Articles importants dans Nature, Science ou Cell

[Enro]

Je me permets de mentionner ici un nouveau blog (pas de moi) qui va s'atteler à des comptes-rendus (critiques) en français des dernières publis en bio-informatique, génétique et biologie moléculaire, parues dans les revues les plus importantes :

Papiers aléatoires

[LXR]

Salut,

Voici un Nature qui a un bon potentiel de "scoop" : Cdk1 est la seule Cdk vraiment essentielle au cycle cellulaire chez les mammifères! Un gros paquet de résultats et des KO dans tous les sens, typique d'un bon Nature!!

Cdk1 is sufficient to drive the mammalian cell cycle

J'avais oublié de dire que les travaux ont été dirigés par Mariano Barbacid, une des références dans l'étude du cycle cellulaire.

A+. Greg.

[Vinc]

J'avais oublié de dire que les travaux ont été dirigés par Mariano Barbacid, une des références dans l'étude du cycle cellulaire.

Moi je l'ai vu en confeeeeeeee!

V.

[ThinSwing]

Bonjour a tous je voudrais proposer un extrait ds nature biotechnology prometteur je pense ,

RNase H-mediated retrovirus destruction in vivo
triggered by oligodeoxynucleotides
Kathrin Matzen1–3, Lina Elzaouk1,3, Alexey A Matskevich1,3, Anja Nitzsche2, Jochen Heinrich1 &
Karin Moelling1
The HIV-1 RNase H can be prematurely activated by
oligodeoxynucleotides targeting the highly conserved polypurine
tract required for second strand DNA synthesis1–5. This inhibits
retroviral replication in cell-free HIV particles and newly
infected cells1–4. Here we extend these studies to an
in vivo model of retroviral replication. Mice that are chronically
infected with the spleen focus-forming virus and treated with
oligodeoxynucleotides that target the polypurine tract, exhibit
either transient or long-term reductions in plasma virus titer,
depending on the therapeutic regimen. Treatment prior to,
during or shortly after infection can delay disease progression,
increase survival rates and prevent viral infection. This strategy
destroys viral RNA template in virus particles in serum as well
as early retroviral replication intermediates in infected cells.
As it targets events common to the replication cycle of all
retroviruses, this approach may be broadly applicable to
retroviruses of medical and agricultural importance.

L.

[Squalor]

Petit article sur la découverte de la réponse UPR...

Science 3 December 1999:
Vol. 286. no. 5446, pp. 1888 - 1893
DOI: 10.1126/science.286.5446.1888

Review

Posttranslational Quality Control: Folding, Refolding, and Degrading Proteins

Sue Wickner, 1 Michael R. Maurizi, 2 Susan Gottesman 1*

Polypeptides emerging from the ribosome must fold into stable three-dimensional structures and maintain that structure throughout their functional lifetimes. Maintaining quality control over protein structure and function depends on molecular chaperones and proteases, both of which can recognize hydrophobic regions exposed on unfolded polypeptides. Molecular chaperones promote proper protein folding and prevent aggregation, and energy-dependent proteases eliminate irreversibly damaged proteins. The kinetics of partitioning between chaperones and proteases determines whether a protein will be destroyed before it folds properly. When both quality control options fail, damaged proteins accumulate as aggregates, a process associated with amyloid diseases.

1 Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD 20892-4255, USA.
2 Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892-4255, USA.

Un article génial et des conséquences immenses avec la découverte de la réponse UPR , les liens avec l'apoptose ("role of the unfolded protein reponse in cell death" 2006, Apoptosis, R.Kim, M. Emi,...) et les liens vers de nombreuses maladies...

Amicalement,

Greg

[stillnacht]

Bonjour a tous

Alors voila moi chui microbiologiste. Et voila le ti papier que je propose.

Bug juice: Harvesting electricity with microorganisms
Lovley D Nature Reviews Microbiolgy vol 4 July 2006 497-508

tres interesant. Les microbes sont nos amis (enfin qq uns).

