Multiple cell populations generate macrophage progenitors in the early yolk sac.

Yolk sac (YS) CSF1 receptor positive (CSF1R+) cells are thought to be the progenitors for tissue-resident macrophages present in various tissues. The YS progenitors for tissue-resident macrophages are referred to as erythroid-myeloid progenitors (EMPs). However, diverse types of hematopoietic progenitors are present in the early YS, thus it is not precisely known which type of hematopoietic cell gives rise to the CSF1R+ lineage. In this study, an analysis was conducted to determine when CSF1R+ progenitors appeared in the early YS. It showed that CSF1R+ cells appeared in the YS as early as embryonic day 9 (E9) and that the earliest hematopoietic progenitors that differentiate into CSF1R+ cells were found in E8. Since these progenitors possessed the capability to generate primitive erythroid cells, it was likely that primitive erythroid lineages shared progenitors with the CSF1R+ lineage. Mutual antagonism appears to work between PU.1 and GATA1 when CSF1R+ cells appear in the early YS. One day later (E9), multiple progenitors, including myeloid-restricted progenitors and multipotent progenitors, in the YS could immediately generate CSF1R+ cells. These results suggest that EMPs are not an exclusive source for the CSF1R+ lineage; rather, multiple hematopoietic cell populations give rise to CSF1R+ lineage in the early YS.

Isolation of CD35+ follicular dendritic cells and its role in the differentiation from B cells to IgA+GL7+ cells.

Follicular dendritic cells (FDCs) are non-hematopoietic cells that are localized in the germinal centers (GCs) of lymph nodes (LNs) and are involved in humoral immunity. FDCs are a rare population that are sensitive to mechanical and chemical stimuli, making their isolation for analysis difficult. In Peyer's Patches, which are the main IgA-inductive sites, FDCs have been reported to be activated by retinoic acid receptor (RAR) and toll-like receptor (TLR) signals to induce IgA production. However, little is known about FDCs in mesenteric LNs (MLNs), although MLNs are also an IgA-inductive site. In this study, we efficiently isolated FDCs as CD35+ cells using anti-CD35 antibodies (Abs) and magnetic bead sorting. We found that CD35+ FDCs facilitated differentiation from B220+ B cells into IgA+GL7+ GC B-like cells but not IgA+CD138+ plasma cells. Furthermore, using CD35+ FDCs from LPS-resistant C3H/HeJ mice, the generation of IgA+GL7+ GC B-like cells was not altered significantly between wild-type and LPS-resistant mice. Moreover, the addition of RAR antagonists and agonists revealed that differentiation into IgA+GL7+ GC B-like cells required the activation of RAR, especially RAR-ß, in FDCs. The differentiation of IgA+GL7+ cells was promoted by FDCs in peripheral LNs as well as MLNs in our in vitro assay. Taken together, these results indicate that magnetic bead sorting with anti-CD35 Abs enable the efficient isolation of FDCs. Our data suggested that CD35+ FDCs can support differentiation of B cells into IgA+GL7+ GC B-like cells in environments that are not limited to MLNs, which can be stimulated by retinoic acid.

Cellular Basis of Embryonic Hematopoiesis and Its Implications in Prenatal Erythropoiesis.

Primitive erythrocytes are the first hematopoietic cells observed during ontogeny and are produced specifically in the yolk sac. Primitive erythrocytes express distinct hemoglobins compared with adult erythrocytes and circulate in the blood in the nucleated form. Hematopoietic stem cells produce adult-type (so-called definitive) erythrocytes. However, hematopoietic stem cells do not appear until the late embryonic/early fetal stage. Recent studies have shown that diverse types of hematopoietic progenitors are present in the yolk sac as well as primitive erythroblasts. Multipotent hematopoietic progenitors that arose in the yolk sac before hematopoietic stem cells emerged likely fill the gap between primitive erythropoiesis and hematopoietic stem-cell-originated definitive erythropoiesis and hematopoiesis. In this review, we discuss the cellular origin of primitive erythropoiesis in the yolk sac and definitive hematopoiesis in the fetal liver. We also describe mechanisms for developmental switches that occur during embryonic and fetal erythropoiesis and hematopoiesis, particularly focusing on recent studies performed in mice.

Spatially Arranged Sparse Recurrent Neural Networks for Energy Efficient Associative Memory.

