The concentration of ethanol affects its penetration rate in bovine cardiac and hepatic tissues
- Dunster-Jones, Matthew, Steicke, Michelle, Mackie, James, Guthrie, Rachel, Dinh, Tam, Ahmady, Fahima, Golledge, Jonathan, Wang, Yutang
- Authors: Dunster-Jones, Matthew , Steicke, Michelle , Mackie, James , Guthrie, Rachel , Dinh, Tam , Ahmady, Fahima , Golledge, Jonathan , Wang, Yutang
- Date: 2018
- Type: Text , Journal article
- Relation: Folia Histochemica et Cytobiologica Vol. 56, no. 2 (2018), p. 92-97
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Introduction. Ethanol is a commonly used fixative. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether the concentration of ethanol affects its penetration into tissues. This study aimed to compare the penetration rates of 50% and 100% ethanol into bovine heart and liver tissues. Materials and methods. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of the heart and liver tissues before and after immersion in ethanol at 20°C for 2, 6, 24 or 30 hours. The penetration coefficients were calculated as the slope of the regression line using the linear regression function between the penetration distance and square root of fixation time. Differences in tissue shrinkage or expansion and penetration distance at various time points between the two concentrations of ethanol were analysed using a mixed design ANOVA followed by Bonferroni’s post-hoc test. Results. The penetration distance of 100% ethanol was significantly greater in both heart and liver tissues compared with that of 50% ethanol (n = 4, p < 0.05 for both). 100% ethanol shrank immersed liver tissue significantly more than 50% ethanol (p = 0.002), but the shrinkage of the heart tissue caused by two concentrations of ethanol did not significantly differ (p = 0.054). The greater penetration distance of 100% over 50% ethanol remained unchanged after normalising the penetration distance to the individual tissue’s shrinkage (n = 4, p < 0.001). The mean penetration coefficient of 100% ethanol was significantly greater than 50% ethanol in the heart tissue (0.906 vs. 0.442, p = 0.003) and in the liver tissue (0.988 vs. 0.622, p = 0.028). Conclusions. It was proven that in two types of tissue that substantially differ in histological structures, 100% ethanol penetrated tissue significantly faster than 50% ethanol.
- Authors: Dunster-Jones, Matthew , Steicke, Michelle , Mackie, James , Guthrie, Rachel , Dinh, Tam , Ahmady, Fahima , Golledge, Jonathan , Wang, Yutang
- Date: 2018
- Type: Text , Journal article
- Relation: Folia Histochemica et Cytobiologica Vol. 56, no. 2 (2018), p. 92-97
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Introduction. Ethanol is a commonly used fixative. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether the concentration of ethanol affects its penetration into tissues. This study aimed to compare the penetration rates of 50% and 100% ethanol into bovine heart and liver tissues. Materials and methods. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of the heart and liver tissues before and after immersion in ethanol at 20°C for 2, 6, 24 or 30 hours. The penetration coefficients were calculated as the slope of the regression line using the linear regression function between the penetration distance and square root of fixation time. Differences in tissue shrinkage or expansion and penetration distance at various time points between the two concentrations of ethanol were analysed using a mixed design ANOVA followed by Bonferroni’s post-hoc test. Results. The penetration distance of 100% ethanol was significantly greater in both heart and liver tissues compared with that of 50% ethanol (n = 4, p < 0.05 for both). 100% ethanol shrank immersed liver tissue significantly more than 50% ethanol (p = 0.002), but the shrinkage of the heart tissue caused by two concentrations of ethanol did not significantly differ (p = 0.054). The greater penetration distance of 100% over 50% ethanol remained unchanged after normalising the penetration distance to the individual tissue’s shrinkage (n = 4, p < 0.001). The mean penetration coefficient of 100% ethanol was significantly greater than 50% ethanol in the heart tissue (0.906 vs. 0.442, p = 0.003) and in the liver tissue (0.988 vs. 0.622, p = 0.028). Conclusions. It was proven that in two types of tissue that substantially differ in histological structures, 100% ethanol penetrated tissue significantly faster than 50% ethanol.
The penetration of methanol into bovine cardiac and hepatic tissues is faster than ethanol and formalin
- Steicke, Michelle, Yang, Guang, Dinh, Tam, Dunster-Jones, Matthew, Sargisson, Owen, Ahmady, Farah, Golledge, Jonathan, Wang, Yutang
- Authors: Steicke, Michelle , Yang, Guang , Dinh, Tam , Dunster-Jones, Matthew , Sargisson, Owen , Ahmady, Farah , Golledge, Jonathan , Wang, Yutang
- Date: 2018
- Type: Text , Journal article
- Relation: European Journal of Histochemistry Vol. 62, no. 1 (2018), p. 98-104
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Methanol, ethanol and formalin are commonly used as fixatives to preserve biological tissues from decay in the preparation of histological sections. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether methanol penetrates tissues at similar rates to other fixatives. This study aimed to compare the penetration rates of methanol, ethanol and formalin into bovine heart and liver tissues. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of tissue before and after immersion in different fixatives for 1, 2, 6 or 10 h. Data were analysed using two-way ANOVA, followed by Bonferroni’s post-hoc test. The penetration distance of methanol was significantly greater in both heart and liver tissues compared with that of ethanol (N=4, P<0.001). Methanol or ethanol immersion led to similar shrinkage of both tissues (P>0.05). The penetration rate of formalin was similar to that of ethanol in both tissues however it was significantly slower than methanol (N=4, P<0.005 in the heart; P<0.001 in the liver). The mean penetration coefficients of methanol, formalin and ethanol in the heart tissue were 2.609, 1.994 and 1.801, respectively, and 3.012, 2.153 and 2.113, respectively, in the liver tissue. The penetration coefficient of methanol was significantly greater than that of ethanol or formalin in both tissues (P<0.001 for each comparison). In conclusion, methanol penetrates tissue significantly faster than ethanol and formalin.
- Authors: Steicke, Michelle , Yang, Guang , Dinh, Tam , Dunster-Jones, Matthew , Sargisson, Owen , Ahmady, Farah , Golledge, Jonathan , Wang, Yutang
- Date: 2018
- Type: Text , Journal article
- Relation: European Journal of Histochemistry Vol. 62, no. 1 (2018), p. 98-104
- Relation: http://purl.org/au-research/grants/nhmrc/1062671
- Full Text:
- Reviewed:
- Description: Methanol, ethanol and formalin are commonly used as fixatives to preserve biological tissues from decay in the preparation of histological sections. Fixation of the inner layers of the tissue depends on the ability of the fixative to diffuse into the tissue. It is unknown whether methanol penetrates tissues at similar rates to other fixatives. This study aimed to compare the penetration rates of methanol, ethanol and formalin into bovine heart and liver tissues. The penetration distance and tissue shrinkage or expansion were measured by analysing the digital images of tissue before and after immersion in different fixatives for 1, 2, 6 or 10 h. Data were analysed using two-way ANOVA, followed by Bonferroni’s post-hoc test. The penetration distance of methanol was significantly greater in both heart and liver tissues compared with that of ethanol (N=4, P<0.001). Methanol or ethanol immersion led to similar shrinkage of both tissues (P>0.05). The penetration rate of formalin was similar to that of ethanol in both tissues however it was significantly slower than methanol (N=4, P<0.005 in the heart; P<0.001 in the liver). The mean penetration coefficients of methanol, formalin and ethanol in the heart tissue were 2.609, 1.994 and 1.801, respectively, and 3.012, 2.153 and 2.113, respectively, in the liver tissue. The penetration coefficient of methanol was significantly greater than that of ethanol or formalin in both tissues (P<0.001 for each comparison). In conclusion, methanol penetrates tissue significantly faster than ethanol and formalin.
