Emergency laparotomy and endoscopic gastrostomy in patients on extra-corporeal membrane oxygenation (ECMO) support.

INTRODUCTION: An infrequent yet known complication of ECMO is abdominal compartment syndrome requiring emergency laparotomy. Also, the need for prolonged enteral nutrition while on ECMO may require endoscopic gastrostomy to maintain adequate nutritional status. Here we describe our experience with emergency laparotomy and endoscopic gastrostomy in patients on ECMO support. METHODS: We retrieved patient histories from our clinical archives and performed a retrospective description of all patients taken to an emergency laparotomy or endoscopic gastrostomy while on ECMO support at our cardiovascular referral center from July 2019 through June 2024. RESULTS: During the research period of 5 years a total of 401 patients were placed on ECMO support for either cardiogenic shock or respiratory failure. A total of 27 (7%) patients required an abdominal intervention while on ECMO. 14 (3.5%) patients required emergency laparotomy and 13 (3.2%) of patients required endoscopic gastrostomy tube placement. Overall 30-day mortality of all patients requiring a general surgery procedure while on ECMO support was 33%. CONCLUSION: ECMO support can result in many complications despite its many benefits. Patients who require emergency laparotomy while on ECMO have lower survival-to-discharge and higher mortality at 30 days. Endoscopic gastrostomy however, can be safely performed on ECMO with little to no bleeding complications despite anticoagulation.

Shifting stoichiometry: Long-term trends in stream-dissolved organic matter reveal altered C:N ratios due to history of atmospheric acid deposition.

Dissolved organic carbon (DOC) and nitrogen (DON) are important energy and nutrient sources for aquatic ecosystems. In many northern temperate, freshwater systems DOC has increased in the past 50 years. Less is known about how changes in DOC may vary across latitudes, and whether changes in DON track those of DOC. Here, we present long-term DOC and DON data from 74 streams distributed across seven sites in biomes ranging from the tropics to northern boreal forests with varying histories of atmospheric acid deposition. For each stream, we examined the temporal trends of DOC and DON concentrations and DOC:DON molar ratios. While some sites displayed consistent positive or negative trends in stream DOC and DON concentrations, changes in direction or magnitude were inconsistent at regional or local scales. DON trends did not always track those of DOC, though DOC:DON ratios increased over time for ~30% of streams. Our results indicate that the dissolved organic matter (DOM) pool is experiencing fundamental changes due to the recovery from atmospheric acid deposition. Changes in DOC:DON stoichiometry point to a shifting energy-nutrient balance in many aquatic ecosystems. Sustained changes in the character of DOM can have major implications for stream metabolism, biogeochemical processes, food webs, and drinking water quality (including disinfection by-products). Understanding regional and global variation in DOC and DON concentrations is important for developing realistic models and watershed management protocols to effectively target mitigation efforts aimed at bringing DOM flux and nutrient enrichment under control.

Stream Hydrology Controls the Longitudinal Bioreactive Footprint of Urban-Sourced Fine Particles.

The relevance of wastewater treatment plant (WWTP) effluents in fluvial networks is increasing as urbanization grows in catchments. Urban-sourced fine particles from WWTP effluents deposit and accumulate in the streambed sediment of receiving streams over time and can fuel respiration rates, which can thus potentially increase rates of biogeochemical reactions and CO2 emissions to the atmosphere. We aimed to provide a quantitative assessment of the influence of WWTP-sourced fine particles deposited in the streambed sediment on stream metabolic activity for 1 year in an intermittent Mediterranean stream. More nutrient-rich and metabolically active fine particle standing stocks were observed downstream of the WWTP, propagating to the end of the 820 m study reach, especially during the dry period (i.e., when the dilution capacity of the stream to WWTP inputs is <40%). Based on the longitudinal patterns of fine particle standing stocks and their metabolic activity, we estimated that the in-stream bioreactive capacity associated with these fine particles could potentially lead to substantial carbon dioxide emissions to the atmosphere (3.1 g C/m2/d). We show the importance of incorporating fine particle standing stocks downstream of point source inputs, particularly WWTPs in intermittent streams, into carbon budgets.

