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Intermediate filaments are critical for cell and tissue homeostasis and for stress responses. Cytoplasmic intermediate filaments form versatile and dynamic assemblies that interconnect cellular organelles, participate in signaling and protect cells and tissues against stress. Here we have focused on their involvement in redox signaling and oxidative stress, which arises in numerous pathophysiological situations. We pay special attention to type III intermediate filaments, mainly vimentin, because it provides a physical interface for redox signaling, stress responses and mechanosensing. Vimentin possesses a single cysteine residue that is a target for multiple oxidants and electrophiles. This conserved residue fine tunes vimentin assembly, response to oxidative stress and crosstalk with other cellular structures. Here we integrate evidence from the intermediate filament and redox biology fields to propose intermediate filaments as redox sentinel networks of the cell. To support this, we appraise how vimentin detects and orchestrates cellular responses to oxidative and electrophilic stress.

The consequences of plant–animal interactions often transcend the mere encounter stage, as those encounters are followed by a chain of subsequent stages on the plant's reproductive cycle that ultimately determine fitness. Yet, the dissemination and recruitment stages of animal-mediated seed dispersal are seldom analysed jointly, hindering a full understanding of the ecology of seed dispersal. We analyse the dispersal and recruitment of a fleshy-fruited plant (Pistacia lentiscus), from fruit production to seedling survival up to their second year. We link early reproductive investment of individual plants to seedling recruitment and explore the role played by seed viability, the coterie of frugivores and microhabitat seed deposition. The proportion of viable seeds was generally low (mean = 34%) but highly variable among individual plants (range: 0%–95%). Seed viability did not seem to have a direct effect on individual plant's recruitment. We recorded 28 bird species feeding on P. lentiscus fruits or seeds. Their contribution to plant recruitment was mainly determined by their intensity of fruit consumption and probability to disperse viable seeds. Most frugivores presented non-random microhabitat preferences, delivering uneven seed contributions to different sites. Post-dispersal seed predation by rodents was the most limiting phase in P. lentiscus recruitment. Yet, microhabitats showing the lowest predation rates received the lowest seed rain. Hence, we found a decoupling of the dissemination and recruitment stages: most seeds do not arrive at the most suitable microhabitats. We estimate P. lentiscus plants need to produce c. 5 × 105 fruits to recruit a single seedling that survives to its second summer in our study site. Its success as a prevalent species in Mediterranean lowland landscapes relies on its high fecundity and thorough fruit removal and dispersal by a diversified frugivore assemblage, which compensates for the high seed unviability characteristic of t

Intermediate filaments (IFs) are cytoskeletal elements involved in mechanotransduction and in the integration of cellular responses. They are versatile structures and their assembly and organization are finely tuned by posttranslational modifications. Among them, type III IFs, mainly vimentin, have been identified as targets of multiple oxidative and electrophilic modifications. A characteristic of most type III IF proteins is the presence in their sequence of a single, conserved cysteine residue (C328 in vimentin), that is a hot spot for these modifications and appears to play a key role in the ability of the filament network to respond to oxidative stress. Current structural models and experimental evidence indicate that this cysteine residue may occupy a strategic position in the filaments in such a way that perturbations at this site, due to chemical modification or mutation, impact filament assembly or organization in a structure-dependent manner. Cysteine-dependent regulation of vimentin can be modulated by interaction with divalent cations, such as zinc, and by pH. Importantly, vimentin remodeling induced by C328 modification may affect its interaction with cellular organelles, as well as the cross-talk between cytoskeletal networks, as seems to be the case for the reorganization of actin filaments in response to oxidants and electrophiles. In summary, the evidence herein reviewed delineates a complex interplay in which type III IFs emerge both as targets and modulators of redox signaling.

Radionuclides can provide key information on the temporal dimension of environmental processes, given their well-known rates of radioactive decay and production. Naturally occurring radionuclides, such as 234Th and 210Po, have been used as powerful particle tracers in the marine environment to study particle cycling and vertical export. Since their application to quantify the magnitude of particulate organic carbon (POC) export in the 1990s, 234Th and, to a lesser extent, 210Po have been widely used to characterize the magnitude of the biological carbon pump (BCP). Combining both radionuclides, with their different half-lives, biogeochemical behaviors, and input sources to the ocean, can help to better constrain POC export and capture BCP dynamics that would be missed by a single tracer. Here, we review the studies that have simultaneously used 234Th and 210Po as tracers of POC export, emphasizing what can be learned from their joint application, and provide recommendations and future directions

African swine fever virus (ASFV) belongs to the family of Asfarviridae, part of the group of nucleocytoplasmic large DNA viruses (NCLDV). Little is known about the internalization of ASFV in the host cell and the fusion membrane events that take place at early stages of the infection. Poxviruses, also members of the NCLDV and represented by vaccinia virus (VACV), are large, enveloped, double-stranded DNA viruses. Poxviruses were considered unique in having an elaborate entry-fusion complex (EFC) composed of 11 highly conserved proteins integrated into the membrane of mature virions. Recent advances in methodological techniques have again revealed several connections between VACV EFC proteins. In this study, we explored the possibility of an analogous ASFV EFC by identifying ten candidate proteins exhibiting structural similarities with VACV EFC proteins. This could reveal key functions of these ASFV proteins, drawing attention to shared features between the two virus families, suggesting the potential existence of an ASFV entry-fusion complex.

Amyotrophic lateral sclerosis is a fatal neurodegenerative disease without a cure to reverse its progression. Its main hallmark is the nuclear protein TDP-43, which undergoes different post-translational modifications leading to a loss of function in the nucleus and an increase in toxicity in the cytoplasm. Previous reports have indicated that pathogenic TDP-43 exhibits prion-like propagation in various contexts. With the aim of advancing therapeutics focused on preventing the propagation of TDP-43 pathology, we studied the potential role of pathogenic TDP-43 in lymphoblasts from sporadic ALS patients. We used lymphoblastoid cell lines from sporadic ALS patients as a source of pathogenic forms of TDP-43, and healthy human cells (lymphoblasts, myoblasts, neuroblastoma SH-SY5Y, or osteosarcoma U2OS) as recipient cells to investigate the seeding and spread of TDP-43 proteinopathy. Furthermore, we evaluated the potential of targeting TDP-43 phosphorylation with a CK-1 inhibitor to prevent the propagation of the pathology. The results presented herein indicate that pathogenic forms of TDP-43 are secreted into the extracellular medium of sporadic ALS lymphoblasts and could be transported by extracellular vesicles, spreading TDP-43 pathology to healthy cells. Moreover, tunneling nanotubes have also been discovered in pathological cells and may be involved in the transport of TDP-43. Interestingly, targeting TDP-43 phosphorylation with an in-house designed CK-1 inhibitor (IGS2.7) was sufficient to halt TDP-43 pathology transmission, in addition to its known effects on restoring the homeostasis of TDP-43 protein in patients-derived cells.