Specific humoral response of hosts with variable schistosomiasis susceptibility
- Driguez, Patrick, McWilliam, Hamish, Gaze, Soraya, Piedrafita, David, Pearson, Mark, Nakajima, Rie, Duke, Mary, Trieu, Angela, Doolan, Denise, Cardoso, Fernanda, Jasinskas, Algis, Gobert, Geoffrey, Felgner, Philip, Loukas, Alex, Meeusen, Els, McManus, Donald
- Authors: Driguez, Patrick , McWilliam, Hamish , Gaze, Soraya , Piedrafita, David , Pearson, Mark , Nakajima, Rie , Duke, Mary , Trieu, Angela , Doolan, Denise , Cardoso, Fernanda , Jasinskas, Algis , Gobert, Geoffrey , Felgner, Philip , Loukas, Alex , Meeusen, Els , McManus, Donald
- Date: 2016
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 94, no. 1 (2016), p. 52-65
- Full Text:
- Reviewed:
- Description: The schistosome blood flukes are some of the largest global causes of parasitic morbidity. Further study of the specific antibody response during schistosomiasis may yield the vaccines and diagnostics needed to combat this disease. Therefore, for the purposes of antigen discovery, sera and antibody-secreting cell (ASC) probes from semi-permissive rats and sera from susceptible mice were used to screen a schistosome protein microarray. Following Schistosoma japonicum infection, rats had reduced pathology, increased antibody responses and broader antigen recognition profiles compared with mice. With successive infections, rat global serological reactivity and the number of recognized antigens increased. The local antibody response in rat skin and lung, measured with ASC probes, increased after parasite migration and contributed antigen-specific antibodies to the multivalent serological response. In addition, the temporal variation of anti-parasite serum antibodies after infection and reinfection followed patterns that appear related to the antigen driving the response. Among the 29 antigens differentially recognized by the infected hosts were numerous known vaccine candidates, drug targets and several S. japonicum homologs of human schistosomiasis resistance markers - the tegument allergen-like proteins. From this set, we prioritized eight proteins that may prove to be novel schistosome vaccine and diagnostic antigens. © 2016 Australasian Society for Immunology Inc. All rights reserved.
- Authors: Driguez, Patrick , McWilliam, Hamish , Gaze, Soraya , Piedrafita, David , Pearson, Mark , Nakajima, Rie , Duke, Mary , Trieu, Angela , Doolan, Denise , Cardoso, Fernanda , Jasinskas, Algis , Gobert, Geoffrey , Felgner, Philip , Loukas, Alex , Meeusen, Els , McManus, Donald
- Date: 2016
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 94, no. 1 (2016), p. 52-65
- Full Text:
- Reviewed:
- Description: The schistosome blood flukes are some of the largest global causes of parasitic morbidity. Further study of the specific antibody response during schistosomiasis may yield the vaccines and diagnostics needed to combat this disease. Therefore, for the purposes of antigen discovery, sera and antibody-secreting cell (ASC) probes from semi-permissive rats and sera from susceptible mice were used to screen a schistosome protein microarray. Following Schistosoma japonicum infection, rats had reduced pathology, increased antibody responses and broader antigen recognition profiles compared with mice. With successive infections, rat global serological reactivity and the number of recognized antigens increased. The local antibody response in rat skin and lung, measured with ASC probes, increased after parasite migration and contributed antigen-specific antibodies to the multivalent serological response. In addition, the temporal variation of anti-parasite serum antibodies after infection and reinfection followed patterns that appear related to the antigen driving the response. Among the 29 antigens differentially recognized by the infected hosts were numerous known vaccine candidates, drug targets and several S. japonicum homologs of human schistosomiasis resistance markers - the tegument allergen-like proteins. From this set, we prioritized eight proteins that may prove to be novel schistosome vaccine and diagnostic antigens. © 2016 Australasian Society for Immunology Inc. All rights reserved.
High CD26 and low CD94 expression identifies an IL-23 responsive Vδ2+ T Cell subset with a MAIT cell-like transcriptional profile
- Wragg, Kathleen, Tan, Hyon, Kristensen, Anne, Nguyen-Robertson, Catriona, Kelleher, Anthony, Parsons, Matthew, Wheatley, Adam, Berzins, Stuart, Pellicci, Daniel, Kent, Stephen, Juno, Jennifer
- Authors: Wragg, Kathleen , Tan, Hyon , Kristensen, Anne , Nguyen-Robertson, Catriona , Kelleher, Anthony , Parsons, Matthew , Wheatley, Adam , Berzins, Stuart , Pellicci, Daniel , Kent, Stephen , Juno, Jennifer
- Date: 2020
- Type: Text , Journal article
- Relation: Cell Reports Vol. 31, no. 11 (2020), p.
- Full Text:
- Reviewed:
- Description: Vδ2+ T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2+ T cell subsets. Despite distinct antigen specificities, CD26hiCD94lo Vδ2+ cells exhibit substantial similarities to CD26hi mucosal-associated invariant T (MAIT) cells, although CD26− Vδ2+ cells exhibit cytotoxic, effector-like profiles. At birth, the Vδ2+Vγ9+ population is dominated by CD26hiCD94lo cells; during adolescence and adulthood, Vδ2+ cells acquire CD94/NKG2A expression and the relative frequency of the CD26hiCD94lo subset declines. Critically, exposure of the CD26hiCD94lo subset to phosphoantigen in the context of interleukin-23 (IL-23) and CD26 engagement drives the acquisition of a cytotoxic program and concurrent loss of the MAIT cell-like phenotype. The ability to modulate the cytotoxic potential of CD26hiCD94lo Vδ2+ cells, combined with their adenosine-binding capacity, may make them ideal targets for immunotherapeutic expansion and adoptive transfer. Wragg et al. identify a population of human gd T cells with striking similarities to MAIT cells. These cells dominate the cord blood Vd2 population and upregulate an effector-like program upon antigen and IL-23 stimulation, providing a potential mechanism by which cytotoxic Vd2 cells may accumulate during adolescence and adulthood. © 2020
- Description: National Health and Medical Research Council, NHMRC
- Authors: Wragg, Kathleen , Tan, Hyon , Kristensen, Anne , Nguyen-Robertson, Catriona , Kelleher, Anthony , Parsons, Matthew , Wheatley, Adam , Berzins, Stuart , Pellicci, Daniel , Kent, Stephen , Juno, Jennifer
- Date: 2020
- Type: Text , Journal article
- Relation: Cell Reports Vol. 31, no. 11 (2020), p.
- Full Text:
- Reviewed:
- Description: Vδ2+ T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2+ T cell subsets. Despite distinct antigen specificities, CD26hiCD94lo Vδ2+ cells exhibit substantial similarities to CD26hi mucosal-associated invariant T (MAIT) cells, although CD26− Vδ2+ cells exhibit cytotoxic, effector-like profiles. At birth, the Vδ2+Vγ9+ population is dominated by CD26hiCD94lo cells; during adolescence and adulthood, Vδ2+ cells acquire CD94/NKG2A expression and the relative frequency of the CD26hiCD94lo subset declines. Critically, exposure of the CD26hiCD94lo subset to phosphoantigen in the context of interleukin-23 (IL-23) and CD26 engagement drives the acquisition of a cytotoxic program and concurrent loss of the MAIT cell-like phenotype. The ability to modulate the cytotoxic potential of CD26hiCD94lo Vδ2+ cells, combined with their adenosine-binding capacity, may make them ideal targets for immunotherapeutic expansion and adoptive transfer. Wragg et al. identify a population of human gd T cells with striking similarities to MAIT cells. These cells dominate the cord blood Vd2 population and upregulate an effector-like program upon antigen and IL-23 stimulation, providing a potential mechanism by which cytotoxic Vd2 cells may accumulate during adolescence and adulthood. © 2020
- Description: National Health and Medical Research Council, NHMRC
Best practice data life cycle approaches for the life sciences
- Griffin, Philippa, Khadake, Jyoti, LeMay, Kate, Lewis, Suzanna, Orchard, Sandra, Pask, Andrew, Pope, Bernard, Roessner, Ute, Russell, Keith, Seemann, Torsten, Treloar, Andrew, Tyagi, Sonika, Christiansen, Jeffrey, Dayalan, Saravanan, Gladman, Simon, Hangartner, Sandra, Hayden, Helen, Ho, William, Keeble-Gagnère, Gabriel, Korhonen, Pasi, Neish, Peter, Prestes, Priscilla, Richardson, Mark, Watson-Haigh, Nathan, Wyres, Kelly, Young, Neil, Schneider, Maria
- Authors: Griffin, Philippa , Khadake, Jyoti , LeMay, Kate , Lewis, Suzanna , Orchard, Sandra , Pask, Andrew , Pope, Bernard , Roessner, Ute , Russell, Keith , Seemann, Torsten , Treloar, Andrew , Tyagi, Sonika , Christiansen, Jeffrey , Dayalan, Saravanan , Gladman, Simon , Hangartner, Sandra , Hayden, Helen , Ho, William , Keeble-Gagnère, Gabriel , Korhonen, Pasi , Neish, Peter , Prestes, Priscilla , Richardson, Mark , Watson-Haigh, Nathan , Wyres, Kelly , Young, Neil , Schneider, Maria
- Date: 2018
- Type: Text , Journal article
- Relation: F1000 Research Vol. 6, no. (2018), p. 1-28
- Full Text:
- Reviewed:
- Description: Throughout history, the life sciences have been revolutionised by technological advances; in our era this is manifested by advances in instrumentation for data generation, and consequently researchers now routinely handle large amounts of heterogeneous data in digital formats. The simultaneous transitions towards biology as a data science and towards a 'life cycle' view of research data pose new challenges. Researchers face a bewildering landscape of data management requirements, recommendations and regulations, without necessarily being able to access data management training or possessing a clear understanding of practical approaches that can assist in data management in their particular research domain. Here we provide an overview of best practice data life cycle approaches for researchers in the life sciences/bioinformatics space with a particular focus on 'omics' datasets and computer-based data processing and analysis. We discuss the different stages of the data life cycle and provide practical suggestions for useful tools and resources to improve data management practices. © 2018 Griffin PC et al.
