Existing research on the security of the supply of critical materials for clean energy generally aggregates information at the country level, a practice that obscures the extensive role of foreign... Show moreExisting research on the security of the supply of critical materials for clean energy generally aggregates information at the country level, a practice that obscures the extensive role of foreign direct investment (FDI) in the production of critical materials. FDI refers to an ownership stake in a company or project by an overseas investor. Here we establish a database for global mining of lithium, cobalt, nickel and platinum at company level, covering 240 countries and regions. We show that 47% of lithium, 71% of cobalt, 41% of nickel and 34% of platinum mined in 2019 were under FDI. We then explore how FDI may affect supply risks by proposing a supply risk index that allocates production of the critical materials to the country of origin of investors instead of the country where production is located. We present upper and lower bounds of the supply risk index that reflect scenarios where either all investors or only state investors prioritize the home-country demand, respectively. This study presents an approach for assessing the national supply risks of critical materials, considering the geographical allocation of FDI. Show less
Tissue resident memory T (TRM) cells are a T-cell subset that resides at the site of prior antigen recognition to protect the body against reoccurring encounters. Besides their protective function,... Show moreTissue resident memory T (TRM) cells are a T-cell subset that resides at the site of prior antigen recognition to protect the body against reoccurring encounters. Besides their protective function, TRM cells have also been implicated in inflammatory disorders. TRM cells are characterized by the expression of CD69 and transcription factors Hobit (homolog of Blimp-1 [B lymphocyte-induced maturation protein 1] in T cells) and Blimp-1. As the majority of T cells in the arterial intima expresses CD69, TRM cells may contribute to the pathogenesis of atherosclerosis as well. Here, we aimed to assess the presence and potential role of TRM cells in atherosclerosis.To identify TRM cells in human atherosclerotic lesions, a single-cell RNA-sequencing data set was interrogated, and T-cell phenotypes were compared with that of integrated predefined TRM cells. The presence and phenotype of TRM in atherosclerotic lesions was corroborated using a mouse model that enabled tracking of Hobit-expressing TRM cells. To explore the function of TRM cells during atherogenesis, RAG1-/- (RAG1 deficient) LDLr-/- (low-density lipoprotein receptor knockout) mice received a bone marrow transplant from HobitKO/CREBlimp-1flox/flox mice, which exhibit abrogated TRM cell formation, whereafter the mice were fed a Western-type diet for 10 weeks.Human atherosclerotic lesions contained T cells that exhibited a TRM cell-associated gene signature. Moreover, a fraction of these T cells clustered together with predefined TRM cells upon integration. The presence of Hobit-expressing TRM cells in the atherosclerotic lesion was confirmed in mice. These lesion-derived TRM cells were characterized by the expression of CD69 and CD49α. Moreover, we demonstrated that this small T-cell subset significantly affects lesion composition, by reducing the amount of intralesional macrophages and increasing collagen content.TRM cells, characterized by the expression of CD69 and CD49α, constitute a minor population in atherosclerotic lesions and are associated with increased lesion stability in a Hobit and Blimp-1 knockout mouse model. Show less
Wright, K.; Koenders, M.; Douglas, K.M.; Faurholt-Jepsen, M.; Lewandowski, K.E.; Miklowitz, D.J.; ... ; Mesman, E. 2024
Feeling loved by one's parents is critical for children's health and well-being. How can such feelings be fostered? A vital feature of loving interactions is reciprocal self-disclosure, where... Show moreFeeling loved by one's parents is critical for children's health and well-being. How can such feelings be fostered? A vital feature of loving interactions is reciprocal self-disclosure, where individuals disclose intimate information about themselves. In a proof-of-concept experiment, we examined whether encouraging reciprocal self-disclosure in parent-child dyads would make children feel more loved during the conversation. Participants were 218 children (ages 8-13, 50% girls, 94% Dutch) and one of their parents (ages 28-56, 62% women, 90% Dutch). Parent-child dyads received a list of 14 questions and took turns asking them each other for 9 min. Dyads were assigned randomly to engage in self-disclosure (questions invoking escalated intimacy) or small talk (questions invoking minimal intimacy). Before and after, children reported how loved they felt by their parent during the conversation. Self-disclosure made children feel more loved during the conversation than did small talk. Compared to small talk, self-disclosure did not instigate conversations that were lengthier or more positive; rather, it instigated conversations that were more emotionally charged (reflecting anger, anxiety, and sadness), social (discussing family and friends), reflective (creating insight), and meaningful (addressing deeply personal topics, including the passing of loved ones). The dyad's gender composition did not significantly moderate these effects. Our research suggests that reciprocal self-disclosure can make children feel more loved in the moment, uncovers linguistic signatures of reciprocal self-disclosure, and offers developmental scientists a tool to examine causal effects of reciprocal self-disclosure in parent-child dyads. Future work should examine long-term effects in everyday parent-child interactions. RESEARCH HIGHLIGHTS: How can parents make children feel more loved by them in the moment? We theorize that these feelings can be cultivated through reciprocal self-disclosure. In a proof-of-concept experiment, we examined effects of reciprocal self-disclosure versus small talk in 218 parent-child dyads, with children aged 8-13. Self-disclosure (vs. small talk) made children feel more loved during the conversation. Linguistically, self-disclosure instigated conversations that were more emotionally charged, social, reflective, and meaningful. This research provides an experimental method to study self-disclosure in parent-child dyads and suggests that self-disclosure can make children feel more loved in the moment. Show less
This interdisciplinary study, coupling philosophy of law with empirical cognitive science, presents preliminary insight into the role of emotion in criminalization decisions, for both laypeople and... Show moreThis interdisciplinary study, coupling philosophy of law with empirical cognitive science, presents preliminary insight into the role of emotion in criminalization decisions, for both laypeople and legal professionals. While the traditional approach in criminalization theory emphasizes the role of deliberative and reasoned argumentation, this study hypothesizes that affective and emotional processes (i.e., disgust, as indexed by a dispositional proneness to experience disgust) are also associated with the decision to criminalize behavior, in particular virtual child pornography. To test this empirically, an online study (N = 1402) was conducted in which laypeople and legal professionals provided criminalization ratings on four vignettes adapted from criminal law, in which harmfulness and disgustingness were varied orthogonally. They also completed the 25-item Disgust Scale-Revised (DS-R-NL). In line with the hypothesis, (a) the virtual child pornography vignette (characterized as low in harm, high in disgust) was criminalized more readily than the financial harm vignette (high in harm, low in disgust), and (b) disgust sensitivity was associated with the decision to criminalize behavior, especially virtual child pornography, among both lay participants and legal professionals. These findings suggest that emotion can be relevant in shaping criminalization decisions. Exploring this theoretically, the results could serve as a stepping stone towards a new perspective on criminalization, including a “criminalization bias”. Study limitations and implications for legal theory and policymaking are discussed. Show less
Adaptive immunity plays a profound role in atherosclerosis pathogenesis by regulating antigen-specific responses, inflammatory signaling and antibody production. However, as we age, our immune... Show moreAdaptive immunity plays a profound role in atherosclerosis pathogenesis by regulating antigen-specific responses, inflammatory signaling and antibody production. However, as we age, our immune system undergoes a gradual functional decline, a phenomenon termed "immunosenescence". This decline is characterized by a reduction in proliferative naïve B- and T cells, decreased B- and T cell receptor repertoire and a pro-inflammatory senescence associated secretory profile. Furthermore, aging affects germinal center responses and deteriorates secondary lymphoid organ function and structure, leading to impaired T-B cell dynamics and increased autoantibody production. In this review, we will dissect the impact of aging on adaptive immunity and the role played by age-associated B- and T cells in atherosclerosis pathogenesis, emphasizing the need for interventions that target age-related immune dysfunction to reduce cardiovascular disease risk. Show less