Effect of Three Emergent Macrophyte Species on Nutrient Retention in Aquatic Environments under Excess Nutrient Loading.

Emergent macrophyte species selection is critical for the effectiveness of nature-based engineered solutions aiming to address excess nutrient concentrations in freshwater ecosystems. Yet, the mechanisms with which macrophytes enhance nutrient retention need to be further understood. Here, we compared nutrient retention among 12 artificial flumes fed with effluents from a wastewater treatment plant and subjected to four treatments: absence of macrophytes (control) and presence of three different macrophyte species (Iris pseudacorus L., Phragmites australis L., and Schoenoplectus lacustris L.). We estimated the net and gross nutrient uptake based on the longitudinal profiles of ambient concentrations and on pulse injections of ammonium (NH4+) and soluble reactive phosphorus. Further, we investigated the influence of subsurface hydrological retention, attributed to the architectural differences in the roots of these macrophytes, on nutrient retention. Results showed a species-specific effect of macrophytes on nutrient retention and confirmed root-associated subsurface hydrological retention as a driving factor. Schoenoplectus showed both high net and gross NH4+ uptake, thereby being the most effective species to address N loading, compared to Iris and Phragmites. This work contributes to improve our mechanistic understanding of the role of emergent macrophytes on nutrient retention in aquatic environments.

Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy.

Diabetic nephropathy (DN) is a multifactorial disease characterized by hyperglycemia and close interaction of hemodynamic, metabolic and inflammatory factors. Nuclear factor-κB (NF-κB) is a principal matchmaker linking hyperglycemia and inflammation. The present work investigates the cell-permeable peptide containing the inhibitor of kappa B kinase γ (IKKγ)/NF-κB essential modulator (NEMO)-binding domain (NBD) as therapeutic option to modulate inflammation in a preclinical model of type 2 diabetes (T2D) with DN. Black and tan, brachyuric obese/obese mice were randomized into 4 interventions groups: Active NBD peptide (10 and 6 µg/g body weight); Inactive mutant peptide (10 µg/g); and vehicle control. In vivo/ex vivo fluorescence imaging revealed efficient delivery of NBD peptide, systemic biodistribution and selective renal metabolization. In vivo administration of active NBD peptide improved albuminuria (>40% reduction on average) and kidney damage, decreased podocyte loss and basement membrane thickness, and modulated the expression of proinflammatory and oxidative stress markers. In vitro, NBD blocked IKK-mediated NF-κB induction and target gene expression in mesangial cells exposed to diabetic-like milieu. These results constitute the first nephroprotective effect of NBD peptide in a T2D mouse model that recapitulates the kidney lesions observed in DN patients. Targeting IKK-dependent NF-κB activation could be a therapeutic strategy to combat kidney inflammation in DN.

Leachates from Helophyte Leaf-Litter Enhance Nitrogen Removal from Wastewater Treatment Plant Effluents.

Bioengineering techniques are currently used  in a wide variety of wastewater treatment systems. Aquatic plants (i.e., helophytes) used in these techniques reduce excess nitrogen (N) from water column via assimilation. Moreover, leachates from plant leaf-litter can serve as an additional source of labile dissolved organic matter (DOM), which can promote aerobic respiration and N removal via denitrification. We tested the influence of leaf-litter leachates from  Iris pseudacorus and Phragmites australis on the structure and activity of freshwater biofilms grown in flumes fed by effluent from a wastewater treatment plant (WWTP). The responses of the epilithic biofilm to the inputs of leaf-litter leachates were compared to those measured using a brewery byproduct rich in sugars and to the WWTP effluent water (i.e., control). All DOM sources significantly enhanced aerobic respiration and denitrification of the biofilm when compared to the controls, with increases in total microbial abundance but not in denitrifier abundance. The results suggest that metabolic activity of biofilms may be limited by bioavailability of DOM in WWTP effluent; and leaf-litter leachates of helophytes used in bioengineering techniques could alleviate this limitation by enhancing microbial N and C uptake.

