COMMD1-deficient dogs accumulate copper in hepatocytes and provide a good model for chronic hepatitis and fibrosis

New therapeutic concepts developed in rodent models should ideally be evaluated in large animal models prior to human clinical application. COMMD1-deficiency in dogs leads to hepatic copper accumulation and chronic hepatitis representing a Wilson's disease like phenotype. Detailed understanding of the pathogenesis and time course of this animal model is required to test its feasibility as a large animal model for chronic hepatitis. In addition to mouse models, true longitudinal studies are possible due to the size of these dogs permitting detailed analysis of the sequence of events from initial insult to final cirrhosis. Therefore, liver biopsies were taken each half year from five new born COMMD1-deficient dogs over a period of 42 months. Biopsies were used for H&E, reticulin, and rubeanic acid (copper) staining. Immunohistochemistry was performed on hepatic stellate cell (HSC) activation marker (alpha-smooth muscle actin, α-SMA), proliferation (Ki67), apoptosis (caspase-3), and bile duct and liver progenitor cell (LPC) markers keratin (K) 19 and 7. Quantitative RT-PCR and Western Blots were performed on gene products involved in the regenerative and fibrotic pathways. Maximum copper accumulation was reached at 12 months of age, which coincided with the first signs of hepatitis. HSCs were activated (α-SMA) from 18 months onwards, with increasing reticulin deposition and hepatocytic proliferation in later stages. Hepatitis and caspase-3 activity (first noticed at 18 months) increased over time. Both HGF and TGF-β1 gene expression peaked at 24 months, and thereafter decreased gradually. Both STAT3 and c-MET showed an increased time-dependent activation. Smad2/3 phosphorylation, indicative for fibrogenesis, was present at all time-points. COMMD1-deficient dogs develop chronic liver disease and cirrhosis comparable to human chronic hepatitis, although at much higher pace. Therefore they represent a genetically-defined large animal model to test clinical applicability of new therapeutics developed in rodent models

Implementation factors for green hydrogen projects : a systematic literature review

The global transition to a low-carbon economy relies on the large-scale deployment of green hydrogen as a clean energy carrier and industrial feedstock. Despite numerous project announcements worldwide, actual implementation remains limited. Accordingly, it is necessary to systematically analyse the critical factors influencing the practical deployment of green hydrogen projects. To this end, the paper conducts a systematic literature review examining the factors that determine green hydrogen project implementation success, analyzing 153 academic publications and key reports from IRENA and IEA. The systematic literature review identifies that the implementation of green hydrogen projects hinges on a complex interplay of techno-economic, site-specific resource, economic, and socio-political factors. Notably, there are significant global disparities, which are particularly evident for developing and least developed economies, often relying on international financing, technology transfer, and strategic partnerships. These disparities are also reflected in the academic landscape, where research predominantly focuses on advanced economies and major emerging markets

Molecular Characterization of the Gastrula in the Turtle Emys orbicularis: An Evolutionary Perspective on Gastrulation

Due to the presence of a blastopore as in amphibians, the turtle has been suggested to exemplify a transition form from an amphibian- to an avian-type gastrulation pattern. In order to test this hypothesis and gain insight into the emergence of the unique characteristics of amniotes during gastrulation, we have performed the first molecular characterization of the gastrula in a reptile, the turtle Emys orbicularis. The study of Brachyury, Lim1, Otx2 and Otx5 expression patterns points to a highly conserved dynamic of expression with amniote model organisms and makes it possible to identify the site of mesoderm internalization, which is a long-standing issue in reptiles. Analysis of Brachyury expression also highlights the presence of two distinct phases, less easily recognizable in model organisms and respectively characterized by an early ring-shaped and a later bilateral symmetrical territory. Systematic comparisons with tetrapod model organisms lead to new insights into the relationships of the blastopore/blastoporal plate system shared by all reptiles, with the blastopore of amphibians and the primitive streak of birds and mammals. The biphasic Brachyury expression pattern is also consistent with recent models of emergence of bilateral symmetry, which raises the question of its evolutionary significance

Unpacking the multilingualism continuum: An investigation of language variety co-activation in simultaneous interpreters

