Browse Articles

Strain-specific propagation of variant Creutzfeldt–Jakob disease prions in humanized neural cells

Prions are self-templating assemblies of the host prion protein in which conformational templating encodes heritable “strain” information. Human prion diseases, including Creutzfeldt–Jakob disease (CJD), are rare but uniformly fatal neurodegenerative disorders with established public-health relevance through epidemic and iatrogenic transmission and provide a paradigm for conformational templating in neurodegeneration. Mechanistic analysis of human prion propagation and development of infectivity assays for public health surveillance have been limited by the absence of mammalian cell systems that replicate authentic infectious human prions. Here, we establish a humanized neural cell system that enables propagation of variant CJD (vCJD) prions and reveals that prion replication is constrained by strain-compatible cellular states. The platform was generated using a silencing-followed-by-reconstitution strategy analogous to that used in transgenic mouse models of human prion disease, combined with high-throughput clonal selection. These cells propagate brain-derived vCJD prions and support chronic infection. Prions propagated in vitro transmit disease to humanized transgenic and wild-type mice while preserving defining biochemical and strain-specific neuropathological features, demonstrating faithful propagation. Propagation is strain specific: The cells are permissive to vCJD but refractory to sporadic CJD isolates, indicating that prion replication is constrained by strain-compatible cellular states. These humanized cells enable quantitative detection of infection at high dilution, support systematic genetic manipulation, and are readily adaptable to automation. By overcoming a longstanding barrier of propagating authentic human prions, this platform enables mechanistic dissection of the cellular determinants of prion replication and strain specificity and provides a scalable system for genetic analysis and sensitive detection of infectious human prions.

Contrasting life history in the diminutive Dimetrodon species from North America and Germany

Abstract The sphenacodontid Dimetrodon is best known from lower Permian marginal-marine deposits of North America (NA), where it occupied apex predator roles in aquatic-based food chains. Dimetrodon teutonis , the smallest documented species and only known representative of this genus outside NA, comes from the fully terrestrial and resource-limited ecosystem of the upper Asselian Bromacker locality, Germany. To evaluate its growth strategy and diminutive nature, we present the first osteohistological analysis of D. teutonis . We also reassess NA material from four localities spanning distinct depositional settings. In contrast to the thick and highly vascularized woven to parallel-fibered bone cortices of most NA species, including the small-bodied D. natalis , D. teutonis exhibits thin cortices composed of poorly vascularized parallel-fibered bone. The presence of an external fundamental system indicates somatic maturity and confirms its diminutive nature. These data suggest extended and slow growth throughout ontogeny, likely linked to seasonal resource limitation and low predation pressure in the unique Bromacker ecosystem. In contrast, NA diminutive species inhabiting lowland ecosystems grew rapidly and matured early, in response to competition and high predation pressure. These contrasting life histories in small Dimetrodon species reflect differing ecological pressures and illustrate diverging evolutionary pathways to dwarfism in this iconic genus.

Development of a robust method to derive human trophoblast stem cells from late-gestation placentas and its application to preeclampsia

Trophoblasts are multifunctional cells in the placenta and essential for normal pregnancy. Although trophoblast dysfunction can cause pregnancy complications, the underlying mechanisms remain unclear, and effective treatments are limited, partly because of the scarcity of appropriate experimental models. We previously reported the derivation of human trophoblast stem cells (hTSCs) from 1st-trimester placentas and blastocysts, providing a powerful tool to investigate human trophoblast development and function. However, the difficulty in deriving hTSCs from late-gestation placentas has limited their application to pregnancy complication research. Here we report a robust technique to derive hTSCs from term placentas based on the transient expression of a p53 dominant negative mutant, SALL4, and shRNAs against cyclin-dependent kinase inhibitors. Using this technique, we derived and characterized hTSCs from placentas obtained from patients with early-onset preeclampsia (PE). PE-derived hTSCs exhibit impaired trophoblast invasion and reduced placental growth factor secretion, consistent with trophoblast abnormalities reported in PE. Therefore, this study provides a technological basis for investigating pregnancy complications associated with trophoblast dysfunction.

