Publications by authors named "Michael Grace"

90 Publications

Pit organ-based infrared discrimination sensitivity and signal transduction in the Burmese python (Python molurus bivitattus).

Behav Brain Res 2022 07 2;429:113910. Epub 2022 May 2.

School of Behavior Analysis, Florida Institute of Technology, Melbourne, FL, USA.

Burmese pythons (Python molurus bivitattus) use a unique infrared (IR) targeting system to acquire prey, avoid predators and seek thermoregulatory sites through detection of IR energy in the environment. Previous studies of sensitivity of the python IR system that relied on analysis of complex, natural behaviors lacked robust, reliable responses in animals habituated to experiments, and in vitro electrophysiological study failed to test behavioral function of the implicated protein thermoreceptor, TRPA1. The present study used conditioned discrimination procedures to analyze behavioral sensitivity and signal transduction in the python IR system. Pythons trained to behaviorally discriminate thermal stimuli averaged 70% correct choices, but failed to make correct choices when pit organs were physically occluded with IR-blocking material. The pythons exhibited greater sensitivity to thermal stimuli than previously reported, evident by correct choices that exceeded chance in response to a 14 × 10 W cm irradiance contrast, or 0.5 °C thermal differential. Finally, in a test of the behavioral role of the putative thermoreceptor protein TRPA1, despite pit organ treatment with a TRPA1 inhibitor, python performance exceeded chance and was similar to baseline discrimination and control trials. Collectively, the results suggest that the IR system is a high sensitivity, broad-spectrum thermosensor that may operate through different and/or multiple thermoreceptive proteins with overlapping spectral response profiles. The findings reported here provide a better understanding of the relationship between the brain, behavior and environment in driving survival and ecological success of the Burmese python, especially as an invasive megapredator in the southern United States.
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http://dx.doi.org/10.1016/j.bbr.2022.113910DOI Listing
July 2022

Une révolution tranquille dans les décisions des collèges.

Can Fam Physician 2021 11;67(11):e314-e316

Candidat au baccalauréat en sciences médicales à l'Université Western.

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http://dx.doi.org/10.46747/cfp.6711e314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589140PMC
November 2021

A quiet revolution in college decisions.

Can Fam Physician 2021 11;67(11):e312-e313

Bachelor of Medical Sciences candidate at Western University.

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http://dx.doi.org/10.46747/cfp.6711e312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8589145PMC
November 2021

Pilot study evaluating the feasibility of stereotactic body radiation therapy for canine anal sac adenocarcinomas.

Vet Radiol Ultrasound 2021 Sep 14;62(5):621-629. Epub 2021 Jun 14.

Oncology Department, Animal Referral Hospital, Homebush West, New South Wales, Australia.

The use of stereotactic body radiation therapy (SBRT) to treat many canine tumors is rapidly expanding. However, published studies are lacking regarding use of SBRT for management of canine anal sac adenocarcinoma (ASAC), primarily due to concerns regarding intolerable late effects. The objective of this retrospective, pilot study was to describe the efficacy and safety profile of coarse fractions administered with an SBRT regime to manage a group of dogs with ASAC. A total of 12 dogs with ASAC that received SBRT as a component of their treatment were sampled. Three patients had macroscopic primary tumors irradiated, while nine patients received SBRT following incomplete surgical resection. Seven patients also received metastatic regional lymph node irradiation. Primary tumor and nodal irradiation sites received three fractions totaling 22-24 Gy and 22.5-24 Gy, respectively, over three consecutive days. All patients developed acute effects including mild colitis, alopecia, and erythema. Late effects included alopecia, variable dermal pigmentation and leuko- or melanotrichia within radiation fields, and rectal stricture in one patient. A median progression free survival time of 549 days and median survival time of 991 days were achieved in this study. These results should be considered preliminary data suggesting that coarse fractionation administered with an SBRT technique is a safe and effective treatment regime for the management of canine ASAC, with the aim to conduct prospective studies in the future.
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http://dx.doi.org/10.1111/vru.12998DOI Listing
September 2021

Approaching quantum-limited imaging resolution without prior knowledge of the object location.

J Opt Soc Am A Opt Image Sci Vis 2020 Aug;37(8):1288-1299

Passive imaging receivers that demultiplex an incoherent optical field into a set of orthogonal spatial modes prior to detection can surpass canonical diffraction limits on spatial resolution. However, these mode-sorting receivers exhibit sensitivity to contextual nuisance parameters (e.g., the centroid of a clustered or extended object), raising questions on their viability in realistic scenarios where prior information about the scene is limited. We propose a multistage detection strategy that segments the total recording time between different physical measurements to build up the required prior information for near quantum-optimal imaging performance at sub-Rayleigh length scales. We show, via Monte Carlo simulations, that an adaptive two-stage scheme that dynamically allocates recording time between a conventional direct detection measurement and a binary mode sorter outperforms idealized direct detection alone when no prior knowledge of the object centroid is available, achieving one to two orders of magnitude improvement in mean squared error for simple estimation tasks. Our scheme can be generalized for more sophisticated tasks involving multiple parameters and/or minimal prior information.
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http://dx.doi.org/10.1364/JOSAA.392116DOI Listing
August 2020

Total body irradiation in Australia and New Zealand: results of a practice survey.

Phys Eng Sci Med 2020 Sep 1;43(3):825-835. Epub 2020 Jul 1.

The Peter MacCallum Cancer Centre, Grattan St, Melbourne, 3000, Australia.

