Principles of early human development and germ cell program from conserved model systems.

Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate during weeks 2-3 of early post-implantation development. Using in vitro models of hPGC induction, recent studies have suggested that there are marked mechanistic differences in the specification of human and mouse PGCs. This may be due in part to the divergence in their pluripotency networks and early post-implantation development. As early human embryos are not accessible for direct study, we considered alternatives including porcine embryos that, as in humans, develop as bilaminar embryonic discs. Here we show that porcine PGCs originate from the posterior pre-primitive-streak competent epiblast by sequential upregulation of SOX17 and BLIMP1 in response to WNT and BMP signalling. We use this model together with human and monkey in vitro models simulating peri-gastrulation development to show the conserved principles of epiblast development for competency for primordial germ cell fate. This process is followed by initiation of the epigenetic program and regulated by a balanced SOX17-BLIMP1 gene dosage. Our combinatorial approach using human, porcine and monkey in vivo and in vitro models provides synthetic insights into early human development.

The impact of oocyte central granularity on ICSI practice: developmental competence of dysmorphic and morphologically normal companion oocytes.

PURPOSE: To assess the effects of oocyte central granularity and its underlying endocrine environment on developmental competence of dysmorphic and morphologically normal oocytes. METHODS: Retrospective cohort study including 1,082 patients undergoing autologous ICSI cycles. Of these, 211 patients provided 602 oocytes with central granularity (CG) and 427 morphologically normal cycle companion oocytes (NCG). The remaining 871 patients provided only morphologically normal oocytes in cycles not yielding dysmorphic oocytes (N). Patient profile associated with CG was characterized, and fertilization rates, early morphokinetics and live birth rates were compared between N, CG and NCG groups. Patient characteristics associated with implantation and delivery performance of CG-derived embryos were assessed. RESULTS: CG was associated with higher maternal age, basal FSH concentrations and total FSH dose, but with lower circulating AMH (p ≤ 0.035). Fertilization rates were reduced and early morphokinetic parameters were delayed in CG (p < 0.025) and NCG (p < 0.05) groups as compared to the N group. Embryos derived from CG oocytes achieved a markedly lower live birth rate (14.9%) as compared to those derived from NCG (36.8%; p = 0.03) and N oocytes (29.8%; p = 0.002). The negative relationship between CG and live birth was confirmed by a multivariate analysis controlling for potential confounders (OR:2.59, IC:1.27-5.31; P = 0.009). Implantation and delivery rates following transfers of CG-derived embryos were inversely associated with maternal age. CONCLUSION: CG oocytes, but not their morphologically normal cycle companions, have severely compromised developmental competence. Maternal age should be a key parameter in deciding whether or not to utilize CG oocytes in ICSI cycles.

Ka mura ka muri: understandings of organ donation and transplantation in Aotearoa New Zealand.

In this article, we refer to the separation of solid organs from the body as bio-objects. We suggest that the transfer of these bio-objects is connected to emotions and affects that carry a range of different social and cultural meanings specific to the context of Aotearoa New Zealand. The discussion draws on research findings from a series of qualitative indepth interview studies conducted from 2008 to 2013 with Maori (the Indigenous people of Aotearoa New Zealand) and Pakeha (European settler New Zealanders) concerning their views on organ donation and transplantation. Our findings show both differences and similarities between Maori and Pakeha understandings of transplantation. Nevertheless, while many Maori draw on traditional principles, values and beliefs to reflect on their experiences in relation to embodiment, gift-giving, identity and well-being, Pakeha tend to subscribe to more Western understandings of identity in terms of health and well-being, in line with international literature on the topic. Rather than reflecting individualistic notions of the body and transplantation as the endpoint of healthcare as do Pakeha, Maori views are linked to wider conceptions of family, ancestry and belonging, demonstrating how different rationalities and ontologies affect practices and understandings surrounding organ transfer technology. In the article, we focus predominantly on Maori perspectives of organ transfer, contextualising the accounts and experiences of our research participants against the backdrop of a long history of settler colonialism and health inequalities in Aotearoa New Zealand.

Defining the gonadotrophin requirement for the selection of a single dominant follicle in cattle.

