Lenghu on the Tibetan Plateau as an astronomical observing site.

On Earth's surface, there are only a handful of high-quality astronomical sites that meet the requirements for very large next-generation facilities. In the context of scientific opportunities in time-domain astronomy, a good site on the Tibetan Plateau will bridge the longitudinal gap between the known best sites1,2 (all in the Western Hemisphere). The Tibetan Plateau is the highest plateau on Earth, with an average elevation of over 4,000 metres, and thus potentially provides very good opportunities for astronomy and particle astrophysics3-5. Here we report the results of three years of monitoring of testing an area at a local summit on Saishiteng Mountain near Lenghu Town in Qinghai Province. The altitudes of the potential locations are between 4,200 and 4,500 metres. An area of over 100,000 square kilometres surrounding Lenghu Town has a lower altitude of below 3,000 metres, with an extremely arid climate and unusually clear local sky (day and night)6. Of the nights at the site, 70 per cent have clear, photometric conditions, with a median seeing of 0.75 arcseconds. The median night temperature variation is only 2.4 degrees Celsius, indicating very stable local surface air. The precipitable water vapour is lower than 2 millimetres for 55 per cent of the night.

Reciprocal Regulation of the TOR Kinase and ABA Receptor Balances Plant Growth and Stress Response.

As sessile organisms, plants must adapt to variations in the environment. Environmental stress triggers various responses, including growth inhibition, mediated by the plant hormone abscisic acid (ABA). The mechanisms that integrate stress responses with growth are poorly understood. Here, we discovered that the Target of Rapamycin (TOR) kinase phosphorylates PYL ABA receptors at a conserved serine residue to prevent activation of the stress response in unstressed plants. This phosphorylation disrupts PYL association with ABA and with PP2C phosphatase effectors, leading to inactivation of SnRK2 kinases. Under stress, ABA-activated SnRK2s phosphorylate Raptor, a component of the TOR complex, triggering TOR complex dissociation and inhibition. Thus, TOR signaling represses ABA signaling and stress responses in unstressed conditions, whereas ABA signaling represses TOR signaling and growth during times of stress. Plants utilize this conserved phospho-regulatory feedback mechanism to optimize the balance of growth and stress responses.

Investigation of acousto-optic interaction with momentum mismatching considering acoustic anisotropy in birefringent crystal.

In this work, the momentum mismatching based on which the acousto-optic (AO) transfer function and diffraction efficiency was acquired, was calculated considering the properties of AO crystals in AO interactions in acousto-optic tunable filter (AOTF). Transfer functions were obtained using a 4f optical system combined with AOTF and compared with theoretical calculations. It demonstrated the influence of acoustic energy shift on the AO interaction which should be considered in the design of AOTF.

Red light-upregulated MPK11 negatively regulates red light-induced stomatal opening in Arabidopsis.

Stomatal movements allow the uptake of CO2 for photosynthesis and water loss through transpiration, therefore play a crucial role in determining water use efficiency. Both red and blue lights induce stomatal opening, and the stomatal apertures under light are finetuned by both positive and negative regulators in guard cells. However, the molecular mechanisms for precisely adjusting stomatal apertures under light have not been completely understood. Here, we provided evidence supporting that Arabidopsis thaliana mitogen-activated protein kinase 11 (MPK11) plays a negative role in red light-induced stomatal opening. First, MPK11 was found to be highly expressed in guard cells, and MPK11-GFP signals were detected in both nuclear and cytoplasm of guard cells. The transcript levels of MPK11 in guard cells were upregulated by white light, and the stomata of mpk11 opened wider than that of wild type under white light. Consistent with the larger stomatal aperture, mpk11 mutant exhibited higher stomatal conductance and CO2 assimilation rate under white light. The transcript levels of the genes responsible for osmolytes increases were higher in guard cells of mpk11 than that of wild type, which may contribute to the larger stomatal aperture of mpk11 under white light. Furthermore, MPK11 transcript levels in guard cells were upregulated by red light, and mpk11 mutant showed a larger stomatal aperture under red light. Taken together, these results demonstrate that red light-upregulated MPK11 plays a negative role in stomatal opening, which finetuning the stomatal opening apertures and preventing excessive water loss by transpiration under light.

PhyB-dependent phosphorylation of mitogen-activated protein kinase cascade MKK2-MPK2 positively regulates red light-induced stomatal opening.