- Authors: Griffin, Philippa , Khadake, Jyoti , LeMay, Kate , Lewis, Suzanna , Orchard, Sandra , Pask, Andrew , Pope, Bernard , Roessner, Ute , Russell, Keith , Seemann, Torsten , Treloar, Andrew , Tyagi, Sonika , Christiansen, Jeffrey , Dayalan, Saravanan , Gladman, Simon , Hangartner, Sandra , Hayden, Helen , Ho, William , Keeble-Gagnère, Gabriel , Korhonen, Pasi , Neish, Peter , Prestes, Priscilla , Richardson, Mark , Watson-Haigh, Nathan , Wyres, Kelly , Young, Neil , Schneider, Maria
- Date: 2018
- Type: Text , Journal article
- Relation: F1000 Research Vol. 6, no. (2018), p. 1-28
- Full Text:
- Reviewed:
- Description: Throughout history, the life sciences have been revolutionised by technological advances; in our era this is manifested by advances in instrumentation for data generation, and consequently researchers now routinely handle large amounts of heterogeneous data in digital formats. The simultaneous transitions towards biology as a data science and towards a 'life cycle' view of research data pose new challenges. Researchers face a bewildering landscape of data management requirements, recommendations and regulations, without necessarily being able to access data management training or possessing a clear understanding of practical approaches that can assist in data management in their particular research domain. Here we provide an overview of best practice data life cycle approaches for researchers in the life sciences/bioinformatics space with a particular focus on 'omics' datasets and computer-based data processing and analysis. We discuss the different stages of the data life cycle and provide practical suggestions for useful tools and resources to improve data management practices. © 2018 Griffin PC et al.
Molecular dynamics studies on the buffalo prion protein
- Zhang, Jiapu, Wang, Feng, Chatterjee, Subhojyoti
- Authors: Zhang, Jiapu , Wang, Feng , Chatterjee, Subhojyoti
- Date: 2016
- Type: Text , Journal article
- Relation: Journal of Biomolecular Structure and Dynamics Vol. 34, no. 4 (2016), p. 762-777
- Full Text:
- Reviewed:
- Description: It was reported that buffalo is a low susceptibility species resisting to transmissible spongiform encephalopathies (TSEs) (same as rabbits, horses, and dogs). TSEs, also called prion diseases, are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of species (except for rabbits, dogs, horses, and buffalo), manifesting as scrapie in sheep and goats; bovine spongiform encephalopathy (BSE or "mad-cow" disease) in cattle; chronic wasting disease in deer and elk; and Creutzfeldt-Jakob diseases, Gerstmann-Straüssler-Scheinker syndrome, fatal familial insomnia, and Kulu in humans etc. In molecular structures, these neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrPC), predominantly with α-helices, into insoluble abnormally folded infectious prions (PrPSc), rich in β-sheets. In this article, we studied the molecular structure and structural dynamics of buffalo PrPC (BufPrPC), in order to understand the reason why buffalo is resistant to prion diseases. We first did molecular modeling of a homology structure constructed by one mutation at residue 143 from the NMR structure of bovine and cattle PrP(124-227); immediately we found that for BufPrPC(124-227), there are five hydrogen bonds (HBs) at Asn143, but at this position, bovine/cattle do not have such HBs. Same as that of rabbits, dogs, or horses, our molecular dynamics studies also revealed there is a strong salt bridge (SB) ASP178-ARG164 (O-N) keeping the β2-α2 loop linked in buffalo. We also found there is a very strong HB SER170-TYR218 linking this loop with the C-terminal end of α-helix H3. Other information, such as (i) there is a very strong SB HIS187-ARG156 (N-O) linking α-helices H2 and H1 (if mutation H187R is made at position 187, then the hydrophobic core of PrPC will be exposed (L.H. Zhong (2010). Exposure of hydrophobic core in human prion protein pathogenic mutant H187R. Journal of Biomolecular Structure and Dynamics 28(3), 355-361)), (ii) at D178, there is a HB Y169-D178 and a polar contact R164-D178 for BufPrPC instead of a polar contact Q168-D178 for bovine PrPC (C.J. Cheng, & V. Daggett. (2014). Molecular dynamics simulations capture the misfolding of the bovine prion protein at acidic pH. Biomolecules 4(1), 181-201), (iii) BufPrPC owns three 310 helices at 125-127, 152-156, and in the β2-α2 loop, respectively, and (iv) in the β2-α2 loop, there is a strong π-π stacking and a strong π-cation F175-Y169-R164.(N)NH2, has been discovered. © 2015 Taylor and Francis.
- Authors: Zhang, Jiapu , Wang, Feng , Chatterjee, Subhojyoti
- Date: 2016
- Type: Text , Journal article
- Relation: Journal of Biomolecular Structure and Dynamics Vol. 34, no. 4 (2016), p. 762-777
- Full Text:
- Reviewed:
- Description: It was reported that buffalo is a low susceptibility species resisting to transmissible spongiform encephalopathies (TSEs) (same as rabbits, horses, and dogs). TSEs, also called prion diseases, are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of species (except for rabbits, dogs, horses, and buffalo), manifesting as scrapie in sheep and goats; bovine spongiform encephalopathy (BSE or "mad-cow" disease) in cattle; chronic wasting disease in deer and elk; and Creutzfeldt-Jakob diseases, Gerstmann-Straüssler-Scheinker syndrome, fatal familial insomnia, and Kulu in humans etc. In molecular structures, these neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrPC), predominantly with α-helices, into insoluble abnormally folded infectious prions (PrPSc), rich in β-sheets. In this article, we studied the molecular structure and structural dynamics of buffalo PrPC (BufPrPC), in order to understand the reason why buffalo is resistant to prion diseases. We first did molecular modeling of a homology structure constructed by one mutation at residue 143 from the NMR structure of bovine and cattle PrP(124-227); immediately we found that for BufPrPC(124-227), there are five hydrogen bonds (HBs) at Asn143, but at this position, bovine/cattle do not have such HBs. Same as that of rabbits, dogs, or horses, our molecular dynamics studies also revealed there is a strong salt bridge (SB) ASP178-ARG164 (O-N) keeping the β2-α2 loop linked in buffalo. We also found there is a very strong HB SER170-TYR218 linking this loop with the C-terminal end of α-helix H3. Other information, such as (i) there is a very strong SB HIS187-ARG156 (N-O) linking α-helices H2 and H1 (if mutation H187R is made at position 187, then the hydrophobic core of PrPC will be exposed (L.H. Zhong (2010). Exposure of hydrophobic core in human prion protein pathogenic mutant H187R. Journal of Biomolecular Structure and Dynamics 28(3), 355-361)), (ii) at D178, there is a HB Y169-D178 and a polar contact R164-D178 for BufPrPC instead of a polar contact Q168-D178 for bovine PrPC (C.J. Cheng, & V. Daggett. (2014). Molecular dynamics simulations capture the misfolding of the bovine prion protein at acidic pH. Biomolecules 4(1), 181-201), (iii) BufPrPC owns three 310 helices at 125-127, 152-156, and in the β2-α2 loop, respectively, and (iv) in the β2-α2 loop, there is a strong π-π stacking and a strong π-cation F175-Y169-R164.(N)NH2, has been discovered. © 2015 Taylor and Francis.
B-type lamins in health and disease
- Authors: Hutchison, Chris
- Date: 2014
- Type: Text , Journal article
- Relation: Seminars in Cell and Developmental Biology Vol. 29, no. (2014), p. 158-163
- Full Text:
- Reviewed:
- Description: For over two decades, B-type lamins were thought to have roles in fundamental processes including correct assembly of nuclear envelopes, DNA replication, transcription and cell survival. Recent studies have questioned these roles and have instead emphasised the role of these proteins in tissue building and tissue integrity, particularly in tissues devoid of A-type lamins. Other studies have suggested that the expression of B-type lamins in somatic cells influences the rate of entry into states of cellular senescence. In humans duplication of the LMNB1 gene (encoding lamin B1) causes an adult onset neurodegenerative disorder, termed autosomal dominant leukodystrophy, whilst very recently, LMNB1 has been implicated as a susceptibility gene in neural tube defects. This is consistent with studies in mice that reveal a critical role for B-type lamins in neuronal migration and brain development. In this review, I will consider how different model systems have contributed to our understanding of the functions of B-type lamins and which of those functions are critical for human health and disease. © 2014 The Author.
