Blood Clot Formation Does Not Affect Metastasis Formation or Tumor Growth in a Murine Model of Breast Cancer

Cancer is associated with increased fracture risk, due either to metastasis or associated osteoporosis. After a fracture, blood clots form. Because proteins of the coagulation cascade and activated platelets promote cancer development, a fracture in patients with cancer often raises the question whether it is a pathologic fracture or whether the fracture itself might promote the formation of metastatic lesions. We therefore examined whether blood clot formation results in increased metastasis in a murine model of experimental breast cancer metastasis. For this purpose, a clot was surgically induced in the bone marrow of the left tibia of immundeficient mice. Either one minute prior to or five minutes after clot induction, human cancer cells were introduced in the circulation by intracardiac injection. The number of cancer cells that homed to the intervention site was determined by quantitative real-time PCR and flow cytometry. Metastasis formation and longitudinal growth were evaluated by bioluminescence imaging. The number of cancer cells that homed to the intervention site after 24 hours was similar to the number of cells in the opposite tibia that did not undergo clot induction. This effect was confirmed using two more cancer cell lines. Furthermore, no difference in the number of macroscopic lesions or their growth could be detected. In the control group 72% developed a lesion in the left tibia. In the experimental groups with clot formation 79% and 65% developed lesions in the left tibia (p = ns when comparing each experimental group with the controls). Survival was similar too. In summary, the growth factors accumulating in a clot/hematoma are neither enough to promote cancer cell homing nor support growth in an experimental model of breast cancer bone metastasis. This suggests that blood clot formation, as occurs in traumatic fractures, surgical interventions, and bruises, does not increase the risk of metastasis formation

Fibronectin Protects from Excessive Liver Fibrosis by Modulating the Availability of and Responsiveness of Stellate Cells to Active TGF-β

Fibrotic tissue in the liver is mainly composed of collagen. Fibronectin, which is also present in fibrotic matrices, is required for collagen matrix assembly in vitro. It also modulates the amount of growth factors and their release from the matrix. We therefore examined the effects of the absence of fibronectin on the development of fibrosis in mice

Tannerella forsythia, a periodontal pathogen entering the genomic era

Several questions need to be addressed to evaluate whether Tannerella forsythia is to be considered a periodontal pathogen. T. forsythia has been detected in periodontal health and disease, so could it be a pathogen? The species was not detected in many studies despite finding other putative pathogens, so could it be important in pathogenicity? The challenges of working with T. forsythia include its fastidious and anaerobic growth requirements for cultural detection. Thus, studies associating T. forsythia with periodontal and other oral infections have used noncultural approaches (immunoassays and DNA-based assays) in addition to cultural approaches. We feel the timing of this review represents an interesting transition period in our understanding of the relationships of species with infection. Information from the recently released full genome sequence data of T. forsythia will provide new approaches and tools that can be directed to assess pathogenicity. Furthermore, molecular assessment of gene expression will provide a new understanding of the pathogenical potential of the species, and its effect on the host. T. forsythia, was described in reviews focusing on periodontal pathogens associated with herpesvirus detection (200), species for which genome projects were underway (41), members of polybacterial periodontal pathogenic consortium (91), and participants in periodontal microbial ecology (202). We will describe the history, taxonomy, and characteristics of T. forsythia, and related species or phylotypes in the genus Tannerella. To assess the pathogenic potential of T. forsythia, we first describe species associations with periodontal and other infections, including animal models, as has been the traditional approach arising from Koch’s postulates (203). Criteria for pathogenicity were expanded to incorporate sequence- derived information (58), and again more recently to include molecular signatures of pathogens and disease (170). We used sequence and genome-derived information, in addition to biofilm, pathogenic mediators, and host responses, to further explore the pathogenic potential of T. forsythia

New constraints on oscillation parameters from Ve appearance and Vu disappearance in the NOvA experiment

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First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA

The NOvA experiment has seen a 4.4σ signal of ν̄e appearance in a 2 GeV ν̄μ beam at a distance of 810 km. Using 12.33×1020 protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 ν̄μ→ν̄e candidates with a background of 10.3 and 102 ν̄μ→ν̄μ candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Δm322|=2.48-0.06+0.11×10-3 eV2/c4 and sin2θ23 in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near δCP=π/2 for the inverted mass hierarchy by more than 3σ and favor the normal neutrino mass hierarchy by 1.9σ and θ23 values in the upper octant by 1.6σ

Measurement of the Double-Differential Muon-neutrino Charged-Current Inclusive Cross Section in the NOvA Near Detector

We report cross-section measurements of the final-state muon kinematics for \numu charged-current interactions in the NOvA near detector using an accumulated 8.09$\times10^{20}$ protons-on-target (POT) in the NuMI beam. We present the results as a double-differential cross section in the observed outgoing muon energy and angle, as well as single-differential cross sections in the derived neutrino energy, $E_\nu$, and square of the four-momentum transfer, $Q^2$. We compare the results to inclusive cross-section predictions from various neutrino event generators via $\chi^2$ calculations using a covariance matrix that accounts for bin-to-bin correlations of systematic uncertainties. These comparisons show a clear discrepancy between the data and each of the tested predictions at forward muon angle and low $Q^2$, indicating a missing suppression of the cross section in current neutrino-nucleus scattering models

An Improved Measurement of Neutrino Oscillation Parameters by the NOvA Experiment

We present new $\nu_\mu\rightarrow\nu_e$, $\nu_\mu\rightarrow\nu_\mu$, $\overline{\nu}_\mu\rightarrow\overline{\nu}_e$, and $\overline{\nu}_\mu\rightarrow\overline{\nu}_\mu$ oscillation measurements by the NOvA experiment, with a 50% increase in neutrino-mode beam exposure over the previously reported results. The additional data, combined with previously published neutrino and antineutrino data, are all analyzed using improved techniques and simulations. A joint fit to the $\nu_e$, $\nu_\mu$, $\overline{\nu}_e$, and $\overline{\nu}_\mu$ candidate samples within the 3-flavor neutrino oscillation framework continues to yield a best-fit point in the normal mass ordering and the upper octant of the $\theta_{23}$ mixing angle, with $\Delta m^{2}_{32} = (2.41\pm0.07)\times 10^{-3}$ eV$^2$ and $\sin^2\theta_{23} = 0.57^{+0.03}_{-0.04}$. The data disfavor combinations of oscillation parameters that give rise to a large asymmetry in the rates of $\nu_e$ and $\overline{\nu}_e$ appearance. This includes values of the CP-violating phase in the vicinity of $\delta_\text{CP} = \pi/2$ which are excluded by $>3\sigma$ for the inverted mass ordering, and values around $\delta_\text{CP} = 3\pi/2$ in the normal ordering which are disfavored at 2$\sigma$ confidence.Comment: 11 pages, 6 figures. Supplementary material attached (7 figures

Seasonal Variation of Multiple-Muon Cosmic Ray Air Showers Observed in the NOvA Detector on the Surface

We report the rate of cosmic ray air showers with multiplicities exceeding 15 muon tracks recorded in the NOvA Far Detector between May 2016 and May 2018. The detector is located on the surface under an overburden of 3.6 meters water equivalent. We observe a seasonal dependence in the rate of multiple-muon showers, which varies in magnitude with multiplicity and zenith angle. During this period, the effective atmospheric temperature and surface pressure ranged between 210 K to 230 K and 940mbar to 990mbar, respectively; the shower rates are anti-correlated with the variation in the effective temperature. The variations are about 30% larger for the highest multiplicities than the lowest multiplicities and 20% larger for showers near the horizon than vertical showers

Search for multimessenger signals in NOvA coincident with LIGO/Virgo detections

Using the NOvA neutrino detectors, a broad search has been performed for any signal coincident with 28 gravitational wave events detected by the LIGO/Virgo Collaboration between September 2015 and July 2019. For all of these events, NOvA is sensitive to possible arrival of neutrinos and cosmic rays of GeV and higher energies. For five (seven) events in the NOvA Far (Near) Detector, timely public alerts from the LIGO/Virgo Collaboration allowed recording of MeV-scale events. No signal candidates were found