The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens

Macrophages play pleiotropic roles in maintaining the balance between immune tolerance and inflammatory responses in the gut. Here, we identified transcription factor RBP-J as a crucial regulator of colonic macrophage-mediated immune responses against the enteric pathogen Citrobacter rodentium. In the immune response phase, RBP-J promoted pathogen clearance by enhancing intestinal macrophage-elicited Th17 cell immune responses, which was achieved by maintenance of C/EBPβ-dependent IL-6 production by overcoming miRNA-17∼92-mediated suppressive effects. RBP-J deficiency-associated phenotypes could be genetically corrected by further deleting miRNA-17∼92 in macrophages. In the late phase, noneradicated pathogens in RBP-J KO mice recruited abundant IL-1β-expressing CD64+Ly6C+ colonic macrophages and thereby promoted persistence of ILC3-derived IL-22 to compensate for the impaired innate and adaptive immune responses, leading to ultimate clearance of pathogens. These results demonstrated that colonic macrophage-intrinsic RBP-J dynamically orchestrates intestinal immunity against pathogen infections by interfacing with key immune cells of T and innate lymphoid cell lineages

Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPκ, μ, ρ and PCP-2)

BACKGROUND: Four genes designated as PTPRK (PTPκ), PTPRL/U (PCP-2), PTPRM (PTPμ) and PTPRT (PTPρ) code for a subfamily (type R2B) of receptor protein tyrosine phosphatases (RPTPs) uniquely characterized by the presence of an N-terminal MAM domain. These transmembrane molecules have been implicated in homophilic cell adhesion. In the human, the PTPRK gene is located on chromosome 6, PTPRL/U on 1, PTPRM on 18 and PTPRT on 20. In the mouse, the four genes ptprk, ptprl, ptprm and ptprt are located in syntenic regions of chromosomes 10, 4, 17 and 2, respectively. RESULTS: The genomic organization of murine R2B RPTP genes is described. The four genes varied greatly in size ranging from ~64 kb to ~1 Mb, primarily due to proportional differences in intron lengths. Although there were also minor variations in exon length, the number of exons and the phases of exon/intron junctions were highly conserved. In situ hybridization with digoxigenin-labeled cRNA probes was used to localize each of the four R2B transcripts to specific cell types within the murine central nervous system. Phylogenetic analysis of complete sequences indicated that PTPρ and PTPμ were most closely related, followed by PTPκ. The most distant family member was PCP-2. Alignment of RPTP polypeptide sequences predicted putative alternatively spliced exons. PCR experiments revealed that five of these exons were alternatively spliced, and that each of the four phosphatases incorporated them differently. The greatest variability in genomic organization and the majority of alternatively spliced exons were observed in the juxtamembrane domain, a region critical for the regulation of signal transduction. CONCLUSIONS: Comparison of the four R2B RPTP genes revealed virtually identical principles of genomic organization, despite great disparities in gene size due to variations in intron length. Although subtle differences in exon length were also observed, it is likely that functional differences among these genes arise from the specific combinations of exons generated by alternative splicing

On Glauber modes in Soft-Collinear Effective Theory

Gluon interactions involving spectator partons in collisions at hadronic machines are investigated. We find a class of examples in which a mode, called Glauber gluons, must be introduced to the effective theory for consistency.Comment: 19 pages, three figures. Uses JHEP3.cl

Non-L\'evy mobility patterns of Mexican Me'Phaa peasants searching for fuelwood

We measured mobility patterns that describe walking trajectories of individual Me'Phaa peasants searching and collecting fuelwood in the forests of "La Monta\~na de Guerrero" in Mexico. These one-day excursions typically follow a mixed pattern of nearly-constant steps when individuals displace from their homes towards potential collecting sites and a mixed pattern of steps of different lengths when actually searching for fallen wood in the forest. Displacements in the searching phase seem not to be compatible with L\'evy flights described by power-laws with optimal scaling exponents. These findings however can be interpreted in the light of deterministic searching on heavily degraded landscapes where the interaction of the individuals with their scarce environment produces alternative searching strategies than the expected L\'evy flights. These results have important implications for future management and restoration of degraded forests and the improvement of the ecological services they may provide to their inhabitants.Comment: 15 pages, 4 figures. First version submitted to Human Ecology. The final publication will be available at http://www.springerlink.co

Quantum Gravity in Everyday Life: General Relativity as an Effective Field Theory

This article is meant as a summary and introduction to the ideas of effective field theory as applied to gravitational systems. Contents: 1. Introduction 2. Effective Field Theories 3. Low-Energy Quantum Gravity 4. Explicit Quantum Calculations 5. ConclusionsComment: 56 pages, 2 figures, JHEP style, Invited review to appear in Living Reviews of Relativit

A Triple Protostar System Formed via Fragmentation of a Gravitationally Unstable Disk

