Search

Abstract Though new targeted therapies for colorectal cancer, which progresses from local intestinal tumors to metastatic disease, are being developed, tumor specificity remains an important problem, and side effects a major concern. Here, we show that the protein-fatty acid complex BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) can act as a peroral treatment for colorectal cancer. Apc Min/+ mice, which carry mutations relevant to hereditary and sporadic human colorectal cancer, that received BAMLET in the drinking water showed long-term protection against tumor development and decreased expression of tumor growth-, migration-, metastasis- and angiogenesis-related genes. BAMLET treatment via drinking water inhibited the Wnt/β-catenin and PD-1 signaling pathways and prolonged survival without evidence of toxicity. Systemic disease in the lungs, livers, spleens, and kidneys, which accompanied tumor progression, was inhibited by BAMLET treatment. The metabolic response to BAMLET included carbohydrate and lipid metabolism, which were inhibited in tumor prone Apc Min/+ mice and weakly regulated in C57BL/6 mice, suggesting potential health benefits of peroral BAMLET administration in addition to the potent antitumor effects. Together, these findings suggest that BAMLET administration in the drinking water maintains antitumor pressure by removing emergent cancer cells and reprogramming gene expression in intestinal and extra-intestinal tissues.

Throughout the world, emerging barriers in river systems block longitudinal connectivity for migrating fish, causing significant impacts by precluding them from carrying out vital life cycle activities. Fishways are still the main mitigation solution implemented, where barrier removal is not feasible. Within the multiple technical fish passage devices, the vertical slot fishway (VSF) is considered the most reliable. Early design guidelines, established for cyprinids, indicate that the volumetric dissipation power (Pv) in the pools should be Pv < 150 Wm−3, while most frequent slope values range from 10 to 12%. In this study, an experimental approach was conducted to question and debate the validity of these recommendations. For this, the Iberian barbel (Luciobarbus bocagei, Steindachner, 1864) passage performance was assessed in a full-scale fishway that exceeded Pv design guidelines, under different configurations. These varied in discharge (Q) and mean pool water depth (hm): VSF1 (Q = 81 Ls−1; hm = 0.55 m); VSF2 (Q = 110 Ls−1; hm = 0.80 m); and the same design was equipped with a deep notch: DN1 (Q = 71 Ls−1; hm = 0.55 m); DN2 (Q = 99 Ls−1; hm = 0.80 m). The slope was set to 15.2% while the head drop per pool was Δh = 0.28 m, which generated a Pv that ranged from 222 in VSF1 to 187 Wm−3 in DN2. Passage behaviour was assessed using PIT telemetry and time-to-event analysis to evaluate the barbel upstream passage using standardized metrics: (i) motivation (ii) ascend success, and (iii) transit time. The hydrodynamic scenarios experienced by fish were characterized through a numerical model using computational fluid dynamics (CFD). The results, contrary to what was expected, showed a higher performance in VSF1 confirmed by the ascent analysis and transit time. Although no differences were found in fish motivation, the results indicate that larger fish displayed lower times to perform the first passage attempt. The CFD results show that, although maximum velocities and turbulence (turbulent kinetic energy (TKE) and Reynolds shear stress (RSS)) do not change significantly between configurations, their distribution in the pools is quite different. Regarding TKE, larger volumes with magnitudes higher than 0.05 m2s−2 were notorious in both DN1 and DN2 configurations compared to VSF1, influencing passage efficiency which is in line with the ascent and transit time metrics results. Overall, the present research undeniably debates the literature design guidelines and reinforces the need to jointly assess species-specific fish passage criteria and fishway hydrodynamics, whereas precaution should be taken when using very general recommendations.

Hydropower can have significant impacts on riverine ecosystems due to hydropeaking (i.e., artificial rapid and short-term fluctuations in water flow and water levels downstream and upstream of hydropower stations) that negatively affect downstream fish. However, when it comes to analyzing species habitat use and availability above and below small hydropower plants (SHPPs), studies conducted at the microhabitat scale are scarcer, particularly in Mediterranean rivers. The goal of this study is to assess the seasonal (early and late summer) and size-related (juveniles and adults) microhabitat use by native fish above and below SHPPs. Fish were sampled by a modified point electrofishing procedure, and a multivariate approach was used to analyze microhabitat use and availability data from sites located upstream (reference) and downstream (disturbed) from two SHPPs in northeast Portugal. Cover and water depth were the most influential variables in the use of microhabitat for all species at both the reference and disturbed sites, although some differences in the variable rankings were found. Leuciscids exhibited similar patterns of non-random (i.e., selective) microhabitat use between the reference and the disturbed sites. Overall, the seasonal and size-related patterns in species microhabitat use were similar, with the majority of species displaying seasonal patterns in microhabitat use from early summer to late summer. This study showed that differences in fish microhabitat use between downstream SHPP and upstream reference sites were negligible. Cover might have had a significant role in tempering the effects of detrimental environmental conditions, namely, peaking flows, by providing hydraulic shelter, highlighting the need to maintain riparian vegetation strips and mosaics of submerged aquatic macrophytes, as well as the provision of coarse substrata that can be critical for fish. Future studies are needed to better clarify how different size classes of fish select microhabitats when facing past and present hydropeaking conditions.

