Nabokov y un recuerdo de infancia.

El presente trabajo se propone indagar los alcances del concepto de infancia como experiencia y formación en la literatura moderna. Para ello se analizan las relaciones existentes entre formación sensible y forma artística de autopercepción en las relaciones infancia-mundo, infanciaintimidad. El trabajo se centrar en el análisis de las escenas-encubridoras del discurso autobiográfico montado por Nabokov en Habla, memoria, lo cual posibilita pensar una subjetividad de la infancia que, de algún modo, es un leguaje de la patria recuperada como Baudelaire ya en 1850 lo pensara respecto a una moral del juguete, y que Agamben nombrara como “historia mayor”.The present work intends to investigate the scope of the concept of childhood as experience and training in modern literature. To this end, the relationships between sensitive formation and artistic self-perception in childhood-world relationships, childhood-intimacy, are analyzed. The work focuses on the analysis of the scenes-concealing of the autobiographical discourse mounted by Nabokov in Speak, memory, which makes it possible to think of a subjectivity of childhood that, in a way, is a language of the country recovered as Baudelaire as early as 1850 he will think about a toy moral, and that Agamben will name it as a “major story”.Fil: Surghi, Carlos. Universidad Nacional de Córdoba; Argentina

Trapping and Characterization of a Reaction Intermediate in Carbapenem Hydrolysis by \u3cem\u3eB. cereus\u3c/em\u3e Metallo-β-lactamase

Metallo-β-lactamases hydrolyze most β-lactam antibiotics. The lack of a successful inhibitor for them is related to the previous failure to characterize a reaction intermediate with a clinically useful substrate. Stopped-flow experiments together with rapid freeze−quench EPR and Raman spectroscopies were used to characterize the reaction of Co(II)−BcII with imipenem. These studies show that Co(II)−BcII is able to hydrolyze imipenem in both the mono- and dinuclear forms. In contrast to the situation met for penicillin, the species that accumulates during turnover is an enzyme−intermediate adduct in which the β-lactam bond has already been cleaved. This intermediate is a metal-bound anionic species with a novel resonant structure that is stabilized by the metal ion at the DCH or Zn2 site. This species has been characterized based on its spectroscopic features. This represents a novel, previously unforeseen intermediate that is related to the chemical nature of carbapenems, as confirmed by the finding of a similar intermediate for meropenem. Since carbapenems are the only substrates cleaved by B1, B2, and B3 lactamases, identification of this intermediate could be exploited as a first step toward the design of transition-state-based inhibitors for all three classes of metallo-β-lactamases

Splicing factors Sf3A2 and Prp31 have direct roles in mitotic chromosome segregation

This is the final version. Available from eLife Sciences Publications via the DOI in this record.Several studies have shown that RNAi-mediated depletion of splicing factors (SFs) results in mitotic abnormalities. However, it is currently unclear whether these abnormalities reflect defective splicing of specific pre-mRNAs or a direct role of the SFs in mitosis. Here, we show that two highly conserved SFs, Sf3A2 and Prp31, are required for chromosome segregation in both Drosophila and human cells. Injections of anti-Sf3A2 and anti-Prp31 antibodies into Drosophila embryos disrupt mitotic division within 1 min, arguing strongly against a splicing-related mitotic function of these factors. We demonstrate that both SFs bind spindle microtubules (MTs) and the Ndc80 complex, which in Sf3A2- and Prp31-depleted cells is not tightly associated with the kinetochores; in HeLa cells the Ndc80/HEC1-SF interaction is restricted to the M phase. These results indicate that Sf3A2 and Prp31 directly regulate interactions among kinetochores, spindle microtubules and the Ndc80 complex in both Drosophila and human cells.Italian Association for Cancer ResearchItalian Association for Cancer Researc

Quality of life changes over time and predictors in a large head and neck patients’ cohort: secondary analysis from an Italian multi-center longitudinal, prospective, observational study—a study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) head and neck working group

