Long-Term Continuous Corticosterone Treatment Decreases VEGF Receptor-2 Expression in Frontal Cortex

Objective: Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under longterm continuous glucocorticoid exposure has not been elucidated. Material and Methods: We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. Results: We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. Conclusions: The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecula

A global agenda for advancing freshwater biodiversity research

This manuscript is a contribution of the Alliance for Freshwater Life (www.allianceforfreshwaterlife.org). We thank Nick Bond, Lisa Bossenbroek, Lekima Copeland, Dean Jacobsen, Maria Cecilia Londo?o, David Lopez, Jaime Ricardo Garcia Marquez, Ketlhatlogile Mosepele, Nunia Thomas-Moko, Qiwei Wei and the authors of Living Waters: A Research Agenda for the Biodiversity of Inland and Coastal Waters for their contributions. We also thank Peter Thrall, Ian Harrison and two anonymous referees for their valuable comments that helped improve the manuscript. Open access funding enabled and organised by Projekt DEAL

Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease

Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation of neurotrophic factors in several areas of the central nervous system and in peripheral tissues are hallmarks of Huntington\u2019s disease (HD). As there is no therapy for this hereditary, neurodegenerative fatal disease, further effort should be made to slow the progression of neurodegeneration in patients through the definition of early therapeutic interventions. For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression and response to treatment need to be identified. In the attempt to contribute to the research of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing the HD mutation at different clinical stages of the disease and 54 sex- and agematched controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and premanifest HD subjects. Our results provide a potentially new candidate molecular biomarker for monitoring the progression of this disease and contribute to understanding some early events that might have a role in triggering cellular dysfunctions in HD

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation

A global agenda for advancing freshwater biodiversity research

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.Peer reviewe

Multi-decadal improvements in the ecological quality of European rivers are not consistently reflected in biodiversity metrics

Humans impact terrestrial, marine and freshwater ecosystems, yet many broad-scale studies have found no systematic, negative biodiversity changes (for example, decreasing abundance or taxon richness). Here we show that mixed biodiversity responses may arise because community metrics show variable responses to anthropogenic impacts across broad spatial scales. We first quantified temporal trends in anthropogenic impacts for 1,365 riverine invertebrate communities from 23 European countries, based on similarity to least-impacted reference communities. Reference comparisons provide necessary, but often missing, baselines for evaluating whether communities are negatively impacted or have improved (less or more similar, respectively). We then determined whether changing impacts were consistently reflected in metrics of community abundance, taxon richness, evenness and composition. Invertebrate communities improved, that is, became more similar to reference conditions, from 1992 until the 2010s, after which improvements plateaued. Improvements were generally reflected by higher taxon richness, providing evidence that certain community metrics can broadly indicate anthropogenic impacts. However, richness responses were highly variable among sites, and we found no consistent responses in community abundance, evenness or composition. These findings suggest that, without sufficient data and careful metric selection, many common community metrics cannot reliably reflect anthropogenic impacts, helping explain the prevalence of mixed biodiversity trends.We thank J. England for assistance with calculating ecological quality and the biomonitoring indices in the UK. Funding for authors, data collection and processing was provided by the European Union Horizon 2020 project eLTER PLUS (grant number 871128). F.A. was supported by the Swiss National Science Foundation (grant numbers 310030_197410 and 31003A_173074) and the University of Zurich Research Priority Program Global Change and Biodiversity. J.B. and M.A.-C. were funded by the European Commission, under the L‘Instrument Financier pour l’Environnement (LIFE) Nature and Biodiversity program, as part of the project LIFE-DIVAQUA (LIFE18 NAT/ES/000121) and also by the project ‘WATERLANDS’ (PID2019-107085RB-I00) funded by the Ministerio de Ciencia, Innovación y Universidades (MCIN) and Agencia Estatal de Investigación (AEI; MCIN/AEI/10.13039/501100011033/ and by the European Regional Development Fund (ERDF) ‘A way of making Europe’. N.J.B. and V.P. were supported by the Lithuanian Environmental Protection Agency (https://aaa.lrv.lt/) who collected the data and were funded by the Lithuanian Research Council (project number S-PD-22-72). J.H. was supported by the Academy of Finland (grant number 331957). S.C.J. acknowledges funding by the Leibniz Competition project Freshwater Megafauna Futures and the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung or BMBF; 033W034A). A.L. acknowledges funding by the Spanish Ministry of Science and Innovation (PID2020-115830GB-100). P.P., M.P. and M.S. were supported by the Czech Science Foundation (GA23-05268S and P505-20-17305S) and thank the Czech Hydrometeorological Institute and the state enterprises Povodí for the data used to calculate ecological quality metrics from the Czech surface water monitoring program. H.T. was supported by the Estonian Research Council (number PRG1266) and by the Estonian national program ‘Humanitarian and natural science collections’. M.J.F. acknowledges the support of Fundação para a Ciência e Tecnologia, Portugal, through the projects UIDB/04292/2020 and UIDP/04292/2020 granted to the Marine and Environmental Sciences Centre, LA/P/0069/2020 granted to the Associate Laboratory Aquatic Research Network (ARNET), and a Call Estímulo ao Emprego Científico (CEEC) contract.Peer reviewe

