Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells

The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1α, we established hypoxia-inducible factor-1α-transfectants and dominant negative hypoxia-inducible factor-1α-transfectants. Transfection with hypoxia-inducible factor-1α and dominant-negative hypoxia-inducible factor-1α enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis

Cellular and Molecular Bases of the Initiation of Fever

All phases of lipopolysaccharide (LPS)-induced fever are mediated by prostaglandin (PG) E(2). It is known that the second febrile phase (which starts at ~1.5 h post-LPS) and subsequent phases are mediated by PGE(2) that originated in endotheliocytes and perivascular cells of the brain. However, the location and phenotypes of the cells that produce PGE(2) triggering the first febrile phase (which starts at ~0.5 h) remain unknown. By studying PGE(2) synthesis at the enzymatic level, we found that it was activated in the lung and liver, but not in the brain, at the onset of the first phase of LPS fever in rats. This activation involved phosphorylation of cytosolic phospholipase A(2) (cPLA(2)) and transcriptional up-regulation of cyclooxygenase (COX)-2. The number of cells displaying COX-2 immunoreactivity surged in the lung and liver (but not in the brain) at the onset of fever, and the majority of these cells were identified as macrophages. When PGE(2) synthesis in the periphery was activated, the concentration of PGE(2) increased both in the venous blood (which collects PGE(2) from tissues) and arterial blood (which delivers PGE(2) to the brain). Most importantly, neutralization of circulating PGE(2) with an anti-PGE(2) antibody both delayed and attenuated LPS fever. It is concluded that fever is initiated by circulating PGE(2) synthesized by macrophages of the LPS-processing organs (lung and liver) via phosphorylation of cPLA(2) and transcriptional up-regulation of COX-2. Whether PGE(2) produced at the level of the blood–brain barrier also contributes to the development of the first phase remains to be clarified

Primary fallopian tube carcinoma: review of MR imaging findings

Objectives To review the epidemiological and clinical features of primary fallopian tube carcinoma (PFTC), and to illustrate the spectrum of MRI findings, with pathological confirmation. Methods This article reviews the relevant literature on the epidemiological, clinical, and imaging features of primary fallopian tube carcinoma, with pathological confirmation, using illustrations from the authors' teaching files. Results Primary fallopian tube carcinoma came under focus over the last few years due to its possible role on the pathogenesis of high-grade serous epithelial ovarian and peritoneal cancers. Typical symptoms, together with the presence of some of the most characteristic MRI signs, such as a "sausage-shaped" pelvic mass, hydrosalpinx, and hydrometra, may signal the presence of primary fallopian cancer, and allow the radiologist to report it as a differential diagnosis. Conclusions Primary fallopian tube carcinoma has a constellation of clinical symptoms and magnetic resonance imaging features, which may be diagnostic. Although these findings are not present together in the majority of cases, radiologists who are aware of them may include the diagnosis of primary fallopian tube cancer in their report more frequently and with more confidence. Teaching Points PFTC may be more frequent than previously thought PFTC has specific clinical and MRI characteristics Knowledge of typical PFTC signs enables its inclusion in the differential diagnosis PFTC is currently staged under the 2013 FIGO system PFTC is staged collectively with ovarian and peritoneal neoplasmsinfo:eu-repo/remantics/publishedVersio

Differential Encoding of Factors Influencing Predicted Reward Value in Monkey Rostral Anterior Cingulate Cortex

Background: The value of a predicted reward can be estimated based on the conjunction of both the intrinsic reward value and the length of time to obtain it. The question we addressed is how the two aspects, reward size and proximity to reward, influence the responses of neurons in rostral anterior cingulate cortex (rACC), a brain region thought to play an important role in reward processing. Methods and Findings: We recorded from single neurons while two monkeys performed a multi-trial reward schedule task. The monkeys performed 1–4 sequential color discrimination trials to obtain a reward of 1–3 liquid drops. There were two task conditions, a valid cue condition, where the number of trials and reward amount were associated with visual cues, and a random cue condition, where the cue was picked from the cue set at random. In the valid cue condition, the neuronal firing is strongly modulated by the predicted reward proximity during the trials. Information about the predicted reward amount is almost absent at those times. In substantial subpopulations, the neuronal responses decreased or increased gradually through schedule progress to the predicted outcome. These two gradually modulating signals could be used to calculate the effect of time on the perception of reward value. In the random cue condition, little information about the reward proximity or reward amount is encoded during the course of the trial before reward delivery, but when the reward is actually delivered the responses reflect both the reward proximity and reward amount

