The human cytidine deaminase Apobec3F (h-A3F) a protein linked to the previously recognized antiviral factor Apobec3G (h-A3G) has antiviral activity against individual immunodeficiency virus type 1 (HIV-1) thats suppressed with the viral protein Vif. E3 ubiquitin ligase. Disturbance with Cul5-E3 ligase function by depletion of Cul5 through RNA disturbance or overexpression of Cul5 mutants obstructed the power of HIV-1 Vif to suppress h-A3F. A BC-box mutant of HIV-1 Vif that didnt recruit Cul5-E3 ligase but was still in a position to connect to h-A3F didnt suppress h-A3F. Oddly enough disturbance with Cul5-E3 ligase function or overexpression of h-A3F or h-A3G also elevated the balance of HIV-1 Vif recommending that just like the substrate substances h-A3F and h-A3G the substrate receptor proteins Vif is certainly itself also governed by Cul5-E3 ligase. Our outcomes indicate that Cul5-E3 ligase is apparently a common pathway hijacked by HIV-1 Vif to beat both h-A3F and h-A3G. Developing ...

Quantitative RT-PCR analysis of activation-induced cytidine deaminase expression in tissue samples from mantle cell lymphoma and B-cell chronic lymphocytic leukemia patients ...

Source: NIH.gov. A set of proteins involved in the bodys natural defences produces a large number of mutations in human DNA, according to a study led by researchers at the National Institutes of Health. The findings suggest that these naturally produced mutations are just as powerful as known cancer-causing agents in producing tumors.. The proteins are part of a group called apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) cytidine deaminases. The investigators found that APOBEC mutations can outnumber all other mutations in some cancers, accounting for over two-thirds in some bladder, cervical, breast, head and neck, and lung tumours.. The scientists published their findings online July 14 in the journal Nature Genetics. Dmitry Gordenin, Ph.D., is corresponding author of the paper and a senior associate scientist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH. He said scientists knew the main functions of APOBEC cytosine deaminases were ...

Affinity maturation and class switching of antibodies requires activation-induced cytidine deaminase (AID)-dependent hypermutation of Ig V(D)J rearrangements and Ig S areas, respectively, in activated B cells. in DT40 cells elevated the pace of AID-induced BMS-754807 gene conversion as much as 5-collapse. Furthermore, DNA-PKcs-deficiency appeared to reduce point mutation. The data provide strong evidence that double-strand DNA ends capable of recruiting the DNA-dependent protein kinase complex are important intermediates in Ig V gene conversion. Author Summary To generate highly specific antibodies in response to an immune challenge, the antibody genes in triggered B cells mutate at a very high rate over a period of several days. The enzyme that initiates antibody gene mutation is definitely activation-induced cytidine deaminase (AID), the 1st protein recognized to directly edit DNA genomes BMS-754807 in vivo. AID induces point mutation of antibody V genes in all vertebrates, as well as transfer ...

To investigate whether the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway participates in the regulation of APOBEC3G (Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) gene transcription and to study the molecular mechanisms of interferon resistance in patients with chronic hepatitis B (CHB), changes in APOBEC3G and STAT-1 expression levels in HepG2.2.15 cells after treatment with various concentrations of IFN-a, were detected using real-time RT-PCR and Western-blot. In addition, the differences in STAT-1 and APOBEC3G expression in liver tissues were also observed in patients with different anti-viral responses to IFN-a. It is found that IFN-a suppressed HBV replication and expression markedly in HepG2.2.15 cells, and simultaneously enhanced APOBEC3G expression in a dose- or time-dependent manner within a certain range. Moreover, a corresponding gradual increase in STAT-1 expression levels was also observed. The expression levels of STAT-1 and

Activation-induced cytidine deaminase (AID) was discovered by Muramatsu et al. (7) as an APOBEC1 homolog with cytidine deaminase properties in stimulated B cell lines. Muramatsu et al. (8) showed that AID is necessary for somatic hypermutation and class switch recombination, because AID−/− B lymphocytes do not undergo class switch recombination and fail to accumulate mutations upon Ag stimulation. Mutations in the human AID gene causing lack of function underlie one type of hyper-IgM syndrome. In this syndrome, B cells fail to switch from IgM to other isotypes, and somatic hypermutation of the Ig V regions does not occur (9). This syndrome seemingly connects AID with Ig isotype class switch and somatic hypermutation. Arakawa et al. (10) demonstrated that AID is also required for Ig gene conversion in chicken B cell lines. Thus, AID participates in three different processes that contribute to the diversification of Abs: somatic hypermutation, isotype class switch recombination, and gene ...

Activation-induced deaminase (AID) is expressed only in germinal center B cells. There, it is required for somatic hypermutation, gene conversion and class switch recombination of antibody variable region segments, three processes that diversify antibodies during immune responses. Although AID has homology to RNA-editing enzymes, three recent reports suggest it could initiate the diversification processes by deaminating cytidine residues within the antibody genes themselves.

TY - JOUR. T1 - Ubiquitylated PCNA plays a role in somatic hypermutation and class-switch recombination and is required for meiotic progression. AU - Roa, Sergio. AU - Avdievich, Elena. AU - Peled, Jonathan U.. AU - MacCarthy, Thomas. AU - Werling, Uwe. AU - Fei, Li Kuang. AU - Kan, Rui. AU - Zhao, Chunfang. AU - Bergman, Aviv. AU - Cohen, Paula E.. AU - Edelmann, Winfried. AU - Scharff, Matthew D.. PY - 2008/10/21. Y1 - 2008/10/21. N2 - Somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes are dependent upon activation-induced cytidine deaminase (AID)-induced mutations. The scaffolding properties of proliferating cell nuclear antigen (PCNA) and ubiquitylation of its residue K164 have been suggested to play an important role organizing the error-prone repair events that contribute to the AID-induced diversification of the Ig locus. We generated knockout mice for PCNA (Pcna-/-), which were embryonic lethal. Expression of PCNA with the K164R mutation rescued the lethal ...

