Modelo computacional del cerebro humano

NEUROSCIENCE

Building the Human Brain 

1. Christian K. Machens

+Author Affiliations

1. Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Av. Brasilia, 1400-038 Lisbon, Portugal.

1. E-mail: christian.machens@neuro.fchampalimaud.org
2. 
   
3. alinaquevedo@yahoo.com
4. 
   

El presente trabajo es inspirador y muy importante. Mediante un modelo por ordenador, se simulan las redes neuronales del cerebro humano y lo que es mejor, sus funciones. Hagan un esfuerzo imaginativo y lleven el presente pasito en neurociencias hacia el futuro lejano: un ordenador que "reproduce" las vivencias humanas. Pues eso, de momento todo un hito.

The human brain is exceedingly complex and studying it encompasses gathering information across a range of levels, from molecular processes to behavior. The sheer breadth of this undertaking has perhaps led to an increased specialization of brain research and a concomitant fragmentation of our knowledge. A potential solution is to integrate all of this knowledge into a coherent simulation of the brain (1). However, simply “building” a brain from the bottom up by replicating its parts, connections, and organization fails to capture its essential function—complex behavior (2). Instead, just as engineers can only construct cars and computers because they know how they work, we will only be able to construct a brain if we know how it works—that is, if we understand the computations that are carried out in individual brain areas, and how these computations are implemented on the level of neural networks. On page 1202 of this issue, Eliasmith et al. (3) make headway toward this benchmark by presenting just such a large-scale computational model of the human brain that can simulate a variety of complex behaviors.

Variaciones dentro del genoma humano

Past 5,000 years prolific for changes to human genome

High-resolution sequencing study emphasizes importance of rare variants in disease.

• by Nidhi Subbaraman

28 November 2012

Humans are carrying around more harmful mutations in the last 5,000 years.

CHRIS DASCHER / GETTY IMAGES

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Aquí va un artículo fundamental que cualquier persona debería al menos conocer. Se trata de estudios sobre la naturaleza íntima del genoma humano. Al parecer el genoma humano no ha dejado de cambiar a lo largo de los 5,000 años de evolución transcurridos. Las poblaciones humanas han crecido exponencialmente, y como resultado, en cada generación se han producido nuevas mutaciones genéticas. Lo que saca a la luz el presente trabajo es que hoy en día los humanos poseen una vasta y abundante colección de variantes genéticas raras dentro del ADN que codifica proteínas (es decir, los genes que sirven de "plantilla" para la producción de determinadas proteínas). El estudio del que "Nature" da cuenta de esas variaciones raras. Los científicos han empleado la secuenciación en profundidad ( como pesca a profundidad) para localizar y registrar más de un millón de variantes de un nucleótido (por ejemplo gataca y gacaca). No lo duden, el ADN es el producto más valioso del planeta ya que quienes patenten determinadas secuencias relacionadas con enfermedades tienen las puertas abiertas para la "producción" de terapias génicas. En el esquema se explica el proceso de transcripción y traducción.

"The human genome has been busy over the past 5,000 years. Human populations have grown exponentially, and new genetic mutations arise with each generation. Humans now have a vast abundance of rare genetic variants in the protein-encoding sections of the genome^1, 2.

A study published today in Nature³ now helps to clarify when many of those rare variants arose. Researchers used deep sequencing to locate and date more than one million single-nucleotide variants — locations where a single letter of the DNA sequence is different from other individuals — in the genomes of 6,500 African and European Americans. Their findings confirm early work by Akey¹ suggesting that the majority of variants, including potentially harmful ones, were picked up during the past 5,000–10,000 years. Researchers also saw the genetic stamp of the diverging migratory history of the two groups.

The large sample size — 4,298 North Americans of European descent and 2,217 African Americans — has enabled the researchers to mine down into the human genome, says study co-author Josh Akey, a genomics expert at the University of Washington in Seattle. He adds that the researchers now have “a way to look at recent human history in a way that we couldn’t before.”

Related stories

• Humans riddled with rare genetic variants
• Largest yet survey of human genetic diversity
• On the origin of deleterious mutations

More related stories

Akey and his colleagues were able to dig out genetic variants occurring in less than 0.1% of the sample population — a resolution that is a full order of magnitude finer than that achieved in previous studies, says Alon Keinan, a statistical geneticist at Cornell University in Ithaca, New York, who was not involved with the study.

Of 1.15 million single-nucleotide variants found among more than 15,000 protein-encoding genes, 73% in arose the past 5,000 years, the researchers report.

On average, 164,688 of the variants — roughly 14% — were potentially harmful, and of those, 86% arose in the past 5,000 years. “There’s so many of [variants] that exist that some of them have to contribute to disease,” says Akey

Genetic bottleneck

The researchers found that the European Americans had a larger proportion of potentially harmful variants — probably an artefact of their original migration out of Africa. The first small group of humans that left Africa for Europe experienced a sudden drop in genetic diversity — a ‘bottleneck’ — owing to the smaller pool of possible mating partners. In the rapid expansion in population size that followed, selection was slow to catch up to and weed out potentially harmful mutations.

More broadly, the results suggest that humans are carrying around larger numbers of deleterious mutations than they did a few thousand years ago. But this doesn’t mean that humans now are more susceptible to disease, says Akey. Rather, it suggests that most diseases arecaused by more than one variant, and that diseases could operate through different genetic pathways and mechanisms in different people.

The findings further undermine the idea that common diseases are caused by common variations, says Sarah Tishkoff, a geneticist at the University of Pennsylvania in Philadelphia. When genomics researchers first began looking at the genome for links to diseases, that was their assumption, but they quickly saw it fall short (see Nature 456, 18–21; 2008).

“This type of study nails home the point that we need to be looking at rare variation,” Tishkoff says. 

As it becomes cheaper and easier to sequence individuals’ genomes, researchers are likely to see finer genetic patterns and trends in the coming years. They could even see patterns of ancestry within just a few generations, says Akey".

Nature

 

doi:10.1038/nature.2012.11912

Suicidios por desalojos

Cuando termino de escribir el post sobre los suicidios en Asia (a paper made by Science) voy a la página digital de "El País" y allí me doy de cara con la noticia de que un hombre de 59 años se ha quitado la vida, al parecer agobiado por una deuda de alquiler. Y tal vez por terribles circunstancias familiares. Entonces me parece que hablar, o postear, sobre los suicidios en China es casi un insulto para todos esos ciudadanos que en cualquier punto de Spain están desesperados, deprimidos en grado extremo. Esas y esos que no ven salida y no encuentran modo de encausar su vida en las terribles condiciones de las que no controlan nada. Parados mayores de 45 años que se sienten como mercancía caducada. Recién graduados universitarios con idiomas, masters y cuanto se pueda pedir que han de largarse forzosamente a buscar un empleo digno fuera de España. Pequeños empresarios hundidos  hasta el cuello. Que ya no saben como ponerse para evitar cerrar el negocio. Y entonces me vienen a la neurona insomne ellas/ellos. Los ungidos por la fortuna. Los promotores de chiringuitos caritativos. Las/los muy nobles protagonistas del papel couché. Mientras los médicos y las enfermeras tienen que salir con sus batas blancas a protestar en las calles de Madrid por los recortes contra la sanidad pública. Y se imparten clases fuera de las aulas universitarias. Que frivolidad de blog tengo. Hablar de suicidios en China.

Medusas inmortales

La próxima vez que en la playa les pique una medusa, porfa no la maldigan demasiado. Son invertebrados interesantísimos de los que los científicos sacan mucho provecho. El motivo tiene que ver con la posibilidad que tienen de rejuvenecer. Algo que en el magnífico reportaje de N. Rich para el magazine del NYT se describe como un proceso hacia la inmortalidad. Vamos como si un pollo regresara al estado de huevo. Aquí he escogido algunos buenos motivos por los que las "sencillas" medusas resultan un banco de pruebas muy útil.

