Bio21 - Research Publications
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ItemGrowth of Gold Nanorods: A SAXS Study(AMER CHEMICAL SOC, 2021-09-16)Using simultaneous, in situ optical spectroscopy and time-resolved, small-angle X-ray scattering (SAXS), we have directly monitored the seeded growth of nearly monodisperse gold nanorods using hydroquinone as the reductant. Growth of the rods is much slower than with the ascorbate ion, allowing the rate of growth along both the longitudinal and transverse directions to be independently determined. The thickness of the stabilizing CTAB layer (3.2 ± 0.3 nm) has also been extracted. We find that increasing the hydrogen tetrachloroaurate(III) concentration produces longer rods, while conversely, increasing the hydroquinone concentration reduces the final aspect ratio. The final number of gold rods is smaller than the initial number of seed particles and decreases in the presence of larger concentrations of HAuCl4. The SAXS data reveal an early transition from a spherical morphology to an ellipsoidal one and then to spherically capped cylinders. The growth curve exhibits at least three distinct regimes: an initial phase comprising spherical seed growth, followed by symmetry breaking and slow elongation. A third phase is marked by rapid rod growth and increases in the aspect ratio. This process is temporally well resolved from the initial symmetry breaking but typically occurs when the rods are around 6 nm in diameter using hydroquinone as the reductant. The results provide qualitative support for the “popcorn model” proposed by Edgar et al. [ Formation of Gold Nanorods by a Stochastic “Popcorn” Mechanism. ACS Nano 2012, 6, 1116 1125 ].
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ItemA sandwich-like structural model revealed for quasi-2D perovskite films(Royal Society of Chemistry, 2021-04-28)The excellent performance and stability of perovskite solar cells (PSCs) based on quasi-2D Ruddlesden–Popper perovskites (RPPs) holds promise for their commercialization. Further improvement in the performance of 2D PSCs requires a detailed understanding of the microstructure of the quasi-2D perovskite films. Based on scanning transmission electron microscopy (STEM), time-resolved photoluminescence, and transient absorption measurements, a new sandwich-like structural model is proposed to describe the phase distribution of RPPs. In contrast to the conventional gradient distribution, it is found that small-n RPPs are sandwiched between large-n RPP phase layers at the front and back sides owing to crystallization initiated from both interfaces during film formation. This sandwich-like distribution profile facilitates excitons funneling from the film interior to both surfaces for dissociation while free carriers transport via large-n channels that permeate the film to ensure efficient charge collection by the corresponding electrodes, which is favorable for high-performance photovoltaics. This discovery provides a new fundamental understanding of the operating principles of 2D PSCs and has valuable implications for the design and optimization strategies of optoelectronic devices based on quasi-2D RPPs films.
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ItemCharacterising the influence of milk fat towards an application for extrusion-based 3D-printing of casein-whey protein suspensions via the pH-temperature-route(ELSEVIER SCI LTD, 2021-09)This study presents the design and characterisation of casein−whey protein suspensions (8.0/10.0% (w/w) casein and 2.0/2.5% (w/w) whey protein) mixed with dairy fat (1.0, 2.5 and 5.0% (w/w) total fat) processed via the pH−temperature-route in preparation for 3D-printing. Mechanical treatment was applied to significantly decrease the particle size of the milk fat globules and increase surface area, creating small fat globules (<1 μm) covered with proteins, which could act as pseudo protein particles during gelation. Different proteins covered the fat globule surface after mechanical treatment, as a result of differences in the pH adjusted just prior to heating (6.55, 6.9 or 7.1). The protein-fat suspensions appeared similar by transmission electron cryogenic microscopy and the zeta-potential of all particles was unchanged by the heating pH, with a similar charge to the solution (~−20 mV) occurring after acidification (pH 4.8/5.0) at low temperatures (2 °C). A low heating pH (6.55) resulted in increased sol−gel transition temperatures (G՛ = 1 Pa) and a decreased rate of aggregation for protein−fat suspensions. A higher heating pH (6.9 and 7.1) caused an increased rate of aggregation (aggregation rate ≥ 250 Pa/10 K), resulting in materials more promising for application in extrusion-based printing. 3D-printing of formulations into small rectangles, inclusive of a sol−gel transition in a heated nozzle, was conducted to relate the aggregation rate towards printability.