Binary and multiple star systems are a frequent outcome of the star formation process, and as a result, almost half of all sun-like stars have at least one companion star. Theoretical studies indicate that there are two main pathways that can operate concurrently to form binary/multiple star systems: large scale fragmentation of turbulent gas cores and filaments or smaller scale fragmentation of a massive protostellar disk due to gravitational instability. Observational evidence for turbulent fragmentation on scales of $>$1000~AU has recently emerged. Previous evidence for disk fragmentation was limited to inferences based on the separations of more-evolved pre-main sequence and protostellar multiple systems. The triple protostar system L1448 IRS3B is an ideal candidate to search for evidence of disk fragmentation. L1448 IRS3B is in an early phase of the star formation process, likely less than 150,000 years in age, and all protostars in the system are separated by $<$200~AU. Here we report observations of dust and molecular gas emission that reveal a disk with spiral structure surrounding the three protostars. Two protostars near the center of the disk are separated by 61 AU, and a tertiary protostar is coincident with a spiral arm in the outer disk at a 183 AU separation. The inferred mass of the central pair of protostellar objects is $\sim$1 M$_{sun}$, while the disk surrounding the three protostars has a total mass of $\sim$0.30 M_{\sun}. The tertiary protostar itself has a minimum mass of $\sim$0.085 M$_{sun}$. We demonstrate that the disk around L1448 IRS3B appears susceptible to disk fragmentation at radii between 150~AU and 320~AU, overlapping with the location of the tertiary protostar. This is consistent with models for a protostellar disk that has recently undergone gravitational instability, spawning one or two companion stars.Comment: Published in Nature on Oct. 27th. 24 pages, 8 figure

Validity of the Walter Reed Visual Assessment Scale to measure subjective perception of spine deformity in patients with idiopathic scoliosis

BACKGROUND: The Walter Reed Visual Assessment Scale (WRVAS) was designed to allow idiopathic scoliosis patients to describe their perception of their deformity. In a previous stduy, the scale has shown good correlation with magnitude of the curve METHODS: The study included 70 patients (60 women and 10 men), mean age 19.4 years (range 12–40), with idiopathic scoliosis. Each patient filled out the WRVAS and the SRS-22 questionnaire. Thoracic and lumbar curve angles were determined in standing X-rays and the largest was named Cobbmax. WRVAS internal consistency was assessed with Cronbach's alpha. Correlation coefficients were calculated between Cobbmax and the various WRVAS questions, and Cobbmax and the SRS-22 scales. The correlation between the WRVAS and SRS-22 was also determined RESULTS: Mean magnitudes were thoracic curve, 36.6° and lumbar curve, 33.2°; average Cobbmax was 37.9°. The mean total WRVAS score was 15.6. Mean scores for the various SRS-22 scales were function 4.6, pain 4.3, self-image 3.7, mental health 4.2, and total score 84.1. Internal consistency for the WRVAS was excellent (Cronbach's alpha, 0.9), and there were no signs of collinearity among the seven questions (tolerance range 0.2–0.5). All the items on the WRVAS correlated significantly with Cobbmax (correlation coefficients, 0.4 to 0.7). The correlation between the total WRVAS and total SRS-22 score was -0.54 (P = .0001) and between WRVAS total score and SRS-22 image domain score was -0.57 (p = 0.0001) CONCLUSION: The WRVAS showed excellent internal consistency and absence of collinearity. There was a highly significant correlation between the results of the test and the magnitude of the deformity. The WRVAS correlated significantly with the SRS-22 image scale. The WRVAS is a valid instrument to assess scoliosis patients perception of their deformit

Changes in Russian managerial values: a test of the convergence hypothesis?

This paper considers how Russian managerial values are developing in the context of the sweeping economic, political and social changes associated with the transition of Russia to a market economy. By replicating earlier research (Holt et al., 1994; Ralston et al., 1997), it was possible to overcome the weaknesses of previous cross-sectional studies by tracking changes in Russian managers' values over time. The paper concludes that some convergence between the values of Russian and US managers can be observed, but that the form of this convergence is not uniform. In addition, the way in which Russian managers act upon these values in the context of their own national context means that considerable divergence in managerial behaviour is still evident. Implications for international human resource management are discussed

Radio Emission from Ultra-Cool Dwarfs

The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed that these objects can generate and dissipate powerful magnetic fields. Radio observations provide unparalleled insight into UCD magnetism: detections extend to brown dwarfs with temperatures <1000 K, where no other observational probes are effective. The data reveal that UCDs can generate strong (kG) fields, sometimes with a stable dipolar structure; that they can produce and retain nonthermal plasmas with electron acceleration extending to MeV energies; and that they can drive auroral current systems resulting in significant atmospheric energy deposition and powerful, coherent radio bursts. Still to be understood are the underlying dynamo processes, the precise means by which particles are accelerated around these objects, the observed diversity of magnetic phenomenologies, and how all of these factors change as the mass of the central object approaches that of Jupiter. The answers to these questions are doubly important because UCDs are both potential exoplanet hosts, as in the TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag