University of Otago
  • Dunedin, Otago, New Zealand
Recent publications
Soluble amyloid precursor protein-alpha (sAPPα) is a regulator of neuronal and memory mechanisms, while also having neurogenic and neuroprotective effects in the brain. As adult hippocampal neurogenesis is impaired in Alzheimer’s disease, we tested the hypothesis that sAPPα delivery would rescue adult hippocampal neurogenesis in an APP/PS1 mouse model of Alzheimer’s disease. An adeno-associated virus-9 (AAV9) encoding murine sAPPα was injected into the hippocampus of 8-month-old wild-type and APP/PS1 mice, and later two different thymidine analogues (XdU) were systemically injected to label adult-born cells at different time points after viral transduction. The proliferation of adult-born cells, cell survival after eight weeks, and cell differentiation into either neurons or astrocytes was studied. Proliferation was impaired in APP/PS1 mice but was restored to wild-type levels by viral expression of sAPPα. In contrast, sAPPα overexpression failed to rescue the survival of XdU ⁺ -labelled cells that was impaired in APP/PS1 mice, although it did cause a significant increase in the area density of astrocytes in the granule cell layer across both genotypes. Finally, viral expression of sAPPα reduced amyloid-beta plaque load in APP/PS1 mice in the dentate gyrus and somatosensory cortex. These data add further evidence that increased levels of sAPPα could be therapeutic for the cognitive decline in AD, in part through restoration of the proliferation of neural progenitor cells in adults.
Background Our understanding of the peripheral human immunodeficiency virus type 1 (HIV-1) reservoir is strongly biased towards subtype B HIV-1 strains, with only limited information available from patients infected with non-B HIV-1 subtypes, which are the predominant viruses seen in low- and middle-income countries (LMIC) in Africa and Asia. Results In this study, blood samples were obtained from well-suppressed ART-experienced HIV-1 patients monitored in Uganda (n = 62) or the U.S. (n = 50), with plasma HIV-1 loads < 50 copies/ml and CD4 ⁺ T-cell counts > 300 cells/ml. The peripheral HIV-1 reservoir, i.e., cell-associated HIV-1 RNA and proviral DNA, was characterized using our novel deep sequencing-based EDITS assay. Ugandan patients were slightly younger (median age 43 vs 49 years) and had slightly lower CD4 ⁺ counts (508 vs 772 cells/ml) than U.S. individuals. All Ugandan patients were infected with non-B HIV-1 subtypes (31% A1, 64% D, or 5% C), while all U.S. individuals were infected with subtype B viruses. Unexpectedly, we observed a significantly larger peripheral inducible HIV-1 reservoir in U.S. patients compared to Ugandan individuals (48 vs. 11 cell equivalents/million cells, p < 0.0001). This divergence in reservoir size was verified measuring proviral DNA (206 vs. 88 cell equivalents/million cells, p < 0.0001). However, the peripheral HIV-1 reservoir was more diverse in Ugandan than in U.S. individuals (8.6 vs. 4.7 p-distance, p < 0.0001). Conclusions The smaller, but more diverse, peripheral HIV-1 reservoir in Ugandan patients might be associated with viral (e.g., non-B subtype with higher cytopathicity) and/or host (e.g., higher incidence of co-infections or co-morbidities leading to less clonal expansion) factors. This highlights the need to understand reservoir dynamics in diverse populations as part of ongoing efforts to find a functional cure for HIV-1 infection in LMICs.
