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Clayoquot Sound . . . Keep it Wild!
The health of the global environment depends on intact ecosystems.
We act as peaceful and courageous advocates for all marine and terrestrial life in Clayoquot Sound. »Read More
Clayoquot Salmon Festival 2019 is HERE!
From August 30 – September 7 there will be a variety of events, with something for everyone. The festival aims to offer residents and visitors an opportunity to reflect upon, and build an active appreciation for, the irreplaceable value of salmon in Clayoquot Sound. At least 137 different species depend on the marine-rich nutrients that wild salmon provide. Millions of people around the Pacific rely on salmon as a healthy and reliable source of protein. Pacific salmon fuel a multi-billion dollar industry, supporting tens of thousands of jobs and local economies and communities around the Pacific Rim. Click Here for the SCHEDULE!» Read More
Free Public Summer Presentations: "Striking Balance Together"
Friends of Clayoquot Sound and Tribal Parks Allies present a multimedia exploration of environmental conservation solutions in Clayoquot Sound.
"Striking Balance Together": Film and Photo Presentations
Wednesdays in July (July 3, 10, 17, 24, & 31) & August (August 7, 14, 21, & 28)
Clayoquot Sound Community Theatre
380 Campbell St. Tofino
2019 Summer Newsletter is here!
The summer 2019 edition of our twice-yearly newsletter is out, with articles including:
- Assessing the Wild Salmon Emergency
- The Green New Deal & Global Climate Strike
- August Deadline for Imperial Metals Charge
- Remembering Meares Island
plus updates on our campaigns, and action items for you to take forward. Take a read and please share!» Read More
Celebrating & Protecting Salmon!
Clayoquot Salmon Festival was an awesome week! From September 1-7th, we had 8 public events and hundreds attended!!» Read More
Clayoquot Salmon Festival Sept 1-7!
The salmon are returning and we are reminded of what we are fighting for. Please join us for the Clayoquot Salmon Festival, Saturday, September 1 – Friday, September 7 to help us protect, educate about, and celebrate the irreplaceable backbone of the coast!» Read More
Victoria Ecotourism Outfitter and Environmental Advocates Invite Trudeaus to Bear Witness to Orcas' Wake
In an effort to hold Trudeau accountable as a decision maker, Friends of Clayoquot Sound reached out to the South Island ecotourism operator, Ocean Ecoventures, to invite the Trudeaus on a reality tour to bear witness to the orcas' mournful wake.» Read More
"No Means No Crudeau!" Rally Builds Solidarity Across West Coast While Trudeau Vacations in Tofino
Press release for the "No Means No Crudeau" Beach Rally in Tofino.» Read More
Letter to the Tofino Chamber of Commerce
Dear businesses, residents, and tourists of Clayoquot Sound and the Pacific Rim:
With Trudeau coming here as a tourist, there are a number of ways that we can act to protect the west coast. Here are some ideas:
Why I confronted Justin Trudeau on Vacation in Clayoquot Sound
During Trudeau's visit it was unusually smoky due to BC's forest fires in the interior that have now burned together to create a single blaze that is 4,700 square kilometres in size, the largest fire ever recorded in BC. Over the past four decades, the area burned by forest fires in Canada has increased as summer season temperatures have warmed. Climate change is real.» Read More
2018 Summer Newsletter is here!
The summer 2018 edition of our twice-yearly newsletter is out, with tons of articles
plus updates on our campaigns, and action items for you to take forward. Take a read and please share!
'So Many People Giving a Damn':
War in the Woods Resonates 25 years later with New Environmental Battle on B.C. Coast edited from full article by Megan Thomas» Read More
Crown Decision to Quash Mount Polley Private Prosecution Makes No Sense
How can the worst tailings pond disaster in Canadian history not have legal consequences?
The BC Prosecution Service announced Tuesday that they were taking over and quashing the private prosecution of Mount Polley Mining Corporation over the tailings dam disaster. The charges were laid by Bev Sellars, Grandmother, former Chief of Xat'sull First Nation (Soda Creek), author, and indigenous advocate.» Read More
Winter 2017 - 2018 Newsletter Is Out Now!
The Friends of Clayoquot Sound Winter 2017 – 2018 newsletter is out with an in-depth look at the major issues in Clayoquot Sound and the work we have been doing over the last several months, including updates on our campaigns.» Read More
Ancient Rainforest Logging in Clayoquot Sound's Intact Valleys
Since large scale logging began on Vancouver Island, an area equivalent to approximately two soccer fields of old-growth rainforest has been cut every hour. In light of how few old-growth forest ecosystems remain on Vancouver Island and the current battles to protect the little that remains, we believe the value of these areas for clean air, water, climate, tourism and recreation as part of diverse local Indigenous and non-Indigenous economies will be significantly greater if left unlogged and intact to allow long-term preservation combined with conservation financing and carbon revenue.» Read More
Indigenous Advocate Files Charges Against Imperial Metals Over Canada's Biggest Mining Spill
On the third anniversary of the Mount Polley mine disaster, and deadline for Provincial charges, August 4, 2017, Indigenous advocate Bev Sellars filed a private prosecution against Imperial Metals Mount Polley Mining Corporation at the Provincial Court of British Columbia in Vancouver. Sellars was Chief of Xat'sull First Nation when the disaster struck near her community 3 years earlier and needs funds to support her legal case.» Read More
Frontlines Update at the BC Legislature
"For 30 years we have been saying 'No!' to fish farms, and for 30 years we have been watching salmon returns decline. My relatives have no fish in their freezers," emphasized Sherry Moon, of the Musgamagw Dzawada'enuxw. "Enough is enough!"» Read More
Now we call on our supporters to prepare for a solidarity rally which will bring frontline occupiers to the BC Legislature in Victoria on Thursday, November 2nd. The rally will begin at 11am, so bring your family, friends, drums, and signs of support!» Read More
2017 Friends Of Clayoquot Sound AGM
Join our annual AGM as we present what we have been up to this last year in FOCS!
This is also an incredible opportunity to take part on the Environmental Social Movement happening locally and around the globe.» Read More
2017 Clayoquot Salmon Festival Wrap up
With over 700 attendees, the 2017 Clayoquot Salmon Festival was a huge success in celebrating and advocating for wild salmon. We are already looking forward to next year!» Read More
Trail Building sessions in Clayoquot Sound
FOCS has launched this year's Trail Building with Friends program, aimed at supporting First Nations' management of trails found within Clayoquot Sound.» Read More
Cypress Che Seitcher is FOCS new Summer Student!
Please join FOCS in welcoming Cypress Che Seitcher to the FOCS team as our new summer student and the Earth Keepers Organizer!» Read More
Friends of Clayoquot Sound officially endorse Unsettling Canada 150: A Call to Action from Idle No More & Defenders of the Land!
Unsettling Canada 150
In honour of Arthur Manuel, we call for a National Day of Action in support of Indigenous self-determination over land, territories, and resources
UNsettling Canada 150 Webinar» Read More
Action Alert for Imperial Metals AGM in Coquitlam
Come stand with Friends of Clayoquot Sound as we support Indigenous Land Defenders & Water Protectors of Imperial No More in banning Imperial Metals from destructive mining in their territories. Together we will confront Imperial Metals Mining Corp major shareholders and executives to hold them accountable at the Imperial Metals Annual General Meeting. We will rally for the Imperial NO MORE Action outside the Executive Plaza Hotel (405 North Road) in Coquitlam @ 8 am. Bring your solidarity presence, cameras, hand drums, banners, noise makers, & signs! It's time for action!!!» Read More
FOCS is Hiring a Summer Student!
Friends of Clayoquot Sound is seeking a motivated and energetic student to join the team from June to the end of August. This student will play a key role in supporting the planning and organizing various events and activities including the "Trail Building with Friends" project and the Clayoquot Salmon Festival. The position presents a unique opportunity to learn about the various strategies used to promote a healthy relationship with the environment in Clayoquot Sound.» Read More
25 International Environmental Organizations Call for Urgent Action for Vancouver Island's Rainforest and Communities
Twenty-five international environmental organizations are calling for immediate action to protect and restore Vancouver Island's endangered old-growth rainforest and its species diversity, carbon storage and benefits for a diverse economy including forestry, tourism and wild salmon in Indigenous and non-Indigenous communities on Canada's west coast.» Read More
Tla-o-qui-aht Members Seek Alternative to Colonial Logging Systems
Tsimka Martin and Gisele Martin wrote the following statement on behalf of the Tla-o-qui-aht Initiative for Interconnected Community Health. "All remaining old-growth forest in Tla-o-qui-aht First Nation territory must be permanently protected from any industrial logging."» Read More
"The Yes Man Are Revolting" film screening at the Tofino Film Festival
Do you enjoy comic documentaries about pressing current events? This latest Yes Men film documents activist-pranksters doing outrageous stunts designed to draw awareness to climate change. The latest film by the Yes Men will play as part of the Tofino Film Festival on Friday, February 17th, 7 pm in the Clayoquot Sound Theatre.» Read More
The Ahousaht Hawiih (hereditary chiefs) publicly announced their nation's new comprehensive Land Use Vision for their territory, which sits within the heart of the Clayoquot Sound UNESCO Biosphere Reserve. Representatives of the Clayoquot Sound Conservation Alliance (CSCA) (comprised of Greenpeace, Friends of Clayoquot Sound, Sierra Club BC, STAND.earth and Wilderness Committee) were present to support and congratulate the Hawiih for this initiative.» Read More
Kinder Morgan Pipeline Will Never Operate Despite Trudeau's Foolish Approval
Tofino, Clayoquot Sound – The approval of the Kinder Morgan pipeline by Prime Minister Trudeau breaks his commitments to Indigenous rights, while declaring a war on the climate and coastal ecosystems. The Kinder Morgan pipeline and tanker project would release 100 million tonnes of carbon annually, negating climate commitments of the Liberal government. The pipeline would also bring another 400 tankers a year, putting communities and ecosystems at much greater risk of catastrophic oil spills.» Read More
Fall/winter 2016 newsletter now available
The fall/winter 2016 edition of our twice-yearly newsletter is out. Articles include:
-A promise of environmental protection: Welcoming home Weeping Cedar Woman
-Clayoquot Salmon Festival Wrap Up
-Warriors for Yaakswiis
-Tla-o-qui-aht members seek alternative to colonial logging systems
Plus updates on our campaigns, and action items for you to take forward. Take a read and please share!