Electronic skins (e-skins), composed of various flexible sensors, mimic the sensing functions of human skin aiming for both healthcare monitoring and prosthetics development applications. So far different multi-component e-skin devices aimed to fulfill different requirements (biocompatibility, skin adhesion, flexibility, conductivity, sensitivity towards biological stimuli and stretchability) have been reported. However, the obtaining of such devices combining all the above requirements within a single material that simplifies not only cost but specially functioning still remains a challenge. For this, catechol-based materials have attracted special attention due to their adhesive properties, compatibility and melanin-like electrical conduction. In this work, 2,3,6,7,10,11 – hexahydroxy triphenylene (HHTP) was used as catechol moiety in a typical melanin-like polymerization, resulting in a free-standing melanin-inspired film (MN-film). The obtained MN-film showcased good conductivities with dual charge carriers (electrons and ions) under different environments, i.e. pure water and buffers simulating sweat. Large biocompatibility, adhesion and conformability to skin were obtained as well, allowing to implement the film in wearable electronic on-skin devices on porcine skin. Measurements in wearable devices indicated large sensitivity towards different stimuli (strain, motion and temperature) under sweat-like conditions.

Soil arthropod diversity contributes to a high proportion of the total biodiversity on Earth. However, most soil arthropods are still undescribed, hindering our understanding of soil functioning and global biodiversity estimations. Inventorying soil arthropods using conventional taxonomical approaches is particularly difficult and costly due to the great species richness, abundance and local-scale heterogeneity of mesofauna communities and the poor taxonomic background knowledge of most lineages. To alleviate this situation, we have designed and implemented a molecular barcoding framework adapted to soil fauna. This pipeline includes different steps, starting with a morphology-based selection of specimens which are imaged. Then, DNA is extracted non-destructively. Both images and voucher specimens are used to assign a taxonomic identification, based on morphology that is further checked for consistency with molecular information. Using this procedure, we studied 239 specimens of mites from the Canary Islands including representatives of Mesostigmata, Sarcoptiformes and Trombidiformes, of which we recovered barcode sequences for 168 specimens that were morphologically identified to 49 species, with nine specimens that could only be identified at the genus or family levels. Multiple species delimitation analyses were run to compare molecular delimitations with morphological identifications, including ASAP, mlPTP, BINs and 3% and 8% genetic distance thresholds. Additionally, a species-level search was carried out at the Biodiversity Databank of the Canary Islands (BIOTA) to evaluate the number of species in our dataset that were not previously recorded in the archipelago. In parallel, a sequence-level search of our sequences was performed against BOLD Systems. Our results reveal that multiple morphologically identified species correspond to different molecular lineages, which points to significant levels of unknown cryptic diversity within the archipelago. In addition

West Nile virus (WNV) is the most widely distributed mosquito-borne flavivirus in the world. This flavivirus can infect humans causing in some cases a fatal neurological disease and birds are the main reservoir hosts. WNV is endemic in Spain, and human cases have been reported since 2004. Although different studies analyse how climatic conditions can affect the dynamics of WNV infection, very few use long-term datasets. Between 2003 and 2020 a total of 2,724 serum samples from 1,707 common coots (Fulica atra) were analysed for the presence of WNV-specific antibodies. Mean (SD) annual seroprevalence was 24.67% (0.28) but showed high year-to-year variations ranging from 5.06% (0.17) to 68.89% (0.29). Significant positive correlations (p < 0.01) were observed between seroprevalence and maximum winter temperature and mean spring temperature. The unprecedented WNV outbreak in humans in the south of Spain in 2020 was preceded by a prolonged period of escalating WNV local circulation. Given current global and local climatic trends, WNV circulation is expected to increase in the next decades. This underscores the necessity of implementing One Health approaches to reduce the risk of future WNV outbreaks in humans. Our results suggest that higher winter and spring temperatures may be used as an early warning signal of more intense WNV circulation among wildlife in Spain, and consequently highlight the need of more intense vector control and surveillance in human inhabited areas.

Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.

RNA-binding proteins are emerging as critical modulators of oncogenic cell transformation, malignancy and therapy resistance. We have previously found that the RNA-binding protein Cold Shock Domain containing protein E1 (CSDE1) promotes invasion and metastasis of melanoma, the deadliest form of skin cancer and also a highly heterogeneous disease in need of predictive biomarkers and druggable targets. Here, we design a monoclonal antibody useful for IHC in the clinical setting and use it to evaluate the prognosis potential of CSDE1 in an exploratory cohort of 149 whole tissue sections including benign nevi and primary tumors and metastasis from melanoma patients. Contrary to expectations for an oncoprotein, we observed a global decrease in CSDE1 levels with increasing malignancy. However, the CSDE1 cytoplasmic/nuclear ratio exhibited a positive correlation with adverse clinical features of primary tumors and emerged as a robust indicator of progression free survival in cutaneous melanoma, highlighting the potential of CSDE1 as a biomarker of prognosis. Our findings provide a novel feature for prognosis assessment and highlight the intricacies of RNA-binding protein dynamics in cancer progression.

We report for the first time the occurrence of the alien ant Cardiocondyla obscurior Wheeler, 1929 on the Greek island of Crete. Cardiocondyla obscurior is one of many congeneric taxa with worldwide success as tramp species, having attained a cosmopolitan distribution while having Indomalayan origins. It was first detected in Europe in 1999, and since 2015 it has started to be found outdoors in Southern European countries. Our record is the first in Europe in which the species is observed to be established outdoors in an agricultural area instead of an urban environment. Introduced Cardiocondyla ants are generally thought to have little ecological impact, although targeted studies have been lacking. Cardiocondyla obscurior is the third species of its genus to be found on the island of Crete, which is characterized by a remarkable ant diversity.

Extremely halophilic archaea (Haloarchaea, Nanohaloarchaeota, Methanonatronarchaeia and Halarchaeoplasmatales) thrive in saturating salt concentrations where they must maintain osmotic equilibrium with their environment. The evolutionary history of adaptations enabling salt tolerance remains poorly understood, in particular because the phylogeny of several lineages is conflicting. Here we present a resolved phylogeny of extremely halophilic archaea obtained using improved taxon sampling and state-of-the-art phylogenetic approaches designed to cope with the strong compositional biases of their proteomes. We describe two uncultured lineages, Afararchaeaceae and Asbonarchaeaceae, which break the long branches at the base of Haloarchaea and Nanohaloarchaeota, respectively. We obtained 13 metagenome-assembled genomes (MAGs) of these archaea from metagenomes of hypersaline aquatic systems of the Danakil Depression (Ethiopia). Our phylogenomic analyses including these taxa show that at least four independent adaptations to extreme halophily occurred during archaeal evolution. Gene-tree/species-tree reconciliation suggests that gene duplication and horizontal gene transfer played an important role in this process, for example, by spreading key genes (such as those encoding potassium transporters) across extremely halophilic lineages.

