⒈ Theme Of Power Imbalance In Of Mice And Men

Thursday, August 26, 2021 2:05:35 AM

Theme Of Power Imbalance In Of Mice And Men



The first period occurs between Theme Of Power Imbalance In Of Mice And Men and 6 weeks of the gestation. That is how you build the fire. It is commendable for the wealthy to help in Theme Of Power Imbalance In Of Mice And Men preparations for the wedding feast based on the hadith narrated by Anas about the Prophet's marriage to Rhus tox for chicken pox "Then, when we were on the road, Umm Sulaim prepared her Safiya for him the Prophet and brought her to him Theme Of Power Imbalance In Of Mice And Men night, and so the the Prophet awoke the next Theme Of Power Imbalance In Of Mice And Men a new bridgegroom. The Prophet was asked about this, and Allaah revealed the Theme Of Power Imbalance In Of Mice And Men. Averting said paradox is the entire reason that Claude gets involved in the plot, and part Theme Of Power Imbalance In Of Mice And Men the reason why the villainous Prototypes Theme Of Power Imbalance In Of Mice And Men trying to unify humanity under their rule is to get them ready to fight Theme Of Power Imbalance In Of Mice And Men Ebon Fleet. Households that cannot hire additional Theme Of Power Imbalance In Of Mice And Men for domestic duties limit the hours women Phaedra And Medea Essay able to work outside their homes—having to do both outside and inside labor results in the uncompensated "second shift", expanding the gap.

How Does John Steinbeck Present The Theme Of Lonelines In Of Mice and Men?

Waking this energy up again and filling your whole body with it can reverse the aging process, it can make you younger! I am really grateful to Shakti, because she has brought a certain playfulness back into my work. I had become very serious about my practice. DAN: I have discovered that any technique can have a hypnotic effect. However, if the technique becomes more important than the one who practices it, then that is not so good.

My basic practice is to simply bring awareness to my breath as often as possible and in as many situations and activities as possible. The two techniques are watching the breath and playing with the breath. There are a few basic or core techniques that everyone can benefit form, and so I teach and practice those. I encourage people to explore the basics, to build on those core techniques, and to do so in their own way. They are buying into a philosophy. They have been taught to deny their sacred nature. They are living out of a spiritual ego. This ego lives in sinners and saints, monks and murderers.

It takes over and runs them. It hides in those monks who suppress and deny their natural feelings and desires. He has been sitting on the mountain for 30 years, meditating. He has been celibate for 30 years, drinking no wine, eating no meat. Then his teacher looks at him and decides he is ready to wake up. So he sends a dakini to the student. A dakini is a woman like me who teaches the sacred sexual practices of tantra. So the dakini goes to the monk, seduces the monk.

The monk cannot resist her, he makes love to her. The monk as he makes love to her, his spiritual ego has such a big shock, and this last powerful but very subtle ego is shattered. She will seduce him into breaking all his spiritual rules. If still the shock has not been big enough to break his ego, then she will start to teach him the sexual practices of Tantra. She will teach him how to wake up his sexual energy, how to take it up his body, how to wake up every cell in his body. She will teach him how to let his heart have an orgasm, so that his heart is blown open to the whole world. She will teach him how to let his sexual energy explode through his crown chakra, so that he can feel that he is at one with everything. When your orgasmic energy goes through the crown of your head, you will know unmistakably that you are one with everything and everyone, that there is no separation.

The beloved is everywhere. Things are accelerating on the planet, they are intensifying. Something is happening. You could pass a Buddha on the street and not know it. You could sit on the side of a Buddha on the metro and not know it. You could live next door to a Buddha and not know it. And if you are not careful, you could be a Buddha and not know it! Time does not enter into the process of awakening. Time is not a factor. The ancient monks had the right idea. They pulled themselves out of the world because no one around them wanted to wake up. They put themselves in a place where everyone around them wanted to wake up, and so it was easier. But then they practiced these rituals and then they developed an identity linked to these rituals, and so their practice at some point became the obstacle to the very thing they wanted to achieve.

And this is true of everything. Something that is meant to help us can actually get in the way. And something that the priests and politicians say is bad and will hurt us can actually set us free. If you are ready, whatever you do will work. The next book you read, the next teacher you meet, the next technique you practice, will bring your liberation. It has nothing to do with the book, the technique or the teacher. Well, it has something to do with that. But the real thing, the thing that matters most, is your readiness. One breath is enough if you are truly, genuinely, and totally ready. You breathe ten to twenty thousand breaths per day.

How many of those breaths do you use? How many do you take advantage of? How many do you put toward your liberation? Become conscious of your breath right now. Feel it, watch it, listen to it. Be with it moment to moment, totally. Disappear into that moment when the in-breath and the-out breath touch, when they come together. Becoming free might be a lot easier than we have been led to believe. More and more people are waking up. The vibrations on this planet, the energy of the planet itself is getting higher, and this is lifting people up. And the energies in people are getting higher, and this raises the vibrations of the planet. Everything is coming together, creating a great acceleration. For many thousands of years we walked around with clubs—cavemen with big sticks.

