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Rapid Release of Ca2+ from Endoplasmic Reticulum Mediated by Na+/Ca2+ Exchange

Phototransduction in Drosophila is mediated by phospholipase C (PLC) and Ca2+-permeable TRP channels, but the function of endoplasmic reticulum (ER) Ca2+ stores in this important model for Ca2+ signaling remains obscure. We therefore expressed a low affinity Ca2+ indicator (ER-GCaMP6-150) in the ER, and measured its fluorescence both in dissociated ommatidia and in vivo from intact flies of both sexes. Blue excitation light induced a rapid (tau ~0.8 s), PLC-dependent decrease in fluorescence, representing depletion of ER Ca2+ stores, followed by a slower decay, typically reaching ~50% of initial dark-adapted levels, with significant depletion occurring under natural levels of illumination. The ER stores refilled in the dark within 100–200 s. Both rapid and slow store depletion were largely unaffected in InsP3 receptor mutants, but were much reduced in trp mutants. Strikingly, rapid (but not slow) depletion of ER stores was blocked by removing external Na+ and in mutants of the Na+/Ca2+ exchanger, CalX, which we immuno-localized to ER membranes in addition to its established localization in the plasma membrane. Conversely, overexpression of calx greatly enhanced rapid depletion. These results indicate that rapid store depletion is mediated by Na+/Ca2+ exchange across the ER membrane induced by Na+ influx via the light-sensitive channels. Although too slow to be involved in channel activation, this Na+/Ca2+ exchange-dependent release explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors exposed to Ca2+-free solutions.

SIGNIFICANCE STATEMENT Phototransduction in Drosophila is mediated by phospholipase C, which activates TRP cation channels by an unknown mechanism. Despite much speculation, it is unknown whether endoplasmic reticulum (ER) Ca2+ stores play any role. We therefore engineered flies expressing a genetically encoded Ca2+ indicator in the photoreceptor ER. Although NCX Na+/Ca2+ exchangers are classically believed to operate only at the plasma membrane, we demonstrate a rapid light-induced depletion of ER Ca2+ stores mediated by Na+/Ca2+ exchange across the ER membrane. This NCX-dependent release was too slow to be involved in channel activation, but explains the decades-old observation of a light-induced rise in cytosolic Ca2+ in photoreceptors bathed in Ca2+-free solutions.




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Carbon Monoxide, a Retrograde Messenger Generated in Postsynaptic Mushroom Body Neurons, Evokes Noncanonical Dopamine Release

Dopaminergic neurons innervate extensive areas of the brain and release dopamine (DA) onto a wide range of target neurons. However, DA release is also precisely regulated. In Drosophila melanogaster brain explant preparations, DA is released specifically onto α3/α'3 compartments of mushroom body (MB) neurons that have been coincidentally activated by cholinergic and glutamatergic inputs. The mechanism for this precise release has been unclear. Here we found that coincidentally activated MB neurons generate carbon monoxide (CO), which functions as a retrograde signal evoking local DA release from presynaptic terminals. CO production depends on activity of heme oxygenase in postsynaptic MB neurons, and CO-evoked DA release requires Ca2+ efflux through ryanodine receptors in DA terminals. CO is only produced in MB areas receiving coincident activation, and removal of CO using scavengers blocks DA release. We propose that DA neurons use two distinct modes of transmission to produce global and local DA signaling.

SIGNIFICANCE STATEMENT Dopamine (DA) is needed for various higher brain functions, including memory formation. However, DA neurons form extensive synaptic connections, while memory formation requires highly specific and localized DA release. Here we identify a mechanism through which DA release from presynaptic terminals is controlled by postsynaptic activity. Postsynaptic neurons activated by cholinergic and glutamatergic inputs generate carbon monoxide, which acts as a retrograde messenger inducing presynaptic DA release. Released DA is required for memory-associated plasticity. Our work identifies a novel mechanism that restricts DA release to the specific postsynaptic sites that require DA during memory formation.




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The Frog Motor Nerve Terminal Has Very Brief Action Potentials and Three Electrical Regions Predicted to Differentially Control Transmitter Release

The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ.

SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies.




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Release of FAO's resource mobilization annual report, Resources, Partnerships, Impact – 2019


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Release of FAO + Switzerland Report

The latest FAO + Switzerland partnership report shows the catalytic achievements and innovative solutions of FAO’s collaboration with one of our strongest partners.

