Retail pork products in the U.S. have a higher prevalence of methicillin-resistant Staphylococcus aureus bacteria (MRSA) than previously identified, according to new research by the University of Iowa College of Public Health and the Institute for Agriculture and Trade Policy. MRSA can occur in the environment and in raw meat products, and is estimated to cause around 185,000 cases of food poisoning each year. The bacteria can also cause serious, life-threatening infections of the bloodstream, skin, lungs and other organs. MRSA is resistant to a number of antibiotics.
The study, published Jan. 19 in the online science journal PLoS ONE, represents the largest sampling of raw meat products for MRSA contamination to date in the U.S. The researchers collected 395 raw pork samples from 36 stores in Iowa, Minnesota and New Jersey. Of these samples, 26 -- or about 7 percent -- carried MRSA.
"This study shows that the meat we buy in our grocery stores has a higher prevalence of staph than we originally thought," says lead study author Tara Smith, Ph.D., interim director of the UI Center for Emerging and Infectious Diseases and assistant professor of epidemiology. "With this knowledge, we can start to recommend safer ways to handle raw meat products to make it safer for the consumer."
The study also found no significant difference in MRSA contamination between conventional pork products and those raised without antibiotics or antibiotic growth promotants.
"We were surprised to see no significant difference in antibiotic-free and conventionally produced pork," Smith says. "Though it's possible that this finding has more to do with the handling of the raw meat at the plant than the way the animals were raised, it's certainly worth exploring further."
**Source: University of Iowa
23 January 2012
Ron Fouchier en EL PAIS: "Debemos compartir los datos del H5N1 para prevenir una posible pandemia”
La libertad de investigación y divulgación de experimentos científicos y el temor a que estos descubrimientos sean utilizados para ataques bioterroristas libran un duro pulso. Dos equipos de expertos en enfermedades infecciosas, en Europa y Estados Unidos, han descubierto las mutaciones genéticas necesarias para la transmisión del virus H5N1 entre personas, que podría tener consecuencias letales. Y se ha producido un hecho sin precedentes. Science y Nature, las más prestigiosas revistas científicas, han retrasado la presentación de los trabajos ante las presiones del Consejo Asesor Científico estadounidense para la Bioseguridad, órgano asesor del Gobierno. Las revistas anunciaron simultáneamente la semana pasada la suspensión, durante 60 días, de las publicaciones.
En Holanda, Ron Fouchier, virólogo del Centro Médico Universitario Erasmus, de Rotterdam, y responsable de uno de los estudios, sostiene que publicar los resultados de la investigación es esencial para proteger la salud pública mundial. “Si no compartimos la información con el resto de la comunidad científica, será difícil prevenir una posible pandemia”, afirmó a este diario Fouchier desde su despacho la víspera de la moratoria.
En Washington, por el contrario, los expertos en bioseguridad afirman que solo suprimiendo los detalles metodológicos “podrá evitarse que caiga en manos equivocadas”. En otras palabras, es mejor no dejar rastro técnico para que nadie se lance a crear un arma biológica. Yoshihiro Kawaoka, de la Universidad de Wisconsin (Madison), ha descubierto las mismas mutaciones.
Tanto Fouchier como Kawaoka y su colega español Adolfo García Sastre, de la Escuela de Medicina del Hospital Mount Sinai (Nueva York), asumieron la moratoria voluntaria. En una carta firmada por todos los investigadores (39 en total) explican que así quieren dar tiempo al debate sobre el riesgo que puedan suponer sus trabajos, y reconocen la alarma surgida. Ahora, los científicos y las direcciones de Science y Nature estudian publicarlo en dos fases.
En Holanda, Ron Fouchier, virólogo del Centro Médico Universitario Erasmus, de Rotterdam, y responsable de uno de los estudios, sostiene que publicar los resultados de la investigación es esencial para proteger la salud pública mundial. “Si no compartimos la información con el resto de la comunidad científica, será difícil prevenir una posible pandemia”, afirmó a este diario Fouchier desde su despacho la víspera de la moratoria.