We killed animals with big sticks and we ate the meat. Everything was about survival. Then we discovered each other… that if we do things together, we are safer. We learned that we could plant seeds and grow our own fields. Men thought that women were divine. They sensed that God, the Source, was a woman because women gave birth. Men did not realize that they had anything to do with it. So in those years, God was seen as being a woman. Men would pay to have sex with the priestess in the temple, because they understood that through entering the priestess they could have direct access to the Goddess.

But then the world changed. About five thousand years ago was the beginning of patriarchy. That was the time men took over, and they made a new story. The symbol of the Goddess which was the snake became the symbol of the Devil. They say that Eve ate the apple, and because she bit the apple, everyone got thrown out of the Garden of Eden. We created a split between the sacred and the sexual form.

Either you are a virgin or you are a whore. A split we still struggle with that today. The world has lost the beauty and the power of the feminine. It is time for woman to reclaim their beauty and their sacredness. It is time for us to accept again that our sexuality is a gateway to the divine. I know that men want to love and worship the feminine… that men want to love and adore women. They are waiting for women… for us to be willing to accept ourselves, and to celebrate our own sexuality. When a man enters a woman and she deeply opens to her own divinity, she can take him into the deepest mystery.

And that is what all men are waiting for. So that the time we are living in now, is a time when the masculine and the feminine have to marry inside of us. It is the time of deep merging of the masculine and the feminine. It is the age of the waking up of the heart. Patriarchy is over, the old structures are not working any more. We have to live in the way of the heart, and to get there we have to connect with our desire and our devotion to the divine, that lives in all of us. I have worked with many women who are menopausal. Many of those women have lived most of their sexual lives suppressed.

In fact for many women, the only sex they have ever had has been to please a man, doing what the man needs. Many women have not discovered the real pleasure of sex. Many women are not in touch with their own bodies. So in my work, I teach women how to connect with their pleasure again. Just through the breath, just through relaxing, just from starting to feel from the inside out. And I see women who are menopausal or older becoming orgasmic. Even without touching themselves, even without touching anybody else.

They become exquisitely beautiful because they are opening to their own energy. DAN: This Buddha nature we are talking about is within us. Everyone is carrying it. When we begin to recognize our own Buddha nature, we begin to notice it in other people. You can look at the surface and see your reflection or you can look through and see the fish swimming underneath by adjusting your focus. So something happens in us. You are looking at the ugliness, the pain and suffering of the world, and then suddenly something happens, suddenly… this amazing beauty is right there, right here.

Or you are looking inside at your own confusion, and your problems and your emotions and your negative thoughts. And then suddenly the real nature of those things is seen, something happens. If you try and strain to make it happen it gets further away. So it is interesting. We have this paradox. We have this yearning, this longing to wake up. It makes us look and seek and try and work. They are right here! So there is something about opening up and simply letting go. We can use the breath to do that, we can use each other to do that. And we can use this beautiful play of male and female energies to do that, and in the process of playing something happens. DAN: You combine breathing with thought, sound, visualization, movement.

You can develop a conscious relationship to the basic elements of life: earth, air, water, fire, space. You use the breath to embody the essence of those elements. We play with a couple of basic things. You know the philosophy, the stories. We are in a bookstore here, surrounded by answers. But how do you translate information into a real, actual experience. Every system offers a different approach. For every idea or method there is an opposite idea or method. So if we draw from our own nature, if we take from what we are naturally given to enjoy, and begin to work with that, things become simple….

For example, a simple sigh of relief. When you let go of the breath, you can let go of many other things. And when you pull in air, you not only pull in air, you pull in energy. Every breath can be a prayer; every breath is a blessing. When you let go of the breath, you can let go of whatever is holding you back. If you practice letting go of the breath, you develop the ability to let go of many other things. And if you can let go completely, just for a moment, then everything opens up to us. If you learn to let go of the breath quickly and completely, then you can build on that skill. There is tremendous organic pleasure in a sigh of relief.

If you focus on it, you can generate joy. Is it possible to be in pain and breathe like this? Have you ever seen anyone who is in pain breathe like this? Can you be afraid, can you be frozen in fear and breathe like this? Notice that whenever you are in pain and the pain goes away, you breathe like that… something happens to the breath. When you move from one state to another state, from pain to no pain, that breath happens by itself. The same thing happens when you are afraid and then the fear goes away: that breath happens. That breathing response is hard-wired into us. If you practice that breath consciously, you prompt the system to moving from one state to another. And the fact is you now have pain. And you carry fear.

And so what we have discovered is, if you make this breath a habit of your system; expanding, opening, letting go, relaxing. If we make it a habit of our system, so that it happens automatically, something amazing happens. It has to be automatic. It has to just flow from you unconsciously. Then you make real music! So in the beginning you practice certain things, you develop the skill. With deep practice it becomes second nature, an unconscious ability. Then real music happens! So it is with this sigh of relief, this coming home breath. Do the math. We have been practicing math at my seminars.

