A Real-world <em>What-Where-When</em> Memory Test

Episodic memory is a complex memory system which allows recall and mental re-experience of previous episodes from one&#39;s own life. Real-life episodic ...

Comparisons of functionally important changes at the molecular level in model systems have identified key adaptations driving isolation and speciation. In cichlids, for example, long wavelength-sensitive (LWS) opsins appear to play a role in mate choice and male color variation within and among species. To test the hypothesis that the evolution of elaborate coloration in male guppies (Poecilia reticulata) is also associated with opsin gene diversity, we sequenced long wavelength-sensitive (LWS) opsin genes in six species of the family Poeciliidae.

The molecular basis of color vision in colorful fish: four long wave-sensitive (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid substitutions at key functional sites.

The T:G mismatch specific DNA glycosylase (TDG) is known as an important enzyme in repairing damaged DNA. Recent studies also showed that TDG interacts with a p160 protein, steroid receptor coactivator 1 or nuclear receptor coactivator 1 (SRC1), and is involved in transcriptional activation of the estrogen receptor. However, whether other members of the p160 family are also involved in TDG-interaction and signal transduction regulation remains to be seen. In this study, we employed the mammalian two-hybrid system to investigate the interaction between TDG and another member of the p160 family, nuclear receptor coactivator 3 (NCoA-3). We found that a DXXD motif from aa 294-297 within TDG was responsible for the TDG-NCoA-3 interaction, we also found that a LLXXXL motif (X means any amino acid) from aa 1029-1037 (LLRNSL) and a merged LLXXL motif (LLDQLHTLL) from aa 1053-1061 in NCoA-3 were important for the TDG-NCoA-3 interactions. Mutation of the two aspartic acids (aa 294 and 297) into two alanines in TDG significantly affected the interaction and subsequent transcriptional activation of several steroid hormone receptors including, estrogen-, androgen- and progesterone- receptors in Huh7 cells. We also identified that mutations of NCoA-3 at either leucines 1029-1030 or 1053-1054 (replaced by alanines) also reduced the interaction activity between TDG and NCoA1. These data indicated that the TDG-NCoA-3 interaction is important for broad range activation of steroid hormone nuclear receptors, and may also contribute significantly to further understanding of TDG-related nuclear receptor regulation.

The interaction between thymine DNA glycosylase and nuclear receptor coactivator 3 is required for the transcriptional activation of nuclear hormone receptors.

T:G Missverh&auml;ltnis spezifische DNA Glycosylase (TDG) ist bekannt als ein wichtiges Enzym in der Reparatur besch&auml;digter DNA. Neuere Studien zeigten auch, dass die TDG interagiert mit p160 Protein, Steroid-Rezeptor Coactivator 1 oder Kernempf&auml;nger Coactivator 1 (SRC1) und transkriptionelle Aktivierung der &Ouml;strogen-Rezeptor beteiligt ist. Allerdings, ob andere Mitglieder der Familie p160 sind auch TDG-Interaktion und signal-Transduktion Verordnung bleibt abzuwarten. In dieser Studie haben wir die S&auml;ugetier-zwei-Hybrid-System, die Interaktion zwischen TDG und ein weiteres Mitglied der p160 Familie, Nuklear-Rezeptor Coaktivator 3 (Umzugspr&uuml;fung-3) zu untersuchen. Wir fanden, dass ein DXXD Motiv von aa 294-297 innerhalb TDG verantwortlich f&uuml;r die TDG-Umzugspr&uuml;fung-3-Interaktion, wir fanden auch, dass ein LLXXXL Motiv (X bedeutet jede Aminos&auml;ure) von aa 1029-1037 (LLRNSL) und einem zusammengef&uuml;hrten LLXXL Motiv (LLDQLHTLL) von aa 1053-1061 Umzugspr&uuml;fung-3 f&uuml;r die TDG-Umzugspr&uuml;fung-3-Interaktionen wichtig waren. Mutation der zwei Aspartic S&auml;uren (aa 294 und 297) in zwei Alanines im TDG beeinflusst wesentlich die Interaktion und die anschlie&szlig;ende transkriptionelle Aktivierung von mehreren Steroidhormon-Rezeptoren einschlie&szlig;lich, &Ouml;strogen, Androgen und Progesteron-Rezeptoren in den Huh7 Zellen. Wir wurden auch die Mutationen Umzugspr&uuml;fung-3 bei Leucine 1029-1030 oder 1053-1054 (durch Alanines ersetzt) auch die Aktivit&auml;t der Interaktion zwischen TDG und NCoA1 reduziert. Diese Daten zeigten, dass die TDG-Umzugspr&uuml;fung-3-Interaktion wichtig f&uuml;r die breite Palette Aktivierung Steroidhormon Kernrezeptoren ist und m&ouml;glicherweise auch wesentlich zur weiteren Verst&auml;ndnis des TDG im Zusammenhang mit nuklearen Rezeptorregulation tragen.

