Tags: biosermons

thinking

Фекалии и разумный дизайн

Вопрос задали: "Человеческие фекалии источают сложные запахи. Зачем?"

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Пусть у нас есть органическая жизнь на планете Х. Для нее нужен источник энергии. Какие-то вещества будут этим источником ("еда"), какие-то - конечным продуктом метаболизма ("фекалии"). Извлечение энергии из фекалий возможно, но не для всякого метаболизма. Это м.б. неразумно, т.к. в рамках химического процесса требует больше энергозатрат, чем ее в продукте содержится доступной энергии. Даже если конечным источником еды будет, скажем, свет, его надо превратить в химическую форму, и тогда сразу возникает возможность использовать эту уже готовую форму в виде "еды", что мы, собственно, и делаем.

Как организовать метаболизм? Например так: взять полимер и навешать на него функциональные группы. Такие полимеры можно производить универсальным способом, делать из них структуры, катализаторы и т. п. Групп надо взять на все случаи жизни, прежде всего кислот и оснований. Основания могут быть алифатическими или ароматическими. Берем и те и другие. Как получить последние? Делаем пятиатомное ароматическое кольцо, засовываем туда азот. Больше атомов азота - больше основность и больше способность образовывать связь с ионами металлов. Это хорошо: многие реакции легче катализировать металлоорганическими комплексами, нужны лиганды. Но и плохо: не всегда ведь именно этого надо. Поэтому ароматических оснований нужно как минимум два: сильное и слабое.

Ароматическое основание надо связать с полимером (через кольцо). Такая связь очень прочная, и если ее разбить, можно получить много энергии (из "еды"). Значит, ее надо разбить прежде, чем отправить в "фекалии". С сильным основанием это может выйти себе дороже : свободное основание будет связываться с ионами металлов. Зато более слабое основание можно безнаказанно отщепить. Разбивать ароматические связи дальше - накладное занятие, требует внешний источник энергии.

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Это были общие рассуждения в мире чистого разума. Переведем их в наш подлунный мир. Многофункциональные полимеры мы называем белками. Ароматических оснований действительно два: триптофан (с одним азотом в пятиатомном кольце) и гистидин (имидазол с двумя азотами). Гистидин - лиганд в огромном количестве металлопротеинов (гемоглобин, например), он же используется как переносчик протонов. Чтобы триптофан не был слишком основным (для этого ведь есть гистидин, аргинин, и т. д.) добавлено еще одно ароматическое кольцо, что добавляет гидрофобности. Из этого можно делать десятки разных соединений - или засунуть триптофан в гидрофобные карманы (чтобы были гидрофобные взаимодействия с молекулами) или каталитические центры. Полезная штука.

Индол в триптофане связан с пептидной цепочкой, и разбивание этой связи - отличный источник энергии. У некоторых из анаэробных бактерий в нашем кишечнике есть триптофаназа, которая делает именно это: превращает триптофан в индол + пировиноградную кислоту. Это восстановительное деаминирование; у аэробов же другой способ избавится от триптофана (окислительный). Триптофаназа не работает в окислительной среде, это изобретение анаэробных бактерий.

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Теперь начинается чертовщина.

С химической точки зрения, наше пищеварение - безумие. Мы живем на планете, в атмосфере которой 20% кислорода, мы им дышим. Дышим = используем кислород как окислитель для производства энергии из "еды". Безумие заключается в том, что это окисление происходит у нас в тканях, а вовсе не там, куда "еда" сперва попадает. Попадает же она туда, где условия ровно те, которые существовали миллиарды лет тому назад, когда кислорода на Земле не было. Там царствует анаэробная микробная жизнь, которой мы делегировали пищеварение. Вся наша роль в том, чтобы слегка пощепить белки и всосать то, что легче всего всосать. Остальное делают симбиотические бактерии. Мы делимся с ними "едой", они делятся с нами метаболитами, и на этом основан наш симбиоз. Проблема в том, что анаэробная ферментация очень неэффективна, и для нас от такого симбиоза мало проку. Аэробное пищеварение было бы куда более эффективно. По всем законам, Б-жеским и человеческим, от такого союза давно пора отказаться. Но поди от него откажись...

Почему так вышло? Животные начинались в воде. Кислорода в ней мало, еле хватает на дыхание. Использовать его еще и на пищеварение - расточительно, поневоле приходится использовать анаэробное пищеварение. Но это когда было-то... С тех пор мы уж 300,000,000 лет на суше, где кислорода завались, а пищеварение с тех пор не изменилось. Да и как оно может измениться? Наши симбионты в этом не заинтересованы. Если мы попробуем изменить ситуацию, они нас убьют, так как для них мы просто источник "еды" для анаэробной ферментации, и более никакой ценности не представляем. Мы от них полностью зависим, а они могут себе и другой источник еды найти. Поэтому изменить ситуацию теперь может только чудо. Смысла в таком пищеварении мало, но по историческим причинам избавиться от установленного порядка себе дороже. За радость побегать по травке на солнышке приходится платить сотрудничеством с мафиозной компанией внутри.