Clayoquot Salmon Festival Wrap-up
Over 300 people joined Friends of Clayoquot Sound at the Clayoquot Salmon Festival to celebrate the return of wild salmon to the Pacific Northwest. From October 12th to the 19th, the Festival provided residents and visitors with the opportunity to reflect upon, and build an active appreciation for, the irreplaceable value of salmon in Clayoquot Sound.» Read More
Join us at the "Clayoquot Salmon Festival"
Salmon play an integral role for coastal livelihoods, cultures, and ecosystems in Clayoquot Sound. And they lead incredible lives, starting in fresh water then migrating to the ocean. Salmon stay at sea for years before their homing instincts guide them back, to the fresh water systems they were conceived in, to reproduce. Celebrating this magnificent species is what inspires Friends of Clayoquot Sound to organise the annual Clayoquot Salmon Festival!
summer 2016 newsletter is here!
Our latest newsletter is now available online and on paper all around Vancouver Island and BC. Click the "Read more" link to view the newsletter from the comfort of your home!» Read More
Friends Of Clayoquot Sound 2016 AGM
join us at the Friends Of
Clayoquot Sound AGM:
Wednesday August 24 – 7:30 to 8:30 pm
CBT Office 316 Main Street Tofino,BC
All Welcome!» Read More
Introducing the "Earth Keepers: Youth Arts Engagement Program"
Earth Keepers: Youth Arts Engagement Program is a pilot project created by Friends Of Clayoquot Sound that engages local youth (13-21) from Tofino, Opitsaht, Esowista, and Ty-Histanis in the creation of artistic projects aimed at building youth leadership, artistic voice, environmental stewardship, and regional connectedness.» Read More
Kalilah Rampanen - hassatuk (nuučaan̓uł) is FOCS new Summer Student!
Please join me in welcoming Kalilah Rampanen to the FOCS team as our new summer student and the Earth Keepers Organizer! Kalilah's heritage stems from Ahousaht, Tla-o-qui-aht, Cree and Finnish ancestry. She is an established musician, songwriter and performer that is actively involved with raising awareness about Indigenous rights, way of life and the environment. She will be leading the Earth Keepers: Youth Arts Engagement Project» Read More
Imperial No More Holds Imperial Metals President, Executives, and Big Shareholders Accountable
On Friday May 27th, 2016 Imperial Metal shareholders gambled and lost, by holding their annual general meeting at the River Rock Casino in Richmond BC. The Imperial Metals CEO, shareholders, and executives were confronted at their AGM by the Imperial No More activist network of Indigenous land defenders and allies. With representation from the Secwepemc Women's Warrior Society, No One Is Illegal, Mining Justice Alliance, and Friends of Clayoquot Sound, Imperial No More rallied took action at the River Rock Casino Conference Centre to hold Imperial Metals accountable for the company's continuing disrespect for Indigenous rights and ongoing environmental destruction.» Read More
The Wild Salmon Paddle Continues Strong!
After launching in Victoria B.C. the expedition will end in Juneau, Alaska, journeying a distance of more than 2,000 kilometers. Following the migration routes of wild salmon, the expedition is taking place from early April to August of 2016. Simon Behman leads the expedition from Victoria, BC to the finale in Glacier Bay, Alaska. "I want to give back to the coast that has given me so much by fundraising for salmon conservation for Friends of Clayoquot Sound, educating through social media, and engaging communities along the way about the importance of salmon," said Behman.
The Wild Salmon Paddle is an example of the commitment needed to protect the irreplaceable value of wild salmon. The funds raised will support the Friends of Clayoquot Sound organizing the Clayoquot Salmon Festival, participating in the Clayoquot Sound Salmon Roundtable, and contributing to salmon conservation efforts. To donate to this initiative please follow this Link.» Read More
The "Wild Salmon Paddle" Expedition Begins!
The sea kayaking expedition will cover a distance of more than 2000 kilometres, following the migration routes of wild salmon. Simon Behman will lead the expedition from Victoria, BC to the finale in Juneau, Alaska in July. The expedition's main goal is fundraising for salmon conservation, promoting public education on the issues facing wild salmon, and engaging communities along the way in the topic. The funds raised will support the Clayoquot Salmon Festival and wild salmon conservation efforts of Friends of Clayoquot Sound.» Read More
Collective action is the solution to the climate crisis
Resistance to carbon intensive projects begins at the community level but must also be felt in the corridors of power where there is institutional inertia to change. For example, the National Energy Board (NEB) is supposed to be a legal body of the Government of Canada that considers evidence on proposed oil and gas pipelines and then decide if the project in the "public interest." Yet, the NEB approves almost every project.» Read More
Global Climate March Comes to Clayoquot Sound
In Clayoquot Sound, there have also been some real victories in the past months. Leadership from both the Hesquiaht Nation and the Ahousaht Nation have announced bans on industrial logging in their territories. These moratoriums, protecting the forests, are hugely significant for ecosystem health and climate action.» Read More
Fall 2015 newsletter now online
Our latest newsletter is now available online (in colour!) and on paper around Tofino and BC. This bi-annual issue includes articles on:
> Ahousaht salmon farm eviction
> Is BC a climate leader or laggard?
> Hesquiaht say NO to logging
> Transition Town movement in Tofino-Ucluelet
Ahousaht Chiefs announce industrial logging moratorium
Stunning news! Today the Maaqutusiis Hahoulthee Stewardship Society issued a press release announcing an end to industrial logging on Ahousaht territory. Here's the historic release, plus a congratulatory reaction from the Clayoquot Sound Conservation Alliance.» Read More
Huge salmon die-off at Cermaq farm
At least 25 tonnes of farmed Atlantic salmon died in a 24-hour period last week, at the company's Mussel Rock farm site in Clayoquot Sound. The company cites an unseasonable algae bloom for the sudden demise.» Read More
Ahousaht salmon farm eviction sets global precedent
The newest salmon farm in Clayoquot Sound–Yaakswiis–had a life span of only two weeks, and never saw any fish before grassroots Ahousaht protesters forced its removal by its owner, Cermaq. This marks a first in BC and the world.» Read More


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Disco, Games & Food Party Package in Portsmouth
We will come and Set the party up 1 hour before your party starts, where we will do everything to make your child's day one to remember.
Price £260
Addtional children at £4.99 each.
Additional Extras can be added to any of our party packages if it's not included already:
Popcorn £25 (up to 20 children then £1 per child after)
Cupcakes 20 for £20
Snow Cone ice machines £25
Glitter tattoos £25 (up to 20 children then £1 per child after)
Sweet Cones £1.50
Lucky dip wrapped presents £3.00 each
Bouncy Castle £50
All deposits are non refundable.
All prices are based on Portsmouth area, other areas will occur a surcharge please email for advice.

subset: commoncrawl


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Original Research ARTICLE
Front. Aging Neurosci., 11 December 2009 | https://doi.org/10.3389/neuro.24.003.2009
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA
Mitochondrial oxidative stress and dysfunction has been implicated as a possible mechanism for the onset and progression of Parkinson-like neurodegeneration. However, long-term mitochondrial defects in chronic animal neurodegenerative models have not been demonstrated. In this study, we investigated the function of striatal mitochondria 6 weeks after the induction of a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (MPD). Although severe depression of mitochondrial respiration was observed immediately after acute administrations of MPTP, we failed to detect a significant mitochondrial inhibition in presence of striatal dopamine (DA) deficit 6 weeks after the chronic MPD induction in young adult mice. In contrast, when aged mice were chronically treated with MPTP and at 6 weeks post-treatment, these animals suffered an inhibition of the basal (state 4) and adenosine 5′-diphosphate-stimulated (state 3) respiration and a fall in adenosine triphosphate level in the striatal mitochondria. The aged chronic MPD also brought about a sustained diminution of striatal anti-oxidant enzyme levels including that of superoxide dismutases and cytochrome c. The mitochondrial deficits in the striatum of aged chronic MPD 6 weeks after treatment were further correlated with significant losses of striatal DA, tyrosine hydroxylase, DA uptake transporter, and with impaired movement when tested on a challenging beam. Our findings suggest that MPTP may trigger the neurodegenerative process by obstructing the mitochondrial function; however, striatal mitochondria in young animals may potentially rejuvenate, whereas mitochondrial dysfunction is sustained in the aged chronic MPD. Therefore, the aged chronic MPD may serve as a suitable investigative model for further elucidating the integral relationship between mitochondrial dysfunction and neurodegenerative disorder, and for assessing the therapeutic efficacy of mitochondrial protective agents as potential neuroprotective drugs.
