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Madre e hijo

Al escuchar el brusco ruido, la madre y su pequeñito se arrinconaron como ratones en una jaula. La madre, quien dependía de sus otros sentidos debido a problemas hereditarios de vista, rompió en llanto al darse cuenta que el intruso pretendía despojarla de su hijo. ¡Piedad!, gritaba la indefensa mujer, pero cada palabra que intentaba articular no era más que un chillido incomprensible para el intruso. Por su cuenta, el pequeñito se había refugiado instintivamente bajo los brazos de su madre. Pese a su breve edad y la confusión del momento, el crío estaba congelado, pálido y aterrado como si fuese consciente de la tragedia que le acechaba. Al contrario de su madre, el niño permanecía absorbido en un mortífero silencio. Su respirar era detectable sólo para su madre quien le estrujaba contra su pecho. Lo protegía, lo abrazaba, lo mantenía tan cercano a ella como si intentase meterle nuevamente en su vientre.

Para el intruso, ellos no eran más que dos seres desechables. Animales. Bestias. Parásitos. Cualquiera pagaría para exterminarles, así que el intruso tenía todo derecho de hacer y deshacer con ellos. Además, era por una buena causa: la ciencia. El intruso precisaba de un cerebro joven para sus fines intelectuales. Las neuronas de los chiquillos como éste estaban bastante cotizadas debido a su resistencia y plasticidad. Grandes hallazgos y publicaciones motivaban a miles de intrusos como el de esta historia.

Sin escrúpulos, el intruso arrebató al pequeñito de los brazos de su madre y lo arrojó a una celda de cristal. El crío comenzó a sentir un baño de electricidad recorriéndole la piel. Sus frágiles piernas parecían dos cuerdas que vibraban al son de los gritos de su madre. En un par de segundos, el chiquillo se desplomó. Había perdido la conciencia a causa del isoflurano, un anestésico que colmaba el interior de su celda. El intruso observaba en la comodidad de su lejanía y al mirar que el pequeño apenas respiraba, lo tomó del lomo y lo decapitó. El carmín le cubría su cabellera castaña como un aura mientras el intruso le extirpaba la piel como si fuese una máscara. Al retirar todo el cuero de la cabeza, el intruso había expuesto el cráneo del crío. Allí en sus huesos parecía formarse una cruz que se conocía como el bregma: un punto anatómico para el intruso, un mal augurio para la madre.

Para terminar el rito, el intruso tomó un par de tijeras y comenzó a cortar desde el tronco cerebral hasta lo que solía ser la frente del pequeñito. Al sonido de dos chasquidos, el intruso había desprendido los huesos del cráneo y el tesoro de sustancia gris se asomaba. El intruso retiró la masa gelatinosa y comenzó a rebanarla como jamón. Este era el trabajo del intruso, día a día, crío a crío, cerebro a cerebro. Se estimaba que rebanaba unos doce cerebros en cada jornada de trabajo. ¡Qué ultraje a la humanidad! Pobres niños, pobres madres. Mas para el alivio del lector, es preciso revelar que se trata de ratones y no de humanos.

 

 

 

The link between Herpes and Alzheimer’s Disease

One of the distinctive features of Alzheimer’s disease (AD) is the accumulation of a group of insoluble protein fibrils (Amyloid-β peptide fibrilization) as β-amyloid plaques . In the past, scientists thought that amyloid-β peptide (Aβ) was just a useless secondary product of biochemical pathways that was eventually eliminated in healthy cells. This assumption, however, was inconsistent when considering the high genetic conservation of Aβ across different species. Recently, researchers have discovered that this apparently annoying protein is not as worthless as it was once thought. In fact, Aβ seems to be an immune system super hero that fights against the bad guys in our body. Formally speaking, Aβ is an antimicrobial peptide (AMP) that starts to agglutinate (Aβ oligomerization) when it detects certain pathogens. As a result of the Aβ deposition in cells, the brain has a neuroinflammatory response. Apparently, this immune response leads to neural death in order to prevent the infection from spreading to other brain regions. Aβ oligomerization can end up protecting our brain if the neuroinflammatory response is controlled, otherwise, the accumulation of Aβ oligomers will lead to more neuronal death, which is the underlying pathology for multiple human diseases, including Alzheimer’s disease.

