Profile ekspresji fragmentów pochodzących
Profile ekspresji fragmentów pochodzących z tRNA i ich potencjalne function w szpiczaku mnogim
Background: A number of myeloma is an incurable hematologic malignancy. The invention of mechanisms could assist to seek out new therapeutic targets and delay survival. tRNA-related fragments (tRF) and tRNA halves (tiRNA) are small RNA derived from tRNAs and implicated in all kinds of pathological processes, together with most cancers initiation and development. Nonetheless, there are virtually no analysis reporting the function of those tRNA derived fragments in myeloma so far as we all know.
Strategies: On this research, we proposed the expression profiles of tRFs/tiRNAs in myeloma by means of RNA-sequencing in new recognized myeloma and wholesome donors. The expression of chosen tRFs/tiRNAs was additional validated in scientific specimens by qPCR. Bioinformatic evaluation was carried out to foretell their potential roles in a number of myeloma.
Outcomes: A complete of 33 upregulated tRFs/tiRNAs and 22 downregulated tRFs/tiRNAs have been recognized. GO enrichment and KEGG pathway evaluation have been carried out to research the features of 1 considerably up-regulated and one considerably down-regulated tRNA-derived fragments. tRFs/tiRNAs could also be concerned in MM initiation and development.
Conclusion: We concluded that tRFs/tiRNAs have been dysregulated and may very well be potential biomarkers for a number of myeloma.
 Polyclonal Goat Anti-RAE1 Antibody |
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| APG00265G | Leading Biology | 0.1mg | EUR 484 |
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Description: A polyclonal antibody raised in Goat that recognizes and binds to Human Goat Anti-RAE1 . This antibody is tested and proven to work in the following applications: |
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 RAE1 antibody |
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| 22381-100ul | SAB | 100ul | EUR 390 |
RAE1 antibody |
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| 70R-12978 | Fitzgerald | 100 ul | EUR 457 |
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Description: Affinity purified Rabbit polyclonal RAE1 antibody |
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RAE1 antibody |
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| 39124-100ul | SAB | 100ul | EUR 252 |
 RAE1 Antibody |
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| DF8442 | Affbiotech | 200ul | EUR 304 |
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Description: RAE1 Antibody detects endogenous levels of total RAE1. |
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RAE1 antibody |
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| 70R-4675 | Fitzgerald | 50 ug | EUR 467 |
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Description: Rabbit polyclonal RAE1 antibody |
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RAE1 antibody |
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| 70R-4676 | Fitzgerald | 50 ug | EUR 467 |
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Description: Rabbit polyclonal RAE1 antibody |
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RAE1 Antibody |
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| 1-CSB-PA019276ESR1HU | Cusabio |
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Description: A polyclonal antibody against RAE1. Recognizes RAE1 from Human, Mouse. This antibody is Unconjugated. Tested in the following application: ELISA, WB, IHC; Recommended dilution: WB:1:1000-1:5000, IHC:1:20-1:200 |
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RAE1 Antibody |
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| ABD8442 | Lifescience Market | 100 ug | EUR 438 |
 Rae1/ Rat Rae1 ELISA Kit |
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| ELI-52491r | Lifescience Market | 96 Tests | EUR 886 |
 RAE1 Conjugated Antibody |
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| C39124 | SAB | 100ul | EUR 397 |
 RAE1 siRNA |
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| 20-abx904450 | Abbexa |
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RAE1 siRNA |
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| 20-abx930796 | Abbexa |
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RAE1 siRNA |
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| 20-abx930797 | Abbexa |
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) Polyclonal RAE1 Antibody (Center) |
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| APR04909G | Leading Biology | 0.1ml | EUR 484 |
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Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human RAE1 (Center). This antibody is tested and proven to work in the following applications: |
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Polyclonal RAE1 Antibody (Center) |
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| APR06961G | Leading Biology | 0.1ml | EUR 484 |
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Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human RAE1 (Center). This antibody is tested and proven to work in the following applications: |
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 RAE1 Blocking Peptide |
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| 33R-2670 | Fitzgerald | 100 ug | EUR 180 |
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Description: A synthetic peptide for use as a blocking control in assays to test for specificity of RAE1 antibody, catalog no. 70R-4675 |
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RAE1 Blocking Peptide |
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| 33R-8290 | Fitzgerald | 100 ug | EUR 180 |
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Description: A synthetic peptide for use as a blocking control in assays to test for specificity of RAE1 antibody, catalog no. 70R-4676 |
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RAE1 Blocking Peptide |
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| DF8442-BP | Affbiotech | 1mg | EUR 195 |
 RAE1 cloning plasmid |
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| CSB-CL019276HU-10ug | Cusabio | 10ug | EUR 233 |
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Description: A cloning plasmid for the RAE1 gene. |
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 RAE1 Rabbit pAb |
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| A6713-100ul | Abclonal | 100 ul | EUR 308 |
RAE1 Rabbit pAb |
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| A6713-200ul | Abclonal | 200 ul | EUR 459 |
RAE1 Rabbit pAb |
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| A6713-20ul | Abclonal | 20 ul | EUR 183 |
RAE1 Rabbit pAb |
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| A6713-50ul | Abclonal | 50 ul | EUR 223 |
) Polyclonal RAE1 Antibody (N-Term) |
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| APR04887G | Leading Biology | 0.1ml | EUR 484 |
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Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human RAE1 (N-Term). This antibody is tested and proven to work in the following applications: |
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 Polyclonal Goat anti-GST α-form |
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| GST-ANTI-1 | Detroit R&D | 50 uL | EUR 280 |
 Polyclonal Goat anti-GST μ-form |
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| GST-ANTI-2 | Detroit R&D | 50 uL | EUR 280 |
 Polyclonal Goat anti-GST p-form |
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| GST-ANTI-3 | Detroit R&D | 50 uL | EUR 280 |
 RAE1 ELISA KIT|Human |
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| EF002293 | Lifescience Market | 96 Tests | EUR 689 |
 Rat RAE1 shRNA Plasmid |
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| 20-abx990353 | Abbexa |
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 Mouse RAE1 shRNA Plasmid |
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| 20-abx975736 | Abbexa |
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 Human RAE1 shRNA Plasmid |
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| 20-abx955559 | Abbexa |
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) RAE1 Recombinant Protein (Human) |
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| RP042709 | ABM | 100 ug | Ask for price |
) RAE1 Recombinant Protein (Mouse) |
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| RP166550 | ABM | 100 ug | Ask for price |
) RAE1 Recombinant Protein (Rat) |
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| RP223505 | ABM | 100 ug | Ask for price |
 Polyclonal RAE1 antibody - C-terminal region |
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| APR00780G | Leading Biology | 0.05mg | EUR 528 |
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Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human RAE1 - C-terminal region. This antibody is tested and proven to work in the following applications: |
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Polyclonal RAE1 antibody - C-terminal region |
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| APR00781G | Leading Biology | 0.05mg | EUR 528 |
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Description: A polyclonal antibody raised in Rabbit that recognizes and binds to Human RAE1 - C-terminal region. This antibody is tested and proven to work in the following applications: |
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 Antibody) Ribonucleic Acid Export 1 (RAE1) Antibody |
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| 20-abx005150 | Abbexa |
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) Polyclonal MRNP41 / RAE1 Antibody (C-Terminus) |
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| APG01100G | Leading Biology | 0.05mg | EUR 484 |
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Description: A polyclonal antibody raised in Goat that recognizes and binds to Human MRNP41 / RAE1 (C-Terminus). This antibody is tested and proven to work in the following applications: |
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Ribonucleic Acid Export 1 (RAE1) Antibody |
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| abx237086-100ug | Abbexa | 100 ug | EUR 551 |
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Ribonucleic Acid Export 1 (RAE1) Antibody |
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| 20-abx322391 | Abbexa |
