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DryBell offers B-Stock V-1 pedals
DryBell, the manufacturer of the Vibe Machine V-1 effect pedals, offers some of their models discounted as part as their B-Stock.
The Vibe Machine V-1 is widely inspired by the famous Uni-Vibe from which it retains most of the features in a compact format. It uses custom photocells and you can connect an expression or volume pedal to modulate the oscillation speed.
DryBell also added some interesting features, such as in internal jumper that offers a Leslie cab simulation option, which can also be controlled via an expression or volume pedal, a Bright switch that enables a JFET buffer and an output buffer that can be useful if you use long cables
The V-1 also includes a TFC (Traffic Control) output, which is active only when the pedal is on, and allows for enabling other pedals in your pedalboard using looper pedals.
The Vibe Machine V-1 has a regular price of 300 €/$ approximately, but you can save around 60€/$ with a B-Stock model.
The Vibe Machine V-1 B-Stock are fully functional but feature slight cosmetic defaults. They are covered by the same warranty as the A-Stock pedals. Contact email@example.com if you’re interested.
More info about the Vibe Machine V-1 at www.drybell.com.
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- The T-Rex Fat Shuga available worldwide Until now, T-Rex only offered its Fat Shuga reverb/boost effect pedal to US guitar players. The stompbox is now distributed worldwide.
- TC Electronic introduces PolyTune Clip Still polyphonic, still white, but even smaller, the new TC Electronic PolyTune tuner for guitar and bass will glow on your instrument headstock.


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WASHINGTON (CBSDFW.COM/AP) – A Texas native and former Marine is free after Russia and the United States carried out a prisoner exchange on Wednesday. Trevor Reed, who had been jailed in Moscow, was traded for a convicted Russian drug trafficker serving a prison sentence in America.
The surprise deal would have been a notable diplomatic maneuver even in times of peace, but it was all the.
As part of the exchange, Russia released Reed, who was arrested in the summer of 2019 after Russian authorities said he assaulted an officer while being driven by police to a police station following a night of heavy drinking.and the U.S. government has described him as unjustly detained.
After news of his release, Joey, Paula, and Taylor Reed sent a statement that said, in part –
“Trevor has been wrongfully detained for a “crime” the U.S. Ambassador to Russia has said “obviously did not occur” and our family has been living a nightmare. Today, our prayers have been answered and Trevor is safely on his way back to the United States.”
The U.S. agreed to return Konstantin Yaroshenko, a Russian pilot serving a 20-year federal prison sentence in Connecticut for conspiracy to smuggle cocaine into the U.S. after he was arrested in Liberia in 2010 and extradited to the U.S.
Russia had sought his return for years while also rejecting entreaties by high-level U.S. officials to release Reed, who was nearing his 1,000th day in custody and whose health had recently been worsening, according to his family.
The two prisoners were swapped in a European country. Though officials would not say where the transfer took place, in the hours before it happened commercial flight trackers identified a plane belonging to Russia’s federal security service as flying to Ankara, Turkey. The U.S. Bureau of Prisons also updated its website overnight to reflect that Yaroshenko was no longer in custody.
The White House released a statement that said, in part –
“Today, we welcome home Trevor Reed and celebrate his return to the family that missed him dearly. Trevor, a former U.S. Marine, is free from Russian detention. I heard in the voices of Trevor’s parents how much they’ve worried about his health and missed his presence. And I was delighted to be able to share with them the good news about Trevor’s freedom.”
The prisoner swap marks the highest-profile release during the Biden administration of an American deemed wrongly detained abroad and comes even as families of detainees who have met over the last year with administration officials had described them as cool to the idea of an exchange.
In their statement, the Reed family also thanked President Joe Biden “for making the decision to bring Trevor home” as well as other administration officials and Bill Richardson, the former U.S. ambassador to the United Nations whom the family said traveled to Moscow in the hours before the Ukraine war began in hopes of securing Reed’s release.
Reed was one of several Americans known to be held by Russia,who was detained in February after authorities said a search of her bag revealed a cannabis derivative, and Michigan corporate security executive Paul Whelan, who is being held on espionage-related charges his family says are bogus. It was unclear what if any impact Wednesday’s action might have on their cases.
in March. They had stood weeks earlier along his motorcade route during a presidential visit to Texas in hopes of attracting his attention, then later demonstrated outside the White House to ask for a meeting.
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Majestic Premium Cocoa Powder
Dark Chocolate Covered Blueberries
3-Stack Gold Polka Dot Tower
Blue/Gold Sauce Pumps - 18ct. Bulk Individually Wrapped
Enjoy a free hot cocoa pouch with every purchase!
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THE PROPERTY: Set within the historic surroundings of Grade II-listed Preston Hall, this two-bedroom apartment offers an elegant mix of contemporary and period design.
THE LOCATION: Preston Hall is reached via a formal tree-lined road, giving the whole estate privacy and seclusion. The grounds, covering approximately 2.5 acres, include beautifully manicured gardens, formal lawns, sculptures and a dramatic stone fountain. Just over a mile away lies the picturesque village of Aylesford, while the wide-ranging amenities of Maidstone are also within reach.
THE INTERIOR: Beyond the manor’s impressive communal Grand Reception Hall, the apartment opens into a space with double-height ceilings and a white marbled floor. The property features a ground-floor master suite with carved oak panelling on the walls and bookcases, a mezzanine second bedroom, and a modern kitchen and living area. A pair of French doors, framed within a bay window, offer delightful views and direct access onto the grounds and the North Kent Downs beyond.
WHY WE LOVE IT: This is a rare opportunity to live in one of Kent’s most historic homes. While the Hall was completed in 1850, the associated estate dates back to the Norman period, and was owned by the Culpepper family for more than 400 years. During the First World War, the Hall was used as a hospital and home for servicemen, and housed the notable writer George Orwell.
BUY IT NOW: £675,000 with Fine and Country

domain: history


- Product Features
- Photos & Videos
Product FeaturesThis is a handy 3-channel Red-Green-Blue dimmer. It's very easy to use. Just connect your 4-wire (common anode) RGB strips to the output and apply 12 or 24 volts DC, whichever is required by your strips.
- Output is 12 or 24 VDC, matching the driver you use.
- Smooth pulse width modulation dimming all the way down to 0%.
- 3 amps per channel maximum output (3 x 12 volts = 36 watts per channel, at 12 volts; 3 x 24 volts = 72 watts per channel, at 24 volts.).
- Terminal block outputs and inputs, with plastic touch guard.
- 700 Hertz output.
ApplicationsUsed for dimming our 12 or 24 volt LED Red-Green-Blue strips. In vehicular installations, be sure to put some input protection in front of the dimmer (and LED strips), as usual, to protect the LEDs from over-voltage conditions that result when the alternator charges the system battery at 13 or 14 volts.
Input Voltage 12 or 24 DC Output Voltage 12 or 24 DC Length (English) 5.13 in Length (Metric) 130 mm Width (English) 1.57 in Width (Metric) 40 mm Height (English) 2.06 in Height (Metric) 52 mm Warranty 1 year
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I'm new to this forum but I've been posting at bodybuilding.com for a while now. Here's a link to my workout journal over there, which I will also continue here.
My long term goals are to get bigger and stronger while staying lean, so next fall I can run track in college. Currently I am lean bulking but I seem to be burning off fat slowly but surely as well... works for me!
2800-3000 calories, roughly 40/30/30 ratio for carbs/protein/fats
I eat a lot of chicken breast and lean beef, occasional fish, and two whey protein shakes daily (breakfast and post-workout). My carbs currently come mainly from oats, Barilla Plus pasta, whole grains, and a lot of fruits and veggies. I really like sweet potatoes so I eat them whenever I can. For fats, it's mostly olive oil and peanut butter, and some fats from meat, cheese (I love string cheese), and legumes (big fan of the Campbell's Chunky Chili). I'm about to start a cycle of Molecular Nutrition's X-Factor so I will be really cutting back on the EFAs, especially the enriched Barilla Plus pasta, peanut butter, and olive oil... fats will be primarily from meat and cheese for a while.
I have used two creatine/NO stacks extensively in the past... Controlled Labs' White Blood and Green Bulge, and Universal Nutrition's Shock Therapy and Storm. My last run of White Blood and Green Bulge, I also took CL's GlycerGrow (GG) and I liked that a lot. Currently I'm just taking GG and creatine (the leftover Storm) and will continue that while on XF. I also take an active multivitamin twice daily (breakfast and post-workout/dinner).
I've done pyramids in the past but my current split is a modified 5x5. I much prefer split-body to full body and I've honed in on what works best for me at this stage.
Monday - chest/triceps
5x5 bench press, incline DB press, weighted dips
Tuesday - back/biceps
5x5 deadlift, weighted pullups, Dorian rows
3x8-10 DB curls
Thursday - shoulders
5x5 overhead press, rear upright rows, Arnold press, rear delt rows
Friday - legs
5x5 squat, stiff-legged deadlift, leg press, leg curls
I train core every lifting day, alternating between low reps-high weight and adding weight with moderate reps and also between strictly abs, direct oblique work, and a mix. Core training is boring, so I like to switch it up to keep it fresh. On my off days, I like to do some full body circuit training to promote recovery and sprint intervals.
So yeah... here's my journal. Feel free to post in here or PM me if you've got any questions, comments, suggestions, or whatever!