- Authors: Hutchison, Chris
- Date: 2014
- Type: Text , Journal article
- Relation: Seminars in Cell and Developmental Biology Vol. 29, no. (2014), p. 158-163
- Full Text:
- Reviewed:
- Description: For over two decades, B-type lamins were thought to have roles in fundamental processes including correct assembly of nuclear envelopes, DNA replication, transcription and cell survival. Recent studies have questioned these roles and have instead emphasised the role of these proteins in tissue building and tissue integrity, particularly in tissues devoid of A-type lamins. Other studies have suggested that the expression of B-type lamins in somatic cells influences the rate of entry into states of cellular senescence. In humans duplication of the LMNB1 gene (encoding lamin B1) causes an adult onset neurodegenerative disorder, termed autosomal dominant leukodystrophy, whilst very recently, LMNB1 has been implicated as a susceptibility gene in neural tube defects. This is consistent with studies in mice that reveal a critical role for B-type lamins in neuronal migration and brain development. In this review, I will consider how different model systems have contributed to our understanding of the functions of B-type lamins and which of those functions are critical for human health and disease. © 2014 The Author.
Divergent SATB1 expression across human life span and tissue compartments
- Nüssing, Simone, Koay, Hui-Fern, Sant, Sneha, Loudovaris, Thomas, Mannering, Stuart, Lappas, Martha, d′Udekem, Yves, Konstantinov, Igor, Berzins, Stuart, Rimmelzwaan, Guus, Turner, Stephen, Clemens, Bridie, Godfrey, Dale, Nguyen, Thi, Kedzierska, Katherine
- Authors: Nüssing, Simone , Koay, Hui-Fern , Sant, Sneha , Loudovaris, Thomas , Mannering, Stuart , Lappas, Martha , d′Udekem, Yves , Konstantinov, Igor , Berzins, Stuart , Rimmelzwaan, Guus , Turner, Stephen , Clemens, Bridie , Godfrey, Dale , Nguyen, Thi , Kedzierska, Katherine
- Date: 2019
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 97, no. (2019), p. 498-511
- Full Text:
- Reviewed:
- Description: Special AT-rich binding protein-1 (SATB1) is a global chromatin organizer capable of activating or repressing gene transcription in mice and humans. The role of SATB1 is pivotal for T-cell development, with SATB1-knockout mice being neonatally lethal, although the exact mechanism is unknown. Moreover, SATB1 is dysregulated in T-cell lymphoma and proposed to suppress transcription of the Pdcd1 gene, encoding the immune checkpoint programmed cell death protein 1 (PD-1). Thus, SATB1 expression in T-cell subsets across different tissue compartments in humans is of potential importance for targeting PD-1. Here, we comprehensively analyzed SATB1 expression across different human tissues and immune compartments by flow cytometry and correlated this with PD-1 expression. We investigated SATB1 protein levels in pediatric and adult donors and assessed expression dynamics of this chromatin organizer across different immune cell subsets in human organs, as well as in antigen-specific T cells directed against acute and chronic viral infections. Our data demonstrate that SATB1 expression in humans is the highest in T-cell progenitors in the thymus, and then becomes downregulated in mature T cells in the periphery. Importantly, SATB1 expression in peripheral mature T cells is not static and follows fine-tuned expression dynamics, which appear to be tissue- and antigen-dependent. Furthermore, SATB1 expression negatively correlates with PD-1 expression in virus-specific CD8 + T cells. Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
- Authors: Nüssing, Simone , Koay, Hui-Fern , Sant, Sneha , Loudovaris, Thomas , Mannering, Stuart , Lappas, Martha , d′Udekem, Yves , Konstantinov, Igor , Berzins, Stuart , Rimmelzwaan, Guus , Turner, Stephen , Clemens, Bridie , Godfrey, Dale , Nguyen, Thi , Kedzierska, Katherine
- Date: 2019
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 97, no. (2019), p. 498-511
- Full Text:
- Reviewed:
- Description: Special AT-rich binding protein-1 (SATB1) is a global chromatin organizer capable of activating or repressing gene transcription in mice and humans. The role of SATB1 is pivotal for T-cell development, with SATB1-knockout mice being neonatally lethal, although the exact mechanism is unknown. Moreover, SATB1 is dysregulated in T-cell lymphoma and proposed to suppress transcription of the Pdcd1 gene, encoding the immune checkpoint programmed cell death protein 1 (PD-1). Thus, SATB1 expression in T-cell subsets across different tissue compartments in humans is of potential importance for targeting PD-1. Here, we comprehensively analyzed SATB1 expression across different human tissues and immune compartments by flow cytometry and correlated this with PD-1 expression. We investigated SATB1 protein levels in pediatric and adult donors and assessed expression dynamics of this chromatin organizer across different immune cell subsets in human organs, as well as in antigen-specific T cells directed against acute and chronic viral infections. Our data demonstrate that SATB1 expression in humans is the highest in T-cell progenitors in the thymus, and then becomes downregulated in mature T cells in the periphery. Importantly, SATB1 expression in peripheral mature T cells is not static and follows fine-tuned expression dynamics, which appear to be tissue- and antigen-dependent. Furthermore, SATB1 expression negatively correlates with PD-1 expression in virus-specific CD8 + T cells. Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
Zinc transporters maintain longevity by influencing insulin/IGF-1 activity in Caenorhabditis elegans
- Novakovic, Stevan, Molesworth, Luke, Gourley, Taylin, Boag, Peter, Davis, Gregory
- Authors: Novakovic, Stevan , Molesworth, Luke , Gourley, Taylin , Boag, Peter , Davis, Gregory
- Date: 2020
- Type: Text , Journal article
- Relation: FEBS Letters Vol. 594, no. 9 (2020), p. 1424-1432
- Full Text:
- Reviewed:
- Description: Adequate dietary intake of essential metals such as zinc is important for maintaining homeostasis. Abnormal zinc intake in Caenorhabditis elegans has been shown to increase or decrease normal lifespan by influencing the insulin/IGF-1 pathway. Distribution of zinc is achieved by a family of highly conserved zinc transport proteins (ZIPT in C. elegans). This study investigated the role of the zipt family of genes and showed that depletion of individual zipt genes results in a decreased lifespan. Moreover, zipt-16 and zipt-17 mutants synthetically interact with the insulin/IGF cofactors daf-16 and skn-1, and cause abnormal localisation of DAF-16. This study suggests that the zipt family of genes are required for maintaining normal lifespan through influencing the insulin/IGF-1 pathway. © 2019 Federation of European Biochemical Societies
- Description: This study was supported by the resources at Federation University; no external funding was used to fund this study. We acknowledge the Caenorhabditis elegans Genetics Centre for the strains used in this study and Hannah Tatnell (Federation University) for technical assistance.
Zinc transporters maintain longevity by influencing insulin/IGF-1 activity in Caenorhabditis elegans
- Authors: Novakovic, Stevan , Molesworth, Luke , Gourley, Taylin , Boag, Peter , Davis, Gregory
- Date: 2020
- Type: Text , Journal article
- Relation: FEBS Letters Vol. 594, no. 9 (2020), p. 1424-1432
- Full Text:
- Reviewed:
- Description: Adequate dietary intake of essential metals such as zinc is important for maintaining homeostasis. Abnormal zinc intake in Caenorhabditis elegans has been shown to increase or decrease normal lifespan by influencing the insulin/IGF-1 pathway. Distribution of zinc is achieved by a family of highly conserved zinc transport proteins (ZIPT in C. elegans). This study investigated the role of the zipt family of genes and showed that depletion of individual zipt genes results in a decreased lifespan. Moreover, zipt-16 and zipt-17 mutants synthetically interact with the insulin/IGF cofactors daf-16 and skn-1, and cause abnormal localisation of DAF-16. This study suggests that the zipt family of genes are required for maintaining normal lifespan through influencing the insulin/IGF-1 pathway. © 2019 Federation of European Biochemical Societies
- Description: This study was supported by the resources at Federation University; no external funding was used to fund this study. We acknowledge the Caenorhabditis elegans Genetics Centre for the strains used in this study and Hannah Tatnell (Federation University) for technical assistance.