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ItemAdvances in understanding meso-cortico-limbic-striatal systems mediating risky reward seeking.(Wiley, 2021-06)The risk of an aversive consequence occurring as the result of a reward-seeking action can have a profound effect on subsequent behavior. Such aversive events can be described as punishers, as they decrease the probability that the same action will be produced again in the future and increase the exploration of less risky alternatives. Punishment can involve the omission of an expected rewarding event ("negative" punishment) or the addition of an unpleasant event ("positive" punishment). Although many individuals adaptively navigate situations associated with the risk of negative or positive punishment, those suffering from substance use disorders or behavioral addictions tend to be less able to curtail addictive behaviors despite the aversive consequences associated with them. Here, we discuss the psychological processes underpinning reward seeking despite the risk of negative and positive punishment and consider how behavioral assays in animals have been employed to provide insights into the neural mechanisms underlying addictive disorders. We then review the critical contributions of dopamine signaling to punishment learning and risky reward seeking, and address the roles of interconnected ventral striatal, cortical, and amygdala regions to these processes. We conclude by discussing the ample opportunities for future study to clarify critical gaps in the literature, particularly as related to delineating neural contributions to distinct phases of the risky decision-making process.
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ItemEstimating the number of new hepatitis C infections in Australia in 2015, prior to the scale-up of direct-acting antiviral treatment(WILEY, 2021-08)BACKGROUND AND AIM: The recent downward revision of the estimated number of people living with chronic hepatitis C in Australia means that the annual number of new hepatitis C infections should also be revised. We aimed to estimate the annual number of new hepatitis C infections among people who inject drugs (PWID) in Australia in 2015, prior to the introduction of direct-acting antiviral (DAA) treatment for hepatitis C, as an updated baseline measure for assessing the impact of DAAs on hepatitis C incidence over the next 10 years. METHODS: A systematic review identified articles estimating hepatitis C incidence rates among PWID between 2002 and 2015. Reported incidence rates were adjusted to account for unrepresentative needle and syringe program (NSP) coverage among study participants compared with PWID overall. The total number of PWID in Australia and the hepatitis C RNA prevalence among PWID were taken from published estimates. The annual number of new infections was estimated by multiplying the pooled NSP coverage-adjusted incidence rate by the number of susceptible PWID in 2015. RESULTS: Five studies were included, with unadjusted incidence rates ranging from 7.6 to 12.8 per 100 person-years. The overall pooled incidence rate (after adjusting for NSP coverage) was 9.9 per 100 person-years (95% confidence interval: 8.3-11.8). This led to an estimate of 4126 (range 2499-6405) new hepatitis C infections in 2015. CONCLUSIONS: Our updated estimate provides an important baseline for evaluating the impact of hepatitis C elimination efforts and can be used to validate outcomes of future modeling studies.
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ItemNo Preview AvailableEffects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction.(Elsevier BV, 2021-01-01)Deficiencies in the ability to extinguish fear is a hallmark of Trauma- and stressor-related disorders, Anxiety disorders, and certain other neuropsychiatric conditions. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear is of significant translational relevance. Previous studies in rodents have shown that glutamatergic projections from the infralimbic prefrontal cortex (IL) to basolateral amygdala (BLA) play a crucial instructional role in the formation of extinction memories, and also indicate that variation in the strength of this input correlates with extinction efficacy. To further examine the relationship between the IL→BLA pathway and extinction we expressed three different titers of the excitatory opsin, channelrhodopsin (ChR2), in IL neurons and photostimulated their projections in the BLA during partial extinction training. The behavioral effects of photoexcitation differed across the titer groups: the low titer had no effect, the medium titer selectively facilitated extinction memory formation, and the high titer produced both an acute suppression of fear and a decrease in fear during (light-free) extinction retrieval. We discuss various possible explanations for these titer-specific effects, including the possibility of IL-mediated inhibition of BLA fear-encoding neurons under conditions of sufficiently strong photoexcitation. These findings further support the role of IL→BLA pathway in regulating fear and highlight the importance of methodological factors in optogenetic studies of neural circuits underling behavior.
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ItemNo Preview AvailableAmygdala Circuit Substrates for Stress Adaptation and Adversity.(Elsevier BV, 2021-05-01)Brain systems that promote maintenance of homeostasis in the face of stress have significant adaptive value. A growing body of work across species demonstrates a critical role for the amygdala in promoting homeostasis by regulating physiological and behavioral responses to stress. This review focuses on an emerging body of evidence that has begun to delineate the contribution of specific long-range amygdala circuits in mediating the effects of stress. After summarizing the major anatomical features of the amygdala and its connectivity to other limbic structures, we discuss recent findings from rodents showing how stress causes structural and functional remodeling of amygdala neuronal outputs to defined cortical and subcortical target regions. We also consider some of the environmental and genetic factors that have been found to moderate how the amygdala responds to stress and relate the emerging preclinical literature to the current understanding of the pathophysiology and treatment of stress-related neuropsychiatric disorders. Future effort to translate these findings to clinics may help to develop valuable tools for prevention, diagnosis, and treatment of these diseases.
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ItemNo Preview AvailableIntercalated amygdala clusters orchestrate a switch in fear state.(Springer Science and Business Media LLC, 2021-06)Adaptive behaviour necessitates the formation of memories for fearful events, but also that these memories can be extinguished. Effective extinction prevents excessive and persistent reactions to perceived threat, as can occur in anxiety and 'trauma- and stressor-related' disorders1. However, although there is evidence that fear learning and extinction are mediated by distinct neural circuits, the nature of the interaction between these circuits remains poorly understood2-6. Here, through a combination of in vivo calcium imaging, functional manipulations, and slice physiology, we show that distinct inhibitory clusters of intercalated neurons (ITCs) in the mouse amygdala exert diametrically opposed roles during the acquisition and retrieval of fear extinction memory. Furthermore, we find that the ITC clusters antagonize one another through mutual synaptic inhibition and differentially access functionally distinct cortical- and midbrain-projecting amygdala output pathways. Our findings show that the balance of activity between ITC clusters represents a unique regulatory motif that orchestrates a distributed neural circuitry, which in turn regulates the switch between high- and low-fear states. These findings suggest that the ITCs have a broader role in a range of amygdala functions and associated brain states that underpins the capacity to adapt to salient environmental demands.
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ItemNo Preview AvailableAntifungal versus antibacterial defence of insect wings(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2021-12)HYPOTHESIS: The ability exhibited by insect wings to resist microbial infestation is a unique feature developed over 400 million years of evolution in response to lifestyle and environmental pressures. The self-cleaning and antimicrobial properties of insect wings may be attributed to the unique combination of nanoscale structures found on the wing surface. EXPERIMENTS: In this study, we characterised the wetting characteristics of superhydrophobic damselfly Calopteryx haemorrhoidalis wings. We revealed the details of air entrapment at the micro- and nano scales on damselfly wing surfaces using a combination of spectroscopic and electron microscopic techniques. Cryo-focused-ion-beam scanning electron microscopy was used to directly observe fungal spores and conidia that were unable to cross the air-liquid interface. By contrast, bacterial cells were able to cross the air-water interface to be ruptured upon attachment to the nanopillar surface. The robustness of the air entrapment, and thus the wing antifungal behaviour, was demonstrated after 1-week of water immersion. A newly developed wetting model confirmed the strict Cassie-Baxter wetting regime when damselfly wings are immersed in water. FINDINGS: We provide evidence that the surface nanopillar topography serves to resist both fungal and bacterial attachment via a dual action: repulsion of fungal conidia while simultaneously killing bacterial cells upon direct contact. These findings will play an important role in guiding the fabrication of biomimetic, anti-fouling surfaces that exhibit both bactericidal and anti-fungal properties.
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ItemModular Platform for the Development of Recombinant Hemoglobin Scavenger Biotherapeutics.(American Chemical Society (ACS), 2021-08-02)Cell-free hemoglobin (Hb) is a driver of disease progression in conditions with intravascular or localized hemolysis. Genetic and acquired anemias or emergency medical conditions such as aneurysmal subarachnoid hemorrhage involve tissue Hb exposure. Haptoglobin (Hp) captures Hb in an irreversible protein complex and prevents its pathophysiological contributions to vascular nitric oxide depletion and tissue oxidation. Preclinical proof-of-concept studies suggest that human plasma-derived Hp is a promising therapeutic candidate for several Hb-driven diseases. Optimizing the efficacy and safety of Hb-targeting biotherapeutics may require structural and functional modifications for specific indications. Improved Hp variants could be designed to achieve the desired tissue distribution, metabolism, and elimination to target hemolytic disease states effectively. However, it is critical to ensure that these modifications maintain the function of Hp. Using transient mammalian gene expression of Hp combined with co-transfection of the pro-haptoglobin processing protease C1r-LP, we established a platform for generating recombinant Hp-variants. We designed an Hpβ-scaffold, which was expressed in this system at high levels as a monomeric unit (mini-Hp) while maintaining the key protective functions of Hp. We then used this Hpβ-scaffold as the basis to develop an initial proof-of-concept Hp fusion protein using human serum albumin as the fusion partner. Next, a hemopexin-Hp fusion protein with bispecific heme and Hb detoxification capacity was generated. Further, we developed a Hb scavenger devoid of CD163 scavenger receptor binding. The functions of these proteins were then characterized for Hb and heme-binding, binding of the Hp-Hb complexes with the clearance receptor CD163, antioxidant properties, and vascular nitric oxide sparing capacity. Our platform is designed to support the generation of innovative Hb scavenger biotherapeutics with novel modes of action and potentially improved formulation characteristics, function, and pharmacokinetics.