You are probably wondering now what the relevance of the herpes viruses is in this story. Let me begin by saying that all of us have at least a herpes virus. Yes, herpes, which in Greek means “to creep” but don’t freak out! Genital herpes is not the only type of herpes virus. There are multiple herpes viruses and they are known as the herpesviridae family. Nine herpes viruses affect humans and five of them are present in around 90% of the human population. In the case of Alzherimer’s disease, herpes simplex virus 1 (HSV1) has been shown to be correlated to an increase in Aβ deposition. This is why a group of scientists in Harvard decided to explore the question of whether Aβ oligomerization in the brain had a protective role against herpes virus infection.

To answer this question, the researchers investigated three herpes viruses (HSV1, HHV6A, and HHV6B, the latter two standing for human herpesvirus 6A and 6B, respectively) in vivo and in vitro. For the in vivo experiments, they used a transgenic mouse model used in AD research known as 5XFAD. These animals have high levels of Aβ protein in their first weeks of life, which allows the researchers to explore whether more Aβ protein can protect the brain from herpes virus infection. They injected wild type (WT) and 5XFAD mice’s brains with a high dose of HSV1 only (no HHV6A/B were used because mice lack homologous receptors for these human viruses in their neurons). Subsequently, the researchers observed how long it took mice to die. Of course, the researchers had a control group of mice that went through surgery but did not get a lethal injection of HSV1. The results indicated that 5XFAD had a higher survival rate than WT animals (see fig.1). This increase in survival rate was, presumably, due to the protective effects of Aβ protein against HSV1 in 5XFAD mice.

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Fig 1. Higher survival rate in 5XFAD mice over expressing Aβ42 after being infected with HSV1. Image taken from https://doi.org/10.1016/j.neuron.2018.06.030

The next piece of evidence that supports the interpretation of this result was the examination of brain sections from 5XFAD and WT mice that were infected with HSV1. The authors used antibodies to visualize the location of HSV1 and Aβ protein in the hippocampus of these mice. The results showed that HSV1 and Aβ were co-localized in the brain of 5XFAD (see fig.2). More specifically, the presence of Aβ proteins in 5XFAD brains led to agglutination of Aβ around the herpes virus, apparently as a form of protection against viral infection.

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Fig.2. Co-localization of Aβ oligomers and HSV1 in 5XFAD brain sections using fluorescent markers. Image taken from https://doi.org/10.1016/j.neuron.2018.06.030

The in vitro experiments were in line with the findings in vivo. The researchers found that those cell cultures where Aβ protein was expressed showed a lower percent of infection by HSV1 than those where Aβ was eliminated (immunodepleted: reducing a protein by means of antibodies). Similarly, the authors performed transmission electron micrographs (TEMs which is a very powerful form of microscopy) and found that cells infected with HSV1, HHV6A, or HHV6B, and expressing Aβ protein presented fibrilization(the formation of protein fibers) around the virus (see Fig. 3).

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Fig. 3. Formation of Aβ protein around the viral envelops of HSV1 and HHV6A/B. Image taken from https://doi.org/10.1016/j.neuron.2018.06.030

Taken together, these results suggest that Aβ protein might have a protective role against herpes viruses in the brain. These findings do not directly demonstrate a relationship between AD and herpes virus, but they are strong evidence that Aβ protein oligomerization can be triggered by pathogens such as herpes virus. Because this is one of the major underlying pathologies of Alzheimer’s disease, it is logical to think that the exposure of the brain to herpes virus might lead to a higher risk of developing AD. As we get older, the brain blood barrier (our friendly bouncer of undesired substances in the brain) gets leaky, so our brain gets exposed to a wider set of substances, including pathogens. It is possible that this is one of the events triggering Aβ protein agglutination in aging populations because herpes viruses are now able to move from the peripheral system to the central nervous system.

 

For more information:

Eimer WA, Vijaya Kumar DK, Navalpur Shanmugam NK, Rodriguez AS, Mitchell T, Washicosky KJ, Gyorgy B, Breakefield XO, Tanzi RE, Moir RD (2018)Alzheimer’s Disease-Associated beta-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection. Neuron 99:56-63 e53.

Dicen que la muerte es fácil

Dicen que la muerte es fácil. ¿La muerte, una salida fácil, un escape para los cobardes? ¿Acaso hay más valor, más fortaleza en aquel hombre que arrastra la vida hasta el final que en el hombre que toma una pistola y se apunta a la cabeza mirando al espejo? ¿Será que el hombre que camina en círculos antes de encontrar su vía al precipicio merece más honor que aquel que corre y salta de golpe al vacío? ¿Y el inocente mártir que espera en su celda hasta el día de su ejecución en público, merece él más crédito por sus hazañas que la víctima que de manera autónoma y solitaria sube los peldaños de la plataforma hasta la guillotina y deja caer la cuchilla sobre su cuello? Sólo un ingenuo o un mojigato vería con desdeño al suicidio. No os estoy alentando a saltar del quinto piso, pero insisto en que hay ocasiones en que la vida ya no tiene vuelta atrás.

