Publications by authors named "Stuart Brown"

142 Publications

Cryopreservation of mammalian cells using protic ionic liquid solutions.

J Colloid Interface Sci 2021 Jun 17;603:491-500. Epub 2021 Jun 17.

School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, Australia. Electronic address:

Cryopreservation has facilitated considerable advances in both medical technology and scientific research. However, further developments have been limited by the relatively low number of effective cryoprotective agents. Even after fifty years of research, most protocols rely on the same two toxic agents, i.e. dimethylsulfoxide or glycerol. Ionic liquids are a class of promising solvents which are known glass formers and may offer a less-toxic alternative. The research presented here investigates ten protic ionic liquids as potential cryoprotective agents. The liquids are screened for key properties including cellular toxicity, permeability and thermal behaviour. The most promising, ethylammonium acetate, was then tested as a cryoprotective agent on a model cell line and was found to be as effective as the common cryoprotectant, dimethylsulfoxide. This work reports the first use of a protic ionic liquid as an effective cryoprotective agent for a mammalian cell line. This will inform the development of a suite of potential new ionic liquid-based cryoprotectants that could potentially allow the cryopreservation of new cell types.
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http://dx.doi.org/10.1016/j.jcis.2021.06.096DOI Listing
June 2021

Evidence for even parity unconventional superconductivity in SrRuO.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Department of Physics & Astronomy, University of California, Los Angeles, CA 90095;

Unambiguous identification of the superconducting order parameter symmetry in [Formula: see text] has remained elusive for more than a quarter century. While a chiral p-wave ground state analogue to superfluid He-A was ruled out only very recently, other proposed triplet-pairing scenarios are still viable. Establishing the condensate magnetic susceptibility reveals a sharp distinction between even-parity (singlet) and odd-parity (triplet) pairing since the superconducting condensate is magnetically polarizable only in the latter case. Here field-dependent O Knight shift measurements, being sensitive to the spin polarization, are compared to previously reported specific heat measurements for the purpose of distinguishing the condensate contribution from that due to quasiparticles. We conclude that the shift results can be accounted for entirely by the expected field-induced quasiparticle response. An upper bound for the condensate magnetic response of <10% of the normal state susceptibility is sufficient to exclude all purely odd-parity candidates.
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http://dx.doi.org/10.1073/pnas.2025313118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237678PMC
June 2021

Case control study comparing the HPV genome in patients with oral cavity squamous cell carcinoma to normal patients using metagenomic shotgun sequencing.

Sci Rep 2021 Feb 16;11(1):3867. Epub 2021 Feb 16.

Department of Pathology, New York University School of Medicine, New York, 10016, USA.

The aim of this study was to carry out a case control study comparing the HPV genome in patients with oral cavity squamous cell carcinoma (OC-SCC) to normal patients using metagenomic shotgun sequencing. We recruited 50 OC-SCC cases which were then matched with a control patient by age, gender, race, smoking status and alcohol status. DNA was extracted from oral wash samples from all patients and whole genome shotgun sequencing performed. The raw sequence data was cleaned, reads aligned with the human genome (GRCH38), nonhuman reads identified and then HPV genotypes identified using HPViewer. In the 50 patients with OC-SCC, the most common subsite was tongue in 26 (52%). All patients were treated with primary resection and neck dissection. All but 2 tumors were negative on p16 immunohistochemistry. There were no statistically significant differences between the cases and controls in terms of gender, age, race/ethnicity, alcohol drinking, and cigarette smoking. There was no statistically significant difference between the cancer samples and control samples in the nonhuman DNA reads (medians 4,228,072 vs. 5,719,715, P value = 0.324). HPV was detected in 5 cases (10%) of OC-SCC (genotypes 10, 16, 98) but only 1 tumor sample (genotype 16) yielded a high number of reads to suggest a role in the etiology of OC-SCC. HPV was detected in 4 control patients (genotypes 16, 22, 76, 200) but all had only 1-2 HPV reads per human genome. Genotypes of HPV are rarely found in patients with oral cancer.
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http://dx.doi.org/10.1038/s41598-021-83197-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886861PMC
February 2021

Identifying island safe havens to prevent the extinction of the World's largest lizard from global warming.

Ecol Evol 2020 Oct 15;10(19):10492-10507. Epub 2020 Sep 15.

The Environment Institute and School of Biological Sciences The University of Adelaide Adelaide SA Australia.

The Komodo dragon () is an endangered, island-endemic species with a naturally restricted distribution. Despite this, no previous studies have attempted to predict the effects of climate change on this iconic species. We used extensive Komodo dragon monitoring data, climate, and sea-level change projections to build spatially explicit demographic models for the Komodo dragon. These models project the species' future range and abundance under multiple climate change scenarios. We ran over one million model simulations with varying model parameters, enabling us to incorporate uncertainty introduced from three main sources: (a) structure of global climate models, (b) choice of greenhouse gas emission trajectories, and (c) estimates of Komodo dragon demographic parameters. Our models predict a reduction in range-wide Komodo dragon habitat of 8%-87% by 2050, leading to a decrease in habitat patch occupancy of 25%-97% and declines of 27%-99% in abundance across the species' range. We show that the risk of extirpation on the two largest protected islands in Komodo National Park (Rinca and Komodo) was lower than other island populations, providing important safe havens for Komodo dragons under global warming. Given the severity and rate of the predicted changes to Komodo dragon habitat patch occupancy (a proxy for area of occupancy) and abundance, urgent conservation actions are required to avoid risk of extinction. These should, as a priority, be focused on managing habitat on the islands of Komodo and Rinca, reflecting these islands' status as important refuges for the species in a warming world. Variability in our model projections highlights the importance of accounting for uncertainties in demographic and environmental parameters, structural assumptions of global climate models, and greenhouse gas emission scenarios when simulating species metapopulation dynamics under climate change.
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http://dx.doi.org/10.1002/ece3.6705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548163PMC
October 2020

Physicochemical characterisation of novel tetrabutylammonium aryltrifluoroborate ionic liquids.

