Ocean weather, biological rates, and unexplained global ecological patterns.

As on land, oceans exhibit high temporal and spatial temperature variation. This "ocean weather" contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (<12.5 m) across different zones of latitude. We collated hundreds of in situ, high temporal-frequency ocean temperature time series globally to produce an intuitive measure of temperature variability, ranging in scale from quarter-diurnal to annual time spans. To estimate organismal sensitivity of ectotherms (i.e. microbes, algae, and animals whose body temperatures depend upon ocean temperature), we computed the corresponding range of biological rates (such as metabolic rate or photosynthesis) for each time span, assuming an exponential relationship. We found that subtropical regions had the broadest temperature ranges at time spans equal to or shorter than a month, while temperate and tropical systems both exhibited narrow (i.e. stable) short-term temperature range estimates. However, temperature-dependent biological rates in tropical regions displayed greater ranges than in temperate systems. Hence, our results suggest that tropical ectotherms may be relatively more sensitive to short-term thermal variability. We also highlight previously unexplained macroecological patterns that may be underpinned by short-term temperature variability.

A sustainable blue economy may not be possible in Tanzania without cutting emissions.

Balancing blue growth with the conservation of wild species and habitats is a key challenge for global ocean management. This is exacerbated in Global South nations, such as Tanzania, where climate-driven ocean change requires delicate marine spatial planning (MSP) trade-offs to ensure climate resilience of marine resources relied upon by coastal communities. Here, we identified challenges and opportunities that climate change presents to the near-term spatial management of Tanzania's artisanal fishing sector, marine protected areas and seaweed farming. Specifically, spatial meta-analysis of climate modelling for the region was carried out to estimate the natural distribution of climate resilience in the marine resources that support these socially important sectors. We estimated changes within the next 20 and 40 years, using modelling projections forced under global emissions trajectories, as well as a wealth of GIS and habitat suitability data derived from globally distributed programmes. Multi-decadal analyses indicated that long-term climate change trends and extreme weather present important challenges to the activity of these sectors, locally and regionally. Only in few instances did we identify areas exhibiting climate resilience and opportunities for sectoral expansion. Including these climate change refugia and bright spots in effective ocean management strategies may serve as nature-based solutions: promoting adaptive capacity in some of Tanzania's most vulnerable economic sectors; creating wage-gaining opportunities that promote gender parity; and delivering some economic benefits of a thriving ocean where possible. Without curbs in global emissions, however, a bleak future may emerge for globally valuable biodiversity hosted in Tanzania, and for its coastal communities, despite the expansion of protected areas or curbs in other pressures. Growing a sustainable ocean economy in this part of the Global South remains a substantial challenge without global decarbonization.

Cross-basin and cross-taxa patterns of marine community tropicalization and deborealization in warming European seas.

Ocean warming and acidification, decreases in dissolved oxygen concentrations, and changes in primary production are causing an unprecedented global redistribution of marine life. The identification of underlying ecological processes underpinning marine species turnover, particularly the prevalence of increases of warm-water species or declines of cold-water species, has been recently debated in the context of ocean warming. Here, we track changes in the mean thermal affinity of marine communities across European seas by calculating the Community Temperature Index for 65 biodiversity time series collected over four decades and containing 1,817 species from different communities (zooplankton, coastal benthos, pelagic and demersal invertebrates and fish). We show that most communities and sites have clearly responded to ongoing ocean warming via abundance increases of warm-water species (tropicalization, 54%) and decreases of cold-water species (deborealization, 18%). Tropicalization dominated Atlantic sites compared to semi-enclosed basins such as the Mediterranean and Baltic Seas, probably due to physical barrier constraints to connectivity and species colonization. Semi-enclosed basins appeared to be particularly vulnerable to ocean warming, experiencing the fastest rates of warming and biodiversity loss through deborealization.

Incorporating climate-readiness into fisheries management strategies.

Tropical oceans are among the first places to exhibit climate change signals, affecting the habitat distribution and abundance of marine fish. These changes to stocks, and subsequent impacts on fisheries production, may have considerable implications for coastal communities dependent on fisheries for food security and livelihoods. Understanding the impacts of climate change on tropical marine fisheries is therefore an important step towards developing sustainable, climate-ready fisheries management measures. We apply an established method of spatial meta-analysis to assess species distribution modelling datasets for key species targeted by the Philippines capture fisheries. We analysed datasets under two global emissions scenarios (RCP4.5 and RCP8.5) and varying degrees of fishing pressure to quantify potential climate vulnerability of the target community. We found widespread responses to climate change in pelagic species in particular, with abundances projected to decline across much of the case study area, highlighting the challenges of maintaining food security in the face of a rapidly changing climate. We argue that sustainable fisheries management in the Philippines in the face of climate change can only be achieved through management strategies that allow for the mitigation of, and adaptation to, pressures already locked into the climate system for the near term. Our analysis may support this, providing fisheries managers with the means to identify potential climate change hotspots, bright spots and refugia, thereby supporting the development of climate-ready management plans.

Envolvimento dos pais na promoção do desenvolvimento infantil dos filhos / Parental involvement in promoting children's early childhood development

Sem resumo.

Genome-wide DNA methylation analysis in an antimigraine-treated preclinical model of cortical spreading depolarization.

BACKGROUND: Cortical spreading depolarization, the cause of migraine aura, is a short-lasting depolarization wave that moves across the brain cortex, transiently suppressing neuronal activity. Prophylactic treatments for migraine, such as topiramate or valproate, reduce the number of cortical spreading depression events in rodents. OBJECTIVE: To investigate whether cortical spreading depolarization with and without chronic treatment with topiramate or valproate affect the DNA methylation of the cortex. METHODS: Sprague-Dawley rats were intraperitoneally injected with saline, topiramate or valproate for four weeks when cortical spreading depolarization were induced and genome-wide DNA methylation was performed in the cortex of six rats per group. RESULTS: The DNA methylation profile of the cortex was significantly modified after cortical spreading depolarization, with and without topiramate or valproate. Interestingly, topiramate reduced by almost 50% the number of differentially methylated regions, whereas valproate increased them by 17%, when comparing to the non-treated group after cortical spreading depolarization induction. The majority of the differentially methylated regions lay within intragenic regions, and the analyses of functional group over-representation retrieved several enriched functions, including functions related to protein processing in the cortical spreading depolarization without treatment group; functions related to metabolic processes in the cortical spreading depolarization with topiramate group; and functions related to synapse and ErbB, MAPK or retrograde endocannabinoid signaling in the cortical spreading depolarization with valproate group. CONCLUSIONS: Our results may provide insights into the underlying physiological mechanisms of migraine with aura and emphasize the role of epigenetics in migraine susceptibility.

Identifying and protecting macroalgae detritus sinks toward climate change mitigation.

Harnessing natural solutions to mitigate climate change requires an understanding of carbon fixation, flux, and sequestration across ocean habitats. Recent studies have suggested that exported seaweed particulate organic carbon is stored within soft-sediment systems. However, very little is known about how seaweed detritus disperses from coastlines, or where it may enter seabed carbon stores, where it could become the target of conservation efforts. Here, focusing on regionally dominant seaweed species, we surveyed environmental DNA (eDNA) from natural coastal sediments, and studied their connectivity to seaweed habitats using a particle tracking model parameterized to reproduce seaweed detritus dispersal behavior based on laboratory observations of seaweed fragment degradation and sinking. Experiments showed that seaweed detritus density changed over time, differently across species. This, in turn, modified distances traveled by released fragments until they reached the seabed for the first time, during model simulations. Dispersal pathways connected detritus from the shore to the open ocean but, importantly, also to coastal sediments, and this was reflected by field eDNA evidence. Dispersion pathways were also affected by hydrodynamic conditions, varying in space and time. Both the properties and timing of released detritus, individual to each macroalgal population, and short-term near-seabed and medium-term water-column transport pathways, are thus seemingly important in determining the connectivity between seaweed habitats and potential sedimentary sinks. Studies such as this one, supported by further field verification of sedimentary carbon sequestration rates and source partitioning, are still needed to help quantify the role of seaweed in the ocean carbon cycle. Such studies will provide vital evidence to inform on the potential need to develop blue carbon conservation mechanisms, beyond wetlands.

