Immunohistochemical detection of macrophage migration inhibitory factor in fetal and adult bovine epididymis: Release by the apocrine secretion mode?

Originally defined as a lymphokine inhibiting the random migration of macrophages, the macrophage migration inhibitory factor (MIF) is an important mediator of the host response to infection. Beyond its function as a classical cytokine, MIF is currently portrayed as a multifunctional protein with growth-regulating properties present in organ systems beyond immune cells. In previous studies, we detected substantial amounts of MIF in the rat epididymis and epididymal spermatozoa, where it appears to play a role during post-testicular sperm maturation and the acquisition of fertilization ability. To explore its presence in other species not yet examined in this respect, we extended the range of studies to the bull. Using a polyclonal antibody raised against MIF purified from bovine eye lenses, we detected MIF in the epithelium of the adult bovine epididymis with the basal cells representing a prominently stained cell type. A distinct accumulation of MIF at the apical cell pole of the epithelial cells and in membranous vesicles localized in the lumen of the epididynnal duct was obvious. In the fetal bovine epididymis, we also detected MIF in the epithelium, whereas MIF accumulation was evident at the apical cell surface and in apical protrusions. By immuno-electron microscopy of the adult bovine epididymis, we localized MIF in apical protrusions of the epithelial cells and in luminal membrane-bound vesicles that were found in close proximity to sperm cells. Although the precise origin of the MIF-containing vesicles remains to be delineated, our morphological observations support the hypothesis that they become detached from the apical surface of the epididymal epithelial cells. Additionally, an association of MIF with the outer dense fibers of luminal spermatozoa was demonstrated. Data obtained in this study suggest MIF release by an apocrine secretion mode in the bovine epididymis. Furthermore, MIF localized in the basal cells of the epithelium and in the connective tissue could be responsible for regulating the migration of macrophages in order to avoid contact of immune cells with spermatozoa that carry a wide range of potent antigens. Copyright (c) 2006 S. Karger AG, Basel

Bone pain induced by multiple myeloma is reduced by targeting V-ATPase and ASIC3

Multiple myeloma (MM) patients experience severe bone pain (MMBP) that is undertreated and poorly understood. In this study, we studied MMBP in an intratibial mouse xenograft model which employs JJN3 human MM cells. In this model, mice develop MMBP associated in bone with increased sprouting of calcitonin gene-related peptide-positive (CGRP+) sensory nerves and in dorsal root ganglia (DRG) with upregulation of phosphorylated ERK1/2 (pERK1/2) and pCREB, two molecular indicators of neuron excitation. We found that JJN3 cells expressed a vacuolar proton pump (V-ATPase) that induced an acidic bone microenvironment. Inhibition of JJN3-colonized bone acidification by a single injection of the selective V-ATPase inhibitor, bafilomycin A1, decreased MMBP, CGRP+ SN sprouting, and pERK1/2 and pCREB expression in DRG. CGRP+ sensory nerves also expressed increased levels of the acid-sensing nociceptor ASIC3. Notably, a single injection of the selective ASIC3 antagonist APETx2 dramatically reduced MMBP in the model. Mechanistic investigations in primary DRG neurons co-cultured with JJN3 cells showed increased neurite outgrowth and excitation inhibited by bafilomycin A1 or APETx2. Further, combining APETx2 with bafilomycin A1 reduced MMBP to a greater extent than either agent alone. Lastly, combining bafilomycin A1 with the osteoclast inhibitor zoledronic acid was sufficient to ameliorate MMBP which was refractory to zoledronic acid. Overall, our results show that osteoclasts and MM cooperate to induce an acidic bone microenvironment that evokes MMBP as a result of the excitation of ASIC3-activated sensory neurons. Further, they present a mechanistic rationale for targeting ASIC3 on neurons along with the MM-induced acidic bone microenvironment as a strategy to relieve MMBP in patients

Thermal Bremsstrahlung photons probing the nuclear caloric curve

Hard-photon (E$_{\gamma}>$ 30 MeV) emission from second-chance nucleon-nucleon Bremsstrahlung collisions in intermediate energy heavy-ion reactions is studied employing a realistic thermal model. Photon spectra and yields measured in several nucleus-nucleus reactions are consistent with an emission from hot nuclear systems with temperatures $T\approx$ 4 - 7 MeV. The corresponding caloric curve in the region of excitation energies $\epsilon^\star\approx$ 3{\it A} - 8{\it A} MeV shows lower values of $T$ than those expected for a Fermi fluid.Comment: 13 pages, 3 figures. To appear in Physics Letters

Identification of the Changbaishan ‘Millennium’ (B-Tm) eruption deposit in the Lake Suigetsu (SG06) sedimentary archive, Japan: Synchronisation of hemispheric-wide palaeoclimate archives

