The lncRNA Crossfirre was identified as an imprinted X-linked gene, and is transcribed antisense to the trans-acting lncRNA Firre. The Firre locus forms an inactive-X-specific interaction with Dxz4, both loci providing the platform for the largest conserved chromatin structures. Here, we characterize the epigenetic profile of these loci, revealing them as the most female-specific accessible regions genome-wide. To address their in vivo role, we perform one of the largest X-linked knockout studies by deleting Crossfirre, Firre, and Dxz4 individually and in combination. Despite their distinct epigenetic features observed on the X chromosome, our allele-specific analysis uncovers these loci as dispensable for imprinted and random X chromosome inactivation. However, we provide evidence that Crossfirre affects autosomal gene regulation but only in combination with Firre. To shed light on the functional role of these sex-specific loci, we perform an extensive standardized phenotyping pipeline and uncover diverse knockout and sex-specific phenotypes. Collectively, our study provides the foundation for exploring the intricate interplay of conserved X-linked loci in vivo.
View lessIntroduction
Increasing soil organic carbon (SOC) in croplands is a natural climate mitigation effort that can also enhance crop yields. However, there is a lack of comprehensive field studies examining the impact of SOC on crop yields across wide climatic, soil, and farming gradients. Furthermore, it is largely unknown how water retention, soil microbial diversity, and nutrient availability modulate the SOC-crop yield relationship.
Materials and Methods
We conducted an observational study across 127 cereal fields along a 3000 km north-south gradient in Europe, measured topsoil (0–20 cm) organic C content, and collected data on climate, soil properties, crop yield and farming practices. Additionally, we explored the relationship between crop yield, particulate organic carbon (POC) and mineral-associated organic carbon (MAOC) contents at three soil depths (0–20, 20–40 and 40–60 cm) in a subset of sites.
Results
Relative yield increases levelled off at 1.4% SOC, indicating an optimal SOC content for cereals along a European gradient. The quadratic relationship between SOC and cereal yield was conspicuous even after controlling for large differences in climate, soil and farming practices across countries. The relationship varied significantly across soil depths and C fractions. MAOC dominated the SOC pool, and was significantly related to relative yield up to an optimal level that varied with soil depth. Soil microbial diversity and nutrient availability emerged as main drivers of the SOC-yield relationship, while water retention did not exhibit a notable influence.
Conclusions
Our study demonstrates that SOC is as a key determinant of cereal yield along a European gradient, and identifying this threshold can inform soil management strategies for improved carbon capture based on initial SOC levels. Nevertheless, the complex SOC-yield relationship highlights the necessity for tailored soil management strategies that consider specific site conditions to optimize C storage and crop yield.
View lessDespite the multifaceted and diverse challenges that refugees, migrants, and asylum-seekers experience when entering a new country, they remain notably underrepresented in the evaluation and understanding of the health and wellbeing impacts of outdoor health interventions. We addressed this knowledge gap by a mixed-methods evaluation (questionnaires, focus groups and photo elicitation activity) facilitated by a community researcher. Qualitative data (focus groups and photo elicitation activity) revealed that the participants saw the social component of outdoor activities as a critical factor in improving their wellbeing, an insight not captured by established quantitative wellbeing scales. Given the diverse backgrounds of refugee, migrant, and asylum-seeker populations, we underline the importance of a transdisciplinary, collaborative, and mixed-methods research approach.
View lessMany super-Earths are on very short orbits around their host star and, therefore, more likely to be tidally locked. Because this locking can lead to a strong contrast between the dayside and nightside surface temperatures, these super-Earths could exhibit mantle convection patterns and tectonics that could differ significantly from those observed in the present-day solar system. The presence of an atmosphere, however, would allow transport of heat from the dayside toward the nightside and thereby reduce the surface temperature contrast between the two hemispheres. On rocky planets, atmospheric and geodynamic regimes are closely linked, which directly connects the question of atmospheric thickness to the potential interior dynamics of the planet. Here, we study the interior dynamics of super-Earth GJ 486b (R=1.34 R circle plus, M=3.0 M circle plus, Teq approximate to 700 K), which is one of the most suitable M-dwarf super-Earth candidates for retaining an atmosphere produced by degassing from the mantle and magma ocean. We investigate how the geodynamic regime of GJ 486b is influenced by different surface temperature contrasts by varying possible atmospheric circulation regimes. We also investigate how the strength of the lithosphere affects the convection pattern. We find that hemispheric tectonics, the surface expression of degree-1 convection with downwellings forming on one hemisphere and upwelling material rising on the opposite hemisphere, is a consequence of the strong lithosphere rather than surface temperature contrast. Anchored hemispheric tectonics, where downwellings und upwellings have a preferred (day/night) hemisphere, is favored for strong temperature contrasts between the dayside and nightside and higher surface temperatures.
View lessCryomyces antarcticus , a melanized cryptoendolithic fungus endemic to Antarctica, can tolerate environmental conditions as severe as those in space. Particularly, its ability to withstand ionizing radiation has been attributed to the presence of thick and highly melanized cell walls, which—according to a previous investigation—may contain both 1,8‐dihydroxynaphthalene (DHN) and L‐3,4 dihydroxyphenylalanine (L‐DOPA) melanin. The genes putatively involved in the synthesis of DHN melanin were identified in the genome of C. antarcticus. Most important is capks1 encoding a non‐reducing polyketide synthase (PKS) and being the ortholog of the functionally characterized kppks1 from the rock‐inhabiting fungus Knufia petricola . The co‐expression of CaPKS1 or KpPKS1 with a 4′‐phosphopantetheinyl transferase in Saccharomyces cerevisiae resulted in the formation of a yellowish pigment, suggesting that CaPKS1 is the enzyme providing the precursor for DHN melanin. To dissect the composition and function of the melanin layer in the outer cell wall of C. antarcticus , non‐melanized mutants were generated by CRISPR/Cas9‐mediated genome editing. Notwithstanding its slow growth (up to months), three independent non‐melanized Δ capks1 mutants were obtained. The mutants exhibited growth similar to the wild type and a light pinkish pigmentation, which is presumably due to carotenoids. Interestingly, visible light had an adverse effect on growth of both melanized wild‐type and non‐melanized Δ capks1 strains. Further evidence that light can pass the melanized cell walls derives from a mutant expressing a H2B‐GFP fusion protein, which can be detected by fluorescence microscopy. In conclusion, the study reports on the first genetic manipulation of C. antarcticus , resulting in non‐melanized mutants and demonstrating that the melanin is rather of the DHN type. These mutants will allow to elucidate the relevance of melanization for surviving extreme conditions found in the natural habitat as well as in space.
View lessTopical treatment of oral inflammatory diseases is challenging due to the intrinsic physicochemical barriers of the mucosa and the continuous flow of saliva, which dilute drugs and limit their bioavailability. Nanocarrier technology can be an innovative approach to circumvent these problems and thus improve the efficacy of topical drug delivery to the mucosa. Core‐multishell (CMS) nanocarriers are putative delivery systems with high biocompatibility and the ability to adhere to and penetrate the oral mucosa. Ester‐based CMS nanocarriers release the anti‐inflammatory compound dexamethasone (Dx) more efficiently than a conventional cream. Mussel‐inspired functionalization of a CMS nanocarrier with catechol further improves the adhesion of the nanocarrier and may enhance the efficacy of the loaded drugs. In the present study, the properties of the ester‐based CMS 10‐E‐15‐350 nanocarrier (CMS‐NC) are further evaluated in comparison to the catechol‐functionalized variant (CMS‐C0.08). While the mucoadhesion of CMS‐NC is inhibited by saliva, CMS‐C0.08 exhibits better mucoadhesion in the presence of saliva. Due to the improved adhesion properties, CMS‐C0.08 loaded with dexamethasone (Dx‐CMS‐C0.08) shows a better anti‐inflammatory effect than Dx‐CMS‐NC when applied dynamically. These results highlight the superiority of CMS‐C0.08 over CMS‐NC as an innovative drug delivery system (DDS) for the treatment of oral mucosal diseases.
View lessMany of the world's rifts and rifted margins have developed within former orogens. The South China Sea (SCS) formed during Cenozoic rifting by utilizing pre‐existing orogenic structures, like thrust faults, thickened crust, and corresponding thermal weaknesses. The mechanisms explaining how inherited structures influence the spatiotemporal evolution of a rift remain a topic of on‐going research. Here, we explore the impact of orogenic inheritance on rift evolution through a numerical forward model that reproduces geodynamic and landscape evolution processes. By imposing time‐dependent phases of shortening and extension, we model rifted margin formation that is consistent with the available geological and geophysical observations of the SCS. Our numerical models allow us to identify thrust faults that are reactivated as normal faults during extensional phases. Not all pre‐existing thrust faults, however, undergo full reactivation, as their behavior is influenced by variations in lithospheric strength and the pre‐existing structural discontinuities. We further show that inherited orogenic structures compete with each other during extensional reactivation and ultimately govern the location of continental breakup. Our results provide valuable insights into the broader implications of inherited orogenic structures and how they affect subsequent rift system evolution.
View lessPublic administration in governments strives to develop forward‐looking capacities. Foresight has come to the fore as a set of practices that is mobilized to counter political myopia. Despite this increasing interest in governmental foresight, research suggests that diverging institutional practices, organizational structures, and epistemic cultures between foresight practices and policy‐making result in loose coupling. This article aims to contribute to understanding these complicated foresight‐policy interactions. To this end, we draw on findings from public administration scholarship. The concept of institutionalization is employed to analyze how foresight aligns with working practices and routines in government. Based on an in‐depth case study on the institutionalization of foresight practices within the German Federal Government, we demonstrate that scrutinizing the multiple dimensions of institutionalization helps not only to understand where and why loose ends occur but also provides new insights into some of the causes of the lacking impact. The article does not aim to provide an easy fix. Instead, we want to sensitize foresight practitioners, reduce both disappointment and overstating regarding the role of foresight in policy‐making, and provide a nuanced understanding of foresight practices in government.
View lessCorrosion and biofouling are wetting‐related phenomena that limit the effective use of metals in aqueous media. Nonwettable surfaces can mitigate the adverse effects of wetting by minimizing contact with water. However, current achievements in this field fall short of meeting industrial requirements due to the short lifetime of plastrons. This study proposes a method to measure the protective sustainability of plastron. Superhydrophobic (SHS) and aerophilic (APhS) surfaces are constructed on lightweight aluminum and are initially analyzed by conventional goniometry, which show comparable values. However, the plastron that develops underwater is substantially different. While SHS exhibit unevenly broken plastron, APhS show uniform, continuous plastron. As an example of the sustained protective performance of plastron, the corrosion resistance of SHS and APhS is presented. Potentiodynamic polarization, impedance spectroscopy, and long‐term immersion in seawater show a drastic enhancement in corrosion resistance, exclusively for APhS. In fact, almost no electrochemical signals are measurable, and no pitting corrosion is observed after 415 days of immersion in seawater. Conversely, SHS show no noticeable improvement and corrode faster than bare Al due to plastron loss. Since goniometric measurements do not provide information on plastron, it is essential to analyze the plastron for any non‐wettable surface utilized underwater.
View lessActive deformation and landscape evolution in North Chilean forearc involve multiscale tectonic processes, such as crustal thickening causing orogenic‐scale uplift and faulting modulating the mountain‐front landscape. In the Central Depression, faults redirecting Quaternary drainages are poorly understood due to their subtle surface expressions and limited structural data acquisition. To address this, we combined remote‐sensing analysis of high‐resolution DEMs, satellite and UAV imagery, new geomorphic mapping, structural data, and morphometric analysis with available surface age dating to identify and give temporal constraints on previously unmapped faults impacting drainages across this region. Our findings reveal the reactivation of east‐vergent NNW‐SSE reverse to transpressive and NW‐SE strike‐slip faults over approximately 100 km of latitude. Faults movement can be summarized into two main stages (a) A Late Miocene‐Pliocene stage, dominated by east‐vergent reverse faults inverting the Andean piedmont in the northern study area. (b) A Pliocene‐Quaternary stage, characterized by transpressive activity of these east‐vergent faults extending southward, alongside structures of the West Vergent Thrust System. The tectonic evolution of the east‐vergent structures relates to the ongoing deformation of the coastal forearc, encroaching into the Central Depression. Minimum vertical and strike‐slip displacement rates since the Quaternary are 12 m/Ma and 90 m/Ma, respectively, with the potential for higher rates depending on the onset of displacement. Drainage pattern modification, driven by incremental vertical displacement rates, provides insights to qualitatively evaluate individual fault activity rates. Numerous recently detected structures represent previously unknown sources of seismic hazard, requiring further dating of geomorphic markers and high‐resolution monitoring.
View lessAims
Metformin has been attributed to cardiovascular protection even in the absence of diabetes. Recent observations suggest that metformin influences the gut microbiome. We aimed to investigate the influence of metformin on the gut microbiota and hypertensive target organ damage in hypertensive rats.
Methods
Male double transgenic rats overexpressing the human renin and angiotensinogen genes (dTGR), a model of angiotensin II‐dependent hypertension, were treated with metformin (300 mg/kg/day) or vehicle from 4 to 7 weeks of age. We assessed gut microbiome composition and function using shotgun metagenomic sequencing and measured blood pressure via radiotelemetry. Cardiac and renal organ damage and inflammation were evaluated by echocardiography, histology, and flow cytometry.
Results
Metformin treatment increased the production of short‐chain fatty acids (SCFA) acetate and propionate in feces without altering microbial composition and diversity. It significantly reduced systolic and diastolic blood pressure and improved cardiac function, as measured by end‐diastolic volume, E/A, and stroke volume despite increased cardiac hypertrophy. Metformin reduced cardiac inflammation by lowering macrophage infiltration and shifting macrophage subpopulations towards a less inflammatory phenotype. The observed improvements in blood pressure, cardiac function, and inflammation correlated with fecal SCFA levels in dTGR. In vitro, acetate and propionate altered M1‐like gene expression in macrophages, reinforcing anti‐inflammatory effects. Metformin did not affect hypertensive renal damage or microvascular structure.
Conclusion
Metformin modulated the gut microbiome, increased SCFA production, and ameliorated blood pressure and cardiac remodeling in dTGR. Our findings confirm the protective effects of metformin in the absence of diabetes, highlighting SCFA as a potential mediators.
View lessInformation on restoration science and practice is dispersed across large numbers of scientific papers, reports, books, and other resources, and there is a lack of synthetic approaches and of linkages between ecological theory and practice. With recent calls for scaling up ecological restoration, there is an urgent need for improving the effectiveness of restoration ecology by presenting existing knowledge in an organized and accessible form. Practitioners benefit from knowing which theories explain patterns and processes in a specific ecosystem, and scientists need an overview of empirical evidence supporting current theories. Strengthening links between restoration practice and science benefits both areas. Based on a new approach used for organizing and assessing hypotheses in invasion biology, we suggest the development of an interactive online platform that promotes the integration of restoration science and practice by (1) presenting an overview of restoration ecology; (2) mapping theoretical work relevant for ecological restoration; (3) displaying direct links to relevant publications; and (4) providing summaries of empirical evidence for ecological theories in specific settings. This online knowledge base should be developed in an open process, bringing together the restoration community with experts in semantic web and natural language processing, library scientists, web designers, and other specialists. The platform should become an evolving, searchable, openly accessible, and intuitively organized tool for future ecological restoration.