En Washington, por el contrario, los expertos en bioseguridad afirman que solo suprimiendo los detalles metodológicos “podrá evitarse que caiga en manos equivocadas”. En otras palabras, es mejor no dejar rastro técnico para que nadie se lance a crear un arma biológica. Yoshihiro Kawaoka, de la Universidad de Wisconsin (Madison), ha descubierto las mismas mutaciones.
Tanto Fouchier como Kawaoka y su colega español Adolfo García Sastre, de la Escuela de Medicina del Hospital Mount Sinai (Nueva York), asumieron la moratoria voluntaria. En una carta firmada por todos los investigadores (39 en total) explican que así quieren dar tiempo al debate sobre el riesgo que puedan suponer sus trabajos, y reconocen la alarma surgida. Ahora, los científicos y las direcciones de Science y Nature estudian publicarlo en dos fases.
-El holandés Fouchier descubrió cómo el virus puede saltar entre personas
“En Science habrá una versión recortada y divulgativa, y otra más larga para los científicos sujeta a requisitos de confidencialidad señalados por Estados Unidos”, dice Fouchier, que se muestra tan educado como contundente. “Sabíamos que era posible encontrar las mutaciones genéticas [cinco en este caso] para que el virus H5N1 pudiera transmitirse entre humanos por vía aérea, con toses y estornudos. Trabajamos en condiciones de máxima seguridad biológica y hay riesgos, claro que sí. Pero es mayor el beneficio que supone prevenir una posible pandemia de gripe aviar. Estas trabas entorpecen el desarrollo científico. En EE UU, sin embargo, el peligro de bioterrorismo les parece enorme”.
La gripe aviar es una enfermedad infecciosa que afecta a las aves y se transmite entre ellas a través de las heces, el agua y los alimentos, o bien por vía aérea. El contagio del animal al ser humano es excepcional y requiere un contacto directo y constante. De momento, el único indicio de transmisión entre personas ha sido hallado por la Organización Mundial de la Salud en una familia indonesia que vivía hacinada.
“Desde 2003, se han registrado varios brotes del virus H5N1 en aves, y para contenerlos hay que sacrificarlas. Ha habido episodios en Asia, Oriente Próximo y África, países donde es difícil erradicarla. Cuando apareció en Holanda hace ocho años, hubo que matar a 30 millones de aves de corral y domésticas. Una operación muy difícil en zonas en desarrollo con escasez de alimentos. El brote de 2003 empezó en Asia y se propagó por no actuar inmediatamente”, recuerda Fouchier.
Durante su experimento utilizó hurones, un mamífero cuya respuesta ante la gripe es como la de los humanos. Una vez modificado el virus H5N1, se consiguió una variante que pasa con facilidad de un animal a otro. “No nos parecemos en nada y, sin embargo, cuando el virus se adhiere a los receptores de las células en el tracto respiratorio, el animal y nosotros sufrimos igual. Incluso si desemboca en neumonía”.
“En Science habrá una versión recortada y divulgativa, y otra más larga para los científicos sujeta a requisitos de confidencialidad señalados por Estados Unidos”, dice Fouchier, que se muestra tan educado como contundente. “Sabíamos que era posible encontrar las mutaciones genéticas [cinco en este caso] para que el virus H5N1 pudiera transmitirse entre humanos por vía aérea, con toses y estornudos. Trabajamos en condiciones de máxima seguridad biológica y hay riesgos, claro que sí. Pero es mayor el beneficio que supone prevenir una posible pandemia de gripe aviar. Estas trabas entorpecen el desarrollo científico. En EE UU, sin embargo, el peligro de bioterrorismo les parece enorme”.
La gripe aviar es una enfermedad infecciosa que afecta a las aves y se transmite entre ellas a través de las heces, el agua y los alimentos, o bien por vía aérea. El contagio del animal al ser humano es excepcional y requiere un contacto directo y constante. De momento, el único indicio de transmisión entre personas ha sido hallado por la Organización Mundial de la Salud en una familia indonesia que vivía hacinada.
