Symmetric tensors on the intersection of two quadrics and Lagrangian fibration

Let X be a n-dimensional (smooth) intersection of two quadrics, and let T*X be its cotangent bundle. We show that the algebra of symmetric tensors on X is a polynomial algebra in n variables. The corresponding map F: T*X -- > C^n is a Lagrangian fibration, which admits an explicit geometric description; its general fiber is a Zariski open subset of an abelian variety, quotient of a hyperelliptic Jacobian by a 2-torsion subgroup. For n = 3 F is the Hitchin fibration of the moduli space of rank 2 bundles with fixed determinant on a curve of genus 2

Holomorphic symmetric differentials and a birational characterization of Abelian Varieties

A generically generated vector bundle on a smooth projective variety yields a rational map to a Grassmannian, called Kodaira map. We answer a previous question, raised by the asymptotic behaviour of such maps, giving rise to a birational characterization of abelian varieties. In particular we prove that, under the conjectures of the Minimal Model Program, a smooth projective variety is birational to an abelian variety if and only if it has Kodaira dimension 0 and some symmetric power of its cotangent sheaf is generically generated by its global sections.Comment: UPDATED: more details added on main proo

GOLM1 depletion modifies cellular sphingolipid metabolism and adversely affects cell growth

Golgi membrane protein 1 (GOLM1) is a Golgi-resident type 2 transmembrane protein known to be overexpressed in several cancers, including he-patocellular carcinoma (HCC), as well as in viral in-fections. However, the role of GOLM1 in lipid metabolism remains enigmatic. In this study, we employed siRNA-mediated GOLM1 depletion in Huh -7 HCC cells to study the role of GOLM1 in lipid metabolism. Mass spectrometric lipidomic analysis in GOLM1 knockdown cells showed an aberrant accu-mulation of sphingolipids, such as ceramides, hex-osylceramides, dihexosylceramides, sphinganine, sphingosine, and ceramide phosphate, along with cholesteryl esters. Furthermore, we observed a reduction in phosphatidylethanolamines and lyso-phosphatidylethanolamines. In addition, Seahorse extracellular flux analysis indicated a reduction in mitochondrial oxygen consumption rate upon GOLM1 depletion. Finally, alterations in Golgi struc-ture and distribution were observed both by electron microscopy imaging and immunofluorescence mi-croscopy analysis. Importantly, we found that GOLM1 depletion also affected cell proliferation and cell cycle progression in Huh-7 HCC cells. The Golgi structural defects induced by GOLM1 reduction might potentially affect the trafficking of proteins and lipids leading to distorted intracellular lipid ho-meostasis, which may result in organelle dysfunction and altered cell growth. In conclusion, we demon-strate that GOLM1 depletion affects sphingolipid metabolism, mitochondrial function, Golgi structure, and proliferation of HCC cells.Peer reviewe

Insulin-inducible THRSP maintains mitochondrial function and regulates sphingolipid metabolism in human adipocytes

Background Thyroid hormone responsive protein (THRSP) is a lipogenic nuclear protein that is highly expressed in murine adipose tissue, but its role in humans remains unknown. Methods We characterized the insulin regulation of THRSP in vivo in human adipose tissue biopsies and in vitro in Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. To this end, we measured whole-body insulin sensitivity using the euglycemic insulin clamp technique in 36 subjects [age 40 +/- 9 years, body mass index (BMI) 27.3 +/- 5.0 kg/m(2)]. Adipose tissue biopsies were obtained at baseline and after 180 and 360 min of euglycemic hyperinsulinemia for measurement of THRSP mRNA concentrations. To identify functions affected by THRSP, we performed a transcriptomic analysis of THRSP-silenced SGBS adipocytes. Mitochondrial function was assessed by measuring mitochondrial respiration as well as oxidation and uptake of radiolabeled oleate and glucose. Lipid composition in THRSP silencing was studied by lipidomic analysis. Results We found insulin to increase THRSP mRNA expression 5- and 8-fold after 180 and 360 min of in vivo euglycemic hyperinsulinemia. This induction was impaired in insulin-resistant subjects, and THRSP expression was closely correlated with whole-body insulin sensitivity. In vitro, insulin increased both THRSP mRNA and protein concentrations in SGBS adipocytes in a phosphoinositide 3-kinase (PI3K)-dependent manner. A transcriptomic analysis of THRSP-silenced adipocytes showed alterations in mitochondrial functions and pathways of lipid metabolism, which were corroborated by significantly impaired mitochondrial respiration and fatty acid oxidation. A lipidomic analysis revealed decreased hexosylceramide concentrations, supported by the transcript concentrations of enzymes regulating sphingolipid metabolism. Conclusions THRSP is regulated by insulin both in vivo in human adipose tissue and in vitro in adipocytes, and its expression is downregulated by insulin resistance. As THRSP silencing decreases mitochondrial respiration and fatty acid oxidation, its downregulation in human adipose tissue could contribute to mitochondrial dysfunction. Furthermore, disturbed sphingolipid metabolism could add to metabolic dysfunction in obese adipose tissue.Peer reviewe

B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR) signaling in maintaining MCL survival. However, it remains unclear which role MALT1, an essential component of the CARD11-BCL10-MALT1 complex that links BCR signaling to the NF-κB pathway, plays in the biology of MCL. Here we show that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene expression profiling following MALT1 inhibition demonstrated that MALT1 controls an MYC-driven gene expression network predominantly through increasing MYC protein stability. Thus, our analyses identify a previously unappreciated regulatory mechanism of MYC expression. Investigating primary mouse splenocytes, we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL, but represents a common mechanism. MYC itself is pivotal for MCL survival because its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL models. Collectively, these results provide a strong mechanistic rationale to investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL patients

Population genetic structure of Calanoides natalis (Copepoda, Calanoida) in the eastern Atlantic Ocean and Benguela upwelling system

The population genetic structure of Calanoides natalis (ex Calanoides carinatus; Copepoda, Calanoida), an ecologically important component of African upwelling systems, was studied in order to (i) search for potential cryptic species, (ii) describe spatial patterns in the distribution of genetic variance and (iii) identify potential barriers to gene flow. Samples were obtained in the eastern Atlantic Ocean from the Iberian Peninsula to Namibia. Analysis of mitochondrial (cytochrome c oxidase subunit I; COI) and nuclear (citrate synthase; CS) marker genes revealed a genetically cohesive population of C. natalis with a prevalent shift in allele frequencies. The discovery of a deep split solely present in the mitochondrial dataset does not point to cryptic speciation, but rather suggests the occurrence of nuclear mitochondrial pseudogenes or incomplete reproductive isolation upon secondary contact. Genetic differentiation between the northern and southern hemisphere was significant, which may point to a potential, but permeable barrier close to the equator. No vertical genetic structuring was detected in the northern Benguela implying that horizontal differentiation was more pronounced than vertical structuring. Retention mechanisms and the oxygen minimum zone did not have a strong impact on genetic differentiation of C. natalis in the Benguela region