Total body irradiation (TBI) is an important treatment modality for the preparation of patients for bone marrow transplants. It is technically challenging and the actual delivery may vary from clinic to clinic. Knowledge of the pattern of practice may be helpful for clinics to determine future practice. We carried out an email survey from April to September 2019 sending 48 TBI related questions to all radiotherapy clinics in Australia and New Zealand via the Australasian College of Physical Scientists in Medicine email distribution list. Centres not performing TBI were not expected to complete the survey and centres that had participated in a previous survey, or that were known to perform the treatment, were followed up if no response was received. Of a total of approximately 70 centres, 14 clinics responded to the survey. The vast majority of clinics use conventional lateral and/or anterior-posterior beams at extended SSD for TBI treatment delivery. However, treatment planning, ancillary equipment (used for immobilisation/modulation), beam energy and prescribed lung doses vary considerably-with some clinics delivering the prescription dose to the lungs and some aiming to deliver a lung dose which is lower than the prescription dose. Only one clinic reported using an advanced delivery technique with modulated arcs at extended SSD. Centres either said they had no access to outcome data or did not answer this question. Compared with an earlier survey from 2005, 3 clinics have lowered their linac dose rate and 7 are the same or similar. The TBI practice in Australia and New Zealand remains varied, with considerable differences in treatment planning, beam energy, accepted lung doses and delivered dose rates.
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http://dx.doi.org/10.1007/s13246-020-00878-zDOI Listing
September 2020

A highly efficient red-emitting luminescent paper-based chemosensor for hydrogen sulfide.

Chem Commun (Camb) 2020 May;56(42):5605-5608

School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.

The first discrete bimetallic europium(iii)/copper(ii) complex for the fast, sensitive and selective luminescent detection of both aqueous and gaseous hydrogen sulfide has been developed. The chemosensor displayed an impressive response time of 30 seconds and a low theoretical limit of detection (100 ppb) for gaseous hydrogen sulfide.
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http://dx.doi.org/10.1039/d0cc00745eDOI Listing
May 2020

Radiation-Stimulated Translocation of CD166 and CRYAB to the Endothelial Surface Provides Potential Vascular Targets on Irradiated Brain Arteriovenous Malformations.

Int J Mol Sci 2019 Nov 20;20(23). Epub 2019 Nov 20.

Department of Clinical Medicine, Macquarie University, Sydney 2109, Australia.

Vascular targeting with pro-thrombotic antibody-conjugates is a promising biological treatment for brain arteriovenous malformations (bAVMs). However, targeted drug delivery relies on the identification of unique or overexpressed markers on the surface of a target cell. In the absence of inherent biological markers, stereotactic radiosurgery may be used to prime induction of site-specific and targetable molecular changes on the endothelial surface. To investigate lumen-accessible, endothelial targets induced by radiation, we combined Gamma knife surgery in an AVM animal model with in vivo biotin-labeling and comparative proteomics. Two proteins, αB-crystallin (CRYAB)-a small heat shock protein that normally acts as an intracellular chaperone to misfolded proteins-and activated leukocyte cell adhesion molecule CD166, were further validated for endothelial surface expression after irradiation. Immunostaining of endothelial cells in vitro and rat AVM tissue ex vivo confirmed de novo induction of CRYAB following irradiation (20 Gy). Western analysis demonstrated that CRYAB accumulated intracellularly as a 20 kDa monomer, but, at the cell surface, a novel 65 kDa protein was observed, suggesting radiation stimulates translocation of an atypical CRYAB isoform. In contrast, CD166 had relatively high expression in non-irradiated cells, localized predominantly to the lateral surfaces. Radiation increased CD166 surface exposure by inducing translocation from intercellular junctions to the apical surface without significantly altering total protein levels. These findings reinforce the dynamic molecular changes induced by radiation exposure, particularly at the cell surface, and support further investigation of radiation as a priming mechanism and these molecules as putative targets for focused drug delivery in irradiated tissue.
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http://dx.doi.org/10.3390/ijms20235830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929092PMC
November 2019

Time-Resolved Terbium-Based Probe for the Detection of Zinc(II) Ions: Investigation of the Formation of a Luminescent Ternary Complex.

Inorg Chem 2020 Jan 27;59(1):118-127. Epub 2019 Aug 27.

School of Chemistry , Monash University , Clayton , Victoria 3800 , Australia.

Because of their unique photochemical and photophysical properties, luminescent lanthanide-based complexes have long captivated chemists. In recent years, the number of reports of luminescent lanthanide complex-based probes for monitoring of biological and environmental processes has dramatically increased, namely, because of their selectivity for particular analytes, lower limits of detection, and the fact that they allow monitoring of analytes in real time. Lanthanide-based probes need to be paired with an appropriate antenna/sensitizer to allow maximum energy transfer, with the antenna typically covalently attached to the stable lanthanide chelate. We have recently investigated "dark" lanthanide-based probes where the sensitizer is not covalently linked to the lanthanide chelate. Herein we report the use of a luminescent lanthanide-based probe system for the detection of Zn ions based on the formation of a ternary complex between a "dark" terbium complex, lumazine, and Zn. The terbium(III)-based probe incorporates a 1,4,7,10-tetraazacyclododecane-1,4,7,10-triacetic acid macrocyclic chelator covalently attached to a cyclen moiety, which is the Zn ion binding group. In the presence of Zn ions and lumazine (a strongly UV-absorbing sensitizer), a 1:1:1 ternary complex forms. The resulting complex is highly luminescent and selective for Zn ions over other cations of environmental significance. Furthermore, with a limit of detection of 1.2 μM, this probe can detect the level of chronic zinc(II) concentrations denoted by the U.S. Environmental Protection Agency.
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http://dx.doi.org/10.1021/acs.inorgchem.9b01771DOI Listing
January 2020

Volume not number of metastases: Gamma Knife radiosurgery management of intracranial lesions from an Australian perspective.

Radiother Oncol 2019 04 14;133:43-49. Epub 2019 Jan 14.

