vendredi 17 octobre 2014
schéma-bilan :
http://www.biologieenflash.net/sommaire.html
→ géologie interne → subduction
Sujet
bac 2013 Partie I (8 points)
Le magmatisme en zone de
subduction
Les zones de subduction, domaines de convergence
de la lithosphère, sont le siège d'une importante activité
magmatique. Celle-ci aboutit à une formation de croûte
continentale.
Question : Décrire comment dans un contexte de
subduction se met en placel’activité magmatique et préciser
comment celle-ci intervient dans la production de nouveaux matériaux
continentaux.
L’exposé doit être structuré avec une
introduction et une conclusion et sera accompagné d’un schéma de
synthèse.
jeudi 16 octobre 2014
Ebola-Infected Nurse Flew
The second healthcare worker to have contracted Ebola within the U.S. flew on a commercial airline after having cared for a Dallas patient who died from the virus.
By Kerry Grens | October 15, 2014
FLICKR, NIAIDAmber Vinson, a registered nurse who cared for a now-deceased Ebola patient in Dallas, flew to Cleveland between the time she treated her patient and when she developed symptoms. Vinson’s preliminary test results have come back positive for the infection, making her the second person to have contracted Ebola on US soil.
“She should not have traveled on a commercial airliner,” Thomas Frieden, the director of the Centers for Disease Control and Prevention (CDC), told reporters. “From this moment forward we will make sure that any individual who is being monitored” will not take public transportation.
Vinson flew on Frontier Airlines flight 1143 on October 13, and the CDC is contacting her fellow passengers to interview them about the flight and answer any questions, the agency said in a statement. Frieden said that because Vinson was not symptomatic at the time, the risk to others of catching Ebola on the plane is very low.
The incident highlights what some are calling poor preparation by the US hospitals to grapple with a pathogen that has pummeled communities and medical teams in Africa. The Associated Press reported that National Nurses United received statements from nurses describing the situation at the Dallas hospital where Vinson’s patient, Thomas Eric Duncan, was cared for. “The union described how Duncan was left in an open area of the emergency room for hours. It said staff treated Duncan for days without the correct protective gear, that hazardous waste was allowed to pile up to the ceiling and safety protocols constantly changed.”
Vinson’s colleague, Nina Pham, who also cared for Duncan, was the first person to have contracted Ebola virus in the U.S. Federal health officials acknowledged that they should have had more experts present in Dallas. "We could’ve sent a more robust hospital infection control team and been more hands-on with the hospital from day one about exactly how this should be managed,’’ Frieden said.
Pham is being treated in Dallas, while Vinson will be cared for at Emory University Hospital in Atlanta.
A3/ Répartition mondiale du volcanisme de subduction / site CNRS
B/ Schématisation des étapes pétrograhiques / logiciel
logiciel
subduction (Perez) :
http://pedagogie.ac-toulouse.fr/svt/serveur/lycee/perez/subduction/subduction.htm
métabasalte+métagabbros
contiennent des minéraux hydratés
éclogite
faite de minéraux anhydres
=>
métabasalte+métagabbros déshydratés
=>déshydratation
croûte océanique
=>
hydratation manteau lithosphrique continental susjacent
=>
baisse du solidus (point du fusion)
=>
fusion partielle des péridotites du manteau continental =>
plutonisme (granitoïdes, diorite) + volcanisme (rhyolite, andésites)
continentaux = Accrétion continentale
schéma-bilan
Compléter le schéma-bilan
B.1.4/ Magmatisme de subduction
Les
zones de subduction sont le siège d'une importante activité
magmatique qui aboutit à une production de croûte
continentale.
Dans
les zones de subduction, des volcans émettent des laves
souvent visqueuses associées à des gaz et leurs
éruptions sont fréquemment explosives. La
déshydratation des matériaux de la croûte océanique
subduite libère de l'eau qu'elle a emmagasinée au cours de
son histoire, ce qui provoque la fusion partielle des
péridotites du manteau sus-jacent. Si une fraction des magmas
arrive en surface (volcanisme), la plus grande partie cristallise en
profondeur et donne des roches à structure grenue de type
granitoïde. Un magma, d'origine mantellique, aboutit ainsi à
la création de nouveau matériau continental.
Séismes en milieu océanique : une meilleure compréhension de leur phase préparatoire
Publiée le 14 septembre dernier dans Nature Geoscience, l'étude menée par des chercheurs de plusieurs instituts, en particulier l'Ifremer, le CNRS et l'IFSTTAR, propose pour la première fois un modèle physique permettant d'expliquer la phase préparatoire d'un séisme en milieu océanique. Des travaux d'autant plus novateurs qu'ils reposent sur des mesures quantitatives, permettant d'établir l'existence d'une relation entre les précurseurs observés et le choc principal d'un séisme. Une piste prometteuse qui devrait orienter les futures recherches sur les signaux détectables.