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Обратно в царство разума: если бы у нас было аэробное пищеварение, то триптофан бы окислялся в нелетучие соединения, как это и происходит в нашем теле. Но при анаэробном пищеварении это, увы, невозможно: нет источника энергии; остается восстановительное деаминирование с летучим индолом в качестве продукта. Гистидин так метаболизировать ни-ни: кольцо надо разбить, чтоб имидазол не связывался с чем попало. Его превращают имидазолон и расщепляют на глутамат и формамид. Энергии из этого мало, но жизнь дороже. А от индола вреда мало. Можно выкинуть в "фекалии". Анаэробными реакциями из него энергию не извлечь; теперь очередь аэробных бактерий - уже снаружи. Вот, если бы они жили у нас внутри... Но об этом можно только мечтать. Да и кто знает: будут ли те, другие, с нами делиться? С этих разбойников хоть какой-то толк. Черт, которого знаешь, лучше, чем черт, которого не знаешь, ведь так?

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Фекалии пахнут индолом и его производным - скатолом. Анаэробный рэкет, который мы себе навязали миллиард лет тому назад, дурно пахнет - удивительно ли, что его продукт пахнет не лучше?

Затем фекалии пахнут? Чтоб мы помнили об этом и мотали себе на ус. Одного раза, по-моему, достаточно.

thinking

О непротивлении злу (экскременты фагоцитов)

Я знаю, почему Толстой (см. предыдущий пост) так разошелся из-за экскрементов фагоцитов.

На их примере природа учит, как надобно непротивляться злу. Об этом полезно и детишкам послушать, и не только детишкам.

Один из типов фагоцитов - нейтрофилы, которые составляют большинство лейкоцитов крови. Известны крестьянской детворе из-за зеленого цвета соплей (к вопросу, являются ли экскременты фагоцитов эзотерикой). После поглощения бактерии клетка выпускает из гранул в фагосомы меилопероксидазу; энзим содержит гем, который придает ему зеленый цвет. Гем использует перекись водорода для превращения хлора в хлорку и тирозина в феноксильный радикал; ими нейтрофилы морят бактерии. Полагали, что фагоцитоз и выпуск пероксидаз из мертвых нейтрофилов - два способа противления микробному злу. Десять лет назад открыли третий метод. Запрещенная русская википедия описывает эго так:

...В 2004 г. был открыт важный механизм, посредством которого нейтрофилы осуществляют защитные функции, названные нетозом (от англ. NETosis (от NET — Neutrophil Extracellular Trap)). Нетоз является третьим основным типом клеточной смерти нейтрофилов. При нетозе нейтрофил проходит стадии деконденсации хроматина, наработки реактивных форм кислорода (ROS — Reactive Oxigen Species), дегрануляции; затем следует выброс ДНК-сети, связанной с ROS, гистонами, миелопероксидазой и другими молекулами, повреждающими патоген. Патогены, а именно бактерии, грибы, паразиты и вирусы «запутываются» в сетях и гибнут.
https://en.wikipedia.org/wiki/Neutrophil_extracellular_traps

В мертвом нейтрофиле хроматин (свернутая ДНК) быстро распутывается, соединяется со специальными белками и образует большую сеть, запутавшись в которой, гибнут бактерии. Для верности в нее встроены протеиназы для уничтожения бактериальных белков и гистоны для спутывания с микробной ДНК.

Непротивление злу - не новый метод. Известeн сотни миллионов лет, прекрасно работает. Если бы не оно, микробы бы сперва направили удар по самой иммунной системе. Но они предусмотрительно этого он не делают, потому что себе выйдет дороже. Хочет бактерия убить нейтрофил - пожалуйста, сопротивления не будет. Но мертвый нейтрофил бактерии хуже, чем живой. От живого можно удрать. Мертвый напустит хлорки, опутает с ног до головы ядовитой сетью. Поэтому бактерии не атакуют иммунные клетки.

Вот от этого Толстого и перекосило всего; нутром чует подвох. Правильно поставленное непротивление злу выглядит не совсем так, как это описывает Лев Николаевич. Поглядите, как зло от непротивляющегося ему добра бегает, только пятки сверкают:

thinking

The fruits of falsification...

...The sabre-toothed blenny mimics the "dance" of a similarly colored species of cleaner wrasse. It tricks large fish into offering their underparts to be cleaned. Instead of eating parasites from the scales of the fish, the sabre-toothed blenny bites the victim and rushes away. Clients often react violently, and thereafter trust neither wrasse nor the wrasse-mimicking blenny. (Wiki)

thinking

America for Americans!

