Detecting Regulatory Sites Using PhyloGibbs

2007 ◽  
pp. 381-402
Author(s):  
Rahul Siddharthan ◽  
Erik van Nimwegen
Keyword(s):  
Regulatory Sites

COMPARATIVE STUDY FOR GENERIC DRUG APPROVAL PROCESS AND THEIR REGISTRATION AS PER CTD IN EUROPE, USA AND BRAZIL

2016 ◽  
Vol 4 (2) ◽  
pp. 1-9
Author(s):  
Lincy Joseph ◽  
Mathew George ◽  
Kalpesh K Malaviya ◽  
Kalpesh K Malaviya ◽  
Bincy K Chacko ◽  
...  
Keyword(s):  
Generic Drug ◽  
Drug Approval ◽  
Evaluation Agency ◽  
Approval Process ◽  
Registration Process ◽  
Regulatory Guidelines ◽  
Food Drug Administration ◽  
Government Websites ◽  
Drug Approval Process ◽  
Regulatory Sites

This aims to compare the generic drug approval and registration process in the regulatory market of Europe, USA andBrazil. Based on the information collected from various sources such as regulatory sites, Government websites,discussion with regulatory agent, interviewing pharma professionals and literature survey from various journals, aclear picture on the generic drug approval and registration process of each country was drawn. The differentauthorities’ viz. European Medicines Evaluation Agency (EMEA) of Europe, Food Drug Administration (FDA) ofUSA and National Health Surveillance Agency (ANVISA) of Brazil carried out the generic drug approval andregistration process in the respective countries. After analysing the various requirements for the generic drug approvalin the above stated countries, it was concluded that the regulatory guidelines of Europe and Brazil was not welldefined. But FDA gives very much well defined requirements. 

scholarly journals Binding of an X-Specific Condensin Correlates with a Reduction in Active Histone Modifications at Gene Regulatory Elements

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 729-742 ◽  
Author(s):  
Lena Annika Street ◽  
Ana Karina Morao ◽  
Lara Heermans Winterkorn ◽  
Chen-Yu Jiao ◽  
Sarah Elizabeth Albritton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Histone Modifications ◽  
Chromatin Immunoprecipitation ◽  
Protein Complexes ◽  
Regulatory Elements ◽  
Evolutionarily Conserved ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Gene Regulatory Elements ◽  
Gene Regulatory ◽  
Regulatory Sites

Condensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In Caenorhabditis elegans, a specialized condensin, which forms the core of the dosage compensation complex (DCC), binds to and represses X chromosome transcription. Here, we analyzed DCC localization and the effect of DCC depletion on histone modifications, transcription factor binding, and gene expression using chromatin immunoprecipitation sequencing and mRNA sequencing. Across the X, the DCC accumulates at accessible gene regulatory sites in active chromatin and not heterochromatin. The DCC is required for reducing the levels of activating histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3. In X-to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces gene expression, thus establishing a direct link between DCC binding and repression. Together, our results indicate that DCC-mediated transcription repression is associated with a reduction in the activity of X chromosomal gene regulatory elements.

POU2F1 (Oct-1) Differently Autoregulates the Alternative Promoters of Its Own Gene by Binding to Different Regulatory Sites

2021 ◽  
Vol 55 (6) ◽  
pp. 854-862
Author(s):  
E. V. Pankratova ◽  
T. N. Portseva ◽  
A. A. Makarova ◽  
B. M. Lyanova ◽  
S. G. Georgieva ◽  
...  
Keyword(s):  
Alternative Promoters ◽  
Regulatory Sites

Protein phosphatase 2A potentiates activity of promoters containing AP-1-binding elements

1993 ◽  
Vol 13 (4) ◽  
pp. 2104-2112
Author(s):  
A S Alberts ◽  
T Deng ◽  
A Lin ◽  
J L Meinkoth ◽  
A Schönthal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Protein Phosphatase ◽  
Signal Transduction Pathways ◽  
Marker Genes ◽  
Direct Mechanism ◽  
Phosphatase 2A ◽  
Beta Galactosidase ◽  
Regulatory Sites