The role of helophyte species on nitrogen and phosphorus retention from wastewater treatment plant effluents.

In the Mediterranean region, water scarcity compromises stream water quality particularly downstream of wastewater treatment plants (WWTP). We tested the potential of four helophyte species to reduce dissolved inorganic nitrogen (N) and phosphorus (P) from WWTP effluents. We conducted an 11-month mesocosm experiment to assess differences in N and P content among plant compartments and among species. Moreover, we quantified the relative contribution of above and belowground parts of the plants to N and P retention. The experiment was conducted at the Urban River Laboratory (www.urbanriverlab.com) in artificial channels (12 m long x 0.6 m wide x 0.4 m deep) planted with monospecific stands of Iris pseudoacorus, Typha angustifolia, Phragmites australis and Scirpus lacustris. Channels (three replicates per species) received water from the WWTP effluent, which flowed at a constant rate of 5 L min-1 through the sub-surface. The helophytes were planted in November 2014 and biomass standing stocks of carbon (C), N and P were measured in October 2015 at the time of maximum plant biomass. Differences in the concentration of N and P were larger among plant compartments than among species. The highest N concentration was measured in leaves while rhizomes showed the highest P concentration. The total plant biomass varied greatly among species from 11.4 to 4.6 Kg DW m-2 for Iris and Scirpus, respectively. Iris accumulated the highest amount of N (256 g N m-2) and P (27 g P m-2) in biomass. Plants retained from 8% (Scirpus) to 19% (Iris) of total dissolved inorganic N inputs to the channels (10.4 kg N) during the experiment, and from 6% (Phragmites) to 14% (Iris) of total dissolved inorganic P inputs (1.3 kg P). This study provides quantitative evidence to water managers of the potential role of helophytes to improve water quality in freshwater ecosystems receiving water from WWTP effluents.

SOCS1-targeted therapy ameliorates renal and vascular oxidative stress in diabetes via STAT1 and PI3K inhibition.

Oxidative stress resulting from excessive production of reactive oxygen species (ROS) or impaired antioxidant defenses is closely related to the development of diabetic vascular complications, including nephropathy and atherosclerosis. Chronic activation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to diabetic complications by inducing expression of genes involved in cell proliferation, fibrosis, inflammation, and oxidative stress. Suppressors of cytokine signaling (SOCS) family of endogenous JAK/STAT regulators is an attractive target for therapeutic intervention. We investigated the beneficial effect of two different SOCS1-targeted therapies (adenovirus-mediated gene transfer and kinase-inhibitory region peptidomimetic) to combat oxidative stress injury in an experimental diabetes model of concomitant renal and macrovascular disease (streptozotocin-induced diabetic apolipoprotein E-deficient mouse). Diabetes resulted in progressive alteration of redox balance in mice, as demonstrated by increased ROS levels and decreased antioxidant activity, which ultimately led to renal dysfunction and vascular injury. The molecular and pathological alterations in early diabetes were partially reversed by preventive intervention with SOCS1-targeted therapies. Importantly, SOCS1 peptidomimetic provided reno- and atheroprotection in diabetic mice even in a setting of established disease. Compared with untreated controls, kidney and aorta from SOCS1-treated mice exhibited significantly lower levels of superoxide anion, DNA oxidation marker and NADPH oxidase (Nox) subunits, along with higher expression of antioxidant enzymes. These trends correlated with a reduction in parameters of renal damage (albuminuria, creatinine and tubular injury), atherosclerosis (lesion size) and inflammation (leukocytes and chemokines). Mechanistic studies in renal, vascular and phagocytic cells exposed to cytokines and high-glucose showed that SOCS1 blocked ROS generation by inhibiting both Nox complex assembly and Nox subunit expression, an effect mediated by inactivation of JAK2, STAT1, and PI3K signaling pathways. This study provides evidence for SOCS1-targeted therapies, especially SOCS1 peptidomimetic, as an alternative antioxidant strategy to limit the progression of diabetic micro- and macrovascular complications.