domain: health


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The Omicron Deception
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Biden’s Numbers Tank…as US Rattles Sabers At Russia
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The Ron Paul Liberty Report Podcast:
The “Strategic Petroleum Reserve” Boondoggle -- Abolish It!
It's not the business of the U.S. federal government to "stockpile" anything. But as usual with government, the "emergency" and "fear" cards are used as excuses for it to stockpile oil. However, we know not only from theory, but from practical experience, that in any emergency, the very last people that you want allocating resources are people in the federal government.
Published Nov. 26, 2021
Should We 'Cancel' Thanksgiving?
In the effort to politicize every single thing in our lives, news outlets such as MSNBC have taken to attacking Thanksgiving as a celebration of "white supremacy." It's all absurd and should stop immediately. In response, Ron Paul shares a bit about what his Thanksgiving will be like this year...and he has one very funny story to tell.
Published Nov. 25, 2021
Fauci: Critics Of Me 'Are Killing People'!
Fauci made another circuit through the adoring media yesterday, again accusing anyone of pointing out his lack of honesty and constant moving the goal posts of "killing people." Senator Paul has a great retort to this absurd and, frankly, unhinged claim. Also today: "Don't call looting looting!"
Streamed LIVE Nov. 24, 2021
NIH Director: Fauci Critics 'Must Be Brought To Justice!'
Outgoing National Institutes of Health Director Francis Collins told the Washington Post that critics of Fauci and his organization are spreading misinformation and should be "brought to justice." He continues the "I am science" argument of Fauci even as the multitude of flip-flops and failed promises have undermined public confidence. Also today: Australia goes full gulag, medical devices are "racist," and the corporate elite are desperate to sell Africa drugs they don't seem to need...
Streamed LIVE Nov. 23, 2021
Fauci Now Claims The Vax Doesn't Protect Against Serious Covid!
In an interview with the New York Times earlier this month, Fauci made a startling revelation: the vaccine wanes so seriously that it doesn't even protect against hospitalization and death! His solution? MORE shots. Will America keep listening to him? Also today: South Korea got fully vaxxed...then they all got covid! What's going on here?
Streamed LIVE Nov. 22, 2021


Pep Guardiola issues tongue-in-cheek message to Liverpool’s opponents Southampton
Pep Guardiola says he is relishing Manchester City’s final-day clash with Aston Villa after jokingly urging Southampton to “beat Liverpool 4-0” on Tuesday.
The Manchester City boss was asked if he had a message for Liverpool’s midweek opponents after watching City’s 2-2 draw with West Ham.
The champions were 2-0 down at the break, but hit back through goals from Jack Grealish and an own goal. They also missed a penalty as they earned a deserved point.
The draw keeps the title in their hands, but if Saints defeat Liverpool on Tuesday they will be champions once more.
A win for Liverpool will move Jurgen Klopp’s men to a solitary point behind. City will host Steven Gerrard’s Aston Villa and Liverpool are at home to Wolves.
Asked if he Guardiola had a message for Southampton, he told Sky Sports: “I would say, beat Liverpool four-zero!
“The big, big privilege we have is that, at home, it’s in our hands. We don’t have to look at anything else other than ourselves. We just have to give everything.
“I said [to the players], ‘Don’t be sad today because we gave a really good performance. It’s fair, against this opponent, to arrive at the last day to decide who gets the title because both teams are so good’.
“Against this Liverpool you cannot win the league with four games ago. You have to fight until the end.
“Next week our stadium will be sold out, we will give them our lives and they will give theirs, all together. To do it is an incredible privilege, after many years.
“To have our chance with our people, to win one game to be champions. I’m looking forward to it.
Guardiola: ‘Aguero moment belongs to Mancini’
“We are going to rest for one or two days, mentally disconnect, and then train three or four days to prepare the game against Aston Villa.”
City had unveiled a statue of Sergio Aguero at The Etihad this week. A celebration of the 10-year anniversary of Aguero’s last-gasp title clincher against QPR and Guardiola was keen to avoid similar drama.
“No please, not in that moment,” he added. “That moment a decade ago belongs to Sergio, Roberto Mancini and all of the players who were there.
“I’d say it is similar because it depends on us. It will be tough because there is one part that is emotional, and you have to analyse exactly what you have to do to beat Aston Villa.
“We will give everything that we have over 95 minutes to win the title.”
READ MORE: Guardiola knew exactly what ‘almost perfect’ Liverpool would do after paying Man City star ultimate compliment


Mstislav Rostropovich opened his third season as music director of the National Symphony Orchestra last night at the Kennedy Center, leading the orchestra in the opening concert of its 49th year. He began things with a rousing reading of "The Star-Spangled Banner," which many of the large audience joined.
His formal program took off with William Schuman's power-packed American Festival Overture, which will celebrate its 40th birthday in two weeks. It easily holds its place as one of the best pieces of music any American composer has written.
There were some new touches to be heard in the overture, as is often the case any time a top conductor takes up a work he has not previously conducted. While the outer sections went with all their usual fiery spirit, Rostropovich found some new voices and accents in the quiet middle of the overture. It was altogether a beautiful performance.
The remainder of the evening was Russian, with the brash, breezy Ninth Symphony by Shostakovich, and the First Symphony of the youthful Tchaikovsky. The sound theory that every composer foreshadows his mature style in his early works was proven in both of these symphonies.
Often during the Shostakovich Ninth there were passages that looked directly back into the heart of his First Symphony, written two decades before. But the later symphony, written immediately after World War II, has an assurance about it, to say nothing of a willingness to be lighthearted, even nose-thumbing. That perky theme in the opening movement is perfect impure Shostakovich.
There are beautiful solos scattered through the symphony, and after its strong conclusion, Rostropovich walked through the orchestra and beckoned to the solo bassoon, piccolo and violin to stand and acknowledge the applause with him.
The orchestra was in fine form all evening. This was not a seasonal opening after which to apply the phrase, "It is too early to discuss the orchestra's merits." The musicians sounded at a real peak, with the brass choir in shining form and the strings frequently of a special sheen.
At intermission, board president Austin Kiplinger brought onstage two players who are retiring after this week's concerts: cellist Franz Vlashek, who has been in the National Symphony for 27 years, and percussionist John Kane, a member for 17 years. The audience applauded them generously as it had before the program when Rostropovich had brought them out in front of their colleagues.
In the Tchaikovsky the process was reversed from that in the Shostakovich: Much in the lovely music strongly forecasts characteristic harmonies and instrumental textures that will be part of the fabric of the greatest Tchaikovsky to come. The slow movement, especially, presages the last act of "The Queen of Spades," while often there are pre-echoes of "Swan Lake."
The oboe in the slow movement was a thing of particular beauty, joined in a touching trio by bassoon and flute, over muted strings. The finale has problems in getting going, but none in reaching a roaring closing. The audience was shouting when it was all over. It made for a hearty beginning to the season.


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Non-Executive Director & Deputy Chairman
Mike became a Non-Executive Director when he retired from his clinical role as a consultant gynaecologist for the Trust, which he had held since 1992.
After qualifying and initial training in Obstetrics and Gynaecology, Mike spent 12 years as a GP before retraining to become a Consultant Obstetrician and Gynaecologist, and was appointed in Worthing in 1992.
In 2013 Mike was elected as a Staff Governor representing the Trust’s medical workforce on the Council of Governors.
Outside of his gynaecology role, Mike has also been chair of the BMA local negotiating committee, chair of the Sussex gynaecological tumour group, a member of the speciality training committee of the Royal College of Obstetricians and Gynaecologists and chair of the medical advisory committee of Goring Hall Hospital.
Mike is a Trustee and Board member of St Barnabas Hospice and a Board member of the East Sussex Clinical Commissioning Group.
His wealth of clinical knowledge and expertise, as well as his experience as an employee of the Trust, make him an ideal member of the Board.

