It may be a dog-eat-dog world* out there, but nowhere is the competition fiercer than in the female reproductive tract.

Biologically speaking, the goal of every male is to produce as many offspring as possible. To do this, males need to have some kick-ass sperm, but according to a recent study, too much kick-ass sperm can cause problems.

Human males, thanks to thousands of years of evolution, now over-produce crazy-fast, majorly-aggressive sperm known as “super-sperm.” One super-sperm reaches the egg first. If another sperm binds to the egg after the winning sperm has lodged itself in the egg, the egg will die. Of course, there’s a defense system to prevent this from happening.

As soon as the winning sperm binds to the egg, a biochemical barrier begins to form around the egg. The barrier is complete in just a few minutes, but (BAM!) another super-sperm enters the egg before the barrier is sealed and the fertilized egg dies.

Over those thousands of years of evolution, women’s bodies have evolved as well. To prevent one overly aggressive second place super-sperm from ruining a perfectly good zygote, the female reproductive tract does everything possible to keep sperm out. To survive the sperm will have to become even super-er.

Human sperm are not the only sperm with a mission. Meadow voles, earthworms, damselflies, field crickets and red junglefowl depend on stellar sperm to win the sperm war. You see, in many species, a fertile female will mate with multiple males. All of the males are shooting for the ultimate prize (paternity), but only one—or in some cases, a few—will win.

Different species have different sperm competition strategies. Some, like chimpanzees and rhesus macaques, produce super-speedy sperm. Others vary the amount and quality of sperm they ejaculate based on the situation. If a meadow vole smells other males nearby, he will contribute more sperm than he would in a more private setting. Field crickets and earthworms give significantly more viable sperm to “experienced” partners than to virgins. And red junglefowl produce higher velocity sperm when they mate with attractive females than when they mate with unattractive females.

Some males—like male black-winged damselflies—play it safe no matter what the girl looks like. During mating, the male black-winged damselfly pumps his scrub brush-like penis up and down to remove 90 to 100 percent of the sperm from the female’s spermatheca (her sperm storage tank). Once he’s done cleaning, he deposits his own sperm.

Alas, males and their speedy my-sperm-is-better-than-your-sperm sperm don’t always get to control who scores paternity. A recent study found that female crickets control how much sperm they store from each of their mates. By storing more sperm from appealing males and less from unappealing (related) males, the female determines a male’s chances of fathering her offspring—no matter how “super” his sperm might be.

*Siblings kill each other, lovers eat their mates and parents eat their offspring, scoring a mate isn’t nearly as easy as it is for humans and making a baby is a downright dangerous proposition.

Hasson, O., & Stone, L. (2009). Male infertility, female fertility and extrapair copulations Biological Reviews, 84 (2), 225-244 DOI: 10.1111/j.1469-185X.2008.00068.x

BRETMAN, A., NEWCOMBE, D., & TREGENZA, T. (2009). Promiscuous females avoid inbreeding by controlling sperm storage Molecular Ecology, 18 (16), 3340-3345 DOI: 10.1111/j.1365-294X.2009.04301.x

1. Cahill tonight! Excited about that, but sad to read this:

Roy Steele, the A’s main public-address announcer since the team arrived in Oakland in 1968, is unlikely to handle PA duties the first month of the season because of poor health.

Roy Steele anchors my baseball memories in the same way Bill King does. The soundtrack of my youth, so to speak. Bill King, Roy Steele, REM, and the endless procession of guidance counselors lecturing me about the tragic gap between my “potential” and my performance. (Maybe this is premature, but I’m going to call it anyway: that D in 8th grade World History did not actually derail my hopes and dreams)

2. Wherein Bob Geren’s alleged affinity for The Book is discussed. Tango posts lots of numbers I did not read. MGL gets huffy. Etc.

3. Another tale of monkeys on the loose, this time in Oregon.

Famed Hillsboro rhesus include ANDi, the first “transgenic” primate, born in 2001 with jellyfish genes inserted into his genetic code

Movie pitch:

So there’s this monkey. Rhesus Macaques. Cute little bugger but we can make it fierce, don’t worry, that’s what CGI is for. It’s in a lab. Cages, guys with glasses and white coats, clipboards, computers. There’ll be a hot young lab assistant – I’m thinking Hilary Duff in a breakout role – and a kindly elder statesman professor-type, Anthony Hopkins maybe. With a beard. Has to have a beard. We’ll have a love interest, obviously, and an evil scientist (Magneto to Hopkins’ Professor X), maybe a slightly less hot but dependable – and wry! – girlfriend for the lab assistant.

