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Although various methods have been developed for sequencing cytosine modifications, it is still challenging for specific and quantitative sequencing of individual modification at base-resolution. For example, to obtain both true 5-methylcytosine (5mC) and true 5-hydroxymethylcytosine (5hmC) information, the two major epigenetic modifications, it usually requires subtraction of two methods, which increases noise and requires high sequencing depth. Recently, we developed TET-assisted pyridine borane sequencing (TAPS) for bisulfite-free direct sequencing of 5mC and 5hmC. Here we demonstrate that two sister methods, TAPSβ and chemical-assisted pyridine borane sequencing (CAPS), can be effectively used for subtraction-free and specific whole-genome sequencing of 5mC and 5hmC, respectively. We also demonstrate pyridine borane sequencing (PS) for whole-genome profiling of 5-formylcytosine and 5-carboxylcytosine, the further oxidized derivatives of 5mC and 5hmC. This work completes the set of versatile borane reduction chemistry-based methods as a comprehensive toolkit for direct and quantitative sequencing of all four cytosine epigenetic modifications. Specific and quantitative sequencing of cytosine modifications is challenging at base-resolution. Here the authors present TAPSβ and CAPS for subtraction-free whole genome sequencing of 5mC and 5hmC.

A bstract Based on the D5-brane realization of Wilson line operators in anti-symmetric representations, we propose brane expansion formulas for I N,k , the Schur index of N = 4 U( N ) SYM decorated by line operators in the anti-symmetric representation of rank k . For the large N index I ∞,k we propose a double-sum expansion, and for finite N index I N,k we propose a quadruple-sum expansion. Objects causing finite k and finite N corrections are disk D3-branes ending on the D5-brane.

How does the central nervous system (CNS) control our bodies, including hundreds of degrees of freedom (DoFs)? A hypothesis to reduce the number of DoFs posits that the CNS controls groups of joints or muscles (i.e., modules) rather than each joint or muscle independently. Another hypothesis posits that the CNS primarily controls motion components relevant to task achievements (i.e., task-relevant components). Although the two hypotheses are examined intensively, the relationship between the two concepts remains unknown, e.g., unimportant modules may possess task-relevant information. Here, we propose a framework of task-relevant modules, i.e., modules relevant to task achievements, while combining the two concepts mentioned above in a data-driven manner. To examine the possible role of the task-relevant modules, we examined the modulation of the task-relevant modules in a motor adaptation paradigm in which trial-to-trial modifications of motor output are observable. The task-relevant modules, rather than conventional modules, showed adaptation-dependent modulations, indicating the relevance of task-relevant modules to trial-to-trial updates of motor output. Our method provides insight into motor control and adaptation via an integrated framework of modules and task-relevant components.

Wireless electrocorticography (ECoG) recording from unrestrained nonhuman primates during behavioral tasks is a potent method for investigating higher-order brain functions over extended periods. However, conventional wireless neural recording devices have not been optimized for ECoG recording, and few devices have been tested on freely moving primates engaged in behavioral tasks within their home cages. We developed a compact, low-power, 32-channel wireless ECoG headstage specifically designed for neuroscience research. To evaluate its efficacy, we established a behavioral task setup within a home cage environment. The developed headstage weighed merely 1.8 g and had compact dimensions of 25 mm × 16 mm × 4 mm. It was efficiently powered by a 100-mAh battery (weighing 3 g), enabling continuous recording for 8.5 h. The device successfully recorded data from an unrestrained monkey performing a center-out joystick task within its home cage. The device demonstrated excellent capability for recording ECoG data from freely moving primates in a home cage environment. This versatile device enhances task design freedom, decrease researchers' workload, and enhances data collection efficiency.

Maintenance of cell volume against osmotic change is crucial for proper cell functions. Leucine-rich repeat-containing 8 proteins are anion-selective channels that extrude anions to decrease the cell volume on cellular swelling. Here, we present the structure of human leucine-rich repeat-containing 8A, determined by single-particle cryo-electron microscopy. The structure shows a hexameric assembly, and the transmembrane region features a topology similar to gap junction channels. The LRR region, with 15 leucine-rich repeats, forms a long, twisted arc. The channel pore is located along the central axis and constricted on the extracellular side, where highly conserved polar and charged residues at the tip of the extracellular helix contribute to permeability to anions and other osmolytes. Two structural populations were identified, corresponding to compact and relaxed conformations. Comparing the two conformations suggests that the LRR region is flexible and mobile, with rigid-body motions, which might be implicated in structural transitions on pore opening.

