Abstract: Provided herein are methods for measuring a molecular flux rate proteins and polypeptides based on analysis of isotopologue abundances of immonium ion fragments within a mass isotopomer using a high resolution mass spectrometric measurement. Such methods may be used, inter alia, to calculate a fraction of newly synthesized protein or polypeptide molecules of interest, a replacement rate of target molecules of interest, and/or a rate of breakdown or degradation of target molecules of interest, e.g., based on isotopologue relative abundances.

Abstract: Provided herein are methods for measuring a molecular flux rate based on analysis of isotopologue abundance within a mass isotopomer, e.g., using a high resolution mass spectrometric measurement. Such methods may be used, inter alia, to calculate a fraction of newly synthesized target molecules of interest, a replacement rate of target molecules of interest, and/or a rate of breakdown or degradation of target molecules of interest, e.g., based on isotopologue relative abundance.

Abstract: The present invention relates to novel diagnostic, prognostic, predictive and pharmacodynamic properties with regard to amyotrophic lateral sclerosis (ALS) and/or Parkinson's disease (PD) with and without dementia components. The methods described herein will prove very useful in the development of diagnostic as well as treatment strategies for patients with amyotrophic lateral sclerosis (ALS) and/or Parkinson's disease (PD).

Abstract: The present invention relates to peptide-phospholipid formulations, methods of generating these formulations and methods of administering these formulations for treatment. The present disclosure also provides methods for increasing cholesterol efflux, inducing anti-atherosclerotic activity, increasing pre-? HDL, inducing anti-inflammatory activity, inhibiting cytokine release (including cytokines TNF-?, IL-1?, and/or IL-6 or a combination thereof) and increasing cholesterol mobilization and/or esterification by administering the peptide-phospholipid formulations disclosed.

Abstract: Provided herein are method for measuring the rate of synthesis, breakdown, transport, or other kinetic parameters of a protein in a tissue of medical interest, without requiring physical sampling of the tissue, by a measurement of the protein in a body fluid.

Abstract: The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules in neurons); a method for measuring the state of activity of this therapeutic target in subjects with established, incipient, or potential motoneuron disease; the discovery of drug agents that modulate neuronal microtubule dynamics in living subjects with motoneuron diseases; the discovery that administration of such agents, alone or in combinations, can provide marked neuroprotective therapy for living subjects with motoneuron diseases including delay in symptoms and prolongation of survival; and the discovery that monitoring of neuronal microtubule dynamics in subjects with motoneuron diseases, in response to therapeutic interventions, allows diagnostic monitoring for optimization of therapeutic regimen and strategy for individual subjects or for drug trials.

Abstract: Hydrocarbon stapling of apolipoprotein mimetic peptides increases the helicity of the peptides, enhances their ability to promote cholesterol efflux by multiple mechanisms and makes them resistant to proteolysis. Hydrocarbon stapled amphipathic helical peptides are useful in the treatment of cardiovascular diseases and other disorders.

Abstract: A method of treating a fibrotic disease or condition in a patient comprising administering noscapine and a pharmaceutical carrier to said patient.

Abstract: The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules in neurons); methods for measuring the state of activity of this therapeutic target in subjects with established, incipient, or potential motoneuron disease; the discovery of drug agents that modulate neuronal microtubule dynamics in living subjects with motoneuron diseases; the discovery that administration of such agents, alone or in combinations, can improve MT-mediated transport of “synaptic vesicle cargo” molecules along and through axons; the discovery that such modulation of altered microtubule dynamics and improvement in MT-transport of molecules along axons can provide marked neuroprotective therapy for living subjects with motoneuron diseases, including delay in symptoms and prolongation of survival; and the discovery that monitoring of neuronal microtubule dynamics in response to therapeutic interventions in subjects with motoneuron diseases, allows diagnostic monitoring, to

Abstract: Stable isotope labeling was used to measure dynamics of tubulin incorporation into microtubule subpopulations representing different neuronal compartments in the murine hippocampus. Neuronal microtubules were largely static. Basal turnover was highest in tau-associated (axona) and growth cone), lower in MAP2-associated (somatodendritic), and lowest in cold stable (axonal shaft) subpopulations. Intracerebroventricular glutamate injection stimulated label incorporation into axonal shaft and somatodendritic microtubules, the latter dependent on cAMP-PKA. Hippocampus-dependent memory formation after contextual fear conditioning was accompanied by increased assembly of MAP2- and cold stable-microtubules. Both microtubule assembly and memory formation were inhibited by the microtubule depolymerizing drug, nocodazole. This approach allows for correlation with behavioral measures of learning and memory and for the screening of candidate agents for stimulatory activities on learning memory.

Abstract: The methods of the present invention allow for the measurement of proliferation, clonal expansion trafficking and/or recruitment of lymphocytes into lymphoid tissue in an in vivo setting. Proliferation, clonal expansion, recruitment and/or trafficking of lymphocytes are measured by using stable isotopes to label newly synthesized DNA, isolating the newly-labeled DNA, and quantifying enrichment of the isolated DNA with mass spectrometry or other appropriate techniques. Such methods are useful in screening candidate drugs for stimulatory or inhibitory effects on proliferation, clonal expansion, recruitment and/or trafficking of lymphocytes. The methods also allow for the discovery of therapeutic agents in disorders of immune regulation such as HIV infection and for optimizing vaccine efficacy.

Abstract: The proliferation and activation of microglia is emerging as an important etiologic factor and target for therapeutic intervention in several CNS diseases, including Alzheimer's disease and multiple sclerosis. Here, we have discovered that retinoic acids dramatically inhibit microglial proliferation in an in vivo model including the widely-used animal model of multiple sclerosis, the experimental autoimmune encephalomyelitis (EAE) mouse model.

Abstract: The invention disclosed herein describes a novel therapeutic target for motoneuron diseases (altered dynamics of microtubules in neurons); a method for measuring the state of activity of this therapeutic target in subjects with established, incipient, or potential motoneuron disease; the discovery of drug agents that modulate neuronal microtubule dynamics in living subjects with motoneuron diseases; the discovery that administration of such agents, alone or in combinations, can provide marked neuroprotective therapy for living subjects with motoneuron diseases including delay in symptoms and prolongation of survival; and the discovery that monitoring of neuronal microtubule dynamics in subjects with motoneuron diseases, in response to therapeutic interventions, allows diagnostic monitoring for optimization of therapeutic regimen and strategy for individual subjects or for drug trials.

Abstract: The methods of the present invention allow for the measurement of ribonucleotide reductase (RR) activity, an important enzyme in the de novo DNA synthesis pathway. Ribonucleotide reductase converts all four ribonucleotides to their deoxy form and is a rate-controlling step in this pathway. Biosynthetic pathways of deoxyribonucleotides (dN) have received considerable attention in the context of anti-proliferative chemotherapy. Inhibitors of various steps in dN biosynthesis, including inhibitors of RR are among the most useful chemotherapeutic agents in cancer, viral infections, and other therapeutic uses. DNA synthesis from the dN salvage pathway is also an important component to DNA replication. The relative contributions from RR vs. salvage pathways are critical to the actions and effectiveness of chemotherapeutic agents that act on nucleoside metabolic pathways. Until now, however, it has not been possible to study these metabolic processes in vivo.