Combined effects of river hydromorphological disturbances on macroinvertebrate communities: Multispatial scales analysis of central European rivers.

Hydro-morphological threats impact the natural physical characteristics of river ecosystems, such as flow regimes, sediment transport, and channel morphology. These negative effects can occur at multiple scales, ranging from local microhabitats to geographic regions. Understanding these interactions can be useful for an integrated conservation approach and is needed for effective freshwater management. The aim of the study was to elucidate the combined effects of hydro-morphological threats on macroinvertebrates at three spatial scales: macroscale, including whole catchments, mesoscale (hydro-morphological changes in individual river sections) and the microscale, describing the microhabitat conditions of European rivers. The diversity and trophic structure of 1120 local macroinvertebrate communities in 28 catchments of various hydro-morphological disturbance levels, ranging from 0 to 2400 m asl, were analyzed. The response of macroinvertebrates to the main disturbance gradient differed between mountain and lowland communities. Random forest analysis indicated that the most important predictor of the ecological, diversity, and trophic indices was described by flow rate reduction. Generalized additive mixed models showed that decreased flow combined with river incision explained most of the variation in macroinvertebrate indices. Our results emphasize that based on multi-spatial scale analysis, hydro-morphological threats are very important factors in invertebrates biodiversity loss. Thus, to implement effective river management, we should pay more attention to the combined effects of geomorphological threats.

Estimating effects of health policy interventions using interrupted time-series analyses: a simulation study.

BACKGROUND: A classic methodology used in evaluating the impact of health policy interventions is interrupted time-series (ITS) analysis, applying a quasi-experimental design that uses both pre- and post-policy data without randomization. In this paper, we took a simulation-based approach to estimating intervention effects under different assumptions. METHODS: Each of the simulated mortality rates contained a linear time trend, seasonality, autoregressive, and moving-average terms. The simulations of the policy effects involved three scenarios: 1) immediate-level change only, 2) immediate-level and slope change, and 3) lagged-level and slope change. The estimated effects and biases of these effects were examined via three matched generalized additive mixed models, each of which used two different approaches: 1) effects based on estimated coefficients (estimated approach), and 2) effects based on predictions from models (predicted approach). The robustness of these two approaches was further investigated assuming misspecification of the models. RESULTS: When one simulated dataset was analyzed with the matched model, the two analytical approaches produced similar estimates. However, when the models were misspecified, the number of deaths prevented, estimated using the predicted vs. estimated approaches, were very different, with the predicted approach yielding estimates closer to the real effect. The discrepancy was larger when the policy was applied early in the time-series. CONCLUSION: Even when the sample size appears to be large enough, one should still be cautious when conducting ITS analyses, since the power also depends on when in the series the intervention occurs. In addition, the intervention lagged effect needs to be fully considered at the study design stage (i.e., when developing the models).

YAP Circular RNA, circYap, Attenuates Cardiac Fibrosis via Binding with Tropomyosin-4 and Gamma-Actin Decreasing Actin Polymerization.

Cardiac fibrosis is a common pathological feature of cardiac hypertrophy. This study was designed to investigate a novel function of Yes-associated protein (YAP) circular RNA, circYap, in modulating cardiac fibrosis and the underlying mechanisms. By circular RNA sequencing, we found that three out of fifteen reported circYap isoforms were expressed in nine human heart tissues, with the isoform hsa_circ_0002320 being the highest. The levels of this isoform in the hearts of patients with cardiac hypertrophy were found to be significantly decreased. In the pressure overload mouse model, the levels of circYap were reduced in mouse hearts with transverse aortic constriction (TAC). Upon circYap plasmid injection, the cardiac fibrosis was attenuated, and the heart function was improved along with the elevation of cardiac circYap levels in TAC mice. Tropomyosin-4 (TMP4) and gamma-actin (ACTG) were identified to bind with circYap in cardiac cells and mouse heart tissues. Such bindings led to an increased TPM4 interaction with ACTG, resulting in the inhibition of actin polymerization and the following fibrosis. Collectively, our study uncovered a novel molecule that could regulate cardiac remodeling during cardiac fibrosis and implicated a new function of circular RNA. This process may be targeted for future cardio-therapy.

