The conservation, restoration, and improved management of terrestrial forests significantly contributes to mitigate climate change and its impacts, as well as providing numerous co-benefits. The ...pressing need to reduce emissions and increase carbon removal from the atmosphere is now also leading to the development of natural climate solutions in the ocean. Interest in the carbon sequestration potential of underwater macroalgal forests is growing rapidly among policy, conservation, and corporate sectors. Yet, our understanding of whether carbon sequestration from macroalgal forests can lead to tangible climate change mitigation remains severely limited, hampering their inclusion in international policy or carbon finance frameworks. Here, we examine the results of over 180 publications to synthesise evidence regarding macroalgal forest carbon sequestration potential. We show that research efforts on macroalgae carbon sequestration are heavily skewed towards particulate organic carbon (POC) pathways (77% of data publications), and that carbon fixation is the most studied flux (55%). Fluxes leading directly to carbon sequestration (e.g. carbon export or burial in marine sediments) remain poorly resolved, likely hindering regional or country-level assessments of carbon sequestration potential, which are only available from 17 of the 150 countries where macroalgal forests occur. To solve this issue, we present a framework to categorize coastlines according to their carbon sequestration potential. Finally, we review the multiple avenues through which this sequestration can translate into climate change mitigation capacity, which largely depends on whether management interventions can increase carbon removal above a natural baseline or avoid further carbon emissions. We find that conservation, restoration and afforestation interventions on macroalgal forests can potentially lead to carbon removal in the order of 10's of Tg C globally. Although this is lower than current estimates of natural sequestration value of all macroalgal habitats (61-268 Tg C year
), it suggests that macroalgal forests could add to the total mitigation potential of coastal blue carbon ecosystems, and offer valuable mitigation opportunities in polar and temperate areas where blue carbon mitigation is currently low. Operationalizing that potential will necessitate the development of models that reliably estimate the proportion of production sequestered, improvements in macroalgae carbon fingerprinting techniques, and a rethinking of carbon accounting methodologies. The ocean provides major opportunities to mitigate and adapt to climate change, and the largest coastal vegetated habitat on Earth should not be ignored simply because it does not fit into existing frameworks.
With the dramatic consequences of bacterial resistance to antibiotics, nanomaterials and molecular transporters have started to be investigated as alternative antibacterials or anti-infective carrier ...systems to improve the internalization of bactericidal drugs. However, the capability of nanomaterials/molecular transporters to overcome the bacterial cell envelope is poorly understood. It is critical to consider the sophisticated architecture of bacterial envelopes and reflect how nanomaterials/molecular transporters can interact with these envelopes, being the major aim of this review. The first part of this manuscript overviews the permeability of bacterial envelopes and how it limits the internalization of common antibiotic and novel oligonucleotide drugs. Subsequently we critically discuss the mechanisms that allow nanomaterials/molecular transporters to overcome the bacterial envelopes, focusing on the most promising ones to this end – siderophores, cyclodextrins, metal nanoparticles, antimicrobial/cell-penetrating peptides and fusogenic liposomes. This review may stimulate drug delivery and microbiology scientists in designing effective nanomaterials/molecular transporters against bacterial infections.
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Proteases are an integral part of plant defence systems, and their role in plant-pathogen interactions is unequivocal. Emerging evidence suggests that different protease families contribute to the ...establishment not only of hypersensitive response, priming, and signalling, but also of recognition events through complex proteolytic cascades. Moreover, they play a crucial role in pathogen/microbe-associated molecular pattern (PAMP/MAMP)-triggered immunity as well as in effector-triggered immunity. However, despite important advances in our understanding of the role of proteases in plant defence, the contribution of proteases to pathogen defence in grapevine remains poorly understood. In this review, we summarize current knowledge of the main grapevine pathosystems and explore the role of serine, cysteine, and aspartic proteases from both the host and pathogen point of views.
Objective
We aimed to explore the association between dehydroepiandrosterone sulphate (DHEAS) levels at age 7, pubertal development between ages 10 and 13, and age at menarche.
Design and ...participants
This is a longitudinal study of 603 individuals (301 girls, 302 boys) from the Generation XXI cohort.
Measurements
Evaluation of the participants at ages 7, 10 and 13 included anthropometry and Tanner staging. Pubertal development between ages 10 and 13 was categorized using latent class analysis, based on Tanner stages. The association between DHEAS at age 7 and pubertal development between ages 10 and 13 was conducted with binomial logistic regression, adjusted for BMI z‐score. The variation of age at menarche in relation to DHEAS levels at age 7, controlling for maternal age at menarche, birth weight z‐score and BMI z‐score, was estimated fitting a linear regression model.
Results
Pubertal development at ages 10−13 was categorized into two classes—Class 1 had a higher probability for the lower Tanner stage (less advanced sexual maturation) and Class 2 had a higher probability for the higher Tanner stage (more advanced sexual maturation). In girls, taking Class 1 as a reference, Class 2 was positively associated with BMI z‐score and DHEAS. In boys, Class 2 was positively associated with BMI, but not with DHEAS. DHEAS levels at age 7 were negatively associated with age at menarche, after adjustment for maternal age at menarche, birth weight and BMI.
Conclusion
In girls, but not in boys, DHEAS at age 7 was positively associated with more advanced pubertal development between ages 10 and 13, and with earlier age at menarche.