"Until recently, the notion that human beings might have anything of value to learn from a jellyfish would have been considered absurd. Your typical cnidarian does not, after all, appear to have much in common with a human being. It has no brains, for instance, nor a heart. It has a single orifice through which its food and waste pass — it eats, in other words, out of its own anus. But the Human Genome Project, completed in 2003, suggested otherwise. Though it had been estimated that our genome contained more than 100,000 protein-coding genes, it turned out that the number was closer to 21,000. This meant we had about the same number of genes as chickens, roundworms and fruit flies. In a separate study, published in 2005, cnidarians were found to have a much more complex genome than previously imagined.

“There’s a shocking amount of genetic similarity between jellyfish and human beings,” said Kevin J. Peterson, a molecular paleobiologist who contributed to that study, when I visited him at his Dartmouth office. From a genetic perspective, apart from the fact that we have two genome duplications, “we look like a damn jellyfish.”

This may have implications for medicine, particularly the fields of cancer research and longevity. Peterson is now studying microRNAs (commonly denoted as miRNA), tiny strands of genetic material that regulate gene expression. MiRNA act as an on-off switch for genes. When the switch is off, the cell remains in its primitive, undifferentiated state. When the switch turns on, a cell assumes its mature form: it can become a skin cell, for instance, or a tentacle cell. MiRNA also serve a crucial role in stem-cell research — they are the mechanism by which stem cells differentiate. Most cancers, we have recently learned, are marked by alterations in miRNA. Researchers even suspect that alterations in miRNA may be a cause of cancer. If you turn a cell’s miRNA “off,” the cell loses its identity and begins acting chaotically — it becomes, in other words, cancerous.

Hydrozoans provide an ideal opportunity to study the behavior of miRNA for two reasons. They are extremely simple organisms, and miRNA are crucial to their biological development. But because there are so few hydroid experts, our understanding of these species is staggeringly incomplete.

“Immortality might be much more common than we think,” Peterson said. “There are sponges out there that we know have been there for decades. Sea-urchin larvae are able to regenerate and continuously give rise to new adults.” He continued: “This might be a general feature of these animals. They never really die.”

Las causas del suicidio en Asia

Making Sense of a Senseless Act ( artículo procedente de "Science")
Mara Hvistendahl

He escogido el presente trabajo por ofrecer alguna luz sobre algo tan desconocido como los motivos y mecanismos que conducen al suicidio. Al parecer, en algunos países asiáticos constituye un verdadero problema de salud pública. Cuadros clínicos como la depresión aguda pueden llevar al suicidio. Pero existen tratamientos farmacológicos que previenen tal conducta extrema.

:Summary

China accounts for an estimated 22% of global suicides, or roughly 200,000 deaths every year. In India, twice as many people took their own lives in 2010 as died from HIV/AIDS. By comparison, the World Health Organization estimates that suicides in high-income countries total only 140,000 a year. Suicide rates in Japan and South Korea, however, are similar to China's (see sidebar), suggesting that this is a regional public health issue. And yet suicide in Asia is poorly understood. Emerging research is now filling that gap—and overturning prevailing notions. While mental illness remains an important correlate in Asia, researchers may learn more from a victim's family, religion, education, and personality. New findings suggest that some researchers may have misread correlation as causation.

Marcadores genéticos en la esclerosis múltiple

Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

"Nature" ha publicado el presente trabajo en el que un extenso grupo de investigadores españoles adscritos a instituciones públicas exploran las raices genéticas de la esclerosis múltiple (EM). Ojalá que los recortes en los presupuestos no malogren estudios de excelencia como el que aquí doy a conocer. De momento España ocupa el lugar número 9 en publicaciones científicas internacionales.