Purpose: The present study examined the longitudinal trajectories, through hierarchical modeling, of quality of life among patients with head and neck cancer, specifically symptoms burden, during radiotherapy, and in the follow-up period (1, 3, 6, and 12 months after completion of radiotherapy), through the M.D. Anderson Symptom Inventory Head and Neck questionnaire, formed by three factors. Furthermore, analyses were conducted controlling for socio-demographic as well as clinical characteristics. Methods: Multi-level mixed-effects linear regression was used to estimate the association between quality of life and time, age, gender, household, educational level, employment status, ECOG performance status, human papilloma virus (HPV) status, surgery, chemotherapy, alcohol intake, and smoking. Results: Among the 166 participants, time resulted to be a predictor of all the three questionnaire factors, namely, general and specific related symptoms and interference with daily life. Moreover, regarding symptom interference with daily activities factor, HPV-positive status played a significant role. Considering only HPV-negative patients, only time predicted patients' quality of life. Differently, among HPV-positive patients, other variables, such as gender, educational level, alcohol use, surgery, age at diagnosis, employment status, and ECOG status, resulted significant. Conclusion: It was evident that quality of life of patients with head and neck cancer declined during RT, whereas it slowly improved after ending treatment. Our results clarified the role of some socio-demographic and clinical variables, for instance, HPV, which would allow to develop treatments tailored to each patient

Chemotherapy-induced immunogenic modulation of tumor cells enhances killing by cytotoxic T lymphocytes and is distinct from immunogenic cell death

Certain chemotherapeutic regimens trigger cancer cell death while inducing dendritic cell maturation and subsequent immune responses. However, chemotherapy-induced immunogenic cell death (ICD) has thus far been restricted to select agents. In contrast, several chemotherapeutic drugs modulate antitumor immune responses, despite not inducing classic ICD. In addition, in many cases tumor cells do not die after treatment. Here, using docetaxel, one of the most widely used cancer chemotherapeutic agents, as a model, we examined phenotypic and functional consequences of tumor cells that do not die from immunogenic cell death. Docetaxel treatment of tumor cells did not induce ATP or HMGB1 secretion, or cell death. However, calreticulin exposure was observed in all cell lines examined after chemotherapy treatment. Killing by CEA, MUC-1, or PSA-specific CD8+ CTLs was significantly enhanced after docetaxel treatment. This killing was associated with increases in components of antigen-processing machinery, and mediated largely by calreticulin membrane translocation, as determined by functional knockdown of calreticulin, PERK, or calreticulin-blocking peptide. A docetaxel-resistant cell line was selected (MDR-1+, CD133+) by continuous exposure to docetaxel. These cells, while resistant to direct cytostatic effects of docetaxel, were not resistant to the chemomodulatory effects that resulted in enhancement of CTL killing. Here, we provide an operational definition of “immunogenic modulation,” where exposure of tumor cells to nonlethal/sublethal doses of chemotherapy alters tumor phenotype to render the tumor more sensitive to CTL killing. These observations are distinct and complementary to immunogenic cell death and highlight a mechanism whereby chemotherapy can be used in combination with immunotherapy

Blockade of MCP-1/CCR4 signaling-induced recruitment of activated regulatory cells evokes an antitumor immune response in head and neck squamous cell carcinoma

published_or_final_versio

Duplication of a well-conserved homeodomain-leucine zipper transcription factor gene in barley generates a copy with more specific functions

