Differential associations of hypoxia, sleep fragmentation, and depressive symptoms with cognitive dysfunction in obstructive sleep apnea
- Alomri, Ridwan, Kennedy, Gerard, Wali, Siraj, Ahejaili, Faris, Robinson, Stephen
- Authors: Alomri, Ridwan , Kennedy, Gerard , Wali, Siraj , Ahejaili, Faris , Robinson, Stephen
- Date: 2021
- Type: Text , Journal article
- Relation: Sleep Vol. 44, no. 4 (2021), p.
- Full Text:
- Reviewed:
- Description: Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete cessation of breathing during sleep and increased effort to breathe. This study examined patients who underwent overnight polysomnographic studies in a major sleep laboratory in Saudi Arabia. The study aimed to determine the extent to which intermittent hypoxia, sleep disruption, and depressive symptoms are independently associated with cognitive impairments in OSA. In the sample of 90 participants, 14 had no OSA, 30 mild OSA, 23 moderate OSA, and 23 severe OSA. The findings revealed that hypoxia and sleep fragmentation are independently associated with impairments of sustained attention and reaction time (RT). Sleep fragmentation, but not hypoxia, was independently associated with impairments in visuospatial deficits. Depressive symptoms were independently associated with impairments in the domains of sustained attention, RT, visuospatial ability, and semantic and episodic autobiographical memories. Since the depressive symptoms are independent of hypoxia and sleep fragmentation, effective reversal of cognitive impairment in OSA may require treatment interventions that target each of these factors. © Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.
- Authors: Alomri, Ridwan , Kennedy, Gerard , Wali, Siraj , Ahejaili, Faris , Robinson, Stephen
- Date: 2021
- Type: Text , Journal article
- Relation: Sleep Vol. 44, no. 4 (2021), p.
- Full Text:
- Reviewed:
- Description: Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete cessation of breathing during sleep and increased effort to breathe. This study examined patients who underwent overnight polysomnographic studies in a major sleep laboratory in Saudi Arabia. The study aimed to determine the extent to which intermittent hypoxia, sleep disruption, and depressive symptoms are independently associated with cognitive impairments in OSA. In the sample of 90 participants, 14 had no OSA, 30 mild OSA, 23 moderate OSA, and 23 severe OSA. The findings revealed that hypoxia and sleep fragmentation are independently associated with impairments of sustained attention and reaction time (RT). Sleep fragmentation, but not hypoxia, was independently associated with impairments in visuospatial deficits. Depressive symptoms were independently associated with impairments in the domains of sustained attention, RT, visuospatial ability, and semantic and episodic autobiographical memories. Since the depressive symptoms are independent of hypoxia and sleep fragmentation, effective reversal of cognitive impairment in OSA may require treatment interventions that target each of these factors. © Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.
Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants
- Britton, Kathryn, Pickering, Janessa, Pomat, William, de Gier, Camilla, Greenhill, Andrew
- Authors: Britton, Kathryn , Pickering, Janessa , Pomat, William , de Gier, Camilla , Greenhill, Andrew
- Date: 2021
- Type: Text , Journal article
- Relation: Vaccine Vol. 39, no. 38 (2021), p. 5401-5409
- Full Text:
- Reviewed:
- Description: Background: Papua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world. Methods: Nasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray. Results: Pneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log10 genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes. Conclusion: PNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered. © 2021 The Authors. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Andrew Greenhill" is provided in this record**
- Authors: Britton, Kathryn , Pickering, Janessa , Pomat, William , de Gier, Camilla , Greenhill, Andrew
- Date: 2021
- Type: Text , Journal article
- Relation: Vaccine Vol. 39, no. 38 (2021), p. 5401-5409
- Full Text:
- Reviewed:
- Description: Background: Papua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world. Methods: Nasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray. Results: Pneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log10 genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes. Conclusion: PNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered. © 2021 The Authors. **Please note that there are multiple authors for this article therefore only the name of the first 5 including Federation University Australia affiliate “Andrew Greenhill" is provided in this record**
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- Surendran, Praveen, Feofanova, Elena, Lahrouchi, Najim, Ntalla, Ionna, Karthikeyan, Savita, Cook, James, Chen, Lingyan, Mifsud, Borbala, Yao, Chen, Kraja, Aldi, Cartwright, James, Hellwege, Jacklyn, Giri, Ayush, Tragante, Vinicius, Thorleifsson, Gudmar, Liu, Dajiang, Prins, Bram, Stewart, Isobel, Cabrera, Claude, Eales, James, Akbarov, Artur, Auer, Paul, Charchar, Fadi, Howson, Joanna, LifeLines Cohort, Study, Epic, C. V. D., Epic InterAct, Understanding Society Scientific, Group, Million Veteran, Program
- Authors: Surendran, Praveen , Feofanova, Elena , Lahrouchi, Najim , Ntalla, Ionna , Karthikeyan, Savita , Cook, James , Chen, Lingyan , Mifsud, Borbala , Yao, Chen , Kraja, Aldi , Cartwright, James , Hellwege, Jacklyn , Giri, Ayush , Tragante, Vinicius , Thorleifsson, Gudmar , Liu, Dajiang , Prins, Bram , Stewart, Isobel , Cabrera, Claude , Eales, James , Akbarov, Artur , Auer, Paul , Charchar, Fadi , Howson, Joanna , LifeLines Cohort, Study , Epic, C. V. D. , Epic InterAct , Understanding Society Scientific, Group , Million Veteran, Program
- Date: 2020
- Type: Text , Journal article
- Relation: Nature Genetics Vol. 52, no. 12 (2020), p. 1314-1332
- Full Text:
- Reviewed:
- Description: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. There are 286 authors of this articles not all are listed in this record.
