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Dysregulated insulin signaling and inflammation contribute to the pathogenesis of Alzheimer's disease:From animal models to human cells
No full textTemporal Proteomic Remodeling of Cerebral Arteries in Male Hypertensive Rats
No full textBACKGROUND: Hypertension is a significant risk factor for several neurological disorders, including stroke and dementia, yet the molecular mechanisms underlying these risks remain poorly understood. In this study, we investigated temporal proteomic remodeling of the cerebrovasculature in male spontaneously hypertensive rats and normotensive Wistar-Kyoto controls at 30 and 40 weeks of age, representing the effect of untreated hypertension from early adulthood to midlife. METHODS: Using male 30- and 40-week-old spontaneously hypertensive rats and Wistar-Kyoto rats, we have performed discovery-based proteomics, histological imaging, and RNA-sequencing data analysis. RESULTS: Proteomic analysis displayed a significant age-dependent change in the protein composition of the cerebrovasculature in the spontaneously hypertensive rat model, which is partly mediated via reduced SRF (serum response factor) expression and associated regulon. Pathway analysis revealed a transient upregulation of mitotic (M-phase) proteins at 30 weeks, indicative of maladaptive smooth muscle proliferation. By 40 weeks, the expression of these proteins was normalized; however, ECM (extracellular matrix)-associated proteins diverged substantially. The ECM remodeling was supported by increased media-to-circumference ratio and collagen deposition from histological analysis. CONCLUSIONS: Our findings demonstrate that hypertension drives a temporal shift in cerebrovascular remodeling, transitioning from early maladaptive smooth muscle proliferation to later ECM-driven structural changes. This progression suggests that the pathogenic mechanisms underlying hypertensive vascular injury are dynamic across the life course, with distinct phases that may require different and timely therapeutic approaches to mitigate the risks of neurovascular diseases.</p
Dual-Mode Solar-Blind Ultraviolet Imaging Application Based on -Ga<sub>2</sub>O<sub>3</sub> MSM Photodetector Array
No full textNitrated products formed on α-synuclein are preferentially incorporated into oligomers but excluded from fibrils:A mechanism for accumulation of neurotoxic species
No full textPost-translational modifications (PTMs) such as nitration of Tyr (Y) residues and di-tyrosine (DT) formation are known to impact the aggregation behavior of α-synuclein (α-syn), a protein closely linked to Parkinson's disease. Using tetranitromethane (TNM) as a model nitrating agent, we systematically investigated the chemical modifications of α-syn and their consequences for aggregation. Mass spectrometry analysis revealed site-selective nitration of all four Tyr residues, with Y39 and Y125 being most susceptible. DT crosslinks were also observed, primarily involving Y39, but were disfavored at higher TNM concentrations, indicating competition between nitration and crosslinking pathways. Higher TNM concentrations favored nitration over crosslinking, consistent with common radical intermediates. Even sub-stoichiometric amounts of TNM-modified α-syn significantly inhibited fibril elongation, suggesting that nitration disrupts the templated addition of monomers into the ordered fibrillar structure. Consistent with this, TNM-modified α-syn was strongly excluded from fibrillar assemblies. In contrast, they were preferentially incorporated into soluble oligomers, underlining the promiscuous ability of oligomers to act as a sink for chemically modified α-syn monomers, with potential implications for neurotoxicity.</p
Mental health and body mass index in early pregnancy:a secondary analysis of three randomised controlled trials
No full textOBJECTIVE: Overweight and obesity in pregnant women have been associated with an increased risk of depression and anxiety, but the strength of these associations and the influence of confounders remain uncertain. Understanding these associations may help identify women at risk in early pregnancy and guide targeted support. This study aimed to quantify associations between maternal body mass index (BMI) and symptoms of depression, anxiety, and health-related quality of life (HRQoL) in early pregnancy and to assess whether they persisted after adjustment for confounders.METHODS: This secondary analysis pooled baseline data from three randomised controlled trials including women at gestational week 10 + 0 to 20 + 0: LIMIT (BMI ≥ 25.0 kg/m²), GRoW (BMI ≥ 25.0 kg/m²) and OPTIMISE (BMI ≥ 18.5 to ≤ 24.9 kg/m²). LIMIT and OPTIMISE randomised participants to lifestyle intervention or standard care. In GRoW all women received a lifestyle intervention and were randomised to metformin or placebo. At baseline, women completed questionnaires assessing symptoms of depression, anxiety, and HRQoL (SF-12 or SF-36).RESULTS: 2961 pregnant women (mean BMI: 29.3 kg/m2; mean age: 30.1 years) completed at least one questionnaire, including 1815 (61%) from LIMIT, 513 (17%) from GRoW, and 633 (21%) from OPTIMISE. Higher BMI was associated with an increase in depressive and anxiety symptoms in unadjusted analyses. After adjustment, only the association with depressive symptoms remained significant (β = 0.05, 95% CI 0.02, 0.08). BMI was inversely associated with physical HRQoL (βSF-12=-0.36, 95% CI -0.45, -0.27; βSF-36=-0.18, 95% CI -0.25, -0.11). Mental HRQoL was positively associated with BMI using SF-12 (βSF-12 = 0.18, 95% CI 0.08, 0.29) but showed no association with BMI using SF-36 (βSF-36=-0.07, 95% CI -0.15, 0.02).CONCLUSION: Increasing BMI was associated with higher depressive symptoms and poorer physical HRQoL in early pregnancy, but effect sizes were small, inconsistent, and attenuated after adjustment, suggesting modest associations partly explained by confounding. These findings highlight the need for a holistic approach to supporting mental health in pregnant women with overweight or obesity, as multiple factors beyond body weight likely contribute.TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry; LIMIT (ACTRN12607000161426, 9 March 2007); OPTIMISE (ACTRN12614000583640, 30 May 2014); GRoW (ACTRN12612001277831, 10 December 2012).</p
Transformative Feminisms:Nordic Art in the Transcultural Present
No full textThis is the first major publication in any language to re-evaluate the problematics that enmesh feminism, gender, and contemporary Nordic art. The book probes the shifting nature of the "Nordic" to challenge its popular image as liberal when it comes to genders, sexualities, and ethnicities. It questions the so-called wave model to suggest instead a history of sporadic (re)surfacings and submersions of feminism’s impact on Nordic art over the last sixty years. The intersectional, transhistorical, and transcultural focus nuances the Nordic and demystifies common tropes while reflecting the principal concerns of feminist art scholars working today: the welfare model; gender, sexuality, and the body; transculturality and decolonialization, and posthuman feminism and glitches
One dies, the other survives – A comparison of the early transcriptomic immune responses in zebrafish and rainbow trout infected with <i>Ichthyophthirius multifiliis</i>
No full textIchthyophthirius multifiliis (Ich) is the causative agent of white spot disease which is associated with high mortality, morbidity, and significant economic losses. While the majority of freshwater fish species are susceptible to the infection the zebrafish exhibits natural resistance. Acute immune responses during early stage infection have been suggested to play a role for the subsequent disease severity. Therefore, this study provides the first comparative transcriptomic investigation of the early gill immune responses to Ich infection in zebrafish (naturally resistant) and rainbow trout (susceptible), which was further supported by real-time qPCR analyses. Zebrafish and rainbow trout were infected with Ich, and gill samples were collected at 2, 24, 48, and 72 hours post-infection (hpi). Zebrafish mounted a rapid response that peaked at 24 hpi, whereas rainbow trout showed a delayed and markedly weaker response. In zebrafish, differentially expressed genes (DEGs) at 24 hpi were linked to six downregulated immune-related pathways; Toll-like, NOD-like, C-type lectin, RIG-I-like receptor signaling pathways, Cytosolic DNA-sensing pathway and Intestinal immune network for IgA production, suggesting a controlled resolution of the response following an early parasite clearance. This was supported by a decrease in Ich genome transcripts in zebrafish indicating disease clearance, whereas transcript numbers increased in rainbow trout indicating disease progression. Upregulation of several cytokines and chemokines in zebrafish, including Cxcl8a, Cxcl11 (24 hpi) and Cxcl13 (48 hpi) highlights the involvement of cellular and mucosal immune mechanisms in early resistance. This study underscores the importance of early immune responses in determining the severity of Ich infection and provide new insights into host–parasite interactions.</p
Beyond Preferences:Rethinking shared decision-making through the Lens of care
No full textEfforts to involve patients in medical decision-making have led to the development of various models for structuring clinical encounters. Among them, Shared Decision-Making (SDM) is now a cornerstone of contemporary healthcare, based on the ethical imperative to involve patients through the articulation of preferences. However, in practice, SDM often relies on a rationalist model of deliberation that prioritizes autonomy, clarity, and informed choice—often overlooking the relational, affective, and embodied dynamics of care.Drawing on ethnographic fieldwork in France, Spain, and Denmark with patients undergoing long-term anticoagulant therapy following unprovoked venous thromboembolism (VTE), this article examines the contexts in which decisions are made, as well as patients' attitudes toward those decisions and their treatment. We argue that “preferences”—the conceptual hinge of SDM—are not stable expressions of autonomous will, but rather fragile, contingent, and emergent responses. Especially as understood and operationalized by practitioners, preferences often obscure other forms through which patient agency is exercised, both within and beyond the clinical consultation.Engaging Annemarie Mol's “logic of care”, we show how patient agency unfolds not as a rational choice between predefined options, but as an ongoing, situated negotiation of treatment that extends beyond the consultation. Furthermore, focusing on care, rather than choice, allows for a medical approach attentive to the patient's needs, demands, and hesitations—not solely to their stable preferences regarding treatment duration. These findings call for broadening participation beyond preference articulation, toward more responsive and context-sensitive forms of engagement.Efforts to involve patients in medical decision-making have led to the development of various models for structuring clinical encounters. Among them, Shared Decision-Making (SDM) is now a cornerstone of contemporary healthcare, based on the ethical imperative to involve patients through the articulation of preferences. However, in practice, SDM often relies on a rationalist model of deliberation that prioritizes autonomy, clarity, and informed choice—often overlooking the relational, affective, and embodied dynamics of care. Drawing on ethnographic fieldwork in France, Spain, and Denmark with patients undergoing long-term anticoagulant therapy following unprovoked venous thromboembolism (VTE), this article examines the contexts in which decisions are made, as well as patients' attitudes toward those decisions and their treatment. We argue that “preferences”—the conceptual hinge of SDM—are not stable expressions of autonomous will, but rather fragile, contingent, and emergent responses. Especially as understood and operationalized by practitioners, preferences often obscure other forms through which patient agency is exercised, both within and beyond the clinical consultation. Engaging Annemarie Mol's “logic of care”, we show how patient agency unfolds not as a rational choice between predefined options, but as an ongoing, situated negotiation of treatment that extends beyond the consultation. Furthermore, focusing on care, rather than choice, allows for a medical approach attentive to the patient's needs, demands, and hesitations—not solely to their stable preferences regarding treatment duration. These findings call for broadening participation beyond preference articulation, toward more responsive and context-sensitive forms of engagement.</p