Et puis apres quand on postule chez EDF en recherche et dev ya rien! Pfff

Aller a plus les cocos

[Vinc]

Bonjour à tous!
Un papier assez vieux que j'aurai dû mettre il y a longtemps...


J Biol Chem. 2004 Oct 1;279(40):41414-21. Epub 2004 Jul 14.

The Tumor Suppressor Protein p16INK4a and the Human Papillomavirus Oncoprotein-58 E7 Are Naturally Occurring Lysine-less Proteins That Are Degraded by the Ubiquitin System.
DIRECT EVIDENCE FOR UBIQUITINATION AT THE N-TERMINAL RESIDUE.

Ronen Ben-Saadon, Ifat Fajerman, Tamar Ziv, Ulf Hellman¶, Alan L. Schwartz||**, and Aaron Ciechanover

Conjugation of ubiquitin to an internal lysine is the initial step in the degradation of the majority of the substrates of the ubiquitin system. For several substrates, it has been shown that the first ubiquitin moiety is conjugated to the N-terminal residue. In all these substrates, however, the internal lysines also played a role in modulating their stability. To better understand the physiological significance of this novel mode of modification, it was important to identify proteins in which degradation is completely dependent on N-terminal ubiquitination. Also, although the experimental evidence for N-terminal ubiquitination is rather strong, nevertheless, it has remained indirect. Here we demonstrate that an important group of proteins that are targeted via N-terminal ubiquitination are the naturally occurring lysine-less proteins such as the human papillomavirus (HPV)-58 E7 oncoprotein and the cell cycle inhibitor and tumor suppressor p16(INK4a). For these proteins, the only residue that can be targeted is the N-terminal residue. Interestingly, p16(INK4a) is degraded in a cell density-dependent manner. Importantly, we provide for the first time direct evidence for N-terminal ubiquitination. Analysis of tryptic digest of the ubiquitin conjugate of HPV-58 E7 revealed a fusion peptide that is composed of the C-terminal domain of ubiquitin and the N-terminal domain of E7. With the abundance of native lysine-less proteins, among which are important viral and cell regulators, this novel mode of protein targeting has implications for both physiological and pathophysiological processes.


L'article est accecible gratuitement, merci JBC....

http://www.jbc.org/cgi/reprint/279/40/41414http://www.jbc.org/cgi/reprint/279/40/41414

Pour la petite histoire, Aaron Ciechanover a reçu le Prix Nobel de chimie en 2004 (avec 2 autres chercheurs) pour la découverte de l'UPS...

V.

[Igothigh]

Je ne peux pas resister a poster cet article paru dans le dernier numero de Nature (450, p56-62)
(lien)... un bel exemple de l'utilisation des techniques de recombinaisons Cre-lox dans la souris et de la puissance de l'imagerie multicouleur... ce papier n'est juste que la validation d'une technique qui pourrait (pour ceux qui en auront la patience et les moyens!!) avoir de nombreuses applications.

Transgenic strategies for combinatorial expression of fluorescent
proteins in the nervous system pp56 - 62
A combination of genetic tricks and fancy fluorescent proteins is used
to develop the Technicolor version of Golgi staining, 'Brainbow', in
which hundreds of individual neurons are painted, each with a
distinctive hue. This technology should not only boost mapping efforts
in normal or diseased brains, but could also be applied to other
complex cell populations, such as the immune system.

[Vinc]

Oui rien que pour les photos ca vaut le coup!! Très beau papier en effet...

V.

[Vinc]

Aller un autre pour le plaisir... toujours chez Nature:

Characterizing the cancer genome in lung adenocarcinoma.


