摘要:
The present invention describes a method for identifying one or more of a plurality of sequences differing by one or more single base changes, insertions, deletions, or translocations in a plurality of target nucleotide sequences. The method includes a ligation phase, a capture phase, and a detection phase. The ligation phase utilizes a ligation detection reaction between one oligonucleotide probe, which has a target sequence-specific portion and an addressable array-specific portion, and a second oligonucleotide probe, having a target sequence-specific portion and a detectable label. After the ligation phase, the capture phase is carried out by hybridizing the ligated oligonucleotide probes to a solid support with an array of immobilized capture oligonucleotides at least some of which are complementary to the addressable array-specific portion. Following completion of the capture phase, a detection phase is carried out to detect the labels of ligated oligonucleotide probes hybridized to the solid support. The ligation phase can be preceded by an amplification process. The present invention also relates to a kit for practicing this method, a method of forming arrays on solid supports, and the supports themselves.
摘要:
Dinucleotide cap analogs are disclosed, modified at different phosphate positions with a boranophosphate group or a phosphoroselenoate group. The analogs are useful as reagents in the preparation of capped mRNAs and have increased stability both in vitro and in vivo . They may be used as inhibitors of cap-dependent translation. Optionally, the boranophosphate or phosphoroselenoate group has a 2'-O or 3'-O-alkyl group, preferably a methyl group, producing analogs called BH 3 -ARCAs or Se-ARCAs. ARCAs may be modified with α-, β-, or γ-boranophosphate or phosphoroselenoate groups.
摘要:
Methods of treating a subject who has chronic tissue ischemia are disclosed. The methods can include administering to the subject a pharmaceutical composition comprising inorganic nitrite or a pharmaceutically acceptable salt thereof, for a time and in an amount sufficient to result in blood vessel growth in the ischemic tissue. The subject can be diagnosed as having a medical condition that results in persistent or recurring restriction of blood supply to a tissue, for example, peripheral artery disease, diabetes, atherosclerotic cardiovascular disease or defective wound healing. The methods can include the step of identifying a suitable subject.
摘要:
A soft tissue fixation device for use in ACL or CrCL reconstruction has a base member provided with a tissue passageway extending perpendicularly from its top surface through its bottom surface. An affixing member is attachable to the base member. Teeth may extend from the affixing member. Tissue glue or at least one perpendicularly extending spike is used to secure the base member to bone.
摘要:
The expression of a mRNA encoding a putative 76 amino acid, secreted protein ('Swirl') was found to negatively correlate with fasting triglyceride and cholesterol levels. A recombinant adenovirus was used to increase the expression of Swirl mRNA in two mouse models of obesity, KK-Ay and Lepob/Lepob mice. Over-expression of Swirl by adenovirus injection significantly, and reproducibly, reduced fasting triglyceride and cholesterol levels in both models. In addition, transgenic mice strains were made that over express Swirl protein. The expression of a key gene involved in lipogenesis (fatty acid synthase) and FAS protein levels were reduced by SWIRl adenoviral treatment in Lepob/Lepob mice. Full-length SWIRl peptide, or peptide derivatives, homologues, analogues, or mimetics thereof, delivered by oral intake, injection, subcutaneous patch, or intranasal routes, could be used as therapeutic or diagnostic agents for hypercholesterolemia, hypertriglyceridemia, insulin resistance, obesity, diabetes, and/or energy imbalance.
摘要:
Genes encoding the transcription factors controlling the core circadian oscillator (BMAL, Clock, NPAS, Per) and their regulatory targets (Rev-erba, Rev-erb) have been found in adipose tissue. The circadian pattern of these genes was entrained using restricted feeding. The circadian gene expression profiles were examined in mice and in undifferentiated and adipocyte-differentiated human adipose stem cells following exposure to nuclear hormone receptor ligands (dexamethasone or thiazolidinedione) or 30% fetal bovine serum. All three agents induced the initiation of a cyclic expression profile in representative circadian genes in the human adipose stem cells. The circadian genes studied displayed an oscillatory expression profile, characterized by both a zenith and nadir within a 24-28 hr phase. The circadian gene pattern has been lengthened with use of an inhibitor of glycogen synthase kinase 3 beta. Modulation of the circadian pattern to lengthen or shorten can be used to affect weight gain or loss, respectively.
摘要:
It has been surprisingly discovered that administration of nitrite to subjects causes a reduction in blood pressure and an increase in blood flow to tissues. The effect is particularly beneficial, for example, to tissues in regions of low oxygen tension. This discovery provides useful treatments to regulate a subject's blood pressure and blood flow, for example, by the administration of nitrite salts. Provided herein are methods of administering a pharmaceutically-acceptable nitrite salt to a subject, for treating, preventing or ameliorating a condition selected from: (a) ischemia-reperfusion injury (e.g., hepatic or cardiac or brain ischemia-reperfusion injury); (b) pulmonary hypertension (e.g., neonatal pulmonary hypertension); or (c) cerebral artery vasospasm.
摘要:
This invention relates to a method for inhibiting the growth of neoplasms, in a mammal having a prolactin profile. This method involves comparing the prolactin profile of the afflicted mammal to a standard prolactin profile for healthy mammals of the same species and sex and adjusting the prolactin profile of the afflicted mammal to conform to or approach the standard prolactin profile for a mammal of the same species and sex of the afflicted mammal, thereby inhibiting the neoplastic growth.
摘要:
Administration of modified transposon-based vectors has been used to achieve stable incorporation of exogenous genes into animals. These transgenic animals produce transgenic progeny. Further, these transgenic animals produce large quantities of desired molecules encoded by the transgene. Transgenic egg-laying animals produce large quantities of desired molecules encoded by the transgene and deposit these molecules in the egg.
摘要:
Noni juice and a protein-free, alcohol precipitate of Noni juice inhibited angiogenesis in in vitro human angiogenesis models. When growth medium contained Noni juice at least over the range from about 2.5% to about 33% (by volume), angiogenesis was blocked. Moreover, Noni juice and an ethanol precipitate were able to destroy a pre-existing angiogenic response as well as prevent the development of new vessels. Noni juice was effective in inhibiting the growth of angiogenic vessels from breast cancer explants. It will also be effective in treating cancers and non-cancerous diseases whose response includes an increase in angiogenesis, e.g., retinopathy of prematurity, neovascular glaucoma, diabetic retinopathy, and psoriasis. The primary antiangiogenic component is believed to be a carbohydrate with a molecular weight less than about 6000 Daltons. In an initial experiment, oral administration of Noni juice appeared to adversely affect the antioangiogenic component(s) in the juice.