From 2008 to 2018, Switzerland supported FAO in [...]




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Release of 2019 Technical Cooperation Programme Report

The 2019 Report of the Technical Cooperation Programme (TCP) examines the role of the TCP to deliver FAO technical assistance for agriculture, food and nutrition in response to countries’ most [...]




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FAO releases COVID-19 Q&As to help government policymakers

As the novel coronavirus disease COVID-19 continues to spread, questions have been raised about the potential impact on food supply and availability and on livelihoods around the globe.

FAO



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Council to mull hospital lease: Scrutinizes Metlakatla power tie-in




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Official disputes EPA toxic chemical release analysis




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Smithsonian Channel Has Released 68 Free ‘Aerial America’ Episodes for Your Quarantine Viewing

Do some armchair traveling and see the breathtaking vistas of all 50 states while learning about their histories




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Stephen S Poloz: Release of the Monetary Policy Report

Opening statement by Mr Stephen S Poloz, Governor of the Bank of Canada, at the press conference following the release of the Monetary Policy Report, Ottawa, Ontario, 15 April 2020.





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Bengaluru’s all-woman music collective Metronome to release a track for Mother’s Day – Times of India

Bengaluru's all-woman music collective Metronome to release a track for Mother's Day  Times of India



  • IMC News Feed

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NFL schedule released per usual as league continues to plan for normal season

The Kansas City Chiefs will open defence of their Super Bowl championship by hosting Houston on Sept. 10 in the NFL's annual kickoff game — pending developments in the coronavirus pandemic, of course.



  • Sports/Football/NFL

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Giant, record-class walleye caught and released near Dryden, Ont.

A man from Vermilion Bay, Ont., caught and released a fish that he says could have challenged a 70-year-old record for walleye last weekend.



  • News/Canada/Thunder Bay

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Essex County OPP release sketch of man who allegedly impersonated an officer

According to OPP, a man allegedly pulled over a woman on April 23 driving on Naylor Side Road near the intersection of North Talbot Road, while "wearing clothing resembling the uniform of a police officer."



  • News/Canada/Windsor

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A Simple Method To Detect Point Mutations in Aspergillus fumigatus cyp51A Gene Using a Surveyor Nuclease Assay [Analytical Procedures]

One of the main mechanisms of azole resistance of Aspergillus fumigatus is thought to be a reduction in the drug’s affinity for the target molecule, Cyp51A, due to its amino acid mutation(s). It is known that the azole resistance pattern is closely related to the mutation site(s) of the molecule. In this study, we tried to develop a simple and rapid detection method for cyp51A mutations using the endonuclease Surveyor nuclease. The Surveyor nuclease assay was verified using several azole-resistant strains of A. fumigatus that possess point mutations in Cyp51A. For validation of the Surveyor nuclease assay, blind tests were conducted using 48 strains of A. fumigatus (17 azole-resistant and 31 azole-susceptible strains). The Surveyor nuclease assay could rapidly detect cyp51A mutations with one primer set. Also, all the tested strains harboring different cyp51A single point mutations could be clearly distinguished from the wild type. The Surveyor nuclease assay is a simple method that can detect cyp51A mutations rapidly.




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Apple releases fourth developer betas of macOS 10.15.5, watchOS 6.2.5, tvOS 13.4.5



Following the release of the fourth betas of iOS 13.5 and iPadOS 13.5, Apple has followed through with fourth betas for macOS 10.15.5, watchOS 6.2.5, and tvOS 13.4.5.



  • Mac OS X/Apple TV/Apple Watch/macOS

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Coronavirus in Scotland: Prison governors to have final say over early releases

PRISON governors have been handed the power to veto prisoners they have concerns over being released early - as plans are pushed forward for up to 450 prisoners to be freed to allow inmates to socially distance in cells.




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Opinion: Doug Marr: No extension of house arrest for the over-70s, please

IN the years BC (Before Covid), my morning routine was consistent. First, perusal of the paper, starting with the sport followed by the death notices. Continued absence from the latter represented a pretty good start to the day. Omnipresent coronavirus has reversed that order. Now, my first port of call is the ever-expanding family notices. Worryingly, for a man in his eighth decade, the deaths section lengthens daily. Equally concerning, is my proximity to the average age of those whose demise




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Teacher-Performance Scores Primed for Release in Virginia

A state court ruled that Virginia must turn over growth data by school and classroom teacher, without redacting the teachers' names.