The apolipoprotein B messenger RNA-editing, enzyme-catalytic, polypeptide-like 3 (APOBEC3) family of cytidine deaminases plays an important role in the innate immune response to viral infections by editing viral genomes. However, the cytidine deaminase activity of APOBEC3 enzymes also induces somatic mutations in host genomes, which may drive cancer progression. Recent studies of human papillomavirus (HPV) infection and disease outcome highlight this duality. HPV infection is potently inhibited by one family member, APOBEC3A. Expression of APOBEC3A and APOBEC3B is highly elevated by the HPV oncoproteins E6 and E7 during persistent virus infection and disease progression. Furthermore, there is a high prevalence of APOBEC3A and APOBEC3B mutation signatures in HPV-associated cancers. These findings suggest that induction of an APOBEC3-mediated antiviral response during HPV infection may inadvertently contribute to cancer mutagenesis and virus evolution. Here, we discuss current understanding of APOBEC3A

A variety of mutations are accumulated in the genome of HTLV-1 infected T-cells during ATL development. To elucidate the mechanism of ATL development a mouse model of ATL was established by infecting HTLV-1 to humanized NOG mice and the infected mice recapitulate the ATL-like symptoms and die of leukemia within several months of infection. Analysis of gene expressions in the humanized mouse model of ATL demonstrated the induction of APOBEC3B (A3B) gene in the HTLV-1 infected human T-cells. A3B is a member of the APOBEC family of cellular cytidine deaminase and was recently identified as the mutational source in multiple human cancers. We have previously shown that HTLV-1 infected CD25 (-) CD4 T-cells but not CD25 (+) CD4 T-cells in ATL model mouse express a small amount of Tax mRNA even though both cell populations consist of identical infected-cell clones. As the A3B expression in HTLV-1 infected CD25 (+) T-cells was similar to, or rather higher than that in CD25 (-)T-cells, Tax appears not to ...

Induced overexpression of AID in CH12F3-2 B lymphoma cells augmented class switching from IgM to IgA without cytokine stimulation. AID deficiency caused a complete defect in class switching and showed a hyper-IgM phenotype with enlarged germinal centers containing strongly activated B cells before o …

This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008 ...

Activation-induced deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) by inducing mutations and double-strand breaks at the immunoglobulin (Ig) locus in B cells. AID converts deoxycytidine (dC) to deoxyuridine (dU) in single-stranded DNA (ssDNA). This deaminat …

Sigma-Aldrich offers abstracts and full-text articles by [Yi Hu, Ida Ericsson, Kathrin Torseth, Stephen P Methot, Ottar Sundheim, Nina B Liabakk, Geir Slupphaug, Javier M Di Noia, Hans E Krokan, Bodil Kavli].

Bacteroides induce higher IgA production than Lactobacillus by increasing activation-induced cytidine deaminase expression in B cells in murine Peyers patches.[2009] DataPunk.Net Data INHIBITED BY Walnuts Sucralose (Splenda) Whole-grain barley β-Glucan Polymannuronic acid ENHANCED BY Stevia Low fat diets Tannic acid Gallic acid Red wine Fructo-oligosaccharides Saccharin L-citrulline Resistant starch (type IV) High meat diet ANTIBIOTIC RESISTANCE Streptogramin b …

1. Esnault C, Heidmann O, Delebecque F, Dewannieux M, Ribet D, Hance AJ, et al. APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses. Nature. 2005;433(7024):430-3. Epub 2005/01/28. doi: 10.1038/nature03238 15674295.. 2. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, et al. DNA deamination mediates innate immunity to retroviral infection. Cell. 2003;113(6):803-9. Epub 2003/06/18. doi: 10.1016/s0092-8674(03)00423-9 12809610.. 3. Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D. Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature. 2003;424(6944):99-103. Epub 2003/06/17. doi: 10.1038/nature01709 12808466.. 4. Suspene R, Aynaud MM, Koch S, Pasdeloup D, Labetoulle M, Gaertner B, et al. Genetic editing of herpes simplex virus 1 and Epstein-Barr herpesvirus genomes by human APOBEC3 cytidine deaminases in culture and in vivo. J Virol. 2011;85(15):7594-602. Epub 2011/06/03. doi: ...

Activation-induced cytidine deaminase (AID) is critical in normal B cells to initiate somatic hypermutation and immunoglobulin class switch recombination. Accumulating evidence suggests that AID is also prooncogenic, inducing cancer-promoting mutations or chromosome rearrangements. In this context, we find that AID is expressed in |40% of primary human chronic lymphocytic leukemia (CLL) cases, consistent with other reports. Using a combination of human B lymphoid leukemia cells and mouse models, we now show that AID expression can be harnessed for antileukemic effect, after inhibition of the RAD51 homologous recombination (HR) factor with 4,4-diisothiocyanatostilbene-2-2-disulfonic acid (DIDS). As a proof of principle, we show that DIDS treatment inhibits repair of AID-initiated DNA breaks, induces apoptosis, and promotes cytotoxicity preferentially in AID-expressing human CLL. This reveals a novel antineoplastic role of AID that can be triggered by inhibition of HR, suggesting a potential new

Assay Cytidine Deaminase with Cytidine Deaminase Assay Kit ab239723. Abcam offers | 1,000 assay kits cited in | 3,500 publications.

Activation-induced cytidine deaminase (AICDA) antibody | Q9GZX7 | Activation-induced cytidine deaminase (AICDA), Cytidine aminohydrolase, AID

TY - JOUR. T1 - A method to avoid errors associated with the analysis of hypermutated viral sequences by alignment-based methods. AU - Alinejad-Rokny, Hamid. AU - Ebrahimi, Diako. PY - 2015/12/1. Y1 - 2015/12/1. N2 - The human genome encodes for a family of editing enzymes known as APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like3). They induce context dependent G-to-A changes, referred to as hypermutation, in the genome of viruses such as HIV, SIV, HBV and endogenous retroviruses. Hypermutation is characterized by aligning affected sequences to a reference sequence. We show that indels (insertions/deletions) in the sequences lead to an incorrect assignment of APOBEC3 targeted and non-target sites. This can result in an incorrect identification of hypermutated sequences and erroneous biological inferences made based on hypermutation analysis.. AB - The human genome encodes for a family of editing enzymes known as APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic ...

