Alan Herbert
Charlestown
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Articles by Alan Herbert
Humans have evolved invasive retroelements into defenders of their genome
The alternative DNA conformations formed by the different retroelements that are shown in panels E-F. B-DNA is the well-known Watson and Crick Structure. The SINE family includes Alu repeats. The top panel shows host defense pathways activated by Z-RNAs formed by retroelements. The lower panel illustrates how circular RNAs form from Alu SINEs. They can form Z-RNA and induce the decay of RNAs necessary for cell survival.
Flipons, Repeat RNAs, and IDRs Enable the Rapid 2-D Search of Large Genomes Through the Holographic Hashing of Condensate Surfaces
This version is not peer-reviewed. You are already at the latest version Questions arise about how well early bacterial models of gene regulation generalize to eukaryotes and whether metazoan repetitive sequences are merely genomic spandrels. The repeats are recognized by sequence-specific RNA-binding proteins that play multiple roles in RNA biology. A subset, called flipons, adopts non-B-DNA conformations under physiological conditions without any sequence change or backbone cleavage.
OmiXAI: An ensemble XAI pipeline for interpretable deep learning in omics data
Abstract Deep learning methods have become methods of choice in the analysis of genomic data. The performance of deep learning models depends on the information available for training. A growing trend in deep learning applications involves leveraging multi-omics data – spanning genomics, transcriptomics, epigenomics, proteomics, metabolomics, and other domains.
Flipons help Intrinsically Disordered Proteins Fold into Cellular Machines
Flipons help Intrinsically Disordered Proteins Fold into Cellular Machines Triplexes can induce folding of disordered protein to create cellular machines that modulate the readout of information from genes. Different DNA Structures Nucleate the Folding of Proteins to form specific complexes that modulate the readout of genetic information Self-organization is inherent in the way Nature has engineered cells.
The Dynamic Targeting of Regulatory Proteins to Genes
The Dynamic Targeting of Regulatory Proteins to Genes Transcription Factor chains bind to left-handed Z-DNA and Z-RNA structures formed by Active Genes. The exchange of chains on the Z-DNA surface generates new combinations that bind to different B-DNA sequences, activating site-dependent responses.
A G-quadruplex-hemin peroxidase complex as a source of oxidative stress in neurological diseases
A G-quadruplex-hemin peroxidase complex as a source of oxidative stress in neurological diseases The complex formed by an RNA G-quadruplex (blue) and Hemin (orange) catalyzes the formation of oxygen radicals (with unpaired electrons shown in red) from molecular oxygen, producing neuronal damage in LAS and FTD.
No longer controversial: a new biological role for Z-DNA in cells
No longer controversial: a new biological role for Z-DNA in cells The left-handed spiral of each Z-DNA strand is highlighted on the left. Binding and bonding of the two zinc finger domains (shown in red) from the CTCF protein to Z-DNA (shown in blue). This protein helps to bridge chromosomal segments in the nucleus. People gave up looking for left-handed Z-DNA-binding proteins long ago. This paper shows that many Z-DNA-binding proteins exist in a cell.
Host cell Z-RNAs activate ZBP1 during virus infections - Nature
Abstract Herpes simplex virus 1 (HSV-1) and Influenza A viruses (IAV) induce Z-form nucleic acid Binding Protein 1 (ZBP1)-initiated cell death1-8. ZBP1 is activated by Z-RNA1,7,9, and the Z-RNAs which trigger ZBP1 during HSV-1 and IAV infections were assumed to be of viral origin1. However, we show here that host cell-encoded Z-RNAs are major and sufficient ZBP1 activating ligands following infection by these two human pathogens.
Cells make Z-RNAs as the first line of defense against pathogenic viruses
Expression of Z-RNAs encoded by “junk” DNA flipons induces the death of virally infected cells. The Z-RNA is encoded by endogenous retroelements (EREs) that are transcribed when viral proteins prevent the normal termination of host RNAs as a strategy to s Viruses attack by taking control of a cell. To avoid becoming a virus factory, infected cells trigger rapid cell death by producing Z-RNAs made from "junk" DNA.