Phys Chem Chem Phys 2020 Oct;22(40):23374-23384

College of Science, Engineering and Health, RMIT University, 124 La Trobe Street, Melbourne, Victoria, Australia.

While there have been many studies on the physicochemical characterisation of ILs, little work has previously been reported on the properties unique to the trifluoroborate anion. Here we have characterised the thermal properties, viscosity, liquid nanostructure and intramolecular interactions of 15 novel aryltrifluoroborate ILs. These ILs all contained a tetrabutylammonium cation paired with either meta- or para-substituted aryltrifluoroborate anions, or di-anionic substituted aryltrifluroborate anions. It was found that of the 15 samples analysed, 4 would technically be considered molten salts as they have melting points greater than 100 °C. Overall the structure-property relationship trends of these samples are similar to those previously reported for alkyl and perfluoroalkyltrifluoroborate ILs which contained K+ or Cs+ cations, with the big difference being the ILs in this study having considerably lower melting points.
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http://dx.doi.org/10.1039/d0cp03994bDOI Listing
October 2020

StableClim, continuous projections of climate stability from 21000 BP to 2100 CE at multiple spatial scales.

Sci Data 2020 10 12;7(1):335. Epub 2020 Oct 12.

The Environment Institute and School of Biological Sciences, University of Adelaide, South Australia, 5005, Australia.

Paleoclimatic data are used in eco-evolutionary models to improve knowledge of biogeographical processes that drive patterns of biodiversity through time, opening windows into past climate-biodiversity dynamics. Applying these models to harmonised simulations of past and future climatic change can strengthen forecasts of biodiversity change. StableClim provides continuous estimates of climate stability from 21,000 years ago to 2100 C.E. for ocean and terrestrial realms at spatial scales that include biogeographic regions and climate zones. Climate stability is quantified using annual trends and variabilities in air temperature and precipitation, and associated signal-to-noise ratios. Thresholds of natural variability in trends in regional- and global-mean temperature allow periods in Earth's history when climatic conditions were warming and cooling rapidly (or slowly) to be identified and climate stability to be estimated locally (grid-cell) during these periods of accelerated change. Model simulations are validated against independent paleoclimate and observational data. Projections of climatic stability, accessed through StableClim, will improve understanding of the roles of climate in shaping past, present-day and future patterns of biodiversity.
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http://dx.doi.org/10.1038/s41597-020-00663-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550347PMC
October 2020

Using paleo-archives to safeguard biodiversity under climate change.

Science 2020 08;369(6507)

Center for Macroecology, Evolution, and Climate, GLOBE Institute, University of Copenhagen, Copenhagen Ø 2100, Denmark.

Strategies for 21st-century environmental management and conservation under global change require a strong understanding of the biological mechanisms that mediate responses to climate- and human-driven change to successfully mitigate range contractions, extinctions, and the degradation of ecosystem services. Biodiversity responses to past rapid warming events can be followed in situ and over extended periods, using cross-disciplinary approaches that provide cost-effective and scalable information for species' conservation and the maintenance of resilient ecosystems in many bioregions. Beyond the intrinsic knowledge gain such integrative research will increasingly provide the context, tools, and relevant case studies to assist in mitigating climate-driven biodiversity losses in the 21st century and beyond.
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http://dx.doi.org/10.1126/science.abc5654DOI Listing
August 2020

Author Correction: Parkinson's disease and bacteriophages as its overlooked contributors.

Sci Rep 2020 Jul 16;10(1):12078. Epub 2020 Jul 16.

Human Microbiology Institute, New York, NY, 10027, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-69086-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363888PMC
July 2020

Evolutionary history and past climate change shape the distribution of genetic diversity in terrestrial mammals.

Nat Commun 2020 05 22;11(1):2557. Epub 2020 May 22.

Center for Macroecology, Evolution, and Climate, GLOBE Institute, University of Copenhagen, 2100, Copenhagen Ø, Denmark.

Knowledge of global patterns of biodiversity, ranging from intraspecific genetic diversity (GD) to taxonomic and phylogenetic diversity, is essential for identifying and conserving the processes that shape the distribution of life. Yet, global patterns of GD and its drivers remain elusive. Here we assess existing biodiversity theories to explain and predict the global distribution of GD in terrestrial mammal assemblages. We find a strong positive covariation between GD and interspecific diversity, with evolutionary time, reflected in phylogenetic diversity, being the best predictor of GD. Moreover, we reveal the negative effect of past rapid climate change and the positive effect of inter-annual precipitation variability in shaping GD. Our models, explaining almost half of the variation in GD globally, uncover the importance of deep evolutionary history and past climate stability in accumulating and maintaining intraspecific diversity, and constitute a crucial step towards reducing the Wallacean shortfall for an important dimension of biodiversity.
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http://dx.doi.org/10.1038/s41467-020-16449-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7244709PMC
May 2020

Models of spatiotemporal variation in rabbit abundance reveal management hot spots for an invasive species.