How many conscious breaths is that? You must be avoiding it! Focus on your heart as you open and expand and let go. You could not have practiced it. You can only walk a path so many times before the path becomes a big wide highway. Soon, the heart connection is open all the time. And it hurts to close it, so you have no interest in closing it. Just the opposite: more and more, every breath becomes orgasmic! But you actually have to do it. Just read another book.

Put more information in your head. Satisfy your mind. The element of fire is interesting, because you can use the element of fire to wake up. You can use the heart fire of sexual energy to wake up your sexual identity. Breathe like this:. Encouraging people to make pleasurable sounds on the exhale, breathing out thru the mouth. Breathing in thru the nose… hold your breath… Do you feel the heat? Let go. Feel the warmth. No wonder making love feels so good!

It is too exciting. It is too stimulating- the man gets too hot. His sexual energy gets too hot. He gets too excited, so he ejaculates. Now the woman has just started making love because we can go for a long time so we get frustrated. We start thinking sex is not about our pleasure. But it is possible for the man to learn how to ride the wave of his sexual energy. In the beginning you can build up the heat, but when the man gets very aroused he has to notice before it is too late, and slow down, hold the beloved closer, and breathe deeply. He can still be in penetration, but now we are going into the deep rhythm of the body. We are letting the heat ripple through the whole body.

Have you noticed that they are often portrayed as blue? I think it is because they understand the secret of sex. I think it is because those gods understand the secret of sex. Every part of your body gets set alive. It gets set on fire. But it is a cool fire. It is a fire that can go on and on. If you have a lot of wood and you make a big bonfire, you light the match, you light the fire, you burn up all the wood. How long do people make love? But another way is to build a small fire, to build up the heat slowly. When it gets too hot, you slow down. You add one log at a time. You go deeper, you go slower. You recycle the breath with your partner.

You let the fire spread through your whole body. You feel it rippling through your skin. That is how you build the fire. When the man is ready, you can build a hot fire again, then you can go fast again, then when it gets too hot you slow down, you ride the wave. The first time I experienced this was with my teacher, the orgasm went on for the whole weekend. Then it only stopped because I had to go home. So in Tantra, the only question we ask is how much bliss can you stand? Can you cope with more pleasure, or do you have to throw it off by having an ejaculation? Can you open to more pleasure? Can you keep building the bliss? DAN: You see, at some point the body cannot tell the difference between intense pain and intense pleasure.

All the body knows is that it is too intense. So when you approach your limit to pleasure, your system reacts the same way as it does to pain. The muscles get tense, you hold your breath, and you try to escape and withdraw from the intensity. So you have to train your body to relax into intensity. Pain is not the problem. Everybody is very good at tolerating pain. And I think the Russians hold the world record! No doubt! So pleasure is the real problem. You can watch your body react as you approach ecstasy. You have no personal desire, but the desire of existence moves through you.

So if it is meant to be that you will have children, you will. DAN: And when you are free, you do things consciously, not because it is an unconscious program. I know two awakened people who recently had a child, Ivonne and Toby. They had a child. And he chose them. There is too much control, so I teach breathing through the mouth- especially good for women- relaxing. DAN: Do what feels good, then practice the opposite until it also feels good. Breathe the energy of the moment. When you see or hear or feel something, breathe it in, connect to the energy of it with the breath. SHAKTI: The master of the practices would go into deep meditation and the energy of the practice would run through his body.

Students would write down what they see, then they would make calculations and draw diagrams. They would develop a system based upon what they saw happening in the master. Then it became all about the system. They forgot that the master did it naturally. All you have to do is get everything out of the way of the natural. It is natural for your body to want to wake up. It is natural for your body to be orgasmic. All you have to do is get out of the way, let your ego get out of the way.

Be with people who experience this. By spending time with us you have the chance to experience this in your own body. When erect the male penis can be inserted into the vagina of the female as shown here. The vagina easily expands to accommodate any size penis. During this most intimate act the penis is moved in and out of the vagina until orgasm and ejaculation occur. It is desirable, when one goes into his wife on his wedding night, to show her kindness, such as presenting her with something to drink, etc. This is found in the hadith narrated by Asmaa' bint Yazid ibn As-Sakan who said: "I beautified 'As'ishah for Allaah's Messenger, then called him to come to see her unveiled.

He came, sat next to her, and brought a large cup of milk from which he drank. Then, he offered it to 'Aa'ishah, but she lowered her head and felt shy. I scolded her and said to her: "Take from the hand of the Prophet. Then, the Prophet said to her, "Give some to your companion. I sat down and put it on my kness. Then, I began rotating it and following it with my lips in order that I might hit the spot from which the Prophet had drunk. Then, the Prophet said about some women who were there with me: "Give them some. The Prophet said: "Do not combine hunger and fibbing! Ahmad reports it with 2 isnaads - one of which supports the other, and it is supported The husband should, at the time of consummating the marriage with his wife or before that, place his hand on the front part of her head, mention the name of Allah Most High, and pray for Allah's blessings.

