Identification of rho as a substrate for botulinum toxin C3-catalyzed ADP-ribosylation

AbstractRecombinant Aplysia rho and a GTP-binding protein purified from human neutrophil membranes (G22K) were ADP-ribosylated by botulinum toxin C3 with stoichiometries of 0.8 and 0.6, respectively. Rho and G22K appeared to be different proteins since (i) rho migrated faster on polyacrylamide gels, (ii) unlike G22K, rho did not require the presence of cytosol to be ADP-ribosylated, (iii) G22K was not recognized by an anti-rho antiserum, and (iv) antibody 142-24E05 recognized G22K effectively but only poorly cross reacted with rho. ADP-ribosylation had no effect on the ability of rho to bind or hydrolyse GTP. Therefore, it appears that there are multiple botulinum toxin C3 substrates and that the toxin exerts its effects on cell function by a mechanism other than modulating the GTPase activity of rho

Mid-infrared quantum optics in silicon

Applied quantum optics stands to revolutionise many aspects of information technology, provided performance can be maintained when scaled up. Silicon quantum photonics satisfies the scaling requirements of miniaturisation and manufacturability, but at 1.55 $\mu$m it suffers from unacceptable linear and nonlinear loss. Here we show that, by translating silicon quantum photonics to the mid-infrared, a new quantum optics platform is created which can simultaneously maximise manufacturability and miniaturisation, while minimising loss. We demonstrate the necessary platform components: photon-pair generation, single-photon detection, and high-visibility quantum interference, all at wavelengths beyond 2 $\mu$m. Across various regimes, we observe a maximum net coincidence rate of 448 $\pm$ 12 Hz, a coincidence-to-accidental ratio of 25.7 $\pm$ 1.1, and, a net two photon quantum interference visibility of 0.993 $\pm$ 0.017. Mid-infrared silicon quantum photonics will bring new quantum applications within reach.Comment: 8 pages, 4 figures; revised figures, updated discussion in section 3, typos corrected, added referenc

Amplification of TLO Mediator Subunit Genes Facilitate Filamentous Growth in Candida Spp

Funding: This work was funded by the National Institutes of Allergy and Infectious Disease (AI113390, LCM) and the National Institutes of General Medical Sciences (GM62483, LCM). The funders had no role in study design, data collection and analysis, decision topublish, or preparation of the manuscript.Non peer reviewedPublisher PD

Single Cell Analysis of Transcriptional Activation Dynamics

Gene activation is thought to occur through a series of temporally defined regulatory steps. However, this process has not been completely evaluated in single living mammalian cells.To investigate the timing and coordination of gene activation events, we tracked the recruitment of GCN5 (histone acetyltransferase), RNA polymerase II, Brd2 and Brd4 (acetyl-lysine binding proteins), in relation to a VP16-transcriptional activator, to a transcription site that can be visualized in single living cells. All accumulated rapidly with the VP16 activator as did the transcribed RNA. RNA was also detected at significantly more transcription sites in cells expressing the VP16-activator compared to a p53-activator. After alpha-amanitin pre-treatment, the VP16-activator, GCN5, and Brd2 are still recruited to the transcription site but the chromatin does not decondense.This study demonstrates that a strong activator can rapidly overcome the condensed chromatin structure of an inactive transcription site and supercede the expected requirement for regulatory events to proceed in a temporally defined order. Additionally, activator strength determines the number of cells in which transcription is induced as well as the extent of chromatin decondensation. As chromatin decondensation is significantly reduced after alpha-amanitin pre-treatment, despite the recruitment of transcriptional activation factors, this provides further evidence that transcription drives large-scale chromatin decondensation

Damping device for a stationary labyrinth seal

A stationary labyrinth seal system includes a seal housing having an annular cavity, a plurality of damping devices, and a retaining ring. The damping devices are positioned within the annular cavity and are maintained within the annular cavity by the retaining ring