Une étape clé des réactions allergiques dévoilée
En étudiant le mode d'action de la protéine interleukine-33, un signal d'alarme pour les globules blancs, une équipe de l'Institut de pharmacologie et de biologie structurale (CNRS/Université Toulouse III - Paul Sabatier) a pu mettre en évidence des formes tronquées de cette protéine qui fonctionnent comme de puissants activateurs des cellules à l'origine des réactions allergiques. Cette avancée majeure dans la compréhension des mécanismes de l'allergie pourrait avoir des applications importantes pour le traitement de l'asthme et des autres maladies allergiques telles que l'eczéma et la rhinite allergique. Ces travaux codirigés par Corinne Cayrol, chercheur CNRS, et Jean-Philippe Girard, directeur de recherche Inserm, sont publiés dans la revue PNAS du 13 octobre 2014.
Le papillomavirus humain associé à une maladie auto-immune
Le lichen plan érosif muqueux (LPEM) est une maladie dermatologique auto-immune dans laquelle le système immunitaire s'active anormalement contre les cellules des muqueuses. Des chercheurs de l'Institut Pasteur, de l'Inserm, de l'Université Toulouse III – Paul Sabatier et du CNRS apportent aujourd'hui la preuve que les cellules immunitaires impliquées dans le LPEM sont les mêmes que celles qui sont activées en réaction à une infection par le papillomavirus humain (de type HPV-16), ce qui indiquerait un lien entre la maladie et le HPV. Ces résultats sont publiés dans la revue Journal of Investigative Dermatology.
Ebola en RDC : une nouvelle souche du virus
Alors qu'une épidémie d'Ebola fait rage depuis mars 2014 en Afrique de l'Ouest, un foyer de cette fièvre hémorragique est apparu en République démocratique du Congo (RDC) au mois d'août dernier, laissant craindre une propagation du virus en Afrique centrale. Une étude associant l'IRD, l'Institut Pasteur, le CNRS, le CIRMF au Gabon, l'INRB en RDC et l'OMS, publiée dans la revue New England Journal of Medicine le 16 octobre 2014, confirme qu'il s'agit d'une épidémie d'Ebola. Mais celle-ci est due à une souche locale du virus, différente de celle qui sévit à l'Ouest du continent. Si ce résultat montre que les deux épidémies ne sont pas liées, il illustre l'accélération de l'émergence de la maladie, dont il devient urgent de comprendre les modalités de propagation.
Le rôle majeur des « oasis » océaniques dans les interactions entre organismes marins
Une étude internationale, coordonnée par des chercheurs de l'IRD, de l'Institut de la mer du Pérou (IMARPE), de Télécom Bretagne et du CNRS, a permis de comprendre le rôle majeur joué par la dynamique océanique dans la structuration de l'écosystème marin. La turbulence océanique crée des « oasis » qui concentrent la majorité des organismes marins, du zooplancton aux oiseaux. L'identification de ce processus contribuera, à terme, à améliorer les mesures de gestion spatialisées des ressources marines. Ces résultats sont publiés dans la revue Nature Communications, le 15 octobre.
A3/ Tracé du plan de Wadati Benioff / logiciels Sismolog + Educarte
Utiliser
les logiciels pour imprimer une coupe d'une zone de subduction puis
tracer le plan de Wadati Benioff et deux isothermes.
Le plan
de Wadati Benioff est formé par les séismes provoqués par le
frottement de la lithosphère plongeante dans une zone de subduction.
Les
isothermes sont les courbes formées par les températures
identiques.
Sur la carte
photocopiée colorier les zones de divergence en rouge, les zones de
convergence en jaune et les
zones de subduction en vert
pour
localiser les zones de subduction :
http://www.cnrs.fr/cw/dossiers/dosgeol/01_decouvrir/02_subduction/02_carte/carteok.htm
Tracé
du plan de WB sur une zone de subduction dans Sismolog :
- afficher les séismes toutes magnitudes, toutes profondeurs
- dans Educarte : placer la coupe perpendiculairement à la fosse de subduction à l'aide de la souris ou dans Sismolog : choisir dans le menu « outils » → coupe → définir → tracer
- calibrer la largeur et la longueur de la coupe pour avoir un tracé le plus complet & précis possible
- faire vérifier la vue à imprimer par le professeur puis imprimer la coupe
- titrer et légender la coupe (pays, océans, séismes, volcans, fosse, croûte, manteau, lithosphère, asthénosphère)
- tracer le plan de Wadati-Benioff passant par les séismes, montrant la plaque plongeante
- à l'aide du graphe des isothermes, tracer un ou deux isothermes sur la coupe
isotherme d’une zone de subduction :
FT fournies au TP
de Bac (ECE) :
http://pedagogie.ac-toulouse.fr/svt/serveur/bankact/index.php?m=1&sm=1
pour
télécharger le logiciel Educarte :
http://www.edusismo.org/docs/outils/educarte/index.htm
pour
télécharger le logiciel tectoglob :
http://pedagogie.ac-amiens.fr/svt/info/logiciels/Tectoglob/index.html
plan de Wadati Benioff / sismolog :
http://svt.ac-dijon.fr/dyn/IMG/Subduction_ocean_continent.jpg
mercredi 15 octobre 2014
Lab-Made Insulin-Secreting Cells
Researchers craft hormone-producing pancreas cells from human embryonic stem cells, paving the way for a cell therapy to treat diabetes.
