We present a histological study of the cell death of cerebellar neuroepithelial neuroblasts following treatment with the cytotoxic agent hydroxyurea (HU) during the embryonic life. Pregnant rats were ...treated with a single dose of HU (300 mg/kg) at embryonic days 13, 14, or 15 of gestation, and their fetuses were studied from 5 to 35 h after treatment to elucidate the mechanisms of HU-induced fetotoxicity. Quantification of several parameters such as the density of pyknotic, mitotic, and PCNA-immunoreactive cells indicated that HU compromises the survival of the cerebellar neuroepithelium neuroblasts. On the other hand, our light and electron microscopic investigations during the course of prenatal development indicated that HU leads to two types of cell death: apoptosis and cells presenting cytoplasmic vacuolization, altered organelles, and a recognizable cell nucleus. Both modalities of cell death resulted in a substantial loss of cerebellar neuroepithelium cells. Current results suggest that HU exposure during gestation is toxic to the cerebellar neuroepithelium. Moreover, they allow to examine the mechanisms of HU-induced toxicity during the early development of the central nervous system. Our data also suggest that it is essential to avoid underestimating the adverse effects of HU when administered during early prenatal life.
An important step in bromodeoxyuridine (BrdU) immunohistochemistry is the production of single-stranded DNA to make the incorporated BrdU accessible to the antibodies. This paper examines the effect ...of distinct DNA denaturation pretreatments (DNase I, sodium citrate buffer, endonuclease Eco RI and exonuclease III, and HCl hydrolysis) on detection of BrdU. We found that all the methods used in the partial denaturation of DNA combined good nuclear immunostaining with acceptable tissue integrity. We also observed that these immunohistochemical protocols revealed a spatial pattern in the distribution of DNA-synthesizing cells within the cerebellar external granular layer (EGL) of 10-day-old rats, allowing us to estimate the fraction of S-phase cells. Our results indicate that detection of BrdU-stained cells is affected by the distinct histological procedures used in such detection. Additionally, as the duration and phases of the cell cycle in EGL neuroblasts are estimated in accordance with BrdU detection, an effect on this detection can render the measurement of cell cycle inaccurate. The present work shows that DNase I and citrate buffer, at appropriate conditions, may be good alternatives for acid denaturation. However, they are less sensitive than autoradiographic techniques that use
3
H-thymidine administration. Finally, current data reveal that short survival times after a single BrdU exposure do not seem to affect the cell cycle progression of the EGL neuroblasts.
The time courses of apoptosis and autophagy activation were investigated in neuroblasts of the cerebellar external granular layer (EGL) following the treatment with a single dose (2 mg/g) of ...hydroxyurea (HU), a cytotoxic agent. The rats were examined at postnatal day 9 and sacrificed at appropriate times ranging from 10 to 60 h after drug administration. We used the Feulgen method, the TUNEL assay, immunohistochemistry for active caspase-3, and LC3B and p62/SQSTM1 immunoperoxidase procedures. The resulting data indicated that the administration of HU leads to the activation of apoptotic cellular events that began to increase 10 h after HU exposure, peaked at 30 h, and decrease thereafter. It also showed that apoptosis was followed by autophagy activation. Interestingly, LC3B and p62/SQSTM1-stained cells, as well as mitotic cells, started to appear 20 h after the HU injection and their counts increased until 40 h. Afterwards, the values remained stable. The current results highlight an important role of the apoptotic and autophagic processes in the EGL after HU administration. Moreover, they provide a clue for studying the mechanism of chemoresistance triggered by proliferating cells exposed to anticancer agents.
The current paper presents a histological analysis of the cell death in the cerebellar external granular layer (EGL) following the treatment with a single dose (2 mg/g) of hydroxyurea (HU). The rats ...were examined at postnatal days (P) 5, 10, and 15, and sacrificed at appropriate times ranging from 6 to 48 h after treatment administration. Studies were done in each cortical lobe (anterior, central, posterior, and inferior). The quantification of several parameters, such as density of 5-bromo-2′-deoxyuridine, TUNEL, vimentin, and tomato lectin-stained cells, revealed that HU compromises the viability of EGL cells. Our results indicate that P10 is a time of high vulnerability to injury. We also show here that the anterior and central lobes are the cortical regions most susceptible to the action of the HU. Additionally, our data also indicate that from 6 to 24 h after HU-exposure is a time-window of high sensibility to this agent. On the other hand, our ultrastructural analysis confirmed that HU administration produces the activation of apoptotic cellular events in the EGL, resulting in a substantial number of dying cells. Different stages of apoptosis can be observed in all cortical lobes at all investigated postnatal ages and survival times. Moreover, we observed that dying neuroblasts were covered by laminar processes of Bergmann glia, and that these unipolar astrocytes presented cytological features of phagocytes engulfing apoptotic bodies and cell debris. The electron microscopy study also revealed the participation of ameboid microglial cells in the phagocytosis of apoptotic cells in the regions of the EGL with extensive cell death.
