Processing of insect retrotransposons by self-cleaving ribozymes

We show that several classes of insect non-LTR retrotransposons harbor self-cleaving ribozymes of the HDV family at their 5′ termini. In Drosophila the R2 ribozymes exhibit highly differential in vivo expression and robust in vitro activity, modulated by an upstream sequence originating from the insertion site. Our data suggest a role for self-cleaving ribozymes in co-transcriptional processing of retrotransposons with implications for downstream events, including translation and retrotransposition

Assessment of Human Anthropometry With a Markerless Motion Capture System

In this methodological study, we evaluate the accuracy and repeatability of the Theia markerless motion capture system for determining accurate anthropometric measurements. We will assess the correlation between linear measurements from a sample of human subjects (limb, torso, shoulder, limb segment lengths, bi-illiac breadth, body height, etc) as measured by the markerless system to those same measurements as assessed by hand. We will also calculate the intra-observer error of the markerless system’s measurements by repeating measurement sessions for each subject multiple times over several days. We hypothesize that the markerless system will demonstrate low intra-observer error and a high correlation with hand-measured anthropometric measurements. If our results support this hypothesis, the markerless system will be used for our project investigating the relationship between anthropometry and the biomechanics of ascending steep inclines. Being able to use the markerless system in our slope-walking project would not only allow for more consistent data collection, it would remove the risk of introducing inter-observer by having multiple individuals collect anthropometric measurements by hand. In assessing the accuracy and repeatability of the Theia markerless system for anthropometric measurements, we can determine if it is a useful method of data collection for our lab’s larger biomechanics project

DNA Based Carbon Nanotube Porphyrin Nanohybrids Molecular Recognization and Regeneration

In the search to improve solar cells, scientists are exploring new materials that will provide better current transfer. One material that has emerged as a strong contender is the single walled carbon nanotube (SWNT). Current DNA-SWNT based films combined with chromophores have poor operational lifetimes compared to commercial solar cells. Once exposed to light the chromophore begins to degrade, eventually rendering the solar cell unusable. To solve this problem, we used a method involving multiple steps. First we found which DNA sequences formed structures around the SWNT that could hold the most chromophores by using a spectrophotometer to test the concentration of chromophores on each film. Secondly we determined which chromophores generated the strongest current when exposed to light by testing the photocurrent of each film. Finally we searched for a chemical, or solution, that would remove damaged chromophores without damaging or removing the DNA or SWNTs from the film. Currently it has been found that DNA sequences high in guanine, which form G-quadruplexes, are ideal for holding chromophores. Through testing, we found that zinc porphyrin created the strongest current of the chromophores tried. Research still needs to be done to find an ideal solution for removing damaged chromophores, but progress has been made into making organic solar cells viable. Eventually automating this process, a solar cell could be repeatedly refunctionalized, thus extending the life of the solar cells indefinitely

An in vitro study of factors which may alter the production of high density lipoproteins in the human body

Thesis (B.S.) in Biochemistry -- University of Illinois at Urbana-Champaign, 1987.Bibliography: leaf 23-24.Microfiche of typescript. [Urbana, Ill.]: Photographic Services, University of Illinois, U of I Library, [1987]. 2 microfiches (42 frames): negative

Qualidade E Inovação No Serviço Público: Desafios Do Estado Brasileiro

Trata o presente artigo da análise sobre a utilização da qualidade e inovação enquanto instrumentos alternativos para minimizar a crise, sem precedentes, instalada em setores estratégicos do Estado brasileiro

