SUMMARY Corticotropin-releasing factor (CRF) that is released from the paraventricular nucleus (PVN) of the hypothalamus is essential for mediating stress response by activating the hypothalamic-pituitary-adrenal (HPA) axis. CRF-releasing PVN neurons receive inputs from multiple brain regions that convey stressful events, but their neuronal dynamics on the timescale of behavior remain unknown. Here, our recordings of PVN CRF neuronal activity in freely behaving mice revealed that CRF neurons are activated immediately by a range of aversive stimuli. By contrast, CRF neuronal activity starts to drop within a second of exposure to appetitive stimuli. Optogenetic activation or inhibition of PVN CRF neurons was sufficient to induce a conditioned place aversion (CPA) or preference (CPP), respectively. Furthermore, CPA or CPP induced by natural stimuli was significantly decreased by manipulating PVN CRF neuronal activity. Together, these findings suggest that the rapid, biphasic responses of PVN CRF neurons encode the positive and negative valences of stimuli.

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.

BackgroundNuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4–NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored.Patients and methodsWe investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes.ResultsHere, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4–NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4–NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4–NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%−75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells.ConclusionTaken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.

A B S T R A C T This paper reports recent achievements of novel structural health monitoring (SHM) techniques for damage diagnosis for critical members of civil, mechanical and aerospace structures using electro-mechanical impedance sensors. The basic concept of this technique is to use simultaneously both high-frequency structural excitations and responses employing piezoelectric sensors to monitor the local area of a structure for changes in structural impedance that would indicate imminent damage. In this paper, several principal software and hardware issues on these topics are described. A new impedance model is proposed that incorporates the effects of sensor and bonding defects for sensor selfdiagnosis. Temperature effects-free impedance-based damage detection algorithm using effective frequency shifts based on cross-correlation coefficients is presented. In a sense of tailoring wireless sensing technology to the impedance methods, an active sensor node incorporating a miniaturized impedance sensing device, an on-board microcontroller, and a radio frequency (RF) telemetry is introduced. A data compression algorithm is embedded into the on-board chip of the active sensor node to enhance its local data processing-capability. Finally, this paper concludes with a discussion of further studies and future applications.

Sodium appetite is a powerful form of motivation that can drive ingestion of high, yet aversive concentrations of sodium in animals depleted of sodium. However, in normal conditions sodium appetite is suppressed to prevent homeostatic deviations. While molecular and neural mechanisms underlying the stimulation of sodium appetite received much attention recently, those that inhibit sodium appetite remain largely obscure. Here, we report that serotonin 2c receptor (Htr2c)-expressing neurons in the lateral parabrachial nucleus (LPBN Htr2c neurons) inhibit sodium appetite. Activity of these neurons is regulated by bodily sodium content and their activation can rapidly suppress sodium intake. Conversely, inhibition of these neurons specifically drives sodium appetite, even during euvolemic conditions. Importantly, the physiological role of Htr2c expressed by LPBN neurons is to disinhibit sodium appetite. Our results suggest that LPBN Htr2c neurons act as a brake against sodium appetite and that its alleviation is required for the full manifestation of sodium appetite.