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- Biomarkers of Auditory Information Processing and Neural Synchrony Predict Targeted Cognitive Training Exercise Completion in a Transdiagnostic Population (Griffin Hall) - Apr 14, 2024 - Abstract #SOBP2024SOBP_784;
A package of biomarkers consisting of auditory information processing and neural synchrony measures show promise in predicting TCT exercise completion in transdiagnostic applications. suggest that testing the predictive value of this package over a full 30 h course of TCT is warranted.
- || Review, Journal: Taming AID mutator activity in somatic hypermutation. (Pubmed Central) - Apr 13, 2024
Recent research has revealed several hidden features of AID-initiated mutagenesis: preferential activity on flexible DNA substrates, restrained activity within chromatin loop domains, unique DNA repair factors to differentially decode AID-caused lesions, and diverse consequences of aberrant deamination. Here, we depict the multifaceted regulation of AID activity with a focus on emerging concepts/factors and discuss their implications for the design of base editors (BEs) that install somatic mutations to correct deleterious genomic variants.
- B cell Tet2 promotes maturation of antibody responses through active DNA demethylation and OGT-mediated histone O-glycosylation of Aicda and Prdm1 loci (Exhibit Hall F1; Posterboard Number: 711) - Mar 29, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_1633;
Further, Tet2 and OGT inhibitors synergistically reduced Aicda and Prdm1 expression, CSR and plasma cell differentiation in human and mouse B cells, while Tet2 activator vitamin C increased Aicda and Prdm1 expression, CSR and plasma differentiation. Thus, B cell-Tet2 upregulates AID and Blimp-1 through catalytic DNA demethylation and non-catalytic OGT activity.
- Reverse Genetic Screens Reveal Mechanisms of Transcriptional Regulation in B cell Differentiation (Exhibit Hall F1; Posterboard Number: 720) - Mar 29, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_1586;
Interestingly Aicda also was shown to be a positive regulator in the TI condition. These hits along with the hits from the TD ASC differentiation screen reveal mechanisms of transcriptional regulation in ASC differentiation.
- tamoxifen / Generic mfg.
The transcription factor RORa plays a major role in generation and maintenance of human and mouse memory B cells (Room W184) - Mar 22, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_505;
Integrated RNA-seq and Cut&Tag analyses in human and mouse swMBCs provided comprehensive insights into the role of RORa in epigenetic regulation of such B cell transcriptional programs. Thus, our findings establish RORa as a critical regulator of swMBC generation and maintenance, thereby opening new avenues of investigation in the mechanisms of B cell differentiation and possibly vaccine development.
- Reverse Genetic Screens Reveal Mechanisms of Transcriptional Regulation in B cell Differentiation (Room W184) - Mar 22, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_504;
Interestingly Aicda also was shown to be a positive regulator in the TI condition. These hits along with the hits from the TD ASC differentiation screen reveal mechanisms of transcriptional regulation in ASC differentiation.
- Lymph node lymphangiogenesis constrains the germinal center structure to enhance selection and functional antibody production during cutaneous virus infection (Room W178) - Mar 22, 2024 - Abstract #IMMUNOLOGY2024IMMUNOLOGY_207;
With VEGFR2-deficient lymphatic vessels, draining LNs show decreased perifollicular lymphatic growth and a surprising increase in GC area, which associated with lower levels of VacV-specific IgG2b. To determine whether the change in GC structure altered functionality, we blocked VEGFR2 in GC B cells fate-mapper Aicdacre/+ Rosa26Confetti/Confetti mice, here GCs exhibited less selection, which together with reduced VacV-specific IgG2b indicates that lymphatic-dependent GC restraint optimizes GC fitness and thereby anti-viral immunity.