Multimodal Molecular Imaging of the Tumour Microenvironment.

The tumour microenvironment (TME) surrounding tumour cells is a highly dynamic and heterogeneous composition of immune cells, fibroblasts, precursor cells, endothelial cells, signalling molecules and extracellular matrix (ECM) components. Due to the heterogeneity and the constant crosstalk between the TME and the tumour cells, the components of the TME are important prognostic parameters in cancer and determine the response to novel immunotherapies. To improve the characterization of the TME, novel non-invasive imaging paradigms targeting the complexity of the TME are urgently needed.The characterization of the TME by molecular imaging will (1) support early diagnosis and disease follow-up, (2) guide (stereotactic) biopsy sampling, (3) highlight the dynamic changes during disease pathogenesis in a non-invasive manner, (4) help monitor existing therapies, (5) support the development of novel TME-targeting therapies and (6) aid stratification of patients, according to the cellular composition of their tumours in correlation to their therapy response.This chapter will summarize the most recent developments and applications of molecular imaging paradigms beyond FDG for the characterization of the dynamic molecular and cellular changes in the TME.

Intensified agriculture favors evolved resistance to biological control.

Increased regulation of chemical pesticides and rapid evolution of pesticide resistance have increased calls for sustainable pest management. Biological control offers sustainable pest suppression, partly because evolution of resistance to predators and parasitoids is prevented by several factors (e.g., spatial or temporal refuges from attacks, reciprocal evolution by control agents, and contrasting selection pressures from other enemy species). However, evolution of resistance may become more probable as agricultural intensification reduces the availability of refuges and diversity of enemy species, or if control agents have genetic barriers to evolution. Here we use 21 y of field data from 196 sites across New Zealand to show that parasitism of a key pasture pest (Listronotus bonariensis; Argentine stem weevil) by an introduced parasitoid (Microctonus hyperodae) was initially nationally successful but then declined by 44% (leading to pasture damage of c. 160 million New Zealand dollars per annum). This decline was not attributable to parasitoid numbers released, elevation, or local climatic variables at sample locations. Rather, in all locations the decline began 7 y (14 host generations) following parasitoid introduction, despite releases being staggered across locations in different years. Finally, we demonstrate experimentally that declining parasitism rates occurred in ryegrass Lolium perenne, which is grown nationwide in high-intensity was significantly less than in adjacent plots of a less-common pasture grass (Lolium multiflorum), indicating that resistance to parasitism is host plant-dependent. We conclude that low plant and enemy biodiversity in intensive large-scale agriculture may facilitate the evolution of host resistance by pests and threaten the long-term viability of biological control.

Temperature fluctuations inside savanna termite mounds: Do size and plant shade matter?

Mound building termites are key ecosystem engineers of subtropical savanna regions. Mounds allow termites to maintain suitable conditions for termite reproduction and food cultivation ('fungus gardens'). We studied how the internal mound temperature of Macrotermes natalensis, a dominant mound-building termite of the subtropical savanna of southern Africa, responds to a number of environmental variables. We used general additive mixed models (GAMM) to determine how external temperature, mound size (volume) and the amount of vegetation shade affects mound internal temperature over a 24-h period. Internal mound temperature varied daily following changes of the external temperature, although the range of variation was much smaller. Active termite mounds maintained a higher internal temperature than inactive ones, and mound activity reinforced the positive effect of mound size and moderated the negative effect of vegetation shade on internal temperatures. In turn, external temperature fluctuations equally affected active and inactive mounds. Large mounds maintained near optimal internal temperatures compared to smaller sized mounds. We therefore conclude that termite mound size is a stronger determinant of internal mound temperature stability compared to plant shade cover.

Multilook SAR Image Segmentation with an Unknown Number of Clusters Using a Gamma Mixture Model and Hierarchical Clustering.