Red light induces stomatal opening by affecting photosynthesis, metabolism and triggering signal transductions in guard cells. Phytochrome B (phyB) plays a positive role in mediating red light-induced stomatal opening. However, phyB-mediated red light guard cell signalling is poorly understood. Here, we found that phyB-mediated sequential phosphorylation of mitogen-activated protein kinase kinase 2 (MAPKK2, MKK2) and MPK2 in guard cells is essential for red light-induced stomatal opening. Mutations in MKK2 and MPK2 led to reduced stomatal opening in response to white light, and these phenotypes could be observed under red light, not blue light. MKK2 interacted with MPK2 in vitro and in plants. MPK2 was directly phosphorylated by MKK2 in vitro. Red light triggered the phosphorylation of MKK2 in guard cells, and MKK2 phosphorylation was greatly reduced in phyB mutant. Simultaneously, red light-stimulated MPK2 phosphorylation in guard cells was inhibited in mkk2 mutant. Furthermore, mkk2 and mpk2 mutants exhibit significantly smaller stomatal apertures than that of wild type during the stomatal opening stage in the diurnal stomatal movements. Our results indicate that red light-promoted phyB-dependent phosphorylation of MKK2-MPK2 cascade in guard cells is essential for stomatal opening, which contributes to the fine-tuning of stomatal opening apertures under light.

Epidemiology of depressive disorders among youth during Gaokao to college in China: results from Hunan Normal University mental health survey.

BACKGROUND: Given the serious consequences of depression and the lack of information about it during the crucially developmental period from the National College Entrance Exam (CEE, i.e., Chinese gaokao) to college, this study aimed to estimate the cumulative incidence, prevalence, age of onset, correlates, and service use of depressive disorders (DDs) among youth who passed the CEE and were enrolled at Hunan Normal University in China. METHODS: A two-stage cross-sectional epidemiological survey of DDs was conducted from October to December, 2017 among 6,922 incoming college students (98.5% effective response, N = 6,818, 71.4% female, age range: 16-25 years, mean age = 18.6). Using a stratified sampling method based on the risk of depression, 926 participants (mean age = 18.5, 75.2% female) were selected and subsequently interviewed with the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and lifetime version (K-SADS-PL). RESULTS: The sex-adjusted 9-month (i.e., 3 months pre-CEE, 3 months after CEE, and 3 months post-matriculation) incidence of new-onset DDs was 2.3% (standard error [S.E.] 0.3%), and the sex-adjusted 1-month, 6-month and lifetime prevalence were 0.7 (S.E. 0.3%), 1.7 (S.E. 0.2%) and 7.5% (S.E. 1.3%), respectively. The median age of onset was 17 (interquartile range: 16-18) years. Critically, over one-third (36.5%, S.E. 0.6) of depressed youth had their new onset during the 9-month period. The risk factors for depression included having mothers with higher education, experiencing major life events, being female, and experiencing parental divorce or death. The adjusted lifetime treatment rate was 8.7%. CONCLUSION: The 9-month incidence of new-onset depression from gaokao to college among the youth sample in China is similar to the global annual incidence (3.0%), but the 1-month and lifetime prevalence are significantly lower than the global point (7.2%) and lifetime prevalence (19%). These findings suggest a high proportion of new-onset depression during the CEE to college among the sample youth in China. The risk of depression is associated with familial and stress correlates. Low treatment is a serious concern. Emphasis on early prevention and available treatment for adolescent and young adult depression is a critical need in China.

Mapping proteome-wide targets of protein kinases in plant stress responses.

Protein kinases are major regulatory components in almost all cellular processes in eukaryotic cells. By adding phosphate groups, protein kinases regulate the activity, localization, protein-protein interactions, and other features of their target proteins. It is known that protein kinases are central components in plant responses to environmental stresses such as drought, high salinity, cold, and pathogen attack. However, only a few targets of these protein kinases have been identified. Moreover, how these protein kinases regulate downstream biological processes and mediate stress responses is still largely unknown. In this study, we introduce a strategy based on isotope-labeled in vitro phosphorylation reactions using in vivo phosphorylated peptides as substrate pools and apply this strategy to identify putative substrates of nine protein kinases that function in plant abiotic and biotic stress responses. As a result, we identified more than 5,000 putative target sites of osmotic stress-activated SnRK2.4 and SnRK2.6, abscisic acid-activated protein kinases SnRK2.6 and casein kinase 1-like 2 (CKL2), elicitor-activated protein kinase CDPK11 and MPK6, cold-activated protein kinase MPK6, H2O2-activated protein kinase OXI1 and MPK6, and salt-induced protein kinase SOS1 and MPK6, as well as the low-potassium-activated protein kinase CIPK23. These results provide comprehensive information on the role of these protein kinases in the control of cellular activities and could be a valuable resource for further studies on the mechanisms underlying plant responses to environmental stresses.