Mitochondria are dynamic organelles that are present in all mammalian cells. They are functionally well known for generating adenosine triphosphate (ATP) as the source of energy, for sequestering excess cytoplasmic Ca++, for producing and disposing of reactive superoxide free radicals, and for supporting cell survival and preventing cell death (Chan, 2006 ). Briefly, the generation of ATP by mitochondria involves oxidative phosphorylation of a number of protein complexes within the electron transport chain system located in the inner mitochondrial membrane. During the process of mitochondrial respiration and ATP production, small amounts of molecular oxygen are naturally reduced to form reactive oxygen species (ROS) as byproducts, like superoxide free radicals. Under healthy conditions, the basal level of ROS produced within cells is quite low and not harmful. Furthermore, a number of mitochondrial anti-oxidant enzymes such as the superoxide dismutase (SOD) and cytochrome c can scavenge any abnormally elevated ROS from internal and external sources and prevent further damages to mitochondrial and cellular DNA, proteins, and lipids.
Conceivably, neurons are extremely active cells that require constant supply of energy in order for them to carry out highly specialized functions such as regulating the activities of neuronal transmission, receptors, ion channels, transporters and synapses. Thus, mitochondria are vital for maintaining the homeostasis and integrity of neuronal functions; and mitochondrial damage and dysfunction may lead to neurological disorders (Schon and Manfredi, 2003 ; Chan, 2006 ).
With exception of a few well characterized familial cases in connection with specific gene mutations, Parkinson's disease (PD) is commonly a sporadic, adult-onset, neurological disorder. Pathophysiologically, PD is considered as a movement disorder due to severe loss of dopamine (DA)-producing cells in the substantia nigra pars compacta, although the true origin of PD neurodegeneration is still unclear. Nevertheless, recent advances in PD research have reached a consensus suggesting that PD is not likely caused by a single factor but rather a combination of genetic and environmental factors leading to a complex clinical phenotype with underlying loss of nigrostriatal DA neurons (Bronstein et al., 2009 ). Therefore, potential success for preventing and treating PD could not be easily achieved by a monotherapeutic approach.
Many plausible genetic and environmental factors have been investigated and linked to both the initiation and progression of PD neurodegeneration. Amongst them, neuronal oxidative stress and mitochondrial dysfunction have emerged as part reasons for instigating the demise of nigrostriatal DA neurons through a series of deleterious cellular and molecular events. It is generally believed that due to intrinsic genetic and extrinsic environmental factors that may cause ROS accumulation and/or fail to eradicate ROS, neuronal mitochondria will undergo oxidative damage involving depletion of anti-oxidant proteins and activation of a series of caspase-dependent or caspase-independent molecular signaling events leading to apoptotic cell death (Dawson and Dawson, 2003 ; Vila and Przedborski, 2003 ).
On the genetic basis, a number of published reports have associated point mutations of mitochondrial DNA (mtDNA) with PD neurodegeneration (Wallace, 1997 ; Gu et al., 2002 ; Bender et al., 2006 ; Kraytsberg et al., 2006 ). Furthermore, patients who are identified with mtDNA defects show progressive and disabling Parkinsonian features (Filosto et al., 2007 ; DiMauro and Schon, 2008 ).
The scientific evidence implicating that exposure to environmental toxic chemicals as a possible contributing factor for causing cellular oxidative damage and mitochondrial dysfunction in association with Parkinson's disorder has been widely examined (Sherer et al., 2002 ). Self-administration of an illicit designer's drug, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) that results in human Parkinsonism is an early indication of chemically induced toxicity to the nigrostriatal DA neurons (Langston et al., 1983 ). Later, MPTP is found to inhibit oxidative phosphorylation involving mitochondrial nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase (complex-1) of the electron transport chain, to increase mitochondrial ROS production, and to deplete ATP (Ramsay and Singer, 1986 ; Ali et al., 1994 ). Infusion of other complex-1 inhibitors, such as rotenone and trichloroethylene to rodents results in loss of the nigral DA neurons and produces Parkinsonian phenotype suggesting mitochondrial dysfunction in PD pathogenesis (Betarbet et al., 2000 ; Gash et al., 2008 ). The concept of neuronal oxidative stress and mitochondrial complex-1 inhibition has also been verified in the substantia nigra pars compacta from human PD (Parker Jr. et al., 1989 ; Schapira et al., 1990 ; Mann et al., 1992 ; Floor and Wetzel, 1998 ).
Genetically modified animal models are of particular interest as they provide evidence that reducing mtDNA expression and disrupting mitochondrial function can lead to respiratory chain breakdown and neuronal death reminiscent of PD phenotype (Ekstrand et al., 2007 ). Over-expression of α-synuclein in cell culture and in transgenic mice impairs mitochondrial function and increases their vulnerability to MPTP neurotoxicity (Hsu et al., 2000 ; Song et al., 2004 ). On the other hand, α-synuclein knock-out mice are resistant to toxicity produced by respiratory chain inhibitors, such as MPTP (Dauer et al., 2002 ; Klivenyi et al., 2006 ). These findings strongly divulge a role of mitochondrial deficiency in α-synucleinopathy that is relevant to PD pathogenesis.
As depicted above, most of the findings that associate mitochondrial dysfunction with PD-like DA neuron degeneration have been derived from in vitro experiments with isolated mitochondria and neuronal cells or from short-term investigations using an acute or subacute animal PD model. To further substantiate the functional role of mitochondria for the survival of nigrostriatal DA neurons, the objective of this research was to examine the long-term integrity of striatal mitochondria in a chronic mouse model of Parkinson's disease (MPD).
Two different age groups of male, C57BL/6 mice, 6–10 weeks (young adult) and 6–10 months (aged retired-breeder), weighing 25–28 and 35–40 g, respectively were used (Harlan Sprague Dawley, Inc., Indianapolis, IN, USA). Mice were housed in single cages with food pellets and water available ad libitum. The room was maintained at a constant temperature and humidity on a 12-h/12-h light/dark cycle. All animal treatments were carried out strictly in accordance to the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23, revised 1996) and were approved by the Institutional Animal Care and Use Committee from the University of Houston. Our experimental procedures did not cause significant animal suffering. A total of 98 mice were used in the present study.
Chronic Mouse Model of Parkinson's Disease
To prepare the chronic MPD, mice were injected with a total of 10 doses of MPTP hydrochloride (25 and 15 mg/kg/injection in saline, s.c. for young and aged mice, respectively) in combination with an adjuvant, probenecid (250 mg/kg/injection dissolved in dimethyl sulfoxide, i.p.) as previously described (Lau et al., 1990 ; Petroske et al., 2001 ). The 10-dose regimen was administered on a 5-week schedule with an interval of 3.5 days between injections. MPTP hydrochloride and probenecid were purchased from Sigma Chemical Co. (St. Louis, MO, USA). Experiments were conducted 6 weeks post-chronic treatment. Safety precautions for the use of MPTP during chemical preparation and animal injections were taken according to the procedures previously described (Lau et al., 2005 ). Control mice were treated with probenecid only. Probenecid was used to inhibit the rapid clearance and excretion of MPTP and its metabolites from the brain and kidney, and it alone did not produce any significant neurotoxic effect; but in combination it potentiated the neurotoxicity of MPTP (Lau, 2005 ; Lau et al., 2005 ; Barber-Singh et al., 2009 ). For comparison, we also included a group of acute MPTP-treated young mice, which were injected with two doses of MPTP hydrochloride (25 mg/kg/injection in saline, s.c.) 2 h apart. Experiments were conducted 2 h post-acute treatment.
The chronic MPD used in this study has been well characterized. In contrast to the most commonly used acute and subacute MPTP mouse models of PD, in which neurological and behavioral deficits are short-lived and spontaneously reversed soon after the treatment, the chronic MPD has long-term neurological deficits showing many features resembling that of the Parkinson's syndrome lasting for at least 6 months (Lau, 2005 ). The observed features include marked depletion of DA content and terminal DA uptake in association with significant behavioral deficit and loss of DA cells in the substantia nigra (Lau et al., 1990 ; Petroske et al., 2001 ; Pothakos et al., 2009 ). Early neuronal apoptosis and delayed appearance of α-synuclein-positive inclusion bodies along with ultrastructural neuronal damage in the substantia nigra pars compacta have also been demonstrated (Meredith et al., 2002 ; Novikova et al., 2006 ).
Isolation of Striatal Mitochondria
Due to tissue limitation, a crude striatal mitochondrial preparation that was modified according to the protocol of Sullivan et al. (2000 ) was used for the mitochondrial respiration assay in this study. Briefly, striata from each animal were isolated and homogenized with a dounce homogenizer in 1 ml of an ice-cold isolation buffer containing mannitol (215 mM), sucrose (75 mM), bovine serum albumin (BSA, 0.1%), EGTA (1 mM), and HEPES (20 mM) at a pH of 7.2. All subsequent procedures were carried out at 4°C. The homogenate was centrifuged at 1,300 rpm for 3 min. The supernatant was transferred to a new tube and the pellet was suspended in 0.5 ml of the isolation buffer and centrifuged again at 1,300 rpm for 3 min. The supernatants from both spins were combined and centrifuged at 13,000 rpm for 10 min. This latter supernatant was discarded and the pellet containing the mitochondrial fraction was suspended in 0.1 ml of a respiration buffer containing mannitol (215 mM), sucrose (75 mM), BSA (0.1%), HEPES (20 mM), MgCl2 (2 mM), and KH2PO4 (2.5 mM) at a pH of 7.2. The mitochondrial protein concentration was determined with the Pierce micro BCA protein assay kit (Rockford, IL, USA) measured at an absorbance of 595 nm with a Beckman DU 640 spectrophotometer (Fullerton, CA, USA).
