Nations' water footprints and virtual water trade of wood products

[EN] Several studies addressed the water footprint (WF) of countries and virtual water (VW) trade in agricultural and industrial products, but freshwater use associated with wood products has received little attention. Yet, international trade in wood products has been growing, and forestry competes with other forest ecosystem services over limited freshwater resources. Therefore, the objective of this paper is to assess nations' WFs of consumption of wood products, the sustainability of these WFs, and the VW flows associated with international trade in wood products. We account nations' WFs of and VW trade in wood products with a Multi-regional Input-Output model (MRIO-forest) that tracks wood flows along global supply chains (production, processing, trade, and final uses) for the period 1997-2017 and assess the sustainability of the green and blue WF of wood products in 2017. The WF of wood production increased from 8.37 x 1011 m(3)/y in 1997 to 9.87 x 1011 m(3)/y in 2017. About 38% (3.76 x 1011 m3/y) of this WF relates to wood products for export (in 2017), which means that VW trade associated with wood products ranks in between agricultural and industrial products in absolute volumes. About 10% (9.9 x 1010 m3/y) of the green WF and 11% (3.4 x 109 m3/y) of the blue WF of wood products in 2017 are unsustainable, meaning that they are located in areas where the total green/blue WF exceeds the maximum sustainable green/blue WF. The unsustainable green WF occurs mainly in Germany, Indonesia, the Czech Republic and the UK, and mainly relates to coniferous sawnwood, paper and paperboard other than newsprint, fibreboard and non-coniferous sawnwood. The unsustainable blue WF, which is much smaller, occurs in the USA, Russia. Nigeria, Canada and India, and mainly relates to fuelwood, paper and paperboard other than newsprint, sawnwood and fibreboard. This study increases our understanding of how forest evaporation flows link to the final consumption of wood products and contributes to the wider debate on the allocation of freshwater resources in the global economy.BC3 authors thank the support of the Spanish Ministry of Science, Innovation and Universities through the project Modeling and analysis of low carbon transitions (MALCON, RTI2018-099858-A-I00), and the Spanish State Research Agency through María de Maeztu Excellence Unit accreditation 2018-2022 (Ref. MDM-2017-0714, funded by MCIN/AEI/10.13039/501100011033/) and Basque Government BERC 2022-2025 Programme. I. Cazcarro thanks the support of the Spanish Ministry of Science, Innovation and Universities (State Research Agency. 2019 Call for R+D+i) PID2019-106822RB-I0 “Multisectoral and multiregional models, innovation and dynamics, for economic, social and environmental sustainability. J.F. Schyns was supported by funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (Earth@lternatives project, grant agreement No 834716). This article has been also a parallel study to one developed on land footprints under Letter of Agreement between the Food and Agriculture Organization of the United Nations (FAO, UN-REDD Programme) and the Basque Centre for Climate Change (BC3). BC3 authors thank the staff of the FAO and BC3 for their comments, discussions and suggestions related to forest data and policy. We are especially grateful to Malgorzata Buszko-Briggs and Tina Vahanen (FAO Forestry Department) for their contribution to frame and coordinate the research, and to Salar Tayyib, Daniela Di Filippo, Tomasz Filipczuk (FAO Statistics Division) and Arvydas Lebedys (FAO Forestry Department) for providing datasets and for their discussions and comments on data and methodological issues

Bayesian Networks for Decision-Making and Causal Analysis under Uncertainty in Aviation

Most decisions in aviation regarding systems and operation are currently taken under uncertainty, relaying in limited measurable information, and with little assistance of formal methods and tools to help decision makers to cope with all those uncertainties. This chapter illustrates how Bayesian analysis can constitute a systematic approach for dealing with uncertainties in aviation and air transport. The chapter addresses the three main ways in which Bayesian networks are currently employed for scientific or regulatory decision-making purposes in the aviation industry, depending on the extent to which decision makers rely totally or partially on formal methods. These three alternatives are illustrated with three aviation case studies that reflect research work carried out by the authors

Clinical proteomics in kidney disease as an exponential technology: Heading towards the disruptive phase

Exponential technologies double in power or processing speed every year, whereas their cost halves. Deception and disruption are two key stages in the development of exponential technologies. Deception occurs when, after initial introduction, technologies are dismissed as irrelevant, while they continue to progress, perhaps not as fast or with so many immediate practical applications as initially thought. Twenty years after the first publications, clinical proteomics is still not available in most hospitals and some clinicians have felt deception at unfulfilled promises. However, there are indications that clinical proteomics may be entering the disruptive phase, where, once refined, technologies disrupt established industries or procedures. In this regard, recent manuscripts in CKJ illustrate how proteomics is entering the clinical realm, with applications ranging from the identification of amyloid proteins in the pathology lab, to a new generation of urinary biomarkers for chronic kidney disease (CKD) assessment and outcome prediction. Indeed, one such panel of urinary peptidomics biomarkers, CKD273, recently received a Food and Drug Administration letter of support, the first ever in the CKD field. In addition, a must-read resource providing information on kidney disease-related proteomics and systems biology databases and how to access and use them in clinical decision-making was also recently published in CKJ.Grant support was received from: ISCIII and FEDER funds PI13/00047; EUTOX, CP12/03262, CP14/00133, PI15/00298, PI14/00386, PI15/01460, PI16/01900, PI16/02057; Diabetes Cancer Connect PIE13/00051; Sociedad Española de Nefrologia; FRIAT; and ISCIII-RETIC REDinREN RD016/009. Salary support was received from: ISCIII Miguel Servet to A.B.S., A.M.R. and M.D.S.-N.; Joan Rodes to B.F.-F; and Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to A.O