This paper presents a novel multilook SAR image segmentation algorithm with an unknown number of clusters. Firstly, the marginal probability distribution for a given SAR image is defined by a Gamma mixture model (GaMM), in which the number of components corresponds to the number of homogeneous regions needed to segment and the spatial relationship among neighboring pixels is characterized by a Markov Random Field (MRF) defined by the weighting coefficients of components in GaMM. During the algorithm iteration procedure, the number of clusters is gradually reduced by merging two components until they are equal to one. For each fixed number of clusters, the parameters of GaMM are estimated and the optimal segmentation result corresponding to the number is obtained by maximizing the marginal probability. Finally, the number of clusters with minimum global energy defined as the negative logarithm of marginal probability is indicated as the expected number of clusters with the homogeneous regions needed to be segmented, and the corresponding segmentation result is considered as the final optimal one. The experimental results from the proposed and comparing algorithms for simulated and real multilook SAR images show that the proposed algorithm can find the real number of clusters and obtain more accurate segmentation results simultaneously.

Long-term phenological trends, species accumulation rates, aphid traits and climate: five decades of change in migrating aphids.

Aphids represent a significant challenge to food production. The Rothamsted Insect Survey (RIS) runs a network of 12·2-m suction-traps throughout the year to collect migrating aphids. In 2014, the RIS celebrated its 50th anniversary. This paper marks that achievement with an extensive spatiotemporal analysis and the provision of the first British annotated checklist of aphids since 1964. Our main aim was to elucidate mechanisms that advance aphid phenology under climate change and explain these using life-history traits. We then highlight emerging pests using accumulation patterns. Linear and nonlinear mixed-effect models estimated the average rate of change per annum and effects of climate on annual counts, first and last flights and length of flight season since 1965. Two climate drivers were used: the accumulated day degrees above 16 °C (ADD16) indicated the potential for migration during the aphid season; the North Atlantic Oscillation (NAO) signalled the severity of the winter before migration took place. All 55 species studied had earlier first flight trends at rate of ß = -0·611 ± SE 0·015 days year(-1). Of these species, 49% had earlier last flights, but the average species effect appeared relatively stationary (ß = -0·010 ± SE 0·022 days year(-1)). Most species (85%) showed increasing duration of their flight season (ß = 0·336 ± SE 0·026 days year(-1)), even though only 54% increased their log annual count (ß = 0·002 ± SE <0·001 year(-1)). The ADD16 and NAO were shown to drive patterns in aphid phenology in a spatiotemporal context. Early in the year when the first aphids were migrating, the effect of the winter NAO was highly significant. Further into the year, ADD16 was a strong predictor. Latitude had a near linear effect on first flights, whereas longitude produced a generally less-clear effect on all responses. Aphids that are anholocyclic (permanently parthenogenetic) or are monoecious (non-host-alternating) were advancing their phenology faster than those that were not. Climate drives phenology and traits help explain how this takes place biologically. Phenology and trait ecology are critical to understanding the threat posed by emerging pests such as Myzus persicae nicotianae and Aphis fabae cirsiiacanthoidis, as revealed by the species accumulation analysis.

Locating Nesting Sites for Critically Endangered Galápagos Pink Land Iguanas (Conolophus marthae).

Invasive alien species control is recognized worldwide as a priority action to preserve global biodiversity. However, a lack of general life history knowledge for threatened species can impede the effectiveness of conservation actions. Galápagos pink land iguanas (Conolophus marthae) are endemic to Wolf Volcano, Galápagos, Ecuador. These iguanas are threatened by invasive alien species, particularly feral cats, that may affect their small population size. To guarantee the long-term survival of C. marthae, the Galápagos National Park Directorate is considering, along with an ongoing campaign of feral cat control, the implementation of a head-start program. However, the success of this management strategy necessarily relies on the identification of pink iguana nesting grounds, which were still unknown at the onset of this study. We modeled the movement patterns of male and female iguanas during the reproductive season, using location data collected from custom-made remote tracking devices installed on adult pink iguanas in April 2021. We first calculated for each individual the vector of distances from its starting location, which was defined as net displacement. We then used net displacement as the response variable in a generalized additive mixed model with day of the year as the predictor. Based on the hypothesis that males and females may behaviorally differ after mating, we looked for female-specific migratory behavior suggesting females were moving toward nesting areas. The results obtained confirmed our hypothesis, as females exhibited a distinct migratory behavior, reaching a small plateau area inside of Wolf Volcano's caldera and ca. 400 m below the volcano's northern rim. Moreover, once inside the caldera, females displayed a more aggregated distribution pattern. The movement data obtained allowed Galápagos National Park rangers to locate individual pink iguana nests and subsequently to sight and collect the first observed hatchlings of the species. This work constitutes a necessary baseline to perform dedicated studies of pink iguana nests and emerging hatchling iguanas, which is an essential step toward the development of an effective head-start program.