By Bob Grant | October 13, 2014
WIKIMEDIA, MASURScientists claim to have successfully grown insulin-secreting pancreatic beta cells from human embryonic stem cells. Douglas Melton, a Harvard University stem cell scientist, and colleagues reported the in vitro feat on Thursday (October 9) in Cell. Though the work is far from achieving clinical relevance, it presents a possibility for a cell therapy that could treat diabetes. “We’re tired of curing mice,” Melton told The Boston Globe. “Most patients are sick of hearing that something’s just around the corner; I’m sick of thinking things are just around the corner. But I do believe in the big picture.”
Dieter Egli, assistant professor in the pediatrics department at Columbia University Medical Center, told The Globe that his laboratory will try to repeat Melton’s experiment immediately. “It’s a wonderful result,” he said, “something we’ve been waiting for quite awhile.”
Melton’s procedure requires six steps, involving chemicals and growth factors, and takes 40 days to go from either embryonic or adult stem cells to mature pancreatic beta cells. And the process yielded billions of the insulin-secreting cells. “You’ll be able to create buckets and buckets of cells,” Albert Hwa, a scientist at JDRF, a New York-based advocacy group focused on diabetes that partially funded the Harvard research, told the Washington Post. “Numbers will no longer be a limitation.”
Researchers are already trying to replicate the work and are seeking ways to scale the process using robotics, according to Susan Solomon, chief executive of the New York Stem Cell Foundation, who also spoke to the Washington Post.
A2/ Lames minces roches magmatiques / µscopes
FT fournies au TP de Bac (ECE) :
http://pedagogie.ac-toulouse.fr/svt/serveur/bankact/index.php?m=1&sm=1
Granite,
rhyolite, diorite, andésite, …
laves
visqueuses => gaz, éruptions explosives
© TP_roches.odg
- observer à l'oeil nu : aspect général : minéraux, couleurs, structure
- observer les lames minces au microscope en LPnA puis LPA: structure de la roche : grenue, microgrenue, microlithique et minéraux en présence
- réaliser un dessin d'observation légendé
pour apprendre à reconnaître les minéraux et
roches : manuel p.398-399
tableau
récapitulatif Dijon (doc) :
http://svt.ac-dijon.fr/dyn/article.php3?id_article=261
collection de roches :
http://geoeco.ifrance.com/g%E9ologie/collec.html
collection de lames minces :
http://www2.ac-lyon.fr/enseigne/biologie/photossql/photos.php?TopicID=Lames
clef de détermination Tlse (html) :
http://pedagogie.ac-toulouse.fr/svt/serveur/lycee/segui/mineralogie/fiche.htm
clef de détermination Oehmichen (pdf) :
http://www.google.fr/url?sa=t&rct=j&q=identification+min%C3%A9raux+microscope&source=web&cd=1&ved=0CCUQFjAA&url=http%3A%2F%2Fwww.lyc-oehmichen.ac-reims.fr%2Fcontenu%2Fdiscipline%2Fsvt%2F01_Pour_Observation2%2FIdentification_des_mineraux.pdf&ei=ih9kUP_rKorM0AWbjoCoCg&usg=AFQjCNHuA10fkEWvcu9xBWoHpXz13EnO9Q
clef de détermination Grbl :
http://www.ac-grenoble.fr/svt/SITE/prof/outiensei.htm
atlas rocks & minerals / Ratajeski :
http://www.geolab.unc.edu/Petunia/IgMetAtlas/mainmenu.html
atlas minerals / Siddall, London :
http://www.ucl.ac.uk/~ucfbrxs/PLM/PLMhome.html
atlas de roches et minéraux webminéral BRGM :
atlas de minéraux :
http://www.brocku.ca/earthsciences/people/gfinn/minerals/database.htm
atlas de lames minces Minéraux et roches / Aubry,
Caen :
http://www.discip.crdp.ac-caen.fr/svt/cgaulsvt/travaux/Micropol/index.html
mardi 14 octobre 2014
Eyes on the Prize
A handful of stem cell therapeutics for vision disorders are showing promise in early-stage trials, and still more are in development. But there’s a long road to travel before patients see real benefit.