The story of peaches on our land is a continuous saga of ruthless colonization, betrayal and manipulation of people, intentional spread of disease, and oppression of indigenous culture. But the tide is turning. There is a grassroots movement that will rewrite this history setting things straight. Hear the good tidings, brothers and sisters:

Peach, a fruit that is as Asiatic in its origin as in its ways, was one of the first to cross the ocean with the white devils. Generally, North American Indians, being of ancient and virtuous stock, were indifferent to European agricultural innovations, and patriotically supported native American plants, but even these Mother Nature's own people, being only human, regrettably lapsed making a great exception for peaches. To put it mildly, the Indians were bonkers about them, seduced by the sugary taste and the surprising lack of alkaloids. Such cheap seductiveness has never been the American way. However, little could've been done to show the invader its rightful place.

In a hundred years the Indians spread their peaches from Florida to Pennsylvania, so that when the English started their own colonial project in the 17th century, the peach was already well established, and the fools took it for a native plant. By the late 18th century so many peaches escaped into the wild that the plant established itself as a major forest tree in the South. The abomination of a "Peach State" was born.

...peach trees merged into the surrounding vegetation so completely that the earliest natural historians, even John Bartram, America's first great botanist, [who explored northeast Georgia] assumed the peach was a native tree. In fact, the peach was introduced either by the Spanish settlers in St. Augustine, Florida in 1565 or by the French to an isolated Gulf of Mexico settlement in 1562. It was probably grown in Mexico at an even earlier date. Native American peach culture migrated north with the travels of Jesuit and Franciscan missionaries and with the Native Americans themselves. At the same time, the cultivated trees escaped into the landscape. William Penn observed wild, Indian peaches as far north as Philadelphia in 1683, and a few years later John Banister wrote that, in Virginia, Peaches and Nectarines I believe to be Spontaneous ... for the Indians have, and ever had greater variety, and finer sorts of them than we ...” Luigi Castiglioni noted in 1787 that, Peach trees are so abundant in Virginia that often, upon cutting away a pine wood ... they cover the whole terrain.” http://unioncountyhistory.org/page43/page59/page75/styled-7/page151.html

Yet every devilry has the seeds of its own destruction. With these peaches came green peach aphids.
http://entnemdept.ufl.edu/creatures/veg/aphid/green_peach_aphid.htm
These aphids winter on peaches and plums and feed on the sap in the early spring, but spend the rest of the year on other plants. These aphids are relatively harmless, but they spread plant viruses, in particular, PLRV - potato leafroll virus. PRLV causes net necrosis of the tuber: blotchy brownish discoloration of the flesh. This discoloration has no effect on the taste, but it can be seen in a cooked potato. To put it in a nutshell, you can't make French fries from such potatoes. So it is impossible to sell them. There has been a major outbreak of PLRV since 1975, and controlling PLRV became the major concern of the farmers. Naturally, this means controlling the aphids.

The remarkable thing about these aphids is that in 40 years they developed resistance to all of the main groups of insecticides. Most of these are carbamates and organophosphates targeting cholinesterase and disrupting synaptic action -- or nicotine-like molecules that block postsynaptic receptors. The problem is that we have the same targets in our bodies, which makes these insecticides very toxic. The aphids have acquired knockdown resistance to pyrethroids and modified acethylcholinesterases for carbamates. The last line of resistance are organophosphates, because aphid's strategy is to amplify carboxyesterase genes. This means increasing the concentration of the pesticide, so do not be surprised how cleanly washed are the potatoes sold in the supermarkets. To have a potato that can be turned into French fries, one needs to exclude PLRV, which means drenching the fields in the worst of the pesticides.

Meanwhile the peaches have been hunted down in the potato-producing areas, and everywhere else becoming agricultural pariahs. The peaches are next only to apples in the amount and variety of insecticides thrown at them. The reason is not only the damage to the trees by the aphids, but also the paranoia of local farmers that regard these peach trees as the winter quarters of the pests devastating their fields. The aphids can feed on 40 kinds of plants, including most of the vegetables grown by these farmers.

So it is an interesting example of a native plant (potato) fighting back a highly successful invasive species (peaches) subtly using the preferences of their grazers (people). One would think that the peaches will have the upper hand in this battle, because people can't resist their sugar. But the potato turned it around. It grew in size and emerged victorious in the form of French fries, the combination of caramelized starch and fats that we find even more irresistible than the fruity taste. The setting for revenge was ready. All that was missing was an unexpected move to catch the enemy unawares.

The newly developed vulnerability of potato tubers to PLRV was this strategic move. It does not inconvenience the plant but the desease forces the French-fries-obsessed people to use toxic pesticides killing all animal life in the field and, more importantly, directing their ire towards the arch-enemy, the peach. As the pesticides in peaches are more difficult to remove than in potatoes, the potatoes are slowly winning this game, as people are turned away from the once prized fruit, fearing all these pesticides. It is only their evil craving for fructose that still protects the once-mighty orchards from being destroyed. But the moment of the final restitution is coming. The peaches will go the way of the gooseberries.