Epigenome-wide analysis of T-cell large granular lymphocytic leukemia identifies BCL11B as a potential biomarker.

BACKGROUND: The molecular pathogenesis of T-cell large granular lymphocytic leukemia (T-LGLL), a mature T-cell leukemia arising commonly from T-cell receptor αß-positive CD8+ memory cytotoxic T cells, is only partly understood. The role of deregulated methylation in T-LGLL is not well known. We analyzed the epigenetic profile of T-LGLL cells of 11 patients compared to their normal counterparts by array-based DNA methylation profiling. For identification of molecular events driving the pathogenesis of T-LGLL, we compared the differentially methylated loci between the T-LGLL cases and normal T cells with chromatin segmentation data of benign T cells from the BLUEPRINT project. Moreover, we analyzed gene expression data of T-LGLL and benign T cells and validated the results by pyrosequencing in an extended cohort of 17 patients, including five patients with sequential samples. RESULTS: We identified dysregulation of DNA methylation associated with altered gene expression in T-LGLL. Since T-LGLL is a rare disease, the samples size is low. But as confirmed for each sample, hypermethylation of T-LGLL cells at various CpG sites located at enhancer regions is a hallmark of this disease. The interaction of BLC11B and C14orf64 as suggested by in silico data analysis could provide a novel pathogenetic mechanism that needs further experimental investigation. CONCLUSIONS: DNA methylation is altered in T-LGLL cells compared to benign T cells. In particular, BCL11B is highly significant differentially methylated in T-LGLL cells. Although our results have to be validated in a larger patient cohort, BCL11B could be considered as a potential biomarker for this leukemia. In addition, altered gene expression and hypermethylation of enhancer regions could serve as potential mechanisms for treatment of this disease. Gene interactions of dysregulated genes, like BLC11B and C14orf64, may play an important role in pathogenic mechanisms and should be further analyzed.

Patient-Derived Multiple Myeloma 3D Models for Personalized Medicine-Are We There Yet?

Despite the wide variety of existing therapies, multiple myeloma (MM) remains a disease with dismal prognosis. Choosing the right treatment for each patient remains one of the major challenges. A new approach being explored is the use of ex vivo models for personalized medicine. Two-dimensional culture or animal models often fail to predict clinical outcomes. Three-dimensional ex vivo models using patients' bone marrow (BM) cells may better reproduce the complexity and heterogeneity of the BM microenvironment. Here, we review the strengths and limitations of currently existing patient-derived ex vivo three-dimensional MM models. We analyze their biochemical and biophysical properties, molecular and cellular characteristics, as well as their potential for drug testing and identification of disease biomarkers. Furthermore, we discuss the remaining challenges and give some insight on how to achieve a more biomimetic and accurate MM BM model. Overall, there is still a need for standardized culture methods and refined readout techniques. Including both myeloma and other cells of the BM microenvironment in a simple and reproducible three-dimensional scaffold is the key to faithfully mapping and examining the relationship between these players in MM. This will allow a patient-personalized profile, providing a powerful tool for clinical and research applications.

Multiple Myeloma-Derived Extracellular Vesicles Modulate the Bone Marrow Immune Microenvironment.

Multiple myeloma (MM), the third most frequent hematological cancer worldwide, is characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM). One of the hallmarks of MM is a permissive BM microenvironment. Increasing evidence suggests that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line, MOPC315.BM, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as granzyme B and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment.

4D marine conservation networks: Combining 3D prioritization of present and future biodiversity with climatic refugia.

Given the accelerating rate of biodiversity loss, the need to prioritize marine areas for protection represents a major conservation challenge. The three-dimensionality of marine life and ecosystems is an inherent element of complexity for setting spatial conservation plans. Yet, the confidence of any recommendation largely depends on shifting climate, which triggers a global redistribution of biodiversity, suggesting the inclusion of time as a fourth dimension. Here, we developed a depth-specific prioritization analysis to inform the design of protected areas, further including metrics of climate-driven changes in the ocean. Climate change was captured in this analysis by considering the projected future distribution of >2000 benthic and pelagic species inhabiting the Mediterranean Sea, combined with climatic stability and heterogeneity metrics of the seascape. We identified important areas based on both biological and climatic criteria, where conservation focus should be given in priority when designing a three-dimensional, climate-smart protected area network. We detected spatially concise, conservation priority areas, distributed around the basin, that protected marine areas almost equally across all depth zones. Our approach highlights the importance of deep sea zones as priority areas to meet conservation targets for future marine biodiversity, while suggesting that spatial prioritization schemes, that focus on a static two-dimensional distribution of biodiversity data, might fail to englobe both the vertical properties of species distributions and the fine and larger-scale impacts associated with climate change.