The B-Tm tephra, dispersed during the highly explosive Changbaishan ‘Millennium’ eruption (ca. 940–950 CE) and a key marker layer within the Greenland ice cores, has now been identified in the Lake Suigetsu (SG06) sedimentary sequence, central Japan. The major element geochemistry of the volcanic glasses within this tephra layer are compared to a new glass dataset from the distal type-locality (Tomakomai Port, Hokkaido) and other published ‘Millennium’ eruption/B-Tm deposits, to verify this correlation. The discovery of the B-Tm tephra in the Lake Suigetsu record provides, to date, the most southerly identification of this ash and, crucially, the first direct tie-point between this high-resolution, mid-latitude palaeoclimate archive and the Greenland ice cores. These findings present significant encouragement for on-going research into the tephrostratigraphy of East Asia, focusing on the identification of widely-dispersed tephra layers which can facilitate the synchronisation of disparate palaeoclimate archives and thus enable the assessment of spatio-temporal variations in past climatic change

Isolation of Flow and Nonflow Correlations by Two- and Four-Particle Cumulant Measurements of Azimuthal Harmonics in sNN=\sqrt{s_{_{\rm NN}}} = 200 GeV Au+Au Collisions

A data-driven method was applied to measurements of Au+Au collisions at $\sqrt{s_{_{\rm NN}}} =$ 200 GeV made with the STAR detector at RHIC to isolate pseudorapidity distance $\Delta\eta$-dependent and $\Delta\eta$-independent correlations by using two- and four-particle azimuthal cumulant measurements. We identified a component of the correlation that is $\Delta\eta$-independent, which is likely dominated by anisotropic flow and flow fluctuations. It was also found to be independent of $\eta$ within the measured range of pseudorapidity $|\eta|<1$. The relative flow fluctuation was found to be $34\% \pm 2\% (stat.) \pm 3\% (sys.)$ for particles of transverse momentum $p_{T}$ less than $2$ GeV/$c$. The $\Delta\eta$-dependent part may be attributed to nonflow correlations, and is found to be $5\% \pm 2\% (sys.)$ relative to the flow of the measured second harmonic cumulant at $|\Delta\eta| > 0.7$

Charged-to-neutral correlation at forward rapidity in Au+Au collisions at sNN\sqrt{s_{NN}}=200 GeV

Event-by-event fluctuations of the ratio of inclusive charged to photon multiplicities at forward rapidity in Au+Au collision at $\sqrt{s_{NN}}$=200 GeV have been studied. Dominant contribution to such fluctuations is expected to come from correlated production of charged and neutral pions. We search for evidences of dynamical fluctuations of different physical origins. Observables constructed out of moments of multiplicities are used as measures of fluctuations. Mixed events and model calculations are used as baselines. Results are compared to the dynamical net-charge fluctuations measured in the same acceptance. A non-zero statistically significant signal of dynamical fluctuations is observed in excess to the model prediction when charged particles and photons are measured in the same acceptance. We find that, unlike dynamical net-charge fluctuation, charge-neutral fluctuation is not dominated by correlation due to particle decay. Results are compared to the expectations based on the generic production mechanism of pions due to isospin symmetry, for which no significant (<1%) deviation is observed.Comment: 14 pages, 6 figure

System size and energy dependence of near-side di-hadron correlations

Two-particle azimuthal ($\Delta\phi$) and pseudorapidity ($\Delta\eta$) correlations using a trigger particle with large transverse momentum ($p_T$) in $d$+Au, Cu+Cu and Au+Au collisions at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV and 200~GeV from the STAR experiment at RHIC are presented. The \ns correlation is separated into a jet-like component, narrow in both $\Delta\phi$ and $\Delta\eta$, and the ridge, narrow in $\Delta\phi$ but broad in $\Delta\eta$. Both components are studied as a function of collision centrality, and the jet-like correlation is studied as a function of the trigger and associated $p_T$. The behavior of the jet-like component is remarkably consistent for different collision systems, suggesting it is produced by fragmentation. The width of the jet-like correlation is found to increase with the system size. The ridge, previously observed in Au+Au collisions at $\sqrt{s_{{NN}}}$ = 200 GeV, is also found in Cu+Cu collisions and in collisions at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV, but is found to be substantially smaller at $\sqrt{s_{{NN}}}$ =\xspace 62.4 GeV than at $\sqrt{s_{{NN}}}$ = 200 GeV for the same average number of participants ($\langle N_{\mathrm{part}}\rangle$). Measurements of the ridge are compared to models.Comment: 17 pages, 14 figures, submitted to Phys. Rev.

Beam energy dependent two-pion interferometry and the freeze-out eccentricity of pions in heavy ion collisions at STAR

We present results of analyses of two-pion interferometry in Au+Au collisions at $\sqrt{s_{NN}}$ = 7.7, 11.5, 19.6, 27, 39, 62.4 and 200 GeV measured in the STAR detector as part of the RHIC Beam Energy Scan program. The extracted correlation lengths (HBT radii) are studied as a function of beam energy, azimuthal angle relative to the reaction plane, centrality, and transverse mass ($m_{T}$) of the particles. The azimuthal analysis allows extraction of the eccentricity of the entire fireball at kinetic freeze-out. The energy dependence of this observable is expected to be sensitive to changes in the equation of state. A new global fit method is studied as an alternate method to directly measure the parameters in the azimuthal analysis. The eccentricity shows a monotonic decrease with beam energy that is qualitatively consistent with the trend from all model predictions and quantitatively consistent with a hadronic transport model.Comment: 27 pages; 27 figure