1,223 research outputs found
The primary structure of mitochondrial aspartate aminotrasferase from human heart
The complete amino acid sequence of the mitochondrial asparate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) from human heart has been determined based mainly on analysis of peptides obtained by digestion with trypsin and by chemical cleavage with cyanogen bromide. Comparison of the sequence with those of the isotopic isoenzymes from pig, rat and chicken showed 27, 29 and 55 differences, respectively, out of a total of 401 amino acid residues. Evidence for structural microheterogeneity at position 317 has also been obtained
Preface: BITS2014, the annual meeting of the Italian Society of Bioinformatics
This Preface introduces the content of the BioMed Central journal Supplements related to BITS2014 meeting, held in Rome, Italy, from the 26th to the 28th of February, 2014
Iterative focused screening with biological fingerprints identifies selective Asc-1 inhibitors distinct from traditional high throughput screening
N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer’s disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine–serine–cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs. To identify novel Asc-1 inhibitors, two different screening approaches were performed with whole-cell amino acid uptake in heterologous cells stably expressing human Asc-1: (1) a high-throughput screen (HTS) of 3 M compounds measuring 35S l-cysteine uptake into cells attached to scintillation proximity assay beads in a 1536 well format and (2) an iterative focused screen (IFS) of a 45 000 compound diversity set using a 3H d-serine uptake assay with a liquid scintillation plate reader in a 384 well format. Critically important for both screening approaches was the implementation of counter screens to remove nonspecific inhibitors of radioactive amino acid uptake. Furthermore, a 15 000 compound expansion step incorporating both on- and off-target data into chemical and biological fingerprint-based models for selection of additional hits enabled the identification of novel Asc-1-selective chemical matter from the IFS that was not identified in the full-collection HTS
Academic expectations profiles of spanish and portuguese higher education students
Las expectativas académicas de los
estudiantes son hoy reconocidas como una
variable importante en la explicación de su
adaptación y éxito académico. Esa importancia
es mayor en los alumnos del primer año, ya
que, frecuentemente presentan expectativas
iniciales muy elevadas que no siempre llegan
a concretarse. Con la pretensión de conocer
cuáles son esas expectativas iniciales, el trabajo que se presenta analiza el perfil de las mismas en estudiantes de Enseñanza Superior (ES) de primer año. La muestra está
compuesta por 719 estudiantes de diversas
titulaciones académicas de las Universidades
de Vigo-Campus de Ourense y Minho. A los
participantes se les aplicó el Cuestionario
de Percepciones Académicas (CPA). Los
resultados han sido analizados tomando
la nacionalidad y el ámbito de estudio (cientifico, juridico-social, tecnológico). Los resultados muestran que los estudiantes
portugueses tienden a presentar expectativas
más elevadas en general, traduciéndose en
una valoración superior de su entrada en la Universidad. A su vez, considerando las siete
dimensiones de expectativas evaluadas, se comprueba un perfil similar para ambos paÃses en relación a las expectativas más o menos
valoradas. Se destacan las expectativas de
obtener una formación que permita acceder
a un buen empleo o carrera, en primer lugar,
y las expectativas de tener en la Universidad
oportunidades de desarrollo personal y social,
en segundo lugar, como las más valoradas por
los estudiantes.Academic expectations are recognized as
an important variable for students’ adjustment
and academic success. This importance is higher for first year students, because they often present initial expectations that may
not be met. Aiming at identifying these initial
expectations, this study presents and analyses the profile of first year students' academic expectations. The sample included 719
students attending different undergraduate
programs at University of Vigo - Campus
of Ourense, and at University of Minho.
Participants completed the Academic
Perceptions Questionnaire (APQ). Analyses
were based on students’ nationality and study domain (scientific, juridical-social, technological). Results show that Portuguese
students present higher expectations, in
general, which shows they attribute a higher
value to their access to University. On the other
hand, and regarding the seven dimensions of
assessed expectations, we can see that this
difference in average scores is not structural,
because there is a similar pattern of higher and
lower expectations, for both countries. The most valued expectations are, in first place, expectations of having an education that will
lead to a good job or career, and in second
place, expectations of having opportunities of
personal and social development in University
Known drugs identified by structure-based virtual screening are able to bind sigma-1 receptor and increase growth of huntington disease patient-derived cells
Huntington disease (HD) is a devastating and presently untreatable neurodegenerative disease characterized by progressively disabling motor and mental manifestations. The sigma-1 receptor (σ1R) is a protein expressed in the central nervous system, whose 3D structure has been recently determined by X-ray crystallography and whose agonists have been shown to have neuro-protective activity in neurodegenerative diseases. To identify therapeutic agents against HD, we have implemented a drug repositioning strategy consisting of: (i) Prediction of the ability of the FDA-approved drugs publicly available through the ZINC database to interact with σ1R by virtual screening, followed by computational docking and visual examination of the 20 highest scoring drugs; and (ii) Assessment of the ability of the six drugs selected by computational analyses to directly bind purified σ1R in vitro by Surface Plasmon Resonance and improve the growth of fibro-blasts obtained from HD patients, which is significantly impaired with respect to control cells. All six of the selected drugs proved able to directly bind purified σ1R in vitro and improve the growth of HD cells from both or one HD patient. These results support the validity of the drug repositioning procedure implemented herein for the identification of new therapeutic tools against HD
Inverse Modeling for MEG/EEG data
We provide an overview of the state-of-the-art for mathematical methods that
are used to reconstruct brain activity from neurophysiological data. After a
brief introduction on the mathematics of the forward problem, we discuss
standard and recently proposed regularization methods, as well as Monte Carlo
techniques for Bayesian inference. We classify the inverse methods based on the
underlying source model, and discuss advantages and disadvantages. Finally we
describe an application to the pre-surgical evaluation of epileptic patients.Comment: 15 pages, 1 figur
Clinical features of patients with type 2 diabetes with and without Covid-19: a case control study (CoViDiab I)
Aims: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. Methods: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. Results: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59–3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42–9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18–8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13–0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12–0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16–0.93, p = 0.033) were found among cases. Conclusions: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes
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