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Results Reflection: The 12 Ride Flat Pedal Challenge
An inspiring and useful course completion report from Renzo who just finished The 12 Ride Flat Pedal Challenge. Thanks Renzo!…
Completion Reflection Questions and Answers from Renzo:
1) How would you describe the increase of connection to and with your bike from Ride #1 and now after Ride #12?
a) Before starting the flat pedal challenge, I would have described my connection to my bike as a good combination of line choice assisted by being clipped in, with the "clipless" (man, I hate that paradox) aspect providing forgiveness for flawed technique. I was "one with the bike" in a more literal, mechanical sense due to being grabbed by the clipless system. That allowed me to force the bike into following me instead of working with it to achieve a goal in a smoother way.
b) Currently, I'd say I'm "one with the bike" in a more metaphorical or spiritual sense. I'm more aware of the feedback that I'm receiving through the soles of my feet, and I'm using my body suspension much more. Additionally, my technique has improved significantly, with me being more active on the bike and using these skills to stay on the bike safely. I'm now more conscious of how much I still have to improve to get to where I want to be. I wasn't doing as well as I thought before starting this challenge.
2) What aspects of your riding technique have changed?
a) I'm improving my proactive movements, allowing me to be better set up when going into technical features; once in these features, my body suspension and improved technique are helping me stay on the bike and with better body position.
3) What part of riding on flats has been the most fun?
a) I've had the most fun working on becoming a more dynamic rider, using my body suspension, weight, position, and foot position to use the terrain more effectively. That includes pumping, hopping, being light or heavy on the pedals, and other valuable techniques that help me keep my feet on the pedals with more confidence. I really enjoy looking for features that can be used as launchers for small and fun jumps, drops and turns.
4) How would you say your riding style has changed?
a) I believe that I'm approaching obstacles with more confidence and better prepared to move according to both what's coming next and what's happening below me. I like to think that I'm riding with a smoother style, because it certainly feels that way. I've felt more naturally supported by platforms than I did with the clipless setup. My calves used to feel very tired during and after rides due to the spindle being beneath the balls of my feet, but that has disappeared with flats.
5) What was the biggest overall benefit to flat pedals that you have discovered?
a) Challenging myself to improve on basic skills has been fun and rewarding. Using flats has ensured that I develop proper technique instead of relying on a handicap to achieve a desired result.
6) What was the biggest challenge with riding flat pedals?
a) Starting the process of helping my body forget all those terrible techniques I'd adopted with those crutches (clipless system). Clipless may be helpful in many situations, but good technique will help me improve whether I'm clipped in or not, and that's something many people refuse to accept.
7) Will you continue to ride with flats from now on, or will you ride clipless, or both? I'd love to know your rationale for that answer!
a) I plan to mainly ride flats from now on, though I will keep my Mallet DH pedals for occasional use. I feel that the dynamism I've added to my rides by going to flats is something worth keeping, and it's clear to me that my skills still require lots of practice to get to where I'd like to be.
b) Having experienced how much of a crutch a clipless system can be for poor technique, forgiving many bad habits and even fomenting them, I believe that skill progression will be done on flats, not clipless. There will be occasions for clipless, but I will now consider that to be an alternative, not my preferred system. This challenge has made me ride in a more fun way, and even though I know I can take this to clipless, I believe doing so will interrupt the positive progression I'm having, probably making me revert to the bad habits that I'm barely breaking free from at this time.
8) What else have you learned from this challenge?
a) I've learned that most riders are extremely skeptical about most of what I've said here, probably because of sheep mentality and peer pressure in favor of clipless systems. It's a shame that so few people in my area are interested in giving it a try! Most people are wrongly coached, and end up believing that clipless is safer (with no need to develop correct technique), and that all you need is a combination of your clips, unclipping skills, and good cadence.
b) On a more personal note, I've learned that I'd developed some pretty bad habits, and my skills were lower than what I'd estimated. I've discovered many opportunities in my riding which I hope to continue to improve on in the near future.
9) What would you tell someone interested in trying flat pedals for the first time?
a) Both clipless and flat pedal systems can be used to develop our skills, but the best results towards proper technique will come when we rid ourselves of the clipless crutch. You can always go back if they make you feel safer, but you'll be a better rider because you learned the proper way.
Thank you for the challenge, Ryan and Team. I look forward to working with you again in the near future!
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2 picks as well as the 2016 Miami No."That's why you want to push like hell.The Rams are attempting to load up for a Super Bowl run with this mindset.If you would like to search for all players born on a certain day, for example all players born on December 25th in any year, choose the month and day with the drop down boxes and then choose the 'Month and Day Search' option.I spent some time getting in my own way.
In the spring of 2017, a wide majority of major publications pegged him as the top quarterback in their mock drafts.Louis-record 11-game winning streak to jump back into playoff contention and finish third in the Central Division, one point behind the first-place Nashville Predators.And we won't stop until we track them all down �?including you, person who owns .Just to come and witness the amazing work that's happening out here is incredible.
Perlini was acquired by the Blackhawks with forward in a trade with the Arizona Coyotes for forward on Nov.Griffin is from Oklahoma and had long been linked to the Thunder.What is strange, though, is that Panarin is third on that line in scoring in each of the top line's past 12 games.The gamble paid off.
Thus, they can concentrate on streamlining the organization, making cost-efficient decisions with the promise of future spending, you know, This was popularized by the Cubs and the Astros, teams that cut their payroll for years of noncompetitive seasons while repopulating their farm systems with talent, then spending when their teams were ready; both franchises won World Series as a result.Stephen Curry Likely Set For 200 Percent Increase On Next Contract Sep 28 12 PM If Stephen Curry decides to re-sign with the Golden State Warriors, he could sign a five-year, $165 million max deal based off the current cap estimates.Birthday: June 16 Considered one of the best and most influential musicians of any decade, Tupac was a central figure in West Coast hip-hop.

subset: commoncrawl


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4500 lm400 lm
1.25 h12 h
4500 lm400 lm
1.25 h12 h
Ledlenser iF8R Spotlight
POWERFUL WORK LIGHT WITH BLUETOOTH APP FOR REMOTE CONTROLConstruction site. Not enough light. Your light source is suspended 10 feet above you on a steel beam and you want to light up the dark as quick as possible? No problem! With the Ledlenser iF8R's bluetooth control via the Ledlenser Connect App, you can control and program light settings directly from your smartphone. With up to 4,500 extremely powerful lumens, the iF8R provides optimum illumination for up to 12 hours (on low power mode) of continued use. It's got a magnetic base, and can easily be tilted or pivoted to get light to where you need to see most. And if you need a quick recharge on your phone, this work spotlight also has a built-in power bank feature to charge it right back up.
Regular price $377.95
Special Information
Light Functions
- Power - high light output for every situation
- Mid Power - medium light output for every situation
- Low Power - economical light for long battery life, glare-free reading and working
- Multifunctional Switch - multi-function switch for quick and easy control of individual light functions
Special functions
- Remote control - control the light via Bluetooth app on your smartphone
- Built-in power bank - supplies power for cellphones and other devices
- Efficient cooling element - for a long life and optimum performance
- Built-in magnet - to easily attach to metal surfaces (e.g. steel beams)
- IP54 - Protection against water projected in powerful spray
Did you know that conventional, disposable batteries can require up to 500 times more electricity to produce than they can release? By opting for rechargeable batteries, not only are you saving money in the long-run by reusing the same batteries, but you're no longer throwing disposables away, which is a plus for Mother Earth.
Technical Details
Ledlenser iF8R Spotlight
- LED Configuration 1 x 66W COB LED
- Luminosity MAX 4500 lm - MIN 400 lm
- Battery Duration1 MAX 12 h - MIN 1.25 h
Battery and Casing
- Battery 1 x Li-ion 11.1V
- Battery Duration2 44.40 Wh
- Water Resistance IP54
- Rechargeable Yes
Height and Weight
- Width 307 mm
- Height 142 mm
- Depth 44 mm
- Weight 1740 g


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Sarah Paulson introducing Kathy Bates..... name a better friendship pic.twitter.com/B8Q15b09tX— p.c ? (@90sIover) March 27, 2017
@enews @cubagoodingjr ???I'm going to give you a chance to explain yourself. What on earth possesed you to lift up a lady's skirt in public?— New Beginnings? (@Ltkforever) March 27, 2017
Cuba Gooding Jr. has just embarrassed himself at #AHS Paleyfest. This is junior high behavior. Leave the women alone https://t.co/wdMdJR161O— Margaret Holt (@chicagomargaret) March 27, 2017
So not okay. A man doing that to a woman is shameful https://t.co/Qo96foU49i— SallyThatTwirl (@SupremelyOne) March 27, 2017
How would @cubagoodingjr react if a man walked up to his daughter, Piper and lifted her dress up behind her back? #itsneverok— SallyThatTwirl (@SupremelyOne) March 27, 2017
Um... so is @cubagoodingjr allowed to get away with lifting @MsSarahPaulson skirt at @paleycenter? Total disrespect to a woman— WinterThreds (@piratepenzan) March 27, 2017
@cubagoodingjr hi, dude. did you apologize to Sarah? you should if you didn't bc what you did was Gross and Disrespectful— kommissar (@choirgirI) March 27, 2017
Okay, yes I went back to screenshot this. But does he seriously think this is okay? @cubagoodingjr @MsSarahPaulson pic.twitter.com/xHEnURhY3H— Elle ☪ (@Heavenly_Sarah) March 27, 2017


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Resources for Indigenous Students
The faculty is committed to encouraging increased enrolment by Indigenous students and working with Indigenous students who are currently enrolled, to assist them to complete their studies successfully.
Within the Faculty
The Liaison Officer for Indigenous Students acts as a contact point for indigenous students, to provide mentoring and advice regarding: academic progress, career path development and personal issues.
Within the University
The William Cooper Institute provides support services for indigenous students.