Mitochondrial Respiration Assay
Since mitochondria are vital organelles responsible for catalyzing the oxidation of various substrates through an electron transport chain system and for generating ATP to support cell function and survival, the respiratory activity of striatal mitochondria was measured polarographically with a Clark-type oxygen electrode in a sealed, thermo-controlled, and continuously stirred chamber (Oxytherm System, Hansatech Instruments, Norfolk, England). Crude mitochondrial protein at a concentration of 0.5 mg/ml in respiration buffer (see above) was initially equilibrated in the electrode chamber at 30°C. The rate of oxygen consumption (nmol/min/mg mitochondrial protein) was calculated based on the slope of polarographic tracings obtained during state 3 and state 4 respiration. All mitochondria preparations had an average respiratory control ratio of at least 4.5 when pyruvate (5 mM) and malate (2.5 mM) were used as NADH-linked substrates. The state 3 respiration was initiated by adding adenosine 5′-diphosphate (ADP, 150 μM).
Measurement of Mitochondrial ATP
Striatal mitochondrial samples were prepared under conditions identical to those of the respiration study. After the completion of respiration experiment, the mitochondrial suspension from the chamber was recovered and mixed with an equal volume of lysing buffer provided in the ATP bioluminescence assay kit (PerkinElmer, Waltham, MA, USA). The mitochondrial content of ATP was measured according to the manufacturer's instruction. Light emitted from luciferase-mediated reaction was captured in a luminometer (Wallac Victor II, PerkinElmer) and the sample ATP content was extrapolated from a standard curve constructed with a series of known ATP concentrations (Tieu et al., 2003 ).
Western Blot Analysis
Besides serving as energy generating organelles, mammalian mitochondria also play a pivotal role in regulating the production and removal of ROS from internal or external sources. Several key anti-oxidant enzymes have been widely studied. Mn SOD (SOD2) is located in the mitochondrial matrix where it protects mitochondrial targets against the internally generated superoxides. Cu–Zn SOD (SOD1) and cytochrome c are capable of removing the superoxides generated by external triggers. These anti-oxidant enzymes are important for scavenging the elevated ROS and preventing them from reaching a toxic level that will cause mitochondrial damage and cell death (McCord, 1993 ; Pereverzev et al., 2003 ). Therefore, loss of anti-oxidant enzymes and release of cytochrome c in association with mitochondrial dysfunction in the DA neurons may lead to substantial ROS accumulation and cause PD-like neurodegeneration. Thus, we measured the levels of mitochondrial anti-oxidant enzymes in conjunction with the striatal DA synthesizing enzyme and DA uptake protein in the present study.
For western blot analysis of anti-oxidant protein expression, crude striatal mitochondria were prepared according to the procedure as described above, except that mitochondria were finally suspended in Tris–HCl buffer (50 mM, pH 7.4) containing the protease inhibitor cocktail purchased from Sigma Chemical Co. The mitochondrial protein concentration in each sample was determined with the Pierce micro BCA protein assay kit and diluted to an appropriate final concentration in a protein solubilization solution containing SDS (2%), Tris–HCl (62.5 mM, pH 6.8), glycerol (10%), 2-mercaptoethanol (5%), bromophenol blue (0.001%). The sample was boiled for 5 min and 25 μg of each sample was applied to SDS polyacrylamide (12%) gel electrophoresis. The resolved proteins were transferred to a PVDF membrane, which was probed with polyclonal rabbit anti-Mn-SOD (1:1000, Upstate, Lake Placid, NY, USA), polyclonal anti Cu/Zn-SOD (1:1000, Stressgen Bioreagents, Victoria, BC, Canada), monoclonal mouse anti-cytochrome c (1:750, Chemicon, Temecula, CA, USA), mouse anti-tyrosine hydroxylase (anti-TH, 1:1000, Millipore, Temecula, CA, USA), rat anti-DA uptake transporter (anti-DAT, 1:1000, Chemicon) and monoclonal mouse anti-glyceraldehyde 3 phosphate dehydrogenase (anti-GAPDH, 1:3000, Chemicon). Immunoreactivity was visualized by a horseradish peroxidase-conjugated goat anti-rabbit (1:2000, Chemicon) or goat anti-rat (1:2000, Chemicon) or goat anti-mouse IgG (1:1500, Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA) with an enhanced NuGlo chemiluminescent substrate (Alpha Diagnostic International Inc., San Antonio, TX, USA). The exposure time of the blot on film was confined to the linear scale of detection without exceeding the saturation limit. The intensity of the protein bands was measured by densitometry (Fluorochem 8800, Alpha Innotech Corporation, San Leandro, CA, USA) and expressed as a ratio to that of GAPDH to ensure that changes of protein level are not simply due to differences in the amount of sample loading.
Assay for Striatal Dopamine and 3,4-Dihydroxyphenylacetic Acid Content
The striatal levels of DA and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) were determined as previously described (Lau et al., 2005 ). Briefly, striata from each animal were isolated, weighed and suspended in 0.5 ml of 0.2 N perchloric acid. Each sample was sonicated and centrifuged at 11,000×g for 15 min at 4°C. The supernatant was filtered through a 4-mm nylon syringe filter with a pore size of 0.45 μm (National Scientific, Rockwood, TN, USA). An aliquot of the filtrate was injected into a high performance liquid chromatography (HPLC Model 1525, Waters Corporation, Milford, MA, USA) equipped with a C18 reverse phase, 3 μ LUNA column (100 mm × 2.0 mm, Phenomenex, Torrance, CA, USA). The sample was eluted by a mobile phase made of 25 mM NaH2PO4, 50 mM Na-citrate, 0.03 mM EDTA, 10 mM diethylamine HCl, and 2.2 mM sodium octyl sulfate (pH 3.2), 30 ml/l methanol and 22 ml/l dimethylacetamide at a flow rate of 0.4 ml/min. DA and DOPAC peaks were determined by the Coulometric electrochemical detector (Model Coulochem III, ESA, Inc., Chelmsford, MA, USA) and were calculated by extrapolating the peak area from a standard curve (ranging 0.05–1 ng of each chemical standard) constructed under the same conditions during each run.
Animal Balance Performance on a Challenging Beam
We monitored the ability of the aged chronic MPD in maintaining balance on a challenging beam 6 weeks post-chronic treatment as previously described with the young adult mice (Pothakos et al., 2009 ). The challenging beam was a 1-m long wooden beam suspended 23 cm above a bench top, which was covered with soft pads to protect the mouse in case of a fall. The beam was divided in four gradually narrowing sections (25 cm/section) leading to the mouse's home cage. The beam widths of the four sections were 3.5, 2.5, 1.5, and 0.5 cm in decreasing order. The beam was covered with surgical tape that provided sufficient surface traction for the animals to walk on. There were 1 cm wide ledges hanging 1 cm below each side of the beam to encourage the mice to use their normal gait strategies even when their limbs slipped. All mice were pre-trained for two consecutive days (five trials per day) with an inter-trial interval (ITI) of 10–12 s on traversing the beam. On the third day, each mouse was given five trials (ITI = 10–12 s). The average number of videotaped limb slips per trial and the time latency for returning to the home cage were recorded and compared with control mice for statistical analysis. Slips were counted only while the mouse was in forward motion.
Statistical Analysis
Statistical comparisons of values between control and treated groups were carried out by Student's t-test. In all cases, a P value of <0.05 was considered to be significant. All data are represented as mean ± SEM.
For studying the hypothesis of striatal mitochondrial dysfunction in the chronic MPD, we initially used young adult mice at the age of 6–10 weeks. We first replicated the animal model by demonstrating striatal dopaminergic deficit resulting from a 5-week, 10-dose treatment with MPTP (25 mg/kg) and probenecid (250 mg/kg) as shown in previous studies (Lau et al., 1990 ; Petroske et al., 2001 ). Thus, 6 weeks after chronic MPD treatment, we detected a sustained 74.9 and 70.9% loss of striatal DA and DOPAC, respectively (Table 1 ). Acute treatment in young mice with two doses of MPTP (25 mg/kg) caused a rapid depletion of 54.1% DA and 48.3% DOPAC in the striatum 2 h later (Table 1 ). These results indicate that MPTP has an acute effect in depleting the vesicular DA stores; and when administered chronically with probenecid, MPTP produces a persistent loss of DA in the striatum.
Mitochondrial respiration in the striatum was measured and compared between acute and chronic MPD. The basal rates of mitochondrial respiration (state 4 respiration) in young adult mice were not significantly different between acute control, acute MPD, chronic control, and chronic MPD groups (Table 2 ). The ADP-stimulated mitochondrial respiration (state 3 respiration) in young acute MPD was markedly reduced when compared with the acute control animals (Table 2 ). To our surprise, the young chronic MPD showed no signs of respiratory depression in the striatal mitochondria when compared with that in the chronic control mice (Table 2 ). These data demonstrate that although MPTP has an immediate toxic effect on mitochondrial respiration, this defect is not sustained 6 weeks after the chronic MPTP/probenecid treatment.
