The transcription factor Nurr1 has been identified to be ectopically induced in the striatum of rodents expressing l-DOPA-induced dyskinesia (LID). In the present study, we sought to characterize Nurr1 as a causative factor in LID expression. We used rAAV2/5 to overexpress Nurr1 or GFP in the parkinsonian striatum of LID-resistant Lewis or LID-prone Fischer-344 (F344) male rats. In a second cohort, rats received the Nurr1 agonist amodiaquine (AQ) together with l-DOPA or ropinirole. All rats received a chronic DA agonist and were evaluated for LID severity. Finally, we performed single-unit recordings and dendritic spine analyses on striatal medium spiny neurons (MSNs) in drug-naïve rAAV-injected male parkinsonian rats. rAAV-GFP injected LID-resistant hemi-parkinsonian Lewis rats displayed mild LID and no induction of striatal Nurr1 despite receiving a high dose of l-DOPA. However, Lewis rats overexpressing Nurr1 developed severe LID. Nurr1 agonism with AQ exacerbated LID in F344 rats. We additionally determined that in l-DOPA-naïve rats striatal rAAV-Nurr1 overexpression (1) increased cortically-evoked firing in a subpopulation of identified striatonigral MSNs, and (2) altered spine density and thin-spine morphology on striatal MSNs; both phenomena mimicking changes seen in dyskinetic rats. Finally, we provide postmortem evidence of Nurr1 expression in striatal neurons of l-DOPA-treated PD patients. Our data demonstrate that ectopic induction of striatal Nurr1 is capable of inducing LID behavior and associated neuropathology, even in resistant subjects. These data support a direct role of Nurr1 in aberrant neuronal plasticity and LID induction, providing a potential novel target for therapeutic development.

SIGNIFICANCE STATEMENT The transcription factor Nurr1 is ectopically induced in striatal neurons of rats exhibiting levodopa-induced dyskinesia [LID; a side-effect to dopamine replacement strategies in Parkinson's disease (PD)]. Here we asked whether Nurr1 is causing LID. Indeed, rAAV-mediated expression of Nurr1 in striatal neurons was sufficient to overcome LID-resistance, and Nurr1 agonism exacerbated LID severity in dyskinetic rats. Moreover, we found that expression of Nurr1 in l-DOPA naïve hemi-parkinsonian rats resulted in the formation of morphologic and electrophysiological signatures of maladaptive neuronal plasticity; a phenomenon associated with LID. Finally, we determined that ectopic Nurr1 expression can be found in the putamen of l-DOPA-treated PD patients. These data suggest that striatal Nurr1 is an important mediator of the formation of LID.

‘What on earth were they doing there?’ one researcher asks

Scientists discover neurotoxin-producing bacteria living on the skin of rough-skinned newts

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

The freedom fighter may have once used the structure to conspire against English forces

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

An abstract aerial view of a sand dune at sunset at Imperial Sand Dunes, Glamis, California.

A woman is going up stairs.

The government of the Northwest Territories has made an exemption on border restrictions for a veterinarian from Alberta to practice in the territory, after he received public and political support.

Closing arguments were presented at the trial of Phillip Lionel Levac on Friday at Regina Court of Queen's Bench.

An industrial building in Thunder Bay was slightly damaged in a fire late Thursday afternoon.

The following is a post by Kristi Finefield, Reference Specialist in the Prints & Photographs Division, and member of the Picture This blog team. Images have a way of opening our eyes to new aspects of a well-known story. When I think of singer Marian Anderson, an image of her performing at the Lincoln Memorial […]

Successful modification of the bacterial artificial chromosome (BAC) after two-step BAC engineering is confirmed in two separate polymerase chain reactions (PCRs). The first reaction (5' co-integrate PCR) uses a forward 5' co-integrate primer (a sequence located upstream of the 5' end of the A-box) and a reverse 3' primer on the vector (175PA+50AT) or within the reporter sequence or mutated region as appropriate. The second reaction (3' co-integrate PCR) uses a forward 5' primer on the recA gene (RecA1300S) and a reverse 3' co-integrate primer (a sequence located downstream from the 3' end of the B-box). Those colonies shown to be positive in PCR analysis are further tested for sensitivity to UV light. After the resolution, colonies that have lost the excised recombination vector including sacB and recA genes become UV light sensitive.

