Pneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis.

In pneumococcal meningitis, bacterial growth in the cerebrospinal fluid results in lysis, the release of toxic factors, and subsequent neuroinflammation. Exposure of primary murine glia to Streptococcus pneumoniae lysates leads to strong proinflammatory cytokine and chemokine production, blocked by inhibition of the intracellular innate receptor Nod1. Lysates enhance dynamin-dependent endocytosis, and dynamin inhibition reduces neuroinflammation, blocking ligand internalization. Here we identify the cholesterol-dependent cytolysin pneumolysin as a pro-endocytotic factor in lysates, its elimination reduces their proinflammatory effect. Only pore-competent pneumolysin enhances endocytosis in a dynamin-, phosphatidylinositol-3-kinase- and potassium-dependent manner. Endocytic enhancement is limited to toxin-exposed parts of the membrane, the effect is rapid and pneumolysin permanently alters membrane dynamics. In a murine model of pneumococcal meningitis, mice treated with chlorpromazine, a neuroleptic with a complementary endocytosis inhibitory effect show reduced neuroinflammation. Thus, the dynamin-dependent endocytosis emerges as a factor in pneumococcal neuroinflammation, and its enhancement by a cytolysin represents a proinflammatory control mechanism

Hurwitz spaces of quadruple coverings of elliptic curves and the moduli space of abelian threefolds A_3(1,1,4)

We prove that the moduli space A_3(1,1,4) of polarized abelian threefolds with polarization of type (1,1,4) is unirational. By a result of Birkenhake and Lange this implies the unirationality of the isomorphic moduli space A_3(1,4,4). The result is based on the study the Hurwitz space H_{4,n}(Y) of quadruple coverings of an elliptic curve Y simply branched in n points. We prove the unirationality of its codimension one subvariety H^{0}_{4,A}(Y) which parametrizes quadruple coverings \pi:X --> Y with Tschirnhausen modules isomorphic to A^{-1}, where A\in Pic^{n/2}Y, and for which \pi^*:J(Y)--> J(X) is injective. This is an analog of the result of Arbarello and Cornalba that the Hurwitz space H_{4,n}(P^1) is unirational.Comment: 28 pages, amslatex, to appear in Mathematische Nachrichte

Difference in Brain Densities Between Chronic Alcoholic and Normal Control Patients.

The densities of the brains of 11 chronic alcoholics were compared with those of 11 age-matched normal control subjects. Densities were determined from the density numbers generated by computerized tomography at three levels of the brain-the highest level of the lateral ventricles and the next two higher levels-with adjustments made to control for possible artifacts in the data. The advantage of the dominant hemisphere over the nondominant hemisphere was lessened in alcoholic

Cloud Condensation Nuclei properties of model and atmospheric HULIS

Humic like substances (HULIS) have been identified as a major fraction of the organic component of atmospheric aerosols. These large multifunctional compounds of both primary and secondary sources are surface active and water soluble. Hence, it is expected that they could affect activation of organic aerosols into cloud droplets. We have compared the activation of aerosols containing atmospheric HULIS extracted from fresh, aged and pollution particles to activation of size fractionated fulvic acid from an aquatic source (Suwannee River Fulvic Acid), and correlated it to the estimated molecular weight and measured surface tension. A correlation was found between CCN-activation diameter of SRFA fractions and number average molecular weight of the fraction. The lower molecular weight fractions activated at lower critical diameters, which is explained by the greater number of solute species in the droplet with decreasing molecular weight. The three aerosol-extracted HULIS samples activated at lower diameters than any of the size-fractionated or bulk SRFA. The Köhler model was found to account for activation diameters, provided that accurate physico-chemical parameters are known

Orientifolds, Unoriented Instantons and Localization

We consider world-sheet instanton effects in N=1 string orientifolds of noncompact toric Calabi-Yau threefolds. We show that unoriented closed string topological amplitudes can be exactly computed using localization techniques for holomorphic maps with involution. Our results are in precise agreement with mirror symmetry and large N duality predictions.Comment: 25 pages, 10 figures, published version; v4: typos correcte

