Expression and Function of Ca2+-Activated K+ Channels in Uterine Arteries

Chronic hypoxia during pregnancy is one of the most common insults to the maternal cardiovascular system and fetal development, and is associated with increased uterine vascular tone and heightened risk of preeclampsia and fetal intrauterine growth restriction (IUGR). The present study tested the hypothesis that calcium-activated potassium (KCa) channels play an essential role in uterine vascular adaptation to pregnancy, which is inhibited by chronic hypoxia during gestation. Uterine arteries (UAs) were isolated from nonpregnant ewes (NPUAs) and near-term pregnant ewes (PUAs) that had been maintained at sea level (~300 m) or exposed to high altitude (3,801 m) for 110 days. In normoxic animals, both BKCa and SKCa channels were expressed in uterine arterial smooth muscle cells and endothelial cells. Pregnancy selectively enhanced the protein abundances and mRNA levels of BKCa subunit 1 and SKCa subtype 2 and 3 in uterine arteries, resulting in enhanced both BKCa and SKCa channels activities and their-mediated relaxations, and decreased uterine vascular tone in PUAs as compared with those in NPUAs. Chronic treatment of NPUA with 17β-estradiol (E2β) and progesterone significantly increased BKCa and SKCa channel exspression and enhanced both BKCa activator NS1619- and SKCa activator NS309-induced relaxations of NPUAs. Chronic hypoxia during gestation significantly attenuated both NS1619- and NS309-induced relaxations of UAs, which was associated with decreases in BKCa and SKCa channel expression and their activities. Chronic hypoxia enhanced the inhibitory role of oxidative stress and PKC on KCa channel activities and their-mediated uterine arterial relaxation. In addition, chronic hypoxia ettenuated the effect of 17β-estradiol and progesterone in KCa-mediated relaxations in NPUAs. In conclusion, our results suggest an important role of KCa channels in the regulation of basal uterine vascular tone. Pregnancy-mediated decrease in uterine vascular tone is associated with an enhanced KCa channel expression and their activities, which is regulated by steroid hormones. Chronic hypoxia during gestation attenuates the effect of steroid hormone on KCa channels, resulting in decreased KCa channel-mediated relaxations and increased uterine vascular tone

MANAGEMENT OF VERSIONED MAP DATA TILES STORED ON A CLIENT DEVICE

A pre-fetching map data system and method identifies a subset of map data to corresponding to one or more points of interest to be displayed on the map. The map data is stored on a remote map database and in the form of map data tiles bearing version numbers. The pre-fetching map data system identifying those map data tiles that correspond to the subset of map data corresponding to the one or more points of interest, where the identified pre-fetch map data tiles are sent from the remote database to a client device for storing the pre-fetch map data tiles. During pre-fetching the version number of the received map data tiles is examined to determine if a version update for additional map data tiles should be scheduled and executed to update out of date map data on the client device

Synthetic multistability in mammalian cells

In multicellular organisms, gene regulatory circuits generate thousands of molecularly distinct, mitotically heritable states, through the property of multistability. Designing synthetic multistable circuits would provide insight into natural cell fate control circuit architectures and allow engineering of multicellular programs that require interactions among cells in distinct states. Here we introduce MultiFate, a naturally-inspired, synthetic circuit that supports long-term, controllable, and expandable multistability in mammalian cells. MultiFate uses engineered zinc finger transcription factors that transcriptionally self-activate as homodimers and mutually inhibit one another through heterodimerization. Using model-based design, we engineered MultiFate circuits that generate up to seven states, each stable for at least 18 days. MultiFate permits controlled state-switching and modulation of state stability through external inputs, and can be easily expanded with additional transcription factors. Together, these results provide a foundation for engineering multicellular behaviors in mammalian cells

ChIP-seq identifies McSLC35E2 as a novel target gene of McNrf2 in Mytilus coruscus, highlighting its role in the regulation of oxidative stress response in marine mollusks

NF-E2-related factor 2 (Nrf2) plays a crucial role in the oxidative regulatory process, which could trigger hundreds of antioxidant elements to confront xenobiotics. In the previous study, we identified Nrf2 from the marine mussel Mytilus coruscus, and the findings demonstrated that McNrf2 effectively protected the mussels against oxidative stress induced by benzopyrene (Bap). In order to delve deeper into the underlying mechanism, we utilized Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) technology to systematically identify potential novel target genes of McNrf2. A total of 3,465 potential target genes were screened, of which 219 owned binding sites located within the promoter region. During subsequent experimental verification, it was found that McSLC35E2, a candidate target gene of McNrf2, exhibited negative regulation by McNrf2, as confirmed through dual luciferase and qRT-PCR detection. Further, the enzyme activity tests demonstrated that McNrf2 could counteract Bap induced oxidative stress by inhibiting McSLC35E2. The current study provides valuable insights into the application of ChIP-seq technology in the research of marine mollusks, advancing our understanding of the key role of Nrf2 in antioxidant defense mechanisms, and highlighting the significance of SLC35E2 in the highly sophisticated regulation of oxidative stress response in marine invertebrates

Robust elbow angle prediction with aging soft sensors via output-level domain adaptation

Wearable devices equipped with soft sensors provide a promising solution for body movement monitoring. Specifically, body movements like elbow flexion can be captured by monitoring the stretched soft sensors’ resistance changes. However, in addition to stretching, the resistance of a soft sensor is also influenced by its aging, which makes the resistance a less stable indicator of the elbow angle. In this paper, we leverage the recent progress in Deep Learning and address the aforementioned issue by formulating the aging-invariant prediction of elbow angles as a domain adaption problem. Specifically, we define the soft sensor data (i.e., resistance values) collected at different aging levels as different domains and adapt a regression neural network among them to learn domain-invariant features. However, unlike the popular pairwise domain adaptation problem that only involves one source and one target domain, ours is more challenging as it has “infinite” target domains due to the non-stop aging. To address this challenge, we novelly propose an output-level domain adaptation approach which builds on the fact that the elbow angles are in a fixed range regardless of aging. Experimental results show that our method enables robust and accurate prediction of elbow angles with aging soft sensors, which significantly outperforms supervised learning ones that fail to generalize to aged sensor data