We further examined the expression of striatal mitochondrial anti-oxidant proteins by western blot analysis. In young acute MPD, the levels of Mn SOD, Cu–Zn SOD, and cytochrome c were not significantly altered in the striatal mitochondria (Figures 1 A–C). Similarly, the contents of these three proteins 6 weeks after chronic MPTP/probenecid treatment were not different from either control or acute MPD group of young mice (Figures 1 A–C). Since the basal levels of these proteins in acute saline-treated and chronic probenecid-treated young mice were not statistically different, only the control data from chronic probenecid-treated group were presented.
Figure 1. Protein expression of (A) Mn SOD, (B) Cu–Zn SOD, and (C) cytochrome c in the striatum of young control, acute MPTP, and 6-week post-chronic MPTP/probenecid-treated parkinsonian (MPD) mice. Western blot technique and densitometry analysis were used to detect and quantify the respective anti-oxidant protein bands and GAPDH. The protein contents of Mn SOD, Cu–Zn SOD, and cytochrome c were expressed as a ratio to that of GAPDH to ensure that the changes in protein levels were not due to sample loading variances. A representative image of western blot protein bands was correspondingly shown above each set of bar graph. Each data point represents mean ± SEM, N = 6 per group of animals. The levels of Mn SOD, Cu–Zn SOD, and cytochrome c in the striatum of young control, acute MPTP, and 6-week post-chronic MPD mice were not statistically different from each other.
It is possible that the functionality of mitochondria may gradually recover in young adult mice after the toxic species of MPTP are dissipated from the brain. Before ruling out the possible association between Parkinson-like neurodegeneration and mitochondrial disorder, we were curious to investigate whether mitochondrial dysfunction may exist and can be demonstrated in aged chronic MPD. Since aged mice are known to be more sensitive to MPTP neurotoxicity (Ricaurte et al., 1987 ) and also based on our own experience that aged mice will not survive the same chronic MPTP/probenecid regimen as in young adult mice, therefore we treated the aged chronic MPD with a lesser dose of MPTP (15 mg/kg) in the present study. Indeed, the 6- to 10-month-old mice when treated with 10 doses of MPTP (15 mg/kg, s.c.) and probenecid (250 mg/kg, i.p.) over 5 weeks had all survived and they displayed 64.6 and 53.3% loss of DA and DOPAC, respectively 6 weeks after the cessation of treatment (Table 3 ). Analyses of TH and DAT expression in the striatal tissue further revealed that there were significant losses of TH and DAT contents in the aged chronic MPD 6 weeks after treatment when compared with that of the control animals (Figures 2 A,B). These results implicate that this modified chronic MPD treatment in aged mice generates a moderate and sustained loss of dopaminergic transmission and function in the striatum.
Figure 2. Western blot analysis of (A) TH and (B) DAT expression in the striatum of aged chronic probenecid control and aged chronic MPD mice. A representative image of western blot protein bands was correspondingly shown above each set of bar graph. The protein contents of TH and DAT were expressed as a ratio to that of GAPDH and each data point represents mean ± SEM (N = 5 for chronic control and N = 8 for chronic MPD). Western blots revealed that there were significant reductions of TH and DAT content in the striatum of aged MPD 6 weeks after chronic treatment when compared with that of the control mice (*P < 0.001).
Interestingly, both the basal (state 4) and ADP-stimulated (state 3) mitochondrial respiration in the striatum of aged chronic MPD mice were significantly impaired when compared to the chronic control animals (Table 4 ). There was a 50.8 and 41.0% reduction of state 3 and state 4 respiration, respectively 6 weeks after the chronic MPD treatment (Table 4 ). The mitochondrial ATP level was also decreased by 46.9% (Table 4 ). These data demonstrate that 6 weeks after chronic MPTP/probenecid treatment in the aged mice, there is a sustained attenuation of mitochondrial respiration and ATP production in the striatum. Western blot analyses of anti-oxidant proteins additionally showed that the levels of Mn SOD, Cu–Zn SOD, and cytochrome c were significantly reduced in the striatal mitochondria of the aged chronic MPD 6 weeks after treatment (Figures 3 A–C).
Figure 3. Protein expression of (A) Mn SOD, (B) Cu–Zn SOD, and (C) cytochrome c in the striatum of aged chronic probenecid control and aged chronic MPD mice. A representative image of western blot protein bands was correspondingly shown above each set of bar graph. The protein contents of Mn SOD, Cu–Zn SOD, and cytochrome c were expressed as a ratio to that of GAPDH and each data point represents mean ± SEM, N = 6 per group of animals. Statistical analyses revealed that the levels of Mn SOD, Cu–Zn SOD, and cytochrome c in the striatum of aged chronic MPD 6 weeks after chronic treatment were significantly lower than that of chronic control animals (*P < 0.05).
Although the absolute value of the state 3 respiration in aged mice (Table 4 ) appeared to be higher than that in the young mice (Table 2 ), statistical comparison between them was not performed because these two sets of experiments were not performed at the same time and under the same conditions. Furthermore, the chronic MPD in young and aged animals were treated with a different dose of MPTP due to age-related sensitivity. Thus, the aim and design of the present study was to directly compare mitochondrial respiration between age-matched control and chronic MPD groups under the same experimental conditions.
We used the challenging beam in this study to examine the animal's balance and motor coordination skills. Six weeks after MPTP/probenecid treatment, the chronic MPD group exhibited a significantly greater number of foot slips on the challenging beam than that of the control group (Table 5 ). In addition, the aged chronic MPD mice were more hesitant and took longer time than the control animals on the balance beam before returning to the home cage (Table 5 ).
There is a large body of in vitro and acute in vivo research findings suggesting a possible link between mitochondrial dysfunction and neurodegenerative disorders. However, very few investigations have been conducted and results are inconclusive involving the long term defects of mitochondria in chronic neurodegenerative models. In the present study, we investigated mitochondrial respiration and measured mitochondrial anti-oxidant enzyme levels 6 weeks after the induction of Parkinsonism in a chronic MPD. In contrast to our initial hypothesis stating that long-term mitochondrial deficiency is associated with chronic Parkinsonism, we failed to detect a significant inhibition of either the basal (state 4) or ADP-stimulated (state 3) mitochondrial respiration in the striatum of young adult chronic MPD mice at 6–10 weeks of age, although considerable loss of striatal DA neurotransmitter persisted in these animals. Furthermore, we did not ascertain any noticeable change in the levels of mitochondrial anti-oxidant enzymes including Mn SOD, Cu–Zn SOD, and cytochrome c. Our results may be interpreted as either mitochondrial impairment is not an obligatory pathophysiological factor for chronic neurodegenerative process or MPTP may instigate oxidative stress and inflammation to the mitochondria in other types of striatal cells in addition to the DA neurons; consequently, striatal mitochondria in the non-DA cells plus or minus DA neurons in young animals may have the capability to rejuvenate their functionality over time when the neurotoxin clears away from the brain. The latter possibility on cell specificity was not tested in the present study due to tissue limitation.
For comparison, we confirmed that acute injections of MPTP caused an immediate depletion of striatal DA and simultaneously suppressed the state 3 mitochondrial respiration. These observations are in line with the premise that neurodegeneration may be provoked by MPTP causing accumulation of excitotoxic mediators, production of oxidative free radicals, disruption of Ca++ homeostasis, and ATP depletion in association with an inhibition of the neuronal mitochondrial complex I component of the electron transport chain (Przedborski and Jackson-Lewis, 1998 ; Blum et al., 2001 ). However, whether neurodegeneration follows a progressive course or not would depend on how rapid and how long the brain is exposed to neurotoxic chemicals. Indeed, the DA depleting effect of MPTP, when it is administered acutely or subacutely in mice, tends to be short-lived and reversible (Lau, 2005 ). In addition, as expected and shown in our results, we did not detect an immediate action of MPTP on turning over the anti-oxidant enzyme levels of SODs and cytochrome c in acutely treated young mice. We did not further carry out the long-term investigation of acute MPTP on mitochondrial respiration, SODs and cytochrome c contents. We do not anticipate that acute MPTP will cause any sustained mitochondrial changes, because even chronically repeated administration of MPTP/probenecid in young mice did not generate any significant alterations in mitochondrial respiration and anti-oxidant enzyme levels at 6 weeks after treatment.
To address the possibility that striatal mitochondria in young animals may have the potential for functional recovery over time when the neurotoxin is eliminated from the brain, we decided to examine the long-term neuronal and mitochondrial toxic effects of chronic MPTP/probenecid in an aged group of animals (6–10 months old). Resembling the observations from young adult animals, even with a reduced dose of MPTP (15 mg/kg/injection), the aged chronic MPD acquired significant losses of striatal DA, DOPAC, TH and DAT to a moderate level at 6 weeks post-treatment. In contrast to the young animals, the aged chronic MPD consistently suffered an inhibition of the basal and ADP-stimulated respiration and a fall in ATP production in the striatal mitochondria. Chronic MPTP/probenecid treatment in aged mice also brought about a sustained diminution of striatal anti-oxidant enzyme levels including that of Mn SOD, Cu–Zn SOD, and cytochrome c. The striatal neurochemical and mitochondrial deficits in aged chronic MPD 6 weeks after treatment were further supported by behavioral observations showing that these animals made more foot-slip errors and it took twice as long for them to complete the challenging beam test.