I have a dream: Soon, very soon, the potato will win the battle of pesticides with the peach and hordes of axe-wielding farmers will converge on the pestilential orchards. The Indians will be forgiven their temporary infatuation, and once again the expanded potato fields will be tended by their loving hands. Happiness will descend on the battered continent, interrupted by an occasional sight of a tomato supplying ketchup for the French fries. Of course, tomatoes are not potatoes, but, at least, they are family.

America for Americans!

thinking

On apples

The story of American apples begins with the Bible, more precisely, with the 17th century Protestant literalists. Like their modern counterpart (who are spitting brimstone about smoking tobacco while rhapsodizing the virtues of medicinal marijuana) the first generation of prudes settled on the equally grotesque hypocrisy. Puritan reading of the Scriptures was that the Old Testament passages against drink relate, exclusively, to wine and beer but not to hard cider. Wine drinking was linked to the corruptions of the Great Whore, the Catholic Church, while drinking cider was a Puritan virtue. When the first Puritan settlers crossed the ocean, they brought apple grafts with them, but all of these grafts died in winter. Transplanting apples to the New Jerusalem did not work.

However, they also had apple seeds, and some of the pippins that grew from these seeds proved resistant; all of our apples are derived from these New England pippins. The apples were inedible, but after 100 years of selection, there were enough varieties to resume grafting. Even these grafted apples were unappetizing. No one was interested in eating apples: the modern varieties are breeds introduced at the beginning of Prohibition campaign of the 1890s when cider producers faced threat from such progressive organizations as Women’s Christian Temperance Union (see the photo below).

The new generation of aggressive zealots wanted to put the apple trees to ax with the same passion apple growing was promotred a generation before. The modern concept of a healthy, wholesome apple “a day to keep the doctor away” was born in those tumultuous times; for two centuries, apples were grown to produce cider. The harsh winters provided refrigeration for freezing water out of cider and producing 66 proof liquor, applejack. An average homestead produced a few thousand gallons of cider for internal consumption. While edible apples required grafting, cider could be produced from the pippins (apple sedling trees). Johnny Appleseed was about the delights of heavy drinking.

There was another reason the settlers went gaga about their apples: Northwestern Territorial Law required a settler to set out 50+ pear or apple trees as the deed condition, as a measure to prevent land speculation (as the orchard takes ten years to fruit). Apple trees were needed to prove one’s residence. Only pippins were able to satisfy the growing demand, but these were good only for liquor. Hence the endless cider orchards of the 19th century America. The law required orchards; the fruit was turned into a theologically acceptable drink.

It was the perfect combination, and the farmers indulged accordingly. Prohibition ended this Eden, and apples were reinvented as vitamin packages. Among the millions of pippins grown in the US, there were a few edible ones, and the supermarket varieties (Jonathan, Red and Golden Delicious) are such rare finds. Each such cultivar was a heavenly gift with an incredible story behind it. Here is Golden Delicious:

It was born in 1876 on the farm where that apple tree later became famous. My dad owned the farm. "Now one day, when I was about 15 years old, that would have been about 1891, dad sent me out with a big old mowin' scythe to mow the pasture field. "I was swingin' away with the scythe when I came across a little apple tree that had grown about 20 inches tall. It was just a new little apple tree that had volunteered there. There wasn't another apple tree right close by anywhere. "I thought to myself, 'Now young feller, I'll just leave you there,' and that's what I did. I mowed around it and on other occasions I mowed around it again and again, and it grew into a nice lookin' little apple tree and eventually it was a big tree and bore apples. " This tree started the Golden Delicious apple line, for it was that tree that has produced every last one of the Golden Delicious apple trees that have ever grown anywhere. (Wiki)

Fuji and Gala are derived from these chance American finds; genetically, our apples are virtual clones, and the same cultivars are grown everywhere in the world. The co-evolution of apples and their pests was stopped, and commercial growing of apples involves the prodigious quantity and variety of pesticides. Apples, peaches, and stawberries require more pesticides than any other food crops. A fruit that contains, on average, 47 pesticides may not be too good at keeping the doctor away. Whatever health effect apples used to have became undermined by the monoculture, which itself is the consequence of switching from alcoholic cider to “healthy” fruit. The only way to grow this fruit is to poison the apple.

The choice of an apple as the forbidden fruit is an apt one: the last 400 years of its history is the continuing story of Puritan zeal with its persistent gospel of spiritual and earthly rewards. The next step in this unrolling saga is campaigning for organic apples as opposed to the evil supermarket variety. The humble fruit satisfies the most American of all passions: aggressive, zealous preaching.

