title: Drug delivery by electroporation: Review

authors: Talele, Sadhana

subjects: Cancerous tissues

abstract: Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Most common routes of administration include the preferred non-invasive peroral (through the mouth), topical (skin), transmucosal (nasal, buccal/sublingual, vaginal, ocular and rectal) and inhalation routes. Current effort in the area of drug delivery include the development of targeted delivery in which the drug is only active in the target area of the body (for example, in cancerous tissues) and sustained release formulations in which the drug is released over a period of time in a controlled manner from a formulation. This is achieved by combining electroporation with the input of drugs at a location. This paper reviews the process of electroporation and then further discusses the electrochemotherapy, one of the most upcoming application of electroporation in biotechnology.

text: Drug delivery by electroporation: Review Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Most common routes of administration include the preferred non-invasive peroral (through the mouth), topical (skin), transmucosal (nasal, buccal/sublingual, vaginal, ocular and rectal) and inhalation routes. Current effort in the area of drug delivery include the development of targeted delivery in which the drug is only active in the target area of the body (for example, in cancerous tissues) and sustained release formulations in which the drug is released over a period of time in a controlled manner from a formulation. This is achieved by combining electroporation with the input of drugs at a location. This paper reviews the process of electroporation and then further discusses the electrochemotherapy, one of the most upcoming application of electroporation in biotechnology.

year: 2013

title: The Structure of the Oligomerization Domain of Lsr2 from Mycobacterium tuberculosis Reveals a Mechanism for Chromosome Organization and Protection

authors: Summers, Emma Louise

subjects: Science & Technology

abstract: Lsr2 is a small DNA-binding protein present in mycobacteria and related actinobacteria that regulates gene expression and influences the organization of bacterial chromatin. Lsr2 is a dimer that binds to AT-rich regions of chromosomal DNA and physically protects DNA from damage by reactive oxygen intermediates (ROI). A recent structure of the C-terminal DNAbinding domain of Lsr2 provides a rationale for its interaction with the minor groove of DNA, its preference for AT-rich tracts, and its similarity to other bacterial nucleoid-associated DNA-binding domains. In contrast, the details of Lsr2 dimerization (and oligomerization) via its N-terminal domain, and the mechanism of Lsr2-mediated chromosomal crosslinking and protection is unknown. We have solved the structure of the N-terminal domain of Lsr2 (N-Lsr2) at 1.73 A˚ resolution using crystallographic ab initio approaches. The structure shows an intimate dimer of two ß–ß–a motifs with no close homologues in the structural databases. The organization of individual N-Lsr2 dimers in the crystal also reveals a mechanism for oligomerization. Proteolytic removal of three N-terminal residues from Lsr2 results in the formation of an anti-parallel b-sheet between neighboring molecules and the formation of linear chains of N-Lsr2. Oligomerization can be artificially induced using low concentrations of trypsin and the arrangement of N-Lsr2 into long chains is observed in both monoclinic and hexagonal crystallographic space groups. In solution, oligomerization of N-Lsr2 is also observed following treatment with trypsin. A change in chromosomal topology after the addition of trypsin to full-length Lsr2-DNA complexes and protection of DNA towards DNAse digestion can be observed using electron microscopy and electrophoresis. These results suggest a mechanism for oligomerization of Lsr2 via protease-activation leading to chromosome compaction and protection, and concomitant down-regulation of large numbers of genes. This mechanism is likely to be relevant under conditions of stress where cellular proteases are known to be upregulated.

text: The Structure of the Oligomerization Domain of Lsr2 from Mycobacterium tuberculosis Reveals a Mechanism for Chromosome Organization and Protection Lsr2 is a small DNA-binding protein present in mycobacteria and related actinobacteria that regulates gene expression and influences the organization of bacterial chromatin. Lsr2 is a dimer that binds to AT-rich regions of chromosomal DNA and physically protects DNA from damage by reactive oxygen intermediates (ROI). A recent structure of the C-terminal DNAbinding domain of Lsr2 provides a rationale for its interaction with the minor groove of DNA, its preference for AT-rich tracts, and its similarity to other bacterial nucleoid-associated DNA-binding domains. In contrast, the details of Lsr2 dimerization (and oligomerization) via its N-terminal domain, and the mechanism of Lsr2-mediated chromosomal crosslinking and protection is unknown. We have solved the structure of the N-terminal domain of Lsr2 (N-Lsr2) at 1.73 A˚ resolution using crystallographic ab initio approaches. The structure shows an intimate dimer of two ß–ß–a motifs with no close homologues in the structural databases. The organization of individual N-Lsr2 dimers in the crystal also reveals a mechanism for oligomerization. Proteolytic removal of three N-terminal residues from Lsr2 results in the formation of an anti-parallel b-sheet between neighboring molecules and the formation of linear chains of N-Lsr2. Oligomerization can be artificially induced using low concentrations of trypsin and the arrangement of N-Lsr2 into long chains is observed in both monoclinic and hexagonal crystallographic space groups. In solution, oligomerization of N-Lsr2 is also observed following treatment with trypsin. A change in chromosomal topology after the addition of trypsin to full-length Lsr2-DNA complexes and protection of DNA towards DNAse digestion can be observed using electron microscopy and electrophoresis. These results suggest a mechanism for oligomerization of Lsr2 via protease-activation leading to chromosome compaction and protection, and concomitant down-regulation of large numbers of genes. This mechanism is likely to be relevant under conditions of stress where cellular proteases are known to be upregulated.