View lessWe consider the Koopman operator semigroup (Kt)t≥0 associated with stochastic differential equations of the form dXt=AXtdt+BdWt with constant matrices A and B and Brownian motion Wt. We prove that the reproducing kernel Hilbert space HC generated by a Gaussian kernel with a positive definite covariance matrix C is invariant under each Koopman operator Kt if the matrices A, B, and C satisfy the following Lyapunov‐like matrix inequality: AC2+C2A⊤≤2BB⊤. In this course, we prove a characterization concerning the inclusion HC1⊂HC2 of Gaussian RKHSs for two positive definite matrices C1 and C2. The question of whether the sufficient Lyapunov‐condition is also necessary is left as an open problem.
View lessCrystallographic fragment screening (CFS) has recently matured into an important method for the early stages of drug discovery projects. It is based on high‐throughput structure determination and thus requires a high degree of automation as well as specialized workflows and robust analysis tools. Consequently, large‐scale research facilities such as synchrotrons have embraced the method, and developed platforms to perform CFS campaigns with the help of crystallography experts and specific tools. The BESSY II synchrotron, operated by the Helmholtz–Zentrum Berlin (HZB), is one of these synchrotron facilities that offer a CFS platform, named the F2X‐facility. Here, the specialized F2X workflow is described along with the relevant differences to other existing CFS platforms, and the ongoing developments aimed at supporting users of the facility. The different stages of a CFS campaign including requirements, beamline capabilities, and the software environment are detailed and explained. A unique F2X‐GO kit is featured, which allows users the possibility of performing all sample preparation in their home laboratories. Furthermore, at the HZB a computational workflow has been built to support users beyond the hit identification stage. The advantages of the F2X‐facility at HZB are described and references are provided to successfully conduct CFS.
View lessLiterature on platform governance is focused on keystone organizations that exclusively own a platform and control its complementors and users. However, emerging network-driven platform ecosystems—such as European data spaces—represent a shift in focus by allowing stakeholders to share platform ownership and decision rights. To investigate this emerging phenomenon, we conduct a qualitative-explorative case study, interviewing 32 representatives of Catena-X, a European data space in the automotive industry. To conceptually grasp the co-development and management of network-driven platform ecosystems, we employ a network governance perspective as the theoretical lens. We contribute to platform governance literature with (1) a conceptualization of shared platform ownership recognizing the dichotomy of inner and outer governance, and (2) a process model and a conceptual model of an interorganizational network governing the emergence of a platform ecosystem.
View lessStacked graphene oxide (GO) proton membranes are promising candidates for use in energy devices due to their proton conductivity. Identification of through-plane channels in these membranes is critical but challenging due to their anisotropic nature. Here, we present an electrochemical reduction method for identifying and quantifying through-plane proton channels in GO membranes. The simplicity lies in the operando optical observation of the change in contrast as GO is electrochemically reduced. Here, we find three proton-dominated three-phase interfaces, which are critical for the reduction reactions of GO membranes. Based on these findings, a method is proposed to identify and quantify through-plane channels in stacked GO proton membranes using a simple three-electrode device in combination with real-time imaging of the membrane surface.
