Airlift bioreactor-based strategies for prolonged semi-continuous cultivation of edible Agaricomycetes.

Submerged cultivation of edible filamentous fungi (Agaricomycetes) in bioreactors enables maximum mass transfer of nutrients and has the potential to increase the volumetric productivity of fungal biomass compared to solid state cultivation. These aspects are paramount if one wants to increase the range of bioactives (e.g. glucans) in convenient time frames. In this study, Trametes versicolor (M9911) outperformed four other Agaricomycetes tested strains (during batch cultivations in an airlift bioreactor). This strain was therefore further tested in semi-continuous cultivation. Continuous and semi-continuous cultivations (driven by the dilution rate, D) are the preferred bioprocess strategies for biomass production. We examined the semi-continuous cultivation of T. versicolor at dilution rates between 0.02 and 0.1 h-1. A maximum volumetric productivity of 0.87 g/L/h was obtained with a D of 0.1 h-1 but with a lower total biomass production (cell dry weight, CDW 8.7 g/L) than the one obtained at lower dilution rates (12.3 g/L at D of 0.04 and vs 13.4 g/L, at a D of 0.02 h-1). However, growth at a D of 0.1 h-1 resulted in a very short fermentation (18 h) which terminated due to washout (the specific D exceeded the maximum growth rate of the fungal biomass). At a D of 0.04 h-1, a CDW of 12.3 g/L was achieved without compromising the total residence time (184 h) of the fermentation. While the D of 0.04 h-1 and 0.07 h-1 achieved comparable volumetric productivities (0.5 g/L/h), the total duration of the fermentation at D of 0.07 h-1 was only 85 h. The highest glucan content of cells (27.8 as percentage of CDW) was obtained at a D of 0.07 h-1, while the lowest glucan content was observed in T. versicolor cells grown at a D of 0.02 h-1. KEY POINTS: • The highest reported volumetric productivity for fungal biomass was 0.87 g/L/h. • Semi-continuous fermentation at D of 0.02 h-1 resulted in 13.4 g/L of fungal biomass. • Semi-continuous fermentation at D of 0.07 h-1 resulted in fungal biomass with 28% of total glucans.

The SARS-CoV-2 Conserved Macrodomain Is a Mono-ADP-Ribosylhydrolase.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-related CoVs encode 3 tandem macrodomains within nonstructural protein 3 (nsp3). The first macrodomain, Mac1, is conserved throughout CoVs and binds to and hydrolyzes mono-ADP-ribose (MAR) from target proteins. Mac1 likely counters host-mediated antiviral ADP-ribosylation, a posttranslational modification that is part of the host response to viral infections. Mac1 is essential for pathogenesis in multiple animal models of CoV infection, implicating it as a virulence factor and potential therapeutic target. Here, we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose. SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) Mac1 domains exhibit similar structural folds, and all 3 proteins bound to ADP-ribose with affinities in the low micromolar range. Importantly, using ADP-ribose-detecting binding reagents in both a gel-based assay and novel enzyme-linked immunosorbent assays (ELISAs), we demonstrated de-MARylating activity for all 3 CoV Mac1 proteins, with the SARS-CoV-2 Mac1 protein leading to a more rapid loss of substrate than the others. In addition, none of these enzymes could hydrolyze poly-ADP-ribose. We conclude that the SARS-CoV-2 and other CoV Mac1 proteins are MAR-hydrolases with similar functions, indicating that compounds targeting CoV Mac1 proteins may have broad anti-CoV activity.IMPORTANCE SARS-CoV-2 has recently emerged into the human population and has led to a worldwide pandemic of COVID-19 that has caused more than 1.2 million deaths worldwide. With no currently approved treatments, novel therapeutic strategies are desperately needed. All coronaviruses encode a highly conserved macrodomain (Mac1) that binds to and removes ADP-ribose adducts from proteins in a dynamic posttranslational process that is increasingly being recognized as an important factor that regulates viral infection. The macrodomain is essential for CoV pathogenesis and may be a novel therapeutic target. Thus, understanding its biochemistry and enzyme activity are critical first steps for these efforts. Here, we report the crystal structure of SARS-CoV-2 Mac1 in complex with ADP-ribose and describe its ADP-ribose binding and hydrolysis activities in direct comparison to those of SARS-CoV and MERS-CoV Mac1 proteins. These results are an important first step for the design and testing of potential therapies targeting this unique protein domain.