By Jeffrey M. Perkel | October 1, 2014
IMAGE BY ANAI GONZALEZ-CORDERIn mid-June, Newark, California–based StemCells, Inc. announced interim results of its ongoing Phase 1/2 trial for the treatment of dry age-related macular degeneration, a form of progressive blindness common in the elderly. Seven patients with advanced disease who had been dosed with the experimental therapeutic—multipotent neural stem cells derived from fetal brain tissue—showed slowed retinal atrophy at one year post-transplant, and four had not just stabilized but improved visual function, the company reported.
“They’ve actually had gains in their visual ability to sense contrast, which is the difference between light and dark,” explains Stephen Huhn, the company’s chief medical officer and vice president for central nervous system (CNS) clinical research. “It’s very powerful to see that this early in the trial.”
StemCells’ announcement is the latest in a series of promising developments in the area of cell-based therapeutics for blindness. Advanced Cell Technology (ACT) has several ongoing trials based on differentiated cells derived from human embryonic stem cells (hESCs), and last year, Japanese researchers launched the first clinical study to use induced pluripotent stem cells (iPSCs) derived from adult human cells for the treatment of age-related macular degeneration. Still other strategies are in development, and excitement is high.
“I’ve been amazed at just how quickly the field has grown and how fast it has progressed toward clinical trials,” says David Gamm, an associate professor of ophthalmology and visual sciences and director of the McPherson Eye Research Institute at the University of Wisconsin School of Medicine and Public Health.
It’s still early days, he warns. While initial results are promising, that’s all they are at the moment. Nobody with blindness has yet been “cured” with a stem-cell therapeutic. And there are substantial safety issues to contend with when implanting live cells in the eye. “We’re pushing the boundaries of this technology,” Gamm says. “And as such, we expect there to be probably more bumps in the road than smooth parts.”
Why the eye?
The eye was not the first organ to receive transplanted stem cells. StemCells tested its cells in the brain and spinal cord before moving to the eye, and Geron, the first company authorized by the US Food and Drug Administration (FDA) to launch an hESC-based trial, targeted the spinal cord as well. (The company has since abandoned the field, selling its stem cell portfolio to BioTime subsidiary Asterias Biotherapeutics, which on August 27 announced it had received FDA approval to launch a new Phase 1/2a trial in 13 patients with spinal cord injury.) Other researchers are targeting the brain and spinal cord as well, not to mention the blood, pancreas, heart, and other nonneural tissues. A search of clinicaltrials.gov for “stem cell transplant” returns some 3,329 hits.
But for many stem-cell researchers and drug developers, the eye is the ideal organ for treatment with stem-cell therapeutics. It is small, and therefore requires relatively few cells for efficacy; and it is immune-privileged, meaning allogeneic (nonself) transplants may be used with little risk of immune rejection. Function is easily quantified in the eye, and even incremental improvements can yield large benefits for the patients.
As a practical matter, the eye is also the only part of the central nervous system (CNS) that is externally visible and accessible, and researchers can track transplanted cells noninvasively using techniques such as optical coherence tomography (OCT). Like a high-resolution optical version of ultrasound imaging, the technique provides “histological detail down to a micron or so resolution,” says Michael Young, associate professor of ophthalmology and codirector of the Ocular Regenerative Medicine Institute at Harvard Medical School. “That turns out to be, from a therapeutic point of view and from an endpoint-analysis point of view, a great tool for us in trying to figure out whether these things work or not, and secondarily, is something wrong.”
Another important advantage of targeting the eye, says Young, is safety. The eye is relatively self-contained and, disturbing as it may sound, nonessential. “Imagine a stem-cell transplant for Parkinson’s disease, where you inject stem cells into the middle of the brain, and something goes wrong. What do you do? The answer is nothing, you can’t do anything. In the eye, if something goes wrong, and in these early stages something can go wrong, you can actually remove the eye and remove the cells,” he says.
This is particularly important for therapies derived from hESCs or iPSCs, which, unlike adult stem cells, can divide indefinitely and differentiate into any cell type of the entire body. As such, they also pose a risk of tumorigenesis in transplant recipients should undifferentiated cells accidentally be introduced into a patient.
Providing new support
Though there are hundreds, if not thousands, of diseases that affect the eye, most cell therapeutic programs to date have focused on macular degeneration, “the commonest cause of sight loss in the Western world,” says James Bainbridge, a professor of retinal studies at the University College London Institute of Ophthalmology and the chief investigator of ACT’s UK-based trials. “We can all expect to develop it if we live long enough.” More than 2 million Americans were suffering from age-related macular degeneration in 2010, according to the National Eye Institute.