Dual seasonal pattern for hemorrhagic fever with renal syndrome and its potential determinants in China.

Hemorrhagic fever with renal syndrome (HFRS) continued to affect human health across Eurasia, which complicated by climate change has posed a challenge for the disease prevention measures. Nation-wide surveillance data of HFRS cases were collected during 2008-2020.The seasonality and epidemiological features were presented by combining the HFRS incidence and the endemic types data. Factors potentially involved in affecting incidence and shaping disease seasonality were investigated by generalized additive mixed model, distributed lag nonlinear model and multivariate meta-analysis. A total of 76 cities that reported totally 111,054 cases were analyzed. Three endemic types were determined, among them the Type I cities (Hantaan virus-dominant) were related to higher incidence level, showing one spike every year in Autumn-Winter season; Type II (Seoul virus-dominant) cities were related to lower incidence, showing one spike in Spring, while Type III (Hantaan/Seoul-mixed type) showed dual peaks with incidence lying between. Persistently heavy rainfall had significantly negative influence on HFRS incidence in Hantaan virus-dominant endemic area, while a significantly opposite effect was identified when continuously heavy rainfall induced floods, where temperature and relative humidity affected HFRS incidence via an approximately parabolic or linear manner, however few or no such effects was shown in Seoul virus-dominant endemic areas, which was more vulnerable to temperature variation. Dual seasonal pattern of HFRS was depended on the dominant genotypes of hantavirus, and impact of climate on HFRS was greater in Hantaan virus-dominant endemic areas, than in Seoul virus-dominant areas.

Struggling with L2 alphabet: The role of proficiency in orthographic learning.

The present study examined the process of L2 orthographic learning in bilinguals with distant L1-L2 orthographies. Chinese-English bilinguals with various English proficiency levels were trained with novel L2 words during a reading task. In contrast to higher proficient learners, those with lower L2 proficiency exhibited increased effects of length, frequency, and lexicality across exposures and at-chance recognition of trained words. Importantly, an additional post-training task assessing the lexical integration of trained words evidenced the engagement in different L1-L2 reading strategies across different levels of L2 proficiency, hence suggesting the L1 holistic processing at the base of the effortful establishment of L2 orthographic representations shown by lower-proficient learners. Overall, these findings indicate the role of L2 proficiency in the influence that cross-linguistic variation exerts on L2 orthographic learning and highlight the need for English education programmes to tackle specific grapheme-to-phoneme skills in non-alphabetic target communities.

Role of Stereotactic Radiosurgery in Skull Base Paragangliomas - A Narrative Review.

Skull base paragangliomas, also known as glomus tumors, are grouped as glomus jugulare or glomus tympanicum. Paragangliomas are rare tumors, with an estimated incidence of 1 case per million persons. They occur more commonly in females and are more common in the fifth or sixth decade of life. Management of these tumors traditionally involved surgical excision. However, surgical excision can result in high complication rates, particularly cranial nerve palsies. Stereotactic radiosurgery has been shown to yield tumor control rates of more than 90%. A recent meta-analysis reported improvement in neurological status in 48.7% of cases, while it stabilized in 39.3% of patients. Transient deficits such as headache, nausea, vomiting, and hemifacial spasm developed following SRS in 5.8% of patients, while 2.1% of patients developed permanent deficits. There is no difference in the rate of tumor control between different radiosurgery techniques. Dose-fractionated SRS can be used for large tumors to decrease the risk of radiation-induced complications.

Historical analysis of an imperiled fish species: environmental variables modeling, biotic interactions, extirpation, and current restricted-range.

