Angus Wilson- Ph.D.
- Head of Faculty at New York University
Angus Wilson
- Ph.D.
- Head of Faculty at New York University
About
95
Publications
14,429
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3,494
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Introduction
By day I am a molecular virologist and by night (well, day actually) I am an ornithologist of sorts.
Current institution
Additional affiliations
January 1991 - July 1996
July 1996 - present
Position
- Foundations in Cell and Molecular Biology (Graduate School) Host-Defense/Virology (Medical School
Education
August 1986 - January 1991
September 1982 - June 1986
Publications
Publications (95)
Nanopore direct RNA sequencing (DRS) enables the capture and full-length sequencing of native RNAs, without recoding or amplification bias. Resulting data sets may be interrogated to define the identity and location of chemically modified ribonucleotides, as well as the length of poly(A) tails, on individual RNA molecules. The success of these anal...
High-resolution annotations of transcriptomes from all domains of life are essential for many sequencing-based RNA analyses, including Nanopore direct RNA sequencing (DRS), which would otherwise be hindered by misalignments and other analysis artefacts. DRS allows the capture and full-length sequencing of native RNAs, without recoding or amplificat...
Most individuals are latently infected with herpes simplex virus type 1 (HSV-1), and it is well-established that HSV-1 establishes latency in sensory neurons of peripheral ganglia. However, it was recently proposed that latent HSV-1 is also present in immune cells recovered from the ganglia of experimentally infected mice. Here, we reanalyzed the s...
Most individuals are latently infected with herpes simplex virus type 1 (HSV-1) and it is well-established that HSV-1 establishes latency in sensory neurons of peripheral ganglia. However, it was recently proposed that latent virus is also present in immune cells recovered from ganglia in a mouse model used for studying latency. Here, we reanalyzed...
Herpes simplex virus type-1 (HSV-1) protein ICP27 is an essential immediate early (IE) protein that promotes the expression of viral early (E) and late (L) genes via multiple mechanisms. Our understanding of this complex regulatory protein has been greatly enhanced by the characterization of HSV-1 mutants bearing engineered alterations in the ICP27...
Adenovirus is a common human pathogen that relies on host cell processes for transcription and processing of viral RNA and protein production. Although adenoviral promoters, splice junctions, and polyadenylation sites have been characterized using low-throughput biochemical techniques or short read cDNA-based sequencing, these technologies do not f...
A signature trait of neurotropic α-herpesviruses (α-HV) is their ability to establish stable non-productive infections of peripheral neurons termed latency. This specialized gene expression program is the foundation of an evolutionarily successful strategy to ensure lifelong persistence in the host. Various physiological stresses can induce reactiv...
Herpes simplex virus-1 (HSV-1) enters a latent infection in neurons and periodically reactivates. Reactivation manifests as a variety of clinical symptoms.
Motivation
The chemical modification of ribonucleotides regulates the structure, stability and interactions of RNAs. Profiling of these modifications using short-read (Illumina) sequencing techniques provides high sensitivity but low-to-medium resolution i.e. modifications cannot be assigned to specific transcript isoforms in regions of sequence ov...
Methylation at the N⁶-position of either adenosine (m⁶A) or 2′-O-methyladenosine (m⁶Am) represents two of the most abundant internal modifications of coding and non-coding RNAs, influencing their maturation, stability and function. Additionally, although less abundant and less well-studied, monomethylation at the N¹-position (m¹A) can have profound...
An understanding of the molecular events that regulate entry of herpes simplex virus type 1 (HSV-1) into a latent infection of neurons and subsequent reactivation requires model systems. However, establishing a latent-like infection in cultured neurons is problematic as the release of any infectious virus can potentially superinfect the cultures. H...
Single-cell RNA sequencing (scRNA-seq) is a powerful technique for dissecting the complexity of normal and diseased tissues, enabling characterization of cell diversity and heterogeneous phenotypic states in unprecedented detail. However, this technology has been underutilized for exploring the interactions between the host cell and viral pathogens...
Significance
Herpes simplex virus infections cause painful lesions, blindness, and viral encephalitis. At the cellular level, infection causes a dramatic shutdown of host gene expression, allowing the virus to monopolize the transcriptional and translational machinery. One of the viral proteins responsible is ICP27, which disrupts cellular RNA proc...
N6-methyladenosine (m6A) is an abundant internal RNA modification, influencing transcript fate and function in uninfected and virus-infected cells. Installation of m6A by the nuclear RNA methyltransferase METTL3 occurs cotranscriptionally; however, the genomes of some cytoplasmic RNA viruses are also m6A-modified. How the cellular m6A modification...
Adenovirus is a nuclear replicating DNA virus reliant on host RNA processing machinery. Processing and metabolism of cellular RNAs can be regulated by METTL3, which catalyzes the addition of N6-methyladenosine (m⁶A) to mRNAs. While m⁶A-modified adenoviral RNAs have been previously detected, the location and function of this mark within the infectio...
The genomes of DNA viruses encode deceptively complex transcriptomes evolved to maximize coding potential within the confines of a relatively small genome. Defining the full range of viral RNAs produced during an infection is key to understanding the viral replication cycle and its interactions with the host cell. Traditional short‐read (Illumina)...
We describe a primary neuronal culture system suitable for molecular characterization of herpes simplex virus type 1 (HSV-1) infection, latency, and reactivation. While several alternative models are available, including infections of live animal or explanted ganglia, these are complicated by the presence of multiple cell types, including immune ce...
Adenovirus is a common human pathogen that relies on host cell processes for production and processing of viral RNA. Although adenoviral promoters, splice junctions, and cleavage and polyadenylation sites have been characterized using low-throughput biochemical techniques or short read cDNA-based sequencing, these technologies do not fully capture...
Adenovirus is a nuclear replicating DNA virus reliant on host RNA processing machinery. Processing and metabolism of cellular RNAs can be regulated by METTL3, which catalyzes the addition of N6-methyladenosine (m6A) to mRNAs. While m6A-modified adenoviral RNAs have been previously detected, the location and function of this mark within the infectio...
Meeting Report on the 9th Annual Symposium of the Colorado Alphaherpesvirus Latency Society (CALS) held on May 8–11, 2019, in Vail, CO.
The mTOR pathway integrates both extracellular and intracellular signals and serves as a central regulator of cell metabolism, growth, survival, and stress responses. Neurotropic viruses, such as herpes simplex virus-1 (HSV-1), also rely on cellular AKT-mTORC1 signaling to achieve viral latency. Here, we define a novel genotoxic response whereby sp...
Characterizing complex viral transcriptomes by conventional RNA sequencing approaches is complicated by high gene density, overlapping reading frames, and complex splicing patterns. Direct RNA sequencing (direct RNA-seq) using nanopore arrays offers an exciting alternative whereby individual polyadenylated RNAs are sequenced directly, without the r...
The mTOR pathway integrates both extracellular and intracellular signals and serves as a central regulator of cell metabolism, growth, survival and stress responses. Neurotropic viruses, such as herpes simplex virus-1 (HSV-1), also rely on cellular AKT-mTORC1 signaling to achieve viral latency. Here, we define a novel genotoxic response whereby spa...
Transcriptome profiling has become routine in studies of many biological processes. However, the favored approaches such as short-read Illumina RNA sequencing are giving way to long-read sequencing platforms better suited to interrogating the complex transcriptomes typical of many RNA and DNA viruses. Here, we provide a guide-tailored to molecular...
Viral genomes exhibit a higher gene density and more diversified transcriptome than the host cell. Coding potential is maximized through the use of multiple reading frames, placement of genes on opposing strands, inefficient or modified use of termination signals, and the deployment of complex alternative splicing patterns. As a consequence, detail...
We document a sighting of the Critically Endangered New Zealand
Storm Petrel Fregetta maoriana made during a pelagic expedition in May 2017 off
Gau Island, Fiji. This is the first confirmed record of this recently rediscovered
species away from New Zealand, and provides evidence of long-distance dispersal
by failed or non-breeders to tropical water...
We present observations of five little-known tubenoses made during a pelagic expedition from Vanuatu to New Ireland, Melanesia, in January 2017: Beck's Petrel Pseudobulweria becki, an all-dark Pseudobulweria, Magnificent Petrel Pterodroma (brevipes) magnificens, Vanuatu Petrel P. (cervicalis) occulta and Heinroth's Shearwater Puffinus heinrothi. Ou...
This report summarises our observations of seabirds seen during an expedition from Chile to the Juan Fernández archipelago and return, with six days in the Humboldt Current. Observations are summarised by marine habitat – Humboldt Current, oceanic passages between the Humboldt Current and the Juan Fernández archipelago, and waters around the Juan F...
Infection with herpes simplex virus-1 (HSV-1) brings numerous changes in cellular gene expression. Levels of most host mRNAs are reduced, limiting synthesis of host proteins, especially those involved in antiviral defenses. The impact of HSV-1 on host microRNAs (miRNAs), an extensive network of short non-coding RNAs that regulate mRNA stability/tra...
What exactly is a 'blue' fulmar? Angus Wilson and Bob Flood examine the continuing mysteries of plumage colour morphs in one of our most familiar yet enigmatic seabirds.
Herpes simplex virus 1 (HSV-1) uses latency in peripheral ganglia to persist in its human host, however, recurrent reactivation from this reservoir can cause debilitating and potentially life-threatening disease. Most studies of latency use live-animal infection models, but these are complex, multilayered systems and can be difficult to manipulate....
How type I and II interferons prevent periodic reemergence of latent pathogens in tissues of diverse cell types remains unknown. Using homogeneous neuron cultures latently infected with herpes simplex virus 1, we show that extrinsic type I or II interferon acts directly on neurons to induce unique gene expression signatures and inhibit the reactiva...
Herpes simplex virus type (HSV) establishes a latent reservoir in neurons of human peripheral nerves. In this quiescent state the viral genome persists as a circular, histone-associated episome and transcription of viral lytic-cycle genes is largely suppressed through epigenetic processes. Periodically latent virus undergoes reactivation whereby ly...
We describe a primary neuronal culture system suitable for molecular characterization of herpes simplex virus type 1 (HSV-1) infection, latency, and reactivation. While several alternative models are available, including infections of live animal and explanted ganglia, these are complicated by the presence of multiple cell types, including immune c...
To facilitate studies of herpes simplex virus 1 latency, cell culture models of quiescent or latent infection have been developed.
Using deep sequencing, we analyzed the expression of viral microRNAs (miRNAs) in two models employing human fibroblasts and
one using rat neurons. In all cases, the expression patterns differed from that in productively...
After replicating in surface epithelia, herpes simplex virus type-1 (HSV-1) enters the axonal terminals of peripheral neurons. The viral genome translocates to the nucleus, where it establishes a specialized infection known as latency, re-emerging periodically to seed new infections. Studies using cultured neuron models that faithfully recapitulate...
Latent herpes simplex virus-1 (HSV1) genomes in peripheral nerve ganglia periodically reactivate, initiating a gene expression program required for productive replication. Whether molecular cues detected by axons can be relayed to cell bodies and harnessed to regulate latent genome expression in neuronal nuclei is unknown. Using a neuron culture mo...
Herpes simplex virus type-1 (HSV-1) establishes a life-long latent infection in peripheral neurons. This latent reservoir is the source of recurrent reactivation events that ensure transmission and contribute to clinical disease. Current antivirals do not impact the latent reservoir and there are no vaccines. While the molecular details of lytic re...
Nuclear localization of the HCF-1 associated factors Ash2L and LSD1 in HeLa cells and unstimulated SCG neurons. SCG-derived neurons were seeded onto glass coverslips and cultured for 7 days under conditions that support the establishment of HSV-1 latency before being fixed with 4% PFA. After quenching with 100 mM ammonium chloride, the samples were...
Lytic proteins ICP0 and ICP27 are expressed in Phase I and are localized to the nucleus. Week old SCG neuronal cultures were infected with either in1814 (A) or HSV GFP-Us11 (B) at MOI = 1 in the presence of ACV. After one week of establishing latency period, the cultures were induced with media lacking ACV but containing 20 µM LY294002. Samples wer...
Acute replication of HSV-1 in primary rat embryo fibroblasts (REFs). One day before infection, REFs were seeded into 6-well plates at a density of 2.0×105 cells/well. The next day, HSV-1 GFP-Us11 was added at a multiplicity of 3 (MOI = 3) and incubated at 4°C for 1.5 h to promote synchronous infection. The temperature was then shifted to 37°C (time...
