What is claimed is:
1. An isolated nucleic acid encoding a G-protein coupled receptor, the receptor comprising greater than 70% amino acid identity to an amino acid sequence of SEQ ID NO:1, orSEQ ID NO:2.
2. The isolated nucleic acid of claim 1, wherein the nucleic acid encodes a receptor that specifically binds to polyclonal antibodies generated against SEQ ID NO:1, or SEQ ID NO:2.
3. The isolated nucleic acid of claim 1, wherein the nucleic acid encodes a receptor that has G-protein coupled receptor activity.
4. The isolated nucleic acid of claim 1, wherein the nucleic acid encodes a receptor comprising an amino acid sequence of SEQ ID NO:1, or SEQ ID NO:2.
5. The isolated nucleic acid sequence of claim 1, wherein the nucleic acid comprises a nucleotide sequence of SEQ ID NO:3, or SEQ ID NO:4.
6. The isolated nucleic acid of claim 1, wherein the nucleic acid is from a human, or a mouse.
7. The isolated nucleic acid of claim 1, wherein the nucleic acid encodes a receptor having a molecular weight of about between 38-42 kDa.
8. An isolated nucleic acid encoding a G-protein coupled receptor, wherein the nucleic acid specifically hybridizes under highly stringent conditions to a nucleic acid having the sequence of SEQ ID NO:3, or SEQ ID NO:4.
9. An isolated nucleic acid encoding a G-protein coupled receptor, the receptor comprising greater than 70% amino acid identity to a polypeptide having a sequence of SEQ ID NO:1, or SEQ ID NO:2, wherein the nucleic acid selectively hybridizes under moderately stringent hybridization conditions to a nucleotide sequence of SEQ ID NO:3, or SEQ ID NO:4.
10. An isolated nucleic acid encoding an extracellular domain of a G-protein coupled receptor, the extracellular domain having greater than 70% amino acid sequence identity to the extracellular domain of SEQ ID NO:1.
11. The isolated nucleic acid of claim 10, wherein the nucleic acid encodes the extracellular domain linked to a nucleic acid encoding a heterologous polypeptide, forming a chimeric polypeptide.
12. The isolated nucleic acid of claim 10, wherein the nucleic acid encodes the extracellular domain of SEQ ID NO:1.
13. An isolated nucleic acid encoding a transmembrane domain of a G-protein coupled receptor, the transmembrane domain comprising greater than 70% amino acid sequence identity to the transmembrane domain of SEQ ID NO:1.
14. The isolated nucleic acid of claim 13, wherein nucleic acid encodes the transmembrane domain linked to a nucleic acid encoding a heterologous polypeptide, forming a chimeric polypeptide.
15. The isolated nucleic acid of claim 13, wherein the nucleic acid encodes the transmembrane domain of SEQ ID NO:1.
16. The isolated nucleic acid of claim 13, wherein the nucleic acid further encodes a cytoplasmic domain comprising greater than 70% amino acid identity to the cytoplasmic domain of SEQ ID NO:1.
17. The isolated nucleic acid of claim 16, wherein the nucleic acid encodes the cytoplasmic domain of SEQ ID NO:1.
18. An isolated G-protein coupled receptor, the receptor comprising greater than 70% amino acid sequence identity to an amino acid sequence of SEQ ID NO:1, or SEQ ID NO:2.
19. The isolated receptor of claim 18, wherein the receptor specifically binds to polyclonal antibodies generated against SEQ ID NO:1, or SEQ ID NO:2.
20. The isolated receptor of claim 18, wherein the receptor has G-protein coupled receptor activity.
21. The isolated receptor of claim 18, wherein the receptor has an amino acid sequence of SEQ ID NO:1, or SEQ ID NO:2.
22. The isolated receptor of claim 18, wherein the receptor is from a human, or a murine.
23. An isolated polypeptide comprising an extracellular domain of a G-protein coupled receptor, the extracellular domain comprising greater than 70% amino acid sequence identity to the extracellular domain of SEQ ID NO:1.
24. The isolated polypeptide of claim 23, wherein the polypeptide encodes the extracellular domain of SEQ ID NO:1.
25. The isolated polypeptide of claim 23, wherein the extracellular domain is covalently linked to a heterologous polypeptide, forming a chimeric polypeptide.
