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4650 results for "uj127&pageNo=74&view=list"

4650 Results for: "uj127&pageNo=74&view=list"

Ultra-low temperature refrigerated circulators

Ultra-low temperature refrigerated circulators

Supplier: JULABO GmbH

Ultra-low temperature refrigerated circulators for heating and cooling. The units are suitable for external temperature applications with simultaneous operation in the bath tank. The units provide particularly high heating and cooling capacities for rapid heating and cooling times even for large volume, external systems. FP models offer proportional cooling control to ensure energy saving performance and to reduce heat generation to the environment. Models with the designation W are water cooled. All models have handles and castors which allow easy transportation and drain ports for conveniently draining the bath fluid. The units offer an improved insulation to prevent ice formation and have a filling level display. Typical applications: Temperature control of jacketed reaction vessels, autoclaves, mini plant installations, kilo labs, freezing point determination, calibration at low temperatures and petroleum testing.

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Cooled Incubators, Series 4

Cooled Incubators, Series 4

Supplier: LMS

LMS Series 4 cooled incubators are temperature controlled cabinets with fan assisted air circulation via a pre-mixing chamber. The units have a stainless steel exterior, stainless steel lined interior with polyurethane foam insulation, and feature a door lock and magnetic door gasket. Corrosion resistant inner chamber is easy to clean, disinfection procedures are detailed in the user manual.

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Cubis® II MCA 226S Ultra-High Resolution Semi-Micro Balances

Cubis® II MCA 226S Ultra-High Resolution Semi-Micro Balances

Supplier: Sartorius Balances

The Cubis® II laboratory balances are modular, therefore they allow to choose between applications and configurations which suit the best to the needs. These balances can be configured at the level of display, draftshields, software applications and hardware functions.

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Cubis® II MCA 125S Ultra-High Resolution Semi-Micro Balances

Cubis® II MCA 125S Ultra-High Resolution Semi-Micro Balances

Supplier: Sartorius Balances

The Cubis® II laboratory balances are modular, therefore they allow to choose between applications and configurations which suit the best to the needs. These balances can be configured at the level of display, draftshields, software applications and hardware functions.

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UNIT INJECTION FOR WD 230 1 * 1 items

Supplier: BELIMED

UNIT INJECTION FOR WD 230 1 * 1 items

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Cooled incubators, Series 1A

Cooled incubators, Series 1A

Supplier: LMS

LMS Series 1A cooled incubators are temperature controlled cabinets with fan assisted air circulation via a pre-mixing chamber. The units have a white enamelled sheet steel exterior, white pre-coated aluminium interior and polyurethane foam insulation, and feature a door lock and magnetic door gasket. The inner chamber is easy to clean, disinfection procedures are detailed in the user manual.

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Cubis® II MCA 225P Ultra-High Resolution Semi-Micro Balances

Cubis® II MCA 225P Ultra-High Resolution Semi-Micro Balances

Supplier: Sartorius Balances

The Cubis® II laboratory balances are modular, therefore they allow to choose between applications and configurations which suit the best to the needs. These balances can be configured at the level of display, draftshields, software applications and hardware functions.

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Anti-CHEK2 Rabbit Polyclonal Antibody

Anti-CHEK2 Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by Chk2 gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Three transcript variants encoding different isoforms have been found for this gene.

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Anti-CD209 Rabbit Polyclonal Antibody

Anti-CD209 Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

Pathogen-recognition receptor expressed on the surface of immature dendritic cells (DCs) and involved in initiation of primary immune response. Thought to mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. The receptor returns to the cell membrane surface and the pathogen-derived antigens are presented to resting T-cells via MHC class II proteins to initiate the adaptive immune response. Probably recognizes in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens, including HIV-1 gp120, HIV-2 gp120, SIV gp120, ebolavirus glycoproteins, cytomegalovirus gB, HCV E2, dengue virus gE, Leishmania pifanoi LPG, Lewis-x antigen in Helicobacter pylori LPS, mannose in Klebsiella pneumonae LPS, di-mannose and tri-mannose in Mycobacterium tuberculosis ManLAM and Lewis-x antigen in Schistosoma mansoni SEA. On DCs it is a high affinity receptor for ICAM2 and ICAM3 by binding to mannose-like carbohydrates. May act as a DC rolling receptor that mediates transendothelial migration of DC presursors from blood to tissues by binding endothelial ICAM2. Seems to regulate DC-induced T-cell proliferation by binding to ICAM3 on T-cells in the immunological synapse formed between DC and T-cells.

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Anti-RNF74 Rabbit Polyclonal Antibody (Cy5®)

Supplier: Bioss

Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination.