“Desde 2003, se han registrado varios brotes del virus H5N1 en aves, y para contenerlos hay que sacrificarlas. Ha habido episodios en Asia, Oriente Próximo y África, países donde es difícil erradicarla. Cuando apareció en Holanda hace ocho años, hubo que matar a 30 millones de aves de corral y domésticas. Una operación muy difícil en zonas en desarrollo con escasez de alimentos. El brote de 2003 empezó en Asia y se propagó por no actuar inmediatamente”, recuerda Fouchier.
Durante su experimento utilizó hurones, un mamífero cuya respuesta ante la gripe es como la de los humanos. Una vez modificado el virus H5N1, se consiguió una variante que pasa con facilidad de un animal a otro. “No nos parecemos en nada y, sin embargo, cuando el virus se adhiere a los receptores de las células en el tracto respiratorio, el animal y nosotros sufrimos igual. Incluso si desemboca en neumonía”.
-“La presión en EEUU es tremenda y priman los expertos en bioseguridad”
Según Fouchier, algunas de las mutaciones del virus halladas en el laboratorio ya se habrían producido de forma natural en varias zonas del mundo. “Puede que nunca desencadenen una pandemia, pero nuestra tarea es preparar y probar vacunas y antivirales y compartir los datos con los países y laboratorios que la necesitan para prevenir una posible pandemia. Fíjese lo mucho que aprendimos en 2005 estudiando la gripe española [que mató a 40 millones de personas entre 1918 y 1919]. Era un virus destructivo y no pasó nada con los datos de las investigaciones”, prosigue.
Uno de los aspectos que más le molesta es el tiempo invertido en explicar su postura. “Estoy inmerso en una vorágine y he observado que en Europa la campaña de información es mesurada y hablan los científicos. En EE UU, las presiones son tremendas y priman los expertos en bioseguridad”. Él ha recibido fondos del Instituto Nacional de Salud estadounidense. “El actual clima político mundial puede explicar estas diferencias. Aunque lo más lógico sería que los virólogos dijeran lo que debe hacerse, y los especialistas en bioseguridad recomendaran cómo hacerlo. Pensamos que habría reticencias, pero no esto”, sostiene.
Pese a que el virus de la gripe muta deprisa, y las pandemias suelen ser cíclicas —a la gripe española le siguieron la asiática (1957), de Hong Kong (1968) y Rusia (1977)—, la vacuna solo puede lograrse si surge el subtipo capaz de llegar a las personas. “Hay que prepararse. La posibilidad de una pandemia es pequeña, pero sus efectos serían tremendos”, concluye el virólogo holandés.
Según Fouchier, algunas de las mutaciones del virus halladas en el laboratorio ya se habrían producido de forma natural en varias zonas del mundo. “Puede que nunca desencadenen una pandemia, pero nuestra tarea es preparar y probar vacunas y antivirales y compartir los datos con los países y laboratorios que la necesitan para prevenir una posible pandemia. Fíjese lo mucho que aprendimos en 2005 estudiando la gripe española [que mató a 40 millones de personas entre 1918 y 1919]. Era un virus destructivo y no pasó nada con los datos de las investigaciones”, prosigue.
Uno de los aspectos que más le molesta es el tiempo invertido en explicar su postura. “Estoy inmerso en una vorágine y he observado que en Europa la campaña de información es mesurada y hablan los científicos. En EE UU, las presiones son tremendas y priman los expertos en bioseguridad”. Él ha recibido fondos del Instituto Nacional de Salud estadounidense. “El actual clima político mundial puede explicar estas diferencias. Aunque lo más lógico sería que los virólogos dijeran lo que debe hacerse, y los especialistas en bioseguridad recomendaran cómo hacerlo. Pensamos que habría reticencias, pero no esto”, sostiene.
Pese a que el virus de la gripe muta deprisa, y las pandemias suelen ser cíclicas —a la gripe española le siguieron la asiática (1957), de Hong Kong (1968) y Rusia (1977)—, la vacuna solo puede lograrse si surge el subtipo capaz de llegar a las personas. “Hay que prepararse. La posibilidad de una pandemia es pequeña, pero sus efectos serían tremendos”, concluye el virólogo holandés.
**Foto de CORDON PRESS
**Publicado en "EL PAIS"
Autism redefined: Yale researchers study impact of proposed diagnostic criteria
Getting an autism diagnosis could be more difficult in 2013 when a revised diagnostic definition goes into effect. The proposed changes may affect the proportion of individuals who qualify for a diagnosis of autism spectrum disorder, according to preliminary data presented by Yale School of Medicine researchers at a meeting of the Icelandic Medical Association. The proposed changes to the diagnostic definition would be published in the fifth edition of the American Psychiatric Association's (APA) "Diagnostic and Statistical Manual of Mental Disorders (DSM-5)."
"Given the potential implications of these findings for service eligibility, our findings offer important information for consideration by the task force finalizing DSM-5 diagnostic criteria," said Yale Child Study Center (CSC) director Fred Volkmar, M.D., who conducted the study with CSC colleagues Brian Reichow and James McPartland.
Volkmar and his team found that in a group of individuals without intellectual disabilities who were evaluated during the 1994 DSM-IV field trial, it was estimated that approximately half might not qualify for a diagnosis of autism under the proposed new definition.
Volkmar stressed that these preliminary findings relate only to the most cognitively able and may have less impact on diagnosis of more cognitively disabled people. "Use of such labels, particularly in the United States, can have important implications for service," he said. "Major changes in diagnosis also pose issues for comparing results across research studies."
Volkmar first presented the preliminary research results in September at Yale and in October at the Institute On Autism American Academy of Child Adolescent Psychiatry Meeting In Toronto. Volkmar and colleagues will publish full study results in the April print edition of the Journal of the American Academy of Child and Adolescent Psychiatry. The study may be available online as early as late February or early March.
**Source: Yale University
"Given the potential implications of these findings for service eligibility, our findings offer important information for consideration by the task force finalizing DSM-5 diagnostic criteria," said Yale Child Study Center (CSC) director Fred Volkmar, M.D., who conducted the study with CSC colleagues Brian Reichow and James McPartland.
Volkmar and his team found that in a group of individuals without intellectual disabilities who were evaluated during the 1994 DSM-IV field trial, it was estimated that approximately half might not qualify for a diagnosis of autism under the proposed new definition.
Volkmar stressed that these preliminary findings relate only to the most cognitively able and may have less impact on diagnosis of more cognitively disabled people. "Use of such labels, particularly in the United States, can have important implications for service," he said. "Major changes in diagnosis also pose issues for comparing results across research studies."
Volkmar first presented the preliminary research results in September at Yale and in October at the Institute On Autism American Academy of Child Adolescent Psychiatry Meeting In Toronto. Volkmar and colleagues will publish full study results in the April print edition of the Journal of the American Academy of Child and Adolescent Psychiatry. The study may be available online as early as late February or early March.
**Source: Yale University
Sweeping genetic analysis of rare disease yields common mechanism of hypertension
Analyzing all the genes of dozens of people suffering from a rare form of hypertension, Yale University researchers have discovered a new mechanism that regulates the blood pressure of all humans. The findings by an international research team headed by Yale scientists, published online Jan. 22 in the journal Nature, may help explain what goes wrong in the one billion people who suffer from high blood pressure. The study also demonstrates the power of new DNA sequencing methods to find previously unknown disease-causing genes.
The team used a technique called whole exome sequencing -- an analysis of the makeup of all the genes -- to study a rare inherited form of hypertension characterized by excess levels of potassium in the blood. They found mutations in either of two genes that caused the disease in affected members of 41 families suffering from the condition.
The two genes interact with one another in a complex that targets other proteins for degradation, and they orchestrate the balance between salt reabsorption and potassium secretion in the kidney.
"These genes were not previously suspected to play a role in blood pressure regulation, but if they are lost, the kidney can't put the brakes on salt reabsorption, resulting in hypertension," said Richard Lifton, Sterling Professor and chair of the Department of Genetics at Yale and senior author of the paper.
The mutations had previously been difficult to find because there were very few affected members in each family, so traditional methods to map the genes' locations had been ineffective.
"The mutations in one gene were almost all new mutations found in affected patients but not their parents, while mutations in the other gene could be either dominant or recessive. The exome sequencing technology was ideally suited to cutting through these complexities," said Lynn Boyden of Yale, the first author of the paper.