Macquarie Neurosurgery, Macquarie University Hospital, Sydney, Australia.

Background And Purpose: To assess the response of the first cohort of patients treated with Gamma Knife radiosurgery in Australia.

Materials And Methods: A prospectively collected cohort of 180 patients with intracranial metastases from different primaries was treated between August 2010 and July 2017. Survival was calculated using the Kaplan-Meier's method. Cox regression was used for multivariate analysis.

Results: Currently 141 patients (78.3%) have died of their disease. The median survival for the group as a whole was 9.2 months, with observed differences resulting from the volume of tumor burden (11.4 months for volumes <3.2 cm to 5.16 months for volume >9.1 cm). Overall 2-year survival was 20.7%.

Conclusion: Results from the first Gamma Knife radiosurgery center in Australia showed that the treatment is feasible and effective, consistent with the international experience. For patients with larger numbers of intracranial metastases, the total volume of the intracranial burden may be of more significance in predicting outcomes. While there appeared to be a difference in survival by histologic origin, this could be related to concurrent systemic immunotherapy available for certain tumors.
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http://dx.doi.org/10.1016/j.radonc.2018.12.018DOI Listing
April 2019

Role of organic carbon, nitrate and ferrous iron on the partitioning between denitrification and DNRA in constructed stormwater urban wetlands.

Sci Total Environ 2019 May 15;666:608-617. Epub 2019 Feb 15.

Water Studies Centre, School of Chemistry, Monash University, Clayton, Australia. Electronic address:

Denitrification (DNF) and dissimilatory nitrate reduction to ammonium (DNRA) are two competing nitrate reduction pathways that remove or recycle nitrogen, respectively. However, factors controlling the partitioning between these two pathways are manifold and our understanding of these factors is critical for the management of N loads in constructed wetlands. An important factor that controls DNRA in an aquatic ecosystem is the electron donor, commonly organic carbon (OC) or alternatively ferrous iron and sulfide. In this study, we investigated the role of natural organic carbon (NOC) and acetate at different OC/NO ratios and ferrous iron on the partitioning between DNF and DNRA using the N-tracer method in slurries from four constructed stormwater urban wetlands in Melbourne, Australia. The carbon and nitrate experiments revealed that DNF dominated at all OC/NO ratios. The higher DNF and DNRA rates observed after the addition of NOC indicates that nitrate reduction was enhanced more by NOC than acetate. Moreover, addition of NOC in slurries stimulated DNRA more than DNF. Interestingly, slurries amended with Fe showed that Fe had significant control on the balance between DNF and DNRA. From two out of four wetlands, a significant increase in DNRA rates (p < .05) at the cost of DNF in the presence of available Fe suggests DNRA is coupled to Fe oxidation. Rates of DNRA increased 1.5-3.5 times in the Fe treatment compared to the control. Overall, our study provides direct evidence that DNRA is linked to Fe oxidation in some wetland sediments and highlights the role of Fe in controlling the partitioning between removal (DNF) and recycling (DNRA) of bioavailable N in stormwater urban constructed wetlands. In our study we also measured anammox and found that it was always <0.05% of total nitrate reduction in these sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2019.02.225DOI Listing
May 2019

Proteomics identification of radiation-induced changes of membrane proteins in the rat model of arteriovenous malformation in pursuit of targets for brain AVM molecular therapy.

Clin Proteomics 2018 26;15:43. Epub 2018 Dec 26.

1Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW Australia.

Background: Rapid identification of novel targets and advancement of a vascular targeting strategy requires a comprehensive assessment of AVM endothelial membrane protein changes in response to irradiation. The aim of this study is to provide additional potential target protein molecules for evaluation in animal trials to promote intravascular thrombosis in AVM vessels post radiosurgery.

Methods: We employed in vivo biotinylation methodology that we developed, to label membrane proteins in the rat model of AVM post radiosurgery. Mass spectrometry expression (MS) analysis was used to identify and quantify surface protein expression between irradiated and non irradiated rats, which mimics a radiosurgical treatment approach.

Results: Our proteomics data revealed differentially expressed membrane proteins between irradiated and non irradiated rats, e.g. profilin-1, ESM-1, ion channel proteins, annexin A2 and lumican.

Conclusion: This work provides additional potential target protein molecules for evaluation in animal trials to promote intravascular thrombosis in AVM vessels post radiosurgery.
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http://dx.doi.org/10.1186/s12014-018-9217-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305998PMC
December 2018

Interaction of Nucleotides with a Trinuclear Terbium(III)-Dizinc(II) Complex: Efficient Sensitization of Terbium Luminescence by Guanosine Monophosphate and Application to Real-Time Monitoring of Phosphodiesterase Activity.

Inorg Chem 2019 Jan 18;58(1):495-505. Epub 2018 Dec 18.

School of Chemistry , Monash University , Clayton , Victoria 3800 , Australia.

An in-depth study of the interaction of a trinuclear terbium(III)-dizinc(II) complex with an array of nucleotides differing in the type of nucleobase and number of phosphate groups, as well as cyclic versus acyclic variants, is presented. The study examined the nature of the interaction and the efficiency at which guanine was able to sensitize terbium(III) luminescence. Competitive binding and titration studies were performed to help establish the nature/mode of the interactions. These established that (1) interaction occurs by the coordination of phosphate groups to zinc(II) (in addition to uridine in the case of uridine monophosphate), (2) acyclic nucleotides bind more strongly than cyclic counterparts because of their higher negative charge, (3) guanine-containing nucleotides are able to sensitize terbium(III) luminescence with the efficiency of sensitization following the order guanosine monophosphate (GMP) > guanosine diphosphate > guanosine triphosphate because of the mode of binding, and (4) nucleoside monophosphates bind to a single zinc(II) ion, whereas di- and triphosphates appear to bind in a bridging mode between two host molecules. Furthermore, it has been shown that guanine is a sensitizer of terbium(III) luminescence. On the basis of the ability of GMP to effectively sensitize terbium(III)-based luminescence while cyclic GMP (cGMP) does not, the complex has been utilized to monitor the catalytic conversion of cGMP to GMP by a phosphodiesterase enzyme in real time using time-gated luminescence on a benchtop fluorimeter. The complex has the potential to find broad application in monitoring the activity of enzymes that process nucleotides (co)substrates, including high-throughput drug-screening programs.
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http://dx.doi.org/10.1021/acs.inorgchem.8b02731DOI Listing
January 2019

A diverse suite of pharmaceuticals contaminates stream and riparian food webs.