- Authors: Surendran, Praveen , Feofanova, Elena , Lahrouchi, Najim , Ntalla, Ionna , Karthikeyan, Savita , Cook, James , Chen, Lingyan , Mifsud, Borbala , Yao, Chen , Kraja, Aldi , Cartwright, James , Hellwege, Jacklyn , Giri, Ayush , Tragante, Vinicius , Thorleifsson, Gudmar , Liu, Dajiang , Prins, Bram , Stewart, Isobel , Cabrera, Claude , Eales, James , Akbarov, Artur , Auer, Paul , Charchar, Fadi , Howson, Joanna , LifeLines Cohort, Study , Epic, C. V. D. , Epic InterAct , Understanding Society Scientific, Group , Million Veteran, Program
- Date: 2020
- Type: Text , Journal article
- Relation: Nature Genetics Vol. 52, no. 12 (2020), p. 1314-1332
- Full Text:
- Reviewed:
- Description: Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10−8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. There are 286 authors of this articles not all are listed in this record.
Gut microbiota composition in obese and non-obese adult relatives from the highlands of Papua New Guinea
- Jonduo, Marinjho, Wawae, Lorry, Masiria, Geraldine, Suda, Wataru, Hattori, Masahira, Takayasu, Lena, Abdad, Mohammad, Greenhill, Andrew, Horwood, Paul, Pomat, William, Umezaki, Masahiro
- Authors: Jonduo, Marinjho , Wawae, Lorry , Masiria, Geraldine , Suda, Wataru , Hattori, Masahira , Takayasu, Lena , Abdad, Mohammad , Greenhill, Andrew , Horwood, Paul , Pomat, William , Umezaki, Masahiro
- Date: 2020
- Type: Text , Journal article
- Relation: FEMS microbiology letters Vol. 367, no. 19 (2020), p.
- Full Text:
- Reviewed:
- Description: Obesity is a condition that results from an imbalance between energy intake and expenditure. Recently, obesity has been linked to differences in the composition of gut microbiota. To examine this association in Papua New Guinea (PNG) highlanders, fecal samples were collected from 18 adults; nine obese participants were paired with their non-obese relative. Amplification of the 16S rRNA gene targeting the V1-V2 region was performed on DNA extracts for each participant, with high-quality sequences selected and used for operational taxonomic unit clustering. The data showed Firmicutes and Bacteroidetes were the two dominant phyla, while at genus level Prevotella was the most dominant genus in all of the samples. Nonetheless, statistical evaluation of potential association between nutritional status and bacterial abundance at both phyla and genus levels showed no significant difference. Further studies, ideally in both rural and urban areas, are needed to evaluate the role of the gut microbiome in the occurrence of obesity in PNG and other resource-limited settings. © The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.
- Authors: Jonduo, Marinjho , Wawae, Lorry , Masiria, Geraldine , Suda, Wataru , Hattori, Masahira , Takayasu, Lena , Abdad, Mohammad , Greenhill, Andrew , Horwood, Paul , Pomat, William , Umezaki, Masahiro
- Date: 2020
- Type: Text , Journal article
- Relation: FEMS microbiology letters Vol. 367, no. 19 (2020), p.
- Full Text:
- Reviewed:
- Description: Obesity is a condition that results from an imbalance between energy intake and expenditure. Recently, obesity has been linked to differences in the composition of gut microbiota. To examine this association in Papua New Guinea (PNG) highlanders, fecal samples were collected from 18 adults; nine obese participants were paired with their non-obese relative. Amplification of the 16S rRNA gene targeting the V1-V2 region was performed on DNA extracts for each participant, with high-quality sequences selected and used for operational taxonomic unit clustering. The data showed Firmicutes and Bacteroidetes were the two dominant phyla, while at genus level Prevotella was the most dominant genus in all of the samples. Nonetheless, statistical evaluation of potential association between nutritional status and bacterial abundance at both phyla and genus levels showed no significant difference. Further studies, ideally in both rural and urban areas, are needed to evaluate the role of the gut microbiome in the occurrence of obesity in PNG and other resource-limited settings. © The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.
Regulation of the rabbit's once-daily pattern of nursing : A circadian or hourglass-dependent process?