Background Intravenous vitamin C administration in septic shock may have a sparing effect on vasopressor requirements, and vitamin C’s enzyme cofactor functions provide a mechanistic rationale. Our study aimed to determine the effect of intravenous vitamin C administration on vasopressor requirements and other outcomes in patients with septic shock. Methods This was a double-blind, randomised placebo-controlled trial in 40 patients with septic shock who were randomised (1:1) to receive intravenous vitamin C (at a dose of 25 mg/kg of body weight every 6 h) or placebo (intravenous 5% dextrose) for up to 96 h, or until death or discharge. The primary outcome was intravenous vasopressor requirements (dose and duration), and secondary outcomes included Sequential Organ Failure Assessment (SOFA) scores, intensive care unit (ICU) and hospital length of stay, and mortality. In addition, blood samples were collected to determine vitamin C kinetics and inflammatory marker concentrations. Results Median plasma vitamin C concentrations were deficient at baseline (9.2 [4.4, 12] µmol/L) and increased to 408 (227, 560) µmol/L following 72 h of intervention. The mean duration of intravenous vasopressor infusion in the vitamin C group was 48 (95% CI 35–62) hours and in the placebo group was 54 (95% CI 41–62) hours (p = 0.52). The dose of vasopressor delivered over time was comparable between the two groups, as were SOFA scores (p > 0.05). The median ICU length of stay in the intervention group was 3.8 (2.2, 9.8) days versus 7.1 (3.1, 20) days in the placebo group (p = 0.12). The median hospital length of stay for the vitamin C group was 18 (11, 35) days versus 22 (10, 52) days for the placebo group (p = 0.65). Mortality was comparable between the two groups (p > 0.05). Of the inflammatory markers, neutrophil counts were elevated in the vitamin C group relative to placebo by 72 h (p = 0.01). C-reactive protein and myeloperoxidase concentrations were elevated at baseline, however, the two groups were comparable over time (p > 0.05). Conclusions Our pilot study indicated that intravenous vitamin C did not provide significant decreases in the mean dose or duration of vasopressor infusion. Further research that takes into account the potential impact of intervention timing, dose and duration, and location of trial, may provide more definitive evidence. Trial registration ACTRN12617001184369 (11/8/2017).
Objective Human intestinal organoids (hIOs) have potential as a model for investigating intestinal diseases. The hIO system faces logistic challenges including limited access to biopsies or low expression of epithelial cell types. Previous research identified the feasibility of tissue from the transverse (TC) or sigmoid colon (SC), or from cryopreserved biopsies from regions of the gastrointestinal tract. We aimed to create a protocol for robust hIO generation that could be implemented across multiple centres, allowing for development of a consistent biobank of hIOs from diverse patients. Results TC and SC hIOs were expanded from fresh or frozen biopsies with standard or refined media. The expression of epithelial cells was evaluated via PCR. Growth of TC and SC hIO from healthy donors was reproducible from freshly acquired and frozen biopsies. A refined media including insulin-like growth factor (IGF)-1 and fibroblast growth factor (FGF)-2 enabled the expression of epithelial cells, including higher expression of goblet cells and enterocytes compared to standard organoid media. We identified a consistent time point where hIOs generated from frozen biopsies reflect similar hIO composition from freshly acquired samples. Feasibility of hIOs as a tool for research and clinical use, including the use of frozen biopsies, was demonstrated.
Background Insects have exceptionally fast smelling capabilities, and some can track the temporal structure of odour plumes at rates above 100 Hz. It has been hypothesized that this fast smelling capability is an adaptation for flying. We test this hypothesis by comparing the olfactory acuity of sympatric flighted versus flightless lineages within a wing-polymorphic stonefly species. Results Our analyses of olfactory receptor neuron responses reveal that recently-evolved flightless lineages have reduced olfactory acuity. By comparing flighted versus flightless ecotypes with similar genetic backgrounds, we eliminate other confounding factors that might have affected the evolution of their olfactory reception mechanisms. Our detection of different patterns of reduced olfactory response strength and speed in independently wing-reduced lineages suggests parallel evolution of reduced olfactory acuity. Conclusions These reductions in olfactory acuity echo the rapid reduction of wings themselves, and represent an olfactory parallel to the convergent phenotypic shifts seen under selective gradients in other sensory systems (e.g. parallel loss of vision in cave fauna). Our study provides evidence for the hypothesis that flight poses a selective pressure on the speed and strength of olfactory receptor neuron responses and emphasizes the energetic costs of rapid olfaction.