Suppressor of Cytokine Signaling-1 Peptidomimetic Limits Progression of Diabetic Nephropathy.

Diabetes is the main cause of CKD and ESRD worldwide. Chronic activation of Janus kinase and signal transducer and activator of transcription (STAT) signaling contributes to diabetic nephropathy by inducing genes involved in leukocyte infiltration, cell proliferation, and extracellular matrix accumulation. This study examined whether a cell-permeable peptide mimicking the kinase-inhibitory region of suppressor of cytokine signaling-1 (SOCS1) regulatory protein protects against nephropathy by suppressing STAT-mediated cell responses to diabetic conditions. In a mouse model combining hyperglycemia and hypercholesterolemia (streptozotocin diabetic, apoE-deficient mice), renal STAT activation status correlated with the severity of nephropathy. Notably, compared with administration of vehicle or mutant inactive peptide, administration of the SOCS1 peptidomimetic at either early or advanced stages of diabetes ameliorated STAT activity and resulted in reduced serum creatinine level, albuminuria, and renal histologic changes (mesangial expansion, tubular injury, and fibrosis) over time. Mice treated with the SOCS1 peptidomimetic also exhibited reduced kidney leukocyte recruitment (T lymphocytes and classic M1 proinflammatory macrophages) and decreased expression levels of proinflammatory and profibrotic markers that were independent of glycemic and lipid changes. In vitro, internalized peptide suppressed STAT activation and target gene expression induced by inflammatory and hyperglycemic conditions, reduced migration and proliferation in mesangial and tubuloepithelial cells, and altered the expression of cytokine-induced macrophage polarization markers. In conclusion, our study identifies SOCS1 mimicking as a feasible therapeutic strategy to halt the onset and progression of renal inflammation and fibrosis in diabetic kidney disease.

Green light: gross primary production influences seasonal stream N export by controlling fine-scale N dynamics.

Monitoring nutrient concentrations at fine-scale temporal resolution contributes to a better understanding of nutrient cycling in stream ecosystems. However, the mechanisms underlying fine-scale nutrient dynamics and its implications for budget catchent fluxes are still poorly understood. To gain understanding of patterns and controls of fine-scale stream nitrogen (N) dynamics and to assess how they affect hydrological N fluxes, we explored diel variation in stream nitrate (NO3-) concentration along a headwater stream with increasing riparian area and channel width. At the downstream site, the highest day-night variations occurred in early spring, when stream NO3- concentrations were 13% higher at night than at daytime. Such day-night variations were strongly related to daily light inputs (R2 = 0.74) and gross primary production (GPP; R2 = 0.74), and they showed an excellent fit with day-night NO- variations predicted from GPP (R2 = 0.85). These results suggest that diel fluctuations in stream NO3- concentration were mainly driven by photoautotrophic N uptake. Terrestrial influences were discarded because no simultaneous diel variations in stream discharge, riparian groundwater level, or riparian solute concentration were observed. In contrast to the downstream site, no diel variations in NO3- concentration occurred at the upstream site, likely because water temperature was colder (10 degrees C vs. 12 degrees C) and light availability was lower (4 vs. 9 mol x m(-2) x d(-1)). Although daily GPP was between 10- and 100-fold lower than daily respiration, photoautotrophic N uptake contributed to a 10% reduction in spring NO3- loads at the downstream site. Our study clearly shows that the activity of photoautotrophs can substantially change over time and along the stream continuum in response to key environmental drivers such as light and temperature, and further, that its capacity to regulate diel and seasonal N fluxes can be important even in low-productivity streams.

Complex response of the forest nitrogen cycle to climate change.