Ecol Appl 2020 06 9;30(4):e02083. Epub 2020 Mar 9.

The Environment Institute and School of Biological Sciences, University of Adelaide, Adelaide, South Australia, 5005, Australia.

The European rabbit (Oryctolagus cuniculus) is a notorious economic and environmental pest species in its invasive range. To better understand the population and range dynamics of this species, 41 yr of abundance data have been collected from 116 unique sites across a broad range of climatic and environmental conditions in Australia. We analyzed this time series of abundance data to determine whether interannual variation in climatic conditions can be used to map historic, contemporary, and potential future fluctuations in rabbit abundance from regional to continental scales. We constructed a hierarchical Bayesian regression model of relative abundance that corrected for observation error and seasonal biases. The corrected abundances were regressed against environmental and disease variables in order to project high spatiotemporal resolution, continent-wide rabbit abundances. We show that rabbit abundance in Australia is highly variable in space and time, being driven primarily by internnual variation in temperature and precipitation in concert with the prevalence of a non-pathogenic virus. Moreover, we show that internnual variation in local spatial abundances can be mapped effectively at a continental scale using highly resolved spatiotemporal predictors, allowing "hot spots" of persistently high rabbit abundance to be identified. Importantly, cross-validated model performance was fair to excellent within and across distinct climate zones. Long-term monitoring data for invasive species can be used to map fine-scale spatiotemporal fluctuations in abundance patterns when accurately accounting for inherent sampling biases. Our analysis provides ecologists and pest managers with a clearer understanding of the determinants of rabbit abundance in Australia, offering an important new approach for predicting spatial abundance patterns of invasive species at the near-term temporal scales that are directly relevant to resource management.
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http://dx.doi.org/10.1002/eap.2083DOI Listing
June 2020

Mitochondrial somatic mutations and the lack of viral genomic variation in recurrent respiratory papillomatosis.

Sci Rep 2019 11 12;9(1):16625. Epub 2019 Nov 12.

Otolaryngology-Head and Neck Surgery, New York University School of Medicine, New York, NY, USA.

Recurrent Respiratory Papillomatosis (RRP) is a rare disease of the aerodigestive tract caused by the Human Papilloma Virus (HPV) that manifests as profoundly altered phonatory and upper respiratory anatomy. Current therapies are primarily symptomatic; enhanced insight regarding disease-specific biology of RRP is critical to improved therapeutics for this challenging population. Multiplex PCR was performed on oral rinses collected from twenty-three patients with adult-onset RRP every three months for one year. Twenty-two (95.6%) subjects had an initial HPV positive oral rinse. Of those subjects, 77.2% had an additional positive oral rinse over 12 months. A subset of rinses were then compared to tissue samples in the same patient employing HPViewer to determine HPV subtype concordance. Multiple HPV copies (60-787 per human cell) were detected in RRP tissue in each patient, but a single dominant HPV was found in individual samples. These data confirm persistent oral HPV infection in the majority of patients with RRP. In addition, three novel HPV6 isolates were found and identical HPV strains, at very low levels, were identified in oral rinses in two patients suggesting potential HPV subtype concordance. Finally, somatic heteroplasmic mtDNA mutations were observed in RRP tissue with 1.8 mutations per sample and two nonsynonymous variants. These data provide foundational insight into both the underlying pathophysiology of RRP, but also potential targets for intervention in this challenging patient cohort.
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http://dx.doi.org/10.1038/s41598-019-53148-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851396PMC
November 2019

Type 1 Diabetes: an Association Between Autoimmunity, the Dynamics of Gut Amyloid-producing E. coli and Their Phages.

Sci Rep 2019 07 4;9(1):9685. Epub 2019 Jul 4.

Human Microbiology Institute, New York, NY, 10013, USA.

The etiopathogenesis of type 1 diabetes (T1D), a common autoimmune disorder, is not completely understood. Recent studies suggested the gut microbiome plays a role in T1D. We have used public longitudinal microbiome data from T1D patients to analyze amyloid-producing bacterial composition and found a significant association between initially high amyloid-producing Escherichia coli abundance, subsequent E. coli depletion prior to seroconversion, and T1D development. In children who presented seroconversion or developed T1D, we observed an increase in the E. coli phage/E. coli ratio prior to E. coli depletion, suggesting that the decrease in E. coli was due to prophage activation. Evaluation of the role of phages in amyloid release from E. coli biofilms in vitro suggested an indirect role of the bacterial phages in the modulation of host immunity. This study for the first time suggests that amyloid-producing E. coli, their phages, and bacteria-derived amyloid might be involved in pro-diabetic pathway activation in children at risk for T1D.
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http://dx.doi.org/10.1038/s41598-019-46087-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609616PMC
July 2019

Elucidation of drug resistance mutations in Mycobacterium tuberculosis isolates from North India by whole-genome sequencing.

J Glob Antimicrob Resist 2020 03 20;20:11-15. Epub 2019 May 20.

Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India.

Objectives: Rapid diagnosis of drug-resistant tuberculosis (TB) is required for better patient management and treatment outcomes. Whole-genome sequencing (WGS) can be used to detect single nucleotide polymorphisms (SNPs) and deletions/insertions that are responsible for mostMycobacterium tuberculosis drug resistance. WGS is being performed at scale in high-income countries, but there are limited reports of its use in India.

Methods: In this study, 33 clinicalM. tuberculosis isolates from the Mycobacterial Repository in Chandigarh underwent WGS. Phenotypic drug susceptibility testing was performed according to World Health Organization (WHO) recommendations. Four isolates were excluded from the analysis due to culture contamination or mislabelling during the study.

Results: Among the remaining 29 isolates, 21 (72.4%) were multidrug-resistant TB (MDR-TB) and 1 (3.4%) was extensively-drug resistant TB (XDR-TB). The most common mutations observed for isoniazid, rifampicin, ofloxacin and kanamycin resistance werekatG(S315T), rpoB(S450L), gyrA(A90V) and rrs(A1401G), respectively. The isolates mainly belonged to lineages 2 and 3, with most MDR-TB among lineage 2 isolates.

Conclusion: WGS ofM. tuberculosis isolates allows the detection of drug resistance to all drugs in a single test and also provides insight into the evolution and drug-resistant TB.
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http://dx.doi.org/10.1016/j.jgar.2019.05.019DOI Listing
March 2020

Cradles of diversity are unlikely relics of regional climate stability.

Curr Biol 2019 05;29(10):R356-R357

Center for Macroecology, Evolution, and Climate, Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen O, Denmark; Department of Life Sciences, Imperial College London, Ascot SL5 7PY, UK.

The stability of regional climates on millennial timescales is theorised to be a primary determinant of nearby diversification [1-5]. Using simulated patterns of past temperature change at monthly timescales [6], we show that the locations of climatically stable regions are likely to have varied considerably across and within millennia during glacial-interglacial cycles of the Late Quaternary. This result has important implications for the role of regional climate stability in theories of speciation, because long-term climate refugia are typically presumed to be 'cradles' of diversity (areas of high speciation) only if they remain stable across Milankovitch climate oscillations [1-5], which operate on multi-millennial time scales [7].
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http://dx.doi.org/10.1016/j.cub.2019.04.001DOI Listing
May 2019

A compact acoustic spanner to rotate macroscopic objects.

Sci Rep 2019 May 1;9(1):6757. Epub 2019 May 1.

SUPA, School of Physics and Astronomy, University of Glasgow, Glasgow, G12 8QQ, UK.

Waves can carry both linear and angular momentum. When the wave is transverse (e.g. light), the angular momentum can be characterised by the "spin" angular momentum associated with circular polarisation, and the "orbital" angular momentum (OAM) arising from the phase cross-section of the beam. When the wave is longitudinal (e.g. sound) there is no polarization and hence no spin angular momentum. However, a suitably phase-structured sound beam can still carry OAM. Observing the transfer of OAM from sound to a macroscopic object provides an excellent opportunity to study the exchange of energy between waves and matter. In this paper we show how to build a compact free-space acoustic spanner based on a 3D-printed sound-guiding structure and common electronic components. We first characterise the sound fields by measuring both phase and amplitude maps, and then show a video of our free-space acoustic spanner in action, in which macroscopic objects spin in a circular motion and change direction of rotation according to the handedness of the OAM acoustic field.
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http://dx.doi.org/10.1038/s41598-019-43046-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494813PMC
May 2019

The Australian National Rabbit Database: 50 yr of population monitoring of an invasive species.

Ecology 2019 07 20;100(7):e02750. Epub 2019 May 20.

Parks Victoria, Victoria, 3000, Australia.

With ongoing introductions into Australia since the 1700s, the European rabbit (Oryctolagus cuniculus) has become one of the most widely distributed and abundant vertebrate pests, adversely impacting Australia's biodiversity and agroeconomy. To understand the population and range dynamics of the species and its impacts better, occurrence and abundance data have been collected by researchers and citizens from sites covering a broad spectrum of climatic and environmental conditions in Australia. The lack of a common and accessible repository for these data has, however, limited their use in determining important spatiotemporal drivers of the structure and dynamics of the geographical range of rabbits in Australia. To meet this need, we created the Australian National Rabbit Database, which combines more than 50 yr of historical and contemporary survey data collected from throughout the range of the species in Australia. The survey data, obtained from a suite of complementary monitoring methods, were combined with high-resolution weather, climate, and environmental information, and an assessment of data quality. The database provides records of rabbit occurrence (689,265 records) and abundance (51,241 records, >120 distinct sites) suitable for identifying the spatiotemporal drivers of the rabbit's distribution and for determining spatial patterns of variation in its key life-history traits, including maximum rates of population growth. Because all data are georeferenced and date stamped, they can be coupled with information from other databases and spatial layers to explore the potential effects of rabbit occurrence and abundance on Australia's native wildlife and agricultural production. The Australian National Rabbit Database is an important tool for understanding and managing the European rabbit in its invasive range and its effects on native biodiversity and agricultural production. It also provides a valuable resource for addressing questions related to the biology, success, and impacts of invasive species more generally. No copyright or proprietary restrictions are associated with the use of this data set other than citation of this Data Paper.
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http://dx.doi.org/10.1002/ecy.2750DOI Listing
July 2019

MGS-Fast: Metagenomic shotgun data fast annotation using microbial gene catalogs.

Gigascience 2019 04;8(4)

Department of Biological Sciences and Center for Translational and Basic Research, Belfer Research Building, Hunter College of The City University of New York, 333 E 38th St, New York, NY, 10016, US.