Molecular dynamics studies on 3D structures of the hydrophobic region PrP(109-136)
- Authors: Zhang, Jiapu , Zhang, Yuanli
- Date: 2013
- Type: Text , Journal article
- Relation: Acta Biochimica et Biophysica Sinica Vol. 45, no. 6 (2013), p. 509-519
- Full Text:
- Reviewed:
- Description: Prion diseases, traditionally referred to as transmissible spongiform encephalopathies, are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species, manifesting as scrapie in sheep, bovine spongiform encephalopathy (or 'madcow' disease) in cattle, and Creutzfeldt-Jakob disease, Gerstmann-Strussler-Scheinker syndrome, fatal familial insomnia (FFI), and Kulu in humans, etc. These neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrPC) into insoluble abnormally folded infectious prions (PrPSc). The hydrophobic region PrP(109-136) controls the formation of diseased prions: the normal PrP(113-120) AGAAAAGA palindrome is an inhibitor/blocker of prion diseases and the highly conserved glycine-xxx-glycine motif PrP(119- 131) can inhibit the formation of infectious prion proteins in cells. This article gives detailed reviews on the PrP(109- 136) region and presents the studies of its three-dimensional structures and structural dynamics. © The Author 2013.
- Description: 2003011134
- Authors: Zhang, Jiapu , Zhang, Yuanli
- Date: 2013
- Type: Text , Journal article
- Relation: Acta Biochimica et Biophysica Sinica Vol. 45, no. 6 (2013), p. 509-519
- Full Text:
- Reviewed:
- Description: Prion diseases, traditionally referred to as transmissible spongiform encephalopathies, are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species, manifesting as scrapie in sheep, bovine spongiform encephalopathy (or 'madcow' disease) in cattle, and Creutzfeldt-Jakob disease, Gerstmann-Strussler-Scheinker syndrome, fatal familial insomnia (FFI), and Kulu in humans, etc. These neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrPC) into insoluble abnormally folded infectious prions (PrPSc). The hydrophobic region PrP(109-136) controls the formation of diseased prions: the normal PrP(113-120) AGAAAAGA palindrome is an inhibitor/blocker of prion diseases and the highly conserved glycine-xxx-glycine motif PrP(119- 131) can inhibit the formation of infectious prion proteins in cells. This article gives detailed reviews on the PrP(109- 136) region and presents the studies of its three-dimensional structures and structural dynamics. © The Author 2013.
- Description: 2003011134
The attributes of plakins in cancer and disease: perspectives on ovarian cancer progression, chemoresistance and recurrence
- Wesley, Tamsin, Berzins, Stuart, Kannourakis, George, Ahmed, Nuzhat
- Authors: Wesley, Tamsin , Berzins, Stuart , Kannourakis, George , Ahmed, Nuzhat
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Cell Communication and Signaling Vol. 19, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: The plakin family of cytoskeletal proteins play an important role in cancer progression yet are under-studied in cancer, especially ovarian cancer. These large cytoskeletal proteins have primary roles in the maintenance of cytoskeletal integrity but are also associated with scaffolds of intermediate filaments and hemidesmosomal adhesion complexes mediating signalling pathways that regulate cellular growth, migration, invasion and differentiation as well as stress response. Abnormalities of plakins, and the closely related spectraplakins, result in diseases of the skin, striated muscle and nervous tissue. Their prevalence in epithelial cells suggests that plakins may play a role in epithelial ovarian cancer progression and recurrence. In this review article, we explore the roles of plakins, particularly plectin, periplakin and envoplakin in disease-states and cancers with emphasis on ovarian cancer. We discuss the potential role the plakin family of proteins play in regulating cancer cell growth, survival, migration, invasion and drug resistance. We highlight potential relationships between plakins, epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) and discuss how interaction of these processes may affect ovarian cancer progression, chemoresistance and ultimately recurrence. We propose that molecular changes in the expression of plakins leads to the transition of benign ovarian tumours to carcinomas, as well as floating cellular aggregates (commonly known as spheroids) in the ascites microenvironment, which may contribute to the sustenance and progression of the disease. In this review, attempts have been made to understand the crucial changes in plakin expression in relation to progression and recurrence of ovarian cancer. [MediaObject not available: see fulltext.] © 2021, The Author(s).
- Authors: Wesley, Tamsin , Berzins, Stuart , Kannourakis, George , Ahmed, Nuzhat
- Date: 2021
- Type: Text , Journal article , Review
- Relation: Cell Communication and Signaling Vol. 19, no. 1 (2021), p.
- Full Text:
- Reviewed:
- Description: The plakin family of cytoskeletal proteins play an important role in cancer progression yet are under-studied in cancer, especially ovarian cancer. These large cytoskeletal proteins have primary roles in the maintenance of cytoskeletal integrity but are also associated with scaffolds of intermediate filaments and hemidesmosomal adhesion complexes mediating signalling pathways that regulate cellular growth, migration, invasion and differentiation as well as stress response. Abnormalities of plakins, and the closely related spectraplakins, result in diseases of the skin, striated muscle and nervous tissue. Their prevalence in epithelial cells suggests that plakins may play a role in epithelial ovarian cancer progression and recurrence. In this review article, we explore the roles of plakins, particularly plectin, periplakin and envoplakin in disease-states and cancers with emphasis on ovarian cancer. We discuss the potential role the plakin family of proteins play in regulating cancer cell growth, survival, migration, invasion and drug resistance. We highlight potential relationships between plakins, epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) and discuss how interaction of these processes may affect ovarian cancer progression, chemoresistance and ultimately recurrence. We propose that molecular changes in the expression of plakins leads to the transition of benign ovarian tumours to carcinomas, as well as floating cellular aggregates (commonly known as spheroids) in the ascites microenvironment, which may contribute to the sustenance and progression of the disease. In this review, attempts have been made to understand the crucial changes in plakin expression in relation to progression and recurrence of ovarian cancer. [MediaObject not available: see fulltext.] © 2021, The Author(s).
New algorithms for multi-class cancer diagnosis using tumor gene expression signatures
- Bagirov, Adil, Ferguson, Brent, Ivkovic, Sasha, Saunders, Gary, Yearwood, John
- Authors: Bagirov, Adil , Ferguson, Brent , Ivkovic, Sasha , Saunders, Gary , Yearwood, John
- Date: 2003
- Type: Text , Journal article
- Relation: Bioinformatics Vol. 19, no. 14 (2003), p. 1800-1807
- Full Text:
- Reviewed:
- Description: Motivation: The increasing use of DNA microarray-based tumor gene expression profiles for cancer diagnosis requires mathematical methods with high accuracy for solving clustering, feature selection and classification problems of gene expression data. Results: New algorithms are developed for solving clustering, feature selection and classification problems of gene expression data. The clustering algorithm is based on optimization techniques and allows the calculation of clusters step-by-step. This approach allows us to find as many clusters as a data set contains with respect to some tolerance. Feature selection is crucial for a gene expression database. Our feature selection algorithm is based on calculating overlaps of different genes. The database used, contains over 16 000 genes and this number is considerably reduced by feature selection. We propose a classification algorithm where each tissue sample is considered as the center of a cluster which is a ball. The results of numerical experiments confirm that the classification algorithm in combination with the feature selection algorithm perform slightly better than the published results for multi-class classifiers based on support vector machines for this data set.
- Description: C1
- Description: 2003000439
- Authors: Bagirov, Adil , Ferguson, Brent , Ivkovic, Sasha , Saunders, Gary , Yearwood, John
- Date: 2003
- Type: Text , Journal article
- Relation: Bioinformatics Vol. 19, no. 14 (2003), p. 1800-1807
- Full Text:
- Reviewed:
- Description: Motivation: The increasing use of DNA microarray-based tumor gene expression profiles for cancer diagnosis requires mathematical methods with high accuracy for solving clustering, feature selection and classification problems of gene expression data. Results: New algorithms are developed for solving clustering, feature selection and classification problems of gene expression data. The clustering algorithm is based on optimization techniques and allows the calculation of clusters step-by-step. This approach allows us to find as many clusters as a data set contains with respect to some tolerance. Feature selection is crucial for a gene expression database. Our feature selection algorithm is based on calculating overlaps of different genes. The database used, contains over 16 000 genes and this number is considerably reduced by feature selection. We propose a classification algorithm where each tissue sample is considered as the center of a cluster which is a ball. The results of numerical experiments confirm that the classification algorithm in combination with the feature selection algorithm perform slightly better than the published results for multi-class classifiers based on support vector machines for this data set.