- | Journal: Adaptive Intermediate Class-Wise Distribution Alignment: A Universal Domain Adaptation and Generalization Method for Machine Fault Diagnosis. (Pubmed Central) - Mar 21, 2024
Meanwhile, to ensure the classification performance of the AICDA mechanism, AdaSoftmax loss is proposed for boosting the separability of Softmax loss. Finally, in order to evaluate the effectiveness and universality of the AICDA diagnosis model to the most degree, various multisource mixed fault transfer diagnosis tasks of wind turbine planetary gearboxes, including DA and domain generalization (DG), are implemented, and the experimental results indicate that our proposed AICDA model has a higher diagnosis accuracy and a stronger generalization ability than other state-of-the-art transfer learning methods.
- APOBEC3 enzymes induce chromosomal translocations in solid cancer (Section 17) - Mar 5, 2024 - Abstract #AACR2024AACR_2913;
Finally, in order to evaluate the effectiveness and universality of the AICDA diagnosis model to the most degree, various multisource mixed fault transfer diagnosis tasks of wind turbine planetary gearboxes, including DA and domain generalization (DG), are implemented, and the experimental results indicate that our proposed AICDA model has a higher diagnosis accuracy and a stronger generalization ability than other state-of-the-art transfer learning methods. A3 enzymes induced chromosomal translocations with distinct patterns compared to AID and facilitated chromosomal translocation formation in solid cancers.
- Disruption of Intestinal Germinal Centers During HIV Infection (Poster hall) - Mar 5, 2024 - Abstract #CROI2024CROI_191;
A3 enzymes induced chromosomal translocations with distinct patterns compared to AID and facilitated chromosomal translocation formation in solid cancers. HIV infection is associated with a profound loss of intestinal GC B cells and may represent a major source of perturbation of humoral immunity at these sites of viral replication.
- || Review, Journal: Somatic hypermutation mechanisms during lymphomagenesis and transformation. (Pubmed Central) - Mar 2, 2024
A key challenge in understanding SHM and aSHM is determining how AID targets and mutates specific DNA sequences in the Ig loci to generate antibody diversity and non-Ig genes to initiate lymphomagenesis. Herein, we discuss some current advances regarding the regulation of AID's DNA mutagenesis activity in B cells.
- | Preclinical, Journal: 5-Chloro-2'-deoxycytidine Induces a Distinctive High-Resolution Mutational Spectrum of Transition Mutations In Vivo. (Pubmed Central) - Feb 23, 2024
In summary, this work shows that 5CldC induces a distinct pattern of mutations in cells. Moreover, that pattern resembles human mutational signatures induced by inflammatory processes, such as those triggered in certain malignancies.
- | Journal: A Novel Heterozygous Variant in AICDA Impairs Ig Class Switching and Somatic Hypermutation in Human B Cells and is Associated with Autosomal Dominant HIGM2 Syndrome. (Pubmed Central) - Feb 20, 2024
Interestingly, patients' B cells carrying the L189X variant exhibited not only greatly impaired CSR but also SHM in vivo, as well as CSR and production of IgG and IgA in vitro. Our findings demonstrate that the NES domain of AID can be essential for SHM, as well as for CSR, thereby refining the correlation between AICDA genotype and SHM phenotype as well as broadening our understanding of the pathophysiology of HIGM disorders.
- Intranasal Allergen Exposure Drives Lymphoid Aggregate Formation, Local Class-switching and Ige+Plasma Cell Accumulation in the Lung (San Diego Convention Center, Room 31A-C (Upper Level)) - Feb 20, 2024 - Abstract #ATS2024ATS_7646;
These data demonstrate that allergen-induced chronic inflammation triggers the formation of LAs in the lung, which can serve as an immediate site for inducing local B cell class-switching. Moreover, we found that IgE+ PCs arise during acute HDM exposure where allergic inflammation is occurring, localize near the airway, and accumulate during chronic allergic inflammation.