year: 2012-06-13

title: Māori transitions into tertiary education

authors: Amundsen, Diana Leigh

subjects: Maori

abstract: This thesis critically examines Māori transitions into tertiary education. The research explored the lived transition experiences of 20 Māori tertiary education students in the Bay of Plenty region. Historical and contemporary factors in Aotearoa influencing effective Māori student transitions into tertiary education were investigated. Data were collected and analysed through repeated semistructured interviews and focus groups over the 2016-2018 period with 20 Māori students enrolled in a wānanga, a polytechnic and a university. Participants experienced their transition as a journey, continuously evolving their identities and agency in relation to the tertiary education environments and social structures they encountered.
The findings suggest that transitions to tertiary education for Māori students involve a reciprocal interplay of identity, agency and structure which support or constrain transition experiences. Effective transition experiences were underpinned by processes of continuity enabling identity growth. Support was central to how well participants perceived their transition—racism and lack of support were significant barriers; suitable support was a significant enabler.
An over-riding theme from this research related to the interplay of power relations and Māori identity. How effectively participants developed a sense of belonging (or alienation) and identity growth linked to the tertiary education environments they encountered during their transition. Within wānanga, participants felt their Māori cultural identity was highly valued; within polytechnics, there was a sense that Māori culture is included but more could be done; within universities, a need for more inclusive practices to support Māori learner requirements was identified.
Lastly, this research was conducted by a Pākehā researcher working across kaupapa Māori spaces within interpretive and critical paradigms. Unexpected moments of struggle, discomfort and vulnerability opened up new and deeper understanding of implications for Pākehā educators and researchers engaging across Māori research spaces. This thesis argues for Pākehā to use their privilege to foster more equitable social structures. Equitable social structures would be beneficial for Māori transitions into tertiary education environments.

text: Māori transitions into tertiary education This thesis critically examines Māori transitions into tertiary education. The research explored the lived transition experiences of 20 Māori tertiary education students in the Bay of Plenty region. Historical and contemporary factors in Aotearoa influencing effective Māori student transitions into tertiary education were investigated. Data were collected and analysed through repeated semistructured interviews and focus groups over the 2016-2018 period with 20 Māori students enrolled in a wānanga, a polytechnic and a university. Participants experienced their transition as a journey, continuously evolving their identities and agency in relation to the tertiary education environments and social structures they encountered.
The findings suggest that transitions to tertiary education for Māori students involve a reciprocal interplay of identity, agency and structure which support or constrain transition experiences. Effective transition experiences were underpinned by processes of continuity enabling identity growth. Support was central to how well participants perceived their transition—racism and lack of support were significant barriers; suitable support was a significant enabler.
An over-riding theme from this research related to the interplay of power relations and Māori identity. How effectively participants developed a sense of belonging (or alienation) and identity growth linked to the tertiary education environments they encountered during their transition. Within wānanga, participants felt their Māori cultural identity was highly valued; within polytechnics, there was a sense that Māori culture is included but more could be done; within universities, a need for more inclusive practices to support Māori learner requirements was identified.
Lastly, this research was conducted by a Pākehā researcher working across kaupapa Māori spaces within interpretive and critical paradigms. Unexpected moments of struggle, discomfort and vulnerability opened up new and deeper understanding of implications for Pākehā educators and researchers engaging across Māori research spaces. This thesis argues for Pākehā to use their privilege to foster more equitable social structures. Equitable social structures would be beneficial for Māori transitions into tertiary education environments.

year: 2019