K0SK0S and K0SK± femtoscopy in pp collisions at √s = 5.02 and 13 TeV

Femtoscopic correlations with the particle pair combinations (KSKS0)-K-0 and (KSK +/-)-K-0 are studied in pp collisions at root s= 5.02 and 13 TeV by the ALICE experiment. At both energies, boson source parameters are extracted for both pair combinations, by fitting models based on Gaussian size distributions of the sources, to the measured two-particle correlation functions. The interaction model used for the (KSKS0)-K-0 analysis includes quantum statistics and strong final-state interactions through the f(0) (980) and a(0) (980) resonances. The model used for the (KSK +/-)-K-0 analysis includes only the final-state interaction through the a(0) resonance. Source parameters extracted in the present work are compared with published values from pp collisions at root s = 7 TeV and the different pair combinations are found to be consistent. From the observation that the strength of the (KSKS0)-K-0 correlations is significantly greater than the strength of the (KSK +/-)-K-0 correlations, the new results are compatible with the a(0) resonance being a tetraquark state of the form (q(1), (q(2)) over bar, s, (s) over bar), where q(1) and q(2) are uor d quarks. (C) 2022 European Organization for Nuclear Research, ALICE. Published by Elsevier B.V

Hypertriton Production in p-Pb Collisions at √sNN = 5.02 TeV

The study of nuclei and antinuclei production has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. The first measurement of the production of ${\rm ^{3}_{\Lambda}\rm H}$ in p-Pb collisions at $\sqrt{s_{\rm{NN}}}$ = 5.02 TeV is presented in this Letter. Its production yield measured in the rapidity interval -1 < y < 0 for the 40% highest multiplicity p-Pb collisions is ${\rm d} N /{\rm d} y =[\mathrm{6.3 \pm 1.8 (stat.) \pm 1.2 (syst.) ] \times 10^{-7}}$. The measurement is compared with the expectations of statistical hadronisation and coalescence models, which describe the nucleosynthesis in hadronic collisions. These two models predict very different yields of the hypertriton in small collision systems such as p-Pb and therefore the measurement of ${\rm d} N /{\rm d} y$ is crucial to distinguish between them. The precision of this measurement leads to the exclusion with a significance larger than 6$\sigma$ of some configurations of the statistical hadronisation, thus constraining the production mechanism of loosely bound states

K∗(892)0 and φ(1020) production in p-Pb collisions at √s NN = 8.16 TeV

The production of K*(892)(0) and phi(1020) resonances has been measured in p-Pb collisions at root s(NN) = 8.16 TeV using the ALICE detector. Resonances are reconstructed via their hadronic decay channels in the rapidity interval -0.5 8 GeV/c), the R-pPb values of all hadrons are consistent with unity within uncertainties. The R-pPb of K*(892)(0) and phi(1020) at root s(NN) = 8.16 and 5.02 TeV show no significant energy dependence

General balance functions of identified charged hadron pairs of (pi,K,p) in Pb-Pb collisions at 2.76 TeV

First measurements of balance functions (BFs) of all combinations of identified charged hadron ( π , K, p) pairs in Pb–Pb collisions at √sNN = 2.76 TeV recorded by the ALICE detector are presented. The BF measurements are carried out as two-dimensional differential correlators versus the relative rapidity (delta-y) and azimuthal angle (delta-φ) of hadron pairs, and studied as a function of collision centrality. The delta-φ dependence of BFs is expected to be sensitive to the light quark diffusivity in the quark–gluon plasma. While the BF azimuthal widths of all pairs substantially decrease from peripheral to central collisions, the longitudinal widths exhibit mixed behaviors: BFs of π π and cross-species pairs narrow significantly in more central collisions, whereas those of KK and pp are found to be independent of collision centrality. This dichotomy is qualitatively consistent with the presence of strong radial flow effects and the existence of two stages of quark production in relativistic heavy-ion collisions. Finally, the first measurements of the collision centrality evolution of BF integrals are presented, with the observation that charge balancing fractions are nearly independent of collision centrality in Pb–Pb collisions. Overall, the results presented provide new and challenging constraints for theoretical models of hadron production and transport in relativistic heavy-ion collisions

Characterizing the initial conditions of heavy-ion collisions at the LHC with mean transverse momentum and anisotropic flow correlations

Correlations between mean transverse momentum and anisotropic flow coefficients or are measured as a function of centrality in Pb–Pb and Xe–Xe collisions at sqrt(sNN) = 5.02 TeV and 5.44 TeV, respectively, with ALICE. In addition, the recently proposed higher-order correlation between [pt], v2, and v3 is measured for the first time, which shows an anticorrelation for the presented centrality ranges. These measurements are compared with hydrodynamic calculations using IP-Glasma and TRENTO initial-state shapes, the former based on the Color Glass Condensate effective theory with gluon saturation, and the latter a parameterized model with nucleons as the relevant degrees of freedom. The data are better described by the IP-Glasma rather than the TRENTO based calculations. In particular, Trajectum and JETSCAPE predictions, both based on the TRENTO initial state model but with different parameter settings, fail to describe the measurements. As the correlations between [pt] and vn are mainly driven by the correlations of the size and the shape of the system in the initial state, these new studies pave a novel way to characterize the initial state and help pin down the uncertainty of the extracted properties of the quark–gluon plasma recreated in relativistic heavy-ion collisions