Nature advance online publication 4 November 2007 | doi:10.1038/nature06358; Received 12 April 2007; Accepted 10 October 2007; Published online 4 November 2007


Somatic alterations in cellular DNA underlie almost all human
cancers1. The prospect of targeted therapies2 and the development
of high-resolution, genome-wide approaches3–8 are now spurring
systematic efforts to characterize cancer genomes. Here we report
a large-scale project to characterize copy-number alterations in
primary lung adenocarcinomas. By analysis of a large collection
of tumours (n5371) using dense single nucleotide polymorphism
arrays, we identify a total of 57 significantly recurrent events. We
find that 26 of 39 autosomal chromosome arms show consistent
large-scale copy-number gain or loss, of which only a handful have
been linked to a specific gene. We also identify 31 recurrent focal
events, including 24 amplifications and 7 homozygous deletions.
Only six of these focal events are currently associated with known
mutations in lung carcinomas. The most common event, amplification
of chromosome 14q13.3, is found in 12% of samples.
On the basis of genomic and functional analyses, we identify
NKX2-1 (NK2 homeobox 1, also called TITF1), which lies in the
minimal 14q13.3 amplification interval and encodes a lineagespecific
transcription factor, as a novel candidate proto-oncogene
involved in a significant fraction of lung adenocarcinomas. More
generally, our results indicate that many of the genes that are
involved in lung adenocarcinoma remain to be discovered.


http://www.nature.com/nature/journal...ture06358.htmlhttp://www.nature.com/nature/journal...ture06358.html


V.

[Vinc]

C'est quand même pas mal Nature cette semaine......


Identification of Tim4 as a phosphatidylserine receptor.

Masanori Miyanishi1,2, Kazutoshi Tada2{, Masato Koike3, Yasuo Uchiyama3, Toshio Kitamura4 & Shigekazu Nagata1,2,5


In programmed cell death, a large number of cells undergo apoptosis,
and are engulfed by macrophages to avoid the release of
noxious materials from the dying cells1,2. In definitive erythropoiesis,
nuclei are expelled from erythroid precursor cells and
are engulfed by macrophages. Phosphatidylserine is exposed on
the surface of apoptotic cells3 and on the nuclei expelled from
erythroid precursor cells4; it works as an ‘eat me’ signal for phagocytes5,6.
Phosphatidylserine is also expressed on the surface of
exosomes involved in intercellular signalling7. Here we established
a library of hamster monoclonal antibodies against mouse peritoneal
macrophages, and found an antibody that strongly inhibited
the phosphatidylserine-dependent engulfment of apoptotic
cells. The antigen recognized by the antibody was identified by
expression cloning as a type I transmembrane protein called Tim4
(T-cell immunoglobulin- and mucin-domain-containing molecule;
also known as Timd4)8. Tim4 was expressed in Mac11 cells
in various mouse tissues, including spleen, lymph nodes and fetal
liver. Tim4 bound apoptotic cells by recognizing phosphatidylserine
via its immunoglobulin domain. The expression of Tim4 in
fibroblasts enhanced their ability to engulf apoptotic cells. When
the anti-Tim4 monoclonal antibody was administered into mice,
the engulfment of apoptotic cells by thymic macrophages was
significantly blocked, and the mice developed autoantibodies.
Among the other Tim family members, Tim1, but neither Tim2
nor Tim3, specifically bound phosphatidylserine. Tim1- or Tim4-
expressing Ba/F3 B cells were bound by exosomes via phosphatidylserine,
and exosomes stimulated the interaction between Tim1
and Tim4. These results indicate that Tim4 and Tim1 are phosphatidylserine
receptors for the engulfment of apoptotic cells, and
may also be involved in intercellular signalling in which exosomes
are involved.

http://www.nature.com/nature/journal...ture06307.htmlhttp://www.nature.com/nature/journal...ture06307.html


V.

[MaliciaR]

Salut,
Voilà un truc sympa :

A single positively selected West Nile viral mutation confers increased virogenesis in American Crows

Brault AC, Huang CY, Langevin SA, Kinney RM, Bowen RA, Ramey WN, Panella NA, Holmes EC, Powers AM, Miller BR.

Center for Vector-Borne Diseases and Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California 95616, USA.