Macular degeneration involves the loss of retinal pigment epithelium (RPE) cells, which secrete growth factors, remove metabolic waste, and recycle the photopigment retinal that is required for the function of the adjacent rods and cones. “They’re basically a support cell for the photoreceptors,” says stem-cell biologist Dennis Clegg of the University of California, Santa Barbara (UCSB). As the RPE beneath the macula, or center of the retina, begins to deteriorate, the photoreceptor neurons begin to die as well, and central vision—critical for reading and writing, recognizing faces, and low-light vision, among other functions—is lost. (See illustration.) One way to halt disease, then, is to replace the RPE cells or provide a substitute to stem the continued degeneration of the photoreceptors.
StemCells’ HuCNS-SC transplantation works by supplementing a patient’s remaining RPE cell function with neural progenitor cells not normally found in the eye. Although derived from donated fetal brain tissue—“obtained through a nonprofit tissue procurement agency following an elective abortion,” according to Huhn—StemCells’ therapeutic is technically an adult stem-cell product, in that the cells have lost the pluripotency that defines embryonic stem cells. Neural stem cells extracted from the fetal brain tissue are expanded and cryopreserved; once thawed and implanted into patients, the cells can differentiate into neurons, astrocytes, and oligodendrocytes. “The broad category of mechanism of action is probably some type of neurotrophic effect,” Huhn says.
I’ve been amazed at just how quickly the field has grown and how fast it has progressed toward clinical trials.——David Gamm, McPherson Eye Research Institute, University of Wisconsin School of Medicine
and Public Health
Janssen Research & Development’s CNTO-2476, an allogeneic cell therapy derived from human umbilical cord tissue, is believed to secrete trophic factors that support diseased retinal tissue, according to a company spokesperson. The therapy has been tested in trials for age-related macular degeneration and retinitis pigmentosa, and a large, randomized trial for macular degeneration is being planned to further assess its efficacy and safety.
ACT’s strategy is more direct: supply new RPE cells to replace and repair the native RPE layer. ACT has initiated four Phase 1/2 trials testing its hESC-derived RPE therapy for the treatment of the dry form of age-related macular degeneration (dry AMD); a heritable form of the disease called Stargardt’s; and myopic macular degeneration, a form of vision loss caused by abnormal elongation of the eyeball. The company described its initial findings for the first dry AMD and Stargardt’s disease patients in a 2012 Lancet paper, with results pointing to the protocol’s safety and hinting at its efficacy (379:713-20). One patient, for instance, improved from 20/500 to 20/320 vision, which corresponded to a modest improvement in ability to read an eye chart, albeit with “mild visual function increases in the fellow [untreated] eye.” In 2013, ACT announced that one of the more recently treated dry AMD patients had experienced an improvement from 20/400 to 20/40.
These promising results, along with those from StemCells’ Phase 1/2 trial this summer, suggest that restoring or replacing RPE function can not only halt the spread of macular degeneration, but partially reverse it—essentially kick-starting photoreceptors that were dying but not yet dead.
UCSB’s Clegg and his colleagues at the nonprofit California Project to Cure Blindness and elsewhere are also pursuing the RPE approach. The team plans to transplant sheets of RPE cells derived from hESCs deposited on an artificial substrate called parylene, which mimics the extracellular matrix layer of the RPE. With $19 million in funding from the California Institute for Regenerative Medicine, the researchers hope to file an investigational new-drug (IND) application for dry AMD with the FDA by the end of the year, Clegg says.
Researchers at the RIKEN Institute in Japan have also announced plans to differentiate and transplant RPE cells for AMD, this time using iPSCs. The team, led by Masayo Takahashi, will generate iPSCs from patients’ skin cells, a process RIKEN says will take 10 months to complete. The cells will then be differentiated into 1.3 mm x 3 mm sheets of RPE cells and transplanted back into the patient the cells were taken from. If successful, the therapy would avoid the moral complications that accompany hESCs, which are created from human embryos. “There are a significant number of people who are not comfortable with ES cells,” says the University of Wisconsin’s Gamm.
Replacing photoreceptors
IMAGE BY DR ANAI GONZALEZ-CORDEROOnce rods and cones are dead, however, even an infinite supply of RPE cells cannot help. To more fully restore vision in patients with retinal degeneration, researchers are looking to replace the photoreceptors themselves. This strategy is more complicated than the RPE approach, however. To be functional, photoreceptors must not only implant and survive, but extend neural processes and form synaptic connections with downstream bipolar neurons. (See photograph at right.) Fortunately, it’s a relatively short gap to fill, says Matthew Vincent, ACT’s Director of Business Development. “If you’re going to think about replacing a neuron with a stem cell, that’s probably the best one you could imagine doing.”
