Explore the vast range of titles available.

Developing early warning signals to predict regime shifts in ecosystems is a central issue in current ecological research. While there are many studies addressing temporal early warning indicators, research into spatial indicators is far behind, with field experiments even more rare. Here, we tested the performance of spatial early warning signals in an intertidal macroalgal system, where removal of algal canopies pushed the system toward a tipping point (corresponding to approximately 75% of canopy loss), marking the transition between a canopy- to a turf-dominated state. We performed a two-year experiment where spatial early warning indicators were assessed in transects where the canopy was differentially removed (from 0 to 100%). Unlike Moran correlation coefficient at lag-1, spatial variance, skewness, and spatial spectra at low frequency increased along the gradient of canopy degradation and dropped, or did not show any further increase beyond the transition point from a canopy- to a turf-dominated state (100% canopy removal). Our study provides direct evidence of the suitability of spatial early warning signals to anticipate regime shifts in natural ecosystems, emphasizing the importance of field experiments as a powerful tool to establish causal relationships between environmental stressors and early warning indicators.

Triple Negative Breast Cancer (TNBC) is a heterogeneous disease lacking known molecular drivers and effective targeted therapies. Cytotoxic chemotherapy remains the mainstay of treatment for TNBCs, which have significantly poorer survival rates compared to other breast cancer subtypes. In addition to changes within the coding genome, aberrant enhancer activity is a well-established contributor to tumorigenesis. Here we use H3K27Ac chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map the active cis-regulatory landscape in TNBC. We identify distinct disease subtypes associated with specific enhancer activity, and over 2,500 unique superenhancers acquired by tumor cells but absent from normal breast tissue. To identify potential actionable disease drivers, we probed the dependency on genes that associate with tumor-specific enhancers by CRISPR screening. In this way we identify a number of tumor-specific dependencies, including a previously uncharacterized dependency on the TGFβ pseudo-receptor BAMBI.

Since their discovery in the late 1970s, protein kinase C (PKC) isozymes represent one of the most extensively studied signaling kinases. PKCs signal through multiple pathways and control the expression of genes relevant for cell cycle progression, tumorigenesis and metastatic dissemination. Despite the vast amount of information concerning the mechanisms that control PKC activation and function in cellular models, the relevance of individual PKC isozymes in the progression of human cancer is still a matter of controversy. Although the expression of PKC isozymes is altered in multiple cancer types, the causal relationship between such changes and the initiation and progression of the disease remains poorly defined. Animal models developed in the last years helped to better understand the involvement of individual PKCs in various cancer types and in the context of specific oncogenic alterations. Unraveling the enormous complexity in the mechanisms by which PKC isozymes have an impact on tumorigenesis and metastasis is key for reassessing their potential as pharmacological targets for cancer treatment.

Alpha-particle self-heating, the process of deuterium–tritium fusion reaction products depositing their kinetic energy locally within a fusion reaction region and thus increasing the temperature in the reacting region, is essential for achieving ignition in a fusion system. Here, we report new inertial confinement fusion experiments where the alpha-particle heating of the plasma is dominant with the fusion yield produced exceeding the fusion yield from the work done on the fuel (pressure times volume change) by a factor of two or more. These experiments have achieved the highest yield (26 ± 0.5 kJ) and stagnation pressures (≍220 ± 40 Gbar) of any facility-based inertial confinement fusion experiments, although they are still short of the pressures required for ignition on the National Ignition Facility (∼300–400 Gbar). These experiments put us in a new part of parameter space that has not been extensively studied so far because it lies between the no-alpha-particle-deposition regime and ignition. Inertial confinement fusion, based on laser-heating a deuterium–tritium mixture, is one of the approaches towards energy production from fusion reactions. Now, record energy-yield experiments are reported—bringing us closer to ignition conditions.

Artificial light at night (ALAN) is a globally spreading anthropogenic stressor, affecting more than 20% of coastal habitats. The alteration of the natural light/darkness cycle is expected to impact the physiology of organisms by acting on the complex circuits termed as circadian rhythms. Our understanding of the impact of ALAN on marine organisms is lagging behind that of terrestrial ones, and effects on marine primary producers are almost unexplored. Here, we investigated the molecular and physiological response of the Mediterranean seagrass, Posidonia oceanica (L.) Delile, as model to evaluate the effect of ALAN on seagrass populations established in shallow waters, by taking advantage of a decreasing gradient of dim nocturnal light intensity (from < 0.01 to 4 lx) along the NW Mediterranean coastline. We first monitored the fluctuations of putative circadian-clock genes over a period of 24 h along the ALAN gradient. We then investigated whether key physiological processes, known to be synchronized with day length by the circadian rhythm, were also affected by ALAN. ALAN influenced the light signalling at dusk/night in P. oceanica , including that of shorter blue wavelengths, through the ELF3 – LUX1 – ZTL regulatory network , and suggested that the daily perturbation of internal clock orthologs in seagrass might have caused the recruitment of PoSEND33 and PoPSBS genes to mitigate the repercussions of a nocturnal stress on photosynthesis during the day. A long-lasting impairment of gene fluctuations in sites characterised by ALAN could explain the reduced growth of the seagrass leaves when these were transferred into controlled conditions and without lighting during the night. Our results highlight the potential contribution of ALAN to the global loss of seagrass meadows, posing questions about key interactions with a variety of other human-related stressors in urban areas, in order to develop more efficient strategies to globally preserve these coastal foundation species.

