridization ◽  
The Core ◽  
B Virus ◽  
Nuclease Mapping

We studied the expression of the core region of the hepatitis B virus genome in mammalian cells with recombinant plasmid vectors. Stably transformed rat fibroblast cell lines were established by transfection with vectors containing subgenomic and genome-length hepatitis B virus DNA, followed by G418 selection. The RNA transcripts directed by the core region were characterized by Northern blot hybridization and S1 nuclease mapping. Using the chloramphenicol acetyltransferase gene expression system, the promoter activity located upstream of the core open reading frame was confirmed. The synthesis of core and e polypeptides was studied with a commercial radioimmunoassay. These studies show that partial deletion of the precore sequences abolished secretion of the e antigen, but there was pronounced synthesis of the core antigen in transfected cells.

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