VP16 contributes to viral gene expression during Phase II. (A) Time course of viral mRNA accumulation in SCG cultures latently infected with HSV-1 in1814 (MOI = 1) and induced to reactivate with 20 µM LY294002 in media lacking ACV. (B) Quantitative PCR analysis of viral genomic DNA of in1814 or in1814R at 0 or 72 hours in the presence or absence of...
Herpes simplex virus type-1 (HSV-1) establishes latency in peripheral neurons, creating a permanent source of recurrent infections. The latent genome is assembled into chromatin and lytic cycle genes are silenced. Processes that orchestrate reentry into productive replication (reactivation) remain poorly understood. We have used latently infected c...
The four Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded interferon (IFN) regulatory factor homologues (vIRF1 to vIRF4) are used to counter innate immune defenses and suppress p53. The vIRF genes are arranged in tandem but differ in function and expression. In KSHV-infected effusion lymphoma lines, K10.5/vIRF3 and K11/vIRF2 mRNAs are readily...
Reactivation of herpes simplex virus type 1 (HSV-1) in geniculate ganglion neurons (GGNs) is an etiologic mechanism of Bell's palsy (BP) and delayed facial palsy (DFP) after otologic surgery.
Several clinical studies, including temporal bone studies, antibody, titers, and intraoperative studies, suggest that reactivation of HSV-1 from latently infe...
Vestibular neuritis is a common cause of both acute and chronic vestibular dysfunction. Multiple pathologies have been hypothesized to be the causative agent of vestibular neuritis; however, whether herpes simplex type I (HSV1) reactivation occurs within the vestibular ganglion has not been demonstrated previously by experimental evidence. We devel...
Herpes simplex virus-1 (HSV-1) establishes life-long latency in peripheral neurons where productive replication is suppressed. While periodic reactivation results in virus production, the molecular basis of neuronal latency remains incompletely understood. Using a primary neuronal culture system of HSV-1 latency and reactivation, we show that conti...
For Kaposi's sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8 [HHV8]), the switch from latency to active lytic replication requires RTA, the product of open reading frame 50 (ORF50). RTA activates transcription from nearly 40 early and delayed-early viral promoters, mainly through interactions with cellular DNA binding proteins...
Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells express the latency-associated nuclear antigen (LANA) involved in the regulation of host and viral gene expression and maintenance of the KSHV latent episome. Performance of these diverse functions involves a 7-amino-acid chromatin-binding motif (CBM) situated at the amino terminus of LA...
In response to numerous signals, latent herpesvirus genomes abruptly switch their developmental program, aborting stable host-cell colonization in favor of productive viral replication that ultimately destroys the cell. To achieve a rapid gene expression transition, newly minted capped, polyadenylated viral mRNAs must engage and reprogram the cellu...
TPA+DOX treatment of TREx BCBL1-RTA cells results in the production of infectious KSHV particles. A. Using a luciferase reporter cell line to detect infectious KSHV produced by TREx BCBL1-RTA cultures in the presence and absence of inducer. Asynchronous cultures of TREx BCBL1-RTA cells (150 ml total seeded at 2×105 cells /ml) were induced with TPA+...
Protein ubiquitination provides an efficient and reversible mechanism to regulate cell cycle progression and checkpoint control.
Numerous regulatory proteins direct the addition of ubiquitin to lysine residues on target proteins, and these are countered
by an army of deubiquitinating enzymes (DUBs). BRCA1-associated protein-1 (Bap1) is a ubiquitin...
E2F transcription factors control the expression of numerous genes involved in the G1/S cell-cycle transition, initiation of DNA synthesis, and mitosis and also link DNA-damage recognition pathways to key cell-cycle checkpoints (reviewed in Cam and Dynlacht [2003]). Individual E2F proteins can be classified as activators (E2F1, E2F2, and E2F3a) or...
Kaposi's sarcoma-associated herpesvirus (KSHV) maintains a latent infection in primary effusion lymphoma cells but can be induced to enter full lytic replication by exposure to a variety of chemical inducing agents or by expression of the KSHV-encoded replication and transcription activator (RTA) protein. During latency, only a few viral genes are...
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of three malignancies associated with AIDS and immunosuppression.