The role of PGC-1α and mitochondrial biogenesis in kidney diseases

Chronic kidney disease (CKD) is one of the fastest growing causes of death worldwide, emphasizing the need to develop novel therapeutic approaches. CKD predisposes to acute kidney injury (AKI) and AKI favors CKD progression. Mitochondrial derangements are common features of both AKI and CKD and mitochondria-targeting therapies are under study as nephroprotective agents. PGC-1α is a master regulator of mitochondrial biogenesis and an attractive therapeutic target. Low PGC-1α levels and decreased transcription of its gene targets have been observed in both preclinical AKI (nephrotoxic, endotoxemia, and ischemia-reperfusion) and in experimental and human CKD, most notably diabetic nephropathy. In mice, PGC-1α deficiency was associated with subclinical CKD and predisposition to AKI while PGC-1α overexpression in tubular cells protected from AKI of diverse causes. Several therapeutic strategies may increase kidney PGC-1α activity and have been successfully tested in animal models. These include AMP-activated protein kinase (AMPK) activators, phosphodiesterase (PDE) inhibitors, and anti-TWEAK antibodies. In conclusion, low PGC-1α activity appears to be a common feature of AKI and CKD and recent characterization of nephroprotective approaches that increase PGC-1α activity may pave the way for nephroprotective strategies potentially effective in both AKI and CKD.Supported by ISCIII-FIS, FEDER funds, CP14/00133, PI16/02057, PI16/01900, PI18/01366, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009, Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT), ISCIII Miguel Servet (A.B.S., M.D.S.-N.), ISCIII Sara Borrell (J.M.M.-M.), Comunidad de Madrid CIFRA2 B2017/BMD-3686 (M.F.-B. and D.M.-S.

Histone lysine crotonylation during acute kidney injury in mice

Acute kidney injury (AKI) is a potentially lethal condition for which no therapy is available beyond replacement of renal function. Posttranslational histone modifications modulate gene expression and kidney injury. Histone crotonylation is a recently described posttranslational modification. We hypothesized that histone crotonylation might modulate kidney injury. Histone crotonylation was studied in cultured murine proximal tubular cells and in kidneys from mice with AKI induced by folic acid or cisplatin. Histone lysine crotonylation was observedintubularcells from healthy murine and human kidney tissue. Kidney tissue histone crotonylation increased during AKI. This was reproducedbyexposure tothe protein TWEAK incultured tubular cells. Specifically, ChIP-seq revealed enrichment of histone crotonylation at the genes encoding the mitochondrial biogenesis regulator PGC-1α and the sirtuin-3 decrotonylase in both TWEAK-stimulated tubular cells and in AKI kidney tissue. To assess the role of crotonylation in kidney injury, crotonate was used to increase histone crotonylation in cultured tubular cells or in the kidneys in vivo. Crotonate increased the expression of PGC-1α and sirtuin-3, and decreased CCL2 expression in cultured tubular cells and healthy kidneys. Systemic crotonate administration protected from experimental AKI, preventing the decrease in renal function and in kidney PGC-1α and sirtuin-3 levels as well as the increase in CCL2 expression. For the first time, we have identified factors such as cell stress and crotonate availability that increase histone crotonylation in vivo. Overall, increasing histone crotonylation might have a beneficial effect on AKI. This is the first observation of the in vivo potential of the therapeutic manipulation of histone crotonylation in a disease state.This work was supported by the Instituto de Salud Carlos III (ISCIII) [grant numbers PI13/00047, PIE13/00051, PI14/00386, PI15/00298, CP12/03262, CP14/00133, RETIC REDinREN RD12/0021]; the European Regional Development Funds [Fondo Europeo de DesarrolloRegional (FEDER)]; European Uremic Toxin (EUTox) Work Group of the ESAO; the Sociedad Española de Nefrologia (SEN) [9749/002]; Comunidad de Madrid (CIFRA) [grant number S2010/BMD-2378]; and Fundación Renal Iñigo Álvarez de Toledo (FRIAT) [9749/001]. Salary support was provided by ISCIII Miguel Servet MS12/03262 and MS14/00133 to A.B.S. and M.D.S.-N., MECD to O.R.-A. and programa Intensificación Actividad Investigadora (ISCIII/Agencia Laı́n-Entralgo/CM) to A.O. IIS-FJD Biobank RD09/0076/0010