La muerte digna, la muerte que uno elige, requiere una mente fría. La decisión de evaporarse de una vez por todas precisa de un análisis casi matemático sobre lo que queda por ganar y por perder en la vida. Lo inexorable, la muerte, podría catalizarse con una sobre dosis de euforia o ralentizarse criónicamente con un baño de nitrógeno líquido. ¿Pero para qué evitar lo inevitable cuando ya no queda más por hacer, por ganar o por perder, por sufrir o por disfrutar? Me refiero a los enfermos terminales, a los ancianos, a los desahuciados, paralizados, heridos, mutilados en el alma o en la carne, a aquellos que están confinados a vivir sin vivir. Uno no decide cuándo ni cómo nacer, pero uno puede fulminarse cómo y cuándo le plazca.

Así que piedad, piedad al que se fuga del dolor de esta vida. No es fácil bajar las manos. No es fácil beber la cicuta. Así que no subestiméis a los prófugos de esta vida, pues descansar en paz es derecho y condena de todos.

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Farewell to Wellesley College

My Vesta,

I was your orphan.

In your arms, my mother,

I felt home

And I felt a foreigner.

 

I came to you naked

And you drowned me in a lake full of wisdom,

The more we learned,

The more ignorant I felt.

 

You brought to me love,

But not the love of the flesh,

Nor the love of men,

Nor the love of silver,

Nor the love of women.

A calcining passion,

A world full of beauty,

An endless thirst of curiosity.

 

My friend,

My solitude,

My muse,

My demon,

 

My love,

My nightmare,

 

This is the nostalgia of a farewell I always wished for.

I’ll miss you very much, but don’t you dare to come back.

 

My Alma Mater,

Grateful and salty,

This is our goodbye.

June 1st, 2018

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The Epiphany of her Mother’s Transformation

Not many people in this world would ever see their mothers as she did. She used to wake up every morning around six and put in the microwave a jar of that green jelly smoothie that they used to call “mommy’s pudding”.

Beep. Beep. The food was ready, but before this matutinal banquet, she would change her mother’s diaper. Involuntarily, the smell of the urine would always bring her back to those late nights in Rue de la Verrerie, which was the street where all the bars were at in Aix-en-Provence. “It smells like a street full of bars”, she would tell her mother and she would laugh with her eyes still closed.

Mmmmhhhh. Ahhhhhh. Mmmmmh. Ahhhhhhhh. The pain of stretching every morning. Her mother looked like a little caterpillar moving up and down, but not going anywhere. All her movements had been slowly effaced until she became confined to her own body. She was indeed a caterpillar, but without the promise of metamorphosing into a butterfly.  There was a feeding tube in her stomach that allowed her daughter to pour and pump some mommy’s pudding. She would then close the feeding tube and go back to bed.

One day, she couldn’t fall asleep, so she decided to read a book with the hope of eventually going back to the arms of Morpheus. Searching among her high school books, she stumbled upon a collection of Kafka’s stories. Die Verwandlung caught her attention. She remembered reading that novel when she was a fifteen-year-old. It was the bizarre story of Gregor Samsa, a man who wakes up one morning converted into a massive and monstrous bug.

Back in the days, Gregor’s transformation seemed so absurd and grotesque that she struggled to see any meaning at all in his story. Now, as a young adult and with a mother suffering from a gradual and deadly motor disease, she felt like Kafka had written a novel describing every aspect of her daily routine at home. Just like Gregor Samsa, her mother would open her eyes every dawn transformed into a giant bug. She would utter sounds that did not translate into words. Her psyche was disconnected from her body and her condition seemed monstrous to everyone. She did not even have the right to have fresh food anymore. Like an insect, she was condemned to be fed with a revolting green pudding that no other human would ever want to taste. In the past, she used to be the provider for her family, but had now become a financial burden. With tears in her eyes, she wondered whether she would also feel an immense relief once her mother died just like Gregor’s family did in the story.

The agony of such an intense realization took her back to bed.

Maybe I am the real hideous bug for my horrendous psyche does not match my physic either.

Not many people in this world would ever see themselves and their mothers as she did. They used to wake up every morning transformed into massive monstrous bugs.