Climate exerts a powerful influence on biological processes, but the effects of climate change on ecosystem nutrient flux and cycling are poorly resolved. Although rare, long-term records offer a unique opportunity to disentangle effects of climate from other anthropogenic influences. Here, we examine the longest and most complete record of watershed nutrient and climate dynamics available worldwide, which was collected at the Hubbard Brook Experimental Forest in the northeastern United States. We used empirical analyses and model calculations to distinguish between effects of climate change and past perturbations on the forest nitrogen (N) cycle. We find that climate alone cannot explain the occurrence of a dramatic >90% drop in watershed nitrate export over the past 46 y, despite longer growing seasons and higher soil temperatures. The strongest climate influence was an increase in soil temperature accompanied by a shift in paths of soil water flow within the watershed, but this effect explained, at best, only ∼40% of the nitrate decline. In contrast, at least 50-60% of the observed change in the N export could be explained by the long-lasting effect of forest cutting in the early 1900s on the N cycle of the soil and vegetation pools. Our analysis shows that historic events can obscure the influence of modern day stresses on the N cycle, even when analyses have the advantage of being informed by 0.5-century-long datasets. These findings raise fundamental questions about interpretations of long-term trends as a baseline for understanding how climate change influences complex ecosystems.

Benthic sediment as stores and sources of bacteria and viruses in streams: A comparison of baseflow vs. stormflow longitudinal transport and residence times.

The presence of bacteria and viruses in freshwater represents a global health risk. The substantial spatial and temporal variability of microbes leads to difficulties in quantifying the risks associated with their presence in freshwater. Fine particles, including bacteria and viruses are transported and accumulated into shallow streambed (i.e., benthic) sediment, delaying the downstream transmission during baseflow conditions but contributing to their resuspension and transport downstream during stormflow events. Direct measurements of pathogen accumulation in benthic sediments are rare. Until now, the dynamic role of benthic sediment as both a store and source of microbes, has not been quantified. In this study, we analyze microbial abundance in benthic sediment along a 1 km reach of an intermittent Mediterranean stream receiving inputs from the effluent of a wastewater treatment plant, a known point source of microbes in streams. We sampled benthic sediment during a summer drought when the wastewater effluent constituted 100 % of the stream flow, and thus, large accumulation and persistence of pathogens along the streambed was expected. We measured the abundance of total bacteria, Escherichia coli (as a fecal indicator), and presence of enteric rotavirus (RoV) and norovirus (NoV). The abundance of E. coli, based on qPCR detection, was high (4.99∙102 gc /cm2) along the first 100 m downstream of the wastewater effluent input and in general decreased with distance from the source, with presence of RoV and NoV along the study reach. A particle tracking model was applied, that uses stream water velocity as an input, and accounts for microbial exchange into, immobilization, degradation, and resuspension out of benthic sediment during baseflow and stormflow. Rates of exchange into benthic sediment were 3 orders of magnitude higher during stormflow, but residence times were proportionately lower, resulting in increased longitudinal connectivity from up to downstream during stormflow. Model simulations demonstrated mechanistically how the rates of exchange into and out of the benthic sediment resulted in benthic sediment to act as a store during baseflow and a source during stormflow.