Preclinical work suggests the strategy can work. In 2012, researchers in Robin Ali’s group at University College London reported in Nature that transplanting murine photoreceptor precursor cells yields functional improvements in mice that lack rods (485:99-103). And while no photoreceptor-based strategy has yet entered clinical trials, several are in development.
Young’s group at Harvard Medical School, for example, is working on a strategy for treating retinitis pigmentosa that involves transplanting human fetal retinal progenitor cells, which develop into rods. Retinal progenitor cells, he explains, are proliferative cells that are “one stage less developed” than the precursor cells Ali used in his mouse study and are thus easier to grow. Furthermore, human retinal progenitor cells have been safely banked under good-manufacturing-practice (GMP) conditions and are ready for a future trial, Young says. He and his partners, including UK-based ReNeuron, will meet with the FDA later this year and hope to launch a clinical trial in early 2015.
ACT is also preparing to launch clinical trials based on hESC-derived photoreceptors, says Vincent, possibly also early next year. “I think the photoreceptor progenitors will likely be the next ‘IND-able’ . . . program for the company.”
Gamm, meanwhile, has worked out methods to differentiate iPSCs into photoreceptor precursors and other retinal cells, and is working with Clegg on a strategy for treating dry AMD that involves both RPE and photoreceptor precursors. But rather than deriving such cells from individual patients, as the RIKEN group is doing, Gamm and his colleagues figure that it will be less expensive and faster to bank a wide variety of HLA-typed iPSCs. (See “Banking on iPSCs,” The Scientist, September 2014.) “Similar to how you might get a close match, but not perfect match, for an organ transplant, we could do the same thing for all cell types derived from certain iPS [cell] lines,” Gamm explains.
To the clinic
As cell therapies make their way into the clinic, there’s one overriding concern clinicians and regulators have, says Gamm: “Safety, safety, safety.” Indeed, Geron, the first company to get an hESC-based therapeutic into clinical trials, submitted an IND application that was reportedly some 22,000 pages long—the largest ever approved by the FDA.
ACT, the second company to win IND approval for an hESC therapy, went to considerable effort to assure the FDA that the risk of tumor formation from its hESC-derived RPE cells was as low as possible—among other measures, developing a new proprietary method for detecting contaminating undifferentiated cells that is some five orders of magnitude more sensitive than PCR, says Vincent. “The first, second, and third issue for the FDA really was safety,” he said: “prove to us that there is no risk that these patients are going to develop tumors as a consequence [of] these cells that you’re injecting.” The company’s first IND took a year to get the nod, though subsequent applications were approved in less than one month each, he noted.
As these companies and researchers lay the groundwork, other players should have an easier time. (See “Stem Cells Off the Line,” The Scientist, April 2014.) Now, says Gamm, the challenge is managing expectations. At the moment, things are looking up for the field, and research is advancing rapidly. But at some point, he says, “we’re going to hit something that will take us a while to figure out.” Gamm says he tries to make that clear when talking to patients and disease foundations. Riffing on the customary disclaimer accompanying mutual fund literature, he says, “Past performance is not a guarantee of future progress.”
lundi 13 octobre 2014
The Ocular Microbiome
Researchers are beginning to study in depth the largely uncharted territory of the eye’s microbial composition.
By Rina Shaikh-Lesko | October 1, 2014
© LESTYAN4/ISTOCKPHOTO.COMWhen researchers started using modern molecular diagnostic tools such as PCR and genome sequencing to study the microbes living on and in the human body, they found much more complex ecosystems than previous generations had imagined. The Human Microbiome Project undertook a massive effort to characterize microbial communities from five sites—the gut, mouth, nose, skin, and urogenital tract. But it did not include many areas of the body that harbor microbial life, including the surface of the eye.
Ophthalmologists have treated pathogenic eye infections for several decades, and the advent of contact lenses has made such infections more common. But little is known about the bacteria that live on the surface of a healthy human eye, and how this microbial makeup differs when a pathogenic strain takes over. Many bacteria known to live on the eye are difficult to culture, making them virtually invisible to researchers. Adapting sequencing technologies to study the ocular microbiome has opened up new avenues for understanding what’s really happening under the eyelids.
About five years ago, Valery Shestopalov of the Bascom Palmer Eye Institute at the University of Miami was speaking with his microbiology colleagues about the bacteria found on healthy eyes. Conventional wisdom at that time held that healthy eyes don’t harbor much microbial life—tears and blinking tend to clear away foreign objects, including bacteria. But Shestopalov’s early tests revealed something different. “The tests ran positive. All exposed mucosal epithelium are populated densely,” he said. In 2009, Shestopalov began the Ocular Microbiome Project with funds from his institution. Eventually, he secured a grant from the National Eye Institute and began collaborating with Russell Van Gelder at the University of Washington, who had been developing PCR-based diagnostic tests to identify bacteria and fungi on the eye. The project now has a dozen collaborators at five universities.