Bacterial artificial chromosome (BAC) clones are rendered electrocompetent and transformed with the recombinant shuttle vector, pLD53SCAB/AB-box. Cointegrates are selected by growth on chloramphenicol and ampicillin to ensure recombination of the shuttle vector into the BAC.

Plasmid DNA is prepared from the recombinant shuttle vector pLD53.SCAB/A-B created by cloning of the A and B homology arms for two-step bacterial artificial chromosome (BAC) engineering. To confirm that the A-box and B-box arms have been successfully incorporated into pLD53.SCAB, the pattern of enzyme digestion of the modified plasmid is compared with that of the unmodified pLD53.SCAB. Once the shuttle vector is shown to carry the proper sequences, it is ready for transfer into the BAC host.

This protocol describes the preparation of the shuttle vector before its introduction into bacterial artificial chromosome (BAC) host cells for BAC two-step engineering. The homology arm sequences, prepared previously, are introduced by ligation into the digested shuttle vector DNA to provide sites for recombination within the BAC clone. Crude lysates of individual bacterial transformants serve as templates in polymerase chain reaction (PCR) analysis to confirm the presence of the homology arms in the recombinant shuttle vector.

The 700-bp A homology arm (A-box) and the 700-bp B homology arm (B-box) are amplified by polymerase chain reaction (PCR) using purified bacterial artificial chromosome (BAC) DNA as template for two-step BAC engineering. The resulting A-box PCR product contains an AscI site at its 5' end (the 5' primer incorporates an AscI site, and the 3' primer does not incorporate any restriction sites). The B-box PCR product contains an XmaI site at its 3' end (the 5' primer does not incorporate any restriction sites, and the 3' primer incorporates an XmaI site). The amplification products are then digested with the appropriate restriction endonucleases to render them suitable for cloning into the shuttle vector.

In two-step bacterial artificial chromosome (BAC) engineering, a single plasmid is introduced into the BAC-carrying cell lines. The shuttle vector pLD53.SCAB (or pLD53.SCAEB) carries the recA gene and the R6K origin, which requires the protein to replicate. PIR2 cells, expressing , are typically used for the amplification of the vector and maintain about 15 copies/cell of the donor vector, which is relatively stable in this host.

The American Geriatrics Society annually honors researchers, clinicians, educators, and emerging health professionals who have made outstanding contributions to high-quality, person-centered care for older people.

A randomized, controlled clinical trial evaluating the safety and efficacy of a treatment regimen of the investigational antiviral remdesivir plus the anti-inflammatory drug baricitinib for coronavirus disease 2019 (COVID-19) has begun.

A Dalhousie University scientist and a NSCAD textile professor are teaming up to create a new fabric. It could be used to locally manufacture personal protective equipment like surgical masks. As the CBC's Colleen Jones reports, they have received a COVID-19 grant to study the idea.

Florian Schneider (date: 5/9/2020 - Rank: 10)

Publication by Mr Dimitar Radev, Governor of the Bulgarian National Bank, in the Quarterly Bulletin of the Association of Banks in Bulgaria, issue 61, March 2020.

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.

The province has extended the deadline for people to leave tent cities in Victoria until May 20. The original deadline was May 9 for campers to be out of Vancouver's Oppenheimer Park as well as Topaz and Pandora parks in Victoria.

The Federal Reserve's monthly index of industrial production and the related capacity indexes and capacity utilization rates cover manufacturing, mining, and electric and gas utilities. The industrial sector, together with construction, accounts for the bulk of the variation in national output over the course of the business cycle. The production index measures real output and is expressed as a percentage of real output in a base year, currently 2012. The capacity index, which is an estimate of sustainable potential output, is also expressed as a percentage of actual output in 2012. The rate of capacity utilization equals the seasonally adjusted output index expressed as a percentage of the related capacity index.