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Pestle,porcelain,unglazed,length 250mm, head diameter 74mm 1 * 1 items

Supplier: MORGAN ADVANCED MATERIALS HALD

Pestle,porcelain,unglazed,length 250mm, head diameter 74mm 1 * 1 items

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Anti-LCK Rabbit Polyclonal Antibody

Anti-LCK Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

Tyrosine kinase that plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR.

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Anti-RELB Rabbit Polyclonal Antibody

Anti-RELB Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

NF-κ-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-κ-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-κ-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-κ-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-κ-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-κ-B complex which translocates to the nucleus. NF-κ-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49.

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Anti-LCK Rabbit Polyclonal Antibody

Anti-LCK Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

Tyrosine kinase that plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR.

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Vacuum drying chambers, VD and VDL series

Vacuum drying chambers, VD and VDL series

Supplier: Binder

The VD series of vacuum drying chambers provide fast gentle drying of non flammable solvents, delivering impressive performance through their precise temperature control and gentle drying. Expansion rack technology also ensures optimal heat transfer, shelves provide flexible placement, and the interior of the chamber is easy to clean. The VDL series of safety vacuum drying chambers ensures maximum safety when drying flammable organic solvents, and have been safety tested by a state recognised test institute (GS mark). VD/VDL units can also be purchased as modular options with vacuum pump and pump chamber to form a complete system.

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Anti-RNF74 Rabbit Polyclonal Antibody (Alexa Fluor® 647)

Supplier: Bioss

Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination.

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[FR] 8 COMPOSES 100MG/L CHAQUE DANS HNO3 2% 1 * 125 mL

Supplier: CUSTOM MADE CHEMICALS LAB

[FR] 8 COMPOSES 100MG/L CHAQUE DANS HNO3 2% 1 * 125 mL

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Water baths and circulators, stainless steel, Optima™

Water baths and circulators, stainless steel, Optima™

Supplier: GRANT INSTRUMENTS

The Grant Optima™ range consists of both general purpose and advanced performance thermostats combined with premium stainless steel baths (drain tap on 12, 18, 26 and 38 litre baths). Stirred circulation within the bath ensures excellent temperature stability and uniformity. Units can also be used with accessory C1G and C2G immersion coolers for operation below ambient temperatures.

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Cooled Incubators, Series 2

Cooled Incubators, Series 2

Supplier: LMS

LMS Series 2 cooled incubators are temperature controlled cabinets with fan assisted air circulation via a pre-mixing chamber. The units have a white enamelled sheet steel exterior, high impact plastic interior and polyurethane foam insulation, and feature a door lock and magnetic door gasket. The corrosion resistant inner chamber is easy to clean, disinfection procedures are detailed in the user manual.

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Biological upright microscopes, fixed Koehler LED, BA 210 LED

Biological upright microscopes, fixed Koehler LED, BA 210 LED

Supplier: MOTIC

Microscopes for basic work in biology life science. Fixed Koehler set-up gives adequate power resources for upgrading the microscope with contrast methods like phase contrast, polarisation or darkfield. The Motic BA 210 is a robust, ready to use with pre-installed set-up of optics and 3 W LED illumination.

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Plasmid Screening ToothPick™ and ToothPick™-PCR

Plasmid Screening ToothPick™ and ToothPick™-PCR

Supplier: G-Biosciences

Plasmid Screening ToothPick™ allows the rapid screening of bacteria for transformed plasmids. Simply pick a colony, add to Plasmid Screening ToothPick™ reagents and then analyse using restriction enzymes.

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Anti-RELB Rabbit Polyclonal Antibody

Anti-RELB Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

NF-κ-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-κ-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-κ-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-κ-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-κ-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-κ-B complex which translocates to the nucleus. NF-κ-B heterodimeric RelB-p50 and RelB-p52 complexes are transcriptional activators. RELB neither associates with DNA nor with RELA/p65 or REL. Stimulates promoter activity in the presence of NFKB2/p49.

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Anti-CARM1 Rabbit Polyclonal Antibody

Anti-CARM1 Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' and activates transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-κ-B. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.

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Anti-MAP2K6 Rabbit Polyclonal Antibody

Anti-MAP2K6 Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

MEK6 is a member of MAPKK protein kinase family. By using degenerate oligonucleotide primers from the conserved kinase domains of MKK3 and MKK4 two human cDNAs and 1 murine cDNA encoding closely related proteins of the MKK family were cloned. The two human clones appear to be different isoforms of the same gene generated by differential splicing: the shorter clone was designated MKK6, encodes a 278-amino acid protein, while the longer clone, designated MKK6b, encodes a 334-amino acid protein. MKK6 is about 80% identical to MKK3 and 40% identical to MKK4. 1.7-kb human MKK6 transcript is highly expressed in skeletal muscle, while an MKK6b-specific probe detected mRNA bands of 1.8, 2.4, and 4.5 kb that are enriched in heart, skeletal muscle, pancreas and liver. MKK6 plays an important role in intracellular signaling pathways leading toward activation of the p38 MAP kinase. MEK6 phosphorylates and activates p38 in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAPK mediated signal transduction pathway, this gene is involved in many cellular processes such as stress induced cell cycle arrest, transcription activation and apoptosis.