The aim was to define the pattern and physiological concentrations of FSH and LH required for the selection of a single dominant follicle in mono-ovulatory species. A series of five experiments was carried out using gonadotrophin-releasing hormone agonist-induced hypogonadal heifers. Animals were infused with different patterns of either FSH and/or LH followed by an ovulatory dose of human chorionic gonadotrophin. Follicular response was monitored by ultrasound scanning and blood samples were collected to measure concentrations of FSH, LH, oestradiol and progesterone. The main findings were: (1) physiological concentrations of FSH given as a continuous infusion and for an adequate duration, in the presence of basal LH, with or without LH pulses, are capable of inducing a superovulatory response, (2) initial exposure to FSH followed by LH pulses alone stimulate the development of multiple preovulatory follicles, confirming that ovarian follicles are capable of transferring dependence on gonadotrophins from FSH to LH, (3) while LH pulses appear not to have a major effect on the pattern of preovulatory follicle development, adequate LH pulsatile support is required for full oestradiol synthesis and (4) the duration of initial exposure to FSH and the ability to transfer the dependence from FSH to LH are critical for the selection of a single dominant follicle. In conclusion, this experimental series confirms that the duration of initial exposure to FSH and the ability of the selected follicle to transfer its gonadotrophic dependence from FSH to LH are critical for the selection of a single dominant follicle in cattle.

Characterizing Cation Chemistry for Anion Exchange Membranes-A Product Study of Benzylimidazolium Salt Decompositions in the Base.

Imidazolium functionality has played a prominent role in research on anion exchange membranes for use in alkaline electrochemical devices. Base stability and degradation of these materials has been much studied, but in many instances, product pathways have not been thoroughly delineated. We report an NMR study of base-induced decomposition products from three benzylimidazolium salts bearing varying extents of methyl substitution on the imidazolium ring. The major products are consistent with a hydrolytic ring fragmentation pathway as the principal mode of decomposition. We observe several new products not previously reported in the literature on imidazolium salt degradation, including benzilic acid rearrangement products formally derived from intermediate 1,2-dicarbonyl compounds or their equivalents. However, the overall reactions are complex, the yields of observed products do not account for all consumed starting materials, and mechanistic ambiguities remain.

A calcineurin antifungal strategy with analogs of FK506.

A novel antifungal strategy targeting the inhibition of calcineurin is described. To develop a calcineurin based inhibitor of pathogenic fungi, analogs of FK506 were synthesized that were able to permeate mammalian but not fungal cells. Antagonists in combination with FK506 were not immunosuppressive and retained antifungal activity in A. fumigatus. To reduce the dosage burden of the antagonist, murine oral PK was improved an order of magnitude relative to previous FK506 antagonists.

A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A.

Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC50 values ⩽1µM and 11 effective at ⩽2µM in an ex vivo assay.

Paracrine effects of embryo-derived FGF4 and BMP4 during pig trophoblast elongation.

The crosstalk between the epiblast and the trophoblast is critical in supporting the early stages of conceptus development. FGF4 and BMP4 are inductive signals that participate in the communication between the epiblast and the extraembryonic ectoderm (ExE) of the developing mouse embryo. Importantly, however, it is unknown whether a similar crosstalk operates in species that lack a discernible ExE and develop a mammotypical embryonic disc (ED). Here we investigated the crosstalk between the epiblast and the trophectoderm (TE) during pig embryo elongation. FGF4 ligand and FGFR2 were detected primarily on the plasma membrane of TE cells of peri-elongation embryos. The binding of this growth factor to its receptor triggered a signal transduction response evidenced by an increase in phosphorylated MAPK/ERK. Particular enrichment was detected in the periphery of the ED in early ovoid embryos, indicating that active FGF signalling was operating during this stage. Gene expression analysis shows that CDX2 and ELF5, two genes expressed in the mouse ExE, are only co-expressed in the Rauber's layer, but not in the pig mural TE. Interestingly, these genes were detected in the nascent mesoderm of early gastrulating embryos. Analysis of BMP4 expression by in situ hybridisation shows that this growth factor is produced by nascent mesoderm cells. A functional test in differentiating epiblast shows that CDX2 and ELF5 are activated in response to BMP4. Furthermore, the effects of BMP4 were also demonstrated in the neighbouring TE cells, as demonstrated by an increase in phosphorylated SMAD1/5/8. These results show that BMP4 produced in the extraembryonic mesoderm is directly influencing the SMAD response in the TE of elongating embryos. These results demonstrate that paracrine signals from the embryo, represented by FGF4 and BMP4, induce a response in the TE prior to the extensive elongation. The study also confirms that expression of CDX2 and ELF5 is not conserved in the mural TE, indicating that although the signals that coordinate conceptus growth are similar between rodents and pigs, the gene regulatory network of the trophoblast lineage is not conserved in these species.