West Nile virus (WNV), first recognized in North America in 1999, has been responsible for the largest arboviral epiornitic and epidemic of human encephalitis in recorded history. Despite the well-described epidemiological patterns of WNV in North America, the basis for the emergence of WNV-associated avian pathology, particularly in the American crow (AMCR) sentinel species, and the large scale of the North American epidemic and epiornitic is uncertain. We report here that the introduction of a T249P amino acid substitution in the NS3 helicase (found in North American WNV) in a low-virulence strain was sufficient to generate a phenotype highly virulent to AMCRs. Furthermore, comparative sequence analyses of full-length WNV genomes demonstrated that the same site (NS3-249) was subject to adaptive evolution. These phenotypic and evolutionary results provide compelling evidence for the positive selection of a mutation encoding increased viremia potential and virulence in the AMCR sentinel bird species.

Nat Genet. 2007 Sep;39(9):1162-6. Epub 2007 Aug 12

Cordialement,

[MaliciaR]

Pas mal, pas mal En accès libre sur PubMed

(A)symmetric stem cell replication and cancer.
Dingli D, Traulsen A, Michor F.

Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, United States of America.

Most tissues in metazoans undergo continuous turnover due to cell death or epithelial shedding. Since cellular replication is associated with an inherent risk of mutagenesis, tissues are maintained by a small group of stem cells (SCs) that replicate slowly to maintain their own population and that give rise to differentiated cells. There is increasing evidence that many tumors are also maintained by a small population of cancer stem cells that may arise by mutations from normal SCs. SC replication can be either symmetric or asymmetric. The former can lead to expansion of the SC pool. We describe a simple model to evaluate the impact of (a)symmetric SC replication on the expansion of mutant SCs and to show that mutations that increase the probability of asymmetric replication can lead to rapid mutant SC expansion in the absence of a selective fitness advantage. Mutations in several genes can lead to this process and may be at the root of the carcinogenic process.

PLoS Comput Biol. 2007 Mar 16;3(3):e53. Epub 2007 Feb 1.

[Exuperance]

Je ne sais pas dans quel journal c'est publié... Z'avez entendu parlé des deux équipes qui ont réussit a réversé des cellules de peau en cellules souches ?

[sed s/war/peace/ *]

Bonjour,
pour ceux qui ont un peu de temps à perdre je conseille la video proposée en supplementary material de l'article du Nature de cette semaine consacré à l'étude du (mega !)-complexe protéique qui forme le pore nucléaire des eucaryotes (dans cet article, il s'agit évidemment du pore nucleaire de la levure).

---------------------------------
Article

Nature 450, 695-701 (29 November 2007) | doi:10.1038/nature06405; Received 20 April 2007; Accepted 22 October 2007

The molecular architecture of the nuclear pore complex

Frank Alber1,4, Svetlana Dokudovskaya2,4,5, Liesbeth M. Veenhoff2,4,5, Wenzhu Zhang3, Julia Kipper2,5, Damien Devos1,5, Adisetyantari Suprapto2,5, Orit Karni-Schmidt2,5, Rosemary Williams2, Brian T. Chait3, Andrej Sali1 & Michael P. Rout2

Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50 MDa that selectively transport cargoes across the nuclear envelope. To determine the molecular architecture of the yeast NPC, we collected a diverse set of biophysical and proteomic data, and developed a method for using these data to localize the NPC's 456 constituent proteins (see the accompanying paper). Our structure reveals that half of the NPC is made up of a core scaffold, which is structurally analogous to vesicle-coating complexes. This scaffold forms an interlaced network that coats the entire curved surface of the nuclear envelope membrane within which the NPC is embedded. The selective barrier for transport is formed by large numbers of proteins with disordered regions that line the inner face of the scaffold. The NPC consists of only a few structural modules that resemble each other in terms of the configuration of their homologous constituents, the most striking of these being a 16-fold repetition of 'columns'. These findings provide clues to the evolutionary origins of the NPC.

-----------------------------------------------

Pour la vidéo :
http://www.nature.com/nature/journal...ture06405.html