As in the statement of the Prophet: "When any of you marries a woman It is desirable for the husband and wife to pray 2 rakaat together on their wedding night. This has been narrated from the earliest generation of Muslims, as in the following 2 narrations:. When the prayer was called, Abu Dharr began to step forward when the others said to him: 'No! They taught me, saying: 'When your wife comes to you, pray 2 rakaat. Then, ask Allaah for the good of that which has come to you, and seek refuge in Him from its evil. Then it is up to you and it is up to your wife.

Second: On the authority of Shaqeeq who said: "A man named Abu Hareez came and said: 'I have married a young girl, and I am afraid that she will despise me. So, when your wife comes to you, tell her to pray behind you 2 rakaat. O Allaah join us together as long as You join us in good, and split us apart if You send to us that which is better. About this, the Prophet said: "After that, if Allah decrees that they will have a child, the devil will never be able to harm that child". It is allowed for a Muslim man to enter his wife in her vagina from any direction he wishes - from behind or from the front. About this Allaah revealed the following verse:. On the authority of Jaabir who said: "The Jews used to say that if a man entered his wife in the vagina but from behind, their child would be cross-eyed!

Then Allaah revealed the verse: "Your wives are as a tilth unto you; so approach your tilth when or how ye will;" [al-Baqarah ]. The Prophet said : "From the front or the back, as long as it is in the vagina". On the authority of Ibn 'Abbaas who said: "The Ansaar, who had been polytheists, lived with the Jews, who were people of the book. The former viewed the latter as being superior to them in knowledge, and used to follow their example in many things. The people of the book would only make love to their wives from the side, this being the most modest way for the woman, and the Ansaar had followed their example in that. These people from the Quraish, on the other hand, used to expose their women in an uncomely manner.

They took pleasure in them from the front, from the back, or laid out flat. When the Makkans came to al-Madeenah at the time of the Hijrah, one of them married a woman from among the Ansaar, and began doing that with her. She disapproved of it and told him: "We used only to be approached from the side, so do that or stay away from me! So Allaah, revealed the verse: "Your wives are as a tilth unto you, so approach your tilth when or how ye will;" [al-Baqarah ] ie. What is meant here is the entry which produces children. It is forbidden for a Muslim man to enter his wife in her anus.

This is understood from the verse quoted above i. There are also other hadith on the subject, among them:. The women of the Muhajireen used to lie on their faces during intercourse , while the women of the Ansaar never did it that way. Then, one of the men of the Muhajireen wanted his wife to do that. She refused until such time as she could ask the Prophet about it. She went to the Prophet but was embarassed to ask the question, adn so Umm Salama asked him. Then the verse was revealed which says: "Your wives are as a tilth unto you; so approach your tilth when or how ye will;" [al-Baqarah ]. The Prophet gave him no answer and when the revelation came and the verse was revealed which says: "Your wives are as a tilth unto you; so approach your tilth when or how ye will;" [al-Baqarah ] and the Prophet said: "From the front and from the back, just beware of her anus and her menses".

In which of the 2 openings did you mean? If what you meant was from her rear and in her vagina, then yes. But if what you meant was from her rear and in her anus, then no. Verily Allaah is not ashamed of the truth - do not enter your wives in their anuses! Fourth: "Allaah does not look at one who comes to his wife in her anus". Fifth: "Cursed are those who come to their wives in their anuses. Sixth: "Whoever has sexual intercourse with a mentruating woman, or a woman in her anus, or approaches a soothsayer and believes what he is told has disbelieved in that which was revealed to Muhammad. When a Muslim man has had sexual intercourse with his wife in the legal manner and then wishes to return another time, he should first perform wudhuu', based on the statement of the Prophet : "When one of you comes to his wife and then wishes to return another time, let him perform wudhuu' between the 2 times In another version, the same wudhuu' which he performs for prayer for verily, it will invigorate his return.

Bathing, however, is preferable to merely making wudhuu' in such situations. Abu Raafi' narrates: "That the Prophet made the rounds of all his wives one night, bathing in the house of each one. The Prophet answered : "This way is purer, cleaner and better". It is permissible for the husband and wife to bath together in the same place even though he sees her private parts, and she sees his. This is established by a number of authentic hadith, among them:. On the authority of 'Aa'ishah radiallahu anha who said: "I used to bathe with the Prophet from a single container of water which was placed between us such that our hands collided inside it.

It is best for husband and wife not to sleep after having sex until they first perform wudhuu'. There are various hadith about this, among them:. First: On the authority of 'Aa'shah who said: "Whenever the Prophet wished to sleep or eat while in a state of Janaba i. In another version: "Perform wudhuu' and wash your private parts, and then sleep. And, in another version: "Yes, you can perform wudhuu', sleep, and bathe whenever you want. And, in still another version: "Yes, and perform wudhuu' if you wish. Third: On the authority of 'Ammaar ibn Yaasir, the Prophet said: "There are three which the angels will never approach: The corpse of a disbeliever; a man who wears perfume of women; and, one who has had sex until he performs wudhuu'.