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Ribonucleic Acid Export 1 (RAE1) Antibody |
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| abx433213-200ul | Abbexa | 200 ul | EUR 384 |
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) Human mRNA export factor (RAE1) |
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| 1-CSB-EP019276HU | Cusabio |
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Description: Recombinant Human mRNA export factor(RAE1) expressed in E.coli |
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 (pORF)) Rae1 ORF Vector (Rat) (pORF) |
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| ORF074503 | ABM | 1.0 ug DNA | EUR 506 |
 (pORF)) RAE1 ORF Vector (Human) (pORF) |
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| ORF014237 | ABM | 1.0 ug DNA | EUR 354 |
 (pORF)) Rae1 ORF Vector (Mouse) (pORF) |
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| ORF055518 | ABM | 1.0 ug DNA | EUR 506 |
) Rae1 sgRNA CRISPR Lentivector set (Rat) |
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| K7169401 | ABM | 3 x 1.0 ug | EUR 339 |
) RAE1 sgRNA CRISPR Lentivector set (Human) |
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| K1780301 | ABM | 3 x 1.0 ug | EUR 339 |
) Rae1 sgRNA CRISPR Lentivector set (Mouse) |
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| K3793301 | ABM | 3 x 1.0 ug | EUR 339 |
 ELISA kit) Rat mRNA export factor(RAE1) ELISA kit |
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| E02M0433-192T | B-Gene | 192 tests | EUR 1270 |
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Description: A competitive ELISA for quantitative measurement of Rat mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rat mRNA export factor(RAE1) ELISA kit |
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| E02M0433-48 | B-Gene | 1 plate of 48 wells | EUR 520 |
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Description: A competitive ELISA for quantitative measurement of Rat mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rat mRNA export factor(RAE1) ELISA kit |
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| E02M0433-96 | B-Gene | 1 plate of 96 wells | EUR 685 |
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Description: A competitive ELISA for quantitative measurement of Rat mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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 ELISA kit) Human mRNA export factor(RAE1) ELISA kit |
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| E01M0433-192T | B-Gene | 192 tests | EUR 1270 |
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Description: A competitive ELISA for quantitative measurement of Human mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Human mRNA export factor(RAE1) ELISA kit |
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| E01M0433-48 | B-Gene | 1 plate of 48 wells | EUR 520 |
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Description: A competitive ELISA for quantitative measurement of Human mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Human mRNA export factor(RAE1) ELISA kit |
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| E01M0433-96 | B-Gene | 1 plate of 96 wells | EUR 685 |
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Description: A competitive ELISA for quantitative measurement of Human mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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 ELISA kit) Rabbit mRNA export factor(RAE1) ELISA kit |
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| E04M0433-192T | B-Gene | 192 tests | EUR 1270 |
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Description: A competitive ELISA for quantitative measurement of Rabbit mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rabbit mRNA export factor(RAE1) ELISA kit |
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| E04M0433-48 | B-Gene | 1 plate of 48 wells | EUR 520 |
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Description: A competitive ELISA for quantitative measurement of Rabbit mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Rabbit mRNA export factor(RAE1) ELISA kit |
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| E04M0433-96 | B-Gene | 1 plate of 96 wells | EUR 685 |
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Description: A competitive ELISA for quantitative measurement of Rabbit mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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 ELISA kit) Mouse mRNA export factor(RAE1) ELISA kit |
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| E03M0433-192T | B-Gene | 192 tests | EUR 1270 |
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Description: A competitive ELISA for quantitative measurement of Mouse mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Mouse mRNA export factor(RAE1) ELISA kit |
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| E03M0433-48 | B-Gene | 1 plate of 48 wells | EUR 520 |
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Description: A competitive ELISA for quantitative measurement of Mouse mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Mouse mRNA export factor(RAE1) ELISA kit |
