Nuclear access of DNlg3 c-terminal fragment and its function in regulating innate immune response genes.

Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and HEK293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism.

Effects of Two Environmental Enrichment Methods on Cognitive Ability and Growth Performance of Juvenile Black Rockfish Sebastes schlegelii.

A widely used approach to restoring marine fishery resources is stock enhancement using hatchery-reared fish. However, artificial rearing environments, which are often lacking in enrichment, may negatively affect the cognition, welfare, and adaptive capacity to new environments of juvenile fish, thereby leading to low post-release survival rates. This study examined the effects of habitat and social enrichment on the growth performance and cognitive ability of Sebastes schlegelii. Following seven weeks of environmental enrichment, a T-maze experiment was conducted, and the telencephalon and visceral mass of the fish were sampled to measure the growth (growth hormone: GH; insulin-like growth factor-1: IGF-1; and somatostatin: SS) and cognitive abilities (brain-derived neurotrophic factor: BDNF; and nerve growth factor: NGF)-related indicator levels. The results indicated that, although the final body length, final body weight, and specific growth rate of both enrichment groups were lower than those of the control group, both methods of enrichment had a positive impact on growth-related factors (increased GH, increased IGF-1, and decreased SS). The enrichment groups demonstrated a stronger learning ability in the T-maze test, and the levels of BDNF and NGF in the telencephalon were significantly higher in the enrichment groups than those in the control group. Additionally, there was a significant interaction between the two enrichment methods on the NGF level. This study confirms that a more complex and enriching environment is beneficial for cultivating the cognitive abilities of cultured juvenile S. schlegelii, and the result can provide a reference for the improvement of the stock enhancement of this species.

A Comparative Study on Two Territorial Fishes: The Influence of Physical Enrichment on Aggressive Behavior.

Intraspecific aggression is detrimental to body/fin damage, physiological stress, and other problems in aquaculture. Environmental enrichment has been proposed to have positive effects on fish aggressive behavior, physiological stress, and fish welfare, but there are mixed results. Here, we examine the impact of physical enrichment levels (i.e., the intensity of physical enrichment) on aggression in black rockfish (Sebastes schlegelii) and fat greenling (Hexagrammos otakii). Generally, with the increase in the enrichment level, the frequency of the aggressive behavior of black rockfish gradually decreased. In contrast, a non-monotonous effect of the enrichment level on aggression was observed for fat greenling, with low and intermediate levels leading to no or more aggression, while a high enrichment level reduced aggression. After three days, the high-level enrichment groups in both rockfish and greenling reached social stability (i.e., a relatively stable social structure indicated by lower aggression), while aggression in the other groups continued increased. These results show the significant regulatory effect of enrichment levels on the aggressive behavior in both black rockfish and fat greenling. This study may promote the development of environmental enrichment measures, and it provides useful information for reducing fish aggression and improving fish welfare in aquaculture.

Barren environment damages cognitive abilities in fish: Behavioral and transcriptome mechanisms.

The surrounding environments that animals inhabit shape their behavioral phenotypes, physiological status and molecular processes. As one of the driving forces for the adaptation and evolution of marine animals, environmental complexity has been shown to affect several behavioral characteristics in fish. However, little is known about the effects of environmental complexity on fish spatial cognition and about the relevant regulatory mechanisms. To address this theoretical gap, black rockfish Sebastes schlegelii, which is a typical rock fish species, were exposed to laboratory-based small-scale contrasting environments (i.e., spatially complex environment vs. spatially barren environment) for seven weeks. Subsequently, the spatial cognitive abilities and behavioral performance during captive period were determined, and transcriptome sequencing and analyses for fish telencephalon were conducted. In general, the fish from barren environment had significantly lower spatial learning and memory abilities compared with the fish from complex environment (i.e., the complex fish exited the maze faster). During the whole captive period, the frequency of aggressive behavior among barren fish was significantly higher than complex fish. And meanwhile, the group dispersion index of barren group was also significantly higher than complex group, which indicated that complex fish tended to distribute in a more homogeneous pattern than barren fish. Through transcriptomic analyses, a series of differentially expressed genes and pathways which may underpin the damaged effects of barren environment on fish spatial cognition were identified, and these genes mainly related to stress response, metabolism, organism systems and neural plasticity. However, no significant differences in growth performance, locomotor activity (indicated by swimming behavior and rotatory behavior) between treatments were detected. Based on these results, mechanisms in the levels of behavior and molecule were proposed to explain the environmental effects on fish cognition. This study may provide fundamental information for deeply understanding the environmental effects on marine animals.

Design and synthesis of a novel class of furan-based molecules as potential 20S proteasome inhibitors.

A novel class of furan-based compounds as potential 20S proteasome inhibitors have been designed and synthesized, among which nine compounds are peptide derivatives and six molecules are statine peptidomimetics. The C-terminal furanyl moiety was introduced to target molecules as furan-based amino acids. All the compounds were obtained steadily with moderate to high yield. Compound 12 was a selective moderate potent proteasome peptidomimetic inhibitor. It inhibited HepG2 and HL-60 proliferation effectively.