The next step is to establish how these new components are involved in regulating sodium reabsorption in the kidney, in hopes of finding new ways intervene in hypertension, a major global health problem.
"We are finding all the individual parts to a complicated machine, and we need to understand how they are all put together to make the machine work," said Lifton, who is also an investigator of the Howard Hughes Medical Institute.
Physicians from 10 countries and 17 states in the United States recruited patients and families with this rare disease and participated in the research.
**Source: Yale University
Nike lanza una pulsera para ponerse en forma
Es posible que a estas alturas, con el año recién estrenado, tenga ya una aplicación de fitness en su teléfono móvil. Me refiero a una de esas que llevan el control del ejercicio realizado, la velocidad a la que se corre, las distancias. Ese tipo de cosas.
Han tenido un crecimiento espectacular durante 2011 y se supone que es uno de los campos con mayor potencial de crecimiento de los próximos dos años. En 2010, las aplicaciones de salud móvil suponían un mercado de 1,700 millones de dólares. En 2014 se espera que llegue a los 4.100 millones.
Ya se trate de Runkeeper, Nike+, Endomondo o Runtastic, estas apps suelen tener algunos denominadores en común. Utilizan el GPS y los acelerómetros del teléfono y en algunos casos algún tipo de sensor externo para completar las medidas con el ritmo cardiaco, guardan un archivo histórico de los ejercicios realizados y permiten comprar y competir con otros usuarios y, por último, incluyen formas de compartir de forma automática los resultados en redes sociales.
Era evidente que el concepto tenía que evolucionar y lo está haciendo gracias a sensores más avanzados, capaces de medir, por ejemplo, el movimiento durante las fases de sueño. Algunos sistemas, como Jawbone Up, también animan al usuario a llevar un control de los alimentos ingeridos durante el día. La idea es que cuantos más datos se tengan de las actividades realizadas más sencillo es ver la evolución del rendimiento y alcanzar las metas elegidas.
La última apuesta la ha hecho Nike. La semana pasada un nuevo sensor, Fuel, que al igual que Jawbone Up es una pulsera. La diferencia es que además de tener acelerómetros integrados cuenta con una aplicación que es capaz de calcular los niveles de consumo de oxígeno que tiene nuestro cuerpo cuando realiza diferentes actividades. En base a ese consumo elabora crea una serie de puntuaciones que permiten medir el nivel de actividad del día. Unas luces LED en la superficie de la pulsera indican como de lejos o cerca estamos de cumplir los objetivos marcados y el número general de actividad puede leerse en una pequeña pantalla integrada.
Por ahora la pulsera funciona sólo como accesorio para dispositivos iOS (iPhone o iPod Touch) pero está en camino una app para teléfonos Android. Sale a la venta con un precio aproximado de 115 euros.
Han tenido un crecimiento espectacular durante 2011 y se supone que es uno de los campos con mayor potencial de crecimiento de los próximos dos años. En 2010, las aplicaciones de salud móvil suponían un mercado de 1,700 millones de dólares. En 2014 se espera que llegue a los 4.100 millones.
Ya se trate de Runkeeper, Nike+, Endomondo o Runtastic, estas apps suelen tener algunos denominadores en común. Utilizan el GPS y los acelerómetros del teléfono y en algunos casos algún tipo de sensor externo para completar las medidas con el ritmo cardiaco, guardan un archivo histórico de los ejercicios realizados y permiten comprar y competir con otros usuarios y, por último, incluyen formas de compartir de forma automática los resultados en redes sociales.
Era evidente que el concepto tenía que evolucionar y lo está haciendo gracias a sensores más avanzados, capaces de medir, por ejemplo, el movimiento durante las fases de sueño. Algunos sistemas, como Jawbone Up, también animan al usuario a llevar un control de los alimentos ingeridos durante el día. La idea es que cuantos más datos se tengan de las actividades realizadas más sencillo es ver la evolución del rendimiento y alcanzar las metas elegidas.