Maybe it was not such a bad idea to keep this fruit from us…

thinking

Ye shall not steal: hydromedusiod theory of property

Death, where is your sting? Hades, where is your victory? (1 Cor 15:55)

For natural law theories, property rights are a formidable problem, because our animal nature is fully compatible with theft. There can be made an argument that property is needed for one's survival, but this does not involve all property or the survival of the others that may depend on alienating one's property. So one needs to appeal to some other nature than biological one; e.g., one's rational nature.

One school of natural theology is that this "other" nature is the better nature we were endowed with during the Creation; the Fall corrupted this original nature but it still has a hold on us, and the moral norms are the remnants of this nature that is cast on our hearts. This nature is not what we presently are but what we supposed to be, ought to be, and will become. We've started as sin-free immortal creatures; it is our own fault that we are mortal, sinful, and thieving. On this theory, property rights derive from our prelapsarian nature, and to explain property one needs to explain how the protection of property naturally emerges from this nature.

We do not have too many examples of immortal animals around, but we do have some polyps that can endlessly regenerate themselves, and T. nutricula mentioned in the previous post is the most complex example of this kind: after releasing the gametes, its adult medusa form undergoes transformation back to the juvenile form, the colonial polyp state, by cell transdifferentiation. Like most other animals, we gradually age and die through senescence after we reach sexual maturity and produce offspring. In contrast, these jellies go back to the cradle, so to speak. It is the endless cycle of maturation followed by rejuvenation, back and forth, back and forth. This cycling is the most advanced form of immortality seen on this planet.

Suppose you have immortal rational creatures of this type. I argue that the sanctity of property is the natural condition of such creatures. Indeed, as the regeneration occurs, all memories of one's self disappear: the new self is the same genetically, so the death is cheated, but the personhood does not survive, there is no continuity of experience. The old self and the new self cannot communicate biologically, so the only way of preserving continuing personality is through externalizing it: creating a reflection of one self in the material world that serves as a template for regaining one's older self after the regeneration. This material reflection is one's property. You can think of it, say, as a diary that your older self writes for the younger self guiding this younger self towards its previous incarnation. But it does not have to be a manual - anything would do to provide the connection. It serves another role, too: as the memories are being lost during the rejuvenation (which may take as long as our aging), one needs the reminders of one's own past; again, think of keeping mementos reminding you of your own past, but subtract the morbidity.

It is easy to see why rational creature of this type would not destroy or steal property. Property is the repository of personality and stealing/destroying property means destroying this personality: the personhood is preserved by means of all these connections between the self and the material world and it is required for continuity of personal existence, however imperfect. Theft means murder, it is just another way of achieving the same end. You shall not steal is another form of "you shall not murder" in the world of such creatures. Transfer of property is the transfer of one's personality to another being: an act of ultimate self-sacrifice.

We are the inverse of these creatures: from their middle life they become younger and get reborn and we become older and die. These type of creatures ARE our own distant eumetazoan past; their nature is the very "elusive" higher nature the natural theory seeks in the prelapsarian man. This nature was our natural condition and - who knows? - it can be our future condition again: the cellular toolkit needed for continuous transdifferentiation does exist for us to use; we've been provided. I think that property still serves the same role for us as them, although this role has been corrupted, as all other parts of our nature: we externalize our personhood to communicate our younger selves to our older selves and to our children. Retaining property is less crucial for us, but the sacred status of property could be the gold standard for rational creatures in general; quite possibly, such a life cycle is the only possibility of achieving physical immortality compatible with our animal nature.

So there is a nature that makes property rights natural, in the most unambiguous sense.

thinking

To-morrow, and to-morrow, and to-morrow...

To-morrow, and to-morrow, and to-morrow,
Creeps in this petty pace from day to day,
To the last syllable of recorded time;
And all our yesterdays have lighted fools
The way to dusty death. Out, out, brief candle!
Life's but a walking shadow, a poor player
That struts and frets his hour upon the stage
And then is heard no more. It is a tale
Told by an idiot, full of sound and fury
Signifying nothing.


Are we brief candles? What is the clock that turns yesterdays into tomorrows lighting our way to dusty death? If you believe the telomere theory of ageing, we are candles, quite literally. The candle burns every time our cells divide. The chromosomes are capped by repetitive DNA sequences (telomeres); a short stretch is being lost every time a cell divides. When the telomeres become too short, the cells cannot divide any more. Some birds can elongate the telomeres in their somatic cells; mammals can't. This burning candle is said to protect us from cancer by tumor supression, but it also makes it certain that we'll die. The choice (in the absence of disease, harm, and predation) boils down to dying from the programmed senescence or inevitable cancer. Some choice...

But there are better players around. Bacteria have circular DNA; there is no "candle" to burn. They can go on multiplying to the last syllable of recorded time, but can they tell apart today and tomorrow?

