An isolated peptide being no longer than 20 amino acids comprising a sequence at least 95% homologous to the sequence GQLNHILGILGX.sub.1PX.sub.2QED (SEQ ID NO: 4), wherein X.sub.1 and X.sub.2 are any amino acid, the peptide being capable of preventing extracellular signal-regulated kinase1/2 (ERK) translocation into the nucleus.

The present application generally relates to the discovery that glycogen synthase kinase 3 (GSK-3) is an upstream signalling molecule that controls PD-1 transcription and Tbet expression by immune cells and in particular T-cells. Based on this discovery, and in view of the known immunosuppressive effect of PD-1 on immunity and the promoting effect of Tbet on T cell immunity, the present invention relates to the use of GSK-3 inhibitors to promote immunity, including cytotoxic T cell immunity in subjects in need thereof, especially subjects with chronic conditions wherein inhibiting PD-1 expression and/or blockade or Tbet up-regulation is therapeutically desirable such as cancer and infectious conditions. Further, based on this discovery the present invention relates to the use of compounds which promote GSK-3 expression or activity to suppress immunity, especially aberrant T cell immunity in subjects in need thereof, e.g., subjects with chronic conditions wherein PD-1 upregulation or Tbet down regulation is therapeutically desirable such as allergic, autoimmune or inflammatory conditions. Also, screening methods for identifying immune agonists and antagonists, especially antibodies, are provided.

The present invention is based, in part, on the identification of an IRE1-XBP1-cMyc axis in NK cell immunity. The present invention provides compositions and methods for treating conditions that would benefit from modulating (e.g., upregulating or downregulating) an immune response using an agent that modulates the IRE1-XBP1 pathway, or a composition comprising modified NK cells.

The present invention relates to a modified microorganism having, compared to its wildtype,a reduced activity of an enzyme encoded by the ptsA-gene,a reduced activity of an enzyme encoded by the ptsH-gene ora reduced activity of an enzyme encoded by the ptsA-gene and a reduced activity of an enzyme encoded by the ptsH-gene, wherein the wildtype from which the modified microorganism has been derived belongs to the family of Pasteurellaceae. The present invention also relates to a method for producing succinic acid and to the use of modified microorganisms.

An isolated or a purified nucleic acid sequence for enhancing expression levels of a protein of interest, in 5 to 3 direction, comprises: a cytomegalovirus (CMV) promoter; an eEF-1 intron repeat (eEF-1 IR); and a regular sequence, which comprises: at least one tag element, a fixable linker sequence, wherein the fixable sequence is TEV sequence; and a multiple cloning site (MCS). By means of the array of the specific promoter and eEF-1 IR, the expression and purity of the recombinant protein could be enhanced; wherein eEF-1 IR can reduce the length of vector and assist RNA polymerase II transcription. Besides, TEV sequence of the fixable linker sequence of the regular sequence can remove a tag on recombinant protein; a specific target can be inserted into the multiple cloning site.

Provided herein are methods, compounds, and compositions for reducing expression of a DMPK mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for preferentially reducing CUGexp DMPK RNA, reducing myotonia or reducing spliceopathy in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate type 1 myotonic dystrophy, or a symptom thereof.

The present invention provides an enzyme and the like that phosphorylates a 2 hydroxyl group of RNA.