BACKGROUND: Analyses of spatial and temporal patterns and interactions are important for determining the abiotic factors limiting populations and the impact from other species and different anthropogenic stressors that promote the extirpation of species. The fish Hubbsina turneri de Buen (1940) was studied as a model species in a historical context at varying locations. Originally distributed only in the Lerma-Chapala basin, the main lake complex in Mexico, this species has not been collected from Lake Cuitzeo (LC) and now is restricted to Lake Zacapu (LZ). At present, the Highland splitfin is classified as critically endangered. METHODS: Historical information of LC and historical and current information from LZ were explored by applying cluster analysis and generalized additive mixed model (GAMM) to describe the biotic interactions among fish species and the relationship between density and environmental variables, respectively. The two lakes' contrasting abiotic/biotic characteristics provided elements to describe some species distribution limits in chemical ion gradients. Extirpation calendar dates were estimated using an optimal linear estimation method. Finally, a bibliographic review was conducted on the causes that promoted the extirpation and restriction of H. turneri and the prognosis for its reestablishment and conservation. RESULTS: Clusters showed the fishes relationship according to their distribution along the lakes. GAMM indicated that high H. turneri density is related to low hardness/fecal coliforms, medium depth/suspended solids, and high oxygen concentration. Estimated extirpation dates were between the years 2013 and 2018. The extirpation was linked to an abrupt drop in the LC volume, water quality degradation, increased biotic interactions within macrophytes habitats with native and introduced species, and fisheries bycatches. The current restricted range of H. turneri resulted from the draining of the larger lake, forcing the remaining populations to small spring-fed remnants. Recent samplings in LZ resulted in a low number of individuals. CONCLUSIONS: The integration of ecological interactions derived from statistical models, extirpation dates from nonparametric tests, and the exhaustive analysis of historical information can be applied to define the current situation of imperiled, ecologically relevant species, in different aquatic ecosystems. We are confident that this general framework is important for determining (1) the requirements and limitations of populations regarding abiotic variables, (2) biotic interactions (trophic and spatial) with native and introduced species, and (3) different anthropogenic stressors within and around the ecosystem. This knowledge will also allow understanding those aspects that contribute to the extirpation of populations and could help the restoration of the habitat and the reintroduction of extirpated species.

Harmful algae and climate change on the Canadian East Coast: Exploring occurrence predictions of Dinophysis acuminata, D. norvegica, and Pseudo-nitzschia seriata.

Harmful algal blooms (HABs) are a threat to human health, local economies, and coastal ecosystems. Generalized additive mixed models (GAMMs) were fitted using a 24-y database in order to predict future occurrences of three distinct species of HABs on the Canadian East Coast, the dinoflagellates Dinophysis acuminata and D. norvegica, and the diatom Pseudo-nitzschia seriata. GAMMs produced for each species were combined with two downscaled climate simulations (MPI-ESM-LR and CanESM2) under the representative concentration pathway (RCP) 8.5 over the 21st century. D. acuminata, D. norvegica, and P. seriata GAMMs were fitted using sea surface salinity and sea surface temperature, with wind speed averaged over seven days added to the P. seriata model. GAMMs succeeded at various degrees at reproducing past HAB events, with D. acuminata and D. norvegica being accurately modelled, and P. seriata producing less precise model results. Both climate simulations lead to similar conclusions in regards to the spatio-temporal shift in occurrences of the three studied species. D. acuminata and D. norvegica blooms (≥ 1000 cells L - 1) are predicted to increase in the future, whereas P. seriata bloom events (≥ 5000 cells L - 1) will tend to stabilise/decrease overall on the Canadian East Coast. Dinophysis blooms are most likely to increase in the St. Lawrence Estuary. Pseudo-nitzschia blooms will move to the northeastern part of the Gulf of St. Lawrence and will increase in the Bay of Fundy/Gulf of Maine regions. On average, earlier blooms and larger seasonal windows of opportunity are predicted across all species investigated. We conclude that changes in D. acuminata, D. norvegica, and P. seriata bloom dynamics and their spatial distributions could threaten aquaculture industries and ecosystem health on Canada's East Coast in localities and during seasons which were not previously impacted by these species.

Seasonality in daily movement patterns of mandrills revealed by combining direct tracking and camera traps.

