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Sadaghiani, A.,Lee, S.,Odegaard, Justin I.,Leveson-Gower, Dennis B.,McPherson, Olivia M.,Novick, P.,Kim, M.,Koehler, Angela N.,Negrin, R.,Dolmetsch, Ricardo E.,Park, C. Current Biology Ltd ; Elsevier Science Ltd 2014 Chemistry & biology Vol.21 No.10
Store-operated calcium (SOC) channels are vital for activation of the immune cells, and mutations in the channel result in severe combined immunodeficiency in human patients. In lymphocytes, SOC entry is mediated by the Orai1 channel, which is activated by direct binding of STIM1. Here we describe an alternative approach for identifying inhibitors of SOC entry using minimal functional domains of STIM1 and Orai1 to screen a small-molecule microarray. This screen identified AnCoA4, which inhibits SOC entry at submicromolar concentrations and blocks T cell activation in vitro and in vivo. Biophysical studies revealed that AnCoA4 binds to the C terminus of Orai1, directly inhibiting calcium influx through the channel and also reducing binding of STIM1. AnCoA4, unlike other reported SOC inhibitors, is a molecule with a known binding site and mechanism of action. These studies also provide proof of principle for an approach to ion channel drug discovery.
Rana, Anshul,Yen, Michelle,Sadaghiani, Amir Masoud,Malmersjö,, Seth,Park, Chan Young,Dolmetsch, Ricardo E.,Lewis, Richard S. The Rockefeller University Press 2015 The Journal of cell biology Vol.209 No.5
<P>Store-operated calcium entry (SOCE) regulates a wide variety of essential cellular functions. SOCE is mediated by STIM1 and STIM2, which sense depletion of ER Ca<SUP>2+</SUP> stores and activate Orai channels in the plasma membrane. Although the amplitude and dynamics of SOCE are considered important determinants of Ca<SUP>2+</SUP>-dependent responses, the underlying modulatory mechanisms are unclear. In this paper, we identify STIM2β, a highly conserved alternatively spliced isoform of STIM2, which, in contrast to all known STIM isoforms, is a potent inhibitor of SOCE. Although STIM2β does not by itself strongly bind Orai1, it is recruited to Orai1 channels by forming heterodimers with other STIM isoforms. Analysis of STIM2β mutants and Orai1-STIM2β chimeras suggested that it actively inhibits SOCE through a sequence-specific allosteric interaction with Orai1. Our results reveal a previously unrecognized functional flexibility in the STIM protein family by which alternative splicing creates negative and positive regulators of SOCE to shape the amplitude and dynamics of Ca<SUP>2+</SUP> signals.</P>
Javad Aliakbarlu,Surur Khalili Sadaghiani,Shadieh Mohammadi 한국식품과학회 2013 Food Science and Biotechnology Vol.22 No.6
The antioxidant potency, anti food bornebacterial activity, and total phenolic contents of essentialoils (EOs) from avishane shirazi (Zataria multiflora), clove(Syzgium aromaticum), cinnamon (Cinnamomum zeylanicum),cumin (Cuminum cyminum), black cumin (Buniumpersicum), spearmint (Mentha spicata), horsemint (Menthalongifolia), coriander (Coriandrum sativum), sage (Salviaofficinalis), and ginger (Zingiber officinale) were evaluated. In 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, free radicalscavenging activities of clove and avishane shirazi EOswere 90.69% and 88.63%, respectively. In reducing powerassay, the EO of clove showed the highest reducingcapacity. The highest concentrations of total phenolics(66.01 mg and 44.81 mg GAE/gram sample) were alsodetected for the EOs of clove and avishane shirazi,respectively. The results of disc diffusion assay showedthat the EOs of avishane shirazi, cinnamon, and clovestrongly inhibited growth of the tested bacteria. The EO ofcinnamon had the lowest minimal inhibitory concentration(MIC) (0.312 mg/mL).
Morteza Ghorbani,Abdolali Khalili Sadaghiani,Mehmet Yidiz,Ali Koşar 대한기계학회 2017 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.31 No.1
In this study, the effect of upstream pressure on cavitation flows inside a microchannel with an inner diameter of 152 µm and resulting spray structure were experimentally and numerically investigated. The effects of bubble number density on two-phase flow hydrodynamics were studied using the numerical approach, where transient model was utilized to obtain the changes in vapor quality inside the microchannel and velocity field near the inlet and outlet of the nozzle. Spray visualization was carried out at a distance of 4.5 mm from the tip of the microchannel using the high speed visualization system. The experimental results showed that the spray cone angle increased with upstream pressure, and beyond the upstream pressure of 50 bar, the liquid jet flow changed to the cloudy spray flow. The bubble collapse was recorded at upstream pressures of 100 and 120 bar, where the cavitation bubbles extended to the outlet of the microchannel, and their collapse took place around the spray.
Magnetic Resonance Imaging Features of Adenosis in the Breast
Masoumeh Gity,Ali Arabkheradmand,Elham Taheri,Madjid Shakiba,Yassaman Khademi,Bijan Bijan,Mohammad Salehi Sadaghiani,Amir Hossein Jalali 한국유방암학회 2015 Journal of breast cancer Vol.18 No.2
Purpose: Adenosis lesions of the breast, including sclerosing adenosis and adenosis tumors, are a group of benign proliferative disorders that may mimic the features of malignancy on imaging. In this study, we aim to describe the features of breast adenosis lesions with suspicious or borderline findings on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods: In our database, we identified 49 pathologically proven breast adenosis lesions for which the final assessment of the breast MRI report was classified as either category 4 (n=45) or category 5 (n=4), according to the Breast Imaging Reporting and Data System (BI-RADS) published by the American College of Radiology (ACR). The lesions had a final diagnosis of either pure adenosis (n=33, 67.3%) or mixed adenosis associated with other benign pathologies (n=16, 32.7%). Results: Of the 49 adenosis lesions detected on DCE-MRI, 32 (65.3%) appeared as enhancing masses, 16 (32.7%) as nonmass enhancements, and one (2.1%) as a tiny enhancing focus. Analysis of the enhancing masses based on the ACR BI-RADS lexicon revealed that among the mass descriptors, the most common features were irregular shape in 12 (37.5%), noncircumscribed margin in 20 (62.5%), heterogeneous internal pattern in 16 (50.0%), rapid initial enhancement in 32 (100.0%), and wash-out delayed enhancement pattern in 21 (65.6%). Of the 16 nonmass enhancing lesions, the most common descriptors included focal distribution in seven (43.8%), segmental distribution in six (37.5%), clumped internal pattern in nine (56.3%), rapid initial enhancement in 16 (100.0%), and wash-out delayed enhancement pattern in eight (50%). Conclusion: Adenosis lesions of the breast may appear suspicious on breast MRI. Awareness of these suspicious- appearing features would be helpful in obviating unnecessary breast biopsies.