Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation

The mechanisms underlying the regenerative capacity of the liver are not fully understood. Here, the authors show that the acute regenerative response to liver injury in mice is regulated by the communication involving the vagus nerve, macrophages, and hepatocytes, leading to hepatic FoxM1 activation and promotion of overall survival

Search for Anisotropy of Ultra-High Energy Cosmic Rays with the Telescope Array Experiment

We study the anisotropy of Ultra-High Energy Cosmic Ray (UHECR) events collected by the Telescope Array (TA) detector in the first 40 months of operation. Following earlier studies, we examine event sets with energy thresholds of 10 EeV, 40 EeV, and 57 EeV. We find that the distributions of the events in right ascension and declination are compatible with an isotropic distribution in all three sets. We then compare with previously reported clustering of the UHECR events at small angular scales. No significant clustering is found in the TA data. We then check the events with E>57 EeV for correlations with nearby active galactic nuclei. No significant correlation is found. Finally, we examine all three sets for correlations with the large-scale structure of the Universe. We find that the two higher-energy sets are compatible with both an isotropic distribution and the hypothesis that UHECR sources follow the matter distribution of the Universe (the LSS hypothesis), while the event set with E>10 EeV is compatible with isotropy and is not compatible with the LSS hypothesis at 95% CL unless large deflection angles are also assumed. We show that accounting for UHECR deflections in a realistic model of the Galactic magnetic field can make this set compatible with the LSS hypothesis.Comment: 10 pages, 9 figure

Paradoxical expression of cell cycle inhibitor p27 in endometrioid adenocarcinoma of the uterine corpus – correlation with proliferation and clinicopathological parameters

p27 is regarded as a cyclin-dependent kinase inhibitor of the G1-to-S cell cycle progression by suppressing the kinase activity of cyclin/cyclin-dependent kinase complex. This study aimed to investigate p27 expression in the normal endometrium and endometrioid adenocarcinoma of the uterine corpus and the correlation of its expression with cell proliferation and clinicopathological parameters. Tissue samples of 127 endometrioid adenocarcinomas and 15 normal endometria were used in the study. Immunohistochemical staining for detecting p27 and Ki-67 was performed by the labelled streptavidin-biotin method on formalin-fixed and paraffin-embedded tissue samples. The expression was given as the labelling index, which indicates the percentage of positive nuclei. p27 staining was observed in the nuclei of the glandular cells in the functional layer of the secretory phase endometrium, whereas it was negative in those of the proliferative phase. In endometrioid adenocarcinomas, the labelling index of p27 expression paradoxically increased more significantly in the higher histological grades and was correlated with that of Ki-67. The high level of p27 expression was associated with clinicopathological parameters such as FIGO stage, lymph node metastasis, lymphovascular space involvement and myometrial invasion. High p27 expression was linked to higher grades of endometrioid adenocarcinoma, cell proliferation and some clinical prognostic factors. These results indicate that p27 might be an indicator of poor prognosis

Combined analysis of cell growth and apoptosis-regulating proteins in HPVs associated anogenital tumors

<p>Abstract</p> <p>Background</p> <p>The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors.</p> <p>Methods</p> <p>We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity.</p> <p>Results</p> <p>Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (<it>p </it>< 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (<it>p </it>< 0.001, <it>p </it>< 0.001, <it>p </it>= 0.022, respectively) and normal skin (<it>p </it>< 0.001, <it>p </it>= 0.002, <it>p </it>= 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression.</p> <p>Conclusion</p> <p>Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.</p

Human Mena Associates with Rac1 Small GTPase in Glioblastoma Cell Lines

Mammarian enabled (Mena), a member of the Enabled (Ena)/Vasodilator-stimulated phosphoprotein (VASP) family of proteins, has been implicated in cell motility through regulation of the actin cytoskeleton assembly, including lamellipodial protrusion. Rac1, a member of the Rho family GTPases, also plays a pivotal role in the formation of lamellipodia. Here we report that human Mena (hMena) colocalizes with Rac1 in lamellipodia, and using an unmixing assisted acceptor depletion fluorescence resonance energy transfer (u-adFRET) analysis that hMena associates with Rac1 in vivo in the glioblastoma cell line U251MG. Depletion of hMena by siRNA causes cells to be highly spread with the formation of lamellipodia. This cellular phenotype is canceled by introduction of a dominant negative form of Rac1. A Rac activity assay and FRET analysis showed that hMena knock-down cells increased the activation of Rac1 at the lamellipodia. These results suggest that hMena possesses properties which help to regulate the formation of lamellipodia through the modulation of the activity of Rac1

