How mucosal epithelia deal with stress: Role of NKG2D/NKG2D ligands during inflammation

Mucosal epithelia encounter both physicochemical and biological stress during their life and have evolved several mechanisms to deal with them, including regulation of immune cell functions. Stressed and damaged cells need to be cleared to control local inflammation and trigger tissue healing. Engagement of the activating NKG2D receptor is one of the most direct mechanisms involved in the recognition of stressed cells by the immune system. Indeed, injured cells promptly express NKG2D ligands that in turn mediate the activation of lymphocytes of both innate and adaptive arms of the immune system. This review focuses on different conditions that are able to modulate NKG2D ligand expression on the epithelia. Special attention is given to the mechanisms of immunosurveillance mediated by natural killer cells, which are finely tuned by NKG2D. Different types of stress, including viral and bacterial infections, chronic inflammation, and cigarette smoke exposure, are discussed as paradigmatic conditions for NKG2D ligand modulation, and the implications for tissue homeostasis are discussed

Elastic isotropy of hcp-Fe under Earth core conditions

Our first-principles calculations show that both the compressional and shear waves of hcp-Fe become elastically isotropic under the high temperatures of Earth inner core conditions, with the variation in sound velocities along different angles from the c axis within 1%. We computed the thermoelasticity at high pressures and temperatures from quasiharmonic linear response linear-muffin-tin-orbital calculations in the generalized-gradient approximation. The calculated anisotropic shape and magnitude in hcp-Fe at ambient temperature agree well with previous first-principles predictions, and the anisotropic effects show strong temperature dependences. This implies that other mechanisms, rather than the preferential alignment of the hcp-Fe crystal along the Earth rotation axis, account for the seismic P-wave travel time anomalies. Either the inner core is not hcp iron, and/or the seismologically observed anisotropy is caused by inhomogeneity, i.e. multiple phases.Comment: 16 pages, 3 figure

CXCL16/CXCR6 axis drives microglia/macrophages phenotype in physiological conditions and plays a crucial role in glioma

Microglia are patrolling cells that sense changes in the brain microenvironment and respond acquiring distinct phenotypes that can be either beneficial or detrimental for brain homeostasis. Anti-inflammatory microglia release soluble factors that might promote brain repair; however, in glioma, anti-inflammatory microglia dampen immune response and promote a brain microenvironment that foster tumor growth and invasion. The chemokine CXCL16 is expressed in the brain, where it is neuroprotective against brain ischemia, and it has been found to be over-expressed in glioblastoma (GBM). Considering that CXCL16 specific receptor CXCR6 is diffusely expressed in the brain including in microglia cells, we wanted to investigate the role of CXCL16 in the modulation of microglia cell activity and phenotype, and in the progression of glioma. Here we report that CXCL16 drives microglia polarization toward an anti-inflammatory phenotype, also restraining microglia polarization toward an inflammatory phenotype upon LPS and IFN? stimulation. In the context of glioma, we demonstrate that CXCL16 released by tumor cells is determinant in promoting glioma associated microglia/macrophages (GAMs) modulation toward an anti-inflammatory/pro-tumor phenotype, and that cxcr6ko mice, orthotopically implanted into the brain with GL261 glioma cells,survive longer compared to wild-type mice. We also describe that CXCL16/CXCR6 signaling acts directly on mouse glioma cells, as well as human primary GBM cells, promoting tumor cell growth, migration and invasion. All together these data suggest that CXCL16 signaling could represent a good target to modulate microglia phenotype in order to restrain inflammation or to limit glioma progression

«Vovó não quer casca de coco no terreiro para não lembrar do tempo do cativeiro». Memoria y mediación en los terreiros de umbanda

