Tradiciones de discurso y Santa Teresa

Para los historiadores del español un problema conocido es la evaluación filológica de la obra de Santa Teresa. Según una tradición, representa una forma espontánea del español que corresponde a su habla cotidiana, proporcionando así evidencia de un registro que remeda el lenguaje hablado de su época; otra tradición, sin embargo, recalca los rasgos cultos de su prosa, atribuyendo lo «vulgar» de su estilo a su deseo de rehuir la afectación y erudición. En este artículo intentamos situar el estilo de Santa Teresa dentro de las tradiciones discursivas del Siglo de Oro, arguyendo que mientras que determinados rasgos lingüísticos del Libro de la vida están determinados por los parámetros del registro lingüístico propuestos por Halliday, otros son propios de ella. A continuación estudiamos dos de estos, las construcciones relativas y la supresión del complementante que, a base de datos recuperados de los corpus lingüísticos y textos coetáneos.A notable problem for historians of Spanish is the philological evaluation of Santa Teresa's writings. One tradition sees her language as a spontaneous form of Spanish corresponding to her everyday speech, providing valuable evidence of a register which is more typical of the spoken language of the time, while another points to cultured and literary features of her style and attributes the «vulgar» features of her style to a deliberate avoidance of affectation and erudition. This article attempts to situate Teresa's writing within the discourse traditions of the Golden Age, arguing that while certain linguistic features of the Libro de la vida are determined by the parameters of linguistic register proposed by Halliday, others are more distinctively her own. It then draws on evidence gathered from linguistic corpora and contemporaneous texts to investigate two of these distinctive features, relative structures and the suppression of the que complementiser

Metabolomic profiling of macrophages determines the discrete metabolomic signature and metabolomic interactome triggered by polarising immune stimuli

Priming and activating immune stimuli have profound effects on macrophages, however, studies generally evaluate stimuli in isolation rather than in combination. In this study we have investigated the effects of pro-inflammatory and anti-inflammatory stimuli either alone or in combination on macrophage metabolism. These stimuli include host factors such as IFNγ and ovalbumin-immunoglobulin immune complexes, or pathogen factors such as LPS. Untargeted LC-MS based metabolomics provided an in-depth profile of the macrophage metabolome, and revealed specific changes in metabolite abundance upon either individual stimuli or combined stimuli. Here, by factoring in an interaction term in the linear model, we define the metabolome interactome. This approach allowed us to determine whether stimuli interact in a synergistic or antagonistic manner. In conclusion this study demonstrates a robust approach to interrogate immune-metabolism, especially systems that model host-pathogen interactions

Drug resistance and treatment failure in leishmaniasis: A 21st century challenge

Reevaluation of treatment guidelines for Old and New World leishmaniasis is urgently needed on a global basis because treatment failure is an increasing problem. Drug resistance is a fundamental determinant of treatment failure, although other factors also contribute to this phenomenon, including the global HIV/AIDS epidemic with its accompanying impact on the immune system. Pentavalent antimonials have been used successfully worldwide for the treatment of leishmaniasis since the first half of the 20th century, but the last 10 to 20 years have witnessed an increase in clinical resistance, e.g., in North Bihar in India. In this review, we discuss the meaning of “resistance” related to leishmaniasis and discuss its molecular epidemiology, particularly for Leishmania donovani that causes visceral leishmaniasis. We also discuss how resistance can affect drug combination therapies. Molecular mechanisms known to contribute to resistance to antimonials, amphotericin B, and miltefosine are also outlined

Global communication part 1: the use of apparel CAD technology

Trends needed for improved communication systems, through the development of future computer-aided design technology (CAD) applications, is a theme that has received attention due to its perceived benefits in improving global supply chain efficiencies. This article discusses the developments of both 2D and 3D computer-aided design capabilities, found within global fashion supply chain relationships and environments. Major characteristics identified within the data suggest that CAD/CAM technology appears to be improving; however, evidence also suggest a plateau effect, which is accrediting forced profits towards information technology manufactures, and arguably compromising the industry's competitive advantage. Nevertheless, 2D CAD increases communication speed; whereas 3D human interaction technology is seen to be evolving slowly and questionably with limited success. The article discusses the findings and also presents the issues regarding human interaction; technology education; and individual communication enhancements using technology processes. These are still prevalent topics for the future developments of global strategy and cultural communication amalgamation