- Comprehensive Analysis of Mutational Signatures in Chronic Lymphocytic Leukemia: Uncovering Genomic Patterns and Prognostic Implications (BCC Room 339) - Feb 18, 2024 - Abstract #USCAP2024USCAP_905;
Although there were signatures that correlated loosely with SHM status, these were not sufficient to replace traditional SHM testing. However, a combined signature "score" was developed that could predict overall survival.
- PAIRED TRANSCRIPTOMIC ANALYSIS OF TRANSITIONAL B CELLS IN SYSTEMIC SCLEROSIS HIGHLIGHTS DEFECTIVE PERIPHERAL TOLERANCE (South Hall 2B) - Feb 13, 2024 - Abstract #SSWC2024SSWC_445;
Additionally, we provide further evidence for a potential breach in peripheral tolerance of SSc patients. Further studies are underway to identify key pathways that underpin B cell pathogenesis in SSc and explore the relevance of such findings for better targeted therapies.
- | Journal: CD30 plays a role in T-dependent immune response and T (Pubmed Central) - Dec 17, 2023
High-throughput RNA sequencing analysis revealed that CD30 deficiency led to a decrease of FOXO-autophagy axis in T cells upon TCR stimulation. Thus, CD30 positively regulates T-cell-dependent immune response and T cell proliferation.
- The prognostic value of mutational signatures in pancreatic cancer. (Poster Bd # M18) - Dec 6, 2023 - Abstract #ASCOGI2024ASCO_GI_603;
Thus, CD30 positively regulates T-cell-dependent immune response and T cell proliferation. We identified three mutational signatures
- | Journal: Cold-blooded vertebrates evolved organized germinal center like structures. (Pubmed Central) - Dec 4, 2023
Our findings demonstrate that ectotherms evolved organized SLMs with GC-like roles. Moreover, our results also point to primordially conserved mechanisms by which M-LAs and mammalian polyclonal GCs develop and function.
- | Journal: Alternative splicing of chitin deacetylase 2 regulates chitin and fatty acid metabolism in Asian citrus psyllid, Diaphorina citri. (Pubmed Central) - Nov 27, 2023
Furthermore, silencing DcCDA2a and DcCDA2b significantly suppressed D. citri chitin and fatty acid metabolism. Our results indicated that DcCDA2 might play crucial roles in regulating D. citri chitin and fatty acid metabolism, and it could be used as a potential target for controlling D. citri.
- | Journal: RPA guides UNG to uracil in ssDNA to facilitate antibody class switching and repair of mutagenic uracil at the replication fork. (Pubmed Central) - Nov 25, 2023
By contrast, the interaction had no significant impact on total genomic uracil levels. Thus, RPA coordinates UNG during CSR and pre-replicative repair of mutagenic uracil in ssDNA but is not essential in post-replicative and canonical BER of uracil in dsDNA.
- | Journal: Enhanced C-To-T and A-To-G Base Editing in Mitochondrial DNA with Engineered DdCBE and TALED. (Pubmed Central) - Nov 21, 2023
Finally, these engineered mitochondrial base editors are shown to be efficient in installing mtDNA mutations in human cells or mouse embryos for disease modeling. Collectively, the study shows broad implications for the basic study and therapeutic applications of optimized DdCBE and TALED.
- | Journal: Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells. (Pubmed Central) - Nov 15, 2023
Ours is the first report on the interaction of genome mutator enzyme AID with UBN1. Nevertheless, the fate of interaction between UBN1 and AID is yet to be explored in the context of SHM or CSR.
- Genomic characteristics and its therapeutic implications in breast cancer patients with detectable molecular residual disease (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_573;
The tumor biology is probably the main driver of detectable MRD. We also found the vast majority of patients with detectable MRD have the opportunity to access targeted therapy.
- Comparing hippocampal mossy cell ablation vs silencing on the maturation of adult-born dentate granule cells (WCC 144) - Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_1126;
In contrast, preliminary studies of TeLC silencing of mossy cells revealed modifications in immature DGC density and migration of these cells away from the subgranular zone, without changing the laminar structure of molecular layer inputs. This suggests that functional synaptic innervation at proximal dendritic sites might critically regulate adult neurogenesis, demonstrating the importance of early functional synaptic innervation in the regulation of abDGCs.
