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Immunoepigenetics is a growing field, as there is mounting evidence on the key role played by epigenetic mechanisms in the regulation of tumor immune cell recognition and control of immune cell anti-tumor responses. Moreover, it is increasingly acknowledgeable a tie between epigenetic regulation and prostate cancer (PCa) development and progression. PCa is intrinsically a cold tumor, with scarce immune cell infiltration and low inflammatory tumor microenvironment. However, Natural Killer (NK) cells, main anti-tumor effector immune cells, have been frequently linked to improved PCa prognosis. The role that epigenetic-related mechanisms might have in regulating both NK cell recognition of PCa tumor cells and NK cell functions in PCa is still mainly unknown. Epigenetic modulating drugs have been showing boundless therapeutic potential as anti-tumor agents, however their role in immune cell regulation and recognition is scarce. In this review, we focused on studies addressing modulation of epigenetic mechanisms involved in NK cell-mediated responses, including both the epigenetic modulation of tumor cell NK ligand expression and NK cell receptor expression and function in different tumor models, highlighting studies in PCa. The integrated knowledge from diverse epigenetic modulation mechanisms promoting NK cell-mediated immunity in various tumor models might open doors for the development of novel epigenetic-based therapeutic options for PCa management.

Novelty influences hippocampal-dependent memory through metaplasticity, i.e., experience-dependent adaptations in synaptic plasticity. In this respect, mismatch novelty is known to activate the hippocampal CA1 area in humans and to enhance rat hippocampal-dependent learning and exploration. Mismatch novelty training (NT) by varying spatial configuration of objects in a known environment, enhances rat hippocampal synaptic plasticity. Prefrontal cortex GABAergic projections targeting hippocampal VIP interneurons promote exploration. Since VIP, acting on VPAC1receptors, restrains both hippocampal LTP and depotentiation by modulating disinhibition we now investigated the impact of NT on VPAC1receptor modulation of hippocampal synaptic plasticity.NT enhanced both CA1 hippocampal long-term potentiation (LTP) and depotentiation. Blockade of VIP VPAC1receptors with PG 97-269 (100nM) enhanced both LTP and depotentiation in naïve animals but was much less effective in enhancing LTP and depotentiation in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). Modulation of depotentiation by endogenous VIP was absent in animals exposed to a fixed configuration of objects (FT) or in HT animals. HT and FT animals, but not NT; showed mildly enhanced synaptic VPAC1receptor expression.Altogether this suggests that NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons. Also, upregulation of VIP VPAC1receptors maintains VIP control of LTP in FT and HT rats, the absence of this in NT rats leading to enhanced LTP but not influencing depotentiation. This may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs.Graphical abstractImpairment of endogenous VIP VPAC1receptor modulation of hippocampal CA1 LTP and depotentiation upon mismatch novelty training.HighlightsMismatch novelty training (NT) enhances hippocampal CA1 LTP and depotentiation.Endogenous VIP VPAC1receptor modulation of synaptic plasticity is lessened by NT.NT does not influence hippocampal levels of VIP or VPAC1receptors.NT and VIP likely impact coincident paths to control LTP and depotentiation.