The cyanobacteria can. Their 24 hour circadian clock works in the dark, keeping time for a few weeks. No one believed that such a clock might be possible: the bacteria divide much faster than the period of the clock; yet the rhythm persists during the division. Actually, it persists in vitro, in a solution containing ATP: there are three kaiABC proteins that run through a 24 hr cycle of phosphorylation of the kaiC hexamer. The clock itself is chemical (it is a system of reactions with a double-negative-feedback loop) but it is also a global switch: the transcription of 800 genes (out of the total of 2700) is turned on in the morning and turned off in the evening.

How can one protein affect the transcription of 800 genes? There is strong indication that kaiC changes the topology of DNA (the oscilloid model). Bacterial DNA is a loop that is further rolled into supercoiled domains. The clock protein flips the DNA between two superhelical states. In one of these states the coils are looser, so the translation is faster. Like a flower, the DNA of a bacterium opens in the morning and closes in the evening -- to-morrow, and to-morrow, and to-morrow -- for what has already been 3.8 billion years.

Isn't it great that someone upon this stage can always look forward to another tomorrow?



http://download.journals.elsevierhealth.com/pdfs/journals/0014-5793/PIIS0014579309009144.pdf
http://www.sciencemag.org/cgi/reprint/sci;318/5851/757.pdf
http://www.cas.vanderbilt.edu/johnsonlab/publications/reprints/pmid11463211.pdf
http://onlinelibrary.wiley.com/doi/10.1002/jcb.20519/pdf
http://www.pnas.org/content/106/52/22564.full
http://www.pnas.org/content/104/47/18819.full
thinking

To be or not to be...

To be, or not to be: that is the question:
Whether 'tis nobler in the mind to suffer
The slings and arrows of outrageous fortune,
Or to take arms against a sea of troubles,
And by opposing end them? To die: to sleep;
No more; and by a sleep to say we end
The heart-ache and the thousand natural shocks
That flesh is heir to, 'tis a consummation
Devoutly to be wish'd. To die, to sleep.


To be or not to be? Is there a third way?

Yes, there is. The dilemma has a solution that occurs in Gram positive bacteria. It is the ability of such bacteria to resolve the unresolvable conflict that makes them so dangerous to us, as it disinclines the cocci causing pneumonia, meningitis, and sepsis to reduce their virulence.

As a bacterial colony grows, it reaches the so-called stationary state in which its growth is checked by starvation. At this point the colony becomes susceptible to GASP (growth advantage in stationary phase) mutants that grow faster than the rest of the cells - a kind of cancer. The takeover of the colony can take only 4-5 generations. As the mutant takes over, other cells starve to death. Their remains are cannibalized by the mutant, which uses these dead cells as the source of raw nutrients. In the stationary state, the colony is GASPing for life: every few days a new GASP mutant emerges. It steadily wipes out the mother strain, and then becomes eclipsed by the next GASP mutant. The population slowly declines but the recycling of the dead cells by the GASP mutants is the name of the game.

What it means to the mother strain is that their genes are wasted: the next reincarnation of the colony is all daughter GASP mutants. That's not good for the mother strain. This may also be detrimental to survival of the colony, as these GASP mutants are only good at taking over the colony and digesting dead cells. For example, the GASP mutants may undergo abrupt aerobic-anaerobic shifts or have other metabolic anomalies. When the conditions change once again, these mutants will not be viable and the colony will die. The frequency of GASP mutation is about 1e-7. If the colony grows to 1e6-1e8, the hostile takeover will occur with certainty; the only question is when. A starving colony produces GASP waves every few day; see http://www.pnas.org/content/96/7/4023.full
http://www.nature.com/nrmicro/journal/v4/n2/full/nrmicro1340.html

The danger of this GASP takeover exceeds the danger of pathogens, competition, predation, lack of nutrients, antimicrobials, etc. Slowing down the mutation rates only delays the inevitable. The dominant strain (including the GASP strain at the peak of its power) cannot "be" by being, because being is a ticket to nonbeing. The longer the colony exists, the more likely is the annihilation of the mother strain by the GASP mutants it itself produces. On the other hand, not having mutations is out of question because the spectrum of possibility needs be constantly explored for survival. "Not to be" is also out of question, as the whole point of bacterial life is not giving up. This is one heck of a problem.

Some bacteria are GASPing until they die or disperse, but other bacteria do have a strategy. If the population is reduced very dramatically, say 100-1000 times, the colony would be too small for a GASP mutant to arise, statistically speaking, and the mother type will "be" in the future. Their solution of the dilemma is mass suicide. The bacteria can get away with this strategy because they are clones. It does not matter if 99.9% die because they are almost exact copies of each other. But they are not exact copies, so what's in it for those that die? When they die, the DNA released from the dead cells is imported by the surviving "competent" cells (this is called transformation). Part of this DNA is used as food, but some of it is incorporated into the genomes of the survivors and/or used as a template for DNA repairs: sex with the dead. Only a small fraction of the bacterial cells in a colony are competent. The trait is random.