Movement is a fundamental characteristic of animals, but challenging to measure noninvasively. Noninvasive methods for measuring travel have different weaknesses, so multiple techniques need to be applied multiple techniques for reliable inferences. We used two methods, direct tracking and camera trapping, to examine the variation in time and seasonal differences in movement rates of mandrills (Mandrillus sphinx), an elusive primate that lives in large groups in central Africa. In a 400-km2 rainforest area in Moukalaba-Doudou National Park, Gabon, we tracked unidentified groups 46 times from 2009 to 2013. We systematically placed 157 terrestrial camera traps in the same area from 2012 to 2014 and recorded groups 309 times. Generalized additive mixed models (GAMMs) of the tracking data indicated that the group travel speed varied with time and season. In the fruiting season, the movement rate fluctuated with time in a bimodal pattern, whereas in the nonfruiting season, it increased monotonously with time. The predicted day range was longer in the fruiting season (6.98 km) than in the nonfruiting season (6.06 km). These seasonal differences suggest responses to changes in food resources and temperature. Camera-trap detection rates showed similar temporal and seasonal patterns to the tracking data, allowing us to generalize our findings to the population level. Moreover, cameras never detected mandrills at night, and we observed that they slept high in trees and hardly moved until the next morning, all suggesting their strict avoidance of nighttime movement. This study demonstrated the significance of the multiple-method approach in drawing robust conclusions on temporal patterns of animal movement.

Le mouvement est une caractéristique fondamentale des animaux, mais il est difficile de le mesurer de manière non invasive. Les méthodes non invasives de mesure des déplacements présentent des faiblesses différentes, de sorte que nous devons appliquer plusieurs techniques à un même sujet pour obtenir des déductions fiables. Nous avons utilisé deux méthodes, le suivi direct et le piégeage photographique, pour examiner les variations temporelles et la différence saisonnière des taux de déplacement des mandrills (Mandrillus sphinx), un primate insaisissable vivant en grands groupes. Dans une zone de forêt tropicale humide de 400 km2 du parc national de Moukalaba-Doudou au Gabon, nous avons suivi des groupes non identifiés 46 fois entre 2009 et 2013. Dans la même zone, nous avons systématiquement placé 157 pièges photographiques terrestres de 2012 à 2014 et enregistré des groupes 309 fois. Les modèles mixtes additifs généralisés (GAMM) des données de suivi ont indiqué que la vitesse de déplacement des groupes variait en fonction du temps et des saison. Pendant la saison de fructification, la vitesse de déplacement fluctuait dans le temps selon un schéma bimodal, tandis que pendant la saison de non-fructification, elle augmentait de façon monotone avec le temps. Les distances journalières prédites étaient plus longues pendant la saison de fructification (6,98 km) que pendant la saison de non-fructification (6,06 km). Ces différences saisonnières suggèrent des réponses aux changements de ressources alimentaires et de température. Les taux de détection des pièges photographiques ont montré des tendances temporelles et saisonnières similaires à celles des données de suivi, ce qui nous permet de généraliser nos conclusions au niveau de la population. De plus, les caméras n'ont jamais détecté les mandrills la nuit, et nous avons observé qu'ils dormaient haut dans les arbres et ne bougeaient pratiquement pas jusqu'au lendemain matin, ce qui suggère qu'ils évitent strictement de se déplacer la nuit. Cette étude a démontré l'importance de l'approche à méthodes multiples pour tirer des conclusions solides sur les modes temporels de déplacement des animaux.

The protective role of tissue-resident interleukin 17A-producing gamma delta T cells in Mycobacterium leprae infection.

Mycobacterium leprae is a kind of disease-causing bacteria and results in leprosy in human. Gamma delta (γδ) T cell is a T-cell subset that is presented in both human dermis and epidermis. These cells bridge innate and adaptive immune responses and play critical roles in regulating anti-microbial defense, wound healing, and skin inflammation. Here, we investigated skin resident γδ T cells in patients with leprosy. Our data showed that γδ T cells significantly accumulated in skin lesions of leprosy patients with tuberculoid (TT) form. IL-23 can predominantly stimulate dermal γδ T cells to produce interleukin 17 (IL-17), a cytokine which may lead to disease protection. These γδ T cells expressed a specific set of surface molecules, and majority of these cells were Vδ1+. Also, IL-23 can stimulate the expansion of dermal γδ T cells expansion. Moreover, our results revealed that the transcription factor RORγt was responsible for IL-17A expression in leprosy lesion. Therefore, these data indicated that IL-23-responsive dermal γδ T cells were the major resource of IL-17A production in the skin and could be a potential target in the treatment of leprosy.

