A Characterization of Compact-friendly Multiplication Operators

Answering in the affirmative a question posed in [Y.A.Abramovich, C.D.Aliprantis and O.Burkinshaw, Multiplication and compact-friendly operators, Positivity 1 (1997), 171--180], we prove that a positive multiplication operator on any $L_p$-space (resp. on a $C(\Omega)$-space) is compact-friendly if and only if the multiplier is constant on a set of positive measure (resp. on a non-empty open set). In the process of establishing this result, we also prove that any multiplication operator has a family of hyperinvariant bands -- a fact that does not seem to have appeared in the literature before. This provides useful information about the commutant of a multiplication operator.Comment: To appear in Indag. Math., 12 page

Gut microbiota induce IGF-1 and promote bone formation and growth

New interventions are needed to improve bone health and reduce the risk for osteoporosis and fracture. Dysbiosis is increasingly linked to metabolic abnormalities, although the effect of the microbiota on skeletal health is poorly understood. Previous studies suggest microbiota are detrimental to bone by increasing resorption. In this report, we show that the gut resident microbiota promote bone formation, as well as resorption, with long-term exposure to microbiota resulting in net skeletal growth. Microbiota induce the hormone insulin-like growth factor 1 (IGF-1), which promotes bone growth and remodeling. Short-chain fatty acids (SCFAs), produced when microbiota ferment fiber, also induce IGF-1, suggesting a mechanism by which microbiota affect bone health. Manipulating the microbiome or its metabolites may afford opportunities to optimize bone health and growth

Maurey-Rosenthal domination for abstract Banach lattices

We extend the Maurey-Rosenthal theorem on integral domination and factorization of p-concave operators from a p-convex Banach function space through Lp-spaces for the case of operators on abstract p-convex Banach lattices satisfying some essential lattice requirements - mainly order density of its order continuous part - that are shown to be necessary. We prove that these geometric properties can be characterized by means of an integral inequality giving a domination of the pointwise evaluation of the operator for a suitable weight also in the case of abstract Banach lattices. We obtain in this way what in a sense can be considered the most general factorization theorem of operators through Lp-spaces. In order to do this, we prove a new representation theorem for abstract p-convex Banach lattices with the Fatou property as spaces of p-integrable functions with respect to a vector measure.The authors are supported by grants MTM2011-23164 and MTM2012-36740-C02-02 of the Ministerio de Economia y Competitividad (Spain).Juan Blanco, MA.; Sánchez Pérez, EA. (2013). Maurey-Rosenthal domination for abstract Banach lattices. Journal of Inequalities and Applications. (213). https://doi.org/10.1186/1029-242X-2013-213S213Defant A: Variants of the Maurey-Rosenthal theorem for quasi Köthe function spaces. Positivity 2001, 5: 153–175. 10.1023/A:1011466509838Defant A, Sánchez Pérez EA: Maurey-Rosenthal factorization of positive operators and convexity. J. Math. Anal. Appl. 2004, 297: 771–790. 10.1016/j.jmaa.2004.04.047Defant A, Sánchez Pérez EA: Domination of operators on function spaces. Math. Proc. Camb. Philos. Soc. 2009, 146: 57–66. 10.1017/S0305004108001734Fernández A, Mayoral F, Naranjo F, Sáez C, Sánchez-Pérez EA: Vector measure Maurey-Rosenthal type factorizations and l -sums of L 1 -spaces. J. Funct. Anal. 2005, 220: 460–485. 10.1016/j.jfa.2004.06.010Palazuelos C, Sánchez Pérez EA, Tradacete P: Maurey-Rosenthal factorization for p -summing operators and Dodds-Fremlin domination. J. Oper. Theory 2012, 68(1):205–222.Luxemburg WAJ, Zaanen AC: Riesz Spaces I. North-Holland, Amsterdam; 1971.Zaanen AC: Riesz Spaces II. North-Holland, Amsterdam; 1983.Lindenstrauss J, Tzafriri L: Classical Banach Spaces II. Springer, Berlin; 1979.Aliprantis CD, Burkinshaw O: Positive Operators. Academic Press, New York; 1985.Curbera GP, Ricker WJ: Vector measures, integration and applications. Trends Math. In Positivity. Birkhäuser, Basel; 2007:127–160.Okada S, Ricker WJ, Sánchez Pérez EA: Optimal domains and integral extensions of operators acting in function spaces. 180. In Operator Theory Advances and Applications. Birkhäuser, Basel; 2008.Delgado O: L 1 -spaces of vector measures defined on δ -rings. Arch. Math. 2005, 84: 432–443. 10.1007/s00013-005-1128-1Calabuig, JM, Delgado, O, Juan, MA, Sánchez Pérez, EA: On the Banach lattice structure of L w 1 of a vector measure on a δ-ring. Collect. Math. doi:10.1007/s13348–013–0081–8Calabuig JM, Delgado O, Sánchez Pérez EA: Factorizing operators on Banach function spaces through spaces of multiplication operators. J. Math. Anal. Appl. 2010, 364: 88–103. 10.1016/j.jmaa.2009.10.034Delgado O:Optimal domains for kernel operators on [ 0 , ∞ ) × [ 0 , ∞ ) .Stud. Math. 2006, 174: 131–145. 10.4064/sm174-2-2Delgado O, Soria J: Optimal domain for the Hardy operator. J. Funct. Anal. 2007, 244: 119–133. 10.1016/j.jfa.2006.12.011Jiménez Fernández E, Juan MA, Sánchez Pérez EA: A Komlós theorem for abstract Banach lattices of measurable functions. J. Math. Anal. Appl. 2011, 383: 130–136. 10.1016/j.jmaa.2011.05.010Curbera, GP: El espacio de funciones integrables respecto de una medida vectorial. PhD thesis, Univ. of Sevilla (1992)Sánchez Pérez EA: Compactness arguments for spaces of p -integrable functions with respect to a vector measure and factorization of operators through Lebesgue-Bochner spaces. Ill. J. Math. 2001, 45(3):907–923.Fernández A, Mayoral F, Naranjo F, Sáez C, Sánchez-Pérez EA: Spaces of p -integrable functions with respect to a vector measure. Positivity 2006, 10: 1–16. 10.1007/s11117-005-0016-zCalabuig JM, Juan MA, Sánchez Pérez EA: Spaces of p -integrable functions with respect to a vector measure defined on a δ -ring. Oper. Matrices 2012, 6: 241–262.Lewis DR: On integrability and summability in vector spaces. Ill. J. Math. 1972, 16: 294–307.Masani PR, Niemi H: The integration theory of Banach space valued measures and the Tonelli-Fubini theorems. I. Scalar-valued measures on δ -rings. Adv. 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Appl. 2007, 328: 287–294. 10.1016/j.jmaa.2006.04.086Aliprantis CD, Border KC: Infinite Dimensional Analysis. Springer, Berlin; 1999.Delgado, O: Optimal extension for positive order continuous operators on Banach function spaces. Glasg. Math. J. (to appear

