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A bioenergetics and population dynamics coupled model that includes a full life cycle and size/growth-dependent mortality function was developed to better understand stock fluctuations. As an example, the model was applied to chub mackerel (Scomber japonicus) as it shows large stock fluctuations in the western North Pacific. The mortality dependency parameters for growth/size were adjusted to achieve realistic stock fluctuations in the model from 1998 to 2018. Two types of mortality functions were used in the model: one based on both size and growth, and the other based solely on size. An increasing trend of stock fluctuation of chub mackerel in the 2010s was reproduced in the simulation by contributions of several strong monthly cohorts that formed strong year classes using both types of mortality functions. The reproducibility of the stock fluctuation was not markedly different between the models with the two types of mortality functions, which indicates the importance of size-dependent mortality on the stock fluctuations of chub mackerel. The influence of sea surface temperature (SST) and chlorophyll-a was evaluated separately by using the climatological values for one of the forcings, and the model results revealed that the stock fluctuations of chub mackerel during 1998–2018 were mainly controlled by chlorophyll-a, whereas the increasing stock during 2010–2014 was strongly influenced by chlorophyll-a, and that after 2014 was influenced by SST. When integrated with different fishing pressures, the model showed that high fishing pressure hinders the recovery of chub mackerel stocks, highlighting the importance of effective fishery management.

Retinal vessels play an important role in judging many eye-related diseases, so accurate segmentation of retinal vessels has become the key to auxiliary diagnosis. In this paper, we present a Cascaded Residual Attention U-Net (CRAUNet) that can be regarded as a set of U-Nets, that allows coarse-to-fine representations. In the CRAUNet, we introduce a DropBlock regularization similar to the frequently-used dropout, which greatly reduces the overfitting problem. In addition, we propose a multi-scale fusion channel attention (MFCA) module to explore helpful information, and then merge this information instead of using a direct skip-connection. Finally, to prove the effectiveness of our method, we conduct extensive experiments on DRIVE and CHASE_DB1 datasets. The proposed CRAUNet achieves area under the receiver operating characteristic curve (AUC) of 0.9830 and 0.9865, respectively, for the two datasets. Compared to other state-of-the-art methods, the experimental results demonstrate that the performance of the proposed method is superior to that of others.

Environmental DNA (eDNA) is increasingly used to noninvasively monitor aquatic animals in freshwater and coastal areas. However, the use of eDNA in the open ocean (hereafter referred to OceanDNA) is still limited because of the sparse distribution of eDNA in the open ocean. Small pelagic fish have a large biomass and are widely distributed in the open ocean. We tested the performance of two OceanDNA analysis methods—species-specific qPCR (quantitative polymerase chain reaction) and MiFish metabarcoding using universal primers—to determine the distribution of small pelagic fish in the open ocean. We focused on six small pelagic fish species (Sardinops melanostictus, Engraulis japonicus, Scomber japonicus, Scomber australasicus, Trachurus japonicus, and Cololabis saira) and selected the Kuroshio Extension area as a testbed, because distribution of the selected species is known to be influenced by the strong frontal structure. The results from OceanDNA methods were compared to those of net sampling to test for consistency. Then, we compared the detection performance in each target fish between the using of qPCR and MiFish methods. A positive correlation was evident between the qPCR and MiFish detection results. In the ranking of the species detection rates and spatial distribution estimations, comparable similarity was observed between results derived from the qPCR and MiFish methods. In contrast, the detection rate using the qPCR method was always higher than that of the MiFish method. Amplification bias on non-target DNA and low sample DNA quantity seemed to partially result in a lower detection rate for the MiFish method; the reason is still unclear. Considering the ability of MiFish to detect large numbers of species and the quantitative nature of qPCR, the combined usage of the two methods to monitor quantitative distribution of small pelagic fish species with information of fish community structures was recommended.

Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa, IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system.

Glaucoma is an optic neuropathy commonly associated with elevated intraocular pressure (IOP) resulting in progressive loss of retinal ganglion cells (RGCs) and optic nerve degeneration, leading to blindness. New therapeutic approaches that better preserve the visual field by promoting survival and health of RGCs are highly needed since RGC death occurs despite good IOP control in glaucoma patients. We have developed a novel approach to reliably induce chronic IOP elevation in mouse using a photopolymerizable biomatrix, hyaluronic acid glycidyl methacrylate. This is achieved by rapid in vivo crosslinking of the biomatrix at the iridocorneal angle by a flash of ultraviolet A (UVA) light to impede the aqueous outflow pathway with a controllable manner. Sustained IOP elevation was induced after a single manipulation and was maintained at ~45% above baseline for >4 weeks. Significant thinning of the inner retina and ~35% reduction in RGCs and axons was noted within one month of IOP elevation. Optic nerve degeneration showed positive correlation with cumulative IOP elevation. Activation of astrocytes and microglia appeared to be an early event in response to IOP elevation preceding detectable RGC and axon loss. Attenuated glial reactivity was noted at later stage where significant RGC/axon loss had occurred suggesting astrocytes and microglia may play different roles over the course of glaucomatous degeneration. This novel murine glaucoma model is reproducible and displays cellular changes that recapitulate several pathophysiological features of glaucoma.