La última apuesta la ha hecho Nike. La semana pasada un nuevo sensor, Fuel, que al igual que Jawbone Up es una pulsera. La diferencia es que además de tener acelerómetros integrados cuenta con una aplicación que es capaz de calcular los niveles de consumo de oxígeno que tiene nuestro cuerpo cuando realiza diferentes actividades. En base a ese consumo elabora crea una serie de puntuaciones que permiten medir el nivel de actividad del día. Unas luces LED en la superficie de la pulsera indican como de lejos o cerca estamos de cumplir los objetivos marcados y el número general de actividad puede leerse en una pequeña pantalla integrada.
Por ahora la pulsera funciona sólo como accesorio para dispositivos iOS (iPhone o iPod Touch) pero está en camino una app para teléfonos Android. Sale a la venta con un precio aproximado de 115 euros.
**Publicado en "EL MUNDO"
Gladstone scientists identify genetic mechanism linked to congenital heart disease
Scientists at the Gladstone Institutes have identified a finely tuned mechanism by which fetal heart muscle develops into a healthy and fully formed beating heart -- offering new insight into the genetic causes of congenital heart disease and opening the door to one day developing therapies to fight this chronic and potentially fatal disorder. In a paper being published online in Nature Genetics, researchers in the laboratory of Gladstone Senior Investigator Benoit Bruneau, PhD, describe the roles that two genes -- Ezh2 and Six1 -- play in embryonic heart development, while also uncovering how the genetic basis of embryonic heart formation can have profound health consequences later in life.
This research highlights the emerging importance of a biological process called "epigenetics," in which a genetic change that is inherited by a cell or organism early during development has long-term consequences. Epigenetics is of particular interest in heart development, as the incorrect activation of genes in fetal development can lead to congenital heart disease into adulthood.
"Approximately 1.3 million children and adults in the United States live with congenital heart disease -- requiring daily medications, surgeries and for some, heart transplants," said Dr. Bruneau, who is also a professor of Pediatrics at the University of California, San Francisco, with which Gladstone is affiliated. "An understanding of the epigenetic regulation of heart development could someday bring us closer to improving the lives of these individuals."
At specific times during healthy heart development, Ezh2 acts as a "master regulator," shutting off genes that are no longer needed or that need to be kept off. In the past, the focus has been on which genes get switched on during normal heart development. But in this paper, Dr. Bruneau, along with Gladstone Postdoctoral Scholar Paul Delgado-Olguin, PhD, investigated which genes must remain off to ensure the development of a healthy heart.
In laboratory experiments, Drs. Bruneau and Delgado-Olguin removed Ezh2 from mice at various developmental stages, monitoring any ensuing genetic or physical changes and comparing them to mice whose Ezh2 remained intact. Surprisingly, mice without Ezh2 developed normally in the uterus. It wasn't until after birth that they began to show problems. Their hearts became enlarged and weakened and were unable to pump blood efficiently. An enlarged heart is a hallmark feature of cardiomyopathy, a form of congenital heart disease that afflicts thousands of children each year and for which the only manifestation may be sudden death.
Further analysis revealed that Six1 is normally on only for a brief period during heart development, after which Ezh2 shuts it off for good. But without Ezh2 to act as a regulator, Six1 remains on -- leading to heart problems later in life.
"When Six1 remains active for too long in Ezh2-deficient mice, it boosts the activity of other genes that shouldn't be activated in heart-muscle cells -- such as genes that make skeletal muscle," said Dr. Delgado-Olguin. "The enlargement and thickening of the mice's hearts over time eventually led to heart failure."
This breakthrough may help researchers improve their understanding of the genetic causes of congenital heart disease while also pointing the way to potential therapies. For example, a type of congenital heart disease called dilated cardiomyopathy is caused by mutations in Eya4, a gene that is also regulated by Ezh2 in the heart.
"Six1 is just one of many Ezh2-regulated genes that are vital for heart development," said Dr. Bruneau. "Our next goal is to find out exactly how Ezh2 regulates these other genes, so that we can begin to develop a complete genomic blueprint of how a heart becomes a heart."
This research highlights the emerging importance of a biological process called "epigenetics," in which a genetic change that is inherited by a cell or organism early during development has long-term consequences. Epigenetics is of particular interest in heart development, as the incorrect activation of genes in fetal development can lead to congenital heart disease into adulthood.
