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New district maps could spur more competitive races
Preliminary congressional districts
(Shaffer Grubb)
The panel charged with redrawing political boundaries released a set of preliminary maps Friday that could have sweeping implications on future elections in San Diego County and across the state.
How California's 40 senate, 80 assembly and 53 congressional districts are shaped could determine their partisan breakdown, who gets elected and what issues and positions are advocated for residents.
For local lawmakers, it appears that no incumbents would have to challenge another in the same district. But many would have to run for re-election in new areas and appeal to different voters in more competitive districts.
The boundaries until now were drawn once every decade by state legislators in a process that many considered an inherent conflict of interest. The result was incumbents were protected. Since 2001, just one congressional district out of 53 changed parties — the 11th District in the Central Valley and East Bay Area.
In 2008, reform-minded voters fed up with gridlock narrowly passed Proposition 11 to establish an independent commission for the sole purpose of mapping new districts based on population — not politics.
It won't be easy. At the same time commissioners try to fulfill their legal mandate, they also must reflect the will of people who want their communities kept together and others who crave more competitive elections.
The five Republican, five Democrat and four unaffiliated commissioners are barred from considering how boundaries would affect incumbents or political parties. Draft results were unveiled Friday, with final maps due Aug. 15.
Gil Ontai, an architect and San Diego Republican who serves on the commission, said the process will lead to "change in very meaningful ways that will allow them (Californians) to have direct engagement in the political process."
Experts predict that Democrats' numbers in the California congressional delegation could grow. In San Diego County, which has three Republicans and two Democratic congressional members, no one is predicting a drastic turnover. But at least two seats could be in play.
The new maps also could increase the competitiveness for future Senate and Assembly races across the state and county.
Tony Quinn, a political analyst who worked for legislative Republicans on redistricting in the 1970s and 1980s, said he expects the maps to change. His message to politicians: "Don't call the moving vans yet."
Among the local highlights gleaned from experts and political observers:
• Incumbents won't be required to square off against each other unlike in some other regions. That was welcome news to many who praised the commission for its work. "With a state as large and diverse as ours, it is certainly no easy task to configure representational maps to best reflect the changing landscape," said Rep. Susan Davis, D-San Diego, whose district moves off the coast to include more inland areas — and more Republican voters.
State lawmakers must live in their districts. Congressional members do not have such requirements, but the vast majority make their homes within their own political boundaries.
• East County's House seat was not lumped in with Imperial County. For months, leaders in both counties insisted there was far more than a border separating them. Many stressed the economic and demographic differences.
The proposed maps show Republican Rep. Duncan Hunter's 52nd District stretching into East County and North County. The district would come down state Route 78 about midway between Escondido and Oceanside. However, state Sen. Joel Anderson, R-La Mesa, picks up large swathes of Imperial County. Democratic Rep. Bob Filner's South County 51st District gains some northern territory before shooting east into Imperial County. Filner recently announced that he is running for mayor of San Diego next year.
• The most significant geographical shift involves Republican Reps. Darrell Issa and Brian Bilbray. Issa's current 49th District encompasses Vista, Oceanside, Fallbrook, Temecula, Murrieta and Lake Elsinore. Bilbray's 50th District includes northern coastline areas, along with Escondido and San Marcos.
If the realignment were to become final, Issa said he would seek re-election in the new congressional district that includes south Orange County and North County San Diego, stretching from Dana Point to Del Mar. Camp Pendleton, Oceanside, his hometown of Vista and the surrounding coastal communities have been the heart of the districts he's represented since being elected in 2000.
Bilbray, who moved in December from Carlsbad to Clairemont because of a family crisis, would seek re-election for a seat that sweeps south from Poway through Clairemont, La Jolla, downtown San Diego and Coronado. The new district would pickup more Democrats as it moves southwest.
"I am concerned about breaking up the North County to some degree," Bilbray said. "This is our constitutional responsibility and we all swear to uphold the constitution whether we like it our not. This makes it more interesting and maybe more interesting for voters."
When state lawmakers controlled the process, they carved out heavily Democratic and Republican districts to make them safe for incumbents. But critics said that also led to more partisan members, making it difficult to break stalemates on the budget and other issues. Some say many of the new districts would be more evenly balanced, resulting in more candidates who appeal to voters in the middle of the political spectrum.
The process remains significant for voters, yet few understand it, said Sen. Mark Wyland, a Solana Beach Republican who will be termed out in 2014.
"It's almost as important as people voting," said Wyland, who is running for a state Board of Equalization post. The largest concern issue, he said, is whether the maps "are fair to the voters."
Another slate of draft maps is scheduled to be released July 7. Many expect those maps to be redrafted before Aug. 15. Ontai said the release of the maps Friday marks the beginning, so political futures should not be staked to this round.
There will be a series of hearings on the draft maps, including 6 p.m. June 20 in San Diego Council Chambers at 202 C Street.
"Tell us if we're wrong or right. If you think we're wrong, give us a real solution. This is a process involving the public," he said.
How Joe Biden won friends in Hollywood by helping studios get their movies into China
Joe Biden has delivered more for Hollywood for years longer than any of his rivals. Now industry donors are delivering for him.
Why pick just one? Hollywood donors fund numerous Democrats in bid to beat Trump
San Diego congresswoman's effort to address military family food insecurity faces hurdles
A Basic Needs Allowance for low-income military members passed by the House on Friday faces "strong objection" from the White House
The House rejects a vote on articles of impeachment a day after condemning Trump's tweets as racist.
Refugee mothers separated at border to sue Trump administration for $3 million each
Some immigrants seeking asylum are part of a novel legal strategy to seek redress for being separated from their families at the border. They are suing the US for emotional distress.
Trump's losing battle on immigration
The president's gyrations on raids and asylum come as list of policy failures grows
Stevens, the independent-minded jurist whose bright bow ties and courteous manner symbolized an old-fashioned style of integrity, died Tuesday.
Hunter leads opponents in second quarter fundraising, but burns a lot of cash
Rep. Duncan Hunter raised nearly $500,000 in second quarter but trails opponent in cash on hand after expenses, some of them unusual.
California doesn't have enough doctors. To recruit them, the state is paying off medical school debt
Facing a massive shortage of doctors, California is stepping up recruitment and training programs for healthcare providers. But is it enough?
Rep. Duncan Hunter's new mailer is called Islamophobic, an attack on opponent
Hunter criticizes two Muslim congresswomen and Ammar Campa-Najjar over deceased grandfather's alleged ties to a terrorist attack in new campaign mailer.
County has $703,000 in unclaimed refunds to return to San Diego residents
The San Diego County Treasurer-Tax Collector is hoping to return 1,928 refunds totaling $703,000 to county residents.
Rep. Peters visits Texas-Mexico border, describes poor conditions and room for government action
Visiting detention facilities in McAllen, Texas, a day after Vice President Mike Pence, Rep. Scott Peters described poor conditions and stressed the need for government action.


