Histone Acetylation-Mediated Regulation of the Hippo Pathway

The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. © 2013 Basu et al

Genome-Wide Identification of MicroRNAs in Response to Low Nitrate Availability in Maize Leaves and Roots

BACKGROUND: Nitrate is the major source of nitrogen available for many crop plants and is often the limiting factor for plant growth and agricultural productivity especially for maize. Many studies have been done identifying the transcriptome changes under low nitrate conditions. However, the microRNAs (miRNAs) varied under nitrate limiting conditions in maize has not been reported. MiRNAs play important roles in abiotic stress responses and nutrient deprivation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the SmartArray™ and GeneChip® microarray systems to perform a genome-wide search to detect miRNAs responding to the chronic and transient nitrate limiting conditions in maize. Nine miRNA families (miR164, miR169, miR172, miR397, miR398, miR399, miR408, miR528, and miR827) were identified in leaves, and nine miRNA families (miR160, miR167, miR168, miR169, miR319, miR395, miR399, miR408, and miR528) identified in roots. They were verified by real time stem loop RT-PCR, and some with additional time points of nitrate limitation. The miRNAs identified showed overlapping or unique responses to chronic and transient nitrate limitation, as well as tissue specificity. The potential target genes of these miRNAs in maize were identified. The expression of some of these was examined by qRT-PCR. The potential function of these miRNAs in responding to nitrate limitation is described. CONCLUSIONS/SIGNIFICANCE: Genome-wide miRNAs responding to nitrate limiting conditions in maize leaves and roots were identified. This provides an insight into the timing and tissue specificity of the transcriptional regulation to low nitrate availability in maize. The knowledge gained will help understand the important roles miRNAs play in maize responding to a nitrogen limiting environment and eventually develop strategies for the improvement of maize genetics

Conductivity/activation energy relationships for cement-based materials undergoing cyclic thermal excursions

The electrical conductivity of a range of concrete mixes, with and without supplementary cementitious materials (SCM), is studied through multiple cycles of heating and cooling over the extended temperature range -30/?70 C. When presented in an Arrhenius format, the experimental results display hysteresis effects at the lowtemperature end of the thermal cycle and, in those concretes containing supplementary cementitious materials at higher water/binder ratios, hysteresis effects were evident over the entire temperature range becoming more discernible with increasing number of thermal cycles. The depression in both the freezing and thawing point could be clearly identified and was used to estimate pore-neck and pore-cavity radii. A simplified approach is presented to evaluate the volumetric ratio of frozen pore water in terms of conductivity measurements. The results also show that the conductivity and activation energy of the concrete specimens were related to the water/binder ratio, type of SCM, physical state of the pore water and the thermal cycling regime

Fraction of χc\chi_c decays in prompt J/ψJ/\psi production measured in pPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV

The fraction of $\chi_{c1}$ and $\chi_{c2}$ decays in the prompt $J/\psi$ yield, $F_{\chi c}=\sigma_{\chi_c \to J/\psi}/\sigma_{J/\psi}$, is measured by the LHCb detector in pPb collisions at $\sqrt{s_{NN}}=8.16$ TeV. The study covers the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions, where $y^*$ is the $J/\psi$ rapidity in the nucleon-nucleon center-of-mass system. Forward and backward rapidity samples correspond to integrated luminosities of 13.6 $\pm$ 0.3 nb$^{-1}$ and 20.8 $\pm$ 0.5 nb$^{-1}$, respectively. The result is presented as a function of the $J/\psi$ transverse momentum $p_{T,J/\psi}$ in the range 1$<p_{T, J/\psi}<20$ GeV/$c$. The $F_{\chi c}$ fraction at forward rapidity is compatible with the LHCb measurement performed in $pp$ collisions at $\sqrt{s}=7$ TeV, whereas the result at backward rapidity is 2.4 $\sigma$ larger than in the forward region for $1<p_{T, J/\psi}<3$ GeV/$c$. The increase of $F_{\chi c}$ at low $p_{T, J/\psi}$ at backward rapidity is compatible with the suppression of the $\psi$(2S) contribution to the prompt $J/\psi$ yield. The lack of in-medium dissociation of $\chi_c$ states observed in this study sets an upper limit of 180 MeV on the free energy available in these pPb collisions to dissociate or inhibit charmonium state formation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-028.html (LHCb public pages

