The Abstract wrote:Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.

GenesForLife wrote:I thought the club was restricted to openly accessible articles?

During the initial stages of carcinogenesis, transformation events occur in a single cell within an epithelial monolayer. However, it remains unknown what happens at the interface between normal and transformed epithelial cells during this process. In Drosophila, it has been recently shown that normal and transformed cells compete with each other for survival in an epithelial tissue; however the molecular mechanisms whereby “loser cells” undergo apoptosis are not clearly understood. Lgl (lethal giant larvae) is a tumor suppressor protein and plays a crucial role in oncogenesis in flies and mammals. Here we have examined the involvement of Lgl in cell competition and shown that a novel Lgl-binding protein is involved in Lgl-mediated cell competition. Using biochemical immunoprecipitation methods, we first identified Mahjong as a novel binding partner of Lgl in both flies and mammals. In Drosophila, Mahjong is an essential gene, but zygotic mahjong mutants (mahj−/−) do not have obvious patterning defects during embryonic or larval development. However, mahj−/− cells undergo apoptosis when surrounded by wild-type cells in the wing disc epithelium. Importantly, comparable phenomena also occur in Mahjong-knockdown mammalian cells; Mahjong-knockdown Madin-Darby canine kidney epithelial cells undergo apoptosis, only when surrounded by non-transformed cells. Similarly, apoptosis of lgl−/− cells is induced when they are surrounded by wild-type cells in Drosophila wing discs. Phosphorylation of the c-Jun N-terminal kinase (JNK) is increased in mahj−/− or lgl−/− mutant cells, and expression of Puckered (Puc), an inhibitor of the JNK pathway, suppresses apoptosis of these mutant cells surrounded by wild-type cells, suggesting that the JNK pathway is involved in mahj- or lgl-mediated cell competition. Finally, we have shown that overexpression of Mahj in lgl−/− cells strongly suppresses JNK activation and blocks apoptosis of lgl−/− cells in the wild-type wing disc epithelium. These data indicate that Mahjong interacts with Lgl biochemically and genetically and that Mahjong and Lgl function in the same pathway to regulate cellular competitiveness. As far as we are aware, this is the first report that cell competition can occur in a mammalian cell culture system.

natselrox wrote:May I propose this article as the next one? It would be an interesting read and could potentially lead to discussions on vision and other fascinating discoveries in opthalmology (one of the subjects in my ongoing semester ). Optogenetics is also a fascinating new discipline!

Most importantly, I need someone to mail the whole article to me!

The Abstract wrote:Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.

Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa

Mr.Samsa wrote:I don't mind which article comes up next, but Natselrox, this article is open access: http://www.hal.inserm.fr/docs/00/49/67/ ... mall-2.pdf

natselrox wrote:

Mr.Samsa wrote:I don't mind which article comes up next, but Natselrox, this article is open access: http://www.hal.inserm.fr/docs/00/49/67/ ... mall-2.pdf

Like I said, you're a ROCKSTAR!!!!

Thanks!

rEvolutionist wrote::popcorn:

*Although, if the articles are too technically specific in a field I'm not familiar with, then I might not be so interested. I haven't read all the preceding pages yet, so don't know if this has been suggested, but would it be a good idea to limit the articles to ones of a more general nature, so as not to disenfranchise those who don't know the specifics?

rEvolutionist wrote:Oh, yeah. I just saw the date of the post previous to mine.

I'll ask our library what the copyright issues are with some of the journals. I know that it is legal to copy up to about 10% of a bound book (so that includes a bound journal of multiple volumes/issues), and that in some cases it is ok to use that for educational purposes. I suspect you are right that we couldn't post a whole article from Nature or Science, but I'll ask anyway, and see what answer I get. We might be able to get away with posting the Abstract/Introduction and Conclusions perhaps?

rEvolutionist wrote:Oh, yeah. I just saw the date of the post previous to mine.

I'll ask our library what the copyright issues are with some of the journals. I know that it is legal to copy up to about 10% of a bound book (so that includes a bound journal of multiple volumes/issues), and that in some cases it is ok to use that for educational purposes. I suspect you are right that we couldn't post a whole article from Nature or Science, but I'll ask anyway, and see what answer I get. We might be able to get away with posting the Abstract/Introduction and Conclusions perhaps?

In this paper five conditions are specified which must be met before reciprocal altruism, rather than kin selection, should be invoked. Four purported mammalian examples-- social grooming in coati, cluster position in roosting pallid bats, information exchange among greater spear-nosed bats, and blood regurgitation among vampire bats--are examined to determine if reciprocal altruism is necessary to plausibly explain each situation. Results from a computer simulation which apportions the relative selective advantage of vampire bat food sharing to kin selection and reciprocal altruism are then presented. The results demonstrate that the increase in individual survivorship due to reciprocal food sharing events in this species provides a greater increase in inclusive fitness than can be attributed to aiding relatives. This analysis suggests that reciprocal altruism can be selectively more important than kin selection when altruistic behaviors in a relatively large social group occur frequently and provide a major fitness benefit to the recipient even when that recipient is related to the donor.

Notwithstanding the provisions of sections 17 U.S.C. § 106 and 17 U.S.C. § 106A, the fair use of a copyrighted work, including such use by reproduction in copies or phonorecords or by any other means specified by that section, for purposes such as criticism, comment, news reporting, teaching (including multiple copies for classroom use), scholarship, or research, is not an infringement of copyright. In determining whether the use made of a work in any particular case is a fair use the factors to be considered shall include:

1. the purpose and character of the use, including whether such use is of a commercial nature or is for nonprofit educational purposes;
2. the nature of the copyrighted work;
3. the amount and substantiality of the portion used in relation to the copyrighted work as a whole; and
4. the effect of the use upon the potential market for or value of the copyrighted work.

The fact that a work is unpublished shall not itself bar a finding of fair use if such finding is made upon consideration of all the above factors.[1]

3. the amount and substantiality of the portion used in relation to the copyrighted work as a whole; and