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| E03M0433-96 | B-Gene | 1 plate of 96 wells | EUR 685 |
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Description: A competitive ELISA for quantitative measurement of Mouse mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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 ELISA kit) Goat mRNA export factor(RAE1) ELISA kit |
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| E06M0433-192T | B-Gene | 192 tests | EUR 1270 |
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Description: A competitive ELISA for quantitative measurement of Goat mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Goat mRNA export factor(RAE1) ELISA kit |
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| E06M0433-48 | B-Gene | 1 plate of 48 wells | EUR 520 |
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Description: A competitive ELISA for quantitative measurement of Goat mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Goat mRNA export factor(RAE1) ELISA kit |
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| E06M0433-96 | B-Gene | 1 plate of 96 wells | EUR 685 |
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Description: A competitive ELISA for quantitative measurement of Goat mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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 ELISA kit) Dog mRNA export factor(RAE1) ELISA kit |
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| E08M0433-192T | B-Gene | 192 tests | EUR 1270 |
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Description: A competitive ELISA for quantitative measurement of Canine mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Dog mRNA export factor(RAE1) ELISA kit |
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| E08M0433-48 | B-Gene | 1 plate of 48 wells | EUR 520 |
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Description: A competitive ELISA for quantitative measurement of Canine mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Dog mRNA export factor(RAE1) ELISA kit |
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| E08M0433-96 | B-Gene | 1 plate of 96 wells | EUR 685 |
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Description: A competitive ELISA for quantitative measurement of Canine mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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 ELISA kit) Pig mRNA export factor(RAE1) ELISA kit |
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| E07M0433-192T | B-Gene | 192 tests | EUR 1270 |
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Description: A competitive ELISA for quantitative measurement of Porcine mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Pig mRNA export factor(RAE1) ELISA kit |
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| E07M0433-48 | B-Gene | 1 plate of 48 wells | EUR 520 |
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Description: A competitive ELISA for quantitative measurement of Porcine mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Pig mRNA export factor(RAE1) ELISA kit |
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| E07M0433-96 | B-Gene | 1 plate of 96 wells | EUR 685 |
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Description: A competitive ELISA for quantitative measurement of Porcine mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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 ELISA kit) Monkey mRNA export factor(RAE1) ELISA kit |
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| E09M0433-192T | B-Gene | 192 tests | EUR 1270 |
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Description: A competitive ELISA for quantitative measurement of Monkey mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Monkey mRNA export factor(RAE1) ELISA kit |
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| E09M0433-48 | B-Gene | 1 plate of 48 wells | EUR 520 |
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Description: A competitive ELISA for quantitative measurement of Monkey mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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Monkey mRNA export factor(RAE1) ELISA kit |
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| E09M0433-96 | B-Gene | 1 plate of 96 wells | EUR 685 |
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Description: A competitive ELISA for quantitative measurement of Monkey mRNA export factor(RAE1) in samples from blood, plasma, serum, cell culture supernatant and other biological fluids. This is a high quality ELISA kit developped for optimal performance with samples from the particular species. |
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 Mouse mRNA export factor, Rae1 ELISA KIT |
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| ELI-13997m | Lifescience Market | 96 Tests | EUR 865 |
 Porcine mRNA export factor, RAE1 ELISA KIT |
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| ELI-19560p | Lifescience Market | 96 Tests | EUR 928 |
 Bovine mRNA export factor, RAE1 ELISA KIT |
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| ELI-35553b | Lifescience Market | 96 Tests | EUR 928 |
 Human mRNA export factor, RAE1 ELISA KIT |