So what do we do? We combine the monkey with a jellyfish, that’s what! So now it’s a transgendered monkey. No, wait transgenic. Shit. Sorry! It’s not a bisexual monkey. Not that that’s what transgendered is, but you get what I’m saying. It’s got jellyfish genes, is the point. In any case, the monkey is translucent and kind of glowing and it has these tentacle things sprouting everywhere. Pretty soon they have to put wet sand and water in its cage, and Anthony Hopkins is warning everyone about all the ethical dangers. Violation of nature, stuff like that.

This is where Magneto comes in. He wants to push it further. He won’t take no for an answer. Pretty soon, this monkey has giraffe genes, starfish genes, labradoodle genes, even human genes. Now it’s a wild-eyed jellyfish/giraffe/starfish/labradoodle/human/monkey beast of a thing, all the other lab monkeys are going batshit crazy, screaming, jumping around, but Magneto won’t stop. And now the Pentagon is involved, Professor X is killed in a mysterious lab accident, Hilary Duff is on the run, fleeing special ops forces and Magneto and terrorists – you don’t think al-Qaeda would want to get their hands on a mutant rhesus macaques? – and obviously the monkey itself, which has broken free from the lab and is terrorizing downtown Chicago.

We’re not sure how it ends but that’s why we need an advance – to finish the script. We know the monkey is gonna have human traits, it might even talk at some point, it’ll have emotions but it’s still a killer, maybe King Kong crossed with Deep Blue Sea crossed with Marley and Me crossed with Terminator. Hilary Duff gets captured but escapes, there’s some kind of antidote or serum involved – hey, we could do that scene from Temple of Doom where Indy gets poisoned and there’s chaos in the ballroom and before you know it they’re tumbling down a waterfall in raft and people are getting their hearts ripped out of their chests – anyway, she saves the day and gets the guy and we either kill the monkey – but in a sad, wrenching kind of way – or we un-mutate it, reverse the transgendering, transgenicing, whatever it’s called, and release it into the African wild where it rejoins its natural monkey clan. Maybe Hilary Duff moves to Africa, becomes, shit, what do you call those people? You know what I mean, like Sigourney Weaver in Gorillas in the Mist, except hotter and blonder and always in a tank top, plus the love interest and the girlfriend move out there with her – they just want to get away from the rat race, right? And maybe Professor X didn’t get killed after all, maybe he was just in a coma but recovered thanks to the healing properties of that anti-transwhatever serum.

There you go. It’s gold. Last shot, camera slowly pans back, and you’ve got Hilary Duff and the love interest and the plain girlfriend all surrounding Professor X on a wooden porch in an African game preserve, everybody is grinning, the sunset is beautiful, the music is swelling, and hey, what’s that? Why it’s the monkey, goddamnit, back to normal, scuttling around gaily, eating apples from Hilary Duff’s hand. Fade to black, do not pass go, collect $300 million.

It is a small Monkey Tuesday, because I am lazy and tired.

“The chunky monkeys who have been put on a diet after being overfed by tourists”

They look like they’re melting!

Conga Gibbons (~~Nelly~~)

Dancin’ like monkeys.

Creepy Lemur (joyrex)

Lemurs look so little like the other primates, and are yet still very recognizable. They also look like they want to eat your eyeballs.

Baaaaaby Bonobo! (Frank Peters)

BABY BONOBOS ARE SO CUTE

… So, everyone, feel free to suggest monkey-related items for future Tuesdays: news, photos, videos, stories, articles, links, personal anecdotes, whatever!

Olá malta…

Já eram quase 3 da manhã quando terminei de editar esta edição e codificava o mp3 respectivo. Quem corre por gosto não cansa!

Desta feita encontrei um artigo na sequência da edição anterior – continuamos no mundo do SIV e das suas respostas imunológicas, sobre introdução de mutações in vivo num peptideo apresentado pelas moleculas do complexo major de histocompatibilidade de classe 1 (MHC mamu-B*17).

