35 research outputs found
Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery
Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose-based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self-assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co-assemblies can be molded by fine-tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo. Outstanding organ selectivities can then be programmed with no need of incorporating a biorecognizable motif in the formulation. The results provide a versatile strategy for the construction of fully synthetic and perfectly monodisperse nonviral gene delivery systems uniquely suited for optimization schemes by making cyclooligosaccharide patchiness the focus.Ministerio de Ciencia, Innovación y Universidades y Agencia Estatal de Investigación de España. RTI2018-097609-B-C21, RTI2018-097609-B-C22 y PID2019-105858RB-I00Universidad de Alcalá de Henares, Madrid. CCG19/CC-03
Brief cognitive assessment instruments in schizophrenia and bipolar patients, and healthy control subjects: A comparison study between the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) and the Screen for Cognitive Impairment in Psychiatry (SCIP)
Cognitive impairment in schizophrenia and psychosis is ubiquitous and acknowledged as a core feature of clinical expression, pathophysiology, and prediction of functioning. However, assessment of cognitive functioning is excessively time-consuming in routine practice, and brief cognitive instruments specific to psychosis would be of value. Two screening tools have recently been created to address this issue, i.e., the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) and the Screen for Cognitive Impairment in Psychiatry (SCIP). The aim of this research was to examine the comparative validity of these two brief instruments in relation to a global cognitive score. 161 patients with psychosis (96 patients diagnosed with schizophrenia and 65 patients diagnosed with bipolar disorder) and 76 healthy control subjects were tested with both instruments to examine their concurrent validity relative to a more comprehensive neuropsychological assessment battery. Scores from the B-CATS and the SCIP were highly correlated in the three diagnostic groups, and both scales showed good to excellent concurrent validity relative to a Global Cognitive Composite Score (GCCS) derived from the more comprehensive examination. The SCIP-S showed better predictive value of global cognitive impairment than the B-CATS. Partial and semi-partial correlations showed slightly higher percentages of both shared and unique variance between the SCIP-S and the GCCS than between the B-CATS and the GCCS. Brief instruments for assessing cognition in schizophrenia and bipolar disorders, such as the SCIP-S and B-CATS, seem to be reliable and promising tools for use in routine clinical practice
Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery
Instilling segregated cationic and lipophilic domains
with an angular disposition in a trehalose-based trifaceted
macrocyclic scaffold allows engineering patchy molecular
nanoparticles leveraging directional interactions that emulate
those controlling self-assembling processes in viral capsids.
The resulting trilobular amphiphilic derivatives, featuring a
Mickey Mouse architecture, can electrostatically interact with
plasmid DNA (pDNA) and further engage in hydrophobic
contacts to promote condensation into transfectious nanocomplexes.
Notably, the topology and internal structure of
the cyclooligosaccharide/pDNA co-assemblies can be molded
by fine-tuning the valency and characteristics of the cationic
and lipophilic patches, which strongly impacts the transfection
efficacy in vitro and in vivo. Outstanding organ
selectivities can then be programmed with no need of
incorporating a biorecognizable motif in the formulation. The
results provide a versatile strategy for the construction of fully
synthetic and perfectly monodisperse nonviral gene delivery
systems uniquely suited for optimization schemes by making
cyclooligosaccharide patchiness the focus.Peer reviewe
Exome reanalysis and proteomic profiling identified TRIP4 as a novel cause of cerebellar hypoplasia and spinal muscular atrophy (PCH1)
TRIP4 is one of the subunits of the transcriptional coregulator ASC-1, a ribonucleoprotein complex that participates in transcriptional coactivation and RNA processing events. Recessive variants in the TRIP4 gene have been associated with spinal muscular atrophy with bone fractures as well as a severe form of congenital muscular dystrophy. Here we present the diagnostic journey of a patient with cerebellar hypoplasia and spinal muscular atrophy (PCH1) and congenital bone fractures. Initial exome sequencing analysis revealed no candidate variants. Reanalysis of the exome data by inclusion in the Solve-RD project resulted in the identification of a homozygous stop-gain variant in the TRIP4 gene, previously reported as disease-causing. This highlights the importance of analysis reiteration and improved and updated bioinformatic pipelines. Proteomic profile of the patient’s fibroblasts showed altered RNA-processing and impaired exosome activity supporting the pathogenicity of the detected variant. In addition, we identified a novel genetic form of PCH1, further strengthening the link of this characteristic phenotype with altered RNA metabolism
CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative
Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research
Validation of an Academic Self-Attribution Questionnaire for Primary and Secondary School Students: Implications of Gender and Grade
The way in which students attribute causes to their successes and failures in school has important implications for their development. The objectives of our research were to validate the Academic Success and Failure Attribution Questionnaire (ASFAQ) and to analyze the gender and grade differences in the ASFAQ data for primary and secondary school students in Spain. For the construction and analysis of the psychometric characteristics of the scale, an exploratory factor analysis (EFA) and a confirmatory factor analysis (CFA) were performed. To compare the ASFAQ scores based on gender and school year, a parametric t-test for independent samples and a one-way analysis of variance (ANOVA) was used. A total of 562 students in the fifth (n = 228) and sixth year (n = 186) of primary studies and the first (n = 134) and second year (n = 94) of secondary studies participated in the research. The results showed the adequate factorial structure, internal consistency, and validity of the ASFAQ, in addition to statistically significant differences by gender and school year. This research provides scientific evidence about the psychometric properties of the ASFAQ to assess and understand attributional style in the educational context, as well as current and consistent empirical evidence related to gender and grade differences in the attributional patterns of academic success and failure for primary and secondary school students
Trifaceted Mickey Mouse Amphiphiles for Programmable Self‐Assembly, DNA Complexation and Organ‐Selective Gene Delivery
Instilling segregated cationic and lipophilic domains
with an angular disposition in a trehalose-based trifaceted
macrocyclic scaffold allows engineering patchy molecular
nanoparticles leveraging directional interactions that emulate
those controlling self-assembling processes in viral capsids.
The resulting trilobular amphiphilic derivatives, featuring a
Mickey Mouse architecture, can electrostatically interact with
plasmid DNA (pDNA) and further engage in hydrophobic
contacts to promote condensation into transfectious nanocomplexes.
Notably, the topology and internal structure of
the cyclooligosaccharide/pDNA co-assemblies can be molded
by fine-tuning the valency and characteristics of the cationic
and lipophilic patches, which strongly impacts the transfection
efficacy in vitro and in vivo. Outstanding organ
selectivities can then be programmed with no need of
incorporating a biorecognizable motif in the formulation. The
results provide a versatile strategy for the construction of fully
synthetic and perfectly monodisperse nonviral gene delivery
systems uniquely suited for optimization schemes by making
cyclooligosaccharide patchiness the focus.Peer reviewe