Overexpression of activation-induced cytidine deaminase (AID) or other cytidine deaminases causes high rates of deoxyribonucleic acid (DNA) damage (mutations, double strand DNA breaks, and chromosome rearrangements) in a high number of patients with B-cell malignancies, such as NHL, MM, and CLL, and in a subset of patients with solid tumors, such as non-small cell lung cancer (NSCLC), sarcoma, breast cancer, ovarian cancer, and squamous cell carcinoma of the head and neck. Cancer cells that overexpress AID and other cytidine deaminases rely on RAD51, a protein involved in homologous recombination, to repair the DNA damage caused by cytidine deaminases. Inhibition of RAD51 with CYT-0851 in preclinical models induces cell death, tumor growth delay or tumor regression.. The Phase 1 part of the study will follow an accelerated titration design, which includes enrollment of single patient cohorts until certain criteria are met, followed by a standard 3+3 design. This design will allow for ...

Single-stranded DNA-specific cytidine deaminase. Involved in somatic hypermutation (SHM), gene conversion, and class-switch recombination (CSR) in B-lymphocytes by deaminating C to U during transcription of Ig-variable (V) and Ig-switch (S) region DNA. Required for several crucial steps of B-cell terminal differentiation necessary for efficient antibody responses. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation.

Activation induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class-switch recombination (CSR). AID initiates the processes that carry out immunoglobulin diversity by deaminating cytosine residues within variable (V) and switch (S) regions on the Ig locus during active transcription. The resulting G:U mispairs can then be replicated or repaired by cellular repair mechanisms to give rise to isotype-switched and antigen-specific mature antibodies.; In this study I have identified two novel phosphorylation sites, serine 41 and serine 43, and demonstrated their importance in AID activity as well as confirmed the importance of serine 38 phosphorylation. Phosphorylation null mutants generated by replacing serine with alanine are much less active than wild-type AID, as is non-phosphorylated AID purified from E. coli. In contrast, phosphorylation charge mimic mutants generated by replacing serine with aspartic acid, are (3-4) fold more active than wild-type AID. ...

Activation induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class-switch recombination (CSR). AID initiates the processes that carry out immunoglobulin diversity by deaminating cytosine residues within variable (V) and switch (S) regions on the Ig locus during active transcription. The resulting G:U mispairs can then be replicated or repaired by cellular repair mechanisms to give rise to isotype-switched and antigen-specific mature antibodies.; In this study I have identified two novel phosphorylation sites, serine 41 and serine 43, and demonstrated their importance in AID activity as well as confirmed the importance of serine 38 phosphorylation. Phosphorylation null mutants generated by replacing serine with alanine are much less active than wild-type AID, as is non-phosphorylated AID purified from E. coli. In contrast, phosphorylation charge mimic mutants generated by replacing serine with aspartic acid, are (3-4) fold more active than wild-type AID. ...

A significant leap forward got here in 2000 with the invention that activation-induced deaminase (AID) is actually required for hypermutation. This used to be in 2002 by means of proof that reduction without delay edits the DNA that encodes an antibody in an activated B mobile. a lot has seeing that been learnt concerning the biochemistry and rules of reduction, however the mechanism during which it truly is recruited particularly to antibody-encoding genes continues to be enigmatic. figuring out this recruitment is clinically major simply because off-target relief job at oncogenes may end up in chromosomal translocations and tumorigenesis ...

Aberrant targeting of the enzyme activation-induced cytidine deaminase (AID) results in the accumulation of somatic mutations in ∼25% of expressed genes in germinal center B cells. Observations in Ung−/− Msh2−/− mice suggest that many other genes efficiently repair AID-induced lesions, so that up to 45% of genes may actually be targeted by AID. It is important to understand the mechanisms that recruit AID to certain genes, because this mistargeting represents an important risk for genome instability. We hypothesize that several mechanisms combine to target AID to each locus. To resolve which mechanisms affect AID targeting, we analyzed 7.3 Mb of sequence data, along with the regulatory context, from 83 genes in Ung−/− Msh2−/− mice to identify common properties of AID targets. This analysis identifies three transcription factor binding sites (E-box motifs, along with YY1 and C/EBP-β binding sites) that may work together to recruit AID. Based on previous knowledge and these ...

During B cell activation, the DNA lesions that initiate somatic hypermutation and class switch recombination are introduced by activation-induced cytidine deaminase (AID). AID is a highly mutagenic protein that is maintained in the cytoplasm at steady state, however AID is shuttled across the nuclear membrane and the protein transiently present in the nucleus appears sufficient for targeted alteration of immunoglobulin loci. AID has been implicated in epigenetic reprogramming in primordial germ cells and cell fusions and in induced pluripotent stem cells (iPS cells), however AID expression in non-B cells is very low. We hypothesised that epigenetic reprogramming would require a pathway that instigates prolonged nuclear residence of AID. Here we show that AID is completely re-localised to the nucleus during drug withdrawal following etoposide treatment, in the period in which double strand breaks (DSBs) are repaired. Re-localisation occurs 2-6 hours after etoposide treatment, and AID remains in the

APOBEC proteins have evolved in mice and humans as potent innate defences against retroviral infections. APOBEC3G (hA3G) in humans and mouse APOBEC3 (mA3) deaminate cytidine in single-stranded DNA which ultimately results in hypermutation of newly synthesized proviral DNA. Other deaminase-independent mechanisms of inhibition have been identified, such as directly inhibiting reverse transcription. Both HIV and murine leukemia viruses (MuLVs) have evolved mechanisms to evade the action of the APOBEC proteins. HIV encodes the Vif protein which binds to hA3G and facilitates its rapid degradation through the proteasome. The mechanism(s) by which exogenous MuLVs evade mA3 inhibitory activity is unknown. Exogenous MuLVs encode a glycosylated gag protein (gGag) originating from an alternate CUG start site upstream of the AUG start site of the Gag structural polyproteins. gGag is synthesized to similar amounts as the structural Gag polyprotein in MuLV infected cells but is glycosylated in the endoplasmic

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However, we overlooked a mechanism natural has adopted for rapid evolution of proteins: adaptive immunity that generates a huge pool of antibodies.It is well-known that B-cells are capable of producing a large pool of new antibodies upon antigen stimuli, which is a most important protective mechanism for animals. People have been curious about the molecular mechanism of antibody generation. Recent works have revealed that an enzyme: Activation-Induced (Cytidine) Deaminase (AID) serves as an essential protein in three processes for antibody diversity, namely somatic hypermutation (SHM), class switch recombination (CSR) and gene conversion. Briefly speaking, AID converts cytidine to uracil by oxidizing the amino group to carbonyl group, resulting in mismatch of Watson-Crick base pair. Then DNA lesion repair pathways (base excision repair, BER; mismatch repair, MMR)are employed to bring DNA back to normal. In this process, the coding sequence for the hypervariable region of immunoglobulin is ...