Se este fenómeno não tem nada de muito invulgar no mundo dos virus. Mas, o que é invulgar e se torna o apelativo deste artigo chamado ” AIDS virus-specific CD8+ T lymphocytes against an imunodominant cryptic epitope select for viral escape” JEM 2007 2004: 2505 por Maness et al é o facto ser proveniente de um quadro de leitura alternativo (ou altered reading frame) do gene env do SIV. Mais curioso ainda é que este peptideo é significativamente imunogénico (capaz de induzir respostas imunológicas mediadas por linfócitos T CD8) e as respostas induzidas dominantes comparadas com outros peptideos do mesmo virus.

Vai disto, o virus para escapar a pressão imunológica exercida pelos linfócitos T CD8 específicos deste peptideo criptico que são capazes de reconhecer células infectadas com o virus em causa, realizam a mutação particular do peptideo de modo a alterar a sua sequência e reduzir a afinidade para a molécula de MHC classe I mamu-B*17. O peptideo mutado tem muita menos afinidade e não é imunogénico e logo incapaz de mobilizar os linfócitos T CD8 e estes não consegue reconhecer células infectadas com virus contendo a mutação em causa. Também interessante o facto que a mutação introduzida só afectar o peptideo criptico, pois a mesma mutação não altera a sequência de amino ácidos do gene env de onde o peptideo é proveniente (mutação sinónima).

Estamos portanto em face de um fenómeno estremamente curioso que dá muito que pensar sobre as estratégias que os virus podem introduzir de modo a escapar ao controlo imunológico, e não podemos deixar de estrapolar situações semelhantes que podem ocorrer para as células tumorais. Estamos perante portanto a uma situação de “ImunoEditing” ou modificação antigénica mediada pelo sistema imunológico.

Que tal?

Um abraço e boas leituras… ler é aprender e abrir horizontes!

Pedro

PS: o ficheiro pode ser descarregado aqui.

Click here to get your own player.

Olá malta…

Após um mês de Janeiro cheio de peripécias, consegui gravar uma nova edição do podcast. Desta feita, descrevo-vos um artigo onde se utiliza a estratégia de “prime-boost” amelhorada com CpG e FLT3L para aumentar a sua eficácia objectiva num ensaio pre-clinico em macacos para o virus SIV.

O artigo chama-se “Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus” publicado em 2007 no jornal JOURNAL EXPERIMENTAL MEDICINE.

Eu achei este artigo muito interessante por ser um artigo relatando um ensaio pré-clinico em primatas (Rhesus macaques), e tratar-se de um modelo de HIV (human immudeficiency virus) – SIDA em português. É claro que neste experimental de primatas tenta-se tratar os animais com a variante símia (SIV).

Outro factor interessante no artigo é o uso de uma estratégia de vacinação onde se utilizam dois vectores virais de origens distintas expressando os mesmo antigénios (SIV gag e pol) e HIV (Env e Nef). O uso de dois vectores distintos sequêncialmente chama-se prime-boost. O objectivo é evitar a neutralização do vector viral modificando a sua origem mantendo em comum o antigénio de interesse. Assim sendo o vector inicial é o virus Vaccinia e depois o vector seguinte é o virus Ankara.

Os autores testam o ligando de Toll-like receptor9 (Desoxiribonucleotideos CpG) e o uso de Flt3 ligand para potenciar os efeitos da estratégia de prime-boost. Os autores descrevem que a vacina assim utilizada induz uma elevada mobilização de células dendriticas (células apresentadoras de antigénios profissionais do sistema imunológico) e em estado maturo de diferenciação. Como resultados os autores mostram que no grupo de animais tratado com Flt3L e CpG, o número de linfócitos T CD8 especificos do antigénio Gag do SIV é superior a todos os outros grupos animais testados, e que em termos clinicos a vacina tem efeitos profiláticos na protecção dos animais contra um infecção mucosal por via rectal com o virus SIV.

Os dados apresentados são extremamente encorajadores para o uso desta estratégia prime-boost com CpG e Flt3L em estudos pré-clinicos em humanos.

Dêem uma olhada e deixem os vossos comentários…

Pedro

O ficheiro pode ser obtido aqui…