The index of industrial production is available nationally by market and industry groupings. The major groupings are comprised of final products (such as consumer goods, business equipment and construction supplies), intermediate products and materials. The industry groupings are manufacturing (further subdivided into durable and nondurable goods), mining and utilities. The capacity utilization rate -- reflecting the resource utilization of the nation's output facilities -- is available for the same market and industry groupings.

Industrial production was also revised to NAICS (North American Industry Classification System) in the early 2000s. Unlike other economic series that lost much historical data prior to 1992, the Federal Reserve Board was able to reconstruct historical data that go back more than 30 years.

OM partner finds young men on the street and offers them jobs and a place to study the Bible.

This summer nearly 1,000 Roma children in Roma villages throughout Central and Eastern Europe heard the Gospel.

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Denver Newsroom, May 7, 2020 / 06:01 pm (CNA).- A young Catholic artist has drawn an image of the Blessed Virgin Mary on her parents' driveway bringing religious art to her local community during the quarantine.

The Diocese of Fargo posted on Facebook May 4 an image of Our Lady of Lourdes drawn by Maria Loh, a 17-year old who grew up in Fargo. She said it was an enjoyable experience to share her faith and art with her neighborhood.

“Being able to interact with people when they walked by was very moving in a way because a lot of people have never really seen sidewalk art done like that locally. So being able to share in that kind of experience, it was very, very good,” she told CNA.

Loh has recently been inspired by chalk art and pastels, which, she said, have vibrant and beautiful colors. She has drawn on the sidewalks a few times, including two images of Mary - Madonna of the Lillies and the Pieta by William Adolphe-Bouguereau.

Her most recent chalk drawing was Our Lady of Lourdes by Hector Garrido - an image she had seen as a magnet on her grandparents' refrigerator growing up. The picture has always been an inspiration, she said, noting that she decided to replicate it after Our Lady of Lourdes Shrine in France had temporarily closed due to the coronavirus pandemic.

“I heard that the shrine had been temporarily closed off to the public, and I remember … thinking that's really sad because especially in this time, we’re really looking for healing in more ways than one, like physically and mentally and spiritually,” she said.

“It really felt like people wouldn't be able to go to experience that. So I felt like drawing this image of Our Lady of Lourdes would be a good way to remind people that Our Lady is still with us even if we can’t go to her shrine.”

Loh, the oldest of five, has been involved with art projects and drawing for her entire life. She said, growing up in a Catholic family, she has been inspired by her faith and the religious art in churches.

“I see our faith as so precious... Especially in the form of the Eucharist - the actual body and blood of Christ, I've seen that we are very blessed to have that in our faith. It's something that has impacted a lot of my life growing up,” she said.

While she was working on the piece, Loh said, a majority of passersby did not know who the lady in the image was. She expressed hope that the picture would help remind people of Mary and the beauty of the Church, which, she said, is a powerful attraction to the faith.

“One thing that I hope this kind of art and image will evoke is a desire to come to know who Mary is and how rich our faith is. … All the beautiful art that can be seen in Catholic churches, especially like in Rome, there's almost a transcendental beauty to them that draws people into the faith to come to know things that they've never dreamed of before,” she said.

As Loh finishes her junior year of high school, she expressed the possibility of art school after graduation, but, while she is still uncertain of the future, said art will not be dropped anytime soon.

“I can definitely see [art school] being a possibility. I’ll have to spend some time, especially with God trying to figure out what he wants me to do. But, I don't think art is going out of my life anytime soon,” she said.

This SOLIDWORKS tutorial is for a Wooden Canvas Teepee, the tutorial focuses on the use of Circular Patterns of part bodies and the use of 3D sketch for extrusions between guide points, and profile sweeps along a path. This is a fun tutorial that if you follow, you can create you own Teepee model, and apply a range of designs to with decals. The decal swatches seen in the video are available to download in the description below.