- Imbruvica (ibrutinib) / AbbVie, J&J
Investigation into Intraclonal Heterogeneity of CXCR4DimCD5Bright Chronic Lymphocytic Leukemia Cells Identifies Distinct Activation Signatures (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_4196;
To permit a focused analysis of PF that would allow us to intercept this evolutionary loop, we characterized the single cell transcriptomes of PF from 4 U-CLL and 4 M-CLL patients immediately prior to ibrutinib treatment...To extend on these observations, we have documented that the unique surface markers expressed in these PF subfractions positively correlate with our transcriptomic results. Taken together, these results not only highlighted the molecular heterogeneity of CLL, but also lead to the identification of two PF subpopulations that may provide novel actionable therapeutic targets to significantly halt CLL clonal evolution.
- Integrative Single-Cell RNA-Seq and Single-Cell ATAC-Seq Analysis of Human Plasma Cell Differentiation (Grand Hyatt - Harbor Ballroom) - Nov 3, 2023 - Abstract #ASH2023ASH_992;
These results and the supporting data generated with our PCD model provide a resource for the identification of molecular circuits that are crucial for early and mature PC biological function and survival. These data thus provide critical insights into epigenetic- and transcriptional-mediated reprogramming events that sustain PCD.
- | Journal: Borrelia burgdorferi Infection-Induced Persistent IgM Secretion Controls Bacteremia, but Not Bacterial Dissemination or Tissue Burden. (Pubmed Central) - Oct 2, 2023
Consistent with the notion that B. burgdorferi infection drives production of IgM over more tissue-penetrable IgG, we demonstrated increased short- and long-term IgM Ab responses also to a coadministered, unrelated Ag. Thus, the continued production of IgM may explain the absence of B. burgdorferi in the blood.
- | Journal: A comprehensive immunoinformatic analysis of chitin deacetylase's and MP88 for designing multi-epitope vaccines against Cryptococcus neoformans. (Pubmed Central) - Sep 19, 2023
Both candidates also generated robust immune profiles comprising innate, adaptive and humoral immune responses. Taken together, experimental validations of our findings through extensive in
- | Journal, Lymphopenia: Late-Onset Lymphopenia and ITP in a Patient with Hyper IgM Syndrome Due to a Homozygous Variant in AICDA. (Pubmed Central) - Sep 14, 2023
Taken together, experimental validations of our findings through extensive in No abstract available
- | Bexxar (iodine I 131 tositumomab) / GSK, Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
Journal, IO biomarker: Subclonal TP53 mutation are frequent and predict resistance to radio-immunotherapy in follicular lymphoma. (Pubmed Central) - Aug 29, 2023
In summary, subclonal TP53 mutations are common in FL and are a distinct phenomenon from AICDA-mediated genetic heterogeneity. The absence of a detectable subclonal mutation in TP53 defined a population that particularly benefited from RIT.
- || Review, Journal: The off-target effects of AID in carcinogenesis. (Pubmed Central) - Aug 25, 2023
The primary focus of this review is to understand how and when AID targets specific gene loci and how this affects carcinogenesis. Overall, this review aims to provide a comprehensive understanding of the physiological and off-target effects of AID, which will contribute to the development of novel therapeutic strategies for autoimmune diseases, hematological neoplasms, and solid tumors.
- | Journal: Co-Occurrence of Pallister-Killian Syndrome and Burkitt Lymphoma in a Patient with Near-Normal Neurocognitive Development. (Pubmed Central) - Aug 17, 2023
The localization of AICDA, a gene for which overexpression has been implicated in promoting t(8;14) noted in our patient's lymphoma, raises a potential mechanism of pathogenesis. In addition, this case indicates that children with PKS can demonstrate near-normal cognitive development.
- Loss of AID exacerbates the malignant progression of CLL () - Aug 14, 2023 - Abstract #IWCLL2023IWCLL_284;
This upregulation of XBP1 is transcriptionally augmented by the increased secretory IgM found in AID-deficient B cells. The higher levels of XBP1s found in AID-/-/E?-TCL1 CLL cells support BCR signaling, contributing to CLL growth and survival.
- Patients with unmutated IgHV_1-69; 1-02; 3-30; 4-39 and high expression of AID enzyme need earlier treatment. () - Aug 14, 2023 - Abstract #IWCLL2023IWCLL_187;
Considering our previous study analyzing the South American cohort, n = 900 [1], the percentage of patients corresponding to the sub-group_1 is 27%. Hence, we can assume that the new entity described here (U-CLL/AIDpos/Sub-group_1) represents ?15% of the total CLL population, thus, accurate prediction of this sub-group could result in a useful tool to be incorporated in clinical practice after validation.
- | Journal: The APOBEC3B c.783delG Truncating Mutation Is Not Associated with an Increased Risk of Breast Cancer in the Polish Population. (Pubmed Central) - Aug 2, 2023
We conclude the APOBEC3B deleterious mutation p.Val262Phefs does not confer breast cancer risk. These data do not support the hypothesis that APOBEC3B is a breast cancer susceptibility gene.
- | Journal: IgH 3'RR recombination uncovers a non-germinal center imprint and c-MYC-dependent IgH rearrangement in unmutated chronic lymphocytic leukemia. (Pubmed Central) - Jul 27, 2023
In addition to the proposals already made concerning the CLL cell of origin, our study highlights that analysis of IGH recombinatory activity can identify CLL cases from different origins. Finally, on-going S?-3'RRrec in S?-3'RRrecHigh cells appeared to presumably be the consequence of high c-MYC expression, as c-MYC overexpression potentiated IGH rearrangements and S?-3'RRrec, even in the absence of AID for the latter.
- Differential expression of 5mC epigenomic regulators in Alzheimer (In-Person) - Jul 6, 2023 - Abstract #AAIC2023AAIC_2543;
Conclusion : Our findings indicate that changes in 5mC/5hmC/5fC effector protein expression are associated with AD and its neuropathology. The characterisation of 5fC localisation in human brain indicates high abundance within the cytoplasm of hippocampal cells suggesting that 5fC may be involved in pre- and post-transcriptional control of memory processing pathways and, when disrupted, may lead to neurodegenerative disease.
- | Preclinical, Journal: Activation-induced cytidine deaminase displays an alternative co-factor for modulating PIM1 expression in diffuse large B cell lymphoma cell lines. (Pubmed Central) - Jun 14, 2023
Our findings demonstrate that AID interacts with either DNMT1 or TET2 to form a complex to bind with a PIM1 promoter and thus is responsible for the modulation of PIM1 expression. These results provide insights into an alternative role of AID to DLBCL-associated genes.
- Zydelig (idelalisib) / Gilead, Imbruvica (ibrutinib) / AbbVie, J&J
B-cell-receptor inhibitors induce AID-mediated genome instability in Chronic Lymphocytic Leukaemia (Poster and Exhibition Hall) - Jun 13, 2023 - Abstract #EACR2023EACR_448;
This effect could be involved in the development of drug resistance and should be carefully evaluated during long-term therapies. The identification of specific loci targeted by AID could be used to develop a biomarker for risk assessment.
- | Journal: Activation-induced cytidine deaminase (AID) involved in the regulation of B cell immune senescence (Pubmed Central) - Jun 3, 2023
It decreases during immune senescence and is considered to be a biomarker of decreased B cell function in aging mice and humans. Understanding the inherent defects of B-cell immune senescence and the regulation mechanism of AID in the aging process can provide new research ideas for the susceptibility, prevention and treatment of diseases in the elderly.