This wudhuu' is not obligatory, but is very highly and definitely commendable. This i. This is also supported by other hadith, among them a hadith narrated by 'Aa'ishah who said: "The Prophet used to sleep in a state of janaba without having touched water, until he would get up later and bathe. In another version narrated by 'Aa'ishah , she said: ""He used to spend the night in a state of janaba until Bilal came in the morning to make the adhaan.

Then, he would get up, bathe while I looked at the water dripping from his head, and go out. Then, I would hear his voice in the Fajr prayer. Then, he would remain fasting. It is also permissible to make Tayammum sometimes instead of wudhuu' before sleeping. This is based on a hadith of 'Aa'ishah in which she said: "When the Prophet was in a state of janaba and wished to sleep, he used to make wudhuu' or Tayammum. Did he bathe before sleeping or sleep before bathing? Sometimes he bathe and then slept. And sometimes he performed wudhuu' and then slept. It is forbidden for a Muslim man to have sexual intercourse with his wife when she is menstruating. This is clear in the following verse of the Qur'an:. First: "Whoever has sexual intercourse with a menstruating woman, or a woman in her anus, or approaches a soothsayer and believes what he is told has disbelieved in that which was revealed to Muhammad.

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All presenters are required to join the session 30 mins before the scheduled start time to enable the Technical Chair to run through the set up with you. Questions will be submitted via a chat function and the session chair will read the questions to you, and then you can answer. Find out what an ePoster is here. The support page for Physiology can be found here. You can also view the ePoster showcase for Future Physiology here. There will be both oral communication competitions and ePoster competitions for Early Career Researchers as part of Physiology More information will be available shortly. Opportunities to take part in Physiology will be available shortly. For all informal enquiries, please email events physoc. Educating our expanding undergraduate student cohorts in whole body physiology is complex, and to do this effectively can sometimes be a challenge.

However, the recent global COVID Pandemic has hit physiology education hard with restrictions on face-to-face on-campus teaching and instructors have had to be more and more imaginative to delivery high quality online teaching. In this presentation, therefore we will explore the challenges of physiology education with a specific focus on practical skills and human physiology looking back at our traditional approach, how we responded to the COVID-Pandemic and the ways we might be educating our students in the socially distanced future within our Institutions. This symposium talk aims to give an overview of the role played by the cardiac sodium channel in the decline in function of the heart as it begins to fail. The following summary will provide some background for the talk.

In adapting to disease and loss of tissue the heart shows great phenotypic plasticity that involves changes to its structure, composition and electrophysiology. In parallel, global cardiovascular adaptations occur involving stimulation of the sympathetic nervous system, release of natriuretic peptides and activation of the renin-angiotensin-aldosterone pathway. These adaptations provide compensation for the initial decline in cardiac function but, for reasons not understood, do not provide continued benefit in the longer term. Heart failure is a chronic and progressive condition with very poor prognosis.

There is a reduction in T-tubule density in myocytes from failing hearts leading to an increased spatial separation of the junctional SR from the T-tubule membrane. It is likely that these structural and electrophysiological responses occur at the expense of 1 increasing the likelihood of arrhythmogenesis, 2 activating hypertrophic and apoptotic signalling pathways and 3 decreasing the efficiency of EC coupling. The cardiac sodium channel plays an important role in the passage of the heart from function to dysfunction. The cardiac sodium channel Nav1. Mutations in SCN5A are associated with a myriad of clinical syndromes, including Brugada syndrome, Long QT syndrome type 3, cardiac conduction disease, and overlap syndromes.

Yet, some Nav1. An emerging concept that may explain the large disease spectrum associated with SCN5A mutations centres around the diversity, complexity and multifunctionality of the Nav1. For instance, alterations in Nav1. In addition, subcellular pools of Nav1. The trafficking pathways through which sodium channels reach their various subcellular destinations within the cardiomyocyte are now coming into focus. This lecture will address these recent insights and discuss the potential implications for the development of novel therapeutic strategies. The cardiac sodium channel, Nav1. We have utilized a combination of electrophysiological, biochemical and cell-biological techniques to evaluate the functional behaviour of the Nav1.

One mutation is a novel in-frame threonine deletion within the extracellular Ig domain recently identified in a BrS patient in the absence of any other causative mutations. Yet this mutation did not abolish the Nav1. Our work highlights multiple structural and functional interactions between Nav1. Future experiments will investigate the stoichiometry of these interactions and how mutations affect the oligomeric structures. Voltage-gated sodium channels enable the translocation of sodium ions across cell membranes and play crucial roles in electrical signalling by initiating the action potential.

