Lie algebroid structures on a class of affine bundles

We introduce the notion of a Lie algebroid structure on an affine bundle whose base manifold is fibred over the real numbers. It is argued that this is the framework which one needs for coming to a time-dependent generalization of the theory of Lagrangian systems on Lie algebroids. An extensive discussion is given of a way one can think of forms acting on sections of the affine bundle. It is further shown that the affine Lie algebroid structure gives rise to a coboundary operator on such forms. The concept of admissible curves and dynamical systems whose integral curves are admissible, brings an associated affine bundle into the picture, on which one can define in a natural way a prolongation of the original affine Lie algebroid structure.Comment: 28 page

Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier

Breast cancer brain metastasis is a major clinical challenge and is associated with a dismal prognosis. Understanding the mechanisms underlying the early stages of brain metastasis can provide opportunities to develop efficient diagnostics and therapeutics for this significant clinical challenge. We have previously reported that breast cancer-derived extracellular vesicles (EVs) breach the blood–brain barrier (BBB) via transcytosis and can promote brain metastasis. Here, we elucidate the functional consequences of EV transport across the BBB. We demonstrate that brain metastasis-promoting EVs can be internalized by astrocytes and modulate the behavior of these cells to promote extracellular matrix remodeling in vivo. We have identified protein and miRNA signatures in these EVs that can lead to the interaction of EVs with astrocytes and, as such, have the potential to serve as targets for development of diagnostics and therapeutics for early detection and therapeutic intervention in breast cancer brain metastasis

Cdc42-Dependent Transfer of mir301 from Breast Cancer-Derived Extracellular Vesicles Regulates the Matrix Modulating Ability of Astrocytes at the Blood–Brain Barrier

Breast cancer brain metastasis is a major clinical challenge and is associated with a dismal prognosis. Understanding the mechanisms underlying the early stages of brain metastasis can provide opportunities to develop efficient diagnostics and therapeutics for this significant clinical challenge. We have previously reported that breast cancer-derived extracellular vesicles (EVs) breach the blood–brain barrier (BBB) via transcytosis and can promote brain metastasis. Here, we elucidate the functional consequences of EV transport across the BBB. We demonstrate that brain metastasis-promoting EVs can be internalized by astrocytes and modulate the behavior of these cells to promote extracellular matrix remodeling in vivo. We have identified protein and miRNA signatures in these EVs that can lead to the interaction of EVs with astrocytes and, as such, have the potential to serve as targets for development of diagnostics and therapeutics for early detection and therapeutic intervention in breast cancer brain metastasis

Egorov's theorem for transversally elliptic operators on foliated manifolds and noncommutative geodesic flow

The main result of the paper is Egorov's theorem for transversally elliptic operators on compact foliated manifolds. This theorem is applied to describe the noncommutative geodesic flow in noncommutative geometry of Riemannian foliations.Comment: 23 pages, no figures. Completely revised and improved version of dg-ga/970301

Nambu-Poisson manifolds and associated n-ary Lie algebroids

We introduce an n-ary Lie algebroid canonically associated with a Nambu-Poisson manifold. We also prove that every Nambu-Poisson bracket defined on functions is induced by some differential operator on the exterior algebra, and characterize such operators. Some physical examples are presented

Serum Protein Signatures Using Aptamer-Based Proteomics for Minimal Change Disease and Membranous Nephropathy

Introduction: Minimal change disease (MCD) and membranous nephropathy (MN) are glomerular diseases (glomerulonephritis [GN]) that present with the nephrotic syndrome. Although circulating PLA2R antibodies have been validated as a biomarker for MN, the diagnosis of MCD and PLA2R-negative MN still relies on the results of kidney biopsy or empirical corticosteroids in children. We aimed to identify serum protein biomarker signatures associated with MCD and MN pathogenesis using aptamer-based proteomics. Methods: Quantitative SOMAscan proteomics was applied to the serum of adult patients with MCD (n = 15) and MN(n = 37) and healthy controls (n = 20). Associations between the 1305proteins detected with SOMAscan were assessed using multiple statistical tests, expression pattern analysis, and systems biology analysis. Results: A total of 208 and 244 proteins were identified that differentiated MCD and MN, respectively, with high statistical significance from the healthy controls (Benjamin-Hochberg [BH] P \u3c 0.0001). There were 157 proteins that discriminated MN from MCD (BH P \u3c 0.05). In MCD, 65 proteins were differentially expressed as compared with MN and healthy controls. When compared with MCD and healthy controls, 44 discriminatory proteins were specifically linked to MN. Systems biology analysis of these signatures identified cell death and inflammation as key pathways differentiating MN from MCD and healthy controls. Dysregulation of fatty acid metabolism pathways was confirmed in both MN and MCD as compared with the healthy subjects. Conclusion: SOMAscan represents a promising proteomic platform for biomarker development in GN. Validation of a greater number of discovery biomarkers in larger patient cohorts is needed before these data can be translated for clinical care

Aptamer Proteomics of Serum Exosomes From Patients With Primary Raynaud\u27s and Patients With Raynaud\u27s at Risk of Evolving into Systemic Sclerosis

BACKGROUND: A major unmet need for Systemic Sclerosis (SSc) clinical management is the lack of biomarkers for the early diagnosis of patients with Raynaud\u27s Phenomenon at high risk of evolving into SSc. OBJECTIVE: To identify proteins contained within serum exosomes employing an aptamer proteomic analysis that may serve to reveal patients with Raynaud\u27s Phenomenon at risk of developing SSc. METHODS: Exosomes were isolated from serum samples from patients with Primary Raynaud\u27s Phenomenon and from patients with Raynaud\u27s Phenomenon harbouring serum antinuclear antibodies (ANA) who may be at high risk of evolving into SSc. The expression of 1,305 proteins was quantified using SOMAscan aptamer proteomics, and associations of the differentially elevated or reduced proteins with the clinical subsets of Raynaud\u27s Phenomenon were assessed. RESULTS: Twenty one differentially elevated and one differentially reduced (absolute fold change \u3e|1.3|) proteins were identified. Principal component analysis using these 22 most differentially expressed proteins resulted in excellent separation of the two Raynaud\u27s Phenomenon clinical subsets. Remarkably, the most differentially elevated proteins are involved in enhanced inflammatory responses, immune cell activation and cell migration, and abnormal vascular functions. CONCLUSION: Aptamer proteomic analysis of circulating exosomes identified differentially elevated or reduced proteins between Raynaud\u27s Phenomenon at high risk of evolving into SSc and Primary Raynaud\u27s Phenomenon patients. Some of these proteins are involved in relevant biological pathways that may play a role in SSc pathogenesis including enhanced inflammatory responses, immune cell activation, and endothelial cell and vascular abnormalities

Poisson-Jacobi reduction of homogeneous tensors

The notion of homogeneous tensors is discussed. We show that there is a one-to-one correspondence between multivector fields on a manifold $M$, homogeneous with respect to a vector field $\Delta$ on $M$, and first-order polydifferential operators on a closed submanifold $N$ of codimension 1 such that $\Delta$ is transversal to $N$. This correspondence relates the Schouten-Nijenhuis bracket of multivector fields on $M$ to the Schouten-Jacobi bracket of first-order polydifferential operators on $N$ and generalizes the Poissonization of Jacobi manifolds. Actually, it can be viewed as a super-Poissonization. This procedure of passing from a homogeneous multivector field to a first-order polydifferential operator can be also understood as a sort of reduction; in the standard case -- a half of a Poisson reduction. A dual version of the above correspondence yields in particular the correspondence between $\Delta$-homogeneous symplectic structures on $M$ and contact structures on $N$.Comment: 19 pages, minor corrections, final version to appear in J. Phys. A: Math. Ge

Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes

Chromosome aberrations in two glioma cell lines were analyzed using biotinylated DNA library probes that specifically decorate chromosomes 1, 4, 7, 18 and 22 from pter to qter. Numerical changes, deletions and rearrangements of these chromosomes were radily visualized in metaphase spreads, as well as in early prophase and interphase nuclei. Complete chromosomes, deleted chromosomes and segments of translocated chromosomes were rapidly delineated in very complex karyotypes. Simultaneous hybridizations with additional subregional probes were used to further define aberrant chromosomes. Digital image analysis was used to quantitate the total complement of specific chromosomal DNAs in individual metaphase and interphase cells of each cell line. In spite of the fact that both glioma lines have been passaged in vitro for many years, an under-representation of chromosome 22 and an over-representation of chromosome 7 (specifically 7p) were observed. These observations agree with previous studies on gliomas. In addition, sequences of chromosome 4 were also found to be under-represented, especially in TC 593. These analyses indicate the power of these methods for pinpointing chromosome segments that are altered in specific types of tumors

Preliminary Biomarkers for Identification of Human Ascending Thoracic Aortic Aneurysm

Background: Human ascending thoracic aortic aneurysms (ATAAs) are life threatening and constitute a leading cause of mortality in the United States. Previously, we demonstrated that collagens α2(V) and α1(XI) mRNA and protein expression levels are significantly increased in ATAAs. Methods and Results: In this report, the authors extended these preliminary studies using high‐throughput proteomic analysis to identify additional biomarkers for use in whole blood real‐time RT‐PCR analysis to allow for the identification of ATAAs before dissection or rupture. Human ATAA samples were obtained from male and female patients aged 65±14 years. Both bicuspid and tricuspid aortic valve patients were included and compared with nonaneurysmal aortas (mean diameter 2.3 cm). Five biomarkers were identified as being suitable for detection and identification of ATAAs using qRT‐PCR analysis of whole blood. Analysis of 41 samples (19 small, 13 medium‐sized, and 9 large ATAAs) demonstrated the overexpression of 3 of these transcript biomarkers correctly identified 79.4% of patients with ATAA of ≥4.0 cm (P<0.001, sensitivity 0.79, CI=0.62 to 0.91; specificity 1.00, 95% CI=0.42 to 1.00). Conclusion: A preliminary transcript biomarker panel for the identification of ATAAs using whole blood qRT‐PCR analysis in men and women is presented