Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. We recently showed, in aged female rhesus monkeys, that systemic administration of MSC-EVs enhances recovery of function after injury of the primary motor cortex, likely through enhancing plasticity in perilesional motor and premotor cortices. Here, using in vitro whole-cell patch-clamp recording and intracellular filling in acute slices of ventral premotor cortex (vPMC) from rhesus monkeys (Macaca mulatta) of either sex, we demonstrate that MSC-EVs reduce injury-related physiological and morphologic changes in perilesional layer 3 pyramidal neurons. At 14-16 weeks after injury, vPMC neurons from both vehicle- and EV-treated lesioned monkeys exhibited significant hyperexcitability and predominance of inhibitory synaptic currents, compared with neurons from nonlesioned control brains. However, compared with vehicle-treated monkeys, neurons from EV-treated monkeys showed lower firing rates, greater spike frequency adaptation, and excitatory:inhibitory ratio. Further, EV treatment was associated with greater apical dendritic branching complexity, spine density, and inhibition, indicative of enhanced dendritic plasticity and filtering of signals integrated at the soma. Importantly, the degree of EV-mediated reduction of injury-related pathology in vPMC was significantly correlated with measures of behavioral recovery. These data show that EV treatment dampens injury-related hyperexcitability and restores excitatory:inhibitory balance in vPMC, thereby normalizing activity within cortical networks for motor function.

SIGNIFICANCE STATEMENT Neuronal plasticity can facilitate recovery of function after cortical injury, but the underlying mechanisms and efficacy of therapeutic interventions promoting this plasticity in primates are not well understood. Our recent work has shown that intravenous infusions of mesenchymal-derived extracellular vesicles (EVs) that are involved in cell-to-cell inflammatory and trophic signaling can enhance recovery of motor function after injury in monkey primary motor cortex. This study shows that this EV-mediated enhancement of recovery is associated with amelioration of injury-related hyperexcitability and restoration of excitatory-inhibitory balance in perilesional ventral premotor cortex. These findings demonstrate the efficacy of mesenchymal EVs as a therapeutic to reduce injury-related pathologic changes in the physiology and structure of premotor pyramidal neurons and support recovery of function.

Stress alters brain function by modifying the structure and function of neurons and astrocytes. The fine processes of astrocytes are critical for the clearance of neurotransmitters during synaptic transmission. Thus, experience-dependent remodeling of glial processes is anticipated to alter the output of neural circuits. However, the molecular mechanisms that underlie glial structural plasticity are not known. Here we show that a single exposure of male and female mice to an acute stress produced a long-lasting retraction of the lateral processes of cerebellar Bergmann glial cells. These cells express the GluA1 subunit of AMPA-type glutamate receptors, and GluA1 knockdown is known to shorten the length of glial processes. We found that stress reduced the level of GluA1 protein and AMPA receptor-mediated currents in Bergmann glial cells, and these effects were absent in mice devoid of CPEB3, a protein that binds to GluA1 mRNA and regulates GluA1 protein synthesis. Administration of a β-adrenergic receptor blocker attenuated the reduction in GluA1, and deletion of adenylate cyclase 5 prevented GluA1 suppression. Therefore, stress suppresses GluA1 protein synthesis via an adrenergic/adenylyl cyclase/CPEB3 pathway, and reduces the length of astrocyte lateral processes. Our results identify a novel mechanism for GluA1 subunit plasticity in non-neuronal cells and suggest a previously unappreciated role for AMPA receptors in stress-induced astrocytic remodeling.

SIGNIFICANCE STATEMENT Astrocytes play important roles in synaptic transmission by extending fine processes around synapses. In this study, we showed that a single exposure to an acute stress triggered a retraction of lateral/fine processes in mouse cerebellar astrocytes. These astrocytes express GluA1, a glutamate receptor subunit known to lengthen astrocyte processes. We showed that astrocytic structural changes are associated with a reduction of GluA1 protein levels. This requires activation of β-adrenergic receptors and is triggered by noradrenaline released during stress. We identified adenylyl cyclase 5, an enzyme that elevates cAMP levels, as a downstream effector and found that lowering GluA1 levels depends on CPEB3 proteins that bind to GluA1 mRNA. Therefore, stress regulates GluA1 protein synthesis via an adrenergic/adenylyl cyclase/CPEB3 pathway in astrocytes and remodels their fine processes.

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.

Angry historians say the stretch of concrete was one of the largest remaining sections of the inner wall

Currently in the works, the new monument will honor her contributions and legacy with a contemplative space

The remote cabin could be the difference between life and death for travellers stuck on the territory’s long winter road. It was built to remember Stella Barnaby, who would have been 55 this Saturday.