Urban–rural structuring of mosquito assemblages in Moyen-Ogooué, Gabon reveals widespread dominance of Aedes albopictus

Abstract Mosquito-borne arboviruses such as dengue, chikungunya, Zika, yellow fever, West Nile and Rift Valley fever circulate widely in Central Africa, yet vector ecology, especially outside major cities, remains poorly characterized. Between March 2023 and January 2025, we conducted bimonthly entomological surveys to investigate the ecological patterns of mosquito communities across an urban (Lambaréné), peri-urban and rural gradient in Moyen-Ogooué province, central Gabon. Larvae were sampled with WHO ovitraps, and adult mosquitoes were collected using light traps and Prokopack aspirators. In total, 22,216 mosquitoes were collected, representing 21 species from 8 genera. Aedes (57.2%) and Culex. (23.3%) predominated, alongside Mansonia. (16.3%) and lower abundances of Anopheles , Lutzia , Coquillettidia , Uranotaenia and Erethmapodites . Three species dominated overall: Ae. albopictus (52.5%), Ma. uniformis (16.2%) and Cx. quinquefasciatus (11.3%). Six species have been firstly reported in Gabon including Ae. argenteopunctatus , Ae. opok , Cx. bitaeniorhynchus , Cx. giganteus , Cx. poicilipes , and Cx. tritaeniorhynchus . Rural areas harboured the highest richness (up to 21 species), including numerous rare and functionally specialized taxa. Urban communities were species-poor and strongly dominated by Ae. albopictus and Cx. quinquefasciatus . Diversity indices and NMDS ordination showed clear, seasonally modulated assemblages across landscapes, with peri-urban sites forming ecological transition zones with intermediate species richness and dominance levels. These findings validate and extend evidence for an Aedes and Culex. species shift and reveal a highly structured, seasonally dynamic mosquito community in Gabon. Crucially, the coexistence of dominant vectors with a broad array of less common species shows that arboviral transmission potential in central Gabon is shaped by the entire mosquito community. Biodiversity-wide surveillance, not only of major vectors, is therefore essential for understanding and anticipating arbovirus circulation in this ecologically complex region.

Phase-selective Floquet engineering in a charge density wave material

Floquet engineering has emerged as a powerful approach for dynamically tailoring the electronic structures of quantum materials through time-periodic light fields. The light fields generated by ultrafast laser pulses can transiently dress Bloch electrons, creating novel electronic states inaccessible in equilibrium. While such temporal modulation provides a dynamic control, spatially periodic modulations, such as those arising from charge density wave (CDW) order, can also dramatically reconstruct the electronic structure through real-space symmetry breaking. The interplay between these two distinct forms of modulation—temporal and spatial—opens a frontier in phase-selective Floquet engineering. Here we demonstrate this concept experimentally in the prototypical CDW material 1T-TiSe 2 . Using time- and angle-resolved photoemission spectroscopy with mid-infrared pumping, we observe a striking momentum-dependent pump-induced instantaneous downshift of the valence band maximum (VBM), which is in sharp contrast to the subsequent upward shift on picosecond timescale associated with CDW melting. Remarkably, the light-induced VBM downshift is observed exclusively in the CDW phase and only when the pump pulse is present, reaching maximum when pumping near resonance with the CDW gap. These observations unequivocally reveal the critical role of CDW in enabling the phase-selective Floquet engineering of TiSe 2 . Our work demonstrates how time-periodic drives can synergistically couple to spatially periodic modulations, establishing a paradigm for phase-selective Floquet engineering enabled by spontaneous symmetry breaking.