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Need for Surface Surface Modelling is a method used to create and represent complex shapes with high curvature controls. Generally, surfaces are used as an alternative where a particular feature is difficult to create using solid modeling. It is helpful

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This SOLIDWORKS Tutorial for a Insulated ceramic coffee cup focuses on the combine tool, and uses an assembly to create the layout of the final design before saving back into a part, and turned in to a functional coffee cup. Decals for the tutorial are available to download in the description.

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This is a SOLIDWORKS tutorial to create a pot of gold money jar. This tutorial demonstrates a range of modelling tools, but also highlights the use of the centreline sketch tool as a guide for sketches, new planes, and axis for pattern or move features. The decals and coin part for this design are available to download in the tutorials blog description.

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This SOLIDWORKS Tutorial for a Ceramic Cup Plaster Mold walks you through start to finish of the process of creating a model for a plaster mold and a 3 part cup mold. The tutorial focuses on copying bodies and combing them with each other to finish the tutorial with a 3 piece mold. The final ceramic cup is available to download in the description.

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For this SOLIDWORKS tutorial, you can follow to create a Goldfish shaped Cat Treat Toy ready for 3D printing. The DXF files for this tutorial are available to download from the blog below. You can also download and 3D print this design yourself as the STL files are also available to download.

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In part 1 of this 2-part SOLIDWORKS Tutorial you will learn how to create the body of a Pinata. Part 2 of the tutorial involves shelling the model to turn it into a 2-part jar, and applying decals. The DXF file used in this tutorial are available to download from the blog description.

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Hungarian children get excited about the Easter message

Many schools experienced a new international flavour this year when the OM puppet outreach team was joined by a supporting Finnish church.

Two OMers are riding unicycles across the US this summer in aid of Syrian refugees and displaced people.

Rome, Italy, May 7, 2020 / 09:30 am (CNA).- A Eucharistic blessing of the city of Rome has been offered each day from the doorstep of Rome’s largest Marian basilica as coronavirus measures restricted the public from attending Masses.

The daily Eucharistic procession and benediction takes place in the Papal Basilica of St. Mary Major immediately following a livestreamed Mass at 11 a.m. local time from the chapel containing the Marian icon Salus Populi Romani, Mary Protection of the Roman People.

“The cardinal archpriest, all the canons, priests and religious of this basilica wish to give testimony to the Real Presence of Our Lord Jesus Christ, Doctor and Medicine for humanity tried by this pandemic,” states a caption for the video of a benediction from the loggia on March 21. 

As Rome entered phase two of coronavirus restrictions this week, more people have been able to witness the Eucharistic procession and blessing in person. In the second phase of Italy’s lockdown, which began May 4, residents are allowed to exercise and go for walks in the city with facemasks.

 

A Eucharistic procession and blessing of the city of Rome is offered daily from the doorstep of the Basilica of St. Mary Major during the coronavirus pandemic. pic.twitter.com/LSmHBloK8N

— Courtney Mares (@catholicourtney) May 7, 2020  

On the first day of the eased restrictions, a tour guide in Rome stumbled upon the Eucharistic procession in the basilica.

“I saw that confession was available and adoration was taking place. Following adoration, the priests processed the Blessed Sacrament through the church and into the piazza for a benediction over the city. They then walked to the back door and out into that piazza for another benediction,” Mountain Butorac told CNA. 

“This being one of my first experiences in church in nearly two months brought tears to my eyes and hope to my heart,” he said.

Public Masses will be able to resume in the Diocese of Rome and throughout Italy beginning on May 18, 70 days after the restrictions on Mass went into effect.

During Rome’s lockdown, Pope Francis made a brief walking pilgrimage to the Basilica of St. Mary Major to pray for the Virgin Mary’s protection from the coronavirus pandemic affecting Italy and the world.

