African American Vernacular English: an analysis of verbs in the film "The Color Purple".

openThe dissertation focuses on African American Vernacular English (AAVE) and it aims to present the origins and structures of the language, as well as the social impacts that AAVE has on its speakers. Theories about its origins are introduced in the first part, together with an analysis of some typical grammatical structures of verb tenses, negative sentences and some phonological aspects.The second part focuses on impacts that AAVE has on its speakers, taking into account three main areas, in which AAVE speakers may encounter social issues: the education, the job market and the justice system. The last part aims to provide a further representation of verbs of AAVE found in the film “The Color Purple ''.The dissertation focuses on African American Vernacular English (AAVE) and it aims to present the origins and structures of the language, as well as the social impacts that AAVE has on its speakers. Theories about its origins are introduced in the first part, together with an analysis of some typical grammatical structures of verb tenses, negative sentences and some phonological aspects.The second part focuses on impacts that AAVE has on its speakers, taking into account three main areas, in which AAVE speakers may encounter social issues: the education, the job market and the justice system. The last part aims to provide a further representation of verbs of AAVE found in the film “The Color Purple ''

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Yeast membrane engineering to improve acetic acid tolerance for lignocellulose conversion.

Global issues such as climate change, exploitation and waste of resources raise the need for solutions for a more sustainable future. Fossil based chemicals, fuels and energy should be replaced by more sustainable alternatives. Lignocellulose biomass is one of the most abundant raw material on earth, which make it easy to use it for such purposes. However, research involved in transforming this resource into desired products still has issues linked to achieving high yields and productivity. One of those problems is the presence of inhibitory compounds produced during the lignocellulosic biomass pre-treatments, which contribute to reduce the fermentation performances. Inhibitors such acetic acid can, in fact, penetrate inside of yeast cells and alter their metabolism. Studies in this field have shown that the yeast membrane composition and especially its sphingolipids content could be a key point to overcome the acid stress. The specific aim of this thesis was to investigate the role of the different genes involved in the sphingolipid’s biosynthetic pathway in Zygosaccharomyces bailii. This study was conducted to better understand how to engineer the Saccharomyces cerevisiae cell membrane to minimize acetic acid intake. Gene expression analysis showed that genes involved in the biosynthesis of sphingolipids (NVJ2, SAC1, AUR1, LRO1, DGA1, KEI1) are overexpressed while the cells are exposed to acetic acid. This suggested that in the analysed conditions the sphingolipids pathway is highly active. From this study it was possible to select four relevant genes: NVJ2, SAC1, AUR1 and KEI1 which have been subsequently overexpressed in Saccharomyces cerevisiae to observe how the modified strains would react when exposed to acetic acid

Loss-of-function mutations in the CABLES1 gene are a novel cause of Cushing's disease.

The CABLES1 cell cycle regulator participates in the adrenal-pituitary negative feedback, and its expression is reduced in corticotropinomas, pituitary tumors with a largely unexplained genetic basis. We investigated the presence of CABLES1 mutations/copy number variations (CNVs) and their associated clinical, histopathological and molecular features in patients with Cushing's disease (CD). Samples from 146 pediatric (118 germline DNA only/28 germline and tumor DNA) and 35 adult (tumor DNA) CD patients were screened for CABLES1 mutations. CNVs were assessed in 116 pediatric CD patients (87 germline DNA only/29 germline and tumor DNA). Four potentially pathogenic missense variants in CABLES1 were identified, two in young adults (c.532G > A, p.E178K and c.718C > T, p.L240F) and two in children (c.935G > A, p.G312D and c.1388A > G, and p.D463G) with CD; no CNVs were found. The four variants affected residues within or close to the predicted cyclin-dependent kinase-3 (CDK3)-binding region of the CABLES1 protein and impaired its ability to block cell growth in a mouse corticotropinoma cell line (AtT20/D16v-F2). The four patients had macroadenomas. We provide evidence for a role of CABLES1 as a novel pituitary tumor-predisposing gene. Its function might link two of the main molecular mechanisms altered in corticotropinomas: the cyclin-dependent kinase/cyclin group of cell cycle regulators and the epidermal growth factor receptor signaling pathway. Further studies are needed to assess the prevalence of CABLES1 mutations among patients with other types of pituitary adenomas and to elucidate the pituitary-specific functions of this gene

A Novel Mutation in the Upstream Open Reading Frame of the CDKN1B Gene Causes a MEN4 Phenotype

PubMed ID: 23555276This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Rapid proteasomal degradation of mutant proteins is the primary mechanism leading to tumorigenesis in patients with missense AIP mutations