A New Fast Control Strategy of Terminal Sliding Mode with Nonlinear Extended State Observer for Voltage Source Inverter.

To overcome the sensitivity of voltage source inverters (VSIs) to parameter perturbations and their susceptibility to load variations, a fast terminal sliding mode control (FTSMC) method is proposed as the core and combined with an improved nonlinear extended state observer (NLESO) to resist aggregate system perturbations. Firstly, a mathematical model of the dynamics of a single-phase voltage type inverter is constructed using a state-space averaging approach. Secondly, an NLESO is designed to estimate the lumped uncertainty using the saturation properties of hyperbolic tangent functions. Finally, a sliding mode control method with a fast terminal attractor is proposed to improve the dynamic tracking of the system. It is shown that the NLESO guarantees convergence of the estimation error and effectively preserves the initial derivative peak. The FTSMC enables the output voltage with high tracking accuracy and low total harmonic distortion and enhances the anti-disturbance ability.

An Efficient End-to-End Multitask Network Architecture for Defect Inspection.

Recently, computer vision-based methods have been successfully applied in many industrial fields. Nevertheless, automated detection of steel surface defects remains a challenge due to the complexity of surface defects. To solve this problem, many models have been proposed, but these models are not good enough to detect all defects. After analyzing the previous research, we believe that the single-task network cannot fully meet the actual detection needs owing to its own characteristics. To address this problem, an end-to-end multi-task network has been proposed. It consists of one encoder and two decoders. The encoder is used for feature extraction, and the two decoders are used for object detection and semantic segmentation, respectively. In an effort to deal with the challenge of changing defect scales, we propose the Depthwise Separable Atrous Spatial Pyramid Pooling module. This module can obtain dense multi-scale features at a very low computational cost. After that, Residually Connected Depthwise Separable Atrous Convolutional Blocks are used to extract spatial information under low computation for better segmentation prediction. Furthermore, we investigate the impact of training strategies on network performance. The performance of the network can be optimized by adopting the strategy of training the segmentation task first and using the deep supervision training method. At length, the advantages of object detection and semantic segmentation are tactfully combined. Our model achieves mIOU 79.37% and mAP@0.5 78.38% on the NEU dataset. Comparative experiments demonstrate that this method has apparent advantages over other models. Meanwhile, the speed of detection amount to 85.6 FPS on a single GPU, which is acceptable in the practical detection process.

Circular RNA_0001742 has potential to predict advanced tumor stage and poor survival profiles in tongue squamous cell carcinoma management.

BACKGROUND: Circular RNA_0001742 (circ_0001742) has been reported to be upregulated in tongue squamous cell carcinoma (TSCC) tissues/cells and regulate TSCC cell proliferation, migration, and invasion. This study aimed to further investigate the clinical significance of circ_0001742 in TSCC management. METHODS: Totally, 146 TSCC patients underwent surgical treatment were reviewed. Their fresh-frozen tumor tissue and adjacent tissue were acquired for detecting circ_0001742 expression via reverse transcription-quantitative polymerase chain reaction. According to circ_0001742 expression in tumor tissue, all patients were classified as tumor circ_0001742 low (0%-50% percentile) and high (50%-100% percentile) patients, the latter were further divided into the tumor circ_0001742 high+ (50%-75% percentile), high++ (75%-90% percentile), and high+++ (90%-100% percentile) patients, respectively. RESULTS: Circ_0001742 expression was increased in TSCC tumor tissue compared with adjacent tissue, and it presented good value in discriminating tumor tissue from adjacent tissue (area under the curve (AUC): 0.870, 95% CI: 0.831-0.910). Tumor high circ_0001742 expression was associated with higher T stage, N stage, and TNM stage, but not age, gender, or pathological grade. Furthermore, OS was reduced in tumor circ_0001742 high patients compared with tumor circ_0001742 low patients; moreover, OS was the shortest in tumor circ_0001742 high+++ patients, followed by tumor circ_0001742 high++ patients and tumor circ_0001742 high+ patients, and the longest in tumor circ_0001742 low patients. In addition, multivariate Cox's regression analysis revealed that higher tumor circ_0001742 expression was an independent predictive factor for decreased OS. CONCLUSION: Circ_0001742 serves as a potential biomarker for advanced tumor stage and poor survival in TSCC patients.