Background: Current methods used for annotating metagenomics shotgun sequencing (MGS) data rely on a computationally intensive and low-stringency approach of mapping each read to a generic database of proteins or reference microbial genomes.

Results: We developed MGS-Fast, an analysis approach for shotgun whole-genome metagenomic data utilizing Bowtie2 DNA-DNA alignment of reads that is an alternative to using the integrated catalog of reference genes database of well-annotated genes compiled from human microbiome data. This method is rapid and provides high-stringency matches (>90% DNA sequence identity) of the metagenomics reads to genes with annotated functions. We demonstrate the use of this method with data from a study of liver disease and synthetic reads, and Human Microbiome Project shotgun data, to detect differentially abundant Kyoto Encyclopedia of Genes and Genomes gene functions in these experiments. This rapid annotation method is freely available as a Galaxy workflow within a Docker image.

Conclusions: MGS-Fast can confidently transfer functional annotations from gene databases to metagenomic reads, with speed and accuracy.
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http://dx.doi.org/10.1093/gigascience/giz020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446249PMC
April 2019

Spatial resilience of the Great Barrier Reef under cumulative disturbance impacts.

Glob Chang Biol 2019 07 6;25(7):2431-2445. Epub 2019 May 6.

Australian Institute of Marine Science, Townsville MC, Townsville, Qld, Australia.

In the face of increasing cumulative effects from human and natural disturbances, sustaining coral reefs will require a deeper understanding of the drivers of coral resilience in space and time. Here we develop a high-resolution, spatially explicit model of coral dynamics on Australia's Great Barrier Reef (GBR). Our model accounts for biological, ecological and environmental processes, as well as spatial variation in water quality and the cumulative effects of coral diseases, bleaching, outbreaks of crown-of-thorns starfish (Acanthaster cf. solaris), and tropical cyclones. Our projections reconstruct coral cover trajectories between 1996 and 2017 over a total reef area of 14,780 km , predicting a mean annual coral loss of -0.67%/year mostly due to the impact of cyclones, followed by starfish outbreaks and coral bleaching. Coral growth rate was the highest for outer shelf coral communities characterized by digitate and tabulate Acropora spp. and exposed to low seasonal variations in salinity and sea surface temperature, and the lowest for inner-shelf communities exposed to reduced water quality. We show that coral resilience (defined as the net effect of resistance and recovery following disturbance) was negatively related to the frequency of river plume conditions, and to reef accessibility to a lesser extent. Surprisingly, reef resilience was substantially lower within no-take marine protected areas, however this difference was mostly driven by the effect of water quality. Our model provides a new validated, spatially explicit platform for identifying the reefs that face the greatest risk of biodiversity loss, and those that have the highest chances to persist under increasing disturbance regimes.
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http://dx.doi.org/10.1111/gcb.14625DOI Listing
July 2019

Differential effects of depot medroxyprogesterone acetate administration on vaginal microbiome in Hispanic White and Black women.

Emerg Microbes Infect 2019 ;8(1):197-210

b Department of Medicine , New York University School of Medicine , New York , NY , USA.

The use of depot medroxyprogesterone acetate (DMPA), a 3-monthly injectable hormonal contraceptive, is associated with an increased risk of HIV acquisition possibly through alteration of the vaginal microbiome. In this longitudinal interventional study, we investigated the impact of DMPA administration on the vaginal microbiome in Hispanic White and Black women at the baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) following DMPA treatment by using 16S rRNA gene sequencing. No significant changes in the vaginal microbiome were observed after DMPA treatment when Hispanic White and Black women were analysed as a combined group. However, DMPA treatment enriched total vaginosis-associated bacteria (VNAB) and Prevotella at visit 2, and simplified the correlational network in the vaginal microbiome in Black women, while increasing the network size in Hispanic White women. The microbiome in Black women became more diversified and contained more VNAB than Hispanic White women after DMPA treatment. While the Firmicutes to Bacteroidetes (F/B) ratio and Lactobacillus to Prevotella (L/P) ratio were comparable between Black and Hispanic White women at visit 1, both ratios were lower in Black women than in Hispanic White women at visit 2. In conclusion, DMPA treatment altered the community network and enriched VNAB in Black women but not in Hispanic White women. The Lactobacillus deficiency and enrichment of VNAB may contribute to the increased risk of HIV acquisition in Black women. Future studies on the impact of racial differences on the risk of HIV acquisition will offer insights into developing effective strategies for HIV prevention. Abbreviations: DMPA: depot medroxyprogesterone acetate; PCR: polymerase chain reaction; OTU: operational taxonomic unit; STI: sexually transmitted infections; VNAB: vaginosis-associated bacteria.
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http://dx.doi.org/10.1080/22221751.2018.1563458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455113PMC
July 2019

Draft Genome Sequence of Streptococcus halitosis sp. nov., Isolated from the Dorsal Surface of the Tongue of a Patient with Halitosis.

Microbiol Resour Announc 2019 Jan 24;8(4). Epub 2019 Jan 24.

Human Microbiology Institute, New York, New York, USA.

Here, we report the draft genome of Streptococcus halitosis sp. nov. strain VT-4, a novel bacterium isolated from the dorsal part of the tongue of a patient with halitosis. The genome comprised 1,880,608 bp with a GC content of 41.0%. There were 1,782 predicted protein-coding genes, including those associated with virulence and antibiotic resistance.
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http://dx.doi.org/10.1128/MRA.01704-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346211PMC
January 2019

Periodontal pathogens are a risk factor of oral cavity squamous cell carcinoma, independent of tobacco and alcohol and human papillomavirus.