Autores

M L Cavanillas^1,16, O Fernández^2,16, M Comabella^3,16, A Alcina⁴, M Fedetz⁴, G Izquierdo⁵, M Lucas⁶, M C Cénit¹, R Arroyo⁷, K Vandenbroeck^8,9, I Alloza⁸, M García-Barcina¹⁰, A Antigüedad¹¹, L Leyva¹², C L Gómez², J Olascoaga¹³, D Otaegui¹⁴, Y Blanco¹⁵, A Saiz¹⁵, X Montalbán³, F Matesanz^4,16 and E Urcelay^1,16

1. ¹Immunology Department Hospital Clínico S. Carlos, Madrid, Spain
2. ²Inst. de Neurociencias Clínicas, Hospital Carlos Haya, Málaga, Spain
3. ³Centre d’Esclerosi Múltiple de Catalunya, CEM-Cat, Unitat de Neuroimmunologia Clínica, Hospital Universitari Vall d’Hebron (HUVH), Barcelona, Spain
4. ⁴Instituto de Parasitología y Biomedicina ‘López Neyra’, C. S. I. C., Granada, Spain
5. ⁵Unidad de Esclerosis Múltiple. Hospital Virgen Macarena, Sevilla, Spain
6. ⁶Servicio de Biología Molecular. Hospital Virgen Macarena, Sevilla, Spain
7. ⁷Multiple Sclerosis Unit, Neurology Department, Hospital Clínico S. Carlos, Madrid, Spain
8. ⁸Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Leioa, Spain
9. ⁹IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
10. ¹⁰Servicio de Genética, Hospital de Basurto, Bilbao, Spain
11. ¹¹Servicio de Neurología, Hospital de Basurto, Bilbao, Spain
12. ¹²Laboratorio de Investigación, Hospital Civil, Málaga, Spain
13. ¹³Servicio de Neurología, Unidad de Esclerosis Múltiple, Hospital Donostia, San Sebastián, Spain
14. ¹⁴Área de Neurociencias, Insti. Investigación Sanitaria Biodonostia, San Sebastián, Spain
15. ¹⁵Neurology Service, Hospital Clinic and Institut d’Investigació Biomèdica Pi i Sunyer (IDIBAPS), Barcelona, Spain

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune origin, triggered by genetic and environmental risk factors. A recent genome-wide association study conducted on MS identified new biallelic markers outside the HLA (human leucocyte antigen) region involved in disease susceptibility: rs1109670(DDEF2); rs1458175 (PDZRN4); rs1529316 and rs2049306 (CSMD1);rs16914086 (TBC1D2); rs1755289 (SH3GL2); rs1841770 (ZIC1); rs651477(EN1); rs7607490 (TRIB2); rs397020 (C20orf46); rs908821 (SLC25A36);rs7672826 (MGC45800) and rs9523762 (GPC5). We aimed at replicating these top association signals in a Spanish cohort of 2863 MS patients and 2930 sex- and age-matched controls. Only rs9523762 mapping in theGPC5 gene was significantly associated (G allele, P=1.6 × 10⁻⁵; odds ratio (95% confidence interval)=1.23 (1.12–1.36)), supporting a role for this proteoglycan in MS predisposition. The independent replication of association signals to validate data generated by genome-wide association scans is a first step in the effort to improve patient care.

Keywords: 

multiple sclerosis; genetics; GWAS; GPC5

Urdangarencias sanitarias

Este señor, al que los incautos ciudadanos creíamos apartado de la vera de la Royal Family, pues parece que no es así. El todavía presunto chorizo de Palma visita al Jefe del Estado como si tal cosa. Es que da vergüenza ajena. Se podían cortar un poquito. Meterlo por la puerta de atrás. Pero de eso nada. Vamos que es como si nos escupieran en la cara. Somos cornudos y apaleados. Pero eso sí, iguales ante la ley.

El cerebro lector es culturalmente universal

Brain's 'reading centres' are culturally universal

Whether you are reading in Chinese or French, the same brain areas light up.