Nat Commun 2018 11 6;9(1):4491. Epub 2018 Nov 6.

Water Studies Centre, School of Chemistry, Monash University, Clayton, 3800, Victoria, Australia.

A multitude of biologically active pharmaceuticals contaminate surface waters globally, yet their presence in aquatic food webs remain largely unknown. Here, we show that over 60 pharmaceutical compounds can be detected in aquatic invertebrates and riparian spiders in six streams near Melbourne, Australia. Similar concentrations in aquatic invertebrate larvae and riparian predators suggest direct trophic transfer via emerging adult insects to riparian predators that consume them. As representative vertebrate predators feeding on aquatic invertebrates, platypus and brown trout could consume some drug classes such as antidepressants at as much as one-half of a recommended therapeutic dose for humans based on their estimated prey consumption rates, yet the consequences for fish and wildlife of this chronic exposure are unknown. Overall, this work highlights the potential exposure of aquatic and riparian biota to a diverse array of pharmaceuticals, resulting in exposures to some drugs that are comparable to human dosages.
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http://dx.doi.org/10.1038/s41467-018-06822-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219508PMC
November 2018

Determination of selected emerging contaminants in freshwater invertebrates using a universal extraction technique and liquid chromatography accurate mass spectrometry.

J Sep Sci 2018 Oct 4;41(19):3706-3715. Epub 2018 Sep 4.

Australian Centre of Research on Separation Science, School of Chemistry, Faculty of Science, Monash University, Clayton, VIC, Australia.

A simple sample preparation method based on a modified liquid-phase extraction approach to extract selected pharmaceuticals and personal care products from freshwater organisms is described. Extracted samples were analysed using liquid chromatography with Q-Exactive plus hybrid quadrupole Orbitrap mass spectrometry, using 2.6 μm C18 media. A 0.1% v/v acetic acid/acetonitrile mobile phase was applied over a 20 min gradient. Method detection limits in full scan mode were ca. 0.04-2.38 ng of analyte per g of sample. Linearity ranged from 0.9750 to 0.9996 over the calibration range of 0.01-100 μg/L; MS mass accuracy was <2 ppm for most analytes. This method was applied to quantify six pharmaceuticals and personal care products in seven invertebrate samples. For tandem mass spectrometry analysis, selection of precursor ions was performed for each pharmaceutical, with Mass Frontier software illustrating the fragmentation mechanism. Effects of collision energy on intensities of ions was further investigated. The tandem mass spectrometry condition resulting in the highest signal of respective selected product ion was selected to confirm each pharmaceutical, which was initially observed in the full scan mode. Results indicate that pharmaceuticals and personal care products found to be present in water-ways, may be incorporated into organisms that live in the environment of affected water streams.
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http://dx.doi.org/10.1002/jssc.201800507DOI Listing
October 2018

Altered environmental light drives retinal change in the Atlantic Tarpon (Megalops atlanticus) over timescales relevant to marine environmental disturbance.

BMC Ecol 2018 01 18;18(1). Epub 2018 Jan 18.

Department of Biological Sciences, Florida Institute of Technology, 150 W. University Boulevard, Melbourne, FL, 32901, USA.

Background: For many fish species, retinal function changes between life history stages as part of an encoded developmental program. Retinal change is also known to exhibit plasticity because retinal form and function can be influenced by light exposure over the course of development. Aside from studies of gene expression, it remains largely unknown whether retinal plasticity can provide functional responses to short-term changes in environmental light quality. The aim of this study was to determine whether the structure and function of the fish retina can change in response to altered light intensity and spectrum-not over the course of a developmental regime, but over shorter time periods relevant to marine habitat disturbance.

Results: The effects of light environment on sensitivity of the retina, as well as on cone photoreceptor distribution were examined in the Atlantic tarpon (Megalops atlanticus) on 2- and 4-month timescales. In a spectral experiment, juvenile M. atlanticus were placed in either 'red' or 'blue' light conditions (with near identical irradiance), and in an intensity experiment, juveniles were placed in either 'bright' or 'dim' light conditions (with near identical spectra). Analysis of the retina by electroretinography and anti-opsin immunofluorescence revealed that relative to fish held in the blue condition, those in the red condition exhibited longer-wavelength peak sensitivity and greater abundance of long-wavelength-sensitive (LWS) cone photoreceptors over time. Following pre-test dark adaption of the retina, fish held in the dim light required less irradiance to produce a standard retinal response than fish held in bright light, developing a greater sensitivity to white light over time.

Conclusions: The results show that structure and function of the M. atlanticus retina can rapidly adjust to changes in environmental light within a given developmental stage, and that such changes are dependent on light quality and the length of exposure. These findings suggest that the fish retina may be resilient to disturbances in environmental light, using retinal plasticity to compensate for changes in light quality over short timescales.
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http://dx.doi.org/10.1186/s12898-018-0157-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774114PMC
January 2018

Circadian Rhythms of Retinomotor Movement in a Marine Megapredator, the Atlantic Tarpon, Megalops atlanticus.