Hydromorphological restoration stimulates river ecosystem metabolism

Both ecosystem structure and functioning determine ecosystem status and are important for the provision of goods and services to society. However, there is a paucity of research that couples functional measures with assessments of ecosystem structure. In mid-sized and large rivers, effects of restoration on key ecosystem processes, such as ecosystem metabolism, have rarely been addressed and remain poorly understood. We compared three reaches of the third-order, gravel-bed river Ruhr in Germany: two reaches restored with moderate (R1) and substantial effort (R2) and one upstream degraded reach (D). Hydromorphology, habitat composition, and hydrodynamics were assessed. We estimated gross primary production (GPP) and ecosystem respiration (ER) using the one-station open-channel diel dissolved oxygen change method over a 50-day period at the end of each reach. Moreover, we estimated metabolic rates of the combined restored reaches (R1 + R2) using the two-station open-channel method. Values for hydromorphological variables increased with restoration intensity (D  <  R1  <  R2). Restored reaches had lower current velocity, higher longitudinal dispersion and larger transient storage zones. However, fractions of median travel time due to transient storage were highest in R1 and lowest in R2, with intermediate values in D. The share of macrophyte cover of total wetted area was highest in R2 and lowest in R1, with intermediate values in D. Station R2 had higher average GPP and ER than R1 and D. The combined restored reaches R1 + R2 also exhibited higher GPP and ER than the degraded upstream river (station D). Restoration increased river autotrophy, as indicated by elevated GPP : ER, and net ecosystem production (NEP) of restored reaches. Temporal patterns of ER closely mirrored those of GPP, pointing to the importance of autochthonous production for ecosystem functioning. In conclusion, high reach-scale restoration effort had considerable effects on river hydrodynamics and ecosystem functioning, which were mainly related to massive stands of macrophytes. High rates of metabolism and the occurrence of dense macrophyte stands may increase the assimilation of dissolved nutrients and the sedimentation of particulate nutrients, thereby positively affecting water quality

A Novel Gravity Wave Transport Parametrization for Global Chemistry Climate Models: Description and Validation

The gravity wave drag parametrization of the Whole Atmosphere Community Climate Model (WACCM) has been modified to include the wave-driven atmospheric vertical mixing caused by propagating, non-breaking, gravity waves. The strength of this atmospheric mixing is represented in the model via the “effective wave diffusivity” coefficient (Kwave). Using Kwave, a new total dynamical diffusivity (KDyn) is defined. KDyn represents the vertical mixing of the atmosphere by both breaking (dissipating) and vertically propagating (non-dissipating) gravity waves. Here we show that, when the new diffusivity is used, the downward fluxes of Fe and Na between 80 and 100 km largely increase. Larger meteoric ablation injection rates of these metals (within a factor 2 of measurements) can now be used in WACCM, which produce Na and Fe layers in good agreement with lidar observations. Mesospheric CO2 is also significantly impacted, with the largest CO2 concentration increase occurring between 80 and 90 km, where model-observations agreement improves. However, in regions where the model overestimates CO2 concentration, the new parametrization exacerbates the model bias. The mesospheric cooling simulated by the new parametrization, while needed, is currently too strong almost everywhere. The summer mesopause in both hemispheres becomes too cold by about 30 K compared to observations, but it shifts upward, partially correcting the WACCM low summer mesopause. Our results highlight the far-reaching implications and the necessity of representing vertically propagating non-breaking gravity waves in climate models. This novel method of modeling gravity waves contributes to growing evidence that it is time to move away from dissipative-only gravity wave parametrizations