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Off-Label Use of Inhaled Nitric Oxide After Release of NIH Consensus Statement

Off-label prescription of inhaled nitric oxide (iNO) to neonates <34 weeks’ gestation has increased during the past decade. In early 2011, the National Institutes of Health determined that the available evidence did not support iNO use in this population.

Use of iNO among neonates <34 weeks’ gestation has increased since 2011, entirely from greater use in extremely preterm neonates. Off-label prescription of this drug now accounts for nearly half of all iNO use in American NICUs. (Read the full article)




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Canon Releases Details on Flagship EOS-1D X Mark III SLR

Canon is lifting the lid on the tech inside its upcoming EOS-1D X Mark III SLR. It's a fully pro, and fully loaded camera, with 20fps Raw imaging and 5.5K Raw video capture.




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Rapid-Release Griffithsin Fibers for the Dual Prevention of HSV-2 and HIV-1 Infections [Antiviral Agents]

The biologic Griffithsin (GRFT) has recently emerged as a candidate to safely prevent sexually transmitted infections (STIs) including human immunodeficiency virus (HIV-1) and herpes simplex virus 2 (HSV-2). However, to date, there are few delivery platforms that are available to effectively deliver biologics to the female reproductive tract (FRT). The goal of this work was to evaluate rapid-release polyethylene oxide (PEO), polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) fibers, that incorporate GRFT, in in vitro (HIV-1 and HSV-2) and in vivo (HSV-2) infection models. GRFT loading was determined via ELISA, and the bioactivity of GRFT fibers was assessed using in vitro HIV-1 pseudovirus and HSV-2 plaque assays. Afterwards, the efficacy of GRFT fibers was assessed in a murine model of lethal HSV-2 infection. Finally, murine reproductive tracts and vaginal lavages were evaluated for histology and cytokine expression, 24 and 72 hr after fiber administration, to determine safety. All rapid-release formulations achieved high levels of GRFT incorporation and were completely efficacious against in vitro HIV-1 and HSV-2 infections. Importantly, all rapid-release GRFT fibers provided potent protection in a murine model of HSV-2 infection. Moreover, histology and cytokine levels, evaluated from collected murine reproductive tissues and vaginal lavages treated with blank fibers, showed no increased cytokine production or histological aberrations, demonstrating the preliminary safety of rapid-release GRFT fibers in vaginal tissue.




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Instructions released for Alternative Grade Calculator and Request Tool

Instructions for using the new Alternative Grade Calculator and Request Tool in LionPATH are now available for undergraduates and students enrolled in the Graduate School.




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Holocaust Education Initiative releases first set of free instructional material

To help teachers remotely engage their students during the coronavirus crisis, Penn State’s Holocaust, Genocide and Human Rights Education Initiative has released its first set of free learning resources.




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Crisis Group Releases Landmark Report on al-Qaeda and the Islamic State




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UEFA pleased with CAS decision on Málaga CF




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Aid workers kidnapped in Iraq released

CNA Staff, Mar 27, 2020 / 11:19 am (CNA).- Four men working in Iraq for the French humanitarian organization SOS Chrétiens d'Orient who went missing in Baghdad in January have been released by their kidnappers, the French president announced Thursday.

Emmanuel Macron announced March 26 that he “welcomes the release of our three nationals Antoine Brochon, Julien Dittmar, Alexandre Goodarzy and Iraqi Tariq Mattoka.”

The men disappeared Jan. 20 after they made a trip to an appointment by car. SOS Chrétiens d'Orient tried to contact them the following day, unsuccessfully.

The missing employees had gone to Baghdad “to renew their visas and the registration of association with the Iraqi authorities and to monitor the association's operations” in the country.

Macron's office said it had made “every effort” to secure their release, and he expressed “gratitude to the Iraqi authorities for their co-operation.”

SOS Chrétiens d'Orient said last week that they had received no ransom demand, and no group had claimed responsibility for the abduction.

The organization works to support Eastern Christians with humanitarian material aid; it has permanent missions in Syria, Iraq, Lebanon, and Egypt.

Christians in Iraq have suffered persecution in recent years, especially during the invasion of the Islamic State.

Prior to the United States invasion of Iraq in 2003, there were about 1.5 million Iraqi Christians. Today, that number is believed to be fewer than 500,000.



