215 research outputs found

    As COVID-19 hits Australian universities hard, how have online writing groups enabled researchers to stay connected and sustain their work?

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    The COVID-19 crisis has amplified the instability of funding streams in Australian universities, resulting in an already precarious system for researchers being exacerbated. However, in the face of an ongoing retraction of income which is threatening research and the livelihood of researchers, Dr Lisa Hodge and Dr Jason Murphy discuss the flourishing forms of academic community that have persevered by adapting and moving online. They discuss academic writing groups and the affective support that these groups engender and consider how online academic writing communities are providing examples of how those working in higher education can support each other and foster research – both now and beyond this pandemic

    Qualification of low drift single-use pH sensors for use in single-use bioreactor platforms

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    The biopharmaceutical industry is currently limited by access to low drift, gamma stable, easy-to-integrate single-use pH sensors for application in single-use bioreactors (S.U.B.). Hamilton Company has developed the OneFerm VP 70 sensor, a unique single-use glass electrode, which provides an additional option for customers wishing to implement reliable single-use pH sensing capabilities in the S.U.B. platform. In order to demonstrate the efficacy of these devices, a series of qualification experiments were carried out using a Thermo Fisher Scientific 50L bioprocess container (BPC) custom-fitted with Hamilton OneFerm sensors. BPCs were manufactured in a cGMP facility and allowed to age for a pre-established period (either 30 or 180 days). A 14 day fed-batch cell run was executed using an in-house CHO-S cell line (mAb producing clone) and standard operating conditions. Online pH was controlled with a Hamilton EasyFerm pH sensor; reactor pH was controlled using CO2 without acid or base. Each BPC was built with 6 OneFerm sensors (containing 2 each from 3 different production lots), which were monitored using stand-alone transmitters. Offline samples were evaluated every 24 hours using an Oakton pH sensor. The results from the initial 30 day aged BPC evaluation demonstrate functional activity of the OneFerm sensors over a 14 day fed-batch cell run using a TruBio DeltaV S.U.B. controller. Functional stability of these sensors was demonstrated by maintaining the devices in sterile culture conditions for a period of 60 days; 5 out of 6 sensors met all manufacturers’ specifications during this hold period. To determine if BPC storage time contributes to loss in sensor functionality, a 14 day fed-batch cell run was repeated using a 180 day aged BPC. All 6 OneFerm sensors met manufacturer’s specifications after the cell run with no sensor exhibiting a gross pH drift greater than 0.11 during the entire 14 day period. Additionally, all 6 sensors also met manufacturer’s specifications during the 60 day hold period with no sensor exhibiting an average gross pH drift greater than 0.15 during this extended time. Furthermore, all sensors demonstrated an average response time of less than 10 seconds following the 60 day hold period. The results of these experiments demonstrate the effectiveness of Hamilton OneFerm sensors in the Thermo Fisher Scientific HyPerforma S.U.B. platform. Thermo Fisher Scientific has since developed a custom polycarbonate probe port adapter to robustly integrate the OneFerm sensor in a S.U.B. BPC. Future work will continue to evaluate the performance of sensors aged in BPCs for 24 to 36 months. We are excited to share this growing body of data with the bioprocess industry as probe drift, ionic strength sensitivity, and shelf life have greatly limited implementation of SU pH over the past decade. These results appear to indicate a viable technology is now available and is suitable for cGMP bio manufacturing

    The Biot-Savart operator and electrodynamics on subdomains of the three-sphere

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    We study steady-state magnetic fields in the geometric setting of positive curvature on subdomains of the three-dimensional sphere. By generalizing the Biot-Savart law to an integral operator BS acting on all vector fields, we show that electrodynamics in such a setting behaves rather similarly to Euclidean electrodynamics. For instance, for current J and magnetic field BS(J), we show that Maxwell's equations naturally hold. In all instances, the formulas we give are geometrically meaningful: they are preserved by orientation-preserving isometries of the three-sphere. This article describes several properties of BS: we show it is self-adjoint, bounded, and extends to a compact operator on a Hilbert space. For vector fields that act like currents, we prove the curl operator is a left inverse to BS; thus the Biot-Savart operator is important in the study of curl eigenvalues, with applications to energy-minimization problems in geometry and physics. We conclude with two examples, which indicate our bounds are typically within an order of magnitude of being sharp.Comment: 24 pages (was 28 pages) Revised to include a new introduction, a detailed example, and results about helicity; other changes for readabilit

    Evolutionary and network analysis of virus sequences from infants infected with an Australian recombinant strain of human parechovirus type 3

