Contact-dependent progress inhibition (CDI) methods allow the direct switch of protein toxins between competing Gram-negative micro organism. CDI+ strains produce cell floor CdiA effector proteins that bind particular receptors on neighboring micro organism to provoke toxin supply. Three lessons of CdiA effectors that acknowledge totally different outer membrane protein receptors have been characterised in Escherichia coli so far.
Right here, we describe a fourth effector class that makes use of the lipopolysaccharide (LPS) core as a receptor to determine goal micro organism. Choice for CDI-resistant goal cells yielded waaF and waaP “deep-rough” mutants, that are unable to synthesize the complete LPS core.
The CDI resistance phenotypes of different waa mutants counsel that phosphorylated inner-core heptose residues kind a crucial CdiA recognition epitope. Class IV cdi loci additionally encode putative lysyl acyltransferases (CdiC) which might be homologous to enzymes that lipidate repeats-in-toxin (RTX) cytolysins. We discovered that catalytically energetic CdiC is required for full goal cell killing exercise, and we offer proof that the acyltransferase appends 3-hydroxydecanoate to a selected Lys residue inside the CdiA receptor-binding area.
We suggest that the lipid moiety inserts into the hydrophobic leaflet of lipid A to anchor CdiA interactions with the core oligosaccharide. Thus, LPS-binding CDI methods seem to have co-opted an RTX toxin-activating acyltransferase to extend the affinity of CdiA effectors for the goal cell outer membrane.
IMPORTANCE Contact-dependent progress inhibition (CDI) is a typical type of interbacterial competitors during which cells use CdiA effectors to ship poisonous proteins into their neighbors. CdiA acknowledges goal micro organism via particular receptor molecules on the cell floor. Right here, we describe a brand new household of CdiA proteins that use lipopolysaccharide as a receptor to determine goal micro organism.
Goal cell recognition is considerably enhanced by a novel fatty acid that’s appended to the receptor-binding area of CdiA. We suggest that the linked fatty acid inserts into the goal cell outer membrane to stabilize the interplay. The CdiA receptor-binding area seems to imitate the biophysical properties of polymyxins, that are potent antibiotics used to disrupt the outer membranes of Gram-negative micro organism.
Human Monoclonal Antibodies towards NS1 Protein Defend towards Deadly West Nile Virus An infection
Envelope protein-targeted vaccines for flaviviruses are restricted by issues of antibody-dependent enhancement (ADE) of infections. Nonstructural protein 1 (NS1) offers an alternate vaccine goal that avoids this threat since this protein is absent from the virion. Past its intracellular function in virus replication, extracellular types of NS1 operate in immune modulation and are acknowledged by host-derived antibodies. The rational design of NS1-based vaccines requires an in depth understanding of the antigenic websites on NS1, particularly these focused by protecting antibodies.
Right here, we remoted human monoclonal antibodies (MAbs) from people beforehand naturally contaminated with WNV, mapped their epitopes utilizing structure-guided mutagenesis, and evaluated their efficacy in vivo towards deadly WNV problem. Essentially the most protecting epitopes clustered at three antigenic websites which might be uncovered on cell floor types of NS1: (i) the wing versatile loop, (ii) the outer, electrostatic floor of the wing, and (iii) the spaghetti loop face of the β-ladder.
One extra MAb mapped to the distal tip of the β-ladder and conferred a decrease stage of safety towards WNV regardless of not binding to NS1 on the floor of contaminated cells. Our research defines the epitopes and modes of binding of protecting anti-NS1 MAb antibodies following WNV an infection, which can inform the event of NS1-based countermeasures towards flaviviruses.
IMPORTANCE Therapeutic antibodies towards flaviviruses typically promote neutralization by focusing on the envelope protein of the virion. Nonetheless, this strategy is hindered by a doable concern for antibody-dependent enhancement of an infection and paradoxical worsening of illness. Instead technique, antibodies focusing on flavivirus nonstructural protein 1 (NS1), which is absent from the virion, can defend towards illness and don’t trigger enhanced an infection.
Right here, we consider the structure-function relationships and protecting exercise of West Nile virus (WNV) NS1-specific monoclonal antibodies (MAbs) remoted from the reminiscence B cells of a naturally contaminated human donor. We determine a number of anti-NS1 MAbs that defend mice towards deadly WNV problem and map their epitopes utilizing cost reversal mutagenesis. Antibodies focusing on particular areas within the NS1 construction may function the premise for countermeasures that management WNV an infection in people.
Peptides Derived From S and N Proteins of Extreme Acute Respiratory Syndrome Coronavirus 2 Induce T Cell Responses: A Proof of Idea for T Cell Vaccines
The emergence of extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape vaccine-induced neutralizing antibodies has indicated the significance of T cell responses towards this virus. On this research, we spotlight the SARS-CoV-2 epitopes that induce potent T cell responses and focus on whether or not T cell responses alone are enough to confer safety towards SARS-CoV-2 and describe the administration of 20 peptides with an RNA adjuvant in mice.