The ciliary epithelium (CE) of adult mammals has been reported to provide a source of retinal stem cells (RSCs) that can give rise to all retinal cell types in vitro. A recent study, however, suggests that CE-derived cells possess properties of pigmented ciliary epithelial cells and display little neurogenic potential. Here we show that the neurogenic potential of CE-derived cells is negatively regulated by ephrin-A3, which is upregulated in the CE of postnatal mice and presents a strong prohibitory niche for adult RSCs. Addition of ephrin-A3 inhibits proliferation of CE-derived RSCs and increases pigment epithelial cell fate. In contrast, absence of ephrin-A3 promotes proliferation and increases expression of neural progenitor cell markers and photoreceptor progeny. The negative effects of ephrin-A3 on CE-derived RSCs are mediated through activation of an EphA4 receptor and suppression of Wnt3a/β-catenin signaling. Together, our data suggest that CE-derived RSCs contain the intrinsic machinery to generate photoreceptors and other retinal neurons, while the CE of adult mice expresses negative regulators that prohibit the proliferation and neural differentiation of RSCs. Manipulating ephrin and Wnt/β-catenin signaling may, thus, represents a viable approach to activating the endogenous neurogenic potential of CE-derived RSCs for treating photoreceptor damage and retinal degenerative disorders.

Irreversible vision loss is often caused by the loss of retinal neurons, and one reason that retinal degenerative diseases are devastating is that, once retinal neurons are lost, they do not grow back. Stem cell-based neuron replacement strategy for retinal degenerative diseases are leading the way in clinical trials of transplantation therapy, and the exciting findings in both human and animal models point to the possibility of restoring vision through a cell replacement approach. Presumably, a less invasive method of retinal regeneration by mobilizing endogenous stem cells to replace those lost is highly desirable and promising for restoring vision. However, many obstacles remain, including mobilization of endogenous stem cells for restoration of lost cells, directed differentiation of progenitor cells, and establishment of functional connectivity in order to regain vision. The field of retinal self-repair is progressing at a rapid pace and encouraging outcomes.

Nanotechnology is an important and emerging industry with a projected annual market of around one trillion US dollars by 2011-2015. Concerns about the toxicity of nanomaterials in humans, however, have recently been raised. Although studies of nanoparticle toxicity have focused on lung disease the molecular link between nanoparticle exposure and lung injury remained unclear. In this report, we show that cationic Starburst polyamidoamine dendrimer (PAMAM), a class of nanomaterials that are being widely developed for clinical applications can induce acute lung injury in vivo. PAMAM triggers autophagic cell death by deregulating the Akt-TSC2-mTOR signaling pathway. The autophagy inhibitor 3-methyladenine rescued PAMAM dendrimer-induced cell death and ameliorated acute lung injury caused by PAMAM in mice. Our data provide a molecular explanation for nanoparticle-induced lung injury, and suggest potential remedies to address the growing concerns of nanotechnology safety.

Neurons in the mammalian central nervous system (CNS) undergo a developmental loss in their ability to grow axons as they mature, which is a critical contributing factor to the failure of nerve regeneration and repair after injury. This growth failure can be attributed, at least in part, to the induction of molecular programs preventing cellular overgrowth and termination of axonal growth on maturation. Key intracellular signals and transcription factors, including Bcl-2, cyclic adenine monophospate (cAMP), mammalian target of rapamycin (mTOR), and Kruppel-like transcription factors (KLFs), have been identified as playing central roles in this process. This chapter will provide an overview introducing the functions of these intracellular signals in their regulation of CNS axon regeneration.

Plasmalemmal and vesicular gamma-aminobutyric acid (GABA) transporters influence neurotransmission by regulating high-affinity GABA uptake and GABA release into the synaptic cleft and extracellular space. Postnatal expression of the plasmalemmal GABA transporter-1 (GAT-1), GAT-3, and the vesicular GABA/glycine transporter (VGAT) were evaluated in the developing mouse retina by using immunohistochemistry with affinity-purified antibodies. Weak transporter immunoreactivity was observed in the inner retina at postnatal day 0 (P0). GAT-1 immunostaining at P0 and at older ages was in amacrine and displaced amacrine cells in the inner nuclear layer (INL) and ganglion cell layer (GCL), respectively, and in their processes in the inner plexiform layer (IPL). At P10, weak GAT-1 immunostaining was in Müller cell processes. GAT-3 immunostaining at P0 and older ages was in amacrine cells and their processes, as well as in Müller cells and their processes that extended radially across the retina. At P10, Müller cell somata were observed in the middle of the INL. VGAT immunostaining was present at P0 and older ages in amacrine cells in the INL as well as processes in the IPL. At P5, weak VGAT immunostaining was also observed in horizontal cell somata and processes. By P15, the GAT and VGAT immunostaining patterns appear similar to the adult immunostaining patterns; they reached adult levels by about P20. These findings demonstrate that GABA uptake and release are initially established in the inner retina during the first postnatal week and that these systems subsequently mature in the outer retina during the second postnatal week.

We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNPIGF-TD cells displayed enhanced survival, and increased neurite extension and branching as compared to hNPTD or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNPIGF-TD cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNPIGF-TD cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma.