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 .

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.

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.

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.

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.

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.

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.

The activity and expression of adenylosuccinate lyase were reduced during modern human evolution, affecting brain and behavior.

Adenylosuccinate lyase (ADSL), an enzyme that is crucial for purine biosynthesis, carries an amino acid substitution that is present in almost all humans today but absent in Neandertals and Denisovans. This substitution reduces the stability of the enzyme, but what functional consequences it has are unknown. Here, we show that when introduced into mice, this substitution causes substrates of the enzyme to accumulate in amounts that correlate negatively with ADSL expression levels.

TOB Proteins Repress Translation via the CCR4-NOT Deadenylase Complex Independent of Deadenylation.

Transducer of ErbB2 (TOB) proteins have been shown to promote mRNA decay through interactions with the CCR4-NOT complex and poly(A)-binding protein (PABP). While their role in deadenylation-mediated mRNA degradation is well established, their potential function in translational control remains to be elucidated. Here, we employed an in vitro translation system combined with an RNA tethering strategy to examine the function of TOB1 and TOB2 in translation.

Stabilizing an optical cavity containing a bulk diamond crystal at millikelvin temperatures in a cryogen-free dilution refrigerator.

We successfully stabilized a Fabry-Pérot optical cavity incorporating a bulk diamond crystal at millikelvin temperatures in a cryogen-free dilution refrigerator with the pulse-tube cryocooler running. In stark contrast to previous demonstrations where lasers were locked to the cavities, our setup locks the cavity to the laser, thereby ensuring that emitted photons remain at a stable, predetermined frequency. This stability is advantageous for efficient quantum networking applications (e.

Flat Elastic Disc Suspensions Are Indistinguishable from Solutions of Long Flexible Polymers within Planar Incompressible Flows.

We prove analytically that the two fundamental rheological equations for (elastic) disc suspensions and long flexible polymers, the so-called Oldroyd-A and -B models, respectively, predict the same flow and total stress fields in any planar incompressible flow. We illustrate this equivalence for creeping flow in a cross-slot channel and investigate differences arising from three-dimensional effects in a weakly elastic Taylor-Couette flow. Finally, we discuss implications for understanding elastic instabilities, controlling inertial turbulence, and deriving constitutive models for complex fluids.

Adaptive pangenomic remodeling in the Azolla cyanobiont amid a transient microbiome.

Plants fix nitrogen in concert with diverse microbial symbionts, often recruiting them from the surrounding environment each generation. Vertical transmission of a microbial symbiont from parent to offspring can produce extreme evolutionary consequences, including metabolic codependence, genome reduction, and synchronized life cycles. One of the few examples of vertical transmission of N-fixing symbionts occurs in Azolla ferns, which maintain an obligate mutualism with the cyanobacterium Trichormus azollae-but the genomic consequences of this interaction, and whether the symbiosis involves other vertically transmitted microbial partners, are currently unknown.

A Max-Flow Approach to Random Tensor Networks.

The entanglement entropy of a random tensor network (RTN) is studied using tools from free probability theory. Random tensor networks are simple toy models that help in understanding the entanglement behavior of a boundary region in the anti-de Sitter/conformal field theory (AdS/CFT) context. These can be regarded as specific probabilistic models for tensors with particular geometry dictated by a graph (or network) structure.

Active Microfluidic Platforms for Particle Separation and Integrated Sensing Applications.

The active manipulation and separation of particles in microfluidic systems using externally applied forces, such as acoustic, electric, magnetic, and optical fields, have transformed our capacity to detect pathogens, biomarkers, and environmental analytes with high precision and adaptability. These active microfluidic approaches offer enhanced control over particle trajectories, tunable separation thresholds, and compatibility with diverse sample types, making them highly promising for integration with downstream sensing platforms. This Perspective outlines recent advances in active microfluidic separation strategies and explores their synergies with biochemical assays, such as lateral flow tests, electrochemical sensors, and next-generation sequencing.

Evaluation of DNA barcoding reference databases for marine species in the western and central Pacific Ocean.

DNA barcoding is a widely used tool for species identification, with its reliability heavily dependent on reference databases. While the quality of these databases has long been debated, a critical knowledge gap remains in their comprehensive evaluation and comparison at regional scales. Marine metazoan species in the western and central Pacific Ocean (WCPO), a region characterized by high biodiversity and limited sequencing efforts, are an example of this gap.