We study the possible influences of the Russia-Ukraine War on Russia’s research productivity and international collaboration in science. For this purpose, we introduce and apply two recently... Show moreWe study the possible influences of the Russia-Ukraine War on Russia’s research productivity and international collaboration in science. For this purpose, we introduce and apply two recently developed indicators of relative intensity and balance in international collaboration. To see whether longitudinal trends have changed recently, we combine a long-term perspective based on annual updates since the year 2000 with a short-term perspective based on monthly updates since the beginning of 2022. The clearest change is that the productivity of Russian science, as measured within Web of Science, has dramatically decreased after several years of growth. There is also a clear decline in the degree of international collaboration in fields of research that heavily rely on large multinational infrastructures established through state agreements. In other fields, however, the degree of international collaboration is more stable. The general decline in Russian science seems to be more driven by internal factors than by loss of partnerships abroad. Show less
Observations of low-lying dark states in several photosynthetic complexes challenge our understanding of the mechanisms behind their efficient energy transfer processes. Computational models are... Show moreObservations of low-lying dark states in several photosynthetic complexes challenge our understanding of the mechanisms behind their efficient energy transfer processes. Computational models are necessary for providing novel insights into the nature and function of dark states, especially since these are not directly accessible in spectroscopy experiments. Here, we will focus on signatures of dark-type states in chlorosomes, a light-harvesting complex from green sulfur bacteria well-known for uniting a broad absorption band with very efficient energy transfer. In agreement with experiments, our simulations of two-dimensional electronic spectra capture the ultrafast exciton transfer occurring in 100s of femtoseconds within a single chlorosome cylinder. The sub-100 fs process corresponds to relaxation within the single-excitation manifold in a single chlorosome tube, where all initially created populations in the bright exciton states are quickly transferred to dark-type exciton states. Structural inhomogeneities on the local scale cause a redistribution of the oscillator strength, leading to the emergence of these dark-type exciton states, which dominate ultrafast energy transfer. The presence of the dark-type exciton states suppresses energy loss from an isolated chlorosome via fluorescence quenching, as observed experimentally. Our results further question whether relaxation to dark-exciton states is a leading process or merely competes with transfer to the baseplate within the photosynthetic apparatus of green sulfur bacteria. Show less
Castonguay, L.G.; Atzil‑Slonim, D.; Jong, K. de; Youn, S.J. 2024
Research Integrity (RI) is high on the agenda of both institutions and science policy. The European Union as well as national ministries of science have launched ambitious initiatives to combat... Show moreResearch Integrity (RI) is high on the agenda of both institutions and science policy. The European Union as well as national ministries of science have launched ambitious initiatives to combat misconduct and breaches of research integrity. Often, such initiatives entail attempts to regulate scientifc behavior through guidelines that institutions and academic communities can use to more easily identify and deal with cases of misconduct. Rather than framing misconduct as a result of an information defcit, we instead conceptualize Questionable Research Practices (QRPs) as attempts by researchers to reconcile epistemic and social forms of uncertainty in knowledge production. Drawing on previous literature, we defne epistemic uncertainty as the inherent intellectual unpredictability of scientifc inquiry, while social uncertainty arises from the human-made conditions for scientifc work. Our core argument—developed on the basis of 30 focus group interviews with researchers across diferent felds and European countries—is that breaches of research integrity can be understood as attempts to loosen overly tight coupling between the two forms of uncertainty. Our analytical approach is not meant to relativize or excuse misconduct, but rather to ofer a more fne-grained perspective on what exactly it is that researchers want to accomplish by engaging in it. Based on the analysis, we conclude by proposing some concrete ways in which institutions and academic communities could try to reconcile epistemic and social uncertainties on a more collective level, thereby reducing incentives for researchers to engage in misconduct. Show less
Paus, L.V. de; Yu, A.; Janssen, A.P.A.; Berg, R.J.B.H.N. van den; Heitman, L.H.; Stelt, M. van der 2024
The cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor... Show moreThe cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor localization, expression and occupancy. Previously, we have reported a photoaffinity probe LEI-121 that stabilized the inactive conformation of the CB2R. Here, we report the structure-based design of a novel bifunctional probe that captures the active conformation of the CB2R upon irradiation with light. An alkyne handle was incorporated to visualize the receptor using click-chemistry with fluorophore-azides. These probes may hold promise to study different receptor conformations in relation to their cellular localization and function. Show less