Int J Mol Sci 2017 Sep 28;18(10). Epub 2017 Sep 28.

College of Science, Florida Institute of Technology, 150 West University Blvd, Melbourne, FL 32901, USA.

Many ecologically and economically important marine fish species worldwide spend portions of their lives in coastal regions that are increasingly inundated by artificial light at night. However, while extensive research illustrates the harmful effects of inappropriate light exposure on biological timing in humans, rodents and birds, comparable studies on marine fish are virtually nonexistent. This study aimed to assess the effects of light on biological clock function in the marine fish retina using the Atlantic tarpon () as a model. Using anti-opsin immunofluorescence, we observed robust rhythms of photoreceptor outer segment position (retinomotor movement) over the course of the daily light-dark cycle: cone outer segments were contracted toward the inner retina and rods were elongated during the day; the opposite occurred at night. Phase shifting the daily light-dark cycle caused a corresponding shift of retinomotor movement timing, and cone retinomotor movement persisted in constant darkness, indicating control by a circadian clock. Constant light abolished retinomotor movements of both photoreceptor types. Thus, abnormally-timed light exposure may disrupt normal clock function and harm vision, which in turn may affect prey capture and predator avoidance. These results should help inform efforts to mitigate the effects of coastal light pollution on organisms in marine ecosystems.
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http://dx.doi.org/10.3390/ijms18102068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666750PMC
September 2017

In vivo imaging of endothelial cell adhesion molecule expression after radiosurgery in an animal model of arteriovenous malformation.

PLoS One 2017 26;12(9):e0185393. Epub 2017 Sep 26.

Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.

Focussed radiosurgery may provide a means of inducing molecular changes on the luminal surface of diseased endothelium to allow targeted delivery of novel therapeutic compounds. We investigated the potential of ionizing radiation to induce surface expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells (EC) in vitro and in vivo, to assess their suitability as vascular targets in irradiated arteriovenous malformations (AVMs). Cultured brain microvascular EC were irradiated by linear accelerator at single doses of 0, 5, 15 or 25 Gy and expression of ICAM-1 and VCAM-1 measured by qRT-PCR, Western, ELISA and immunocytochemistry. In vivo, near-infrared (NIR) fluorescence optical imaging using Xenolight 750-conjugated ICAM-1 or VCAM-1 antibodies examined luminal biodistribution over 84 days in a rat AVM model after Gamma Knife surgery at a single 15 Gy dose. ICAM-1 and VCAM-1 were minimally expressed on untreated EC in vitro. Doses of 15 and 25 Gy stimulated expression equally; 5 Gy was not different from the unirradiated. In vivo, normal vessels did not bind or retain the fluorescent probes, however binding was significant in AVM vessels. No additive increases in probe binding were found in response to radiosurgery at a dose of 15 Gy. In summary, radiation induces adhesion molecule expression in vitro but elevated baseline levels in AVM vessels precludes further induction in vivo. These molecules may be suitable targets in irradiated vessels without hemodynamic derangement, but not AVMs. These findings demonstrate the importance of using flow-modulated, pre-clinical animal models for validating candidate proteins for vascular targeting in irradiated AVMs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185393PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614630PMC
October 2017

Liquid chromatography - quadrupole Orbitrap mass spectrometry method for selected pharmaceuticals in water samples.

J Chromatogr A 2017 Sep 3;1515:164-171. Epub 2017 Aug 3.

Australian Centre of Research on Separation Science, School of Chemistry, Faculty of Science, Monash University, Clayton, VIC 3800, Australia. Electronic address:

This study developed an analytical approach for sub-ppb level detection and confirmation of 13 pharmaceuticals and personal care products (PPCPs) in water samples using ultra high pressure liquid chromatography hyphenated with a quadrupole Orbitrap mass spectrometer (UHPLC- Q-Orbitrap-MS). Sample preparation was performed by using solid phase extraction (SPE) employing hydrophilic-lipophilic balance cartridges, with elution of sorbed analytes using methanol. Acceptable automatic gain control (AGC) target and maximum injection time (IT) were 1×10 and 200ms, respectively, resulting in a mass accuracy <2ppm. High response signals with sufficient data points per peaks (20-30) were obtained whilst maintaining high resolution of approximately 70,000 full width at half maximum. Extracted ion chromatograms provided quantitative analysis with linearity (R) ranging from 0.9875 to 0.9993 and method detection limits ranging from 0.01-0.61ngmL. Compounds were further analysed by MS/MS analysis, with the MS operated in parallel reaction monitoring (PRM) mode under precursor ion analysis intervals and collision energies chosen for the different PPCPs. The developed method was applied to analyse water samples obtained from sources in Victoria, Australia.
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http://dx.doi.org/10.1016/j.chroma.2017.08.003DOI Listing
September 2017

Thin ferrihydrite sediment capping sequestrates phosphorus experiencing redox conditions in a shallow temperate lacustrine wetland.