This study examines the phonological co-activation of a task-irrelevant language variety in mono- and bivarietal speakers of German with and without simultaneous interpreting (SI) experience during German comprehension and production. Assuming that language varieties in bivarietal speakers are co-activated analogously to the co-activation observed in bilinguals, the hypothesis was tested in the Visual World paradigm. Bivarietalism and SI experience were expected to affect co-activation, as bivarietalism requires communication-context based language-variety selection, while SI hinges on concurrent comprehension and production in two languages; task type was not expected to affect co-activation as previous evidence suggests the phenomenon occurs during comprehension and production. Sixty-four native speakers of German participated in an eye-tracking study and completed a comprehension and a production task. Half of the participants were trained interpreters and half of each sub-group were also speakers of Swiss German (i.e., bivarietal speakers). For comprehension, a growth-curve analysis of fixation proportions on phonological competitors revealed cross-variety co-activation, corroborating the hypothesis that co-activation in bivarietals’ minds bears similar traits to language co-activation in multilingual minds. Conversely, co-activation differences were not attributable to SI experience, but rather to differences in language-variety use. Contrary to expectations, no evidence for phonological competition was found for either same- nor cross-variety competitors in either production task (interpreting- and word-naming variety). While phonological co-activation during production cannot be excluded based on our data, exploring the effects of additional demands involved in a production task hinging on a language-transfer component (oral translation from English to Standard German) merit further exploration in the light of a more nuanced understanding of the complexity of the SI task

Country risk impacts on export costs of green hydrogen and its synthetic downstream products from the Middle East and North Africa

Green hydrogen, produced from renewable energy sources such as wind and solar, is increasingly recognized as a critical enabler of the global energy transition and the decarbonization of industrial and transport sectors. The successful adoption of green hydrogen and its derivatives is closely linked to production costs, which can vary substantially between countries, depending not only on resource potential but also on country-specific financing conditions. These differences arise from country-specific risk factors that affect the costs of capital, ultimately influencing investment decisions. However, comprehensive assessments that integrate these risks with future cost projections for renewable energy, green hydrogen, and its synthetic downstream products are lacking. Using the Middle East and North Africa (MENA) as an example, this study introduces a novel approach that allows to incorporate mainly qualitative country-specific investment risks into quantitative analyses such as cost-potential and energy modelling. Our methodology calculates weighted average costs of capital (WACC) for 17 MENA countries under different risk scenarios, providing a more nuanced assessment compared to traditional models that use uniform cost of capital assumptions. The results indicate significant variations in WACC, such as between 4.67% in the United Arab Emirates and 24.84% in Yemen or Syria in the business-as-usual scenario. The incorporation of country-specific capital cost scenarios in quantitative analysis is demonstrated by modelling the cost-potential of Fischer-Tropsch (FT) fuels. The results show that country-specific investment risks significantly impact costs. For instance, by 2050, the starting LCOFs in high-risk scenarios can be up to 180% higher than in lower-risk contexts. This underlines that while renewable energy potential and its cost are important, it are the country-specific risk factors—captured through WACC - that have a greater influence in determining the competitiveness of exports and, consequently, the overall development of the renewable energy, green hydrogen and synthetic fuel sectors

Considerations of a possible global hydrogen energy trade

Scientific literature and the energy policies of many countries indicate that hydrogen and its derivatives, such as ammonia and synthetic hydrocarbons, are likely to play an important role in future energy systems and economies. Global plans indicate that import-export energy markets will likely continue to be part of future energy systems, but there has been limited literature on the specific evolution of international energy trade with regards to magnitudes, potential energy carriers, and influence of social and economic factors. Here we review and discuss various aspects of hydrogen's potential for becoming a globally tradeable energy commodity in the context of the Frontiers in Energy Research Topic: "Export and import of electrolytic hydrogen using renewable energy and subsequent synthetic fuels between regions–assessment of technology routes, potentials, and strategies". Technical challenges are likely to impact that hydrogen potential including the form of energy being transported, primary energy and raw material availability and costs, hydrogen generation, derivative synthesis, and transport infrastructure. Timing of infrastructure development is a key consideration due to the potential economic impacts of unusable infrastructure if export, import, and transport capabilities become available at different times. Additionally, we identify and review social and market considerations including hydrogen certification, water availability and use, ecologic considerations, social acceptance, other human factors, investment risk, and market development. Based on those considerations, we propose factors that would benefit nations and investors to consider as they contemplate investments in hydrogen systems and set the stage for further research contributions to this Frontiers in Energy Research Topic