26. An isolated polypeptide comprising a transmembrane domain of a G-protein coupled receptor, the transmembrane domain comprising greater than 70% amino acid sequence identity to the transmembrane domain of SEQ ID NO:1.
27. The isolated polypeptide of claim 26, wherein the polypeptide encodes the transmembrane domain of SEQ ID NO:1.
28. The isolated polypeptide of claim 26, further comprising a cytoplasmic domain comprising greater than 70% amino acid identity to the cytoplasmic domain of SEQ ID NO:1.
29. The isolated polypeptide of claim 28, wherein the polypeptide encodes the cytoplasmic domain of SEQ ID NO:1.
30. The isolated polypeptide of claim 26, wherein the transmembrane domain is covalently linked to a heterologous polypeptide, forming a chimeric polypeptide.
31. The isolated polypeptide of claim 30, wherein the chimeric polypeptide has G-protein coupled receptor activity.
32. An antibody that selectively binds to the receptor of claim 18.
33. An expression vector comprising the nucleic acid of claim 1.
34. A host cell transfected with the vector of claim 33.
35. A method for identifying a compound that modulates signaling in islet cells, the method comprising the steps of:
(i) contacting the compound with a polypeptide comprising an extracellular domain of a G-protein coupled receptor, the extracellular domain comprising greater than 70% amino acid sequence identity to the extracellular domain of SEQ ID NO:1, or SEQ ID NO:2; and
(ii) determining the functional effect of the compound upon the extracellular domain.
36. The method of claim 35, wherein the polypeptide is a G-protein coupled receptor, the receptor comprising greater than 70% amino acid identity to a polypeptide encoding SEQ ID NO:1, or SEQ ID NO:2.
37. The method of claim 36, wherein polypeptide comprises an extracellular domain that is covalently linked to a heterologous polypeptide, forming a chimeric polypeptide.
38. The method of claim 36 or 37, wherein the polypeptide has G-protein coupled receptor activity.
39. The method of claim 35, wherein the extracellular domain is linked to a solid phase.
40. The method of claim 39, wherein the extracellular domain is covalently linked to a solid phase.
41. The method of claim 36 or 37, wherein the functional effect is determined by measuring changes in intracellular cAMP, IP3, or Ca2.
42. The method of claim 35, wherein the functional effect is a chemical effect.
43. The method of claim 35, wherein the functional effect is determined by measuring binding of the compound to the extracellular domain.
44. The method of claim 35, wherein the polypeptide is recombinant.
45. The method of claim 35, wherein the polypeptide is from a murine, or a human.
46. The method of claim 35, wherein the polypeptide comprises an amino acid sequence of SEQ ID NO:1, or SEQ ID NO:2.
47. The method of claim 36 or 37, wherein the polypeptide is expressed in a cell or cell membrane.
48. The method of claim 47, wherein the cell is a eukaryotic cell.
49. The method of claim 48, wherein the eukaryotic cell is an islet cell.
50. A method for identifying a compound that modulates signaling in islet cells, the method comprising the steps of:
(i) contacting the compound with a polypeptide comprising a transmembrane domain of a G-protein coupled receptor, the transmembrane domain comprising greater than 70% amino acid sequence identity to the transmembrane domain of SEQ ID NO:1, or SEQ ID NO:2; and
(ii) determining the functional effect of the compound upon the transmembrane domain.
51. The method of claim 50, wherein the polypeptide comprises an transmembrane domain that is covalently linked to a heterologous polypeptide, forming a chimeric polypeptide.
52. The method of claim 50, wherein the chimeric polypeptide has G-protein coupled receptor activity.
53. The method of claim 50, wherein the functional effect is determined by measuring changes in intracellular cAMP, IP3, or Ca2.
54. The method of claim 50, wherein the functional effect is a chemical effect.
55. The method of claim 50, wherein the functional effect is a physical effect.
56. The method of claim 50, wherein the polypeptide is recombinant.
57. The method of claim 50, wherein the polypeptide is from a murine, or a human.
58. The method of claim 50 or 51, wherein the polypeptide is expressed in a cell or cell membrane.
59. The method of claim 58, wherein the cell is a eukaryotic cell.
60. The method of claim 59, wherein the eukaryotic cell is an islet cell.
61. A method for treating a patient diagnosed with type I or type II diabetes, the method comprising administering a therapeutically effective amount of the compound identified by the method of claim 35 or claim 50.