The peptides have been synthesized based mostly on SARS-CoV-2 spike and nucleocapsid protein sequences. Our research demonstrates that immunization with these peptides considerably will increase the proportion of effector reminiscence T cell inhabitants and interferon-γ (IFN-γ)-, interleukin-4 (IL-4)-, tumor necrosis factor-α (TNF-α)-, and granzyme B-producing T cells. Of those 20 peptides, 4 induce the era of IFN-γ-producing T cells, elicit CD8+ T cell (CTL) responses in a dose-dependent method, and induce cytotoxic T lymphocytes that remove peptide-pulsed goal cells in vivo.
Though it’s not statistically important, these peptide vaccines cut back viral titers in contaminated hamsters and alleviate pulmonary pathology in SARS-CoV-2-infected human ACE2 transgenic mice. These findings might support the design of efficient SARS-CoV-2 peptide vaccines, whereas offering insights into the function of T cells in SARS-CoV-2 an infection.
Promyelocytic leukemia protein targets MK2 to advertise cytotoxicity
Promyelocytic leukemia protein (PML) is a tumor suppressor possessing a number of modes of motion, together with induction of apoptosis. We unexpectedly discover that PML promotes necroptosis along with apoptosis, with Pml-/- macrophages being extra immune to TNF-mediated necroptosis than wild-type counterparts and PML-deficient mice displaying resistance to TNF-induced systemic inflammatory response syndrome. Lowered necroptosis in PML-deficient cells is related to attenuated receptor-interacting protein kinase 1 (RIPK1) activation, as revealed by lowered RIPK1[S166] phosphorylation, and attenuated RIPK1-RIPK3-MLKL necrosome complicated formation.
We present that PML deficiency results in enhanced TNF-induced MAPK-activated kinase 2 (MK2) activation and elevated RIPK1[S321] phosphorylation, which suppresses necrosome formation. MK2 inhibitor therapy or MK2 knockout abrogates resistance to cell demise induction in PML-null cells and mice. PML binds MK2 and p38 MAPK, thereby inhibiting p38-MK2 interplay and MK2 activation.
Furthermore, PML participates in autocrine manufacturing of TNF induced by mobile inhibitors of apoptosis 1 (cIAP1)/cIAP2 degradation, since PML-knockout attenuates autocrine TNF. Thus, by focusing on MK2 activation and autocrine TNF, PML promotes necroptosis and apoptosis, representing a novel tumor-suppressive exercise for PML.
Sp100 Nuclear Antigen (Sp100) Polyclonal Antibody (Mouse), APC-Cy7 |
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| 4-PAA326Mu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Mouse Sp100 Nuclear Antigen (Sp100). This antibody is labeled with APC-Cy7. |
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Sp100 Nuclear Antigen (Sp100) Polyclonal Antibody (Rat), APC-Cy7 |
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| 4-PAA326Ra01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Rat Sp100 Nuclear Antigen (Sp100). This antibody is labeled with APC-Cy7. |
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Ribonuclease III, Nuclear (RNASEN) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAD163Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Ribonuclease III, Nuclear (RNASEN). This antibody is labeled with APC-Cy7. |
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Human Nuclear pore complex protein Nup153 (NUP153) |
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| 1-CSB-EP016190HU | Cusabio |
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Description: Recombinant Human Nuclear pore complex protein Nup153(NUP153),partial expressed in E.coli |
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Nuclear pore complex protein Nup98 (315-360) |
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| HY-P1730 | MedChemExpress | 1mg | EUR 1368 |
Recombinant human Nuclear pore complex protein Nup133 |
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| P2220 | FN Test | 100ug | Ask for price |
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Description: Recombinant protein for human Nuclear pore complex protein Nup133 |
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Proliferating Cell Nuclear Antigen (PCNA) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-CAA591Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Proliferating Cell Nuclear Antigen (PCNA). This antibody is labeled with APC-Cy7. |
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Proliferating Cell Nuclear Antigen (PCNA) Monoclonal Antibody (Human), APC-Cy7 |
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| 4-CAA591Hu22-APC-Cy7 | Cloud-Clone |
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Description: A Mouse monoclonal antibody against Human Proliferating Cell Nuclear Antigen (PCNA). This antibody is labeled with APC-Cy7. |
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Nuclear Factor Kappa B (NFkB) Polyclonal Antibody (Chicken), APC-Cy7 |
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| 4-PAB824Ga01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Chicken Nuclear Factor Kappa B (NFkB). This antibody is labeled with APC-Cy7. |
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Nuclear Factor Kappa B (NFkB) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAB824Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Nuclear Factor Kappa B (NFkB). This antibody is labeled with APC-Cy7. |
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Nuclear Factor Kappa B (NFkB) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAB824Hu02-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Nuclear Factor Kappa B (NFkB). This antibody is labeled with APC-Cy7. |
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Nuclear Factor Kappa B (NFkB) Polyclonal Antibody (Rat), APC-Cy7 |
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| 4-PAB824Ra01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Rat Nuclear Factor Kappa B (NFkB). This antibody is labeled with APC-Cy7. |
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Nuclear Factor Kappa B2 (NFkB2) Polyclonal Antibody (Chicken), APC-Cy7 |
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| 4-PAB825Ga01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Chicken Nuclear Factor Kappa B2 (NFkB2). This antibody is labeled with APC-Cy7. |
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Nuclear Factor Kappa B2 (NFkB2) Polyclonal Antibody (Mouse), APC-Cy7 |
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| 4-PAB825Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Mouse Nuclear Factor Kappa B2 (NFkB2). This antibody is labeled with APC-Cy7. |