The quest for nanomaterial-based imaging probes that can provide positive contrast in MRI is fueled by the necessity of developing novel diagnostic applications with potential for clinical translation that current gold standard probes cannot provide. Although interest in nanomaterials for positive contrast has increased in recent years, their study is less developed than that of traditional negative contrast probes in MRI. In our search for new magnetic materials with enhanced features as positive contrast probes for MRI, we decided to explore the chemical space to comprehensively analyze the effects of different metals on the performance of iron oxide nanomaterials already able to provide positive contrast in MRI. To this end, we synthesized 30 different iron oxide-based nanomaterials. Thorough characterization was performed, including multivariate analysis, to study the effect of different variables on their relaxometric properties. Based on these results, we identified the best combination of metals for in vivo imaging and tested them in different experiments. First, we tested its performance on magnetic resonance angiography using a concentration ten times lower than that clinically approved for Gd. Finally, we studied the capability of these nanomaterials to cross the affected blood–brain barrier in a glioblastoma model. The results showed that the selected nanomaterials provided excellent positive contrast at large magnetic field and were able to accumulate at the tumor site, highlighting the affected tissue.

The presence of gauge symmetry in 1+1 dimensions is known to be redundant, since it does not imply the existence of dynamical gauge bosons. As a consequence, in the continuum, the Abelian-Higgs model (i.e., the theory of bosonic matter interacting with photons) just possesses a single phase, as the higher-dimensional Higgs and Coulomb phases are connected via nonperturbative effects. However, recent research published in Phys. Rev. Lett. 128, 090601 (2022)0031-900710.1103/PhysRevLett.128.090601 has revealed an unexpected phase transition when the system is discretized on the lattice. This transition is described by a conformal field theory with a central charge of c=3/2. In this paper, we aim to characterize the two components of this c=3/2 theory - namely the free Majorana fermionic and bosonic parts - through equilibrium and out-of-equilibrium spectral analyses.

CuBiO is one of the most studied potential candidates for photoelectrocatalytic solar fuel generation, from H production, to CO reduction, or even N fixation. Hence, understanding its performance and catalytic behavior is key to use this material under real working conditions. Herein, Ag nanocorals are successfully deposited over CuBiO photocathodes for enhancing its performance as a promising candidate for photoelectrocatalytic reduction reactions. An in-depth study of this novel structure through a combination of several materials’ characterization techniques, confirming the tetragonal structure and the stoichiometric proportion of the elemental components, is presented. In addition, the different charge transfer processes and catalytic mechanisms behind the performance of Ag-decorated CuBiO photocathodes are unveiled through a combination of electrochemical impedance spectroscopy and transient absorption spectroscopy. The combination of these advanced spectroscopies reveals that Ag is acts as a true catalyst, enhancing the charge extraction and decreasing the charge accumulation and the recombination at the CuBiO surface, thus boosting the photocathode performance.

Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a’s function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.

Soft photonic elements with optical waveguiding ability based on biocompatible hydrogels have become increasingly important in optical techniques for medical diagnosis and phototherapy, among others. Supramolecular hydrogels based on peptides with interesting optical properties are rarely reported and explored. Although robust crystals based on short peptides have shown optical waveguiding capabilities, their rigidity is the main issue to overcome in the quest for soft biocompatible materials. Here, we report on the microfluidic-assisted formation of a heterochiral short peptide hydrogel that exhibits active optical waveguiding properties thanks to the incorporation of two different dyes, thioflavin T and rhodamine B, into the hydrogel structure. Using our microfluidic platform, different parameters such as the concentration of a peptide, type of dye and its concentration, and flow rate have been rapidly explored, with remarkable low reagent consumption. In this way, it was possible to develop peptide hydrogel waveguides with good optical loss values, modulating the emission in diverse spectral regions. The use of microfluidics to prepare these hydrogels makes possible the preparation of structures of high length-to-diameter aspect ratios, which otherwise are hard to devise from bulk conditions. Overall, this work broadens the use of supramolecular self-assembly of peptides to create functional materials with additional versatility to polymeric hydrogels, thanks to the possibility of tuning the structure by changing amino acid sequences. Additionally, the optical properties can be easily modulated by quick optimization of experimental parameters via microfluidic technology.

During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs' projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development. Here, we demonstrate that precise developmental regulation of inhibition is key for the retraction of S1L4 PNs' callosal projections. Ablation of somatostatin INs leads to premature inhibition from parvalbumin INs onto S1L4 PNs and prevents them from acquiring their barrel-restricted local connectivity pattern. As a result, adult S1L4 PNs retain interhemispheric projections responding to tactile stimuli, and the mice lose whisker-based texture discrimination. Overall, we show that temporally ordered IN activity during development is key to shaping local ipsilateral S1L4 PNs' projection pattern, which is required for fine somatosensory processing.

Monitoring vegetation moisture conditions is paramount to better understand and assess drought impacts on vegetation, enhance crop yield predictions, and improve ecosystem models. Passive microwave remote sensing allows retrievals of the vegetation optical depth (VOD; [unitless]), which is directly proportional to the vegetation water content (VWC; in units of water mass per unit area [kg/m2]). However, VWC is largely dependent on the dry biomass and structure imprints on the VOD signal. Previously, statistical models have been used to isolate the water component from the biomass and structure components. Physically-based approaches have not yet been proposed for this goal. In this study, we present a multi-sensor semi-physical approach to retrieve the vegetation moisture from the VOD and express it as Live Fuel Moisture Content (LFMC [%]; the percentage of water mass per dry biomass unit). The study is performed in the western United States for the period April 2015 – December 2018. There, in situ LFMC samples are available for assessment. We rely on a VOD model based on vegetation height data from GEDI/Sentinel-2 and radar backscatter from Sentinel-1, which account for the biomass and structure components. Vegetation moisture is retrieved at L-, X- and Ku-bands by minimizing the difference between the modeled VOD and the VOD estimates from SMAP (L-band) and AMSR-2 (X- and Ku-band) satellites. Results show that the LFMC retrievals are independent of canopy height, land cover, and radar backscatter, demonstrating the capability of the proposed algorithm to separate water dynamics from the biomass/structure component in VOD. LFMC estimates at X- and Ku-bands reproduce well the expected spatio-temporal dynamics of in situ LFMC. Results show good agreement with in situ at a regional scale, with Pearson's correlations (r) between in situ LFMC samples and LFMC estimates of 0.64 (Ku-band), 0.60 (X-band) and 0.47 (L-band). Similar results are obtained independently for shr