Invasive and Subcutaneous Infections Caused by Filamentous Fungi: Report from a Portuguese Multicentric Surveillance Program.

Invasive fungal infections (IFI) have significantly increased over the past years due to advances in medical care for the at-risk immunocompromised population. IFI are often difficult to diagnose and manage, and can be associated with substantial morbidity and mortality. This study aims to contribute to understanding the etiology of invasive and subcutaneous fungal infections, their associated risk factors, and to perceive the outcome of patients who developed invasive disease, raising awareness of these infections at a local level but also in a global context. A laboratory surveillance approach was conducted over a seven-year period and included: (i) cases of invasive and subcutaneous fungal infections caused by filamentous/dimorphic fungi, confirmed by either microscopy or positive culture from sterile samples, (ii) cases diagnosed as probable IFI according to the criteria established by EORTC/MSG when duly substantiated. Fourteen Portuguese laboratories were enrolled. Cases included in this study were classified according to the new consensus definitions of invasive fungal diseases (IFD) published in 2020 as follows: proven IFI (N = 31), subcutaneous fungal infection (N = 23). Those proven deep fungal infections (N = 54) totalized 71.1% of the total cases, whereas 28.9% were classified as probable IFI (N = 22). It was possible to identify the etiological fungal agent in 73 cases (96%). Aspergillus was the most frequent genera detected, but endemic dimorphic fungi represented 14.47% (N = 11) of the total cases. Despite the small number of cases, a high diversity of species were involved in deep fungal infections. This fact has implications for clinical and laboratory diagnosis, and on the therapeutic management of these infections, since different species, even within the same genus, can present diverse patterns of susceptibility to antifungals.

Effect of the Lights4Violence intervention on the sexism of adolescents in European countries.

BACKGROUND: Sexism results in a number of attitudes and behaviors that contribute to gender inequalities in social structure and interpersonal relationships. The objective of this study was to evaluate the effectiveness of Lights4Violence, an intervention program based on promoting health assets to reduce sexist attitudes in young European people. METHODS: We carried out a quasi-experimental study in a non-probabilistic population of 1146 students, aged 12-17 years. The dependent variables were the difference in the wave 1 and wave 2 values in the subscales of the Ambivalent Sexism Inventory: benevolent sexism (BS) and hostile sexism (HS). The effect of the intervention was evaluated through linear regression analyses stratified by sex. The models were adjusted by baseline subscales scores, socio-demographic and psychological variables. RESULTS: In girls, we observed a decrease in BS in the intervention group compared to the control group (ß = - 0.101; p = 0.006). In the wave2,, BS decreased more in the intervention group compared to the control group in girls with mothers with a low level of education (ß = - 0.338; p = 0.001), with a high level of social support (ß = - 0.251; p < 0.001), with greater capacity for conflict resolution (ß = - 0.201; p < 0.001) and lower levels of aggressiveness (ß = - 0.232, p < 0.001). In boys, the mean levels of HS and BH decreased in wave 2 in both the control and intervention groups. The changes observed after the wave 2 were the same in the control group and in the intervention group. No significant differences were identified between both groups. CONCLUSIONS: The implementation of the Lights4Violence was associated with a significant reduction in BS in girls, which highlights the potential of interventions aimed at supporting the personal competencies and social support. It is necessary to reinforce the inclusion of educational contents that promote reflection among boys about the role of gender and the meaning of the attributes of masculinity. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03411564 . Unique Protocol ID: 776905. Date registered: 26-01-2018.

Bright spots as climate-smart marine spatial planning tools for conservation and blue growth.