EXTRACELLULAR SPHINGOSINE-1-PHOSPHATE: A NOVEL ACTOR IN HUMAN GLIOBLASTOMA STEM CELL SURVIVAL PROPERTIES

Glioblastoma multiforme (GBM) is the most frequent and aggressive intracranial tumour in humans. The prognosis of GBM patients remains unfavourable even after aggressive treatments based on multiple approaches, due to the high proliferation rate, migrating-invasive properties, and resistance to therapeutic intervention. The introduction of the alkylating agent TMZ in glioblastoma therapy has improved patient survival, but drug resistance mechanisms limit its benefits. The aim of this study was to provide a contribution to the understanding of the malignant and chemoresistance properties in GBM by focusing on the role of the bioactive sphingoid molecules ceramide and S1P, which act as antagonists in regulating cell properties and survival. Accumulating literature indicates that ceramide is a tumour suppressor sphingolipid, able to induce antiproliferative and apoptotic responses, and that it is able to act as a major player in the mechanism of action of many chemotherapeutic drugs. We demonstrated that the treatment of T98G human glioblastoma cells with cytotoxic TMZ concentrations results in a significant increase in intracellular ceramide, which in turn promotes cell death. On the other hand, TMZ is not able to induce ceramide accumulation in TMZ-resistant glioblastoma cells (TMZ-R). These data suggest a role of ceramide as a mediator of TMZ-induced toxicity. A large amount of evidence underlines the role of S1P as an important tumour-promoting sphingolipid, acting predominantly in the extracellular milieu after interaction with specific G protein-coupled receptors and exerting opposite effects on cell survival compared to ceramide. Parallel studies demonstrated that S1P secretion in TMZ-R cells is functional to inhibit the cytotoxic effect of ceramide and to confer TMZ-resistant properties to glioblastoma cells. Stimulated by these findings, we next evaluated the role of sphingolipid mediators in the malignant features of glioblastoma stem cells (GSCs), a cell subpopulation within the tumour mass involved in the aberrant expansion and therapy resistance properties of glioblastomas. To this purpose we used GSCs isolated from the human U87-MG glioblastoma cell line and GSCs isolated from a primary culture of human glioblastoma. We found that both GSC models efficiently form typical neurosphere structures in mitogen-defined medium and express high levels of recognized cancer stem cell markers. Moreover, GSCs exhibit resistance to TMZ at concentrations that are cytotoxic in U87-MG, despite not expressing the DNA repair protein MGMT, a major contributor to TMZ-resistance. Even though a large amount of evidence underlines that S1P is able to favor growth, invasion and chemotherapy resistance of glioblastoma cells, so far little is known on the possible role of S1P as a factor modulating GSCs malignant properties. Further experiments revealed that glioblastoma cells and GSCs are able to efficiently synthesize S1P and also to release it in the culture medium. Notably the intracellular S1P level was found much lower in GSC models than in the glioblastoma cell line; meanwhile the extracellular S1P level was significantly higher in GSC models than in U87-MG cells. These differences resulted in an extracellular S1P-intracellular S1P ratio at least 10 times higher in GSCs compared to U87-MG. Furthermore, this ratio is about 1:1 in both GSCs, thus suggesting that these cells are an efficient source of S1P in the extracellular microenvironment. Furthermore we found that ceramide-extracellular S1P ratio is at least 2-fold lower in GSCs than in U87-MG. Since S1P and ceramide exert opposing effects on cell survival, according to the \u201csphingolipid rheostat\u201d model, this different ratio could promote GSC survival observed after TMZ treatment. Interestingly, enzyme activity assays excluded the presence of sphingosine kinase (SK), the enzyme responsible for S1P byosinthesis, in GSC medium, implicating an efficient secretion of S1P in GSCs. The analyses of the expression of the ABC-transporters known to be involved in S1P export (ABCG2, ABCA1 and ABCC1), revealed that only ABCA1 is expressed in GSCs. Notwithstanding, after ABCA1 inhibition, no variations in S1P release was observed, suggesting that other mechanisms different from those known are involved. We also investigated the role of S1P in glioblastoma resistance to TMZ. A first interesting finding was that exogenously administered S1P protected U87-MG cells against TMZ cytotoxic effects. In addition, we found that, after co-treatment with TMZ and an inhibitor of S1P biosynthesis, GSCs became sensitive to the toxic effect of the drug. Of note, exogenous S1P administration was able to revert this effect. These data strongly support extracellular S1P as an important mediator in TMZ-resistance of GSCs. Furthermore, results obtained in GSCs isolated from two patients affected by glioblastoma with different aggressive phenotype, revealed that the extracellular release of S1P was significantly higher by cells isolated from the most aggressive tumour, suggesting that the release and thus the levels of extracellular S1P might be related to tumour aggressiveness and patient prognosis. In conclusion, our data implicate for the first time GSCs as an important source of S1P in the extracellular microenvironment, where, on its turn, S1P can act as an autocrine/paracrine messenger able to contribute to the GSC survival properties. A better understanding of S1P role in GSCs aggressive phenotype could represent a critical start point that sets the bases for the development of new compounds able to sensitize GSCs to chemotherapeutic treatments, thus improving survival rates in GBM patients

O fim final da imaginação: sobre a relação entre ideal moral e reflexividade na Crítica de Immanuel Kant sobre o Poder do Juízo