It should be emphasized that a close correlation between neuronal, mitochondrial, and behavioral deficits 6 weeks after chronic Parkinsonism in the aged animals would suggest an important role of mitochondrial function in maintaining neuronal plasticity. However, such a positive correlation alone is not sufficient for establishing a cause-and-effect relationship between mitochondrial disorder and Parkinson-like neurodegeneration. Furthermore, our failure for demonstrating long-term mitochondrial deficiency in the young chronic MPD would not dispute the possibility that neurotoxins like MPTP can cause mitochondrial oxidative dysfunction and trigger the neurodegenerative process, but the mitochondria may potentially revive from the initial insult in young animals. This is well demonstrated in the present study that mitochondrial functions are fully intact whereas neuronal functions are severely impaired 6 weeks after chronic MPD treatment in young mice. The main significance of this investigation is the finding of coexisted phenotype between neurodegenerative and mitochondrial defects in the aged chronic MPD. This will provide an appropriate model for continuously establishing whether these two disorders are cause-and-effect related and for using these altered neurobiological indicators as biomarkers for potential neuroprotective targets in preclinical tests. One of the approaches that we currently undertake using this model in our laboratory is to elucidate whether long-term physical exercise could simultaneously offer mitochondrial as well as neuronal protection in the neostriatum.
The topic on deterioration of mitochondrial functions associated with normal aging or correlated with age-related diseases has been widely reviewed (Calabrese et al., 2001 ; Bertoni-Freddari et al., 2004 ; Crompton, 2004 ; Martin, 2006 ; Arduino et al., 2009 ; Swerdlow, 2009 ). In the laboratory, neurons isolated from the brains of aged rats show deficiency in cytochrome c and inner mitochondrial membrane-associated cardiolipin levels that would preempt normal mitochondrial respiration and oxidative phosphorylation (Jones and Brewer, 2009 ). A single dose of MPTP (40 mg/kg) does not acutely generate ROS in young mice, but significantly releases ROS in old mice (Ali et al., 1994 ). Moreover, although attempts have been made to link mutations of mtDNA directly to normal aging or age-related disease states, it has not been confirmed that mtDNA mutations are either the primary cause or the result of aging or disease process (Arnheim and Cortopassi, 1992 ; Wallace, 1997 ; Kang and Hamasaki, 2005 ; Reeve et al., 2008 ). For translational consideration, one can envision that the capacity of mitochondria for carrying out oxidative respiration and generating ATP and for coping with acute oxidative insult in the neuron of a 20-year-old would be much greater than that of a 70-year-old individual. In other words, the mitochondria and neurons of an aged person would be more subject to irreparable injuries following chronic exposure to endogenous or exogenous toxic chemical species. As implicated in the present study, our results are in agreement with the notion that the anti-oxidant capacity and the recovery potential for mitochondria and neurons post-injury are expected to decline with increase in age (Beal, 2005 ).
It is reasonable to presume that normal physiological release of ROS from mitochondria is insignificantly low and is unlikely to cause neuronal death. Therefore, intentional reduction of endogenously produced ROS below its basal physiological level would not be considered health beneficial. However, if chronic exposure to neurotoxic chemicals like MPTP results in lasting depletion of anti-oxidant enzymes such as SODs and cytochrome c in the aged subject, as demonstrated in the current study, the loss of mitochondrial anti-oxidant protection can certainly exacerbate neurotoxicity and cell death initiated by the elevated ROS. Thus, developing new approaches for protecting the capacity of mitochondrial defense system, for eradicating the elevated ROS level, and for restoring the mitochondrial respiratory functions would be important strategies for preventing and treating progressive cell death under oxidative stress conditions.
In summary, the present study examined the role of striatal mitochondrial function in the chronic MPD. Although we confirmed that MPTP acutely suppressed mitochondrial respiration, it did not cause a long-lasting inhibitory effect or deplete anti-oxidant enzymes in the young chronic MPD. These data suggest that MPTP may initiate neurodegenerative process by blocking mitochondrial respiration, yet the mitochondria in the striatum of young animals have the potential for recovery. However, we demonstrated that aged mice were more vulnerable to chronic MPTP toxicity. Long-term inhibition of mitochondrial respiration, depletion of anti-oxidant enzymes and ATP were displayed in aged mice coincided with marked loss of striatal DA neuronal functions and impaired motor response. These results indicate that aged chronic MPD may serve as a suitable investigative model for further elucidating the integral relationship between mitochondrial dysfunction and neurodegenerative disorder, and for assessing the therapeutic efficacy of mitochondrial protective agents as potential neuroprotective drugs.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors thank Drs. Mostafa Badr, Patrick Sullivan, and Donald Fox for their advice on the preparation of striatal mitochondria and on the measurement of mitochondrial respiration. We appreciate the advice and help of Dr. Konstantinos Pothakos on the assessment of animal's balance behavior. Preliminary results of this study were published in abstract form at the Experimental Biology meeting in San Diego, CA, USA, April 5–9, 2008. This study was supported by a grant from the National Institute of Neurological Disorders and Stroke (NS 47920).
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Song, D. D., Shults, C. W., Sisk, A., Rockenstein, E., and Masliah, E. (2004). Enhanced substantia nigra mitochondrial pathology in human alpha-synuclein transgenic mice after treatment with MPTP. Exp. Neurol. 186, 158–172.
Sullivan, P. G., Geiger, J. D., Mattson, M. P., and Scheff, S. W. (2000). Dietary supplement creatine protects against traumatic brain injury. Ann. Neurol. 48, 723–729.
Swerdlow, R. H. (2009). The neurodegenerative mitochondriopathies. J. Alzheimers Dis. [Epub ahead of print].
Tieu, K., Perier, C., Caspersen, C., Teismann, P., Wu, D. C., Yan, S. D., Naini, A., Vila, M., Jackson-Lewis, V., Ramasamy, R., and Przedborski, S. (2003). D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J. Clin. Invest. 112, 892–901.
Vila, M., and Przedborski, S. (2003). Targeting programmed cell death in neurodegenerative diseases. Nat. Rev. Neurosci. 4, 365–375.


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Notifications With Pushbullet
This post looks at notification systems on Android, Chrome and Android Wear and provides a simple way to insert your own notifications in to the stream with Pushbullet. I presented this at the Google Developers Group in Brisbane this week, the post is a longer form of the presentation. The slide deck I used is available here, I've enabled commenting on the document so please feel free to leave your feedback. What are Notifications? Before we look at specific implementations we need to describe what a notification actually is, or more specifically what an idealised version of a notification is.…Read more »


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Odesza Saskatoon Tickets
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Fish & Seafood
Halibut & Hazelnut Romesco
Served on Yukon Gold Potatos
Romesco and Fish
2 tomatos (about 10 oz), peeled, seeded and diced
3/4 c hazelnuts, skinned and chopped
1/2 c piquillo peppers from jar, diced
4 Tbsp extra virgin olive oil, divided
2 cloves garlic, minced
2 tsp smoked paprika
1 Tbsp dry sherry
1/2 tsp salt
1/4 tsp cayenne
Juice from 1/2 lemon
1 T butter
4-5oz halibut fillets
salt and pepper to taste
3/4 c chicken stock
chopped fresh parsley 12 oz Yukon gold potatos, 1/2 inch dice and steamed
Place tomatos, hazelnuts, piquillo peppers, 2 Tbsp of the oil, garlic, smoked paprika, sherry, salt, cayenne and lemon juice in food processor; puree until smooth. Transfer romesco to mixing bowl; set aside.
Heat saute pan over medium-high heat; add remaining 2 Tbsp olive oil and butter. Fry halibut for 2 minutes on each side; transfer to a plate and set aside. Add chicken stock to the same pan and bring to a boil; whisk in romesco sauce. Reduce heat to medium-low, add Halibut. Cover pan with a lid and cook until done, about 2-4 more minutes. Serve with steamed potatoes.


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I sat in the evening session of Stake Conference last night as scrambled as a Kal-toh game. Organize kids to help, pick tomatoes, wash and boil and icewater and skin them (the tomatoes), cut and squeeze and blend and boil them, add spices, chop onions and peppers and add them, turn down to simmer, hurry and shower, dress and run, sit and hope for clarity. With wet curls and fast makeup and my most comfortable clothes, I was there, sitting in the back with my notebook and two pens, hoping for a revelation to order this chaos of late.
Kal-toh is the perfect analogy. A Vulcan strategy game highlighted in the last series of Star Trek, Kal-toh is a holographic jumble of rods that one can move one at a time to form an icosidodecahedron. The goal of the game is to find within the chaos the seeds of order, and when one finds and places the final piece, the rods suddenly move from a collapsed and unrecognizable mess to a beautiful, ordered shape. It happens in a moment, this transition, often to the surprise of all watching, just as we often find in our lives that a single change alters the whole structure of our chaos to sensibility and order.
As it turned out, a young woman with a tremulous voice pointed to my next move. She talked about digging a well with her father when she was a child. It was hard work at first, digging with a shovel larger than she was, but they moved the hard, rocky soil, then the sandy soil, then the wet clay. She was tired and the hole was deep and dark but she trusted her father who knew that there was water to be found there and knew the progression of the earth's layers. After the wet clay they found heavy, black mud.
"Mud's gross," she breathed tiredly, and the congregation tittered. "Yes, it is," I thought, exhausted. Chaotic, messy, and not very useful for drinking, especially after tedious, hope-draining digging.
Her father was elated, however, and pressed on excitedly. To him, the mud was the last layer before the water. And so it was. Her theme was our stake theme this year, taken from the soothing, melodic words of Isaiah: "Therefore with joy shall ye draw water out of the wells of salvation." To draw that water, one must dig the well, pressing through the layered rock and silt and compressed life of wet clay to the heavy mud that signals water is close. When that last, heavy shovelful lifts, the water begins to pour into the well one has created. Like a Kal-toh game when the last seed of order has been discovered, the work suddenly ceases and the beautiful, ordered shape of it all appears.