Three spikelets are formed at each rachis node of the cultivated barley (Hordeum vulgare ssp. vulgare) spike. In two-rowed barley, the central one is fertile and the two lateral ones are sterile, whereas in the six-rowed type, all three are fertile. This characteristic is determined by the allelic constitution at the six-rowed spike 1 (vrs1) locus on the long arm of chromosome 2H, with the recessive allele (vrs1) being responsible for the six-rowed phenotype. The Vrs1 (HvHox1) gene encodes a homeodomain-leucine zipper (HD-Zip) transcription factor. Here, we show that the Vrs1 gene evolved in the Poaceae via a duplication, with a second copy of the gene, HvHox2, present on the short arm of chromosome 2H. Micro-collinearity and polypeptide sequences were both well conserved between HvHox2 and its Poaceae orthologs, but Vrs1 is unique to the barley tribe. The Vrs1 gene product lacks a motif which is conserved among the HvHox2 orthologs. A phylogenetic analysis demonstrated that Vrs1 and HvHox2 must have diverged after the separation of Brachypodium distachyon from the Pooideae and suggests that Vrs1 arose following the duplication of HvHox2, and acquired its new function during the evolution of the barley tribe. HvHox2 was expressed in all organs examined but Vrs1 was predominantly expressed in immature inflorescence

Stem cells and cancer immunotherapy: Arrowhead’s 2nd annual cancer immunotherapy conference

Investigators from academia and industry gathered on April 4 and 5, 2013, in Washington DC at the Arrowhead’s 2nd Annual Cancer Immunotherapy Conference. Two complementary concepts were discussed: cancer “stem cells” as targets and therapeutic platforms based on stem cells

Nicotiana attenuata NaHD20 plays a role in leaf ABA accumulation during water stress, benzylacetone emission from flowers, and the timing of bolting and flower transitions

Homeodomain-leucine zipper type I (HD-Zip I) proteins are plant-specific transcription factors associated with the regulation of growth and development in response to changes in the environment. Nicotiana attenuata NaHD20 was identified as an HD-Zip I-coding gene whose expression was induced by multiple stress-associated stimuli including drought and wounding. To study the role of NaHD20 in the integration of stress responses with changes in growth and development, its expression was silenced by virus-induced gene silencing (VIGS), and control and silenced plants were metabolically and developmentally characterized. Phytohormone profiling showed that NaHD20 plays a positive role in abscisic acid (ABA) accumulation in leaves during water stress and in the expression of some dehydration-responsive genes including ABA biosynthetic genes. Moreover, consistent with the high levels of NaHD20 expression in corollas, the emission of benzylacetone from flowers was reduced in NaHD20-silenced plants. Additionally, bolting time and the opening of the inflorescence buds was decelerated in these plants in a specific developmental stage without affecting the total number of flowers produced. Water stress potentiated these effects; however, after plants recovered from this condition, the opening of the inflorescence buds was accelerated in NaHD20-silenced plants. In summary, NaHD20 plays multiple roles in N. attenuata and among these are the coordination of responses to dehydration and its integration with changes in flower transitions

Why Iranian married women use withdrawal instead of oral contraceptives? A qualitative study from Iran

<p>Abstract</p> <p>Background</p> <p>Withdrawal as a method of birth control is still used in Iran. The aim of this study was to explore married women's perspectives and attitudes on withdrawal use instead of oral contraceptive (OC) in Tehran, Iran.</p> <p>Methods</p> <p>This was a qualitative study. Participants were 50 married women, not currently pregnant, not desiring pregnancy and who had been using withdrawal for contraception. Face-to face interviews were conducted to collect data. Content analysis was performed to analyze the data.</p> <p>Results</p> <p>Four major themes were extracted from the interviews: advantages, disadvantages, barriers for OC use, and husband-related factors. Advantages of withdrawal use were identified as: easy to use, convenient, ease of access, natural. Even those participants who had experienced unwanted pregnancy while using withdrawal, relied on withdrawal as their contraceptive method. Disadvantages of OC included concerns about side effects. Barriers related to use of OC included the need for medical advice, vaginal examination and daily use. Husband-related factors included: the husband wanted to be the primary decision maker on the number of children and that he preferred withdrawal.</p> <p>Conclusion</p> <p>Health providers should address misunderstandings that exist about OC and highlight the non-contraceptive health benefits of OC to balance the information provided for women. We suggest that not only women but also their spouses be advised in family planning programs.</p