Expression and alternative splicing of the neural cell adhesion molecule NCAM in human granulosa cells during luteinization

Freshly aspirated human granulosa cells from pre-ovulatory follicles and granulosa cells luteinized in culture possess the neural cell adhesion molecule (NCAM) of approximate molecular mass of 140,000 and NCAM mRNA as confirmed by S1-nuclease protection assays and RT-PCR. Moreover, in the process of luteinization the NCAM isoform pattern is modified. Isoforms containing an insert of 10 amino acids (termed VASE) in the extracellular domain of NCAM were supplemented by alternatively spliced isoforms without this insert. NCAM immunoreactivity, at light and electron microscope levels, was associated with the cell membrane of most granulosa cells which formed clusters. During time in culture an increasing subpopulation of granulosa cells, devoid of NCAM immunoreactivity, spread out and formed monolayers. This differential expression and the alternative splicing of NCAM during luteinization of granulosa cells raise the possibility that NCAM could be involved in folliculogenesis and the formation of the corpus luteum in the human

Villous Mucinous Cystadenoma of the Appendix in a Postmenopausal Woman

Because a significant number of mucoceles are caused by mucinous cystadenocarcinoma, the authors stress that a general surgeon be consulted in cases of right lower quadrant “dumbbell shaped” abdominal cysts

An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells.

Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin-glycoprotein complex. Here we show the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem cells generated from fibroblasts of mice lacking both dystrophin and utrophin. We correct the phenotype of dystrophic induced pluripotent stem cells using a Sleeping Beauty transposon system carrying the micro-utrophin gene, differentiate these cells into skeletal muscle progenitors and transplant them back into dystrophic mice. Engrafted muscles displayed large numbers of micro-utrophin-positive myofibers, with biochemically restored dystrophin-glycoprotein complex and improved contractile strength. The transplanted cells seed the satellite cell compartment, responded properly to injury and exhibit neuromuscular synapses. We also detect muscle engraftment after systemic delivery of these corrected progenitors. These results represent an important advance towards the future treatment of muscular dystrophies using genetically corrected autologous induced pluripotent stem cells

The wave equation on singular space-times

We prove local unique solvability of the wave equation for a large class of weakly singular, locally bounded space-time metrics in a suitable space of generalised functions.Comment: Latex, 19 pages, 1 figure. Discussion of class of metrics covered by our results and some examples added. Conclusion more detailed. Version to appear in Communications in Mathematical Physic

Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a stem cell (SC) neoplasm characterized by the BCR/ABL1 oncogene. Although mechanisms of BCR/ABL1-induced transformation are well-defined, little is known about effector-molecules contributing to malignant expansion and the extramedullary spread of leukemic SC (LSC) in CML. We have identified the cytokine-targeting surface enzyme dipeptidylpeptidase-IV (DPPIV/CD26) as a novel, specific and pathogenetically relevant biomarker of CD34+/CD38─ CML LSC. In functional assays, CD26 was identified as target enzyme disrupting the SDF-1-CXCR4-axis by cleaving SDF-1, a chemotaxin recruiting CXCR4+ SC. CD26 was not detected on normal SC or LSC in other hematopoietic malignancies. Correspondingly, CD26+ LSC decreased to low or undetectable levels during successful treatment with imatinib. CD26+ CML LSC engrafted NOD-SCID-IL-2Rγ−/− (NSG) mice with BCR/ABL1+ cells, whereas CD26─ SC from the same patients produced multilineage BCR/ABL1– engraftment. Finally, targeting of CD26 by gliptins suppressed the expansion of BCR/ABL1+ cells. Together, CD26 is a new biomarker and target of CML LSC. CD26 expression may explain the abnormal extramedullary spread of CML LSC, and inhibition of CD26 may revert abnormal LSC function and support curative treatment approaches in this malignancy

Continuous Equilibrium in Affine and Information-Based Capital Asset Pricing Models

We consider a class of generalized capital asset pricing models in continuous time with a finite number of agents and tradable securities. The securities may not be sufficient to span all sources of uncertainty. If the agents have exponential utility functions and the individual endowments are spanned by the securities, an equilibrium exists and the agents' optimal trading strategies are constant. Affine processes, and the theory of information-based asset pricing are used to model the endogenous asset price dynamics and the terminal payoff. The derived semi-explicit pricing formulae are applied to numerically analyze the impact of the agents' risk aversion on the implied volatility of simultaneously-traded European-style options.Comment: 24 pages, 4 figure