Homo sapiens apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3D (putative) (APOBEC3D), mRNA. (H00140564-R01) - Products - Abnova

Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates somatic hypermutation (SH) and class switch recombination (CSR) by deaminating cytosine to uracil. The targeting of AID and therefore SH and CSR to Ig genes is a central process of the immune system, but the trans-acting factors mediating the specific targeting have remained elusive. Here we show that defective calmodulin inhibition of the transcription factor E2A after activation of the B cell receptor (BCR) leads to reduced BCR, IL4 plus CD40 ligand stimulated CSR to IgE and instead CSR to other Ig classes. AID that initiates CSR is shown to be in a complex with the transcription factors E2A, PAX5 and IRF4 on key sequences of the Igh locus. Calmodulin shows proximity with each of them after BCR stimulation. BCR signaling reduces binding of the proteins to some of the target sites on the Igh locus, and calmodulin resistance of E2A blocks these reductions. AID binds directly to the bHLH domain of E2A and to ...

From the host immune perspective, the generation of genomic diversity is used as both a defensive and an offensive weapon. Host mutator enzymes such as Activation-Induced Cytidine Deaminase (AID) seed diversity in the adaptive immune system by introducing targeted mutations into the immunoglobulin locus that result in antibody maturation. Related deaminases of the innate immune system can directly attack retroviral threats by garbling the pathogen genome through mutation, as accomplished by the deaminase APOBEC3G, which restricts infection with HIV. Immune mutator enzymes, however, also pose a risk to the host, as overexpression or dysregulation have been associated with oncogenesis ...

By creating an extremely diverse antibody repertoire, B cells protect the body against numerous infectious pathogens. Generation of this antibody repertoire depends on immunoglobulin gene modification events driven by four different molecular processes: V(D)J recombination, somatic hypermutation, class switch recombination, and gene conversion. The enzyme AID (activation-induced cytidine deaminase) is known to be involved in somatic hypermutation and class switch recombination. In their Perspective, Fugmann and Schatz explain that AID is also essential for gene conversion ( Arakawa et al.) and discuss how AID could operate in these three quite different processes. ...

The APOBEC family members are involved in diverse biological functions. APOBEC3G restricts the replication of human immunodeficiency virus (HIV), hepatitis B virus and retroelements by cytidine deamination on single-stranded DNA or by RNA binding. Here we report the high-resolution crystal structure of the carboxy-terminal deaminase domain of APOBEC3G (APOBEC3G-CD2) purified from Escherichia coli. The APOBEC3G-CD2 structure has a five-stranded beta-sheet core that is common to all known deaminase structures and closely resembles the structure of another APOBEC protein, APOBEC2 (ref. 5). A comparison of APOBEC3G-CD2 with other deaminase structures shows a structural conservation of the active-site loops that are directly involved in substrate binding. In the X-ray structure, these APOBEC3G active-site loops form a continuous substrate groove around the active centre. The orientation of this putative substrate groove differs markedly (by 90 degrees) from the groove predicted by the NMR ...

Activation-induced cytidine deaminase (AID) is essential for two processes of immunoglobulin diversification in germinal center B cells: somatic hypermutation (SHM), in which mutations are introduced into immunoglobulin (Ig) genes, and class-switch recombination (CSR), in which genomic constant regions are recombined to encode antibodies of different isotypes. Both of these processes require AID-catalyzed C-to-U lesions at the Ig loci, which are resolved to generate point mutations or double-stranded DNA breaks in the cases of SHM and CSR, respectively. Despite over a decade of intense study, a number of open issues remain surrounding AID. The diversity of findings regarding AIDs role in DNA demethylation raises the question of the scope of its involvement in this process. Additionally, while it is clear that AID-mediated damage occurs, the effects of this damage on the average B cell have not been characterized. Finally, the issue of whether AID is able to edit RNA in vivo has never been rigorously

It has recently been demonstrated that memory B cells can reenter and reengage germinal center (GC) reactions, opening the possibility that multi-hit lymphomagenesis gradually occurs throughout life during successive immunological challenges. Here, we investigated this scenario in follicular lymphoma (FL), an indolent GC-derived malignancy. We developed a mouse model that recapitulates the FL hallmark t(14;18) translocation, which results in constitutive activation of antiapoptotic protein B cell lymphoma 2 (BCL2) in a subset of B cells, and applied a combination of molecular and immunofluorescence approaches to track normal and t(14;18)+ memory B cells in human and BCL2-overexpressing B cells in murine lymphoid tissues. BCL2-overexpressing B cells required multiple GC transits before acquiring FL-associated developmental arrest and presenting as GC B cells with constitutive activation-induced cytidine deaminase (AID) mutator activity. Moreover, multiple reentries into the GC were necessary for ...

Catalytic component of the apolipoprotein B mRNA editing enzyme complex which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in the APOB mRNA. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation.

We have identified that autoimmune BXD2 mice exhibit unique features, including spontaneous formation of germinal centers, increased expression of activation-induced cytidine deaminase (AID), increased production of pathogenic autoantibodies that are polyreactive, significantly increased percentage of IL-17high CD4 TH cells (TH-17) and IL-17Rhigh B cells, and significantly increased numbers of type I interferon producing plasmacytoid dendritic cells in the spleens of these mice. We are currently studying the inter-connection of high IL-17, high type I IFN and the development of autoreactive B cells related to B-cell tolerance loss at the transitional stage and the germinal center stage in BXD2 mice.. We currently study the close interaction between spleen marginal zone (MZ) B cells and MZ macrophages, and the implication of disrupting this close interaction in disease relapse following B-cell depletion therapy (BCDT) in systemic lupus erythematosus (SLE). In healthy individuals, the MZ B cells ...

Our system to produce antibodies is critical for our survival against numerous infections, but it causes also many tumors. B-lymphocytes can modify their immunoglobulin (Ig) genes to generate specific antibodies with a new isotype and enhanced affinity against an antigen. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates these processes by deaminating cytosine to uracil. How somatic hypermutation (SH) and class switch recombination (CSR) are targeted is key to understanding the defect DNA integrity in lymphomas and also in other tumors where inflammatory signals aberrantly induces AID. The trans-acting factors mediating specific targeting of AID and thereby SH and CSR have remained elusive. Here we show that mutant E2A with defect inhibition by the Ca2+sensor protein calmodulin results in reduced B cell receptor- (BCR-), IL4-plus CD40 ligand-stimulated CSR to IgE and instead aberrant CSR. AID is shown to be together with the transcription factors E2A, ...

Problems occur when massive genetic mutations and DNA damage veer off course and impact genes that regulate cell growth and function. The result: B cell leukemias and lymphomas.. McBrides research at the Virginia Harris Cockrell Cancer Research Center at MD Andersons Science Park in Smithville, Texas, focuses on the molecular processes used by B cells to make antibodies.. In particular, his team studies activation-induced deaminase (AID), an enzyme that launches hypermutation and double-strand breaks, usually in a beneficial manner.. The vast majority of lymphomas occur in B cells that have gone through the process in which they express AID, McBride says.. By understanding the basic science, McBride and colleagues are illuminating both proper immune system function and the path to B cell malignancies.. ...

Reduced AID degradation in REG-γ−/− mice might also be expected to lead to a more general increase in genomic instability. However, REG-γ−/− mice on a normal background do not show any marked increase in tumor incidence, possibly reflecting p53 and other checkpoints (Jankovic et al., 2010). Only a small increase in the frequency of c-myc-IgH translocations was detected in cultured B cells from REG-γ-deficient (as opposed to REG-γ-proficient) mice in which AID overexpression had been induced by retroviral transduction (Fig. S3), possibly reflecting the ubiquitin-dependent degradation of such overexpressed AID (Fig. 3 D). Thus, although the results suggest that the dramatically increased class-switching in REG-γ-deficient mice is likely to be at least in part a direct consequence of the increased AID abundance, we cannot exclude the possibility that there is an additional contribution from some as yet unidentified effect of REG-γ deficiency (e.g., a perturbation of AIDs interaction ...

Inflammation predisposes to tumorigenesis in various organs by potentiating a susceptibility to genetic aberrations. The mechanism underlying the enhanced genetic instability through chronic inflammation, however, is not clear. Here we demonstrated that TNF-α stimulation induced transcriptional downregulation of MSH2, a member of the mismatch repair family, via nuclear factor-κB-dependent miR-21 expression in hepatocytes. Liver cancers developed in ALB-MSH2-/-AID+, ALB-MSH2-/-, and ALB-AID+ mice in which MSH2 is deficient and/or activation-induced cytidine deaminase (AICDA) is expressed in cells with albumin-producing hepatocytes. The mutation signatures in the tumors developed in these models, especially ALB-MSH2-/-AID+ mice, closely resembled those of human hepatocellular carcinoma. Our findings demonstrated that inflammation-mediated dysregulation of MSH2 may be a mechanism of genetic alterations during hepatocarcinogenesis. ...

Here we describe a potential new synthetic lethal therapeutic approach for the treatment of AID-expressing B cell malignancies: attenuation of RAD51-mediated HR to inhibit repair of endogenous AID-generated DSBs, culminating in cytotoxicity. This approach uses inherent recombinase activity, rather than systemically administered genotoxic agents, to induce cell-lethal genomic damage. As such, this strategy represents a special case of synthetic lethal therapy. We establish the proof of principle, showing that AID-expressing human CLL cells are hypersensitive to DIDS, a RAD51 inhibitor. Using a combination of primary patient-derived CLLs and genetic mouse models, we establish that DIDS treatment inhibits repair of AID-mediated DSBs in AID-expressing, patient-derived CLL cells. These findings establish that HR attenuation may be a therapeutically viable approach to selectively targeted treatment of cancers (and other pathologies) involving AID-expressing cells. Because AID mRNA expression is found ...

My work focuses on the etiology of autoimmune diseases affecting millions of individuals in the world by identifying molecules and pathways involved in the establishment of B-cell tolerance through the investigation of rare patients with primary immunodeficiency (PID), enrolled at Yale and through an international network.. Patients with PID provide opportunities to study the impact of specific gene defects on the regulation of B-cell tolerance and the removal of developing autoreactive B cells in humans. Using a RT-PCR based strategy that allows us to assess the frequency of autoreactive B cells, we found that alterations in B-cell receptor (BCR) signaling in patients lacking functional BTK or CD19, or mutations in molecules mediating TLR signaling such as TACI, IRAK4, MyD88 as well as in adenosine deaminase (ADA) and activation-induced cytidine deaminase (AID) all result in a defective central checkpoint and a failure to counterselect developing autoreactive B cells in the bone marrow. ...

Scientists at The Scripps Research Institute (TSRI) and Weill Cornell Medical College of have determined the first atomic-level structure of the tripartite HIV envelope protein-long considered one of the most difficult targets in structural biology and of great value for medical science.

AID (activation-induced cytidine deaminase ) er et mutator-protein som deaminerer cytosin til uracil i immunoglobulin (Ig)-genene i B-celler. AID er essensielt i vårt adaptive immunforsvar, mens feilregulert AID-aktivitet er relatert til mutasjoner og kreft. Vi har studert aktivitet, intracellulær transport og regulering av AID. For å bekjempe nye infeksjoner produserer stimulerte B celler antistoffer med økt affinitet og endrede beskyttelsesfunksjoner. Dette skjer ved at mutasjoner introduseres med høy frekvens i Ig-genene, og AID er proteinet som initierer disse prosessene ved å deaminere cytosin til uracil. Ved feil regulering av AID vil uracil som er generert i proto-oncogener være en tidlig og kritisk hendelse ved utvikling av B-celle lymfom. Ekspresjon, enzymatisk aktivitet og intracellulær lokalisering må derfor være nøye regulert for å unngå uønskede mutasjoner. AID er i hovedsak lokalisert til cytoplasma, og for at AID skal deaminere cytosin til uracil i Ig-genene må det ...