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Faith in Humanity Restored -- 8-yo Girl With Brain Cancer Uses Her Make-A-Wish to Clean Up Trash
Kansas City, MO -- In this consumerist world, where so many are infatuated with immediate gratification, those of us who see it from the outside in can often become overwhelmed with the rampant carelessness and complacency surrounding us. So, when something or someone breaks free from this paradigm of self-destruction and shines a light into the darkness, that light should be shared.
Thanks to the kind-hearted founders of the Make-a-Wish Foundation, children throughout the United States and its territories, who are facing life-threatening medical conditions, are granted a wish every 37 minutes.
Most of the wishes of the children are for trips to Disney World, or to meet their favorite singer -- and there is absolutely nothing wrong with that notion. The very idea of a dying child wishing for something outside of their own desires seemed mind-blowingly impossible -- until now.
Meet 8-year-old Amelia Meyer. When Amelia was just a little girl; she was diagnosed with brain cancer. Despite her bleak prognosis Amelia loved to go outside and play, and she did so often, as she had a fondness for nature.
"She's always been that kid I cannot get inside," her mother Jill Meyer said.
Earlier this year, Amelia was granted a wish by the Make-a-Wish Foundation and last Saturday, that wish came true. But Amelia didn't wish to meet Mickey Mouse or Taylor Swift -- she wished to pick up trash.
"I know some kids might want to go to Disneyworld and stuff, or meet famous people, but I really feel like Amelia picked the right wish," Amelia's best friend Samantha Asquith said to WDAF.
Recommended for You
She could have had anything she wanted and this selfless, beautiful, marvelous little girl chose to clean up other people's messes.
"It doesn't look nice and another reason is because it can stay dirty and it can get animals sick," Amelia said.
According to WDAF,
Thanks to the help of Helzberg Diamonds, The Kansas City Missouri Parks and Recreation Department, the Kansas City Fire Department, the Kansas City Police Department, and hundreds of volunteers, Amelia pulled up to Swope Park, to a scene fit for a queen. She said, "I thought there was just going to be some people, not this much."
She seemed most comfortable in her own element, walking and running hand in hand with her best friends. Samantha said, "I've known her since preschool and she's just been my very best friend. She's been really nice to me and really supportive of me when I have rough times."
Hundreds helped Amelia pick up trash at Swope Park and other parks around the city. Mayor Sly James read a proclamation, naming February 27, 2016 "Amelia Meyer's Take Care Of The World Day." People in cities across the country and the world picked up trash in their hometowns in honor of Amelia. Followers on social media also joined in with by tagging posts and photos with #AmeliasWish
The selflessness and caring exhibited by Amelia are awe-inspiring. When all the negativity in the world seems overwhelming, these small, yet infinitely profound moments have a way of restoring our faith in our fellow human. Her actions should serve as an example to all. Please share her story with your friends and family so that they may be inspired by this little girl's astounding kindness.
Matt Agorist is an honorably discharged veteran of the USMC and former intelligence operator directly tasked by the NSA. This prior experience gives him unique insight into the world of government corruption and the American police state. Agorist has been an independent journalist for over a decade and has been featured on mainstream networks around the world.


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I am so excited at how quickly this quilt is coming together! who knew that having the blocks already sewn would be such a headstart?! ( -;
In the previous scene, we cut sashing strips from three different fabrics and sewed the A sashing strips to the four edges of the blocks, framing them, like this:
press toward the sashing strips (purple)
Next, we will sew up the sashing B and C strips to create the center of our quilt.
in the first step, you cut 6 strips of sashing B each 1 1/2″ by the width of fabric. From those strips, cut sixteen short strips 2 1/2″ x 1 1/2″. Set the remaining B strips aside for now.
From Sashing fabric C you have 10 strips 2 1/2″ by width of fabric. From these strips cut 8 strips *13 1/2″ x 2 1/2″; plus 4 strips *12 1/2″ x 2 1/2″
*these measurements are for sampler blocks that are 12″ finished. Adjust according to your block size. For example, if your blocks will finish 9″ cut 8 strips 10 1/2″ and 4 strips 9 1/2″
Cut 4 squares from cornerstone fabric 2 1/2″x 2 1/2″
Sew one 2 1/2″ B strip to one end of each of the eight *13 1/2″ C strips like this:
Press toward the green (larger) strip
|Make 8: B strip plus C strip
Sew one 2 1/2″ B strip to BOTH ends of the four *12 1/2″ C strips like this:
press toward the green (larger) strip
|Make 4: 2 B strips plus 1 C strip
Next, you will combine the sashing strips created above with the corner stone squares to create longer sashings to sew between blocks. Press away from the corner squares (toward the B sashings)
|Make 2
Next, sew two of the longer sashing strips created above (the *13 1/2″ plus one B strip) between three of the sampler blocks like this:
(huge apology for the bad photos)
press toward the green sashing (away from the blocks/purple sashing strips)
|Make 2
Then sew the final two shorter sashings (the *12 1/2″ plus two B strips) between the final three sampler blocks like this:
|Make 1 (center row of blocks)
This makes three rows of three blocks with sashings between them, plus two long sashing strips that include the corner stones. Lay the pieces out to form the full quilt center
Sew it all together!
isn't it pretty?
|just before sewing them all together…
Next we sew the remaining strips of Sashing C (the green) to all four sides to frame the entire square.
Measure the first width of the quilt and piece/trim your sashing C strips to the correct length,
Sew the two strips of this length to opposite sides of the quilt.
Measure in the same way to determine the length of the remaining two opposite sides and sew them on.
Here is mine so far. Finally had a day dry enough to take an outdoor picture! yippee.
next scene is the two borders, then finished.
<<click here>> for next step
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The Kampan Hand Mirror is a wiggley wobbley hand mirror that functions as a wall piece or tabletop vanity mirror. Comes with a L-hook for wall display.
This product is final sale. Due to the delicate nature of this object, we will not be able to offer any returns or exchanges.
Size: 11" L x 7" W
Material: Clay & glass
Please Note: All of our prices are in USD.
The Kampan Hand Mirror is a wiggley wobbley hand mirror that functions as a wall piece or tabletop vanity mirror. Comes with a L-hook for wall display.
Open Editions
{We offer free shipping within the U.S for orders over $100, and free international shipping for orders over $400 (excluding Switzerland, Sweden and select countries in Africa).
Order Processing: All orders ship out of the USA. Please allow 1-3 business days for your items to ship out. You will receive a shipping confirmation email, with tracking as soon as your package goes out.
Local Pickup: You will receive an email when your order is ready for pickup. Please allow 2-4 days for your order to be ready. All local pickup orders are processed at our warehouse and transported to our retail location. Please contact us by phone or email for any questions: 626-714-7414 firstname.lastname@example.com.
International Orders: All international orders are subject to customs, taxes, import duties, brokerage fees, or any additional charges by your local government. As the recipient, you are solely responsible for any of these charges.
Returns: All returns must be made within 30 days of purchase. All items must be in original condition, packaging, and arrive back to us undamaged. Please note, if you received free shipping, we will be deducting the original shipping costs from your refund. We do offer free return postage on all domestic orders. Please contact firstname.lastname@example.com for further instructions.
Final Sale: All ceramics are final sale. Due to their delicate nature, we will not be able to offer any returns or exchanges.
Get In Touch: If you have any issues or questions about your order, please contact us at firstname.lastname@example.com