Baltimore Orioles outfielder and first baseman Trey Mancini revealed Tuesday he is in the midst of six months of chemotherapy as he fights Stage III colon cancer.

Derek Jeter, Larry Walker and the rest of this year's Baseball Hall of Fame class will have to wait another year for their big moment at Cooperstown.

Planned Parenthood's president says many states used the pandemic to restrict abortion access; Director Eliza Hittman on her new film about abortion, "Never Rarely Sometimes Always"; Science journalist Tanya Lewis on drugs being tested to treat COVID-19.

In a Democracy Now! exclusive, singer-songwriter Fiona Apple discusses her acclaimed new album, Fetch the Bolt Cutters; and Native American activist Eryn Wise of Seeding Sovereignty talks about land acknowledgment and COVID-19 in Indigenous communities.

President Trump lashes out at the U.S. Postal Service. His attacks could threaten voting by mail; We look at the impact of the coronavirus on schools, universities, students, parents and teachers, and who is at the table to shape what happens next.

French economist Thomas Piketty on how the economic crisis triggered by the pandemic may be a catalyst to address global inequality; longtime WHO adviser Lawrence Gostin on Trump's order barring states from closing meatpacking plants with virus outbreaks.

Workers call for a general strike on May Day; Joe Biden denies Tara Reade's sexual assault allegations. We speak with her neighbor from the 1990s who says Reade told her the story decades ago; Protesters demand more COVID-19 relief & tests in Puerto Rico.

As meat plant workers get sick and die from COVID-19, workers protest conditions, and LULAC calls for Meatless May Mondays; McConnell seeks to protect corporations from liability; Dr. Richard Levitan says patients unknowingly suffer oxygen deprivation.

As the Navajo Nation suffers the third most COVID-19 cases, we talk to the partner of a 28-year-old victim and doctors treating patients; 80 percent of prisoners at Marion prison test positive; Prof. Ruth Wilson Gilmore on the case for prison abolition.

As President Trump starts to reopen the country, Pulitzer Prize-winning science writer Laurie Garrett predicts the pandemic will last at least 36 months; Did a former Green Beret mastermind a failed coup attempt in Venezuela? Two Americans were arrested.

We get an update from Moscow on the pandemic in Russia, which has the second-highest infection rate in the world; We look at who gets access to drugs like remdesivir being developed by pharmaceutical giant Gilead, which is poised to make massive profits.

Two white men are charged with the murder of Ahmaud Arbery, more than two months after his killing; The pandemic hits African Americans hardest. We speak with NYT Magazine's Linda Villarosa; Dr. Leana Wen on what the U.S. faces as states begin to reopen.

Japan’s Yuzuru Hanyu believes he was born to figure skate, but that doesn’t mean he’s immune to pressure and expectations.

On March 29, the musical world lost a giant - Polish composer and conductor Krzysztof Penderecki. The Library of Congress Music Division remains connected to Penderecki through primary sources in our collections, and we hope that you can remain connected to him in this way, as well.

Vincent Novara, Head of the Music Division's Acquisitions & Processing Section, describes his section's new teleworking practices during a global pandemic.

The European repo market has held up well amid the initial volatility created by the economic slowdown caused by COVID-19,...

The post European Repo Demonstrates Its Resilience appeared first on OpenMarkets.

Calgary Flames general manager Brad Treliving will watch Thursday's remote NFL draft and is planning to focus on how his football counterparts deal with the realities of their world during the COVID-19 pandemic.

The battle for humanity and solidarity in the post-American world.

Paramedics who come back from COVID-19 related calls have to remove and either discard or wash their PPE. They are getting help from students called doffing assistants.

Scuffles broke out at Hong Kong's legislature Friday, with security guards ejecting several pro-democracy lawmakers, including one who was carried out by medics on a stretcher after he was injured.

As British Columbians maintain physical distancing recommendations during the COVID-19 pandemic, this year’s Easter celebrations will have to change. In Kamloops, B.C., organizations are working to make sure Easter is as fun and social as it can be. 

Just when you thought you watched the best shot of the Brier, another best shot of the Brier appears at the 2020 Canadian men's curling championship being held in Kingston, Ont.

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Bank of Spain Working Papers by Henrique S. Basso and Juan F. Jimeno

The Penn State Mont Alto campus held its annual Academic and Leadership Awards Ceremony online on Sunday, April 19. Eighty-eight students were recognized for their academic achievements and campus leadership during the 2019-20 academic year. Three faculty members and one staff member were also recognized for their above-and-beyond contributions to the learning environment at Penn State Mont Alto.

Authoritarian rule may be just around the corner.

Instead of every meeting attendee staring at a flat Zoom screen, Apple is looking to the future of video conferencing with Memoji-style avatars arranged in augmented reality around each meeting attendee.