- Description: C1
- Description: 2003000439
Human blood MAIT cell subsets defined using MR1 tetramers
- Gherardin, Nicholas, Souter, Michael, Koay, Hui-Fern, Mangas, Kirstie, Seemann, Torsten, Stinear, Timothy, Eckle, Sidonia, Berzins, Stuart, d'Udekem, Yves, Konstantinov, Igor, Fairlie, David, Ritchie, David, Neeson, Paul, Pellicci, Daniel, Uldrich, Adam, McCluskey, James, Godfrey, Dale
- Authors: Gherardin, Nicholas , Souter, Michael , Koay, Hui-Fern , Mangas, Kirstie , Seemann, Torsten , Stinear, Timothy , Eckle, Sidonia , Berzins, Stuart , d'Udekem, Yves , Konstantinov, Igor , Fairlie, David , Ritchie, David , Neeson, Paul , Pellicci, Daniel , Uldrich, Adam , McCluskey, James , Godfrey, Dale
- Date: 2018
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 96, no. 5 (2018), p. 507-525
- Full Text:
- Reviewed:
- Description: Mucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18R
- Authors: Gherardin, Nicholas , Souter, Michael , Koay, Hui-Fern , Mangas, Kirstie , Seemann, Torsten , Stinear, Timothy , Eckle, Sidonia , Berzins, Stuart , d'Udekem, Yves , Konstantinov, Igor , Fairlie, David , Ritchie, David , Neeson, Paul , Pellicci, Daniel , Uldrich, Adam , McCluskey, James , Godfrey, Dale
- Date: 2018
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 96, no. 5 (2018), p. 507-525
- Full Text:
- Reviewed:
- Description: Mucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18R
Signatures of miR-181a on the renal transcriptome and blood pressure
- Marques, Francine, Romaine, Simon, Denniff, Matthew, Eales, James, Dormer, John, Garrelds, Ingrid, Wojnar, Lukasz, Musialik, Katarzyna, Duda-Raszewska, Barbara, Kiszka, Bartlomiej, Duda, Magdalena, Morris, Brian, Samani, Nilesh, Jan Danser, Jan, Bogdanski, Pawel, Zukowska-Szczechowska, Ewa, Charchar, Fadi, Tomaszewski, Maciej
- Authors: Marques, Francine , Romaine, Simon , Denniff, Matthew , Eales, James , Dormer, John , Garrelds, Ingrid , Wojnar, Lukasz , Musialik, Katarzyna , Duda-Raszewska, Barbara , Kiszka, Bartlomiej , Duda, Magdalena , Morris, Brian , Samani, Nilesh , Jan Danser, Jan , Bogdanski, Pawel , Zukowska-Szczechowska, Ewa , Charchar, Fadi , Tomaszewski, Maciej
- Date: 2015
- Type: Text , Journal article
- Relation: Molecular Medicine Vol. 21, no. (2015), p. 739-748
- Full Text: false
- Reviewed:
- Description: MicroRNA-181a binds to the 3’ untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a. Elevated miR-181a levels correlated positively with systolic and diastolic blood pressure in TRANSLATE, and this association was independent of circulating renin. The association between serum miR-181a and systolic blood pressure was replicated in 199 subjects from the Genetic Regulation of Arterial Pressure of Humans In the Community (GRAPHIC) study. Renal immunohistochemistry and in situ hybridization showed that colocalization of miR-181a and renin was most prominent in collecting ducts where renin is not released into the systemic circulation. Analysis of 69 human kidneys characterized by RNA sequencing revealed that miR-181a was associated with downregulation of four mitochondrial pathways and upregulation of 41 signaling cascades of adaptive immunity and inflammation. We conclude that renal miR-181a has pleiotropic effects on pathways relevant to blood pressure regulation and that circulating levels of miR-181a are both a measurable proxy of renal miR-181a expression and a novel biochemical correlate of blood pressure.
Comparative effectiveness of three exercise types to treat clinical depression in older adults : a systematic review and network meta-analysis of randomised controlled trials
- Miller, Kyle, Gonçalves-Bradley, Daniela, Areerob, Pinyadapat, Hennessy, Declan, Mesagno, Christopher, Grace, Fergal
- Authors: Miller, Kyle , Gonçalves-Bradley, Daniela , Areerob, Pinyadapat , Hennessy, Declan , Mesagno, Christopher , Grace, Fergal
- Date: 2020
- Type: Text , Journal article , Review
- Relation: Ageing Research Reviews Vol. 58 (2020).
- Full Text:
- Reviewed:
- Description: Background: Few studies have directly compared the effects of different exercise therapies on clinical depression in older adults. Thus, we conducted a systematic review and network meta-analysis of current evidence from randomised controlled trials (RCTs) to compare the effectiveness of three major exercise types (aerobic, resistance, and mind-body exercise) in clinically depressed older adults. Methods: We followed PRISMA-NMA guidelines and searched databases for eligible RCTs (inception – September 12th, 2019). RCTs were eligible if they included clinically depressed adults aged >65 years, implemented one or more exercise therapy arms using aerobic, resistance, or mind-body exercise, and assessed depressive symptoms at baseline and follow-up using a validated clinical questionnaire. Results: A network meta-analysis was performed on 15 eligible RCTs comprising 596 participants (321 treatment and 275 controls), including aerobic (n = 6), resistance (n = 5), and mind-body (n = 4) exercise trials. Compared with controls, mind-body exercise showed the largest improvement on depressive symptoms (g = −0.87 to −1.38), followed by aerobic exercise (g = −0.51 to −1.02), and resistance exercise (g = −0.41 to −0.92). Notably, there were no statistically significant differences between exercise types: aerobic versus resistance (g = −0.10, PrI = −2.23, 2.03), mind-body versus aerobic (g = −0.36, PrI = −2.69, 1.97), or mind-body versus resistance (g = −0.46, PrI = −2.75, 1.83). Conclusions: These findings should guide optimal exercise prescription for allied health professionals and stakeholders in clinical geriatrics. Notably, clinically depressed older adults may be encouraged to self-select their preferred exercise type in order to achieve therapeutic benefit on symptoms of depression. In coalition with high levels of compliance, these data provide encouraging evidence for the antidepressant effect of either aerobic, resistance, or mind-body exercise as effective treatment adjucts for older adults presenting with clinical depression. © 2019
- Authors: Miller, Kyle , Gonçalves-Bradley, Daniela , Areerob, Pinyadapat , Hennessy, Declan , Mesagno, Christopher , Grace, Fergal
- Date: 2020
- Type: Text , Journal article , Review
- Relation: Ageing Research Reviews Vol. 58 (2020).
- Full Text:
- Reviewed:
- Description: Background: Few studies have directly compared the effects of different exercise therapies on clinical depression in older adults. Thus, we conducted a systematic review and network meta-analysis of current evidence from randomised controlled trials (RCTs) to compare the effectiveness of three major exercise types (aerobic, resistance, and mind-body exercise) in clinically depressed older adults. Methods: We followed PRISMA-NMA guidelines and searched databases for eligible RCTs (inception – September 12th, 2019). RCTs were eligible if they included clinically depressed adults aged >65 years, implemented one or more exercise therapy arms using aerobic, resistance, or mind-body exercise, and assessed depressive symptoms at baseline and follow-up using a validated clinical questionnaire. Results: A network meta-analysis was performed on 15 eligible RCTs comprising 596 participants (321 treatment and 275 controls), including aerobic (n = 6), resistance (n = 5), and mind-body (n = 4) exercise trials. Compared with controls, mind-body exercise showed the largest improvement on depressive symptoms (g = −0.87 to −1.38), followed by aerobic exercise (g = −0.51 to −1.02), and resistance exercise (g = −0.41 to −0.92). Notably, there were no statistically significant differences between exercise types: aerobic versus resistance (g = −0.10, PrI = −2.23, 2.03), mind-body versus aerobic (g = −0.36, PrI = −2.69, 1.97), or mind-body versus resistance (g = −0.46, PrI = −2.75, 1.83). Conclusions: These findings should guide optimal exercise prescription for allied health professionals and stakeholders in clinical geriatrics. Notably, clinically depressed older adults may be encouraged to self-select their preferred exercise type in order to achieve therapeutic benefit on symptoms of depression. In coalition with high levels of compliance, these data provide encouraging evidence for the antidepressant effect of either aerobic, resistance, or mind-body exercise as effective treatment adjucts for older adults presenting with clinical depression. © 2019
Caucasian and south Asian men show equivalent improvements in surrogate biomarkers of cardiovascular and metabolic health following 6-weeks of supervised resistance training
- Knox, Allan, Sculthorpe, Nicholas, Grace, Fergal
- Authors: Knox, Allan , Sculthorpe, Nicholas , Grace, Fergal
- Date: 2018
- Type: Text , Journal article
- Relation: F1000Research Vol. 7, no. (2018), p. 1-16
- Full Text:
- Reviewed:
- Description: Background: The South Asian population have greater cardiovascular risk than their age-matched Caucasian counterparts, characterized by unfavorable biomarkers. South Asians may also be partially resistant to the pleiotropic benefits of physical activity on cardiovascular health. There is a current absence of studies that compare markers of cardio-metabolic health between Caucasians and South Asians employing resistance exercise. This study set out to compare the response in biomarkers of cardio-metabolic health in Caucasians and South Asians in response to resistance exercise. Methods: Caucasian (n=15, 25.5 ± 4.8 yrs) and South Asian (n=13, 25.4 ± 7.0 yrs) males completed a 6-week progressive resistance exercise protocol. Fasting blood glucose, insulin, and their product insulin resistance (HOMA-IR), triglycerides (TRIGS), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC), vascular endothelial growth factor (VEGF), asymmetric dimythylarginine (ADMA), L-arginine (L-ARG) and C-reactive protein (CRP) were established at baseline and following resistance exercise. Results: There were significant improvements in fasting glucose, TC, LDL, HDL and VEGF in both groups following resistance exercise ( p<0.05, for all). No change was observed in insulin, HOMA-IR, TRIGS, ADMA, L-ARG following resistance exercise ( p>0.05, in both groups). CRP increased in the South Asian group ( p<0.05) but not the Caucasian group ( p>0.05) Conclusions: The cardio-metabolic response to resistance exercise is comparable in young Caucasian and South Asian males though inflammatory response to exercise may be prolonged in South Asians.