The presence of activating IgG Fc receptors in macrophages aggravates the development of experimental abdominal aortic aneurysm. / La presencia de receptores Fc de IgG activadores en macrófagos agrava el desarrollo de aneurisma aórtico abdominal experimental.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a multifactorial, degenerative disease characterized by progressive aortic dilation and chronic activation of inflammation, proteolytic activity, and oxidative stress in the aortic wall. The immune response triggered by antibodies against antigens present in the vascular wall participates in the formation and progression of AAA through mechanisms not completely understood. This work analyses the function of specific IgG receptors (FcγR), especially those expressed by monocytes/macrophages, in the development of experimental AAA. METHODS: In the elastase-induced AAA model, the abdominal aortas from wildtype and FcγR deficient mice with/without macrophage adoptive transfer were analysed by histology and quantitative PCR. In vitro, mouse macrophages were transfected with RNA interference of FcγRIV/CD16.2 or treated with Syk kinase inhibitor before stimulation with IgG immune complexes. RESULTS: Macrophage adoptive transfer in FcγR deficient mice increased the susceptibility to AAA development. Mice receiving macrophages with functional FcγR exhibited higher aortic diameter increase, higher content of macrophages and B lymphocytes, and upregulated expression of chemokine CCL2, cytokines (TNF-α and IL-17), metalloproteinase MMP2, prooxidant enzyme NADPH oxidase-2, and the isoforms FcγRIII/CD16 and FcγRIV/CD16.2. In vitro, both FcγRIV/CD16.2 gene silencing and Syk inhibition reduced cytokines and reactive oxygen species production induced by immune complexes in macrophages. CONCLUSIONS: Activation of macrophage FcγR contributes to AAA development by inducing mediators of inflammation, proteolysis, and oxidative stress. Modulation of FcγR or effector molecules may represent a potential target for AAA treatment.

Pulse, Shunt and Storage: Hydrological Contraction Shapes Processing and Export of Particulate Organic Matter in River Networks.

Streams and rivers act as landscape-scale bioreactors processing large quantities of terrestrial particulate organic matter (POM). This function is linked to their flow regime, which governs residence times, shapes organic matter reactivity and controls the amount of carbon (C) exported to the atmosphere and coastal oceans. Climate change impacts flow regimes by increasing both flash floods and droughts. Here, we used a modelling approach to explore the consequences of lateral hydrological contraction, that is, the reduction of the wet portion of the streambed, for POM decomposition and transport at the river network scale. Our model integrates seasonal leaf litter input as generator of POM, transient storage of POM on wet and dry streambed portions with associated decomposition and ensuing changes in reactivity, and transport dynamics through a dendritic river network. Simulations showed that the amount of POM exported from the river network and its average reactivity increased with lateral hydrological contraction, due to the combination of (1) low processing of POM while stored on dry streambeds, and (2) large shunting during flashy events. The sensitivity analysis further supported that high lateral hydrological contraction leads to higher export of higher reactivity POM, regardless of transport coefficient values, average reactivity of fresh leaf litter and differences between POM reactivity under wet and dry conditions. Our study incorporates storage in dry streambed areas into the pulse-shunt concept (Raymond and others in Ecology 97(1):5-16, 2016. 10.1890/14-1684.1), providing a mechanistic framework and testable predictions about leaf litter storage, transport and decomposition in fluvial networks. Supplementary Information: The online version contains supplementary material available at 10.1007/s10021-022-00802-4.

Cyclic mimetics of kinase-inhibitory region of Suppressors of Cytokine Signaling 1: Progress toward novel anti-inflammatory therapeutics.

Herein we investigated the structural and cellular effects ensuing from the cyclization of a potent inhibitor of JAK2 as mimetic of SOCS1 protein, named PS5. The introduction of un-natural residues and a lactam internal bridge, within SOCS1-KIR motif, produced candidates that showed high affinity toward JAK2 catalytic domain. By combining CD, NMR and computational studies, we obtained valuable models of the interactions of two peptidomimetics of SOCS1 to deepen their functional behaviors. Notably, when assayed for their biological cell responses mimicking SOCS1 activity, the internal cyclic PS5 analogues demonstrated able to inhibit JAK-mediated tyrosine phosphorylation of STAT1 and to reduce cytokine-induced proinflammatory gene expression, oxidative stress generation and cell migration. The present study well inserts in the field of low-molecular-weight proteomimetics with improved longtime cellular effects and adds a new piece to the puzzled way for the conversion of bioactive peptides into drugs.

Fcγ receptor activation mediates vascular inflammation and abdominal aortic aneurysm development.