domain: medical


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Unusual necklace with three rows of white baroque and oval circled pearls and 14K yellow gold elements. The length of the necklace is approximately 41 cm
Ask our Jewelry Experts:
Στείλτε μας μήνυμα ή καλέστε μας:
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Risk warning: Trading foreign exchange on margin carries a high level of risk, and may not be suitable for all investors. The high degree of leverage can work against you as well as for you. Before deciding to invest in foreign exchange you should carefully consider your investment objectives, level of experience, and risk appetite. All information provided by Myforexchart is for educational purposes only. Myforexchart does not take any responsibility and/or liability for any financial investing of any sort that was initiated and/or carried out based upon or using information from Myforexchart or and/or its affiliates.
Forex is one of those areas that most people feel is complicated. In reality, it's like many other forms of investment, a little knowledge can be dangerous. The good news for people out there looking for forex investing strategies is that there are enough strategies out there to meet any investment goal. You can be a simple long-term investor, or you can sit and watch the market every day looking for profit at every turn. As long as you want to learn forex trading, you can find a method that's right.
Fusion Media sitede yer alan bilgilerin gerçek zamanlı ya da isabetli olacağının mutlak olmadığını hatırlatır. Tüm borsa fiyatları, endeksler, vadeli işlemler, Forex ve kripto para fiyatları, borsalardan değil piyasa düzenleyicileri tarafından oluşturulur, bu sebeple fiyatlar isabetli olmayabilir ve gerçek piyasa fiyatlarından farklı olabilir, bu da buradaki fiyatların fikir verme amaçlı olduğunu ve ticari amaçlar için uygun olmadığını gösterir. Fusion Media veya herhangi bir sağlayıcı, buradaki bilgileri kullanmanız sonucu oluşacak olası kayıplarınızdan ötürü sorumluluk taşımamaktadır.
End-users of the NetDania software that make use of the trading integration features as direct clients of integrated brokers, should be aware of the level of risk carried by trading in financial markets. Trading foreign exchange and or other financial instruments on margin carries a high level of risk, and may not be suitable for all investors. The high degree of leverage can work against you as well as for you. Before deciding to invest you should carefully consider your investment objectives, level of experience, and risk appetite. The possibility exists that you could sustain a loss of some or more of your initial investment, and therefore you should not invest money that you cannot afford to lose. You should be aware of all the risks associated with trading, and seek advice from your broker and or an independent financial advisor if you have any doubts. Anyone opening a live trading account needs to adhere to the laws of their local country as such laws may differ from country to country.
While Forex trading can feel complicated, it's something that anyone with patience and the ability to learn from their mistakes can gain some skill at over time. It takes some persistence. The system is designed in a way that frustrates most people. You need to step back, keep an eye on the big picture, and trade small, at least in the beginning. It's also smart to avoid those "100 percent accurate forex trading systems" on the internet until you have some experience under your belt.
The owners of the website and the website hereby waive any liability whatsoever due to the use of the website and/or information. Use of the website, the content and the information is made on the user's sole liability. The user hereby releases the owners of the website from any liability for damage caused to his computer, in any, through the use of the website and/or its content and/or its various services. The user hereby releases the owners of the website, the website, their partners, agents, employees, officers, managers, directors, shareholders, etc. from any liability for losses and/or financial damages and/or personal bodily damages and/or fraud, caused through the use of the website.
Shortened as “Vol.” in the economic calendar and depicted as yellow/orange/red bars, the volatility is an indicator of the expected impact of a data on currencies. Shall a bar be red and long, market observers expect this data to have great probability to move the Forex market. Shall this bar be yellow and short, the probability is viewed as low. In orange, we’re just in between.
I showed this fractal several times lately, since it has been a nice guideline so far. The red circles are not really the same though. Back then we had a good double bottom, this time we don't but have been moving bit similar up nonetheless. The right shoulder is very different this time compared to 2017, that one was completed much faster and the rally was much...
Map out the magnitude of price moves with Retracements and Arcs. These tools let you draw studies about the possible developments of a price based on its previous move. It can be calculated following different mathematical concepts (Fibonacci, Gann…). While retracements are concerned with just the magnitude of moves, Arcs factor both magnitude and time, offering areas of future support or resistance that will move as time progresses. How to add Retracements and Arcs
Hello all - DuncanForex with another trade idea. With NFP coming in strong on Friday and USD gaining strength - the question is: Is this short term sentiment and will the FED support further USD strength or will the FED still suggest a rate cut and in turn will USD weaken,? Therefore, the recent price action being a stop loss hunt before heading higher quite...
Little happened across the FX board these last few days, with a US holiday in the middle and a scarce macroeconomic calendar exacerbating the lack of action. Such picture changed Friday with the release of the US Nonfarm Payroll report. Ahead of it, the market was convinced that the global economic slowdown would mean easy money coming. Stocks soared, with Wall Street flirting with record highs, while safe-haven assets benefited from those fears, and government bond yields fell to multi-year lows.
DailyFX provides traders with an easy to use and customizable real-time calendar that updates automatically during announcements. Keep track of significant events that traders care about. As soon as event data is released, the DailyFX calendar automatically updates to provide traders with instantaneous information that they can use to formulate their trading decisions.
Bulls in full control right now with uptrends on the weekly, daily, 4H and hourly charts. When we lose the hourly uptrend, we look for a 4H higher low, When we lose the 4H uptrend we look for a daily higher low. I personally will hold my swing positions as long as we are in a daily uptrend. The odds of a bull break over $13.8k vs. a weekly lower high continue...
Aviso legal: Las operaciones con instrumentos financieros o criptomonedas implican un elevado riesgo, incluyendo la pérdida parcial o total del capital invertido, y pueden no ser adecuadas para todos los inversores. Los precios de las criptomonedas son extremadamente volátiles y pueden verse afectados por factores externos de tipo financiero, regulatorio o político. Operar sobre márgenes aumenta los riesgos financieros.

domain: finance


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Category:World War II naval ships of Japan
From Wikipedia, the free encyclopedia
This category is for naval ships designed, built, or operated by Japan during World War II (1939–1945).
This category has the following 8 subcategories, out of 8 total.
- ► World War II aircraft carriers of Japan (1 C, 27 P)
- ► World War II battleships of Japan (14 P)
- ► World War II cruisers of Japan (53 P)
- ► World War II destroyers of Japan (154 P)
- ► World War II mine warfare vessels of Japan (1 C, 13 P)
- ► World War II patrol vessels of Japan (4 P)
- ► World War II submarines of Japan (1 C, 67 P)
Pages in category "World War II naval ships of Japan"
The following 72 pages are in this category, out of 72 total. This list may not reflect recent changes (learn more).
- No.1-class auxiliary minelayer
- No.1-class auxiliary minesweeper
- No.1-class auxiliary patrol boat
- No.1-class auxiliary submarine chaser
- No.1-class minesweeper
- No.1-class submarine chaser
- No.1-class landing ship
- No.1-class patrol boat
- No.101-class landing ship
- No.13-class minesweeper
- No.13-class submarine chaser
- No.19-class minesweeper


1978 Camaro Fuse Box Diagram
Last updated on
1978 Camaro Fuse Box Diagram
1978 Camaro Fuse Box Diagram. The wiring diagram on the opposite hand is particularly beneficial to an outside electrician. Sometimes wiring diagram may also refer to the architectural wiring program. The simplest approach to read a home wiring diagram is to begin at the source, or the major power supply.
19/09/2018 · Pontiac Firebird (1979) - fuse box diagram
13/11/2017 · Chevy Camaro & Firebird Fuse box locations and OBD 2 computer hookup port. ... Abandoned 1978 Pontiac Trans Am Driven From Grave After 10 Years ... Fuse Pull 5&20 v8 Camaro - …
You should always have some extra fuses and relays to make a replacement when it's needed. CARiD is ready to provide you with reliable 1978 chevy camaro electrical parts 7 days a week 24 hours a day.
Second Generation Camaro Owners Group - Camaro Wiring and Electrical Information. The electrical system is critical to your cars operation. It might seem like a complex and confusing mess, but if you approach this logically and use the sites wiring diagrams …
23/12/2008 · The only fuse box i know of on the 91 Firebird is located under the dash Above your left leg. I am not sdure if that is the same for all engine sizes and models.
1978 camaro fuse box diagram thank you for visiting our site, this is images about 1978 camaro fuse box diagram posted by Maria Nieto in 1978 category on Oct 24, 2019. You can also find other images like images wiring diagram, images parts diagram, images replacement parts, images electrical diagram, images repair manuals, images engine diagram, images engine scheme diagram, images …
All Chevrolet Fuse Box Diagram Models Fuse Box Diagram and detailed description of fuse locations.
22/05/2018 · Ford Mustang (1974 - 1978) - fuse box diagram
1978 corvette fuse box wiring diagram thanks for visiting our site, this is images about 1978 corvette fuse box wiring diagram posted by Ella Brouillard in 1978 category on Oct 27, 2019. You can also find other images like corvette wiring diagram, corvette parts diagram, corvette replacement parts, corvette electrical diagram, corvette repair manuals, corvette engine diagram, corvette engine ...
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He tottered over to the thermostat and there it was: treachery. Despite a long-fought household compromise standard of 74 degrees, someone — Adler’s suspicions instantly centered on his wife — had nudged the temperature up to 78.
For the sleepy freelance writer, it was time to set things right . . . right at 65 degrees. “I just kept pushing that down arrow,” he said of his midnight retaliation. “It was a defensive maneuver.”
The article suggests that women generally prefer higher thermostat settings than men. (It is the opposite in my household.) The focus is on air conditioning in the summer and I wonder whether this ranking reverses in the winter. (My wife prefers more moderate temperatures: cooler in the summer, warmer in the winter. )