- | Journal: One Step Purification-Vaccine Delivery System. (Pubmed Central) - May 27, 2023
The GP-Ni-Cda2 vaccine was shown to be comparable to our previous approach utilizing mouse serum albumin (MSA) and yeast RNA trapping of Cda2 in GPs in a mouse infection model. This novel GP-Ni approach allows for the one-step binding of His-tagged vaccine antigens and encapsulation in an effective delivery vehicle to target vaccines to antigen-presenting cells (APCs), antigen discovery, and vaccine development.
- | Journal: Serpentine and Vermiform Are Produced Autonomously to Fulfill Their Function in Drosophila Wings. (Pubmed Central) - May 26, 2023
Furthermore, we showed that inhibition of serp or verm in the developing wing caused wing morphology and permeability deficiency. Taken together, the production of Serp and Verm in the wing was autonomous and independent of the fat body.
- B cell Tet2 promotes maturation of the antibody response (Room 202B) - May 17, 2023 - Abstract #IMMUNOLOGY2023IMMUNOLOGY_2147;
- | Journal: Mesoscale DNA feature in antibody-coding sequence facilitates somatic hypermutation. (Pubmed Central) - May 15, 2023
Taken together, the production of Serp and Verm in the wing was autonomous and independent of the fat body. We demonstrated that mesoscale sequence alterations tune the in
- IGH 3'RR RECOMBINATION UNCOVERS A NON-GC IMPRINT AND C-MYC- DEPENDENT IGH REARRANGEMENT ACTIVITY IN UNMUTATED CHRONIC LYMPHOCYTIC LEUKEMIA () - May 12, 2023 - Abstract #EHA2023EHA_2787;
We demonstrated that mesoscale sequence alterations tune the in Our results separated CLLs into two groups on the basis of S
- MEASUREMENT OF INTRACLONAL DIVERSIFICATION REFINES THE PROGNOSTIC IMPACT OF IGHV MUTATIONS IN CLL (Poster area) - May 12, 2023 - Abstract #EHA2023EHA_2193;
By applying this approach, we provide evidence that: i) ID prevalently affects M-CLL; ii) patients affected by M-CLL with ID have better outcome than M- CLL cases without ID; iii) ID identifies a subset of M-CLL with specific molecular/biological features and clinicalcharacteristics. IGH, Prognostic factor, Chronic lymphocytic leukemia
- | Journal: Necessity of HuR/ELAVL1 for activation-induced cytidine deaminase-dependent decrease in topoisomerase 1 in antibody diversification. (Pubmed Central) - May 7, 2023
Additionally, reduction of CSR to IgG3 in HuR-KO cells is rescued by knockdown of Top1, indicating that elimination of the AID-dependent Top1 decrease is the cause of the inefficiency of DNA cleavage, CSR, and hypermutation in HuR-KO cells. These results show that HuR is required for initiation of antibody diversification and acquired immunity through the regulation of AID-dependent DNA cleavage by repressing Top1 protein synthesis.
- | Journal: Optimal AID expression and efficient immunoglobulin class switch recombination are dependent on the Hypoxia-Inducible Factor. (Pubmed Central) - May 5, 2023
and HIF-1? subunits of the HIF transcription factor in murine CH12 B cells results in defective CSR and that this is due to the suboptimal induction of AID expression.
- Explaining Variance in Auditory Targeted Cognitive Training Performance Across a Heterogeneous Veteran Sample Engaged in Mental Health Rehabilitation (Sapphire AB) - Apr 29, 2023 - Abstract #SOBP2023SOBP_242;
PHQ-9, IMI, MMN and MCCB predicted performance over one or both ATCT levels, with similar beta weights; GAD-7 and P3a were not significant predictors. Conclusions Depressive symptoms, motivational factors, and electrophysiological and cognitive measures predict initial performance on ATCT across a diagnostically diverse psychiatric cohort, and may help stratify which individuals may respond to a full course of ATCT.