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Well, with the anticipation of fall just around the corner we have been planting our new little seedlings into the ground. They were lovingly nurtured all summer long to reach for the sky and grow tall and strong from within their "red solo cup" pots.
Michelle cleared out some space in our existing inventory/seedling bed to make room for all the new babies. It is so great to see them growing up!
Michelle replanted this bed to make more room as well.
This new bed was our planting table area. Do you see a theme developing here? Of course each year we have plants to dig up and divide, so we needed
new beds for those, as well as additional pot-in-pot inventory plants.
Michelle has been diligently trying to find new bed space without totally giving up all the grassy areas of the yard. I thought she liked mowing the grass.
Thanks to our neighbors for helping us move from Red Solo Cups to real planting containers.
This new bed will eventually be for our planted inventory that can be dug up upon request.
Bicycle Bed Expansion
We've expanded the "Bicycle Bed" to include another path and a few more plants to dig up as needed
We had a great summer and amazingly, even our Plumeria plant does not want to say goodbye to the warm weather. There is one last bloom that still wants to open.
Of course, one of the most fall activities is the harvesting of our seeds. We hybridized a few plants this year but Mother Nature sure did her thing as well. We harvested the seeds and have them drying out so we can put them in the refrigerator for a few months until we plant them.
And last but not least, we cut back all the plants getting ready for the snow blankets of winter. Of course Coco had to help too!
Even though the main growing season is over, there will still be a lot of activity in the garden, so stop back often to see what's happening! Thanks for stopping by and we hope to see you again next month!
Dee & Michelle
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- Research article
- Open Access
- Published:
Muscle-fiber transdifferentiation in an experimental model of respiratory chain myopathy
Arthritis Research & Therapy volume 14, Article number: R233 (2012)
5424 Accesses
21 Citations
Skeletal muscle fiber composition and muscle energetics are not static and change in muscle disease. This study was performed to determine whether a mitochondrial myopathy is associated with adjustments in skeletal muscle fiber-type composition.
Ten rats were treated with zidovudine, an antiretroviral nucleoside reverse transcriptase inhibitor that induces a myopathy by interfering with mitochondrial functions. Soleus muscles were examined after 21 weeks of treatment. Ten untreated rats served as controls.
Zidovudine induced a myopathy with mitochondrial DNA depletion, abnormalities in mitochondrial ultrastructure, and reduced cytochrome c oxidase activity. Mitochondrial DNA was disproportionally more diminished in type I compared with type II fibers, whereas atrophy predominated in type II fibers. Compared with those of controls, zidovudine-exposed soleus muscles contained an increased proportion (256%) of type II fibers, whereas neonatal myosin heavy chains remained repressed, indicating fiber-type transformation in the absence of regeneration. Microarray gene-expression analysis confirmed enhanced fast-fiber isoforms, repressed slow-fiber transcripts, and reduced neonatal fiber transcripts in the mitochondrial myopathy. Respiratory chain transcripts were diminished, whereas the enzymes of glycolysis and glycogenolysis were enhanced, indicating a metabolic adjustment from oxidative to glycolytic capacities. A coordinated regulation was found of transcription factors known to orchestrate type II fiber formation (upregulation of MyoD, Six1, Six2, Eya1, and Sox6, and downregulation of myogenin and ERRγ).
The type I to type II fiber transformation in mitochondrial myopathy implicates mitochondrial function as a new regulator of skeletal muscle fiber type.
Low muscle endurance and fatigue are frequent symptoms of patients with diseases that limit the oxygen supply of muscles by its capillaries or muscular oxygen use by its mitochondria. Muscle capillaries are lost in dermatomyositis [1], systemic sclerosis [2–4], and chronic obstructive pulmonary disease (COPD) [5], and qualitative or quantitative defects of respiratory chain components are found in the mitochondrial myopathies [6, 7]. Ultrastructural changes in mitochondria and respiratory-chain dysfunction can also be induced by medications (statins [8], zidovudine, and other antiretroviral nucleoside analogues [9], and potentially, alcohol [10]). The physiological explanations for muscle fatigue and the adjustments of muscle metabolism to such respiratory compromise have, however, been only poorly addressed.
In humans, most skeletal muscles are equipped with more than one fiber type to accommodate a wide range of forces, kinetics, and endurance. Muscles specialized for maintaining postural tone have a high proportion of fibers that contract slowly (type 1 fibers), whereas muscles specialized for rapid movements contain a high proportion of fast-twitch (type 2) fibers. To account for fiber-type diversity, virtually every contractile protein of muscle fibers exists in different isoforms. Muscle-fiber types have also developed fine-tuned systems of energy delivery, which result in diverse metabolic profiles and oxygen requirements. Fiber types are, however, not static, as endurance training, weight loading, or hormonal factors can promote fiber-type transformation, even in adult muscles, by means of a coordinated antithetic regulation of fast and slow gene programs [11–13]. No study has investigated skeletal muscle fiber-type adjustments in response to a primary defect of the mitochondrial respiratory chain.
We therefore investigated how skeletal muscles adjust to mitochondrial dysfunction and whether they can alter their fiber-type composition. In this study, we modeled a mitochondrial myopathy by feeding rats with zidovudine, a nucleoside-analogue reverse transcriptase inhibitor that impairs with the replication of mitochondrial DNA and interferes with mitochondrial function through a variety of mechanisms, including competition with the normal nucleotide triphosphates for incorporation into replicating mtDNA chains, impairment of chain elongation, and excision-repair steps (extensively reviewed elsewhere) [14]. On a global basis, zidovudine is widely used in the treatment of human immunodeficiency virus (HIV) infections and can also cause a myopathy in humans [9, 15]. Our experiments are the first to describe the ability of skeletal muscle to change fiber-type composition by downregulating the proportion of slow fibers and upregulating fast fibers in response to mitochondrial dysfunction. The changes in fiber-type composition are accompanied by metabolic adjustments from oxidative to more glycolytic capacities.
Materials and methods
Male Wistar rats were purchased at Charles River (Sulzfeld, Germany), were fed a normal rat chow (SSniff R/M-H; Spezialdiäten, Soest, Germany) ad libitum, and were housed in a normal night-day rhythm under standard conditions of temperature and humidity. At 7 weeks of age, 10 rats received zidovudine (kindly provided by GlaxoSmithKline, Munich, Germany) in the drinking water (100 mg/kg/d). This daily dose of zidovudine corresponds to the human dosage adjusted for body area and the higher metabolic and drug-disposal rate of rodents and was calculated on the basis of a daily liquid consumption of 20 ml [16, 17]. Control rats (n = 10) did not receive any zidovudine.
Observations for fluid consumption, clinical signs, and mortality were carried out daily; body weights were recorded weekly. All rats were killed by cervical dislocation at age 28 weeks, immediately before organ collection and postmortem examination. Soleus muscle was snap frozen and cryopreserved in liquid nitrogen until subsequent analysis. Muscle aliquots were fixed in glutaraldehyde (3%) for subsequent electron microscopy. Serum was collected by puncture of the Venae saphenae laterales [18] before cervical dislocation in anesthesia with isoflurane (Abbott, Wiesbaden, Germany). All animal work was performed after animal welfare board approval (Regierungspräsidium Freiburg; Department 3, Nr. 35/9185/.81/G-07/67) and conformed to institutional guidelines as well as to the NIH policy [19].
Histopathology and mitochondrial ultrastructure
Soleus muscle-fiber diameters were morphometrically quantified in all rats on three randomly selected 0.09-mm2 areas of 8 μm thick, hematoxylin and eosin-stained sections, by using an automated image-analysis and processing software (Leica QWin Standard v2.7; Leica Microsystems, Imaging Solutions, Cambridge, UK). The histochemical assay for myofibrillar ATPase activity (pH 4.35 or 10.5) was used to distinguish and morphometrically count fast and slow muscle fibers [20]. On 4-μm cryostat muscle transverse sections, succinate dehydrogenase (SDH) and cytochrome c-oxidase (COX) histochemistry was performed [21]. The evaluating person was blinded to the group status of all animals. Two randomly selected soleus muscle samples from each group were examined with electron microscopy, as described [22].
Myosin heavy-chain immunohistochemistry
Fiber-type analyses were confirmed in muscle cryosections (8 μm) incubated overnight with 1:100 diluted antibodies against fast or slow myosin heavy-chain isoforms (clones WB-MHCF and WB-MHCS; Novocastra, Newcastle, UK). To determine signs of regenerating fibers, we used anti-neonatal myosin heavy-chain antibody (clone WB-MHCn; Novocastra). An Alexa-fluor 488 conjugated secondary antibody (IgG anti-mouse; Novacastra) was used. In images obtained from immunohistochemistry, muscle fiber-type composition was also quantified by using automated image analysis (Leica QWin Standard v2.7; Leica Microsystems). The evaluating person was blinded to the group status of the animals.
Respiratory-chain enzyme activities
Histochemical COX and SDH staining is difficult to quantify reliably. We therefore measured the activities of COX, SDH, and nicotinamide adenine dinucleotide hydrogen dehydrogenase (NADH-DH) in freshly prepared soleus muscle extracts with spectrophotometric assays, as described [23]. NADH-DH and COX are the multisubunit complexes I and IV of the mitochondrial respiratory chain and are encoded partly by nuclear DNA (nDNA) and partly by mtDNA, whereas SDH is a respiratory chain component (complex II), which is encoded entirely by nDNA.
Serum parameters
Serum concentrations of creatinine kinase, resting lactate, glucose, aspartate aminotransferase, alanine aminotransferase, and creatinine levels were determined photometrically by using a Roche/Hitachi 917/Modular P analyzer (Mannheim, Germany), according to the manufacturer's instructions.
Single-fiber mtDNA copy numbers
In each animal, three fast and three slow fibers were picked with a microcapillary under an inverted microscope from a 14-μm-thick, ATPase activity (pH 10.5) typed, transverse soleus muscle section [24]. Total DNA from single fibers was released with 5 μl of a solution containing 200 mM KOH and 50 mM dithiothreitol (incubated for 1 hour at 65°C), followed by a neutralizing buffer (5 μl) containing 900 mM Tris-HCl, pH 8.3, and 200 mM HCl [24]. MtDNA and nDNA copy numbers were quantified from 2 μl of the solute by quantitative PCR, as described [25]. Amplifications of mitochondrial and nuclear products were performed in triplicate. Absolute mtDNA and nDNA copy numbers were calculated by using serial dilutions of plasmids with known copy numbers.
Microarray analysis
RNA was extracted from eight randomly selected frozen muscles from each group with the Uneasy Kit (Qiagen, Hilden, Germany). Quantity and integrity of the RNA were verified by using RNA 6000 nano chips (2100 Bioanalyzer; Agilent, Palo Alto, CA, USA). RNA samples (500 ng) with an RNA integrity number of greater than 9 were further processed with the GeneChip Whole Transcript Sense Target Labelling Assay from Affymetrix (Santa Clara, CA, USA) according to the manufacturer's instructions.
Arrays were scanned with the Affymetrix GeneChip Scanner 3000 7G, and raw data were imported into the Refiner module of Genedata Expressionist software (Martinsried, Germany, version 5.3.5), in which quantile normalization and probe summarization was performed by using its Refiner condensing algorithm [26]. The microarray data were uploaded (ArrayExpress accession number: E-MEXP-3642) in the ArrayExpress Archive [27].
The Kolmogorov-Smirnov test was used to analyze for normal distribution. Groups were then compared with ANOVA, Mann-Whitney, unpaired t test, or Wilcoxon analysis, as appropriate. Skewed data are provided as median plus interquartile ranges (IQRs), and normally distributed data, as group means and standard deviation (SD). Correlations were computed as nonlinear exponential regressions. All graphics and calculations were performed by using the Sigma Plot 2000, version 8.0 (SPSS, Inc.) and the Sigma Stat, version 3.1 (Jandel Inc.) packages.
To identify differentially expressed genes between the groups in microarray analysis, the unpaired Bayes T test (CyberT) [26] with the Bayes confidence estimate value set to 24 and a window size of 101 genes, as well as 100% valid values in each group, was performed with the Analyst module of Expressionist. To estimate the false-discovery rate, the Benjamini-Hochberg q value was calculated in a sequential Bonferroni-type procedure [28]. We then used the "N-fold regulation" activity of Analyst to calculate the median ratio between the experimental groups. Only genes from the categories "main" and "unmapped" (see Affymetrix transcript annotation RaGene-1_0-st-v1.na30.1.rn4.transcript) were included, thereby omitting control probes or genes with uncertain annotation. The false-discovery rate, which estimates the number of false positives within a list of significant genes, was chosen as 10%.
Zidovudine induces a respiratory-chain myopathy
The daily fluid consumption and body weight of the rats was unaffected by zidovudine (data not shown). The autopsy did not reveal macroscopic organ anomalies. Soleus muscle fiber diameters were decreased in the zidovudine group (Figure 1, Table 1). After 28 weeks, groups did not differ in serum levels of creatinine kinase, resting lactate, and glucose. Serum creatinine levels, however, were lower in rats treated with zidovudine, indicating reduced muscle mass (P = 0.001) compared with untreated rats. Electron microscopy revealed a focal disarray of the myofibrillar lattice in the zidovudine group (Figure 2). The crystal architecture was lost in a substantial proportion of the organelles and contained deposits of electron-dense material. Mean mtDNA copy numbers were decreased by 29% (P < 0.001) in zidovudine-treated rats compared with control animals (Table 1). Histochemical COX/SDH staining showed a uniformly downregulated respiratory-chain activity and no clear fiber type-specific pattern. NADH-DH and COX activities in the soleus muscle were depressed in the zidovudine group (P = 0.042 and P = 0.026, respectively; Table 1). In contrast, the activity of SDH was unaffected (P = 0.7; Table 1). These data indicate that zidovudine induced a metabolic myopathy with depleted mtDNA copies and a specific downregulation of mtDNA-encoded respiratory chain activities and consecutive fiber atrophy.
Type II fibers are enhanced in mitochondrial myopathy
Muscle morphometry revealed that the fiber diameter was reduced in both fast and slow fibers of zidovudine-treated rats (Table 1), leading to an increased fiber number per microscopic area (151 ± 20 fibers/μm2 in rats without versus 194 ± 26 fibers/μm2 in rats with zidovudine; P = 0.002). Fast fibers, however, had a disproportionate degree of atrophy (32% reduction of mean fiber diameter; P < 0.001) compared with slow fibers (21% reduction; P = 0.006).
In control muscle, slow fibers and fast fibers contained similar numbers of mtDNA copies (P = 0.15). In zidovudine-treated rats, however, slow fibers had fewer mtDNA copies than did fast fibers (P = 0.002). Zidovudine treatment also induced a greater proportion of mtDNA depletion in slow fibers than in fast fibers (70% versus 38%; P < 0.001; Table 1).
As expected, histomorphometry in ATPase-typed soleus muscle of control rats demonstrated the vast predominance of type 1 slow oxidative fibers (94.8% ± 3.0%) relative to fast glycolytic fibers. In contrast, zidovudine-treated animals, soleus muscles contained a high proportion of fast fibers (256% increase compared with controls; P < 0.001), whereas slow fibers were diminished (Table 1). Fiber-type grouping was not evident. The upregulation of fast fibers in soleus muscle exposed to zidovudine was confirmed with antibodies specific for fast and slow myosin heavy chain (Figure 3). Immunofluorescence studies of zidovudine-treated soleus muscles were carried out with an antibody directed against neonatal MHC. None of the soleus muscle fibers expressed the neonatal myosin heavy-chain isoform, indicating the absence of fiber regeneration (not shown). Furthermore, we did not observe signs of muscle denervation in terms of fiber-type grouping or upregulated neonatal myosin heavy chains (data not shown).
Enhanced fast-fiber and repressed slow-fiber transcripts
Microarray gene expression analysis identified 1,411 genes and 43 pathways to be significantly regulated (P < 0.01) in zidovudine-treated animals relative to control. In zidovudine-exposed rat soleus muscle, fast-fiber transcripts were significantly enhanced, and slow-fiber transcripts, repressed (Figure 4). Consistent with the absence of fiber regeneration in the immunofluorescence studies, embryonal and neonatal myosin heavy-chain transcripts were downregulated [29].
Investigating metabolic adjustments, we found nucleus- and mtDNA-encoded respiratory chain subunits to be coordinately downregulated in zidovudine myopathy, although many changes were not statistically significant. The transcription of the rate-limiting enzymes of glycolysis and glycogenolysis was enhanced (Table 2) and the mitochondrial carnitine shuttle (carnitine palmitoyltransferase, CPT1b), and β-oxidation (3-hydroxy-acyl-CoA dehydrogenase) downregulated.
Regulation of fiber composition
To elicit regulatory mechanisms of fiber transformation, we focused on transcription factors involved in muscle differentiation. In zidovudine-treated muscle, MyoD, which is expressed mainly in type II fibers [30], was upregulated (+4.41-fold; P = 1.01E-16), and the myogenic regulatory factor (MRF) transcribed from myogenin [31]), which is normally expressed predominantly in type I fibers, was downregulated (-3.75-fold; P = 1.78E-09) [32].
The homeodomain transcription factors Six1 and Six2, the transcriptional repressor Sox6, and the transcriptional coactivator Eya1 promote a switch from slow to fast fibers [33, 34]. We found Six1 (+2.05-fold; P = 5.68E-12), Six2 (+5.00-fold; P = 9.39E-13), Eya1 (+1.42-fold; P = 8.09E-06), and Sox6 (+5.20-fold; P = 1.00E-35) upregulated in zidovudine-treated rat soleus muscle.