One main quandary that emerges in the context of Immanuel Kant’s moral ideal, The Highest Good, is that on the one hand Kant sets it as a moral demand, that is, as a principle that must be comprehended as an attainable end for man in practice while, on the other hand, it is set as a moral ideal, i.e. as something that cannot be concretized and realized within the empirical world. The main goal of this paper is to argue for the realizability of the moral ideal by means of the principle of reflective judgment as a form of judgment that in fact clarifies human limitation. I assert that the very recognition of this limitation constitutes the possibility for hope in that ideal, or for striving towards it, and that this striving is the only way that the moral ideal can be concretized. I examine man’s recognition of self-limitation as a response to the moral demand to realize the moral ideal and the necessity of the power of imagination for this, used reflectively. Keywords: culture, final end, Highest Good, hope, imagination, Kant, moral ideal reflective judgment, ultimate end.Um dos principais dilemas que surge no contexto do ideal moral de Immanuel Kant, O Bem Supremo, é que, por um lado, Kant o define como uma demanda moral, isto é, como um princípio que deve ser compreendido como um fim possível para o homem na prática enquanto, por outro lado, é definido como um ideal moral, ou seja, como algo que não pode ser concretizado e realizado dentro do mundo empírico. O objetivo principal deste artigo é argumentar pela realizabilidade do ideal moral por meio do princípio do juízo reflexivo como uma forma de julgamento que de fato esclarece a limitação humana. Afirmo que o próprio reconhecimento dessa limitação constitui a possibilidade da esperança neste ideal, ou para alcançá-lo, e que essa luta é a única maneira de concretizar o ideal moral. Examino o reconhecimento do homem da auto-limitação como uma resposta à demanda moral para realizar o ideal moral e a necessidade do poder da imaginação para isso, usado de forma reflexiva. Palavras-chave: cultura, fim final, bem supremo, esperança, imaginação, Kant, juízo moral reflexivo ideal, fim último

Treatment satisfaction, adherence and behavioral assessment in patients de – escalating from natalizumab to interferon beta

Background: De-escalating natalizumab (NTZ) to interferon beta 1b (IFN B 1B) is a possible treatment option in multiple sclerosis (MS) patients interrupting NTZ because of increased risk of progressive multifocal leukoencephalopathy (PML). The aim of this study was to evaluate satisfaction and adherence to treatment, behavioral and fatigue changes in patients switched to IFN B 1B compared to continued NTZ treatment. Methods: A 1 year, prospective, randomized, rater-blinded, parallel-group study. Nineteen relapsing remitting (RR) MS patients, randomly assigned to undergo either NTZ (n = 10) or IFN B 1B (n = 9) treatment, who had previously received NTZ for at least 12 months with disease stability and fearing or at risk for PML were included. Patients underwent behavioral and treatment assessments at baseline, after 24-week and 1 year follow-up. Behavioral assessment included measures of cognition, fatigue and quality of life. Treatment assessment included measures of satisfaction, persistence and adherence to treatment. Clinical-radiological disease activity and safety were also assessed. Results: Baseline characteristics of patients were similar between groups except for Euro Quality Visual Analogue Scale, being higher in the NTZ group (p = 0.04). Within-group comparisons at the three time points, as well as interaction analysis of treatment effect over time did not show any statistically significant differences in behavioral or treatment assessments, but a coherent trend favoring NTZ over IFN B 1B. Conclusions: De-escalating NTZ to IFN B 1B is feasible and associated with overall good patient related outcome and persistently stable behavioral measures

Voxelwise assessment of the regional distribution of damage in the brains of patients with multiple sclerosis and fatigue

BACKGROUND AND PURPOSE: Fatigue affects up to 90% of patients with MS. We assessed the regional distribution of lesions and atrophy of the normal-appearing WM and GM in patients with RRMS with fatigue compared with HC and patients with similar characteristics, but without fatigue. MATERIALS AND METHODS: From 14 patients with RRMS without fatigue, 10 with RRMS with fatigue, and 14 HC, we acquired brain dual-echo and high-resolution T1-weighted scans. Voxel-wise distributions of GM, WM damage, and T2 lesions were compared between patients with fatigued and nonfatigued MS by using SPM5 software. We report results at P < .05, FWE corrected. RESULTS: T2 lesion distribution and regional WM atrophy did not differ between patients with fatigued and nonfatigued MS. Compared with HC, patients with MS had significant WM atrophy in the posterior part of the corpus callosum and significant GM atrophy of the left superior frontal sulcus, left precentral gyrus, posterior cingulate cortex, right thalamus, and left middle frontal gyrus. No additional areas of atrophy were found in patients with nonfatigued MS compared with HC, whereas patients with fatigued MS also had atrophy of the left central sulcus. Atrophy in the left central sulcus and the precentral gyrus was more severe in patients with fatigued versus nonfatigued MS. In patients with MS, significant correlations were found between fatigue severity and GM atrophy in the left precentral gyrus (r = −0.73, P < .0001 uncorrected). CONCLUSIONS: Atrophy of the primary sensorimotor area is likely to contribute to MS-related fatigue