I've been an avid reader all my life. My habit of continual learning has led me to many wonderful discoveries, but the greatest of all those discoveries can be found in the following spiritual books.
The Best Spiritual Books, Guaranteed to Change Your Life!
Keep in mind that I have read well over 500 non-fiction books in my lifetime, and the following are what I consider to be the MOST life-changing.
Of course, that's just my personal experience and opinion. You may be drawn to different teachings, depending on what you need to learn at this point in your spiritual awakening, but nonetheless, you'll certainly resonate with at least one or two of the following books.
When I first read this book back in 2013, it completely blew my mind and set me on a path that would improve my life in ways that were beyond what I even believed possible at the time.
This book answered so many of my deepest questions about life, things that had perplexed me for years.
Why is there so much negativity in the world?
Is "God" real or just a belief system?
What exactly is spiritual enlightenment?
Is there such a thing os "objective" or absolute truth?
Can Truth be verified or measured?
What is the purpose of life on earth?
Is reincarnation real? How can we know?
All these questions and MANY more will be answered in this incredible book.
Warning: The author utilizes a very large vocabulary, so this can be a difficult read if you are not familiar with certain concepts. You may want to read this book AFTER you read spiritual book #7 by the same author further down the list.
Power vs. Force is the first book in a series of books written by Dr. David R Hawkins. I highly recommend ALL his books for every spiritual seeker, but you'll want to read Power vs. Force and #7 on this list BEFORE you read his other books, otherwise they might not make much sense to you.
There are not many books that I can say made a PROFOUND impact on me, but this was definitely one of them.
Byron Katie had a major spiritual awakening in the 1980's after suffering with suicidal depression and rage for many years. Her story is quite interesting.
Most notable, the energy that emanates from her presence and through her words is incredibly uplifting. I've cried tears of joy on more than one occasion while reading her books.
Loving What Is is an introduction to something Katie calls "The Work", a process of self-inquiry designed to cut through the strongly held beliefs of the ego that create suffering for ourselves.
I would recommend reading this book as a starter before moving onto her other books, which are equally transformative and inspiring.
The Bhagavad Gita is a translation of the ancient teachings of Lord Krishna from the Hindu tradition. The teachings are given in a narrative about Krishna and his disciple Arjuna. Krishna's words cut through Arjuna's doubts about going off to war and what it means for his spiritual fate. There are many profound spiritual truths packed into this story.
I started to read this book many years ago but could never finish it because it didn't make much sense to me. I came back to it years later when I was more 'ripe' and the power of this book was suddenly apparent.
The Bhagavad Gita contains great wisdom and is a worth the read no matter where you are on your path, at least for the purpose of "planting seeds" that could later sprout into full realization.
I prefer the audio version of this book, which you can get on Audible.com. The narrator's voice is very fitting and the words pack a real spiritual punch.
If you don't like all the spiritual 'fluff' and want to get right to the CORE of spiritual truth, then this book is for you. A direct translation of the teachings of 9th century Chinese Zen Master Huang Po that cuts through illusions and spiritual fantasies unlike any other teaching I've come across.
I love this book because of its directness, simplicity, and power. Huang Po does not waste time with fancy spiritual concepts. The path to spiritual enlightenment is a straight and narrow one that requires cutting away all the non-essentials. This book does that perfectly.
This is probably one of my favorite spiritual books of all time. I read it at least twice a year and it always puts my mind more at ease, helping me remember what is Truth and what is illusion.
This book became a worldwide best-seller after Oprah recommend it on her hit TV show. The recognition was well-deserved. The Power of Now provides a practical approach to bringing more presence and spiritual power into our everyday lives.
I think this was the first book about spirituality that really caught my attention and made a profound shift in my state of consciousness. I remember feeling like a brand new person after reading it. I even gave a copy to my mother and she loved it too.
I used to listen to the audio book every day on my commute to work. Somewhere in the book, Eckhart talks about how people who are strongly identified with their ego will become furious when someone cuts in front of them in traffic, and how a person who live in "presence" does not react in such ways. It was very entertaining to practice being a peaceful witness to the drama that people create on their commutes to works. Haha.
The story behind the writing of this book is quite fascinating and perhaps controversial. I'll let you look into it yourself, but I recommend overlooking the irrelevant details and paying attention to the core message contained within this text.
The main theme of A Course in Miracles is what you might call "radical forgiveness." The Course urges us to forgive the world and ourselves without exception so that all our ideas of sin and guilt may be dissolved, allowing Peace to shine forth from our consciousness.
The Course includes a main text, 365 day workbook, and a manual for teachers. It will take you a long time to read as its over 1,000 pages. If you are only going to do a portion of it, I recommend skipping right to the 365 "mind training" course. It's just one short lesson per day.
I have 2 books by the same author on this list because no other teacher has had a greater impact on me. If I could, I would put at least 5 of his books here in the top 7.
Letting Go is probably the most practical spiritual book you will read. It describes a simple but powerful process for releasing suppressed emotions from our minds and bodies, allowing us to experience the Peace at the core of our being.
It is often the simplest things that have the greatest impact. Complicated philosophies and fancy-sounding spiritual concepts only add to the clutter of the mind and tend to strengthen the ego rather than dissolve it. The "Letting Go" technique is extremely simple but shouldn't be overlooked, as it is extremely powerful when used consistently.
If you experience stress, social anxiety, self-doubt, depression, or any other negative emotion on a regular basis, this book can help you permanently eliminate all of those things and ensure they do not continue to sabotage your happiness and success in life.
Which of these spiritual books have you already read? Which one of the 7 will you get today? Do you have a book that you'd recommend I add to the list? Let me know in the comments below!
And before you go, make sure to sign up for the FREE 2-week training course The Enlightened Mind where you'll learn how to start living every day of your life with perfect peace of mind by following a powerful, tested and proven 4-part system and process called Transcendental Mind Training.
Have you ever cried just by letting go? What is your opinion about crying?
Do you think you use willpower to let go or is it a motivated feeling that drive you to let go?
I've tried the release technique and the Sedona method by students of Lester Levenson. And they are very similar to letting go. The release technique is like letting go of desires and the Sedona method is using inquiry questions to let go.
It seems like many teachers teach the same thing with different variations. I'm going to read Letting Go next.
I really like the story of Lester as it reminds me of how similar life with romantic love can be so painful. Thank you for book suggestions.
Right now, I feel very demotivated to use letting go as it looks like it's not working, do you have any tip on noticing it working and increase motivation to do it regularly?
You're always welcome James! I'll let you know if I come across any more books worth mentioning. Chat soon.
Hey Beau, thanks for the list. I have 5 of the seven. Next up, the Zen Teachings and to work seriously through Letting Go. Thank you again.


Thank you, Dolly. I thought this was so appropriate for Easter.
I hope everyone has a blessed Easter weekend. This is a good time to share inspirational posts. Of course every weekend is a good time, but I think Easter is extra special.
Just returned from watching this movie. Wow, it was really powerful. I'm wondering if Hollywood will ever wake up and realize what most people want to see these days. They live in their own little bubble. I highly recommend it. I've loved the song for years and now I know the story behind the song.
Thank you for your condolence comments last week. We went over to California for her memorial service. It was a quick trip but good to see other relatives there. I made a DVD of Vivian's life which they showed at the memorial service. Anybody else out there make DVDs on their computer? I've made over 30 in the past several years. If you haven't tried it and have the programs on your computer to facilitate it, you should try it. It really is a satisfying hobby.
OK. Now it's time to link. Thank you again for your steadfast loyalty to this endeavor.
Now it is time to begin linking again. Thank you for your steadfast encouragement.
You have probably seen this video online, maybe on Facebook. I thought it was so good that I decided to share it here in case someone hasn't seen it. And if you have seen it, you might want to watch it again. Billy Graham inspired so many people and I can just imagine his homecoming a few days ago. Wow. And besides that, Michael W. Smith's music always inspires me too.
Now it is time to start sharing again.Thank you for your faithfulness.
March has just marched in as it does every year. Well, actually sometimes it blows in but I prefer to think of it as marching in. LOL March is one of my least favorite months but now days I'm happy to see another month no matter if it is a favorite or not. I've said so many times and you probably tire of hearing it, but I'm always amazed at how quickly a year goes by. Eternity is ahead. I'm not ready to go just yet but I am looking forward to it.
In the meantime, it's time to link again. Thank you to all who participate.


