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Co-production is an increasingly popular approach for environmental and sustainability research, but what is actually produced through its practice remains understudied. This paper reviews recent examples of co-produced research alongside current theorization on the topic. Focusing on the area of climate change adaptation, we find that co-produced climate change adaptation research appears to be improving knowledge use, among other positive outcomes, but a difference emerges between the range of outcomes reported in practice and the scope of ambition conceived through theory. This raises important questions about how the practice of knowledge co-production should be evaluated and, fundamentally, what we should expect to produce through co-production. We argue that understanding and reconciling the transformative potential of science-practice collaborations within the context of the incremental progress achieved through its current practice will catalyze a more integrated and actionable scholarship and practice.

Researchers, stakeholders and funding organizations have embraced co-production of knowledge to solve sustainability problems. Research focusing on the practice of co-production can help us understand what works in what contexts and how to avoid potentially undesirable outcomes.

Contemporary scientific and technological endeavours face public and political pressure to adopt open, transparent and democratically accountable practices of public engagement. Prior research has identified different ways that experts 'imagine publics' - as uninformed, as disengaged, as a risk to science, and as co-producers of knowledge - but there has yet to be a systematic exploration of how these views emerge, interact and evolve. This article introduces a typology of imagined publics to analyse how publics are constructed in the field of forest genomics. We find that deficit views of publics have not been replaced by co-production. Instead, deficit and co-productive approaches to publics co-exist and overlap, informing both how publics are characterized and how public perceptions are studied. We outline an agenda for deepening and expanding research on public perceptions of novel technologies. Specifically, we call for more diverse and complex methodological approaches that account for relational dynamics over time., Competing Interests: Declaration of conflicting interestsThe author(s) declare that they have no known financial, personal or professional relationships that could have appeared to influence the work reported in this article.

The precautionary approach to fisheries management is a central strategy by which domestic and international fisheries management institutions pursue sustainable resource development. Yet fisheries management institutions have often allocated quota for commercial species in direct contradiction of established precautionary guidelines. We use Fisheries and Oceans Canada (DFO)'s recent allocation of quota for northern cod (Gadus morhua) while the stock is in the critical zone of the institution's precautionary approach as a case study to ask: why do fisheries management institutions circumvent precautionary guidelines? Our results reveal three core tensions characterizing the use of the precautionary approach: stakeholders and rightsholders (1) disagree on the appropriateness and accuracy of the data inputs used to operationalize the precautionary approach, (2) rely on different metrics to gauge risk associated with fishing a stock in the critical zone, and (3) hold competing views concerning what constitutes an appropriate epistemological foundation for the precautionary approach. Our analysis suggests these differing interpretations of precaution and the design of the precautionary approach are central factors explaining why resource allocation decisions differ from precautionary guidelines. We conclude that decisions to allocate quota in contradiction of precautionary guidelines are best explained by stakeholders and rightsholders reframing how decision-makers gauge risk associated with resource exploitation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The need to reverse decades of species and ecosystem decline has created an imperative to understand the governance of recovery. To pursue this imperative, we ask a question at the centre of recovery governance: when is a commercial species recovered? To answer this question we conduct a case study of northern cod (Gadus morhua, NAFO subdivision 2J3KL), a species perhaps best known for the scale of its biological collapse and subsequent socioeconomic consequences. Northern cod has experienced recent biomass growth, raising the question of when the species can once again be the target of commercial fishing. We conducted 26 interviews with key stakeholders from Newfoundland and Labrador's fishing sector and identify three core discourses characterizing the governance of the northern cod recovery: (1) the biological recovery discourse, (2) the industrial recovery discourse, and (3) the community recovery discourse. We find these recovery discourses are composed of five dimensions: (i) epistemic orientation and inputs, (ii) emphasis on institutions and rules, (iii) framings of risk, (iv) stakeholder priorities, goals, and interests, and (v) different lessons learned from the collapse. Our findings suggest that the recovery of a commercial species is not determined only by biological metrics, but also how decision-makers view the value of different knowledge systems, what frames of risk they find most salient, and the lessons they glean from collapse on behalf of the societies they represent. Our discussion notes that co-productive approaches could supplement adaptive approaches as a potential strategy to reconcile competing discourses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Factor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data., Methods: A total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR)., Results: Eight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters., Conclusions: Our observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G., Competing Interests: Author VJ was employed by company Medimpax. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Garam, Cserhalmi, Prohászka, Szilágyi, Veszeli, Szabó, Uzonyi, Iliás, Aigner, Schmidt, Gaggl, Sunder-Plassmann, Bajcsi, Brunner, Dumfarth, Cejka, Flaschberger, Flögelova, Haris, Hartmann, Heilos, Mueller, Rusai, Arbeiter, Hofer, Jakab, Sinkó, Szigeti, Bereczki, Janko, Kelen, Reusz, Szabó, Klenk, Kóbor, Kojc, Knechtelsdorfer, Laganovic, Lungu, Meglic, Rus, Kersnik Levart, Macioniene, Miglinas, Pawłowska, Stompór, Podracka, Rudnicki, Mayer, Rysava, Reiterova, Saraga, Seeman, Zieg, Sládková, Stajic, Szabó, Capitanescu, Stancu, Tisljar, Galesic, Tislér, Vainumäe, Windpessl, Zaoral, Zlatanova, Józsi and Csuka.)