Species-specific performance and nutritional responses of radish and red beet to zinc–manganese in sand culture

Testicular origin of epigenetic inheritance independent of sperm mitochondrial DNA and epididymal exposure

Paternal epigenetic inheritance remains mechanistically unresolved. Recent studies propose that environmental exposures induce mitochondrial DNA (mtDNA)-dependent transcription in sperm during epididymal transit, altering small RNA content and offspring phenotypes. Here, we show that mature murine sperm are effectively devoid of mtDNA, precluding mtDNA-dependent transcription, and that sperm-borne mitochondrial RNAs originate during spermatogenesis. Testicular sperm transmitted diet-induced metabolic traits as efficiently as, and in most cohorts more efficiently than, epididymal sperm. These findings establish testicular inheritance independent of sperm mtDNA transcription and epididymal exposure.

Hybrid CNN–GCN network with dynamic gating and scale-aware preprocessing for pedestrian crossing intention prediction in Indian road conditions

Dark diversity framework reconciles Darwin’s naturalization conundrum for freshwater fish invasions

The spread of invasive species poses a major threat to global biodiversity, yet predicting successful establishment of exotic species in novel environments remains challenging. Darwin’s naturalization conundrum is a longstanding debate over whether exotic species closely or distantly related to native communities are more likely to succeed. Despite its long history, empirical studies continue to yield conflicting evidence. Here, we introduce the dark diversity concept, which refers to species that could theoretically inhabit a site but are currently absent. Combined with observed diversity, dark diversity integrates information on the potential diversity (site-specific species pool size) of the resident community and how completely that pool is locally present (community completeness). Analyzing a 340-y record of successful and failed fish introductions across 516 Swedish lakes, we showed that the effect of phylogenetic relatedness on invasion outcome depends on dark diversity context. Exotics closely related to resident species were more likely to establish in communities with smaller species pools and higher completeness, whereas phylogenetically distant exotic species were more successful in communities with larger species pools and lower completeness. Models with observed species richness obtained considerably less support. Thus, integrating the dark diversity framework clarifies the contrasting effects of phylogenetic relatedness on invasion outcomes, and helps reconcile this 160-y-old conundrum.

Urban expansion and cropland loss drive habitat quality decline in the Huai River Urban agglomeration

Disruption to TFEB signaling and autophagy in newly formed oligodendrocytes leads to aberrant generation of CNS myelin

Myelin is a defining feature of the vertebrate nervous system, yet the cellular and molecular mechanisms governing its integrity remain poorly understood. Here, using volume electron microscopy and a knock-in mouse line targeting newly formed oligodendrocytes, we reconstruct early optic nerve myelination and examine retinal ganglion cell axon ensheathment. We observe that newly formed myelin sheaths exhibit membrane protrusions and occasional degenerative myelin “whorls.” Conditional disruption of the transcription factor EB (TFEB)-autophagy pathway in newly formed oligodendrocytes significantly increases the abundance of these aberrant myelin structures, indicating that this pathway is required for proper myelin formation and integrity. Importantly, this pathway acts independently of the well-established function of TFEB that represses myelin sheath growth. Together, our findings identify a role for TFEB-dependent autophagy in establishing proper myelin structure during development, providing insights into the oligodendrocyte-intrinsic mechanisms that regulate myelin integrity.

A user equilibrium traffic assignment model based on the most reliable paths

Drp1-driven fragmentation of scleral mitochondria promotes myopia development

The global epidemic of myopia constitutes a growing public health concern worldwide. Myopia development is characterized by pathological scleral remodeling through fibroblast-myofibroblast transdifferentiation (FMT) and extracellular matrix (ECM) degradation. Since myopia is progressive, the development of sustainable and safe preventive interventions is imperative. While mitochondrial dynamics critically regulate fibrotic processes in other organs, their role in scleral homeostasis has remained unexplored. Here, we identify pathological mitochondrial fragmentation, caused by increased mitochondrial fission, as a key driver of myopia progression. Using two mammalian animal models, we demonstrate that both genetic and pharmacological enhancement of mitochondrial fission (inducing mitochondrial fragmentation) exacerbates collagen loss and accelerates axial elongation, whereas genetic and pharmacological inhibition of mitochondrial fission prevents collagen degradation and attenuates myopia progression. Hypoxia-induced FMT in cultured human scleral fibroblasts (HSFs) requires activation of mitochondrial fission, revealing overproduction of reactive oxygen species (ROS) as the downstream effector on HSFs and in both animal models. Our multilevel analyses identify the mitochondrial fission-ROS axis as a key pathway linking scleral hypoxia to ECM remodeling. Lycopene, a naturally occurring carotenoid antioxidant, significantly attenuated scleral ROS levels and was found suitable for long-term application, highlighting its potential as a therapeutic agent for myopia control. Collectively, these findings have identified a therapeutic target and agent for controlling myopia progression.