The involvement of serine/threonine protein phosphatases in signaling pathways which modulate the activity of the transcription factor AP-1 was examined. Purified protein phosphatase types 1 (PP1) and 2A (PP2A) were microinjected into cell lines containing stably transfected lacZ marker genes under the control of an enhancer recognized by AP-1. Microinjection of PP2A potentiated serum-stimulated beta-galactosidase expression from the AP-1-regulated promoter. Similarly, transient expression of the PP2A catalytic subunit with c-Jun resulted in a synergistic transactivation of an AP-1-regulated reporter gene. PP2A, but not PP1, potentiated serum-induced c-Jun expression, which has been previously shown to be autoregulated by AP-1 itself. Consistent with these results, PP2A dephosphorylated c-Jun on negative regulatory sites in vitro, suggesting one possible direct mechanism for the effects of PP2A on AP-1 activity. Microinjection of PP2A had no effect on cyclic AMP (cAMP)-induced expression of a reporter gene containing a cAMP-regulated promoter, while PP1 injection abolished cAMP-induced gene expression. Taken together, these results suggest a specific role for PP2A in signal transduction pathways that regulate AP-1 activity and c-Jun expression.

scholarly journals The effects of Mg2+ and adenine nucleotides on the sensitivity of the heart mitochondrial Na+-Ca2+ carrier to extramitochondrial Ca2+. A study using arsenazo III-loaded mitochondria

1987 ◽  
Vol 244 (3) ◽  
pp. 533-538 ◽  
Author(s):  
L H Hayat ◽  
M Crompton
Keyword(s):  
Adenine Nucleotides ◽  
Mitochondrial Protein ◽  
Arsenazo Iii ◽  
Heart Mitochondria ◽  
Small Decrease ◽  
Regulatory Site ◽  
Normal Heart ◽  
Partial Inhibition ◽  
Regulatory Sites

The technique of reversible Ca2+-induced permeabilization [Al Nasser & Crompton (1986) Biochem. J. 239, 19-29, 31-40] has been applied to the preparation of heart mitochondria loaded with the Ca2+ indicator arsenazo III (2 nmol of arsenazo III/mg of mitochondrial protein). The loaded mitochondria (‘mitosomes’) were used to study the control of the Na+-Ca2+ carrier by extramitochondrial Ca2+ mediated by putative regulatory sites. The Vmax. of the Na+-Ca2+ carrier and the degree of regulatory-site-mediated inhibition were similar to normal heart mitochondria. Ca2+ occupation of the sites in mitosomes yields partial inhibition, which is half-maximal with 0.8 microM external free Ca2+. The inhibition consists of a small decrease in Vmax. and a relatively large increase in apparent Km for internal Ca2+. Mg2+ also appears to interact with the sites, but this is largely abolished by ATP and ADP (but not AMP) under conditions in which the free [Mg2+] is maintained constant. The results indicate that the regulatory sites are effective in controlling the Na+-Ca2+ carrier at physiological concentrations of adenine nucleotides, Mg2+, intra- and extra-mitochondrial free Ca2+.

Evolution of catalytic and regulatory sites in phosphorylases

Nature ◽  
1985 ◽  
Vol 313 (6002) ◽  
pp. 500-502 ◽  
Author(s):  
Dieter Palm ◽  
Rudolf Goerl ◽  
Klaus J. Burger
Keyword(s):  
Regulatory Sites

Isoflurane Depresses Baroreflex Control of Heart Rate in Decerebrate Rats

2002 ◽  
Vol 96 (5) ◽  
pp. 1214-1222 ◽  
Author(s):  
Jong S. Lee ◽  
Don Morrow ◽  
Michael C. Andresen ◽  
Kyoung S. K. Chang
Keyword(s):  
Central Nervous System ◽  
Heart Rate ◽  
Nervous System ◽  
Baroreflex Sensitivity ◽  
Baroreflex Control ◽  
Beta Adrenoceptor ◽  
Reflex Bradycardia ◽  
Reflex Tachycardia ◽  
Map Data ◽  
Regulatory Sites

Background Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression. Methods The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically. Results Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups. Conclusions Isoflurane depresses HR baroreflex control by actions that do not require suprapontine central nervous system sites. Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic nervous system.

scholarly journals ACE2 polymorphisms as potential players in COVID-19 outcome

2020 ◽  
Author(s):  
André Salim Khayat ◽  
Paulo Pimentel de Assumpção ◽  
Bruna Claudia Meireles Khayat ◽  
Taíssa Maíra Thomaz Araújo ◽  
Jéssica Almeida Batista-Gomes ◽  
...  
Keyword(s):  
South American ◽  
Angiotensin I ◽  
Biological Aspect ◽  
Death Rates ◽  
Angiotensin I Converting Enzyme ◽  
Protein Receptor ◽  
Biological Explanation ◽  
The Many ◽  
Shed Light ◽  
Regulatory Sites

AbstractThe clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, ACE2 polymorphisms should influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.

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