Activation-induced cytidine deaminase (AID) initiates all postrearrangement processes that diversify the immunoglobulin repertoire by specific deamination of cy

Prof. McGuigan from Cardiff School of Pharmacy, UK along with Prof. Jan Balzarini of Rega Instutute for Medical Research, Belgium have reported an innovative approach to overcome the cancer Resistance mechanism using the pro-tide technology of theirs. They prepared various Nucleotide Phosphoramidates of the known anticancer drug Gemcitabine and were able to find a molecule that was resistant to cytidine deaminase-mediated […]. » Read more ...

Looking for online definition of Cytidine deaminase in the Medical Dictionary? Cytidine deaminase explanation free. What is Cytidine deaminase? Meaning of Cytidine deaminase medical term. What does Cytidine deaminase mean?

Definition of activation-induced cytidine deaminase. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.

To address the physiological significance of AID phosphorylation at Ser38, analysis of a mouse model (in which AIDS38A is expressed at physiological levels utilizing its endogenous control elements) was required. Two recent studies reported the generation and analysis of mice expressing only the AIDS38A mutant protein, which occurred at levels quite comparable with those of wild-type mAID expression in activated B-cells, from their endogenous AID alleles [45,51]. In addition, one of these studies also demonstrated that the AIDS38A protein expressed from the endogenous AID allele failed to associate with RPA in vivo [51]. Both studies found that mice homozygous for the AIDS38A (AIDS38A/S38A) mutation have quite severe CSR defects, demonstrating clearly that the apparently normal levels of CSR reported for this mutant form of AID by others [49] probably resulted from overexpression of the mutant protein as proposed in [47].. Activation of AIDS38A/S38A B-cells with αCD40 and IL-4 (interleukin 4) ...

Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation. The phosphatidylinositol 3-kinase δ (PI3Kδ) pathway regulates AID by suppressing its expression in B cells. Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kδ activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells. Here we show that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutinib, enhanced the expression of AID and increased ...

Author Summary Antibody affinity maturation is a key aspect of an effective immune response to vaccines, likely to have an impact on clinical outcome following exposure to pathogens. Activation-Induced Cytidine Deaminase (AID) in B cells is a key enzyme involved in antibody class switching and somatic hypermutation, required for antibody affinity maturation. This human study demonstrated for the first time that induction of AID following H1N1pdm09 influenza vaccination directly correlated with in-vivo antibody affinity maturation against the hemagglutinin globular domain (HA1), containing most of the protective targets. Importantly, age differences were found. In younger adults, significant affinity maturation to the HA1 globular domain was observed, which associated with higher initial levels of AID and |2-fold-increase in AID after vaccination. With increased age, a drop in AID activity post-vaccination correlated with lower affinity maturation of the polyclonal antibody responses against the pandemic

Deoxyuridine (dU) is a pyrimidine deoxyribonucleoside, and a derivative of the nucleoside uridine, with the only difference being that, in dU, a hydrogen (-H) group is substituted for uridine s OH group located at the 2 -position of the ribose. dU is generated in cellular DNA as a deamination product of dC (deoxycytidine), with the deamination process catalyzed by the enzyme AID (activation-induced cytidine deaminase) (1). AID is a B cell-specific gene that is necessary for antibody gene diversification via class-switch recombination and somatic hypermutation (2, 3). The dC-to-dU conversion(s) by AID occurs in the IgG locus, with various gene diversification pathways arising from the different DNA repair mechanisms used by B-cells to repair the dU lesion (1).. dC-to-dU conversion via cytidine deamination is also implicated in innate immunity to retroviruses. Here deamination of dC is mediated by the enzyme APOBEC3G, which is present in T cells, acting on the first (minus) strand cDNA of ...

Development of long-term humoral immunity is a major goal of vaccination, but the mechanisms involved in the formation of long-term Ab responses are still being determined. In this study, we identify a previously unknown requirement for MyD88, an adaptor molecule that mediates signals at most TLRs, for the generation of long-term humoral immunity during live virus infection. Polyoma virus-infected MyD88 knockout mice generated strong acute T cell-dependent antiviral IgM and IgG responses and developed germinal centers. Activation-induced cytidine deaminase, an enzyme required for isotype switching and somatic hypermutation, was also induced in germinal center B cells, similar to wild-type mice. However, MyD88 knockout mice failed to develop bone marrow plasma cells and did not maintain long-term serum antiviral Ab responses. The isotype distribution of antiviral IgG responses was also altered; serum IgG2a and IgG2b levels were diminished, whereas IgG1 responses were not affected. The requirement for

C hronic infection with hepatitis B virus (HBV) contributes to more than three quarters of hepatocellular carcinoma (HCC) cases worldwide. Genetic predisposit...

Hasham MG, Donghia NM, Coffey E, Maynard J, Snow KJ, Ames J, Wilpan RY, He Y, King BL, and Mills KD. Widespread genomic breaks from activation-induced cytidine deaminase are prevented by homologous recombination. Nat Immunol 2010; 11: 820-826.. Rogler LE, Kosmyna B, Moskowitz D, Bebawee R, Rahimzadeh J, Kutchko K, Laederach A, Notarangelo LD, Giliani S, Bouhassira E, Frenette P, Roy-Chowdhury J, Rogler CE. Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage-hair hypoplasia. Hum Mol Genet. 2014; 23:368-82.. Zeitz MJ, Lerner PP, Ay F, Van Nostrand E, Heidmann JD, Noble WS, Hoffman AR. Implications of COMT long-range interactions on the phenotypic variability of 22q11.2 deletion syndrome. Nucleus 2013; 4: 487-93.. Stoerker J, Goodman TG, Walline HM, Sugalski J 2nd, Holland CA. Evaluation of a BeadXpress assay for a 151-mutation and variant CFTR screening panel after 11,000 samples: implications for practice. Diagn Mol Pathol. 2013; 22:144-8.. ...

Hepatocellular carcinoma (HCC) originates from regenerating liver cells with genetic alterations in chronically inflamed liver. Ductal cells and hepatocytes proliferate for liver regeneration, and proliferating ductal cells (PDC) derived from bile ductules have long been considered putative liver stem/progenitor cells and candidate cellular origins of HCC. The potential of PDC as tumor-originating cells, however, remains controversial in contrast to accumulating evidence that HCC originates from hepatocytes. Here we demonstrate that PDC expressing the established surface and cancer stem cell marker EpCAM give rise to HCC in inflamed liver. EpCAM-expressing PDC were specifically labeled in newly developed EpcamCreERT2 mice and traced in a chemically-induced liver injury model. Stepwise accumulation of genetic alterations in EpCAM-positive cells was induced by the mutagenesis activity of activation-induced cytidine deaminase using conditional transgenic mice. Lineage tracing experiments revealed ...