FSH regulates acetycholine production by ovarian granulosa cells

BACKGROUND: It has been previously shown that cultured granulosa cells (GCs) derived from human ovarian preovulatory follicles contain choline acetyltransferase (ChAT), the enzyme responsible for acetylcholine (ACh) synthesis. They also produce ACh and express functional muscarinic ACh receptors. ACh can act on GCs to increase proliferation, disrupt gap junctional communication, alter intracellular calcium levels, as well as expression of transcription factors, suggesting an unrecognized role of ACh in GC function. To gain further insights into the possible role of ACh in the ovary, we examined ChAT expression in the gland before and after birth, as well as in adults, and studied the regulation of ACh production by FSH. METHODS: ChAT immunohistochemistry was performed using ovarian samples of different species and ages (embryonic, postnatal and adult rats and mice, including embryonic ovaries from mice null for ChAT, neonatal and adult rhesus monkeys and adult humans). ACh was measured by HPLC and/or a fluorescence based method in rat ovaries and in a FSH receptor-expressing cell line (rat GFSHR-17) cultured with or without FSH. RESULTS: In adult rat, as well as in all other species, ovarian ChAT immunoreactivity is associated with GCs of antral follicles, but not with other structures, indicating that GCs are the only ovarian source of ACh. Indeed ACh was clearly detected in adult rat ovaries by two methods. ChAT immunoreactivity is absent from embryonic and/or neonatal ovaries (mouse/rat and monkey) and ovarian development in embryonic mice null for ChAT appears normal, suggesting that ACh is not involved in ovarian or follicular formation. Since ChAT immunoreactivity is present in GCs of large follicles and since the degree of the ChAT immunoreactivity increases as antral follicles grow, we tested whether ACh production is stimulated by FSH. Rat GFSHR-17 cells that stably express the FSH receptor, respond to FSH with an increase in ACh production. CONCLUSION: ACh and ChAT are present in GCs of growing follicles and FSH, the major driving force of follicular growth, stimulates ACh production. Since ACh stimulates proliferation and differentiation processes in cultured GCs, we suggest that ACh may act in the growing ovarian follicle as a local mediator of some of the actions ascribed to FSH

Sub-3mm spatial resolution from a large monolithic LaBr3 (Ce) scintillator

Abstract A Compton camera prototype for ion beam range monitoring via prompt (< 1 ns) gamma detection in hadron therapy is being developed and characterized at the Medical Physics Department of LMU Munich. The system consists of a large (50x50x30 mm3) monolithic LaBr3(Ce) scintillation crystal as absorber component to detect the multi-MeV Compton scattered photons, together with a stack of 6 double-sided silicon strip detectors (DSSSD) acting as scatterer component. Key ingredient of the γ-source reconstruction is the determination of the γ-ray interaction position in the scintillator, which is read out by a 256-fold segmented multi-anode photomultiplier tube (PMT). From simulations an angular resolution of about 1.5o for the photon source reconstruction can be expected for the energy range around 3 – 5 MeV, provided that a spatial resolution of 3 mm can be reached in the absorbing scintillator [1]. Therefore, particular effort was dedicated to characterize this latter property as a function of the γ-ray energy. Intense, tightly collimated 137Cs and 60Co photon sources were used for 2D irradiation scans (step size 0.5 mm) as prerequisite for studying the performance of the "k-Nearest-Neighbors" algorithm developed at TU Delft [2] (together with its variant "Categorical Average Pattern", CAP) and extending its applicability into the energy range beyond the original 511 keV. In this paper we present our most recent interaction position analysis in the absorbing scintillator, leading to a considerably improved value for the spatial resolution: systematic studies were performed as a function of the k-NN parameters and the PMT segmentation. A trend of improving spatial resolution with increasing photon energy was confirmed, resulting in the realization of the presently optimum spatial resolution of 2.9(1) mm @1.3 MeV, thus reaching the design specifications of the Compton camera absorber. The specification goal was reached also for a reduced PMT segmentation of 8x8 anode segments (each with 6x6 mm2 active area), thus allowing to reduce the complexity of the signal processing while preserving the performance

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate