A human striatal-midbrain assembloid model of alpha-synuclein propagation.

Animal models of the pathology of Parkinson's disease (PD) have provided most of the treatments to date, but the disease is restricted to human patients. In vitro models using human pluripotent stem cells (hPSCs)-derived neural organoids have provided improved access to study PD etiology. This study established a method to generate human striatal-midbrain assembloids (hSMAs) from hPSCs for modeling alpha-synuclein (α-syn) propagation and recapitulating basal ganglia circuits, including nigrostriatal and striatonigral pathways.

The helical elongation of π-extended diazahelicenes with amplified circularly polarized luminescence.

Helicenes are circularly polarized luminescence (CPL)-active but suffer from a fundamental tradeoff between fluorescence quantum yield (Φ) and luminescence dissymmetry factor (||). Herein, we present a strategy combining lateral π-extension and helical elongation in carbazole-embedded helicenes to address this challenge. Specifically, π-extended diaza[7]helicene () and diaza[9]helicene () were synthesized and characterized, revealing nearly a 2-fold increase in Φ and a 6-fold enhancement in || from to .

Cell-cell communication as underlying principle governing color pattern formation in fishes.

The diverse pigmentation patterns of animals are crucial for predation avoidance and behavioral display, yet mechanisms underlying this diversity remain poorly understood. In zebrafish, Turing models have been proposed to explain stripe patterns, but it is unclear if they apply to other fishes. In anemonefish (, we identified , a gene orthologous to zebrafish and encoding a connexin involved in pigment cell communication, as responsible for the phenotype.

Anemonefish Chromatophore Distribution and Organization Revealed by TEM Studies.

Anemonefish have a characteristic vertical white barred color pattern on an orange background made by a specific distribution of three types of pigment cells: melanophores, xanthophores, and iridophores. This color pattern is an interesting alternative model to zebrafish to understand the cellular and molecular basis of complex color pattern formation. Using transmission electron microscopic observations, we have investigated the pigment cell composition in the skin of the anemonefish and found that: 1) white skin comprises iridophores and isolated melanophores; 2) orange skin contains xanthophores and scattered melanophores; and 3) black skin encompasses melanophores only.

Adaptive Strategies in Expertise: Optimizing Movement Trajectory for Perception Accuracy.

This study examines the traces of movement trajectories for perception accuracy in expert performance, focusing on table tennis. Twenty participants (10 experts and 10 novices) performed self-generated movements for extended haptic accuracy tasks, and their performance was analyzed for absolute error and movement trajectory. The results reveal that the expert participants exhibited more movement entropy than novices, strategically sacrificing trajectory predictability to enhance haptic perception accuracy.

Study of gas-based charge compensation in an open-cell environmental TEM by off-axis electron holography.

Under electron bombardment, electrically insulating samples accumulate a net charge which can adversely affect measurements in electron microscopy. Here, we present a preliminary study on gas-based charge compensation in TEM quantified through off-axis electron holography. Based on the present data, it appears that the introduction of a gas flow reversibly reduces the degree of charge buildup and fluctuations on a dielectric sample.

Active Inference with Dynamic Planning and Information Gain in Continuous Space by Inferring Low-Dimensional Latent States.

Active inference offers a unified framework in which agents can exhibit both goal-directed and epistemic behaviors. However, implementing policy search in high-dimensional continuous action spaces presents challenges in terms of scalability and stability. Our previously proposed model, T-GLean, addressed this issue by enabling efficient goal-directed planning through low-dimensional latent space search, further reduced by conditioning on prior habituated behavior.

KACQ-DCNN: Uncertainty-Aware Interpretable Kolmogorov-Arnold Classical-Quantum Dual-Channel Neural Network for Heart Disease Detection.

Background: Heart failure remains a critical global health issue, contributing significantly to cardiovascular disease burden and accounting for approximately 17.8 million annual deaths worldwide. Traditional diagnostic approaches face substantial limitations in early detection and intervention planning.

Synthesis of a series of PNC pincer ligand-supported Pt complexes, and an initial exploration of their reactivity.

A Pt-Cl complex supported by a PNC (phosphine, pyridine, and phenyl) donor pincer ligand was synthesized. The complex proved to be remarkably stable under air and ambient conditions. Cationic complexes with coordinated DMSO or CO were obtained from the initial (PNC)-Pt-Cl, with all the complexes characterized structurally and spectroscopically.

The influence of cross-generational warming on the juvenile development of a coral reef fish under ocean warming and acidification.

Marine ecosystems are facing escalating chronic and acute environmental stressors, yet our understanding of how multiple stressors influence individuals is limited. Here, we investigated how projected ocean warming (+1.5 °C) during grandparental (F) and parental (F) generations of the spiny chromis damselfish (Acanthochromis polyacanthus), influences the sensitivity of F juveniles to ocean warming (present-day vs +1.

Proteomics-based receptor-ligand matching enhances differentiation maturity of human-stem-cell-derived neurons.

Human-induced pluripotent stem cell (hiPSC) technology enables generation of various cell types, offering significant potential for regenerative medicine and personalized disease modeling. However, optimizing the functional maturity of differentiated cells is crucial for improving their reliability in research. Here, we introduce a deep-proteomics-based "receptor-ligand matching" (RLM) strategy to inventory surface receptors on differentiated cells and adjust the culture conditions accordingly.

Time-resolved miRNA-mRNA integrated analysis reveals the miRNA-mRNA networks underlying plasma membrane damage-dependent senescence and DNA damage response-dependent senescence in WI-38 normal human fibroblasts.

Cellular senescence is a stable cell cycle arrest associated with upregulated inflammatory responses. Senescent cells contribute to various pathological and physiological processes including organismal ageing and cancer. Cellular senescence can be induced by various cellular stresses including DNA damage, telomere shortening, oncogene activation, and epigenetic alterations.

Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal.

Different signaling pathways connect the mitochondrion with the transcriptional machinery in the nucleus. Redox events are thought to play a substantial role along this axis, however, many open questions about their specificity and mode of action remain. Here, we have employed subtoxic doses of the complex I inhibitor MPP in human neuronal LUHMES cells to characterize the contribution of scavengeable redox signals to mito-nuclear communication.

Molecular mechanism of ultrafast transport by plasma membrane Ca-ATPases.

Tight control of intracellular Ca levels is fundamental as they are used to control numerous signal transduction pathways. Plasma membrane Ca-ATPases (PMCAs) have a crucial role in this process by extruding Ca against a steep concentration gradient from the cytosol to the extracellular space. Although new details of PMCA biology are constantly being uncovered, the structural basis of the most distinguishing features of these pumps, namely, transport rates in the kilohertz range and regulation of activity by the plasma membrane phospholipid PtdIns(4,5)P, has so far remained elusive.

Cryo-EM structure of the Seneca Valley virus A-particle and related structural states.

Picornavirus cell entry requires a series of capsid protein conformational changes leading to genome uncoating. For enteroviruses, receptor binding triggers the transition from a full (F) capsid to an altered (A) particle before releasing its genome and finally converting it into an empty (E) particle. In contrast, non-enteroviruses, such as Aphthovirus, Cardiovirus, or Seneca Valley virus, release their genomes by dissociating the capsid into pentamers.

Influence of the pre-membrane and envelope proteins on structure, pathogenicity, and tropism of tick-borne encephalitis virus.

Unlabelled: Tick-borne encephalitis virus (TBEV) is a neurotropic flavivirus that causes thousands of human infections annually. Viral tropism in the brain is determined by the presence of necessary receptors, entry factors, and the ability of the virus to overcome host defenses. The viral structural proteins, pre-membrane (prM), and envelope (E) play an important role in receptor binding, membrane fusion, particle maturation, and antibody neutralization.

Thymosin beta 4 as an Alzheimer disease intervention target identified using human brain organoids.

The developmental origin of Alzheimer disease (AD) has been proposed but is arguably debated. Here, we developed cerebral organoids from induced pluripotent stem cells (iPSCs) with mutations in amyloid precursor protein (APP) associated with familial AD (fAD) and analyzed the dynamic changes of cellular states. We found that mature neurons induced in fAD organoids markedly decreased compared to that of health control, accompanied with increased cell senescence and β-amyloid (Aβ) production.

CCR4-NOT Transcription Complex Subunit 7 (CNOT7) Protein and Leukocyte-Associated Immunoglobulin-like Receptor-1 in Breast Cancer Progression: Clinical Mechanistic Insights and In Silico Therapeutic Potential.

Metastatic breast cancer (BC) spread underscores the need for novel prognostic biomarkers. This study investigated CCR4-NOT Transcription Complex Subunit 7 (CNOT7) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) in BC progression and natural killer (NK) cell resistance. In the current study, 90 female BC patients (46 non-metastatic, 44 metastatic) were analyzed.

The genomic origin of the unique chaetognath body plan.

The emergence of animal phyla, each with their unique body plan, was a rapid event in the history of animal life, yet its genomic underpinnings are still poorly understood. Here we investigate at the genomic, regulatory and cellular levels, the origin of one of the most distinctive animal phyla, the chaetognaths, whose organismal characteristics have historically complicated their phylogenetic placement. We show that these characteristics are reflected at the cell-type level by the expression of genes that originated in the chaetognath lineage, contributing to adaptation to planktonic life at the sensory and structural levels.

Phylogenomic Analyses Reveal that Panguiarchaeum Is a Clade of Genome-Reduced Asgard Archaea Within the Njordarchaeia.

The Asgard archaea are a diverse archaeal phylum important for our understanding of cellular evolution because they include the lineage that gave rise to eukaryotes. Recent phylogenomic work has focused on characterizing the diversity of Asgard archaea in an effort to identify the closest extant relatives of eukaryotes. However, resolving archaeal phylogeny is challenging, and the positions of 2 recently described lineages-Njordarchaeales and Panguiarchaeales-are uncertain, in ways that directly bear on hypotheses of early evolution.

An Integrated Assessment of Microplastic Pollution in Coastal Surface Water and Sediment of Japan.

The ubiquity of microplastics in the marine environment has been highlighted in recent years, yet the extent of microplastic pollution in coastal areas, especially off the coast of Japan, remains unclear. Here we provide a comprehensive data set of microplastic pollution in surface water and sediment around coastal Japan. The survey encompasses 15 locations along Japanese coasts from the northernmost region in Hokkaido to the southern archipelago of Okinawa.

Impact of degradation and time of sampling on gut Microbiome composition in wild-caught marine fish.

Unlabelled: The gut microbiome has the potential to be an effective indicator of individual and population health in fish given its sensitivity to internal and external stressors. However, without consistent and tested validated sampling protocols, the gut microbiome’s potential as a reliable indicator may be limited. Routine sampling of wild free-living fish caught by commercial fisheries rarely occurs at the time of capture and more commonly occurs hours, days, or weeks after fish capture when the catch is unloaded in port.

The emergence of metabolisms through Earth history and implications for biospheric evolution.

We investigate the evolution of microbial metabolisms from the last universal common ancestor to the extant biota through comparative phylogenomics, reconciling the evolution of the genes that underpin metabolic pathways with a time-calibrated tree of life. We find that the majority of metabolic pathways were established within the first 2 billion years of Earth history, with pathways accreting at different rates. Methanogenesis and acetogenesis are recovered to be among the earliest energy metabolisms, whereas photosynthetic pathways achieved completeness by 2 Ga, much later than most previous studies have envisaged.

Pangeneric analyses reveal the divergent genome evolution and ecologies between morels and truffles in the Morchellaceae.

Morels are iconic macrofungi known for their culinary value and spring emergence. Molecular phylogenetic studies have hitherto failed to elucidate the evolution of the ecological lifestyles of true and false morels, impeding their capacity to resolve longstanding debates regarding the extent of their saprotrophy and the potential for biotrophic associations with plants. In this study, we examined the evolutionary history and molecular innovations of Morchellaceae by generating high-quality genomes from species encompassing all the major clades within this family.

Time-Series RNA-Seq of Acropora tenuis Reveals Molecular Waves Leading to Synchronous Mass Spawning of Scleractinian Corals.

Although mass, synchronised spawning of scleractinian corals is a well-known phenomenon, its underlying molecular mechanisms, especially those that achieve synchronous release of gametes, are still unknown. In the genus Acropora, the dominant scleractinian coral in shallow reefs, spawning timing is synchronised in any given location, but often varies among locations. Here, we report gene expression cascades potentially driving synchronous mass spawning, revealed through transcriptome monitoring of Acropora tenuis, tracking both daily and monthly dynamics during a year-long experiment that included two spawning events.