River artificial fragmentation is arguably the most imperilling threat for freshwater-dependent fish species. Fish need to be able to freely move along river networks as not only spawning grounds but also refuge and feeding areas may be spatially and temporally separated. This incapacity of free displacement may result in genetic depletion of some populations, density reduction and even community changes, which may in turn affect how meta-community balances are regulated, potentially resulting in functional resilience reduction and ecosystem processes’ malfunction. Fishways are the most common and widely used method to improve connectivity for fish species. These structures allow fish to negotiate full barriers, thus reducing their connectivity impairment. Among all technical fishway types, vertical slot fishways (VSF) are considered to be the best solution, as they remain operational even with fluctuating water discharges and allow fish to negotiate each cross-wall at their desired depth. In the present study, we collected both published and original data on fish experiments within VSF, to address two questions, (1) What variables affect fish passage during experimental fishway studies? and (2) What is the best VSF configuration? We used Bayesian Generalized Mixed Models accounting for random effects of non-controlled factors, limiting inherent data dependencies, that may influence the model outcome. Results highlight that fish size, regardless of the species, is a good predictor of fishway negotiation success. Generally, multiple slot fishways with one orifice proved to be the best solution. Future work should be focused on small-sized fish to further improve the design of holistic fishways.

Background and Aims: Atherosclerosis and osteoporosis share common risk factors, as well as inflammatory mechanisms. Our aim was to understand how atherosclerotic lesions are related with disturbances in bone.Methods: Gene expression of pro-inflammatory and bone metabolism related proteins (IL-1β, IL-6, IL-17A, TNF, RANKL, OPG, COL1, CTSK, OCL, TRAP, CBFA1, DKK1, SOST, ADIPOQ, and ADIPOR1) were analyzed in arteries and bones from 45 deceased donors and adipose tissue was used as control. Additionally, in 139 patients with advanced atherosclerosis submitted to carotid endarterectomy we compared calcium content (Alizarin red) and plaque inflammatory scores (CD3+, CD68+, and adiponectin) of patients with normal bone mineral density (BMD) with those with low BMD and explored the associations between gene expression in atherosclerotic plaques and BMD. Serum levels of pro-inflammatory and bone related proteins were measured both in donors and patients. Associations were investigated by the Pearson or Spearman correlation tests, and multivariate regression analyzes were performed when justified.Results: Gene expression of bone remodeling and pro-inflammatory proteins correlated positively in bone and aorta, independently of age and sex of donors, but not in adipose tissue. The expression of bone formation genes was significantly higher in atheroma plaques from endarterectomized patients with normal vs. low BMD as well as inflammatory CD68+ scores, regardless of patients' age and sex, but not of body mass index. No relationship was observed between serum levels and gene expression levels of pro-inflammatory or bone remodeling proteins.Conclusions: Our results suggest that the relationship between bones and vessels in the context of atherosclerotic disease and osteoporosis may rely on the intrinsic connection between the tissues involved, independently of disease stage. Serum measurements of pro-inflammatory and bone-remodeling proteins do not accurately translate tissue pathologic processes.

Requalification of low-head ramped weirs through the addition of substrates (retrofitting) has attracted attention in recent years. However, few studies are available on how this measure affects the negotiation of ramped weirs by fish. This study aimed to assess the performance of an experimental ramped weir (3.00 m long with 10% slope; 0.30 m head-drop) to enhance the passage of a potamodromous cyprinid species, the Iberian barbel (Luciobarbus bocagei). Attention was given to testing the effects of the addition of a substrate, in this case cobbles, to the ramp (Nature) vs. a smooth bottom (Control), and discharge (Q; 55 L·s−1 and 110 L·s−1 (or specific discharge per unit width, q = 92 L·s−1·m−1 and 183 L·s−1·m−1)) on fish passage performance. Fish physiological responses to stress and fatigue, measured by glucose and lactate concentrations in blood samples, were also analysed. Results showed that the Nature design generally increased fish movements and successful upstream passages, and enhanced fish passage performance by enabling faster negotiations. Fish movements were also affected by increasing discharge, registering reductions with 110 L·s−1. Results of the physiological parameters indicate that both glucose and lactate concentrations were also influenced by discharge. The outcomes from this study present important information about fish passage performance across low-head ramped weirs and could provide data needed to help biologists and engineers to develop more effective structures to alleviate small instream obstacles.

In this study, the 3D numerical modelling of flow in a pool-type fishway with bottom orifices was performed using computational fluid dynamics (CFD) software (FLOW-3D®). Numerical results were compared with experimental data obtained from acoustic Doppler velocimetry (ADV) and particle image velocimetry (PIV) measurements. Several hydrodynamic variables that influence fishways efficiencies, such as flow depths, flow patterns, water velocity, turbulent kinetic energy, Reynolds normal stresses, and Reynolds shear stress parallel to the bottom component, were qualitatively and quantitatively compared. The numerical model accurately reproduced the complex flow field, showing an overall good agreement between the numerical model predictions and the experimental data for the analysed variables. The importance of performing a numerical model validation for all the parameters under analyses was highlighted. Additionally, scaling effects were analysed by running an upscaled numerical model of the prototype fishway. The model performed with similar accuracy for both physical model and prototype dimensions with no evidence of scale effects. The present study concludes that CFD models (namely FLOW-3D®) may be used as an adequate and efficient design and analysis tool for new pool-type fishways geometries, reducing and complementing physical model testing.

Pool-type fishways have been increasingly tested to improve fish passage performance and minimize migration delays. Designing cost-effective fishways is essential for a trade-off between water uses and successful longitudinal connectivity restoration. The multislot fishway (MSF) concept, which operates with 30–50% lower discharge than a vertical slot fishway (VSF), was recently developed. This study assessed and compared the entrance performance (entrance time; entry efficiency) and transit times of two cyprinids for VSFs and MSFs. Four configurations, with the same structural characteristics (slope; water depth; head drop; pool width and depth), operating with different discharges (Q), were tested (VSF 1: Q = 112 L·s−1; VSF 2: Q = 80 L·s−1; MSF 1: Q = 58 L·s−1; MSF 2: Q = 37 L·s−1). Hydrodynamics characterization was performed using a numerical model. Results showed that entry efficiency was higher in MSFs than in VSFs, while entrance time and transit time were overall lower. Numerical modelling revealed that velocities were around 30% lower in MSFs, and turbulence could reach a difference of around 70% in Reynolds shear stress and 50% in turbulent kinetic energy. Overall, MSFs can be considered as a cost-effective fishway solution that can balance the trade-offs between divergent interests in water uses.

The rapid river flow variations due to hydropower production during peak demand periods, known as hydropeaking, causes several ecological impacts. In this study, we assessed the potential of an overhead cover and velocity-refuge structure in an indoor flume as an indirect hydropeaking mitigation measure for the cyprinid species Iberian barbel (Luciobarbus bocagei). We designed a lab-scale LUNKERS-type structure using two different materials which were used separately: Wood (opaque) and acrylic (transparent), tested under hydropeaking and base-flow events. Physiological (glucose and lactate) and behavioral (structure use) responses were quantified. The structure use (inside and in the vicinity) and the individual and schooling behavior was assessed. Although there was no evidence that the hydropeaking event triggered a physiological response, the wood structure use was significantly higher than the acrylic one, where the metrics of use increased in the hydropeaking event. Differences between individual and group behavior were only higher for the entrances in the wood structure. The higher frequency of wood structure use under hydropeaking conditions suggests that the visual stimulus conferred by this shaded refuge enables fish to easily find it. The results suggest that the use of overhead and velocity-refuge structures may act as an effective hydropeaking flow-refuge mitigation measure.

The addition of substrates to small instream obstacles, like low-head ramped weirs, has been considered a useful management solution to retrofit those structures and enhance fish passage. Substrate dimensions and spatial arrangement, together with discharge, and consequently water depths, appear as important factors for the creation of hydrodynamic conditions that may facilitate the successful passage of fish, though related studies are scarce to support decision-making. This study assessed the influence of discharge (Q) and different retrofitting designs (RD) on the upstream passage performance of a potamodromous cyprinid, the Iberian barbel (Luciobarbus bocagei). Different substrates (small boulders, large boulders, cobbles) and spatial arrangements (aligned, offset) were tested. Numerical modelling was performed to characterize the hydrodynamics. Results indicate that Q and RD influenced the upstream negotiation of ramped weirs. Cobbles randomly distributed along the ramp (Nature design) was the most successful configuration, recording the highest number of upstream passages. Low velocities along the ramp, and low turbulence downstream, were registered in this configuration, indicating that the use of natural substrate may help to increase the permeability of ramped weirs to fish movements. The outcomes from this work can help engineers and biologists to design more appropriate passage structures for low-head instream obstacles.