In humans, sodium channel mutations give rise to a number of cardiovascular diseases, hence they are important targets for pharmaceutical drugs. The NavMs channel has been shown to be a good model for human channels, based on its high levels of sequence, structural and functional similarities to the human Nav1. Complexes of NavMs have been studied using crystallography, cryo-electron microscopy, and biophysical techniques including circular dichroism spectroscopy, bioinformatics, and molecular dynamics calculations, enabling idenfication of binding sites, molecular interactions, and the functional effects of both on-target and off-target drugs which bind to sodium channels.

These studies can provide crucial infomation for the development of new pharmaceuticals and for the understanding of side-effects of currently-prescribed drugs. Menstrual function can be affected in female athletes with high training loads, ultimately resulting in functional hypothalamic amenorrhea. Can athletes overcome the effect of high training loads while maintaining a busy training and competitive schedule? Since early reports of high prevalence of amenorrhea in athletes in the s, decades of research support the idea that it is not training load per se that induces menstrual dysfunction.

To recover from the chronic effects of the energetic stress induced by low energy availability, it is theorised that athletes have to decrease training load, increase energy intake or both. However, due to the nature of competitive sports, elite athletes are often reluctant to decrease their training load so as to maintain a competitive advantage. Also, because access to elite athletes is very limited to researchers, there are no strictly controlled laboratory-based studies in elite population looking at recovery from low energy availability.

While decades of research have helped developing an understanding of the aetiology of menstrual disturbances in athletes, there is limited research on how to best recover from this condition and a definite answer to this question remains elusive. This invited talk will provide an overview of this topic and present evidence from a recent case study documenting recovery of menses of an amenorrheic elite road cyclist during a 5-year follow up after an episode of significant weight gain, while maintaining —and increasing— a high training load, physical capacity, and remaining competitive at an international level. Data on eumenorrheic females is scarce and is often low to moderate quality, which is due to a number of reasons: i there is a shortage of specialist knowledge on female physiology, in particular endocrinology, in the sport and exercise science community; ii until recently, there has been a reluctance to include female participants in research studies, due to the numerous adaptations, to experimental design, needed to incorporate female specific considerations, such as the menstrual cycle; iii there is no consensus on the terminology and methodological approaches needed to produce high-quality studies.

These issues have undoubtedly slowed the pursuit of knowledge in this field of research. The purpose of this talk is to detail the specific considerations needed when employing eumenorrheic women as participants in sport and exercise science-based research Elliott-Sale et al. These considerations relate to participant selection criteria and adaptations for experimental design. This talk is intended to promote more high-quality research in eumenorrheic females. In recent decades, several research groups have stressed this weakness and called for a better consideration of women and of their hormonal specificities Elliott-sale et al.

Specifically, many adult women of childbearing age use hormonal agents that support menstrual regularity and provide birth control, with oral contraceptives OC being one of the most popular form. Due to their specific nature and concentrations, synthetic ovarian hormones contained in OC could influence physiological responses during exercise. Substrate metabolism during endurance exercise is a key factor of health management but also of sport performance. Carbohydrates and fat are the two major fuels used by muscles for energy production during endurance exercise, and it is acknowledged that substrate partitioning depends on several inter- and intra-individual factors, including exercise intensity and duration, body composition, training and nutritional status, physical activity level and sex.

In addition, due to their specific characteristics, the exogeneous hormones contained in OC are likely to influence substrate metabolism during exercise in women. By analysing the available literature, we will try here to discuss the effect of OC use on substrate metabolism during endurance exercise. Several studies conducted among women using different types of OC showed that substrate oxidation during moderate prolonged exercise was similar to what is observed in non-OC users Bonen et al. Interestingly, some studies specifically reported increased lipolysis or decreased glucose flux without any change in substrate oxidation rates during endurance exercise in women using OC Casazza et al. In addition, we previously reported that although OC use increases lipid mobilization, this effect was blunted by the lipolytic activity that occurs during endurance exercise Isacco et al.

Results on the effect of synthetic ovarian hormones contained in OC on substrate metabolism during endurance exercise remain however unclear to date. While there are important heath and performance implications regarding the use of OC among women, further studies are today needed to better understand this increased lipolytic activity without any substantial or detectable effect on substrate use during endurance exercise in OC users. The fluctuating oestrogen and progesterone concentrations across the menstrual cycle in eumenorrhoeic women can alter substrate utilisation during exercise.

Menstrual phase comparative studies in the late s to early s employed stable-isotopic tracers to study carbohydrate, fat and protein metabolism during exercise and provide the grounding for our current knowledge in the field. More recently, the complexed molecular signalling pathways of oestrogen and progesterone are being uncovered and lends clearer understanding to explain mechanisms and potential magnitude of menstrual phase effect on energy metabolism during exercise. Multiple pathways of genomic and rapid non-genomic effects are described that vary by receptor isoform and tissue, thus explaining menstrual phase-specific differences in hepatic glucose production, whole body glucose uptake, tissue specific lipid storage and fat oxidation, and protein turnover during exercise with added implications during fasted or carbohydrate-restricted training.