BACKGROUND: Abdominal aortic aneurysm (AAA), a degenerative vascular pathology characterized by permanent dilation of the aorta, is considered a chronic inflammatory disease involving innate/adaptive immunity. However, the functional role of antibody-dependent immune response against antigens present in the damaged vessel remains unresolved. We hypothesized that engagement of immunoglobulin G (IgG) Fc receptors (FcγR) by immune complexes (IC) in the aortic wall contributes to AAA development. We therefore evaluated FcγR expression in AAA lesions and analysed whether inhibition of FcγR signaling molecules (γ-chain and Syk kinase) influences AAA formation in mice. METHODS: FcγR gene/protein expression was assessed in human and mouse AAA tissues. Experimental AAA was induced by aortic elastase perfusion in wild-type (WT) mice and γ-chain knockout (γKO) mice (devoid of activating FcγR) in combination with macrophage adoptive transfer or Syk inhibitor treatment. To verify the mechanisms of FcγR in vitro, vascular smooth muscle cells (VSMC) and macrophages were stimulated with IgG IC. RESULTS: FcγR overexpression was detected in adventitia and media layers of human and mouse AAA. Elastase-perfused γKO mice exhibited a decrease in AAA incidence, aortic dilation, elastin degradation, and VSMC loss. This was associated with (1) reduced infiltrating leukocytes and immune deposits in AAA lesions, (2) inflammatory genes and metalloproteinases downregulation, (3) redox balance restoration, and (4) converse phenotype of anti-inflammatory macrophage M2 and contractile VSMC. Adoptive transfer of FcγR-expressing macrophages aggravated aneurysm in γKO mice. In vitro, FcγR deficiency attenuated inflammatory gene expression, oxidative stress, and phenotypic switch triggered by IC. Additionally, Syk inhibition prevented IC-mediated cell responses, reduced inflammation, and mitigated AAA formation. CONCLUSION: Our findings provide insight into the role and mechanisms mediating IgG-FcγR-associated inflammation and aortic wall injury in AAA, which might represent therapeutic targets against AAA disease.

Protective effect of suppressor of cytokine signalling 1-based therapy in experimental abdominal aortic aneurysm.

BACKGROUND AND PURPOSE: Abdominal aortic aneurysm (AAA) is a multifactorial disease characterized by chronic inflammation, oxidative stress and proteolytic activity in the aortic wall. Targeting JAK/signal transducer and activator of transcription (JAK/STAT) pathway is a promising strategy for chronic inflammatory diseases. We investigated the vasculo-protective role of suppressor of cytokine signalling-1 (SOCS1), the negative JAK/STAT regulator, in experimental AAA. EXPERIMENTAL APPROACH: A synthetic, cell permeable peptide (S1) mimic of SOCS1 kinase inhibitory domain to suppress STAT activation was evaluated in the well-established mouse model of elastase-induced AAA by monitoring changes in aortic diameter, cellular composition and gene expression in abdominal aorta. S1 function was further evaluated in cultured vascular smooth muscle cells (VSMC) and macrophages exposed to elastase or elastin-derived peptides. KEY RESULTS: S1 peptide prevented AAA development, evidenced by reduced incidence of AAA, aortic dilation and elastin degradation, partial restoration of medial VSMC and decreased inflammatory cells and oxidative stress in AAA tissue. Mechanistically, S1 suppressed STAT1/3 activation in aorta, down-regulated cytokines, metalloproteinases and altered the expression of cell differentiation markers by favouring anti-inflammatory M2 macrophage and contractile VSMC phenotypes. In vitro, S1 suppressed the expression of inflammatory and oxidative genes, reduced cell migration and reversed the phenotypic switch of macrophages and VSMC. By contrast, SOCS1 silencing promoted inflammatory response. CONCLUSION AND IMPLICATIONS: This preclinical study demonstrates the therapeutic potential of SOCS1-derived peptide to halt AAA progression by suppressing JAK/STAT-mediated inflammation and aortic dilation. S1 peptide may therefore be a valuable option for the treatment of AAA.