1. Trait-based approaches have received increasing interest among freshwater scientists given their capacity to predict community structure and biodiversity effects on ecosystem functioning. However, the inconsistent development and use of trait concepts and terms across freshwater scientific disciplines may have limited realisation of the potential of traits., 2. Here, we reviewed trait definitions and terms use to provide recommendations for their consistent application in freshwater science. To do so, we first reviewed literature to identify established trait definitions, historical and current use of trait terms and challenges restricting the application of trait-based approaches in freshwater science. Next, we surveyed 414 freshwater researchers from 54 countries to assess variability in the current use of trait terminology in relation to respondent characteristics (i.e., professional experience, geographical region, research discipline, and focal freshwater ecosystem, biotic group, and ecosystem function)., 3. Our literature review identified two well-established trait definitions, which emphasise individual phenotypic characteristics that influence either eco-evolutionary aspects (i.e., organism performance and fitness) or ecosystem dynamics and processes (i.e., responses to the environment and/or effects on ecosystem functioning). Publications used a range of trait-related terms and their frequency of use varied among scientific fields. The term functional trait dominated fields such as biodiversity conservation, environmental sciences and ecology, plant sciences and microbiology. In contrast, the terms biological trait, functional trait, and species trait were used with similar frequencies in fields such as entomology, fisheries, marine and freshwater biology, and zoology. We also found that well-established trait definitions are difficult to apply to freshwater unicellular organisms, colonial multicellular organisms, genomic information, and cultural traits., 4. Our survey revealed highly inconsistent use of trait terms among freshwater researchers. Terms including biological trait, functional trait, structural measure, and ecosystem function were commonly used to describe the same traits or functions. Variability in the use of terms was generally explained by research discipline, geographical region, and focal biotic group and ecosystem functions., 5. We propose making the trait concept flexible enough to be applicable to all freshwater biota and their characteristics, while keeping and integrating links to eco-evolutionary and ecosystem aspects. Specifically, our new definition expands the established functional trait definition by considering also supra-individual scales of trait measurement (colonial- or community-mean traits), genotypic traits (e.g., functional gene markers of enzymes) and cultural traits (e.g., feeding behaviours, communication skills). To reduce terminological ambiguity, we also recommend that researchers define trait terms, prioritising the use of functional trait as an overarching term over alternative terms (e.g., biological trait), and restricting specific terms (e.g., morphological trait) to situations in which such precision is desirable. The findings of our integrative study could help to improve terminological consistency across freshwater disciplines and to better recognise the potential of traits to elucidate the mechanisms behind ecological patterns.

[Background]: Poriferans (sponges) are highly adaptable organisms that can thrive in diverse marine and freshwater environments due, in part, to their close associations with internal microbial communities. This sponge microbiome can be acquired from the surrounding environment (horizontal acquisition) or obtained from the parents during the reproductive process through a variety of mechanisms (vertical transfer), typically resulting in the presence of symbiotic microbes throughout all stages of sponge development. How and to what extent the different components of the microbiome are transferred to the developmental stages remain poorly understood. Here, we investigated the microbiome composition of a common, low-microbial-abundance, Atlantic-Mediterranean sponge, Crambe crambe, throughout its ontogeny, including adult individuals, brooded larvae, lecithotrophic free-swimming larvae, newly settled juveniles still lacking osculum, and juveniles with a functional osculum for filter feeding., [Results]: Using 16S rRNA gene analysis, we detected distinct microbiome compositions in each ontogenetic stage, with variations in composition, relative abundance, and diversity of microbial species. However, a particular dominant symbiont, Candidatus Beroebacter blanensis, previously described as the main symbiont of C. crambe, consistently occurred throughout all stages, an omnipresence that suggests vertical transmission from parents to offspring. This symbiont fluctuated in relative abundance across developmental stages, with pronounced prevalence in lecithotrophic stages. A major shift in microbial composition occurred as new settlers completed osculum formation and acquired filter-feeding capacity. Candidatus Beroebacter blanensis decreased significatively at this point. Microbial diversity peaked in filter-feeding stages, contrasting with the lower diversity of lecithotrophic stages. Furthermore, individual specific transmission patterns were detected, with greater microbial similarity between larvae and their respective parents compared to non-parental conspecifics., [Conclusions]: These findings suggest a putative vertical transmission of the dominant symbiont, which could provide some metabolic advantage to non-filtering developmental stages of C. crambe. The increase in microbiome diversity with the onset of filter-feeding stages likely reflects enhanced interaction with environmental microbes, facilitating horizontal transmission. Conversely, lower microbiome diversity in lecithotrophic stages, prior to filter feeding, suggests incomplete symbiont transfer or potential symbiont digestion. This research provides novel information on the dynamics of the microbiome through sponge ontogeny, on the strategies for symbiont acquisition at each ontogenetic stage, and on the potential importance of symbionts during larval development.

Background: Sorting Nexin 27 (SNX27)-retromer complex facilitates cargo recycling from endosomes to the plasma membrane. SNX27 downregulation in neurons, as the result of Trisomy 21 (T21), has been linked with cognitive deficits due to impairment of AMPA and NMDA receptor recycling. Studies in human T cell lines likewise demonstrated that SNX27 regulates the correct delivery of cargoes to the immune synapse limiting the activation of pro-inflammatory pathways. Nevertheless, the physiological consequences of partial SNX27 loss in T cell homeostasis are still unclear. Results: In this study, we have explored the consequences of T cell specific partial SNX27 downregulation in mice. T cells with partial SNX27 deficiency show a marked deficit in the CD4+ T cell pool, a hallmark of aging in mice and humans, and a well-characterized comorbidity of individuals with Down syndrome (DS). When analyzed ex vivo, CD4+ T cells with partial SNX27 deletion demonstrate enhanced proliferation but diminished IL-2 production. In contrast, the CD8+ population show enhanced expression of pro-inflammatory cytokines and lytic enzymes. Conclusions: This mouse model supports the relevance of SNX27 in the organization of the immune synapse, previously described in cell lines, as well as in the control of T cell homeostasis. Individuals with DS experiment an acceleration of the aging process, which particularly affects the immune and central nervous systems. Thus, we hypothesize that reduced SNX27 expression in DS could contribute to the dysregulation of these systems and further research in SNX27 will shed light on the molecular factors underlying the phenotypes observed in people with DS and its contribution to aging.