Discovery of small molecule inhibitors of Plasmodium falciparum apicoplast DNA polymerase.

Malaria is caused by infection with protozoan parasites of the Plasmodium genus, which is part of the phylum Apicomplexa. Most organisms in this phylum contain a relic plastid called the apicoplast. The apicoplast genome is replicated by a single DNA polymerase (apPOL), which is an attractive target for anti-malarial drugs. We screened small-molecule libraries (206,504 compounds) using a fluorescence-based high-throughput DNA polymerase assay. Dose/response analysis and counter-screening identified 186 specific apPOL inhibitors. Toxicity screening against human HepaRG human cells removed 84 compounds and the remaining were subjected to parasite killing assays using chloroquine resistant P. falciparum parasites. Nine compounds were potent inhibitors of parasite growth and may serve as lead compounds in efforts to discover novel malaria drugs.

Water as a Lévy Rotor.

A probability density function describing the angular evolution of a fixed-length atom-atom vector as a Lévy rotor is derived containing just two dynamical parameters: the Lévy parameter α and a rotational time constant τ. A Lévy parameter α<2 signals anomalous (non-Brownian) motion. Molecular dynamics simulation of water at 298 K validates the probability density function for the intramolecular ^{1}H─^{1}H dynamics. The rotational dynamics of water is found to be approximately Brownian at subpicosecond time intervals, becomes increasingly anomalous at longer time intervals due to hydrogen-bond breaking and reforming, before becoming indistinguishable from Brownian dynamics beyond about 25 ps. The Lévy rotor model is used to estimate the intramolecular contribution to the longitudinal nuclear-magnetic-resonance (NMR) relaxation rate R_{1,intra}. It is found that R_{1,intra} contributes 65%±7% to the overall relaxation rate of water at room temperature.

Discovery of sultam-containing small-molecule disruptors of the huntingtin-calmodulin protein-protein interaction.

The aberrant protein-protein interaction between calmodulin and mutant huntingtin protein in Huntington's disease patients has been found to contribute to Huntington's disease progression. A high-throughput screen for small molecules capable of disrupting this interaction revealed a sultam series as potent small-molecule disruptors. Diversification of the sultam scaffold afforded a set of 24 analogs or further evaluation. Several structure-activity trends within the analog set were found, most notably a negligible effect of absolute stereochemistry and a strong beneficial correlation with electron-withdrawing aromatic substituents. The most promising analogs were profiled for off-target effects at relevant kinases and, ultimately, one candidate molecule was evaluated for neuroprotection in a neuronal cell model of Huntington's disease.

Decision Tree Pattern Recognition Model for Radio Frequency Interference Suppression in NQR Experiments.

Radio frequency interference places a major limitation on the in-situ use of unshielded nuclear quadrupole or nuclear magnetic resonance methods in industrial environments for quality control and assurance applications. In this work, we take the detection of contraband in an airport security-type application that is subject to burst mode radio frequency interference as a test case. We show that a machine learning decision tree model is ideally suited to the automated identification of interference bursts, and can be used in support of automated interference suppression algorithms. The usefulness of the data processed additionally by the new algorithm compared to traditional processing is shown in a receiver operating characteristic (ROC) analysis of a validation trial designed to mimic a security contraband detection application. The results show a highly significant increase in the area under the ROC curve from 0.580 to 0.906 for the proper identification of recovered data distorted by interfering bursts.

Advances in the Interpretation of Frequency-Dependent Nuclear Magnetic Resonance Measurements from Porous Material.

Fast-field-cycling nuclear magnetic resonance (FFC-NMR) is a powerful technique for non-destructively probing the properties of fluids contained within the pores of porous materials. FFC-NMR measures the spin-lattice relaxation rate R 1 ( f ) as a function of NMR frequency f over the kHz to MHz range. The shape and magnitude of the R 1 ( f ) dispersion curve is exquisitely sensitive to the relative motion of pairs of spins over time scales of picoseconds to microseconds. To extract information on the nano-scale dynamics of spins, it is necessary to identify a model that describes the relative motion of pairs of spins, to translate the model dynamics to a prediction of R 1 ( f ) and then to fit to the experimental dispersion. The principles underpinning one such model, the 3 τ model, are described here. We present a new fitting package using the 3 τ model, called 3TM, that allows users to achieve excellent fits to experimental relaxation rates over the full frequency range to yield five material properties and much additional derived information. 3TM is demonstrated on historic data for mortar and plaster paste samples.