62. A method of making a G-protein coupled receptor, the method comprising the step of expressing the receptor from a recombinant expression vector comprising a nucleic acid encoding the receptor, wherein the amino acid sequence of the receptor comprises greater than 70% amino acid identity to a polypeptide having a sequence of SEQ ID NO:1, or SEQ ID NO:2.
63. A method of making a recombinant cell comprising a G-protein coupled receptor, the method comprising the step of transducing the cell with an expression vector comprising a nucleic acid encoding the receptor, wherein the amino acid sequence of the receptor comprises greater than 70% amino acid identity to a polypeptide having a sequence of SEQ ID NO:1, or SEQ ID NO:2.
64. A method of making a recombinant expression vector comprising a nucleic acid encoding a G-protein coupled receptor, the method comprising the step of ligating to an expression vector a nucleic acid encoding the receptor, wherein the amino acid sequence of the receptor comprises greater than 70% amino acid identity to a polypeptide having a sequence of SEQ ID NO:1, or SEQ ID NO:2.
65. A method of diagnosing type I or type II diabetes or a predisposition for type I or type II diabetes in a patient, said method comprising:
detecting the level of a polypeptide at least 70% identical to SEQ ID NOs: 1 or 2 in a sample from a patient, wherein a high level of the polypeptide in the sample, compared to level in a non-diabetic individual indicates that the patient is diabetic or is predisposed to some pathological aspects of diabetes.
66. A method of diagnosing type I or type II diabetes or a predisposition for type I or type II diabetes in a patient, said method comprising:
detecting the level of activity of a polypeptide at least 70% identical to SEQ ID NOs: 1 or 2 in a sample from a patient, wherein a high level of activity of the polypeptide in the sample, compared to the level of activity in a non-diabetic individual indicates that the patient is diabetic or is predisposed to some pathological aspects of diabetes.
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 hip abduction orthosis for stabilizing the hip joints of a user, comprising:
a trunk engaging part arranged to be connected with a trunk of a user;
a first thigh engaging part arranged for engaging a thigh of a user; and
a first coupling part connects the first thigh engaging part connecting to the trunk engaging part;
wherein a distance defined between the first thigh engaging part and the trunk engaging part is settable, an abduction angle of the first thigh engaging part is defined between a line operatively extending in the longitudinal direction of a thigh associated with the first thigh engaging part and through a plane of the first thigh engaging part operatively abutting the thigh and a sagittal plane;
wherein the hip abduction orthosis is provided with distance indicating means for indicating the set distance between the first thigh engaging part and the trunk engaging part or a set abduction angle.
2. The hip abduction orthosis according to claim 1, wherein a change of the distance within a predetermined distance range results in a predetermined change of the abduction angle.
3. The hip abduction orthosis according to claim 2, wherein each change of the distance within the predetermined distance range results in a predetermined change of the abduction angle.
4. The hip abduction orthosis according to claim 3, wherein the distance and the abduction angle are set such that, if the set distance increases, the abduction angle coupled therewith decreases.
5. The hip abduction orthosis according to claim 2, wherein the distance range has a length of more than 10 cm.
6. The hip abduction orthosis according to claim 2, wherein the distance range has a length of less than 20 cm.
7. The hip abduction orthosis according to claim 2, wherein the distance range comprises a predetermined curved path.
8. The hip abduction orthosis according to claim 1, wherein a height position of the first thigh engaging part is settable in a height direction of a user.
9. The hip abduction orthosis according to claim 8, wherein the distance, the abduction angle and the height position are coupled such that the first set distance between the first thigh engaging part and the trunk engaging part is coupled with the first set abduction angle and a first set height position and the second set distance different from the first set distance is coupled with the second set abduction angle different from the first set abduction angle and a second set height position different from the first set height position.
10. The hip abduction orthosis according to claim 9, wherein the distance, the abduction angle and the height position are coupled such that the first thigh engaging part is movable along a fixed predetermined path with respect to the trunk engaging part.