Climate regime shifts and biodiversity redistribution in the Bay of Biscay.

Global ocean warming, wave extreme events, and accelerating sea-level rise are challenges that coastal communities must address to anticipate damages in coming decades. The objective of this study is to undertake a time-series analysis of climate change (CC) indicators within the Bay of Biscay, including the Basque coast. We used an integrated and flexible methodology, based on Generalized Additive Mixed Models, to detect trends on 19 indicators (including marine physics, chemistry, atmosphere, hydrology, geomorphology, biodiversity, and commercial species). The results of 87 long-term time series analysed (~512,000 observations), in the last four decades, indicate four groups of climate regime shifts: 1) A gradual shift associated with CC starting in the 1980s, with a warming of the sea surface down to 100 m depth in the bay (0.10-0.25 °C per decade), increase in air temperature and insolation. This warming may have impacted on benthic community redistribution in the Basque coast, favouring warm-water species relative to cold-water species. Weight at age for anchovy and sardine decreased in the last two decades. 2) Deepening of the winter mixed layer depth in the south-eastern bay that probably led to increases in nutrients, surface oxygen, and chlorophyll concentration. Current increases on chlorophyll and zooplankton (i.e., copepods) biomass are contrary to those expected under CC scenarios in the region. 3) Sea-level rise (1.5-3.5 cm per decade since 1990s), associated with CC. 4) Increase of extreme wave height events of 16.8 cm per decade in the south-eastern bay, probably related to stormy conditions in the last decade, with impacts on beach erosion. Estimating accurate rates of sea warming, sea-level rise, extreme events, and foreseeing the future pathways of marine productivity, are key to define the best adaptation measures to minimize negative CC impacts in the region.

Interrogating Glioma-Associated Microglia and Macrophage Dynamics Under CSF-1R Therapy with Multitracer In Vivo PET/MRI.

Glioma-associated microglia and macrophages (GAMMs) are key players in creating an immunosuppressive microenvironment. They can be efficiently targeted by inhibiting the colony-stimulating factor 1 receptor (CSF-1R). We applied noninvasive PET/CT and PET/MRI using 18F-fluoroethyltyrosine (18F-FET) (amino acid metabolism) and N,N-diethyl-2-[4-(2-18F-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (18F-DPA-714) (translocator protein) to understand the role of GAMMs in glioma initiation, monitor in vivo therapy-induced GAMM depletion, and observe GAMM repopulation after drug withdrawal. Methods: C57BL/6 mice (n = 44) orthotopically implanted with syngeneic mouse GL261 glioma cells were treated with different regimens using the CSF-1R inhibitor PLX5622 (6-fluoro-N-((5-fluoro-2-methoxypyridin-3-yl)methyl)-5-((5-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)pyridin-2-amine) or vehicle, establishing a preconditioning model and a repopulation model, respectively. The mice underwent longitudinal PET/CT and PET/MRI. Results: The preconditioning model indicated similar tumor growth based on MRI (44.5% ± 24.8%), 18F-FET PET (18.3% ± 11.3%), and 18F-DPA-714 PET (16% ± 19.04%) volume dynamics in all groups, suggesting that GAMMs are not involved in glioma initiation. The repopulation model showed significantly reduced 18F-DPA-714 uptake (-45.6% ± 18.4%), significantly reduced GAMM infiltration even after repopulation, and a significantly decreased tumor volume (-54.29% ± 8.6%) with repopulation as measured by MRI, supported by a significant reduction in 18F-FET uptake (-50.2% ± 5.3%). Conclusion: 18F-FET and 18F-DPA-714 PET/MRI allow noninvasive assessment of glioma growth under various regimens of CSF-1R therapy. CSF-1R-mediated modulation of GAMMs may be of high interest as therapy or cotherapy against glioma.