View lessAlpha-helical membrane proteins perform numerous critical functions essential for the survival of living organisms. Traditionally, these proteins are extracted from membranes using detergent solubilization and reconstitution into liposomes or nanodiscs. However, these processes often obscure the effects of nanoconfinement and the native environment on the structure and conformational heterogeneity of the target protein. We demonstrate that pulsed dipolar electron spin resonance spectroscopy, combined with the Gd3+-nitroxide spin pair, enables the selective observation of the vitamin B12 importer BtuCD−F in its native cellular envelope. Despite the high levels of non-specific labeling in the envelope, this orthogonal approach combined with the long phase-memory time for the Gd3+ spin enables the observation of the target protein complex at a few micromolar concentrations with high resolution. In the native envelope, vitamin B12 induces a distinct conformational shift at the BtuCD-BtuF interface, which is not observed in the micelles. This approach offers a general strategy for investigating protein-protein and protein-ligand/drug interactions and conformational changes of the alpha-helical membrane proteins in their native envelope context.
View less1. The impact of warming on zooxanthellate corals is widespread, from tropical to temperate seas, with its associated mortalities causing global concern. 2. The temperate coral Cladocora caespitosa is the only zooxanthellate coral with reef building capacity in the Mediterranean Sea, a climate change hotspot with warming rates triple the global average. 3. During the past two decades, C. caespitosa populations have suffered severe mortality events associated with marine heatwaves (MHWs). However, with monitoring efforts beginning, at best, in the 2000s, the occurrence of MHWs before that period, as well as the sublethal effects of these events remain poorly understood. 4. Here, we use sclerochronology to reconstruct the histories of past stress events and long-term sublethal effects on C. caespitosa in three locations along a latitudinal gradient within the NW Mediterranean Sea, each with different environmental conditions. 5. Skeletal extension, density and calcification rates were compared with the in situ seawater temperature of each site to assess their relationship. Furthermore, we assessed the occurrence of skeletal growth anomalies to reconstruct stress events between 1991 and 2021, a period that encompasses the onset and evolution of warming-related mass mortality events in the NW Mediterranean Sea. 6. Our results reveal a positive association between calcification and temperature, following a latitudinal temperature gradient. However, the evolution of the likelihood distribution of growth rates in the warmest site (Columbretes Islands) since the 1990s indicates a decrease in linear extension and calcification rates during the most recent years. With the increase in the frequency of MHWs and growth anomalies during the last decade, this decline suggests recurrent physiological stress events. 7. These results unravel information on the long-term impacts of warming on coral growth and highlight the potential of applying sclerochronology to reconstruct the sublethal effects of warming using C. caespitosa.
View lessAcross countries, young people vote less than older citizens. While a few explanations have been suggested, this paper proposes that one core reason lies in youth under-representation in partisan politics, in particular as issues such as climate change increase the salience of inter-generational conflict. I argue that young people are less likely to vote in elections if they do not feel their age represented by candidates. I test this with data from the Comparative Study of Electoral Systems spanning 223 national elections in 58 countries between 1996 and 2021, combined with data on 980 party leaders and/or presidential candidates in those elections. I find that respondents younger than 30 are up to 4 per cent less likely to vote if the leading candidate of their favourite party is 70 in relation to a leader around 40. However, this effect only appears in more recent years and was nonexistent in the 1990s and early 2000s. Older voters' turnout is unaffected by leaders' and candidates' ages. Two potential mechanisms are the effects of descriptive representation of young voters on their external efficacy and democratic satisfaction. These findings corroborate the possible emergence of age as potential cleavage in contemporary politics and point to an important element of low youth participation as well as to the mobilization potential by parties selecting younger candidates.
View lessAutomated glycan assembly (AGA) streamlines the synthesis of complex oligosaccharides. The reducing end of the oligosaccharide serves as an attachment site to the polymer support to liberate a free reducing end or an aminopentanol for ready conjugation to carrier proteins or surfaces. The facile installation of different aglycons on oligosaccharides has not been possible via AGA until now. Here, we describe a latent-active approach enabled by a traceless photolabile linker that allows for bidirectional AGA and ready introduction of various aglycons. Oligosaccharide thioglycosides, peptidoglycans, prototypical saponins, and click-chemistry-based conjugates are synthesized to illustrate the versatility of the method.
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