For example, oestrogen suppresses, while progesterone either suppresses in euglycaemic, insulin responsive state or enhances in glucose-deficient state hepatic gluconeogenesis. Instead, oestrogen enhances long change fatty acid uptake and oxidation in skeletal muscle and directs lipid availability away from adipose and toward skeletal muscle while progesterone may partially antagonise some of these effects explaining frequently reported increases in fat oxidation during exercise in late follicular or mid-luteal menstrual phases when oestrogen concentration is elevated.

Furthermore, the chemical structure and properties of oestrogen affords cellular protection against the side-effects of metabolic flux by promoting plasma membrane stability, curbing free radical or lipid peroxidative damage and consequently modulating post-exercise inflammatory and exercise-induced damage responses or recovery time that is therefore menstrual phase specific. Thorough consideration of the current trends produces a sensible pattern of effect between menstrual phases that has practical application for future research design aiming to include eumenorrhoeic women and for athletes to optimise training or performance during racing. The lipid scramblase TMEM16F catalyses the exposure of phosphatidylserine in platelets to initiate blood coagulation.

We have combined cryo-EM with patch-clamp electrophysiology and liposomal assays to characterize the dual function of TMEM16F as a lipid scramblase and an ion channel. Cryo-EM analyses of the protein in the absence and presence of calcium reveal rearrangements induced by ligand binding. Functional characterization shows that both processes are activated by the same mechanism, but appear to be catalysed by distinct protein conformations. This strategy is based on data obtained in studies performed almost exclusively in vitro, or under non-inflammatory conditions in vivo.

This should then lead to reduced airway mucus plugging and improved mucociliary clearance. However, in healthy lungs of human and mouse, TMEM16A is only weakly expressed, while in airways of patients with asthma and cystic fibrosis CF , and in lungs of asthmatic mice, TMEM16A is upregulated particularly in glands and airway smooth muscle cells. Niclosamide, an inhibitor of TMEM16A, blocked mucus production and mucus secretion in mice in vivo and in vitro. Both Eact and brevenal induced acute airway contraction. Treatment of airway epithelial cells with niclosamide strongly inhibited expression of the central transcription factor for Th2 inflammation and goblet cell differentiation, SAM-pointed domain—containing ETS-like factor SPDEF.

All animal experiments were approved by the local Ethics Committee and were conducted according to the guidelines of the American Physiologic Society and the German Law for the Welfare of Animals. We examined the presence of calcium-activated chloride channels in taste cells of mouse vallate papillae. Type II and type III cells express taste receptors and respond to tastants, while type I cells mainly have glial-like functions. The three cell types can be identified by the expression of specific proteins and by their electrophysiological fingerprint. By using whole-cell patch-clamp recordings in isolated cells from taste buds, we measured large currents activated by 1. Ion substitution experiments indicated that the current was mainly carried by anions.

ANO1 is expressed in sensory neurons and involved in the process of detecting and relaying signals that arise after painful noxious stimulation. This was also confirmed using superresolution stochastic optical reconstruction microscopy STORM which revealed that all 3 proteins were indeed found in close proximity. Introduction: The carotid body CB contains specialised O2 sensitive cells located at the carotid bifurcation that monitor the blood PaO2 supplying the brain to initiate corrective cardiovascular respiratory reflexes. O2 sensitivity of the CB is modulated by G-protein-coupled-receptor signalling 1. However, little is known about the single molecule distribution of AT1R in CB type I cells or PC12 cells- a closely associated cell line, which may underpin signalling microdomains.

Furthermore, it is not clear if AT1R membrane expression can be altered by exposure to hypoxia. This study aimed to reveal if membrane AT1R are clustered and if expression is altered by chronic hypoxia. At each time point, cells were fixed and stained with primary antibodies anti-AT1R and anti-tyrosine hydroxylase-TH. Cells were stained with secondary F ab fragment antibodies conjugated with Alexa fluor and Confocal imaging demonstrated that cytosolic TH fluorescence levels were significantly elevated after 12 normoxia Furthermore, AT1R fluorescence was also significantly increased after 12 hours normoxia More experiments are required to validate this finding and quantify specific cluster parameters.

In addition, this data shows that AT1R expression is increased in response to hypoxia along with an elevation in TH and cell area. A key next step will be to assess changes in AT1R expression and clustering specifically in primary CB type I cells as a further move towards the generation of potential novel therapies for cardiorespiratory diseases associated with chronic hypoxia. Cardiac alternans is thought to promote arrhythmia via mechanisms including spatial dispersion of refractoriness resulting in wavebreak, thus promoting re-entry Tse et al. One hypothesis is that at high pacing frequencies, alternation in the preceding diastolic interval DI can drive alternans, and that this is promoted when the slope of the restitution curve of dependence of APD on preceding DI exceeds 1 Goldhaber et al.

