Unifying community whole-brain imaging datasets enables robust neuron identification and reveals determinants of neuron position in C. elegans.

We develop a data harmonization approach for C. elegans volumetric microscopy data, consisting of a standardized format, pre-processing techniques, and human-in-the-loop machine-learning-based analysis tools. Using this approach, we unify a diverse collection of 118 whole-brain neural activity imaging datasets from five labs, storing these and accompanying tools in an online repository WormID (wormid.

Oxytocin and Neuroscience of Lactation: Insights from the Molecular Genetic Approach.

In mammals, lactation is essential for the health and growth of infants and supports the formation of the mother-infant bond. Breastfeeding is mediated by the neurohormone oxytocin (OT), which is released into the bloodstream in a pulsatile manner from OT neurons in the hypothalamus to promote milk ejection into mammary ducts. While classical studies using anesthetized rats have illuminated the activity patterns of putative OT neurons during breastfeeding, the molecular, cellular, and neural circuit mechanisms driving the synchronous pulsatile bursts of OT neurons in response to nipple stimulation remain largely elusive.

Transplantation of genome-edited retinal organoids restores some fundamental physiological functions coordinated with severely degenerated host retinas.

We have previously shown that the transplantation of stem cell-derived retinal organoid (RO) sheets into animal models of end-stage retinal degeneration can lead to host-graft synaptic connectivity and restoration of vision, which was further improved using genome-edited Islet1 ROs (gROs) with a reduced number of ON-bipolar cells. However, the details of visual function restoration using this regenerative therapeutic approach have not yet been characterized. Here, we evaluated the electrophysiological properties of end-stage rd1 retinas after transplantation (TP-rd1) and compared them with those of wild-type (WT) retinas using multi-electrode arrays.

Trans-scale live-imaging of an E5.5 mouse embryo using incubator-type biaxial light-sheet microscopy.

During mouse embryonic development, the embryonic day (E) 5.5 stage represents a crucial period for the formation of the primitive body axis, where the symmetry breaking of cellular states influences the multicellular system. Elucidating the detailed mechanisms of this process necessitates a trans-layered dynamic observation of the embryo and all internal cells.

Opioidergic activation of the descending pain inhibitory system underlies placebo analgesia.

Placebo analgesia is caused by inactive treatment, implicating endogenous brain function involvement. However, the neurobiological basis remains unclear. In this study, we found that μ-opioid signals in the medial prefrontal cortex (mPFC) activate the descending pain inhibitory system to initiate placebo analgesia in neuropathic pain rats.

Function of nodal cilia in left-right determination: Mechanical regulation in initiation of symmetry breaking.

Visceral organs in vertebrates are arranged with left-right asymmetry; for example, the heart is located on the left side of the body. Cilia at the node of mouse early embryos play an essential role in determining this left-right asymmetry. Using information from the anteroposterior axis, motile cilia at the central region of the node generate leftward nodal flow.

Girolline is a sequence context-selective modulator of eIF5A activity.

Natural products have a long history of providing probes into protein biosynthesis, with many of these compounds serving as therapeutics. The marine natural product girolline has been described as an inhibitor of protein synthesis. Its precise mechanism of action, however, has remained unknown.

Covalent Plant Natural Product that Potentiates Antitumor Immunity.

Despite the unprecedented therapeutic potential of immune checkpoint antibody therapies, their efficacy is limited partly by the dysfunction of T cells within the cancer microenvironment. Combination therapies with small molecules have also been explored, but their clinical implementation has been met with significant challenges. To search for antitumor immunity activators, the present study developed a cell-based system that emulates cancer-attenuated T cells.

In Vitro Selection of Collagen-Binding Vascular Endothelial Growth Factor Containing Genetically Encoded Mussel-Inspired Adhesive Amino Acids.

Protein immobilization technology is important in medical and industrial applications. We previously reported all-in-one in vitro selection, wherein a collagen-binding vascular endothelial growth factor (CB-VEGF) was identified from a fusion library of random and VEGF sequences. However, its interaction chemistry is mainly limited to the interaction established by the 20 canonical amino acids.

Mesoscale heterogeneity is a critical determinant for spiral pattern formation in developing social amoeba.

Heterogeneity is a critical determinant for multicellular pattern formation. Although the importance of microscale and macroscale heterogeneity at the single-cell and whole-system levels, respectively, has been well accepted, the presence and functions of mesoscale heterogeneity, such as cell clusters with distinct properties, have been poorly recognized. We investigated the biological importance of mesoscale heterogeneity in signal-relaying abilities (excitability) in the self-organization of spiral waves of intercellular communications by studying the self-organized pattern formation in a population of Dictyostelium discoideum cells, a classical signal-relaying system model.

Heme regulates protein interactions and phosphorylation of BACH2 intrinsically disordered region in humoral response.

Heme is known to bind to the intrinsically disordered region (IDR) to regulate protein function. The binding of heme to the IDR of transcription factor BACH2 promotes plasma cell differentiation, but the molecular basis is unknown. Heme was found to increase BACH2 IDR interaction with TANK-binding kinase 1 (TBK1).

Structural dynamics of a designed peptide pore under an external electric field.

Membrane potential is essential in biological signaling and homeostasis maintained by voltage-sensitive membrane proteins. Molecular dynamics (MD) simulations incorporating membrane potentials have been extensively used to study the structures and functions of ion channels and protein pores. They can also be beneficial in designing and characterizing artificial ion channels and pores, which will guide further amino acid sequence optimization through comparison between the predicted models and experimental data.