Mexican Mouthwash drink recipe made with Tequila,Rumplemintz,. How to make a Mexican Mouthwash with all the instructions and ingredients.
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The effects of intravenous, glucose versus saline on ovarian follicles and their levels of some mediators of insulin signalling
Rex John Scaramuzzi1,2,
Nesrine Zouaïdi1,
Jean-Baptiste Menassol1,3 &
Joëlle Dupont1
A short-term increase in food intake and specifically dietary energy can stimulate folliculogenesis and increase ovulation rate in ewes. The mechanism appears to involve the insulin-glucose metabolic system and its interaction with FSH signalling pathways in the granulosa cells of ovarian follicles. This experiment was designed to investigate the interaction between these two systems in the granulosa cells of ovarian follicles.
Thirty six Ile-de-France ewes were used in this controlled experiment to study the effects of intravenous glucose on folliculogenesis. Eighteen ewes were infused with glucose (10 mM/h for 72 h) from day 8 of the oestrous cycle, while the others (controls) received saline. Ovaries were collected when the infusions ended (luteal phase) or 30 h later and after a luteolytic dose of a PGF2α analogue (follicular phase). Follicles were dissected and granulosa cells and follicular fluid harvested. The blood concentrations of glucose, insulin, oestradiol and FSH were monitored over the experiment. The levels of Aromatase P450 and of the phosphorylated and non-phosphorylated forms of Akt, AMPK and ERK in granulosa cells and the concentration of oestradiol in follicular fluid, were determined.
Glucose increased the circulating concentration of glucose (P < 0.05) and insulin (P < 0.05). It also increased the total number of follicles >1.0 mm in diameter (P < 0.05) and small (P < 0.05) follicles (>1.0 to 2.0 mm in diameter) but not medium (>2.0 to 3.5 mm in diameter) or large (>3.5 mm in diameter) follicles. Glucose decreased circulating oestradiol (P < 0.05) but not that of FSH or progesterone. Glucose reduced aromatase P450 (P < 0.05) and decreased the phosphorylation of Akt (P < 0.05), ERK (P < 0.05) and AMPK (P < 0.05) in granulosa cells from oestrogenic follicles. The level of Aromatase P450 was greatest in large oestrogenic follicles and the phosphorylation of Akt (P < 0.05), ERK (P < 0.05) and AMPK (P < 0.05) was lower in small follicles compared to medium and large follicles.
These data suggest that the effect of glucose in small follicles is a direct action of glucose that increases the number of small follicles while the effect of glucose in oestrogenic follicles is an indirect insulin-mediated action.
Reproduction is subject to the influence of several factors related to the animal itself and to its environment. Among these, nutrition is one of the main factors affecting most aspects of the reproductive performance of the animal [1, 2]. Lindsay and his colleagues [1, 2] recognized that an increase in short-term food intake increased the lambing rate in ewes by stimulating ovulation rate. Three effects of nutrition on ovulation rate, the "acute", "dynamic" and "static" effects, have been described [2, 3] although there is uncertainty over the number of mechanisms involved [3]. The acute effect is an effect of diet associated with weight change, the static effect is associated with the absolute level of body weight while the dynamic effect is a short-term dietary effect not accompanied by a change in weight [reviewed in: 2, 3].
There have been numerous investigations of the relationship between diet and ovulation rate in farm animals and particularly sheep [2–4] and of the physiological mechanism(s) responsible for this phenomenon [3, 5, 6]. The inclusion of energy-dense foods such as lupin grain [7–13] or corn with soy meal [14] in the diet will increase both ovulation rate and the number of follicles. Other forms of nutritional manipulation for example, the infusion of leptin [15] or glucose [16–18] have been investigated and shown to increase both the ovulation rate and the number of follicles. So clearly, there is a link between nutrition and folliculogenesis. This relationship could involve effects mediated by the intrafollicular glucose-insulin system [3, 5, 6] and other energy sensing mechanisms such as the AMPK system [6, 19]. Although there is an extensive literature (see references cited above) describing the effects of dietary energy on folliculogenesis and ovulation rate there are relatively few studies of the intrafollicular mechanisms that are affected by the energy content of the diet. The level of Aromatase P450 was reduced in follicles of ewes whose diet was supplemented with lupin grain [20] or infused with glucose [18] and in the former study these effects were associated with alterations in the level of expression of the insulin receptor substrate (IRSs) proteins and in the later study, they were associated with alterations in the levels of Akt and AMPK; and Akt is a phosphorylation target in the insulin signalling pathway. In addition the presence of the insulin dependent glucose transporter (GLUT4 or the sugar transport facilitator [SLC2A-4]) has been confirmed in ovine [21], bovine [22] and rodent [23] ovarian follicles. Finally, insulin has been identified as a factor in several malfunctions of the ovary and its follicles in a number of ovarian pathologies [24]. These data suggest that insulin signalling to granulosa cells is implicated in the effects of dietary energy on folliculogenesis.
To improve the understanding of the interaction between folliculogenesis and the metabolic status of ewes we studied the effect of intravenous glucose on the insulin-signaling pathways in granulosa cells of follicles collected from ewes in either the luteal or follicular phases of the oestrous cycle. Although several potential metabolic sensors have been identified, including the IGF system, GH, and leptin [25, 26] we have focused our attention on the insulin-glucose and AMPK systems. A preliminary report of certain aspects of this study has been published [27].
The experiment was conducted at the INRA laboratory at Nouzilly in France between August and September using 36 Ile-de-France ewes. During the experiment the ewes were housed in group pens until they were fitted bilaterally with catheters in their jugular veins. Following catherization the ewes were placed in individual pens and kept there until the end of the infusion period. Then they were either ovariectomised immediately (the 2 luteal phase groups) or returned to group pens where they were left until ovariectomy 30 h after the end of infusion (the 2 follicular phase groups). During the experiment the ewes were fed a basal diet of good quality hay at maintenance levels [28] with ad libitum access to straw roughage and fresh water. The experiment was carried with local ethical approval and in accordance with French and European regulations on the care and welfare of animals in research and with ethical approval from the Ministry of Agriculture (N° 006259 and 2012-01-2).
The experimental plan is shown in Figure 1, briefly, oestrus was synchronised using progestagen sponges (Chronogest; Intervet/Schering-Plough Animal Health, Angers, France). Eight days after oestrus one group (n = 18) was infused with glucose at 10 mM/h for 72 h. A second group was infused with physiological saline at the same rate (n = 18) and acted as controls. At the end of the infusion ovaries were collected from half the ewes in each treatment group to form the two luteal phase groups. Luteolysis was induced with 125 μg of an analogue of PGF2α (Cloprostenol; Intervet/Schering-Plough Animal Health, Angers, France) in the remaining ewes whose ovaries were collected 30 h after the end of infusion to form the two follicular phase groups. The body weights of the ewes were measured at the start of the infusion and at the time of ovariectomy.
The experimental plan. The oestrous cycles of 36 ewes were synchronised using a combination of progestagen sponges and intramuscular eCG. On day 7 of the cycle following oestrous synchronisation, sampling of jugular venous blood commenced and continued until the time of ovariectomy. The next day (day 8) intravenous infusions of either saline (n = 18) or glucose (n = 18) commenced and continued for 72 hours. Ovariectomies were carried out at two times, the first at the end of the infusion period (luteal phase groups) and the second 30 h later and following the injection of a luteolytic dose on PGF given at the end of the infusion period (follicular phase groups).
Two days before the start of the infusions both jugular veins were fitted with intravenous catheters. One catheter was used exclusively for infusions and the other exclusively for sampling blood. A sterile, 18% (w/v) solution of glucose was used and the rate of infusion was adjusted to deliver glucose at a rate of 10 mM per hour. The controls were infused with sterile saline at the same rate. The infusions were started on day 8 of the oestrous cycle and were continued for 72 h until day 11. Samples (5 mL) of jugular venous blood were collected regularly throughout the experiment as follow: For the determination of the plasma concentrations of oestradiol-17β, progesterone and FSH samples were taken every 6 h from -24 h relative to the start of infusion until ovariectomy. These samples were collected into lithium heparin tubes. For glucose and insulin samples were taken 24 hours before the start of the infusions and then at 0, 3, 9, 24, 48 and 72 hours after the start of the infusion. These samples were collected into fluoride/EDTA tubes. The blood samples were centrifuged at 4°C for 20 minutes at 1,000 g. The plasma was then decanted and stored at -20°C.
Collection and dissection of ovaries
The animals were ovariectomised under pentothal-induced, halothane-maintained anaesthesia, by the laboratory veterinarian. Within a minute of removal, the ovaries were placed in ice-cold sterile saline for transport from the surgery to the laboratory. In the laboratory, the number of corpora lutea was noted, the ovaries were weighed and all follicles >1 mm in diameter were dissected out using fine scissors and fine toothed dissecting forceps. The isolated follicles were placed in ice-cold phosphate buffered saline (0.72 M Na2HPO4.2H20; 0.28 M Na2H2PO4.2H20 and 0.155 M NaCl at pH 7.0) in sterile, plastic Petri dishes and their average diameter measured to the nearest mm (for details, see below). From this point the follicles were processed individually as described [29]. Individual follicles were placed in a sterile plastic mini-Petri dish containing 1 ml of sterile phosphate buffered saline. Each follicle was then hemisected and the granulosa cell layer was gently scraped into the phosphate buffered saline using a fine plastic loop. The follicular shell of mainly theca cells was placed in a 1.5 mL micro-tube, snap frozen and stored at -80°C. The phosphate buffered saline containing, granulosa cells and follicular fluid was then placed into another 1.5 mL micro-tube and centrifuged at 4°C and 1,000 X g for 10 min. Following centrifugation, the supernatant containing diluted follicular fluid was transferred into a 1.5 mL micro-tube snap frozen and stored at -20°C. The separated granulosa cell pellet was also snap-frozen and stored at -80°C.
Measurement and classification of follicles
The diameter of all dissected follicles was measured in two dimensions at 90°, using a graph paper grid placed below the Petri dishes that contained the dissected follicles and the average diameter calculated. The follicles were then grouped into three classes based on their diameters. These were: small >1.0-2.00 mm; medium >2.0 to 3.5 mm and large >3.5 mm. Follicles were also classified on the basis of their oestrogenicity. Oestrogenic follicles were defined as those with a concentration of oestradiol in follicular fluid >100 ng/mL, and non-oestrogenic follicles as those with <100 ng/mL. These definitions allow us to identify the following categories of follicles:
Large (diameter >3.5 mm) oestrogenic follicles
Large non-oestrogenic follicles
Medium (diameter >2.0 to 3.5 mm) oestrogenic follicles
Medium non-oestrogenic follicles
Small (diameter >1.0 to 2.0 mm) oestrogenic follicles.
Small non-oestrogenic follicles.
The volume of follicular fluid volume was calculated as described previously [30].
Glucose and hormone assays
The jugular venous blood samples collected in fluoride EDTA tubes were analysed for glucose and insulin and those collected in heparin-lithium tubes were analysed for progesterone, oestradiol-17β and FSH. Samples of follicular fluid were assayed for oestradiol-17β. All assays were carried out in duplicate.
The concentration of glucose in plasma was determined by colourimetry using the glucose oxidase method (Glucose Assay Kit [cat # G3660] and O-Dianisidine [cat # D2679] Sigma Aldrich Inc., Saint-Quentin Fallavier, France). The assay method followed the instructions provided by the manufacturer of the kit. Plasma samples were diluted in phosphate buffered saline (0.05 M, pH 7.6) as required, to obtain concentrations that fell within the range of the standard curve (2 to 8 mg of glucose per dL). The sensitivity of the assay was 2 mg/dL and the inter-assay and intra-assay coefficients of variation were 8% and 3% respectively.