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    We present the near complete virus genome sequences with phylogenetic and network analyses of potential transmission networks of a total of 18 Australian cases of human parechovirus type 3 (HPeV3) infection in infants in the period from 2012–2015. Overall the results support our previous finding that the Australian outbreak strain/lineage is a result of a major recombination event that took place between March 2012 and November 2013 followed by further virus evolution and possibly recombination. While the nonstructural coding region of unknown provenance appears to evolve significantly both at the nucleotide and amino acid level, the capsid encoding region derived from the Yamagata 2011 lineage of HPeV3 appears to be very stable, particularly at the amino acid level. The phylogenetic and network analyses performed support a temporal evolution from the first Australian recombinant virus sequence from November 2013 to March/April 2014, onto the 2015 outbreak. The 2015 outbreak samples fall into two separate clusters with a possible common ancestor between March/April 2014 and September 2015, with each cluster further evolving in the period from September to November/December 2015

    Use of antipsychotic medication and its relationship with bone mineral density: A population-based study of men and women

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    BackgroundSchizophrenia has been shown to be associated with reduced bone mineral density (BMD) and higher fracture risk. However, less is known whether antipsychotic treatment is associated with reduced BMD. Thus, we aimed to examine associations between antipsychotic use and BMD among men and women drawn from the general population.MethodsThis cross-sectional study involved 793 women and 587 men enrolled in the Geelong Osteoporosis Study (GOS). BMD was determined using dual-energy X-ray absorptiometry at the spine and hip. Information regarding socio-economic status (SES), current medication and/or supplementation use, lifestyle factors, and anthropometry was collected. Association between antipsychotic use and BMD was determined using linear regression after adjusting for potential confounders.ResultsOf the group, 33 women (4.2%) and 16 men (2.7%) currently used antipsychotics. Age was identified as an effect modifier in the association between antipsychotic use and BMD for women. Amongst women aged < 60 years, adjusted mean BMD was 11.1% lower at the spine [1.139 (95%CI 1.063–1.216) vs. 1.250 (95%CI 1.223–1.277) g/cm2, p = 0.005] for antipsychotic users compared to non-users. At the hip, age, weight, and smoking adjusted mean BMD was 9.9% lower [0.893 (95%CI 0.837–0.950) vs. 0.992 (95%CI 0.976–1.007) g/cm2, p < 0.001] for antipsychotic users in comparison with non-users. The pattern persisted following further adjustments. There was no association detected between antipsychotic use and BMD for women aged 60 years and over and for men.ConclusionOur data suggest that antipsychotic medication use is associated with reduced BMD in younger women but not older women or men

    Ethanol-induced alterations of c-Fos immunoreactivity in specific limbic brain regions following ethanol discrimination training

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    The discriminative stimulus properties of ethanol are functionally regulated by ionotropic GABAA and NMDA receptors in specific limbic brain regions including the nucleus accumbens, amygdala, and hippocampus, as determined by microinjection studies. The purpose of the present work was to further investigate potential neural substrates of ethanol’s discriminative stimulus effects by examining if ethanol discrimination learning produces changes in brain regional response to ethanol. To accomplish this goal, immunohistochemistry was used to assess the effects of ethanol (2 g/kg) on c-Fos immunoreactivity (Fos-IR). Comparisons in ethanol-induced Fos-IR were made between a group of rats that was trained to discriminate the stimulus properties of ethanol (2 g/kg, IG) from water (IG) and a drug/behavior-matched control group that did not receive differential reinforcement for lever selection, which precluded acquisition of discriminative stimulus control by ethanol. In some brain regions discrimination training had no effect on ethanol-induced Fos-IR changes (caudate putamen, bed nucleus of the stria terminalis, and CA1 region of the hippocampus). In contrast, discrimination training altered the pattern of ethanol-induced Fos-IR in the nucleus accumbens (core), medial septum, and the hippocampus (dentate and CA3). These results indicate that having behavior under the stimulus control of ethanol can change ethanol-induced Fos-IR in some brain regions. This suggests that learning about the subjective properties of ethanol produces adaptive changes in how the brain responds to acute ethanol exposure