Estrogen-related receptor (ERR) γ enhances mitochondrial biogenesis and function, mtDNA content and the expression of contractile proteins specific to slow muscle and is physiologically highly expressed in soleus muscle [35]. We found ERRγ downregulated in zidovudine-exposed soleus muscle compared with untreated controls (-2.13-fold; P = 1.07E-10).
Thus, mitochondrial dysfunction is associated with a coordinate regulation of a multitude of transcription factors that orchestrate the transformation from type I to type II fibers.
The present study demonstrates a previously undescribed skeletal muscle fiber-type transformation from slow fibers to fast fibers in a mitochondrial myopathy. The changes in fiber-type composition occur in the absence of muscle regeneration and not only are demonstrated at the level of myosin heavy-chain isoforms and isoforms of other contractile proteins, but also are paralleled by adjustments in the metabolic profile and a switch from an oxidative to a more-glycolytic transcriptosome. From a mechanistic perspective, this response of muscle energetics to the primary defect in respiratory chain function may maintain muscle strength via increased recruitment of glycolysis for ATP production, at the expense of increased energetic cost. The switch to more-glycolytic type II fibers, which are characterized by an increased lactate production compared with type I fibers, could contribute to the hyperlactatemia observed in patients with mitochondriopathies [36]. The fact that hyperlactatemia is typically observed only, or at least is aggravated during exercise in patients with inherited mutations in mtDNA [37, 38] can explain the normal lactate levels in our rats in whom blood was collected at rest. Fiber-type switching is also observed in conditions associated with impaired blood oxygenation [39] and diminished muscle microcirculation [40].
In COPD, muscle hypoxia is associated with an increased proportion of type II fibers [39, 41], a reduced number of mitochondria [42], increases in glycolytic enzyme activity, and an impairment of oxidative capacity [43].
Patients with idiopathic inflammatory myopathies also reveal an increased proportion of fast fibers and a lower proportion of slow fibers compared with healthy controls [40]. Even in healthy humans exposed to high altitude, the proportion of type I fibers is decreased [44, 45]. Although we failed to identify a single master switch of type I to type II fiber transformation, these observations indicate that an impairment of mitochondrial respiration of many causes promotes type II fiber formation.
Interestingly, slow fibers showed even less mtDNA content than did fast fibers in zidovudine-treated rats. This observation may be explained by the dynamics of the system (for example, the possibility that these slow fibers could still be in the process of converting). Alternatively, this finding could be explained with a physiologically higher mtDNA turnover in slow (oxidative) fibers compared with fast (glycolytic) fibers, and therefore an increased susceptibility to the inhibition of mtDNA replication conferred by zidovudine. Clearly, regulators of fiber type exist in addition to mtDNA content, and vice versa. Downregulation of the ERRγ may explain some of the biologic processes observed in our model, as ERRγ physiologically promotes a switch to slow muscle fibers and induces oxidative metabolism by increasing mitochondrial number, size, and functions [35].
Type II fibers in our study had a higher degree of atrophy than did type I fibers, despite the fact that the former appeared to be less dependent on mtDNA replication than the latter, as evidenced by a lesser degree of mtDNA depletion. Because muscle disuse affects mainly type I fiber diameters [46, 47], the type II fiber atrophy in our model suggests a mechanism related to mitochondrial dysfunction. This hypothesis is further supported by the predominant type II fiber atrophy in other conditions associated with muscle hypoxia, such as COPD [41], systemic sclerosis [2–4, 48], and inflammatory myopathies [5]. Age-related sarcopenia is also associated with a predominant atrophy of type II fibers and an increased abundance of fast myosin heavy-chain isoforms in soleus muscle [49]. It is interesting to speculate, whether mitochondrial dysfunction, which has also been implicated in aging, may be a driver of these characteristics of the aging muscle [50]. Myostatin has been described as a potent negative regulator of muscle mass, and increased myostatin expression is particularly associated with type II atrophy [51]. Consistent with this, we found a fourfold enhancement of myostatin transcription (Table 2). Sarcopenia, in combination with the disabled aerobic energy supply of slow-twitch fibers, can also explain muscle weakness on static and dynamic exercise, fatigue and muscle atrophy observed in patients with mitochondrial myopathies [52].
The effects of mitochondrial dysfunction and hypoxia on fiber-type composition have important clinical implications for training and rehabilitations programs by suggesting that exercise intolerance in mitochondrial dysfunction may be improved not only by cardiopulmonary mechanisms, but also by promoting fiber type II formation, either by resistance training, or pharmacologically by targeting the calcineurin-dependent nuclear factor of activated T-cells (NFAT) with calcineurin inhibitors [53, 54].
In mitochondrial myopathies, muscle strength and oxidative capacity were improved without type I fiber enhancement [55, 56], and in COPD, muscle strength and oxidative capacity were enhanced without alterations in lung function [41, 57]. In idiopathic inflammatory myopathy, however, endurance training increased type I fiber proportions and diameters [40]. This difference could be explained by the preservation of mitochondrial function in idiopathic inflammatory myopathy, which enables type I fiber formation, and the impairment of mitochondrial function in inherited or acquired defects of the mitochondrial genome, which disables type I fiber formation. Clearly, more research is needed about the different effects of training programs on cardiopulmonary function, skeletal muscle microcirculation, oxidative capacity, and fiber-type composition in these different conditions.
Our work demonstrates a type I to type II fiber transformation in a mitochondrial myopathy and a preferential atrophy in type II fibers. The skeletal muscle fiber-type transformation in the absence of fiber-type regeneration and observed adjustments from oxidative to glycolytic metabolism provide evidence for mitochondrial function as a new regulator of skeletal muscle fiber type and other metabolic capacities. The effects of mitochondrial dysfunction on fiber-type composition have important clinical implications for training and rehabilitations programs.
This work was supported by DFG grant VE 492/2-1. The article-processing charge was funded by the German Research Foundation (DFG) and the Albert Ludwigs University Freiburg in the funding program Open Access Publishing. We also thank Karin Sutter and Carmen Kopp for expert technical assistance.
chronic obstructive pulmonary disease
cytochrome c oxidase
estrogen-related receptor
interquartile ranges
myosin heavy chain
myogenic regulatory factor
- mtDNA:
mitochondrial DNA
nicotinamide adenine dinucleotide hydrogen dehydrogenase
- nDNA:
nuclear DNA
standard deviation
succinate dehydrogenase.
Emslie-Smith AM, Engel AG: Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann Neurol. 1990, 27: 343-356. 10.1002/ana.410270402.
Banker BQ: Dermatomyostis of childhood, ultrastructural alteratious of muscle and intramuscular blood vessels. J Neuropathol Exp Neurol. 1975, 34: 46-75. 10.1097/00005072-197501000-00005.
Kissel JT, Halterman RK, Rammohan KW, Mendell JR: The relationship of complement-mediated microvasculopathy to the histologic features and clinical duration of disease in dermatomyositis. Arch Neurol. 1991, 48: 26-30. 10.1001/archneur.1991.00530130034016.
Fleming JN, Schwartz SM: The pathology of scleroderma vascular disease. Rheum Dis Clin North Am. 2008, 34: 41-55. 10.1016/j.rdc.2008.01.001.
Jobin J, Maltais F, Doyon JF, LeBlanc P, Simard PM, Simard AA, Simard C: Chronic obstructive pulmonary disease: capillarity and fiber-type characteristics of skeletal muscle. J Cardiopulmon Rehabil. 1998, 18: 432-437. 10.1097/00008483-199811000-00005.
DiMauro S: Mitochondrial myopathies. Curr Opin Rheumatol. 2006, 18: 636-641. 10.1097/01.bor.0000245729.17759.f2.
DiMauro S, Schon EA: Mitochondrial respiratory-chain diseases. N Engl J Med. 2003, 348: 2656-2668. 10.1056/NEJMra022567.
Sirvent P, Fabre O, Bordenave S, Hillaire-Buys D, Raynaud De ME, Lacampagne A, Mercier J: Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins. Toxicol Appl Pharmacol. 2012, 259: 263-268. 10.1016/j.taap.2012.01.008.
Lebrecht D, Deveaud C, Beauvoit B, Bonnet J, Kirschner J, Walker UA: Uridine supplementation antagonizes zidovudine-induced mitochondrial myopathy and hyperlactatemia in mice. Arthritis Rheum. 2008, 58: 318-326. 10.1002/art.23235.
Owczarek J, Jasinska M, Orszulak-Michalak D: Drug-induced myopathies: an overview of the possible mechanisms. Pharmacol Rep. 2005, 57: 23-34.
Caiozzo VJ, Baker MJ, Huang K, Chou H, Wu YZ, Baldwin KM: Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions?. Am J Physiol Regul Integr Comp Physiol. 2003, 285: R570-R580.
Termin A, Staron RS, Pette D: Changes in myosin heavy chain isoforms during chronic low-frequency stimulation of rat fast hindlimb muscles: a single-fiber study. Eur J Biochem. 1989, 186: 749-754. 10.1111/j.1432-1033.1989.tb15269.x.
Izumo S, Nadal-Ginard B, Mahdavi V: All members of the MHC multigene family respond to thyroid hormone in a highly tissue-specific manner. Science. 1986, 231: 597-600. 10.1126/science.3945800.
Lewis W, Day BJ, Copeland WC: Mitochondrial toxicity of NRTI antiviral drugs: an integrated cellular perspective. Nat Rev Drug Discov. 2003, 2: 812-822. 10.1038/nrd1201.
Arnaudo E, Dalakas M, Shanske S, Moraes CT, DiMauro S, Schon EA: Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. Lancet. 1991, 337: 508-510. 10.1016/0140-6736(91)91294-5.
Collins ML, Sondel N, Cesar D, Hellerstein MK: Effect of nucleoside reverse transcriptase inhibitors on mitochondrial DNA synthesis in rats and humans. J Acquir Immune Defic Syndr. 2004, 37: 1132-1139. 10.1097/01.qai.0000131585.77530.64.
Deveaud C, Beauvoit B, Hagry S, Galinier A, Carriere A, Salin B, Schaeffer J, Caspar-Bauguil S, Fernandez Y, Gordien JB, Breilh D, Penicaud L, Casteilla L, Rigoulet M: Site specific alterations of adipose tissue mitochondria in 3'-azido-3'-deoxythymidine (AZT)-treated rats: an early stage in lipodystrophy?. Biochem Pharmacol. 2005, 70: 90-101. 10.1016/j.bcp.2005.04.015.
Nau R, Schunck O: Cannulation of the lateral saphenous vein: a rapid method to gain access to the venous circulation in anaesthetized guinea pigs. Lab Anim. 1993, 27: 23-25. 10.1258/002367793781082449.
U.S. Department of Health & Human Services, Office of laboratory animal welfare. [http://grants.nih.gov/grants/olaw/olaw.htm]
Round JM, Matthews Y, Jones DA: A quick, simple and reliable histochemical method for ATPase in human muscle preparations. Histochem J. 1980, 12: 707-710. 10.1007/BF01012026.
Sciacco M, Bonilla E: Cytochemistry and immunocytochemistry of mitochondria in tissue sections. Methods Enzymol. 1996, 264: 509-521.
Lebrecht D, Setzer B, Ketelsen UP, Haberstroh J, Walker UA: Time-dependent and tissue-specific accumulation of mtDNA and respiratory chain defects in chronic doxorubicin cardiomyopathy. Circulation. 2003, 108: 2423-2429. 10.1161/01.CIR.0000093196.59829.DF.
DiMauro S, Mendell JR, Sahenk Z, Bachman D, Scarpa A, Scofield RM, Reiner C: Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency. Neurology. 1980, 30: 795-804. 10.1212/WNL.30.8.795.
Sciacco M, Bonilla E, Schon EA, DiMauro S, Moraes CT: Distribution of wild-type and common deletion forms of mtDNA in normal and respiration-deficient muscle fibers from patients with mitochondrial myopathy. Hum Mol Genet. 1994, 3: 13-19. 10.1093/hmg/3.1.13.
Lebrecht D, Vargas Infante YA, Setzer B, Kirschner J, Walker UA: Uridine supplementation antagonizes zalcitabine-induced microvesicular steatohepatitis in mice. Hepatology. 2007, 15: 72-79.
Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003, 4: 249-264. 10.1093/biostatistics/4.2.249.
EMBL-EBI, ArrayExpress. [http://ebi.ac.uk/arrayexpress]
Benjamini Y, Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995, 289-300. B57
Berg JS, Powell BC, Cheney RE: A millennial myosin census. Mol Biol Cell. 2001, 12: 780-794.
Hughes SM, Taylor JM, Tapscott SJ, Gurley CM, Carter WJ, Peterson CA: Selective accumulation of MyoD and myogenin mRNAs in fast and slow adult skeletal muscle is controlled by innervation and hormones. Development. 1993, 118: 1137-1147.
Hughes SM, Chi MM, Lowry OH, Gundersen K: Myogenin induces a shift of enzyme activity from glycolytic to oxidative metabolism in muscles of transgenic mice. J Cell Biol. 1999, 145: 633-642. 10.1083/jcb.145.3.633.
Voytik SL, Przyborski M, Badylak SF, Konieczny SF: Differential expression of muscle regulatory factor genes in normal and denervated adult rat hindlimb muscles. Dev Dyn. 1993, 198: 214-224. 10.1002/aja.1001980307.
Grifone R, Laclef C, Spitz F, Lopez S, Demignon J, Guidotti JE, Kawakami K, Xu PX, Kelly R, Petrof BJ, Daegelen D, Concordet JP, Maire P: Six1 and Eya1 expression can reprogram adult muscle from the slow-twitch phenotype into the fast-twitch phenotype. Mol Cell Biol. 2004, 24: 6253-6267. 10.1128/MCB.24.14.6253-6267.2004.
Hagiwara N, Ma B, Ly A: Slow and fast fiber isoform gene expression is systematically altered in skeletal muscle of the Sox6 mutant, p100H. Dev Dyn. 2005, 234: 301-311. 10.1002/dvdy.20535.
Rangwala SM, Wang X, Calvo JA, Lindsley L, Zhang Y, Deyneko G, Beaulieu V, Gao J, Turner G, Markovits J: Estrogen-related receptor gamma is a key regulator of muscle mitochondrial activity and oxidative capacity. J Biol Chem. 2010, 285: 22619-22629. 10.1074/jbc.M110.125401.
Chariot P, Monnet I, Mouchet M, Rohr M, Lefaucheur J-P, Dubreuil-Lemaire ML, Chousterman M, Gherardi R: Determination of the blood lactate:pyruvate ratio as a noninvasive test for the diagnosis of zidovudine myopathy. Arthritis Rheum. 1994, 37: 583-586. 10.1002/art.1780370421.
Mancuso M, Orsucci D, LoGerfo A, Rocchi A, Petrozzi L, Nesti C, Galetta F, Santoro G, Murri L, Siciliano G: Oxidative stress biomarkers in mitochondrial myopathies, basally and after cysteine donor supplementation. J Neurol. 2010, 257: 774-781. 10.1007/s00415-009-5409-7.
Munnich A, Rotig A, Chretien D, Saudubray JM, Cormier V, Rustin P: Clinical presentations and laboratory investigations in respiratory chain deficiency. Eur J Pediatr. 1996, 155: 262-274. 10.1007/BF02002711.
Hildebrand IL, Sylven C, Esbjornsson M, Hellstrom K, Jansson E: Does chronic hypoxaemia induce transformations of fibre types?. Acta Physiol Scand. 1991, 141: 435-439. 10.1111/j.1748-1716.1991.tb09102.x.
Dastmalchi M, Alexanderson H, Loell I, Stahlberg M, Borg K, Lundberg IE, Esbjornsson M: Effect of physical training on the proportion of slow-twitch type I muscle fibers, a novel nonimmune-mediated mechanism for muscle impairment in polymyositis or dermatomyositis. Arthritis Rheum. 2007, 57: 1303-1310. 10.1002/art.22996.
Rabinovich RA, Vilaro J: Structural and functional changes of peripheral muscles in chronic obstructive pulmonary disease patients. Curr Opin Pulmon Med. 2010, 16: 123-133. 10.1097/MCP.0b013e328336438d.
Gosker HR, Hesselink MK, Duimel H, Ward KA, Schols AM: Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD. Eur Respir J. 2007, 30: 73-79. 10.1183/09031936.00146906.
Howald H, Pette D, Simoneau JA, Uber A, Hoppeler H, Cerretelli P: Effect of chronic hypoxia on muscle enzyme activities. Int J Sports Med. 1990, 11 (Suppl 1): S10-S14.
Green HJ, Sutton JR, Cymerman A, Young PM, Houston CS: Operation Everest II: adaptations in human skeletal muscle. J Appl Physiol. 1989, 66: 2454-2461.
Bigard AX, Brunet A, Guezennec CY, Monod H: Skeletal muscle changes after endurance training at high altitude. J Appl Physiol. 1991, 71: 2114-2121.
Zhong H, Roy RR, Siengthai B, Edgerton VR: Effects of inactivity on fiber size and myonuclear number in rat soleus muscle. J Appl Physiol. 2005, 99: 1494-1499. 10.1152/japplphysiol.00394.2005.
Booth FW, Gollnick PD: Effects of disuse on the structure and function of skeletal muscle. Med Sci Sports Exerc. 1983, 15: 415-420.
Scarpelli M, Montironi R, Tulli D, Sisti S, Matera G, Magi GC, Collan Y: Quantitative analysis of quadriceps muscle biopsy in systemic sclerosis. Pathol Res Pract. 1992, 188: 603-606. 10.1016/S0344-0338(11)80064-6.
Carter EE, Thomas MM, Murynka T, Rowan SL, Wright KJ, Huba E, Hepple RT: Slow twitch soleus muscle is not protected from sarcopenia in senescent rats. Exp Gerontol. 2010, 45: 662-670. 10.1016/j.exger.2010.04.001.
Trounce I, Byrne E, Marzuki S: Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in aging. Lancet. 1989, i: 637-639.
Jespersen JG, Nedergaard A, Andersen LL, Schjerling P, Andersen JL: Myostatin expression during human muscle hypertrophy and subsequent atrophy: increased myostatin with detraining. Scand J Med Sci Sports. 2011, 21: 215-223. 10.1111/j.1600-0838.2009.01044.x.
Dalakas MC, Illa I, Pezeshkpour GH, Laukaitis JP, Cohen B, Griffin JL: Mitochondrial myopathy caused by long-term zidovudine therapy. N Engl J Med. 1990, 322: 1098-1105. 10.1056/NEJM199004193221602.
Chin ER, Olson EN, Richardson JA, Yang Q, Humphries C, Shelton JM, Wu H, Zhu W, Bassel-Duby R, Williams RS: A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev. 1998, 12: 2499-2509. 10.1101/gad.12.16.2499.
Schiaffino S, Reggiani C: Fiber types in mammalian skeletal muscles. Physiol Rev. 2011, 91: 1447-1531. 10.1152/physrev.00031.2010.
Murphy JL, Blakely EL, Schaefer AM, He L, Wyrick P, Haller RG, Taylor RW, Turnbull DM, Taivassalo T: Resistance training in patients with single, large-scale deletions of mitochondrial DNA. Brain. 2008, 131: 2832-2840. 10.1093/brain/awn252.
Jeppesen TD, Schwartz M, Olsen DB, Wibrand F, Krag T, Duno M, Hauerslev S, Vissing J: Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy. Brain. 2006, 129: 3402-3412. 10.1093/brain/awl149.
Vogiatzis I, Terzis G, Nanas S, Stratakos G, Simoes DC, Georgiadou O, Zakynthinos S, Roussos C: Skeletal muscle adaptations to interval training in patients with advanced COPD. Chest. 2005, 128: 3838-3845. 10.1378/chest.128.6.3838.
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DL and ACV carried out the experiments, participated in the design of the study and participated in writing the manuscript. DP performed the microarray analyses. NV and UAW conceived the study, participated in its design and coordination, analyzed the data, and wrote the manuscript. JBK participated in muscle-fiber analyses. EB carried out the blood analyses. All authors read and approved the final manuscript.
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Venhoff, N., Lebrecht, D., Pfeifer, D. et al. Muscle-fiber transdifferentiation in an experimental model of respiratory chain myopathy. Arthritis Res Ther 14, R233 (2012). https://doi.org/10.1186/ar4076
DOI: https://doi.org/10.1186/ar4076
- Chronic Obstructive Pulmonary Disease
- Zidovudine
- Soleus Muscle
- Idiopathic Inflammatory Myopathy
- Mitochondrial Myopathy