Here, we report the synthesis of BCN-93, a meltable, functionalized, and permanently porous metal–organic polyhedron (MOP) and its subsequent transformation into amorphous or crystalline, shaped, self-standing, transparent porous films via melting and subsequent cooling. The synthesis entails the outer functionalization of a MOP with meltable polymer chains: in our model case, we functionalized a Rh(II)-based cuboctahedral MOP with poly(ethylene glycol). Finally, we demonstrate that once melted, BCN-93 can serve as a porous matrix into which other materials or molecules can be dispersed to form mixed-matrix composites. To illustrate this, we combined BCN-93 with one of various additives (either two MOF crystals, a porous cage, or a linear polymer) to generate a series of mixed-matrix films, each of which exhibited greater CO2 uptake relative to the parent film.

Understanding electron-phonon interactions is fundamentally important and has crucial implications for device applications. However, in twisted bilayer graphene near the magic angle, this understanding is currently lacking. Here, we study electron-phonon coupling using time- and frequency-resolved photovoltage measurements as direct and complementary probes of phonon-mediated hot-electron cooling. We find a remarkable speedup in cooling of twisted bilayer graphene near the magic angle: The cooling time is a few picoseconds from room temperature down to 5 kelvin, whereas in pristine bilayer graphene, cooling to phonons becomes much slower for lower temperatures. Our experimental and theoretical analysis indicates that this ultrafast cooling is a combined effect of superlattice formation with low-energy moiré phonons, spatially compressed electronic Wannier orbitals, and a reduced superlattice Brillouin zone. This enables efficient electron-phonon Umklapp scattering that overcomes electron-phonon momentum mismatch. These results establish twist angle as an effective way to control energy relaxation and electronic heat flow.

Many of the Earth's microbes remain uncultured and understudied, limiting our understanding of the functional and evolutionary aspects of their genetic material, which remain largely overlooked in most metagenomic studies1. Here we analysed 149,842 environmental genomes from multiple habitats2-6 and compiled a curated catalogue of 404,085 functionally and evolutionarily significant novel (FESNov) gene families exclusive to uncultivated prokaryotic taxa. All FESNov families span multiple species, exhibit strong signals of purifying selection and qualify as new orthologous groups, thus nearly tripling the number of bacterial and archaeal gene families described to date. The FESNov catalogue is enriched in clade-specific traits, including 1,034 novel families that can distinguish entire uncultivated phyla, classes and orders, probably representing synapomorphies that facilitated their evolutionary divergence. Using genomic context analysis and structural alignments we predicted functional associations for 32.4% of FESNov families, including 4,349 high-confidence associations with important biological processes. These predictions provide a valuable hypothesis-driven framework that we used for experimental validatation of a new gene family involved in cell motility and a novel set of antimicrobial peptides. We also demonstrate that the relative abundance profiles of novel families can discriminate between environments and clinical conditions, leading to the discovery of potentially new biomarkers associated with colorectal cancer. We expect this work to enhance future metagenomics studies and expand our knowledge of the genetic repertory of uncultivated organisms.

Translation of seed stored mRNAs is essential to trigger germination. However, when RNAPII re-engages RNA synthesis during the seed-to-seedling transition has remained in question. Combining csRNA-seq, ATAC-seq and smFISH in Arabidopsis thaliana we demonstrate that active transcription initiation is detectable during the entire germination process. Features of non-coding regulation such as dynamic changes in chromatin accessible regions, antisense transcription, as well as bidirectional non-coding promoters are widespread throughout the Arabidopsis genome. We show that sensitivity to exogenous ABSCISIC ACID (ABA) during germination depends on proximal promoter accessibility at ABA-responsive genes. Moreover, we provide genetic validation of the existence of divergent transcription in plants. Our results reveal that active enhancer elements are transcribed producing non-coding enhancer RNAs (eRNAs) as widely documented in metazoans. In sum, this study defining the extent and role of coding and non-coding transcription during key stages of germination expands our understanding of transcriptional mechanisms underlying plant developmental transitions.

NEXT-100 is currently being constructed at the Laboratorio Subterráneo de Canfranc in the Spanish Pyrenees and will search for neutrinoless double beta decay using a high-pressure gaseous time projection chamber (TPC) with 100 kg of xenon. Charge amplification is carried out via electroluminescence (EL) which is the process of accelerating electrons in a high electric field region causing secondary scintillation of the medium proportional to the initial charge. The NEXT-100 EL and cathode regions are made from tensioned hexagonal meshes of 1 m diameter. This paper describes the design, characterization, and installation of these parts for NEXT-100. Simulations of the electric field are performed to model the drift and amplification of ionization electrons produced in the detector under various EL region alignments and rotations. Measurements of the electrostatic breakdown voltage in air characterize performance under high voltage conditions and identify breakdown points. The electrostatic deflection of the mesh is quantified and fit to a first-principles mechanical model. Measurements were performed with both a standalone test EL region and with the NEXT-100 EL region before its installation in the detector. Finally, we describe the parts as installed in NEXT-100, following their deployment in Summer 2023.

Diffusion MRI files in Nifti format (DWI in nifti + B-matrix in txt) for 37 pateints with Alcohol use disorders and 20 control subjects. In addition to their demographics

Electrical transport in noncentrosymmetric materials departs from the well-established phenomenological Ohm’s law. Instead of a linear relation between current and electric field, a nonlinear conductivity emerges along specific crystallographic directions. This nonlinear transport is fundamentally related to the lack of spatial inversion symmetry. However, the experimental implications of an inversion symmetry operation on the nonlinear conductivity remain to be explored. Here, we report on a large, nonlinear conductivity in chiral tellurium. By measuring samples with opposite handedness, we demonstrate that the nonlinear transport is odd under spatial inversion. Furthermore, by applying an electrostatic gate, we modulate the nonlinear output by a factor of 300, reaching the highest reported value excluding engineered heterostructures. Our results establish chiral tellurium as an ideal compound not just to study the fundamental interplay between crystal structure, symmetry operations and nonlinear transport; but also to develop wireless rectifiers and energy-harvesting chiral devices.

The functions of electrochemical energy conversion and storage devices rely on the dynamic junction between a solid and a fluid: the electrochemical interface (EI). Many experimental techniques have been developed to probe the EI, but they provide only a partial picture. Building a full mechanistic understanding requires combining multiple probes, either successively or simultaneously. However, such combinations lead to important technical and theoretical challenges. In this Review, we focus on complementary optoelectronic probes and modelling to address the EI across different timescales and spatial scales — including mapping surface reconstruction, reactants and reaction modulators during operation. We discuss how combining these probes can facilitate a predictive design of the EI when closely integrated with theory.