Tumor cells harbor latent virus and express kaposin (open reading frame [ORF] K12), v-FLIP (ORF 71), v-Cyclin (ORF 72), and
latency-associated nuclear antigen (LANA; ORF 73). ORFs 71 to 73 are transcribed as multic...
Bird identification, vagrancy, shorebirds
During latency, the Kaposi's sarcoma-associated herpesvirus genome is maintained as a circular episome, replicating in synchrony
with host chromosomes. Replication requires the latency-associated nuclear antigen (LANA) and an origin of latent DNA replication
located in the viral terminal repeats, consisting of two LANA binding sites (LBSs) and a GC...
In immunocompromised patients, infection with Kaposi's sarcoma-associated herpesvirus (KSHV) can give rise to Kaposi's sarcoma and several lymphoproliferative disorders. In these tumors, KSHV establishes a latent infection in many of the rapidly proliferating and morphologically abnormal cells. Only a few viral gene products are expressed by the la...
HCF-1 is a transcriptional cofactor required for activation of herpes simplex virus immediate-early genes by VP16 as well as less clearly defined roles in cell proliferation, cytokinesis, and spliceosome formation. It is expressed as a large precursor that undergoes proteolysis to yield two subunits that remain stably associated. VP16 uses a degene...
HCF-1 functions as a coactivator for herpes simplex virus VP16 and a number of mammalian transcription factors. Mature HCF-1 is composed of two subunits generated by proteolytic cleavage of a larger precursor at six centrally-located HCF(PRO) repeats. The resulting N- and C-terminal subunits remain tightly associated via two complementary pairs of...
HCF-1 is a cellular protein required by VP16 to activate the herpes simplex virus (HSV) immediate-early genes. VP16 is a component of the viral tegument and, after release into the cell, binds to HCF-1 and translocates to the nucleus to form a complex with the POU domain protein Oct-1 and a VP16-responsive DNA sequence. This VP16-induced complex bo...
In herpes simplex virus, lytic replication is initiated by the viral transactivator VP16 acting with cellular cofactors Oct-1 and HCF-1. Although this activator complex has been studied in detail, the role of HCF-1 remains elusive. Here, we show that HCF-1 contains an activation domain (HCF-1(AD)) required for maximal transactivation by VP16 and it...
When herpes simplex virus infects permissive cells, the viral regulatory protein VP16 forms a specific complex with HCF-1,
a preexisting nuclear protein involved in cell proliferation. The majority of HCF-1 in the cell is a complex of associated
amino (HCF-1N)- and carboxy (HCF-1C)-terminal subunits that result from an unusual proteolytic processin...
Host Cell Factor-1 (HCF-1, C1) was first identified as a cellular target for the herpes simplex virus transcriptional activator VP16. Association between HCF and VP16 leads to the assembly of a multiprotein enhancer complex that stimulates viral immediate-early gene transcription. HCF-1 is expressed in all cells and is required for progression thro...
Human herpesvirus 8 (HHV-8; also known as Kaposi's sarcoma-associated herpesvirus) is the causative agent of Kaposi's sarcoma and certain B-cell lymphomas. In most infected cells, HHV-8 establishes a latent infection characterized by the expression of latency-associated nuclear antigen (LANA) encoded by open reading frame 73. Although unrelated by...
Host cell factor 1 (HCF-1) is a nuclear protein required for progression through G1 phase of the cell cycle and, via its association with VP16, transcriptional activation of the herpes simplex virus immediate-early
genes. Both functions require a six-bladed β-propeller domain encoded by residues 1 to 380 of HCF-1 as well as an additional
amino-term...
Herpes simplex virus infection is initiated by VP16, a viral transcription factor that activates the viral immediate-early (IE) genes. VP16 does not recognize the IE gene promoters directly but instead forms a multiprotein complex with Oct-1 and HCF-1, a ubiquitous nuclear protein required for progression through the G1 phase of the cell cycle. The...
The herpes simplex virus (HSV) regulatory protein VP16 activates HSV immediate-early gene transcription through formation
of a multiprotein-DNA complex on viral promoters that includes the preexisting nuclear proteins HCF and Oct-1. The HCF protein
is a complex of amino- and carboxy-terminal polypeptides derived from a large (approximately 2,000-am...
