The present invention relates to the field of anastasis, i.e., the process of reversal of apoptosis. More specifically, the present invention provides methods and compositions useful for studying anastasis. The present invention also provides a biosensor comprising (a) a split transcription factor complex comprising one half of a split transcription factor linked to a transmembrane domain via an enzyme cleavable linker; (b) a split transcription factor comprising the other half of the split transcription factor linked to a MTS via an enzyme-cleavable linker; and (c) a reporter system comprising (1) a first nucleic acid encoding a site specific recombinase operably linked to the site specific sequence for the transcription factor; and (2) a second nucleic acid comprising a stop codon cassette flanked by site specific recombination sequences, wherein the split transcription factor is Gal 4 or split Q. In other embodiments, the recombinase is Cre or FLP.

The present invention relates to the field of anastasis, i.e., the process of reversal of apoptosis. More specifically, the present invention provides methods and compositions useful for studying anastasis. In one embodiment, a tracking construct of the present invention comprises Lyn11-NES-ERT2-DEVD-rtTA-3xFLAG-DEVD-ERT2-NES. In another embodiment, a construct comprises Lyn11-NES-DEVD-rtTA-3xFLAG. In a further embodiment, a construct comprises ERT2-DEVD-rtTA-3XFLAG-DEVD-ERT2.

Provided herein are methods of identifying a marker for a biological interaction, the method comprising: quantifying genome-wide RNA expression in cells; exposing the cells to a perturbagen for a period of time sufficient to induce the biological interaction in the cells, wherein the induced biological interaction comprises inducing changes in RNA expression in the cells that are exposed to the perturbagen; quantifying genome-wide nascent RNA expression in the cells that were exposed to the perturbagen; calculating a difference in the genome-wide nascent RNA expression between (i) the genome-wide RNA expression in the cells absent the perturbagen and (ii) the genome-wide nascent RNA expression in the cells that were exposed to the perturbagen; and identifying the marker using the calculated difference in the genome-wide nascent RNA expression.

The present invention relates to methods for treating an individual with high grade glioblastoma multiforme by preventing or disrupting the binding of CD95 to its ligand, CD95L, in vivo, whereupon that neutralization of CD95 activity reduces undesirable glial cell migration and invasion into body tissue.

The present invention provides an approach for the determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, expression markers and other criteria, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of modulators of cellular activation allows for characterization of pathways and cell populations.

The disclosure provides nonsteroidal anti-inflammatory compositions and methods of use thereof. Specifically, the disclosure provides cell-free or substantially cell-free regenerative nonsteroidal anti-inflammatory compositions derived from placenta and/or from MSC cells isolated therefrom, methods for producing said compositions, and uses thereof to treat chronic and acute inflammatory conditions and diseases.

The invention is based on a method of modulating the activation or inhibition of Mixed lineage kinase domain-like (MLKL) protein, or a MLKL variant protein, via modulating the intramolecular interaction between the C-terminal helix (Hc) of the psK domain and a hydrophobic groove in the MLKL protein. The invention provides methods and compounds for to selectively target the herein firstly disclosed intramolecular interaction of MLKL protein. Based on the herein disclosed essential intramolecular rearrangement of MLKL, the invention provides small molecules capable of specifically inhibiting mouse or human MLKL. The invention provides uses, including medical applications such as treatments, of MLKL driven conditions including necroptosis, cell trafficking, pathological immune responses and/or inflammation.

Provided is a cyclic peptide (cyclo [Cys-Gln-Arg-Pro-Pro-Arg-Cys] peptide) comprised of the amino acid sequence of SEQ ID NO: 2; and a composition for apoptotic cell detection, drug delivery or imaging, containing the same as an active ingredient. The cyclic peptide (cyclo [Cys-Gln-Arg-Pro-Pro-Arg-Cys] peptide has an excellent effect of binding to apoptotic cells, compared with a linear peptide thereof, thereby greatly facilitating the detection of apoptotic cells and the in vivo imaging of an affected part under apoptosis, while the detection and imaging signal shows a very high correlation in disease prognosis prediction. The cyclic peptide binds to an imaging material, early diagnosing a response of a drug for treating diseases associated with abnormal cell proliferation, and binds to a therapeutic material, selectively delivering a drug to tissues afflicted with Apoptosis-associated diseases.

The present invention relates to the field of anastasis, i.e., the process of reversal of apoptosis. More specifically, the present invention provides methods and compositions useful for studying anastasis. In one embodiment, the present invention provides an in vivo biosensor comprising (a) a transcription factor complex comprising the Gal4 transcription factor linked to an enzyme cleavable linker, wherein the transcription factor complex is tethered to the plasma membrane via a transmembrane domain; and (b) a reporter system comprising (1) a first nucleic acid encoding flippase operably linked to the upstream activating sequence that binds Gal4; and (2) a second nucleic acid comprising an FRT-flanked stop codon cassette separating a constitutive promoter and a fluorescent protein open reading frame.

An object of the present invention is to provide novel apoptosis inhibitors and therapeutic agents for inner ear hearing impairment. As a pharmaceutical agent for this purpose, biguanide compounds represented by the following structural formula (I) or a rapamycin derivative represented by the following structural formula (II) as an active ingredient is provided:

##STR00001##

wherein R.sup.1 to R.sup.7 are each independently selected from a hydrogen atom, a halogen atom, or a C.sub.1-.sub.6 alkyl group, a C.sub.3-.sub.8 cycloalkyl group, a C.sub.6-.sub.10 aryl group, a 5- or 6-membered heteroaryl group, or a 5- or 6-membered non-aromatic heterocyclic group, each of which may have a substituent selected from a halogen atom, a cyano group, a C.sub.1-.sub.6 alkyl group, a C.sub.1-.sub.6 alkoxy group, a C.sub.1-.sub.6 alkoxy carbonyl group, a C.sub.3-.sub.8 cycloalkyl group, a C.sub.2-.sub.6 alkenyl group, a C.sub.2-.sub.6 alkynyl group, and a phenyl group;

##STR00002##

wherein R.sub.1 is a C.sub.1-.sub.6 alkyl or a C.sub.3-.sub.6 alkynyl, R.sub.2 is H, —CH2—OH or —CH2—CH2—OH, and X is ═O, (H, H) or (H, OH).