Immunological aspects of polymyalgia rheumatica and giant cell arteritis

Forty four patients with PMR/GCA have been followed from presentation for a period of 2-4 years. Immunological investigations have been carried out in a search for useful tests to assist in the diagnosis of PMR/GCA and in assessing disease activity. This study has confirmed that ESR and CRP are useful investigations at presentation of PMR/GCA, although even at this stage these tests may not be elevated. During relapses of PMR/GCA both ESR and CRP remain in the normal range in the majority of patients so no reliance should be placed on these investigations to confirm a clinical diagnosis of relapse. Alpha-1-antichymotrypsin (ACT) has shown an interesting pattern of response, in that the raised levels at presentation (1.0g/l) did not fall rapidly on prednisolone treatment but fell gradually over 2-4 years reaching normal levels (0.6g/l) in those patients satisfactorily off prednisolone treatment. An ACT concentration of ≤0.8g/l at 12 months and ≤0.7g/l at 18 months indicated a reduced risk of subsequent relapse. Hence this investigation may be a useful tool in tailoring prednisolone reduction for the individual patient with PMR/GCA. Measurement of the cytokines IL1B, IL6 and soluble IL2 receptor, using ELISA methods, did not add any useful information to the assessment of the individual patient. However the fact that IL1≤ levels were raised at presentation and relapse (albeit to only 4pg/ml and 5pg/ml respectively) does illustrate that this mediator of inflammation is involved in PMR/GCA. The elevation of soluble IL2 receptor at presentation (476 U/ml) compared with controls (366 U/ml) also illustrates that there is immune system activation in PMR/GCA. IL6 levels were not significantly elevated in this study. This study did not find low CD8+ cells in PMR/GCA prior to treatment. %CD8+ cells were significantly reduced after prednisolone treatment commenced, and a study in volunteers confirmed that this was an effect of the prednisolone itself, particularly in the older volunteers

The stroke oxygen pilot study: a randomized control trial of the effects of routine oxygen supplementation early after acute stroke--effect on key outcomes at six months

Introduction: Post-stroke hypoxia is common, and may adversely affect outcome. We have recently shown that oxygen supplementation may improve early neurological recovery. Here, we report the six-month outcomes of this pilot study. Methods: Patients with a clinical diagnosis of acute stroke were randomized within 24 h of admission to oxygen supplementation at 2 or 3 L/min for 72 h or to control treatment (room air). Outcomes (see below) were assessed by postal questionnaire at 6 months. Analysis was by intention-to-treat, and statistical significance was set at p#0.05. Results: Out of 301 patients randomized two refused/withdrew consent and 289 (148 in the oxygen and 141 in the control group) were included in the analysis: males 44%, 51%; mean (SD) age 73 (12), 71 (12); median (IQR) National Institutes of Health Stroke Scale score 6 (3, 10), 5 (3, 10) for the two groups respectively. At six months 22 (15%) patients in the oxygen group and 20 (14%) in the control group had died; mean survival in both groups was 162 days (p= 0.99). Median (IQR) scores for the primary outcome, the modified Rankin Scale, were 3 (1, 5) and 3 (1, 4) for the oxygen and control groups respectively. The covariate-adjusted odds ratio was 1.04 (95% CI 0.67, 1.60), indicating that the odds of a lower (i.e. better) score were non-significantly higher in the oxygen group (p= 0.86). The mean differences in the ability to perform basic (Barthel Index) and extended activities of daily living (NEADL), and quality of life (EuroQol) were also non-significant. Conclusions: None of the key outcomes differed at 6 months between the groups. Although not statistically significant and generally of small magnitude, the effects were predominantly in favour of the oxygen group; a larger trial, powered to show differences in longer-term functional outcomes, is now on-going. Trial Registration: Controlled-Trials.com ISRCTN12362720; Eudract.ema.europa.eu 2004-001866-4

Candida auris-Macrophage Cellular Interactions and Transcriptional Response

The pathogenic yeast Candida auris represents a global threat of the utmost clinical relevance. This emerging fungal species is remarkable in its resistance to commonly used antifungal agents and its persistence in the nosocomial settings. The innate immune system is one the first lines of defense preventing the dissemination of pathogens in the host. C. auris is susceptible to circulating phagocytes, and understanding the molecular details of these interactions may suggest routes to improved therapies. In this work, we examined the interactions of this yeast with macrophages. We found that macrophages avidly phagocytose C. auris; however, intracellular replication is not inhibited, indicating that C. auris resists the killing mechanisms imposed by the phagocyte. Unlike Candida albicans, phagocytosis of C. auris does not induce macrophage lysis. The transcriptional response of C. auris to macrophage phagocytosis is very similar to other members of the CUG clade (C. albicans, C. tropicalis, C. parapsilosis, C. lusitaniae), i.e., downregulation of transcription/translation and upregulation of alternative carbon metabolism pathways, transporters, and induction of oxidative stress response and proteolysis. Gene family expansions are common in this yeast, and we found that many of these genes are induced in response to macrophage co-incubation. Among these, amino acid and oligopeptide transporters, as well as lipases and proteases, are upregulated. Thus, C. auris shares key transcriptional signatures shared with other fungal pathogens and capitalizes on the expansion of gene families coding for potential virulence attributes that allow its survival, persistence, and evasion of the innate immune system