- Authors: Knox, Allan , Sculthorpe, Nicholas , Grace, Fergal
- Date: 2018
- Type: Text , Journal article
- Relation: F1000Research Vol. 7, no. (2018), p. 1-16
- Full Text:
- Reviewed:
- Description: Background: The South Asian population have greater cardiovascular risk than their age-matched Caucasian counterparts, characterized by unfavorable biomarkers. South Asians may also be partially resistant to the pleiotropic benefits of physical activity on cardiovascular health. There is a current absence of studies that compare markers of cardio-metabolic health between Caucasians and South Asians employing resistance exercise. This study set out to compare the response in biomarkers of cardio-metabolic health in Caucasians and South Asians in response to resistance exercise. Methods: Caucasian (n=15, 25.5 ± 4.8 yrs) and South Asian (n=13, 25.4 ± 7.0 yrs) males completed a 6-week progressive resistance exercise protocol. Fasting blood glucose, insulin, and their product insulin resistance (HOMA-IR), triglycerides (TRIGS), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC), vascular endothelial growth factor (VEGF), asymmetric dimythylarginine (ADMA), L-arginine (L-ARG) and C-reactive protein (CRP) were established at baseline and following resistance exercise. Results: There were significant improvements in fasting glucose, TC, LDL, HDL and VEGF in both groups following resistance exercise ( p<0.05, for all). No change was observed in insulin, HOMA-IR, TRIGS, ADMA, L-ARG following resistance exercise ( p>0.05, in both groups). CRP increased in the South Asian group ( p<0.05) but not the Caucasian group ( p>0.05) Conclusions: The cardio-metabolic response to resistance exercise is comparable in young Caucasian and South Asian males though inflammatory response to exercise may be prolonged in South Asians.
Aerobic, resistance, and mind-body exercise are equivalent to mitigate symptoms of depression in older adults: A systematic review and network meta-analysis of randomised controlled trials
- Miller, Kyle, Areerob, Pinyadapat, Hennessy, Declan, Gonçalves-Bradley, Daniela, Mesagno, Christopher, Grace, Fergal
- Authors: Miller, Kyle , Areerob, Pinyadapat , Hennessy, Declan , Gonçalves-Bradley, Daniela , Mesagno, Christopher , Grace, Fergal
- Date: 2020
- Type: Text , Journal article
- Relation: F1000Research Vol. 9, no. (2020), p. 1-51
- Full Text:
- Reviewed:
- Description: Background: Exercise has been identified as an allied health strategy that can support the management of depression in older adults, yet the relative effectiveness for different exercise modalities is unknown. To meet this gap in knowledge, we present a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the head-to-head effectiveness of aerobic, resistance, and mind-body exercise to mitigate depressive symptoms in adults aged ≥ 65 years. Methods: A PRISMA-NMA compliant review was undertaken on RCTs from inception to September 12 th, 2019. PubMed, Web of Science, CINAHL, Health Source: Nursing/Academic Edition, PsycARTICLES, PsycINFO, and SPORTDiscus were systematically searched for eligible RCTs enrolling adults with a mean age ≥ 65 years, comparing one or more exercise intervention arms, and which used valid measures of depressive symptomology. Comparative effectiveness was evaluated using network meta-analysis to combine direct and indirect evidence, controlling for inherent variation in trial control groups. Results: The systematic review included 81 RCTs, with 69 meeting eligibility for the network meta-analysis ( n = 5,379 participants). Pooled analysis found each exercise type to be effective compared with controls (Hedges' g = -0.27 to -0.51). Relative head-to-head comparisons were statistically comparable between exercise types: resistance versus aerobic (Hedges' g = -0.06, PrI = -0.91, 0.79), mind-body versus aerobic (Hedges' g = -0.12, PrI = -0.95, 0.72), mind-body versus resistance (Hedges' g = -0.06, PrI = -0.90, 0.79). High levels of compliance were demonstrated for each exercise treatment. Conclusions: Aerobic, resistance, and mind-body exercise demonstrate equivalence to mitigate symptoms of depression in older adults aged ≥ 65 years, with comparably encouraging levels of compliance to exercise treatment. These findings coalesce with previous findings in clinically depressed older adults to encourage personal preference when prescribing exercise for depressive symptoms in older adults, irrespective of severity. Registration: PROSPERO CRD42018115866 (23/11/2018). © 2020 Miller KJ et al.
- Authors: Miller, Kyle , Areerob, Pinyadapat , Hennessy, Declan , Gonçalves-Bradley, Daniela , Mesagno, Christopher , Grace, Fergal
- Date: 2020
- Type: Text , Journal article
- Relation: F1000Research Vol. 9, no. (2020), p. 1-51
- Full Text:
- Reviewed:
- Description: Background: Exercise has been identified as an allied health strategy that can support the management of depression in older adults, yet the relative effectiveness for different exercise modalities is unknown. To meet this gap in knowledge, we present a systematic review and network meta-analysis of randomised controlled trials (RCTs) to examine the head-to-head effectiveness of aerobic, resistance, and mind-body exercise to mitigate depressive symptoms in adults aged ≥ 65 years. Methods: A PRISMA-NMA compliant review was undertaken on RCTs from inception to September 12 th, 2019. PubMed, Web of Science, CINAHL, Health Source: Nursing/Academic Edition, PsycARTICLES, PsycINFO, and SPORTDiscus were systematically searched for eligible RCTs enrolling adults with a mean age ≥ 65 years, comparing one or more exercise intervention arms, and which used valid measures of depressive symptomology. Comparative effectiveness was evaluated using network meta-analysis to combine direct and indirect evidence, controlling for inherent variation in trial control groups. Results: The systematic review included 81 RCTs, with 69 meeting eligibility for the network meta-analysis ( n = 5,379 participants). Pooled analysis found each exercise type to be effective compared with controls (Hedges' g = -0.27 to -0.51). Relative head-to-head comparisons were statistically comparable between exercise types: resistance versus aerobic (Hedges' g = -0.06, PrI = -0.91, 0.79), mind-body versus aerobic (Hedges' g = -0.12, PrI = -0.95, 0.72), mind-body versus resistance (Hedges' g = -0.06, PrI = -0.90, 0.79). High levels of compliance were demonstrated for each exercise treatment. Conclusions: Aerobic, resistance, and mind-body exercise demonstrate equivalence to mitigate symptoms of depression in older adults aged ≥ 65 years, with comparably encouraging levels of compliance to exercise treatment. These findings coalesce with previous findings in clinically depressed older adults to encourage personal preference when prescribing exercise for depressive symptoms in older adults, irrespective of severity. Registration: PROSPERO CRD42018115866 (23/11/2018). © 2020 Miller KJ et al.