...S. pneumoniae cells that undergo lysis, which enables genetic exchange [the released DNA is picked up by the survivors]. Once the population density becomes dangerously high and likely to produce takeover mutants, a quorum-sensing mechanism triggers lysis. This strategy is essentially preventive suicide. Paradoxically, a smaller, mutant-free population entering stationary state might have a far better chance of ultimately surviving (i.e., producing viable progeny) than a much larger population burdened by mutant cells. For example, a typical clone of 1e8 cells could be reduced by autolysis to about 1000 cells, and given a mutation rate of 1e-7, this small population entering stationary state is likely to be free of takeover mutants and unlikely to create them. DNA exchange probably evolved as a secondary function of lysis, building upon an existing process of preventive suicide. Indeed, decrease in viability upon entering stationary state is common among bacteria, but spontaneous DNA transformation is not. http://mmbr.asm.org/cgi/reprint/64/3/503

The cells monitor their ranks by quorum sensing and check on nutrients. When the sea of trouble arrives, they activate lysis that causes most of them to die, but as the concentration of nutrients increases by the mass lysis, in a small subset of competent cells chosen by lottery the suicide action stops just in time. The survivors enrich their genomes by DNA of the dead; whose DNA is used is also chosen by lottery. The system is as fair as it can realistically be. This "colony-average" mother strain cells start over amid the bounty of nutrients (the remains of their many dead sisters) growing a new colony -- or they sporulate. The evolution is check mated: the arrival of the GASP mutant is prevented and the future of the mother strain is "to be." Egotism, altruism, spite, nepotism, cannibalism, fratricide, and everlasting hope are all rolled into this action.

The solution to "to be or not to be" is to die in order to be. There is no other way.

PS.
http://www.annualreviews.org/doi/pdf/10.1146/annurev.micro.60.080805.142139
http://www.sciencemag.org/cgi/reprint/sci;267/5199/836.pdf
http://www.nature.com/nrmicro/journal/v5/n3/full/nrmicro1613.html
http://mmbr.asm.org/cgi/reprint/72/1/85
http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020135#s1

thinking

Sticks and stones may break my bones (but words will never hurt me)

to http://flying-bear.livejournal.com/985938.html?thread=16722002#t16722002

Going back to fish: how lucky are we (as rational animals) that we live on land!

Whatever words one may say, these cannot directly kill anyone. I have little doubt that had such a possibility presented itself, it would be used by H. sapiens. Words do kill, but only indirectly, and this cannot be helped. But we are spared the worst.

Why is that? Because air is insulating, which cannot be said about water. Everyone knows about electric eels, skates and rays that kill their prey with high-voltage, high-current pulses. Less known is the fact that this weapon started very humbly as a weakly electric organ used for communication and location, just like our own vocal chords. This organ has been developed independently six times
http://jeb.biologists.org/cgi/reprint/211/11/1814
http://electrochem.cwru.edu/encycl/art-f01-fish.htm
and used to generate trains of short mV pulses, mainly for social communication. The 500 V, 1 A pulses of knifefish and 50-200 V, 30 A pulses of Torpedo rays are similar in shape and duration to these pulses, and the electric organs are homologous to the communication organs in weakly electric fish; these organs clearly started as electrocommunication organs. But then the words became louder, louder, and still louder -- and then these words began to kill, literally.

No wonder that fish keep to themselves, talking very little: their silence is self-imposed. If we abuse the gift of the word, we will end up like these fish - through no other miracle than the law of consequences. Perhaps fish are silent to teach us a lesson.
thinking

Russia and the defeat of the Horde

In my boyhood, I was told endless patriotic stories about the heroic struggle between the Russians and their Mongol oppressors, the Golden Horde. The Mongol yoke lasted for a long time and then... kind of disappeared. There was the favorite story of Mamai Khan and Grand Prince Dmitri of Vladimir battling at Kulikovo around 1380, with at least 150,000 on both sides. It is hard to say who won that battle because the losses were heavy on both sides. In any case, the next year the Russian princes resubmitted to Mongol suzerainty and a year later Khan Tohtamysh burnt Moscow. The Muscovy remained the vassalage until 1480. Calling this desperate and largely pointless skirmish the turning point in the history of Russia would be belaboring the truth. But something indeed happened that weakened the Tartars more than the Russians. This part of history was not emphasized in the heroic sagas. The true reason for the decline of the Golden Horde was that it was disproportionally ravaged by the pandemic of the Black Death in the mid-1340s, from which it never recovered. Furthermore, it was the Horde (Janibeg Khan's troops) that passed the plague to Italy from Kaffa, from which it rapidly spread across Europe. It turns out that this was a deliberate act, one of the few documented cases of using biological weaponry in medieval times:

...Jani Beg (? — 1357) was a khan of the Golden Horde. Jani Beg commanded a massive Crimean Tatar force that attacked the Crimean port city of Kaffa (Theodosia) in 1343. The siege was uplifted by an Italian relief force in February, 1344, resulting in 15,000 Mongol deaths and the survivors fleeing east. He returned in 1345 and besieged Kaffa a second time. The next year, however, the Mongols became infected with the Black Plague and gave up the siege.

