1. A method of identifying a candidate p53 pathway modulating agent, said method comprising the steps of:
(a) providing an assay system comprising a SCD polypeptide selected from the group consisting of SEQ ID NOs: 10-12, or a functionally active fragment or derivative thereof;
(b) contacting the assay system with a candidate test agent; and
(c) determining the expression or activity of the SCD polypeptide in the assay system, wherein a change in SCD polypeptide expression or activity between the presence and absence of said candidate test agent indicates the presence of a candidate p53 pathway modulating agent.
2. The method of claim 1, wherein the assay system comprises cultured cells that express the SCD polypeptide.
3. The method of claim 2, wherein the cultured cells additionally have defective p53 function.
4. The method of claim 1, wherein the assay system includes a screening assay comprising a SCD polypeptide and the candidate test agent is a small molecule modulator.
5. The method of claim 4, wherein the screening assay is a desaturase assay.
6. The method of claim 1, wherein the assay system is selected from the group consisting of an apoptosis assay system, a cell proliferation assay system, an angiogenesis assay system, and a hypoxic induction assay system.
7. The method of claim 1, wherein the assay system includes a binding assay comprising a SCD polypeptide and the candidate test agent is an antibody.
8. The method of claim 1, wherein the assay system includes an expression assay comprising a SCD nucleic acid and the candidate test agent is a nucleic acid modulator.
9. The method of claim 8, wherein the nucleic acid modulator is an antisense oligomer.
10. The method of claim 8, wherein the nucleic acid modulator is a PMO.
11. The method of claim 1 additionally comprising:
(d) administering the candidate p53 pathway modulating agent identified in (c) to a model system comprising cells defective in p53 function and, detecting a phenotypic change in the model system that indicates that the p53 function is restored when compared relative to wild-type cells.
12. The method of claim 11, wherein the model system is a mouse model with defective p53 function.
13. A method for modulating a p53 pathway of a cell comprising contacting a cell defective in p53 function with a candidate modulator that specifically binds to a SCD polypeptide comprising an amino acid sequence selected from group consisting of SEQ ID NO: 10, 11, and 12, whereby p53 function is restored.
14. The method of claim 13, wherein the candidate modulator is administered to a vertebrate animal predetermined to have a disease or disorder resulting from a defect in p53 function.
15. The method of claim 13, wherein the candidate modulator is selected from the group consisting of an antibody and a small molecule.
16. The method of claim 1, comprising the additional steps of:
(d) providing a secondary assay system comprising cultured cells or a non-human animal expressing SCD,
(e) contacting the secondary assay system with the test agent of (b) or an agent derived therefrom; and
(f) determining the expression or activity of SCD in the secondary assay system, wherein a change in SCD expression or activity between the presence and absence of said candidate test agent indicates the presence of a candidate p53 pathway modulating agent.
17. The method of claim 16, wherein the secondary assay system comprises cultured cells.
18. The method of claim 16, wherein the secondary assay system comprises a nonhuman animal.
19. The method of claim 18, wherein the non-human animal mis-expresses a p53 pathway gene.
20. A method of modulating p53 pathway in a mammalian cell comprising contacting the cell with an agent that specifically binds a SCD polypeptide or nucleic acid.
21. The method of claim 20, wherein the agent is administered to a mammalian animal predetermined to have a pathology associated with the p53 pathway.
22. The method of claim 20, wherein the agent is a small molecule modulator, a nucleic acid modulator, or an antibody.
23. A method for diagnosing a disease in a patient comprising:
(a) obtaining a biological sample from the patient;
(b) contacting the sample with a probe for SCD expression;
(c) comparing results from step (b) with a control;
(d) determining whether step (c) indicates a likelihood of disease.
24. The method of claim 23, wherein said disease is cancer.
25. The method according to claim 24, wherein said cancer is a cancer as shown in Table 1 as having >25% expression level.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A lens barrel assembly comprising:
a barrel for housing at least a movable lens;
two guide shafts placed in the barrel so as to be parallel to an optical axis; and
a lens holder which holds the movable lens and which is movable along the optical axis under guide by the guide shafts, wherein
in the lens holder, two guide grooves to be respectively fitted to the two guide shafts are provided, and
a direction toward which an opening portion of one guide groove out of the two guide grooves is directed is different from a direction toward which an opening portion of the other guide groove is directed, wherein
the opening portion of the one guide groove is not directed toward a peripheral direction of the lens holder while the opening portion of the other guide groove is directed toward the peripheral direction of the lens holder such that the other guide groove is fitted to the other guide shaft when the lens holder is rotated or slid against the one guide shaft in such a state that the one guide groove is fitted to the one guide shaft.
2. A lens barrel assembly, comprising:
a barrel for housing at least a movable lens;
two guide shafts placed in the barrel so as to be parallel to an optical axis; and
a lens holder which holds the movable lens and which is movable along the optical axis under guide by the guide shafts, wherein
in the lens holder, two guide grooves to be respectively fitted to the two guide shafts are provided, and
a direction toward which an opening portion of one guide groove out of the two guide grooves is directed is different from a direction toward which an opening portion of the other guide groove is directed, wherein
the barrel is divisible in a direction vertical to the optical axis into a first barrel portion including the lens holder and the two guide shafts and a second barrel portion including a driving mechanism for moving the lens holder along the optical axis.
3. The lens barrel assembly as claimed in claim 2, further comprising
an elastic member which is provided at a vicinity of the one guide groove of the lens holder and which presses the vicinity of the one guide groove of the lens holder toward the guide shaft by elastic force caused by press of the second barrel portion when the second barrel portion is coupled to the first barrel portion.
4. The lens barrel assembly as claimed in claim 3, wherein
with regard to the guide groove positioned in the vicinity of the elastic member in the lens holder,
a cross section of the guide groove in a direction perpendicular to the optical axis direction is U-shaped; and
a direction of a line perpendicular to a plane including the optical axis and a straight line given by a string of points at which a bottom wall of the guide groove makes contact with the guide shaft is identical to a direction of a normal line orthogonal to the bottom wall of the guide groove and orthogonal to the straight line, and moreover the guide groove is opened along the direction of the normal line.
5. The lens barrel assembly as claimed in claim 4, wherein
the movable lens and the lens holder that holds the movable lens are provided in a plural quantity, and
for all the lens holders, the one identical guide shaft is to be inserted through the guide groove located in the vicinity of the elastic member.
6. An assembling method for a lens barrel assembly, comprising:
fitting one guide groove out of two guide grooves, which are provided in a lens holder for holding a lens, to one guide shaft out of two guide shafts placed in a barrel in parallel to an optical axis;
with the one guide groove fitted to the one guide shaft, making the lens holder rotated or slid against the one guide shaft so that the other guide groove whose opening portion is directed toward a direction different from a direction toward which an opening portion of the one guide groove is directed is fitted to the other guide shaft; and
pressing a vicinity of the one guide groove in the lens holder toward the guide shaft by an elastic member provided at the vicinity of the one guide groove in the lens holder.