HIGHLIGHTS Feeding rumen-protected choline (RPC) supports cow health and productivity, particularly during the transition period, with beneficial effects on resolving inflammation and modulating the antioxidant capacity. Choline metabolism is complex, and there are no standard bioavailability methods yet to assess the efficacy of protection technologies like lipid encapsulation and micro-encapsulation, the main methods for protecting choline from ruminal degradation. Microencapsulated RPC improved production responses, such as energy-corrected milk and prepartum DMI efficiency, compared to encapsulated RPC or control, with variations due to factors influencing choline bioavailability, such as product concentration and coating technology.

Aim Biological invasions are among the main threats to biodiversity. To promote a mechanistic understanding of the ecological impacts of non-native seaweeds, we assessed how effects on resident organisms vary according to their trophic level. Location Global. Methods We performed meta-analytical comparisons of the effects of non-native seaweeds on both individual species and communities. We compared the results of analyses performed on the whole dataset with those obtained from experimental data only and, when possible, between rocky and soft bottoms. Results Meta-analyses of data from 100 papers revealed consistent negative effects of non-native seaweeds across variables describing resident primary producer communities. In contrast, negative effects of seaweeds on consumers emerged only on their biomass and, limited to rocky bottoms, diversity. At the species level, negative effects were consistent across primary producers' response variables, while only the survival of consumers other than herbivores or predators (e.g. deposit/suspension feeders or detritivores) decreased due to invasion. Excluding mensurative data, negative effects of seaweeds persisted only on resident macroalgal communities and consumer species survival, while switched to positive on the diversity of rocky-bottom consumers. However, negative effects emerged for biomass and, in rocky habitats, density of consumers other than herbivores or predators. Main conclusions Our results support the hypothesis that seaweeds' effects on resident biodiversity are generally more negative within the same trophic level than on higher trophic guilds. Finer trophic grouping of resident organisms revealed more complex impacts than previously detected. High heterogeneity in the responses of some consumer guilds suggests that impacts of non-native seaweeds at higher trophic levels may be more invader- and species-specific than competitive effects at the same trophic level. Features of invaded habitats may further increase variability in seaweeds' impacts. More experimental data on consumers' response to invasion are needed to disentangle the effects of non-native seaweeds from those of other environmental stressors.

BackgroundA few case reports have shown controversial results of rituximab efficacy in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).ObjectiveTo analyse the efficacy of rituximab in a large CIDP cohort.MethodsA retrospective, observational and multicentre study on the use of rituximab in CIDP. 13 Italian CIDP patients were treated with rituximab after the partial or complete lack of efficacy of conventional therapies. Eight patients had co-occurring haematological diseases. Patients who improved by at least two points in standard clinical scales, or who reduced or discontinued the pre-rituximab therapies, were considered as responders.ResultsNine patients (seven with haematological diseases) responded to rituximab: six of them, who were non-responders to conventional therapies, improved clinically, and the other three maintained the improvement that they usually achieved with intravenous immunoglobulin or plasma exchange. Significantly associated with shorter disease duration, rituximab responses started after a median period of 2.0 months (range, 1–6) and lasted for a median period of 1 year (range, 1–5).ConclusionsRituximab seems to be a promising therapeutic choice when it targets both CIDP and co-occurring haematological diseases. Timely post-onset administration of rituximab seems to be associated with better responses.

For environmental monitoring and radioecological studies, organic and inorganic 129 I is often trapped in active charcoal. The analysis of this radionuclide can be difficult because of the low-level activities involved and its physico-chemical properties (e.g., volatility and multiple oxidation degrees). This study proposes a new method for 129 I analysis by ICP-MS/MS, which consists in the extraction of iodine from charcoal by acid digestion followed by purification using a commercial specific resin. This new method allows reaching environmental levels of gaseous 129 I near the fuel reprocessing plant of La Hague (France) with a limit of detection of only 2 mBq sample −1 .

Stars are giant thermonuclear plasma furnaces that slowly fuse the lighter elements in the universe into heavier elements, releasing energy, and generating the pressure required to prevent collapse. To understand stars, we must rely on nuclear reaction rate data obtained, up to now, under conditions very different from those of stellar cores. Here we show thermonuclear measurements of the 2 H(d, n) 3 He and 3 H(t,2n) 4 He S-factors at a range of densities (1.2–16?g?cm −3 ) and temperatures (2.1–5.4?keV) that allow us to test the conditions of the hydrogen-burning phase of main-sequence stars. The relevant conditions are created using inertial-confinement fusion implosions at the National Ignition Facility. Our data agree within uncertainty with previous accelerator-based measurements and establish this approach for future experiments to measure other reactions and to test plasma-nuclear effects present in stellar interiors, such as plasma electron screening, directly in the environments where they occur. Nuclear reactions taking place in stars are not straightforward to study in laboratories on Earth. Now, inertial-confinement fusion implosion experiments are reported that mimic the conditions for the hydrogen-burning phase in main-sequence stars.