As reflexões apresentadas neste artigo propõem uma leitura etnográfica do culto afro-brasileiro da umbanda, a partir de sua vertente política. Durante a cerimônia religiosa, alguns adeptos incorporam entidades espirituais que remetem a figuras sociais típicas da história brasileira, por exemplo, caboclos e pretos velhos, que remetem ao extermínio de indígenas e à escravização de africanos. O objetivo do texto é mostrar como, através do momento ritual da incorporação, o culto da umbanda funciona enquanto estratégia de memória, encenando aspectos do passado colonial e escravocrata do Brasil. Aliás, o retorno destes espíritos nos corpos dos médiuns vincula esses corpos à matriz africana, independentemente da cor da pele, criando assim narrativas novas que permitem superar uma concepção estigmatizante e racista da pessoa. Então, o campo da religiosidade pode ser interpretado como uma arena de negociação identitária, na qual as entidades espirituais aparecem no papel de mediadores.Las reflexiones presentadas en este artículo proponen una lectura etnográfica del culto afrobrasileño de la umbanda, en su vertiente política. Durante la ceremonia religiosa, algunos adeptos incorporan entidades espirituales que remiten a figuras sociales típicas de la historia brasileña, como por ejemplo caboclos y pretos velhos, que aluden al exterminio de indígenas y a la esclavización de africanos. El objetivo del texto es mostrar cómo, por medio del momento ritual de la incorporación, el culto de la umbanda funciona como estrategia de memoria, escenificando aspectos del pasado colonial y esclavista de Brasil. Además, el regreso de estos espíritus en el cuerpo de los médiums vincula estos mismos cuerpos a la matriz africana, independientemente del color de la piel, creando así nuevas narrativas que permiten superar una concepción estigmatizante y racista de la persona. Entonces, el campo de la religiosidad puede interpretarse como una arena de negociación identitaria, en la cual las entidades espirituales aparecen en el papel de mediadores.The reflections presented in this article intend to propose an ethnographic reading of the Afro-Brazilian cult of Umbanda, in its political aspect. During the religious ceremony, some adepts incorporate spiritual entities that refer to typical social figures of Brazilian history, such as caboclos and pretos velhos, who concern the extermination of Indians and the enslavement of Africans. The aim of the text is to show how, through the ritual moment of incorporation, the cult of umbanda works as a strategy of memory, staging aspects of Brazil’s colonial and slave past. In fact, the return of these spirits in the bodies of mediums links these bodies to the African matrix, regardless of the colour of the skin, thus creating new narratives that allow to overcome a stigmatising and racist conception of the person. Then the field of religiousness can be interpreted as an arena of identity negotiation, in which spiritual entities appear in the role of mediators

Sydämen pallo : imaginismin poetiikka V. Šeršenevičin runokokoelmassa ”Hevonen kuin hevonen”