11. The hip abduction orthosis according to claim 10, wherein the fixed predetermined path recedes in lateral direction downwards away from a transversal plane through the hip balls of a user.
12. The hip abduction orthosis according to claim 11, wherein an angle defined between the transversal plane and the predetermined path is smaller than 20 degrees.
13. The hip abduction orthosis according to claim 12, wherein an angle included between the transversal plane and the predetermined path is larger than 2 degrees.
14. The hip abduction orthosis according to claim 1, wherein the distance and the abduction angle are coupled such that each set distance is coupled with an abduction angle coupled therewith.
15. The hip abduction orthosis according to claim 14, wherein the distance and the abduction angle are coupled such that, with respect to the trunk engaging part, the first thigh engaging part is movable along a curved path.
16. The hip abduction orthosis according to claim 15, wherein, at least in top plan view, the first thigh engaging part is movable along one and the same arc.
17. The hip abduction orthosis according to claim 15, wherein a radius of the arc is smaller than 500 mm.
18. The hip abduction orthosis according to claim 1, wherein the hip abduction orthosis is arranged for setting the distance between the first thigh engaging part and the trunk engaging part in a plurality of steps.
19. The hip abduction orthosis according to claim 18, wherein a radius of the arc is larger than 100 mm.
20. The hip abduction orthosis according to claim 18, wherein a step of the plurality of steps is smaller than 2.6 cm.
21. The hip abduction orthosis according to claim 18, wherein a step of the plurality of steps larger than 0.2 cm.
22. The hip abduction orthosis according to claim 1, wherein the first thigh engaging part is rotatable about a rotational axis with respect to the first coupling part.
23. The hip abduction orthosis according to claim 22, wherein the first thigh engaging part is connected with that at least one coupling part via a pivot which directly engages the first thigh engaging part.
24. The hip abduction orthosis according to claim 22, wherein the rotational axis extends through that the first thigh engaging part.
25. The hip abduction orthosis according to claim 1, wherein a circumferential dimension of the first thigh engaging part is settable.
26. The hip abduction orthosis according to claim 25, wherein the first thigh engaging part is provided with circumference setting means arranged to lock in or near the set circumferential dimension.
27. The hip abduction orthosis according to claim 25, wherein the first thigh engaging part is provided with circumference indicating means for showing an indication of the set circumferential dimension.
28. The hip abduction orthosis according to claim 1, wherein the abduction angle of the first thigh engaging part is settable, and the distance and the abduction angle are coupled such that a first set distance between the first thigh engaging part and the trunk engaging part are coupled with a first set abduction angle and a second set distance different from the first set distance is coupled with a second set abduction angle different from the first set abduction angle.
29. The hip abduction orthosis according to claim 28, wherein the first coupling part is provided with a guide for guiding the first thigh engaging part from the first set distance and the first set abduction angle coupled therewith to the second set distance and the second set abduction angle coupled therewith.
30. The hip abduction orthosis according to claim 1, wherein the first thigh engaging part comprises a bistable element for keeping the first thigh engaging part open in a first stable condition for placing a thigh therein and keeping the first thigh engaging part substantially closed in a second stable condition for at least partly enclosing a thigh.
31. The hip abduction orthosis according to claim 30, wherein the bistable element comprises a resilient element.
32. The hip abduction orthosis according to claim 1, wherein the orthosis is arranged for operatively transmitting the force from the first thigh engaging part to a second thigh engaging part arranged for engaging a second thigh of a user exclusively via a back side of the orthosis extending on a back side of a user.
33. The hip abduction orthosis according to claim 32, wherein the first thigh engaging part is connected to the second thigh engaging part exclusively via a back side of the orthosis.
34. The hip abduction orthosis according to claim 1, wherein the hip abduction orthosis is arranged for steplessly setting the distance between the first thigh engaging part and the trunk engaging part.
35. The hip abduction orthosis according to claim 1, wherein the first coupling part is arranged for substantially fixing at least one first fixing point of the first thigh engaging part and at least one second fixing point of a second thigh engaging part arranged for engaging a second thigh of a user, in a first or second position, respectively, with respect to the trunk engaging part.