Herbivory is more prevalent in the tropics than at higher latitudes. If differences in ambient temperature are the direct cause for this phenomenon, then the same pattern should be visible in a ...seasonal gradient, as well as in experiments manipulating temperature. Using ¹⁵N stable isotope analyses of natural populations of the copepod Temora longicornis we indeed observed seasonal differences in the trophic level of the copepod and a decrease in trophic level with increasing temperature. In a grazing experiment, with a mixed diet of the cryptophyte Rhodomonas salina and the heterotrophic dinoflagellate Oxyrrhis marina, T. longicornis preferred the cryptophyte at higher temperatures, whereas at lower temperatures it preferred the non‐autotrophic prey. We explain these results by the higher relative carbon content of primary producers compared to consumers, in combination with the higher demand for metabolic carbon at higher temperatures. Thus, currently increasing temperatures may cause changes in dietary preferences of many consumers.
CD6 immunotherapy to treat psoriasis and rheumatoid arthritis has reached the clinical trial stage with apparent success, and targeting CD6 with mAbs is being used in several animal models of ...autoimmunity and neuroinflammation with promising indications. However, the mode of action of the therapeutic CD6 mAbs is far from being understood, reflecting the uncertainties and controversy surrounding the mechanistic and biological functions of CD6. Initially regarded as a co-stimulatory receptor of T lymphocytes, recent studies suggest that CD6 can instead modulate early as well as late T cell responses. Also, opposing the contribution of CD6 adhesiveness in the establishment and stabilization of immunological synapses, the actual triggering of CD6 might induce anti-proliferative signals to the T lymphocyte. CD6 has an unusually long cytoplasmic tail and its gene undergoes peculiar patterns of activation-dependent alternative splicing that can on one hand determine whether or not the CD6 protein binds to its ligand, and on the other include or exclude intracellular sequences that may transduce positive or negative signaling. In this review we discuss the multiple aspects that determine the nature of the signals transmitted via CD6 and the context that may define a dual role for this important T cell surface molecule.
Objective
To assess the influence of longitudinal weight gain from 0 to 4 years old on dehydroepiandrosterone sulphate (DHEAS) levels at 7 years old.
Design
DHEAS levels were measured at 7 years old ...in a subsample of 587 children from the Generation XXI birth cohort. Weight trajectories (0–4 years of age) were identified using model‐based clustering and categorized as “normal weight gain,” “weight gain during infancy,” “weight gain during childhood” and “persistent weight gain.”
Measurements
Differences in DHEAS levels at age 7 between the four weight trajectories were analysed through analysis of covariance (ANCOVA), adjusted for birth weight (BW) and body mass index (BMI).
Results
In the crude analysis, compared with the “normal weight gain” trajectory (5.53 (95% CI: 5.10–5.98 µmol/L), DHEAS levels were significantly higher in children in the “persistent weight gain” (8.75 95% CI: 7.23–10.49 µmol/L, p < .001 and in children in the “weight gain during infancy” trajectories (7.68 95% CI: 6.22–9.49 µmol/L, p = .021 and marginally significantly higher in children in the “weight gain during childhood” trajectory (6.89 (95% CI: 5.98–8.00) µmol/L; p = .052). In BW‐ and BMI‐adjusted model, a statistically significant difference in DHEAS levels was found between the “persistent weight gain” (7.93 95% CI: 6.43–9.86 µmol/L) and the “normal weight gain” trajectories (5.75 95% CI: 5.32–6.23 µmol/L; p = .039).
Conclusion
Higher DHEAS levels are found in 7‐year‐old children following a trajectory of persistent weight gain from 0 to 4 years, independently of their BW or current BMI, highlighting the impact of exposure to overweight in the first years of life on prepubertal adrenal androgen production.
Functional genomics approaches can overcome limitations-such as the lack of identification of robust targets and poor clinical efficacy-that hamper cancer drug development. Here we performed ...genome-scale CRISPR-Cas9 screens in 324 human cancer cell lines from 30 cancer types and developed a data-driven framework to prioritize candidates for cancer therapeutics. We integrated cell fitness effects with genomic biomarkers and target tractability for drug development to systematically prioritize new targets in defined tissues and genotypes. We verified one of our most promising dependencies, the Werner syndrome ATP-dependent helicase, as a synthetic lethal target in tumours from multiple cancer types with microsatellite instability. Our analysis provides a resource of cancer dependencies, generates a framework to prioritize cancer drug targets and suggests specific new targets. The principles described in this study can inform the initial stages of drug development by contributing to a new, diverse and more effective portfolio of cancer drug targets.
•Nine DNA MTase genes coding for 17 proteins were identified in grapevine.•Hypomethylation characterizes the beginning of the incompatible interaction.•The down-regulation of DNMT and CMT genes ...occurs at 6 hpi in the tolerant cultivar.
Epigenetic regulation has recently gained prominence in the field of plant-pathogen interactions, providing a deeper understanding of the molecular mechanisms associated with plant infection. In grapevine interaction with pathogens, epigenetic regulation still remains a black box. In this work, we characterized grapevine DNA methyltransferase gene family and identified nine DNA methyltransferases genes across eight grapevine chromosomes coding for 17 proteins. We also assessed the modulation of global cytosine methylation and gene expression levels of these genes with the aim of establishing a connection between DNA methylation and grapevine resistance towards downy mildew. Our results revealed that, in the incompatible interaction, an early hypomethylation, coupled with downregulation of DNMT and CMT genes occurs very early after pathogen inoculation. Additionally, the compatible interaction is characterized by a hypermethylation at 6hpi. A temporal delay is evident between the shifts in DNA methyltransferases gene expression in both compatible and incompatible interactions which in turn may be reflected in the global methylation percentage. Overall, we present the first evidence of an epigenetic regulation role in grapevine defense against P. viticola.
Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are ...important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, which will enable association studies of druggable genes for drug target selection and validation in human disease.
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