Die Interaktion zwischen Thymin DNA Glycosylase und Kernempf&auml;nger Coactivator 3 ist erforderlich f&uuml;r die transkriptionelle Aktivierung der nuklearen Hormonrezeptoren.

Cellular tropism of vaccinia virus (VACV) is regulated by host range genes, including K1L, C7L, and E3L. While E3L is known to support viral replication by antagonizing interferon (IFN) effectors, including PKR, the exact functions of K1L and C7L are unclear. Here, we show that K1L and C7L can also inhibit antiviral effectors induced by type I IFN. In human Huh7 and MCF-7 cells, a VACV mutant lacking both K1L and C7L (vK1L-C7L-) replicated as efficiently as wild-type (WT) VACV, even in the presence of IFN. However, pretreating the cells with type I IFN, while having very little effect on WT VACV, blocked the replication of vK1L-C7L- at the step of intermediate viral gene translation. Restoring either K1L or C7L to vK1L(-)C7L(-) fully restored the IFN resistance phenotype. The deletion of K1L and C7L from VACV did not affect the ability of the virus to inhibit IFN signaling or its ability to inhibit the phosphorylation of PKR and the alpha subunit of eukaryotic initiation factor 2, indicating that K1L and C7L function by antagonizing an IFN effector(s) but with a mechanism that is different from those of IFN antagonists previously identified for VACV. Mutations of K1L that inactivate the host range function also rendered K1L unable to antagonize IFN, suggesting that K1L supports VACV replication in mammalian cells by antagonizing the same antiviral factor(s) that is induced by IFN in Huh7 cells.

Vaccinia virus K1L and C7L inhibit antiviral activities induced by type I interferons.

We identified the interaction between HBV X (HBx) protein and the oncogene AIB1 (amplified in breast cancer 1). A serine/proline motif (SSPSPS) in HBx was found to be required for the interaction. Two LXD motifs [LLXX(X)L, X means any amino acids], LLRNSL and LLDQLHTLL in AIB1 were also found to be involved in the HBx-AIB1 interaction. The HBx-AIB1 interaction was important for the activation of NFÎºB signal transduction, the HBx mutant that did not interact with AIB1showed dramatically lower NFÎºB activation activity than the WT HBx. These findings contribute to the new understanding on signal transduction activation mechanisms of HBx.

Article	Year
The molecular basis of color vision in colorful fish: four long wave-sensitive (LWS) opsins in guppies (Poecilia reticulata) are defined by amino acid substitutions at key functional sites. BMC evolutionary biology\| PubMed ID: 18638376	2008
The interaction between thymine DNA glycosylase and nuclear receptor coactivator 3 is required for the transcriptional activation of nuclear hormone receptors. Molecular and cellular biochemistry\| PubMed ID: 19652917	2010
Vaccinia virus K1L and C7L inhibit antiviral activities induced by type I interferons. Journal of virology\| PubMed ID: 19656868	2009
The interaction between hepatitis B virus X protein and AIB1 oncogene is required for the activation of NFÎºB signal transduction. Biochemical and biophysical research communications\| PubMed ID: 22627138	2012

Kevin Dick

Biography

JoVE Journal Publications

Other Publications