text:
Fabric Organic cotton
ORGANIC COTTON 101
Like organic foods 20 years ago, the idea of organic cotton is confusing to many of us. It’s taken a little longer to catch on because the correlation isn’t as direct. We don’t eat cotton fiber (at least we hope you don’t!) However, more people are becoming knowledgeable as to how the organic cotton movement is just as powerful and important as that of organic foods.
In addition to being one of the most widely grown crops in the world, growing conventional cotton is also one of the most chemical-intensive. These chemicals have tremendous impact on the earth’s air, water, soil, and the health of people in cotton-growing areas. They are among the most toxic chemicals as classified by the Environmental Protection Agency.
The problem is even worse in developing countries with uninformed consumers, and lack of stable institutions and property rights. In addition to destroying the land, thousands of farmers die from exposure to these chemicals every year.
So, we’ve decided to put together a little information to help spread the word. Check out our questions and answers below.
QUESTIONS AND ANSWERS
Organic cotton is grown using methods and materials that have a low impact on the environment. Organic production systems replenish and maintain soil fertility, reduce the use of toxic and persistent pesticides and fertilizers, and build biologically diverse agriculture. Third-party certification organizations verify that organic producers use only methods and materials allowed in organic production. Organic cotton is grown without the use of toxic and persistent pesticides and synthetic fertilizers. In addition, federal regulations prohibit the use of genetically engineered seed for organic farming. All cotton sold as organic in the United States must meet strict federal regulations covering how the cotton is grown.
According to the 2011 Textile Exchange Organic Cotton Farm & Fiber Report, approximately 151, 079 metric tons (MT) of organic cotton (693, 900 bales) were grown on 324, 577 hectares (802, 047 acres) in 2010-2011. Organic cotton now equals 0.7 percent of global cotton production.
Organic cotton was grown in 20 countries worldwide in 2010-11, led by India, and including (in order of rank): Syria, China, Turkey, United States, Tanzania, Egypt, Mali, Kyrgyzstan, Peru, Pakistan, Uganda, Burkina Faso, Benin, Paraguay, Israel, Tajikistan, Brazil, Nicaragua, and Senegal. Approximately 219, 000 farmers grew the fiber.
According to a report by Textile Exchange 2010 Global Market Report on Sustainable Textiles, global sales of organic cotton apparel and home textile products reached an estimated $5.16 billion in 2010. This reflects a 20 percent increase from the 2009 market. Companies reported significant growth in their organic cotton programs, and increased adoption of standards. Approximately 219, 000 farmers grew the fiber.
U.S. organic cotton production continues to increase, encouraged by consumer and corporate demand, price premiums, and regulatory shifts that facilitate clear labeling for organic cotton products. According to an OTA survey of U.S. organic cotton production undertaken with funding from Cotton Incorporated, the number of acres planted with organic cotton in the U.S. increased 36 percent from 2009-2010, while bales harvested were up nearly 24 percent. U.S. producers harvested 11, 262 acres of organic cotton in 2010, representing 95 percent of planted acres, and yielding 13, 279 bales.
While 2011 saw the largest number of acres planted since 1999, harvested acres and bales are expected to be down by 38 and 45 percent, respectively, due to a devastating drought in the southern Plains. In fact, the extremely dry conditions in Texas forced farmers there to abandon more than 65 percent of their planted crop in 2011. A modest acreage gain of two percent is forecast for 2012, bringing plantings of U.S. organic cotton to 16, 406 acres. Another two percent net gain is in the five-year forecast, bringing the total to 16, 716 acres. Opportunity exists for significant expansion of U.S. organic acreage, most likely in nascent organic cotton-growing regions such as North Carolina, which harvested its first crop of organic cotton in 2011.
Apparel companies are developing programs that either use 100 percent organically grown cotton, or blend small percentages of organic cotton with conventional cotton in their products. There are a number of companies driving the expanded use of domestic and international organic cotton. For a current list of OTA members with products containing organic fiber, visit The Organic Pages Online™
In 2011, organic fiber sales in the United States grew by 17.1 percent over the previous year, to reach $708 million, according to the Organic Trade Association’s 2012 Organic Industry Survey. The future looks promising, with organic fiber products appearing in more mainstream outlets, led by large and small U.S. textile retailers alike.

domain: agronomy


text:
The first major changes to South Australia’s liquor licensing system in nearly two decades have passed state Parliament, paving the way for a simpler, more effective system.
The changes include:
- new licensing categories, aimed at simplifying the process for venues and events to apply for a licence
- tougher laws around the secondary supply of alcohol to minors, where a person who supplies alcohol to the minor in contravention of the new laws will face a maximum penalty of $10,000 and expiation fee of $500. A minor who consumes or has possession of alcohol in contravention of the new laws will also face a maximum penalty of $2,500 and expiation fee of $210
- cutting red tape for new and existing licensees
- removing outdated restrictions on the sale of liquor on Sundays, Christmas Day, Good Friday, New Year’s Eve and New Year’s Day
- abolishing the anti-competitive “needs test”.
The reforms will be implemented in phases, with consultation to take place with industry on some key elements of the reform prior to their implementation.

domain: law


text:
Trump inherited a booming, successful economy. After a bruising recession, the unemployment rate finally was back to less than 5%. More jobs were being created, the stock market was rising steadily, and wages finally were going up. Most people’s lives were much better than they were when Obama took office eight years earlier. And importantly, following decades of steady deterioration, the quality of jobs finally was going up too.
Now, though, the quality of jobs is declining again. As this article explains, the jobs being created “are increasingly low-quality jobs.” And so wages are stagnant, and many, many people can’t find good jobs.
This is what the GOP does for you. This is what Tom McClintock does for you. Trump and the Republicans decided to squander your taxpayer dollars on a massive giveaway to the wealthy. They gave some of us small, temporary tax cuts, while the 1% got massive, permanent cuts. Instead of an infrastructure bill that would have created good jobs across the country — increasing wages everywhere, as workers took those jobs and employers were forced to raise wages to compete for talent — the GOP chose to pay back their wealthy donors. And Tom McClintock has told us, loudly and clearly, that he’ll do the same thing if we make the mistake of reelecting him.
California’s 4th District deserves better. We deserve a representative who sees our challenges with clear eyes and takes meaningful action to fix them. We deserve a representative who truly cares about what happens in this District. We deserve a representative who will fight for us.
Join us, as we fight to send Tom McClintock back to his own District, and to finally stop him from selling us out, one vote at a time.
Because we know, as Margaret Mead said, that “a small group of thoughtful, committed people can change the world. Indeed, it’s the only thing that ever has.”

