Penetrative nature of high energy showers observed in Chacaltaya emulsion chamber

About 30% of single core showers with E (sup gamma) 10 TeV have stronger penetrating power than that expected from electromagnetic showers (e,gamma). On the other hand, their starting points of cascades in the chamber are found to be as shallow as those of (e,gamma) components. It is suggested that those showers are very collimated bundles of hadron and (e,gamma) component. Otherwise, it is assumed that the collision mean free path of those showers in the chamber is shorter than that of hadron with geometrical value

Near-Infrared Coronagraphic Observations of the T Tauri Binary System UY Aur

We present a near-infrared image of UY Aur, a 0.9" separated binary system, using the Coronagraphic Imager with Adaptive Optics on the Subaru Telescope. Thanks to adaptive optics, the spatial resolution of our image was ~0.1" in the full width at half maximum of the point spread function, the highest achieved. By comparison with previous measurements, we estimated that the orbital period is ~1640 yrs and the total mass of the binary is ~1.73 solar mass. The observed H-band magnitude of the secondary varies by as much as 1.3 mag within a decade, while that of the primary is rather stable. This inconstancy may arise from photospheric variability caused by an uneven accretion rate or from the rotation of the secondary. We detected a half-ring shaped circumbinary disk around the binary with a bright southwest part but a barely detectable northeast portion. The brightness ratio is ~57. Its inner radius and inclination are about 520 AU and 42, respectively. The disk is not uniform but has remarkable features, including a clumpy structure along the disk, circumstellar material inside the inner cavity, and an extended armlike structure. The circumstellar material inside the cavity probably corresponds to a clump or material accreting from the disk onto the binary. The armlike structure is a part of the disk, created by the accretion from the outer region of the disk or encounters with other stellar systems.Comment: 16 pages, 6 figures; accepted for publication in A

Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors

Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of overlapping pathways in trophoblast-endometrial communication. In conclusion, trophoblast signals attract endometrial stromal cells, while PDGF-BB and HB-EGF, although not identified as trophoblast-derived, are local growth factors that may serve to fine-tune directed and non-directed migration at the implantation site

Disruption of LRRK2 Does Not Cause Specific Loss of Dopaminergic Neurons in Zebrafish

Mutations in LRRK2 are genetically linked to Parkinson's disease (PD) but its normal biological function is largely unknown. Sheng et al. recently reported that deletion of the WD40 domain of LRRK2 in zebrafish specifically causes PD-like loss of neurons and behavior defect. However, our similar early study and recent confirming experiments using the same reagents reported by Sheng et al. failed to reproduce the phenotype of the loss of dopaminergic neurons, although the mRNA of LRRK2 was molecularly disrupted. Our study suggests that function of LRRK2 and its usefulness to generate zebrafish PD model needs further evaluation

Interoceptive hypersensitivity and interoceptive exposure in patients with panic disorder: specificity and effectiveness

BACKGROUND: Interoceptive exposure has been validated as an effective component of cognitive behavioral therapy (CBT) for the treatment of panic disorder but has hitherto received little research attention. We examined the effectiveness of various interoceptive exposure exercises using the Body Sensations Questionnaire (BSQ) (Chambless et al., 1984). METHODS: We first performed an exploratory principal factor analysis of all the items contained in the BSQ to obtain meaningful dimensions of interoceptive fears. Next, we examined the correlations between each interoceptive exposure task's degree of similarity to panic attacks and each BSQ factor and then examined whether the BSQ factor scores decreased in comparison with the baseline values when the corresponding exposure tasks were successfully completed by the subjects. RESULTS: The factor analyses revealed four factors, which we named "pseudoneurological fears", "gastrointestinal fears", "cardiorespiratory fears" and "fears of dissociative feelings." Among the nine interoceptive exposure tasks, 'hyperventilation', 'shaking head', 'holding breath' and 'chest breathing' were considered to reproduce pseudoneurological symptoms, 'breathing through a straw' was considered to reproduce gastrointestinal symptoms, and 'spinning' was considered to reproduce both pseudoneurological and dissociative symptoms; none of the interoceptive exercises were found to reproduce cardiorespiratory symptoms. Among each group of patients for whom 'hyperventilation', 'holding breath', 'spinning' or 'chest breathing' was effective, a significant improvement in the BSQ pseudoneurological fears factor scores was observed. On the other hand, no significant difference between the baseline and endpoint values of the BSQ gastrointestinal fears or the BSQ fears of dissociative feelings factor scores were observed among the patients for whom 'spinning' or 'breathing through a straw' was effective. CONCLUSION: Several interoceptive exposure tasks were particularly effective in reducing pseudoneurological fears. New interoceptive tasks, especially tasks related to cardiorespiratory and dissociative feelings, are needed