The present study investigated the cycle length CL -dependence of APD and mechanical sarcomere shortening alternans in ventricular myocytes isolated from male Dunkin-Hartley guinea pigs. Excised hearts were mounted on a modified Langendorff apparatus and ventricular myocytes isolated as described previously Gao et al. Cells were paced in a steady state fashion by a train of 60 stimuli at constant CL during simultaneous recording of membrane potential and sarcomere length. Each train of stimuli were preceded by 20 stimuli at a CL of 1, ms. Alternans was defined as beat-to-beat alternation between long and short APD90 or large and small changes in sarcomere length. APD90 and mechanical alternans were observed to occur in isolation, as well as simultaneously both in- and out-of-phase.

In summary, the data show all cells demonstrated both APD90 and mechanical alternans. In conclusion, guinea pig ventricular myocytes demonstrate APD and mechanical alternans at a range of CLs, with a greater incidence at shorter CLs, which appears not to be dependent on steep APD90 restitution slope dynamics. Further work is required to understand intracellular processes underlying the generation of alternans. Introduction Microcirculatory homeostasis depends on a highly efficient regulation involving multiple sensors and effectors, both central and peripheral. This allows compensatory response to neuroendocrine output affecting cardiorespiratory performance and systemic vascular resistance and local microcirculatory endothelial and myogenic activity.

In previous studies a Prompt Adaptive Hemodynamic Response PAHR affecting systemic hemodynamics was identified in both lower limbs when acute changes of peripheral microcirculatory perfusion were evoked in only one limb. Methods Twelve healthy adults both sexes Procedures respected all the principles of good clinical practice for human research. Protocols differed only in the challenge phase Phase 2 applied to one test limb TL randomly chosen while the other remained inactive IL. Results and discussion In each individual, a perfusion asymmetry was noted at rest as expected, although not significant.

Both protocols evoked similar responses of BP in the tested limb but also in the contralateral inactive limb. In the IL, values fell by an average of With P2, changes were also detected during Phase 2 during movement also increasing perfusion IL measurements were not possible in TL in Phase 2. Nevertheless, perfusion modifications always occurred in the same direction. The recovery was gradually made during the final 5 min interval, with faster recovery noted in P2. Conclusion These exploratory results confirm that the PAHR firstly described in the lower limb can also be detected in the upper limb.

This confirms the interest for the use of this potential clinical outcome for diagnostic purposes and as a reference for the disease recovery process. The cardiac voltage-gated sodium channel, Nav1. The extracellular turrets of the channel extend over the central pore and play a role in ion selectivity and permeation1. Several germ-line mutations within this region have been implicated in cardiopathologies such as Brugada Syndrome BrS , yet it is unclear how they affect channel gating2,3.

From the recent cryogenic electronic microscopy structure of mammalian Nav1. We employed site-directed mutagenesis to systematically examine this region. We also performed in silico Molecular Dynamic MD simulation modelling to investigate the structural stability of the mutants relative to the wild-type channel. Almost all the generated mutants displayed either reduced or no detectable peak currents. Nevertheless, surface biotinylation demonstrated that all the mutants were expressed on the plasma membrane, therefore ruling out defective trafficking. These included all the natural BrS mutants that have been previously identified in this region. The Nav1. For the mutants that retained some gating activity, only peak currents and steady-state activation parameters were perturbed relative to the wild-type channel Table 1.

Steady state inactivation parameters and recovery from inactivation kinetics were not affected. Taken together, these results suggest that the compromised gating behaviour of the mutants is not caused by large-scale protein misfolding. Rather, the mutations are more likely to introduce relatively subtle structural alterations, that selectively block the channel activation step. MD simulations revealed that the mutations destabilised the channel outer and inner vestibules through which the sodium ions move during channel activation. The mutations were also predicted to perturb the geometry of the DEKA selectivity ring that normally traps and concentrates sodium ions in the boundary between the outer and inner vestibules.

We note that this structural feature is strongly conserved in other Nav channel isoforms and pathological mutations in the same region of Nav1. Thus, our findings provide general insights into a class of pathological mutations occurring not only in Nav1. Introduction: Facial cooling is a simple way to stimulate trigeminal nerve receptors and evoke complex hemodynamic response that includes activation of both parasympathetic and sympathetic nervous system[1]. We ought to investigate a very early response to facial cooling in young heathy adults using pulse wave analysis PWA , that enables to examine hemodynamic changes in aorta during cardiac cycle and its implications affecting systolic function of the heart.

Objectives: To investigate an early hemodynamic response to facial cooling in young, healthy adults. Method: Study was conducted according to bioethical standards and Declaration of Helsinki. After 5 min of rest in supine position, brachial BP was measured and pulse waveform was recorded using applanation tonometry. Then participant was exposed to second facial cooling, which was followed by second pulse waveform recording and brachial BP measurement. There was a significant decrease in cT1, while cT2 increased.

However, there was a statistically significant increase in peripheral DBP.

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