Invasive adenoma and pituitary carcinoma: a SEER database analysis

Invasive pituitary adenomas and pituitary carcinomas are clinically indistinguishable until identification of metastases. Optimal management and survival outcomes for both are not clearly defined. The purpose of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to report patterns of care and compare survival outcomes in a large series of patients with invasive adenomas or pituitary carcinomas. One hundred seventeen patients diagnosed between 1973 and 2008 with pituitary adenomas/adenocarcinomas were included. Eighty-three invasive adenomas and seven pituitary carcinomas were analyzed for survival outcomes. Analyzed prognostic factors included age, sex, race, histology, tumor extent, and treatment. A significant decrease in survival was observed among carcinomas compared to invasive adenomas at 1, 2, and 5 years (p=0.047, 0.001, and 0.009). Only non-white race, male gender, and age ≥65 were significant negative prognostic factors for invasive adenomas (p=0.013, 0.033, and <0.001, respectively). There was no survival advantage to radiation therapy in treating adenomas at 5, 10, 20, or 30 years (p=0.778, 0.960, 0.236, and 0.971). In conclusion, pituitary carcinoma patients exhibit worse overall survival than invasive adenoma patients. This highlights the need for improved diagnostic methods for the sellar phase to allow for potentially more aggressive treatment approaches

A New Task: Deriving Semantic Class Targets for the Physical Sciences

We define deriving semantic class targets as a novel multi-modal task. By doing so, we aim to improve classification schemes in the physical sciences which can be severely abstracted and obfuscating. We address this task for upcoming radio astronomy surveys and present the derived semantic radio galaxy morphology class targets.Comment: 6 pages, 1 figure, Accepted at Fifth Workshop on Machine Learning and the Physical Sciences (NeurIPS 2022), Neural Information Processing Systems 202

A systematic policy approach to changing the food system and physical activity environments to prevent obesity

As obesity prevention becomes an increasing health priority in many countries, including Australia and New Zealand, the challenge that governments are now facing is how to adopt a systematic policy approach to increase healthy eating and regular physical activity. This article sets out a structure for systematically identifying areas for obesity prevention policy action across the food system and full range of physical activity environments. Areas amenable to policy intervention can be systematically identified by considering policy opportunities for each level of governance (local, state, national, international and organisational) in each sector of the food system (primary production, food processing, distribution, marketing, retail, catering and food service) and each sector that influences physical activity environments (infrastructure and planning, education, employment, transport, sport and recreation). Analysis grids are used to illustrate, in a structured fashion, the broad array of areas amenable to legal and regulatory intervention across all levels of governance and all relevant sectors. In the Australian context, potential regulatory policy intervention areas are widespread throughout the food system, e.g., land-use zoning (primary production within local government), food safety (food processing within state government), food labelling (retail within national government). Policy areas for influencing physical activity are predominantly local and state government responsibilities including, for example, walking and cycling environments (infrastructure and planning sector) and physical activity education in schools (education sector). The analysis structure presented in this article provides a tool to systematically identify policy gaps, barriers and opportunities for obesity prevention, as part of the process of developing and implementing a comprehensive obesity prevention strategy. It also serves to highlight the need for a coordinated approach to policy development and implementation across all levels of government in order to ensure complementary policy action

Advancing the translation of optical imaging agents for clinical imaging

Despite the development of a large number of promising candidates, few contrast agents for established medical imaging modalities have successfully been translated over the past decade. The emergence of new imaging contrast agents that employ biomedical optics is further complicated by the relative infancy of the field and the lack of approved imaging devices compared to more established clinical modalities such as nuclear medicine. Herein, we propose a navigational approach (as opposed to a fixed “roadmap”) for translation of optical imaging agents that is (i) proposed through consensus by four academic research programs that are part of the cooperative U54 NCI Network for Translational Research, (ii) developed through early experiences for translating optical imaging agents in order to meet distinctly varied needs in cancer diagnostics, and (iii) adaptable to the rapidly changing environment of academic medicine. We describe the pathways by which optical imaging agents are synthesized, qualified, and validated for preclinical testing, and ultimately translated for “first-in-humans” studies using investigational optical imaging devices. By identifying and adopting consensus approaches for seemingly disparate optical imaging modalities and clinical indications, we seek to establish a systematic method for navigating the ever-changing “roadmap” to most efficiently arrive at the destination of clinical adoption and improved outcome and survivorship for cancer patients