Fluorescence High-Throughput Screening for Inhibitors of TonB Action.

Gram-negative bacteria acquire ferric siderophores through TonB-dependent outer membrane transporters (TBDT). By fluorescence spectroscopic hgh-throughput screening (FLHTS), we identified inhibitors of TonB-dependent ferric enterobactin (FeEnt) uptake through Escherichia coli FepA (EcoFepA). Among 165 inhibitors found in a primary screen of 17,441 compounds, we evaluated 20 in secondary tests: TonB-dependent ferric siderophore uptake and colicin killing and proton motive force-dependent lactose transport. Six of 20 primary hits inhibited TonB-dependent activity in all tests. Comparison of their effects on [59Fe]Ent and [14C]lactose accumulation suggested several as proton ionophores, but two chemicals, ebselen and ST0082990, are likely not proton ionophores and may inhibit TonB-ExbBD. The facility of FLHTS against E. coli led us to adapt it to Acinetobacter baumannii We identified its FepA ortholog (AbaFepA), deleted and cloned its structural gene, genetically engineered 8 Cys substitutions in its surface loops, labeled them with fluorescein, and made fluorescence spectroscopic observations of FeEnt uptake in A. baumannii Several Cys substitutions in AbaFepA (S279C, T562C, and S665C) were readily fluoresceinated and then suitable as sensors of FeEnt transport. As in E. coli, the test monitored TonB-dependent FeEnt uptake by AbaFepA. In microtiter format with A. baumannii, FLHTS produced Z' factors 0.6 to 0.8. These data validated the FLHTS strategy against even distantly related Gram-negative bacterial pathogens. Overall, it discovered agents that block TonB-dependent transport and showed the potential to find compounds that act against Gram-negative CRE (carbapenem-resistant Enterobacteriaceae)/ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Our results suggest that hundreds of such chemicals may exist in larger compound libraries.IMPORTANCE Antibiotic resistance in Gram-negative bacteria has spurred efforts to find novel compounds against new targets. The CRE/ESKAPE pathogens are resistant bacteria that include Acinetobacter baumannii, a common cause of ventilator-associated pneumonia and sepsis. We performed fluorescence high-throughput screening (FLHTS) against Escherichia coli to find inhibitors of TonB-dependent iron transport, tested them against A. baumannii, and then adapted the FLHTS technology to allow direct screening against A. baumannii This methodology is expandable to other drug-resistant Gram-negative pathogens. Compounds that block TonB action may interfere with iron acquisition from eukaryotic hosts and thereby constitute bacteriostatic antibiotics that prevent microbial colonization of human and animals. The FLHTS method may identify both species-specific and broad-spectrum agents against Gram-negative bacteria.

Habitat as a mediator of mesopredator-driven mammal extinction.

A prevailing view in dryland systems is that mammals are constrained by the scarcity of fertile soils and primary productivity. An alternative view is that predation is a primary driver of mammal assemblages, especially in Australia, where 2 introduced mesopredators-feral cat (Felis catus) and red fox (Vulpes vulpes)-are responsible for severe declines of dryland mammals. We evaluated productivity and predation as drivers of native mammal assemblage structure in dryland Australia. We used new data from 90 sites to examine the divers of extant mammal species richness and reconstructed historic mammal assemblages to determine proportional loss of mammal species across broad habitat types (landform and vegetation communities). Predation was supported as a major driver of extant mammal richness, but its effect was strongly mediated by habitat. Areas that were rugged or had dense grass cover supported more mammal species than the more productive and topographically simple areas. Twelve species in the critical weight range (CWR) (35-5500 g) that is most vulnerable to mesopredator predation were extirpated from the continent's central region, and the severity of loss of species correlated negatively with ruggedness and positively with productivity. Based on previous studies, we expect that habitat mediates predation from red foxes and feral cats because it affects these species' densities and foraging efficiency. Large areas of rugged terrain provided vital refuge for Australian dryland mammals, and we predict such areas will support the persistence of CWR species in the face of ongoing mammal declines elsewhere in Australia.