- Apel, Sabine, Hudson, Robyn, Coleman, Grahame, Rodel, Heiko, Kennedy, Gerard
- Authors: Apel, Sabine , Hudson, Robyn , Coleman, Grahame , Rodel, Heiko , Kennedy, Gerard
- Date: 2020
- Type: Text , Journal article
- Relation: Chronobiology International Vol. 37, no. 8 (2020), p. 1151-1162
- Full Text:
- Reviewed:
- Description: The European rabbitOryctolagus cuniculushas an unusual pattern of nursing behavior. After giving birth in a nursery burrow (or laboratory nest box), the mother immediately leaves the young and only returns to nurse for a few minutes once approximately every 24 h. It has been assumed this schedule, like a variety of other functions in the rabbit, is under circadian control. This assumption has been largely based on findings from mothers only permitted restricted access to their young once every 24 h. However, in nature and in the laboratory, mothers with free access to young show nursing visits with a periodicity shorter than 24 h, that does not correspond to other behavioral and physiological rhythms entrained to the prevailing 24 h light/dark (LD) cycle. To investigate how this unusual, apparently non-circadian pattern might be regulated, we conducted two experiments using female Dutch-belted rabbits housed individually in cages designed to automatically register feeding activity and nest box visits. In Experiment 1 we recorded the behavior of 17 mothers with free access to their young under five different LD cycles with long photo and short scotoperiods, spanning the limits of entrainment of the rabbit's circadian system. Whereas feeding rhythms were entrained by LD cycles within the rabbit's circadian range of entrainment, nursing visits showed a consistently shorter periodicity regardless of the LD regimen, largely independent of the circadian system. In Experiment 2 we tested further 12 mothers under more conventional LD 16:8 cycles but "trained" by having access to the nest box restricted to 1 h at the same time each day for the first 7 d of nursing. Mothers were then allowed free access either when their young were left in the box (n= 6), or when the litter had been permanently removed (n= 6). Mothers with pups still present returned to nurse them on the following days according to a similarly advancing pattern to the mothers of Experiment 1 despite the previous 7 d of "training" to an experimentally enforced 24 h nursing schedule as commonly used in previous studies of rabbit maternal behavior. Mothers whose pups had been removed entered the box repeatedly several times on the first day of unrestricted access, but on subsequent days did so only rarely, and at times of day apparently unrelated to the previously scheduled access. We conclude that the pattern of the rabbit's once-daily nursing visits has a periodicity largely independent of the circadian system, and that this is reset at each nursing. When nursing fails to occur nest box visits cease abruptly, with mothers making few or no subsequent visits. Together, these findings suggest that the rabbit's once-daily pattern of nursing is regulated by an hourglass-type process with a period less than 24 h that is reset at each nursing, rather than by a circadian oscillator. Such a mechanism might be particularly adaptive for rhythms of short duration that should end abruptly with a sudden change in context such as death or weaning of the young.
- Description: This work was supported by the Australian Federal Government via a Postgraduate PhD Scholarship for Sabibe Apel [APA SA 1].
- Authors: Apel, Sabine , Hudson, Robyn , Coleman, Grahame , Rodel, Heiko , Kennedy, Gerard
- Date: 2020
- Type: Text , Journal article
- Relation: Chronobiology International Vol. 37, no. 8 (2020), p. 1151-1162
- Full Text:
- Reviewed:
- Description: The European rabbitOryctolagus cuniculushas an unusual pattern of nursing behavior. After giving birth in a nursery burrow (or laboratory nest box), the mother immediately leaves the young and only returns to nurse for a few minutes once approximately every 24 h. It has been assumed this schedule, like a variety of other functions in the rabbit, is under circadian control. This assumption has been largely based on findings from mothers only permitted restricted access to their young once every 24 h. However, in nature and in the laboratory, mothers with free access to young show nursing visits with a periodicity shorter than 24 h, that does not correspond to other behavioral and physiological rhythms entrained to the prevailing 24 h light/dark (LD) cycle. To investigate how this unusual, apparently non-circadian pattern might be regulated, we conducted two experiments using female Dutch-belted rabbits housed individually in cages designed to automatically register feeding activity and nest box visits. In Experiment 1 we recorded the behavior of 17 mothers with free access to their young under five different LD cycles with long photo and short scotoperiods, spanning the limits of entrainment of the rabbit's circadian system. Whereas feeding rhythms were entrained by LD cycles within the rabbit's circadian range of entrainment, nursing visits showed a consistently shorter periodicity regardless of the LD regimen, largely independent of the circadian system. In Experiment 2 we tested further 12 mothers under more conventional LD 16:8 cycles but "trained" by having access to the nest box restricted to 1 h at the same time each day for the first 7 d of nursing. Mothers were then allowed free access either when their young were left in the box (n= 6), or when the litter had been permanently removed (n= 6). Mothers with pups still present returned to nurse them on the following days according to a similarly advancing pattern to the mothers of Experiment 1 despite the previous 7 d of "training" to an experimentally enforced 24 h nursing schedule as commonly used in previous studies of rabbit maternal behavior. Mothers whose pups had been removed entered the box repeatedly several times on the first day of unrestricted access, but on subsequent days did so only rarely, and at times of day apparently unrelated to the previously scheduled access. We conclude that the pattern of the rabbit's once-daily nursing visits has a periodicity largely independent of the circadian system, and that this is reset at each nursing. When nursing fails to occur nest box visits cease abruptly, with mothers making few or no subsequent visits. Together, these findings suggest that the rabbit's once-daily pattern of nursing is regulated by an hourglass-type process with a period less than 24 h that is reset at each nursing, rather than by a circadian oscillator. Such a mechanism might be particularly adaptive for rhythms of short duration that should end abruptly with a sudden change in context such as death or weaning of the young.