The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
This narrative review describes efforts to improve the care and prevention of fragility fractures in New Zealand from 2012 to 2022. This includes development of clinical standards and registries to benchmark provision of care, and public awareness campaigns to promote a life-course approach to bone health. Purpose: This review describes the development and implementation of a systematic approach to care and prevention for New Zealanders with fragility fractures, and those at high risk of first fracture. Progression of existing initiatives and introduction of new initiatives are proposed for the period 2022 to 2030. Methods: In 2012, Osteoporosis New Zealand developed and published a strategy with objectives relating to people who sustain hip and other fragility fractures, those at high risk of first fragility fracture or falls and all older people. The strategy also advocated formation of a national fragility fracture alliance to expedite change. Results: In 2017, a previously informal national alliance was formalised under the Live Stronger for Longer programme, which includes stakeholder organisations from relevant sectors, including government, healthcare professionals, charities and the health system. Outputs of this alliance include development of Australian and New Zealand clinical guidelines, clinical standards and quality indicators and a bi-national registry that underpins efforts to improve hip fracture care. All 22 hospitals in New Zealand that operate on hip fracture patients currently submit data to the registry. An analogous approach is ongoing to improve secondary fracture prevention for people who sustain fragility fractures at other sites through nationwide access to Fracture Liaison Services. Conclusion: Widespread participation in national registries is enabling benchmarking against clinical standards as a means to improve the care of hip and other fragility fractures in New Zealand. An ongoing quality improvement programme is focused on eliminating unwarranted variation in delivery of secondary fracture prevention.
Full text available at: Previous studies have suggested that people are sensitive to anticipated cognitive processing demands when deciding which task to perform, but the influence of perceptual processing demands on voluntary task choice is still unclear. The present study tested whether voluntary task choice behavior may be influenced by unpredictable task-specific perceptual processing demands. Across four experiments using different voluntary task choice procedures, we randomly varied the perceptual discriminability of stimuli (easy vs. hard color discrimination) for one of the two tasks. We reasoned that people could only reactively adjust their task choice behavior to the unpredictable discriminability manipulation if they engaged in some perceptual processing before a task goal becomes sufficiently activated to select the task for further processing. The results confirmed this hypothesis: Task performance data demonstrated the presence of perceptual (discriminability effects) and cognitive (switch costs) processing demands. Participants' choice behavior was affected by both types of processing demands (as reflected in a task repetition bias and a bias to select the color task with easy compared to hard discriminations). Thus, the present findings indicate that both perceptual and cognitive processing demands influence voluntary task choice behavior. We propose that higher-level goal activations interact at least partially with early perceptual processes to influence task choice behavior, suggesting a locus of voluntary choices during or after the perceptual stage within the information-processing stream.
The principal function of inflammation is cellular defence against 'danger signals' such as tissue injury and pathogen infection to maintain the homeostasis of the organism. The initiation and progression of inflammation are not autonomous as there is substantial evidence that inflammation is known to be strongly influenced by 'neuroimmune crosstalk', involving the production and expression of soluble signalling molecules that interact with cell surface receptors. In addition, microbiota have been found to be involved in the development and function of the nervous and immune systems and play an important role in health and disease. Herein, we provide an outline of the mechanisms of neuroimmune communication in the regulation of inflammation and immune response and then provide evidence for the involvement of microbiota in the development and functions of the host nervous and immune systems. It appears that the nervous and immune systems in multicellular organisms have co-evolved with the microbiota, such that all components are in communication to maximise the ability of the organism to adapt to a wide range of environmental stresses to maintain or restore tissue homeostasis.
The ultrashort orbital angular momentum pulses, or the ultrashort optical vortex pulses, with the properties of the ultrashort duration and broadband spectrum, open significant applications in various contexts. The controllability of the orbital angular momentum in ultrashort vortex pulses crucially affects its capabilities. We put forward an approach for orbital angular momentum mode selection in an ultrashort laser pulse. This approach depends on an optical mask with multiple spirals rotationally and symmetrically arranged in a model of the spiral array. Both theoretical analyses and experimental work in the context of ultrashort vortex pulses demonstrate that the spiral array enables flexible generation of the structured orbital angular momentum modes. This optical mask shows the advantages of damage resistance, without medium-dispersion, and ease of handling in an ultrafast optical field. Furthermore, the spiral array can be applied to analyzing and generating other matter vortex beams within an axially scalar system.