36. The hip abduction orthosis according to claim 1, wherein each set distance is unambiguously coupled with the set abduction angle coupled therewith.
37. The hip abduction orthosis according to claim 1, wherein the hip abduction orthosis is provided with locking means for fixing the set distance.
38. The hip abduction orthosis according to claim 1, wherein the distance indicating means indicate a distance between two backs of the knees of a user corresponding with the set distance.
39. The hip abduction orthosis according to claim 1, wherein the first thigh engaging part has a conical shape when it has been applied to a thigh of a user.
40. The hip abduction orthosis according to claim 1, wherein the first thigh engaging part and the trunk engaging part comprises a substantially rigid molded part manufactured from plastic.
41. The hip abduction orthosis according to claim 1, wherein the first thigh engaging part and the trunk engaging part is provided with a cushion from a flexible or elastic material operatively facing a user.
42. The hip abduction orthosis according to claim 1, wherein, in use, the trunk engaging part is on a back side of a user, wherein the trunk engaging part extends in a height direction operatively extending substantially parallel to a spine of a user, and wherein the trunk engaging part extends in a width direction operatively extending in a lateral direction with respect to a user.
43. The hip abduction orthosis according to claim 1, wherein the trunk engaging part is provided with a band for operatively attaching the trunk engaging part to the trunk of a user.
44. The hip abduction orthosis according to claim 1, wherein the trunk engaging part comprises at least one bistable element for keeping the trunk engaging part open in a first stable condition for being able to place the trunk therein and keeping the trunk engaging part substantially closed in a second stable condition for at least partly enclosing the trunk.
45. An orthosis for stabilizing a joint of a user, comprising:
a base engaging part arranged to be connected with a body portion of a user;
a first body engaging part arranged for engaging a body part of a user, the first body engaging part defining first and second end portions and an intermediate portion therebetween; and
a first coupling part connects the first body engaging part to the base engaging part;
wherein a distance defined between the first body engaging part and the base engaging part is settable, a first angle of the first body engaging part is defined between a line operatively extending in the longitudinal direction of the body part associated with the first body engaging part and through a plane of the first body engaging part operatively abutting that body part and a sagittal plane.
46. The orthosis according to claim 45, further comprising:
a bistable element belonging to the limb engaging part and arranged to maintain the limb engaging part open in a first stable condition for placing a limb therein and maintain the limb engaging part substantially closed in a second stable condition for at least partly enclosing the body part.
47. The orthosis according to claim 46, wherein the intermediate portion of the first body engaging part connects to the first coupling part, the first and second end portions extending freely from the first coupling part, the first and second portions arranged to move relative to the first coupling part when moving from the first and second stable conditions.
48. The orthosis according to claim 47, wherein the first body engaging part includes a first enclosing part bendably pivotally connected to an intermediate part about a first virtual axis.
49. The orthosis according to claim 48, wherein the bistable element is bendably pivotally connected to the first enclosing part about a second virtual rotational axis.
50. The orthosis according to claim 46, wherein the first and second end portions of the engaging part have closure devices arranged to secure the first and second end portions to one another.
51. An orthosis comprising:
an engaging part arranged to at least partly operatively enclose a body part of a user, the engaging part defining first and second end portions and an intermediate portion therebetween;
a bistable element belonging to the engaging part and arranged to maintain the engaging part open in a first stable condition for placing the body part therein and maintain the engaging part substantially closed in a second stable condition for at least partly enclosing the body part;
wherein the engaging part includes a first enclosing part bendably pivotally connected to an intermediate part about a first virtual axis.
52. The orthosis according to claim 51, wherein the engaging part depends from a frame structure and is arranged to secure the frame structure to a body portion of the wearer.
53. The orthosis according to claim 52, wherein the intermediate portion of the engaging part connects to the frame structure, the first and second end portions extending freely from the frame structure, the first and second portions arranged to move relative to the frame structure when moving from the first and second stable conditions.
54. The orthosis according to claim 51, wherein the bistable element is bendably pivotally connected to the first enclosing part about a second virtual rotational axis.
55. The orthosis according to claim 51, wherein the first and second end portions of the engaging part have closure devices arranged to secure the first and second end portions to one another.