In May, Shestopalov presented preliminary ocular microbiome data at the Association for Vision Research and Ophthalmology annual meeting held in Orlando, Florida. His team sequenced samples from healthy corneas, contact lenses, and conjunctiva—the inner surface of the eyelids—using 16S ribosomal RNA sequencing, along with a new method Van Gelder developed called biome representational in silico karyotyping (BRiSK), which uses high-throughput sequencing to identify bacteria at the species level.
People can have a huge variation in microflora and still have healthy eyes, making our job difficult, but really amazing.—Valery Shestopalov,
Bascom Palmer Eye Institute, University of Miami
The team found that about a dozen bacterial genera dominated the eye’s conjunctiva, a third of which could not be classified. On the corneal surface, the researchers found a slightly different community. Again, about a dozen genera dominated. And everywhere they’ve looked, the researchers have found more than just bacteria. “We haven’t published on this yet, but I have been surprised by how often we find phage or viruses on the normal ocular surface,” Van Gelder told The Scientist in an e-mail.
“People can have a huge variation in microflora and still have healthy eyes, making our job difficult, but really amazing,” Shestopalov said.
The researchers also found that during keratitis infections—infections of the cornea—only about half as many bacterial varieties were present, most prominently Pseudomonas strains. The changes typically occurred well before a diagnosis of an eye infection, suggesting the ocular microbiome could inform future diagnostics, Shestopalov noted. His team is refining the algorithm for predicting infection based on the dynamics of these changes in bacterial composition.
One factor that may be expected to impact the composition of ocular microbiota is the use of contact lenses. Contact lens wear is one of the biggest factors leading to corneal infection. Common bacterial infections that can cause irritation and redness affect an estimated 7 percent to 25 percent of contact lens–wearers, and much rarer keratitis infections can even cause blindness. Researchers believe contact lenses make it easier for pathogens to colonize the surface of the eye by giving the bacteria something to adhere to. Sequencing biofilms from used contact lenses, Shestopalov’s team found evidence of microbial communities that were different from the ocular microbiomes of people who don’t use contacts. On the lenses themselves, the researchers have found much less diversity—many of the bacterial genera that dominate the conjunctiva and cornea were depleted. In their place, Staphylococcus dominated.
To tackle the potential-infection problem, Mark Willcox, a medical microbiologist at the University of New South Wales in Australia, has developed antimicrobial contact lenses. Together with colleagues Debarun Dutta and Jerome Ozkan of the Brien Holden Vision Institute in Sydney, Willcox bonded the naturally occurring antimicrobial peptide melimine to the surface of normal contact lenses. The researchersreported on preclinical studies on rabbits, and in April, on the first phase of human trials, which included 17 volunteers. They found that the antimicrobial lenses appeared as safe as regular lenses and maintained their antimicrobial activity against two major pathogens, P. aeruginosa and S. aureus. The researchers next plan to test the lenses in a larger sample of about 100 to 200 people, but it will be some time before antimicrobial lenses are available on the market.
The lenses are not likely to harm normal, commensal bacteria on the eye. “As the peptide is bound to the surface of the lens we believe it will only affect the growth of those microbes that attempt to bind to the lens surface and not those cultured from the surface of the eye,” Willcox told The Scientist in an e-mail. “But large-scale clinical trials are needed to prove this hypothesis.”
Whether the bacteria identified living on the surface of the eye are permanent residents or transient colonizers remains to be seen. The work of deconstructing the ocular microbiome is just getting started, but preliminary results have suggested it is distinct from the rest of the bacterial community that inhabits our bodies. “It stands apart,” Shestopalov said. “There’s statistical evidence of its difference from any other human microbiome.”
Fecal Pill Treats Gut Infection
In a preliminary study, patients with recurring Clostridium difficile infections found relief from diarrhea by ingesting frozen fecal matter from healthy volunteers.
By Bob Grant | October 11, 2014
WIKIMEDIA, CJC2NDA handful of patients suffering from recurrentClostridium difficile infections (CDI) experienced a cessation of the violent diarrhea that is a hallmark of the disease after ingesting frozen, encapsulated feces from healthy, unrelated volunteers. The results of the preliminary study to test the efficacy of the new twist on fecal microbiota transplantation (FMT) were published today (October 11) in theJournal of the American Medical Association (JAMA).