The Role of Toll-Like Receptor 2 in Inflammation and Fibrosis during Progressive Renal Injury

Tissue fibrosis and chronic inflammation are common causes of progressive organ damage, including progressive renal disease, leading to loss of physiological functions. Recently, it was shown that Toll-like receptor 2 (TLR2) is expressed in the kidney and activated by endogenous danger signals. The expression and function of TLR2 during renal fibrosis and chronic inflammation has however not yet been elucidated. Therefore, we studied TLR2 expression in human and murine progressive renal diseases and explored its role by inducing obstructive nephropathy in TLR2−/− or TLR2+/+ mice. We found that TLR2 is markedly upregulated on tubular and tubulointerstitial cells in patients with chronic renal injury. In mice with obstructive nephropathy, renal injury was associated with a marked upregulation and change in distribution of TLR2 and upregulation of murine TLR2 danger ligands Gp96, biglycan, and HMGB1. Notably, TLR2 enhanced inflammation as reflected by a significantly reduced influx of neutrophils and production of chemokines and TGF-β in kidneys of TLR2−/− mice compared with TLR2+/+ animals. Although, the obstructed kidneys of TLR2−/− mice had less interstitial myofibroblasts in the later phase of obstructive nephropathy, tubular injury and renal matrix accumulation was similar in both mouse strains. Together, these data demonstrate that TLR2 can initiate renal inflammation during progressive renal injury and that the absence of TLR2 does not affect the development of chronic renal injury and fibrosis

Toll-Like Receptor-2 Mediates Diet and/or Pathogen Associated Atherosclerosis: Proteomic Findings

BACKGROUND. Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE+/- mice. METHODS AND RESULTS. To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE+/--TLR2+/+, ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 μl live Porphyromonas gingivalis (P.g) (107 CFU) or vehicle (normal saline). Animals were euthanized 24 weeks after the first inoculation. ApoE+/--TLR2+/+ mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE+/--TLR2+/+ mice were significantly higher than from ApoE+/--TLR2+/- and ApoE+/--TLR2-/- mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE+/--TLR2+/+ mice compared to ApoE+/--TLR2+/- and TLR2-/- mice, irrespective of diet or bacterial challenge. ApoE+/--TLR2+/+ mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist) also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE+/--TLR2-/- mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS) of aortic samples analyzed by 2-dimentional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE+/--TLR2+/+ mice fed the high fat diet and inoculated with P.g compared to any other group. CONCLUSION. Genetic deficiency of TLR2 reduces diet- and/or pathogen-associated atherosclerosis in ApoE+/- mice, along with differences in plaque composition suggesting greater structural stability while TLR-2 ligand-specific activation triggers atherosclerosis. The present data offers new insights into the pathophysiological pathways involved in atherosclerosis and paves the way for new pharmacological interventions aimed at reducing atherosclerosis.National Heart, Lung, and Blood Institute (R01 HL076801