Reverse transcription-derived sequences account for at least half of the human genome. Although these retroelements are formidable motors of evolution, they can occasionally cause disease, and accordingly are inactivated during early embryogenesis through epigenetic mechanisms. In the mouse, at least for endogenous retroviruses, important mediators of this process are the tetrapod-specific KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor TRIM28. The present study demonstrates that KRAB/TRIM28-mediated regulation is responsible for controlling a very broad range of human-specific endogenous retroelements (EREs) in human embryonic stem (ES) cells and that it exerts, as a consequence, a marked effect on the transcriptional dynamics of these cells. It further reveals reciprocal dependence between TRIM28 recruitment at specific families of EREs and DNA methylation. It finally points to the importance of persistent TRIM28-mediated control of ERE transcriptional impact beyond their ...

Now, Rockefeller University scientists have discovered that the same enzyme that enables the immune systems defensive creativity is also responsible for a particular genetic malfunction - a translocation of one piece of DNA to the wrong chromosome - that causes Burkitts lymphoma. The findings, to be published in the December 12 edition of Cell, suggest the enzyme, called activation-induced deaminase (AID), is probably involved in a broader range of cancers as well.. We strongly suspect that many or all of the translocations of human lymphomas in mature B cells are the product of this enzyme, says Michel C. Nussenzweig, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology. And theres more and more data to show that it may be involved in other cancers as well. Its been identified in stomach cancers, for instance.. A very specific translocation causes Burkitts lymphoma, a cancer that plagues children in equatorial Africa. It involves a DNA break in an immune ...

Somatic hypermutation (SH) of V(D)J rearrangements at the IGH and IGL loci diversifies the IG repertoire during the germinal center response. SH is absolutely dependent on the enzyme activation induced cytidine deaminase (AID) that initiates the SH process by deaminating C nucleotides in ssDNA. Mutations from G and C are thought to occur as a result of strand symmetrical deamination of C by AID on the coding and non-coding strands respectively. Mutations from A and Tare introduced in a strand biased way during error prone repair of the AID induced lesion. SH is linked to transcription and it has been proposed that bidirectional transcription across V(D)J rearrangements occurs in activated and quiescent B cells and that it is co-opted to facilitate the accessibility of the two DNA strands by regulating accessibility of single stranded DNA to AID. We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse ...

TY - JOUR. T1 - Identification and antiviral activity of common polymorphisms in the APOBEC3 locus in human populations. AU - Duggal, Nisha K.. AU - Fu, Wenqing. AU - Akey, Joshua M.. AU - Emerman, Michael. N1 - Funding Information: We thank Lily Wu for assistance and Mia Levine and Harmit Malik for comments and advice. This work was supported by R01 AI30937 (ME) and an NSF graduate fellowship to NKD.. PY - 2013/9/1. Y1 - 2013/9/1. N2 - There are seven members of the APOBEC3 family in humans (APOBEC3A through APOBEC3H) that have antiviral activity against retroviruses and/or retroelements. To determine whether variants in APOBEC3 genes in human populations have altered antiviral activity, we identified and functionally tested novel single nucleotide variants (SNVs) in APOBEC3 genes present in the 1000 Genome Project dataset. We found that common variants minor allele frequency (,1%) of APOBEC3A, C, F, and G do not affect protein function. However, we found that two common novel polymorphisms in ...

Nanoparticle albumin-bound (nab)-paclitaxel, an albumin-stabilized paclitaxel formulation, demonstrates clinical activity when administered in combination with gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma (PDA). The limited availability of patient tissue and exquisite sensitivity of xenografts to chemotherapeutics have limited our ability to address the mechanistic basis of this treatment regimen. Here, we used a mouse model of PDA to show that the coadministration of nab-paclitaxel and gemcitabine uniquely demonstrates evidence of tumor regression. Combination treatment increases intratumoral gemcitabine levels attributable to a marked decrease in the primary gemcitabine metabolizing enzyme, cytidine deaminase. Correspondingly, paclitaxel reduced the levels of cytidine deaminase protein in cultured cells through reactive oxygen species-mediated degradation, resulting in the increased stabilization of gemcitabine. Our findings support the concept that suboptimal ...

Line number RuleID ViolationType Message Line #------------ #------------ # Validation for #430725 annotations in 430768 lines #------------ #Line number RuleID ViolationType Message Line #------------ # GO_AR:0000014 Valid GO term ID Error count: 212 3146 GO_AR:0000014 Error The relation has_direct_input in the c16 annotation extension is an obsolete relation MGI MGI:1917115 A1cf GO:0016556 MGI:MGI:4943819,PMID:20541607 IGI MGI:MGI:104663 P APOBEC1 complementation factor 1810073H04Rik,ACF,apobec-1 complementation factor protein taxon:10090 20140709 MGI has_direct_input(MGI:MGI:88052),occurs_in(EMAPA:16900) 9354 GO_AR:0000014 Error The relation has_direct_input in the c16 annotation extension is an obsolete relation MGI MGI:105377 Adam19 GO:0006509 MGI:MGI:3625788,PMID:11116142 IMP P a disintegrin and metallopeptidase domain 19 (meltrin beta) Mltnb protein taxon:10090 20150513 MGI ...

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Brown, M.R.; Crim, J.W.; Lea, A.O., 1986: FMRFamide- and pancreatic polypeptide-like immunoreactivity of endocrine cells in the midgut of a mosquito

Induction phase with Cytarabine (Ara-C) is a mainstay to treat accute myeloid leukemia (AML) and severe/lethal toxicities are frequent. Ara-C is metabolized in the liver by an exclusive enzymatic step by cytidine deaminase (CDA). CDA is a ubiquitous enzyme coded by a highly polymorphic gene, with subsequent phenotypes ranging from poor metabolizer (PM) to ultra metabolizer (UM) patients. To what extent CDA phenotype could help predict clinical outcome in Ara-C-treated patients remains to be established. In this clinical observational study we studied whether CDA deficiency could be at the origin of severe/lethal toxicities in AML patients undergoing induction phase with Ara-C. CDA activity and 79A>C CDA genetic polymorphism was evaluated in 58 adult patients (25F, 33M, mean age 63 ±15 years). All patients were treated following current standard care by Ara-C-containing regimen (i.e., 7+3 protocol) and monitored for toxicity and response. Mean CDA activity was 3.14 ± 3 U/mg. The incidence of ...