Chemosphere 2017 Oct 12;185:673-680. Epub 2017 Jul 12.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China; Joint Key Laboratory of Changbai Mountain Wetland and Ecology, Jilin Province, Changchun 130102, China. Electronic address:

Synthesized ferrihydrite (Fh) with the dosages of 0.3, 0.6 and 0.9 cm thickness (labeled as Fh, 2Fh and 3Fh respectively, equivalent to 248-774 g/m) were deployed to serve as the reactive capping layer covering the Ornamental Lake sediments, the Royal Botanic Garden of Melbourne. The sediments were exposed to an alternating regime of oxic/anoxic conditions using laboratory reactors for 45 days. Dynamics of dissolved oxygen (DO), pH, filterable reactive phosphorus (FRP), filterable ammonium (NH), nitrate and nitrite (NO), total dissolved nitrogen (TDN) and dissolved iron (Fe) of overlying water were examined. After incubation, O and HS profiles across the water-sediment interface were observed with microelectrodes. The element distributions in the upper sediments were tested as well. Results showed that DO and pH kept relatively stable during oxic period, while decreased significantly during anoxic period. Fh cappings decreased both DO and pH, and inhibited the release of FRP. No significant increments of FRP in overlying waters were observedduring anoxic period. Fh cappings prompted the releases of NH and TDN, while inhibited that of NO.NHincreased while NO decreased during anoxic period. Fe(II) and TFe increased only in 3Fh, especially during anoxic conditions. Fh cappings increased O and HS concentrations across the water-sediment interfaces. TP and TN in the sediments decreased after capping, while TFe increased significantly. We concluded that 0.6 cm thickness of (496 g/m) Fh capping could sequestrate P, even experiencing redox conditions.
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http://dx.doi.org/10.1016/j.chemosphere.2017.07.052DOI Listing
October 2017

Spectral Sensitivity Change May Precede Habitat Shift in the Developing Retina of the Atlantic Tarpon (Megalops atlanticus).

Physiol Biochem Zool 2017 Sep/Oct;90(5):553-563

Fish that undergo ontogenetic migrations between habitats often encounter new light environments that require changes in the spectral sensitivity of the retina. For many fish, sensitivity of the retina changes to match the environmental spectrum, but the timing of retinal change relative to habitat shift remains unknown. Does retinal change in fish precede habitat shift, or is it a response to encountered changes in environmental light? Spectral sensitivity changes were examined over the development of the Atlantic tarpon (Megalops atlanticus) retina relative to ontogenetic shifts in habitat light. Opsin gene isoform expression and inferred chromophore use of visual pigments were examined over the course of M. atlanticus development. Spectral sensitivity of the retina was then determined by electroretinography and compared to the spectroradiometric measurements of habitat light encountered by M. atlanticus from juveniles to adults. These data, along with previously known microspectrophotometric measurements of sensitivity in M. atlanticus, indicate retinal spectral sensitivity that matches the dominant wavelengths of environmental light for juvenile and adult fish. For the intervening subadult stage, however, spectral sensitivity does not match the dominant wavelength of light it occupies but better matches the dominant wavelengths of light in the habitat of its forthcoming migration. These results first indicate that the relationship between environmental light spectrum and spectral sensitivity of the retina changes during M. atlanticus development and then suggest that such changes may be programmed to support visual anticipation of new photic environments.
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http://dx.doi.org/10.1086/692993DOI Listing
September 2017

Ionizing radiation reduces ADAM10 expression in brain microvascular endothelial cells undergoing stress-induced senescence.

Aging (Albany NY) 2017 04;9(4):1248-1268

Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, 2109, Australia.

Cellular senescence is associated with aging and is considered a potential contributor to age-associated neurodegenerative disease. Exposure to ionizing radiation increases the risk of developing premature neurovascular degeneration and dementia but also induces premature senescence. As cells of the cerebrovascular endothelium are particularly susceptible to radiation and play an important role in brain homeostasis, we investigated radiation-induced senescence in brain microvascular endothelial cells (EC). Using biotinylation to label surface proteins, streptavidin enrichment and proteomic analysis, we analyzed the surface proteome of stress-induced senescent EC in culture. An array of both recognized and novel senescence-associated proteins were identified. Most notably, we identified and validated the novel radiation-stimulated down-regulation of the protease, a disintegrin and metalloprotease 10 (ADAM10). ADAM10 is an important modulator of amyloid beta protein production, accumulation of which is central to the pathologies of Alzheimer's disease and cerebral amyloid angiopathy. Concurrently, we identified and validated increased surface expression of ADAM10 proteolytic targets with roles in neural proliferation and survival, inflammation and immune activation (L1CAM, NEO1, NEST, TLR2, DDX58). ADAM10 may be a key molecule linking radiation, senescence and endothelial dysfunction with increased risk of premature neurodegenerative diseases normally associated with aging.
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http://dx.doi.org/10.18632/aging.101225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425125PMC
April 2017

Phosphatidylserine Translocation after Radiosurgery in an Animal Model of Arteriovenous Malformation.

Radiat Res 2017 06 17;187(6):701-707. Epub 2017 Apr 17.

a   Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, New South Wales, Australia.

Phosphatidylserine (PS) is asymmetrically distributed across the plasma membrane, located predominantly on the inner leaflet in healthy cells. Translocation of PS to the outer leaflet makes it available as a target for biological therapies. We examined PS translocation after radiosurgery in an animal model of brain arteriovenous malformation (AVM). An arteriovenous fistula was created by end-to-side anastomosis of the left external jugular vein to the common carotid artery in 6-week-old, male Sprague Dawley rats. Six weeks after AVM creation, 15 rats underwent Gamma Knife stereotactic radiosurgery receiving a single 15 Gy dose to the margin of the fistula; 15 rats received sham treatment. Externalization of PS was examined by intravenous injection of a PS-specific near-infrared probe, PSVue-794, and in vivo fluorescence optical imaging at 1, 7, 21, 42, 63 and 84 days postirradiation. Fluorescent signaling indicative of PS translocation to the luminal cell surface accumulated in the AVM region, in both irradiated and nonirradiated animals, at all time points. Fluorescence was localized specifically to the AVM region and was not present in any other anatomical sites. Translocated PS increased over time in irradiated rats (P < 0.001) but not in sham-irradiated rats and this difference reached statistical significance at day 84 (P < 0.05). In summary, vessels within the mature rat AVM demonstrate elevated PS externalization compared to normal vessels. A single dose of ionizing radiation can increase PS externalization in a time-dependent manner. Strict localization of PS externalization within the AVM region suggests that stereotactic radiosurgery can serve as an effective priming agent and PS may be a suitable candidate for vascular-targeting approaches to AVM treatment.
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http://dx.doi.org/10.1667/RR14646.1DOI Listing
June 2017

A luminogenic lanthanide-based probe for the highly selective detection of nanomolar sulfide levels in aqueous samples.