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Nuclear Factor Kappa B2 (NFkB2) Polyclonal Antibody (Mouse), APC-Cy7 |
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| 4-PAB825Mu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Mouse Nuclear Factor Kappa B2 (NFkB2). This antibody is labeled with APC-Cy7. |
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Nuclear Matrix Protein 4 (NMP4) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAB095Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Nuclear Matrix Protein 4 (NMP4). This antibody is labeled with APC-Cy7. |
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Germ Cell Nuclear Factor (GCNF) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAC509Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Germ Cell Nuclear Factor (GCNF). This antibody is labeled with APC-Cy7. |
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Nuclear Factor I/A (NFIA) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAC655Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Nuclear Factor I/A (NFIA). This antibody is labeled with APC-Cy7. |
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Nuclear Transport Factor 2 (NUTF2) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAC671Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Nuclear Transport Factor 2 (NUTF2). This antibody is labeled with APC-Cy7. |
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Proliferating Cell Nuclear Antigen (PCNA) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAA591Mi01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Proliferating Cell Nuclear Antigen (PCNA). This antibody is labeled with APC-Cy7. |
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Thymocyte Nuclear Protein 1 (THYN1) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAC791Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Thymocyte Nuclear Protein 1 (THYN1). This antibody is labeled with APC-Cy7. |
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Thymocyte Nuclear Protein 1 (THYN1) Polyclonal Antibody (Rat), APC-Cy7 |
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| 4-PAC791Ra01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Rat Thymocyte Nuclear Protein 1 (THYN1). This antibody is labeled with APC-Cy7. |
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Nuclear Factor I/B (NFIB) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAF663Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Nuclear Factor I/B (NFIB). This antibody is labeled with APC-Cy7. |
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Nuclear Factor I/X (NFIX) Polyclonal Antibody (Rat), APC-Cy7 |
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| 4-PAF665Ra01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Rat Nuclear Factor I/X (NFIX). This antibody is labeled with APC-Cy7. |
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Nuclear Receptor Coactivator 3 (NCOA3) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAE798Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Nuclear Receptor Coactivator 3 (NCOA3). This antibody is labeled with APC-Cy7. |
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Nuclear Receptor Coactivator 3 (NCOA3) Polyclonal Antibody (Rat), APC-Cy7 |
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| 4-PAE798Ra01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Rat Nuclear Receptor Coactivator 3 (NCOA3). This antibody is labeled with APC-Cy7. |
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Mediator Complex Subunit 1 (MED1) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAC238Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Mediator Complex Subunit 1 (MED1). This antibody is labeled with APC-Cy7. |
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Nuclear Pore Complex-Interacting Protein-Like 2 (NPIPL2) Antibody |
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| abx034938-400ul | Abbexa | 400 ul | EUR 627.6 |
Nuclear Pore Complex-Interacting Protein-Like 2 (NPIPL2) Antibody |
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| abx034938-80l | Abbexa | 80 µl | EUR 343.2 |
Myeloid Cell Nuclear Differentiation Antigen (MNDA) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAB775Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Myeloid Cell Nuclear Differentiation Antigen (MNDA). This antibody is labeled with APC-Cy7. |
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Nuclear Factor Kappa B (NFkB) Polyclonal Antibody (Human, Mouse), APC-Cy7 |
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| 4-PAB824Mu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human, Mouse Nuclear Factor Kappa B (NFkB). This antibody is labeled with APC-Cy7. |
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Small Nuclear Ribonucleoprotein Polypeptide C (SNRPC) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAB374Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Small Nuclear Ribonucleoprotein Polypeptide C (SNRPC). This antibody is labeled with APC-Cy7. |
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Nuclear Mitotic Apparatus Protein 1 (NUMA1) Monoclonal Antibody (Human), APC-Cy7 |
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| 4-MAC332Hu22-APC-Cy7 | Cloud-Clone |
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Description: A Mouse monoclonal antibody against Human Nuclear Mitotic Apparatus Protein 1 (NUMA1). This antibody is labeled with APC-Cy7. |
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Hepatocyte Nuclear Factor 4 Alpha (HNF4a) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAA418Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Hepatocyte Nuclear Factor 4 Alpha (HNF4a). This antibody is labeled with APC-Cy7. |
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Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRPA2B1) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAA323Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRPA2B1). This antibody is labeled with APC-Cy7. |
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Photoreceptor Cell Specific Nuclear Receptor (PNR) Polyclonal Antibody (Human), APC-Cy7 |
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| 4-PAD956Hu01-APC-Cy7 | Cloud-Clone |
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Description: A Rabbit polyclonal antibody against Human Photoreceptor Cell Specific Nuclear Receptor (PNR). This antibody is labeled with APC-Cy7. |
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