Some parasites modify the phenotype of their host in order to increase transmission to another host or to an environment suitable for reproduction. This phenomenon, known as host manipulation, is found across many parasite taxa. Freshwater hairworms are known for the behavioural changes they cause in their terrestrial arthropod hosts, increasing their likelihood of entering water to exit the host and reproduce. Understanding how infected arthropods move around in the natural environment could help uncover alterations in spatial distribution or movement induced by hairworms in their terrestrial definitive hosts. Moreover, few hairworm-host records exist for New Zealand, so any additional record could help elucidate their true host specificity. Here, we investigated whether infected terrestrial arthropods were more likely to approach streams in two subalpine communities of invertebrates, using a spatial grid of specialised pitfall traps. Although hairworm infection could not explain the movements of arthropod hosts near streams, we found several new host records for hairworms, including the first records for the recently described Gordionus maori. We also found some new host-parasite associations for mermithid nematodes. These records show that the host specificity of hairworms is quite low, suggesting that their diversity and distribution may be greater than what is currently known for New Zealand.
Biohydrogen is a green and eco-friendly energy carrier with the potential to reduce our dependency on fossil fuels. Renewable biohydrogen production from waste biomass sources is potentially cheap; however, large-scale commercial production has not yet been achieved. Problems that need to be tackled include identifying industrially competent microorganisms, and appropriate bioreactor designs enabling novel hybrid methods such as integration of dark fermentation with electro-fermentation and utilization of microbial organisms doped with semiconducting nanomaterials for enhanced production. This review focuses on the production of hydrogen by biological methods, highlighting various fermentation processes, the role of enzymes, and different pretreatment methods. The waste materials used are briefly summarized, and current strategies in biological hydrogen production, including biomimetic and synthetic biology approaches, are assessed for their economic feasibility and their potential to contribute to net zero carbon emission. The lignocellulosic waste and the dynamic membrane bioreactor are the best suitable biomass and bioreactor, respectively for biohydrogen production. The integrated method of dark fermentation and electro-fermentation yields 41% higher hydrogen compared with dark fermentation alone. Finally, this review points out that significant efforts focusing on the development of hybrid fermentation technologies along with the development of novel engineered strains are needed for the commercial-scale production of biohydrogen in the future.
This study explores the effect of winning a corporate social responsibility (CSR) Award on firm value. Drawing on the stakeholder value maximization view of stakeholder theory, we analyze a sample of 14,039 US firm-years between 2002 and 2018 and find that winning a CSR Award is value enhancing. We further offer evidence that demonstrates how the CSR dimensions of environmental, social and governance criteria influence the CSR Award–firm value nexus. Our results are supported by a series of robustness tests. As CSR Awards are typically awarded to firms that excel in CSR, our findings are expected to encourage managers to pursue CSR more rigorously so as to attain high firm value.
Intention measures are used as a proxy for future behaviour. Although there is often a gap between intentions and subsequent behaviour, little is known about why the intention-behaviour gap (IB-gap) occurs. This longitudinal study across Australia, New Zealand and China quantifies the IB-gap in the context of donating money, goods, and time to charities. The factors underpinning the IB-gap are documented (i.e., why intenders don’t act and non-intenders do), resulting in the development of a framework summarising 12 key reasons. Findings show that intenders don’t follow through due to perceived time/effort constraints or lack of resources. Non-intenders subsequently give due to heightened awareness and attitudes about a charity/cause, or an intrinsic motivation such as empathy. Our findings allow researchers and marketers to better understand and interpret intention metrics, with guidance on how to minimise barriers to action across three types of support behaviours.
Investors have a central role to play in sustainability transitions, due to their inordinate influence on the governance of the fossil fuel extraction industry. Using network analysis, this paper links fossil fuel firms to equity owners, by distinguishing ownership characteristics of top shareholders and establishing a ranked list of the most prevalent shareholders based on emissions potential and network centrality. Our study reveals that among the most prevalent owners, are government signatories of the Paris accord and prominent American investment managers. We conclude that a concentrated number of investors have the potential to influence the strategic direction and governance of these firms and should consequently be held accountable for financing the economic activities that contribute to climate instability. This paper directly contributes to the fragmented body of academic research on financial systems and sustainability transitions.