I saw other moves last night, and in my prayers this morning began to see the order, and one of the final moves to bring order to this chaos of many jobs to do, disappointment, confusion, and tragedy. Some time ago I was inspired to pray for the ability to do something I had been inspired to do but had no means, and the opportunity simply appeared in answer to the prayer. This morning I realized that this is a pattern.
When we are lost, we must pray for either inspiration or an opportunity, either the knowledge of what and how to do or a door simply opening without commentary. God seems to respond in one of those two ways. Sometimes we forget to keep doing this, even as we continue to drive our shovel into the earth and lift increasingly heavy loads from an increasingly deep well. The fact that the water isn't pouring in yet or the shape hasn't magically transformed doesn't mean you're not successful. You're just not finished yet.
As marathoners and hand well-diggers and people of faith all know, it's hardest at the end. The heaviness in and of itself is encouraging, because it means the goal is close, if we have a larger view. I come from a land of deep wells and large underground aquifers. Sometimes you hit water at 60 feet, but the well might run dry because you've only hit a temporary upper reservoir. The better wells are deeper, 120 feet or so, and tap into the main aquifer. This morning I realized that sometimes it's a blessing when we don't hit water quickly and are forced to dig deeper.
Deep wells are dependable. Those are the kind you can draw from with joy.


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Additional information
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This Replacement Bottle will fit any AMS Retriever® with a 5/8″ threaded bottle cap. If your Retriever was purchased before 2008, your bottle cap may need to be replaced also. (Tie-off button/washer 1033 (Z33-TW) and bottle cap 1027 (Z27) sold separately). Made in USA.
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This past week and a half I have been completely immersed in my most challenging project yet; the bathroom! There were a couple of times on this one, where I really hit a wall and didn't know how I was gonna finish this!
My tiny cottage has an equally tiny bathroom, with no storage, no cabinet, no linen closet, not even a towel rack!! Being a bit of a product-junkie, I have a LOT of stuff that needs to be put away– and now, after my successful bedroom transformation, I really wanted to make something that matched that, and didn't feel claustrophobic or cluttered.
So, I perused Craig's List again, and found a group of small white shelves that I could use as my "raw materials". I have found this to be an easier way to build things– kind of like altering clothes to fit you! The shelves were cheaper than buying wood and starting from scratch, and are easier to cut-and-piece and alter into what you want. And I did a LOT of altering on this one!!
I started by building the over the toilet space-saver/shelf first, and built it almost up to the ceiling! I added doors and lots of small shelves inside to house all my cosmetics! I also traded out the wooden shelf I built for a smaller, less bulky pre-made shelf, which I adjusted to house a hamper on the bottom! ( Don't worry, the wooden shelf is not going to waste, and has moved to the pantry.) I also added a ring of shelves around the ceiling for extra storage.
Next, I built an under the sink cabinet, with a shelf inside. The whole cabinet actually pulls out, in case you need to get to the plumbing! Like in the bedroom, I tried to make most everything free-standing with only a few anchors for safety so as not to mess up the plaster walls.
I'm very proud of myself for pushing through all my doubts and frustrations on this one, and really pleased with my results!! I can't believe I built this all!! WOW!
Here is what I started with– pretty much nothing!


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The signing of this unequal pact is evidence that the corruption and muddleheadedness of the Ma administration exceeds even that of the Qing Dynasty's final years. A century ago, Qing Dynasty subjects understood that they had to rebel and overturn the dynasty.
Taiwan is now a democracy, so how can people continue to accept the corruption and muddleheadedness of Ma and his government? How can Taiwanese let Ma sell Taiwan out to the CCP, and their freedom to a dictator? The service trade agreement is a new version of the 1895 Treaty of Shimonoseki [under which China ceded Taiwan to Japan] and the people of Taiwan must not be sold off again.
This is a matter of life or death that transcends the blue-green divide. The TSU calls on all Taiwanese to stand up and be counted, to stop the Chinese Nationalist Party (KMT) and the CCP from selling the people of Taiwan down the river and to exert pressure on KMT legislators to resist being manipulated by Ma.
The TSU will join hands with all legislators from opposition parties in a legislative scorched earth tactic. We will refuse to budge a single step and we will recapture the right of Taiwanese to be their own masters.
Huang Kun-huei is the chairman of the Taiwan Solidarity Union.
Translated by Perry Svensson


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About Invest in Scottish Properties
A family run business with lots of experience.
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Wynnum Acupuncture
Local Natural Health Clinic
Austin Therapies
Brisbane Acupuncturist
Dr. Sally Austin (Registered Acupuncturist)
Is Your Health on Track?
Austin Therapies natural health therapist, Dr. Sally Austin (Registered Acupuncturist), locally situated and providing Wynnum acupuncture services that are individualised to manage your pain issues. Providing you professional holistic health care that empowers you to take control of your health and getting your health back on track.
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Acupuncture is used to treat a variety of conditions from sporting injuries to irritable bowel syndrome (IBS), infertility to anxiety and eczema to poor posture, acupuncture therapy is undoubtedly one of the most well-known practices of Eastern medicine. And it's effective too – that's why we use it at Austin Therapies Brisbane Acupuncture clinic in our Pain Management Health Care programs.
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Austin Therapies is very conveniently located only minutes from the Gateway Motorway, making it easy to access from the north, south or bay side of Brisbane. We are local to suburbs to: Wynnum, Wynnum West, Carina, Carina Heights, Gumdale, Chandler, Carindale, Tingalpa, Murarrie, Wakerley, Ransome, Capalaba West, Capalaba, Manly, Manly West, Hemmant Mackenzie, Cannon Hill, Birkdale, Thornside, Sheldon, Lota, Wellington Point, Alexandra Hills, Cleveland, Ormiston to name a few, so pick up the phone and call Sally on 0421 411 508 or 3348 8131 right now!


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DOTr committed to modernizing jeepneys by 2020
MANILA The Department of Transportation (DOTr) is sticking with its timeline for jeepneys across the country to be modernized by 2020, an official said Tuesday.
Tuluy-tuloy ang PUV modernization; kailangan po natin sila palitan ng bago. The transition period still remains the same; 2017 napirmahan ang Omnibus Franchising Guidelines, binigyan natin ng three years basically until 2020 (The PUV modernization will push through; the jeepneys must be replaced with new ones. The transition period still remains the same; the Omnibus Franchising Guidelines was signed in 2017, we are giving three years until 2020), DOTr Assistant Secretary for Road Transport and Infrastructure Mark de Leon said in a radio interview.
De Leon was reacting to calls from various sectors to defer the program due to the high costs of acquiring the modern vehicles and concerns on displacement of livelihood of jeepney operators and drivers.
The DOTr official said jeepney operators are given the choice to acquire vehicles suitable for their operations.
Operators have the choice to buy their vehicles kung Euro 4, clean diesel or Euro 5 bahala sila diyan. Or electric kapag sa tingin nila makakatipid sila (Operators have the choice to buy their vehicles whether it is Euro 4, clean diesel or Euro 5 they have the choice. They can also choose electric powered vehicles to save on their costs)," de Leon said.
Hindi po tayo ang namimili ng mga manufacturers. Bahala ang operators na mamili ng manufacturers na gusto nila. Kung sa tingin nila etong jeepney nila ay fit sa ruta nila yun ang pipiliin nila (We are not the ones selecting the manufacturers. Operators have the choice what manufacturing firms they prefer. If they think that this particular kind of jeepney is fit for their routes they will choose it), he added.
The department is implementing a three year transition period since last year that will replace around 179,000 jeepney units nationwide.
Modern public utility vehicles (PUVs) have Euro-4 compliant fuel engines and equipped with closed-circuit television cameras, a GPS navigation system, automated fare collection system, speed limiters, dashboard cameras, and Wi-Fi.
The cost of the modern PUV ranges from PHP1.5-1.8 million compared to jeepney units, which are costing within PHP900,000 to PHP1 million.
An estimated PHP1.5 billion will be given to transport corporations and cooperatives to purchase new PUVs through the Development Bank of the Philippines' Program Assistance to Support Alternative Driving Approaches (PASADA). The program will feature 5-percent equity for vehicle purchase, 6-percent interest rate and seven-year repayment period.
Under PASADA, a maximum of 95 percent of the cost of the vehicle, and a maximum of 75 percent of the cost of the support facilities comprise the total loan per borrower. The government will also offer a maximum subsidy of PHP80,000 to cover the equity payment.
The Land Transportation Franchising and Regulatory Board (LTFRB) will require existing operators to consolidate into cooperatives or consortiums to gain better access to resources, share operations and maintenance costs and maximize profits thru efficient vehicle dispatch.
A total of 486 cooperatives were already formed as of September 2018.
The DOTr is also holding workshops and seminars among local government units to implement their respective route rationalization plans, which will be used for the deployment of modern public utility vehicles based on passenger demand.
Under its Omnibus Franchising Guidelines, public transport routes will be planned by local government units (LGUs) based on the current and projected travel patterns in their respective areas. These routes will be contained in the Local Public Transport Route Plan of LGUs which will serve as basis for franchise issuance by the LTFRB.
To date, the DOTr has opened 15 operational routes for modern jeepneys in the National Capital Region, Western and Central Visayas.