domain: sociology


text:
MicroRNAs are emerging as new mediators in the regulation of adipose tissue biology and the development of obesity. An important role of microRNA-125a has been suggested in the pathogenesis of insulin resistance (IR). Here, we characterized the function of microRNA-125a in adipose tissue in a context of experimentally-induced IR and obesity in mice and in obese patients. We showed time dependent overexpression of the microRNA in adipose tissue of BALB/c and C57BL/6J mice in response to high fat diet (HFD) feeding. MicroRNA-125a expression was downregulated in vitro in insulin resistant 3T3-L1 adipocytes and ex vivo in adipose tissue of obese patients. In vitro modulation of microRNA-125a expression in 3T3-L1 adipocytes did not affect glucose uptake. Gene set enrichment analysis (GSEA) identified significantly altered expression patterns of predicted microRNA-125a gene targets in transcriptomic datasets of adipose tissue from HFD-fed mice and obese patients. Among genes that contributed to global enrichment of altered expression of microRNA-125a targets, Thyrotroph embryonic factor (Tef), Mannan-binding lectin serine peptidase 1, Reticulon 2 and Ubiquitin-conjugating enzyme E2L3 were significantly differentially expressed in adipose tissue in these groups. We showed that Tef expression is reduced in adipose tissue of obese patients following gastric bypass surgery. Our findings indicate that microRNA-125a expression in adipose tissue adapts to IR and may play a role in the development of obesity in mice and obese subjects through uncoupled regulation of the expression of microRNA-125a and its targets.
Citation: Diawara MR, Hue C, Wilder SP, Venteclef N, Aron-Wisnewsky J, Scott J, et al. (2014) Adaptive Expression of MicroRNA-125a in Adipose Tissue in Response to Obesity in Mice and Men. PLoS ONE 9(3): e91375. https://doi.org/10.1371/journal.pone.0091375
Editor: Andrea Cignarella, University of Padova, Italy
Received: November 22, 2013; Accepted: February 9, 2014; Published: March 27, 2014
Copyright: © 2014 Diawara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by grants from the Wellcome Functional Genomics Initiative BAIR (Biological Atlas of IR) (066786), the European Community's Sixth Framework Programme under the grant agreement LSHG-CT-2006-037683 (FGENTCARD), the Société Francophone du Diabète, the Institute of Cardiometabolism and Nutrition (ICAN, ANR-10- IAHU-05) and a Wellcome Senior Fellowship in Basic Biomedical Science (057733) to D. Gauguier. M. Diawara is supported by a PhD studentship from the Ile de France region (CORDDIM). The Direction of Clinical Research (CRC) promoted and supported clinical investigations (PHRC 02076 and CRC FIBROTA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Obesity and type 2 diabetes mellitus (T2DM) are major health issues caused by a complex interplay between genetic risk factors and environmental influences, including sedentary lifestyle and change in feeding behavior , . Insulin resistance (IR) is a cardinal pathophysiological feature in these chronic diseases . Defining molecular signatures of the onset and progression of T2DM and obesity has become crucial to provide a deeper understanding of the mechanisms involved and uncover predictive and therapeutical targets. Owing to the complexity of molecular studies in humans and limitations in access to organ biopsies in patients and controls, animal models of obesity and T2DM represent powerful tools to identify etiological mechanisms of IR. Models of spontaneously-occurring T2DM, such as the Goto Kakizaki (GK) rat , and experimentally-induced obesity by high fat diet (HFD) feeding  are widely used to identify novel genes and gene pathways involved in IR. We have previously demonstrated contrasting pathophysiological responses to HFD in C57BL/6J and BALB/c mice , .
Progress in molecular genetic technologies, which allows deeper analyses of genome expression patterns contributing to, or reactive to, a disease phenotype, has underlined new molecular mechanisms mediated by microRNAs (miRs) in the biology of adipose tissue and the development of obesity , , , . MiR is a family of highly conserved, single-stranded, 19–23 nucleotide long, non-coding, endogenous RNAs, which negatively regulate gene expression either by inhibiting translation or by degrading target mRNAs . One miR can target several mRNAs and one transcript can be targeted by several miRs. Such interactions regulate various aspects of metabolism through pancreatic development, insulin biosynthesis, secretion and signaling, adipocyte differentiation and glucose uptake , .
We have demonstrated differential expression of a series of miRs in the GK rat model of polygenic IR , . Consistent overexpression of miR-125a in both liver and adipose tissue of the GK rat suggested that this miR may play an important role in IR pathogenesis . To further characterize its function in a context of experimentally-induced IR, we investigated the regulation of the expression of this miR and its proposed transcript targets in adipose tissue from C57BL/6J and BALB/c mice fed HFD and from obese patients. Our results indicate that miR-125a expression is reactive to IR and suggest that uncoupled differential expression of miR-125a and its mRNA targets may play a role in the development of obesity.
Seventeen severely obese patients, who were candidates for bariatric surgery and 7 non-obese subjects were included in a study protocol approved by the Ethics Committee of Hotel-Dieu Hospital, and signed informed written consent. Physiological parameters are listed in Table 1. In the group of 17 severely obese patients, 7 patients had T2DM. Body mass index was calculated from the measured body weight and height. Subcutaneous periumbilical adipose and omental biopsies were collected at the time of surgery. Blood samples were obtained at each time point after 12 h overnight fasting and stored at −20°C until assays of plasma total cholesterol, triglycerides, insulin, glucose, leptin, adiponectin, and liver marker, γ-glutamyltransferase (γGT). Pangenomic expression of subcutaneous adipose tissue was conducted before and after gastric surgery as described . Fat and fat-free mass were determined by dual-energy X-ray absorptiometry (GE Lunar Prodigy Corp., Madison, WI). QUICKI was determined by a mathematical calculation using fasting glucose and insulin as described previously by Katz et al. . These evaluations were performed before surgery and during the post-surgery follow-up. Plasma glucose, triglycerides, and total cholesterol levels were measured enzymatically. Serum insulin concentrations were determined with immunoradiometric assay (Bi-INSULIN IRMA CisBio International, Gif-sur-Yvette, France). Serum leptin and adiponectin were determined using radioimmunoassay kits (Linco Research, Saint Louis, MI, USA).
Male C57BL/6J and BALB/c mice were bred from Jackson laboratory stocks. Mice were weaned at 3 weeks and fed a control carbohydrate diet (CHD) containing 5% fat, 19% protein and 3.5% fibers (S&K Universal Ltd, Hull, United Kingdom). At 5 weeks, a group of mice was transferred to 40% HFD (High-fat diet) containing 40% saturated fat, 19% protein, 21% glucose (Special Diet Services, Witham, United Kingdom) ad libitum, whereas the control group remained on CHD. Mice fed HFD for 1 week and 15 weeks, and age-matched controls were killed by CO2 asphyxiation. Epididymal fat pads (EPD) were rapidly dissected and snap frozen in liquid nitrogen and then stored at −80°C. Animal procedures were carried out under United Kingdom Home Office personal and project licences and approved by the ethical review panel of the University of Oxford.
Glucose tolerance and insulin secretion tests in mice
Intraperitoneal glucose tolerance tests were performed in overnight fasted mice. Briefly, mice were anesthetized with an intraperitoneal injection of sodium pentobarbital (Sagatal, Rhône Mérieux, Harlow, United Kingdom) and a solution of glucose (2 g/kg body weight) was injected intraperitoneally. Blood samples were collected from the tail vein before the injection and 15, 30 and 75 min afterward. Blood glucose was immediately determined with a glucose meter (Accucheck, Roche Diagnostics, Burgess Hill, United Kingdom). Plasma samples were stored at −80°C until assayed for immunoreactive insulin (ELISA, Mercodia, Uppsala, Sweden). Cumulative glycemia and insulinemia were calculated as the increment of the values of plasma glucose and insulin, respectively, during the test. Characterization of the short and long-term consequences of fat feeding on the onset and progression of insulin resistance, diabetes and obesity in C57BL/6J and BALB/c is described in Table 2.
In vitro adipocyte differentiation from 3T3-L1 cells and induction of IR
3T3-L1 fibroblasts were differentiated into adipocytes by a protocol adapted from Nugent et al. . 3T3-L1 fibroblasts (LGC standard, Molsheim, France), between passages 4 and 8 were cultured in a growing medium containing DMEM (Life technologies, Saint Aubin, France), 25 mmol/l glucose, 4 mmol/l L-glutamine, 1 mmol/l sodium pyruvate, 10% FBS (PAA laboratories, Velizy-Villacoublay, France), 1% penicillin/streptomycin in humidified air at 37°C and 5% CO2. Two days after confluence, cells were incubated in a differentiating medium containing the growing medium supplemented with 0.25 μmol/l dexamethasone, 500 μmol/l 3-isobutyl-1-methylxanthine (IBMX), 0.4 μmol/l insulin (Sigma Aldrich, Saint Quentin Fallavier, France). After three days, cells were placed in differentiating medium supplemented with 0.4 μmol/l insulin and at day7 mature adipocytes were obtained and maintained in differentiating medium with 5% FBS. After differentiation, 3T3-L1 adipocytes were weaned for two days in a low-glucose-medium (DMEM, 5.5 mmol/l glucose, L-glutamine, sodium pyruvate, 5% FBS). Then, IR was induced in 3T3-L1 adipocytes within 48 h following culture in a high-glucose/high-insulin-medium as described previously , . IR was determined by glucose uptake assay. 3T3-L1 adipocytes were differentiated in 24-well plates and serum starved for 4 h in DMEM. They were then washed with a pre-warmed buffer containing PBS (Phosphate Buffered Saline), 0.5 mmol/l MgCl2, 0.9 mmol/l CaCl2, 0.2% BSA. Insulin (100 nmol/l) stimulation was performed for 20 min. Cells were then incubated with 3H-2-deoxy-glucose (18.5 kBq/well) for 10 min. Cells were solubilized and the radioactivity counted
Modulation of miR-125a expression in vitro in 3T3-L1 adipocytes
After differentiation 3T3-L1 adipocytes were transfected during 48 h with either the mature miriDIAN mimic mmu-miR-125a-5p, cel-miR-67 as a transfection control, or 50 nmol/l mature miriDIAN inhibitor (Thermo Scientific, Dharmacon, Saint Leon-Rot, Germany) miR expression was assessed by q (quantitative) RT-PCR. Mmu-miR-125a-5p mature sequence targeted by miriDIAN inhibitor and corresponding to miriDIAN mimic is UCCCUGAGACCCUUUAACCUGUGA, cel-miR-67 mature sequence is UCACAACCUCCUAGAAAGAGUAGA. 3T3-L1 adipocytes were transfected in a total volume of 500 μl/well. Dharmafect1 (0.25 μl/cm2, Thermo Scientific, Dharmacon, Saint Leon-Rot, Germany) was used as a transfection reagent.
MiR and gene expression
Tissues and cells were homogenized in Qiazol (Qiagen, Courtaboeuf, France). Total RNA was prepared as previously described . The fraction containing miRs was extracted with miRNeasy mini kit (Qiagen, Courtaboeuf, France) and stored at −80°C. RNA concentration was determined with Nanodrop (Nanodrop ND-1000, Thermoscientific, Horsham, UK). QRT-PCR was carried out using either TaqMan microRNA assay (hsa-miR-125a-5p-002198, Life technologies, Saint Aubin, France) or SYBR Green expression assay (miScript reverse transcription kit, miScript SYBR Green PCR Kit, miScript Primer Asssay Mm_miR-125a_1-MS00001533, Rotor-Gene SYBR Green PCR Kit, Qiagen, Courtaboeuf, France). MiR-16-MS00031493, U6-MS00033740, (Qiagen, Courtaboeuf, France) and small nucleolar RNA202-001232 (Life technologies, Saint Aubin, France) were used as normalizing endogenous control for human tissues, cell culture samples and mouse tissues, respectively. Oligonucleotide sequences used are the following: Mouse Rtn2 (Reticulon 2) 5′-CTTTAGCATCGTGTCCGT (forward), 5′-TGCAGCACTTTGCGGTAA (reverse); Mouse Tef (Thyrotroph embryonic factor) 5′-ATGGACCTGGATGAGTTC (forward), 5′-GCAGACTCCTTTCCTTCAA (reverse); Mouse Ube2l3 (Ubiquitin-conjugating enzyme E2L 3) 5′-CCGCAAATGTGGAATGAA (forward), 5′-AGGAACAATAAGCCCTTG (reverse); Mouse Masp1 (Mannan-binding lectin serine peptidase 1) 5′-AAAGATGCTGTGCTGGT (forward), 5′-GAATAGACTCCATAGCGAT (reverse); Mouse β-Actin 5′-GACGATGCTCCCCGGGCTGTATTC (forward), 5′-TCTCTTGCTCTGGGCCTCGTCACC (reverse); Human Rtn2 5′-AGCAGACGGAACGTTTGT (forward), 5′-GAATCCACGAGGTCTTCT (reverse); Human Tef 5′-ATGGACCTGGATGAGTTC (forward), 5′-CAGACTCCTTCCCTTCTA (reverse); Human Ube2l3 5′-AGGAGGCTGATGAAGGAC (forward), 5′-TCGGTGGTTTGAATGGGTA (reverse); Human Masp1 5′-ACAACGACAACAGGACCT (forward), 5′-GGTAAGGGTTTGGGAAGT (reverse); Human β-Actin 5′-CTCTTCCAGCCTTCCTTCCT (forward), 5′-AGCACTGTGTTGGCGTACAG (reverse).
Genome-wide gene transcription profiling
Mice fat fed for 1 week (BALB/c) and 15 weeks (C57BL/6J) and their respective age matched controls, which were used for miR-125a expression analysis, were selected for gene transcription profiling. RNA probes prepared from BALB/c mice were hybridized to Affymetrix expression arrays 430 A and B (Affymetrix UK ltd, High Wycombe, UK), containing 22,690 and 22,576 probesets, respectively, and allowing quantification of the abundance of transcripts corresponding to 13,250 (chip A) and 7577 (chip B) independent gene and EST sequences. Probes prepared from C57BL/6J mice were hybridized to Affymetrix arrays U430 2.0, which were designed to contain all probesets of arrays 430 A and B on a single chip. Experiments are MIAME compliant and full protocols and data are publicly available (www.ebi.ac.uk/arrayexpress/) under the accessions E-BAIR-12 (BALB/c) and E-BAIR-9 (C57BL/6J). Affymetrix-based gene transcription profiling was performed as previously described .
Pathway analysis of gene transcription data
Mouse transcriptomic data were analyzed by Gene Set Enrichment Analysis (GSEA version 2.07, www.broad.mit.edu/gsea)  using a gene set selected through the molecular signature database (MSigDB C3-MIR; www.broadinstitute.org/gsea/msigdb/collections.jsp#C3) for sharing 3′UTR sequences predicted to be targeted by miR-125a. Specific folders were created for each array and GSEA was performed for each transcriptome. Normalized enrichment score (ES) was calculated for each gene set. It reflects the degree to which a gene set is over-represented at the top or bottom of a ranked list of genes created by GSEA for each gene set according to differential gene expression between mice fed HFD or CHD. Positive and negative ES indicated that the gene set was overexpressed or underexpressed, respectively. For miR-125a associated gene set we selected the leading edge subset which is the subset of members of a gene set that contribute the most to the ES. A nominal p-value, estimating the statistical significance of the ES for a single gene set, was calculated after 1,000 permutations of the microarray samples to correct for gene set size and multiple testing, and a false discovery rate (FDR) was calculated. Gene set was considered significantly enriched when its p-value was less than 0.05 and FDR score was less than 0.25.
Statistics were performed with Prism (GraphPad, version 6.0). Parametric student's t-tests were performed to compare means between two groups and ANOVA were performed to compare means between more than two groups.
Processing and analysis of the Affymetrix CEL file data was carried out using the BioConductor packages in the R language and environment as previously reported . Gene chip data were normalised using RMA quantile normalization . To correct for multiple testing, we used the FDR of Benjamini & Hochberg  to control the proportion of false positives at 5%.
MiR-125a shows an opposite expression pattern in sensitive and resistant strains in response to high fat diet feeding
To test causal relationships between IR and miR-125a expression, we used complementary ex vivo and in vitro experimental systems designed to modulate either insulin sensitivity or the expression of this miR. We have characterized the short and long-term consequences of fat feeding on the onset and progression of diabetes and obesity in C57BL/6J and BALB/c (Table 2) , which demonstrate contrasting pathophysiological patterns and dynamics of adaptation to HFD feeding in the two strains. Ex vivo, in adipose tissue of BALB/c mice fed HFD for 1 week, miR-125a was significantly overexpressed when compared to CHD-fed mice (p<0.05) (Fig. 1A). This effect was not replicated in this strain after prolonged HFD feeding. In contrast, in C57BL/6J, miR-125a expression was unchanged in fat in response to 1 week HFD feeding but significantly overexpressed when the dietary stimulus was applied for 15 weeks (Fig. 1B).
MiR-125a expression levels were quantified by q (quantitative) RT-PCR in adipose tissue of mice fed HFD for 1 week (A) or 15 weeks (B). The effect of in vitro insulin resistance (C) on miR-125a expression (D) was tested by qRT-PCR in 3T3-L1 adipocytes. Expression of miR-125a was normalized with small nucleolar (sno) RNA202 in adipose tissue and U6 in cultured cells. Data are expressed as mean ± SEM for 4–5 mice per group and for 3 replicated experiments in cultured cells. *p<0.05 significant differential expression of miR-125a between HFD-fed and control mice of the same strain. £££p<0.001 significant differences in glucose transport stimulated by insulin in 3T3-L1 adipocytes. ∧∧p<0.01 significant differences in miR-125a expression between IR-3T3-L1 adipocytes and control-3T3-L1 adipocytes.
We then tested the effects of miR-125a expression modulation on glucose transport in vitro in 3T3-L1 differentiated adipocytes (Fig. 2). We initially used 3T3-L1 differentiated adipocytes transfected with miR-125a inhibitor, which induced significant down-regulation of the expression of the miR by over 11-fold when compared to controls without inhibitor or with Cel-miR-67 (Fig. 2A). Our results showed that miR-125a inhibition had no significant effects on glucose uptake both in the basal state (without insulin) and after insulin stimulation (Fig. 2B).
The effects of miR-125a expression downregulation (A) and upregulation (C) on glucose transport (B–D) were measured in vitro in 3T3-L1 differentiated adipocytes. Expression of miR-125a was normalized with U6. Data are expressed as mean ± SEM for 3 replicated experiments. $$$p<0.001 significant differences between miR-125a inhibitor/mimic, and control (not transfected cells) and cells transfected with C. elegans (Cel)-miR-67. £££p<0.001, ££p<0.01 significant differences in glucose transport stimulated by insulin in 3T3-L1 adipocytes.
MiR-125a was then overexpressed in 3T3-L1 adipocytes using a specific miR mimic. We obtained a 14-fold stimulation of miR-125a expression when transfected in the cells (Fig. 2C). Again in this system, miR-125a overexpression had no significant effect on glucose transport both in the basal state and after insulin stimulation (Fig. 2D).
Finally, we measured miR-125a expression in response to experimentally-induced IR in 3T3-L1 adipocytes (IR-3T3-L1) obtained after culture in a medium supplemented with high concentrations of glucose and insulin for 48 h (Fig. 1C–D). IR in IR-3T3-L1 adipocytes was characterized by quantification of insulin stimulated glucose uptake which was abolished in these cells (Fig. 1C). We demonstrated that miR-125a expression level was significantly decreased in these IR-3T3-L1 adipocytes when compared to controls (p<0.01) (Fig. 1D). Collectively, these results indicate that altered expression of miR-125a is secondary to IR ex vivo and in vitro rather than a cause of impairment of both glucose transport and insulin sensitivity in vitro in 3T3-L1 adipocytes.
MiR-125a expression is downregulated in adipose tissue of obese patients
To examine whether findings in rodent could be translated in human context, we quantified miR-125a abundance by qRT-PCR in biopsies of subcutaneous (Fig. 3A) and visceral (Fig. 3B) adipose tissue from obese patients with and without diabetes and from non-obese controls. We showed that miR-125a expression was significantly down-regulated in both subcutaneous and visceral fat of obese patients regardless of their diabetic status, when compared to lean subjects. To further document possible associations between miR-125a expression and intermediate phenotypes collected in obese patients, we calculated correlations between miR-125a levels and quantitative values of the phenotypes (Fig. 3C, phenotypes in Table 1). Expression level of miR-125a in subcutaneous adipose tissue negatively correlated with total fat mass (r = −0.50), serum leptin (r = −0.44) and adiponectin (p<0.05, r = −0.58), and positively correlated with fat-free mass (p = 0.05, r = 0.51) as well as with serum triglycerides (p<0.05, r = 0.04) and γGT (p<0.05, r = 0.59).