Non-epileptic seizures are identified as a common epileptogenic trigger. Early metaplasticity following seizures may contribute to epileptogenesis by abnormally altering synaptic strength and homeostatic plasticity. We now studied howin vitroepileptiform activity triggers early changes in CA1 long-term potentiation (LTP) induced by theta-burst stimulation (TBS) in rat hippocampal slices and the involvement of lipid rafts in these early metaplasticity events. Two forms of epileptiform activity (EA) were induced: 1) interictal-like EA triggered by withdrawal of Mg2+and K+elevation to 6mM in the superfusion medium or 2) ictal-like EA induced by bicuculine (10μM) delivery. LTP induced 30 min post EA was impaired, an effect more pronounced after ictal-like EA. LTP recovered to control levels 60 min post interictal-like EA but was still impaired 60 min after ictal-like EA. The synaptic molecular events underlying this altered LTP were investigated 30 min post EA. Synaptosomes isolated from parallel slices showed enhanced AMPA GluA1 Ser831 phosphorylation but decreased Ser 845 phosphorylation and a marked decrease in GluA1/GluA2 ratio. A marked decrease in flotillin-1 and caveolin-1 levels concomitantly with a moderate increase in PSD-95 and marked increase in gephyrin levels.Altogether, EA differentially influences hippocampal CA1 LTP thorough regulation of GluA1/GluA2 levels and AMPA GluA1 phosphorylation suggesting altered LTP post-seizures may be a relevant target of antiepileptogenic therapies. In addition, this metaplasticity is also associated with marked alterations in classic and synaptic lipid raft markers, suggesting these may also constitute promising targets in epileptogenesis prevention.

It has long been hypothesized that hydrogen peroxide (H2O2) may play an essential role in root-to-shoot long-distance signaling during drought conditions. Thus, to better understand the involvement of H2O2 in drought signaling, two experiments were carried out using tomato plants. In the first experiment, a split-root scheme was used, while in the second experiment, the tomato plants were grown in a single pot and subjected to drought stress. In both experiments, H2O2 and catalase were applied together with irrigation. Control plants continued to be irrigated according to the water loss. In the split-root experiment, it was verified that the application of H2O2 to roots induced a clear reduction in plant transpiration compared to untreated or catalase-treated plants. In the second experiment, we observed that H2O2-treated plants exhibited similar transpiration when compared to untreated and catalase-treated plants under drought stress. Similarly, no difference in water use efficiency was observed. Thus, we conclude that the increase in H2O2 in the root system can act as a long-distance signal leading to reduced transpiration even when there is no water limitation in the shoot. But it has little effect when there is a reduction in the shoot water potential. Resumo Tem sido hipotetizado que o peróxido de hidrogênio (H2O2) pode desempenhar um papel essencial na sinalização de longa distância entre a raiz e a parte aérea sob condições de seca. Assim, para melhor entender o envolvimento do H2O2 na sinalização da seca, dois experimentos foram realizados com plantas de tomate. No primeiro, foi utilizado o esquema de raízes divididas, enquanto no segundo, os tomateiros foram cultivados em um único vaso e submetidos ao déficit hídrico. Em ambos os experimentos, o H2O2 e a catalase foram aplicados juntamente com a irrigação. As plantas do grupo controle continuaram a ser irrigadas de acordo com a perda de água. No experimento de raiz dividida, verificou-se que a aplicação de H2O2 nas raízes induziu uma clara redução na transpiração da planta em comparação com plantas não tratadas ou tratadas com catalase. No segundo experimento, observamos que plantas tratadas com H2O2 apresentaram transpiração semelhante quando comparadas com plantas não tratadas e tratadas com catalase sob seca. Da mesma forma, não foi observada diferença na eficiência do uso da água. Assim, concluímos que o aumento do H2O2 no sistema radicular pode atuar como um sinal de longa distância levando à redução da transpiração mesmo quando não há limitação hídrica na parte aérea. Mas tem pouco efeito quando há redução do potencial hídrico da parte aérea.

We carried out electrical resistivity and X-ray diffraction (XRD) studies on the filled skutterudite superconductors LaPt4Ge12 and PrPt4Ge12 under hydrostatic pressure. The superconducting transition temperature Tc is linearly suppressed upon increasing pressure, though the effect of pressure on Tc is rather weak. From the analysis of the XRD data, we obtain bulk moduli of B=106 GPa and B=83 GPa for LaPt4Ge12 and PrPt4Ge12, respectively. The knowledge of the bulk modulus allows us to compare the dependence of Tc on the unit-cell volume from our pressure study directly with that found in the substitution series La1-xPrxPt4Ge12. We find that application of hydrostatic pressure can be characterized mainly as a volume effect in LaPt4Ge12 and PrPt4Ge12, while substitution of Pr for La in La1-xPrxPt4Ge12 yields features going beyond a simple picture.

We study the Stacy-G family, which extends the gamma-G class and provides four of the most well-known forms of the hazard rate function: increasing, decreasing, bathtub, and inverted bathtub. We provide some of its structural properties. We estimate the parameters by maximum likelihood, and perform a simulation study to verify the asymptotic properties of the estimators for the Burr-XII baseline. We construct the log-Stacy-Burr XII regression for censored data. The usefulness of the new models is shown through applications to uncensored and censored real data.

In this study, we evaluated the effectiveness of insecticides sprayed by contact as well as seeds treatment for controlling the burrower bug Cyrtomenus mirabilis (Perti, 1830) (Hemiptera: Cydnidae) under laboratory conditions. In the first experiment, the insecticides were sprayed onto the insects (direct contact). Insect mortality evaluation started 24h after insecticide application and repeated every two days up to 20 days. In the second experiment, peanut seeds were treated with insecticides. The mortality of insects was evaluated at 10, 15, and 20 days after installation. The mixture of fipronil and alpha-cypermethrin in direct contact was the most efficient treatment to control nymphs and adults of C. mirabilis. Regarding the seed treatment, fipronil was the most efficient for controlling adults of C. mirabilis while for nymphs, all insecticides were highly effective.

Racial residential segregation is interconnected with several other phenomena such as income inequalities, property values inequalities, and racial disparities in health and education. Furthermore, recent literature suggests the phenomenon of gentrification as a cause of perpetuation or increase of racial residential segregation in some American cities. In this paper, we analyze the dynamics of racial residential segregation for white, black, Asian, and Hispanic citizens in New York City in 1990, 2000, and 2010. It was possible to observe that segregation between white and Hispanic citizens and between white and Asian ones has grown, while segregation between white and black is relatively stable. Furthermore, we analyzed the per capita income and the Gini coefficient in each segregated zone, showing that the highest inequalities occur in the zones where there is an overlap of high-density zones of pair of races. Focusing on the changing of the density of population across the city during these 20 years, and by analyzing white and black people’s segregation, our analysis reveals that a positive flux of white (black) people is associated with a substantial increase (decrease) of the property values, as compared with the city mean. Furthermore, by clustering the region with the higher density of black citizens, we measured the variation of area and displacement of the four most significant clusters from 1990 to 2010. The large displacements (≈1.6km) observed for two of these clusters, namely, one in the neighborhood of Harlem and the other inside the borough of Brooklyn, led to the emergence of typically gentrified regions.

We use an x-ray free-electron laser to study the ultrafast lattice dynamics following above band-gap photoexcitation of the incipient ferroelectric potassium-tantalate, \kto. % We use ultrafast near-UV (central wavelength 266\,nm and 50 fs pulse duration) laser light to photoexcite charge carriers across the gap and probe the ultrafast lattice dynamics by recording the x-ray diffuse intensity throughout multiple Brillouin zones using pulses from the Linac Coherent Light Source (LCLS) (central wavelength 1.3\,\AA\, and $< 10$~fs pulse duration). We observe changes in the diffuse intensity that we conclude are associated with a hardening of the soft transverse optical and transverse acoustic phonon branches along $\Gamma$ to $X$ and $\Gamma$ to $M$. Using ground- and excited-state interatomic force constants from density functional theory (DFT) and assuming the phonon populations can be described by a time-dependent temperature, we fit the quasi-equilibrium thermal diffuse intensity to the experimental time-dependent intensity. We obtain the instantaneous lattice temperature and density of photoexcited charge carriers as a function of time delay. The DFT calculations demonstrate that photoexcitation transfers charge from oxygen $2p$ derived $\pi$-bonding orbitals to Ta $5d$ derived antibonding orbitals, further suppressing the ferroelectric instability and increasing the stability of the cubic, paraelectric structure., Comment: 8 pages, 4 figures