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Microglial cells are considered as sensors of brain pathology by detecting any sign of brain lesions, infections, or dysfunction and can influence the onset and progression of neurological diseases. They are capable of sensing their neuronal environment via many different signaling molecules, such as neurotransmitters, neurohormones and neuropeptides. The neuropeptide VGF has been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide and has been shown to signal via C3aR1 and C1qBP receptors. The effect of TLQP21 on microglial functions in health or disease is not known. Studying microglial cells in acute brain slices, we found that TLQP21 impaired metabotropic purinergic signaling. Specifically, it attenuated the ATP-induced activation of a K⁺ conductance, the UDP-stimulated phagocytic activity, and the ATP-dependent laser lesion-induced process outgrowth. These impairments were reversed by blocking C1qBP, but not C3aR1 receptors. While microglia in brain slices from male mice lack C3aR1 receptors, both receptors are expressed in primary cultured microglia. In addition to the negative impact on purinergic signaling, we found stimulating effects of TLQP21 in cultured microglia, which were mediated by C3aR1 receptors: it directly evoked membrane currents, stimulated basal phagocytic activity, evoked intracellular Ca²⁺ transient elevations, and served as a chemotactic signal. We conclude that TLQP21 has differential effects on microglia depending on C3aR1 activation or C1qBP-dependent attenuation of purinergic signaling. Thus, TLQP21 can modulate the functional phenotype of microglia, which may have an impact on their function in health and disease.

SIGNIFICANCE STATEMENT The neuropeptide VGF and its peptides have been associated with many metabolic and neurological disorders. TLQP21 is a VGF-derived peptide that activates C1qBP receptors, which are expressed by microglia. We show here, for the first time, that TLQP21 impairs P2Y-mediated purinergic signaling and related functions. These include modulation of phagocytic activity and responses to injury. As purinergic signaling is central for microglial actions in the brain, this TLQP21-mediated mechanism might regulate microglial activity in health and disease. We furthermore show that, in addition to C1qBP, functional C3aR1 responses contribute to TLQP21 action on microglia. However, C3aR1 responses were only present in primary cultures but not in situ, suggesting that the expression of these receptors might vary between different microglial activation states.

Theoretical models and experimental evidence have suggested that connections from the dentate gyrus (DG) to CA3 play important roles in representing orthogonal information (i.e., pattern separation) in the hippocampus. However, the effects of eliminating the DG on neural firing patterns in the CA3 have rarely been tested in a goal-directed memory task that requires both the DG and CA3. In this study, selective lesions in the DG were made using colchicine in male Long–Evans rats, and single units from the CA3 were recorded as the rats performed visual scene memory tasks. The original scenes used in training were altered during testing by blurring to varying degrees or by using visual masks, resulting in maximal recruitment of the DG–CA3 circuits. Compared with controls, the performance of rats with DG lesions was particularly impaired when blurred scenes were used in the task. In addition, the firing rate modulation associated with visual scenes in these rats was significantly reduced in the single units recorded from the CA3 when ambiguous scenes were presented, largely because DG-deprived CA3 cells did not show stepwise, categorical rate changes across varying degrees of scene ambiguity compared with controls. These findings suggest that the DG plays key roles not only during the acquisition of scene memories but also during retrieval when modified visual scenes are processed in conjunction with the CA3 by making the CA3 network respond orthogonally to ambiguous scenes.

SIGNIFICANCE STATEMENT Despite the behavioral evidence supporting the role of the dentate gyrus in pattern separation in the hippocampus, the underlying neural mechanisms are largely unknown. By recording single units from the CA3 in DG-lesioned rats performing a visual scene memory task, we report that the scene-related modulation of neural firing was significantly reduced in the DG-lesion rats compared with controls, especially when the original scene stimuli were ambiguously altered. Our findings suggest that the dentate gyrus plays an essential role during memory retrieval and performs a critical computation to make categorical rate modulation occur in the CA3 between different scenes, especially when ambiguity is present in the environment.

As part of a balanced diet, milk and dairy products can be an important source of dietary energy, protein and fat. But, the scientific evidence is massing up that regular consumption of large quantities of milk can be bad for your health, and campaigners are making noise about the environmental and international costs of large-scale intensive dairy farming. We put together [...]

Buy fresh and seasonal produce at the Farmers’ Market on
Wednesday 26 February from 12.00 – 16.00 hours, and be sure to visit the [...]

Armchair travelers can also enjoy 360-degree views of the city's famed Northern Lights

Research linking air pollution to elevated death rates remains preliminary but scientists hope the pandemic spurs tighter air quality regulations

Catch the musical event, featuring Sting, Death Cab for Cutie front man Ben Gibbard and other artists, on YouTube tonight at 8 p.m. Eastern time

The government of the Northwest Territories is releasing $8.7 million in federal funding to five airlines in the N.W.T. offering schedule-based passenger service.

A 40-year-old man has been arrested and charged in connection with two break-ins at the Thunder Bay District Health unit offices, the Thunder Bay Police Service announced in a written release Friday.

The vessel, formerly known as the Edmonton Queen, got skewered by its own moorings last month as the icy North Saskatchewan River began to thaw.