The development of hardware neural networks, including neuromorphic hardware, has been accelerated over the past few years. However, it is challenging to operate very large-scale neural networks with low-power hardware devices, partly due to signal transmissions through a massive number of interconnections. Our aim is to deal with the issue of communication cost from an algorithmic viewpoint and study learning algorithms for energy-efficient information processing. Here, we consider two approaches to finding spatially arranged sparse recurrent neural networks with the high cost-performance ratio for associative memory. In the first approach following classical methods, we focus on sparse modular network structures inspired by biological brain networks and examine their storage capacity under an iterative learning rule. We show that incorporating long-range intermodule connections into purely modular networks can enhance the cost-performance ratio. In the second approach, we formulate for the first time an optimization problem where the network sparsity is maximized under the constraints imposed by a pattern embedding condition. We show that there is a tradeoff between the interconnection cost and the computational performance in the optimized networks. We demonstrate that the optimized networks can achieve a better cost-performance ratio compared with those considered in the first approach. We show the effectiveness of the optimization approach mainly using binary patterns and apply it also to gray-scale image restoration. Our results suggest that the presented approaches are useful in seeking more sparse and less costly connectivity of neural networks for the enhancement of energy efficiency in hardware neural networks.

Recent advances in physical reservoir computing: A review.

Reservoir computing is a computational framework suited for temporal/sequential data processing. It is derived from several recurrent neural network models, including echo state networks and liquid state machines. A reservoir computing system consists of a reservoir for mapping inputs into a high-dimensional space and a readout for pattern analysis from the high-dimensional states in the reservoir. The reservoir is fixed and only the readout is trained with a simple method such as linear regression and classification. Thus, the major advantage of reservoir computing compared to other recurrent neural networks is fast learning, resulting in low training cost. Another advantage is that the reservoir without adaptive updating is amenable to hardware implementation using a variety of physical systems, substrates, and devices. In fact, such physical reservoir computing has attracted increasing attention in diverse fields of research. The purpose of this review is to provide an overview of recent advances in physical reservoir computing by classifying them according to the type of the reservoir. We discuss the current issues and perspectives related to physical reservoir computing, in order to further expand its practical applications and develop next-generation machine learning systems.

Mouse Yolk Sac Hematopoiesis.

The yolk sac is the first observed site of hematopoiesis during mouse ontogeny. Primitive erythroid cells are the most well-recognized cell lineages produced from this tissue. In addition to primitive erythroid cells, several types of hematopoietic cells are present, including multipotent hematopoietic progenitors. Yolk sac-derived blood cells constitute a transient wave of embryonic and fetal hematopoiesis. However, recent studies have demonstrated that some macrophage and B cell lineages derived from the early yolk sac may persist to adulthood. This review discusses the cellular basis of mouse yolk sac hematopoiesis and its contributions to embryonic and adult hematopoietic systems.

Subjectivity of the Anomalous Sense of Self Is Represented in Gray Matter Volume in the Brain.

The self includes complicated and heterogeneous functions. Researchers have divided the self into three distinct functions called "agency," "ownership," and "narrative self". These correspond to psychiatric symptoms, behavioral characteristics and neural responses, but their relationship with brain structure is unclear. This study examined the relationship between the subjectivity of self-related malfunctions and brain structure in terms of gray matter (GM) volume in 96 healthy people. They completed a recently developed self-reported questionnaire called the Embodied Sense of Self Scale (ESSS) that measures self-related malfunctions. The ESSS has three subscales reflecting the three distinct functions of the self. We also determined the participants' brain structures using magnetic resonance imaging (MRI) and voxel-based morphometry (VBM). Multiple regression analysis revealed a significant negative correlation between ownership malfunction and the insular cortex GM volume. A relationship with brain structure could thus only be confirmed for the ESSS "ownership" subscale. This finding suggests that distinct brain structures feel ownership and that the ESSS could partly screen for distinct brain structures.

A novel rat head gaze determination system based on optomotor responses.

The optomotor response of animals is commonly used to measure their visual performance, e.g., rats of different genetically altered strains or various drug tests. With the presentation of stimuli using computer screens or projectors, the common idea focuses on measuring the eye movement or head and/or body movement to characterize changes of the head gaze. However, traditional methods rely on either the invasive fixation of animals, or the judgment of a human observer who reports the stimulus-tracking movements. In this paper, we propose a novel head gaze determination system to automatically track the head movement of rats without artificial markers. The experiments were done to demonstrate the process of optimizing parameters in image processing. As a result, the head angle curve of the proposed method is consistent with that of ground-truth data annotated manually according to predefined rules. Hence, the proposed method provides a simple, convenient, and objective solution to automatically generate the head gaze orientations from massive amounts of recorded data for further visual performance analysis.