A clay-shoveler's fracture with renal transplantation and osteoporosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Clay-shoveler's fracture is a rare cervicodorsal spinous process fracture and there is little information regarding the prognosis of patients with this condition in conjunction with osteoporosis and corticosteroid use.</p> <p>Case presentation</p> <p>A 39-year-old man was admitted to our institution with a 6-month history of cervicodorsal pain prior to admission. The patient had previously undergone renal transplantation and was on corticosteroids, and had developed osteoporosis. We treated him with a cervical collar, non-steroidal anti-inflammatory agents and alendronate. The patient was advised against performing weight-bearing activities for 6 months.</p> <p>Conclusion</p> <p>Clay-shoveler's fracture with osteoporosis and corticosteroid use presented by fracture of the cervicodorsal aspect of the spinous processes may be successfully treated with a collar, alendronate and long-term rest.</p

Strengthening the Cohomological Crepant Resolution Conjecture for Hilbert-Chow morphisms

Given any smooth toric surface S, we prove a SYM-HILB correspondence which relates the 3-point, degree zero, extended Gromov-Witten invariants of the n-fold symmetric product stack [Sym^n(S)] of S to the 3-point extremal Gromov-Witten invariants of the Hilbert scheme Hilb^n(S) of n points on S. As we do not specialize the values of the quantum parameters involved, this result proves a strengthening of Ruan's Cohomological Crepant Resolution Conjecture for the Hilbert-Chow morphism from Hilb^n(S) to Sym^n(S) and yields a method of reconstructing the cup product for Hilb^n(S) from the orbifold invariants of [Sym^n(S)].Comment: Revised versio

The holomorphic anomaly for open string moduli

We complete the holomorphic anomaly equations for topological strings with their dependence on open moduli. We obtain the complete system by standard path integral arguments generalizing the analysis of BCOV (Commun. Math. Phys. 165 (1994) 311) to strings with boundaries. We study both the anti-holomorphic dependence on open moduli and on closed moduli in presence of Wilson lines. By providing the compactification a' la Deligne-Mumford of the moduli space of Riemann surfaces with boundaries, we show that the open holomorphic anomaly equations are structured on the (real codimension one) boundary components of this space.Comment: 1+14 pages, 6 figures! v2: ref. added v3: section 4 expanded, 1+17 pages, 11 figures!!, to be publ. in JHE

The class of the locus of intermediate Jacobians of cubic threefolds

We study the locus of intermediate Jacobians of cubic threefolds within the moduli space of complex principally polarized abelian fivefolds, and its generalization to arbitrary genus - the locus of abelian varieties with a singular odd two-torsion point on the theta divisor. Assuming that this locus has expected codimension (which we show to be true for genus up to 5), we compute the class of this locus, and of is closure in the perfect cone toroidal compactification, in the Chow, homology, and the tautological ring. We work out the cases of genus up to 5 in detail, obtaining explicit expressions for the classes of the closures of the locus of products of an elliptic curve and a hyperelliptic genus 3 curve, in moduli of principally polarized abelian fourfolds, and of the locus of intermediate Jacobians in genus 5. In the course of our computation we also deal with various intersections of boundary divisors of a level toroidal compactification, which is of independent interest in understanding the cohomology and Chow rings of the moduli spaces.Comment: v2: new section 9 on the geometry of the boundary of the locus of intermediate Jacobians of cubic threefolds. Final version to appear in Invent. Mat

Mechanism of Transcription Anti-termination in Human Mitochondria.

In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA-the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream sliding clamp, providing high processivity to the EC. TEFM also binds near the RNA exit channel to prevent formation of the RNA G-quadruplex structure required for termination and thus synthesis of the replication primer. Our data provide insights into target specificity of TEFM and mechanisms by which it regulates the switch between transcription and replication of mtDNA