- Description: This work was supported by the Australian Federal Government via a Postgraduate PhD Scholarship for Sabibe Apel [APA SA 1].
Safety and immunogenicity of pneumococcal conjugate vaccines in a high-risk population : A randomized controlled trial of 10-valent and 13-valent pneumococcal conjugate vaccine in Papua New Guinean infants
- Pomat, William, Van Den Biggelaar, Anita, Wana, Sandra, Francis, Jacinta, Solomon, Vela, Greenhill, Andrew, Ford, Rebecca, Orami, Tilda, Passey, Megan, Jacoby, Peter, Kirkham, Lea-Ann, Lehmann, Deborah, Richmond, Peter
- Authors: Pomat, William , Van Den Biggelaar, Anita , Wana, Sandra , Francis, Jacinta , Solomon, Vela , Greenhill, Andrew , Ford, Rebecca , Orami, Tilda , Passey, Megan , Jacoby, Peter , Kirkham, Lea-Ann , Lehmann, Deborah , Richmond, Peter
- Date: 2019
- Type: Text , Journal article
- Relation: Clinical Infectious Diseases Vol. 68, no. 9 (2019), p. 1472-1481
- Full Text:
- Reviewed:
- Description: Background. There are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population. Methods. PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age. Results. One month after the third dose of PCV10 or PCV13, 80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85–96) of children vaccinated with PCV10 and 81% (95% CI 72–88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events. Conclusions. Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed. Clinical Trials Registration. NCT01619462.
- Authors: Pomat, William , Van Den Biggelaar, Anita , Wana, Sandra , Francis, Jacinta , Solomon, Vela , Greenhill, Andrew , Ford, Rebecca , Orami, Tilda , Passey, Megan , Jacoby, Peter , Kirkham, Lea-Ann , Lehmann, Deborah , Richmond, Peter
- Date: 2019
- Type: Text , Journal article
- Relation: Clinical Infectious Diseases Vol. 68, no. 9 (2019), p. 1472-1481
- Full Text:
- Reviewed:
- Description: Background. There are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population. Methods. PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age. Results. One month after the third dose of PCV10 or PCV13, 80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85–96) of children vaccinated with PCV10 and 81% (95% CI 72–88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events. Conclusions. Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed. Clinical Trials Registration. NCT01619462.
Proteomic identification of galectin-11 and 14 ligands from Haemonchus contortus
- Sakthivel, Dhanasekaran, Swan, Jaclyn, Preston, Sarah, Shakif-Azam, MD, Faou, Pierre, Jiao, Yaqing, Downs, Rachael, Rajapaksha, Harinda, Gasser, Robin, Piedrafita, David, Beddoe, Travis
- Authors: Sakthivel, Dhanasekaran , Swan, Jaclyn , Preston, Sarah , Shakif-Azam, MD , Faou, Pierre , Jiao, Yaqing , Downs, Rachael , Rajapaksha, Harinda , Gasser, Robin , Piedrafita, David , Beddoe, Travis
- Date: 2018
- Type: Text , Journal article
- Relation: Peerj Vol. 6, no. 3 (2018), p. 1-19
- Full Text:
- Reviewed:
- Description: Haemonchus contortus is the most pathogenic nematode of small ruminants. Infection in sheep and goats results in anaemia that decreases animal productivity and can ultimately cause death. The involvement of ruminant-specific galectin-11 (LGALS-11) and galectin-14 (LGALS-14) has been postulated to play important roles in protective immune responses against parasitic infection; however, their ligands are unknown. In the current study, LGALS-11 and LGALS-14 ligands in H. contortus were identified from larval (L4) and adult parasitic stages extracts using immobilised LGALS-11 and LGALS-14 affinity column chromatography and mass spectrometry. Both LGALS-11 and LGALS-14 bound more putative protein targets in the adult stage of H. contortus (43 proteins) when compared to the larval stage (two proteins). Of the 43 proteins identified in the adult stage, 34 and 35 proteins were bound by LGALS-11 and LGALS-14, respectively, with 26 proteins binding to both galectins. Interestingly, hematophagous stage-specific sperm-coating protein and zinc metalloprotease (M13), which are known vaccine candidates, were identified as putative ligands of both LGALS-11 and LGALS- 14. The identification of glycoproteins of H. contortus by LGALS-11 and LGALS-14 provide new insights into host-parasite interactions and the potential for developing new interventions.