"Approximately 1.3 million children and adults in the United States live with congenital heart disease -- requiring daily medications, surgeries and for some, heart transplants," said Dr. Bruneau, who is also a professor of Pediatrics at the University of California, San Francisco, with which Gladstone is affiliated. "An understanding of the epigenetic regulation of heart development could someday bring us closer to improving the lives of these individuals."
At specific times during healthy heart development, Ezh2 acts as a "master regulator," shutting off genes that are no longer needed or that need to be kept off. In the past, the focus has been on which genes get switched on during normal heart development. But in this paper, Dr. Bruneau, along with Gladstone Postdoctoral Scholar Paul Delgado-Olguin, PhD, investigated which genes must remain off to ensure the development of a healthy heart.
In laboratory experiments, Drs. Bruneau and Delgado-Olguin removed Ezh2 from mice at various developmental stages, monitoring any ensuing genetic or physical changes and comparing them to mice whose Ezh2 remained intact. Surprisingly, mice without Ezh2 developed normally in the uterus. It wasn't until after birth that they began to show problems. Their hearts became enlarged and weakened and were unable to pump blood efficiently. An enlarged heart is a hallmark feature of cardiomyopathy, a form of congenital heart disease that afflicts thousands of children each year and for which the only manifestation may be sudden death.
Further analysis revealed that Six1 is normally on only for a brief period during heart development, after which Ezh2 shuts it off for good. But without Ezh2 to act as a regulator, Six1 remains on -- leading to heart problems later in life.
"When Six1 remains active for too long in Ezh2-deficient mice, it boosts the activity of other genes that shouldn't be activated in heart-muscle cells -- such as genes that make skeletal muscle," said Dr. Delgado-Olguin. "The enlargement and thickening of the mice's hearts over time eventually led to heart failure."
This breakthrough may help researchers improve their understanding of the genetic causes of congenital heart disease while also pointing the way to potential therapies. For example, a type of congenital heart disease called dilated cardiomyopathy is caused by mutations in Eya4, a gene that is also regulated by Ezh2 in the heart.
"Six1 is just one of many Ezh2-regulated genes that are vital for heart development," said Dr. Bruneau. "Our next goal is to find out exactly how Ezh2 regulates these other genes, so that we can begin to develop a complete genomic blueprint of how a heart becomes a heart."
**Source: Gladstone Institutes
Vaccines to boost immunity where it counts, not just near shot site
Researchers at Duke University Medical Center have created synthetic nanoparticles that target lymph nodes and greatly boost vaccine responses, said lead author Ashley St. John, PhD, a researcher at Duke-NUS Graduate Medical School. The paper was published online in the journal Nature Materials on Jan. 22.
Currently all other adjuvants (substances added to vaccines to help to boost the immune response) are thought to enhance immunity at the skin site where the vaccine is injected rather than going to the lymph nodes, where the most effective immune reactions occur.
The current study used mice to show it is possible to shift the delivery path directly to the lymph nodes.
The researchers based their strategy on their observation that mast cells, which are cells that are found in the skin that fight infections, also communicate directly to the lymph nodes by releasing nanoparticles called granules.
"Our strategy is unique because we have based our bioengineered particles on those naturally produced by mast cells, which effectively solve the same problem we are trying to solve of combating infection," said St. John, who is in the Duke-NUS Program in Emerging Infectious Diseases.
The synthetic granules consist of a carbohydrate backbone that holds tiny, encapsulated inflammatory mediators such as tumor necrosis factor (TNF). These particles, when injected, mimic the attributes of the granules found in natural cells, and the synthetic particles also target the draining lymph nodes and provide for the timed release of the encapsulated material.
Traditional vaccine adjuvants may help antigens (the small part of a pathogen that is injected during vaccination that the body reacts to) to persist so the body can have an immune reaction and build antibodies so that when a real pathogen, such as the flu virus arrives, it will be conquered. Alternatively, adjuvants may activate cells called dendritic cells, which pick up pathogen parts and must travel from the skin to lymph nodes where immune reactions are initiated.