Direct and indirect effects of environmental variability on growth and survivorship of pre-reproductive Joshua trees, Yucca brevifolia Engelm. (Agavaceae).

UNLABELLED: • PREMISE OF STUDY: Accurate demographic information about long-lived plant species is important for understanding responses to large-scale disturbances, including climate change. It is challenging to obtain these data from desert perennial plants because seedling establishment is exceptionally rare, and estimates of survival are lacking for their vulnerable early stages. Desert wildfires, urbanization, and climate change influence the persistence of the long-lived Yucca brevifolia. Quantitative demographic attributes are crucial for understanding how populations will respond to disturbances and where populations will recede or advance under future climate scenarios.• METHODS: We measured survival in a cohort of 53 pre-reproductive Y. brevifolia at Yucca Flat, Nevada, USA, for 22 yr and recorded their growth, nurse-plant relationships, and herbivory.• KEY RESULTS: Herbivory by black-tailed jackrabbits (Lepus californicus) caused severe losses of plants during the first and second years (45% and 31%, respectively). Surviving plants experienced <2.5% annual mortality. Survival for the population was 19% over 22 yr. Plants <25 cm in height had lower life expectancy. Average growth rate (± SD) for plants that survived to the last census was 3.12 ± 1.96 cm yr(-1), and growth rates were positively associated with precipitation. Thirty-year-old Y. brevifolia had not yet reproduced.• CONCLUSIONS: A rare establishment event for Y. brevifolia during 1983-1984, triggered by above-average summer rainfall, provided a unique opportunity to track early survival and growth. Infrequent but acute episodes of herbivory during drought influenced demography for decades. Variability in survival among young Y. brevifolia indicates that size-dependent demographic variables will improve forecasts for this long-lived desert species under predicted regional climate change.

Multiple meanings of "gift" and its value for organ donation.

The "gift of life" metaphor is used to promote organ donation where commercialization is prohibited. In this article, we explore how multiple parties involved in organ transfer procedures think of gift terminology by drawing on interview data with transplantation specialists, organ transplant recipients, living directed donors and living nondirected donors. The interviews took place across New Zealand between October 2008 and May 2012, in participants' homes and hospital workplaces. The interviews were transcribed verbatim, coded manually, and thematically analyzed. Although gift language is often viewed as clear-cut, the gift trope has multiple meanings for different constituent and cultural groups, ranging from positive descriptors to obscuring and romanticizing the complexities of transplantation processes. To account for these multiple perspectives, we suggest new ethical models to capture the nuanced phenomenon of organ transfer in ways that recognize the full range of donation and reception experiences.

The C terminus of the catalytic domain of type A botulinum neurotoxin may facilitate product release from the active site.

Botulinum neurotoxins are the most toxic of all compounds. The toxicity is related to a poor zinc endopeptidase activity located in a 50-kDa domain known as light chain (Lc) of the toxin. The C-terminal tail of Lc is not visible in any of the currently available x-ray structures, and it has no known function but undergoes autocatalytic truncations during purification and storage. By synthesizing C-terminal peptides of various lengths, in this study, we have shown that these peptides competitively inhibit the normal catalytic activity of Lc of serotype A (LcA) and have defined the length of the mature LcA to consist of the first 444 residues. Two catalytically inactive mutants also inhibited LcA activity. Our results suggested that the C terminus of LcA might interact at or near its own active site. By using synthetic C-terminal peptides from LcB, LcC1, LcD, LcE, and LcF and their respective substrate peptides, we have shown that the inhibition of activity is specific only for LcA. Although a potent inhibitor with a Ki of 4.5 µm, the largest of our LcA C-terminal peptides stimulated LcA activity when added at near-stoichiometric concentration to three versions of LcA differing in their C-terminal lengths. The result suggested a product removal role of the LcA C terminus. This suggestion is supported by a weak but specific interaction determined by isothermal titration calorimetry between an LcA C-terminal peptide and N-terminal product from a peptide substrate of LcA. Our results also underscore the importance of using a mature LcA as an inhibitor screening target.