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Anti-RAF1 Rabbit Polyclonal Antibody

Anti-RAF1 Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

A-Raf, B-Raf and c-Raf (Raf-1) are the main effectors recruited by GTP-bound Ras to activate the MEK-MAP kinase pathway. Activation of c-Raf is the best understood and involves phosphorylation at multiple activating sites including Ser338, Tyr341, Thr491, Ser494, Ser497 and Ser499. p21-activated protein kinase (PAK) has been shown to phosphorylate c-Raf at Ser338 and the Src family phosphorylates Tyr341 to induce c-Raf activity (3, 4). Ser338 of c-Raf corresponds to similar sites in A-Raf (Ser299) and B-Raf (Ser445), although this site is constitutively phosphorylated in B-Raf. Inhibitory 14-3-3 binding sites on c-Raf (Ser259 and Ser621) can be phosphorylated by Akt and AMPK, respectively (6, 7). While A-Raf, B-Raf and c-Raf are similar in sequence and function, differential regulation has been observed (8). Of particular interest, B-Raf contains three consensus Akt phosphorylation sites (Ser364, Ser428 and Thr439) and lacks a site equivalent to Tyr341 of c-Raf (8, 9). The B-Raf mutation V600E results in elevated kinase activity and is commonly found in malignant melanoma (10). Six residues of c-Raf (Ser29, Ser43, Ser289, Ser296, Ser301 and Ser642) become hyperphosphorylated in a manner consistent with c-Raf inactivation. The hyperphosphorylation of these six sites is dependent on downstream MEK signaling and renders c-Raf unresponsive to

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Anti-MAPK8 / MAPK9 / MAPK10 Rabbit Polyclonal Antibody

Anti-MAPK8 / MAPK9 / MAPK10 Rabbit Polyclonal Antibody

Supplier: ProSci Inc.

Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity. In T-cells, JNK1 and JNK2 are required for polarized differentiation of T-helper cells into Th1 cells By similarity. Phosphorylates heat shock factor protein 4 (HSF4). /Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as c-Jun and ATF2 and thus regulates AP-1 transcriptional activity. In T-cells, JNK1 and JNK2 are required for polarized differentiation of T-helper cells into Th1 cells. JNK2 isoforms display different binding patterns: alpha-1 and alpha-2 preferentially bind to c-Jun, whereas beta-1 and beta-2 bind to ATF2. However, there is no correlation between binding and phosphorylation, which is achieved at about the same efficiency by all isoforms. JUNB is not a substrate for JNK2 alpha-2, and JUND binds only weakly to it./Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as c-Jun and ATF2 and thus regulates AP-1 transcriptional activity. Required for stress-induced neuronal apoptosis and the pathogenesis of glutamate excitotoxicity

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Inverted routine microscopes with fixed stage and Fluo package options, DM IL LED

Inverted routine microscopes with fixed stage and Fluo package options, DM IL LED

Supplier: LEICA MICROSYSTEMS

The Leica DM IL is a fluorescence-ready digital imaging solution designed for use in a variety of laboratory settings including cell culture, micromanipulation, immuno staining and routine live imaging.

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Low voltage cable, 1.2 m length 1st and 2nd side: low-voltage coupler for pin contact Ø 2.1 mm, connection: sample changer TW 7400 < -> rod stirrer TZ 1847, 1 * 1 items

Supplier: SI Analytics

Low voltage cable, 1.2 m length 1st and 2nd side: low-voltage coupler for pin contact Ø 2.1 mm, connection: sample changer TW 7400 < -> rod stirrer TZ 1847, 1 * 1 items

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Rotary Evaporators, Hei-VAP Expert Control

Rotary Evaporators, Hei-VAP Expert Control

Supplier: Heidolph Instruments GmbH & Co.KG

Hei-VAP Expert Control rotary evaporators allow central control of all process parameters: Vacuum, cooling temperature, rotation and heating bath temperature. The units have separate knobs for quick access: Right for direct vacuum control, the left one for rotation has a lock function to prevent accidental adjustment

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Anti-RNF74 Rabbit Polyclonal Antibody (Alexa Fluor® 488)

Supplier: Bioss

Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as a E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination.

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