The Duke team, however, has created a vaccine adjuvant of nanoparticles that are capable of traveling from the point of injection to the lymph nodes where they act on many cell types of the immune system to spur the right reaction for a greatly increased immune response.
The researchers found that they could use this adjuvant in vaccinations of mice with the influenza A virus.
In levels of flu virus exposure that would be lethal in typical mice, the vaccinated mice were able to fight off the disease and had an increased survival rate, thanks to the effective immune response the particles stimulated.
The researchers also showed they could load the same type of particles with a different immune factor, IL-12, that directed a response toward a different set of lymphocytes. This is an important finding since certain types of infections require specialized responses to be overpowered by the body.
St. John said the flexibility of the synthetic particles and their ability to target certain lymph nodes represented a new avenue of personalized medical treatment -- personalized vaccines.
Senior author Soman Abraham, PhD, professor of pathology, immunology and molecular genetics and microbiology at Duke in Durham, NC, and emerging infectious diseases at Duke-NUS, is cautiously optimistic that the mast-cell-inspired synthetic particles could make their way into human use soon.
"It should not be long because all the individual cytokines (immune system factors) and additional materials loaded into these particles are already FDA approved for use in humans," Abraham said. "There is a lot of interest in nanoparticle-based therapy, but we are basing our materials on our observation of mast cells in nature. This is an informed application to deliver the right material to the right place in the body to get the most effective immune reaction."
**Source: Duke University Medical Center
Currently all other adjuvants (substances added to vaccines to help to boost the immune response) are thought to enhance immunity at the skin site where the vaccine is injected rather than going to the lymph nodes, where the most effective immune reactions occur.
The current study used mice to show it is possible to shift the delivery path directly to the lymph nodes.
The researchers based their strategy on their observation that mast cells, which are cells that are found in the skin that fight infections, also communicate directly to the lymph nodes by releasing nanoparticles called granules.
"Our strategy is unique because we have based our bioengineered particles on those naturally produced by mast cells, which effectively solve the same problem we are trying to solve of combating infection," said St. John, who is in the Duke-NUS Program in Emerging Infectious Diseases.
The synthetic granules consist of a carbohydrate backbone that holds tiny, encapsulated inflammatory mediators such as tumor necrosis factor (TNF). These particles, when injected, mimic the attributes of the granules found in natural cells, and the synthetic particles also target the draining lymph nodes and provide for the timed release of the encapsulated material.
Traditional vaccine adjuvants may help antigens (the small part of a pathogen that is injected during vaccination that the body reacts to) to persist so the body can have an immune reaction and build antibodies so that when a real pathogen, such as the flu virus arrives, it will be conquered. Alternatively, adjuvants may activate cells called dendritic cells, which pick up pathogen parts and must travel from the skin to lymph nodes where immune reactions are initiated.
The Duke team, however, has created a vaccine adjuvant of nanoparticles that are capable of traveling from the point of injection to the lymph nodes where they act on many cell types of the immune system to spur the right reaction for a greatly increased immune response.
The researchers found that they could use this adjuvant in vaccinations of mice with the influenza A virus.
In levels of flu virus exposure that would be lethal in typical mice, the vaccinated mice were able to fight off the disease and had an increased survival rate, thanks to the effective immune response the particles stimulated.
The researchers also showed they could load the same type of particles with a different immune factor, IL-12, that directed a response toward a different set of lymphocytes. This is an important finding since certain types of infections require specialized responses to be overpowered by the body.
St. John said the flexibility of the synthetic particles and their ability to target certain lymph nodes represented a new avenue of personalized medical treatment -- personalized vaccines.
Senior author Soman Abraham, PhD, professor of pathology, immunology and molecular genetics and microbiology at Duke in Durham, NC, and emerging infectious diseases at Duke-NUS, is cautiously optimistic that the mast-cell-inspired synthetic particles could make their way into human use soon.
"It should not be long because all the individual cytokines (immune system factors) and additional materials loaded into these particles are already FDA approved for use in humans," Abraham said. "There is a lot of interest in nanoparticle-based therapy, but we are basing our materials on our observation of mast cells in nature. This is an informed application to deliver the right material to the right place in the body to get the most effective immune reaction."
**Source: Duke University Medical Center
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