Marine spatial planning that addresses ocean climate-driven change ('climate-smart MSP') is a global aspiration to support economic growth, food security and ecosystem sustainability. Ocean climate change ('CC') modelling may become a key decision-support tool for MSP, but traditional modelling analysis and communication challenges prevent their broad uptake. We employed MSP-specific ocean climate modelling analyses to inform a real-life MSP process; addressing how nature conservation and fisheries could be adapted to CC. We found that the currently planned distribution of these activities may become unsustainable during the policy's implementation due to CC, leading to a shortfall in its sustainability and blue growth targets. Significant, climate-driven ecosystem-level shifts in ocean components underpinning designated sites and fishing activity were estimated, reflecting different magnitudes of shifts in benthic versus pelagic, and inshore versus offshore habitats. Supporting adaptation, we then identified: CC refugia (areas where the ecosystem remains within the boundaries of its present state); CC hotspots (where climate drives the ecosystem towards a new state, inconsistent with each sectors' present use distribution); and for the first time, identified bright spots (areas where oceanographic processes drive range expansion opportunities that may support sustainable growth in the medium term). We thus create the means to: identify where sector-relevant ecosystem change is attributable to CC; incorporate resilient delivery of conservation and sustainable ecosystem management aims into MSP; and to harness opportunities for blue growth where they exist. Capturing CC bright spots alongside refugia within protected areas may present important opportunities to meet sustainability targets while helping support the fishing sector in a changing climate. By capitalizing on the natural distribution of climate resilience within ocean ecosystems, such climate-adaptive spatial management strategies could be seen as nature-based solutions to limit the impact of CC on ocean ecosystems and dependent blue economy sectors, paving the way for climate-smart MSP.

Benthic fauna contribute to microplastic sequestration in coastal sediments.

Microplastics are ubiquitous in the marine environment, however, the mechanisms governing their uptake by, and burial within, seabed habitats are poorly understood. In this study, microplastic burial and its impact on fauna-mediated sedimentary processes was quantified at three coastal sites, and the potential contribution of burrowing faunal communities to this process assessed via functional trait diversity analysis of field data. In addition, laboratory exposures were used to assess whether sediment-processing undertaken by the brittlestar Amphiura filiformis, a key species in the sampled area, could explain the burial of microplastic fibres. Field observations confirmed broad-scale burial of microplastics across the coastal seabed, consistent across sites and seasons, with microplastic sequestration linked to benthic-pelagic exchange pathways, driven by burrowing fauna. Brittlestars were observed to bury and line their burrow walls with microfibres during experiments, and their burial activity was also modified following exposure to nylon fibres, relative to controls. Collectively, these results indicate that biodiverse and functionally important seabed habitats act as microplastic sinks, with burrowing fauna contributing to this process via well-known benthic-pelagic pathways, the rates of which are modified by plastic exposure.

The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome.

We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive patient-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. Subsequently, we construct a DNA methylation-based mitotic clock called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in the differential diagnosis and prediction of clinical outcome.

DNA methylation profiles in chronic lymphocytic leukemia patients treated with chemoimmunotherapy.

BACKGROUND: In order to gain insight into the contribution of DNA methylation to disease progression of chronic lymphocytic leukemia (CLL), using 450K Illumina arrays, we determined the DNA methylation profiles in paired pre-treatment/relapse samples from 34 CLL patients treated with chemoimmunotherapy, mostly (n = 31) with the fludarabine-cyclophosphamide-rituximab (FCR) regimen. RESULTS: The extent of identified changes in CLL cells versus memory B cells from healthy donors was termed "epigenetic burden" (EB) whereas the number of changes between the pre-treatment versus the relapse sample was termed "relapse changes" (RC). Significant (p < 0.05) associations were identified between (i) high EB and short time-to-first-treatment (TTFT); and, (ii) few RCs and short time-to-relapse. Both the EB and the RC clustered in specific genomic regions and chromatin states, including regulatory regions containing binding sites of transcription factors implicated in B cell and CLL biology. CONCLUSIONS: Overall, we show that DNA methylation in CLL follows different dynamics in response to chemoimmunotherapy. These epigenetic alterations were linked with specific clinical and biological features.