- Authors: Sakthivel, Dhanasekaran , Swan, Jaclyn , Preston, Sarah , Shakif-Azam, MD , Faou, Pierre , Jiao, Yaqing , Downs, Rachael , Rajapaksha, Harinda , Gasser, Robin , Piedrafita, David , Beddoe, Travis
- Date: 2018
- Type: Text , Journal article
- Relation: Peerj Vol. 6, no. 3 (2018), p. 1-19
- Full Text:
- Reviewed:
- Description: Haemonchus contortus is the most pathogenic nematode of small ruminants. Infection in sheep and goats results in anaemia that decreases animal productivity and can ultimately cause death. The involvement of ruminant-specific galectin-11 (LGALS-11) and galectin-14 (LGALS-14) has been postulated to play important roles in protective immune responses against parasitic infection; however, their ligands are unknown. In the current study, LGALS-11 and LGALS-14 ligands in H. contortus were identified from larval (L4) and adult parasitic stages extracts using immobilised LGALS-11 and LGALS-14 affinity column chromatography and mass spectrometry. Both LGALS-11 and LGALS-14 bound more putative protein targets in the adult stage of H. contortus (43 proteins) when compared to the larval stage (two proteins). Of the 43 proteins identified in the adult stage, 34 and 35 proteins were bound by LGALS-11 and LGALS-14, respectively, with 26 proteins binding to both galectins. Interestingly, hematophagous stage-specific sperm-coating protein and zinc metalloprotease (M13), which are known vaccine candidates, were identified as putative ligands of both LGALS-11 and LGALS- 14. The identification of glycoproteins of H. contortus by LGALS-11 and LGALS-14 provide new insights into host-parasite interactions and the potential for developing new interventions.
Scarcity of ecosystem services : an experimental manipulation of declining pollination rates and its economic consequences for agriculture
- Sandhu, Harpinder, Waterhouse, Benjamin, Boyer, Stéphane, Wratten, Steve
- Authors: Sandhu, Harpinder , Waterhouse, Benjamin , Boyer, Stéphane , Wratten, Steve
- Date: 2016
- Type: Text , Journal article
- Relation: PeerJ Vol. 2016, no. 7 (2016), p.
- Full Text:
- Reviewed:
- Description: Ecosystem services (ES) such as pollination are vital for the continuous supply of food to a growing human population, but the decline in populations of insect pollinators worldwide poses a threat to food and nutritional security. Using a pollinator (honeybee) exclusion approach, we evaluated the impact of pollinator scarcity on production in four brassica fields, two producing hybrid seeds and two producing open-pollinated ones. There was a clear reduction in seed yield as pollination rates declined. Open-pollinated crops produced significantly higher yields than did the hybrid ones at all pollination rates. The hybrid crops required at least 0.50 of background pollination rates to achieve maximum yield, whereas in open-pollinated crops, 0.25 pollination rates were necessary for maximum yield. The total estimated economic value of pollination services provided by honeybees to the agricultural industry in New Zealand is NZD $1.96 billion annually. This study indicates that loss of pollination services can result in significant declines in production and have serious implications for the market economy in New Zealand. Depending on the extent of honeybee population decline, and assuming that results in declining pollination services, the estimated economic loss to New Zealand agriculture could be in the range of NZD $295-728 million annually. © 2016 Sandhu et al.
- Authors: Sandhu, Harpinder , Waterhouse, Benjamin , Boyer, Stéphane , Wratten, Steve
- Date: 2016
- Type: Text , Journal article
- Relation: PeerJ Vol. 2016, no. 7 (2016), p.
- Full Text:
- Reviewed:
- Description: Ecosystem services (ES) such as pollination are vital for the continuous supply of food to a growing human population, but the decline in populations of insect pollinators worldwide poses a threat to food and nutritional security. Using a pollinator (honeybee) exclusion approach, we evaluated the impact of pollinator scarcity on production in four brassica fields, two producing hybrid seeds and two producing open-pollinated ones. There was a clear reduction in seed yield as pollination rates declined. Open-pollinated crops produced significantly higher yields than did the hybrid ones at all pollination rates. The hybrid crops required at least 0.50 of background pollination rates to achieve maximum yield, whereas in open-pollinated crops, 0.25 pollination rates were necessary for maximum yield. The total estimated economic value of pollination services provided by honeybees to the agricultural industry in New Zealand is NZD $1.96 billion annually. This study indicates that loss of pollination services can result in significant declines in production and have serious implications for the market economy in New Zealand. Depending on the extent of honeybee population decline, and assuming that results in declining pollination services, the estimated economic loss to New Zealand agriculture could be in the range of NZD $295-728 million annually. © 2016 Sandhu et al.
Acute whole body UVA irradiation combined with nitrate ingestion enhances time trial performance in trained cyclists
- Muggeridge, David, Sculthorpe, Nicholas, Grace, Fergal, Willis, Gareth, Thornhill, Laurence, Weller, Richard, James, Philip, Easton, Chris
- Authors: Muggeridge, David , Sculthorpe, Nicholas , Grace, Fergal , Willis, Gareth , Thornhill, Laurence , Weller, Richard , James, Philip , Easton, Chris
- Date: 2015
- Type: Text , Journal article
- Relation: Nitric Oxide : Biology and Chemistry Vol. 48, no. (2015), p. 3-9
- Full Text:
- Reviewed:
- Description: Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 +/- 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 x 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean +/- SD 1447 +/- 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 +/- 40 s; d = 0.41) or NIT + SHAM (1455 +/- 47 s; d = 0.28) compared to PLA + SHAM (1469 +/- 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve performance in a laboratory setting. A combination of UV-A and NIT, however, does improve cycling TT performance in this environment, which may be due to a larger increase in NO availability.