Is terrorism just another form of criminal activity, as many nations' justice systems assume? We offer an initial answer using face-to-face interviews and structured surveys in thirty-five Spanish ...prisons. Recent theories of extreme sacrifice inform this direct observational and comparative study. Islamist terrorists display levels of self-sacrifice for their primary reference group similar to that of Latino gangs, but greater willingness to sacrifice for primary values than other inmates (non-radical Muslims, Latino gangs, and delinquent bands). This disposition is motivated by stronger perceived injustice, discrimination, and a visceral commitment to such values (risk/radicalization factors). Nevertheless, state authorities, prison staff, and families are (protective/de-radicalization) factors apt to reduce willingness to sacrifice and keep foreign fighters, now being released in large numbers, from returning to terrorism.
Cultural understanding entails a recognition of outgroup values. Combining quantitative and qualitative methods, we analysed the perception of Spaniards of the core values of Moroccan immigrants ...across two online surveys, 139 interviews and an experimental study. In Study 1, participants spontaneously generated the values considered fundamental for Moroccans, rated such values on a continuum of negativity‐positivity and reported their attitudes towards Moroccans. In Study 2, participants were asked about the values that Spaniards and Moroccans (do not) share. In Study 3, participants were interviewed about the core values for Moroccans and those shared with Spaniards. Study 4 experimentally manipulated the salience of value‐sharing. An inductive analysis revealed that the perceived core values for Moroccans were related to family/community, material issues, religion and integrity. Study 2 showed that religion, gender‐universalism and culture/tradition were perceived as different values, whereas integrity, social‐interaction and family/community values were perceived as shared. Study 4 confirmed that making salient the common importance of family for Spaniards and Moroccans indirectly increased the perceived morality of Moroccan immigrants via perceived shared values. Implications for the way lay people think about the values of outgroups are discussed.
Han pasado ya siete años desde que en 2010 James MacDowell detectara una nueva sensibilidad estética y narrativa dentro del cine independiente estadounidense, caracterizada por el equilibrio tonal ...entre el distanciamiento irónico y la sinceridad emocional. Desde entonces, la palabra quirky (peculiar en inglés) se ha asociado a las producciones de directores como Jim Jarmusch, Wes Anderson, o Michel Gondry, convirtiéndose en un adjetivo comodín aplicado a cualquier película protagonizada por personajes excéntricos, dotada de un lenguaje visual perfeccionista, y con una cierta ingenuidad infantil en el tono y en el trato de las situaciones. Estas producciones apelan a la sentimentalidad de un espectador millennial que ya no es tan cínico ni tan comprometido políticamente como sus antecesores; de hecho, las transgresiones narrativas y formales que caracterizan lo quirky nunca llegan al terreno de lo político para plantearse cuestiones de género, raza, o clase, sino que se quedan en la superficie. En este sentido, el estereotipo de la Manic Pixie Dream Girl es perfecto exponente de esta estética de lo peculiar; su ambivalente relación con las ideologías postfeministas (sexualidad neoliberal vs feminidad tradicional) es más una seña de identidad que fruto de un compromiso político, mientras que su aspecto aniñado y su actitud naïve responden a esa ingenuidad buscada de la sensibilidad quirky. Asimismo, la falta de profundidad de Manic Pixie Dream Girls paradigmáticas como Summer (500 días juntos) o Ruby Sparks, definidas más por sus gustos musicales o su manera de vestir que por sus ambiciones o miedos responde al predominio postmoderno de la forma que caracteriza la estética quirky.
Positive intergroup contact, under some conditions, can undermine the interest of members of both socially disadvantaged and advantaged groups to act for equality. However, little is known about ...whether similar effects appear in a unique form of intergroup relations, gender relations. In two correlational studies and two experiments, we investigated the relationships among quality of contact, perceived discrimination, fusion with the feminist movement, and willingness to engage in collective action for women’s rights. For women (Study 1a), positive contact with men was associated with less perceived discrimination, less fusion, and less collective action. For men (Study 1b), the relationships were in the opposite direction. Studies 2a and 2b revealed that recalling experiences of gender discrimination nullified the effects of contact for both women and men as compared to a control condition. Thus, when discrimination is not explicitly recognized, positive contact might have sedative effects on women, but mobilizing effects on men.
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