A Transition From Interindividual Uniformity to Diversity in Appearance and Transcriptional Features at Midlife in Caenorhabditis elegans.

During embryogenesis, organisms function as a robust system that ensures uniformity within individuals, but they lose robustness and develop variations at advanced ages. However, when and how organisms lose this robustness remains largely elusive. Here, we identified a sharp transition from interindividual uniformity to diversity in the appearance and transcriptional features of age-matched Caenorhabditis elegans in midlife.

A nonsecretory antimicrobial peptide mediates inflammatory organ damage in Drosophila renal tubules.

An excessive immune response damages organs, yet its molecular mechanism is incompletely understood. Here, we screened a factor mediating organ damage upon genetic activation of the innate immune pathway using Drosophila renal tubules. We found that an antimicrobial peptide, Attacin-D (AttD), causes organ damage upon immune deficiency (Imd) pathway activation in the Malpighian tubules.

Use of optical techniques to evaluate the ionizing radiation effects on biological specimens.

Radiation induces various changes in biological specimens; however, the evaluation of these changes is usually complicated and can be achieved only through investment in time and labor. Optical methods reduce the cost of such evaluations as they require less pretreatment of the sample, are adaptable to high-throughput screening and are easy to automate. Optical methods are also advantageous, owing to their real-time and onsite evaluation capabilities.

Flexible adjustment of oxytocin neuron activity in mouse dams revealed by microendoscopy.

Oxytocin (OT) neurons in the hypothalamic paraventricular nucleus (PVH) play an important role in various physiological and behavioral processes, including the initiation of milk ejection and the regulation of maternal behaviors. However, their activity patterns at the single-cell level remain poorly understood. Using microendoscopic Ca imaging in freely moving mouse dams, we demonstrate highly correlated pulsatile activity among individual OT neurons during lactation.

Cyclin-dependent kinase inhibitor p18 regulates lineage transitions of excitatory neurons, astrocytes, and interneurons in the mouse cortex.

Neural stem cells (NSCs) can give rise to both neurons and glia, but the regulatory mechanisms governing their differentiation transitions remain incompletely understood. Here, we address the role of cyclin-dependent kinase inhibitors (CDKIs) in the later stages of dorsal cortical development. We find that the CDKIs p18 and p27 are upregulated at the onset of astrocyte generation.

An actin bracket-induced elastoplastic transition determines epithelial folding irreversibility.

During morphogenesis, epithelial sheets undergo sequential folding to form three-dimensional organ structures. The resulting folds are often irreversible, ensuring that morphogenesis progresses in one direction. However, the mechanism establishing folding irreversibility remains unclear.

Parallel labeled-line organization of sympathetic outflow for selective organ regulation in mice.

The sympathetic nervous system is crucial for responding to environmental changes. This regulation is coordinated by the spinal sympathetic preganglionic neurons (SPNs), innervating both postganglionic neurons and the adrenal gland. Despite decades of research supporting the concept of selective control within this system, the neural circuit organization responsible for the output specificity remains poorly understood.

An eGFP-Col4a2 mouse model reveals basement membrane dynamics underlying hair follicle morphogenesis.

Precisely controlled remodeling of the basement membrane (BM) is crucial for morphogenesis, but its molecular and tissue-level dynamics, underlying mechanisms, and functional significance in mammals remain largely unknown due to limited visualization tools. We developed mouse lines in which the endogenous collagen IV gene (Col4a2) was fused with a fluorescent tag. Through live imaging of developing hair follicles, we reveal a spatial gradient in the turnover rate of COL4A2 that is closely coupled with both the BM expansion rate and the proliferation rate of epithelial progenitors.

Evaluation of motor fluctuations in Parkinson's disease: electronic vs. conventional paper diaries.

Background: Paper symptom diaries are a common tool for assessing motor fluctuations in Parkinson's disease (PD) patients, but there are concerns about inaccuracies in the assessment of motor fluctuation due to recall bias and poor compliance. We, therefore, developed an electronic diary with reminder and real-time recording functions.

Objectives And Methods: To evaluate the effectiveness of the electronic diary, we compared compliance and motor fluctuation assessment with a paper diary.

Transcription-coupled changes in genomic region proximities during transcriptional bursting.

The orchestration of our genes heavily relies on coordinated communication between enhancers and promoters, yet the mechanisms behind this dynamic interplay during active transcription remain unclear. Here, we investigated enhancer-promoter (E-P) interactions in relation to transcriptional bursting in mouse embryonic stem cells using sequential DNA/RNA/immunofluorescence-fluorescence in situ hybridization analyses. Our data reveal that the active state of specific genes is characterized by specific proximities between different genomic regions and the accumulation of transcriptional regulatory factors.

Analysis of solid-state NMR data facilitated by MagRO_NMRViewJ with Graph_Robot: Application for membrane protein and amyloid.

Solid-state NMR (ssNMR) methods have continued to be developed in recent years for the efficient assignment of signals and 3D structure modeling of biomacromolecules. Consequently, we are approaching an era in which vigorous applications of these methods are more widespread in research, including functional elucidation of biomacromolecules and drug discovery. However, multidimensional ssNMR methods are not as advanced as solution NMR methods, especially for automated data analysis.

Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential.

Postnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte cell cycle withdrawal. Xanthine metabolism was activated in both postnatal hearts in parallel with cardiomyocyte cell cycle arrest.