While reperfusion, or restoration of coronary blood flow in acute myocardial infarction, is a requisite for myocardial salvage, it can paradoxically induce a specific damage known as ischemia/reperfusion (I/R) injury. Our understanding of the precise pathophysiological molecular alterations leading to I/R remains limited. In this study, we conducted a comprehensive and unbiased time-course analysis of post-translational modifications (PTMs) in the post-reperfused myocardium of two different animal models (pig and mouse) and evaluated the effect of two different cardioprotective therapies (ischemic preconditioning and neutrophil depletion). In pigs, a first wave of irreversible oxidative damage was observed at the earliest reperfusion time (20 min), impacting proteins essential for cardiac contraction. A second wave, characterized by irreversible oxidation on different residues and reversible Cys oxidation, occurred at late stages (6–12 h), affecting mitochondrial, sarcomere, and inflammation-related proteins. Ischemic preconditioning mitigated the I/R damage caused by the late oxidative wave. In the mouse model, the two-phase pattern of oxidative damage was replicated, and neutrophil depletion mitigated the late wave of I/R-related damage by preventing both Cys reversible oxidation and irreversible oxidation. Altogether, these data identify protein PTMs occurring late after reperfusion as an actionable therapeutic target to reduce the impact of I/R injury.

Currently, a clear interest has been given to berries due to their richness in active metabolites, including anthocyanins and non-coloured phenolics. Therefore, the main aim of the present work is to investigate the phenolic profile, antioxidant abilities, and antiproliferative effects on normal human dermal fibroblasts (NHDF) and human colon carcinoma cell line (Caco-2) cells of phenolic-rich extracts from three red fruits highly appreciated by consumers: two species of blackberries (Rubus fruticosus and Rubus ulmifolius) and one species of mulberry (Morus nigra). A total of 19 different phenolics were identified and quantified by HPLC-DAD-ESI/MSn and HPLC-DAD, respectively. Focusing on the biological potential of the phenolic-rich extracts, all of them revealed notable scavenging abilities. Concerning the antiproliferative properties, R. fruticosus presented a cytotoxic selectivity for Caco-2 cells compared to NHDF cells. To deeper explore the biological potential, combinations with positive controls (ascorbic acid and 5-fluorouracil) were also conducted. Finally, the obtained data are another piece of evidence that the combination of phenolic-rich extracts from natural plants with positive controls may reduce clinical therapy costs and the possible toxicity of chemical drugs.

Alcohol use disorder (AUD) is the most prevalent form of addiction, with a great burden on society and limited treatment options. A recent clinical trial reported significant clinical benefits of deep transcranial magnetic stimulations (Deep TMS) targeting midline frontocortical areas. However, the underlying biological substrate remained elusive. Here, we report the effect of Deep TMS on the microstructure of white matter.

[EN] Studying interactions among species and their multiple forms and outcomes has become a central question of ecological research. Mutualisms have changed the way ecologists understand the functioning of ecosystems. Generalised mutualistic networks, especially among free-living species, have been observed to include highly heterogeneous assemblages, in which most species establish few interactions while a minority of species establish a wide range of interactions. These highly connected species are referred to as super-generalists. They are characterised for connecting otherwise isolated groups of interacting species or modules and for providing stronger cohesion to ecological networks. Their characteristics make them fundamental for local biodiversity and the structure and stability of interactions. In this PhD thesis we aim to better comprehend the super-generalist strategy and the mutualistic interactions at the individual level. For this purpose, we use as a model organism Pistacia lentiscus L. (Anacardiaceae), a woody shrub species abundant in the Mediterranean Basin, together with the coterie of frugivorous animals that consume its fruits and disperse its seeds. In Chapter 1 we review sampling methods used to record frugivory interactions, assessing their strengths, caveats, and convenience in different contexts. We discuss different approaches for combining data gathered using different methodologies. In Chapter 2, we explore the effectiveness of the frugivory/seed-dispersal mutualism between individual plants of P. lentiscus and its avian frugivore assemblage, assessing the level of reciprocity in reward exchange and dependence asymmetry among partners. In Chapter 3 we investigate the delayed outcomes of animals’ fruit consumption in early seedling recruitment of P. lentiscus plants. Lastly, in Chapter 4 we analyse individual-based networks of different plant species and regions of the world, we compare their topology and structure with that of species-bas, [ES] Estudiar las interacciones entre especies junto a sus múltiples formas y resultados se ha convertido en una cuestión central de la investigación en ecología. Los mutualismos han cambiado la forma en que los ecólogos entienden el funcionamiento de los ecosistemas. Se ha observado que las redes mutualistas generalizadas, especialmente entre especies de vida libre, incluyen conjuntos muy heterogéneos, en los que la mayoría de las especies establecen pocas interacciones, mientras que una minoría de especies establece una amplia variedad de interacciones. Estas especies altamente conectadas se denominan super-generalistas. Se caracterizan por conectar grupos de especies o módulos que de otro modo estarían aislados, y por proporcionar una mayor cohesión a las redes ecológicas. Sus características las convierten en especies fundamentales para la biodiversidad local así como para la estructura y estabilidad de las interacciones. En esta tesis doctoral pretendemos comprender mejor la estrategia supergeneralista y las interacciones mutualistas a nivel individual. Para ello, utilizamos como organismo modelo Pistacia lentiscus L. (Anacardiaceae), una especie arbustiva leñosa abundantemente distribuida por la cuenca mediterránea, junto a los animales frugívoros que consumen sus frutos y dispersan sus semillas. En el Capítulo 1 se revisan los métodos de muestreo utilizados para registrar las interacciones de frugivoría, evaluando sus ventajas, inconvenientes y conveniencia en diferentes contextos; y se discuten diferentes enfoques para combinar los datos recogidos utilizando diferentes metodologías. En el Capítulo 2, exploramos la eficacia en el mutualismo frugivoría/semilla-dispersión entre plantas individuales de P. lentiscus y las aves frugívoras que consumen sus frutos, evaluando el nivel de reciprocidad en el intercambio de recompensas y la asimetría de dependencia entre los socios. En el Capítulo 3, investigamos los resultados aplazados del consumo de frutos por animal

The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.

Mutualistic interactions among free-living species generally involve low-frequency interactions and highly asymmetric dependence among partners, yet our understanding of factors behind their emergence is still limited. Using individual-based interactions of a super-generalist fleshy-fruited plant with its frugivore assemblage, we estimated the Resource Provisioning Effectiveness (RPE) and Seed Dispersal Effectiveness (SDE) to assess the balance in the exchange of resources. Plants were highly dependent on a few frugivore species, while frugivores interacted with most individual plants, resulting in strong asymmetries of mutual dependence. Interaction effectiveness was mainly driven by interaction frequency. Despite highly asymmetric dependences, the strong reliance on quantity of fruit consumed determined high reciprocity in rewards between partners (i.e. higher energy provided by the plant, more seedlings recruited), which was not obscured by minor variations in the quality of animal or plant service. We anticipate reciprocity will emerge in low-intimacy mutualisms where the mutualistic outcome largely relies upon interaction frequency.

Obesity is associated with adipose tissue dysfunction through the differentiation and expansion of pre-adipocytes to adipocytes (hyperplasia) and/or increases in size of pre-existing adipocytes (hypertrophy). A cascade of transcriptional events coordinates the differentiation of pre-adipocytes into fully differentiated adipocytes; the process of adipogenesis. Although nicotinamide N-methyltransferase (NNMT) has been associated with obesity, how NNMT is regulated during adipogenesis, and the underlying regulatory mechanisms, remain undefined. In present study we used genetic and pharmacological approaches to elucidate the molecular signals driving NNMT activation and its role during adipogenesis. Firstly, we demonstrated that during the early phase of adipocyte differentiation NNMT is transactivated by CCAAT/Enhancer Binding Protein beta (CEBPB) in response to glucocorticoid (GC) induction. We found that Nnmt knockout, using CRISPR/Cas9 approach, impaired terminal adipogenesis by influencing the timing of cellular commitment and cell cycle exit during mitotic clonal expansion, as demonstrated by cell cycle analysis and RNA sequencing experiments. Biochemical and computational methods showed that a novel small molecule, called CC-410, stably binds to and highly specifically inhibits NNMT. CC-410 was, therefore, used to modulate protein activity during pre-adipocyte differentiation stages, demonstrating that, in line with the genetic approach, chemical inhibition of NNMT at the early stages of adipogenesis impairs terminal differentiation by deregulating the GC network. These congruent results conclusively demonstrate that NNMT is a key component of the GC-CEBP axis during the early stages of adipogenesis and could be a potential therapeutic target for both early-onset obesity and glucocorticoid-induced obesity.

Biological dinitrogen (N2) fixation supplies nitrogen to the oceans, supporting primary productivity, and is carried out by some bacteria and archaea referred to as diazotrophs. Cyanobacteria are conventionally considered to be the major contributors to marine N2 fixation, but non-cyanobacterial diazotrophs (NCDs) have been shown to be distributed throughout ocean ecosystems. However, the biogeochemical significance of marine NCDs has not been demonstrated. This review synthesizes multiple datasets, drawing from cultivation-independent molecular techniques and data from extensive oceanic expeditions, to provide a comprehensive view into the diversity, biogeography, ecophysiology, and activity of marine NCDs. A NCD nifH gene catalog was compiled containing sequences from both PCR-based and PCR-free methods, identifying taxa for future studies. NCD abundances from a novel database of NCD nifH-based abundances were colocalized with environmental data, unveiling distinct distributions and environmental drivers of individual taxa. Mechanisms that NCDs may use to fuel and regulate N2 fixation in response to oxygen and fixed nitrogen availability are discussed, based on a metabolic analysis of recently available Tara Oceans expedition data. The integration of multiple datasets provides a new perspective that enhances understanding of the biology, ecology, and biogeography of marine NCDs and provides tools and directions for future research

The surface chemistry of Metal-Organic Polyhedra (MOPs) is crucial to their physicochemical properties because it governs how they interact with external substances such as solvents, synthetic organic molecules, metal ions, and even biomolecules. Consequently, the advancement of synthetic methods that facilitate the incorporation of diverse functional groups onto MOP surfaces will significantly broaden the range of properties and potential applications for MOPs. This study describes the use of copper(I)-catalysed, azide-alkyne cycloaddition (CuAAC) click reactions to post-synthetically modify the surface of alkyne-functionalised cuboctahedral MOPs. To this end, a novel Rh(II)-based MOP with 24 available surface alkyne groups was synthesised. Each of the 24 alkyne groups on the surface of the "clickable" Rh-MOP can react with azide-containing molecules at room temperature, without compromising the integrity of the MOP. The wide substrate catalogue and orthogonal nature of CuAAC click chemistry was exploited to densely functionalise MOPs with diverse functional groups, including polymers, carboxylic and phosphonic acids, and even biotin moieties, which retained their recognition capabilities once anchored onto the surface of the MOP.

Introduction: Sponges harbor diverse, specific, and stable microbial communities, but at the same time, they efficiently feed on microbes from the surrounding water column. This filter-feeding lifestyle poses the need to distinguish between three categories of bacteria: food to digest, symbionts to incorporate, and pathogens to eliminate. How sponges discriminate between these categories is still largely unknown. Phagocytosis is conceivable as the cellular mechanism taking part in such discrimination, but experimental evidence is missing. We developed a quantitative in-vivo phagocytosis assay using an emerging experimental model, the sponge Halichondria panicea. Methods: We incubated whole sponge individuals with different particles, recovered the sponge (host) cells, and tracked the incorporation of these particles into the sponge cells. Fluorescence-activated cell sorting (FACS) and fluorescent microscopy were used to quantify and verify phagocytic activity, defined here as the population of sponge cells with incorporated particles. Sponges were incubated with a green microalgae to test if particle concentration in the seawater affects the percentage of phagocytic activity, and to determine the timing where the maximum of phagocytic cells are captured in a pulse-chase experiment. Lastly, we investigated the application of our phagocytic assay with other particle types (i.e., fluorescently-labelled bacteria and fluorescent beads). Results and discussion: The percentage of sponge cells that had incorporated algae, bacteria, and beads ranged between 5 to 24%. These phagocytic sponge cells exhibited different morphologies and sizes depending on the type of particle presented to the sponge. Particle incorporation into sponge cells was positively related to algal concentration in the seawater, suggesting that sponge cells adjust their phagocytic activity depending on the number of particles they encounter. Our results further revealed that sponge phagocytosis initiates

Background and Aims: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. Approach and Results: C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD+/NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. Conclusions: Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.