- Authors: Muggeridge, David , Sculthorpe, Nicholas , Grace, Fergal , Willis, Gareth , Thornhill, Laurence , Weller, Richard , James, Philip , Easton, Chris
- Date: 2015
- Type: Text , Journal article
- Relation: Nitric Oxide : Biology and Chemistry Vol. 48, no. (2015), p. 3-9
- Full Text:
- Reviewed:
- Description: Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 +/- 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 x 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean +/- SD 1447 +/- 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 +/- 40 s; d = 0.41) or NIT + SHAM (1455 +/- 47 s; d = 0.28) compared to PLA + SHAM (1469 +/- 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve performance in a laboratory setting. A combination of UV-A and NIT, however, does improve cycling TT performance in this environment, which may be due to a larger increase in NO availability.
Generation of a Novel Bacteriophage Library displaying scFv antibody fragments from the natural Buffalo host to identify antigens from adult Schistosoma japonicum for diagnostic development
- Hosking, Christopher, McWilliam, Hamish, Driguez, Patrick, Piedrafita, David, Li, Yuesheng, McManus, Donald, Ilag, Leodevico, Meeusen, Els, De Veer, Michael
- Authors: Hosking, Christopher , McWilliam, Hamish , Driguez, Patrick , Piedrafita, David , Li, Yuesheng , McManus, Donald , Ilag, Leodevico , Meeusen, Els , De Veer, Michael
- Date: 2015
- Type: Text , Journal article
- Relation: PLoS Neglected Tropical Diseases Vol. 9, no. 12 (2015), p. 1-20
- Full Text:
- Reviewed:
- Description: The development of effective diagnostic tools will be essential in the continuing fight to reduce schistosome infection; however, the diagnostic tests available to date are generally laborious and difficult to implement in current parasite control strategies. We generated a series of single-chain antibody Fv domain (scFv) phage display libraries from the portal lymph node of field exposed water buffaloes, Bubalus bubalis, 11–12 days post challenge with Schistosoma japonicum cercariae. The selected scFv-phages showed clear enrichment towards adult schistosomes and excretory-secretory (ES) proteins by immunofluorescence, ELISA and western blot analysis. The enriched libraries were used to probe a schistosome specific protein microarray resulting in the recognition of a number of proteins, five of which were specific to schistosomes, with RNA expression predominantly in the adult life-stage based on interrogation of schistosome expressed sequence tags (EST). As the libraries were enriched by panning against ES products, these antigens may be excreted or secreted into the host vasculature and hence may make good targets for a diagnostic assay. Further selection of the scFv library against infected mouse sera identified five soluble scFv clones that could selectively recognise soluble whole adult preparations (SWAP) relative to an irrelevant protein control (ovalbumin). Furthermore, two of the identified scFv clones also selectively recognised SWAP proteins when spiked into naïve mouse sera. These host B-cell derived scFvs that specifically bind to schistosome protein preparations will be valuable reagents for further development of a cost effective point-of-care diagnostic test. © 2015 Hosking et al.
- Authors: Hosking, Christopher , McWilliam, Hamish , Driguez, Patrick , Piedrafita, David , Li, Yuesheng , McManus, Donald , Ilag, Leodevico , Meeusen, Els , De Veer, Michael
- Date: 2015
- Type: Text , Journal article
- Relation: PLoS Neglected Tropical Diseases Vol. 9, no. 12 (2015), p. 1-20
- Full Text:
- Reviewed:
- Description: The development of effective diagnostic tools will be essential in the continuing fight to reduce schistosome infection; however, the diagnostic tests available to date are generally laborious and difficult to implement in current parasite control strategies. We generated a series of single-chain antibody Fv domain (scFv) phage display libraries from the portal lymph node of field exposed water buffaloes, Bubalus bubalis, 11–12 days post challenge with Schistosoma japonicum cercariae. The selected scFv-phages showed clear enrichment towards adult schistosomes and excretory-secretory (ES) proteins by immunofluorescence, ELISA and western blot analysis. The enriched libraries were used to probe a schistosome specific protein microarray resulting in the recognition of a number of proteins, five of which were specific to schistosomes, with RNA expression predominantly in the adult life-stage based on interrogation of schistosome expressed sequence tags (EST). As the libraries were enriched by panning against ES products, these antigens may be excreted or secreted into the host vasculature and hence may make good targets for a diagnostic assay. Further selection of the scFv library against infected mouse sera identified five soluble scFv clones that could selectively recognise soluble whole adult preparations (SWAP) relative to an irrelevant protein control (ovalbumin). Furthermore, two of the identified scFv clones also selectively recognised SWAP proteins when spiked into naïve mouse sera. These host B-cell derived scFvs that specifically bind to schistosome protein preparations will be valuable reagents for further development of a cost effective point-of-care diagnostic test. © 2015 Hosking et al.