LRRK2 at the interface of autophagosomes, endosomes and lysosomes

Over the past 20 years, substantial progress has been made in identifying the underlying genetics of Parkinson’s disease (PD). Of the known genes, LRRK2 is a major genetic contributor to PD. However, the exact function of LRRK2 remains to be elucidated. In this review, we discuss how familial forms of PD have led us to hypothesize that alterations in endomembrane trafficking play a role in the pathobiology of PD. We will discuss the major observations that have been made to elucidate the role of LRRK2 in particular, including LRRK2 animal models and high-throughput proteomics approaches. Taken together, these studies strongly support a role of LRRK2 in vesicular dynamics. We also propose that targeting these pathways may not only be beneficial for developing therapeutics for LRRK2-driven PD, but also for other familial and sporadic cases

Transmission of Specific Genotype Streptomycin Resistant Strains of Mycobacterium tuberculosis in the Tokyo Metropolitan Area in Japan

<p>Abstract</p> <p>Background</p> <p>From 2003 through to 2004, an outbreak of tuberculosis was identified at a university campus in Yokohama City, located in the southern part of the Tokyo Metropolitan Area (TMA). All <it>Mycobacterium tuberculosis </it>(<it>M. tuberculosis</it>) strains detected with regards to this outbreak turned out to be Streptomycin resistant with matched patterns of 14 IS<it>6110 </it>bands of Restriction Fragment Length Polymorphism (RFLP). The <it>M. tuberculosis </it>bacilli, which had the matched IS<it>6110 </it>band patterns with resistance to Streptomycin to those of bacilli isolated in the outbreak, were also concurrently detected through either the population-based or the hospital-based DNA fingerprinting surveillance of <it>M. tuberculosis </it>either in Shinjuku City or in Kawasaki City respectively.</p> <p>The aim of the present study is to describe the spread of the specific genotype strains of <it>M. tuberculosis </it>in the TMA as observed in the above incident, and to identify the possible transmission routes of the strains among people living in urban settings in Japan.</p> <p>Methods</p> <p>We applied Variable Numbers of Tandem Repeats (VNTR) analysis to all <it>M. tuberculosis </it>isolates which were resistant to Streptomycin with a matched IS<it>6110</it>-RFLP band pattern (M-strains). They were isolated either from cases related to the tuberculosis outbreak that happened at a university, or through DNA fingerprinting surveillance of <it>M. tuberculosis </it>both in Shinjuku City and in Kawasaki City. For VNTR analysis, 12MIRU loci, 4ETR loci, seven loci by Supply, four loci by Murase (QUB15, Mtub24, VNTR2372, VNTR3336) were selected.</p> <p>Results</p> <p>Out of a total of 664 isolates collected during the study period, 46 isolates (6.9%) were identified as M-strains. There was a tendency that there was a higher proportion of those patients whose isolates belonged to M4-substrains, with four copies of tandem repeat at the ETR-C locus, to have visited some of the internet-cafés in the TMA than those whose isolates belonged to M5-substrains, with five copies at the ETR-C locus, although statistically not significant (38.1% vs. 10.0%, Exact p = 0.150).</p> <p>Conclusion</p> <p>Although firm conclusions could not be reached through the present study, it suggested that we have to take into consideration that tuberculosis can be transmitted in congregated facilities like internet cafés where tuberculosis high-risk people and general people share common spaces.</p

NF-κB Mediates Tumor Necrosis Factor α-Induced Expression of Optineurin, a Negative Regulator of NF-κB

