A novel auxiliary subunit critical to BK channel function in caenorhabditis elegans

The BK channel is a Ca(2+)- and voltage-gated potassium channel with many important physiological functions. To identify proteins important to its function in vivo, we screened for C. elegans mutants that suppressed a lethargic phenotype caused by expressing a gain-of-function (gf) isoform of the BK channel α-subunit SLO-1. BKIP-1, a small peptide with no significant homology to any previously characterized molecules was thus identified. BKIP-1 and SLO-1 showed similar expression and subcellular localization patterns, and appeared to interact physically through discrete domains. bkip-1 loss-of-function (lf) mutants phenocopied slo-1(lf) mutants in behavior and synaptic transmission, and suppressed the lethargy, egg-laying defect, and deficient neurotransmitter release caused by SLO-1(gf). In heterologous expression systems, BKIP-1 decreased the activation rate and shifted the conductance-voltage (G-V) relationship of SLO-1 in a Ca(2+)-dependent manner, and increased SLO-1 surface expression. Thus, BKIP-1 is a novel auxiliary subunit critical to SLO-1 function in vivo

Benzoate Catabolite Repression of the Phenol Degradation in Acinetobacter calcoaceticus PHEA-2

Acinetobacter calcoaceticus PHEA-2 exhibited a delayed utilization of phenol in the presence of benzoate. Benzoate supplementation completely inhibited phenol degradation in a benzoate 1,2-dioxygenase knockout mutant. The mphR encoding the transcriptional activator and mphN encoding the largest subunit of multi-component phenol hydroxylase in the benA mutant were significantly downregulated (about 7- and 70-fold) on the basis of mRNA levels when benzoate was added to the medium. The co-transformant assay of E. coli JM109 with mphK::lacZ fusion and the plasmid pETR carrying mphR gene showed that MphR did not activate the mph promoter in the presence of benzoate. These results suggest that catabolite repression of phenol degradation by benzoate in A. calcoaceticus PHEA-2 is mediated by the inhibition of the activator protein MphR

Stomatin Inhibits Pannexin-1-Mediated Whole-Cell Currents by Interacting with Its Carboxyl Terminal

The pannexin-1 (Panx1) channel (often referred to as the Panx1 hemichannel) is a large-conductance channel in the plasma membrane of many mammalian cells. While opening of the channel is potentially detrimental to the cell, little is known about how it is regulated under physiological conditions. Here we show that stomatin inhibited Panx1 channel activity. In transfected HEK-293 cells, stomatin reduced Panx1-mediated whole-cell currents without altering either the total or membrane surface Panx1 protein expression. Stomatin coimmunoprecipitated with full-length Panx1 as well as a Panx1 fragment containing the fourth membrane-spanning domain and the cytosolic carboxyl terminal. The inhibitory effect of stomatin on Panx1-mediated whole-cell currents was abolished by truncating Panx1 at a site in the cytosolic carboxyl terminal. In primary culture of mouse astrocytes, inhibition of endogenous stomatin expression by small interfering RNA enhanced Panx1-mediated outward whole-cell currents. These observations suggest that stomatin may play important roles in astrocytes and other cells by interacting with Panx1 carboxyl terminal to limit channel opening

Sirtuin 1 and Autophagy Attenuate Cisplatin-Induced Hair Cell Death in the Mouse Cochlea and Zebrafish Lateral Line

Cisplatin-induced ototoxicity is one of the major adverse effects in cisplatin chemotherapy, and hearing protective approaches are unavailable in clinical practice. Recent work unveiled a critical role of autophagy in cell survival in various types of hearing loss. Since the excessive activation of autophagy can contribute to apoptotic cell death, whether the activation of autophagy increases or decreases the rate of cell death in CDDP ototoxicity is still being debated. In this study, we showed that CDDP induced activation of autophagy in the auditory cell HEI-OC1 at the early stage. We then used rapamycin, an autophagy activator, to increase the autophagy activity, and found that the cell death significantly decreased after CDDP injury. In contrast, treatment with the autophagy inhibitor 3-methyladenine (3-MA) significantly increased cell death. In accordance with in vitro results, rapamycin alleviated CDDP-induced death of hair cells in zebrafish lateral line and cochlear hair cells in mice. Notably, we found that CDDP-induced increase of Sirtuin 1 (SIRT1) in the HEI-OC1 cells modulated the autophagy function. The specific SIRT1 activator SRT1720 could successfully protect against CDDP-induced cell loss in HEI-OC1 cells, zebrafish lateral line, and mice cochlea. These findings suggest that SIRT1 and autophagy activation can be suggested as potential therapeutic strategies for the treatment of CDDP-induced ototoxicity

Genome Sequence and Transcriptome Analysis of the Radioresistant Bacterium Deinococcus gobiensis: Insights into the Extreme Environmental Adaptations