Companies dealing with industrial products, such as automobiles and laptops, should develop low-cost products with long-term high performance, low environmental load, and long lifespans to achieve a sustainable society. Thus, it is necessary to realize a product architecture in which the products can be easily upgraded and repaired by encouraging various suppliers to participate in the economic sphere of the products by promoting the standardization of components through an appropriate product modularization. In conventional module design, research focuses on reducing development lead time through the common use of components and on deriving appropriate product architecture by creating a design structure matrix based on the functionality of the product. Studies have also been conducted to derive an appropriate supply chain by considering the locations of the production and assembly sites of individual modules. However, few studies have been conducted on the consistent process from the derivation of product architecture candidates to the evaluation of their supply chains. Therefore, in this study, a design structure matrix, defined from multiple perspectives related to product functionality, is used to derive architecture candidates that consider the feasibility of products. Furthermore, we introduce the concept of supply chain management and propose a method that derives product architectures that consider sustainability and their supply chains by comprehensively evaluating product architecture candidates and their supply chains based on quality, cost, lead time, and environmental load. The proposed method is applied to a modularization problem of laptops, and a design structure matrix is created from five different perspectives: size effect, contact effect, power, information, and heat, and two product architecture candidates are derived. The results of the supply chain evaluation of the derived product architectures confirm that it is possible to propose an appropriate product architecture and its supply chain combination to the designer.

There is a growing interest in the use of electrocorticographic (ECoG) signals in brain–machine interfaces (BMIs). However, there is still a lack of studies involving the long-term evaluation of the tissue response related to electrode implantation. Here, we investigated biocompatibility, including chronic tissue response to subdural electrodes and a fully implantable wireless BMI device. We implanted a half-sized fully implantable device with subdural electrodes in six beagles for 6 months. Histological analysis of the surrounding tissues, including the dural membrane and cortices, was performed to evaluate the effects of chronic implantation. Our results showed no adverse events, including infectious signs, throughout the 6-month implantation period. Thick connective tissue proliferation was found in the surrounding tissues in the epidural space and subcutaneous space. Quantitative measures of subdural reactive tissues showed minimal encapsulation between the electrodes and the underlying cortex. Immunohistochemical evaluation showed no significant difference in the cell densities of neurons, astrocytes, and microglia between the implanted sites and contralateral sites. In conclusion, we established a beagle model to evaluate cortical implantable devices. We confirmed that a fully implantable wireless device and subdural electrodes could be stably maintained with sufficient biocompatibility in vivo.

We present direct sequencing methodologies, scTAPS for 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) and scCAPS + specifically for 5hmC, enabling quantitative detection of 5mC and 5hmC at single-base resolution and single-cell level. Achieving approximately 90% mapping efficiency, our plate-based methods accurately recover 5mC and 5hmC profiles in CD8 + T and mouse embryonic stem cells. Notably, scCAPS + reveals a global increase in 5hmC across neuronal and non-neuronal cells in the hippocampus of aging mice. Our methods offer strong potential for seamless integration into high-throughput single-cell multi-omics, facilitating future investigations of epigenomic dynamics in specific biological processes.

[This corrects the article DOI: 10.1371/journal.pone.0310906.].

Repairing products using recycled parts has low environmental impact and cost. However, the product value may be inferior to using a new part. Thus, determining the most appropriate repair option for a user is difficult when balancing the three factors of product value, environmental impact, and cost. Additionally, users have subjective values regarding their cars, such as driving comfort and design. In other words, the importance of various car performance is different from each user. Furthermore, some users are favorable towards recycled parts, while others may be negative. To propose appropriate repair options considering user preferences, a questionnaire was conducted to evaluate four options: “Repair by a reused part,” “Repair by a rebuilt part,” “Repair by a new part,” and “Replace the car.” The questionnaire has three main items: annual mileage, the user’s importance of car performance, and whether the user wants to use recycled parts. The objective is to suggest the most suitable repair option based on the anticipated future usage period of the car. The validity of the proposed method is examined by comparing two different user preferences, using a Kei car engine repair as a case study.