The effect of corrosion inhibitors on microbial communities associated with corrosion in a model flow cell system.

A model flow cell system was designed to investigate pitting corrosion in pipelines associated with microbial communities. A microbial inoculum producing copious amounts of H2S was enriched from an oil pipeline biofilm sample. Reservoirs containing a nutrient solution and the microbial inoculum were pumped continuously through six flow cells containing mild steel corrosion coupons. Two cells received corrosion inhibitor "A", two received corrosion inhibitor "B", and two ("untreated") received no additional chemicals. Coupons were removed after 1 month and analyzed for corrosion profiles and biofilm microbial communities. Coupons from replicate cells showed a high degree of similarity in pitting parameters and in microbial community profiles, as determined by 16S rRNA gene sequence libraries but differed with treatment regimen, suggesting that the corrosion inhibitors differentially affected microbial species. Viable microbial biomass values were more than 10-fold higher for coupons from flow cells treated with corrosion inhibitors than for coupons from untreated flow cells. The total number of pits >10 mils diameter and maximum pitting rate were significantly correlated with each other and the total number of pits with the estimated abundance of sequences classified as Desulfomicrobium. The maximum pitting rate was significantly correlated with the sum of the estimated abundance of Desulfomicrobium plus Clostridiales, and with the sum of the estimated abundance of Desulfomicrobium plus Betaproteobacteria. The lack of significant correlation with the estimated abundance of Deltaproteobacteria suggests not all Deltaproteobacteria species contribute equally to microbiologically influenced corrosion (MIC) and that it is not sufficient to target one bacterial group when monitoring for MIC.

One hundred and six years of change in a Sonoran Desert plant community: Impact of climate anomalies and trends in species sensitivities.

A major restriction in predicting plant community response to future climate change is a lack of long-term data needed to properly assess species and community response to climate and identify a baseline to detect climate anomalies. Here, we use a 106-year dataset on a Sonoran Desert plant community to test the role of extreme temperature and precipitation anomalies on community dynamics at the decadal scale and over time. Additionally, we tested the climate sensitivity of 39 desert plant species and whether sensitivity was associated with growth form, longevity, geographic range, or local dominance. We found that desert plant communities had shifted directionally over the 106 years, but the climate had little influence on this directional change primarily due to nonlinear shifts in precipitation anomalies. Decadal-scale climate had the largest impact on species richness, species relative density, and total plant cover, explaining up to 26%, 45%, and 55% of the variance in each, respectively. Drought and the interaction between the frequency of freeze events and above-average summer precipitation were among the most influential climate factors. Increased drought frequency and wetter periods with frequent freeze events led to larger reductions in total plant cover, species richness, and the relative densities of dominant subshrubs Ambrosia deltoidea and Encelia farinosa. More than 80% of the tested species were sensitive to climate, but sensitivity was not associated with a species' local dominance, longevity, geographic range, or growth form. Some species appear to exhibit demographic buffering, where when they have a higher sensitivity to drought, they also tend to have a higher sensitivity to favorable (i.e., wetter and hotter) conditions. Overall, our results suggest that, while decadal-scale climate variation substantially impacts these desert plant communities, directional change in temperature over the last century has had little impact due to the relative importance of precipitation and drought. With projections of increased drought in this region, we may see reductions in total vegetation cover and species richness due to the loss of species, possibly through a breakdown in their ability to demographically buffer climatic variation, potentially changing community dynamics through a change in facilitative and competitive processes.

Reclaiming freshwater sustainability in the Cadillac Desert.

Increasing human appropriation of freshwater resources presents a tangible limit to the sustainability of cities, agriculture, and ecosystems in the western United States. Marc Reisner tackles this theme in his 1986 classic Cadillac Desert: The American West and Its Disappearing Water. Reisner's analysis paints a portrait of region-wide hydrologic dysfunction in the western United States, suggesting that the storage capacity of reservoirs will be impaired by sediment infilling, croplands will be rendered infertile by salt, and water scarcity will pit growing desert cities against agribusiness in the face of dwindling water resources. Here we evaluate these claims using the best available data and scientific tools. Our analysis provides strong scientific support for many of Reisner's claims, except the notion that reservoir storage is imminently threatened by sediment. More broadly, we estimate that the equivalent of nearly 76% of streamflow in the Cadillac Desert region is currently appropriated by humans, and this figure could rise to nearly 86% under a doubling of the region's population. Thus, Reisner's incisive journalism led him to the same conclusions as those rendered by copious data, modern scientific tools, and the application of a more genuine scientific method. We close with a prospectus for reclaiming freshwater sustainability in the Cadillac Desert, including a suite of recommendations for reducing region-wide human appropriation of streamflow to a target level of 60%.