The laminated sedimentary sequence of Ecuador's Laguna Pallcacocha is one of the most widely cited proxy records of Holocene El Niño Southern Oscillation (ENSO) variability. Previous efforts to reconstruct flood-driven laminae from Laguna Pallcacocha relied solely on sediment color, a useful but non-specific metric of flood events. We improved the chronology with ²¹⁰Pb and additional ¹⁴C dates over the past millennium, which allows for comparison of the sedimentary record with historically documented El Niño events. Additionally, we use elemental composition derived from X-ray Fluorescence (XRF) to reconstruct flood history at Pallcacocha. A principal component analysis (PCA) of the XRF dataset identifies minerogenic flood-driven clastic laminae. The first principal component (PC1) of the XRF data and red color intensity are positively correlated over the past 7.5 kyr, but the color record fails to capture high frequency variability that is preserved in the XRF dataset during the early Holocene (approximately 7.5-11 kyr BP). The new XRF dataset indicates moderate El Niño activity during the early Holocene, suppressed El Niño activity in the middle Holocene, and enhanced El Niño activity during the late Holocene. This pattern is relatively common among other ENSO records, and has been attributed to long-term changes in tropical insolation. Some intervals-most notably between 3-2 kyr BP and during the last millennium-deviate from expected trends if insolation was the sole forcing mechanism. Previously proposed mechanisms linking ENSO to latitudinal displacement of the ITCZ and ocean-atmospheric variabilities in other ocean basins appear to play an additional role in modulating Holocene ENSO development, as demonstrated by statistically significant correlations between the revised Laguna Pallcacocha flood history and proxy records from the Atlantic.
Background Group A streptococcal (GAS) infections can trigger an immune-mediated response resulting in acute rheumatic fever (ARF). The role of social and environmental risk factors for GAS pharyngitis and skin infections are not well understood. This study aimed to identify factors associated with GAS pharyngitis and skin infections, and to determine if these are the same as those for ARF. Methods A case-control study, including 733 children aged 5-14 years, was undertaken between March 2018 and October 2019 in Auckland, New Zealand. Healthy controls (n = 190) and symptomatic cases including GAS pharyngitis (n = 210), GAS seronegative carriers (n = 182), and GAS skin infections (n = 151) were recruited. Trained interviewers administered a comprehensive, pre-tested, face-to-face questionnaire. Findings Multivariable analysis identified strong associations between barriers to accessing primary healthcare and having GAS pharyngitis (adjusted OR 3·3; 95% CI 1·8-6·0), GAS carriage (aOR 2·9; 95% CI 1·5-6·0) or a GAS skin infection (aOR 3·5; 95% CI 1·6-7·6). Children who had GAS skin infections were more likely than all other groups to report living in a crowded home (aOR 1·9; 95% CI 1·0-3·4), have Māori or Pacific grandparents (aOR 3·0; 95% CI 1·2-7·6), a family history of ARF (aOR 2·2; 95% CI 1·1-4·3), or having a previous diagnosis of eczema (aOR 3·9; 95% CI 2·2-6·9). Interpretation Reducing barriers to accessing primary healthcare (including financial restrictions, the inability to book an appointment, lack of transport, and lack of childcare for other children) to treat GAS pharyngitis and skin infections could potentially reduce these infections and lead to a reduction in their sequelae, including ARF. These strategies should be co-designed and culturally appropriate for the communities being served and carefully evaluated. Funding This work was supported by the Health Research Council of New Zealand (HRC), award number 16/005.
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8,970 members
Ramakrishnan Mani
  • School of Physiotherapy
Cheryl Anne Wilson
  • Clothing and Textile Sciences
Sunyoung Ma
  • Department of Oral Rehabilitation
Robert Siebers
  • Department of Medicine (Wellington)
John Leader
  • Department of Medicine (Dunedin)
PO Box 56, 9054, Dunedin, Otago, New Zealand
Head of institution
Professor Harlene Hayne