Towards women-inclusive ecology: Representation, behavior, and perception of women at an international conference.

Conferences are ideal platforms for studying gender gaps in science because they are important cultural events that reflect barriers to women in academia. Here, we explored women's participation in ecology conferences by analyzing female representation, behavior, and personal experience at the 1st Meeting of the Iberian Society of Ecology (SIBECOL). The conference had 722 attendees, 576 contributions, and 27 scientific sessions. The gender of attendees and presenters was balanced (48/52% women/men), yet only 29% of the contributions had a woman as last author. Moreover, men presented most of the keynote talks (67%) and convened most of the sessions. Our results also showed that only 32% of the questions were asked by women, yet the number of questions raised by women increased when the speaker or the convener was a woman. Finally, the post-conference survey revealed that attendees had a good experience and did not perceive the event as a threatening context for women. Yet, differences in the responses between genders suggest that women tended to have a worse experience than their male counterparts. Although our results showed clear gender biases, most of the participants of the conference failed to detect it. Overall, we highlight the challenge of increasing women's scientific leadership, visibility and interaction in scientific conferences and we suggest several recommendations for creating inclusive meetings, thereby promoting equal opportunities for all participants.

Wastewater treatment plant effluent inputs induce large biogeochemical changes during low flows in an intermittent stream but small changes in day-night patterns.

Wastewater treatment plant (WWTP) effluents alter stream water chemistry and metabolic activity. Yet, essential aspects influencing the biogeochemical response of receiving streams such as hydrology and diel oscillations of light and temperature remain largely unexplored. We measured day vs night water chemistry and in-stream net nutrient uptake velocity (Vf) in an intermittent forested stream, upstream and downstream of a WWTP effluent under contrasting hydrological conditions. The WWTP effluent negatively influenced stream water chemistry, especially during the dry period. Despite large diel oscillations in light inputs, day-night differences in nutrient and oxygen concentrations were small, suggesting that heterotrophic respiration drove stream metabolism with a minor contribution of gross primary production. The magnitude of Vf was similar between day and night at the two reaches. Yet, at the downstream reach, in-stream net DIN uptake occurred more often at night, and values of Vf for ammonia and nitrite indicated enhanced in-stream nitrification. The two reaches showed a small capacity to retain DIN and soluble reactive phosphorus from the water column. Positive values of in-stream net nutrient uptake (i.e. uptake > release) occurred mostly during the dry period, highlighting that in-stream biogeochemical processing can contribute to improve water quality in streams receiving point-sources effluents in regions with low water availability.

Antioxidant Effects of PS5, a Peptidomimetic of Suppressor of Cytokine Signaling 1, in Experimental Atherosclerosis.

The chronic activation of the Janus kinase/signal transducer and activator of the transcription (JAK/STAT) pathway is linked to oxidative stress, inflammation and cell proliferation. Suppressors of cytokine signaling (SOCS) proteins negatively regulate the JAK/STAT, and SOCS1 possesses a small kinase inhibitory region (KIR) involved in the inhibition of JAK kinases. Several studies showed that KIR-SOCS1 mimetics can be considered valuable therapeutics in several disorders (e.g., diabetes, neurological disorders and atherosclerosis). Herein, we investigated the antioxidant and atheroprotective effects of PS5, a peptidomimetic of KIR-SOCS1, both in vitro (vascular smooth muscle cells and macrophages) and in vivo (atherosclerosis mouse model) by analyzing gene expression, intracellular O2•- production and atheroma plaque progression and composition. PS5 was revealed to be able to attenuate NADPH oxidase (NOX1 and NOX4) and pro-inflammatory gene expression, to upregulate antioxidant genes and to reduce atheroma plaque size, lipid content and monocyte/macrophage accumulation. These findings confirm that KIR-SOCS1-based drugs could be excellent antioxidant agents to contrast atherosclerosis.