Increased expression of telomere-regulating genes in endurance athletes with long leukocyte telomeres
- Denham, Joshua, O'Brien, Brendan, Prestes, Priscilla, Brown, Nicholas, Charchar, Fadi
- Authors: Denham, Joshua , O'Brien, Brendan , Prestes, Priscilla , Brown, Nicholas , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Applied Physiology Vol. 120, no. 2 (2015), p. 148-158
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Leukocyte telomeres shorten with age, and excessive shortening is associated with age-related cardiometabolic diseases. Exercise training may prevent disease through telomere length maintenance although the optimal amount of exercise that attenuates telomere attrition is unknown. Furthermore, the underlying molecular mechanisms responsible for the enhanced telomere maintenance observed in endurance athletes is poorly understood. We quantified the leukocyte telomere length and analyzed the expression of telomere-regulating genes in endurance athletes and healthy controls (both n = 61), using quantitative PCR. We found endurance athletes have significantly longer (7.1%, 208-416 nt) leukocyte telomeres and upregulated TERT (2.0-fold) and TPP1 (1.3-fold) mRNA expression compared with controls in age-adjusted analysis. The telomere length and telomere-regulating gene expression differences were no longer statistically significant after adjustment for resting heart rate and relative (V) over dotO(2 max) (all P > 0.05). Resting heart rate emerged as an independent predictor of leukocyte telomere length and TERT and TPP1 mRNA expression in stepwise regression models. To gauge whether volume of exercise was associated with leukocyte telomere length, we divided subjects into running and cycling tertiles (distance covered per week) and found individuals in the middle and highest tertiles had longer telomeres than individuals in the lowest tertile. These data emphasize the importance of cardiorespiratory fitness and exercise training in the prevention of biological aging. They also support the concept that moderate amounts of exercise training protects against biological aging, while higher amounts may not elicit additional benefits.
- Authors: Denham, Joshua , O'Brien, Brendan , Prestes, Priscilla , Brown, Nicholas , Charchar, Fadi
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Applied Physiology Vol. 120, no. 2 (2015), p. 148-158
- Relation: http://purl.org/au-research/grants/nhmrc/1009490
- Full Text:
- Reviewed:
- Description: Leukocyte telomeres shorten with age, and excessive shortening is associated with age-related cardiometabolic diseases. Exercise training may prevent disease through telomere length maintenance although the optimal amount of exercise that attenuates telomere attrition is unknown. Furthermore, the underlying molecular mechanisms responsible for the enhanced telomere maintenance observed in endurance athletes is poorly understood. We quantified the leukocyte telomere length and analyzed the expression of telomere-regulating genes in endurance athletes and healthy controls (both n = 61), using quantitative PCR. We found endurance athletes have significantly longer (7.1%, 208-416 nt) leukocyte telomeres and upregulated TERT (2.0-fold) and TPP1 (1.3-fold) mRNA expression compared with controls in age-adjusted analysis. The telomere length and telomere-regulating gene expression differences were no longer statistically significant after adjustment for resting heart rate and relative (V) over dotO(2 max) (all P > 0.05). Resting heart rate emerged as an independent predictor of leukocyte telomere length and TERT and TPP1 mRNA expression in stepwise regression models. To gauge whether volume of exercise was associated with leukocyte telomere length, we divided subjects into running and cycling tertiles (distance covered per week) and found individuals in the middle and highest tertiles had longer telomeres than individuals in the lowest tertile. These data emphasize the importance of cardiorespiratory fitness and exercise training in the prevention of biological aging. They also support the concept that moderate amounts of exercise training protects against biological aging, while higher amounts may not elicit additional benefits.
Interval between infections and viral hierarchy are determinants of viral interference following influenza virus infection in a ferret model
- Laurie, Karen, Guarnaccia, Teagan, Carolan, Louise, Yan, Aada, Aban, Malet, Petrie, Stephen, Cao, Pengxing, Heffernan, Jane, McVernon, Jodie, Mosse, Jennifer, Kelso, Anne, McCaw, James, Barr, Ian
- Authors: Laurie, Karen , Guarnaccia, Teagan , Carolan, Louise , Yan, Aada , Aban, Malet , Petrie, Stephen , Cao, Pengxing , Heffernan, Jane , McVernon, Jodie , Mosse, Jennifer , Kelso, Anne , McCaw, James , Barr, Ian
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Infectious Diseases Vol. 212, no. 10 (2015), p. 1701-1710
- Full Text:
- Reviewed:
- Description: Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
- Authors: Laurie, Karen , Guarnaccia, Teagan , Carolan, Louise , Yan, Aada , Aban, Malet , Petrie, Stephen , Cao, Pengxing , Heffernan, Jane , McVernon, Jodie , Mosse, Jennifer , Kelso, Anne , McCaw, James , Barr, Ian
- Date: 2015
- Type: Text , Journal article
- Relation: Journal of Infectious Diseases Vol. 212, no. 10 (2015), p. 1701-1710
- Full Text:
- Reviewed:
- Description: Background. Epidemiological studies suggest that, following infection with influenza virus, there is a short period during which a host experiences a lower susceptibility to infection with other influenza viruses. This viral interference appears to be independent of any antigenic similarities between the viruses. We used the ferret model of human influenza to systematically investigate viral interference. Methods. Ferrets were first infected then challenged 1-14 days later with pairs of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B viruses circulating in 2009 and 2010. Results. Viral interference was observed when the interval between initiation of primary infection and subsequent challenge was <1 week. This effect was virus specific and occurred between antigenically related and unrelated viruses. Coinfections occurred when 1 or 3 days separated infections. Ongoing shedding from the primary virus infection was associated with viral interference after the secondary challenge. Conclusions. The interval between infections and the sequential combination of viruses were important determinants of viral interference. The influenza viruses in this study appear to have an ordered hierarchy according to their ability to block or delay infection, which may contribute to the dominance of different viruses often seen in an influenza season.