Exploring the link between diabetes duration and cardiovascular disease in patients with type 2 diabetes

The autophagy protein ATG-9 promotes aversive learning in <i>Caenorhabditis elegans</i> through trafficking neuropeptide receptors

Autophagy is a degradative process that maintains cellular homeostasis. Autophagy biogenesis occurs at synapses, but its impact on synaptic functions is incompletely understood. Here we show that, in Caenorhabditis elegans , synaptic ATG-9, the only transmembrane autophagy protein, contributes to aversive learning under mitochondrial stress. Analysis of the neuronal translatome reveals that autophagy is upregulated by stress in the octopaminergic RIC neuron and it promotes aversive learning. Inactivating autophagy genes, including atg-9 , reduces aversive learning. Mitochondrial stress increases synaptic ATG-9 through AP-1- and AP-2-dependent exocytosis and endocytosis, respectively, and reducing synaptic ATG-9 impairs aversive learning. We further identify the FRPR-6 neuropeptide receptor as a substrate of ATG-9 modulation. Both atg-9 and frpr-6 promote aversive learning and RIC activities, and the abundance of FRPR-6 in the RIC neurite depends on atg-9 . We postulate that ATG-9-containing synaptic compartments promote neuronal plasticity through modulating receptor trafficking to enable aversive learning under systemic mitochondrial stress.

Aging in Place - A mixed methods study protocol of how care providers in Sweden organise and adapt granted home care services to the preferences and needs of people living with dementia

The project Aging in Place applies a novel approach to investigate how social care services in Sweden are adapted to preferences and needs of older persons (65 years and older) living at home with dementia, including their partners. The project covers the process that starts when a person is granted to receive services, which are communicated to a care provider – who should organize the services – and finally reach the receiving older person. This approach differs from previous research on elder care, which has focused either on the purchaser or the provider side of Swedish municipal elder care in the purchaser-provider model Sweden adopted since the mid-1990s. The project focuses on: 1) what specific social care services older persons living at home with dementia are granted; if a dementia diagnosis is needed for some services; and the differences between municipalities; 2) how care providers organise granted services and adapt them to people living with dementia; including differences between municipalities and care provider units; 3) how care recipients living with dementia (including co-habiting partners) experience and influence the receiving of services. The ambition is to generate both generalisable knowledge about social care services for people living with dementia in Sweden, including differences between municipalities and care providers, and in-depth, exploratory knowledge about how care providers organise services and how these services are received by care recipients. The project encompasses a necessary combination of methods and materials: register studies, web surveys, as well as observations and interviews. The project will provide important, elemental, knowledge on Swedish dementia- and eldercare. This knowledge is needed as a basis for further studies and as a contribution to discussions on how future social care can be developed to ensure people living with dementia, and their partners, equality, participation, and dignity in later life.

Effects of post-activation performance enhancement on tennis serve velocity and accuracy

IL-4 peptide hydrogel reprograms MSC heterogeneity toward the CD106+ population for enhanced renal repair

Mesenchymal stem cells (MSCs) exhibit significant heterogeneity, which limits their therapeutic efficacy in regenerative medicine. Here, we introduce a self-assembled interleukin-4 (IL-4) peptide hydrogel designed to shift MSC populations toward a homogeneous CD106 + subset with enhanced regenerative and immunomodulatory capabilities. To evaluate their therapeutic potential, MSCs with the IL-4 hydrogel were administered to a murine model of acute kidney injury (AKI) via renal capsule transplantation. Compared with untreated MSCs, encapsulated MSCs exhibited superior engraftment and survival, leading to significant improvements in renal function, as evidenced by reduced serum creatinine levels, attenuated tubular necrosis, and decreased inflammatory infiltrates. These findings highlight the IL-4 peptide hydrogel as a promising platform for overcoming MSC heterogeneity and manufacturing disease-specific MSCs, offering a scalable strategy for advanced cell therapies in AKI and beyond.