Fluency, comprehensibility, and accentedness are considered importantparameters of interpreting quality but have rarely been studiedsystematically in training programs of interpreting. Therefore,... Show moreFluency, comprehensibility, and accentedness are considered importantparameters of interpreting quality but have rarely been studiedsystematically in training programs of interpreting. Therefore, the presentstudy was set up to investigate the effect of fluency training on speechfluency, comprehensibility, and accentedness of interpreter trainees. Twogroups of interpreter trainees at a university in Iran took part in the study,receiving the same amount of instruction and practice (12 hours over 4weeks). The experimental group (N=30) spent 33% of the time (i.e., 4 of the12 hours in the training program) on dedicated fluency strategy training,encouraging the memorization, repetition, and retelling of audio and videomaterials. The remaining 67% was spent on training general speaking skills.The control group (N=30) were only taught general speaking skills in thetraining program but received no dedicated fluency training. Systematicinterviews were run to assess the interpreter trainees’ speech fluency,comprehensibility and accentedness, which were judged independently bythree expert raters at three moments of testing, i.e., pretest, immediateposttest, and delayed posttest (one month later). The findings revealed thatthe fluency training significantly enhanced the interpreter trainees’ fluency,and to a lesser extent the students’ comprehensibility but had only amarginal effect on accentedness. The pedagogical implication would be thatawareness training on speech fluency Show less
Mulholland, M.; Depuydt, M.A.C.; Jakobsson, G.; Ljungcrantz, I.; Grentzmann, A.; To, F.; ... ; Engelbertsen, D. 2024
The interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we... Show moreThe interleukin-1 receptor accessory protein (IL1RAP) is a co-receptor required for signalling through the IL-1, IL-33, and IL-36 receptors. Using a novel anti-IL1RAP-blocking antibody, we investigated the role of IL1RAP in atherosclerosis.Single-cell RNA sequencing data from human atherosclerotic plaques revealed the expression of IL1RAP and several IL1RAP-related cytokines and receptors, including IL1B and IL33. Histological analysis showed the presence of IL1RAP in both the plaque and adventitia, and flow cytometry of murine atherosclerotic aortas revealed IL1RAP expression on plaque leucocytes, including neutrophils and macrophages. High-cholesterol diet fed apolipoprotein E-deficient (Apoe-/-) mice were treated with a novel non-depleting IL1RAP-blocking antibody or isotype control for the last 6 weeks of diet. IL1RAP blockade in mice resulted in a 20% reduction in subvalvular plaque size and limited the accumulation of neutrophils and monocytes/macrophages in plaques and of T cells in adventitia, compared with control mice. Indicative of reduced plaque inflammation, the expression of several genes related to leucocyte recruitment, including Cxcl1 and Cxcl2, was reduced in brachiocephalic arteries of anti-IL1RAP-treated mice, and the expression of these chemokines in human plaques was mainly restricted to CD68+ myeloid cells. Furthermore, in vitro studies demonstrated that IL-1, IL-33, and IL-36 induced CXCL1 release from both macrophages and fibroblasts, which could be mitigated by IL1RAP blockade.Limiting IL1RAP-dependent cytokine signalling pathways in atherosclerotic mice reduces plaque burden and plaque inflammation, potentially by limiting plaque chemokine production. Show less
The clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality... Show moreThe clinical translation of polysarcosine (pSar) as polyethylene glycol (PEG) replacement in the development of novel nanomedicines creates a broad demand of polymeric material in high-quality making high-purity sarcosine N-carboxyanhydride (Sar-NCA) as monomer for its production inevitable. Within this report, we present the use of triethyloxonium tetrafluoroborate in Sar-NCA synthesis with focus on amino acid and chloride impurities to avoid the sublimation of Sar-NCAs. With a view towards upscaling into kilogram or ton scale, a new methodology of monomer purification is introduced by utilizing the Meerwein's Salt triethyloxonium tetrafluoroborate to remove chloride impurities by covalent binding and converting chloride ions into volatile products within a single step. The novel straightforward technique enables access to monomers with significantly reduced chloride content (<100 ppm) compared to Sar-NCA derived by synthesis or sublimation. The derived monomers enable the controlled-living polymerization in DMF and provide access to pSar polymers with Poisson-like molecular weight distribution within a high range of chain lengths (Xn 25-200). In conclusion, the reported method can be easily applied to Sar-NCA synthesis or purification of commercially available pSar-NCAs and eases access to well-defined hetero-telechelic pSar polymers. Show less