Learn how to easily delete a face from a solid or surface body when modeling in SOLIDWORKS. Our #TechTip this week is by Training Manager John Setzer. Video Transcript Hi and welcome to another GSC tech tip. Today we’re going

Author information

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CNA Staff, Apr 30, 2020 / 02:00 pm (CNA).- As the Chinese government makes progress containing the COVID-19 pandemic, authorities have resumed action to remove crosses from buildings and crackdown on religious practice.

The latest round of enforcement actions have included the removal of crosses from buildings belonging to the state-run churches. According to a report from UCA News, priests say they are cooperating in the removal of exterior crosses in hopes that entire church buildings will not be demolished or converted into a building for secular use.  

According to a parishioner in the Chinese province of Anhui named John, Chinese officials cut down the cross from the top of Our Lady of the Rosary Church on April 18. Our Lady of the Rosary belongs to the Chinese Patriotic Catholic Association (CPCA, the Catholic Church officially sanctioned by the Chinese Communist Party and operating both in communion with Rome and under state control. 

The bishops of the CPCA, who were in many cases illicitly consecrated and under official excommunication, were received into full communion with Rome as part of the Vatican’s 2018 provisional agreement with China. The full terms of the China deal were not released to the public but have been reported to include the right of state authorities to propose and veto candidates for the episcopacy in China. 

John, speaking to UCA News, explained that on April 13, the leaders of Our Lady of the Rosary--which does not have a member of the clergy assigned to it, and all religious activities are organized by the laity--asked the city authorities about making repairs to the church building. Three days later, the community director of the city requested keys and access to the church, in order to remove its cross. 

Concerned parishioners went to Bishop Joseph Liux Xinhong of the Diocese of Anhui, who told them to request more information from the local CPCA office. The local CPCA office said they did not know of any plan to remove the cross from the building. 

Xinhong was one of the bishops who had his excommunication lifted and his position recognized by the Vatican following the 2018 provisional deal. 

On April 17, the parish community leader said that he had been given “directions from superiors” regarding removing the cross. The following day, said John, the cross was removed by a “team of young people.”

Elsewhere in the province of Anhui, on April 19 a cross was removed from a church in Suzhou City during pre-dawn hours, presumably to avoid the chance of a crowd protesting its removal. A man from the diocese named Paul told UCA News that the removal had previously been scheduled for the afternoon. 

Paul said that police officers blocked people from entering the church or taking pictures of the removal, and that a cell phone had been confiscated after it captured a picture of the cross coming down. 

In Hefei City, which is also located in the Anhui province, authorities on April 27 took a cross off a building for a Protestant church. 

A priest from the Diocese of Anhui, identified only as “Father Chen,” told UCA News that these sorts of activities are “happening all over the mainland” and are not limited to one diocese or province. 

 “If the churches don’t unite to resist, many more crosses will be removed,” he said.

In September 2017, China enacted strict new regulations concerning religion. Since then, authorities have been vigilant in enforcing permitting requirements. Churches that are not found to be in compliance are destroyed. 

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Logos Hope :: A tribute to Clive Musendami

A group of 10 students, including a translator, participate in a two months training programme in Panama. The Mission Extreme Outreach has its students work amongst Panamanians and indigenous tribes. Un grupo de 10 estudiantes,incluyendo la traductora, participan durante los dos meses de gira en Panamá. Una vez más Misión Extrema está en acción con los latinos y grupos indígenas.

IN THE winding lanes of Barcelona’s historic Barri Gòtic it’s no surprise to find a little cheese shop tucked amongst the boutiques and antique shops. What is unexpected though is that this shop, Formageria La Seu, the only one on the Iberian peninsula to feature artisanal cheese from all over Catalonia and Spain, is owned and run by a Scots woman – Katherine McLaughlin.

OM EAST’s latest publication reaches the Nenets tribe in Siberia—a place where few foreigners have ever been.

THE first cap is the sweetest. For hockey player Alan Forsyth it came on October 19, 2015: Great Britain versus Argentina at Bisham Abbey. He scored on his debut, too, teed up by fellow Scot Chris Grassick after 28 minutes.

STYLE AND SUBSTANCE

LEARNING from the hands of her grandmother in Italy, it was perhaps always going to be Giovanna Eusebi's destiny that she would go on to create culinary masterpieces of her own one day.

IT was on board a supply ship which had docked in the port of Marseille that Barney Roberts learned the news that the war was over.

DRAKE - DARK LANE DEMO TAPES

At first glance, it could seem that teenagers just really, really hate high school. But Yale researchers found deeper student engagement issues.

Mardi Gras in New Orleans has always had a gothic element. The voodoo culture dates from the African American diaspora, though it’s now mostly for tourists. But this year there was an authentically macabre dimension to Fat Tuesday.