Normal and cancer cells express more diversity in proteins than can be accounted for by the predicted number of expressed genomic DNA sequence. Expansion of the genomically encoded expressed sequences through alternative processing of RNA, such as mRNA editing, is a logical hypothesis for how protein diversity and variations seen as tissue-specific and regulated expression of proteins can be achieved. The specific focus of the research is to identify and characterize novel mammalian mRNA editing systems that employ a zinc-dependent deamination mechanism for the post-transcriptional conversion of cytidine to uridine at select sites within mRNAs. Computational modeling has suggested a family of mammalian enzymes known as Cytidine Deaminases Active on RNA or CDARs as responsible for C to U editing of mRNAs ...

Unlike previously described cytidine deaminases, this toxin catalyzes the deamination of cytidines within double-stranded DNA, the researchers said.

La ĉi-suba teksto estas aŭtomata traduko de la artikolo Cytidine article en la angla Vikipedio, farita per la sistemo GramTrans on 2017-08-02 09:00:10. Eventualaj ŝanĝoj en la angla originalo estos kaptitaj per regulaj retradukoj. Se vi volas enigi tiun artikolon en la originalan Esperanto-Vikipedion, vi povas uzi nian specialan redakt-interfacon. Rigardu la artikolon pri WikiTrans por trovi klarigojn pri kiel fari tion. Ankaŭ ekzistas speciala vortaro-interfaco por proponi aŭ kontroli terminojn ...

Researchers hope to improve the early diagnosis of the disease, indicating that lung cancers can remain on hold for many years. The author of the study was Prof. Dr. at the London Research Institute of Cancer Research. . The likelihood of getting out of lung cancer is very low as a result of the limited impact of targeted new treatments. As a result of our understanding of the development of the disease, we have opened the evolutionary rule book of the disease in the hope of predicting the next step. Hast The study also points to the importance of smoking in the development of lung cancer. Most of the early genetic errors occur due to smoking. Since the tumor controlled by the APOBEC protein creates new mutations, the magnitude of these errors does not affect the disease that is evolving. The discovery of a wide range of genetic errors has shown why the success of targeted treatments is limited. Moving to a specific genetic error defined by the biopsy is only effective against the part of the ...

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HIV lacking Vif is susceptible to human APOBEC3 (A3)-mediated restriction, rendering the virus non-infectious. The archetypal family member, A3G, has a well-def...

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Electrical assistance is limited to bursts of up to three seconds, using kinetic energy recuperated under braking. The battery can also be charged by plugging it in between stages, with a full charge taking approximately 25 minutes. The air- and liquid-cooled hybrid system weighs 95 kg and is housed in a ballistic-strength casing to protect against debris and g-forces in an accident.. From 2022 onwards, the championship will also use a fossil-free fuel, blending synthetic and bio-degradable elements that WRC says is 100% sustainable. The prototype will be demonstrated until July 10 by current M-Sport (the team that runs the works operation) driver Adrien Fourmaux and test driver Matthew Wilson before being used as a development vehicle ahead of the 2022 season.. The new era of WRC cars is one of the biggest technological advancements in WRC to date. The introduction of the hybrid means that the cars will be more powerful than ever whilst also directly reflecting the powertrains within their ...

I say it again and again. You denialists love to grab onto a supposed success story of someone living beyond the norm with HIV and you can not stop harping on it as if that should be everyones story. Well, Tony, I am on meds for 15 years and do not have one single horror story about side effects. I have never experienced anything more than nauseau and malaise for a week. No humps, bumps or fat deposit where I dont want it nor fat missing where I need it. Of the many people I know with HIV, my story (and theirs) is the norm and Maggiore was a lucky fluke. Although I doubt her son and husband feel so lucky now. But you go on and praise the few years she had and go on denying the ones she is missing out on! You do that, Tony, and you are just as (ir)responsible as she ...

I am grateful to the dissident movement for educating me about the poisons out there (especially AZT and its sister drugs). Because of this knowledge, I am in a much better place to manage my own HAART (should I decide to go on it temporarily) to kill whatever fungus or growth I have in my gut. For the record, I realize that testing positive simply means that I have 10 positive results to 10 proteins that have something to do with the immune system. I believe that a 10 for 10 positive result means something as well (as is my case). Since being involved with the movement, I have seen 4 deaths from the group b/c of their beliefs. Two guys believed that juicing was the answer - one friend (from Alive and Well) died in San Juan - trying to go all natural and cleanse his body. ...

Semantic Scholar extracted view of Nucleotide metabolism. III. Mono-, di-, and triphosphates of cytidine, guanosine, and uridine. by H. Schmitz et al.

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To protect the genome from serious, potentially oncogenic effects associated with off-target mutations, both AID activity and mutagenic repair are targeted specifically to your Ig genes. A potential player in this process is the DNA-damage-sensing enzyme PARP-1, which recruits DNA … Continue reading →. ...

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Given recent and pending state cuts, Philadelphias AIDS Activities Coordinating Office (AACO) sent memos in February warning local service organizations ...

A CNRS team of scientists said that they have been able to select a mutant protein in the HIV virus and then add it, along with a cancer drug to tumor cells.

Vaccines work simply by producing antibodies, right? Well, probably not. And this misconception coupled with basic ignorance of how they do work is st

Some people, known as HIV nonprogressors, are able to carry an HIV infection for an apparently indefinite period of time without having it progress int...

Seniors with HIV or AIDS may find it difficult to manage their health. However, they can still remain healthy later in life in spite of these conditions.

Are you preparing to take the Installer 1 exam? Are you worried about how to prepare for the written exam? If so, this study aid may be just what you need to put those fears to rest. This study aid includes flashcards, quiz questions, videos, and activities that you can use to prepare for the exam.. Learn More ...

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Since 5G roll-outs are likely even before 4G is extensively deployed, the adopted road map for 5G should ensure that the existing and near-future investments in 4G can be leveraged