Int J Cancer 2019 08 19;145(3):775-784. Epub 2019 Feb 19.

Department of Pathology, New York University School of Medicine, New York, NY.

Over the past decade, there has been a change in the epidemiology of oral cavity squamous cell cancer (OC-SCC). Many new cases of OC-SCC lack the recognized risk factors of smoking, alcohol and human papilloma virus. The aim of this study was to determine if the oral microbiome may be associated with OC-SCC in nonsmoking HPV negative patients. We compared the oral microbiome of HPV-negative nonsmoker OC-SCC(n = 18), premalignant lesions(PML) (n = 8) and normal control patients (n = 12). Their oral microbiome was sampled by oral wash and defined by 16S rRNA gene sequencing. We report that the periodontal pathogens Fusobacterium, Prevotella, Alloprevotella were enriched while commensal Streptococcus depleted in OC-SCC. Based on the four genera plus a marker genus Veillonella for PML, we classified the oral microbiome into two types. Gene/pathway analysis revealed a progressive increase of genes encoding HSP90 and ligands for TLRs 1, 2 and 4 along the controls→PML → OC-SCC progression sequence. Our findings suggest an association between periodontal pathogens and OC-SCC in non smoking HPV negative patients.
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http://dx.doi.org/10.1002/ijc.32152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554043PMC
August 2019

Is palliative care cost-effective in low-income and middle-income countries? A mixed-methods systematic review.

BMJ Support Palliat Care 2019 Jun 1;9(2):120-129. Epub 2018 Oct 1.

Global Health Academy, University of Edinburgh, Edinburgh, Scotland.

Introduction: Of the 40 million people globally in need of palliative care (PC), just 14% receive it, predominantly in high-income countries. Within fragile health systems that lack PC, incurable illness is often marked by pain and suffering, as well as burdensome costs. In high-income settings, PC decreases healthcare utilisation, thus enhancing value. Similar cost-effectiveness models are lacking in low-income and middle-income countries and with them, the impetus and funding to expand PC delivery.

Methods: We conducted a systematic search of seven databases to gather evidence of the cost-effectiveness of PC in low-income and middle-income countries. We extracted and synthesised palliative outcomes and economic data from original research studies occurring in low-income and middle-income countries. This review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and includes a quality appraisal.

Results: Our search identified 10 eligible papers that included palliative and economic outcomes in low-income and middle-income countries. Four provided true cost-effectiveness analyses in comparing the costs of PC versus alternative care, with PC offering cost savings, favourable palliative outcomes and positive patient-reported and family-reported outcomes.

Conclusions: Despite the small number of included studies, wide variety of study types and lack of high-quality studies, several patterns emerged: (1) low-cost PC delivery in low-income and middle-income countries is possible, (2) patient-reported outcomes are favourable and (3) PC is less costly than the alternative. This review highlights the extraordinary need for robust cost-effectiveness analysis of PC in low-income and middle-income countries in order to develop health economic models for the delivery of PC, direct resource allocation and guide healthcare policy for PC delivery in low-income and middle-income countries.
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http://dx.doi.org/10.1136/bmjspcare-2018-001499DOI Listing
June 2019

Hierarchy of human IgG recognition within the Staphylococcus aureus immunome.

Sci Rep 2018 09 5;8(1):13296. Epub 2018 Sep 5.

New York University School of Medicine, Department of Medicine, New York, 10016, USA.

Staphylococcus aureus is an opportunistic pathogen that causes a range of serious infections associated with significant morbidity, by strains increasingly resistant to antibiotics. However, to date all candidate vaccines have failed to induce protective immune responses in humans. We need a more comprehensive understanding of the antigenic targets important in the context of human infection. To investigate infection-associated immune responses, patients were sampled at initial presentation and during convalescence from three types of clinical infection; skin and soft tissue infection (SSTI), prosthetic joint infection (PJI) and pediatric hematogenous osteomyelitis (PHO). Reactivity of serum IgG was tested with an array of recombinant proteins, representing over 2,652 in-vitro-translated open reading frames (ORFs) from a community-acquired methicillin-resistant S. aureus USA300 strain. High-level reactivity was demonstrated for 104 proteins with serum IgG in all patient samples. Overall, high-level IgG-reactivity was most commonly directed against a subset of secreted proteins. Although based on limited surveys, we found subsets of S. aureus proteins with differential reactivity with serum samples from patients with different clinical syndromes. Together, our studies have revealed a hierarchy within the diverse proteins of the S. aureus "immunome", which will help to advance efforts to develop protective immunotherapeutic agents.
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http://dx.doi.org/10.1038/s41598-018-31424-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125462PMC
September 2018

Biosensor libraries harness large classes of binding domains for construction of allosteric transcriptional regulators.

Nat Commun 2018 08 6;9(1):3101. Epub 2018 Aug 6.

Department of Genetics, Harvard Medical School, 77 Av. Louis Pasteur, Boston, MA, 02115, USA.

The ability of bacteria to sense specific molecules within their environment and trigger metabolic responses in accordance is an invaluable biotechnological resource. While many transcription factors (TFs) mediating such processes have been studied, only a handful have been leveraged for molecular biology applications. To expand the repertoire of biotechnologically relevant sensors we present a strategy for the construction and testing of chimeric TF libraries, based on the fusion of highly soluble periplasmic binding proteins (PBPs) with DNA-binding domains (DBDs). We validate this concept by constructing and functionally testing two unique sense-and-respond regulators for benzoate, an environmentally and industrially relevant metabolite. This work will enable the development of tailored biosensors for novel synthetic regulatory circuits.
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http://dx.doi.org/10.1038/s41467-018-05525-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079105PMC
August 2018

Parkinson's disease and bacteriophages as its overlooked contributors.

Sci Rep 2018 Jul 17;8(1):10812. Epub 2018 Jul 17.

Human Microbiology Institute, New York, NY, 10027, USA.

Recent studies suggest that alterations in the gut phagobiota may contribute to pathophysiological processes in mammals; however, the association of bacteriophage community structure with Parkinson's disease (PD) has not been yet characterized. Towards this end, we used a published dataset to analyse bacteriophage composition and determine the phage/bacteria ratio in faecal samples from drug-naive PD patients and healthy participants. Our analyses revealed significant alterations in the representation of certain bacteriophages in the phagobiota of PD patients. We identified shifts of the phage/bacteria ratio in lactic acid bacteria known to produce dopamine and regulate intestinal permeability, which are major factors implicated in PD pathogenesis. Furthermore, we observed the depletion of Lactococcus spp. in the PD group, which was most likely due to the increase of lytic c2-like and 936-like lactococcal phages frequently present in dairy products. Our findings add bacteriophages to the list of possible factors associated with the development of PD, suggesting that gut phagobiota composition may serve as a diagnostic tool as well as a target for therapeutic intervention, which should be confirmed in further studies. Our results open a discussion on the role of environmental phages and phagobiota composition in health and disease.
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http://dx.doi.org/10.1038/s41598-018-29173-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050259PMC
July 2018

Human Memory B Cells Targeting Exotoxins Are Prevalent with Skin and Soft Tissue Infection.

mBio 2018 03 13;9(2). Epub 2018 Mar 13.

New York University School of Medicine, New York, New York, USA

is a Gram-positive opportunistic pathogen that causes superficial and invasive infections in the hospital and community. High mortality from infection emphasizes the need for improved methods for prevention and treatment. Although possesses an arsenal of virulence factors that contribute to evasion of host defenses, few studies have examined long-term humoral and B-cell responses. Adults with acute-phase skin and soft tissue infections were recruited; blood samples were obtained; and isolates, including methicillin-resistant strains, were subjected to genomic sequence analysis. In comparisons of acute-phase sera with convalescent-phase sera, a minority (37.5%) of patients displayed 2-fold or greater increases in antibody titers against three or more antigens, whereas nearly half exhibited no changes, despite the presence of toxin genes in most infecting strains. Moreover, enhanced antibody responses waned over time, which could reflect a defect in B-cell memory or long-lived plasma cells. However, memory B cells reactive with a range of antigens were prevalent at both acute-phase and convalescent-phase time points. While some memory B cells exhibited toxin-specific binding, those cross-reactive with structurally related leucocidin subunits were dominant across patients, suggesting the targeting of conserved epitopes. Memory B-cell reactivity correlated with serum antibody levels for selected exotoxins, suggesting a relationship between the cellular and humoral compartments. Overall, although there was no global defect in the representation of anti- memory B cells, there was evidence of restrictions in the range of epitopes recognized, which may suggest potential therapeutic approaches for augmenting host defenses. The contribution of B-cell memory and long-term antibody responses to host defenses against exotoxins remains poorly understood. Our studies confirmed that infection did not commonly lead to enhanced long-term humoral responses. Whereas circulating memory B cells against secreted exotoxins were prevalent, they were dominated by cross-reactivity with structurally related leucocidin subunits, consistent with recognition of conserved epitopes. These findings also provide the first evidence of a relationship between the reactivity of antistaphylococcal circulating memory B cells and serum antibody levels. In general, infection was not associated with a global defect in B-cell memory for secreted factors, and responses were highly dominated by cross-reactivity to structurally related exotoxins, which arguably may alone be suboptimal in providing host defenses. Our studies illuminate aspects of the host relationship that may better inform strategies for the development of an effective protective vaccine.
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http://dx.doi.org/10.1128/mBio.02125-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850327PMC
March 2018

The Ancient Origins of Neural Substrates for Land Walking.

Cell 2018 02;172(4):667-682.e15

Neuroscience Institute, Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY 10016, USA. Electronic address:

Walking is the predominant locomotor behavior expressed by land-dwelling vertebrates, but it is unknown when the neural circuits that are essential for limb control first appeared. Certain fish species display walking-like behaviors, raising the possibility that the underlying circuitry originated in primitive marine vertebrates. We show that the neural substrates of bipedalism are present in the little skate Leucoraja erinacea, whose common ancestor with tetrapods existed ∼420 million years ago. Leucoraja exhibits core features of tetrapod locomotor gaits, including left-right alternation and reciprocal extension-flexion of the pelvic fins. Leucoraja also deploys a remarkably conserved Hox transcription factor-dependent program that is essential for selective innervation of fin/limb muscle. This network encodes peripheral connectivity modules that are distinct from those used in axial muscle-based swimming and has apparently been diminished in most modern fish. These findings indicate that the circuits that are essential for walking evolved through adaptation of a genetic regulatory network shared by all vertebrates with paired appendages. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cell.2018.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808577PMC
February 2018

The PlusoptiX Photoscreener and the Retinomax Autorefractor as Community-based Screening Devices for Preschool Children.

