Martina McMenami, Anna Berglind and James M. S. Wason; Orphanet Journal of Rare Diseases 201813:81 doi:10.1186/s13023-018-0819-1
In rare diseases where there are few or no available treatments and limited opportunity to test emerging new treatments, the power to detect an effective treatment is of critical importance. The augmented binary method with small sample adjustments offers a substantial improvement for trials in these populations over methods currently being used, which throw away valuable information. We recommend the use of the augmented binary method in relevant rare disease trials using composite endpoints and supply R code to assist with the implementation.
Friday, May 25, 2018
Biomimetic Artificial Epigenetic Code for Targeted Acetylation of Histones
Junichi Taniguchi, Yihong Feng, Ganesh N. Pandian, Fumitaka Hashiya, Takuya Hidaka, Kaori Hashiya, Soyoung Park, Toshikazu Bando, Shinji Ito, and Hiroshi Sugiyama; . Am. Chem. Soc., Article ASAP DOI: 10.1021/jacs.8b01518 Publication Date (Web): May 24, 2018
Recently, Ansari’s group reported a conjugate called Syn-TEF by coupling a PIP with another bromodomain inhibitor(+)-JQ1, selective to the bromodomain and extraterminal(BET) protein family. 45 Syn-TEF1 targeting expanded GAA repeats in the frataxin (FXN) gene successfully recruited BET protein BRD4 (bromodomain 4) to the gene locus in Friedreich’s ataxia (FRDA) patient-derived cells, resulting intranscriptional elongation of FXN. However, Syn-TEF and Bi-PIP target different members of the BD protein family and, therefore, are demonstrated to cause different outcomes; i.e.,while Syn-TEF causes BRD4-dependent transcriptional elongation, Bi-PIP causes P300 dependent histone acetylation. Thus,Bi-PIP and Syn-TEF can be used for different purposes, and this allows us to expand the range of potential applications of the synthetic epigenetic regulators.
Recently, Ansari’s group reported a conjugate called Syn-TEF by coupling a PIP with another bromodomain inhibitor(+)-JQ1, selective to the bromodomain and extraterminal(BET) protein family. 45 Syn-TEF1 targeting expanded GAA repeats in the frataxin (FXN) gene successfully recruited BET protein BRD4 (bromodomain 4) to the gene locus in Friedreich’s ataxia (FRDA) patient-derived cells, resulting intranscriptional elongation of FXN. However, Syn-TEF and Bi-PIP target different members of the BD protein family and, therefore, are demonstrated to cause different outcomes; i.e.,while Syn-TEF causes BRD4-dependent transcriptional elongation, Bi-PIP causes P300 dependent histone acetylation. Thus,Bi-PIP and Syn-TEF can be used for different purposes, and this allows us to expand the range of potential applications of the synthetic epigenetic regulators.
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