The pope later had the basilica’s Byzantine icon of Salus Populi Romani brought to St. Peter’s Square for the extraordinary Urbi et Orbi benediction on March 27. The Marian icon remained inside the basilica throughout the Easter Triduum liturgies.

The Salus Populi Romani icon was also processed through Rome by Pope Gregory I for an end to a plague in 593.

 

The benediction takes place following a livestreamed Mass before the Salus Populi Romani, the same Marian icon processed through Rome by Pope Gregory I for an end to a plague in the 6th century. pic.twitter.com/efIbaJF6Hf

— Courtney Mares (@catholicourtney) May 7, 2020  

Among the four major papal basilicas in Rome, St. Mary Major is the only one that maintained its original structure. Mosaics dating back to the 5th century can be seen in the central nave of the basilica, which also houses the relic of the Holy Crib from the birth of Christ.

According to tradition, the Virgin Mary appeared to both a nobleman named John and to Pope Liberius (352-366) in a dream foretelling the August snow and asking for a church to be built in her honor on the site of the snowfall on Aug. 5 in the year 358. The church was rebuilt by Pope Sixtus III (432-440), after the Council of Ephesus in 431 declared Mary to be the Mother of God.

Vespers and prayers of the holy rosary are offered via livestream each day from the Marian basilica just before 5 p.m. in Rome.

Denver Newsroom, May 7, 2020 / 06:01 pm (CNA).- A young Catholic artist has drawn an image of the Blessed Virgin Mary on her parents' driveway bringing religious art to her local community during the quarantine.

The Diocese of Fargo posted on Facebook May 4 an image of Our Lady of Lourdes drawn by Maria Loh, a 17-year old who grew up in Fargo. She said it was an enjoyable experience to share her faith and art with her neighborhood.

“Being able to interact with people when they walked by was very moving in a way because a lot of people have never really seen sidewalk art done like that locally. So being able to share in that kind of experience, it was very, very good,” she told CNA.

Loh has recently been inspired by chalk art and pastels, which, she said, have vibrant and beautiful colors. She has drawn on the sidewalks a few times, including two images of Mary - Madonna of the Lillies and the Pieta by William Adolphe-Bouguereau.

Her most recent chalk drawing was Our Lady of Lourdes by Hector Garrido - an image she had seen as a magnet on her grandparents' refrigerator growing up. The picture has always been an inspiration, she said, noting that she decided to replicate it after Our Lady of Lourdes Shrine in France had temporarily closed due to the coronavirus pandemic.

“I heard that the shrine had been temporarily closed off to the public, and I remember … thinking that's really sad because especially in this time, we’re really looking for healing in more ways than one, like physically and mentally and spiritually,” she said.

“It really felt like people wouldn't be able to go to experience that. So I felt like drawing this image of Our Lady of Lourdes would be a good way to remind people that Our Lady is still with us even if we can’t go to her shrine.”

Loh, the oldest of five, has been involved with art projects and drawing for her entire life. She said, growing up in a Catholic family, she has been inspired by her faith and the religious art in churches.

“I see our faith as so precious... Especially in the form of the Eucharist - the actual body and blood of Christ, I've seen that we are very blessed to have that in our faith. It's something that has impacted a lot of my life growing up,” she said.

While she was working on the piece, Loh said, a majority of passersby did not know who the lady in the image was. She expressed hope that the picture would help remind people of Mary and the beauty of the Church, which, she said, is a powerful attraction to the faith.

“One thing that I hope this kind of art and image will evoke is a desire to come to know who Mary is and how rich our faith is. … All the beautiful art that can be seen in Catholic churches, especially like in Rome, there's almost a transcendental beauty to them that draws people into the faith to come to know things that they've never dreamed of before,” she said.

As Loh finishes her junior year of high school, she expressed the possibility of art school after graduation, but, while she is still uncertain of the future, said art will not be dropped anytime soon.

“I can definitely see [art school] being a possibility. I’ll have to spend some time, especially with God trying to figure out what he wants me to do. But, I don't think art is going out of my life anytime soon,” she said.