Chem Commun (Camb) 2017 May;53(36):4911-4914

School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.

A bimetallic terbium(iii)/copper(ii) complex (Tb-1·Cu2+) for the time-gated luminescent detection of hydrogen sulfide in aqueous samples is reported. The probe shows excellent selectivity towards HS over various anions and cations, including the ions common to natural waterways and waste water samples, displaying a 73-fold increase in luminescence in the presence of sulfide. The probe exhibits extremely fast reaction times and a low limit of detection (130 nM). The probe was used to quantify sulfide in an industrial "sour water" sample, with the result in excellent agreement with those from two independent assay methods (methylene blue and AzMC).
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http://dx.doi.org/10.1039/c7cc01764bDOI Listing
May 2017

Radiosurgery Alters the Endothelial Surface Proteome: Externalized Intracellular Molecules as Potential Vascular Targets in Irradiated Brain Arteriovenous Malformations.

Radiat Res 2017 01 5;187(1):66-78. Epub 2017 Jan 5.

a   Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.

Stereotactic radiosurgery (SRS) is an established treatment for brain arteriovenous malformations (AVMs) that drives blood vessel closure through cellular proliferation, thrombosis and fibrosis, but is limited by a delay to occlusion of 2-3 years and a maximum treatable size of 3 cm. In this current study we used SRS as a priming tool to elicit novel protein expression on the endothelium of irradiated AVM vessels, and these proteins were then targeted with prothrombotic conjugates to induce rapid thrombosis and vessel closure. SRS-induced protein changes on the endothelium in an animal model of AVM were examined using in vivo biotin labeling of surface-accessible proteins and comparative proteomics. LC-MS/MS using SWATH acquisition label-free mass spectrometry identified 280 proteins in biotin-enriched fractions. The abundance of 56 proteins increased after irradiation of the rat arteriovenous fistula (20 Gy, ≥1.5-fold). A large proportion of intracellular proteins were present in this subset: 29 mitochondrial and 9 cytoskeletal. Three of these proteins were chosen for further validation based on previously published evidence for surface localization and a role in autoimmune stimulation: cardiac troponin I (TNNI3); manganese superoxide dismutase (SOD2); and the E2 subunit of the pyruvate dehydrogenase complex (PDCE2). Immunostaining of AVM vessels confirmed an increase in abundance of PDCE2 across the vessel wall, but not a measurable increase in TNNI3 or SOD2. All three proteins co-localized with the endothelium after irradiation, however, more detailed subcellular distribution could not be accurately established. In vitro, radiation-stimulated surface translocation of all three proteins was confirmed in nonpermeabilized brain endothelial cells using immunocytochemistry. Total protein abundance increased modestly after irradiation for PDCE2 and SOD2 but decreased for TNNI3, suggesting that radiation primarily affects subcellular distribution rather than protein levels. The novel identification of these proteins as surface exposed in response to radiation raises important questions about their potential role in radiation-induced inflammation, fibrosis and autoimmunity, but may also provide unique candidates for vascular targeting in brain AVMs and other vascular tissues.
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http://dx.doi.org/10.1667/RR14518.1DOI Listing
January 2017

Evolutionary loss of cone photoreception in balaenid whales reveals circuit stability in the mammalian retina.

J Comp Neurol 2016 10 28;524(14):2873-85. Epub 2016 Mar 28.

Department of Biological Sciences, Florida Institute of Technology, Melbourne, Florida, 32901.

The classical understanding of mammalian vision is that it occurs through "duplex" retinae containing both rod and cone photoreceptors, the signals from which are processed through rod- and/or cone-specific signaling pathways. The recent discovery of rod monochromacy in some cetacean lineages provides a novel opportunity to investigate the effects of an evolutionary loss of cone photoreception on retinal organization. Sequence analysis of right whale (Eubalaena glacialis; family Balaenidae) cDNA derived from long-wavelength sensitive (LWS) cone opsin mRNA identified several mutations in the opsin coding sequence, suggesting the loss of cone cell function, but maintenance of non-photosensitive, cone opsin mRNA-expressing cells in the retina. Subsequently, we investigated the retina of the closely related bowhead whale (Balaena mysticetus; family Balaenidae) to determine how the loss of cone-mediated photoreception affects light signaling pathways in the retina. Anti-opsin immunofluorescence demonstrated the total loss of cone opsin expression in B. mysticetus, whereas light microscopy, transmission electron microscopy, and bipolar cell (protein kinase C-α [PKC-α] and recoverin) immunofluorescence revealed the maintenance of cone soma, putative cone pedicles, and both rod and cone bipolar cell types. These findings represent the first immunological and anatomical evidence of a naturally occurring rod-monochromatic mammalian retina, and suggest that despite the loss of cone-mediated photoreception, the associated cone signaling structures (i.e., cone synapses and cone bipolar cells) may be maintained for multichannel rod-based signaling in balaenid whales. J. Comp. Neurol. 524:2873-2885, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/cne.23996DOI Listing
October 2016

Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex "Clicked" to a Lipidated Tat Peptide.

Molecules 2016 Feb 5;21(2). Epub 2016 Feb 5.

Monash Institute of Pharmaceutical Sciences, Monash University, Parkville VIC 3163, Australia.