Molecular pathways driving omeprazole nephrotoxicity

Omeprazole, a proton pump inhibitor used to treat peptic ulcer and gastroesophageal reflux disease, has been associated to chronic kidney disease and acute interstitial nephritis. However, whether omeprazole is toxic to renal cells is unknown. Omeprazole has a lethal effect over some cancer cells, and cell death is a key process in kidney disease. Thus, we evaluated the potential lethal effect of omeprazole over tubular cells. Omeprazole induced dose-dependent cell death in human and murine proximal tubular cell lines and in human primary proximal tubular cell cultures. Increased cell death was observed at the high concentrations used in cancer cell studies and also at lower concentrations similar to those in peptic ulcer patient serum. Cell death induced by omeprazole had features of necrosis such as annexin V/7-AAD staining, LDH release, vacuolization and irregular chromatin condensation. Weak activation of caspase-3 was observed but inhibitors of caspases (zVAD), necroptosis (Necrostatin-1) or ferroptosis (Ferrostatin-1) did not prevent omeprazole-induced death. However, omeprazole promoted a strong oxidative stress response affecting mitochondria and lysosomes and the antioxidant N-acetyl-cysteine reduced oxidative stress and cell death. By contrast, iron overload increased cell death. An adaptive increase in the antiapoptotic protein BclxL failed to protect cells. In mice, parenteral omeprazole increased tubular cell death and the expression of NGAL and HO-1, markers of renal injury and oxidative stress, respectively. In conclusion, omeprazole nephrotoxicity may be related to induction of oxidative stress and renal tubular cell deathSupported by FIS CP12/03262, CP14/00133, PI16/02057, PI16/ 01900, PI18/01366, PI19/00588, PI19/00815, DTS18/00032, ERAPerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009 FEDER funds, Sociedad Española de Nefrología, Fundacion Renal Iñigo Álvarez de Toledo (FRIAT), ISCIII Miguel Servet (ABS, MDS-N), ISCIII Sara Borrell (JMM-M), Comunidad de Madrid CIFRA2 B2017/BMD-3686 (MF-B and DM-S

Urinary cyclophilin A as marker of tubular cell death and kidney injury

Background: Despite the term acute kidney injury (AKI), clinical biomarkers for AKI re-flect function rather than injury and independent markers of injury are needed. Tubular cell death, including necroptotic cell death, is a key feature of AKI. Cyclophilin A (CypA) is an intracellular protein that has been reported to be released during necroptosis. We have now explored CypA as a potential marker for kidney injury in cultured tubular cells and in clinical settings of ischemia-reperfusion injury (IRI), characterized by limitations of current diagnostic criteria for AKI. Meth-ods: CypA was analyzed in cultured human and murine proximal tubular epithelial cells exposed to chemical hypoxia, hypoxia/reoxygenation (H/R) or other cell death (apoptosis, necroptosis, fer-roptosis) inducers. Urinary levels of CypA (uCypA) were analyzed in patients after nephron sparing surgery (NSS) in which the contralateral kidney is not disturbed and kidney grafts with initial function. Results: Intracellular CypA remained unchanged while supernatant CypA increased in parallel to cell death induction. uCypA levels were higher in NSS patients with renal artery clamping (that is, with NSS-IRI) than in no clamping (NSS-no IRI), and in kidney transplantation (KT) recipients (KT-IRI) even in the presence of preserved or improving kidney function, while this was not the case for urinary Neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, higher uCypA levels in NSS patients were associated with longer surgery duration and the incidence of AKI increased from 10% when using serum creatinine (sCr) or urinary output criteria to 36% when using high uCypA levels in NNS clamping patients. Conclusions: CypA is released by kidney tubular cells during different forms of cell death, and uCypA increased during IRI-induced clinical kidney injury independently from kidney function parameters. Thus, uCypA is a potential bi-omarker of kidney injury, which is independent from decreased kidney functionResearch by the authors was funded by FIS/ FEDER funds (PI17/00257, PI18/01386, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Salary support: ISCIII Miguel Servet to A.B.S., MICIN Ramon y Cajal to M.D.S.-N., REDinREN RD016/0009 to M.F.-B.,SENEFRO to D.M.-S. and Consejería de Educación, Juventud y Deporte (Comunidad de Madrid/FSE) to A.M.L.-

TWEAK Activates the Non-Canonical NFκB Pathway in Murine Renal Tubular Cells: Modulation of CCL21

TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFκB activation suggestive of engagement of the non-canonical NFκB pathway. We now explore TWEAK-induced activation of NFκB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFα activated different DNA-binding NFκB complexes. TWEAK-induced sustained NFκB activation was associated with NFκB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFα used as control), induced a delayed increase in CCL21a mRNA (3.5±1.22-fold over control) and CCL21 protein (2.5±0.8-fold over control), which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFκB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFα. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h). In vivo, TWEAK induced nuclear NFκB2 and RelB translocation and CCL21a mRNA (1.5±0.3-fold over control) and CCL21 protein (1.6±0.5-fold over control) expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2±0.9 vs 1.3±0.6-fold over healthy control) or deficiency of TWEAK (2±0.9 vs 0.8±0.6-fold over healthy control). Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1±1.4 vs 1.8±1-fold over healthy control). Our results thus identify TWEAK as a regulator of non-canonical NFκB activation and CCL21 expression in tubular cells thus promoting lymphocyte recruitment to the kidney during acute injury