Integration of Gas Exchange With Metabolomics: High-Throughput Phenotyping Methods for Screening Biostimulant-Elicited Beneficial Responses to Short-Term Water Deficit.

Biostimulants are emerging as a feasible tool for counteracting reduction in climate change-related yield and quality under water scarcity. As they are gaining attention, the necessity for accurately assessing phenotypic variables in their evaluation is emerging as a critical issue. In light of this, high-throughput phenotyping techniques have been more widely adopted. The main bottleneck of these techniques is represented by data management, which needs to be tailored to the complex, often multifactorial, data. This calls for the adoption of non-linear regression models capable of capturing dynamic data and also the interaction and effects between multiple factors. In this framework, a commercial glycinebetaine- (GB-) based biostimulant (Vegetal B60, ED&F Man) was tested and distributed at a rate of 6 kg/ha. Exogenous application of GB, a widely accumulated and documented stress adaptor molecule in plants, has been demonstrated to enhance the plant abiotic stress tolerance, including drought. Trials were conducted on tomato plants during the flowering stage in a greenhouse. The experiment was designed as a factorial combination of irrigation (water-stressed and well-watered) and biostimulant treatment (treated and control) and adopted a mixed phenotyping-omics approach. The efficacy of a continuous whole-canopy multichamber system coupled with generalized additive mixed modeling (GAMM) was evaluated to discriminate between water-stressed plants under the biostimulant treatment. Photosynthetic performance was evaluated by using GAMM, and was then correlated to metabolic profile. The results confirmed a higher photosynthetic efficiency of the treated plants, which is correlated to biostimulant-mediated drought tolerance. Furthermore, metabolomic analyses demonstrated the priming effect of the biostimulant for stress tolerance and detoxification and stabilization of photosynthetic machinery. In support of this, the overaccumulation of carotenoids was particularly relevant, given their photoprotective role in preventing the overexcitation of photosystem II. Metabolic profile and photosynthetic performance findings suggest an increased effective use of water (EUW) through the overaccumulation of lipids and leaf thickening. The positive effect of GB on water stress resistance could be attributed to both the delayed onset of stress and the elicitation of stress priming through the induction of H2O2-mediated antioxidant mechanisms. Overall, the mixed approach supported by a GAMM analysis could prove a valuable contribution to high-throughput biostimulant testing.

Imaging temozolomide-induced changes in the myeloid glioma microenvironment.

Rationale: The heterogeneous nature of gliomas makes the development and application of novel treatments challenging. In particular, infiltrating myeloid cells play a role in tumor progression and therapy resistance. Hence, a detailed understanding of the dynamic interplay of tumor cells and immune cells in vivo is necessary. To investigate the complex interaction between tumor progression and therapy-induced changes in the myeloid immune component of the tumor microenvironment, we used a combination of [18F]FET (amino acid metabolism) and [18F]DPA-714 (TSPO, GAMMs, tumor cells, astrocytes, endothelial cells) PET/MRI together with immune-phenotyping. The aim of the study was to monitor temozolomide (TMZ) treatment response and therapy-induced changes in the inflammatory tumor microenvironment (TME). Methods: Eighteen NMRInu/nu mice orthotopically implanted with Gli36dEGFR cells underwent MRI and PET/CT scans before and after treatment with TMZ or DMSO (vehicle). Tumor-to-background (striatum) uptake ratios were calculated and areas of unique tracer uptake (FET vs. DPA) were determined using an atlas-based volumetric approach. Results: TMZ therapy significantly modified the spatial distribution and uptake of both tracers. [18F]FET uptake was significantly reduced after therapy (-53 ± 84%) accompanied by a significant decrease of tumor volume (-17 ± 6%). In contrast, a significant increase (61 ± 33%) of [18F]DPA-714 uptake was detected by TSPO imaging in specific areas of the tumor. Immunohistochemistry (IHC) validated the reduction in tumor volumes and further revealed the presence of reactive TSPO-expressing glioma-associated microglia/macrophages (GAMMs) in the TME. Conclusion: We confirm the efficiency of [18F]FET-PET for monitoring TMZ-treatment response and demonstrate that in vivo TSPO-PET performed with [18F]DPA-714 can be used to identify specific reactive areas of myeloid cell infiltration in the TME.