Optineurin is a ubiquitously expressed multifunctional cytoplasmic protein encoded by OPTN gene. The expression of optineurin is induced by various cytokines. Here we have investigated the molecular mechanisms which regulate optineurin gene expression and the relationship between optineurin and nuclear factor κB (NF-κB). We cloned and characterized human optineurin promoter. Optineurin promoter was activated upon treatment of HeLa and A549 cells with tumor necrosis factor α (TNFα). Mutation of a putative NF-κB-binding site present in the core promoter resulted in loss of basal as well as TNFα-induced activity. Overexpression of p65 subunit of NF-κB activated this promoter through NF-κB site. Oligonucleotides corresponding to this putative NF-κB-binding site showed binding to NF-κB. TNFα-induced optineurin promoter activity was inhibited by expression of inhibitor of NF-κB (IκBα) super-repressor. Blocking of NF-κB activation resulted in inhibition of TNFα-induced optineurin gene expression. Overexpressed optineurin partly inhibited TNFα-induced NF-κB activation in Hela cells. Downregulation of optineurin by shRNA resulted in an increase in TNFα-induced as well as basal NF-κB activity. These results show that optineurin promoter activity and gene expression are regulated by NF-κB pathway in response to TNFα. In addition these results suggest that there is a negative feedback loop in which TNFα-induced NF-κB activity mediates expression of optineurin, which itself functions as a negative regulator of NF-κB

Depletion of Human Histone H1 Variants Uncovers Specific Roles in Gene Expression and Cell Growth

At least six histone H1 variants exist in somatic mammalian cells that bind to the linker DNA and stabilize the nucleosome particle contributing to higher order chromatin compaction. In addition, H1 seems to be actively involved in the regulation of gene expression. However, it is not well known whether the different variants have distinct roles or if they regulate specific promoters. We have explored this by inducible shRNA-mediated knock-down of each of the H1 variants in a human breast cancer cell line. Rapid inhibition of each H1 variant was not compensated for by changes of expression of other variants. Microarray experiments have shown a different subset of genes to be altered in each H1 knock-down. Interestingly, H1.2 depletion caused specific effects such as a cell cycle G1-phase arrest, the repressed expression of a number of cell cycle genes, and decreased global nucleosome spacing. On its side, H1.4 depletion caused cell death in T47D cells, providing the first evidence of the essential role of an H1 variant for survival in a human cell type. Thus, specific phenotypes are observed in breast cancer cells depleted of individual histone H1 variants, supporting the theory that distinct roles exist for the linker histone variants

Time evolution of in vivo articular cartilage repair induced by bone marrow stimulation and scaffold implantation in rabbits

Purpose: Tissue engineering techniques were used to study cartilage repair over a 12-month period in a rabbit model. Methods: A full-depth chondral defect along with subchondral bone injury were originated in the knee joint, where a biostable porous scaffold was implanted, synthesized of poly(ethyl acrylate-co-hydroxyethyl acrylate) copolymer. Morphological evolution of cartilage repair was studied 1 and 2 weeks, and 1, 3, and 12 months after implantation by histological techniques. The 3-month group was chosen to compare cartilage repair to an additional group where scaffolds were preseeded with allogeneic chondrocytes before implantation, and also to controls, who underwent the same surgery procedure, with no scaffold implantation. Results: Neotissue growth was first observed in the deepest scaffold pores 1 week after implantation, which spread thereafter; 3 months later scaffold pores were filled mostly with cartilaginous tissue in superficial and middle zones, and with bone tissue adjacent to subchondral bone. Simultaneously, native chondrocytes at the edges of the defect started to proliferate 1 week after implantation; within a month those edges had grown centripetally and seemed to embed the scaffold, and after 3 months, hyaline-like cartilage was observed on the condylar surface. Preseeded scaffolds slightly improved tissue growth, although the quality of repair tissue was similar to non-preseeded scaffolds. Controls showed that fibrous cartilage was mainly filling the repair area 3 months after surgery. In the 12-month group, articular cartilage resembled the untreated surface. Conclusions: Scaffolds guided cartilaginous tissue growth in vivo, suggesting their importance in stress transmission to the cells for cartilage repair.This study was supported by the Spanish Ministry of Science and Innovation through MAT2010-21611-C03-00 project (including the FEDER financial support), by Conselleria de Educacion (Generalitat Valenciana, Spain) PROMETEO/2011/084 grant, and by CIBER-BBN en Bioingenieria, Biomateriales y Nanomedicina. The work of JLGR was partially supported by funds from the Generalitat Valenciana, ACOMP/2012/075 project. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the - Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Sancho-Tello Valls, M.; Forriol, F.; Gastaldi, P.; Ruiz Sauri, A.; Martín De Llano, JJ.; Novella-Maestre, E.; Antolinos Turpín, CM.... (2015). 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