“You have to wait for a diagnosis first”: Barriers to preventive mental health support and early interventions for children and young people in Sweden

Background Despite increasing attention to youth mental health, children and adolescents in Sweden experience fragmented, inequitable care with regional variation. Delays in diagnosis, limited preventive interventions, and poor inter-sectoral collaboration contribute to significant unmet needs. This study investigates system-level challenges and stakeholder perspectives on opportunities to enhance care pathways. Methods We conducted a qualitative study in the Västra Götaland region, Sweden. Fourteen purposively selected participants – including senior executives, healthcare professionals, and parents took part in semi-structured interviews. We used systematic text condensation, according to Malterud, and the four steps involved in this method for analysing the interviews. Results A central theme across interviews was the requirement for a formal diagnosis before children can access mental health support, particularly in school and primary care settings. Participants described this as a major barrier that delays early intervention and leaves children and young people with complex or atypical presentations without adequate support. Primary care professionals reported increasing mental health caseloads without corresponding increases in staffing or funding, limiting preventive work. Child and adolescent psychiatry (BUP) was described as overwhelmed, with long waiting times and limited continuity of care. A care manager within primary care was proposed as a way to help families navigate fragmented services and improve collaboration, although participants emphasised that such a role would need to be part of broader structural reform. Conclusions Our findings highlight persistent systemic issues in mental health care for children and young people, including inequitable access, insufficient prevention, and fragmented collaboration across sectors. Strengthening primary prevention, reallocating resources to primary and school-based mental health care and implementing well-defined care coordination roles within broader restructuring may improve continuity and equity in service delivery. Comprehensive policy reform is needed to support person-centred, integrated care pathways for children and young people with mental health needs.

Serum profile of IL-29, IL-41, and raftlin in microvascular complications of type 2 diabetes mellitus

Abstract Type 2 diabetes mellitus (T2DM) is a dysfunctional metabolic disorder characterized by low-grade inflammation. Peripheral neuropathy (PN), nephropathy (NE), and retinopathy (RT) are prominent microvascular complications (MICs) associated with T2DM. Interleukin (IL)-29, IL-41, and raftlin are recently identified immunomodulators that are hypothesized to play a pathogenic role in T2DM, but the evidence is not conclusive. Therefore, a study was conducted to characterize serum levels of these markers in T2DM patients with and without MICs (PN, NE, and RT) and to explore their cross‑sectional associations with these MICs. In this case–control study, 154 T2DM patients were included and classified into five groups: 34 newly diagnosed patients (ND), 30 patients without MICs (DM), 30 PN patients, 30 NE patients, and 30 RT patients. In addition, a control group (HC) consisting of 60 individuals was included. Serum IL-29, IL-41, and raftlin concentrations were quantified using ELISA kits. Compared to HC, IL‑41 levels showed a consistent and significant elevation in T2DM groups, particularly in ND and NE patients, whereas IL‑29 and raftlin levels showed modest variations, most of which were not significant changes. Receiver operating characteristic curve analysis revealed that an area under the curve greater than 0.70 was recorded only for IL-41 in all T2DM patients, as well as in ND and DM patients. Logistic regression analysis demonstrated that elevated IL-41 and decreased raftlin levels were linked to significantly high and low odds ratios, respectively, in all patients, and in ND and DM patients. In contrast, no significant association was observed between MICs (PN, NE, and RT) and IL-29, IL-41, or raftlin. These findings suggest that IL-41 and raftlin may represent candidate biomarkers related to inflammatory and metabolic disturbances in T2DM and associated MICs. However, their biological and clinical relevance requires confirmation in larger longitudinal and mechanistic studies.