The temperature-sensitive BHK21 hamster cell line tsBN67 ceases to proliferate at the nonpermissive temperature after a lag of one to a few cell divisions, and the arrested cells display a gene expression pattern similar to that of serum-starved cells. The temperature-sensitive phenotype is reversible and results from a single missense mutation--pr...
![Figure 3. Proteolytic cleavage requires the HCF repeats. (A] The rHCF...](profile/Angus-Wilson-2/publication/15609363/figure/fig2/AS:601690722009093@1520465655143/Proteolytic-cleavage-requires-the-HCF-repeats-A-The-rHCF-ORF-and-derivatives-are-shown_Q320.jpg)
The herpes simplex virus VP16-associated protein HCF is a nuclear host-cell factor that exists as a family of polypeptides encoded by a single gene. The mature HCF polypeptides are amino- and carboxy-terminal fragments of a large approximately 300-kD precursor protein that arise through cleavage at one or more centrally located sites. The sites of...
After herpes simplex virus (HSV) infection, the viral regulatory protein VP16 activates transcription of the HSV immediate-early promoters by directing complex formation with two cellular proteins, the POU-homeo-domaintranscription factor Oct-1 and the host cell factor HCF. The function of HCF in uninfected cells is unknown. Here we show by fluores...
We demonstrate a general role for DNA replication in the activation of gene transcription in transient transfectlon assays.
The effect is observed for a wide range of genes and cell types, transfected by a number of protocols and is independent of
increased template copy number. Replication does not stimulate transcription driven by proximal promot...
Upon lytic infection of permissive cells, the herpes simplex virus (HSV) transactivator protein VP16 associates with an accessory protein termed host cell factor (HCF). Binding to HCF activates VP16 for association with the octamer motif-binding protein Oct-1, to form a multiprotein-DNA complex responsible for activating transcription of the HSV im...
Excerpt
Common features of transcriptional regulation in multicellular organisms are the modular and combinatorial structure of cis-acting DNA sequences and trans-acting proteins. Promoters represent the cis-acting regulatory elements and consist of proximal and basal elements positioned near the transcriptional initiation site and enhancers, which...
The short-term expression of DNA introduced into eukaryotic cells is now widely used to investigate the biological activities of cellular and viral genes or their products. A number of different transfection methods are in common use and can be broadly divided into two categories, based on the method by which DNA is introduced (either as a complex...
Comparative protein binding studies have been performed on the Xenopus beta globin gene promoter. Erythroblast nuclear extracts 'footprint' over the erythroid-specific consensus sequence, AGGATAAG, which is located immediately upstream of the CCAAT footprint. Nonerythroid cell extracts do not give rise to an AGGATAAG footprint but rather to an exte...
Questions
Question (1)
*Avian influenza and the boundaries of acceptable research*
Being a scientist is all about making informed judgements: what experiments to do, what ideas to develop, what will push the boundaries of knowledge in the most effective way. This is something we do every day as part of our own research and as mentors, referees of research papers and of course, as grant reviewers.
The current fierce debate about the ethics of engineering variants of avian influenza [A/H5N1] that can transmit more efficiently in mammals seems to be very much about this fundamental question of priorities. It involves judgements about the types of knowledge want to have, how best to go about getting that knowledge and where to draw a line in terms of benefits versus risks.
When this story first broke, I read an editorial in the New York Times (8 Jan 2012) that came down firmly on the side of banning further research of this kind and supported the idea of limiting the specific information that could be published. The paragraph that jarred the most was the following
"We nearly always champion unfettered scientific research and open publication of the results. In this case it looks like the research should never have been undertaken because the potential harm is so catastrophic and the potential benefits from studying the virus so speculative."
I thought to myself, who are they [a newspaper] to judge the benefits of the findings? Obviously these are very complicated matters with much at stake but this seems a good example of the problem we face as a ever curious species. I feel the same way when reviewing research papers and grants. Shouldn't we just limit ourselves to judging whether the approach is the best one to answer a question rather than question the question?
The discourse among the many experts on this avian flu debate is heating up in the scientific journals and more thoughtful newspapers including the NY Times. To have an open discussion of this nature seems like a very good thing and it will be interesting to watch how it all shakes out.