• Philip Ball

26 November 2012

Reading Chinese characters involves the same brain regions as used when reading French.

PZECHNER / ALAMY

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¿Qué partes del cerebro participan en el proceso de la lectura?, ¿Cómo se maneja el cerebro humano con los signos?. Esa es la fascinante exploración de la que se da cuenta en el presente artículo de "Nature". Y el resultado no deja de ser un poco sorprendente (como casi todo en las neurociencias). Para aprender a leer en chino, recuerden que se examinan caracteres, funcionan las mismas regiones cerebrales que cuando leemos francés. La lectura involucra dos sistemas neurales: uno que reconoce la forma de la palabra y otro que comprueba los movimientos físicos para marcar una página, o hacer señales. Quedan muchos misterios por resolver. Entre ellos si las redes neuronales involucradas en el proceso de lectura digamos que son universales (válidas para cualquier persona) o condicionadas por la cultura a la que pertenezca.

Learning to read Chinese might seem daunting to Westerners used to an alphabetic script, but brain scans of French and Chinese native speakers show that people harness the same brain centres for reading across cultures. The findings are published today in the Proceedings of the National Academy of Sciences¹.

Reading involves two neural systems: one that recognizes the shape of the word and a second that asseses the physical movements used to make the marks on a page, says study leader Stanislas Dehaene, a cognitive neuroscientist the National Institute of Health and Medical Research in Gif-sur-Yvette, France.

But it has been unclear whether the brain networks responsible for reading are universal or culturally distinct. Previous studies have suggested that alphabetic writing systems (such as French) and logographic ones (such as Chinese, in which single characters represent entire words) writing systems might engage different networks in the brain.

To explore this question, Dehaene and his colleagues used functional magnetic resonance imaging to examine brain activity in Chinese and French people while they read their native languages.

The researchers found that both Chinese and French people use the visual and gestural systems while reading their native language, but with different emphases that reflect the different demands of each language.

“Rather than focusing on ear and eye in reading, the authors rightly point out that hand and eye are critical players,” says Uta Frith, a cognitive neuroscientist at University College London. “This could lead into novel directions — for instance, it might provide answers why many people with dyslexia also have very poor handwriting and not just poor spelling.”

Related stories

• Brain connectivity predicts reading skills
• Dyslexic diversity

Understanding how the brain decodes symbols during reading — using both visual and motor centres — might also inform learning strategies for general literacy, and ways to attune them to children or adults.

Subliminal images

There is evidence^2, 3 that for all languages, reading activates a shape-recognition region in the brain’s posterior left hemisphere — the visual word-forming area (VWFA). But some research⁵ has indicated that readers of Chinese — which places great emphasis on the order and direction of writing strokes — also use other brain networks involved in the motor skills that are engaged for writing.

Motor processing is universally used for writing and involves⁴ a brain region known as Exner’s area. The researchers postulated that this region is also activated in reading to interpret the gestures assumed to have gone into making the marks.

To try to isolate the different brain regions involved in reading, Dehaene and his colleagues measured Chinese and French readers' response times in recognizing words on a screen. But unbeknown to the subjects, their responses were being subtly manipulated by a process called priming, in which other words or word-like symbols appear for just 50 milliseconds before the target word is shown — too briefly for the subjects to register the ‘primes’ consciously.

These subliminal images can assist or hinder the recognition process by tampering with the visual or the gestural reading system. For example, the priming word could be the target word written backwards — this slows the recognition process by disrupting the gestural reading system. Or flashing the same target word assists recognition when it is shown properly later.

The researchers found that both the VWFA and Exner’s area were indeed activated in French and Chinese subjects. But there were cultural differences: for example, the effects of gestural direction were stronger for the Chinese.

Frith says that harnessing the gestural system more in education more might help young children with reading. “So far the motor decoding side has been rather neglected in reading education,” she says.

Nature

 

doi:10.1038/nature.2012.11883