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

Enhanced production of Λb0\Lambda_{b}^{0} baryons in high-multiplicity pppp collisions at s=13\sqrt{s} = 13 TeV

The production rate of $\Lambda_{b}^{0}$ baryons relative to $B^{0}$ mesons in $pp$ collisions at a center-of-mass energy $\sqrt{s} = 13$ TeV is measured by the LHCb experiment. The ratio of $\Lambda_{b}^{0}$ to $B^{0}$ production cross-sections shows a significant dependence on both the transverse momentum and the measured charged-particle multiplicity. At low multiplicity, the ratio measured at LHCb is consistent with the value measured in $e^{+}e^{-}$ collisions, and increases by a factor of $\sim2$ with increasing multiplicity. At relatively low transverse momentum, the ratio of $\Lambda_{b}^{0}$ to $B^{0}$ cross-sections is higher than what is measured in $e^{+}e^{-}$ collisions, but converges with the $e^{+}e^{-}$ ratio as the momentum increases. These results imply that the evolution of heavy $b$ quarks into final-state hadrons is influenced by the density of the hadronic environment produced in the collision. Comparisons with a statistical hadronization model and implications for the mechanisms enforcing quark confinement are discussed.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-027.html (LHCb public pages

Search for CP\textit{CP} violation in the phase space of D0→KS0K±π∓D^{0} \rightarrow K_{S}^{0} K^{\pm} \pi^{\mp} decays with the energy test

A search for $\textit{CP}$ violation in $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ and $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ decays is reported. The search is performed using an unbinned model-independent method known as the energy test that probes local $\textit{CP}$ violation in the phase space of the decays. The data analysed correspond to an integrated luminosity of $5.4~$fb$^{-1}$ collected in proton-proton collisions by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=13$~TeV, amounting to approximately 950000 and 620000 signal candidates for the $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ and $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ modes, respectively. The method is validated using $D^{0} \rightarrow K^{-} \pi^{+} \pi^{-} \pi^{+}$ and $D^{0} \rightarrow K_{S}^{0} \pi^{+} \pi^{-}$ decays, where $\textit{CP}$-violating effects are expected to be negligible, and using background-enhanced regions of the signal decays. The results are consistent with $\textit{CP}$ symmetry in both the $D^{0} \rightarrow K_{S}^{0} K^{-} \pi^{+}$ and the $D^{0} \rightarrow K_{S}^{0} K^{+} \pi^{-}$ decays, with $p$-values for the hypothesis of no $\textit{CP}$ violation of 70% and 66%, respectively.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-019.html (LHCb public pages

Observation of strangeness enhancement with charmed mesons in high-multiplicity pPbp\mathrm{Pb} collisions at sNN=8.16 \sqrt {s_{\mathrm{NN}}}=8.16\,TeV

The production of prompt $D^+_{s}$ and $D^+$ mesons is measured by the LHCb experiment in proton-lead ($p\mathrm{Pb}$) collisions in both the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions at a nucleon-nucleon center-of-mass energy of $\sqrt {s_{\mathrm{NN}}}=8.16\,$TeV. The nuclear modification factors of both $D^+_{s}$ and $D^+$ mesons are determined as a function of transverse momentum, $p_{\mathrm{T}}$, and rapidity. In addition, the $D^+_{s}$ to $D^+$ cross-section ratio is measured as a function of the charged particle multiplicity in the event. An enhanced $D^+_{s}$ to $D^+$ production in high-multiplicity events is observed for the whole measured $p_{\mathrm{T}}$ range, in particular at low $p_{\mathrm{T}}$ and backward rapidity, where the significance exceeds six standard deviations. This constitutes the first observation of strangeness enhancement in charm quark hadronization in high-multiplicity $p\mathrm{Pb}$ collisions. The results are also qualitatively consistent with the presence of quark coalescence as an additional charm quark hadronization mechanism in high-multiplicity proton-lead collisions.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-021.html (LHCb public pages