The low endogenous regenerative capacity of the heart, added to the prevalence of cardiovascular diseases, triggered the advent of cardiac tissue engineering in the last decades. The myocardial niche plays a critical role in directing the function and fate of cardiomyocytes; therefore, engineering a biomimetic scaffold holds excellent promise. We produced an electroconductive cardiac patch of bacterial nanocellulose (BC) with polypyrrole nanoparticles (Ppy NPs) to mimic the natural myocardial microenvironment. BC offers a 3D interconnected fiber structure with high flexibility, which is ideal for hosting Ppy nanoparticles. BC-Ppy composites were produced by decorating the network of BC fibers (65 ± 12 nm) with conductive Ppy nanoparticles (83 ± 8 nm). Ppy NPs effectively augment the conductivity, surface roughness, and thickness of BC composites despite reducing scaffolds' transparency. BC-Ppy composites were flexible (up to 10 mM Ppy), maintained their intricate 3D extracellular matrix-like mesh structure in all Ppy concentrations tested, and displayed electrical conductivities in the range of native cardiac tissue. Furthermore, these materials exhibit tensile strength, surface roughness, and wettability values appropriate for their final use as cardiac patches. In vitro experiments with cardiac fibroblasts and H9c2 cells confirmed the exceptional biocompatibility of BC-Ppy composites. BC-Ppy scaffolds improved cell viability and attachment, promoting a desirable cardiomyoblast morphology. Biochemical analyses revealed that H9c2 cells showed different cardiomyocyte phenotypes and distinct levels of maturity depending on the amount of Ppy in the substrate used. Specifically, the employment of BC-Ppy composites drives partial H9c2 differentiation toward a cardiomyocyte-like phenotype. The scaffolds increase the expression of functional cardiac markers in H9c2 cells, indicative of a higher differentiation efficiency, which is not observed with plain BC. Our results hi

1. Many insular plant species inhabiting different archipelagos worldwide present typical ornithophilous floral traits (e.g., copious nectar, red-orange colours), but most of them are visited by insectivorous/granivorous birds and lizards, which act as generalist pollinators. Oceanic islands promote these ecological interactions mainly due to the scarcity of arthropods. Our goal is to understand how these generalist interactions contribute to the shift of floral traits from entomophily (mainland) to ornithophily or saurophily (island), where specialist nectar-feeding birds have not inhabited. 2. We used the well-known pollination interactions occurring in the Canary Islands to evaluate two proposed ecological hypotheses, bee-avoidance or bird-attraction, explaining evolutionary transitions of floral traits. Specifically, we studied the flower colour conspicuousness of bird-pollinated Canarian species visited by birds and lizards with their closest relatives from the mainland mainly visited by bees. We analysed the chromatic contrast of flower colours using visual models of bees, birds, and lizards and the achromatic contrast in visual models of bees. We also compared reflectance spectra marker points of flowers with available spectral discrimination sensitivities of bees and birds. 3. Using a phylogenetically corrected framework of independent plant lineages, our results revealed that bird-pollinated Canarian species showed lower chromatic contrast according to bees and lizard visual models than their mainland relatives, but similar chromatic contrast for bird vision. In addition, reflectance spectra marker points of the Canarian species were displaced to the longest wavelengths, far from the wavelengths of maximum discrimination of bees, but close to birds. 4. We conclude that the avoidance of bees would be a primary ecological strategy explaining the evolutionary transitions of flower colours from melittophily to ornithophily. The lower conspicuousness of bird-pol

Climate change is causing alterations in annual temperature regimes worldwide. Important aspects of this include the reduction of winter chilling temperatures as well as the occurrence of unpredicted frosts, both significantly affecting plant growth and yields. Recent studies advanced the knowledge of the mechanisms underlying cold responses and tolerance in the model plant Arabidopsis thaliana. However, how these cold-responsive pathways will readjust to ongoing seasonal temperature variation caused by global warming remains an open question. In this review, we highlight the plant developmental programmes that depend on cold temperature. We focus on the molecular mechanisms that plants have evolved to adjust their development and stress responses upon exposure to cold. Covering both genetic and epigenetic aspects, we present the latest insights into how alternative splicing, noncoding RNAs and the formation of biomolecular condensates play key roles in the regulation of cold responses. We conclude by commenting on attractive targets to accelerate the breeding of increased cold tolerance, bringing up biotechnological tools that might assist in overcoming current limitations. Our aim is to guide the reflection on the current agricultural challenges imposed by a changing climate and to provide useful information for improving plant resilience to unpredictable cold regimes.

The technical and intellectual capabilities of past societies are reflected in the monuments they were able to build. Tracking the provenance of the stones utilised to build prehistoric megalithic monuments, through geological studies, is of utmost interest for interpreting ancient architectures as well as to contribute to their protection. According to the scarce information available, most stones used in European prehistoric megaliths originate from locations near the construction sites, which would have made transport easier. The Menga dolmen (Antequera, Malaga, Spain), listed in UNESCO World Heritage since July 2016, was designed and built with stones weighting up to nearly 150 tons, thus becoming the most colossal stone monument built in its time in Europe (c. 3800-3600 BC). Our study (based on high-resolution geological mapping as well as petrographic and stratigraphic analyses) reveals key geological and archaeological evidence to establish the precise provenance of the massive stones used in the construction of this monument. These stones are mostly calcarenites, a poorly cemented detrital sedimentary rock comparable to those known as 'soft stones' in modern civil engineering. They were quarried from a rocky outcrop located at a distance of approximately 1 km. In this study, it can be inferred the use of soft stone in Menga reveals the human application of new wood and stone technologies enabling the construction of a monument of unprecedented magnitude and complexity.

[Objective]: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning. [Methods]: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6−/−) mice. [Results]: In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6−/− mice. [Conclusions]: These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1.

Tunable lenses, optical elements able to change their optical power within milliseconds, constitute an emerging technology increasingly used in ophthalmic applications. In this study, 25 subjects looked through tunable lenses at a chromatic stimulus to evaluate the perceptual response of the human visual system to periodic changes in defocus of 0.25D of amplitude and 15 Hz of temporal frequency. These defocus changes produce flicker and chromatic distortions that change with the overall level of defocus. The task in this study was to minimize the flicker by varying the average optical power, and it was performed for different myopic and hyperopic starting points. Subjects also performed a blur-minimization task in a black-and-white stimulus of the same geometry. The flicker-minimization task is more repeatable than the blur-minimization task (standard deviations ±0.17D and ±0.49D). The time per repetition of the flicker-minimization task is only 38s. Cycloplegia severely affects the blur-minimization, but not the flicker-minimization task, confirming that defocus flicker deactivates the accommodative system. This discovery can be used to develop new methods for measuring the refractive error of the eye that does not require supervision and can potentially improve existing subjective methods in terms of accuracy, precision, and measurement time.

Tunable lenses make it possible to measure visual sensitivity to rapid changes in optical power, surpassing the limits imposed by mechanical elements. Using a tunable lens system, we measured, for the first time, the spatiotemporal defocus sensitivity function (STDSF), and the limits of human defocus perception. Specifically, we measured defocus sensitivity using a QUEST adaptive psychophysical procedure for different stimuli (Gabor patches of different spatial frequencies, natural images, and edges) and we developed descriptive models of defocus perception. For Gabor patches, we found on average (across seven subjects) that the maximum sensitivity to defocus is 0.22 D at 14 cpd and 10 Hz, and that the upper limits of sensitivity are 40 cpd and 40 Hz. Our results suggest that accommodation remains fixed while performing the defocus flicker-detection task. These results have implications for new technologies whose working principles make use of fast changes to defocus.