Quasiparticle energy in a strongly interacting homogeneous Bose-Einstein condensate

Using two-photon Bragg spectroscopy, we study the energy of particlelike excitations in a strongly interacting homogeneous Bose-Einstein condensate, and observe dramatic deviations from Bogoliubov theory. In particular, at large scattering length a the shift of the excitation resonance from the free-particle energy changes sign from positive to negative. For an excitation with wave number q, this sign change occurs at a≈4/(πq), in agreement with the Feynman energy relation and the static structure factor expressed in terms of the two-body contact. For a≳3/q we also see a breakdown of this theory, and better agreement with calculations based on the Wilson operator product expansion. Neither theory explains our observations across all interaction regimes, inviting further theoretical efforts

Novel polyhydroxyalkanoate–graphene oxide composites with potential for clinical application against bacterial implant-associated infections in septic surgery

Introduction: Implant-associated infections are a major clinical challenge, often leading to implant failure, revision surgeries, and increased healthcare costs. The development of advanced biomaterials with inherent antimicrobial properties is critical to address this issue. In this study, we present novel two-dimensional (2D) composite films based on polyhydroxyalkanoates (PHAs) combined with graphene oxide (GO) to confer both antimicrobial activity and tailored mechanical properties. Methods: Composites with varying GO concentrations (0.5, 2, and 5 wt%) were fabricated using the solvent casting method, using both a short-chain-length PHA, P(3HB) and a medium-chain-length PHA, P(3HO-co-3HD). Physicochemical characterization (scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and mechanical testing) confirmed successful GO incorporation, changes in surface morphology, and modifications in thermal and mechanical properties. Results: Notably, the incorporation of 2 wt% GO into P(3HB) increased the Young’s modulus from 776 ± 15 MPa to 1,055 ± 28 MPa, indicating enhanced stiffness. Antibacterial testing using ISO 22196 against Staphylococcus aureus and Escherichia coli revealed that P(3HB)/2 wt% GO exhibited the highest antibacterial efficacy. In contrast, the 5 wt% GO composite showed reduced antibacterial activity, likely due to GO agglomeration. Moreover, in vitro cytocompatibility assays using L929 fibroblasts and NG108-15 neuronal cells demonstrated high cell viability across all composites, indicating high cytocompatibility

BMP signals and the transcriptional repressor BLIMP1 during germline segregation in the mammalian embryo

Molecular factors and tissue compartments involved in the foundation of the mammalian germline have been mainly described in the mouse so far. To find mechanisms applicable to mammals in general, we analyzed temporal and spatial expression patterns of the transcriptional repressor BLIMP1 (also known as PRDM1) and the signaling molecules BMP2 and BMP4 in perigastrulation and early neurulation embryos of the rabbit using whole-mount in situ hybridization and high-resolution light microscopy. Both BMP2 and BMP4 are expressed in annular domains at the boundary of the embryonic disc, which—in contrast to the situation in the mouse—partly belong to intraembryonic tissues. While BMP2 expression begins at (pregastrulation) stage 1 in the hypoblast, BMP4 expression commences—distinctly delayed compared to the mouse—diffusely at (pregastrulation) stage 2; from stage 3 onwards, BMP4 is expressed peripherally in hypoblast and epiblast and in the mesoderm at the posterior pole of the embryonic disc. BLIMP1 expression begins throughout the hypoblast at stage 1 and emerges in single primordial germ cell (PGC) precursors in the posterior epiblast at stage 2 and then in single mesoderm cells at positions identical to those identified by PGC-specific antibodies. These expression patterns suggest that function and chronology of factors involved in germline segregation are similar in mouse and rabbit, but higher temporal and spatial resolution offered by the rabbit demonstrates a variable role of bone morphogenetic proteins and makes “blimping” a candidate case for lateral inhibition without the need for an allantoic germ cell niche