AgRP to Kiss1 neuron signaling links nutritional state and fertility.

Mammalian reproductive function depends upon a neuroendocrine circuit that evokes the pulsatile release of gonadotropin hormones (luteinizing hormone and follicle-stimulating hormone) from the pituitary. This reproductive circuit is sensitive to metabolic perturbations. When challenged with starvation, insufficient energy reserves attenuate gonadotropin release, leading to infertility. The reproductive neuroendocrine circuit is well established, composed of two populations of kisspeptin-expressing neurons (located in the anteroventral periventricular hypothalamus, Kiss1AVPV, and arcuate hypothalamus, Kiss1ARH), which drive the pulsatile activity of gonadotropin-releasing hormone (GnRH) neurons. The reproductive axis is primarily regulated by gonadal steroid and circadian cues, but the starvation-sensitive input that inhibits this circuit during negative energy balance remains controversial. Agouti-related peptide (AgRP)-expressing neurons are activated during starvation and have been implicated in leptin-associated infertility. To test whether these neurons relay information to the reproductive circuit, we used AgRP-neuron ablation and optogenetics to explore connectivity in acute slice preparations. Stimulation of AgRP fibers revealed direct, inhibitory synaptic connections with Kiss1ARH and Kiss1AVPV neurons. In agreement with this finding, Kiss1ARH neurons received less presynaptic inhibition in the absence of AgRP neurons (neonatal toxin-induced ablation). To determine whether enhancing the activity of AgRP neurons is sufficient to attenuate fertility in vivo, we artificially activated them over a sustained period and monitored fertility. Chemogenetic activation with clozapine N-oxide resulted in delayed estrous cycles and decreased fertility. These findings are consistent with the idea that, during metabolic deficiency, AgRP signaling contributes to infertility by inhibiting Kiss1 neurons.

Fault Diagnosis for Rolling Bearings Using Optimized Variational Mode Decomposition and Resonance Demodulation.

It is difficult to extract the fault signal features of locomotive rolling bearings and the accuracy of fault diagnosis is low. In this paper, a novel fault diagnosis method based on the optimized variational mode decomposition (VMD) and resonance demodulation technology, namely GNVRFD, is proposed to realize the fault diagnosis of locomotive rolling bearings. In the proposed GNVRFD method, the genetic algorithm and nonlinear programming are combined to design a novel parameter optimization algorithm to adaptively optimize the two parameters of the VMD. Then the optimized VMD is employed to decompose the collected vibration signal into a series of intrinsic mode functions (IMFs), and the kurtosis value of each IMF is calculated, respectively. According to the principle of maximum value, two most sensitive IMF components are selected to reconstruct the vibration signal. The resonance demodulation technology is used to decompose the reconstructed vibration signal in order to obtain the envelope spectrum, and the fault frequency of locomotive rolling bearings is effectively obtained. Finally, the actual data of rolling bearings is selected to testify the effectiveness of the proposed GNVRFD method. The experiment results demonstrate that the proposed GNVRFD method can more accurately and effectively diagnose the fault of locomotive rolling bearings by comparing with other fault diagnosis methods.

LATS2 promotes cardiomyocyte H9C2 cells apoptosis via the Prx3-Mfn2-mitophagy pathways.

Context: The pathogenesis of cardiomyocyte death is closely associated with mitochondrial homeostasis via poorly understood mechanisms.Objective: The aim of our study is to explore the contribution of large tumor suppressor kinase 2 (LATS2) to the apoptosis of cardiomyocyte H9C2 cells.Materials and Methods: Adenovirus-mediated LATS2 overexpression was carried out in H9C2 cells. The cell viability and apoptosis rate were measured via an MTT assay, TUNEL staining, western blotting, an ELISA, and an LDH release assay. Mitophagy was quantified using immunofluorescence and western blotting.Results: The overexpression of LATS2 in H9C2 cells drastically promoted cell death. Molecular investigations showed that LATS2 overexpression was associated with mitochondrial injury, as evidenced by increased mitochondrial ROS production, reduced antioxidant factor levels, increased cyt-c liberation into the nucleus and activated mitochondrial caspase-9-dependent apoptotic pathway activity. Furthermore, our results demonstrated that LATS2-mediated mitochondrial malfunction by repressing mitophagy and that the reactivation of mitophagy could sustain mitochondrial integrity and homeostasis in response to LATS2 overexpression. Furthermore, we found that LATS2 inhibited mitophagy by inactivating the Prx3-Mfn2 axis. The reactivation of Prx3-Mfn2 pathways abrogated the LATS2-mediated inhibition of mitochondrial apoptosis in H9C2 cells.Conclusions: The overexpression of LATS2 induces mitochondrial stress by repressing protective mitophagy in a manner dependent on Prx3-Mfn2 pathways, thus reducing the survival of H9C2 cells.

TCP7 functions redundantly with several Class I TCPs and regulates endoreplication in Arabidopsis.

TCP (TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR) proteins, a family of plant-specific transcription factors, play important roles in many developmental processes. However, genetic and functional redundancy among class I TCP limits the analysis of their biological roles. Here, we identified a dominant-negative mutant of Arabidopsis thaliana TCP7 named leaf curling-upward (lcu), which exhibits smaller leaf cells and shorter hypocotyls than the wild type, due to defective endoreplication. A septuple loss-of-function mutant of TCP7, TCP8, TCP14, TCP15, TCP21, TCP22, and TCP23 displayed similar developmental defects to those of lcu. Genome-wide RNA-sequencing showed that lcu and the septuple mutant share many misexpressed genes. Intriguingly, TCP7 directly targets the CYCLIN D1;1 (CYCD1;1) locus and activates its transcription. We determined that the C-terminus of TCP7 accounts for its transcriptional activation activity. Furthermore, the mutant protein LCU exhibited reduced transcriptional activation activity due to the introduction of an EAR-like repressive domain at its C-terminus. Together, these observations indicate that TCP7 plays important roles during leaf and hypocotyl development, redundantly, with at least six class I TCPs, and regulates the expression of CYCD1;1 to affect endoreplication in Arabidopsis.

The RopGEF2-ROP7/ROP2 Pathway Activated by phyB Suppresses Red Light-Induced Stomatal Opening.

Circadian rhythm of stomatal aperture is mainly regulated by light/darkness. Blue and red light induce stomatal opening through different mechanisms that are mediated by special receptors. ROP2, a member of Rho GTPase family in Arabidopsis (Arabidopsisthaliana), has been found to negatively regulate light-induced stomatal opening. However, the upstream guanine nucleotide exchange factor (GEF) RopGEFs have not been revealed, and it is unclear which photoreceptor is required for the action of RopGEFs-ROPs. Here, we showed that RopGEF2 acted as a negative regulator in phytochrome B (phyB)-mediated red light-induced stomatal opening. Meanwhile, ROP7, another member of ROP family, acting redundantly with ROP2, was regulated by RopGEF2 in this process. RopGEF2 interacted with ROP7 and ROP2 and enhanced their intrinsic nucleotide exchange rates. Furthermore, the direct interactions between phyB and RopGEF2 were detected in vitro and in plants, and phyB enhanced the GEF activity of RopGEF2 toward both ROP7 and ROP2 under light. In addition, RopGEF4 functioned redundantly with RopGEF2 in red light-induced stomatal opening by activating both ROP7 and ROP2, and RopGEF2/RopGEF4 acted genetically downstream of phyB; however, the GEF activity of RopGEF4 was not directly enhanced by phyB. These results revealed that red light-activated phyB enhances the GEF activities of RopGEF2 and RopGEF4 directly or indirectly, and then activate both ROP7 and ROP2 in guard cells. The negative mechanism triggered by phyB prevents the excessive stomatal opening under red light.

Non-radio-frequency signal tuned acousto-optic tunable filter.

As for the common acousto-optic tunable filter (AOTF), the optical wavelength is directly tuned by the frequency of the applied radio frequency (RF) signal. The working wavelength range of the RF controlled AOTF could be limited by the performance of the RF source, especially in the high frequency area. We have proposed a special noncollinear AOTF system, in which the central optical wavelength could be tuned continually by rotating the AOTF, rather than changing its RF. This arrangement is confirmed to be effective to broaden the work wavelength range of a traditional RF based AOTF with the high spectral resolution. Particularly, it is welcomed to the circumstance for the flexible spectral bandwidth. This work has presented not only an original way to tune the wavelength of the filtered optical signal but also a powerful supplement of the RF controlled AOTF. It can lead to a wider applications of a noncollinear AOTF in the field of spectral analysis, hyperspectral imaging, and etc.

Narrowband double-filtering hyperspectral imaging based on a single AOTF.

A method of spectral resolution improvement was presented based on the double filtering in a single AOTF. A special narrowband hyperspectral imaging system using this single-AOTF double-filtering method was established. The spectral bandwidth of double-filtered spectra was 39% narrower than that of the single-filtered optical signal experimentally. We achieved hyperspectral images of the resolution target with better image resolutions than the single-filtering images because of the improved spectral resolution after the double-filtering process.

Design of an acousto-optic tunable filter based on momentum mismatching together with the rotatory property.

Basing on the momentum mismatching together with the crystal rotatory property, we investigate the diffraction performance of an acousto-optic tunable filter (AOTF). The relationship between diffraction efficiency, momentum mismatching, incident optical wave vector, and ultrasound wave vector is analyzed. The correlation between the frequency tuning relation and the incident angle of light is demonstrated, which is usually ignored in the AOTF design. The diffracted wavelength can be decided by a particular acoustic frequency only when the incident angle of light is fixed. Theoretical and experimental analysis indicates that we can acquire a narrowband spectrum and big angular aperture with a proper incident angle.

Species phylogeny and diversification process of Northeast Asian Pungitius revealed by AFLP and mtDNA markers.

Pungitius is a highly diversified genus of sticklebacks (Gasterosteidae) occurring widely in northern parts of the Northern Hemisphere. Several ecologically and genetically divergent types that are largely isolated reproductively but occasionally hybridize in sympatry have been discovered in Northeast Asia, although the taxonomy and evolutionary relationships among them remain unclear. We used amplified fragment length polymorphism (AFLP) and mitochondrial DNA (mtDNA) markers to infer phylogenies among individuals collected from sympatric and allopatric populations, including the type localities of the described species. Phylogenetic analyses based on 2683 polymorphic AFLP loci confirmed seven species, each of which (except for one entirely allopatric species P. platygaster) was clearly differentiated from one or two other sympatric species and constituted a highly supported monophyletic clade with conspecific allopatric populations. The phylogeny showed that two lineages arose early; one gave rise to two species (circumpolar species P. pungitius and Paratethys species P. platygaster) and the other to five species endemic to Northeast Asia (P. sinensis, P. tymensis, P. polyakovi, P. kaibarae, and P. bussei). The brackish-water, freshwater, and Omono types previously discovered in Japan were reidentified as P. pungitius, P. sinensis, and P. kaibarae, respectively. A marked incongruence was noted between the phylogenies of AFLP and mtDNA markers, suggesting the occasional occurrence of hybridization and mtDNA introgression among distinct species. Our results highlight that the marginal seas of Northeast Asia played a key role as barriers to or facilitators of gene flow in the evolution of species diversity of Pungitius concentrated in this region.

Kisspeptin and Gonadotropin-Releasing Hormone Neuronal Excitability: Molecular Mechanisms Driven by 17ß-Estradiol.

Kisspeptin is a neuropeptide that signals via a Gαq-coupled receptor, GPR54, in gonadotropin-releasing hormone (GnRH) neurons and is essential for pubertal maturation and fertility. Kisspeptin depolarizes and excites GnRH neurons primarily through the activation of canonical transient receptor potential (TRPC) channels and the inhibition of K+ channels. The gonadal steroid 17ß-estradiol (E2) upregulates not only kisspeptin (Kiss1) mRNA but also increases the excitability of the rostral forebrain Kiss1 neurons. In addition, a primary postsynaptic action of E2 on GnRH neurons is to upregulate the expression of channel transcripts that orchestrate the downstream signaling of kisspeptin in GnRH neurons. These include not only TRPC4 channels but also low-voltage-activated T-type calcium channels and high-voltage-activated L-, N- and R-type calcium channel transcripts. Moreover, E2 has direct membrane-initiated actions to alter the excitability of GnRH neurons by enhancing ATP-sensitive potassium channel activity, which is critical for maintaining GnRH neurons in a hyperpolarized state for the recruitment of T-type calcium channels that are important for burst firing. Therefore, E2 modulates the excitability of GnRH neurons as well as of Kiss1 neurons by altering the expression and/or function of ion channels; moreover, kisspeptin provides critical excitatory input to GnRH neurons to facilitate burst firing activity and peptide release.