“If reproduced in future studies . . . these results may help make FMT accessible to a wider population of patients, in addition to potentially making the procedure safer,” the authors of theJAMA paper wrote. “The use of capsules obviates the need for invasive procedures for administration, further increasing the safety of FMT . . . and significantly reducing cost.”
CDIs are downright nasty to the human gut. They cause extreme diarrhea, abdominal pain, and, if left unchecked, death. The infections kill about 14,000 people in the U.S. alone every year. Such an insidious malady is apt to drive patients to drastic treatment measures. Direct fecal transplants, which transfer gut microbiota from healthy donors, have shown great promise in treating CDI’s, and last year researchers saw similar successes with the oral administration of beneficial gut microbes extracted from fecal samples donated by health volunteers (typically family members).
In the new study, conducted by Ilan Youngster of Massachusetts General Hospital in Boston and colleagues, the new treatment—which uses frozen fecal matter rather than gelatin coated microbial extracts—cleared up diarrhea in 18 out of 20 CDI patients, and the benefits persisted for up to 8 weeks after administration.
A2/ Comptage de cellules / lames KOVA
comptage KOVA
: http://www.didier-pol.net/3num.htm
la grille
contient 1 µL, elle est divisée en 9 carrés de 9 cases chacun =>
81 cases au total
On considère
que les barres de séparation entre les cases contiennent
l'équivalent de 9 cases => 90 cases au total
IL faut donc
multiplier le nombre de cellules trouvées par case par 90 pour avoir
le nombre de cellules par µL
pour aller plus loin
: http://www.didier-pol.net/2dosglubl.htm
suivi fermentation
: http://svt.ac-rouen.fr/biologie/cidre/fermentation/fermentation.htm
comptage
Malassez: http://www.ac-versailles.fr/tpe/serie-s/yaourt/numeration_sur_lame.htm
http://www.viticulture-oenologie-formation.fr/vitioenoformlycee/champagnisation/comptagelevuresvivantesmalassez.htm
http://www.viticulture-oenologie-formation.fr/vitioenoformlycee/champagnisation/comptagelevuresvivantesmalassez.htm
A3/ Compte-rendu par la démarche expérimentale
utiliser 4 FT : rédiger un CR, schématiser
une expérience, réaliser un graphe, interpréter un graphe.
pb → hyp (réponse provisoire au pb posé) →
conséquences (de l'hypothèse) vérifiables (par l'expérience)
protocole expérimental (schéma)
Résultats → tableau commun :
→ graphe (disque ; histogramme ; courbe ?)
→ interprétation (traduction d'outils mathématique en terme
biologique)
conclusion (infirmer ou confirmer l'hyp →
discussion /auto ou hétérotrophie → ouverture = nouvelle question
que pose la discussion)
impact lumière => rôle de la photosynthèse
=> autotrophie
mat organique inutile pour autotrophes (tube E1B
// E2B) si lumière+minéraux (E1B à obscurité)
mt organique indispensable pour hétérotrophes
[autre ; nourriture] (E2A // B)
+=> rôle du patrimoine génétique (euglènes
mutées) / métabolisme
A4/ Observation de celulles au microscope
1.1.3- Sismologie en profondeur
A1/ Etude de la répartition mondiale des séismes profonds / site CNRS
localisation des zones de subduction :
http://www.cnrs.fr/cw/dossiers/dosgeol/01_decouvrir/02_subduction/02_carte/carteok.htm
subduction
= zone de convergence de plaques
séïsmicité
+ volcanisme particuliers de la subduction : séismes profonds +
volcanisme explosif
reliefs
négatifs = fosse, bassin arrière-arc
reliefs
positifs = cordillère ou arc insulaire
→ schémas 3 types de subduction
A2/ Modélisation à partir de la sismologie / diaporama
D/ subduction.odp
Hodochrone [Hodo = vitesse ; chrone = temps]
= courbes de vitesses d'ondes sismiques à travers le globe
Tomographie [tomê = coupe ; graph = écrit ]
sismique = cartographie de l'intérieur de la terre à partir des
variations vitesses des ondes sismiques = échographie sismique
La propagation d’ondes à travers un même
matériau mais à des températures différentes montre la différence
entre lithosphère et asthénosphère.
Les hodochrones permettent de comparer les
différentes données sismiques à travers la terre et donc de
révéler des différentes discontinuités (limites entre couches
différentes par leur nature ou leur composition) comme celle de
Mohorovicic séparant croûte et manteau ou la LVZ séparant la
lithosphère et l'asthénosphère.
Rhéologie [rhéô « couler » ]
lithosphère
/ asthénosphère;
lithosphère
(océanique ou continentale) plongeant ss\ manteau
plan
de Wadati-Benioff
lithosphère
rigide et cassante / asthénosphère ductile
Inscription à :
Articles (Atom)