title: Bitcoin forks: What drives the branches?

authors: Conlon, Thomas

abstract: Despite frequent Blockchain splits stemming from Bitcoin, few studies have examined the determinants of Bitcoin fork returns. In this paper, we investigate the relationships between the returns of Bitcoin forks and a range of common risk factors, including Bitcoin, currency, network and equity-based factors. From a statistical perspective, we find consistent and significant associations between fork returns, their Bitcoin counterparts, and equity markets. Other common factors, such as the equity small-minus-big factor and changes in the Japanese Yen, are found to have occasional links with fork returns. From an economic perspective, Bitcoin returns are the predominant driver of fork returns, accounting for essentially all of the explained variation. These findings are confirmed using orthogonalised common factors and with an alternative methodology, quantile regression. This research broadens our understanding of Bitcoin forks, indicating that a change in blockchain protocol is insufficient to sever links with the Bitcoin parent.

text: Bitcoin forks: What drives the branches? Despite frequent Blockchain splits stemming from Bitcoin, few studies have examined the determinants of Bitcoin fork returns. In this paper, we investigate the relationships between the returns of Bitcoin forks and a range of common risk factors, including Bitcoin, currency, network and equity-based factors. From a statistical perspective, we find consistent and significant associations between fork returns, their Bitcoin counterparts, and equity markets. Other common factors, such as the equity small-minus-big factor and changes in the Japanese Yen, are found to have occasional links with fork returns. From an economic perspective, Bitcoin returns are the predominant driver of fork returns, accounting for essentially all of the explained variation. These findings are confirmed using orthogonalised common factors and with an alternative methodology, quantile regression. This research broadens our understanding of Bitcoin forks, indicating that a change in blockchain protocol is insufficient to sever links with the Bitcoin parent.

year: 2024

title: Improving bovine donor cell culture conditions for embryo-derived cell transfer cloning

authors: Wilson, Shaan Harker

subjects: Cells

abstract: Cloning by cell transfer offers an efficient method for increasing genetic gain in livestock populations. High-quality genes are routinely induced into embryos with artificial selection-based in vitro fertilisation, or genetic engineering using microinjection. The capacity for large-scale amplification of these superior genes with cell culture is unique to cloning due to its ability to use a single cultured cell as a donor for producing new embryos. Thus, cell transfer cloning could become the primary tool for genetic advancement in the livestock industry if its application is improved. Currently, cell transfer cloning is inefficient in producing viable offspring that survive to term compared to methods such as in vitro production. This is largely caused by epigenetic modifications that arise from the donor cell and the epigenetic abnormalities carried over to the blastocyst generated. Cloning with pluripotent embryonic cells rather than the more widely researched somatic cells may remediate cases of genetic abnormalities. Pluripotent embryo-derived cells are less differentiated than their somatic cell counterparts and can generate cell types from all three of the germ layers, requiring much less reprogramming by the cytoplast. However, the elucidation of optimal conditions to culture pluripotent embryo-derived cells has proved challenging. The primary aim of this research project was to advance methodologies involved in the culture of pluripotent embryo-derived cells in order to increase the efficiency of cell transfer cloning. 
A series of comparative culture experiments were executed on blastocysts produced through in vitro generation. Experiments focused on the effect of substrate and selection of media components on the generation of an embryo-derived outgrowth. Substrate implementation was found to be essential to initial outgrowth generation as well as further growth. Minimal media with cytokines and small molecules removed was unable to produce outgrowths, indicating the importance of the small molecules and cytokines in attachment, cell proliferation, and survival. Immunofluorescent assays were completed on outgrowths to demonstrate proliferation and cell type markers. Pluripotency marker OCT4 was found in 48% of cell nuclei stained 4 days after plating and in 5% of those stained on day 6. Hypoblast marker Gata6 was not detected in any of the outgrowth cells. The DNA synthesis marker EdU was incorporated into the DNA of 49% of cells after 30 min, which is highly relevant to cloning as donors in S-phase are incompatible with the MII arrested cytoplasts used. 
A robust protocol was formed for generating outgrowths from bovine blastocysts. Outgrowths demonstrated proliferation and presence of pluripotency markers was illustrated. Cell transfer cloning was completed successfully using embryo-derived donor cells. However, exact donor cell conditions for improved cell transfer efficiency were not elucidated. Further cell transfer experiments should be conducted with a range of donor cell conditions. Karyotyping of the embryos produced would be required before any in vivo implantation of blastocysts into recipients is attempted.

text: Improving bovine donor cell culture conditions for embryo-derived cell transfer cloning Cloning by cell transfer offers an efficient method for increasing genetic gain in livestock populations. High-quality genes are routinely induced into embryos with artificial selection-based in vitro fertilisation, or genetic engineering using microinjection. The capacity for large-scale amplification of these superior genes with cell culture is unique to cloning due to its ability to use a single cultured cell as a donor for producing new embryos. Thus, cell transfer cloning could become the primary tool for genetic advancement in the livestock industry if its application is improved. Currently, cell transfer cloning is inefficient in producing viable offspring that survive to term compared to methods such as in vitro production. This is largely caused by epigenetic modifications that arise from the donor cell and the epigenetic abnormalities carried over to the blastocyst generated. Cloning with pluripotent embryonic cells rather than the more widely researched somatic cells may remediate cases of genetic abnormalities. Pluripotent embryo-derived cells are less differentiated than their somatic cell counterparts and can generate cell types from all three of the germ layers, requiring much less reprogramming by the cytoplast. However, the elucidation of optimal conditions to culture pluripotent embryo-derived cells has proved challenging. The primary aim of this research project was to advance methodologies involved in the culture of pluripotent embryo-derived cells in order to increase the efficiency of cell transfer cloning. 
A series of comparative culture experiments were executed on blastocysts produced through in vitro generation. Experiments focused on the effect of substrate and selection of media components on the generation of an embryo-derived outgrowth. Substrate implementation was found to be essential to initial outgrowth generation as well as further growth. Minimal media with cytokines and small molecules removed was unable to produce outgrowths, indicating the importance of the small molecules and cytokines in attachment, cell proliferation, and survival. Immunofluorescent assays were completed on outgrowths to demonstrate proliferation and cell type markers. Pluripotency marker OCT4 was found in 48% of cell nuclei stained 4 days after plating and in 5% of those stained on day 6. Hypoblast marker Gata6 was not detected in any of the outgrowth cells. The DNA synthesis marker EdU was incorporated into the DNA of 49% of cells after 30 min, which is highly relevant to cloning as donors in S-phase are incompatible with the MII arrested cytoplasts used. 
A robust protocol was formed for generating outgrowths from bovine blastocysts. Outgrowths demonstrated proliferation and presence of pluripotency markers was illustrated. Cell transfer cloning was completed successfully using embryo-derived donor cells. However, exact donor cell conditions for improved cell transfer efficiency were not elucidated. Further cell transfer experiments should be conducted with a range of donor cell conditions. Karyotyping of the embryos produced would be required before any in vivo implantation of blastocysts into recipients is attempted.

year: 2021

title: Indigenous perspectives and gene editing in Aotearoa New Zealand

authors: Hudson, Maui

subjects: Science & Technology

abstract: Gene editing is arguably the most significant recent addition to the modern biotechnology toolbox, bringing both profoundly challenging and enabling opportunities. From a technical point of view the specificity and relative simplicity of these new tools has broadened the potential applications. However, from an ethical point of view it has re-ignited the debates generated by earlier forms of genetic modification. In New Zealand gene editing is currently considered genetic modification and is subject to approval processes under the Environmental Protection Authority (EPA). This process requires decision makers to take into account Māori perspectives. This article outlines previously articulated Māori perspectives on genetic modification and considers the continuing influence of those cultural and ethical arguments within the new context of gene editing. It also explores the range of ways cultural values might be used to analyse the risks and benefits of gene editing in the Aotearoa New Zealand context. Methods used to obtain these perspectives consisted of (a) review of relevant literature regarding lessons learned from the responses of Maori to genetic modification, (b) interviews of selected ‘key Maori informants’ and (c) surveys of self-selected individuals from groups with interests in either genetics or environmental management. The outcomes of this pilot study identified that while Māori informants were not categorically opposed to new and emerging gene editing technologies a priori, they suggest a dynamic approach to regulation is required where specific uses or types of uses are approved on a case by case basis. This study demonstrates how the cultural cues that Māori referenced in the genetic modification debate continue to be relevant in the context of gene editing but that further work is required to characterize the strength of various positions across the broader community.

text: Indigenous perspectives and gene editing in Aotearoa New Zealand Gene editing is arguably the most significant recent addition to the modern biotechnology toolbox, bringing both profoundly challenging and enabling opportunities. From a technical point of view the specificity and relative simplicity of these new tools has broadened the potential applications. However, from an ethical point of view it has re-ignited the debates generated by earlier forms of genetic modification. In New Zealand gene editing is currently considered genetic modification and is subject to approval processes under the Environmental Protection Authority (EPA). This process requires decision makers to take into account Māori perspectives. This article outlines previously articulated Māori perspectives on genetic modification and considers the continuing influence of those cultural and ethical arguments within the new context of gene editing. It also explores the range of ways cultural values might be used to analyse the risks and benefits of gene editing in the Aotearoa New Zealand context. Methods used to obtain these perspectives consisted of (a) review of relevant literature regarding lessons learned from the responses of Maori to genetic modification, (b) interviews of selected ‘key Maori informants’ and (c) surveys of self-selected individuals from groups with interests in either genetics or environmental management. The outcomes of this pilot study identified that while Māori informants were not categorically opposed to new and emerging gene editing technologies a priori, they suggest a dynamic approach to regulation is required where specific uses or types of uses are approved on a case by case basis. This study demonstrates how the cultural cues that Māori referenced in the genetic modification debate continue to be relevant in the context of gene editing but that further work is required to characterize the strength of various positions across the broader community.

year: 2019