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May 25, 2012
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Lesson 12: Community Loyalty (Sandel, Chapter 9)
If I asked you who you are, chances are you would describe yourself with a list of the groups to which you belong: your family, neighborhood, ethnic group, town, and nation, as well other social affiliations. Sandel claims these communities shape our ethics as much, if not more, than abstract rational reasoning or voluntary choices. We understand who we are, what we believe, and what we are to do by identifying with the stories, histories, and traditions of these communities. It is downright silly that we harp so much on individual freedom, when we are radically dependent on one another in our highly specialized world.
Think of all the profound implications when Lupe's granddaughter, Cassie, reported she does not think of herself in terms of race, but rather as a Bolivian. Consider how much Christian ethics are based on the story told weekly by the Church. When the Old Testament Torah commands care for the weak, it tells the story of how God rescued the Hebrew community when it was enslaved in Egypt. When Christians call for love, they tell the story of Jesus' words and deeds– even dying for us.
As much as we might understand the important role our communities play in passing down the lessons from the past and checking our self-centered pursuit of happiness, we immediately feel the tension between what Sandel labels corporate responsibility and collective selfishness. We feel a deeper loyalty with those in our own group, more common humanity with our families than our nations. Yet we also have to live with some awful past history. Too often we have found our identity by labeling and even oppressing outsiders. What is Western Civilization to make of the Holocaust, or the Church of the Inquisition?
It seems obvious that we must always be ready to correct the stories of our communities, so they are relevant to contemporary situations. We have done that with great effort and sacrifice in overcoming slavery, granting rights to women, accepting gays and lesbians. We, also, need to constantly compliment and check our communal ethics with the natural and voluntary approaches Sandel discussed in previous chapters.
My guess is almost all of us appreciate how our families form our understandings of right and wrong, but what about the other communities to which you belong? Does solidarity with other Americans mean we have an ethical obligation to "buy American"? Does it support an "America first, right or wrong" stance? "American Exceptionalism"? Can we consider patriotism a virtue? If so, what does it involve? How far does it go?
Bob and Derek spoke of the difficulties of individuals engaging in a public conversation about the common good in our large, pluralistic, bureaucratic communities. Is it any easier, if we see the conversation involving our communities rather than individuals? Is the conversation more workable with smaller groups? We have seen the limitations of civil discussion in the global village that has no history or tradition. Does it offer more hope to "Think globally and act locally" as the ecolologists counsel?
Lately, I've heard the word" community" used mostly by online groups, for example referring to "My Facebook community" or my "Facebook friends." Coming a close second would be gays and lesbians speaking of "the community." Are these new forms of community that have the potential to shape ethics?


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If you're reading this and you're a Bayer Leverkusen footballer by the name of Kai Havertz, take a bow, son: you're the most improved player in FIFA 18 (opens in new tab) Ultimate Team.
If you're reading this and you're not Kai Havertz, there's good news for you, too: the clever cookies at futwiz (opens in new tab) have analysed the entire FIFA 18 database, and figured out the biggest year-on-year ratings increases – and the top 20 are listed at the end of this story.
Right-midfielder Havertz comes top with a 16-point overall increase, from 57 in FIFA 17 to 73 this year. Still aged only 18, in 2016 he became the Bundesliga's youngest ever debutant, and earlier this year he earned the honour of Leverkusen's youngest goalscorer. Easily deserving of the ratings bump, then.
Two players based in England finish in joint-second: Manchester United's Portuguese keeper Joel Pereira, and Nottingham Forest centre-back Joe Worrall. Pereira earned his first league start for United in the final game of 2016-17, against Crystal Palace at Old Trafford, while Worrall was called up to the England U-21 squad in August after captaining the U-20 side which won the summer's FIFA U-20 World Cup.
One player always certain to get a gigantic stats increase across the board was Kylain Mbappe. He started last season as a winger on the cusp of the Monaco first team, and ended it as one of Europe's best centre forwards, scoring a season-long loan move to PSG which will turn into a 145-million Euro permanent transfer come the end of the season. Mbappe is joint-sixth on the ratings increase chart, leaping from a 71 in FIFA 17 to 83 this year. Young Watford left back Brandon Mason matches that 12-point leap, going from 54 to 66.
In addition to Pereira, two fellow goalkeepers make the top 20. Ajax's Cameroonian stopper Andre Onana, who seemed to rack up as many special cards in FIFA 17 as he did real-life saves, nabs a nine-point increase from 69 to 78. Cristian Vargas of Atletico Nacional narrowly betters that boost, earning 10 attributes points and a gold card by going from 65 to 75.
Incredibly, three Ajax team-mates join Onana in the hot 20. Right-back Luis Manuel Orejuela upgrades from 57 to 70; centre-back Matthijs de Ligt rises from 63 to 76; and striker Kasper Dolberg increases to 78 from his FIFA 17 rating of 68. Their former team-mate, centre-back Davinson Sanchez – who recently joined Tottenham for a fee in the region of £42million – also gets a monstrous boost, from 71 to 81.
Here's the top 20 in full:
1. Kai Havertz (Bayer Leverkusen) +16, 57 to 73
2=. Joel Pereira (Manchester United) +14, 57 to 71
2=. Joe Worrall (Nottingham Forest) +14, 55 to 69
4=. Luis Manuel Orejuela (Ajax) +13, 57 to 70
4=. Matthijs de Ligt (Ajax) + 13, 63 to 76
6=. Kylian Mbappe (Paris SG) +12, 71 to 83
6=. Brandon Mason (Watford) +12, 54 to 66
8. Lucas Tousart (Lyon) +11, 68 to 78
9=. Deal Fry (Middlesbrough) +10, 56 to 66
9=. Raul (Braga) +10, 68 to 78
9=. Cristian Vargas (Atletico Nacional) +10, 65 to 75
9=. Kasper Dolberg (Ajax) +10, 68 to 78
9=. Ritsu Doan (Groningen) +10, 58 to 68
9=. Thilo Kehrer (Schalke) +10, 61 to 71
9=. Davinson Sanchez (Tottenham) +10, 71 to 81
9=. Georgiy Dzhikiya (Spartak Moscow) +10, 65 to 75
9=. Reuven Niemeijer (Heracles) +10, 57 to 67
18=. Theo Hernandez (Real Madrid) +9, 66 to 75
18=. Andre Onana (Ajax) +9, 69 to 78
18=. Ezgjan Alioski (Leeds) +9, 63 to 72
18=. Christian Pulisic (Dortmind) +9, 69 to 78
18=. Pedro Chirivella (Willem II) +9, 58 to 67
FIFA 18 is out on 29 September– but you can play the demo right now. Before you do so, be sure to check out our FIFA 18 demo tips feature (opens in new tab).


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P4, pregn-4-ene-3,20-dione
Progesterone (Pic.1) is an endogenous steroid and progestogen sex hormone. Progestogens are a class of steroid hormones that bind to and activate the progesterone receptor. The most important progestogen in the body is progesterone (P4). Other endogenous progestogens include progesteron, progestogen, a progestin. The progestogens are named for their function in maintaining pregnancy (i.e., progestational), although they are also present at other phases of the estrous and menstrual cycles. Progesterone is the major progestogen in the body, and plays an important role in brain function as a neurosteroid. In women, progesterone levels are relatively low during the preovulatory phase of the menstrual cycle, rise after ovulation, and are elevated during the luteal phase. Progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. Progesterone levels are relatively low in children and postmenopausal women. Adult males have levels similar to those in women during the follicular phase of the menstrual cycle (Pic. 2).
Reproductive system:
Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before fertilization occurs, though the receptor(s) as yet remain unidentified. Detailed characterization of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes, slow calcium oscillations, now thought to possibly regulate motility.
Progesterone is sometimes called the "hormone of pregnancy", and it has many roles:
Prevention of preterm birth:
Vaginally dosed progesterone is being investigated as potentially beneficial in preventing preterm birth in women at risk for preterm birth. According to a recent study, women with a short cervix that received hormonal treatment with a progesterone gel had their risk of prematurely giving birth reduced. The hormone treatment was administered vaginally every day during the second half of a pregnancy. A subsequent and larger study showed that vaginal progesterone was no better than placebo in preventing recurrent preterm birth in women with a history of a previous preterm birth,but a planned secondary analysis of the data in this trial showed that women with a short cervix at baseline in the trial had benefit in two ways: a reduction in births less than 32 weeks and a reduction in both the frequency and the time their babies were in intensive care. In another trial, vaginal progesterone was shown to be better than placebo in reducing preterm birth prior to 34 weeks in women with an extremely short cervix at baseline.
Progesterone plays an important role in mammary gland development in females. In conjunction with prolactin, it mediates lobuloalveolar maturation of the breasts during pregnancy to allow for milk production, and thus lactation and breastfeeding after childbirth.
Progesterone is also part of hormonal contraceptives:
Other effects of progesterone:
Since most progesterone in males is created during testicular production of testosterone, and most in females by the ovaries, the shutting down (whether by natural or chemical means), or removal, of those inevitably causes a considerable reduction in progesterone levels. Previous concentration upon the role of progestogens in female reproduction, when progesterone was simply considered a "female hormone", obscured the significance of progesterone elsewhere in both sexes.
The tendency for progesterone to have a regulatory effect, the presence of progesterone receptors in many types of body tissue, and the pattern of deterioration (or tumor formation) in many of those increasing in later years when progesterone levels have dropped, is prompting widespread research into the potential value of maintaining progesterone levels in both males and females.
Progesterone enhances the function of serotonin receptors in the brain, so an excess or deficit of progesterone has the potential to result in significant neurochemical issues. This provides an explanation for why some people resort to substances that enhance serotonin activity such as nicotine, alcohol, and cannabis when their progesterone levels fall below optimal levels.
To examine the effects of progesterone on nicotine addiction, participants in one study were either treated orally with a progesterone treatment, or treated with a placebo. When treated with progesterone, participants exhibited enhanced suppression of smoking urges, reported higher ratings of "bad effects" from IV nicotine, and reported lower ratings of "drug liking".These results suggest that progesterone not only alters the subjective effects of nicotine, but reduces the urge to smoke cigarettes.
Sex differences in hormone levels may induce women to respond differently than men to nicotine. When women undergo cyclic changes or different hormonal transition phases (menopause, pregnancy, adolescence), there are changes in their progesterone levels. Therefore, females have an increased biological vulnerability to nicotine's reinforcing effects compared to males and progesterone may be used to counter this enhanced vulnerability. This information supports the idea that progesterone can affect behavior.
Similar to nicotine, cocaine also increases the release of dopamine in the brain. The neurotransmitter is involved in the reward center and is one of the main neurotransmitters involved with substance abuse and reliance. In a study of cocaine users, it was reported that progesterone reduced craving and the feeling of being stimulated by cocaine. Thus, progesterone was suggested as an agent that decreases cocaine craving by reducing the dopaminergic properties of the drug.
The absence of a menstrual period in women of reproductive age.
Male diagnosis connected with male infertility characterised by the complete absence of semen.
Complete absence of sperm in the ejaculate of a man.
Condition causing cervical mucus too thick and hostile to allow the sperm to penetrate the cervix.
Thickening of the lining of the uterus.
A state in which pieces of the tissue alike to the lining of the uterus (endometrium) grow in other parts of the body.
A medical term which describes a diminished functional activity of the gonads – the testes and ovaries.
A genetic condition where the primary symptom is a failure to start puberty or a failure to fully complete puberty.
The set of symptoms that result from two or more X chromosome in males.
The luteinisation of ovulatory follicle without a release of an oocyte.
The time in most women's lives when menstrual periods stop permanently, and the woman is no longer able to have children.
Complete absence of sperm in the ejaculate due to testicular failure.
A disease of excess body fat that can have a negative effect on health, leading to reduced life expectancy and other health problems.
Semen with a low concentration of sperm and is a common finding in male infertility.
A condition in which a woman has an imbalance of female sex hormones. This may lead to changes in the menstrual cycle, cysts in the ovaries, trouble g
Cancer that develops in the testicles.
In the case of cryptorchidism one or both testes are absent from the scrotum. It is is the most common etiologic factor of azoospermy in the adult.
The most common benign smooth muscle tumors of the uterus encountered in women of reproductive age.
The male sex chromosomal disorder characterized by a spectrum of clinical presentations, ranging from ambiguous to normal male genitalia.
Development of ovarian follicles from primordial to tertiary under the stimulation of gonadotropins.
The ovum-producing organs of the internal female reproductive system
Male gonads which produce both sperm and androgens, such as testosterone, and are active throughout the reproductive lifespan of the male.


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Nicola Rehbein is a german born, South African bred photographer currently based in Frankfurt.
Ever since he can remember he has been interested in photography. Being able to capture a moment, a feeling with just a single push of a button has always blown his mind. He tends to live a simplistic life and find beauty in everyday scenarios that most people tend to oversee or don't even bother to take a second look at.
See more of Nicola Rehbein's work here: WEBSITE / FACEBOOK / INSTAGRAM
Model: Fanny Bintz || Stylist: Masha Schubbach


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Most videogames are made for competition, whether it is indirect competition for high scores at the arcade, or fighting your friends side by side or online. There is no denying the popularity of multiplayer. But one organization takes competition to the next step, and that's Major League Gaming, or MLG. People from all over the world take part in MLG tournaments, which host a variety of different games on both console and PC platforms. Popular titles include Starcraft II, Halo, Call of Duty, and League of Legends, though each tournament (one for every season of the year) hosts different games.
While I'm not a very competitive person, I do have some experience with the MLG culture. My friend Cody and I would play Halo 3 almost every single day for hours back in high school, and over time I actually got pretty good. I remember considering myself really good at Halo, but compared to Cody I was terrible. He got more and more competitive, and eventually he got into the MLG multiplayer playlists. These playlists feature exact maps and gametypes that MLG uses in its tournaments. These changes affect the weapons on the map, spawn points, starting weapons, and other things that I remember not caring about when Cody was explaining everything to me. I wasn't interested in the highly competitive, strict rules of MLG, and would have preferred to just play normal multiplayer maps.
Eventually Cody started playing with a few people who were interested in actually attending a tournament, and so I started seeing less and less of him. I would still play some regular games with him, but he would frequently leave once his team signed on for practice. I remember thinking it was absurd that you could "practice" a videogame like you would a sport, and I actually made fun of his meetings, which I dubbed "team-time." He saw the humor in it, but he still kept getting sucked in. He told me stories of people he knew who would snort Adderall, an ADD medication, before games to boost their concentration, which I thought was completely outrageous. He ordered the exact monitor and headphones MLG used in their tournaments, and even fashioned a table that was the regulation height off the ground. We both thought it was kind of ridiculous and we constantly made jokes about the whole situation, but that didn't stop him. Sometimes I would play with his team when they weren't off being serious, which was never fun for a few reasons. First off, they were all much, much better than I was, and I thought I played a lot. Second, they were jerks. I don't know what was more annoying, the cursing or the relentless insults, but I eventually stopped playing with them.
I found out that Cody was actually going to a tournament in Dallas, and that he would probably only be playing with his team when he was online to practice. I stopped going over to his house to play system link as much, and sending him invites to play, and soon stopped playing multiplayer all together. I realized at that point that I wasn't having fun playing the game, I was having fun playing the game with my friend in real life.
They actually did pretty well for a team called "Amateur Hour," a name I thought of as a joke. But after the tournament Cody started playing with his team less and less, and eventually stopped for good. We went back to casually playing, which was ultimately the most fun for us.
There's a divide in the multiplayer universe between casual and competitive/professional, and I discovered a lot about the competitive side. Professional gaming is a strange concept to me, especially when it involves drugs and changes in lifestyle. But my experiences have made me question the difference between sports and multiplayer. Why is it considered acceptable for someone to practice hours at the batting cage but not at the computer? I still don't know, but I do recognize that both categories are very similar, especially when it comes to the competitive mindset. I think that as MLG and videogames become more popular, it will become more socially acceptable for someone to have a videogame "team." I probably wouldn't have made fun of Cody so much if this were more common, and who knows, maybe I would have wanted to join his team. Besides, $20,000 grand prize isn't so bad either.
For more information: http://www.majorleaguegaming.com/


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Scandinavian Miss Kit
This 4"doll is dressed in a general style typical of the early Swedish, Finnish, Norwegian and Danish women and girls that immigrated to the Pacific NW in from the mid-1800's to the early 1900's. Individual countries had many colorful variations of this costume. This little Miss can get you started!


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WGI Sport of the Arts seeks a qualified candidate for the full-time position of Full Stack Web Developer / IT Coordinator to work in our Dayton, OH headquarters.
This position is responsible for administration of the WGI.org website, including but not limited to, updating WordPress, writing custom PHP additions to the existing database system, database optimization, frontend design, and troubleshooting any existing issues. Will be responsible for the performance, integrity, security, planning, development of, and troubleshooting any issues involving the organizations database and website.
· 3-5 years of work experience
· Expert in PHP & MySQL
· Experienced in HTML, CSS, & JavaScript
· Experience with WordPress frontend and backend including custom development
· Experience with managing code in GitHub
· Understanding of web security best practices
· Basic understanding of networks and networking
· Basic knowledge of web performance and caching
· Prefer candidates with experience working with Pantheon web hosting
Candidates must have the ability to troubleshoot and creative problem solve and to work with external technology vendors. Must also have the ability to adapt to changing technologies and priorities.
Resumes should be sent via email to Bart Woodley, Director of Operations at firstname.lastname@example.com, or mailed to: WGI Sport of the Arts, 2405 Cross Pointe Drive, Miamisburg, OH 45342.
WGI Sport of the Arts is the world's premier organization producing indoor color guard, percussion, and wind ensemble competitions. As a non-profit youth organization, WGI serves as the leading governing body of the winter guard and indoor percussion activities. It is called the Sport of the Arts because it brings music to life through performance in a competitive format.


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Local Anesthesia for Plastic Surgery, An Issue of Clinics in Plastic Surgery
Publication Date
The scope of use of local anesthetics in procedures in plastic surgery is covered in this issue of Clinics in Plastic Surgery. Discussion centers on plastic surgeons in private practice in ambulatory facilities and those scheduling time for OR in hospital facilities using local anesthetics while accommodating patient comfort and absence of side-effects post general anesthesia. Presented in this publication are the most common plastic surgeries that can be done under local anesthesia, each with a discussion of the optimal anesthetic, method of administration, and dosage. Video of the procedure or portion of the procedure, as applicable, accompanies the techniques along with a surgical case. The goal of this issue is to provide a concise reference for surgeons' planning surgeries to review and perhaps adapt currently used methods with this latest information on local anesthetics. Surgical Technique is provided in detail with full analysis of Patient Selection and Planning, Complications and Post-procedure Care. Contents include Complications; Basic Science of Locals; Skin Grafts and Flaps; Peripheral Nerve; Foot Surgery; Breast Surgery; Liposuction; Hand Trauma; Oculoplastic Surgery; Ear Surgery; Hair Transplantation; among others.
|Product Format
|Publication Date
|Author Information
|By Nasim Huq, MD, McMaster University & Niagara Plastic Surgery Centre
|Publication Date
|Stock Status
|In Stock
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