Cosmology, cohomology, and compactification

Ashtekar and Samuel have shown that Bianchi cosmological models with compact spatial sections must be of Bianchi class A. Motivated by general results on the symmetry reduction of variational principles, we show how to extend the Ashtekar-Samuel results to the setting of weakly locally homogeneous spaces as defined, e.g., by Singer and Thurston. In particular, it is shown that any m-dimensional homogeneous space G/K admitting a G-invariant volume form will allow a compact discrete quotient only if the Lie algebra cohomology of G relative to K is non-vanishing at degree m.Comment: 6 pages, LaTe

Development of Functional Microfold (M) Cells from Intestinal Stem Cells in Primary Human Enteroids.

Background & aimsIntestinal microfold (M) cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs), and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.MethodsHuman intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.ResultsFunctional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2) in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.ConclusionsHuman intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an in vitro setting. We anticipate that this model can be used to generate large numbers of M cells for further functional studies of these key cells of intestinal immune induction and their impact on controlling enteric pathogens and the intestinal microbiome

Effect of Reducing Atmosphere on the Magnetism of Zn1-xCoxO Nanoparticles

We report the crystal structure and magnetic properties of Zn1-xCoxO nanoparticles synthesized by heating metal acetates in organic solvent. The nanoparticles were crystallized in wurtzite ZnO structure after annealing in air and in a forming gas (Ar95%+H5%). The X-ray diffraction and X-ray photoemission spectroscopy (XPS) data for different Co content show clear evidence for the Co+2 ions in tetrahedral symmetry, indicating the substitution of Co+2 in ZnO lattice. However samples with x=0.08 and higher cobalt content also indicate the presence of Co metal clusters. Only those samples annealed in the reducing atmosphere of the forming gas, and that showed the presence of oxygen vacancies, exhibited ferromagnetism at room temperature. The air annealed samples remained non-magnetic down to 77K. The essential ingredient in achieving room temperature ferromagnetism in these Zn1-xCoxO nanoparticles was found to be the presence of additional carriers generated by the presence of the oxygen vacancies.Comment: 11 pages, 6 figures, submitted to Nanotechnology IO

Evolution of oxygen isotopic composition in the inner solar nebula

Changes in the chemical and isotopic composition of the solar nebula with time are reflected in the properties of different constituents that are preserved in chondritic meteorites. CR carbonaceous chondrites are among the most primitive of all chondrite types and must have preserved solar nebula records largely unchanged. We have analyzed the oxygen and magnesium isotopes in a range of the CR constituents of different formation temperatures and ages, including refractory inclusions and chondrules of various types. The results provide new constraints on the time variation of the oxygen isotopic composition of the inner (<5 AU) solar nebula - the region where refractory inclusions and chondrules most likely formed. A chronology based on the decay of short-lived 26Al (t1/2 ~ 0.73 Ma) indicates that the inner solar nebula gas was 16O-rich when refractory inclusions formed, but less than 0.8 Ma later, gas in the inner solar nebula became 16O-poor and this state persisted at least until CR chondrules formed ~1-2 Myr later. We suggest that the inner solar nebula became 16O-poor because meter-size icy bodies, which were enriched in 17,18O due to isotopic self-shielding during the ultraviolet photo dissociation of CO in the protosolar molecular cloud or protoplanetary disk, agglomerated outside the snowline, drifted rapidly towards the Sun, and evaporated at the snowline. This led to significant enrichment in 16O-depleted water, which then spread through the inner solar system. Astronomical studies of the spatial and/or temporal variations of water abundance in protoplanetary disks may clarify these processes.Comment: 27 pages, 5 figure

Identification of a Novel Staphylococcus aureus Two-Component Leukotoxin Using Cell Surface Proteomics

Staphylococcus aureus is a prominent human pathogen and leading cause of bacterial infection in hospitals and the community. Community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 are highly virulent and, unlike hospital strains, often cause disease in otherwise healthy individuals. The enhanced virulence of CA-MRSA is based in part on increased ability to produce high levels of secreted molecules that facilitate evasion of the innate immune response. Although progress has been made, the factors that contribute to CA-MRSA virulence are incompletely defined. We analyzed the cell surface proteome (surfome) of USA300 strain LAC to better understand extracellular factors that contribute to the enhanced virulence phenotype. A total of 113 identified proteins were associated with the surface of USA300 during the late-exponential phase of growth in vitro. Protein A was the most abundant surface molecule of USA300, as indicated by combined Mascot score following analysis of peptides by tandem mass spectrometry. Unexpectedly, we identified a previously uncharacterized two-component leukotoxin–herein named LukS-H and LukF-G (LukGH)-as two of the most abundant surface-associated proteins of USA300. Rabbit antibody specific for LukG indicated it was also freely secreted by USA300 into culture media. We used wild-type and isogenic lukGH deletion strains of USA300 in combination with human PMN pore formation and lysis assays to identify this molecule as a leukotoxin. Moreover, LukGH synergized with PVL to enhance lysis of human PMNs in vitro, and contributed to lysis of PMNs after phagocytosis. We conclude LukGH is a novel two-component leukotoxin with cytolytic activity toward neutrophils, and thus potentially contributes to S. aureus virulence

3-manifolds which are spacelike slices of flat spacetimes

We continue work initiated in a 1990 preprint of Mess giving a geometric parameterization of the moduli space of classical solutions to Einstein's equations in 2+1 dimensions with cosmological constant 0 or -1 (the case +1 has been worked out in the interim by the present author). In this paper we make a first step toward the 3+1-dimensional case by determining exactly which closed 3-manifolds M^3 arise as spacelike slices of flat spacetimes, and by finding all possible holonomy homomorphisms pi_1(M^3) to ISO(3,1).Comment: 10 page

Constitutive cytoplasmic localization of p21Waf1/Cip1 affects the apoptotic process in monocytic leukaemia

In the present study, we analysed the expression and localization of p21Waf1/Cip1 in normal and malignant haematopoietic cells. We demonstrate that in normal monocytic cells, protein kinase C (PKC)-induced p21 gene activation, which is nuclear factor-κB (NF-κB) independent, results in predominantly cytoplasmic localized p21 protein. In acute monocytic leukaemia (M4, M5), monocytic blasts (N=12) show constitutive cytoplasmic p21 expression in 75% of the cases, while in myeloid leukaemic blasts (N=10), low nuclear and cytoplasmic localization of p21 could be detected, which is also PKC dependent. Constitutive p21 expression in monocytic leukaemia might have important antiapoptotic functions. This is supported by the finding that in U937 cells overexpressing p21, VP16-induced apoptosis is significantly reduced (20.0±0.9 vs 55.8±3.8%, P<0.01, N=5), reflected by a reduced phosphorylation of p38 and JNK. Similarly, AML blasts with high cytoplasmic p21 were less sensitive to VP16-induced apoptosis as compared to AML cases with low or undetectable p21 expression (42.25 vs 12.3%, P<0.01). Moreover, complex formation between p21 and ASK1 could be demonstrated in AML cells, by means of coimmunoprecipitation. In summary, these results indicate that p21 has an antiapoptotic role in monocytic leukaemia, and that p21 expression is regulated in a PKC-dependent and NF-κB independent manner.