    PHAT Stellar Cluster Survey I. Year 1 Catalog and Integrated Photometry

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    The Panchromatic Hubble Andromeda Treasury (PHAT) survey is an on-going Hubble Space Telescope (HST) multi-cycle program to obtain high spatial resolution imaging of one-third of the M31 disk at ultraviolet through near-infrared wavelengths. In this paper, we present the first installment of the PHAT stellar cluster catalog. When completed, the PHAT cluster catalog will be among the largest and most comprehensive surveys of resolved star clusters in any galaxy. The exquisite spatial resolution achieved with HST has allowed us to identify hundreds of new clusters that were previously inaccessible with existing ground-based surveys. We identify 601 clusters in the Year 1 sample, representing more than a factor of four increase over previous catalogs within the current survey area (390 arcmin^2). This work presents results derived from the first \sim25% of the survey data; we estimate that the final sample will include \sim2500 clusters. For the Year 1 objects, we present a catalog with positions, radii, and six-band integrated photometry. Along with a general characterization of the cluster luminosities and colors, we discuss the cluster luminosity function, the cluster size distributions, and highlight a number of individually interesting clusters found in the Year 1 search.Comment: 26 pages, 22 figures, Accepted by Ap

    Cue-induced reinstatement of alcohol-seeking behavior is associated with increased ERK1/2 phosphorylation in specific limbic brain regions: Blockade by the mGluR5 antagonist MPEP

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    Relapse to alcohol use after periods of abstinence is a hallmark behavioral pathology of alcoholism and a major clinical problem. Emerging evidence indicates that metabotropic glutamate receptor 5 (mGluR5) antagonists attenuate relapse to alcohol-seeking behavior but the molecular mechanisms of this potential therapeutic effect remain unexplored. The extracellular signal-regulated kinase (ERK1/2) pathway is downstream of mGluR5 and has been implicated in addiction. We sought to determine if cue-induced reinstatement of alcohol-seeking behavior, and its reduction by an mGluR5 antagonist, is associated with changes in ERK1/2 activation in reward-related limbic brain regions. Selectively bred alcohol-preferring (P) rats were trained to lever press on a concurrent schedule of alcohol (15% v/v) vs. water reinforcement. Following 9 days of extinction, rats were given an additional extinction trial or injected with the mGluR5 antagonist MPEP (0, 1, 3, or 10 mg/kg) and tested for cue-induced reinstatement. Brains were removed 90-min later from the rats in the extinction and MPEP (0 or 10 mg/kg) conditions for analysis of p-ERK1/2, total ERK1/2, and p-ERK5 immunoreactivity (IR). Cue-induced reinstatement of alcohol-seeking behavior was associated with a 3–5 fold increase in p-ERK1/2 IR in the basolateral amygdala and nucleus accumbens shell. MPEP administration blocked both the relapse-like behavior and increase in p-ERK1/2 IR. P-ERK1/2 IR in the central amygdala and NAcb core was dissociated with the relapse-like behavior and the pharmacological effect of mGluR5 blockade. No changes in total ERK or p-ERK5 were observed. These results suggest that exposure to cues previously associated with alcohol self-administration is sufficient to produce concomitant increases in relapse-like behavior and ERK1/2 activation in specific limbic brain regions. Pharmacological compounds, such as mGluR5 antagonists, that reduce cue-induced ERK1/2 activation may be useful for treatment of relapse in alcoholics that is triggered by exposure to environmental events

    Reproductive control via eviction (but not the threat of eviction) in banded mongooses

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    Considerable research has focused on understanding variation in reproductive skew in cooperative animal societies, but the pace of theoretical development has far outstripped empirical testing of the models. One major class of model suggests that dominant individuals can use the threat of eviction to deter subordinate reproduction (the ‘restraint’ model), but this idea remains untested. Here, we use long-term behavioural and genetic data to test the assumptions of the restraint model in banded mongooses (Mungos mungo), a species in which subordinates breed regularly and evictions are common. We found that dominant females suffer reproductive costs when subordinates breed, and respond to these costs by evicting breeding subordinates from the group en masse, in agreement with the assumptions of the model. We found no evidence, however, that subordinate females exercise reproductive restraint to avoid being evicted in the first place. This means that the pattern of reproduction is not the result of a reproductive ‘transaction’ to avert the threat of eviction. We present a simple game theoretical analysis that suggests that eviction threats may often be ineffective to induce pre-emptive restraint among multiple subordinates and predicts that threats of eviction (or departure) will be much more effective in dyadic relationships and linear hierarchies. Transactional models may be more applicable to these systems. Greater focus on testing the assumptions rather than predictions of skew models can lead to a better understanding of how animals control each other's reproduction, and the extent to which behaviour is shaped by overt acts versus hidden threats

    Overexpression of the Steroidogenic Enzyme Cytochrome P450 Side Chain Cleavage in the Ventral Tegmental Area Increases 3 ,5 -THP and Reduces Long-Term Operant Ethanol Self-Administration

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    Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric patholog
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