Measuring and Statistically Testing the Size of the Effect of a Chemical Compound on a Continuous In-Vitro Pharmacological Response Through a New Statistical Model of Response Detection Limit.

Biomolecular screening research frequently searches for the chemical compounds that are most likely to make a biochemical or cell-based assay system produce a strong continuous response. Several doses are tested with each compound and it is assumed that, if there is a dose-response relationship, the relationship follows a monotonic curve, usually a version of the median-effect equation. However, the null hypothesis of no relationship cannot be statistically tested using this equation. We used a linearized version of this equation to define a measure of pharmacological effect size, and use this measure to rank the investigated compounds in order of their overall capability to produce strong responses. The null hypothesis that none of the examined doses of a particular compound produced a strong response can be tested with this approach. The proposed approach is based on a new statistical model of the important concept of response detection limit, a concept that is usually neglected in the analysis of dose-response data with continuous responses. The methodology is illustrated with data from a study searching for compounds that neutralize the infection by a human immunodeficiency virus of brain glioblastoma cells.

Screening of natural compounds as activators of the keap1-nrf2 pathway.

Nuclear factor erythroid 2-related factor 2 is a master regulator that promotes transcription of cytoprotective genes in response to oxidative/electrophilic stress. A large number of natural dietary compounds are thought to protect against oxidative stress, and a few have been reported to induce genes involved in antioxidant defense through activating nuclear factor erythroid 2-related factor 2. Therefore, a library of 54 natural compounds were collected to determine whether they are nuclear factor erythroid 2-related factor 2 activators and to compare their efficacy and potency to activate nuclear factor erythroid 2-related factor 2. The assay utilized AREc32 cells that contain a luciferase gene under the control of antioxidant response element promoters. Each natural compound was tested at 13 concentrations between 0.02 and 30 µM. Known nuclear factor erythroid 2-related factor 2 activators tert-butylhydroquinone and 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide were used as positive controls in parallel with the natural compounds. Among the 54 tested natural compounds, andrographolide had the highest efficacy, followed by trans-chalcone, sulforaphane, curcumin, flavone, kahweol, and carnosol, all of which had better efficacy than tert-butylhydroquinone. Among the compounds tested, 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide was the most potent, having an EC50 of 0.41 µM. Seven of the natural compounds, namely andrographolide, trans-chalcone, sulforaphane, curcumin, flavone, kahweol, and cafestol had lower EC50 values than tert-butylhydroquinone but higher than 2-cyano-3,12-dioxooleana-1,9-diene-28-imidazolide. The present study provides insights into which natural compounds activate the Keap1-nuclear factor erythroid 2-related factor 2 pathway and thus might be useful for detoxifying oxidative/electrophilic stress.

A multi-chromic boron trifluoride-pyridyl Lewis adduct.

A boron trifluoride-pyridyl Lewis adduct is reported, which exhibits various types of chromism and high solid-state photoluminescence quantum yields, as well as excitation-dependent emission in the mechanically ground form. The facile synthetic approach offers a simple and potentially versatile strategy for inducing chromism in pyridyl ligands with donor moieties. We envisage this approach as having a dual benefit: simplicity and extensive applicability.

Mutation of highly conserved residues in loop 2 of the coronavirus macrodomain demonstrates that enhanced ADP-ribose binding is detrimental to infection.

All coronaviruses (CoVs) encode for a conserved macrodomain (Mac1) located in nonstructural protein 3 (nsp3). Mac1 is an ADP-ribosylhydrolase that binds and hydrolyzes mono-ADP-ribose from target proteins. Previous work has shown that Mac1 is important for virus replication and pathogenesis. Within Mac1, there are several regions that are highly conserved across CoVs, including the GIF (glycine-isoleucine-phenylalanine) motif. To determine how the biochemical activities of these residues impact CoV replication, the isoleucine and the phenylalanine residues were mutated to alanine (I-A/F-A) in both recombinant Mac1 proteins and recombinant CoVs, including murine hepatitis virus (MHV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The F-A mutant proteins had ADP-ribose binding and/or hydrolysis defects that led to attenuated replication and pathogenesis in cell culture and mice. In contrast, the I-A mutations had normal enzyme activity and enhanced ADP-ribose binding. Despite increased ADP-ribose binding, I-A mutant MERS-CoV and SARS-CoV-2 were highly attenuated in both cell culture and mice, indicating that this isoleucine residue acts as a gate that controls ADP-ribose binding for efficient virus replication. These results highlight the function of this highly conserved residue and provide unique insight into how macrodomains control ADP-ribose binding and hydrolysis to promote viral replication and pathogenesis.

A change of direction for family policy in Italy: some reflections on the general family allowance (GFA).

We present and discuss the General Family Allowance (GFA), in Italian: Assegno Unico Universale, a measure that the Italian Government and Parliament have put in place from March 2022 addressing the persistent low fertility in Italy. The GFA modernizes monetary transfers in favor of families with children in Italy, covering large groups of families that were previously excluded from full benefits. Even if the aim of the GFA is to support fertility rather than to alleviate child poverty, it is likely that this measure will help to reduce poverty, especially for families with children previously excluded from significant cash contributions, such as recently resident foreigners and the unemployed. In addition, as GFA amounts are modest for wealthier couples, its potential effect on fertility-if there will be any-should be limited to couples with modest incomes. The GFA is also compared with the different systems of monetary transfers in favor of families with children of developed countries.

Nuclear spin relaxation in aqueous paramagnetic ion solutions.

A Brownian shell model describing the random rotational motion of a spherical shell of uniform particle density is presented and validated by molecular dynamics simulations. The model is applied to proton spin rotation in aqueous paramagnetic ion complexes to yield an expression for the Larmor-frequency-dependent nuclear magnetic resonance spin-lattice relaxation rate T_{1}^{-1}(ω) describing the dipolar coupling of the nuclear spin of the proton with the electronic spin of the ion. The Brownian shell model provides a significant enhancement to existing particle-particle dipolar models without added complexity, allowing fits to experimental T_{1}^{-1}(ω) dispersion curves without arbitrary scaling parameters. The model is successfully applied to measurements of T_{1}^{-1}(ω) from aqueous manganese(II), iron(III), and copper(II) systems where the scalar coupling contribution is known to be small. Appropriate combinations of Brownian shell and translational diffusion models, representing the inner and outer sphere relaxation contributions, respectively, are shown to provide excellent fits. Quantitative fits are obtained to the full dispersion curve of each aquoion with just five fit parameters, with the distance and time parameters each taking a physically justifiable numerical value.

Quantification and characterization of biological activities of glansreginin A in black walnuts (Juglans nigra).

Glansreginin A has been reported to be an indicator of the quality of walnuts (Juglans spp.). However, bioactive properties of glansreginin A have not been adequately explored. In the present study, we quantified concentrations of glansreginin A in black walnuts (Juglans nigra) using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and performed an array of in vitro bioassays to characterize biological activities (e.g., antibacterial, antioxidant, anticancer capacities) of this compound. Results from HPLC-MS/MS analysis indicated that glansreginin A was presented in all 12 black cultivars examined and its contents were variable among black walnut cultivars, ranged from 6.8 mg/kg (Jackson) to 47.0 mg/kg (Hay). Glansreginin A possessed moderate antibacterial activities against Gram-positive pathogens (Staphylococcus aureus and Bacillus anthracis). This compound exhibited no antioxidant activities, did not induce the activity of antioxidant response element signaling pathways, and exerted no antiproliferative effects on tumorigenic alveolar epithelial cells and non-tumorigenic lung fibroblast cells.

The Impact of Demographic and Economic Change on the Australian Generational Economy: Financial Sustainability, Intergenerational Inequality, and Material Living Standards.

The generational economy-which is that aspect of the economy that pertains to the economic activities of, and the economic relationships between, different ages and generations-can be evaluated on the basis of a number of different criteria. The most critical of these include the financial sustainability of the generational economy, the intergenerational inequality that the generational economy creates, and the material living standards associated with the generational economy. How the generational economy performs in terms of these three criteria is, moreover, shaped by underlying processes of demographic and economic change. This paper examines how the Australian generational economy can be expected to perform in coming decades in terms of financial sustainability, intergenerational inequality, and material living standards. How the performance of the Australian generational economy is shaped by variations in fertility, mortality, overseas migration, and labour-income growth is also assessed. The results reported in the paper indicate that, because of population aging, consumption can only grow at a substantially lower rate than labour income if financial sustainability is to be maintained. These results also suggest that increasing overseas migration is a distinctly useful policy tool for meeting the challenges posed by population aging, since increasing overseas migration both increases material living standards and decreases intergenerational inequality.