The desert is an excellent model for studying evolution under extreme environments. We present here the complete genome and ultraviolet (UV) radiation-induced transcriptome of Deinococcus gobiensis I-0, which was isolated from the cold Gobi desert and shows higher tolerance to gamma radiation and UV light than all other known microorganisms. Nearly half of the genes in the genome encode proteins of unknown function, suggesting that the extreme resistance phenotype may be attributed to unknown genes and pathways. D. gobiensis also contains a surprisingly large number of horizontally acquired genes and predicted mobile elements of different classes, which is indicative of adaptation to extreme environments through genomic plasticity. High-resolution RNA-Seq transcriptome analyses indicated that 30 regulatory proteins, including several well-known regulators and uncharacterized protein kinases, and 13 noncoding RNAs were induced immediately after UV irradiation. Particularly interesting is the UV irradiation induction of the phrB and recB genes involved in photoreactivation and recombinational repair, respectively. These proteins likely include key players in the immediate global transcriptional response to UV irradiation. Our results help to explain the exceptional ability of D. gobiensis to withstand environmental extremes of the Gobi desert, and highlight the metabolic features of this organism that have biotechnological potential

Regulation of pannexin1 channels by stomatin

The pannexin-1 (Panx1) channel is a large-conductance channel in the plasma membrane of many mammalian cells. Unregulated opening of the channel is detrimental to the cell. However, little is known about how the channel is kept mostly closed under physiological conditions. In this study, I analyzed the effect of stomatin on Panx1 channels in both HEK-293 cells transfected with stomatin and Panx1, and cultured astrocytes and hippocampal neurons. In transfected HEK-293 cells, stomatin inhibited Panx1-mediated whole-cell currents without altering either the total or the membrane surface Panx1 protein expression; stomatin coimmunoprecipitated with full-length Panx1 as well as a Panx1 fragment containing the fourth membrane-spanning domain and the cytosolic carboxyl terminal; and the inhibitory effect of stomatin on Panx1-mediated whole-cell currents was abolished by truncating Panx1 at a site in the cytosolic carboxyl terminal. In cultured astrocytes, inhibition of endogenous stomatin expression by small interfering RNA (siRNA) increased whole-cell membrane current that was sensitive to the specific Panx1 channel blocker 10 Panx1. Stomatin siRNA also increased apoptosis of both astrocytes and hippocampal neuron although this effect was independent of Panx1 channels. These observations establish stomatin as a novel regulator of Panx1 channels, and suggest that stomatin plays an important role in cellular functions by regulating Panx1 channels and, possibly, other channels.

Epithelioid angiosarcoma in pleural fluid: Cytological features and literature review

Epithelioid angiosarcoma is a rare vascular neoplasm with an aggressive clinical course and poor prognosis. The cytological diagnosis of epithelioid angiosarcoma is challenging. Herein, we describe the cytological features of epithelioid angiosarcoma in a pleural fluid as the initial presentation of angiosarcoma in a 52-year-old patient 3 years after mastectomy and radiation therapy for invasive lobular carcinoma of the breast. We describe the cytological characteristics of epithelioid angiosarcoma in body fluid specimens and the differential diagnosis. Keywords: Epithelioid angiosarcoma, Post-radiation angiosarcoma, Body flui

The Roles of CDPKs as a Convergence Point of Different Signaling Pathways in Maize Adaptation to Abiotic Stress

The calcium ion (Ca2+), as a well-known second messenger, plays an important role in multiple processes of growth, development, and stress adaptation in plants. As central Ca2+ sensor proteins and a multifunctional kinase family, calcium-dependent protein kinases (CDPKs) are widely present in plants. In maize, the signal transduction processes involved in ZmCDPKs’ responses to abiotic stresses have also been well elucidated. In addition to Ca2+ signaling, maize ZmCDPKs are also regulated by a variety of abiotic stresses, and they transmit signals to downstream target molecules, such as transport proteins, transcription factors, molecular chaperones, and other protein kinases, through protein interaction or phosphorylation, etc., thus changing their activity, triggering a series of cascade reactions, and being involved in hormone and reactive oxygen signaling regulation. As such, ZmCDPKs play an indispensable role in regulating maize growth, development, and stress responses. In this review, we summarize the roles of ZmCDPKs as a convergence point of different signaling pathways in regulating maize response to abiotic stress, which will promote an understanding of the molecular mechanisms of ZmCDPKs in maize tolerance to abiotic stress and open new opportunities for agricultural applications

The Roles of CDPKs as a Convergence Point of Different Signaling Pathways in Maize Adaptation to Abiotic Stress

The calcium ion (Ca2+), as a well-known second messenger, plays an important role in multiple processes of growth, development, and stress adaptation in plants. As central Ca2+ sensor proteins and a multifunctional kinase family, calcium-dependent protein kinases (CDPKs) are widely present in plants. In maize, the signal transduction processes involved in ZmCDPKs’ responses to abiotic stresses have also been well elucidated. In addition to Ca2+ signaling, maize ZmCDPKs are also regulated by a variety of abiotic stresses, and they transmit signals to downstream target molecules, such as transport proteins, transcription factors, molecular chaperones, and other protein kinases, through protein interaction or phosphorylation, etc., thus changing their activity, triggering a series of cascade reactions, and being involved in hormone and reactive oxygen signaling regulation. As such, ZmCDPKs play an indispensable role in regulating maize growth, development, and stress responses. In this review, we summarize the roles of ZmCDPKs as a convergence point of different signaling pathways in regulating maize response to abiotic stress, which will promote an understanding of the molecular mechanisms of ZmCDPKs in maize tolerance to abiotic stress and open new opportunities for agricultural applications