A new book explores the evolution of cartography throughout more than a century of commercial air travel

The Winnipeg Airports Authority delayed a vote at Winnipeg's city council after it sent a request to move a dispute on development at Polo Park to the provincial municipal board, saying it was doing so "in the name of the government of Canada." But the government of Canada say the WAA can't speak on its behalf.

Michigan officials are ordering a Flint hospital to take steps to reduce the risk of exposure to Legionella bacteria and Legionnaires' disease at the facility.

Nearly 5 ½ years ago, the water source for the city of Flint was switched in an effort to save money. A disaster followed resulting in deaths, illness and mistrust of government. Tuesday at 10:00 p.m. on WKAR-TV, the documentary series Frontlin e examines the crisis by bringing to light conversations and documents never seen on television before. We spoke with Abby Ellis, the Michigan native who is the film’s director.

Ottawa police have arrested a 15-year-old boy in connection with January's shooting. He's charged with first-degree murder and attempted murder.

Canadians Kirsten Moore-Towers and Michael Marinaro won the bronze medal in pairs on Saturday at the ISU Four Continents figure skating competition in Seoul, South Korea.

'Creative Music Making' Documentary to Air on Nine Network - MPress  Maryville University News

In isolation with dog Charlie, Canadian soccer legend Christine Sinclair recalls "dream come true" of 2012 Olympic bronze and "heartbreak" of repeat in Rio in an interview with CBC Sports.

More than 1,000 people looking for work in the tech industry are signed up for a virtual job fair on Thursday afternoon.

The media is allowing disinformation to appear as news.

A B.C. couple who shaved their eyebrows off in the spirit of forcing themselves to stay at home has tackled another isolation challenge — home haircuts. 

The post Steampunk 1577 Changes Lives with Electric Wheelchair Kit Designed in SOLIDWORKS appeared first on SOLIDWORKS Education Blog.

Introductory remarks (by videoconference) by Mr Luis de Guindos, Vice-President of the European Central Bank, to the Committee on Economic and Monetary Affairs of the European Parliament, Frankfurt am Main, 7 May 2020.

B&H Photo has just issued an exclusive discount on Apple's MacBook Air (2019), dropping the price down to a record low $849 with free expedited shipping for AppleInsider readers. Inventory is limited, and this deal may sell out at any time.

When you're having connection problems, or if you find that they are not charging correctly, you may need to reset your AirPods or AirPods Pro. Here's how to get it done.

Apple is shifting a substantial portion of its current AirPods production from China to Vietnam, and appears to be considering a release schedule later than previously predicted for an AirPods refresh.

Before Monday's 13-inch MacBook Pro update, the choice between the 2019 model and the 2020 MacBook Air was very clear. It is less clear today -- but we can help.

Apple's next release in the AirPods family could be its long-rumored over-ear headphones, a leaker claims, with the larger personal audio accessory tipped to have the name "AirPods Studio."

The success of Apple's AirPods line did better than the company "could ever imagine," Apple VP of product marketing Greg Joswiak claims in a profile on the audio accessories' popularity, one that also reveals extensive resources have been put into mapping ears.

In SOLIDWORKS Electrical, we have the capability to create symbols with defined circuits on the fly, or for use with connectors that entail many, many pins. These are traditionally called Black Boxes. See figure 1 & 2.    Figure 1

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The post BLACK BOXES: Not Just For Locating Downed Aircrafts appeared first on SOLIDWORKS Tech Blog.

A weekend camp provides young believers a chance to relax and rededicate themselves to the Lord.

A Muslim man believes Jesus is the Son of God.

Veracruz, Mexico :: Visitors to Logos Hope are delighted to learn they have longer to visit the ship than originally scheduled.

An outreach team learns the value of sharing their personal testimonies and what a little light can do to a community.

A team of dentists and volunteers recently visited an orphanage in the Odessa province to fix 75 young smiles.

OM Panama team members share on a live radio talk show about the upcoming International Intensive School of Missions.

Ryanair has said it expects up to 3,000 jobs to be lost as part of a restructuring of the airline.

SUCCESS in athletics can often be a family affair. Scots such as Callum Hawkins and Eilish McColgan have thrived under the tutelage of their parents, while track star Jake Wightman is another who has preferred to turn to his family to coach him to success on the track.

As expected, the number of passengers at Berlin airports fell in January. Tegel and Schönefeld dealt with a total of 2,252,265 passengers, 6.9% fewer than in the same month last year.

When Berlin Brandenburg Airport is put into operation at the end of October 2020, Schönefeld Airport will become Terminal 5 (T5) of BER. In order to avoid duplicate names of terminal sections, gates and car parks at BER, the building and car park infras...

The expected consolidation in the aviation market has also arrived in Berlin. At the same time, the worldwide spread of the coronavirus is having an impact on the Berlin airports.

Within just a few weeks, the corona crisis has led to a collapse of over 90 percent of flight operations in the capital region. In light of this dramatic situation, the Flughafen Berlin Brandenburg GmbH (FBB) Executive Board concluded a works agreement ...

27,593 passengers departed from and landed at Berlin's airports Schönefeld and Tegel in April. That is just 1 per cent of air traffic in comparison to April 2019. 22,079 passengers flew from Tegel, and 5,541 from Schönefeld.

WHEN we eventually emerge from lockdown the first thing most people will want to do is hug their nearest and dearest, but for some they will be running to their hair stylist to sort out the unruly mass of top of their head.