Rhythmic and sustained oscillations in metabolism and gene expression of Cyanothece sp. ATCC 51142 under constant light
- Gaudana, Sandeep, Krishnakumar, S., Alagesan, Swathi, Digmurti, Madhuri, Viswanathan, Ganesh, Chetty, Madhu, Wangikar, Pramod
- Authors: Gaudana, Sandeep , Krishnakumar, S. , Alagesan, Swathi , Digmurti, Madhuri , Viswanathan, Ganesh , Chetty, Madhu , Wangikar, Pramod
- Date: 2013
- Type: Text , Journal article
- Relation: Frontiers in Microbiology Vol. 4, no. Article 374 (2013), p. 1-11
- Full Text:
- Reviewed:
- Description: Cyanobacteria, a group of photosynthetic prokaryotes, oscillate between day and night time metabolisms with concomitant oscillations in gene expression in response to light/dark cycles (LD). The oscillations in gene expression have been shown to sustain in constant light (LL) with a free running period of 24 h in a model cyanobacterium Synechococcus elongatus PCC 7942. However, equivalent oscillations in metabolism are not reported under LL in this non-nitrogen fixing cyanobacterium. Here we focus on Cyanothece sp. ATCC 51142, a unicellular, nitrogen-fixing cyanobacterium known to temporally separate the processes of oxygenic photosynthesis and oxygen-sensitive nitrogen fixation. In a recent report, metabolism of Cyanothece 51142 has been shown to oscillate between photosynthetic and respiratory phases under LL with free running periods that are temperature dependent but significantly shorter than the circadian period. Further, the oscillations shift to circadian pattern at moderate cell densities that are concomitant with slower growth rates. Here we take this understanding forward and demonstrate that the ultradian rhythm under LL sustains at much higher cell densities when grown under turbulent regimes that simulate flashing light effect. Our results suggest that the ultradian rhythm in metabolism may be needed to support higher carbon and nitrogen requirements of rapidly growing cells under LL. With a comprehensive Real time PCR based gene expression analysis we account for key regulatory interactions and demonstrate the interplay between clock genes and the genes of key metabolic pathways. Further, we observe that several genes that peak at dusk in Synechococcus peak at dawn in Cyanothece and vice versa. The circadian rhythm of this organism appears to be more robust with peaking of genes in anticipation of the ensuing photosynthetic and respiratory metabolic phases.
- Authors: Gaudana, Sandeep , Krishnakumar, S. , Alagesan, Swathi , Digmurti, Madhuri , Viswanathan, Ganesh , Chetty, Madhu , Wangikar, Pramod
- Date: 2013
- Type: Text , Journal article
- Relation: Frontiers in Microbiology Vol. 4, no. Article 374 (2013), p. 1-11
- Full Text:
- Reviewed:
- Description: Cyanobacteria, a group of photosynthetic prokaryotes, oscillate between day and night time metabolisms with concomitant oscillations in gene expression in response to light/dark cycles (LD). The oscillations in gene expression have been shown to sustain in constant light (LL) with a free running period of 24 h in a model cyanobacterium Synechococcus elongatus PCC 7942. However, equivalent oscillations in metabolism are not reported under LL in this non-nitrogen fixing cyanobacterium. Here we focus on Cyanothece sp. ATCC 51142, a unicellular, nitrogen-fixing cyanobacterium known to temporally separate the processes of oxygenic photosynthesis and oxygen-sensitive nitrogen fixation. In a recent report, metabolism of Cyanothece 51142 has been shown to oscillate between photosynthetic and respiratory phases under LL with free running periods that are temperature dependent but significantly shorter than the circadian period. Further, the oscillations shift to circadian pattern at moderate cell densities that are concomitant with slower growth rates. Here we take this understanding forward and demonstrate that the ultradian rhythm under LL sustains at much higher cell densities when grown under turbulent regimes that simulate flashing light effect. Our results suggest that the ultradian rhythm in metabolism may be needed to support higher carbon and nitrogen requirements of rapidly growing cells under LL. With a comprehensive Real time PCR based gene expression analysis we account for key regulatory interactions and demonstrate the interplay between clock genes and the genes of key metabolic pathways. Further, we observe that several genes that peak at dusk in Synechococcus peak at dawn in Cyanothece and vice versa. The circadian rhythm of this organism appears to be more robust with peaking of genes in anticipation of the ensuing photosynthetic and respiratory metabolic phases.
- Beckham, Simone, Piedrafita, David, Phillips, Carolyn, Samarawickrema, Nirma, Law, Ruby, Smooker, Peter, Quinsey, Noelene, Irving, James, Greenwood, Deanne, Verhelst, Steven, Bogyo, Matthew, Turk, Boris, Coetzer, Theresa, Wijeyewickrema, Lakshmi, Spithill, Terry, Pike, Robert
- Authors: Beckham, Simone , Piedrafita, David , Phillips, Carolyn , Samarawickrema, Nirma , Law, Ruby , Smooker, Peter , Quinsey, Noelene , Irving, James , Greenwood, Deanne , Verhelst, Steven , Bogyo, Matthew , Turk, Boris , Coetzer, Theresa , Wijeyewickrema, Lakshmi , Spithill, Terry , Pike, Robert
- Date: 2009
- Type: Text , Journal article
- Relation: International Journal of Biochemistry and Cell Biology Vol. 41, no. 7 (2009), p. 1601-1612
- Full Text: false
- Reviewed:
- Description: The newly excysted juvenile (NEJ) stage of the Fasciola hepatica lifecycle occurs just prior to invasion into the wall of the gut of the host, rendering it an important target for drug development. The cathepsin B enzymes from NEJ flukes have recently been demonstrated to be crucial to invasion and migration by the parasite. Here we characterize one of the cathepsin B enzymes (recombinant FhcatB1) from NEJ flukes. FhcatB1 has biochemical properties distinct from mammalian cathepsin B enzymes, with an atypical preference for Ile over Leu or Arg residues at the P2 substrate position and an inability to act as an exopeptidase. FhcatB1 was active across a broad pH range (optimal activity at pH 5.5–7.0) and resistant to inhibition by cystatin family inhibitors from sheep and humans, suggesting that this enzyme would be able to function in extracellular environments in its mammalian hosts. It appears, however, that the FhcatB1 protease functions largely as a digestive enzyme in the gut of the parasite, due to the localization of a specific, fluorescently labeled inhibitor with an Ile at the P2 position. Molecular modelling and dynamics were used to predict the basis for the unusual substrate specificity: a P2 Ile residue positions the substrate optimally for interaction with catalytic residues of the enzyme, and the enzyme lacks an occluding loop His residue crucial for exopeptidase activity. The unique features of the enzyme, particularly with regard to its specificity and likely importance to a vital stage of the parasite's life cycle, make it an excellent target for therapeutic inhibitors or vaccination.
Molecular dynamics studies of dog prion protein wild-type and its D159N mutant
- Authors: Zhang, Jiapu
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Biomolecular Structure and Dynamics Vol. 39, no. 12 (2021), p. 4234-4242
- Full Text:
- Reviewed:
- Description: Prion diseases (e.g. ‘mad cow’ disease in cattle, chronic wasting disease in deer and elk, Creutzfeldt-Jakob disease in humans) have been a major public health concern affecting humans and almost all animals. However, dogs are strongly resistant to prion diseases. Recently, through transgenic techniques, it was reported that the single (surface) residue D159 is sufficient to confer protection against protein conformational change and pathogenesis, thus provides conformational stability for dog prion protein. This made a big breakthrough in dog prion protein research field. For dog prion protein, another advancement is the produce of its NMR structure in 2005. However, all these breakthroughs are still short of enough structural informatics of dog prion protein. This paper studies dog prion protein wild-type and D159N mutant through molecular dynamics (MD) techniques. Our MD results reveal sufficient structural informatics on the residue at position 159 to understand the mechanism underlying the resistance to prion diseases of dogs. The structural informatics of this paper should be very useful for the medicinal treatment of prion diseases. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group.
- Authors: Zhang, Jiapu
- Date: 2021
- Type: Text , Journal article
- Relation: Journal of Biomolecular Structure and Dynamics Vol. 39, no. 12 (2021), p. 4234-4242
- Full Text:
- Reviewed:
- Description: Prion diseases (e.g. ‘mad cow’ disease in cattle, chronic wasting disease in deer and elk, Creutzfeldt-Jakob disease in humans) have been a major public health concern affecting humans and almost all animals. However, dogs are strongly resistant to prion diseases. Recently, through transgenic techniques, it was reported that the single (surface) residue D159 is sufficient to confer protection against protein conformational change and pathogenesis, thus provides conformational stability for dog prion protein. This made a big breakthrough in dog prion protein research field. For dog prion protein, another advancement is the produce of its NMR structure in 2005. However, all these breakthroughs are still short of enough structural informatics of dog prion protein. This paper studies dog prion protein wild-type and D159N mutant through molecular dynamics (MD) techniques. Our MD results reveal sufficient structural informatics on the residue at position 159 to understand the mechanism underlying the resistance to prion diseases of dogs. The structural informatics of this paper should be very useful for the medicinal treatment of prion diseases. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group.