The concentration of insulin in plasma was measured using a heterologous radioimmunoassay developed in our laboratory [31]. The antiserum was rabbit anti-porcine insulin, the standards were ovine insulin and the second antibody was a goat anti-rabbit IgG (all reagents from Sigma Aldrich Inc., Saint-Quentin Fallavier, France). The sensitivity of the assay was 0.05 ng/mL and the inter-assay and intra-assay coefficients of variation were 10% and 15% respectively. The cross reactivity of the antiserum with ovine insulin was 100% relative to the homologous insulin standard.
Oestradiol-17β
The concentration of oestradiol-17β in plasma was determined by the radioimmunoassay of solvent extracted plasma [32] using a commercial oestradiol assay kit (Estradiol-2 kit P2210; Diasorin, SA, Antony, France). The limit of detection of oestradiol was 0.39 pg/mL and the inter- and intra-assay coefficients of variation were 20.5% and 6.0% respectively. The concentrations of oestradiol-17β in samples of follicular fluid were determined using the same commercial oestradiol radioimmunoassay. Samples of follicular fluid were first diluted 1:10 or 1:100 in phosphate buffered saline (0.05 M, pH 7.6) and assayed without solvent extraction. The concentration of oestradiol-17β in follicular fluid was derived using the theoretical volume of follicular fluid calculated as described [30], and corrected for dilution.
The concentration of FSH in plasma was analysed using an ELISA [33]. The limit detection of FSH was 0.1 ng/mL the inter- and intra-assay coefficients of variation were 16.0% and 12.2% respectively.
The concentration of progesterone in plasma was determined using an ELISA [34]. The limit of detection of progesterone was 0.25 ng/mL the inter- and intra-assay coefficients of variation were 20.5% and 14.3% respectively.
Antibodies for Western blotting
All antibodies were obtained from commercial sources and their details are presented in Table 1. The analysis of Akt used a rabbit polyclonal antibody to Akt (Cell Signalling Technology, Beverly, Ma., USA) and a rabbit polyclonal antibody to phospho-Akt1/2/3 (Ser473; Santa Cruz Biotechnology Inc., Heidelberg, Germany). The analysis of AMPKα1/2 used a rabbit polyclonal antibody to AMPK α1/2 (Cell Signalling Technology, Beverly Ma., USA) and a rabbit polyclonal antibody to phospho-AMPK (thr172; Cell Signalling Technology, Beverly, Ma., USA). The analysis of ERK2 used a polyclonal antibody to ERK2 (Cell Signalling Technology, Beverly, Ma., USA) and a polyclonal antibody to phospho-ERK1/2 (Thr202/Tyr204; Cell Signalling Technology, Beverly, Ma., USA). A mouse monoclonal antibody was used to analyse Aromatase P450 (ABD Serotec, Düsseldorf, Germany) and a mouse monoclonal antibody to vinculin was used as an internal standard (Sigma Aldrich Inc., Saint-Quentin Fallavier, France). All antibodies were used at a dilution of 1/1000 dilution. The secondary antibodies that were used depending on the species used to generate the primary antibody were either a goat anti-mouse IgG (Laboratories Eurobio, Courtaboeuf, France) or a goat anti-rabbit IgG (Laboratories Eurobio, Courtaboeuf, France).
Table 1 Details of the primary and secondary antibodies used for western immuno-blotting in this experiment
Western blotting was used to determine the levels of Aromatase P450 protein relative to vinculin (an internal standard) in granulosa cell lysates from individual follicles greater than 2 mm in diameter [18], Aromatase P450 was not determined in small follicles. The levels of phosphorylated Akt and total Akt [18] were determined in granulosa cell lysates from individual follicles greater than 2 mm in diameter. The granulosa cells harvested from follicles between 1 and 2 mm in diameter were pooled within sheep. Similarly, the levels of phosphorylated AMPK and total AMPK [18] and the levels of phosphorylated ERK1/2 and total ERK2 were determined in granulosa cell lysates from individual follicles greater than 2 mm in diameter and in granulosa cells pooled within ewes from follicles between 1 and 2 mm in diameter. Lysates of granulosa cells were prepared as described [18] and then analysed by western blotting. The concentration of protein in the supernatants was determined by colourimetry using the BCA protein assay reagent (Interchim, Montluçon France). Aliquots of lysate containing 30 μg of protein were re-suspended in Laemmli buffer (glycerol 50%, SDS 10%, Hepes 1 M-pH7.6, beta-Mercaptoethanol 25%, bromophenol blue) and then analysed by western blotting.
Granulosa cell lysates were subjected to electrophoresis on 10% (v/v) SDS-polyacrylamide gels for 2.5 h at 80 V, in the running buffer (H202, 50 mM Tris Base, 400 mM Glycine, 2% EDTA 0.1 M, 1% SDS 10%). The proteins were then transferred onto nitrocellulose membranes for 1.5 h at 80 V, in transfer buffer (H202, 20 mM Tris Base, 200 mM Glycine, 20% Methanol, 0.1% SDS 10%). After washing in TBS Tween (H202, 2 mM Tris Base, 15 mM NaCl, 0.1% Tween 20, pH 7.4), the membranes were incubated for 1 h at room temperature with TBS Tween containing 5% dry milk powder to saturate non-specific sites. Subsequently, membranes were incubated overnight at 4°C with primary antibodies in TBS Tween containing 5% dry milk powder.
After washing in TBS Tween, the membranes were incubated with a horseradish peroxidase (HRP)-conjugated anti-rabbit IgG (Final dilution 1:10 000; Laboratories Eurobio, Courtaboeuf, France) or horseradish peroxidase (HRP)-conjugated anti-mouse IgG (Final dilution 1:10,000; Laboratories Eurobio, Courtaboeuf, France) for 2 h at room temperature in TBS Tween containing 5% dry milk powder. After washing in TBS Tween, the signal was detected by enhanced chemiluminescence (PerkinElmer, Life and Analytical Sciences, Courtaboeuf, France). The membranes were exposed on GE Healthcare film (PerkinElmer, Life and Analytical Sciences, Courtaboeuf, France), and then developed (Kodak AL4) and fixed (Kodak LX24) and dried. The films were analysed and the blots quantified using ScionImage (4.0.3.2 version, Scion Corporation, Frederick, Maryland, USA).
Statistical analyses were performed using specialised software for statistical analysis (SAS Statview version 5.0). Data on hormone concentrations in plasma and body weight were analysed by repeated measures ANOVA with time as the repeated measure. Where it was appropriate, post-hoc paired comparisons within time were carried out using the Bonferroni test. Other data were analysed by univariate ANOVA apart from the data on follicle number which were analysed using the Chi-squared test. The data are presented as the mean ± sem and differences are regarded as significant when P < 0.05.
In a ewe from a glucose-infused group the catheter failed and the infusion was interrupted. This animal was excluded from the experiment.
The average weights in the group infused with glucose at the start of the infusion and at ovariectomy were 47.0 ± 0.72 and 45.6 ± 0.78 kg, respectively. The average weights in the control group at the start of infusion, and at ovariectomy were 48.0 ± 0.73 and 46.0 ± 0.84 kg, respectively. There were no significant differences in the average weights within or between groups.
Ovarian morphology
The ewes in the two luteal phase groups had 3.11 ± 0.80 functional corpora lutea (CLs) in the glucose-infused group and 2.89 ± 0.58 CLs in the control group, confirming that the ewes were as expected, in the luteal phase of the oestrous cycle. The numbers of follicles dissected from the ovaries of control and glucose infused ewes are shown in Table 1. There were significantly more small follicles in the glucose-infused groups compared to controls at the same stage of the oestrous cycle (Table 2) and this is reflected also in the total number of follicles. There were no differences in follicle numbers between stages of the oestrous cycle and the number of medium and large follicles was not different between glucose-infused and control ewes (Table 2).
Table 2 Corpora lutea (CLs) and follicles
Plasma concentrations of metabolites
The concentrations of glucose in plasma are shown in Figure 2, overall there was a significant effect (P = 0.001) of treatment on the concentration of glucose. The plasma concentration of glucose was significantly elevated by 3 h (P <0.01) after the start of the infusion of glucose and remained elevated at 9 h (P <0.01), at 24 h (P <0.01) and at 48 h (P <0.05) but, it had decreased to control concentrations at 72 h. The concentration of plasma glucose in control ewes did not vary significantly during the experiment (Figure 2).
The mean ± sem, concentrations of glucose (upper graph) and insulin (lower graph) in jugular venous plasma of ewes infused with either saline (n = 18; dashed line with open circles) or with 10 mM/h of glucose (n = 17; solid lines with closed circles) for 72 h during the late luteal phase of the oestrous cycle. Within times, an asterisk (*) indicates a significant difference (P < 0.05).
The plasma concentrations of insulin are shown in Figure 2, overall there was a significant effect (P = 0.02) of treatment on the concentration of insulin. Paired comparisons revealed that the concentration of insulin was significantly elevated by 9 h (P <0.05) after the start of the infusion of glucose and remained elevated at 24 h (P <0.01) and at 48 h (P <0.05) but, it had decreased to control concentrations at 72 h. The concentration of insulin in control ewes did not vary significantly during the experiment (Figure 2).
Plasma concentrations of reproductive hormones
The plasma concentrations of oestradiol-17β are shown in Figure 3. The pre-treatment concentrations of plasma oestradiol were not significantly different between the glucose and control groups. However, the plasma concentration of oestradiol was reduced in the glucose-infused groups compared to the control group (P <0.05) during the infusion period between 6 and 66 h after the start of the infusions. There was also a significant effect of time (P <0.05) following luteolysis; the plasma concentration of oestradiol increased significantly in both groups and by 12 h after PG the glucose-infused group was no longer lower than the control group (Figure 3).
The mean ± sem, concentrations of oestradiol-17β (upper graph) and FSH (lower graph) in jugular venous plasma of ewes infused with either saline (n = 18 and n = 9 after 72 h; dashed line with open circles) or with 10 mM/h of glucose (n = 17 and n = 8 after 72 h; solid lines with closed circles) for 72 h during the late luteal phase of the oestrous cycle. Within times, an asterisk (*) indicates a significant difference (P < 0.05).
The concentration of FSH in plasma (0.72 ± 0.040 ng/mL) from glucose-infused ewes was not different from that in control ewes (0.67 ± 0.036 ng/mL). There was a significant effect of time and the concentration of FSH fell significantly following the induction of luteolysis (Figure 3) but, the interaction between time and treatment was not significant.
The profiles of progesterone in plasma (all concentrations above 2 ng/mL prior to the injection of PG and falling to below 1 ng/mL by 30 h after PG) confirmed that all ewes were undergoing normal oestrous cycles and that they were at the correct stage of the oestrous cycle at the time the ovaries were collected.
Concentrations of oestradiol in follicular fluid
The concentrations of oestradiol in follicular fluid are shown in Figure 4. The concentration of oestradiol in oestrogenic follicles was significantly higher compared to non-oestrogenic follicles from all three follicle classes (P < 0.05) and in the follicular phase compared to the luteal phase of the oestrous cycle (P < 0.05; Figure 4). The concentration of oestradiol did not differ significantly among follicle classes in non-oestrogenic follicles but, in oestrogenic follicles the concentration of oestradiol was higher in medium follicles compared to small follicles (P < 0.001) and higher in large follicles compared to medium (P < 0.001) and small follicles (P < 0.001; Figure 4). Finally the infusion of glucose reduced the concentration of oestradiol in large (P < 0.001) oestrogenic follicles collected during the follicular phase of the oestrous cycle and in both medium (P < 0.001) and large (P < 0.001) oestrogenic follicles collected in the luteal phase of the oestrous cycle (Figure 4). Glucose had no effect in non-oestrogenic follicles (Figure 4).
The mean ± sem, concentrations of oestradiol-17β in follicular fluid from small (<2.0 mm), medium (2.0 to 3.5 mm) and large (>3.5 mm) diameter oestrogenic (oestradiol >100 ng/mL) and non-oestrogenic (oestradiol <100 ng/mL) follicles from ewes during the luteal and follicular phases of the oestrous cycle infused with saline (light grey columns) or with 10 mM/h of glucose (dark grey columns) for 72 h during the late luteal phase of the oestrous cycle. Follicle classes with different letters (x, y and z) differ significantly at P < 0.05. Note there is a difference in scale between the luteal and follicular phase diagrams.