Influenza Infectious Dose May Explain the High Mortality of the Second and Third Wave of 1918–1919 Influenza Pandemic

BACKGROUND: It is widely accepted that the shift in case-fatality rate between waves during the 1918 influenza pandemic was due to a genetic change in the virus. In animal models, the infectious dose of influenza A virus was associated to the severity of disease which lead us to propose a new hypothesis. We propose that the increase in the case-fatality rate can be explained by the dynamics of disease and by a dose-dependent response mediated by the number of simultaneous contacts a susceptible person has with infectious ones. METHODS: We used a compartment model with seasonality, waning of immunity and a Holling type II function, to model simultaneous contacts between a susceptible person and infectious ones. In the model, infected persons having mild or severe illness depend both on the proportion of infectious persons in the population and on the level of simultaneous contacts between a susceptible and infectious persons. We further allowed for a high or low rate of waning immunity and volunteer isolation at different times of the epidemic. RESULTS: In all scenarios, case-fatality rate was low during the first wave (Spring) due to a decrease in the effective reproduction number. The case-fatality rate in the second wave (Autumn) depended on the ratio between the number of severe cases to the number of mild cases since, for each 1000 mild infections only 4 deaths occurred whereas for 1000 severe infections there were 20 deaths. A third wave (late Winter) was dependent on the rate for waning immunity or on the introduction of new susceptible persons in the community. If a group of persons became voluntarily isolated and returned to the community some days latter, new waves occurred. For a fixed number of infected persons the overall case-fatality rate decreased as the number of waves increased. This is explained by the lower proportion of infectious individuals in each wave that prevented an increase in the number of severe infections and thus of the case-fatality rate. CONCLUSION: The increase on the proportion of infectious persons as a proxy for the increase of the infectious dose a susceptible person is exposed, as the epidemic develops, can explain the shift in case-fatality rate between waves during the 1918 influenza pandemic.TD acknowledges the support of the Faculdade de Ciencias e Tecnologia through grant PPCDT/AMB/55701/2004. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Measurement of the proton-air cross section with Telescope Array&apos;s Middle Drum detector and surface array in hybrid mode

In this work we are reporting on the measurement of the proton-air inelastic cross section sigma(inel)(p-air) using the Telescope Array detector. Based on the measurement of the sigma(inel)(p-air), the proton-proton cross section sigma(p-p) value is also determined at root s = 95(-8)(+5) TeV. Detecting cosmic ray events at ultrahigh energies with the Telescope Array enables us to study this fundamental parameter that we are otherwise unable to access with particle accelerators. The data used in this report are the hybrid events observed by the Middle Drum fluorescence detector together with the surface array detector collected over five years. The value of the sigma(inel)(p-air) is found to be equal to 567.0 +/- 70.5[Stat](-25)(+29)[Sys] mb. The total proton-proton cross section is subsequently inferred from Glauber formalism and the Block, Halzen and Stanev QCD inspired fit and is found to be equal to 170(-44)(+48)[Stat](-17)(+19)[Sys] mb.open20

Indications of intermediate-scale anisotropy of cosmic rays with energy greater than 57 EeV in the northern sky measured with the surface detector of the Telescope Array experiment

We have searched for intermediate-scale anisotropy in the arrival directions of ultrahigh-energy cosmic rays with energies above 57 EeV in the northern sky using data collected over a 5 yr period by the surface detector of the Telescope Array experiment. We report on a cluster of events that we call the hotspot, found by oversampling using 20?? radius circles. The hotspot has a Li-Ma statistical significance of 5.1??, and is centered at R.A. = 146.??7, decl. = 43.??2. The position of the hotspot is about 19?? off of the supergalactic plane. The probability of a cluster of events of 5.1?? significance, appearing by chance in an isotropic cosmic-ray sky, is estimated to be 3.7 ?? 10-4 (3.4??).open2