Inhibitors of MyD88-Dependent Proinflammatory Cytokine Production Identified Utilizing a Novel RNA Interference Screening Approach

The events required to initiate host defenses against invading pathogens involve complex signaling cascades comprised of numerous adaptor molecules, kinases, and transcriptional elements, ultimately leading to the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha). How these signaling cascades are regulated, and the proteins and regulatory elements participating are still poorly understood.We report here the development a completely random short-hairpin RNA (shRNA) library coupled with a novel forward genetic screening strategy to identify inhibitors of Toll-like receptor (TLR) dependent proinflammatory responses. We developed a murine macrophage reporter cell line stably transfected with a construct expressing diphtheria toxin-A (DT-A) under the control of the TNF-alpha-promoter. Stimulation of the reporter cell line with the TLR ligand lipopolysaccharide (LPS) resulted in DT-A induced cell death, which could be prevented by the addition of an shRNA targeting the TLR adaptor molecule MyD88. Utilizing this cell line, we screened a completely random lentiviral short hairpin RNA (shRNA) library for sequences that inhibited TLR-mediated TNF-alpha production. Recovery of shRNA sequences from surviving cells led to the identification of unique shRNA sequences that significantly inhibited TLR4-dependent TNF-alpha gene expression. Furthermore, these shRNA sequences specifically blocked TLR2 but not TLR3-dependent TNF-alpha production.Thus, we describe the generation of novel tools to facilitate large-scale forward genetic screens in mammalian cells and the identification of potent shRNA inhibitors of TLR2 and TLR4- dependent proinflammatory responses

Human lung cancer cells express functionally active Toll-like receptor 9

BACKGROUND: CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology. METHODS: The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, in situ hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system. RESULTS: We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis. CONCLUSIONS: Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology

NFATc1 controls the cytotoxicity of CD8+ T cells

NFAT nuclear translocation has been shown to be required for CD8+ T cell cytokine production in response to viral infection. Here the authors show NFATc1 controls the cytotoxicity and metabolic switching of activated CD8+ T cells required for optimal response to bacteria and tumor cells

Systemic Stimulation of TLR2 Impairs Neonatal Mouse Brain Development

Background: Inflammation is associated with perinatal brain injury but the underlying mechanisms are not completely characterized. Stimulation of Toll-like receptors (TLRs) through specific agonists induces inflammatory responses that trigger both innate and adaptive immune responses. The impact of engagement of TLR2 signaling pathways on the neonatal brain is still unclear. The aim of this study was to investigate the potential effect of a TLR2 agonist on neonatal brain development. Methodology/Principal Findings: Mice were injected intraperitoneally (i.p.) once a day from postnatal day (PND) 3 to PND11 with endotoxin-free saline, a TLR2 agonist Pam$_{3}$CSK$_{4}$ (5 mg/kg) or Lipopolysaccharide (LPS, 0.3 mg/kg). Pups were sacrificed at PND12 or PND53 and brain, spleen and liver were collected and weighed. Brain sections were stained for brain injury markers. Long-term effects on memory function were assessed using the Trace Fear Conditioning test at PND50. After 9 days of Pam$_{3}$CSK$_{4}$ administration, we found a decreased volume of cerebral gray matter, white matter in the forebrain and cerebellar molecular layer that was accompanied by an increase in spleen and liver weight at PND12. Such effects were not observed in Pam$_{3}$CSK$_{4}$-treated TLR 2-deficient mice. Pam$_{3}$CSK$_{4}$-treated mice also displayed decreased hippocampus neuronal density, and increased cerebral microglia density, while there was no effect on caspase-3 or general cell proliferation at PND12. Significantly elevated levels of IL-1β, IL-6, KC, and MCP-1 were detected after the first Pam$_{3}$CSK$_{4}$ injection in brain homogenates of PND3 mice. Pam$_{3}$CSK$_{4}$administration did not affect long-term memory function nor the volume of gray or white matter. Conclusions/Significance: Repeated systemic exposure to the TLR2 agonist Pam$_{3}$CSK$_{4}$ can have a short-term negative impact on the neonatal mouse brain