Temperature-dependent sex determination is a notable model of phenotypic plasticity. In many reptiles, including the red-eared slider turtle (), the individual's sex is determined by the ambient temperature during egg incubation. In this study, we show that the histone H3 lysine 27 (H3K27) demethylase KDM6B exhibits temperature-dependent sexually dimorphic expression in early embryos before the gonad is distinct. Knockdown of at 26°C (a temperature at which all offspring develop into males) triggers male-to-female sex reversal in >80% of surviving embryos. KDM6B directly promotes the transcription of the male sex-determining gene by eliminating the trimethylation of H3K27 near its promoter. Additionally, overexpression of is sufficient to rescue the sex reversal induced by disruption of This study establishes causality and a direct genetic link between epigenetic mechanisms and temperature-dependent sex determination in a turtle species.

In many reptiles, including the red-eared slider turtle Trachemys scripta elegans (T. scripta), sex is determined by ambient temperature during embryogenesis. We previously showed that the epigenetic regulator Kdm6b is elevated at the male-producing temperature and essential to activate the male pathway. In this work, we established a causal link between temperature and transcriptional regulation of Kdm6b. We show that signal transducer and activator of transcription 3 (STAT3) is phosphorylated at the warmer, female-producing temperature, binds the Kdm6b locus, and represses Kdm6b transcription, blocking the male pathway. Influx of Ca2+, a mediator of STAT3 phosphorylation, is elevated at the female temperature and acts as a temperature-sensitive regulator of STAT3 activation.

Niemann-Pick type C1 disease (NPC1) is a fatal genetic disorder caused by impaired intracellular cholesterol trafficking. Recent studies reported ototoxicity of 2-hydroxypropyl- β-cyclodextrin (HPβCD), a cholesterol chelator and the only promising treatment for NPC1. Because outer hair cells (OHCs) are the only cochlear cells affected by HPβCD, we investigated whether prestin, an OHC-specific motor protein, might be involved. Single, high-dose administration of HPβCD resulted in OHC death in prestin wildtype (WT) mice whereas OHCs were largely spared in prestin knockout (KO) mice in the basal region, implicating prestin’s involvement in ototoxicity of HPβCD. We found that prestin can interact with cholesterol in vitro, suggesting that HPβCD-induced ototoxicity may involve disruption of this interaction. Time-lapse analysis revealed that OHCs isolated from WT animals rapidly deteriorated upon HPβCD treatment while those from prestin-KOs tolerated the same regimen. These results suggest that a prestin-dependent mechanism contributes to HPβCD ototoxicity.

Residential demand response is vital for the efficiency of power system. It has attracted much attention from both academic and industry in recent years. Accurate short-term load forecasting is a fundamental task for demand response. While short-term forecasting for aggregated load data has been extensively studied, load forecasting for individual residential users is still challenging due to the dynamic and stochastic characteristic of single users' electricity consumption behaviors, i.e., the variability of the residential activities. To address this challenge, this paper presents a short-term residential load forecasting framework, which makes use of the spatio-temporal correlation existing in appliances' load data through deep learning. Multiple time series are conducted in the framework to describe electricity consumption behaviors and their internal spatio-temporal relationship. And a method based on deep neural network and iterative ResBlock is proposed to learn the correlation among different electricity consumption behaviors for shortterm load forecasting. Experiments based on real world measurements have been conducted to evaluate the performance of the proposed forecasting approach. The results show that both the appliances' load data and iterative ResBlocks can help to improve the forecasting performance. Compared with existing methods, measurements on Root Mean Squared Error, Mean Absolute Error and Mean Absolute Percentage Error for the proposed approach are reduced by 3.89%-20.00%, 2.18%-22.58% and 0.69%-32.78%. In addition, further experiments are conducted to evaluate the impact of using appliances' load data, iterative ResBlocks as well as other factors for the proposed approach. INDEX TERMS Smart grid, short-term load forecasting, deep learning, residential load forecasting, iterative ResBlocks.

No abstract

No abstract

Prestin (SLC26A5)-mediated voltage-driven elongations and contractions of sensory outer hair cells within the organ of Corti are essential for mammalian cochlear amplification. However, whether this electromotile activity directly contributes on a cycle-by-cycle basis is currently controversial. By restoring motor kinetics in a mouse model expressing a slowed prestin missense variant, this study provides experimental evidence acknowledging the importance of fast motor action to mammalian cochlear amplification. Our results also demonstrate that the point mutation in prestin disrupting anion transport in other proteins of the SLC26 family does not alter cochlear function, suggesting that the potential weak anion transport of prestin is not essential in the mammalian cochlea.

No abstract