In this article, we integrate our authorship experiences with insights from nine interviews of knowledge exchange practitioners at the Canadian Forest Service about challenges and opportunities of digital knowledge exchange (KE) brought on by the COVID-19 pandemic. We aim to inform how best to maintain effective KE practices and processes in a digital-first world. Interpersonal trust and relationships are pivotal to effective knowledge exchange; thus, removing these dimensions risks losing aspects of social learning, informal and meaningful discussions, and personal connections that affect how we interpret and respond to subtle affective and social cues. For KE practitioners, lack of in-person interactions risks internal KE coordination and relevance of KE work, and diminished ability to predict and respond to user needs. However, the accelerated digital adoption has increased reach and accessibility for diverse people to exchange knowledge, and enables more frequent and rapid response to issues and events by virtually gathering diverse people almost instantly. The acceleration in digital innovation and culture has thus resulted in new tools and diversified approaches for the KE toolbox to inform decisions and practices. The long-term sustainability and effectiveness of digital KE depend on two interconnected factors: addressing the persistence of the digital divide and people's abilities to make and maintain meaningful social connections in the absence of regular face-to-face contact. We thus offer three considerations to guide KE efforts and initiative in a digital-first world: (1) consider both digital divide and equity ; (2) revisit user needs and preferences for KE to address the diversity of users , and (3) leverage the diversification of KE approaches and innovations., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd. 2021.)

Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal-epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient's sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met high -expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.

Background: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors., Results: One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF., Conclusions: In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10-15% of IC-MPGN/C3G patients.

Background: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers., Methods: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated., Results: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2., Conclusions: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background/aims: Patients with a failed kidney transplant represent a unique, high-risk chronic kidney disease population that is increasing in number, and may be sub-optimally managed. Our aim was to compare the survival of patients with failed allografts to patients with native kidney failure and to assess whether their survival is affected by the graft resection., Methods: Kaplan-Meier and Cox-regression survival analyses were performed on the data of 57 patients with graft failure and of 123 transplant-naive haemodialysed patients., Results: After adjustment for age and gender, there was no statistically significant difference in the mortality of patients in the two groups. The 43 patients, who had a transplanted kidney nephrectomy had a statistically not significant survival benefit over non-nephrectomised patients (age and gender adjusted hazard ratio: 0.56 95 % confidence interval: 0.24-1.58, p-value: 0.18)., Conclusion: Elective graft resection is a safe, effective alternative for both the treatment and the prevention of the chronic inflammatory state associated with a failed kidney transplant., (Copyright © 2013 S. Karger AG, Basel.)

The main nucleocapsid protein NP (molecular weight--56 kD) of human influenza A virus (IAV) was found to be subject to the N-terminal proteolysis in position Asp16 with production of aNP (molecular weight--53 kD) in the infected cells' apoptosis. It was assumed that NP of avian and animal influenza viruses was not subject to proteolysis since it has Gly16. To verify the above assumption the NP chimeric gene of human influenza virus was developed; Asp16 was replaced by Gly by means of "site-oriented" mutagenesis in the above gene, after that, the A/WSN/33 (H1N1) mutant of human influenza virus with "avian" NP and with point mutation (Gly16) was developed by using the method of "reverse genetics". The "human" influenza virus with "avian" chimeric NP/Gly16 turned out to be viable but had a lower replication velocity versus its wild-nature counterpart. It is noteworthy, that the mutant virus caused the cellular apoptosis in the remote infection period the way the wild virus did; however, NP of the former was found to be resistant to cellular caspasas and was not subject to proteolysis in infected cells. The conclusion is that Asp16 in NP molecule of human IAV is involved into the regulation process of virus replication and is the key element in NP proteolysis by cellular caspasas in cells' apoptosis.

A region responsible for protease binding by influenza virus (Flu) matrix protein M1 was identified. Trypsin binding was attributed to the N-terminal 9-kDa fragment obtained by hydrolyzing M1 with formic acid. The binding was inhibited by monoclonal antibodies (mAb) to the N-terminal moiety and by antiserum to region 21-45 of M1, whereas mAb to the middle and C-terminal regions had no effect. Thus, the protease-binding domain (PBD) was mapped to the N-terminal moiety of M1.