Specific immune priming in the invasive ctenophore Mnemiopsis leidyi

Specific immune priming enables an induced immune response upon repeated pathogen encounter. As a functional analogue to vertebrate immune memory, such adaptive plasticity has been described, for instance, in insects and crustaceans. However, towards the base of the metazoan tree our knowledge about the existence of specific immune priming becomes scattered. Here, we exposed the invasive ctenophore Mnemiopsis leidyi repeatedly to two different bacterial epitopes (Gram-positive or -negative) and measured gene expression. Ctenophores experienced either the same bacterial epitope twice (homologous treatments) or different bacterial epitopes (heterologous treatments). Our results demonstrate that immune gene expression depends on earlier bacterial exposure. We detected significantly different expression upon heterologous compared with homologous bacterial treatment at three immune activator and effector genes. This is the first experimental evidence for specific immune priming in Ctenophora and generally in non-bilaterian animals, hereby adding to our growing notion of plasticity in innate immune systems across all animal phyla

Foreigners vs. Natives: Bank Lending Technologies and Loan Pricing

Can distance-related information asymmetries in credit markets be overcome with contract design and credit scoring models? To answer this question, we explore differences in foreign and domestic banks’ credit contract terms and pricing models. Using a sample of firms that borrow from both domestic and foreign banks in the same month, we show that foreign banks are more likely to demand collateral and grant shorter maturity loans than domestic banks. Foreign banks also base their pricing on internal credit ratings and collateral pledges, while domestic banks price according to the length, depth and breadth of their relationship with a firm. These findings confirm that foreign banks can overcome informational disadvantages using contract design and credit scoring models. However, we also show that there are limitations, with foreign banks facing higher default rates and lower returns on lending if not using collateral and short maturity as disciplining tools

Iteratively regularized Newton-type methods for general data misfit functionals and applications to Poisson data

We study Newton type methods for inverse problems described by nonlinear operator equations $F(u)=g$ in Banach spaces where the Newton equations $F'(u_n;u_{n+1}-u_n) = g-F(u_n)$ are regularized variationally using a general data misfit functional and a convex regularization term. This generalizes the well-known iteratively regularized Gauss-Newton method (IRGNM). We prove convergence and convergence rates as the noise level tends to 0 both for an a priori stopping rule and for a Lepski{\u\i}-type a posteriori stopping rule. Our analysis includes previous order optimal convergence rate results for the IRGNM as special cases. The main focus of this paper is on inverse problems with Poisson data where the natural data misfit functional is given by the Kullback-Leibler divergence. Two examples of such problems are discussed in detail: an inverse obstacle scattering problem with amplitude data of the far-field pattern and a phase retrieval problem. The performence of the proposed method for these problems is illustrated in numerical examples

The Boundary Multiplet of N=4 SU(2)xU(1) Gauged Supergravity on Asymptotically-AdS_5

We consider N=4 SU(2)xU(1) gauged supergravity on asymptotically-AdS_5 backgrounds. By a near-boundary analysis we determine the boundary-dominant components of the bulk fields from their partially gauge-fixed field equations. Subdominant components are projected out in the boundary limit and we find a reduced set of boundary fields, constituting the N=2 Weyl multiplet. The residual bulk symmetries are found to act on the boundary fields as four-dimensional diffeomorphisms, N=2 supersymmetry and (super-)Weyl transformations. This shows that the on-shell N=4 supergravity multiplet yields the N=2 Weyl multiplet on the boundary with the appropriate local N=2 superconformal transformations. Building on these results we use the AdS/CFT conjecture to calculate the Weyl anomaly of the dual four-dimensional superconformal field theories in a generic bosonic N=2 conformal supergravity background.Comment: 23 pages; to appear in JHE

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Theoretical and Phenomenological Constraints on Form Factors for Radiative and Semi-Leptonic B-Meson Decays

We study transition form factors for radiative and rare semi-leptonic B-meson decays into light pseudoscalar or vector mesons, combining theoretical constraints and phenomenological information from Lattice QCD, light-cone sum rules, and dispersive bounds. We pay particular attention to form factor parameterisations which are based on the so-called series expansion, and study the related systematic uncertainties on a quantitative level. In this context, we also provide the NLO corrections to the correlation function between two flavour-changing tensor currents, which enters the unitarity constraints for the coefficients in the series expansion.Comment: 52 pages; v2: normalization error in (29ff.) corrected, conclusion about relevance of unitarity bounds modified; form factor fits unaffected; references added; v3: discussion on truncation of series expansion added, matches version to be published in JHEP; v4: corrected typos in Tables 5 and

Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration

Human genetic factors predispose to tuberculosis (TB). We studied 7.6 million genetic variants in 5,530 people with pulmonary TB and in 5,607 healthy controls. In the combined analysis of these subjects and the follow-up cohort (15,087 TB patients and controls altogether), we found an association between TB and variants located in introns of the ASAP1 gene on chromosome 8q24 (P = 2.6 × 10−11 for rs4733781; P = 1.0 × 10−10 for rs10956514). Dendritic cells (DCs) showed high ASAP1 expression that was reduced after Mycobacterium tuberculosis infection, and rs10956514 was associated with the level of reduction of ASAP1 expression. The ASAP1 protein is involved in actin and membrane remodeling and has been associated with podosomes. The ASAP1-depleted DCs showed impaired matrix degradation and migration. Therefore, genetically determined excessive reduction of ASAP1 expression in M. tuberculosis–infected DCs may lead to their impaired migration, suggesting a potential mechanism of predisposition to TB

The proangiogenic capacity of polymorphonuclear neutrophils delineated by microarray technique and by measurement of neovascularization in wounded skin of CD18-deficient mice

Growing evidence supports the concept that polymorphonuclear neutrophils (PMN) are critically involved in inflammation-mediated angiogenesis which is important for wound healing and repair. We employed an oligonucleotide microarray technique to gain further insight into the molecular mechanisms underlying the proangiogenic potential of human PMN. In addition to 18 known angiogenesis-relevant genes, we detected the expression of 10 novel genes, namely midkine, erb-B2, ets-1, transforming growth factor receptor-beta(2) and -beta(3), thrombospondin, tissue inhibitor of metalloproteinase 2, ephrin A2, ephrin B2 and restin in human PMN freshly isolated from the circulation. Gene expression was confi rmed by the RT-PCR technique. In vivo evidence for the role of PMN in neovascularization was provided by studying neovascularization in a skin model of wound healing using CD18-deficient mice which lack PMN infi ltration to sites of lesion. In CD18-deficient animals, neo- vascularization was found to be signifi cantly compromised when compared with wild- type control animals which showed profound neovascularization within the granulation tissue during the wound healing process. Thus, PMN infiltration seems to facilitate inflammation mediated angiogenesis which may be a consequence of the broad spectrum of proangiogenic factors expressed by these cells. Copyright (c) 2006 S. Karger AG, Basel

Genomics of Divergence along a Continuum of Parapatric Population Differentiation

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1)

Mechanical properties during healing of Achilles tendon ruptures to predict final outcome: A pilot Roentgen stereophotogrammetric analysis in 10 patients

<p>Abstract</p> <p>Background</p> <p>There are presently few methods described for in vivo monitoring of the mechanics of healing human tendon ruptures, and no methods for prediction of clinical outcome. We tested if Roentgen stereophotogrammetric analysis (RSA) can be used to follow the restoration of mechanical properties during healing of ruptured Achilles tendons, and if early measurements can predict clinical results.</p> <p>Methods</p> <p>Achilles tendon repair was studied with RSA in 10 patients with a total rupture. Tantalum beads were implanted in conjunction with surgical repair. The patients were evaluated at 6, 12 and 18 weeks, and after 1 year. RSA was performed with two different mechanical loadings, and the strain induced by increasing load was measured. The transverse area was determined by ultrasound. CT scan at 12 weeks confirmed that the tantalum beads were located within the tendons. Functional testing was done after 1 year. A heel raise index was chosen as primary clinical outcome variable.</p> <p>Results</p> <p>The strain was median 0.90, 0.32 and 0.14 percent per 100 N tendon force at 6 weeks, 18 weeks and one year respectively. The error of measurement was 0.04 percent units at 18 weeks. There was a large variation between patients, which appears to reflect biological variation. From 6 to 18 weeks, there was a negative correlation between increase in transverse area and increase in material properties, suggesting that healing is regulated at the organ level, to maximize stiffness. Modulus of elasticity during this time correlated with a heel raise index at one year (Rho = 0.76; p = 0.02).</p> <p>Conclusion</p> <p>We conclude that the RSA method might have potential for comparing different treatments of Achilles tendon ruptures.</p