English Language Proficiency Among Older Migrants in Australia, 2016-2046.

Australia's population is growing, ageing and exhibiting increasing heterogeneity with respect to birthplace and ethnic composition. Yet, little is understood about the levels of English language proficiency among the next generation of older migrants in Australia. Utilising a modified cohort-component model incorporating detailed language proficiency transition probabilities, we project birthplace populations by levels of English language proficiency to mid-century. Our results show that although Asian-born migrants tend to have lower levels of English proficiency, the majority of older migrants with poor proficiency are currently from a predominantly European background. In the future, we project a strong shift in the population of poor English speakers toward an Asian-born dominance as some European-born migrant groups dwindle in size and cohort flow increases population growth among older Asian migrants. Specifically, most of the population growth among older migrants with poor English proficiency occurs among Chinese and Mainland Southeast Asian migrants. However, we demonstrate that population growth among the total migrant population with poor proficiency is considerably lower than populations with good proficiency or from English-speaking households. Over the projection horizon, the total older migrant population with poor English proficiency increases by under 80,000 compared with an increase of 726,000 with good levels of proficiency and 518,000 in English-speaking households. However, we caution against conflating improved English language proficiency with a policy shift away from ethno-specific aged care services as culture, which is more than language, strongly influences perceptions of quality of aged care.

Repurposing Avasimibe to Inhibit Bacterial Glycosyltransferases.

We are interested in identifying and characterizing small molecule inhibitors of bacterial virulence factors for their potential use as anti-virulence inhibitors. We identified from high-throughput screening assays a potential activity for avasimibe, a previously characterized acyl-coenzyme A: cholesterol acyltransferase inhibitor, in inhibiting the NleB and SseK arginine glycosyltransferases from Escherichia coli and Salmonella enterica, respectively. Avasimibe inhibited the activity of the Citrobacter rodentium NleB, E. coli NleB1, and S. enterica SseK1 enzymes, without affecting the activity of the human serine/threonine N-acetylglucosamine (O-GlcNAc) transferase. Avasimibe was not toxic to mammalian cells at up to 200 µM and was neither bacteriostatic nor bactericidal at concentrations of up to 125 µM. Doses of 10 µM avasimibe were sufficient to reduce S. enterica abundance in RAW264.7 macrophage-like cells, and intraperitoneal injection of avasimibe significantly reduced C. rodentium survival in mice, regardless of whether the avasimibe was administered pre- or post-infection. We propose that avasimibe or related derivates created using synthetic chemistry may have utility in preventing or treating bacterial infections by inhibiting arginine glycosyltransferases that are important to virulence.

Digital Transformation of Faculty Development: Responding and Supporting Academia During Disruptions Caused by the Coronavirus Disease 2019 Pandemic.

INTRODUCTION: The coronavirus disease 2019 pandemic disrupted the current practices for teaching and learning in medical and health professions education, creating challenges and opportunities for rapid transition. The authors describe how McMaster University's Program for Faculty Development (MacPFD) responded to this disruption by engaging in a digital transformation. METHODS: The digital transformation process of MacPFD was mapped to the conceptual framework of digital transformation: Vial's building blocks of the framework. A new website was launched to host and disseminate the content. Subsequently, both the website and the content were promoted using social media tools. Content generation, Google Analytics, event registrations, and Zoom webinar attendance records were data sources for the results. Analysis of the data was based on the reach component of the RE-AIM framework. RESULTS: Six-month data range results were reported as producer-centered and user-centered outcomes. The former consisted of 54 resources from diverse content authors, whereas the latter received 33,045 page views from 26,031 unique users from 89 countries. Live webinar events had 1484 registrants, with 312 (21%) being guests from external institutions. Before the coronavirus disease 2019 disruption, MacPFD was a local program to support its faculty. DISCUSSION: The MacPFD's digital transformation shows a clear transition to a new "glocal" approach: an expanded global reach while still tending to our local development needs of the home institution's faculty members.