In a recent Senate hearing on the PUV Modernization Program, Senator Bam Aquino pushed for a five-year transition period for its implementation as he cited that it would not be feasible for jeepney operators and drivers to afford the new jeepney units within three years. (PNA)
Source: Philippine News Agency


text: Bliss Bridal Boutique in Whitby has been creating memories in Durham Region for over 14 years. Bliss is the largest upscale bridal salon in Durham and the surrounding area. Our mission is to exceed your expectations. With an incredible selection of wedding gowns and bridesmaid's dresses, a bright modern, open concept environment, personalized customer service, topped with a best value guarantee, we are confident that we can earn your business.


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Address: Johannesburg, Gauteng
Location: See on Map
Contact No: 082 553 4757
Website: www.oopsiedaisyflowers.co.za
If you are planning your wedding, a special or corporate event, simply contact Oopsie Daisy Flowers. We will assist you with all your floral and décor requirements and we also offer you expert advice with perfection and flair.
With an eye to detail and focussed on providing outstanding service, let us assist you. We offer you the latest in floral design and we also have a wide variety of décor items, from vases, candelabras, tablecloths etc for you to choose from.
We design your wedding or event and prepare each quote especially for you keeping in mind your unique style, special requirements and off course budget. Therefore, each quote is tailor made. Oopsie Daisy Flowers have been in business since 2007 and is run and owned by Charlene Lubbe. We service the whole of Gauteng and all surrounding areas. Charlene is assisted by her Mother Evelyn and a team of florists which were trained to deliver only the best. Together they make an awesome team.
Find us on Facebook: www.facebook.com/OopsieDaisyFlowers


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The regulations specify that army personnel running the prison camps will prepare an "Inmate Labor Plan" that will comply with 18 U.S.C. 4125(a), governing civilian inmate labor. That section of the U.S. Code allows the U.S. attorney general to make available to the heads of U.S. departments, including the Army, the services of U.S. prisoners to engage in labor, including "constructing or repairing roads, cleaning, maintaining and reforesting public lands, building levees and constructing or repairing any other public ways or works financed wholly or in major part by funds appropriated by Congress." PRISONERS COULD ALSO BE ORDERED TO WORK FOR PRIVATELY OWNED BUSINESSES. Who needs to pay for labor, when you can use the prison population for your slave labor?
In America today anyone can be arrested for pretty much anything. Charges are optional, as long as you can be considered to be an enemy of the state. Having a dissenting opinion makes you fair game. Anyone can be thrown in prison, without trial or even a lawyer to advise them. Once an individual is in prison, they can and likely will be sent off to the "Civilian Inmate Labor Program" camps. The U.S. prison population is working for various industries for a pittance. For the tycoons who have invested in the prison industry, it has been like finding a pot of gold. They don't have to worry about strikes or paying unemployment insurance, vacations or comp time. All of their workers are full-time, and never arrive late or are absent because of family problems; moreover, if they don't like the pay of 25 cents an hour and refuse to work, they are locked up in isolation cells.
There are approximately 2 million inmates in state, federal and private prisons throughout the country. According to California Prison Focus, "no other society in human history has imprisoned so many of its own citizens." The figures show that the United States has locked up more people than any other country: a half million more than China, which has a population five times greater than the U.S. Statistics reveal that the United States holds 25% of the world's prison population, but only 5% of the world's people. From less than 300,000 inmates in 1972, the jail population grew to 2 million by the year 2000. In 1990 it was one million. Ten years ago there were only five private prisons in the country, with a population of 2,000 inmates; now, there are 100, with 62,000 inmates. It is expected that by the coming decade, the number will hit 360,000, according to reports. What has happened over the last 10 years? Why are there so many prisoners?
* Jailing persons convicted of non-violent crimes, and long prison sentences for possession of microscopic quantities of illegal drugs. Federal law stipulates five years' imprisonment without possibility of parole for possession of 5 grams of crack or 3.5 ounces of heroin, and 10 years for possession of less than 2 ounces of rock-cocaine or crack. A sentence of 5 years for cocaine powder requires possession of 500 grams - 100 times more than the quantity of rock cocaine for the same sentence. In Texas, a person may be sentenced for up to two years' imprisonment for possessing 4 ounces of marijuana. In New York, the 1973 Nelson Rockefeller anti-drug law provides for a mandatory prison sentence of 15 years to life for possession of 4 ounces of any illegal drug.
* The passage in 13 states of the "three strikes" laws (life in prison after being convicted of three felonies), made it necessary to build 20 new federal prisons. One of the most disturbing cases resulting from this measure was that of a prisoner who for stealing a car and two bicycles received three 25-year sentences.
* Longer sentences. The passage of laws that require minimum sentencing, without regard for circumstances. . A large expansion of work by prisoners creating profits that motivate the incarceration of more people for longer periods of time.
* More punishment of prisoners, so as to lengthen their sentences.
Who is investing? At least 37 states have legalized the contracting of prison labor by private corporations that mount their operations inside state prisons. The list of such companies contains the cream of U.S. corporate society: IBM, Boeing, Motorola, Microsoft, AT&T, Wireless, Texas Instrument, Dell, Compaq, Honeywell, Hewlett-Packard, Nortel, Lucent Technologies, 3Com, Intel, Northern Telecom, TWA, Nordstrom's, Revlon, Macy's, Pierre Cardin, Target Stores, and many more. All of these businesses are excited about the economic boom generation by prison labor. Just between 1980 and 1994, profits went up from $392 million to $1.31 billion. Inmates in state penitentiaries generally receive the minimum wage for their work, but not all; in Colorado, they get about $2 per hour, well under the minimum. And in privately-run prisons, they receive as little as 17 cents per hour for a maximum of six hours a day, the equivalent of $20 per month. The highest-paying private prison is CCA in Tennessee, where prisoners receive 50 cents per hour for what they call "highly skilled positions." At those rates, it is no surprise that inmates find the pay in federal prisons to be very generous. There, they can earn $1.25 an hour and work eight hours a day, and sometimes overtime. They can send home $200-$300 per month.
Thanks to prison labor, the United States is once again an attractive location for investment in work that was designed for Third World labor markets. A company that operated a maquiladora (assembly plant in Mexico near the border) closed down its operations there and relocated to San Quentin State Prison in California. In Texas, a factory fired its 150 workers and contracted the services of prisoner-workers from the private Lockhart Texas prison, where circuit boards are assembled for companies like IBM and Compaq. Oregon State Representative Kevin Mannix recently urged Nike to cut its production in Indonesia and bring it to his state, telling the shoe manufacturer that "there won't be any transportation costs; we're offering you competitive prison labor (here)."
The prison privatization boom began in the 1980s, under the governments of Ronald Reagan and Bush Sr., but reached its height under William Clinton, when Wall Street stocks were selling like hotcakes. Clinton's program for cutting the federal workforce resulted in the Justice Departments contracting of private prison corporations for the incarceration of undocumented workers and high-security inmates. Private prisons are the biggest business in the prison industry complex. About 18 corporations guard 10,000 prisoners in 27 states. The two largest are Correctional Corporation of America (CCA) and Wackenhut, which together control 75%. Private prisons receive a guaranteed amount of money for each prisoner, independent of what it costs to maintain each one. According to Russell Boraas, a private prison administrator in Virginia, "the secret to low operating costs is having a minimal number of guards for the maximum number of prisoners." The CCA has an ultra-modern prison in Lawrenceville, Virginia, where five guards on dayshift and two at night watch over 750 prisoners. In these prisons, inmates may get their sentences reduced for "good behavior," but for any infraction, they get 30 days added - which means more profits for CCA. According to a study of New Mexico prisons, it was found that CCA inmates lost "good behavior time" at a rate eight times higher than those in state prisons.
Profits are so good that now there is a new business: importing inmates with long sentences, meaning the worst criminals. When a federal judge ruled that overcrowding in Texas prisons was cruel and unusual punishment, the CCA signed contracts with sheriffs in poor counties to build and run new jails and share the profits. According to a December 1998 Atlantic Monthly magazine article, this program was backed by investors from Merrill-Lynch, Shearson-Lehman, American Express and Allstate, and the operation was scattered all over rural Texas. That state's governor, Ann Richards, followed the example of Mario Cuomo in New York and built so many state prisons that the market became flooded, cutting into private prison profits. After a law signed by Clinton in 1996 - ending court supervision and decisions - caused overcrowding and violent, unsafe conditions in federal prisons, private prison corporations in Texas began to contact other states whose prisons were overcrowded, offering "rent-a-cell" services in the CCA prisons located in small towns in Texas. The commission for a rent-a-cell salesman is $2.50 to $5.50 per day per bed. The county gets $1.50 for each prisoner.
Ninety-seven percent of 125,000 federal inmates have been convicted of non-violent crimes. It is believed that more than half of the 623,000 inmates in municipal or county jails are innocent of the crimes they are accused of. Of these, the majority are awaiting trial. Two-thirds of the one million state prisoners have committed non-violent offenses.


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First Annual Student-Parent Graduation Celebration
May 3, 2018 @ 6:00 pm - 8:00 pmFree
You are invited to the First Annual Student-Parent Graduation Celebration. May 3rd, 6-8 p.m. Kansas Union- Kansas Room (Level 6). Open to undergrad and grad students! Celebrate graduation with other student-parents, guardians, caregivers, and their families! The following will be included: Kids activities, photobooth, light refreshments. Each graduate who attends will recieve a small gift! RSVP online by April 25th! Emilytaylorcenter.ku.edu/parent-student-graduation-rsvp. http://emilytaylorcenter.ku.edu/parent-student-graduation-rsvp%E2%80%8B. Questions? Contact email@example.com.