CONTEXT The pathogenic effect of AIP mutations (AIPmuts) in pituitary adenomas is incompletely understood. We have identified the primary mechanism of loss of function for missense AIPmuts. OBJECTIVE To analyze the mechanism/speed of protein turnover of wild-type (WT) and missense AIP variants, correlating protein half-life with clinical parameters. DESIGN Half-life and protein-protein interaction experiments and cross-sectional analysis of AIPmut positive patients' data were performed. SETTING Clinical academic research institution. PATIENTS Data was obtained from our cohort of pituitary adenoma patients and literature-reported cases. INTERVENTIONS Protein turnover of endogenous AIP in two cell lines and fifteen AIP variants overexpressed in HEK293 cells was analyzed via cycloheximide chase and proteasome inhibition. GST pull-down and quantitative mass spectrometry identified proteins involved in AIP degradation; results were confirmed by co-immunoprecipitation and gene knockdown. Relevant clinical data was collected. MAIN OUTCOME MEASURES Half-life of WT and mutant AIP proteins and its correlation with clinical parameters. RESULTS Endogenous AIP half-life was similar in HEK293 and lymphoblastoid cells (43.5 and 32.7h). AIP variants were divided in stable proteins (median 77.7h [IQR 60.7-92.9]), and those with short (27h [21.6-28.7]) or very short (7.7h [5.6-10.5]) half-life; proteasomal inhibition rescued the rapid degradation of mutant proteins. The experimental half-life significantly correlated with age at diagnosis of acromegaly/gigantism (r=0.411, P=0.002). The FBXO3-containing SCF complex was identified as the E3 ubiquitin-ligase recognizing AIP. CONCLUSIONS AIP is a stable protein, driven to ubiquitination by the SCF complex. Enhanced proteasomal degradation is a novel pathogenic mechanism for AIPmuts, with direct implications for the phenotype

Quantification of Microbial Robustness in Yeast

Stable cell performance in a fluctuating environment is essential for sustainable bioproduction and synthetic cell functionality; however, microbial robustness is rarely quantified. Here, we describe a high-throughput strategy for quantifying robustness of multiple cellular functions and strains in a perturbation space. We evaluated quantification theory on experimental data and concluded that the mean-normalized Fano factor allowed accurate, reliable, and standardized quantification. Our methodology applied to perturbations related to lignocellulosic bioethanol production showed that the industrial bioethanol producing strain Saccharomyces cerevisiae Ethanol Red exhibited both higher and more robust growth rates than the laboratory strain CEN.PK and industrial strain PE-2, while a more robust product yield traded off for lower mean levels. The methodology validated that robustness is function-specific and characterized by positive and negative function-specific trade-offs. Systematic quantification of robustness to end-use perturbations will be important to analyze and construct robust strains with more predictable functions

Low adherence to influenza vaccination campaigns: is the H1N1 virus pandemic to be blamed?

<p>Abstract</p> <p>Background</p> <p>Over the last few months, debates about the handling of the influenza virus A (H1N1) pandemic took place, in particular regarding the change of the WHO pandemic definition, economic interests, the dramatic communication style of mass media. The activation of plans to reduce the virus diffusion resulted in an important investment of resources. Were those investments proportionate to the risk? Was the pandemic overrated? The workload of the Pediatric Emergency Room (P.E.R.) at a teaching hospital in Varese (Northern Italy) was investigated in order to evaluate the local diffusion and severity of the new H1N1 influenza epidemic.</p> <p>Discussion</p> <p>A 100% increase of the number of P.E.R. visits, particularly for influenza-like illness, was recorded during weeks 42-46 of 2009 (October, 17 to November, 2); the low rate of hospitalization and the mild presentation of the infection gave rise to the conclusion that the pandemic risk was overrated. Mass media communications concerning the new virus created a disproportionate fear in the population that significantly enhanced the burden of cares at the hospital. In the absence of generally implemented measures for etiological diagnosis, the actual incidence of the H1N1 infection could not be estimated. Virus identification, in fact, was limited to children showing severe symptoms after consultancy with an infectious disease specialist. The alarming nature of the communication campaign and the choice to limit etiologic diagnosis to severe cases created a climate of uncertainty which significantly contributed to the massive admissions to the P.E.R..</p> <p>Summary</p> <p>The communication strategy adopted by the mass media was an important element during the pandemic: the absence of clarity contributed to the spread of a pandemic phobia that appeared to result more from the sensationalism of the campaign than from infection with the novel influenza A variant of human, avian, swine origin virus. One relevant effect of the media coverage was the extremely low adherence rate to the vaccination campaign for the 2009-2010 and 2010-2011, especially among the high- risk population and health care workers. One positive consequence was, however, the spread of preventive hygiene measures, such as hand washing.</p

Aryl Hydrocarbon Receptor Interacting Protein Maintains Germinal Center B Cells through Suppression of BCL6 Degradation

B cell lymphoma-6 (BCL6) is highly expressed in germinal center B cells, but how its expression is maintained is still not completely clear. Aryl hydrocarbon receptor interacting protein (AIP) is a cochaperone of heat shock protein 90. Deletion of Aip in B cells decreased BCL6 expression, reducing germinal center B cells and diminishing adaptive immune responses. AIP was required for optimal AKT signaling in response to B cell receptor stimulation, and AIP protected BCL6 from ubiquitin-mediated proteasomal degradation by the E3-ubiquitin ligase FBXO11 by binding to the deubiquitinase UCHL1, thus helping to maintain the expression of BCL6. AIP was highly expressed in primary diffuse large B cell lymphomas compared to healthy tissue and other tumors. Our findings describe AIP as a positive regulator of BCL6 expression with implications for the pathobiology of diffuse large B cell lymphoma

Yacht Design and Maritime Landscape: Continuity in artisan Culture

The paper highlights the matrices of Mediterranean navigation and the relationship with artisan work processes, as well as how they have continued to characterize the nautical field and how research has identified themes which today seem to be able to characterise a culturally and economically important sector such as that of the production of sports yachts