Curr Eye Res 2018 05 9;43(5):654-658. Epub 2018 Feb 9.

b Department of Ophthalmology, Shiley Eye Center, School of Medicine , University of California-San Diego , La Jolla , CA , USA.

Purpose: To compare the performance of the PlusoptiX S12 mobile photoscreener and the Retinomax K+3 Autorefractor as screening devices in preschool children.

Methods: Children ranging from 3 to 5 years of age from 11 San Diego County preschools underwent vision screening in their schools where ambient light could not always be controlled using both the Retinomax and the PlusoptiX. Cycloplegic refraction on the consented children was subsequently performed on the UCSD EyeMobile for children on-site at the school locations.

Results: A total of 321 children were screened with the PlusoptiX and Retinomax. The PlusoptiX referred 22% of children, of whom 70% of the referrals were read as "unable". The Retinomax referred 13% and there were no "unables". Similar results occurred in the cycloplegic-refracted 182 consented children-64% of the PlusoptiX referrals were read as "unable" . Only one third of these "unables" required glasses. Both devices referred the four children with amblyopia and one case of strabismus. However, PlusoptiX's 3 false negatives had amblyopia risk factors (ARFs) while the one Retinomax's false negative did not have ARFs. The Retinomax screening had 95% sensitivity and 94% specificity. The PlusoptiX screening had 86% sensitivity and 84% specificity.

Conclusion: In this preschool population and environment, the PlusoptiX referred 63% more than the Retinomax in addition to a lower specificity and sensitivity. Adjusting PlusoptiX referral criteria might not substantially improve the specificity of the PlusoptiX due to the high numbers of "unables".
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http://dx.doi.org/10.1080/02713683.2018.1437453DOI Listing
May 2018

HPViewer: sensitive and specific genotyping of human papillomavirus in metagenomic DNA.

Bioinformatics 2018 06;34(12):1986-1995

Department of Pathology.

Motivation: Shotgun DNA sequencing provides sensitive detection of all 182 HPV types in tissue and body fluid. However, existing computational methods either produce false positives misidentifying HPV types due to shared sequences among HPV, human and prokaryotes, or produce false negative since they identify HPV by assembled contigs requiring large abundant of HPV reads.

Results: We designed HPViewer with two custom HPV reference databases masking simple repeats and homology sequences respectively and one homology distance matrix to hybridize these two databases. It directly identified HPV from short DNA reads rather than assembled contigs. Using 100 100 simulated samples, we revealed that HPViewer was robust for samples containing either high or low number of HPV reads. Using 12 shotgun sequencing samples from respiratory papillomatosis, HPViewer was equal to VirusTAP, and Vipie and better than HPVDetector with the respect to specificity and was the most sensitive method in the detection of HPV types 6 and 11. We demonstrated that contigs-based approaches had disadvantages of detection of HPV. In 1573 sets of metagenomic data from 18 human body sites, HPViewer identified 104 types of HPV in a body-site associated pattern and 89 types of HPV co-occurring in one sample with other types of HPV. We demonstrated HPViewer was sensitive and specific for HPV detection in metagenomic data.

Availability And Implementation: HPViewer can be accessed at https://github.com/yuhanH/HPViewer/.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/bty037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658710PMC
June 2018

Bone remodelling in vitro: Where are we headed?: -A review on the current understanding of physiological bone remodelling and inflammation and the strategies for testing biomaterials in vitro.

Bone 2018 05 3;110:38-46. Epub 2018 Feb 3.

Regenerative Biomaterials Group, RAFT Institute, Leopold Muller Building, Mount Vernon Hospital, Northwood HA6 2RN, UK.

Bone remodelling is a dynamic process required for the maintenance of bone architecture in response to the changing mechanical needs. It is also a vital process during the repair of bone tissue following injury. Clinical intervention in terms of autografting or allografting is often required to heal bone injuries where physiological healing fails. The use of biomaterials as alternatives to autografts and allografts has spurred a significant research interest into further development of biomaterials for better clinical outcomes. Unfortunately, many biomaterials fail to make it to the clinic or fail after implantation due to the inconsistencies observed between in vitro and in vivo studies. It is therefore important to mimic the in vivo situation as closely as possible in an in vitro setting for testing biomaterials. The current in vitro models focus mostly on investigating the behaviour of osteoblast progenitors with the biomaterial under development as well as assessing the behaviour of osteoclasts, endothelial cells etc. However, the sequence of events that take place during bone healing or remodelling are not incorporated into the current in vitro models. This review highlights our current understanding of the physiological bone remodelling and the bone healing process followed by strategies to incorporate both the physiological and pathophysiological events into an in vitro environment. Here, we propose three strategies for the assessment of biomaterials for bone, which includes; (1) testing biomaterials in the presence of immune cells, (2) testing biomaterials for osteogenesis, and (3) testing biomaterials in the presence of osteoclasts followed by osteoblasts to recapitulate the physiological events of bone resorption prior to bone formation. The focus of this review is to discuss the third strategy in details as the first two strategies are currently incorporated into a majority of in vitro experiments.
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http://dx.doi.org/10.1016/j.bone.2018.01.015DOI Listing
May 2018
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