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| ELI-36031h | Lifescience Market | 96 Tests | EUR 824 |
 (Target 1)) Rae1 sgRNA CRISPR Lentivector (Rat) (Target 1) |
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| K7169402 | ABM | 1.0 ug DNA | EUR 154 |
 (Target 2)) Rae1 sgRNA CRISPR Lentivector (Rat) (Target 2) |
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| K7169403 | ABM | 1.0 ug DNA | EUR 154 |
 (Target 3)) Rae1 sgRNA CRISPR Lentivector (Rat) (Target 3) |
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| K7169404 | ABM | 1.0 ug DNA | EUR 154 |
 (Target 1)) RAE1 sgRNA CRISPR Lentivector (Human) (Target 1) |
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| K1780302 | ABM | 1.0 ug DNA | EUR 154 |
 (Target 2)) RAE1 sgRNA CRISPR Lentivector (Human) (Target 2) |
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| K1780303 | ABM | 1.0 ug DNA | EUR 154 |
 (Target 3)) RAE1 sgRNA CRISPR Lentivector (Human) (Target 3) |
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| K1780304 | ABM | 1.0 ug DNA | EUR 154 |
 (Target 1)) Rae1 sgRNA CRISPR Lentivector (Mouse) (Target 1) |
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| K3793302 | ABM | 1.0 ug DNA | EUR 154 |
 (Target 2)) Rae1 sgRNA CRISPR Lentivector (Mouse) (Target 2) |
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| K3793303 | ABM | 1.0 ug DNA | EUR 154 |
 (Target 3)) Rae1 sgRNA CRISPR Lentivector (Mouse) (Target 3) |
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| K3793304 | ABM | 1.0 ug DNA | EUR 154 |
 (pPB-C-His)) RAE1 Protein Vector (Rat) (pPB-C-His) |
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| PV298010 | ABM | 500 ng | EUR 603 |
 (pPB-N-His)) RAE1 Protein Vector (Rat) (pPB-N-His) |
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| PV298011 | ABM | 500 ng | EUR 603 |
 (pPM-C-HA)) RAE1 Protein Vector (Rat) (pPM-C-HA) |
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| PV298012 | ABM | 500 ng | EUR 603 |
 (pPM-C-His)) RAE1 Protein Vector (Rat) (pPM-C-His) |
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| PV298013 | ABM | 500 ng | EUR 603 |
 (pPB-C-His)) RAE1 Protein Vector (Human) (pPB-C-His) |
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| PV056945 | ABM | 500 ng | EUR 481 |
 (pPB-N-His)) RAE1 Protein Vector (Human) (pPB-N-His) |
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| PV056946 | ABM | 500 ng | EUR 481 |
 (pPM-C-HA)) RAE1 Protein Vector (Human) (pPM-C-HA) |
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| PV056947 | ABM | 500 ng | EUR 481 |
 (pPM-C-His)) RAE1 Protein Vector (Human) (pPM-C-His) |
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| PV056948 | ABM | 500 ng | EUR 481 |
 (pPB-C-His)) RAE1 Protein Vector (Mouse) (pPB-C-His) |
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| PV222070 | ABM | 500 ng | EUR 603 |
Modulacja aktywności PKR przez mutacje fosfomimetyczne reszt seryny zlokalizowanych trzy aminokwasy powyżej motywów wiążących dwuniciowe RNA
Eukaryotic translation initiation issue 2 alpha kinase 2 (EIF2AK2), higher often known as PKR, performs a key function within the response to viral infections and mobile homeostasis by regulating mRNA translation. Upon binding dsRNA, PKR is activated by means of homodimerization and subsequent autophosphorylation on residues Thr446 and Thr451. On this research, we recognized a novel PKR phosphorylation web site, Ser6, situated three amino acids upstream of the primary double-stranded RNA binding motif (DRBM1).
One other Ser residue happens in PKR at place 97, the exact same place relative to the DRBM2. Ser or Thr residues additionally happen three amino acids upstream DRBMs of different proteins akin to ADAR1 or DICER. Phosphoinhibiting mutations (Ser-to-Ala) launched at Ser6 and Ser97 spontaneously activated PKR. In distinction, phosphomimetic mutations (Ser-to-Asp) inhibited PKR activation following both poly (I:C) transfection or virus an infection. These mutations reasonably affected dsRNA binding or dimerization, suggesting a mannequin the place unfavorable expenses occurring at place 6 and 97 tighten the interplay of DRBMs with the kinase area, thus maintaining PKR in an inactive closed conformation even within the presence of dsRNA. This research supplies new insights on PKR regulation mechanisms and identifies Ser6 and Ser97 as potential targets to modulate PKR exercise for therapeutic functions.
Różnicowa proteomika korzeni sadzonek tytoniu przy wysokich i niskich stężeniach potasu
The consequences of excessive potassium and regular potassium therapies on protein expression in roots of flue-cured tobacco plant HKDN-5 at the seedling stage have been analyzed by an unlabeled protein quantification approach. The outcomes confirmed that 555 proteins have been differentially expressed (245 proteins have been down-regulated and 310 proteins have been up-regulated) in excessive potassium remedy in contrast with regular potassium remedy. Differentially expressed proteins have been concerned in 96 metabolic pathways (42 metabolic pathways, 21 artificial pathways in addition to catabolic pathways, together with fatty acid metabolism, phenylpropane biosynthesis, ketone physique synthesis and degradation, and butyric acid metabolism.