...The plague had traveled from Sarai to the Genoese trading station of Tana, east of the Black Sea. Here Christian merchants were attacked by Tartars and chased to their fortress at Kaffa. The Tartars besieged the city in November, but their siege was cut short when the Black Death struck. Before breaking off their attack, however, they catapulted dead plague victims into the city in the hopes of infecting its residents. The defenders tried to divert the pestilence by throwing the bodies into the sea, but once a walled city had been struck by plague, its doom was sealed. As the inhabitants of Kaffa began to fall to the disease, the merchants boarded ships to sail home. But they could not escape the plague. When they arrived in Genoa and Venice in January of 1348, few passengers or sailors were left alive to tell the tale.
http://historymedren.about.com/library/weekly/aapmaps4.htm

...The Black Death of the 1340s was a major factor contributing to the Golden Horde's eventual downfall. Following the disastrous rule of Jani Beg and his subsequent assassination, the empire fell into a long civil war, averaging one new Khan per annum for the next few decades. By the 1380s, Khwarezm, Astrakhan, and Muscovy attempted to break free of the Horde's power, while the lower reaches of the Dnieper were annexed by Lithuania after its decisive victory in the Battle of Blue Waters and Poland in 1368.

The Russians were able to exploit this weakness because Russia was largely spared by the pandemics that devastated Europe and Asia. Benedictow (The Black Death, 1346-1353: The Complete Jistory, p. 212) claims that

...religious zealotry and violent anti-Christian sentiments appear to have led to intermission or a temporary radical reduction in trade between the Golden Horde and Christian merchants in the Russian principalities. There can be hardly any other explanation for the fact that the Black Death did not move north-westwards into the Russian areas from its original outbreak in the south-eastern lands of the Golden Horde on the Caspian Sea). Instead, the Black Death had to move to the long route from Europe's Mediterranian coasts to the Hanseatic towns and cities on the Baltic Sea before it could launch its attack on Russian territories. The Russia was conquered from north-west and not from south-east, and was the last region of Europe to be attacked.

...It used to be thought that the Black Death originated in China, but new research shows that it began in the spring of 1346 in the steppe region, where a plague reservoir stretches from the north-western shores of the Caspian Sea into southern Russia. People occasionally contract plague there even today. Two contemporary chroniclers identify the estuary of the river Don where it flows into the Sea of Azov as the area of the original outbreak, but this could be mere hearsay, and it is possible that it started elsewhere, perhaps in the area of the estuary of the river Volga on the Caspian Sea. At the time, this area was under the rule of the Mongol khanate of the Golden Horde. Some decades earlier the Mongol khanate had converted to Islam and the presence of Christians, or trade with them, was no longer tolerated. As a result the Silk Road caravan routes between China and Europe were cut off. For the same reason the Black Death did not spread from the east through Russia towards western Europe, but stopped abruptly on the Mongol border with the Russian principalities. As a result, Russia which might have become the Black Death's first European conquest, in fact was its last, and was invaded by the disease not from the east but from the west.

http://www.questia.com/googleScholar.qst;jsessionid=LCJGcwgt2QD7yXwyJBfj4Q22S80Gj3cLTxV9qWT1mXvpJTBv6q1V!956494123?docId=5008814516

The Russians were the lucky beneficiaries of this devastating pandemics and the zealotry of the newly converted Tartars. Would the Tartars be less fanatical, they would infect the Russians themselves rather than via their European proxies. The virulence of the plague at the beginning was extreme, but it subsided as it spread. In Venice and Genoa, where the plague crossed into Europe, 60% died; the European average was only 30%. One would expect that the mortality among the Tartars was extremely high, but the mortality among the Russians was considerably lower, though still high (20-30%). Actually, the only known place where the outbreak was chronicled was Pskov. Other reports are indirect, and it's only guessed that the plague visited Moscow and Kiev around 1353 (there is no physical evidence). More importantly, it seems that only bubonic plague made it there, whereas the pneumonic one (which can spread by air and caused death within 24 hours) did not. The Tartars, however, were at the very epicentre of the disease, and suffered greatly.

The Mongol yoke was not shaken due to the heroism of the Russians or their emerging national identity. These were minor factors. The decisive factor was the combination of Islam and Y. pestis at the right time.

It was this miracle that delivered Russia rather than the Russians themselves.