Los cultismos de cada día (2): los prefijos cultos de intensificación

[ES] Estudiamos un caso de lo que se puede considerar un conato de integración muy reciente de cultismos: el de algunos prefijos cultos de intensificación (super-, hiper- y ultra-). Valiéndonos de los grandes corpus, podemos constatar, primero, que la fecha de la primera atestación de estos elementos varía mucho de prefijo en prefijo, y que se encuentran por primera vez en un número bastante circunscrito de préstamos léxicos sueltos. Segundo, han tardado bastante en desarrollar un uso productivo independiente. Tercero, en la actualidad no todos tienen el mismo grado de independencia, siendo super- el que más libremente se combina con otras palabras e incluso se ha gramaticalizado hasta tal punto que se puede considerar un intensificador nuevo. Al analizar la capacidad combinatoria de estos prefijos, vemos que un buen indicio de su integración es que en la actualidad se pueden juntar tanto con palabras patrimoniales (supergastado, hiperdulce, ultrasencillo) como con préstamos modernos (supercool). Hay cierta rivalidad entre los tres prefijos en el sentido de que con algunas raíces parecen ser sinónimos, si bien en determinados casos sirven para distinguir diferentes conceptos técnicos. Concluimos que a pesar del origen culto de estos prefijos, su auge extraordinario en años recientes se debe más que nada a la influencia de otras lenguas, sobre todo del inglés, lo que ha alentado su productividad en español.[EN] I study a case of what may be considered a very recent process of embedding of learnèd borrowings: that of the intensifying prefixes super-, hiper- and ultra-. Using data collected from the large linguistic corpo-ra, it can be established, first, that the date of first attestation of each of these prefixes varies greatly, and that they are at first limited to a fairly small number of individual lexical borrowings. Secondly, their independent productive use develops much later. Thirdly, they do not all have the same degree of independence today: super- is the one which combines most freely with other words and has even grammati-calised to the extent that it can be considered a new intensifier. Looking at the combinatorial possibilities of these prefixes, it can be seen that a good indication of their integration into the language is that they can today combine both with inherited words (supergastado, hiperdulce, ultrasencillo) and with modern borrowings (supercool). There is some competition between the three prefixes in the sense that with some stems they appear to be synonymous, although in some cases they do distinguish different technical concepts. I conclude that despite the learnèd origin of these prefixes, their extraordinary increase in use in recent times is mainly due to the influence of other languages, most notably English, which has encouraged their productivity in Spanish

Iminosugars counteract the downregulation of the interferon gamma receptor by dengue virus

The antiviral mechanism of action of iminosugars against many enveloped viruses is hypothesized to be a consequence of misfolding of viral N-linked glycoproteins through inhibition of host endoplasmic reticulum alpha-glucosidase enzymes. Iminosugar treatment of dengue virus (DENV) infection results in reduced secretion of virions and hence lower viral titres in vitro and in vivo. We investigated whether iminosugars might also affect host receptors important in DENV attachment and uptake and immune responses to DENV. Using a primary human macrophage model of DENV infection, we investigated the effects of maturation with IL-4, DENV-infection and treatment with N-butyl-1-deoxynojirimycin (NB-DNJ) or N-(9-methoxynonyl)-1-DNJ (MON-DNJ) on expression of 11 macrophage receptors. Whereas iminosugars did not affect surface expression of any of the receptors examined, DENV infection significantly reduced surface IFN gamma receptor amongst other changes to total receptor expression. This effect required infectious DENV and was reversed by iminosugar treatment. Treatment also affected signalling of the IFN gamma receptor and TNF alpha receptor. In addition, iminosugars reduced ligand binding to the carbohydrate receptor-binding domain of the mannose receptor. This work demonstrates that iminosugar treatment of primary macrophages affects expression and functionality of some key glycosylated host immune receptors important in the dengue life cycle

Untargeted metabolomics to understand the basis of phenotypic differences in amphotericin B-resistant

Background: Protozoan Leishmania parasites are responsible for a range of clinical infections that represent a substantial challenge for global health. Amphotericin B (AmB) is increasingly used to treat Leishmania infection, so understanding the potential for resistance to this drug is an important priority. Previously we described four independently-derived AmB-resistant L. mexicana lines that exhibited resistance-associated genetic lesions resulting in altered sterol content. However, substantial phenotypic variation between these lines, including differences in virulence attributes, were not fully explained by these changes. Methods: To identify alterations in cellular metabolism potentially related to phenotypic differences between wild-type and AmB-resistant lines, we extracted metabolites and performed untargeted metabolomics by liquid chromatography-mass spectrometry. Results: We observed substantial differences in metabolite abundance between lines, arising in an apparently stochastic manner. Concerted remodeling of central carbon metabolism was not observed; however, in three lines, decreased abundance of several oligohexoses was observed. Given that the oligomannose mannogen is an important virulence factor in Leishmania, this could relate to loss of virulence in these lines. Increased abundance of the reduced forms of the oxidative stress-protective thiols trypanothione and glutathione was also observed in multiple lines. Conclusions: This dataset will provide a useful resource for understanding the molecular basis of drug resistance in Leishmania, and suggests a role for metabolic changes separate from the primary mechanism of drug resistance in determining the phenotypic profile of parasite lines subjected to experimental selection of resistance