Local immune responses of the Chinese water buffalo, Bubalus bubalis, against Schistosoma japonicum larvae: crucial insights for vaccine design
- McWilliam, Hamish, Piedrafita, David, Li, Yuesheng, Zheng, Mao, He, Yongkang, Yu, Xinling, McManus, Donald, Meeusen, Els
- Authors: McWilliam, Hamish , Piedrafita, David , Li, Yuesheng , Zheng, Mao , He, Yongkang , Yu, Xinling , McManus, Donald , Meeusen, Els
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS Neglected Tropical Diseases. Vol.7, no.9(Art.No: e2460) (2013), p. 1-11
- Full Text:
- Reviewed:
- Description: Asian schistosomiasis is a zoonotic parasitic disease infecting up to a million people and threatening tens of millions more. Control of this disease is hindered by the animal reservoirs of the parasite, in particular the water buffalo (Bubalus bubalis), which is responsible for significant levels of human transmission. A transmission-blocking vaccine administered to buffaloes is a realistic option which would aid in the control of schistosomiasis. This will however require a better understanding of the immunobiology of schistosomiasis in naturally exposed buffaloes, particularly the immune response to migrating schistosome larvae, which are the likely targets of an anti-schistosome vaccine. To address this need we investigated the immune response at the major sites of larval migration, the skin and the lungs, in previously exposed and re-challenged water buffaloes. In the skin, a strong allergic-type inflammatory response occurred, characterised by leukocyte and eosinophil infiltration including the formation of granulocytic abscesses. Additionally at the local skin site, interleukin-5 transcript levels were elevated, while interleukin-10 levels decreased. In the skin-draining lymph node (LN) a predominant type-2 profile was seen in stimulated cells, while in contrast a type-1 profile was detected in the lung draining LN, and these responses occurred consecutively, reflecting the timing of parasite migration. The intense type-2 immune response at the site of cercarial penetration is significantly different to that seen in naive and permissive animal models such as mice, and suggests a possible mechanism for immunity. Preliminary data also suggest a reduced and delayed immune response occurred in buffaloes given high cercarial challenge doses compared with moderate infections, particularly in the skin. This study offers a deeper understanding into the immunobiology of schistosomiasis in a natural host, which may aid in the future design of more effective vaccines.
- Authors: McWilliam, Hamish , Piedrafita, David , Li, Yuesheng , Zheng, Mao , He, Yongkang , Yu, Xinling , McManus, Donald , Meeusen, Els
- Date: 2013
- Type: Text , Journal article
- Relation: PLoS Neglected Tropical Diseases. Vol.7, no.9(Art.No: e2460) (2013), p. 1-11
- Full Text:
- Reviewed:
- Description: Asian schistosomiasis is a zoonotic parasitic disease infecting up to a million people and threatening tens of millions more. Control of this disease is hindered by the animal reservoirs of the parasite, in particular the water buffalo (Bubalus bubalis), which is responsible for significant levels of human transmission. A transmission-blocking vaccine administered to buffaloes is a realistic option which would aid in the control of schistosomiasis. This will however require a better understanding of the immunobiology of schistosomiasis in naturally exposed buffaloes, particularly the immune response to migrating schistosome larvae, which are the likely targets of an anti-schistosome vaccine. To address this need we investigated the immune response at the major sites of larval migration, the skin and the lungs, in previously exposed and re-challenged water buffaloes. In the skin, a strong allergic-type inflammatory response occurred, characterised by leukocyte and eosinophil infiltration including the formation of granulocytic abscesses. Additionally at the local skin site, interleukin-5 transcript levels were elevated, while interleukin-10 levels decreased. In the skin-draining lymph node (LN) a predominant type-2 profile was seen in stimulated cells, while in contrast a type-1 profile was detected in the lung draining LN, and these responses occurred consecutively, reflecting the timing of parasite migration. The intense type-2 immune response at the site of cercarial penetration is significantly different to that seen in naive and permissive animal models such as mice, and suggests a possible mechanism for immunity. Preliminary data also suggest a reduced and delayed immune response occurred in buffaloes given high cercarial challenge doses compared with moderate infections, particularly in the skin. This study offers a deeper understanding into the immunobiology of schistosomiasis in a natural host, which may aid in the future design of more effective vaccines.
Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study
- Fox, Ervin, Young, J. Hunter, Li, Yali, Dreisbach, Albert, Charchar, Fadi
- Authors: Fox, Ervin , Young, J. Hunter , Li, Yali , Dreisbach, Albert , Charchar, Fadi
- Date: 2011
- Type: Text , Journal article
- Relation: Human molecular genetics Vol. 20, no. 11 (June 2011), p. 2273
- Full Text:
- Reviewed:
- Description: The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.
- Authors: Fox, Ervin , Young, J. Hunter , Li, Yali , Dreisbach, Albert , Charchar, Fadi
- Date: 2011
- Type: Text , Journal article
- Relation: Human molecular genetics Vol. 20, no. 11 (June 2011), p. 2273
- Full Text:
- Reviewed:
- Description: The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10−8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10−8). The top IBC association for SBP was rs2012318 (P= 6.4 × 10−6) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10−6) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.
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