Tutkielman aiheena on imaginistisen poetiikan piirteitä Vadim Šeršenevičin (1893–1942) runokokoelmassa Lošad' kak lošad' (1920). Vadim Šeršenevič on venäläisen imaginismin – vuosina 1919–1927 olleen kirjallisuuden koulukunnan – perustaja ja johtaja sekä yksi merkittävimpiä tämän koulukunnan runoilijoita. Hänen runokokoelmaansa Lošad' kak lošad', johon sisältyy vuosien 1915–1919 runoja, pidetään hänen pääteoksenaan. Runoja analysoidaan suhteessa Šeršenevičin luomaan imaginismin teoriaan, jota hän kuvailee kirjas-saan 2x2=5. Listy imažinista (1920). Tutkielmassa käsitellään eri venäläisten ja ulkomaisten kirjallisuudentutkijoiden näkökulmia venäläisen imaginismin alkuperään, kerrotaan Šeršenevičin elämästä ja hänen tiestään ima-ginismiin sekä tarkastellaan hänen imaginismia edeltävän runollisen ja kirjallisuudentutki-muksellisen tuotantonsa kehityksen kahta vaihetta: lyhyesti symbolistista (1911–1912) ja yksityiskohtaisesti futuristista (1913–1916). Varsinaista aihetta tutkitaan käsittelemällä Šeršenevičin teoksessa 2x2=5. Listy imažinista kuvailtua imaginismin poetiikkaa ja selvittämällä poetiikan pääpiirteitä. Seuraavaksi tarkas-tellaan sitä, miten poetiikan periaatteet, kuten runojen runsas metaforisuus, metaforien tekni-nen eikä orgaaninen yhdistäminen runoissa, metaforien teennäisyys, runojen ei-kieliopillisuus, verbittömyys, juonettomuus jne. toteutuvat runokokoelman Lošad' kak lošad' runoissa. Tutkielmassa näin ollen pyritään osoittamaan, missä määrin runokokoelma vastaa imaginismin teoriaa ja missä osin poikkeaa siitä. Tutkielman perusteella voidaan päätellä, että imaginismin teoria aineellistuu runokokoelman runoissa vain osittain. Imaginismin pääperiaatteita vastaavia ovat rationalistiset runojen nimet, runojen epätavallinen graafinen asettelu (oikealla reunalla tasoittaminen), teennäiset, alatyyliset ja järkyttävät metaforat, ei-kieliopillisuus sekä sisällöllinen epäpoliittisuus. Täysin imaginismin estetiikka ei kuitenkaan pääde runokokoelmassa Lošad' kak lošad'. Šeršenevičin teoreettisista näkemyksistä "iloisesta imaginismista" huolimatta runokokoelmassa ovat selvästi läsnä katkeruuden, pettymyksen ja itsemurhan motiivit

The Senescence-Associated Secretory Phenotype (SASP) in the challenging future of cancer therapy and age-related diseases

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies

Thermal Diffusivity and Conductivity Measurements in Diamond Anvil Cells

We have undertaken a study of the feasibility of an innovative method for the determination of thermal properties of materials at extreme conditions. Our approach is essentiality an extension of the flash method to the geometry of the diamond-anvil cell and our ultimate goal is to greatly enlarge the pressure and temperature range over which thermal properties can be investigated. More specifically, we have performed test experiments to establish a technique for probing thermal diffusivity on samples of dimensions compatible with the physical constraints of the diamond anvil cell

Lattice dynamics of MgSiO3_3 perovskite (bridgmanite) studied by inelastic x-ray scattering and ab initio calculations

We have determined the lattice dynamics of MgSiO$_3$ perovskite (bridgmanite) by a combination of single-crystal inelastic x-ray scattering and ab initio calculations. We observe a remarkable agreement between experiment and theory, and provide accurate results for phonon dispersion relations, phonon density of states and the full elasticity tensor. The present work constitutes an important milestone to extend this kind of combined studies to extreme conditions of pressure and temperature, directly relevant for the physics and the chemistry of Earth's lower mantle

Ca2+-activated K+ channels modulate microglia affecting motor neuron survivalin hSOD1G93A mice

Recent studies described a critical role for microglia in amyotrophic lateral sclerosis (ALS), where these CNS-resident immune cells participate in the establishment of an inflammatory microenvironment that contributes to motor neuron degeneration. Understanding the mechanisms leading to microglia activation in ALS could help to identify specific molecular pathways which could be targeted to reduce or delay motor neuron degeneration and muscle paralysis in patients. The intermediate-conductance calcium-activated potassium channel KCa3.1 has been reported to modulate the "pro-inflammatory" phenotype of microglia in different pathological conditions. We here investigated the effects of blocking KCa3.1 activity in the hSOD1G93AALS mouse model, which recapitulates many features of the human disease. We report that treatment of hSOD1G93A mice with a selective KCa3.1 inhibitor, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), attenuates the "pro-inflammatory" phenotype of microglia in the spinal cord, reduces motor neuron death, delays onset of muscle weakness, and increases survival. Specifically, inhibition of KCa3.1 channels slowed muscle denervation, decreased the expression of the fetal acetylcholine receptor γ subunit and reduced neuromuscular junction damage. Taken together, these results demonstrate a key role for KCa3.1 in driving a pro-inflammatory microglia phenotype in ALS