Biological roles for three strand DNA and RNA flipon structures
Biological roles for three strand DNA and RNA flipon structures The RNA cloud formed around genes regulates their readout into RNA. Triplexes help define where in the genome a cloud forms. Proteins and other flipons modulate the levels of gene expression. The processes color each genomic region differently. The cell's version of the multiverse! Here, the focus is on three-stranded DNA and RNA triplex structures. Their biological relevance is now coming into focus.
Zα and Zβ Localize ADAR1 to Flipons That Modulate Innate Immunity, Alternative Splicing, and Nonsynonymous RNA Editing
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
A Compendium of G-Flipon Biological Functions That Have Experimental Validation
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
A Compendium of G-flipon Biological Functions that have Experimental Validation
Preprint Review Version 1 This version is not peer-reviewed Version 1 : Received: 22 August 2024 / Approved: 23 August 2024 / Online: 23 August 2024 (12:23:11 CEST) Herbert, A. A Compendium of G-flipon Biological Functions that have Experimental Validation. Preprints 2024, 2024081688. https://doi.org/10.20944/preprints202408.1688.v1 Herbert, A. A Compendium of G-flipon Biological Functions that have Experimental Validation. Preprints 2024, 2024081688.
Analysis of live cell data with G-DNABERT supports a role for G-quadruplexes in chromatin looping
Abstract Alternative DNA conformation formed by sequences called flipons potentially alter the readout of genetic information by directing the shape-specific assembly of complexes on DNA The biological roles of G-quadruplexes formed by motifs rich in guanosine repeats have been investigated experimentally using many different methodologies including G4-seq, G4 ChIP-seq, permanganate nuclease footprinting (KEx), KAS-seq, CUT&Tag with varying degrees of overlap between the results.
Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases - Genes & Immunity
Abstract Osteogenesis imperfecta type 10 (OI10) is caused by loss of function codon variants in the gene SERPINH1 that encodes heat shock protein 47 (HSP47), rather than in a gene specifying bone formation. The HSP47 variants disrupt the folding of both collagen and the endonuclease IRE1α (inositol-requiring enzyme 1α) that splices X-Box Binding Protein 1 (XBP1) mRNA. Besides impairing bone development, variants likely affect osteoclast differentiation.
The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon
The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon Statistics from Altmetric.com Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. View Full Text Read the full text or download the PDF: Read the full text or download the PDF:
Flipons | The Discovery of Z-DNA and Soft-Wired Genomes | Alan Herbert
Alan Herbert has played a leading part in discovering the biological roles for a high-energy form of DNA twisted to the left rather than to the right. Both Z-DNA and the Z-RNA sensing proteins are critical for protecting hosts against both viruses and cancers. The proteins also play critical roles in the programmed cell death of aging cells. Other types of flipons exist and alter the readout of transcripts from the genome, encoding genetic information by their shape rather than by their sequence.
Flipons: The Discovery of Z-DNA and Soft-Wired Genomes
Table of Contents Book Description 1st Edition By Alan Herbert Copyright 2024 227 Pages 49 Color & 28 B/W Illustrations by CRC Press 227 Pages 49 Color & 28 B/W Illustrations by CRC Press Alan Herbert has played a leading part in discovering the biological roles for a high-energy form of DNA twisted to the left rather than to the right. Both Z-DNA and the Z-RNA sensing proteins are critical for protecting hosts against both viruses and cancers.
Flipons within Junk DNA Enhance Biological Computations by Exchanging Energy for Information
Repeat DNA Adopts Different Conformations. By cycling between different states, DNA can change the readout of information from the genome. The process exchanges metabolic energy for information.
When the Genome Gets it Wrong, but Still Gets it Right
Questions? +1 (202) 335-3939 About News by Country News by Industry Get News Alerts Press Releases Trusted News Since 1995 A service for technology industry professionals · · 669,509,878 Articles · 3+ Million Readers News Search | All News Topics > Technology News Topics: By Country | By State ; Press Releases by Industry Channel > All Technology Press Releases The same play can either win or lose depending on what the other player does.
IJMS | Free Full-Text | The Intransitive Logic of Directed Cycles and Flipons Enhances the Evolution of Molecular Computers by Augmenting the Kolmogorov Complexity of Genomes
All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited. For more information, please refer to https://www.mdpi.com/openaccess.
Z-Flipons conserved between human and mouse are associated with increased transcription initiation rates
Abstract A long-standing question concerns the role of Z-DNA in transcription. Here we use a deep learning approach based on the published DeepZ algorithm that predicts Z-flipons based on DNA sequence, structural properties of nucleotides and omics data. We examined Z-flipons that are conserved between human and mouse genomes after generating whole-genome Z-flipons maps by training DeepZ on ChIP-seq Z-DNA data, then overlapping the results with a common set of omics data features.
Flipons are tiny DNA actuators that play a previously unknown role in gene expression
The flipon cycle enables the “load, fire and reset” of gene promoters during transcription. The flip between B- to Z-DNA is at the core of the reset. It is energized when the negative (-σ) supercoiling from firing offsets the positive (+σ) supercoiling fr Everything you wanted to know about the role of flipons in DNA transcription but were afraid to ask It is very pleasing to see that many groups are now working to unravel both the ancient and modern roles of flipons in cellular biology.
Flipons help ADAR1 turn off inflammation
The red staining indicates inflammation of the brain regions shown. It is more intense with only one copy of the mutant ADAR1 protein.
Dis Dat Podcast with Alan Herbert.: Episode 1: Unleashing Inclusion: A Journey through the Inclusive Africa Conference with Julius Mbura. Head of Legal, Advocacy and Inovations for the Inclusive Africa Conference. on Apple Podcasts
This episode dives into the rich history and inspiring journey of inABLE, the organization behind the Inclusive Africa Conference, as it reaches a significant milestone of 15 years. Join host Alan Herbert as he sits down with Julius Mbura, the head of Advocacy, Legal, and Innovations at the conference. Together, they explore the genesis of the organization's name, the evolution of the conference, and the vision for a future where learners with disabilities have access to assistive technology.
Z-form nucleic acid-binding protein 1 (ZBP1) as a sensor of viral and cellular Z-RNAs: waalking the razor's edge
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Mapping Z-DNA in the Human Genome to Disease Outcomes
Mapping of Z-DNA in the genome by deep learning has revealed a number of different roles for Z-DNA in health and disease The transformer algorithm maps Z-DNA with high accuracy and precision. The zebra stripes to the right mirror the zig-zag backbone for which Z-DNA is named and shows how the output of Z-DNABERT is easy to interpret.
A mystery no longer: Biological Roles for Z-RNA and Z-DNA
There were 2,563 press releases posted in the last 24 hours and 380,689 in the last 365 days. The Z-DNA History is Revealed by Citation Count . Z-DNA was widely heralded when discovered. It took the discovery of the Z-DNA and Z-RNA binding proteins ADAR1 and ZBP1 to unravel the role of this high energy left-handed DNA structure. Unlocking the mystery of Z-DNA Move over Watson-and-Crick.
An RNA Microcode Underlying Embryonic Development
There were 1,786 press releases posted in the last 24 hours and 370,607 in the last 365 days. The RNA microcode targets flipons during embryonic development. By changing the promoter shape, conserved microRNA alter gene expression. Each structure localizes a set of proteins with different functions.
Conserved microRNAs and Flipons Shape Gene Expression during Development by Altering Promoter Conformations
1. Introduction The approach we take follows that of Britten and Davidson, who first proposed the programming of genomes by trans-RNAs that act at locations distant from where they are produced [1]. While there are many classes of trans-RNAs [2], we will focus on miR and examine the DNA sites to which they bind, and their potential role in embryonic development. We will investigate the interactions between miR and flipons, sequences that form NoB under physiological conditions [3].
Z-Flipon Variants reveal the many roles of Z-DNA and Z-RNA in health and disease
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Flipon therapeutics: a Novel Modality for Targeting Treatment Resistant Cancers
There were 2,080 press releases posted in the last 24 hours and 307,077 in the last 365 days. Flipon therapeutics induce a flip of Watson-Crick B-DNA to Z-DNA, activating inflammatory cell death in tumor fibroblasts to fire up immune responses against cancer cells. Responses are enhanced by the PD-1 antibody. The pathway is not expressed by normal cells. Flipon therapeutics induce fibroblast cell death in inflamed tumors to enhance anti-tumor immune responses but spare normal cells.
The Nuclear Batteries in Every Cell
Nucleosomes store mechanical energy in the DNA wound around them. Nucleosome ejection releases the energy, powering a change in DNA conformation. The altered shape is recognized by proteins that use the energy to nucleate the local assembly of cellular machines.
Epstein-Barr Virus: Silencing the Enemy within Original
EBV, the kissing virus that produced infectious mononucleosis, infects over 95% of people. EBV causes 1-1.5% cancers worldwide and autoimmune diseases like systemic lupus erythematosus and multiple sclerosis. Electron-micrograph by Liza Gross (CC BY 2.5) The EBV genome show strong selection against genetic elements called flipons that are more frequent in other types of Herpes viruses. Epstein-Barr virus (EBV) infects most humans and is a major cause of cancer and autoimmune disease.
A flipon signature allows tracing of the SARS virus origin Original
The fingerprint for the human viruses on the top row align with the animal virus from where they came on the bottom row A fingerprint for SARS viruses that allows identification of the hosts from which they originated. Teh discovery of Z-DNA has lead to many unexpected findings both in biology and therapeutics.
Saint-Gaudens’ Model
One of the most stunning coins ever minted is the 1907 ultra high relief Saint-Gaudens double eagle. (Image courtesy Heritage Auctions.) Few would deny that Augustus Saint-Gaudens’ gold double eagle is one of the most attractive coins ever minted. Cornelius Vermeule, in his seminal Numismatic Art in America, termed it, “perhaps the most majestic coin ever to bear our national imprint.”1 Few would deny that Saint-Gaudens was one of the nation’s most accomplished sculptors. John H.
Concern over use of the term Z-DNA
We are writing to express our concern over use of the term Z-DNA to describe a right-handed, double-stranded Watson–Crick helix that incorporates the modified base diaminopurine (also known as 2-aminoadenine; see Nature 593, 181; 2021). This use of Z-DNA is, we contend, confusing to scientists and the general public. Z-DNA is the long-established nomenclature for a left-handed DNA structure first detailed at atomic resolution in 1979 (A. H.-J. Wang et al. Nature 282, 680–686; 1979).
ADAR and Immune Silencing in Cancer
Highlights RNA editing by ADAR is a pan-cancer process that a significant fraction of tumors rely on for survival. It promotes immune silencing and tumor viability. Reducing ADAR expression in tumors increases sensitivity to checkpoint inhibitors in mouse melanoma models. IFN, along with Alu dsRNA and cytoplasmic DNA, trigger expression of the p150 isoform of ADAR that enables tumor progression.
‘Is Auroville a mirage? Have I wasted my life? Of course, the nightmare ends’: Re-entering Auroville
Aficionados of space travel will recall the drama of re-entry; those few minutes when the spacecraft, plunging back into the earth’s atmosphere, is severed from its umbilical link with mission control, and those NASA magicians, after piloting a half-ton lump of high technology faultlessly through interstellar vastnesses, are reduced to gnawing their fingernails and playing nervously with plastic cups. Well, it’s an image that haunts me at the moment.
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