Fluvial disturbances, especially floods and droughts, are the main drivers of the successional patterns of riparian vegetation. Those disturbances control the riparian landscape dynamics through the direct interaction between flow and vegetation. The main aim of this work is to investigate the specific paths by which fluvial disturbances, distributed by its components of groundwater hydrology (grndh) and morphodynamic disturbance (mrphd), drive riparian landscape patterns as characterized by the location (position in the river corridor) and shape (physical form of the patch) of vegetation patches in Mediterranean rivers. Specifically, this work assesses how the different components of fluvial disturbances affect these features in general and particularly in each succession phase of riparian vegetation. grndh and mrphd were defined by time and intensity weighted indexes calculated, respectively, from the mean annual water table elevations and the annual maximum instantaneous discharge shear stresses of the previous decade. The interactions between riparian landscape features and fluvial disturbances were assessed by confirmatory factor analysis using structural equation modeling. Two hypothetical models for patch location and shape were conceptualized and tested against empirical data collected from 220 patches at four different study sites. Both models were successfully fitted, meaning that they adequately depicted the relationships between the variables. Furthermore, the models achieved a good adjustment for the observed data, based on the evaluation of several approximate fit indexes. The patch location model explained approximately 80% of the patch location variability, demonstrating that the location of the riparian patches is primarily driven by grndh, while the mrphd had very little effect on this feature. In a multigroup analysis regarding the succession phases of riparian vegetation, the fitted model explained more than 68% of the variance of the data, confirming the results of the general model. The patch shape model explained nearly 13% of the patch shape variability, in which the disturbances came to have less influence on driving this feature. However, grndh continues to be the primary driver of riparian vegetation between the two disturbance factors, despite the proportional increase of the mrphd effect to approximately a third of the grndh effect.

Most fishway studies are conducted during the reproductive period, yet uncertainty remains on whether results may be biased if the same studies were performed outside of the migration season. The present study assessed fish passage performance of a potamodromous cyprinid, the Iberian barbel (Luciobarbus bocagei), in an experimental full-scale vertical slot fishway during spring (reproductive season) and early-autumn (non-reproductive season). Results revealed that no significant differences were detected on passage performance metrics, except for entry efficiency. However, differences between seasons were noted in the plasma lactate concentration (higher in early-autumn), used as a proxy for muscular fatigue after the fishway navigation. This suggests that, for potamodromous cyprinids, the evaluation of passage performance in fishways does not need to be restricted to the reproductive season and can be extended to early-autumn, when movements associated with shifts in home range may occur. The increased effort during the non-reproductive period suggests that adapting the operational regime of fishways, at biologically meaningful seasons in a year, should be assessed by considering the physiological state of the target species.

Global circulation models forecasts indicate a future temperature and rainfall pattern modification worldwide. Such phenomena will become particularly evident in Europe where climate modifications could be more severe than the average change at the global level. As such, river flow regimes are expected to change, with resultant impacts on aquatic and riparian ecosystems. Riparian woodlands are among the most endangered ecosystems on earth and provide vital services to interconnected ecosystems and human societies. However, they have not been the object of many studies designed to spatially and temporally quantify how these ecosystems will react to climate change-induced flow regimes. Our goal was to assess the effects of climate-changed flow regimes on the existing riparian vegetation of three different European flow regimes. Cases studies were selected in the light of the most common watershed alimentation modes occurring across European regions, with the objective of appraising expected alterations in the riparian elements of fluvial systems due to climate change. Riparian vegetation modeling was performed using the CASiMiR-vegetation model, which bases its computation on the fluvial disturbance of the riparian patch mosaic. Modeling results show that riparian woodlands may undergo not only at least moderate changes for all flow regimes, but also some dramatic adjustments in specific areas of particular vegetation development stages. There are circumstances in which complete annihilation is feasible. Pluvial flow regimes, like the ones in southern European rivers, are those likely to experience more pronounced changes. Furthermore, regardless of the flow regime, younger and more water-dependent individuals are expected to be the most affected by climate change.