MiR-125a expression was quantified by qRT-PCR in subcutaneous (A) and visceral adipose tissue (B) in obese patients (Ob) with or without diabetes (Diab) and controls. MiR-125a expression level in obese patients was correlated with total triglycerides level, circulating leptin, γ-glutamyltransferase (γ-GT) and adiponectin levels, fat mass and fat free mass percentages (C) in males (▪) and females (•). Expression data were normalized with miR-16, an endogenous miR whom expression level do not vary across group of study. Data are the mean ± SEM of 6 non obese subjects for subcutaneous adipose tissue, 7 non obese subjects for visceral adipose tissue, 9 obese non diabetic and 7 obese diabetic patients. Parametric Pearson correlation tests were performed. *p<0.05, **p<0.01, ***p<0.001 significant differences between obese patients and controls.
These results provide confirmatory evidence that miR-125a expression downregulation in adipose tissue is associated with obesity and underline its possible association with intermediate metabolic and hormonal phenotypes directly relevant to human obesity.
Differential expression of miR-125a target genes is enriched in HFD-fed mice
To test the effects of miR-125a on expression patterns of its predicted transcript targets which can be further validated in human obesity, we carried out genome-wide gene expression studies in adipose tissue of mice previously used to demonstrate miR-125a differential expression in response to acute (BALB/c) or chronic (C57BL/6J) HFD feeding. Transcriptome data were initially analyzed globally with GSEA (see methods for details) using an inventory of groups of genes (gene sets) from the Molecular Signature Database C3-MIR that contains genes sharing a 3′-UTR binding motif of miR-125a, which are therefore likely transcript targets of the miR (Table S1). We identified a significant enrichment of miR-125a specific gene sets in the adipose tissue transcriptomes of C57BL/6J after 15 weeks of HFD feeding (p<0.001, FDR = 6.10−4) and BALB/c after 1 week of HFD feeding (p<0.02, FDR = 0.04). MiR-125a gene sets were overexpressed in both transcriptome datasets (ES = 0.17 for C57BL/6J and ES = 0.11 for BALB/c) (Fig. 4A). For each miR-125a associated gene set we selected the leading edge subset in order to retrieve the relevant transcriptome data (Fig. 4B and Table S1). Analysis of leading edge subsets in the two transcriptome datasets indicated that expression of 81 genes is upregulated and that of 30 genes is downregulated in C57BL/6J. Similar trends were found in BALB/c with 60 genes showing upregulated expression and 46 genes showing downregulated expression. Of note, GSEA highlighted largely different sets of enriched genes in the two strains (Fig. 4B, Table S1), which may result in different biological consequences.
Gene set enrichment profiles of miR-125a gene targets (A) were determined for BALB/c mice after 1 week of HFD feeding (left) and C57BL/6J mice after 15 weeks of HFD feeding (right). Heatmap of miR-125a leading edge subsets are shown for fat fed C57BL/6J (top) and BALB/c (bottom) mice (B), alongwith enriched target genes significantly differentially expressed in these mice (C). Expression of Tef, Masp1, Rtn2, Ube2l3 and Adam9 was quantified by qRT-PCR in IR-3T3-L1 (▪) and control (□) adipocytes (D). Expression level was normalized with mouse β-Actin. Data are the mean ± SEM of 4 cultured cell replicates. *p<0.05 significant differences between IR-3T3-L1 adipocytes and control-3T3-L1 adipocytes.
Predominant overexpression of miR-125a targets in mice showing upregulated expression of this miR is counter intuitive with the general effect of miRs on gene transcription regulation and suggests its indirect role on the regulation of HFD induced transcription of the target gene set (Fig. 4A, B). We further investigated miR-125a mRNA targets (Tef (Thyrotroph embryonic factor), Masp1 (Mannan-binding lectin serine peptidase 1), Rtn2 (Reticulon 2), Ube2l3 (Ubiquitin-conjugating enzyme E2L3), Adam9 (Disintegrin and metalloprotease 9)) significantly differentially expressed in response to HFD feeding in the mouse transcriptomes. Expression of these genes was upregulated in response to HFD in C57BL/6J (Tef) or in BALB/c (Rtn2, Ube2l3). On the other hand, we observed significant down-regulation of the expression of the gene encoding Masp1 in BALB/c, which is consistent with the expected transcriptional consequences of miR-125a upregulated expression in this strain. Our results suggest uncoupled regulations of the expression of miR-125a and its target genes in adipose tissue of fat fed mice, which may underlie pathological processes leading to obesity and IR.
To validate the coordinated regulation of the expression of miR-125a and its target genes, we investigated the transcription level of Tef, Masp1, Rtn2, Ube2l3 and Adam9 in IR-3T3-L1 adipocytes (Fig. 4D). The expression of Tef, Masp1 and Rtn2 was consistently significantly downregulated (p<0.05) in IR-3T3-L1 adipocytes when compared to control adipocytes, which cannot be explained by the downregulated expression of miR-125a in this experimental system.
MiR-125a target genes are differentially expressed in adipose tissue of obese patients
Mouse-to-human translational studies of miR function rely on conservation of binding sites in target transcripts. We used Pictar (http://pictar.mdc-berlin.de/), which is an algorithm designed to identify microRNA targets based on 3′ UTR alignments, to verify that human Masp1, Rtn2, Tef and Ube2l3 also contain predicted binding site for miR-125a (http://pictar.mdcberlin.de/cgibin/PicTar_vertebrate.cgi?action=Search%20for%20targets%20of%20a%20miRNA&name2=hsa-miR-125a).
To test transcriptional effects of miR-125a down-regulation in human obesity, we quantified the expression of its target genes Tef, Masp1, Rtn2, Ube2l3 and Adam9 in subcutaneous adipose tissue samples of obese patients (Fig. 5A). Tef and Adam9 were not differentially expressed between obese patients and non-obese controls. In contrast transcript levels of Masp1 and Rtn2 were significantly higher (p<0.05) in obese patients than in non-obese controls, regardless of the diabetic status of the patients, which may underlie a direct effect of miR-125a downregulated expression. Transcript levels of Ube2l3 were significantly lower in subcutaneous adipose tissue of both obese non diabetic (p<0.001) and obese diabetic (p<0.01) patients which is inconsistent with the expected consequence of downregulated expression of miR-125a in obese patients, should Ube2l3 be considered as an indirect target of this miR. In visceral adipose tissue, only Masp1 expression level was significantly lower in obese non diabetic patients (p<0.05) than in non-obese controls (Fig. 5B). These results underline the incomplete concordance in expression patterns of miR-125a and its transcript targets in human obesity, which may indicate that these transcripts are indirect targets of miR-125a and may reflect altered molecular adaptations in obesity potentially contributing to disease pathophysiology.
Expression of Tef, Masp1, Rtn2, Ube2l3 and Adam9 was quantified by qRT-PCR in subcutaneous (A) and visceral (B) adipose tissue of obese patients (Ob) with diabetes (Diab) or without (NonDiab) and non obese subjects (Controls). Expression levels were normalized with human β-Actin. $p<0.05, $$p<0.01, $$$p<0.001 significantly different to non obese subjects.
Target genes of miR-125a show contrasting expression patterns in adipose tissue of obese patients before and after gastric bypass surgery
Gastric bypass in severely obese patients induces weight loss and improved metabolic and inflammatory status . We set out to investigate expression of miR-125a targets in obese patients before and after gastric bypass surgery. First, we analyzed the expression profiles of predicted miR-125a transcript targets, identified in GSEA leading edge subset, in obese patients before and after gastric bypass (Fig. 6A and Table S1). Expression profile analysis showed that 69 transcripts are downregulated and 39 transcripts are upregulated in obese patients when compared to non-obese controls. After gastric bypass more transcripts are differentially regulated in obese patients compared to control patients (80 are upregulated and 81 are downregulated). More specifically Masp1, Tef, Rtn2 and Ube2l3 showed contrasting expression patterns before and after gastric bypass (Fig. 6B) but the effects were statistically significant for Tef only, which highlights a possible specific role of Tef in obesity and IR of obese patients. We found a negative correlation between Tef expression level and fasting insulinemia (p<0.05, r = −0.58) and a positive correlation between Tef expression level and QUICKI, (p<0.05, r = 0.59) (Fig. 7). These findings further support the role of miR-125a and its transcript targets in the adaptation of IR and obesity in humans.
Heatmaps of miR-125a leading edge subsets are shown for obese patients before (top) or after gastric bypass (bottom) when compared to lean subjects (A). Patterns of expression for Tef, Masp1, Rtn2, Ube2l3 and Adam9 in these groups are illustrated. Cells are hatched when differences are not statistically significant (B).
We report reactive expression of miR-125a and its predicted mRNA targets in adipose tissue from HFD-fed mice and obese patients. Expression patterns of this miR varied in response to an acute or chronic dietary stimulus in mice susceptible (C57BL/6J) or resistant (BALB/c) to diet induced obesity, as well as in insulin resistant adipocytes in vitro. Predicted transcript targets of the miR showed altered expression through GSEA of genome-wide transcriptome data in both C57BL/6J and BALB/c, but different subsets of genes contributed to global gene set enrichment in the two strains. Furthermore the expression level of miR-125a transcript target Tef was associated with insulin resistance status and Tef showed evidence of contrasting differential expression in obese patients before and after gastric surgery, a situation known to improve metabolic and inflammatory conditions. These results provide functional links between expression of miR-125a and its transcript targets in adipose tissue and IR and obesity.
MiR-125a shows a broad spectrum of functions, primarily characterized in development and cell differentiation, apoptosis, viral infection, carcinogenesis and autoimmune diseases , . The impact of miR-125a in obesity, T2DM and IR, as well as in inflammation which is an important pathophysiological feature in obesity  relevant to our study have recently emerged from experimental studies in animal models and in humans. Abundance of miR-125a is increased in insulin resistant diabetic GK rats , as observed in fat fed mice in our study. Expression of miR-125a is also increased in macrophages after induction of proinflammatory response by oxidized LDL stimulation . In humans, miR-125a expression is enhanced during adipogenic differentiation of multipotent stromal cells . These observations support an acute physiological reactivity of miR-125a expression in adipose tissue of the genetically different mouse strains tested here, in a situation where adipocyte formation and inflammatory processes are stimulated by HFD-induced IR and obesity in mice showing strong susceptibility (C57BL/6J) and relative resistance (BALB/c) to these anomalies . Conversely, downregulated expression of miR-125a in obese ob/ob mice , as observed in obese patients in our study, may underlie the existence of adaptative pathological mechanisms contributing to obesity pathogenesis in obese individuals.
A central issue in the possible involvement of miR-125a in IR and obesity lies in the definition of causal relationships between its abundance and phenotype alterations. We showed that modulation of miR-125a expression in vitro in 3T3-L1 adipocytes does not significantly affect glucose transport, whereas experimentally induced IR is associated with reduced miR-125a abundance. Our observations suggest that altered expression of miR-125a is reactive to IR and concur with results in obese patients. Correlations between miR-125a abundance and physiological parameters of insulin sensitivity in obese patients also suggest that changes in the expression of this miR reflect highly reactive adaptation to metabolic and/or hormonal changes associated with obesity, but may not play a direct causal role in the disease. Changes in miR-125a expression may have indirect pathophysiological consequences mediated by its transcript targets.
Identification of molecular mechanisms that mediate functional consequences of miR differential expression is a central issue in miR biology. Target genes of miRs share DNA elements that allow interactions between miRs and mRNAs, but the transcripts regulated by a miR do not necessarily share any biological function . The definition of groups of transcripts regulated by miRs can provide crucial information to understand the biological endpoints of miR. However, it remains based on in silico prediction of base pairing interactions that requires experimental validation, for example through combined analysis of miR and gene expression, which allows direct integration of miRs in functional networks . Parallel quantification of miR-125a and genome-wide gene transcription in adipose tissue in the same mice allowed analysis of coordinated expression of miR-125a and its predicted mRNA targets in response to HFD feeding. Following GSEA, we were able to establish a significant enrichment of miR-125a targets among differentially expressed genes in response to acute or chronic HFD feeding in BALB/c and C57BL/6J, respectively, thus providing experimental evidence that the genes encoding these transcripts are, to a large extent, genuine targets of miR-125a. These results also indicate that miR-125a expression reactivity to HFD, obesity and/or IR should have significant functional consequences in adipose tissue. Furthermore, transcripts contributing to gene set enrichment largely differ in C57BL/6J and BALB/c, which may account for metabolic and hormonal divergences in their response to HFD feeding.
We focused further analyses on five differentially expressed genes (Adam9, Masp1, Rtn2, Tef, Ube2l3) in the mouse transcriptome datasets, which we selected for their differential expression between HFD-fed and CHD-fed mice, their leading role in enrichment of miR-125a gene targets, and their known role in the regulation of body weight, insulin signaling or inflammation. Adam9 is an insulin-like growth factor binding protein-5 protease associated with adiponectin, which may modulate the development of the metabolic syndrome . Activation of Masp1 can trigger local inflammation mediated by mannose-binding lectin binding to damaged endothelial cells . The protein Rtn2 plays an important role in membrane translocation of GLUT4  and Ube2l3 interacts with the ubiquitin ligase WWP1, a positive regulator of life span in response to dietary restriction in C. elegans . Finally, Tef contributes to the circadian transcription of genes encoding acyl-CoA thioesterases leading to the release of fatty acids .
Based on expression patterns of the selection of miR-125a predicted targets, we did not find evidence of systematically conserved effects of changes in miR-125a level on transcript abundance in adipose tissue that may significantly contribute to obesity and IR in fat fed mice and in humans. For example, upregulated expression of Masp1 in obese patients could reflect adipose tissue inflammation, whereas Adam9 overexpression may underlie protective mechanisms against the metabolic syndrome. Consistent down-regulated expression of Tef in adipose tissue in C57BL/6J mice and in obese patients may underlie perturbations leading to IR and deteriorated lipid and glucose metabolism. Correlations between Tef transcript level, fasting insulinemia and QUICKI in obese patients support this hypothesis. Furthermore Tef showed contrasting expression patterns in obese patients before and after gastric bypass which may be due to improved insulin sensitivity, which occurs following gastric surgery .
An important challenge in miR studies in experimental systems remains to dissect out direct and indirect effects of miRs on gene expression and phenotypic endpoints. There is a general consensus supporting a predominant effect of miRs on gene expression silencing through various processes, even though examples of transcription stimulation have been reported . One would therefore anticipate that expression of a miR and its mRNA targets should systematically exhibit coordinated regulation. However functional relationships between miR and mRNA are far more complex and miR abundance and activity can be regulated by the target mRNA it binds  These complex mechanisms may explain the general lack of coordinated regulation in the expression of miR-125a and its mRNA targets in fat fed mice and in obese patients. Nevertheless, contrasting expression of miR-125a and Masp1 in both fat fed mice and obese individuals suggests that Masp1 is a direct target of this miR, which mediates the effect of miR-125a on inflammation in the adipose tissue.
Collectively, our findings based on investigations of coordinated expression patterns of miR-125a and its mRNA targets in adipose tissue and cell lines underline the role of miRs in the biology of adipose tissue and contribute to improved knowledge of miR-125a mediated molecular mechanisms, bridging its known function in immunological processes  to novel molecular regulatory mechanisms relevant to IR and obesity pathogenesis in mice and humans. They suggest highly reactive expression of miR-125a in experimentally-induced and spontaneous IR and obesity, which may trigger molecular mechanisms associated with IR and inflammation in adipose tissue. Tissue level of miR-125a and some of its transcript targets may represent molecular markers of obesity and IR, as well as recovery processes from obesity and IR.
Conceived and designed the experiments: SC JS DG. Performed the experiments: MD CH SC KC JAW NV SPW. Analyzed the data: MD SC KC NV DG SPW. Wrote the paper: MD DG SC.
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text:
ad the fever!"
He whirled about and sprang to descend the ladder, but paused to direct the skipper. "I'll command the boat. Men are not to land. D'you take me? There's at least one of the ladies here. Have a sling ready, and tell the stewardess her services will soon be required."
Before Meggs could reply, he was down the ladder and darting across to the side. But there he turned and ran aft to the cabin. The stewardess, a buxom Englishwoman, stood at the head of the companionway, gazing towards the cliff top. At his order, she followed him below. After several minutes he reappeared with a lady's dust-coat folded over his arm. The boat was already lowered and manned. He swung himself outboard and went down the tackle hand under hand.
As he dropped lightly into the sternsheets beside the cockswain he signed the men to thrust off. The boat shot out across the still water, and headed shorewards on a slant for the south corner of the headland. Urged on by their impatient passenger, the rowers bent to the
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“To say my dad died because he was ‘weak’ is something I will not tolerate.”
Earlier this week, the actor and musician shared a photo of herself wearing a mask during a trip to Las Vegas — and some anti-maskers didn’t approve.
Abigail, whose father passed away after a battle with COVID-19 last year, finally decided to clap back after one commenter called her a “pathetic loser.”
“That pathetic loser would be me, someone who lost their dad due to someone not wearing a mask and giving him COVID. You can kindly go fuck off now,” Abigail responded.
She even shared her comment on her Instagram feed, adding, “Sorry not sorry. Although I love ignorant comments (sarcasm obviously), I just can’t tolerate it from someone with the username ‘chesty1987.'”
And while you would think “chesty1987” would back down after Abigail’s response, they only doubled down on their rude remarks.
“I’m pretty sure wearing a mask isn’t going to save anyones life lol. Clearly I know more than her if she thinks someone who wasn’t wearing a mask killed her father when in reality he was weak,” the commenter wrote.
Abigail didn’t directly respond to the disgusting comment made about her father but again shared their post to her feed.
“To say my dad died because he was ‘weak’ is something I will not tolerate,” Abigail wrote on Instagram, asking fans to report the user for their hateful messages.
Thankfully, Abigail was met with tons of support from fans —and it appears the user has since been banned by Instagram.
Source: BuzzFeed – Celebrity


text:
Shane Byrne has completed a hat-trick of victories to start the 2014 MCE Insurance British Superbike Championship after holding off a fast closing Josh Brookes in race one at Oulton Park. The Rapid Solicitors Kawasaki rider led every lap of the race but a blistering burst of speed, including a lap record from Brookes, kept him on his toes until the very end.
The start passed without any major position changes at the front but a moment for Ryuichi Kiyonari on the exit of Old Hall mid-pack caught out the riders behind with his teammate James Westmoreland being forced across the grass and Simon Andrews being brought down altogether. The RAF Reserves Honda cartwheeled across the grass and showered the circuit in dirt, necessitating the safety car while the mess was cleared.
When green flag racing resumed, Brookes’ hopes of challenging Byrne’s lead took a nosedive with James Ellison catching him napping at Old Hall. The GBmoto rider was unable to keep pace with the Kawasaki ahead but seemed to have Brookes under control until he outbraked himself at Hislop’s on lap eleven, falling to third.
Released from behind Ellison, Brookes came alive and wiped out the deficit to Byrne, breaking the eight year old lap record while he was at it. Unfortunately for the Australian, the chequered flag came a lap too early and Shane held on for his third victory out of three. Brookes and Ellison completed the podium with Tommy Bridewell taking fourth after a crash for Chris Walker and a late mechanical problem sidelined Ryuichi Kiyonari.
Stuart Easton’s solid start to the season continued with fifth ahead of Dan Linfoot and Richard Cooper while James Westmoreland produced a brilliant recovery ride to finish eighth, pipping John Kirkham and Jakub Smrz.


Caterina Scorsone Is Pregnant, Actress Expecting First Child
Private Practice actress Caterina Scorsone and husband Rob Giles are expecting their first child.
Scorsone spoke with PEOPLE on Thursday and revealed that the couple are “over the moon” with exciting for the arrival of their little bundle of joy who will arrive this Summer.
Caterina says of her pregnancy:
“I’m starting to show now. Everybody on set has been pretty sweet and is offering me fruit.”
Following in the footsteps of her real life pregnancy viewers of the show will find out this week that Dr. Amelia Shepard is pregnant.
It turns out that after hearing about the pregnancy Private Practice creator Shonda Rhimes was inspired to change things up. Scorsone jokes that her pregnancy can be used for “dramatic purposes” on the show.
Female actresses often carry their real life pregnancies over to their shows characters, one of the most recent examples is Bones star Emily Deschanel who’s character Dr. Temperance “Bones” Brennan became pregnant during the most recent season of Fox’s hit TV series. Deschanel eventually welcomed a healthy baby boy into the world.
While it’s not confirmed we also reported on a story last week in which actress Drew Barrymore was caught carrying a sonogram out of her doctors office, it looks like 2012 could be a big year for celebrity pregnancy.
Are you excited to see how Caterina Scorsone’s character evolves on Private Practice because of the fictional portrayal of her real-life pregnancy?