  • Middle East - Africa



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Delaware State Housing Authority Releases Delaware Housing Needs Assessment 2015-2020

Governor Jack Markell today joined Delaware State Housing Authority (DSHA) for the release of the Delaware Housing Needs Assessment 2015-2020. The report, prepared by GCR Incorporated of New Orleans, Louisiana and The Reinvestment Fund (TRF) of Philadelphia, Pennsylvania, will drive planning for housing resources at DSHA and in communities around the State. With this new analysis of housing needs and market conditions in the state for years 2015-2020, DSHA will be identifying priorities for the next five years and evaluating its programs and strategies.




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Overdose Review Commission releases annual report

Recommendations include expanded residential treatment, public education, and naloxone access The Delaware Drug Overdose Fatality Review Commission (DOFRC) has released its first annual report to Governor John Carney and the General Assembly with recommendations aimed at reducing overdose deaths in Delaware based on review of the circumstances of deaths over the past year. The 23-page […]



  • Department of Justice
  • Department of Justice Press Releases
  • News

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Visit Delaware Releases New Mobile Application for National American Beer Day

Newport, Del.– Discovering Delaware went digital to celebrate National American Beer Day as the Delaware Tourism Office (Visit Delaware) unveiled Delaware on Tap, the new smartphone application version of the state’s popular Beer, Wine & Spirits Trail. The office showcased the app, which is available for free download in the App Store and from Google […]




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Delaware releases historic preservation plan for 2018–2022

Working to preserve Delaware’s heritage for the future, the plan outlines six broad goals for the next five years.




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Tesla's Musk Delays Release Of Roadster Sports Car, Repeats Coronavirus Lockdown Criticism

Tesla Inc Chief Executive Elon Musk said in a podcast interview released on Thursday that the company's planned Roadster sports car would take a backseat to the development of other vehicle models.




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Nikon releases the DX-format Nikon Z 50




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NIKKOR-The Thousand and One Nights (Tale 72)has been released




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Nikon releases the 83x optical zoom COOLPIX P950 compact digital camera




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Nikon releases the NIKKOR Z 70-200mm f/2.8 VR S, a fast telephoto zoom lens for the Nikon Z mount system




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Nikon releases the AF-S NIKKOR 120-300mm f/2.8E FL ED SR VR, a fast telephoto zoom lens compatible with the Nikon FX format




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Nikon releases the D780 digital SLR camera




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Nikon releases the fast, ultra-wide-angle prime NIKKOR Z 20mm f/1.8 S, and the high-power zoom NIKKOR Z 24-200mm f/4-6.3 VR




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Nikon releases the D6 digital SLR camera




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Imaging Products:NIKKOR-The Thousand and One Nights (Tale 73)has been released




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Amazon Prime Announces Third Season Of 'Four More Shots Please!'

"The first season was one of the top 3 most-watched Amazon Original Series from India in 2019," said Aparna Purohit, Head of Amazon Originals




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Delaware Office of State Planning Coordination Announces Release of 2015 Strategies for State Policies and Spending

The Delaware Office of State Planning Coordination announces the release of the draft 2015 Strategies for State Policies and Spending Update.




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Delaware State Government Diversity and Inclusion Study Released

Dover, DE – The Office of Management and Budget today released a report commissioned by Governor Jack Markell earlier this year in an ongoing effort to build a welcoming work environment across State government that fully embraces diversity and equal opportunity for all employees. “I have been clear that my administration is committed to ensuring […]



  • Former Governor Jack Markell (2009-2017)
  • Office of Management and Budget
  • Office of the Governor

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Governor Carney Releases Statewide Anti-discrimination Policy

Policy will allow state to consistently address discrimination in the workplace WILMINGTON, Del. – Governor Carney on Monday released a uniform, anti-discrimination policy that will allow state agencies to consistently respond to reports of discrimination, harassment and retaliation in the workplace – and clearly outlines a consistent policy for state employees to report and resolve […]




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Governor Carney Releases Second Annual Report of Government Efficiency and Accountability Review (GEAR) Board

Board presents recommendations across focus areas to improve efficiency and accountability in state government WILMINGTON, Del. – Governor John Carney on Thursday released the second annual report of the Government Efficiency and Accountability Review (GEAR) Board. Governor Carney established GEAR by Executive Order in February 2017 to identify ways for state government to operate more […]