Aromatase P450
The levels of Aromatase P450 protein in granulosa cells are shown in Figure 5. In oestrogenic follicles Aromatase P450 was significantly (P < 0.05) higher in the follicular phase compared to the luteal phase in both medium and large follicles. The levels of Aromatase P450 were significantly (P < 0.05) lower in non-oestrogenic follicles compared to oestrogenic follicles regardless of their size (Figure 5). The infusion of glucose significantly (P < 0.05) reduced the level of Aromatase P450 in oestrogenic follicles of all sizes but, it had no effect on the level of Aromatase P450 in non-oestrogenic follicles (Figure 5). In non-oestrogenic follicles Aromatase P450 did not vary significantly with either the stage of the oestrous cycle or the diameter of the follicle.
The mean ± sem, level of aromatase P 450 protein in granulosa cell lysates from medium (2.0 to 3.5 mm) and large (>3.5 mm) diameter oestrogenic (oestradiol >100 ng/mL) and non-oestrogenic (oestradiol <100 ng/mL) follicles from ewes during the luteal and follicular phases of the oestrous cycle infused with saline (light grey columns) or with 10 mM/h of glucose (dark grey columns) for 72 h during the late luteal phase of the oestrous cycle. Follicle classes with different letters (x and y) and columns with different letters (a and b) differ significantly at P < 0.05.
Mediators of Insulin-signalling (Akt, ERK and AMPK)
The ratios of phosphorylated to non-phosphorylated forms of Akt (Figure 6), ERK (Figure 7) and AMPK (Figure 8) were all lower (all at P <0.05) in non-oestrogenic follicles compared to oestrogenic follicles while in non-oestrogenic follicles the ratios for all three were unaffected by the diameter of the follicle, the stage of the oestrous cycle or the infusion of glucose (Figures 6, 7 and 8). However, in oestrogenic follicles the infusion of glucose reduced the ratio of phosphorylated non-phosphorylated forms of all three compared to control ewes in medium and large follicles from the luteal phase (all at P <0.05) and in all three follicle classes in follicles from the follicular phase (P <0.05; Figures 6, 7 and 8). Similarly, the ratios for all three were not significantly different in small and medium follicles and they were significantly higher in large follicles (all at P <0.05) compared to small and medium follicles (Figures 6, 7 and 8). There were no significant differences between the follicular and luteal phases between follicle types or among follicle diameters.
The mean ± sem, ratios of phosphorylated to non-phosphorylated Akt in granulosa cell lysates from small (<2.0 mm), medium (2.0 to 3.5 mm) and large (>3.5 mm) diameter oestrogenic (oestradiol >100 ng/mL) and non-oestrogenic (oestradiol <100 ng/mL) follicles from ewes during the luteal and follicular phases of the oestrous cycle infused with saline (light grey columns) or with 10 mM/h of glucose (dark grey columns) for 72 h during the late luteal phase of the oestrous cycle. Columns with different letters (a and b) differ significantly at P < 0.05.
The mean ± sem, ratios of phosphorylated to non-phosphorylated ERK in granulosa cell lysates from small (<2.0 mm), medium (2.0 to 3.5 mm) and large (>3.5 mm) diameter oestrogenic (oestradiol >100 ng/mL) and non-oestrogenic (oestradiol <100 ng/mL) follicles from ewes during the luteal and follicular phases of the oestrous cycle infused with saline (light grey columns) or with 10 mM/h of glucose (dark grey columns) for 72 h during the late luteal phase of the oestrous cycle. Columns with different letters (a and b) differ significantly at P < 0.05.
The mean ± sem, ratios of phosphorylated to non-phosphorylated AMPK in granulosa cell lysates from small (<2.0 mm), medium (2.0 to 3.5 mm) and large (>3.5 mm) diameter oestrogenic (oestradiol >100 ng/mL) and non-oestrogenic (oestradiol <100 ng/mL) follicles from ewes during the luteal and follicular phases of the oestrous cycle infused with saline (light grey columns) or with 10 mM/h of glucose (dark grey columns) for 72 h during the late luteal phase of the oestrous cycle. Columns with different letters (a and b) differ significantly at P < 0.05.
The results of this experiment show that in cyclic ewes during the breeding season, the intravenous infusion of glucose increased the total number of follicles present in their ovaries [17]. These findings agree with those obtained when using anoestrous ewes treated with eCG [18]. Furthermore the present experiment also shows that the effect of intravenous glucose on the follicle population of the ovary is present in both the luteal and follicular phases of the oestrous cycle. The concentrations of glucose achieved by the infusions peaked at 120 mg/dL or about 30% above the upper limit of the normal reference range for sheep (45-80 mg/dL). Additionally, this effect of glucose was also associated with a reduction in the circulating concentrations of oestradiol (Figure 3) but without any associated change in the concentrations of circulating FSH (Figure 3) and a reduction in the level of ovarian Aromatase P450 in oestrogenic follicles (Figure 5). Furthermore, the effect of glucose was accompanied by an increase in the circulating concentration of insulin (Figure 2) and finally it was associated with changes in the insulin signalling and energy sensing mechanisms (Figures 6, 7 and 8) in granulosa cells.
Very similar findings have been reported for the effects of diets that increase the supply of energy. Feeding dietary supplements such as lupin grain [13, 17, 20, 35, 36], a mixture of soya meal and maize [14], or steamed corn flakes [37] or administering by gavage, an energy supplement in the form of a mixture of glycerol and propylene glycol [38, 39] to ewes all increased the number of follicles in their ovaries. In all these studies the nutritional treatment increased the concentrations of glucose and insulin in jugular venous plasma and these changes were associated with an increased number of follicles. Some of these studies also reported reduced concentrations of oestradiol in jugular plasma [20, 35], reduced levels of Aromatase P450 in granulosa cell lysates [13, 20] and lower concentrations of oestradiol in follicular fluid from oestrogenic follicles [13, 20].
There is some controversy over the effects of either glucose or glucogenic diets on the circulating concentrations of oestradiol. We have reported decreased circulating concentrations of oestradiol following the infusion of glucose [18] or the feeding of a lupin grain supplement [20] and other authors have reported similar findings [35]. However other studies from our group found that feeding lupin grain [13] had no effect on oestradiol and other authors have also found no effect of glucogenic diets on the concentrations of oestradiol in jugular venous blood [14]. Using a different experimental model, these authors also reported that a supplement of lupin grain increased oestradiol concentrations and reduced those of FSH [36]. The main reason for these discrepancies is most probably because sheep have particularly low concentrations of oestradiol [40] and the oestradiol assays employed are being used at the very limits of their technical capability. The secretion rate of oestradiol was reduced by feeding a lupin grain supplement to ewes with ovarian auto-transplants [3] and in other experiments the concentration of oestradiol in the follicular fluid was reduced by feeding a supplement of lupin grain [13, 20] or a high energy diet [41] and in this experiment the infusion of glucose reduced the concentration of oestradiol in the follicular fluid of oestrogenic follicles (Figure 4). Furthermore these treatments were associated with reduced levels of Aromatase P450 in granulosa cell lysates from oestrogenic follicles [13, 18, 20, 42]. So on balance we conclude tentatively, that it is very likely that both intravenous glucose and glucogenic diets can reduce the secretion of follicular oestradiol from oestrogenic follicles.
The effect of glucose on ovarian follicles appears to be dependent on the stage of development of the follicles. In the population of small follicles the effect of glucose was to stimulate their growth a conclusion that can be inferred from the increased number of small follicles in glucose-infused ewes (Table 2). Furthermore in small non-oestrogenic follicles this effect was not associated with any detectable change in the level of phosphorylated Akt, ERK1/2 and AMPK (Figures 6, 7 and 8) suggesting that this effect of glucose was not related to altered activity of insulin-signalling pathways in granulosa cells. This leads us to conclude that it is was possibly a direct effect of an increased supply of metabolic fuel (glucose) to the ovary. By contrast, in medium and large follicles glucose had little effect on the number of follicles (Table 2) but, in medium and large oestrogenic follicles it did have substantial effects on their physiological function through an inhibition of the level of aromatase P450 (Figure 5) and a reduction in the concentration of oestradiol in follicular fluid (Figure 4). These actions were associated with changes in insulin signalling pathways and so these follicles are presumed to be responsive to both insulin and glucose and that the effect of glucose is insulin-mediated [43].
Extrapolating further, these data indicate that oestrogenic follicles are insulin-responsive [43] and that non-oestrogenic follicles are not. The population of non-oestrogenic follicles is a mixed population consisting of a sub-population of undifferentiated, small growing follicles and a sub-population of medium and large atretic follicles neither of which are insulin-responsive. Our findings suggest that glucose acts directly in growing follicles to stimulate growth leading to greater numbers of small follicles while in oestrogenic follicles which are physiologically functional but non-growing, glucose acts indirectly through an insulin-mediated mechanism to inhibit the synthesis and secretion of oestradiol [43].
The circulating concentration of IGF-I was not determined in this experiment. However, it was in our earlier experiment [18] where glucose increased the jugular venous concentrations of IGF-I. Despite the fact that IGF-I is a potent stimulator of both follicle growth [29] and oestradiol secretion [29, 44] we consider it unlikely that the effects of glucose in the follicle, in this experiment were mediated by IGF-I. IGF-I is a potent growth factor controlled by hepatic feedback systems that are independent of ovarian follicles [45]. Consequently there are intra-ovartian mechanisms that regulate the activity of IGF-I [46, 47] to protect the follicle from the potentially harmful effects of high concentrations of IGF-I. None-the-less it is possible that the insulin-independent effects of glucose on small follicles (Table 2) are an effect of IGF-I. Interestingly, glucose reduced circulating (Figure 3) and intrafollicular (Figure 4) concentrations of oestradiol suggesting that the intra-follicular bio-activity of IGF-I in oestrogenic follicles is suppressed.
The expected effect of reduced secretion of oestradiol (Figure 3) would be an increase in circulating FSH. How then can we explain the absence of the expected compensatory increase in FSH? Published data on the effects of glucogenic diets on the plasma concentrations of FSH presents a mixed picture. Some authors have reported increased concentrations of FSH and others have reported no change. It has been suggested that the reasons for these differences are technical and associated with the assays employed to measure ovine FSH [45] or that they reflect the dynamic nature of the negative relationship between FSH and the follicle [3]. However, it is also possible that the variation simply indicates the presence of uncontrolled and unidentified physiological differences among animals leading to unconscious bias in randomisation procedures. In an attempt to control this variability, Vinoles and her colleagues [36] used a first wave model to synchronise follicles waves and thus theoretically, reduce between ewe variability in the follicle population. Their results showed that supplementation with a glucogenic diet increased concentrations of oestradiol and reduced those of FSH in jugular plasma. However, the control of FSH by negative feedback from the ovary has two hormonal components namely oestradiol and inhibin and until the effects of glucogenic diets on the secretion of ovarian inhibin have been described a complete understanding of the effects of glucogenic diets on FSH will not be possible. Regrettably, at present there in no satisfactory technique available for measuring the concentration of inhibin in jugular venous plasma from sheep.
It is worth noting that the population of small growing follicles is an important source of inhibin [48]. Because glucogenic diets increase their number then theoretically, these diets should also increase the total secretion of follicular inhibin and the concentration of inhibin in the peripheral circulation. We can speculate that the resulting increase in inhibin negative feedback on FSH may thus compensate for any reduced oestradiol feedback and may explain why in some studies oestradiol decreased but FSH did not increase. We suggest that variability of the FSH responses to glucogenic treatments may reflect subtle changes in the balance of the effects of glucogenic diets on small growing (i.e. inhibin secreting) and large oestrogenic (i.e. oestradiol secreting) follicles.
The follicle has a functional insulin-glucose system [5] and the level of activity in the pathway can be estimated from the ratio of phosphorylated to non-phosphorylated forms of the various protein kinases in the pathway. Some of the kinases activated by insulin, although not exclusively, including Akt, ERK and AMPK have been detected in ovarian follicles from ewes [18, 49–52] and in this experiment the phosphorylation ratios of all three of these were altered by the infusion of glucose. The Irish group [49–51] have shown that both Akt and ERK are implicated in the mechanism of follicle selection and this study confirms their findings [18] showing that intravenous glucose decreased the level of phosphorylation of Akt and AMPK and furthermore, shows for the first time that glucose reduced the level of phosphorylation of ERK. How do these effects relate to the mechanism through which a glucogenic diet can increase ovulation rate? Ovulation rate in sheep is ultimately determined by the number of gonadotrophin-dependent, ovulatory follicles present at the time of the LH surge. The reduction in the secretion of oestradiol by the ovulatory follicle suggests that the effect of glucose is to impair FSH-stimulated synthesis of oestradiol, the reduced levels of Aromatase P450 are consistent with such an action, and reduce its inhibitory influence (or dominance) on subordinate follicles in the cohort thus allowing for the emergence of additional ovulatory follicles. Potential mechanisms probably involve "cross-talk" [53] between the insulin signalling and FSH signalling pathways in granulosa and theca cells of the ovulatory follicle [5]. However, the details of how and where these signalling pathways interact are topics for future research.
These results show that an intravenous glucose that maintains the concentration of blood glucose slightly above the upper end of the normal reference range increased the number of small follicles and altered the function of follicular granulosa cells in large oestrogenic follicles but not in small follicles or non-oestrogenic follicles of any size. The glucose reduced the levels of Aromatase P450 in large oestrogenic follicles and this was reflected in a reduced blood concentration of oestradiol. These reduced levels of Aromatase P450 were associated with reduced levels of phosphorylated Akt, ERK and AMPK in large follicles. However, glucose did not affect the phosphorylation state of the energy sensor, AMPK and mediators of insulin action (Akt, ERK) in small follicles. These data suggest that the effect of glucose in small follicles is a direct action of glucose that increases the number of small follicles while the effect of glucose in large, oestrogenic follicles is an indirect insulin-mediated action that inhibits their capacity to secrete oestradiol.
A Protein kinase B
AMPK:
5' adenosine monophosphate-activated kinase
BCA:
Bicinchoninic acid
Corpus luteum
eCG:
equine chorionic gonadotrophin
Ethylenediaminetetra acetic acid
Enzyme linked immunosorbent assay
ERK:
Extra cellular-related protein kinase
GLUT 4:
Glucose transporter 4
IGF-I:
Insulin-like growth factor 1
IgG:
Immunoglobulin G
INRA:
L'Institut National de la Recherche Agronomique
IRS:
Insulin receptor substrate
PGF2α :
Prostaglandin F2α
SDS:
Sodium dodecyl sulphate
Sem:
Standard error of the mean
SLC2A-4:
Sugar transport facilitator
TBS:
Tris-buffered saline.
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Webb R, Campbell BK, Garverick HA, Gong JG, Gutierrez CG, Armstrong DG: Molecular mechanisms regulating follicular recruitment and selection. J Reprod Fert 1999,54(Suppl):33–48.
Armstrong DG, Gong JG, Webb R: Interactions between nutrition and ovarian activity in cattle: physiological, cellular and molecular mechanisms. Reproduction 2003,61(Suppl):403–14.
Zouaïdi N, Dupont J, Khaldi G, Scaramuzzi RJ: The effect of short-term treatment of ewes with either intravenous glucose or a supplement of soya and maize during the luteal phase on the number of follicles and the AMPK signalling pathway in granulosa and theca cells. In Ruminant Physiology: Proceedings of the XIth International Symposium on Ruminant Physiology. Edited by: Chilliard Y, Glasser F, Faulconnier Y, Bocquier F, Veissier I, Doreau M. Wageningen, The Netherlands: Wageningen Academic Publishers; 2009:786–7.
Agabriel J: INRA Alimentation des Bovines, Ovins et Caprins: Besoins des Animaux – Valeurs des Aliments. Tables INRA 2007, mise à jour 2010. Versailles, France: éditions Quae; 2013.
Campbell BK: Factors affecting ovulation rate in sheep and cattle. PhD thesis. University of Sydney, Department of Animal Science; 1988.
Carson RS, Findlay JK, Clarke IJ, Burger HG: Oestradiol, testosterone, and androstenedione in ovine follicular fluid during growth and atresia of ovarian follicles. Biol Reprod 1981, 24:105–13. 10.1095/biolreprod24.1.105
Menassol J-B, Collet A, Chesneau D, Malpaux B, Scaramuzzi RJ: The interaction between photoperiod and nutrition and its effects on seasonal rhythms of reproduction in the ewe. Biol Reprod 2012, 86:1–12.
Ben Said S, Lomet D, Chesneau D, Lardic L, Canepa S, Guillaume D, et al.: Differential estradiol requirement for the induction of estrus behaviour and the luteinizing hormone surge in two breeds of sheep. Biol Reprod 2007, 76:673–80. 10.1095/biolreprod.106.057406
Faure MO, Nicol L, Fabre S, Fontaine J, Mohoric N, McNeilly AS, et al.: BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary. J Endocrinol 2005, 186:109–21. 10.1677/joe.1.05988
Canépa S, Laine A-L, Bluteau A, Fagu C, Flon C, Monniaux D: Validation d'une méthode immunoenzymatique pour le dosage de la progestérone dans le plasma des ovins et des bovins. Cahier des Techniques de l'INRA 2008, 64:19–30.
Kosior-Korzecka U, Bobowiec R: Changes in the level of endogenous leptin, FSH, 17beta-oestradiol and metabolites during lupin-induced increase in ovulation rate in ewes. J Vet Med A Physiol Pathol Clin Med 2003, 50:343–9. 10.1046/j.1439-0442.2003.00558.x
Viñoles C, Paganoni B, Glover KM, Milton JT, Blache D, Blackberry MA, et al.: The use of a 'first-wave' model to study the effect of nutrition on ovarian follicular dynamics and ovulation rate in the sheep. Reproduction 2010, 140:865–74. 10.1530/REP-10-0196
Letelier C, Gonzalez-Bulnes A, Herve M, Correa J, Pulido R: Enhancement of ovulatory follicle development in maiden sheep by short-term supplementation with steam-flaked corn. Reprod Dom Anim 2008, 43:222–7. 10.1111/j.1439-0531.2007.00885.x
Letelier C, Mallo F, Encinas T, Ros JM, Gonzalez-Bulnes A: Glucogenic supply increases ovulation rate by modifying follicle recruitment and subsequent development of preovulatory follicles without effects on ghrelin secretion. Reproduction 2008, 136:65–72. 10.1530/REP-08-0010
Berlinguer F, Gonzalez-Bulnes A, Contreras-Solis I, Spezzigu A, Torres-Rovira L, Succu S, et al.: Glucogenic supply increases oocyte developmental competence in sheep. Reprod Fert Dev 2012, 24:1055–62. 10.1071/RD11299
Scaramuzzi RJ, Land RB: Oestradiol levels in sheep plasma during the oestrous cycle. J Reprod Fert 1978, 53:167–71. 10.1530/jrf.0.0530167
Ying S, Wang Z, Wang C, Nie H, He D, Jia R, et al.: Effect of different levels of short-term feed intake on folliculogenesis and follicular fluid and plasma concentrations of lactate dehydrogenase, glucose, and hormones in Hu sheep during the luteal phase. Reproduction 2011, 142:699–710. 10.1530/REP-11-0229
Ying SJ, Xiao SH, Wang CL, Zhong BS, Zhang GM, Wang ZY, et al.: Effect of nutrition on plasma lipid profile and mRNA levels of ovarian genes involved in steroid hormone synthesis in Hu sheep during luteal phase. J Anim Sci 2013, 91:5229–39. 10.2527/jas.2013-6450
Downing JA, Joss J, Scaramuzzi RJ: The effect of a direct arterial infusion of insulin and glucose on the ovarian secretion rates of androstenedione and oestradiol in ewes with an autotransplanted ovary. J Endocrinol 1999, 163:531–41. 10.1677/joe.0.1630531
Scaramuzzi RJ, Murray JF, Downing JA, Campbell BK: The effects exogenous growth hormone on follicular steroid secretion and ovulation rate in sheep. Dom Anim Endocrinol 1999, 17:269–77. 10.1016/S0739-7240(99)00043-0
Scaramuzzi RJ, Baird DT, Campbell BK, Driancourt MA, Dupont J, Fortune JE, et al.: Regulation of folliculogenesis and the determination of ovulation rate in ruminants. Reproduction Fertility and Dev 2011, 23:444–67. 10.1071/RD09161
Monget P, Besnard N, Huet C, Pisselet C, Monniaux D: Insulin-like growth factor-binding proteins and ovarian folliculogenesis. Horm Res 1996, 45:211–7. 10.1159/000184790
Monget P, Fabre S, Mulsant P, Lecerf F, Elsen JM, Mazerbourg S, et al.: Regulation of ovarian folliculogenesis by IGF and BMP system in domestic animals. Dom Anim Endocrinol 2002, 23:139–354. 10.1016/S0739-7240(02)00152-2
Campbell BK, Baird DT: Inhibin A is a follicle stimulating hormone-responsive marker of granulosa cell differentiation, which has both autocrine and paracrine actions. J Endocrinol 2001, 169:333–45. 10.1677/joe.0.1690333
Evans AC, Martin F: Kinase pathways in dominant and subordinate ovarian follicles during the first wave of follicular development in sheep. Anim Reprod Sci 2000, 64:221–31. 10.1016/S0378-4320(00)00210-4
Ryan KE, Casey SM, Canty MJ, Crowe MA, Martin F, Evans AC: Akt and Erk signal transduction pathways are early markers of differentiation in dominant and subordinate ovarian follicles in cattle. Reproduction 2007, 133:617–26. 10.1530/REP-06-0130
Ryan KE, Glister C, Lonergan P, Martin F, Knight PG, Evans AC: Functional significance of the signal transduction pathways Akt and Erk in ovarian follicles: in vitro and in vivo studies in cattle and sheep. J Ovar Res 2008, 1:2. doi:10.1186/1757–2215–1-2 10.1186/1757-2215-1-2
Tosca L, Chabrolle C, Dupont J: AMPK: a link between metabolism and reproduction? Med Sci (Paris) 2008, 24:297–300. 10.1051/medsci/2008243297
Taniguchi CM, Emanuelli B, Kahn CR: Critical nodes in signalling pathways: insights into insulin action. Nature Mol Cell Biol 2006, 7:85–96. 10.1038/nrm1837
The research was supported by a grant from the European Union Framework 6 funding program (MEXC-CT-2006-042499). NZ was supported by scholarships from the Tunisian government and INRA. RJS was the recipient of an EU Marie Curie Chair of Excellence (MEXC-CT-2006-042499). We wish to thank Mrs Juliette Cognié for carrying out the ovariectomies, Mr Lionel Lardic for the oestradiol assays, Dr Danielle Monniaux and Dr Sandrine Freret for help with the ovarian dissections, the staff from the INRA experimental station at Nouzilly for their help with experimental animals and Anne-Lyse Laine of the hormone assay laboratory of the UMR PRC for the assays of progesterone and FSH.
L'Institut National de la Recherche Agronomique, Unité Mixte de Recherche 6175, Physiologie de la Reproduction et des Comportements, Nouzilly, 37380, France
Rex John Scaramuzzi, Nesrine Zouaïdi, Jean-Baptiste Menassol & Joëlle Dupont
Department of Comparative Biomedical Sciences, The Royal Veterinary College, Hawkshead Lane, North Mimms, Hertfordshire, AL9 7TA, UK
Rex John Scaramuzzi
L'Institut National de la Recherche Agronomique, UR 1213 URH Unité de Recherches sur les Herbivores, Centre de recherche de Clermont-Ferrand-Theix, Clermont-Ferrand, France
Jean-Baptiste Menassol
Nesrine Zouaïdi
Joëlle Dupont
Correspondence to Rex John Scaramuzzi.
J-BM developed and carried out the immunoassay for insulin and participated in management of the animals, the collection of plasma and tissue samples and drafting the manuscript. JD participated in the design of the study and drafting the manuscript and advised on the western blotting procedure. RJS conceived of the study and participated in its design and coordination and drafted the manuscript and advised on the statistical analysis. NZ participated in the design of the study and carried out management of the animals, the collection of plasma and tissue samples, the laboratory procedures, and the statistical analysis and participated in drafting the manuscript. All authors read and approved the final manuscript.
Scaramuzzi, R.J., Zouaïdi, N., Menassol, JB. et al. The effects of intravenous, glucose versus saline on ovarian follicles and their levels of some mediators of insulin signalling. Reprod Biol Endocrinol 13, 6 (2015). https://doi.org/10.1186/1477-7827-13-6
FSH
Aromatase

redpajama_set_name: RedPajamaCommonCrawl


Jennifer Lopez bought a new home in California last year and, with the help of designer Michelle Workman, created a space of light blues and grays with dark wood accents. Workman explains that she and Lopez went with an old Hollywood glam look for the kitchen.
"There are all tones of gray, and we played with that -- using a bit more of a gray-taupe here, a bit more of a gray-blue there," Workman said. "It's almost like a black-and-white film from the forties."
Lopez's kitchen also features a dark, antique-looking oven that serves as a centerpiece to the kitchen's decor.


Good news for the boys field at the 2017 FLYRA Middle School XC State Championships. 17 of the top 20 runners from 2016 graduated. Belen Jesuit's Adam Magoulas finished 10th last year and would have returned for his final middle school state championship, but the varsity squad was calling, and the Wolverines are in the hunt for a 3A title.
Defending team champion, Tavares Middle School, which has been running under the Red Sea Running Club mantra for most of the season returns two of it's top three runners in 7th graders Matthew Raucci and Riley Novack. Raucci has finished 4th or better in all seven of his races this season including a new PR of 10:37.90 and runner-up finish at the Disney Cross Country Classic. Novak has one upped his teammate with no performance worse than third place this middle school season, but a slightly slower PR of 10:41.65.
One of the favorites will be Tristan McWilliam of Nolan Middle School in Bradenton, McWilliam won the FLRunners.com Invitational middle school race in 10:22.81 and has been consistently around that team in his three major wins this season.
Rheinhardt Harrison (pictured above) of the St. John's Striders is another athlete to watch. Like McWilliams he has won all of his races this season including the Katie Caples Invitational, Florida Horse Park Invitational, and North Florida MS Qualifier. His times of 10:20.00, 10:25.00, and 10:23.00 shows that he can perform well on big stages.
Harrison's toughest competition at Katie Caples came from Elite Runner Fort Myer's Patrick Murphy who was runner-up that day. Murphy has had great success on Holloway with two wins already this year. He opened up his 2017 season with a win at the Jim Ryun Invitational and then followed it with a win at FLR18 in a new personal best time of 10:41.46.
Trey Matschner of Indian Trails Middle School in Winter Springs won the open race last year and is coming off of a win and new PR of 10:38.63 from the Gliders Cross Country Invitational.
The team battle starts with defending champion Tavares and runner-up Belen Jesuit. Can they repeat their success of 2017? Belen won the middle school team title at FLRunners by a large amount and Tavares has been a consistent team all season long. The Wolverines will have Tommy Duque taking over for Magoulas in the top part of their line up.
Much like the girls, the Citrus Park Christian boys are also very young and talented. Thomas McCleod and Braxton Legg went 1-2 at the FLYRA Nature Coast qualifier to help the Eagles win the team title and will also be in the mix.
One thing to note, there are no team trophies for club teams. That doesn't fare well for the likes of the Elite Runner Fort Myers, Miami Elite, & Hillsborough Harriers. Elite Runner won the Katie Caples Invitational and was second at FLR18 just to name a few. These three programs could definitely contend with any team on the course for the top prize.


Our assignment is to create a surface in Maya using dynamics and applying different force fields to manipulate the plane by playing with the goal weight. The purpose of this assignment is to create a surface for a 3-axis milling machine. We had to make sure that there were no undercuts in our designs, since the machine would not account for them.


Feeding difficulties in the NICU are common and can be challenging for even experienced therapists. Premature infants and medically fragile/sick newborns are unique from typically developing healthy newborns. An appreciation of their fragile and immature sub systems, maturation of these subsystems around feeding and swallowing, as well as our ability to impact these systems, are required to be a successful clinician serving this population. This two day seminar will provide a strong foundation in evidence based information, theory and critical analysis of: sub system analysis, swallowing safety and function, appropriate and effective therapeutic interventions, family/caregiver engagement and discharge planning. Infant's communication skills, positioning impact on feeding and swallowing, pre-feeding skills, therapeutic feeding trials, bottle and breast feeding, family involvement, and feeding in palliative care will also be discussed. Along with interactive lectures; videos, pictures, case studies, demonstrations and activities will be used to further expand learning opportunities and empower participants as feeding therapists with this fragile population in the NICU and beyond.
A baby doll with soft movable extremities OR a "NDT doll"
Karin Mitchell is a worldwide respected Speech Language Pathologist specializing in the care and treatment of pediatric feeding and swallowing, developmental care of the medically fragile infant and child, and pediatric traumatic brain injury. Her love of teaching and helping others drives her to create and deliver fun and empowering continuing education courses across the nation and internationally. Areas covered are Developmental Care in the NICU, Cue Based Feeding, pediatric feeding and swallowing analysis and treatment, including the use of VitalStim, swallow studies, enhancing decision making and clinical analysis, breast feeding the medically fragile infant and child, and developmental milestones supporting feeding skill acquisition. Beginning her practice in 1995, Karin sought out learning opportunities and creative ways to teach others. She now serves as a lead therapist for the NICU and Feeding Teams at CHOC Children's Hospital in Orange, CA. With a clinical practice formed by a strong theory base in NDT and SI therapies, Karin is also NOMAS trained and VitalStim certified. She provides ongoing education in-services and hands-on labs for appropriate developmental care, positioning, handling, and feeding skills for clinical staff including medical residents, nurses, physical therapists, occupational therapists, and speech pathologists. Karin was a key player in the development of unit protocols and care plans for evidence-based developmental care in the highly specialized Small Baby Unit (ELBW) at CHOC which includes an ongoing education series required by all medical and support personnel. She is an active committee member for multiple qualities of care committees including Skin to Skin Care, Developmental Care, Infant Driven Feeds, Breast Feeding Coalition, Palliative Care, Neuro NICU Team, Trauma Team, and Family Centered Care. A dedicated leader, Karin devotes much of her time to the support and development of clinicians, serving as a mentor committed to building therapist's skills in clinical analysis and therapeutic effectiveness with medically fragile patients. She is a strong advocate for her patients and their families and speaks at local associations, community centers, local universities, and school districts to support medically fragile infants and children.
Non-financial Disclosure: Karin uses VitalStim in her clinical practice.
Participants who successfully complete this course will receive CEU Certificate at the end of the course.
"Karin's teaching manner was excellent! Her voice was calming, her rate and volume were perfect. She was not rushed. I liked the repetition & format."
"I loved the holistic approach of this course!"
"great, friendly presentation. Thanks for the opportunity to ask questions. "
"Great course! Karin is knowledgable with a wealth of information. Took time to answer questions & help problem solve various cases. Valuable information that I can immediately use in my daily work."
"Really appreciate all Karin's up to date research studies & appreciation. More videos would be great!"
"Karin is an awesome teacher! She's full of knowledge & shares it in an interesting, organized & easy-to-follow way. I feel much more comfortable with my tx skills!"
"I learned more in the first 2 hours than I learned in 75% of my grad school career. Karin was engaging, knowledgeable and encouraging throughout her teaching and it makes me eager to go back to work."
"Love all of Karin's presentations. She is up to date on studies/techniques and treatment and makes sure you get ideas for intervention."
"None. Karin's presentation was excellent. She explained information thoroughly and consistently in a way even a graduate student can benefit from!"
"Karin was a great instructor and very passionate about her job. She is very knowledgable and great at presenting the material in ways that is easy to understand."
"Thank you so much for providing this course via Live Stream! I would not have been able to attend otherwise due to having a newborn at home :)"
"Great info and demonstrations! Seamless and convenient livestream experience"
"This course was fantastic, I was a little worried about taking a course like this online but was blown away at how quick and responsive the staff was when there were technical difficulties or questions. Thank you Karin and CIAO staff!"
"Please keep offering amazing courses like this one. Not many great course like this come to Hawaii. I am willing to continue to wake up at 2am if it means I can grow an learn as therapist for the better of my patients. "
"Ms. Karin is a wonderful and knowledgeable presenter! She teaches in a way that is retainable and opens opportunities for questions!"
"I was given confidence in knowing that I am on the right track in treatment. Also, I have increased confidence in implementing therapeutic strategies. "
"Karin was phenomenal! Experienced, knowledgeable, approachable and passionate. I have learned so much from this course. The CIAO staff was also first-class. Thank you! "
"Advertise or under objectives would be beneficial to mention that the course is intro course. Also offer option to attend only day 2 for experienced therapists. Excellent, Excellent course for the therapist new in NICU!"
"Karin is Excellent, in depth & practical"
"This course was very, very informative and helpful for my real world practice. I look forward to more CIAO courses."
"Loved, loved the second day- lots of useful info. The first day was slow for experienced therapists- maybe move quicker with first material."
"Wonderful course! full of knowledge to truly help these babies eat safely."
"After 39 years of practicing in the field, it is challenging to find courses that offer much new information. Karin provided much new information from beginning to end! Thank you! Excellent!"
"I loved this course and found the presenter engaging and loved her attitude and approach to feeding."
"Awesome course! Love Karin's presentation style, personality and knowledge!"
"This course has given me the skills to be successful in my job and has given me more confidence."
"This will allow me to more confidently assess and treat NICU babies."
"Great class; best NICU course I've ever taken!"
"Karen was very knowledgeable and kept everyone's attention. The course was very enlightening and beneficial in making me aware of the role of OT in NICU's."
"Very informative and applicational, different perspective take on feeding/swallowing. Loved the interactional videos very helpful."
"Excellent/well worth the cost and time. Looking forward to additional courses by this presenter! Lots of info - would be nice if there was more time! More videos would be helpful!"
"This was by far one of the best CEU courses I have been to. Not only did it give me a better understanding of what many of my NICU children have previously experienced but also how NICU SLPs do to support the babies and families which in turn helps me understand where they are coming from when they get to me after NICU discharge. Such an empowering course!!"
"This was a fantastic course with many valuable ideas supported by research."
"Great course and very informative of treatment and assessment skills for transitioning home. Always enjoy Karin and Kathy."
"Loved this course! So much great info! Thank you!!"
"Wonderful course. Karin and Kathy were great. Cindy thank you for everything! This was my first CIAO course and I can not wait for another one. Great organization!"
"Karin is a fantastic presenter! Her knowledge is extensive & her style is professional yet warm."
"Love x 1,000,000. Best NICU course I have been to that provides a strong foundation for the new or expert NICU clinician. "
"Karin was very knowledgeable & articulate during the entire workshop. Wonderful presenter!!"
"I loved the videos and examples of equipment. Did a great job at providing a foundation and explaining in depth."
"Hands down best course I've been to!! The course provided the most important part , the foundation! I can't wait to see my babies on Monday!"
"Great course! Loved the combination of OT and SLP input to the learning process."
"Awesome examples & overall organization of information presentation."
"Very enlightening. Should be a must course (required) for beginning feeding therapists."


text:
Q: We have two list need to filter second list compare with first list using spark scala List1 = (" data center best practice design","essentials advantage","technical and business solution")
List2 = ("data center best","essentials","data","data center","capture","mssp umbrella")

output using Spark-scala:
List_output = ("data center best","essentials","data","data center")

A: You can use the following.
val list_output = parentList filter (childList.toSet)

A: val List_output = List2.filter( p => List1.exists(e => e.matches(s"$p .*")))

redpajama_set_name: RedPajamaStackExchange


text:
Armstrong Confession Could Be Coming
Former champion considering doping admission, say close sources
By afp/bicycling.com
Lance Armstrong before Stage 17 of the 2010 Tour de France. (James Startt)
New York, Jan 4, 2013 (AFP) - Lance Armstrong may confess to using performance-enhancing drugs, reports the New York Times.
In an effort to restore his credibility, reestablish Livestrong's reputation, and become a competitive athlete again, Armstrong has told associates and anti-doping officials he is considering admitting publicly he used blood transfusions and banned drugs, the newspaper reported.
The Times did not name its sources but cited "several people with direct knowledge of the situation." The International Cycling Union (UCI) late last year effectively erased Armstrong from the cycling history books when it decided not to appeal sanctions imposed on the American by the United States Anti-Doping Agency (USADA).
A damning report by USADA concluded that Armstrong helped orchestrate the most sophisticated doping program in the history of sport. The report included hundreds of pages of eyewitness testimony, emails, financial records, and laboratory analysis of blood samples. Armstrong has vehemently denied ever having doped.
Tim Herman, a lawyer for Armstrong, told the Times he was not aware of any admission plans. "I do not know about that. I suppose anything is possible, for sure. Right now, that's really not on the table," Herman was quoted as saying.
Read more at the New York Times: In Reversal, Armstrong Is Said To Weigh Admitting Doping
Armstrong Sued
Armstrong Asks for Fair Treatment
Lance Apology
Watch The Armstrong Lie


Jalel Sager (MA'11), Austin Cappon (ERG minor) and Jonathon Lee of Renewable and Adaptive Energy (CAL-RAE) will pilot their solar microgrid design, bringing low-carbon, round-the-clock power to 15-20 entrepreneurs and families on Kitobo, a fishing island in Lake Victoria.
Read more at Oakland North here.
Also published in the UC Berkeley News Center and on ABC News here and here.
Read about their crowdfunding efforts here.


Op-ed; Labour party members have been under tight scrutiny from the upper echelons of the party since Jeremy Corbyn was elected party leader. Supported by some of its own MPs creating division has appeared at times to be the order of the day.
But now with a general election looking likely to be scheduled for June 8 is the time for unity.
However it is hard to ignore and fail to respond to one bitter self-serving Labour MP John Woodcock.
Mr Woodcock is no stranger to acting the petulant child. He may or may not serve his constituents well but he is now failing the party, its members and its voters around the UK.
As the election was called Mr Woodcock put in place what looks like an existing plan to undermine the party, its leader Jeremy Corbyn and us all.
He has acted like the very worst kind of MP a self-servative usually a term reserved for a Conservative MP.
Calling Mr Woodcock what he has now shown himself to be, a traitor, could result in the expulsion or suspension of a party member but how else can this Yorkshire woman call a spade a spade?
In politics timing is everything and Mr Woodcock timed his work for the government to perfection. The problem is he is not a Tory MP or is he?
Woodcock could yet "cross the floor" and join the Tory party or opt to stand as an independent. The footage and its wide-scale reporting in right-wing sections of the mainstream media includes a veiled threat.
Well John if you are about to quit or switch to your true political party or whatever please get on with it.
People around the country need real political change. They have more to worry about than an MP with an over-inflated ego playing politics so close to a snap election.
Labour Party supporters and voters want real change and the party's main pledges will be a great start. If you cannot see that how can you call yourself Labour?
In the final analysis "Hiding behind working for his constituents Mr Woodcock is giving the Tories a helping hand."
To quote another Bitterite or was it David Cameron "for god's sake man go now."
Op-ed: According to political pundits Shadow Chancellor John McDonnell wrote the Labour briefing piece reproduced on our website a week before it was published.
He has since retracted the article.
It transpires it was written ahead of the two by-elections and on the back of tired old wealthy Labour Party grandees spouting divisive drivel and receiving a great deal of mainstream media air time.
The timing of publishing the Labour Briefing piece was not good but many party members will know there is at least a ring of truth to it.
Watching the BBC Daily politics Monday it was same trash different day as Jeremy Corbyn's Labour Party was put under the spotlight and trashed.
Mr McDonnell is being portrayed as creating division when Corbyn has asked for unity due to the timing of the Labour Briefing post.
But ahead of the by-elections we had Tony Blair asking people to rise up, Lord Peter Mandelson saying he is working every day to undermine Corbyn and old Bitterite spin doctors John McTernan and Alastair Campbell stirring the pot.
They received positive media attention yet Mr McDonnell has one article published and all hell is let loose.
Methinks they protesteth a little too much.
There have been enemies within the Labour Party working against Corbyn, the party, the membership and the electorate for some time.
That is not fake news but fact.
After all fat cat Mandelson put himself on record as an enemy within.
Is there any wonder Mr McDonnell felt it was time to vent his frustration in an article?
Perhaps he was taking a leaf out of so-called Bitterites books?