Contemporary practices of blood glucose management in diabetic patients: a survey of hyperbaric medicine units in Australia and New Zealand.

Introduction: Blood glucose levels may be influenced by hyperbaric oxygen treatment (HBOT). Patients with diabetes mellitus commonly receive HBOT but there is a lack of standardised blood glucose management guidelines. We documented relevant contemporary practices applied for patients with diabetes treated in hyperbaric medicine units. Methods: A survey was administered in 2022 to the directors of all 13 accredited hyperbaric units in Australia and New Zealand to identify policies and practices related to management of patients with diabetes receiving HBOT. Results: Twelve of the 13 units routinely managed patients with diabetes. Three-quarters (9/12) used < 4 mmol·l-1 as their definition of hypoglycaemia, whereas the other three used < 5, < 3.6, and < 3 mmol·l-1. Units reported 26% (range 13-66%) of their patients have a diagnosis of diabetes of which 93% are type 2. Ten (83%) units reported specific written protocols for managing blood glucose. Protocols were more likely to be followed by nursing (73%) than medical staff (45%). Ten (83%) units routinely tested blood glucose levels on all patients with diabetes. Preferred pre-treatment values for treatments in both multiplace and monoplace chambers ranged from ≥ 4 to ≥ 8 mmol·l-1. Seven (58%) units reported continuation of routine testing throughout a treatment course with five (42%) units having criteria-based rules for discontinuing testing for stable patients over multiple treatments. Two-thirds of units were satisfied with their current policy. Conclusions: This survey highlights the burden of diabetes on patients treated with HBOT and identifies considerable variability in practices which may benefit from further study to optimise management of these patients.

Unilateral Supraorbital Keyhole Craniotomy Avoiding the Frontal Sinus for Large and Giant Olfactory-Groove Meningiomas: A Case Series.

OBJECTIVE: There are several different approaches to large and giant olfactory-groove meningiomas (OGMs). Each approach has advantages and disadvantages. We present our series using a unilateral supraorbital keyhole approach avoiding the frontal sinus for the resection of large and giant OGMs without the use of fixed brain retractors or orbital rim removal. MATERIALS AND METHODS: All consecutive patients operated on for large (>3 cm in largest diameter) and giant (>5 cm) OGMs by the senior author from 2016 to 2021 were prospectively identified and retrospectively reviewed. Patients who were operated on using an endoscopic endonasal approach were excluded. No fixed retraction was used. RESULTS: In total, 14 consecutive patients (11 with large, 3 with giant) were included. All patients were female, with an average age ± standard deviation of 59.7 ± 11.5 years. The median [interquartile range] preoperative Karnofsky Performance Status score was 80 [80-88]. The median preoperative tumor diameter and volume were 3.8 [3.2-4.2] cm and 22.2 [10.5-25.2] cm3, respectively. All patients underwent gross total resection. The median hospital stay was 2.7 [2-3] days, with all patients being discharged to home. No patients incurred any postoperative medical and/or surgical complications. Of the 9 patients who had subjective smell preoperatively, 5 stated they had subjective olfaction after surgery. CONCLUSIONS: We demonstrate the utility of a unilateral supraorbital keyhole approach avoiding the frontal sinus for large and giant OGMs. The potential advantages of this approach are minimizing bilateral brain manipulation, avoiding the frontal sinus and potential mucoceles, and reducing the risk of cerebrospinal fluid leaks.

Intelligent design: stablecoins (in)stability and collateral during market turbulence.

How does stablecoin design affect market behavior during turbulent periods? Stablecoins attempt to maintain a "stable" peg to the US dollar, but do so with widely varying structural designs. The spectacular collapse of the TerraUSD (UST) stablecoin and the linked Terra (LUNA) token in May 2022 precipitated a series of reactions across major stablecoins, with some experiencing a fall in value and others gaining value. Using a Baba, Engle, Kraft and Kroner (1990) (BEKK) model, we examine the reaction to this exogenous shock and find significant contagion effects from the UST collapse, likely partially due to herding behavior among traders. We test the varying reactions among stablecoins and find that stablecoin design differences affect the direction, magnitude, and duration of the response to shocks. We discuss the implications for stablecoin developers, exchanges, traders, and regulators.

Outcomes of hyperbaric oxygen treatment for central and branch retinal artery occlusion at a major Australian referral hospital.

Introduction: This study analysed the treatment outcomes of patients that received hyperbaric oxygen treatment (HBOT) for retinal artery occlusion (RAO) at the Royal Brisbane and Women's Hospital in Brisbane, Australia between 2015 and 2021. Methods: Retrospective study from patient records including 22 eyes from 22 patients that received HBOT for either central RAO (17 patients) or branch RAO (five patients). Patients received the Royal Brisbane and Women's Hospital RAO protocol for their HBOT. Analysis included best corrected visual acuity pre- and post-treatment, subjective improvements, side effects and patient risk factors were also recorded. Results: Improvement in best corrected visual acuity was LogMAR -0.2 for central RAO on average with 8/17 (47%) experiencing objective improvement, 5/17 (29%) experienced no change and 4/22 (24%) experienced a reduction in best corrected visual acuity. Subjective improvement (colour perception or visual fields) was reported in an additional 4/17 patients, resulting in 12/17 (71%) reporting improvement either in visual acuity or subjectively. There was no improvement in the best corrected visual acuity of any of the five patients suffering from branch RAO. Cardiovascular risk factors present in the cohort included hypertension, hypercholesterolaemia, previous cardiovascular events, cardiac disease and smoking. Limited side effects were experienced by this patient cohort with no recorded irreversible side effects. Conclusions: Hyperbaric oxygen treatment appears a safe, beneficial treatment for central RAO. No benefit was demonstrated in branch RAO although numbers were small. Increased awareness of HBOT for RAO resulting in streamlined referrals and transfers and greater uptake of this intervention may further improve patient outcomes.

Enabling urban systems transformations: co-developing national and local strategies.

Transformative urban development is urgent to achieve future sustainable development and wellbeing. Transformation can benefit from shared and cumulative learning on strategies to guide urban development across local to national scales, while also reflecting the complex emergent nature of urban systems, and the need for context-specific and place-based solutions. The article addresses this challenge, drawing on extensive transdisciplinary engagement and National Strategy co-development processes for Australia. This includes generation of two frameworks as boundary objects to assist such transdisciplinary strategy development. An 'enabling urban systems transformation' framework comprises four generic overarching transformation enablers and a set of necessary underpinning urban capacities. This also built cumulatively on other sustainability and urban transformation studies. A complementary 'knowledge for urban systems transformation' framework comprises key knowledge themes that can support an integrated systems approach to mission-focused urban transformations, such as decarbonising cities. The article provides insights on the transdisciplinary processes, urban systems frameworks, and scoping of key strategies that may help those developing transformation strategies from local to national scales. Science highlights • Transdisciplinary national urban strategy development is used to distil generic frameworks and strategy scopes with potential international application. • The frameworks also build on other published framings to support convergent, cumulative and transdisciplinary urban science. • The 'enabling transformations' and 'urban knowledge' frameworks include the perspective of those developing sustainable urban systems strategies. • The enabling framework also informs 'National Urban Policy' and 'Knowledge and Innovation Hub' strategies, and prevailing power imbalances. • The knowledge framework can help frame urban challenges, missions and knowledge programs. Policy and practice recommendations • An urban 'transformation imperative' and 'strategic response' can be co-developed from local to national scales. • Local initiative is crucial to drive urban strategies, but sustained national leadership with coherent policy across sectors and scales is also key. • Diversity in engagement participation and processes generates whole-of-urban-systems and local-to-national perspectives. • Urban solutions are context-specific but generic frameworks can help collaborative issue framing and responses. • Collaborative issue framing informed by generic frameworks can bring broader perspectives to context-specific and contested policy and practice issues. Supplementary Information: The online version contains supplementary material available at 10.1186/s42854-023-00049-9.