Root processing of excessive potassium concentrations results in will increase within the synthesis of peroxidase, superoxide dismutase and acyl-coenzyme-A synthetase. Further proteomic variations noticed in tobacco roots grown in excessive potassium embrace proteins concerned with genetic info processing in addition to environmental sensing. Examples embrace RNA helicase, ABC transporters and enormous subunit GTPases. These up-regulated differentially expressed proteins perform primarily in protein translation, ribosome construction and protein synthesis. This means that underneath excessive potassium remedy, root protein artificial processes are accelerated and substance metabolism pathways are enhanced; thus, offering the fabric and energetic foundation for root progress.
Połączone badanie przesiewowe CRISPR identyfikuje m 6 A jako pozytywny regulator aktywacji makrofagów
m6A RNA modification is implicated in a number of mobile responses. Nonetheless, its perform within the innate immune cells is poorly understood. Right here, we recognized main m6A “writers” as the highest candidate genes regulating macrophage activation by LPS in an RNA binding protein centered CRISPR screening. We have now confirmed that Mettl3-poor macrophages exhibited decreased TNF-α manufacturing upon LPS stimulation in vitro. Constantly, Mettl3 flox/flox;Lyzm-Cre mice displayed elevated susceptibility to bacterial an infection and confirmed sooner tumor progress.
Mechanistically, the transcripts of the Irakm gene encoding a unfavorable regulator of TLR4 signaling have been extremely adorned by m6A modification. METTL3 deficiency led to the lack of m6A modification on Irakm mRNA and slowed down its degradation, leading to a better stage of IRAKM, which in the end suppressed TLR signaling-mediated macrophage activation. Our findings display a beforehand unknown function for METTL3-mediated m6A modification in innate immune responses and implicate the m6A equipment as a possible most cancers immunotherapy goal.
Lityczne zakażenie mysim gammaherpeswirusem 68 aktywuje promotory gospodarza i wirusowej polimerazy RNA III i zwiększa niekodującą ekspresję RNA
RNA polymerase III (pol III) transcribes a number of non-coding (nc) RNAs which are important for mobile perform. Pol III-dependent transcription can also be engaged throughout sure viral infections, together with the gammaherpesviruses (γHVs), the place pol III-dependent viral ncRNAs promote pathogenesis. Moreover, a number of host ncRNAs are upregulated throughout γHV an infection and play integral roles in pathogenesis by facilitating viral institution and gene expression. Right here, we sought to research how pol III promoters and transcripts are regulated throughout gammaherpesvirus an infection utilizing the murine gammaherpesvirus 68 (γHV68) system. To check the transcription of host and viral pol III-dependent ncRNAs, we analyzed a sequence of pol III promoters for host and viral ncRNAs utilizing a luciferase reporter optimized to measure pol III exercise. We measured promoter exercise from the reporter gene on the translation stage through luciferase exercise and on the transcription stage through RT-qPCR. We additional measured endogenous ncRNA expression at single cell-resolution by circulation cytometry.
These research demonstrated that lytic an infection with γHV68 elevated the transcription from a number of host and viral pol III promoters, and additional recognized the flexibility of accent sequences to affect each baseline and inducible promoter exercise after an infection. RNA circulation cytometry revealed the induction of endogenous pol III-derived ncRNAs that tightly correlated with viral gene expression. These research spotlight how lytic gammaherpesvirus an infection alters the transcriptional panorama of host cells to extend pol III-derived RNAs, a course of that will additional modify mobile perform and improve viral gene expression and pathogenesis.IMPORTANCEGammaherpesviruses are a first-rate instance of how viruses can alter the host transcriptional panorama to ascertain an infection. Regardless of main insights into how these viruses modify RNA polymerase II-dependent era of messenger RNAs, how these viruses affect the exercise of host RNA polymerase III stays a lot much less clear.
Small non-coding RNAs produced by RNA polymerase III are more and more acknowledged to play important regulatory roles in cell biology and virus an infection. Research of RNA polymerase III dependent transcription are sophisticated by a number of promoter varieties and various RNAs with variable stability and processing necessities. Right here, we characterised a reporter system to straight research RNA polymerase III-dependent responses throughout gammaherpesvirus an infection and utilized single-cell circulation cytometry-based strategies to disclose that gammaherpesvirus lytic replication broadly induces pol III exercise to boost host and viral non-coding RNA expression throughout the contaminated cell.