A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl-naphthalimide fluorophore pendant group has been prepared and its Gd(III) complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I)-catalysed "click" chemistry. The resulting fluorescent conjugate is able to enter CAL-33 tongue squamous carcinoma cells, as revealed by confocal microscopy, producing a very modest anti-proliferative effect (IC50 = 93 µM). Due to the photo-reactivity of the naphthalimide moiety, however, the conjugate's cytotoxicity is significantly enhanced (IC50 = 16 µM) upon brief low-power UV-A irradiation.
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http://dx.doi.org/10.3390/molecules21020194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273236PMC
February 2016

Luminescent Alkyne-Bearing Terbium(III) Complexes and Their Application to Bioorthogonal Protein Labeling.

Inorg Chem 2016 Feb 28;55(4):1674-82. Epub 2016 Jan 28.

Monash Institute of Pharmaceutical Sciences, Monash University , Parkville VIC 3052, Australia.

Two new bifunctional macrocyclic chelate ligands that form luminescent terbium(III) complexes featuring an alkyne group for conjugation to (bio)molecules via the Cu(I)-catalyzed "click" reaction were synthesized. Upon ligation, the complexes exhibit a significant luminescent enhancement when excited at the λ(max) of the "clicked" products. To demonstrate the utility of the complexes for luminescent labeling, they were conjugated in vitro to E. coli aspartate/glutamate-binding protein incorporating a genetically encoded p-azido-L-phenylalanine or p-(azidomethyl)-L-phenylalanine residue. The complexes may prove useful for time-gated assay applications.
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http://dx.doi.org/10.1021/acs.inorgchem.5b02605DOI Listing
February 2016

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations.

J Neurosurg 2016 Jun 2;124(6):1780-7. Epub 2015 Oct 2.

Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University;

OBJECT Stereotactic radiosurgery (SRS) is an established intervention for brain arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after SRS are poorly understood. To improve SRS efficacy, it is important to understand the cellular response of blood vessels to radiation. The molecular changes on the surface of AVM endothelial cells after irradiation may also be used for vascular targeting. This study investigates radiation-induced externalization of phosphatidylserine (PS) on endothelial cells using live-cell imaging. METHODS An immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was cultured and irradiated at different radiation doses using a linear accelerator. PS externalization in the cells was subsequently visualized using polarity-sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity-sensitive probe. Live-cell imaging was used to monitor PS externalization in real time. The effects of radiation on the cell cycle of bEnd.3 cells were also examined by flow cytometry. RESULTS Ionizing radiation effects are dose dependent. Reduction in the cell proliferation rate was observed after exposure to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally inhibited proliferation. In comparison with cells treated with sham radiation, the irradiated cells showed distinct pseudopodial elongation with little or no spreading of the cell body. The percentages of pSIVA-positive cells were significantly higher (p = 0.04) 24 hours after treatment in the cultures that received 25- and 15-Gy doses of radiation. This effect was sustained until the end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS externalization compared with the sham-radiation controls at any time points (p > 0.15). Flow cytometric analysis data indicate that irradiation induced growth arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell cycle. CONCLUSIONS Ionizing radiation causes remarkable cellular changes in endothelial cells. Significant PS externalization is induced by radiation at doses of 15 Gy or higher, concomitant with a block in the cell cycle. Radiation-induced markers/targets may have high discriminating power to be harnessed in vascular targeting for AVM treatment.
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http://dx.doi.org/10.3171/2015.4.JNS142129DOI Listing
June 2016

Ontogenic retinal changes in three ecologically distinct elopomorph fishes (Elopomorpha:Teleostei) correlate with light environment and behavior.

Vis Neurosci 2015 Jan;32:E005

Department of Biological Sciences,Florida Institute of Technology,150 W. University Blvd.,Melbourne,Florida.

Unlike the mammalian retina, the teleost fish retina undergoes persistent neurogenesis from intrinsic stem cells. In marine teleosts, most cone photoreceptor genesis occurs early in the embryonic and larval stages, and rods are added primarily during and after metamorphosis. This study demonstrates a developmental paradigm in elopomorph fishes in which retinas are rod-dominated in larvae, but undergo periods of later cone genesis. Retinal characteristics were compared at different developmental stages among three ecologically distinct elopomorph fishes-ladyfish (Elops saurus), bonefish (Albula vulpes), and speckled worm eel (Myrophis punctatus). The objectives were to improve our understanding of (1) the developmental strategy in the elopomorph retina, (2) the functional architecture of the retina as it relates to ecology, and (3) how the light environment influences photoreceptor genesis. Photoreceptor morphologies, distributions, and spectral absorption were studied at larval, juvenile, and adult stages. Premetamorphic retinas in all three species are rod-dominated, but the retinas of these species undergo dramatic change over the course of development, resulting in juvenile and adult retinal characteristics that correlate closely with ecology. Adult E. saurus has high rod densities, grouped photoreceptors, a reflective tapetum, and longer-wavelength photopigments, supporting vision in turbid, low-light conditions. Adult A. vulpes has high cone densities, low rod densities, and shorter-wavelength photopigments, supporting diurnal vision in shallow, clear water. M. punctatus loses cones during metamorphosis, develops new cones after settlement, and maintains high rod but low cone densities, supporting primarily nocturnal vision. M. punctatus secondary cone genesis occurs rapidly throughout the retina, suggesting a novel mechanism of vertebrate photoreceptor genesis. Finally, in postsettlement M. punctatus, the continuous presence or absence of visible light modulates rod distribution but does not affect secondary cone genesis, suggesting some degree of developmental plasticity influenced by the light environment.
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http://dx.doi.org/10.1017/S0952523815000024DOI Listing
January 2015
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